Publications by authors named "Hiroko Nakamura"

56 Publications

Analgesic Effects of Sokeikakketsuto on Chemotherapy-Induced Mechanical Allodynia and Cold Hyperalgesia in Rats.

Biol Pharm Bull 2021 ;44(2):271-274

Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University.

The anticancer agents including oxaliplatin, paclitaxel, and bortezomib cause severe peripheral neuropathy. The Kampo medicine Sokeikakketsuto (SOKT) has been widely used to treat several types of pain. In this study, the analgesic effects of SOKT on oxaliplatin-, paclitaxel-, and bortezomib-induced peripheral neuropathy were investigated in rat models. Rats were treated with oxaliplatin (4 mg/kg, intraperitoneally (i.p.), twice a week for four weeks), paclitaxel (4 mg/kg, i.p., twice a week for two weeks), or bortezomib (0.2 mg/kg, i.p., twice a week for two weeks). SOKT (0.3 or 1.0 g/kg) or duloxetine hydrochloride (30 mg/kg, as a positive control) was administered orally after neuropathy developed. Mechanical allodynia and cold hyperalgesia were assessed using the von Frey test and the acetone test, respectively. These tests were performed immediately before and 30, 60, 90, and 120 min after the administration of the drugs. Repeated treatment of oxaliplatin induced mechanical allodynia and cold hyperalgesia. A single administration of SOKT (1 g/kg, per os (p.o.)), as well as duloxetine, temporarily reversed both the mechanical allodynia and the cold hyperalgesia. Repeated administration of paclitaxel and bortezomib also induced the mechanical allodynia. SOKT and duloxetine reversed the mechanical allodynia caused by bortezomib, but not by paclitaxel. SOKT might have the potential to become a new drug to relieve the symptom of oxaliplatin- or bortezomib-induced peripheral neuropathy.
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http://dx.doi.org/10.1248/bpb.b20-00620DOI Listing
January 2021

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer.

J Gynecol Oncol 2021 Mar 10;32(2):e16. Epub 2020 Dec 10.

Department of Obstetrics and Gynecology, St. Mary Hospital, Fukuoka, Japan.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.

Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs.

Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%.

Conclusion: Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Trial Registration: ClinicalTrials.gov Identifier: NCT03759600.
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http://dx.doi.org/10.3802/jgo.2021.32.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930437PMC
March 2021

G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus.

PLoS One 2020 17;15(11):e0242380. Epub 2020 Nov 17.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

Thyroid hormone (T3) inhibits thyrotropin-releasing hormone (TRH) synthesis in the hypothalamic paraventricular nucleus (PVN). Although the T3 receptor (TR) β2 is known to mediate the negative regulation of the prepro-TRH gene, its molecular mechanism remains unknown. Our previous studies on the T3-dependent negative regulation of the thyrotropin β subunit (TSHβ) gene suggest that there is a tethering mechanism, whereby liganded TRβ2 interferes with the function of the transcription factor, GATA2, a critical activator of the TSHβ gene. Interestingly, the transcription factors Sim1 and Arnt2, the determinants of PVN differentiation in the hypothalamus, are reported to induce expression of TRβ2 and GATA2 in cultured neuronal cells. Here, we confirmed the expression of the GATA2 protein in the TRH neuron of the rat PVN using immunohistochemistry with an anti-GATA2 antibody. According to an experimental study from transgenic mice, a region of the rat prepro-TRH promoter from nt. -547 to nt. +84 was able to mediate its expression in the PVN. We constructed a chloramphenicol acetyltransferase (CAT) reporter gene containing this promoter sequence (rTRH(547)-CAT) and showed that GATA2 activated the promoter in monkey kidney-derived CV1 cells. Deletion and mutation analyses identified a functional GATA-responsive element (GATA-RE) between nt. -357 and nt. -352. When TRβ2 was co-expressed, T3 reduced GATA2-dependent promoter activity to approximately 30%. Unexpectedly, T3-dependent negative regulation was maintained after mutation of the reported negative T3-responsive element, site 4. T3 also inhibited the GATA2-dependent transcription enhanced by cAMP agonist, 8-bromo-cAMP. A rat thyroid medullary carcinoma cell line, CA77, is known to express the preproTRH mRNA. Using a chromatin immunoprecipitation assay with this cell line where GATA2 expression plasmid was transfected, we observed the recognition of the GATA-RE by GATA2. We also confirmed GATA2 binding using gel shift assay with the probe for the GATA-RE. In CA77 cells, the activity of rTRH(547)-CAT was potentiated by overexpression of GATA2, and it was inhibited in a T3-dependent manner. These results suggest that GATA2 transactivates the rat prepro-TRH gene and that liganded TRβ2 interferes with this activation via a tethering mechanism as in the case of the TSHβ gene.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242380PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671546PMC
January 2021

Innovative CAD/CAM Guide for Mandibular Reconstruction with Metallic Condylar Head and Free Fibular Flap.

Plast Reconstr Surg Glob Open 2020 Sep 23;8(9):e3088. Epub 2020 Sep 23.

