Publications by authors named "Arifa Nazneen"

25 Publications

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Prevalence of COVID-19 in Bangladesh, April to October 2020-a cross-sectional study.

IJID Reg 2021 Dec 14;1:92-99. Epub 2021 Oct 14.

Directorate General of Health Services (DGHS), Dhaka, Bangladesh.

The aim of this study was to estimate the proportion of symptomatic and asymptomatic laboratory-confirmed coronavirus disease 2019 (COVID-19) cases among the population of Bangladesh. A cross-sectional survey was conducted in Dhaka City and other districts of Bangladesh between April 18 and October 12, 2020. A total of 32 districts outside Dhaka were randomly selected, and one village and one mahalla was selected from each district; 25 mahallas were selected from Dhaka City. From each village or mahalla, 120 households were enrolled through systematic random sampling. A total of 44 865 individuals were interviewed from 10 907 households. The majority (70%,  = 31 488) of the individuals were <40 years of age. Almost half of the individuals (49%,  = 21 888) reported more than four members in their household. It was estimated that 12.6% ( = 160) of the households had one or more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals, among whom 0.9% ( = 404) of individuals had at least one COVID-19-like symptom, at the national level. The prevalence of COVID-19 in the general population was 6.4%. Among the SARS-CoV-2-positive individuals, 87% were asymptomatic. The substantial high number of asymptomatic cases all over Bangladesh suggests that community-level containment and mitigation measures are required to combat COVID-19. Future studies to understand the transmission capability could help to define mitigation and control measures.
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http://dx.doi.org/10.1016/j.ijregi.2021.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516147PMC
December 2021

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

IJID Reg 2022 Mar 2;2:198-203. Epub 2022 Feb 2.

International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.

Design: A cross-sectional study was conducted amongst household members in 32 districts of Bangladesh to build knowledge about disease epidemiology and seroepidemiology of coronavirus disease 2019 (COVID-19).

Objective: Antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in people between April and October 2020.

Results: The national seroprevalence rates of immunoglobulin G (IgG) and IgM were estimated to be 30.4% and 39.7%, respectively. In Dhaka, the seroprevalence of IgG was 35.4% in non-slum areas and 63.5% in slum areas. In areas outside of Dhaka, the seroprevalence of IgG was 37.5% in urban areas and 28.7% in rural areas. Between April and October 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in younger participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from patients with COVID-19 and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and day 28 compared with day 1 after enrolment. : SARS-CoV-2 had spread extensively in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.
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http://dx.doi.org/10.1016/j.ijregi.2022.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809641PMC
March 2022

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Trop Med Infect Dis 2022 Mar 25;7(4). Epub 2022 Mar 25.

Programme for Emerging Infections, Infectious Diseases Division, icddr,b, Dhaka 1212, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June-September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 ( = 0.01) and 28 ( = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable ( > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.
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http://dx.doi.org/10.3390/tropicalmed7040053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030026PMC
March 2022

Preparedness of tertiary care hospitals to implement the national TB infection prevention and control guidelines in Bangladesh: A qualitative exploration.

PLoS One 2022 3;17(2):e0263115. Epub 2022 Feb 3.

School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.

