Publications by authors named "Herng-Sheng Lee"

150 Publications

Nasal Cavity Schwannoma-A Case Report and Review of the Literature.

Ear Nose Throat J 2021 Jul 28:1455613211034598. Epub 2021 Jul 28.

Department of Otorhinolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung.

Schwannomas are rare slow-growing benign tumors arising from Schwann cells lining the nerve sheaths. Head and neck schwannomas account for about one-third of all cases, and only 4% of them arise from the sinonasal tract. Its diagnosis is based on histology and immunohistochemistry. Complete surgical excision is the most recommended treatment option, and endoscopic surgery has been widely performed in recent years. In this study, we presented a case of a 55-year-old female with schwannoma arising from the lateral wall of the nasal cavity, causing epistaxis and rhinorrhea. The patient underwent endoscopic excision with prompt resolution of symptoms. The reported cases of nasal cavity schwannoma were reviewed and summarized for educational purposes.
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http://dx.doi.org/10.1177/01455613211034598DOI Listing
July 2021

Cardamonin Attenuates Inflammation and Oxidative Stress in Interleukin-1β-Stimulated Osteoarthritis Chondrocyte through the Nrf2 Pathway.

Antioxidants (Basel) 2021 May 27;10(6). Epub 2021 May 27.

Department of Orthopedics, National Defense Medical Center, Tri-Service General Hospital, Taipei 114, Taiwan.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the deterioration of articular cartilage. The progression of OA leads to an increase in inflammatory mediators in the joints, thereby promoting the destruction of the cartilage matrix. Recent studies have reported on the anti-inflammatory and antioxidant properties of cardamonin, which also appears to interact with cellular targets, such as nuclear erythroid 2-related factor 2 (Nrf2), extracellular signal-regulated kinase (ERK), and mammalian target of rapamycin (mTOR) during the progression of tumors. To date, few studies have investigated the effects of cardamonin on chondrocyte inflammation. In the current study, we determined that treating interleukin-1 beta (IL-1β-stimulated chondrocyte cells) with cardamonin significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) and significantly inhibited the expression of pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Cardamonin was also shown to: (1) inhibit the activation and production of matrix metalloproteinases (MMPs), (2) suppress the nuclear factor-κB (NF-κB) signaling pathway, (3) suppress the expression of toll-like receptor proteins, (4) activate the Nrf2 signaling pathway, and (5) increase the levels of antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The increase in antioxidant proteins led to corresponding antioxidant effects (which were abolished by Nrf2 siRNA). Our findings identify cardamonin as a candidate Nrf2 activator for the treatment and prevention of OA related to inflammation and oxidative stress.
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http://dx.doi.org/10.3390/antiox10060862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227809PMC
May 2021

Hypoperfusion of the infrapatellar fat pad and its relationship to MRI T2* relaxation time changes in a 5/6 nephrectomy model.

Sci Rep 2021 May 11;11(1):9924. Epub 2021 May 11.

Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, 11490, Taiwan.

The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague-Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, k and k) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability k values from 16 weeks (p < 0.05), lower venous washout k value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.
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http://dx.doi.org/10.1038/s41598-021-89336-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113578PMC
May 2021

Secular trends of patients hospitalized for major osteoporotic fractures based on a national claims database.

Arch Osteoporos 2021 04 7;16(1):62. Epub 2021 Apr 7.

Department of Medical Research, Clinical Medicine Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, No. 539, Zhongxiao Rd., East District, Chia-Yi, 600, Taiwan.

There was a reduction in the hospitalization rate for major osteoporotic fractures. As per our analysis, hospitalization for site-specific fractures showed a declining trend for hip and vertebral fractures for both the sexes. However, an increasing trend was noted in women regarding hospitalization for forearm fracture.

Purpose: Major osteoporotic fractures (MOFs) constitute a large proportion of the total expenditures for public healthcare. Knowing the secular trends of MOF will allow for more efficient use of healthcare resources, but such data are insufficient for the current population of Taiwan. Therefore, we investigated the epidemiological data of MOF hospitalization from adults 50 years of age or older in Taiwan during the period 2000-2015.

Methods: The data analyzed were acquired from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2000 and 2015. All study subjects were 50 years of age or older at the time of admission and diagnosed as having MOF.

Results: A general decline was observed in the incidence rate (IR) of MOF hospitalization for the whole population, from 74.52 per 10,000 person-years (PYs) in 2000 to 55.19 in 2015. Females aged ≥65 years had the highest rates of hospitalization for MOF among the subgroups analyzed. Apart from the wrist fracture hospitalization rates in both sexes, which remained steady, all other site-specific fracture hospitalization rates exponentially increased with age. Among men, the IRs of all MOF hospitalization were steady, except for a slight decrease in hip and vertebral fracture hospitalizations. In women, hip and vertebral fracture hospitalization rates gradually decreased, humerus and wrist fracture hospitalization remained steady, and forearm fracture hospitalization increased.