Departments of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

In reconstructions of mandibles and condyles, free fibular flaps and metallic condylar heads (CH) are often used after resection. However, in conventional reconstructions, it is difficult to fix the metallic CH on the same preoperative position because the position is determined visually. Therefore, we have made an original computer-aided design and manufacture (CAD/CAM) guide for mandibular condyle reconstruction, combining a metallic CH with a free fibular flap. A 71-year-old woman with gingival carcinoma underwent hemimandibulectomy. We reconstructed the mandible and condyle with a metallic CH and a free fibular flap. We placed a mark on the CAD/CAM guide showing the correct position for fixing the CH to the fibular blocks. We also designed a surface for attaching to the healthy edge of the mandible. The fibular blocks and metallic CH were fixed as 1 unit before separating the flap from the leg and replacing the diseased tissue. Reconstruction was completed by fixing the attachment surface to the healthy side of the mandible. The guide marks solved the difficulty of conventional reconstruction; during surgery, we fixed the metallic CH to the same position as the original bone using these marks. The postoperative deviation of the condyle from the virtual plan was 4.3 mm, whereas the reported deviation of such prostheses was 3.8 mm (range 1.3-6.7); so our guide was acceptably accurate. Furthermore, it appears that the CAD/CAM guide is more useful for reconstruction after hemimandibulectomy including the condyle than after segmental resection without including condyle.
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http://dx.doi.org/10.1097/GOX.0000000000003088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544273PMC
September 2020

Does an In-House Computer-Aided Design/Computer-Aided Manufacturing Approach Contribute to Accuracy and Time Shortening in Mandibular Reconstruction?

J Craniofac Surg 2020 Oct;31(7):1928-1932

Department Otorhinolaryngology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Mandibular reconstruction using computer-aided design and computer-assisted manufacturing (CAD/CAM) techniques has received recent attention. This technique has theoretical advantages, although this approach can be commercially used in the limited area of the world.The aim is to describe our experience using in-house CAD/CAM guides and the situations in which CAD/CAM may present benefit in the region where commercial guides are unavailable.The authors developed our In-house CAD/CAM approach for mandibular reconstructions with a free fibular flap. Patients were divided into 2 group; CAD/CAM and conventional groups. In the CAD/CAM group, reconstructions were planned virtually using CAD/CAM; these CAD/CAM guides were used in the surgery. In the conventional group, free-hand cutting and fitting of the fibular segments were performed as reconstructions. Later, the bone computed tomographic image was compared with the plan. The averaged deviations and the percentages of the points within 1 mm, 2 mm, and 3 mm deviations were recorded. Total and ischemic time were also recorded.Reconstruction points within 1 mm deviation were 59% of CAD/CAM group (n = 9) and 42% of conventional group (n = 10, P = 0.04), within 2 mm 82% and 69% (P = 0.03). Total time were 1012 and 911 minutes, while flap ischemic time were 147 and 175 minutes (P = 0.03), respectively.In-house CAD/CAM mandibular reconstruction also supported accuracy and shorter flap ischemic time. For a detailed accurate reconstruction, CAD/CAM showed superiority than conventional method. Use of the In-house CAD/CAM guides might be an option where commercial guides are not available.
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http://dx.doi.org/10.1097/SCS.0000000000006699DOI Listing
October 2020

[Coexistence of IgG4-related autoimmune hepatitis and inflammatory pseudotumors of the liver:a case report].

Nihon Shokakibyo Gakkai Zasshi 2020 ;117(6):532-541

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Shirakaba-dai Hospital.

IgG4-related autoimmune hepatitis (IgG4-AIH) is characterized by hepatic inflammation and is considered an IgG4-related disease. Several inflammatory pseudotumors (IPTs) are also considered as IgG4-related diseases;however, there have been no reports of cases wherein both diseases occurred concurrently. An older adult with liver dysfunction was admitted to the hospital and was diagnosed with IgG4-AIH following a liver biopsy;IgG4-positive plasma cell infiltration in the portal tract and high serum IgG4 concentration were detected. A few months following biopsy, imaging studies revealed two IPTs in the liver. The patient was diagnosed with cryptogenic organized pneumonia several months after imaging and was treated with steroids in a different hospital. Her liver dysfunction improved, and one of the two IPTs disappeared in response to steroid treatment. The following is an account of a rare case of IgG4-AIH with IPTs of the liver.
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http://dx.doi.org/10.11405/nisshoshi.117.532DOI Listing
July 2020

Two Cases of the Vascular Territory of a Single-pedicled Deep Inferior Epigastric Perforator Flap with a Vertical Midline Abdominal Scar.

Plast Reconstr Surg Glob Open 2020 Mar 11;8(3):e2684. Epub 2020 Mar 11.

Department of Breast Surgery, Kyoto City Hospital, Kyoto, Japan.

: The deep inferior epigastric perforator (DIEP) flap is becoming the gold standard for breast reconstruction using autologous tissue. If there are scars in the abdomen from previous surgery, it is necessary to judge the indication for using this flap carefully. Particularly in cases with vertical midline scars, the blood flow supply to the zone II can be compromised. Even when patients have a median abdominal scar, it has been reported that the blood flow can extend beyond the scar and reach several centimeters to about half of zone II. We performed breast reconstruction using DIEP flaps for 2 patients with vertical midline scars in the lower abdomen. Indocyanine green angiography was conducted intraoperatively to confirm the vascular territory with a single pedicle before cutting off the flap. One patient showed fluorescence contrast on the contralateral side across the midline scar. However, the fluorescence contrast was absent across the midline scar in the other patient. Based on this result, we investigated the possible vascular territory of a single pedicled DIEP flap in patients with vertical midline abdominal scars. We suggest that successful blood supply to zone II of a single-pedicled DIEP flap in a patient with a vertical midline abdominal scar is related to the location of the perforator and the property of the tissue in the midline near the perforator. However, because it is difficult to predict the vascular territory of a single pedicle before surgery, intraoperative evaluation using such techniques such as indocyanine green fluorescence imaging is important.
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http://dx.doi.org/10.1097/GOX.0000000000002684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253241PMC
March 2020

Liganded T3 receptor β2 inhibits the positive feedback autoregulation of the gene for GATA2, a transcription factor critical for thyrotropin production.