In high tuberculosis (TB) burden countries, health settings, including non-designated TB hospitals, host many patients with pulmonary TB. Bangladesh's National TB Control Program aims to strengthen TB infection prevention and control (IPC) in health settings. However, there has been no published literature to date that assessed the preparedness of hospitals to comply with the recommendations. To address this gap, our study examined healthcare workers knowledge and attitudes towards TB IPC guidelines and their perceptions regarding the hospitals' preparedness in Bangladesh. Between January to December 2019, we conducted 16 key-informant interviews and four focus group discussions with healthcare workers from two public tertiary care hospitals. In addition, we undertook a review of 13 documents [i.e., hospital policy, annual report, staff list, published manuscript]. Our findings showed that healthcare workers acknowledged the TB risk and were willing to implement the TB IPC measures but identified key barriers impacting implementation. Gaps were identified in: policy (no TB policy or guidelines in the hospital), health systems (healthcare workers were unaware of the guidelines, lack of TB IPC program, training and education, absence of healthcare-associated TB infection surveillance, low priority of TB IPC, no TB IPC monitoring and feedback, high patient load and bed occupancy, and limited supply of IPC resources) and behavioural factors (risk perception, compliance, and self and social stigma). The additional service-level gap was the lack of electronic medical record systems. These findings highlighted that while there is a demand amongst healthcare workers to implement TB IPC measures, the public tertiary care hospitals have got key issues to address. Therefore, the National TB Control Program may consider these gaps, provide TB IPC guidelines to these hospitals, assist them in developing hospital-level IPC manual, provide training, and coordinate with the ministry of health to allocate separate budget, staffing, and IPC resources to implement the control measures successfully.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263115PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812944PMC
February 2022

A Case Series Describing the Recurrence of COVID-19 in Patients Who Recovered from Initial Illness in Bangladesh.

Trop Med Infect Dis 2021 Mar 31;6(2). Epub 2021 Mar 31.

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.

To date, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 80 million people globally. We report a case series of five clinically and laboratory confirmed COVID-19 patients from Bangladesh who suffered a second episode of COVID-19 illness after 70 symptom-free days. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), is a leading public health research institution in South Asia. icddr, b staff were actively tested, treated and followed-up for COVID-19 by an experienced team of clinicians, epidemiologists, and virologists. From 21 March to 30 September 2020, 1370 icddr,b employees working at either the Dhaka (urban) or Matlab (rural) clinical sites were tested for COVID-19. In total, 522 (38%) were positive; 38% from urban Dhaka (483/1261) and 36% from the rural clinical site Matlab (39/109). Five patients (60% male with a mean age of 41 years) had real-time reverse transcription-polymerase chain reaction (rRT-PCR) diagnosed recurrence (reinfection) of SARS-CoV-2. All had mild symptoms except for one who was hospitalized. Though all cases reported fair risk perceptions towards COVID-19, all had potential exposure sources for reinfection. After a second course of treatment and home isolation, all patients fully recovered. Our findings suggest the need for COVID-19 vaccination and continuing other preventive measures to further mitigate the pandemic. An optimal post-recovery follow-up strategy to allow the safe return of COVID-19 patients to the workforce may be considered.
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http://dx.doi.org/10.3390/tropicalmed6020041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103235PMC
March 2021

Implementation status of national tuberculosis infection control guidelines in Bangladeshi hospitals.

PLoS One 2021 16;16(2):e0246923. Epub 2021 Feb 16.

Programme for Emerging Infections, Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.

In response to the World Health Organization (WHO) recommendation to reduce healthcare workers' (HCWs') exposure to tuberculosis (TB) in health settings, congregate settings, and households, the national TB control program of Bangladesh developed guidelines for TB infection prevention and control (IPC) in 2011. This study aimed to assess the implementation of the TB IPC healthcare measures in health settings in Bangladesh. Between February and June 2018, we conducted a mixed-method study at 11 health settings. The team conducted 59 key-informant interviews with HCWs to understand the status of and barriers impeding the implementation of the TB IPC guidelines. The team also performed a facility assessment survey and examined TB IPC practices. Most HCWs were unaware of the national TB IPC guidelines. There were no TB IPC plans or committees at the health settings. Further, a presumptive pulmonary TB patient triage checklist was absent in all health settings. However, during facility assessment, we observed patient triaging and separation in the TB specialty hospitals. Routine cough-etiquette advice was provided to the TB patients mentioned during the key-informant interviews, which was consistent with findings from the survey. This study identified poor implementation of TB IPC measures in health settings. Limited knowledge of the guidelines resulted in poor implementation of the recommendations. Interventions focusing on the dissemination of the TB IPC guidelines to HCWs along with regular training may improve compliance. Such initiatives should be taken by hospital senior leadership as well as national policy makers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246923PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886225PMC
August 2021

A tuberculin skin test survey among healthcare workers in two public tertiary care hospitals in Bangladesh.