Conclusions: Hospitalization rates of MOF decreased. The trend of site-specific fracture hospitalization analysis showed that hip and vertebral fractures decreased for both sexes. However, an increasing trend in forearm fracture hospitalization was noticed among females.
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http://dx.doi.org/10.1007/s11657-021-00935-4DOI Listing
April 2021

Distinct JNK/VEGFR signaling on angiogenesis of breast cancer-associated pleural fluid based on hormone receptor status.

Cancer Sci 2021 Feb 7;112(2):781-791. Epub 2021 Jan 7.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer-associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple-negative breast cancer (TNBC) is much more aggressive than that of hormone receptor-positive breast cancer (HPBC). However, BAPF from HPBC (BAPF-HP) and TNBC (BAPF-TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial-mesenchymal transition. Both BAPF-HP and BAPF-TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF-TN. The distinct contribution of p-JNK to endothelial angiogenesis was consequently thought to be induced by BAPF-HP and BAPF-TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF-HP and BAPF-TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p-JNK/VEGFR2 signaling. Distinct responses to blocking p-JNK and VEGFR2 in HUVECs cultured with BAPF-HP or BAPF-TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.
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http://dx.doi.org/10.1111/cas.14772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894017PMC
February 2021

3D composite engineered using supercritical CO decellularized porcine cartilage scaffold, chondrocytes, and PRP: Role in articular cartilage regeneration.

J Tissue Eng Regen Med 2021 02 15;15(2):163-175. Epub 2020 Dec 15.

Department of Orthopedic, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, Republic of China.

At present, no definitive treatment for articular cartilage defects has been perfected. Most of the previous treatments involved multiple drilling and microfracture over defect sites with repair-related substances, which poses a limited therapeutic effect. End-stage therapy includes artificial knee joint replacement. In this study, we prepared a novel decellularized natural cartilage scaffold from porcine articular cartilage by supercritical CO extraction technology and three-dimensional (3D) composites made using decellularized porcine cartilage graft (dPCG) as scaffolds, platelet-rich plasma (PRP), thrombin as signals and chondrocytes as cells for the treatment of articular cartilage defects. In this study, in vitro and in vivo cartilage regeneration and the expression of chondrogenic markers were examined. Decellularized cartilage graft (dPCG) was evaluated for the extent of cell and DNA removal. Residual cartilage ECM structure was confirmed to be type II collagen by SDS PAGE and immunostaining. The new 3D composite with dPCG (100 mg and 2 × 10 chondrocytes) scaffold promotes chondrogenic marker expression in vitro. We found that the in vivo 3D composite implanted cartilage defect showed significant regeneration relative to the blank and control implant. Immunohistochemical staining showed increase of expression including Collagen type II and aggrecan in 3D composite both in vitro and in vivo studies. In this study, the bioengineered 3D composite by combining dPCG scaffold, chondrocytes, and PRP facilitated the chondrogenic marker expression in both in vitro and in vivo models with accelerated cartilage regeneration. This might serve the purpose of clinical treatment of large focal articular cartilage defects in humans in the near future.
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http://dx.doi.org/10.1002/term.3162DOI Listing
February 2021

Using the Fat-Clearing Technique to Improve Lymph Node Retrieval in Colorectal Cancer.

Int J Surg Pathol 2021 Jun 27;29(4):385-391. Epub 2020 Nov 27.

Department of Pathology and Laboratory Medicine, 38024Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

College of American Pathologists recommended that at least 12 lymph nodes should be harvested for adequate staging of colorectal carcinoma. Lymph node harvesting is routinely performed by a manual technique of inspection and palpation, which is laborious and time-consuming. The study assessed the influence of the improved fat-clearing technique on the number of lymph nodes retrieved from colorectal cancer specimens and the clinical efficacy. Seventy colorectal cancer resection specimens were examined and assessed by 4 pathology residents. Thirty-five specimens were handled with the conventional manual technique by inspection and palpation, and the other 35 specimens with the improved fat-clearing technique to retrieve lymph nodes. As a result, compared with the conventional manual technique, the numbers of lymph nodes retrieved with the improved fat-clearing technique were significantly increased from 14.7 ± 6.2 lymph nodes to 20.8 ± 9.0 lymph nodes per specimen ( < .05). Besides, the percentage of cases with at least 12 lymph nodes retrieved increased from 80% to 91%. The result of this study pointed out that using the improved fat-clearing technique to process colorectal specimens could increase the lymph node yield effectively, and was effective, practical, and suitable for routine gross examination.
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http://dx.doi.org/10.1177/1066896920975501DOI Listing
June 2021

High phosphate induces skeletal muscle atrophy and suppresses myogenic differentiation by increasing oxidative stress and activating Nrf2 signaling.