PLoS One 2020 15;15(1):e0227646. Epub 2020 Jan 15.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

The serum concentration of thyrotropin (thyroid stimulating hormone, TSH) is drastically reduced by small increase in the levels of thyroid hormones (T3 and its prohormone, T4); however, the mechanism underlying this relationship is unknown. TSH consists of the chorionic gonadotropin α (CGA) and the β chain (TSHβ). The expression of both peptides is induced by the transcription factor GATA2, a determinant of the thyrotroph and gonadotroph differentiation in the pituitary. We previously reported that the liganded T3 receptor (TR) inhibits transactivation activity of GATA2 via a tethering mechanism and proposed that this mechanism, but not binding of TR with a negative T3-responsive element, is the basis for the T3-dependent inhibition of the TSHβ and CGA genes. Multiple GATA-responsive elements (GATA-REs) also exist within the GATA2 gene itself and mediate the positive feedback autoregulation of this gene. To elucidate the effect of T3 on this non-linear regulation, we fused the GATA-REs at -3.9 kb or +9.5 kb of the GATA2 gene with the chloramphenicol acetyltransferase reporter gene harbored in its 1S-promoter. These constructs were co-transfected with the expression plasmids for GATA2 and the pituitary specific TR, TRβ2, into kidney-derived CV1 cells. We found that liganded TRβ2 represses the GATA2-induced transactivation of these reporter genes. Multi-dimensional input function theory revealed that liganded TRβ2 functions as a classical transcriptional repressor. Then, we investigated the effect of T3 on the endogenous expression of GATA2 protein and mRNA in the gonadotroph-derived LβT2 cells. In this cell line, T3 reduced GATA2 protein independently of the ubiquitin proteasome system. GATA2 mRNA was drastically suppressed by T3, the concentration of which corresponds to moderate hypothyroidism and euthyroidism. These results suggest that liganded TRβ2 inhibits the positive feedback autoregulation of the GATA2 gene; moreover this mechanism plays an important role in the potent reduction of TSH production by T3.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227646PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961892PMC
April 2020

In vitro spermatogenesis in two-dimensionally spread mouse testis tissues.

Reprod Med Biol 2019 Oct 13;18(4):362-369. Epub 2019 Aug 13.

Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science Yokohama City University Association of Medical Science Yokohama Japan.

Purpose: Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients.

Methods: Immature mouse testis tissues placed on agarose gel block were forced to spread flat by covering with a polydimethylsiloxane (PDMS) ceiling chip (PC chip). They were then cultured for weeks and evaluated by the transgene expression of , which reflects the progression of spermatogenesis.

Results: Testis tissues covered with PC chip initiated and maintained spermatogenesis in its wider region than those without PC chip covering. Flow cytometric analysis demonstrated that the PC method yielded more numerous meiotic germ cells than those without PC. Immunohistochemical examination confirmed the authentic histological figure of spermatogenesis from spermatogonia up to round or elongating spermatids.

Conclusions: The PC chip method is simple and effective to improve the efficiency of in vitro spermatogenesis in the organ culture system.
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http://dx.doi.org/10.1002/rmb2.12291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780044PMC
October 2019

Designing CAD/CAM Surgical Guides for Maxillary Reconstruction Using an In-house Approach.

J Vis Exp 2018 08 24(138). Epub 2018 Aug 24.

Department of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine.

Computer-aided design/computer-assisted manufacturing (CAD/CAM) is now being evaluated as a preparative technique for maxillofacial surgery. Because this technique is expensive and available in only limited areas of the world, we developed a novel CAD/CAM surgical guide using an in-house approach. By using the CAD software, the maxillary resection area and cutting planes and the fibular cutting planes and angles are determined. Once the resection area is decided, the necessary faces are extracted using a Boolean modifier. These superficial faces are united to fit the surface of the bones and thickened to stabilize the solids. Not only the cutting guides for the fibula and maxilla but also the location arrangement of the transferred bone segments is defined by thickening the superficial faces. The CAD design is recorded as .stl files and three-dimensionally (3-D) printed as actual surgical guides. To check the accuracy of the guides, model surgery using 3-D-printed facial and fibular models is performed. These methods may be used to assist surgeons where commercial guides are not available.
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http://dx.doi.org/10.3791/58015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231809PMC
August 2018

Neonatal testis growth recreated in vitro by two-dimensional organ spreading.

Biotechnol Bioeng 2018 12 29;115(12):3030-3041. Epub 2018 Sep 29.

Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Association of Medical Science, Yokohama City University, Yokohama, Japan.