PLoS One 2020 17;15(12):e0243951. Epub 2020 Dec 17.

School of Population Health, University of New South Wales, Sydney, Australia.

In Bangladesh, there is currently no data on the burden of latent TB infection (LTBI) amongst hospital healthcare workers (HCWs). This study aimed to determine the prevalence of LTBI and compare the prevalence among HCWs in two public tertiary care hospitals. Between September 2018 and August 2019, we conducted a cross-sectional study in two public tertiary care general hospitals. Using a survey and tuberculin skin test (TST), we assessed risk factors for LTBI, adjusting for known and plausible confounders. In addition, a facility assessment was undertaken to understand the implementation of relevant IPC measures. The prevalence of LTBI among HCWs was 42%. HCWs spent a median of 6 hours (SD = 1.76, IQR 2.00) per day and attended an average of 1.87 pulmonary TB patients per week. HCWs did not receive any TB IPC training, the wards lacked a symptom checklist to screen patients for TB, and no masks were available for coughing patients. Seventy-seven percent reportedly did not use any facial protection (masks or respirators) while caring for patients. In the multivariable model adjusting for hospital level clustering effect, TST positivity was significantly higher among HCWs aged 35-45 years (aOR1.36, 95% CI: 1.06-1.73) and with >3 years of service (aOR 1.67, 95% CI: 1.62-1.72). HCWs working in the medicine ward had 3.65 (95% CI: 2.20-6.05) times, and HCWs in the gynecology and obstetrics ward had 2.46 (95% CI: 1.42-4.27) times higher odds of TST positivity compared to HCWs working in administrative areas. This study identified high prevalence of LTBI among HCWs. This may be due to the level of exposure to pulmonary TB patients, and/or limited use of personal protective equipment along with poor implementation of TB IPC in the hospitals. Considering the high prevalence of LTBI, we recommend the national TB program consider providing preventative therapy to the HCWs as the high-risk group, and implement TB IPC in the hospitals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243951PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745963PMC
February 2021

Hepatitis E as a cause of adult hospitalization in Bangladesh: Results from an acute jaundice surveillance study in six tertiary hospitals, 2014-2017.

PLoS Negl Trop Dis 2020 01 21;14(1):e0007586. Epub 2020 Jan 21.

icddr,b, Dhaka, Bangladesh.

In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death. We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes. From December'2014 to September'2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females-12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth. This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups.
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http://dx.doi.org/10.1371/journal.pntd.0007586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994197PMC
January 2020

A Low-Cost, Community Knowledge Approach to Estimate Maternal and Jaundice-Associated Mortality in Rural Bangladesh.

Am J Trop Med Hyg 2018 12;99(6):1633-1638

Australian Centre for Public and Population Health, Research, University of Technology Sydney, Sydney, Australia.

In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method's sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.
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http://dx.doi.org/10.4269/ajtmh.17-0974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283507PMC
December 2018

The Interaction of Deworming, Improved Sanitation, and Household Flooring with Soil-Transmitted Helminth Infection in Rural Bangladesh.

PLoS Negl Trop Dis 2015 Dec 1;9(12):e0004256. Epub 2015 Dec 1.

School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.

Background: The combination of deworming and improved sanitation or hygiene may result in greater reductions in soil-transmitted helminth (STH) infection than any single intervention on its own. We measured STH prevalence in rural Bangladesh and assessed potential interactions among deworming, hygienic latrines, and household finished floors.