Aging (Albany NY) 2020 11 2;12(21):21446-21468. Epub 2020 Nov 2.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

Skeletal muscle wasting represents both a common phenotype of aging and a feature of pathological conditions such as chronic kidney disease (CKD). Although both clinical data and genetic experiments in mice suggest that hyperphosphatemia accelerates muscle wasting, the underlying mechanism remains unclear. Here, we showed that inorganic phosphate (Pi) dose-dependently decreases myotube size, fusion index, and myogenin expression in mouse C2C12 skeletal muscle cells. These changes were accompanied by increases in reactive oxygen species (ROS) production and Nrf2 and p62 expression, and reductions in mitochondrial membrane potential (MMP) and Keap1 expression. Inhibition of Pi entry, cytosolic ROS production, or Nrf2 activation reversed the effects of high Pi on Nrf2, p62, and myogenin expression. Overexpression of Nrf2 respectively increased and decreased the promoter activity of -Luc and -Luc reporters. Analysis of nuclear extracts from gastrocnemius muscles from mice fed a high-Pi (2% Pi) diet showed increased Nrf2 phosphorylation in sham-operated and 5/6 nephrectomized (CKD) mice, and both increased p62 phosphorylation and decreased myogenin expression in CKD mice. These data suggest that high Pi suppresses myogenic differentiation and promotes muscle atrophy through oxidative stress-mediated protein degradation and both canonical (ROS-mediated) and non-canonical (p62-mediated) activation of Nrf2 signaling.
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http://dx.doi.org/10.18632/aging.103896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695395PMC
November 2020

Architecture distortion score (ADS) in malignancy risk stratification of architecture distortion on contrast-enhanced digital mammography.

Eur Radiol 2021 May 30;31(5):2657-2666. Epub 2020 Oct 30.

Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Objective: To develop a risk predictor model in evaluation of tomosynthesis-detected architectural distortion (AD) based on characteristics of contrast-enhanced digital mammography (CEDM).

Methods: Ninety-four AD lesions on CEDM in combination with tomosynthesis were retrospectively reviewed from 92 consecutive women (mean age, 52.4 years ± 7.9) with abnormal diagnostic or screening mammography. CEDM results were correlated with histology of ADs using cross-tabulation for statistical analysis. Predictors for risk of malignancy from CEDM characteristics (background parenchyma enhancement, degree of AD enhancement, enhancing morphology, size of enhancement, and enhancing spiculations) and patient's age were evaluated using logistic regression. We propose a sum score, termed AD score (ADS), for risk stratification and corresponding suggested BI-RADS category.

Results: Thirty-three of ninety-four (35.1%) of detected AD lesions were malignant. The sensitivity, specificity, PPV, and NPV of CEDM in evaluation of malignant AD are 100%, 42.6%, 48.5%, and 100%, respectively. Absence of AD enhancement on CEDM is highly indicative of no underlying malignancy. On multivariate analysis, the predictors on CEDM with statistical significance are (1) marked intensity of AD enhancement (OR, 22.6; 95%CI 3.1, 166.6; p = .002); and (2) presence of enhancing spiculations (OR, 9.1; 95%CI 2.2, 36.5; p = .002). A prediction model whose scores (ADS) given by ranking of OR of all predictors with AUC of 0.934 and Brier score of 0.0956 was developed.

Conclusion: ADS-based lesion characterization on CEDM enables risk assessment of tomosynthesis-detected AD lesions.

Key Points: • Architecture distortions presenting with marked enhancement intensity and presence of enhancing spiculations are highly associated with risk of malignancy. • Absence of architecture distortion enhancement in minimal or mild background parenchyma enhancement on CEDM indicates low risk of breast malignancy (NPV = 100%).
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http://dx.doi.org/10.1007/s00330-020-07395-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043942PMC
May 2021

Effect of malignant-associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer.

Cancer Sci 2020 Oct 12;111(10):3747-3758. Epub 2020 Aug 12.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant-associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet-like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p-STAT3, HIF-1α and Nf-kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.
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http://dx.doi.org/10.1111/cas.14584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541005PMC
October 2020

Astaxanthin attenuates joint inflammation induced by monosodium urate crystals.

FASEB J 2020 08 10;34(8):11215-11226. Epub 2020 Jul 10.

Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti-inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal-induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays, and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra-articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators. Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis.
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http://dx.doi.org/10.1096/fj.202000558RRDOI Listing
August 2020

Glucose reduces the osmopressor response in connection with the tyrosine phosphorylation of focal adhesion kinase in red blood cells.

Chin J Physiol 2020 May-Jun;63(3):128-136

Department of Anesthesiology, Taipei Veterans General Hospital; Graduate Institute of Life Sciences, National Defense Medical Center; Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension.
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http://dx.doi.org/10.4103/CJP.CJP_32_20DOI Listing
August 2020

Valproic Acid Impacts the Growth of Growth Plate Chondrocytes.

Int J Environ Res Public Health 2020 05 22;17(10). Epub 2020 May 22.

Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.

A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.
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http://dx.doi.org/10.3390/ijerph17103675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277424PMC
May 2020

Histopathologie des Röntgenulkus: Fallserie mit Vergleich zur zirkumskripten Sklerodermie.