Organ culture experiments can be hampered by central degeneration or necrosis due to the inadequate permeation of oxygen and nutrients, which deteriorates the function and growth of cultured tissues. In the current study, we aimed to overcome this limitation of organ culture through spreading the tissue two dimensionally on an agarose gel stand and molding into a disc shape by placing a ceiling of polydimethylsiloxane (PDMS) chip, which is highly oxygen permeable. By this, every part of the tissue can receive a sufficient supply of oxygen through PDMS as well as nutrients through the agarose gel below. This method not only prevented central necrosis of tissues, but also supported the tissue growth over time. In addition, such growth, as volume enlargement, could be easily measured. Under these conditions, we examined the effect of several factors on the growth of neonatal mouse testis, and found that follicle stimulating hormone (FSH) and insulin significantly promoted the growth. These results are in good agreement with previous in vivo reports. Notably, the growth achieved over 7 days in our in vitro system is almost comparable to, about 80% of, that observed in vivo. Thus, we successfully monitored the promotion of tissue growth beyond the limits of the conventional organ culture method. This extremely simple method could offer a unique platform to evaluate the growth as well as functional properties of organs, not only the testis but also others as well.
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http://dx.doi.org/10.1002/bit.26822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283240PMC
December 2018

Effect of fluid shear stress on cultured ureteric bud cells.

Biomicrofluidics 2018 Jul 10;12(4):044107. Epub 2018 Jul 10.

Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.

Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or urine flow. Recent studies suggest that changes in FSS could contribute to the function and injury of these kidney cells. However, it is unclear whether FSS influences kidney development when urinary flow starts in the embryonic kidneys. In this study, we evaluated the influence of FSS on cultured ureteric bud (UB) cells by using a pumpless microfluidic device, which offers the convenience of conducting parallel cell culture experiments while also eliminating the need for cumbersome electronic driven equipment and intricate techniques. We first validated the function of the device by both mathematical model and experimental measurements. UB cells dissected from E15.5 mouse embryonic kidneys were cultured in the pumpless microfluidic device and subjected to FSS in the range of 0.4-0.6 dyn mm for 48 h (dynamic). Control UB cells were similarly cultured in the device and maintained under a no-flow condition (static). We found from our present study that the exposure to FSS for up to 48 h led to an increase in mRNA expression levels of UB tip cell marker genes (, , ) with a decrease in stalk cell marker genes (, ). In further support of the enrichment of UB tip cell population in response to FSS, we also found that exposure to FSS led to a remarkable reduction in the binding of lectin Dolichos Biflorus Agglutinin. In conclusion, results of our present study show that exposure to FSS led to an enrichment in UB tip cell populations, which could contribute to the development and function of the embryonic kidney when urine flow starts at around embryonic age E15.5 in mouse. Since UB tip cells are known to be the proliferative progenitor cells that contribute to the branching morphogenesis of the collecting system in the kidney, our finding could imply an important link between the FSS from the initiation of urine flow and the development and function of the kidney.
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http://dx.doi.org/10.1063/1.5035328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039298PMC
July 2018

Understanding Conditionals in the East: A Replication Study of With Easterners.

Front Psychol 2018 12;9:505. Epub 2018 Apr 12.

Faculty of Literature and Human Sciences, Osaka City University, Osaka, Japan.

The new probabilistic approaches to the natural language conditional imply that there is a parallel relation between indicative conditionals (ICs) "" and conditional bets (CBs) "" in two aspects. First, the probability of an IC and the probability of winning a CB are both the conditional probability, (). Second, both an IC and a CB have a third value "void" (neither true nor false, neither wins nor loses) when the antecedent is false (). These aspects of the parallel relation have been found in Western participants. In the present study, we investigated whether this parallel is also present in Eastern participants. We replicated the study of Politzer et al. (2010) with Chinese and Japanese participants and made two predictions. First, Eastern participants will tend to engage in more holistic cognition and take all possible cases, including , into account when they judge the probability of conditional: Easterners may assess the probability of antecedent out of all possible cases, (), and then may focus on consequent out of , (). Consequently, Easterners may judge the probability of the conditional, and of winning the bet, to be () () = ( & ), and false/losing the bet as () () = ( & ). Second, Eastern participants will tend to be strongly affected by context, and they may not show parallel relationships between ICs and CBs. The results indicate no cultural differences in judging the false antecedent cases: Eastern participants judged false antecedent cases as not making the IC true nor false and as not being winning or losing outcomes. However, there were cultural differences when asked about the probability of a conditional. Consistent with our hypothesis, Eastern participants had a greater tendency to take all possible cases into account, especially in CBs. We discuss whether these results can be explained by a hypothesized tendency for Eastern people to think in more holistic and context-dependent terms than Western people.
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http://dx.doi.org/10.3389/fpsyg.2018.00505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907311PMC
April 2018

A monolayer microfluidic device supporting mouse spermatogenesis with improved visibility.

Biochem Biophys Res Commun 2018 06 30;500(4):885-891. Epub 2018 Apr 30.

Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan; Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan. Electronic address:

In our previous study, we produced a microfluidic device (MFD) which successfully maintained spermatogenesis for over 6 months in mouse testis tissues loaded in the device. In the present study, we developed a new MFD, a monolayer device (ML-D) with a barrier structure consisting of pillars and slits, which is simpler in design and easier to make. This ML-D was also effective for inducing mouse spermatogenesis and maintained it for a longer period than the conventional culture method. In addition, we devised a way of introducing sample tissue into the device during its production, just before bonding the upper layer of polydimethylsiloxane (PDMS) and bottom glass slide. The tissue can obtain nutrients horizontally from the medium running beside it and oxygen vertically from above through PDMS. In addition, the glass slide set at the bottom improved the visibility of the sample tissue with an inverted microscope. When we took photos of cultured tissue of the Acr-Gfp transgenic mouse testis in ML-D sequentially every day, morphological changes of the acrosome during spermiogenesis were successfully recorded. The ML-D is simple in design and useful for culturing testis tissue for inducing and maintaining spermatogenesis with clearer visibility. Due to the new method of sample loading, tissues other than testis should also be applicable.
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http://dx.doi.org/10.1016/j.bbrc.2018.04.180DOI Listing
June 2018

The Mechanism of Negative Transcriptional Regulation by Thyroid Hormone: Lessons From the Thyrotropin β Subunit Gene.