Methodology: We conducted a cross-sectional survey (n = 1,630) in 100 villages in rural Bangladesh to measure three exposures: self-reported deworming consumption in the past 6 months, access to a hygienic latrine, and household flooring material. We collected stool samples from children 1-4 years, 5-12 years, and women 15-49 years. We performed mini-FLOTAC on preserved stool samples to detect Ascaris lumbricoides, Enterobius vermicularis, hookworm, and Trichuris trichiura ova. Approximately one-third (32%) of all individuals and 40% of school-aged children had an STH infection. Less than 2% of the sample had moderate/heavy intensity infections. Deworming was associated with lower Ascaris prevalence (adjusted prevalence ratio (PR) = 0.53; 95% CI 0.40, 0.71), but there was no significant association with hookworm (PR = 0.93, 95% CI 0.60, 1.44) or Trichuris (PR = 0.90, 95% CI 0.74, 1.08). PRs for hygienic latrine access were 0.91 (95% CI 0.67,1.24), 0.73 (95% CI 0.43,1.24), and 1.03 (95% CI 0.84,1.27) for Ascaris, hookworm, and Trichuris, respectively. Finished floors were associated with lower Ascaris prevalence (PR = 0.56, 95% CI 0.32, 0.97) but not associated with hookworm (PR = 0.48 95% CI 0.16,1.45) or Trichuris (PR = 0.98, 95% CI 0.72,1.33). Across helminths and combinations of exposures, adjusted prevalence ratios for joint exposures were consistently more protective than those for individual exposures.

Conclusions: We found moderate STH prevalence in rural Bangladesh among children and women of childbearing age. This study is one of the first to examine independent and combined associations with deworming, sanitation, and hygiene. Our results suggest that coupling deworming with sanitation and flooring interventions may yield more sustained reductions in STH prevalence.
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http://dx.doi.org/10.1371/journal.pntd.0004256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666415PMC
December 2015

Heat shock protein 47: a novel biomarker of phenotypically altered collagen-producing cells.

Acta Histochem Cytochem 2011 Apr 21;44(2):35-41. Epub 2011 Apr 21.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that helps the molecular maturation of various types of collagens. A close association between increased expression of HSP47 and the excessive accumulation of collagens is found in various human and experimental fibrotic diseases. Increased levels of HSP47 in fibrotic diseases are thought to assist in the increased assembly of procollagen, and thereby contribute to the excessive deposition of collagens in fibrotic areas. Currently, there is not a good universal histological marker to identify collagen-producing cells. Identifying phenotypically altered collagen-producing cells is essential for the development of cell-based therapies to reduce the progression of fibrotic diseases. Since HSP47 has a single substrate, which is collagen, the HSP47 cellular expression provides a novel universal biomarker to identify phenotypically altered collagen-producing cells during wound healing and fibrosis. In this brief article, we explained why HSP47 could be used as a universal marker for identifying phenotypically altered collagen-producing cells.
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http://dx.doi.org/10.1267/ahc.11001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096080PMC
April 2011

Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis.

Oncol Rep 2011 Apr 9;25(4):929-35. Epub 2011 Feb 9.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression. Recently, it has been reported that angiopoietin-like 4 (ANGPTL4) expression in cancer cells promotes the metastatic process by increasing vascular permeability. The present study was conducted to examine ANGPTL4 expression and its association with clinicopathological factors and prognosis in human colorectal cancers. We examined 144 cases of surgically-resected human colorectal adenocarcinomas by immunohistochemistry, RT-PCR and Western blot analysis. Also, overall survival was investigated. Among 144 cases of adenocarcinoma, 95 cases (66.0%) showed positive staining in the cytoplasm of the carcinoma cells for ANGPTL4. Histologically, well, moderately, poorly differentiated adenocarcinoma or mucinous carcinoma showed 55.2, 79.3, 61.5 or 44.4% expression of ANGPTL4, respectively. The expression of ANGPTL4 was correlated with the depth of tumour invasion (p<0.0005), Vienna classification (category 3-5)(p<0.00005), venous invasion (p<0.0005) and Duke's classification (p<0.005). However, ANGPTL4 expression was not correlated with overall survival. However, all patients (100%) with distant metastasis showed immunopositivity for ANGPTL4. The mRNA and the protein expression of ANGPTL4 were shown in four resected samples and cultured cell lines by RT-PCR or western blot analysis. These findings suggest that ANGPTL4 is one of the factors involved in the progression of human colorectal cancer, especially venous invasion and distant metastasis.
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http://dx.doi.org/10.3892/or.2011.1176DOI Listing
April 2011

A low-cost approach to measure the burden of vaccine preventable diseases in urban areas.