J Dtsch Dermatol Ges 2020 May;18(5):447-455

Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

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http://dx.doi.org/10.1111/ddg.14092_gDOI Listing
May 2020

Histopathology of fluoroscopy-induced radiation ulcer: a case series study in comparison with morphea.

J Dtsch Dermatol Ges 2020 05;18(5):447-454

Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Background And Objectives: Histopathologic diagnosis of fluoroscopy-induced radiation ulcer (FIRU) can be challenging if the past history of radiation exposure is unknown. Morphea is the most important differential diagnosis. This study was intended to identify clinical and pathologic features that can be used to distinguish FIRU from morphea.

Patients And Methods: We performed a retrospective study on 25 specimens from 15 patients with FIRU and 21 specimens from 21 patients with morphea. Clinical findings and pathological features were analyzed.

Results: Thirteen of 15 patients (86.7 %) with FIRU underwent angioplasty for coronary artery disease, and eleven patients had lesions in the right subscapular area. Compared with morphea, FIRU patients were more likely to display non-inflammatory infiltrates (28 %), bizarre fibroblasts (100 %), sclerosis (48 %), telangiectasia (96 %), vascular damage (64 %), and loss of skin appendages (100 %). In morphea, bizarre fibroblasts were rare (14 %), while telangiectasia (62 %) and loss of skin appendages (62 %) were variable. Loss of CD34+ cells and compression of elastic fibers could not be used to distinguish between FIRU and morphea.

Conclusions: Skin lesion in the right subscapular area with presence of bizarre fibroblasts, sclerosis, telangiectasia, and loss of cutaneous appendages as seen with histology are highly characteristic of the radiation damage associated with fluoroscopic angiography.
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http://dx.doi.org/10.1111/ddg.14092DOI Listing
May 2020

Psychiatric disorders risk in patients with iron deficiency anemia and association with iron supplementation medications: a nationwide database analysis.

BMC Psychiatry 2020 05 11;20(1):216. Epub 2020 May 11.

Clinical Medicine Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, No. 539, Zhongxiao Rd., East District, Chia-Yi City, Taiwan, 60002.

Background: It has been shown that iron deficiency anemia (IDA) is associated with psychosocial consequences and psychiatric morbidity. However, the association between adults with IDA and psychiatric disorders has not been clarified. The purpose of this study was to investigate the psychiatric disorder morbidity of an IDA group in comparison with a non-IDA group and to examine the risk of psychiatric disorders in IDA patients treated with iron supplementation.

Methods: All study subjects were 20 years of age or over with newly diagnosed IDA enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. We matched IDA and non-IDA subjects according to age and gender in a 1:2 ratio. Our primary outcome was diagnosis of psychiatric disorders and the patients were monitored until the end of 2013. A multivariate Cox proportional hazards regression model was used to explore the risk of psychiatric disorders in patients with IDA after adjustment for confounders, including demographic characteristics and comorbidities.

Results: The adjusted hazard ratios (aHRs) of psychiatric disorders was 1.52 (95% CI = 1.45-1.59) in the IDA group compared with the non-IDA group. Among the different types of psychiatric disorders, the IDA group was associated with significantly higher incidence and risks of anxiety disorders, depression, sleep disorders, and psychotic disorders (p <  0.05). Furthermore, iron supplementation in IDA subjects was associated with a significantly lower risk of psychiatric disorders compared to non-iron supplementation in IDA patients.

Conclusions: Our study indicates that IDA subjects had an increased risk of psychiatric disorders, regardless of other confounders. In IDA patients, iron supplementation was associated with a decreased risk of psychiatric disorders. Moreover, IDA patients receiving iron supplementation also had a lower risk of sleep disorders.
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http://dx.doi.org/10.1186/s12888-020-02621-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216322PMC
May 2020

fMRI indicates cortical activation through TRPV1 modulation during acute gouty attacks.

Sci Rep 2019 08 26;9(1):12348. Epub 2019 Aug 26.

Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Gout is one of the most painful disease conditions. The central mechanism of pain processing in this condition remains elusive. Cerebral blood volume (CBV) responses are faithful correlates of brain activity changes; the application of CBV-weighted functional magnetic resonance imaging (fMRI) may shed light on the issue of interest. Transient receptor potential vanilloid 1 (TRPV1) is a critical ion channel expressed both peripherally in nociceptors and centrally in the brain. Whether TRPV1 plays a critical role in gout pain was also explored. Results showed that, in rats with gouty arthritis, noxious stimulation induced CBV increases in the primary somatosensory cortex and thalamus. These increases were correlated with up-regulated TRPV1 protein expression and pain behavior. Selective blockage of central TRPV1 channel activity by intrathecal administration of AMG9810 reversed the induced pain, and abolished the induced CBV increase in thalamocortical regions. The findings support that TRPV1 activation in the central pain pathway is crucial to the augmentation of pain in gouty conditions. This new information supports the development of TRPV1-based drugs for treating gout pain, while fMRI can be useful for repeated evaluation of brain activity changes induced by gout.
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http://dx.doi.org/10.1038/s41598-019-48656-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710282PMC
August 2019

Use of antidepressants and risks of restless legs syndrome in patients with irritable bowel syndrome: A population-based cohort study.