Vitam Horm 2018 18;106:97-127. Epub 2017 Aug 18.

Hamamatsu University School of Medicine, Shizuoka, Japan.

Thyroid hormone (T3) activates (positive regulation) or represses (negative regulation) target genes at the transcriptional level. The molecular mechanism of the former has been elucidated in detail; however, the mechanism for negative regulation has not been established. The best example of the gene that is negatively regulated by T3 is the thyrotropin (thyroid-stimulating hormone) β subunit (TSHβ) gene. Analogous to the T3-responsive element (TRE) in positive regulation, a negative TRE (nTRE) has been postulated in the TSHβ gene. However, TSHβ promoter analysis, performed in the presence of transcription factors Pit1 and GATA2, which are determinants of thyrotroph differentiation in the pituitary, revealed that the nTRE is dispensable for inhibition by T3. We propose a tethering model in which the T3 receptor is tethered to GATA2 via protein-protein interaction and inhibits GATA2-dependent transactivation of the TSHβ gene in a T3-dependent manner.
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http://dx.doi.org/10.1016/bs.vh.2017.06.006DOI Listing
October 2018

Using an In-House Approach to Computer-Assisted Design and Computer-Aided Manufacturing Reconstruction of the Maxilla.

J Oral Maxillofac Surg 2018 Jun 12;76(6):1361-1369. Epub 2017 Dec 12.

Department Head and Professor, Department of Otorhinolaryngology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Purpose: Computer-assisted design (CAD) and computer-aided manufacturing (CAM) techniques are in widespread use for maxillofacial reconstruction. However, CAD/CAM surgical guides are commercially available only in limited areas. To use this technology in areas where these commercial guides are not available, the authors developed a CAD/CAM technique in which all processes are performed by the surgeon (in-house approach). The authors describe their experience and the characteristics of their in-house CAD/CAM reconstruction of the maxilla.

Patients And Methods: This was a retrospective study of maxillary reconstruction with a free osteocutaneous flap. Free CAD software was used for virtual surgery and to design the cutting guides (maxilla and fibula), which were printed by a 3-dimensional printer. After the model surgery and pre-bending of the titanium plates, the actual reconstructions were performed. The authors compared the clinical information, preoperative plan, and postoperative reconstruction data. The reconstruction was judged as accurate if more than 80% of the reconstructed points were within a deviation of 2 mm.

Results: Although on-site adjustment was necessary in particular cases, all 4 reconstructions were judged as accurate. In total, 3 days were needed before the surgery for planning, printing, and pre-bending of plates. The average ischemic time was 134 minutes (flap suturing and bone fixation, 70 minutes; vascular anastomoses, 64 minutes). The mean deviation after reconstruction was 0.44 mm (standard deviation, 0.97). The deviations were 67.8% for 1 mm, 93.8% for 2 mm, and 98.6% for 3 mm. The disadvantages of the regular use of CAD/CAM reconstruction are the intraoperative changes in defect size and local tissue scarring.

Conclusion: Good accuracy was obtained for CAD/CAM-guided reconstructions based on an in-house approach. The theoretical advantage of computer simulation contributes to the accuracy. An in-house approach could be an option for maxillary reconstruction.
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http://dx.doi.org/10.1016/j.joms.2017.11.042DOI Listing
June 2018

Pumpless microfluidic system driven by hydrostatic pressure induces and maintains mouse spermatogenesis in vitro.

Sci Rep 2017 11 13;7(1):15459. Epub 2017 Nov 13.

Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa, 236-0004, Japan.

Three-dimensional aggregation and organ culture methods are critical for recreating in vivo cellular phenomena outside the body. Previously, we used the conventional gas liquid interphase organ culture method to induce complete mouse spermatogenesis. After incorporating microfluidic systems, we achieved a significant increase in efficiency and duration of spermatogenesis. One of the major drawbacks preventing the popularization of microfluidics, however, is the use of a power-pump to generate medium flow. In this study, we produced a pumpless microfluidic device using hydrostatic pressure and a resistance circuit to facilitate slow, longer lasting medium flow. During three months of culture, results in induction and maintenance of spermatogenesis showed no difference between pumpless and pump-driven devices. Correspondingly, the spermatogonial population was favorably maintained in the pumpless device compared to the conventional method. These results show the advantage of using microfluidic systems for organ culture experiments. Our pumpless device could be applied to a variety of other tissues and organs, and may revolutionize organ culture methods as a whole.
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http://dx.doi.org/10.1038/s41598-017-15799-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684205PMC
November 2017

Secondary Maxillary and Orbital Floor Reconstruction With a Free Scapular Flap Using Cutting and Fixation Guides Created by Computer-Aided Design/Computer-Aided Manufacturing.