Vaccine 2010 Jul;28(31):4903-12

International Centre for Diarrheal Diseases Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.

We piloted a low-cost approach to measure the disease burden of Streptococcus pneumoniae, Hib and Salmonella Typhi by leveraging the existing infrastructure of high performing microbiology laboratories at two large paediatric hospitals in Dhaka Bangladesh, and assessing the hospital utilization of the catchment population of these hospitals for different syndromes. S. Typhi was the most common bacterium identified in culture and accounted for an estimated 211 hospitalizations per 100,000 children <5 years of age per year. Meningitis due to S. pneumoniae was the most common cause of mortality accounting for 8.0 deaths per 100,000 children <5 years of age per year. This low-cost approach can provide data to support vaccine introduction and the health impact of newly introduced vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2010.05.040DOI Listing
July 2010

Pathological influence of obesity on renal structural changes in chronic kidney disease.

Clin Exp Nephrol 2009 Aug 29;13(4):332-340. Epub 2009 Apr 29.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: Role of obesity in renal pathological and structural changes remains poorly investigated, and this study was designed to examine the pathological effects of obesity on renal structural components in patients with chronic kidney diseases (CKD).

Methods: The study subjects were obese (body mass index, BMI > or = 25 kg/m2) patients with nonglomerulonephritis (non-GN, n = 26), IgA nephropathy (IgAN, n = 19), benign nephrosclerosis (BNS, n = 15), and thin basement membrane disease (TMD, n = 6), and 65 nonobese controls (n = 20, 20, 10, and 15, respectively). Patients were evaluated for glomerular lesions (mesangial proliferation and focal segmental/global glomerulosclerosis), glomerular size, and thickness of glomerular basement membrane (GBM).

Results: Urinary protein was higher in obese non-GN, IgAN, and BNS groups than in the respective controls. Focal segmental glomerulosclerosis (FSGS) lesions were noted in all obesity groups. The glomeruli were larger in size in obese than in nonobese patients of the non-GN and IgAN groups. The glomeruli of nonobese TMD and BNS patients were significantly larger in size than those of nonobese non-GN patients. GBM were thicker in obese than in nonobese patients irrespective of types of glomerular diseases, but only significantly so in non-GN and BNS groups.

Conclusion: In non-GN, IgAN, and BNS, obesity worsens proteinuria and is associated with structural changes such as glomerulomegaly and GBM thickening, similar to changes observed in obesity-related nephropathy. Obesity seems to worsen the renopathological state in CKD.
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http://dx.doi.org/10.1007/s10157-009-0169-3DOI Listing
August 2009

Unusual glomerulopathy with atypical thickening of the glomerular basement membrane and intramembranous microparticles.

Clin Exp Nephrol 2008 Dec 18;12(6):501-3. Epub 2008 Nov 18.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.

A 57-year-old Japanese female was admitted because of edema, hypoproteinemia and proteinuria. Her histopathological findings of renal biopsy specimen were quite unique. Light microscopic findings suggested membranous glomerulonephritis, but no significant deposition of immunoglobulins or complements was detected in glomeruli by immunofluorescence. Electron microscopic examination revealed irregular thickening of the glomerular basement membrane (GBM). The GBM had no electron-dense deposits, but numerous microparticles varying in shape and size were present in all the thickened GBM and occasionally in the mesangium. The microparticles were round or oval in shape, and the size varied widely, measuring 25-290 nm (mostly 40-120 nm). The cytoplasmic infolding into the GBM by podocytes was seen. The large-sized particles had microgranules, mimicking free ribosomes seen in podocytes or endothelial cells. We conclude that cytoplasmic infolding and subsequent degradation may, partly, contribute to the formation of microparticles in the GBM.
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http://dx.doi.org/10.1007/s10157-008-0103-0DOI Listing
December 2008

Genetic suppression of GH-IGF-1 activity, combined with lifelong caloric restriction, prevents age-related renal damage and prolongs the life span in rats.