PLoS One 2019 1;14(8):e0220641. Epub 2019 Aug 1.

Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR [aHR], 1.91; 95% CI, 1.52-2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51-65 years; aHR, 1.67; 95% CI, 1.09-2.56; and age > 65; aHR, 1.59; 95% CI, 1.02-2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92-9.37), CAD (aHR, 1.70; 95% CI, 1.17-2.48), and depression (aHR, 3.15; 95% CI, 2.14-4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34-6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220641PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675099PMC
March 2020

Nut sensitization profile in Southern Taiwan.

J Microbiol Immunol Infect 2020 Oct 27;53(5):791-796. Epub 2018 Dec 27.

Department of Pathology and Laboratory, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Background/purpose: To evaluate the relationship between serum-specific immunoglobulin E (IgE) to peanuts/tree nuts and their clinical manifestations in atopic diseases.

Method: Serum from people with the classical symptoms of asthma, allergic rhinitis (AR), or atopic dermatitis (AD) was collected for the measurement of serum-specific IgE to peanuts, cashew nuts, Brazil nuts, almonds, and coconuts. Cases with possible sensitization to these nuts (serum specific IgE ≧ 0.35 kU/L) were selected and their clinical relationships with physician-diagnosed asthma, allergic rhinitis, or atopic dermatitis were analyzed.

Result: Compared with non-sensitization group, people with peanut/tree nut sensitization have higher prevalence of atopic dermatitis, but no such difference noted in the prevalence of allergic rhinitis. In the situation of asthma, people with sensitization to peanuts and Brazil nuts, but not other nuts, have higher prevalence of asthma than people without sensitization to any nut (p < 0.001 and p < 0.05, respectively). Binary logistic regression analysis also showed positive associations between peanut (OR: 1.164, p value = 0.017) and Brazil nut (OR: 1.304, p value = 0.055) sensitization and asthma. The associations between peanut and Brazil nut sensitization and asthma were independent of the prevalence of other atopic diseases.

Conclusion: People in Asia may have less severe allergic effects as in Western countries, but sensitization to specific food allergens such as peanuts or Brazil nuts may predispose individuals to asthma, which could be helpful in diagnosis and deserves more attention than previously considered.
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http://dx.doi.org/10.1016/j.jmii.2018.12.005DOI Listing
October 2020

The increase in total knee replacement surgery in Taiwan: A 15-year retrospective study.

Medicine (Baltimore) 2018 Aug;97(31):e11749

School of Public Health Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung Department of Physiology and Biophysics Division of Thoracic Surgery Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei Department of Research and Development, Da-Yeh University, Changhua Department of Nursing Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Total knee replacement (TKR) is considered as one of the most success among clinical interventions for patients with who suffering from knee osteoarthritis (OA). We sought to estimate the incidence of TKR using demographics, incidence rates, lengths of hospital stay, and costs from 1996 to 2010 by analyzing Taiwan's National Health Insurance Research Database. A total of 154,553 patients obtained primary TKR surgery between 1996 and 2010. The diagnosis code for knee OA and the procedure code for TKR were selected from the records. To compare the rate of TKR between covariables, we calculated the TKR risk ratios and 95% confidence interval (CI) of these variables (gender, age, age group, and primary diagnoses). A 2-tailed P-value of .05 was considered statistically significant. The statistical package SPSS version 20.0 (SPSS, Chicago, IL) was used to conduct all the statistical analyzes. We analyzed 154,553 TKRs performed by surgeons in Taiwan from 1996 to 2010. The overall crude incidence increased from 26.4 to 74.55 TKR per 100,000 inhabitants from 1996 to 2010. TKR incidence for the 70 to 79 years age group increased from 227 to 505 per 100,000 people from 1996 to 2010. The age-standardized rate ratios for TKR of women to men ranged from 2.5 to 3.0. The mean average length of stay in hospital was 15 days in 1996 and decreased to 8 days in 2010. During the study period, the adjusted mean cost per patient decreased from US$7485 to US$4827. Health expenditures for TKR were 5% of total National Health Insurance expenditure every year. Over the 15-year period, Taiwan's TKR incidence tripled, which is consistent with population ageing. Arthritis will be a major public health issue in the ageing population in the future.
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http://dx.doi.org/10.1097/MD.0000000000011749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081077PMC
August 2018

Risk of fractures at different anatomic sites in patients with irritable bowel syndrome: a nationwide population-based cohort study.

Arch Osteoporos 2018 07 21;13(1):80. Epub 2018 Jul 21.

Clinical Medicine Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, 600, Taiwan.

This study was to investigate the fracture risk of irritable bowel syndrome (IBS) in comparison with non-IBS group. Our results found that IBS group has increased risk for fracture, in particular of the spine, forearm, hip, and hand.

Introduction: Patients with IBS might also be at increased risk of osteoporosis and osteoporotic fractures. Up to now, the association between IBS and the risk of fractures at different anatomic sites occurrences is not completely clear. We conducted a population-based cohort analysis to investigate the fracture risk of IBS in comparison with non-IBS group.