J Craniofac Surg 2017 Nov;28(8):2060-2062

*Department of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine, Kyoto †Department of Plastic and Reconstructive Surgery, Fukuchiyama City Hospital, Fukuchiyma ‡Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Computer-aided design/computer-aided manufacturing (CAD/CAM) guides are now widely used in maxillofacial reconstruction. However, there are few reports of CAD/CAM guides being used for scapular flaps. The authors performed the secondary maxillary and orbital floor reconstruction using a free latissimus dorsi muscle, cutaneous tissue, and scapular flap designed using CAD/CAM techniques in a 72-year-old man who had undergone partial maxillectomy four years previously. The patient had diplopia, the vertical dystopia of eye position, and a large oral-nasal-cutaneous fistula. After the operation, the authors confirmed that the deviation between the postoperative and preoperative planning three-dimensional images was less than 2 mm. Because scapular guides require 3 cutting surfaces, the shape of the scapular guide is more complex than that of a conventional fibular guide. In orbital floor reconstruction, the use of a CAM technique such as that used to manufacture the authors' fixation guide is as necessary for accurate, safe, and easy reconstruction as is preoperative CAD planning. The production of a fixation guide as well as a cutting guide is particularly useful because it is difficult to determine the angle for reconstructing the orbital floor by freehand techniques. In this case, the orbital floor was reconstructed based on a mirror image of the healthy side to avoid overcompression of the orbital tissue. Although the patient's vertical dystopia of eye position was improved, diplopia was not improved because, for greater safety, the authors did not plan overcorrection of the orbital volume.
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http://dx.doi.org/10.1097/SCS.0000000000004012DOI Listing
November 2017

Dual Vascular Free Anterolateral Thigh Flap.

Plast Reconstr Surg Glob Open 2017 Aug 24;5(8):e1448. Epub 2017 Aug 24.

Department of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; and Department of Otorhinolaryngology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: The optimum number of microvascular anastomoses for safe free tissue transfer is controversial. Although the case for 2 venous anastomoses versus 1 anastomosis has been argued, the use of an additional arterial anastomosis has not been examined in detail.

Methods: Twelve patients who underwent 2 arterial anastomoses for a free flap transfer were identified retrospectively from the medical records of patients undergoing reconstruction for head and neck cancer. The free flaps were limited to anterolateral thigh (ALT) flaps.

Results: All flaps survived. Complications included venous thrombosis (n = 1), reexploration (n = 1), and leakage (n = 3). The vascular patterns of dual-arterialized ALT flaps were classified into 3 groups. Types 1 and 2 were ALT flaps that had 2 vascular sources from the descending and lateral branches of the lateral circumflex femoral artery. The number of accompanying veins differed between type 1 (3 veins) and type 2 (2 veins). Type 3 differed from a conventional ALT flap nourished by the descending branch of the lateral circumflex femoral artery (1 vein) by the addition of anastomosis of an artery branching from the descending branch to the vastus medialis muscle. The total operation times for these 3 types of ALT were similar.

Conclusions: An additional arterial anastomosis to the free cutaneous flap did not cause any congestion or disturb the balance between inflow and outflow. If the surgeon considers that the first arterial anastomosis is unreliable, an additional anastomosis might be an option in ALT transfer.
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http://dx.doi.org/10.1097/GOX.0000000000001448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585440PMC
August 2017

Intraoperative Change in Defect Size during Maxillary Reconstruction Using Surgical Guides Created by CAD/CAM.

Plast Reconstr Surg Glob Open 2017 Apr 20;5(4):e1309. Epub 2017 Apr 20.

Department of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Plastic and Reconstructive Surgery, Fukuchiyama City Hospital, Fukuchiyama, Japan; and Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Surgical osteotomy guides created by computer-aided design/computer-aided manufacturing (CAD/CAM) have been developed and are now widely used in maxillofacial reconstruction. However, there are no standard procedures for dealing with an intraoperative change in defect size. We report on a case in which we used our CAD/CAM guides to deal with an intraoperative change in defect size in a maxillary reconstruction. We planned the maxillary reconstruction using a free fibula flap because of left maxillary sinus cancer in a 73-year-old man. In Japan, we cannot use commercially supplied CAD/CAM guides because these have not been approved by the government. We created novel CAD/CAM guides by using free software and a low-cost 3D printer. We performed model surgery to check the accuracy of the design and to prebend the titanium plates before the operation. The actual defect in the maxilla was found to be smaller than that used in preoperative planning. It was therefore necessary to rearrange the fibular segments and to rebend the plates. Comparison between the preoperative and postoperative 3D images showed that the deviation was 2-4 mm. In case that the CAD/CAM guides become inapplicable because of an intraoperative change in defect size, rearranging both the ends of set-up fibular segments and rebending the plates in situ allows us to deal with the situation. However, because extra time is needed to rearrange and rebend, the total operation and flap ischemic times are not shortened.
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http://dx.doi.org/10.1097/GOX.0000000000001309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426889PMC
April 2017

Spatiotemporal Profiles of Proprioception Processed by the Masseter Muscle Spindles in Rat Cerebral Cortex: An Optical Imaging Study.

Front Neural Circuits 2017 30;11. Epub 2017 Jan 30.

Department of Pharmacology, School of Dentistry, Nihon UniversityTokyo, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, School of Dentistry, Nihon UniversityTokyo, Japan; Molecular Dynamics Imaging Unit, RIKEN Center for Life Science TechnologiesKobe, Japan.