Am J Nephrol 2008 24;28(5):755-64. Epub 2008 Apr 24.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Aim: The aim of this study was to determine the effects of kidney pathology on overall survival and longevity and the combined effects of chronic suppression of growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity and lifelong caloric restriction on age-associated nephropathy.

Methods: We analyzed the kidneys of rats with suppressed GH activity through genetic manipulation with an antisense GH transgene. Rats were fed normally or with a 30% calorie-restricted diet for 24-26 months. The kidneys of male wild-type young (6 months) and old (24-26 months) rats were compared with male hemizygote transgenic young (6 months) and old (24-26 months) rats fed with either regular diet or 30% calorie-restricted diet for their entire life span.

Results: The transgenic rats had relatively less pituitary GH-secreting cells, and the plasma levels of IGF-1 were decreased by 53% in homozygote rats (tg/tg) and by 28% in hemizygote rats (tg/wt) compared to wild-type rats (wt/wt) of the same age (6 months). Wild-type rats fed the regular diet developed age-associated nephropathy as they aged, showing severe inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. In addition, about 83% of the wild-type rats allowed to survive naturally showed signs of nephropathy. In contrast, only 26% of the naturally surviving hemizygote rats showed features of nephropathy, despite the fact that these rats lived 8% longer (maximum survival 171 weeks) than the wild-type rats (maximum survival 158 weeks). When chronic suppression of GH/IGF-1 activity was combined with lifelong caloric restriction, however, age- associated nephropathy was nonexistent in hemizygote transgenic rats, and they showed about 30% increase in survival (maximum survival 204 weeks). There was no significant difference in the rate of neoplastic or nonneoplastic lesions (other than in the kidney) in the regularly fed wild-type rats or in the calorie-restricted hemizygote transgenic rats that survived longer.

Conclusion: We concluded that kidney pathology is an important determinant of overall survival, and that prevention of kidney pathology by dietary restriction, combined with chronic suppression of GH/IGF-1 activity, significantly extends overall survival and longevity.
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http://dx.doi.org/10.1159/000128607DOI Listing
October 2008

Low-dose local kidney irradiation inhibits progression of experimental crescentic nephritis by promoting apoptosis.

Am J Nephrol 2008 1;28(4):555-68. Epub 2008 Feb 1.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Crescentic glomerulonephritis is a rapidly progressive form of nephritis and is usually resistant to therapeutic intervention. Apoptosis plays a role in the resolution of glomerulonephritis. We investigated the effects of local kidney irradiation on the progression of experimental crescentic glomerulonephritis.

Methods: The following three experimental rat groups were generated: (1) Group I, sham-operated control (n = 12); (2) Group II, rats injected intravenously with rabbit anti-rat GBM antibody (nephrotoxic serum, NTS) (n = 23), and (3) Group III, a single low-dose irradiation of 0.5 Gy X-ray to both kidneys at days 6, 13, 20, and 27 after NTS injection (n = 55). Renal function and blood leukocyte count were examined in different groups of rats at various time points. Kidneys obtained at various time points were analyzed to determine the effects of radiation in experimental nephritis.