Methods: We identified 29,505 adults aged ≥ 20 years with newly diagnosed IBS using the Taiwan National Health Insurance Research Database in 2000-2012. A comparison group was constructed of patients without IBS who were matched according to gender and age. The occurrence of fracture was monitored until the end of 2013. We analyzed the risk of fracture events to occur in IBS by using Cox proportional hazards regression models.

Results: Patients with IBS had a higher incidence of osteoporotic fractures compared with the non-IBS group (12.34 versus 9.45 per 1000 person-years) and an increased risk of osteoporotic fractures (adjusted hazard ratio [aHR] = 1.27, 95% confidence interval [CI] = 1.20-1.35). Site-specific analysis showed that the IBS group had a higher risk of fractures for spine, forearm, hip, and hand than did the non-IBS group. With further stratification for gender and age, a higher aHR value for osteoporotic fractures in the IBS group was seen across all age groups in males, but seen in elderly females. In addition, female, elderly, low income, hypertension, coronary artery disease, cerebrovascular disease, and depressive disorders as independent osteoporotic fracture risk factors in IBS patients.

Conclusions: The IBS is considered as a risk factor for osteoporotic fractures, particularly in female individuals and fracture sites located at the spine, forearm, hip, and hand.
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http://dx.doi.org/10.1007/s11657-018-0496-7DOI Listing
July 2018

Molecular surveillance of Vittaforma-like microsporidia by a small-volume procedure in drinking water source in Taiwan: evidence for diverse and emergent pathogens.

Environ Sci Pollut Res Int 2018 Jul 30;25(19):18823-18837. Epub 2018 Apr 30.

Graduate Institute of Life Sciences, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei City, 114, Taiwan.

Vittaforma corneae belongs to microsporidia, which include over 1500 species of opportunistic obligate intracellular fungi infecting almost all known animal taxa. Although outbreaks of ocular infections caused by waterborne V. corneae have been reported in recent years, little is known about the occurrence of this pathogen in aquatic environments. In this study, 50 water samples from rivers and reservoirs around Taiwan in two seasons were analyzed to explore the presence of this pathogen in natural aquatic environments. A high detection rate of Vittaforma-like amplicons (94%; 47/50) was observed in the water samples when examined by nested PCR with primer pairs specific to the small ribosomal subunit (SSU) rRNA gene. After electrophoresis, many lanes showed multiband patterns with expected molecular weights. After confirmation by DNA sequencing and by sequence alignment in the NCBI database, we identified a variety of Vittaforma-like microsporidia with weak sequence similarity, with approximately 85% identity to V. corneae, thus indicating high diversity of microsporidia in aquatic environments. Phylogenetic analysis showed clear-cut microsporidian clade classification and indicated that the most Vittaforma-like microsporidia in this study belong to clade IV and cluster into four major groups. The first group is similar to the microsporidia associated with ocular microsporidiosis. The second group is associated with the diarrheal pathogens, whereas the third and fourth groups are a novel group and a zoonotic group, respectively. This study provides abundant sequencing information, which will be useful for future molecular biological studies on microsporidia. Because microsporidia are important pathogens of animals and humans, it is urgently necessary to determine via a survey whether there are species with potential threats that have not yet been revealed.
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http://dx.doi.org/10.1007/s11356-018-2081-4DOI Listing
July 2018

Dexamethasone Down-regulates Osteocalcin in Bone Cells through Leptin Pathway.

Int J Med Sci 2018 8;15(5):507-516. Epub 2018 Mar 8.

Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.

Glucocorticoid therapy, especially at higher doses, is associated with significant adverse side effects including osteoporosis. Leptin, secreted from adipose tissue, has diverse effects on bone tissue regulation. As glucocorticoids stimulate leptin synthesis and secretion directly in adipose tissue we hypothesised that dexamethasone (DEX) induced osteoporosis may, in part, be mediated by an osteoblast dependent leptin-leptin receptor pathway. Human bone cells expressed leptin and leptin receptors (Ob-Ra and Ob-Rb). DEX increased leptin, Ob-Ra and Ob-Rb expression in a dose-dependent manner while decreasing expression of osteocalcin. In the presence of leptin, Cbfa1 and osteonectin expression showed no significant change, whereas osteocalcin expression was decreased. Recombinant human quadruple antagonist leptin suppressed DEX-induced osteocalcin downregulation. The signaling pathway involved up-regulation of JAK2. In conclusion, upregulation of leptin and Ob-Rb in human bone cells by DEX is associated with down-regulation of osteocalcin expression. The down regulation of osteocalcin by DEX was partially through a leptin autocrine/paracrine loop. Adverse effects of DEX on the skeleton may be modified by targeting leptin signaling pathways.
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http://dx.doi.org/10.7150/ijms.21881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859774PMC
August 2018

Increased risk of fractures in patients with polycystic ovary syndrome: a nationwide population-based retrospective cohort study.