Muscle spindles in the jaw-closing muscles, which are innervated by trigeminal mesencephalic neurons (MesV neurons), control the strength of occlusion and the position of the mandible. The mechanisms underlying cortical processing of proprioceptive information are critical to understanding how sensory information from the masticatory muscles regulates orofacial motor function. However, these mechanisms are mostly unknown. The present study aimed to identify the regions that process proprioception of the jaw-closing muscles using optical imaging with a voltage-sensitive dye in rats under urethane anesthesia. First, jaw opening that was produced by mechanically pulling down the mandible evoked an optical response, which reflects neural excitation, in two cortical regions: the most rostroventral part of the primary somatosensory cortex (S1) and the border between the ventral part of the secondary somatosensory cortex (S2) and the insular oral region (IOR). The kinetics of the optical signal, including the latency, amplitude, rise time, decay time and half duration, in the S1 region for the response with the largest amplitude were comparable to those in the region with the largest response in S2/IOR. Second, we visualized the regions responding to electrical stimulation of the masseter nerve, which activates both motor efferent fibers and somatosensory afferent fibers, including those that transmit nociceptive and proprioceptive information. Masseter nerve stimulation initially excited the rostral part of the S2/IOR region, and an adjacent region responded to jaw opening. The caudal part of the region showing the maximum response overlapped with the region responding to jaw opening, whereas the rostral part overlapped with the region responding to electrical stimulation of the maxillary and mandibular molar pulps. These findings suggest that proprioception of the masseter is processed in S1 and S2/IOR. Other sensory information, such as nociception, is processed in a region that is adjacent to these pulpal regions and is located in the rostral part of S2/IOR, which receives nociceptive inputs from the molar pulps. The spatial proximity of these regions may be associated with the mechanisms by which masseter muscle pain is incorrectly perceived as dental pain.
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http://dx.doi.org/10.3389/fncir.2017.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5276849PMC
October 2017

People Like Logical Truth: Testing the Intuitive Detection of Logical Value in Basic Propositions.

PLoS One 2016 30;11(12):e0169166. Epub 2016 Dec 30.

Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya, Aichi, Japan.

Recent studies on logical reasoning have suggested that people are intuitively aware of the logical validity of syllogisms or that they intuitively detect conflict between heuristic responses and logical norms via slight changes in their feelings. According to logical intuition studies, logically valid or heuristic logic no-conflict reasoning is fluently processed and induces positive feelings without conscious awareness. One criticism states that such effects of logicality disappear when confounding factors such as the content of syllogisms are controlled. The present study used abstract propositions and tested whether people intuitively detect logical value. Experiment 1 presented four logical propositions (conjunctive, biconditional, conditional, and material implications) regarding a target case and asked the participants to rate the extent to which they liked the statement. Experiment 2 tested the effects of matching bias, as well as intuitive logic, on the reasoners' feelings by manipulating whether the antecedent or consequent (or both) of the conditional was affirmed or negated. The results showed that both logicality and matching bias affected the reasoners' feelings, and people preferred logically true targets over logically false ones for all forms of propositions. These results suggest that people intuitively detect what is true from what is false during abstract reasoning. Additionally, a Bayesian mixed model meta-analysis of conditionals indicated that people's intuitive interpretation of the conditional "if p then q" fits better with the conditional probability, q given p.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169166PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201307PMC
July 2017

Low-cost Design and Manufacturing of Surgical Guides for Mandibular Reconstruction Using a Fibula.

Plast Reconstr Surg Glob Open 2016 Jul 15;4(7):e805. Epub 2016 Jul 15.

Department of Plastic and Reconstructive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Surgical cutting guides are used in mandibular reconstruction involving osteotomy of the mandible and fibula. Cutting guides produced using computer-aided design (CAD) and computer-aided manufacturing (CAM) technologies have been reported recently. These guides aim to increase the benefits to patients by improving the accuracy, shortening the operating time, and correcting occlusion. However, the availability of these advanced technologies is limited in some regions of the world. To test whether we could produce low-cost surgical cutting guides, we made surgical guides and investigated their accuracy.

Methods: Using free CAD software, we designed surgical cutting guides for the mandible and fibula and used these to perform virtual mandibular segmental osteotomies and fibula transplants in 12 model surgeries. The cutting guides were printed on a 3-dimensional (3D) printer. The model surgeries were performed using 3D mandibular models and cutting guides to check their accuracy. Deviations between the virtually simulated plan and the actual model surgery were investigated.

Results: CAD and CAM technologies were used to design and 3D print the cutting guides and models. The guided surgeries were performed. The deviations were about 1.3 mm for mandibular osteotomy, less than 1 mm for fibular osteotomy, and within 2.4 mm for reconstructions of the mandible.

Conclusions: Without using expensive software or products, we were able to design surgical cutting guides for the mandible and fibula and used these to perform virtual simulation of mandibular segmental osteotomy and fibular reconstruction. Model surgeries using 3D-printed surgical guides showed that the accuracy of reconstruction was within a 3-mm deviation. In circumstances where commercial CAD/CAM guides are not available, it may be possible to use CAD/CAM surgical guides in the clinic if doctors are willing to volunteer their time for the design and printing.
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http://dx.doi.org/10.1097/GOX.0000000000000682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977133PMC
July 2016

Opposite effects of mu and delta opioid receptor agonists on excitatory propagation induced in rat somatosensory and insular cortices by dental pulp stimulation.

Neurosci Lett 2016 08 28;628:52-8. Epub 2016 May 28.

Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address:

The insular cortex (IC) contributes to nociceptive information processing. IC neurons express opioid receptors, including the mu (MOR), kappa (KOR), and delta (DOR) subtypes. Opioidergic agonists suppress excitatory synaptic transmission in the cerebral cortex. In addition, morphine injection into the IC reduces responses to noxious thermal stimuli. However, the mechanisms of the opioid-dependent modulation of cortical excitation at the macroscopic level, which bridge the cellular and behavioral findings, have remained unknown. The present in vivo optical imaging study aimed to examine the effects of the agonists of each subtype on cortical excitatory propagation in the IC and the neighboring cortices, the primary (S1) and secondary somatosensory (S2) areas. To assess the opioidergic effects on the cortical circuits, we applied electrical stimulation to the maxillary 1st molar pulp, which induced excitation in the ventral part of S1 and the S2/insular oral region (IOR). The initial excitatory response was observed 10-14ms after stimulation, and then excitation propagated concentrically. DAMGO (10-100μM), an MOR agonist, suppressed the amplitude of cortical excitation and shrank the maximum excitation areas in S1 and S2/IOR. In contrast, 10-100μM DPDPE, a DOR agonist, increased the amplitude of excitation and expanded the area of maximum excitation. U50488 (10-100μM), a KOR agonist, had little effect on cortical excitation. These results suggest that MOR-induced suppression of excitatory propagation in the IC is an underlying mechanism of the powerful analgesic effects of MOR agonists. In contrast, DOR may play a minor role in suppressing acute pain.
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http://dx.doi.org/10.1016/j.neulet.2016.05.065DOI Listing
August 2016

Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device.

Sci Rep 2016 Feb 19;6:21472. Epub 2016 Feb 19.

Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.

In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole.
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http://dx.doi.org/10.1038/srep21472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759809PMC
February 2016

Essential Role of GATA2 in the Negative Regulation of Type 2 Deiodinase Gene by Liganded Thyroid Hormone Receptor β2 in Thyrotroph.

PLoS One 2015 16;10(11):e0142400. Epub 2015 Nov 16.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.

The inhibition of thyrotropin (thyroid stimulating hormone; TSH) by thyroid hormone (T3) and its receptor (TR) is the central mechanism of the hypothalamus-pituitary-thyroid axis. Two transcription factors, GATA2 and Pit-1, determine thyrotroph differentiation and maintain the expression of the β subunit of TSH (TSHβ). We previously reported that T3-dependent repression of the TSHβ gene is mediated by GATA2 but not by the reported negative T3-responsive element (nTRE). In thyrotrophs, T3 also represses mRNA of the type-2 deiodinase (D2) gene, where no nTRE has been identified. Here, the human D2 promoter fused to the CAT or modified Renilla luciferase gene was co-transfected with Pit-1 and/or GATA2 expression plasmids into cell lines including CV1 and thyrotroph-derived TαT1. GATA2 but not Pit-1 activated the D2 promoter. Two GATA responsive elements (GATA-REs) were identified close to cAMP responsive element. The protein kinase A activator, forskolin, synergistically enhanced GATA2-dependent activity. Gel-shift and chromatin immunoprecipitation assays with TαT1 cells indicated that GATA2 binds to these GATA-REs. T3 repressed the GATA2-induced activity of the D2 promoter in the presence of the pituitary-specific TR, TRβ2. The inhibition by T3-bound TRβ2 was dominant over the synergism between GATA2 and forskolin. The D2 promoter is also stimulated by GATA4, the major GATA in cardiomyocytes, and this activity was repressed by T3 in the presence of TRα1. These data indicate that the GATA-induced activity of the D2 promoter is suppressed by T3-bound TRs via a tethering mechanism, as in the case of the TSHβ gene.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142400PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646574PMC
June 2016

Cancer Cell Analyses at the Single Cell-Level Using Electroactive Microwell Array Device.

PLoS One 2015 11;10(11):e0139980. Epub 2015 Nov 11.

Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.

Circulating tumor cells (CTCs), shed from primary tumors and disseminated into peripheral blood, are playing a major role in metastasis. Even after isolation of CTCs from blood, the target cells are mixed with a population of other cell types. Here, we propose a new method for analyses of cell mixture at the single-cell level using a microfluidic device that contains arrayed electroactive microwells. Dielectrophoretic (DEP) force, induced by the electrodes patterned on the bottom surface of the microwells, allows efficient trapping and stable positioning of single cells for high-throughput biochemical analyses. We demonstrated that various on-chip analyses including immunostaining, viability/apoptosis assay and fluorescent in situ hybridization (FISH) at the single-cell level could be conducted just by applying specific reagents for each assay. Our simple method should greatly help discrimination and analysis of rare cancer cells among a population of blood cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641639PMC
June 2016

Pre-operative effects of the administration of systemic corticosteroids combined with antibiotics on a lobular capillary hemangioma in the nasal cavity.

Auris Nasus Larynx 2016 Apr 22;43(2):203-6. Epub 2015 Aug 22.

Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba City, Chiba 260-8670, Japan.

Lobular capillary hemangiomas (LCHs), also known as pyogenic granulomas, are benign, rapidly growing hemorrhagic lesions that usually develop in the oral or nasal cavities. In adults, LCHs occur in <5% of all pregnant women. A 30-year-old woman presented with a 4-month history of right-sided nasal obstruction and recurrent epistaxis 2 months post-partum. A fragile, pink-red lobulated tumor existed in the anterior portion of the right inferior turbinate; the biopsy revealed a LCH. Although the patient declined surgery using an external approach, treatment with systemic corticosteroids combined with antibiotics resulted in tumor regression and an endoscopic en bloc resection was possible. No recurrence has been noted to date (>1 year after surgery). Pre-operative treatment with systemic corticosteroids combined with antibiotics may be useful to induce tumor regression and to excise the lesion completely with an endoscopic approach.
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http://dx.doi.org/10.1016/j.anl.2015.08.001DOI Listing
April 2016