Results: Radiation of the kidneys reduced the levels of blood urea nitrogen and serum creatinine compared with Group II nephritic rats of similar age (p < 0.05 or 0.001). No apparent changes in blood leukocyte counts were noted in various experimental groups. Glomerular hypercellularity, crescents, global sclerosis and tubulointerstitial damage developed gradually in Group II rats, but were decreased (p < 0.05 or 0.001) after radiation treatment. The extent of tubulointerstitial damage was also reduced, and radiation-associated histological improvements were accompanied by reduced infiltration of macrophages in the glomeruli and interstitium. The numbers of PCNA- and ED1-positive cells were reduced in the kidneys at 1 day post-irradiation, of rats irradiated at 6 and 13 days after NTS injection, compared with Group II at similar time intervals (p < 0.05). A larger numbers of TUNEL-positive cells were noted at 1 day post-irradiation in rats irradiated at 6 and 13 days after NTS injection, compared with Group II at similar time intervals (p < 0.05). Immunostaining for macrophages ED1 and TUNEL staining of serial sections of irradiated nephritic kidneys showed few ED1-positive macrophages stained for TUNEL. Overexpression of active caspases 3 and 7 was noted in irradiated kidneys, compared with the corresponding Group II rats at similar time intervals. Western blot analysis showed marked increase in active caspase 3 and active caspase 7 expression in irradiated kidneys compared with NTS injection only. A marked increase in the expression of p53 protein, which is closely related to radiation-induced apoptosis, was also observed in irradiated kidneys compared with NTS injection only.

Conclusion: Our study showed that renal radiation can alter acute glomerular inflammation by inducing apoptosis of intrinsic and infiltrating cells in the kidney in a rat model of crescentic glomerulonephritis. Low-dose kidney irradiation can inhibit the progression of experimental nephritis through inducing apoptosis.
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http://dx.doi.org/10.1159/000115290DOI Listing
July 2008

Interstitial expression of heat-shock protein 47 correlates with capillary deposition of complement split product C4d in chronic allograft nephropathy.

Clin Transplant 2005 Dec;19(6):810-6

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN.

Methods: Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and alpha-SMA and the clinical and histopathological parameters were statistically analysed.

Results: No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of alpha-SMA.

Conclusions: The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.
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http://dx.doi.org/10.1111/j.1399-0012.2005.00426.xDOI Listing
December 2005

Cisplatin-associated nephrotoxicity and pathological events.

Contrib Nephrol 2005 ;148:107-121

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Cisplatin (cis-diamminedichloroplatinum(II)) is an effective chemotherapeutic agent, and is successfully used in the treatment of a wide range of tumors. Despite its effectiveness as an anti-tumor drug, nephrotoxic side effects have significantly restricted its clinical use. Tubular epithelial cell deletion following cisplatin treatment is a major cause of renal injury. Oxidative stress significantly contributes to cisplatin-associated cytotoxicity, and use of antioxidants could counteract such cytotoxic effects of cisplatin. The renal microenvironmental changes following cisplatin treatment is a complex process and could be broadly categorized into three main pathological events, which at times might overlap: initial cytotoxic events, inflammatory events and fibroproliferative events. Stress responses and heat shock proteins generated following cisplatin treatment are actively involved in the initiation and progression of these events. In this article, we will briefly summarize factors involved in various phases of cisplatin-induced renal injuries.
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http://dx.doi.org/10.1159/000086055DOI Listing
August 2005

Incidental detection of renomedullary interstitial cell tumour in a renal biopsy specimen.

Nephrol Dial Transplant 2004 Apr;19(4):1007-8

Department of Internal Medicine, Nagasaki Municipal Medical Center, 20-5 Fuchi-machi, Nagasaki 852-8012, Japan.

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http://dx.doi.org/10.1093/ndt/gfg596DOI Listing
April 2004

Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy.