J Bone Miner Metab 2018 Nov 26;36(6):741-748. Epub 2017 Dec 26.

Clinical Medicine Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, 600, Taiwan.

Polycystic ovary syndrome (PCOS) is a complex disorder; various features of this disorder may influence bone metabolism and skeletal mass. The contribution of PCOS to lower bone mineral density has been recognized. However, the impact of PCOS on the long-term risks for fractures remains inconclusive. The aim of this study was to determine the risk of overall fracture and fractures at different anatomic sites in patients with PCOS. Using a nationwide health insurance claims database, we included 11,106 subjects, aged 15-80 years, with newly diagnosed PCOS (ICD-9-CM: 254.4X) during 2000-2012. Patients with PCOS and respective age-matched (1:4) controls without PCOS were enrolled. The occurrence of fracture was monitored until the end of 2013. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of PCOS among women with fractures. The PCOS and non-PCOS groups were comprised of 11,106 patients with PCOS and 44,424 participants without PCOS, respectively. Patients with PCOS had a higher incidence of any fractures compared with non-PCOS group (10.16 versus 8.07 per 1000 person-years) and a greater risk of any fractures [adjusted hazard ratio (aHR) = 1.23, 95% CI = 1.13-1.33], osteoporotic fractures (aHR = 1.33, 95% CI = 1.15-1.54), spine fractures (aHR = 1.36, 95% CI = 1.11-1.66) and forearm fractures (aHR = 1.39, 95% CI = 1.07-1.80), but the risk for femur or hip fracture, humerus, wrist and non-osteoporotic fractures were not increased. In conclusion, the PCOS group had a higher occurrence rate of fractures than the non-PCOS group. These results provide evidence for the adverse effects of PCOS on the risk of fractures.
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http://dx.doi.org/10.1007/s00774-017-0894-8DOI Listing
November 2018

Infusion of Porcine-Derived Amniotic Fluid Stem Cells for Treatment of Experimental Colitis in Mice.

Chin J Physiol 2017 Dec;60(6):345-352

Institute of Biotechnology, National Taiwan University, Taipei 10672, Taiwan, Republic of China.

Recently, stem cells have offered an alternative treatment for inflammatory bowel disease (IBD) or colitis to overcome the poor outcomes associated with current therapies. Amniotic fluid-derived stem cells (AFSCs) have the potential for the regeneration of impaired organs and the recovery of normal physiologic functions of damaged tissues without ethical concerns or risk of tumor formation. In this work, we aimed to examine the therapeutic effects of infusion of porcine AFSCs (pAFSCs) in dextran sulfate sodium (DSS)-induced colitis in mice. Treatment with pAFSCs was shown to inhibit the shortening of the colon after induction of colitis and dramatically ameliorated the body weightloss induced by the DSS treatment. In addition, pAFSCs could also reduce the extent of the inflamed area represented by epithelial mesenchymal transformation in the colitis mice. The levels of the inflammatory cytokines interleukin 6 (IL-6) and interferon gamma (IFN-γ) were also reduced in colitis mice transplanted with pAFSCs. In conclusion, pAFSCs can ameliorate experimental colitis in mice, suggesting that they may be a potential treatment for IBD or colitis.
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http://dx.doi.org/10.4077/CJP.2017.BAG509DOI Listing
December 2017

Pediatric Kikuchi-Fujimoto disease: A clinicopathologic study and the therapeutic effects of hydroxychloroquine.

J Microbiol Immunol Infect 2019 Jun 29;52(3):395-401. Epub 2017 Sep 29.

Department of Pathology and Laboratory, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Background: To investigate the clinical features of Kikuchi-Fujimoto disease (KFD) in children, and place an emphasis on the therapeutic effects of hydroxychloroquine as monotherapy.

Methods: We retrospectively reviewed the medical records of all children diagnosed with KFD during the period January 1992 to September 2016 at a tertiary medical center in Taiwan.

Results: 40 patients were histopathologically confirmed as KFD, and the mean age of the patients was 13.9 ± 3.1 years. The male to female ratio was 1:1. The lymph node involvements were often cervical (95%) with features of unilateral predisposition (75%), polyadenopathy (84.4%) and tenderness (56.3%). Fever, cough, rhinorrhea, and tonsillitis were other common presentations. Laboratory findings included leukopenia (56.5%), monocytosis (63.6%), with positive results of EB-VCA IgG (88.9%), EB-VCA IgM (22.2%), EBEA IgG (22.2%) and EBNA IgG (88.9%). The univariate analyses of prolonged fever with lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology were disclosed as statistically significant (P < 0.05). Corticosteroids and hydroxychloroquine were administered in 15.6% of patients respectively, along with symptomatic treatments for the rest. Recurrence occurred in 13.0% of patients without corticosteroids or hydroxychloroquine treatment. There were neither recurrences nor relevant major adverse effects in all the five KFD cases treated with hydroxychloroquine.