Med Electron Microsc 2002 Dec;35(4):242-7

Department of Pathology, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Cisplatin is an effective antitumor drug, but nephrotoxicity has restricted its clinical use. Renal interstitial fibrosis is a major complication of cisplatin treatment, due to the increased accumulation of extracellular matrix (ECM) proteins. Ets-1 protein plays a role in matrix remodeling by regulating matrix-degrading enzymes. We studied the role of Ets-1, matrix metalloproteinase-1 (MMP-1), and interstitial collagen (type III) in experimental cisplatin nephropathy. Wistar rats ( n = 24) were treated with cisplatin (6 mg/kg), and killed on days 3, 7, and 14, along with control rats. By immunohistochemistry, a significant increase ( P < 0.02) in the number of Ets-1-positive cells (40.09 +/- 1.52) was detected in kidneys of cisplatin-treated rats on day 3, compared with the number in control rat kidneys (29.80 +/- 0.13). The number of Ets-1-positive cells decreased in kidneys from cisplatin-treated rats on days 7 (10.93 +/- 1.20) and 14 (12.16 +/- 0.60). The expression of MMP-1 showed a similar pattern, increasing on day 3, but decreasing on days 7 and 14. The decreased levels of Ets-1 and MMP-1 were associated with increased interstitial accumulation of collagen in kidneys of cisplatin-treated rats on day 14. Molecular interactions among Ets-1, MMP-1, and type III collagens might play a role in matrix remodeling in cisplatin nephropathy.
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http://dx.doi.org/10.1007/s007950200028DOI Listing
December 2002

Severe arteriolar lesion mimicking drug-induced arteriolopathy in a long-term surviving renal allograft.

Clin Transplant 2002 ;16 Suppl 8:72-6

Department of Pathology, Nagasaki University School of Medicine, and Renal Care Unit, Nagasaki University Hospital, Japan.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.
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http://dx.doi.org/10.1034/j.1399-0012.16.s8.13.xDOI Listing
April 2003

Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathy.

Pathol Int 2002 May-Jun;52(5-6):340-7

Second Department of Pathology, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.

The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as alpha-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy.
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http://dx.doi.org/10.1046/j.1440-1827.2002.01362.xDOI Listing
February 2003

Renal expression of the Ets-1 proto-oncogene during progression of rat crescentic glomerulonephritis.

J Am Soc Nephrol 2000 Dec;11(12):2243-2255

Second Department of Pathology, Nagasaki University School of Medicine, Nagasaki, Japan.

The ets-1 proto-oncogene is a member of the transcriptional factor family and was identified by homology to the v-ets oncogene. It was recently demonstrated that Ets-1 protein interacts with the promoter region of the genes coding for proteinases, including matrix metalloproteinase-1 (MMP-1), MMP-3, and urokinase-type plasminogen activator, suggesting that it may play an important role in the regulation of MMP expression. The role of the ets-1 proto-oncogene in advanced glomerular diseases, where extracellular matrix accumulation is observed, remains undefined. In this study, the expression of ets-1 mRNA and protein during the progression of rat crescentic glomerulonephritis was examined using immunohistochemical analysis, reverse transcription-PCR, and in situ hybridization. Passive accelerated anti-glomerular basement membrane-induced nephritis was induced in rats by intravenous injection of nephrotoxic serum. Rats were euthanized on day 7, 14, 21, 28, or 42. Immunohistochemical analysis demonstrated significant upregulation of Ets-1 protein expression in glomeruli and the interstitium in anti-glomerular basement membrane-induced nephritis. The numbers of Ets-1-positive cells were increased 8.8-fold on day 21 in glomeruli (1.2+/-0.1 cells/glomerular cross-section, P<0.001) and sixfold on day 28 in the interstitium (21+/-1.3 cells/mm(2), P<0.001), compared with control samples. Ets-1 protein was predominantly localized in glomerular epithelial cells, endothelial cells, and interstitial cells. A small number of vascular endothelial cells, macrophages, and T cells also expressed Ets-1 protein. MMP-3 deposition was upregulated and positive cells in the interstitium often coexpressed Ets-1, whereas only a few glomerular cells were positive for both MMP-3 and Ets-1 protein. The expression of ets-1 mRNA was also markedly increased in diseased kidneys. The distribution of ets-1 mRNA was similar to that of the protein. These results indicate that overexpression of the ets-1 proto-oncogene by phenotypically altered renal cells might be associated with the pathogenesis of rat crescentic glomerulonephritis.
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http://dx.doi.org/10.1681/ASN.V11122243DOI Listing
December 2000
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