Conclusion: KFD should be suspected in children with febrile cervical lymphadenopathy, especially when concomitant with leukopenia and monocytosis. Lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology are reliable predictors for prolonged fever. Hydroxychloroquine may be an alternative choice to corticosteroids for its favorable effects and safety.
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http://dx.doi.org/10.1016/j.jmii.2017.08.023DOI Listing
June 2019

Knee subchondral bone perfusion and its relationship to marrow fat and trabeculation on multi-parametric MRI and micro-CT in experimental CKD.

Sci Rep 2017 06 8;7(1):3073. Epub 2017 Jun 8.

Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease's progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant k values were significantly decreased, and vascular permeability k was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.
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http://dx.doi.org/10.1038/s41598-017-03059-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465086PMC
June 2017

The Osmopressor-Induced Angiopoietin-1 Secretion in Plasma and Subsequent Activation of the Tie-2/Akt/eNOS Signaling Pathway in Red Blood Cell.

Am J Hypertens 2017 Mar;30(3):295-303

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

Background: Water ingestion induces the osmopressor response, which typically presents as increased total peripheral vascular resistance in young healthy subjects. A previous study has suggested that the RBC membrane receptor is involved in osmopressor stress. Recent studies have indicated nitric oxide synthase phosphorylation in RBCs. However, the main process in signaling pathway activation to elicit such a response is unknown. Herein, we hypothesized that hypo-osmotic stress following water ingestion modulates the eNOS/NO pathway, thereby alternating vascular resistance.

Methods: We included 24 young, healthy subjects. Physiological parameters and blood samples were collected at 5 minutes before and 25 and 50 minutes after 50 ml water, 500 ml water, or 500 ml normal saline ingestion. A human receptor tyrosine kinase (RTK) phosphorylation antibody array was used to simultaneously detect and monitor the biological activation pathways in RBCs.

Results: Of the 71 RTKs assayed during the osmopressor response, several RTKs were significantly upregulated, including Tie-2 and Tie-1. Plasma angiopoietin-1 levels significantly increased at 25 minutes after 500 ml water ingestion compared to those at baseline. Simultaneous phosphorylation of Tie-2, Akt, and eNOS in RBCs occurred. RBCs in vitro were stimulated with angiopoietin-1, Tie-2, or 0.8% saline and showed significant increase in Tie-2, Akt, and eNOS phosphorylation upon angiopoietin-1 treatment and enhanced activation upon cotreatment of angiopoietin-1 and 0.8% saline.

Conclusions: The hypo-osmotic stimulus of water ingestion increases angiopoietin-1 secretion and subsequently activates the Tie-2/Akt/eNOS signaling pathway in RBCs, thereby revealing a novel biological mechanism simultaneously occurring with the osmopressor response.
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http://dx.doi.org/10.1093/ajh/hpw161DOI Listing
March 2017

Assessment of EGFR and ERBB2 (HER2) in Gastric and Gastroesophageal Carcinomas: EGFR Amplification is Associated With a Worse Prognosis in Early Stage and Well to Moderately Differentiated Carcinoma.

Appl Immunohistochem Mol Morphol 2018 07;26(6):374-382

Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital.

Epidermal growth factor receptor 1 (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) are frequently dysregulated in human cancers. We analyzed EGFR and ERBB2 status in 105 gastric and gastroesophageal junction carcinoma and their clinicopathologic features. For EGFR, 92 (88%) tumors were scored as 0, 2 (2%) as 1+, 7 (7%) as 2+, and 4 (3%) as 3+ by immunohistochemistry (IHC) and 4 (4%) tumors showed EGFR amplification by fluorescence in situ hybridization (FISH). For ERBB2, 90 (86%) tumors were scored as 0, 4 (4%) as 1+, 6 (6%) as 2+, and 5 (5%) as 3+ by IHC and 12 (12%) showed ERBB2 amplification by FISH. The concordance rate between IHC and FISH of EGFR was 98.1% (P<0.001) and of ERBB2 was 93.3% (P<0.001). Most tumors with ERBB2 amplification were tubular adenocarcinoma (N=11, P=0.02) and Lauren intestinal type (N=12, P=0.016). There was no statistically significant difference between EGFR amplification and tumor classification. EGFR amplification had significant impact on overall survival in certain subgroups: early stages (stages I and II) (P<0.001), well to moderately differentiated tumors (P=0.001), and fewer regional lymph node metastasis (pN1) (P=0.001). ERBB2 status had little predictive value on overall survival. In conclusion, this study showed ERBB2 amplification was significantly observed in tubular adenocarcinoma and Lauren intestinal-type carcinoma. The IHC scoring criteria for ERBB2 can be applied to EGFR. EGFR amplification had associated with poor prognosis in early, well to moderately differentiated carcinoma.
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http://dx.doi.org/10.1097/PAI.0000000000000437DOI Listing
July 2018

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis.

PLoS One 2016;11(9):e0161754. Epub 2016 Sep 22.

School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.

Background: Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results.

Objective: To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis.

Methods: For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk.

Results: We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%).

Conclusions: The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033346PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161754PLOS
September 2016
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