Papers by Sumathi Ramachandran
Viruses, Jan 15, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Atherosclerosis, 2005
Exercise is recommended both as a prophylactic and also as a therapeutic approach for patients wi... more Exercise is recommended both as a prophylactic and also as a therapeutic approach for patients with established coronary artery disease. In this study, we investigated the effect of a normal chow diet, with or without exercise in LDL r −/− mice with preexisting atherosclerotic lesions. A total of 28 LDL r −/− mice (LDL receptor knock out mice, 4-6 weeks old) were fed a high fat, high cholesterol diet (inductive phase). At the end of the 3 months, eight mice were sacrificed, and plasma autoantibodies to oxidatively modified proteins, cholesterol levels, and surface area of the lesions in the aorta were determined. The remaining mice were divided into two groups, and placed on a normal chow diet alone, or normal chow and exercise for three more months (regressive phase). Plasma autoantibodies to oxidatively modified proteins and cholesterol were measured along with the lesion size. Compared to the group of animals at the end of the inductive phase, both the groups of animals in the regressive phase had very low levels of plasma cholesterol and autoantibodies, and almost a 50% reduction in the aortic lesion area. The group that was exercised had the lowest levels of autoantibodies and aortic lesions as compared to the group without the exercise. However, the plasma cholesterol levels were comparable in both groups. This study demonstrates that reduction of preexisting atherosclerotic lesions is accelerated dramatically by exercise in LDL r −/− mice.
Journal of Hepatology, Jul 1, 2022
Cell systems, Oct 1, 2022
Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodolog... more Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodology faces many challenges. First, few methods account for intra-host viral diversity. Second, maximum parsimony principle continues to be employed, even though maximum likelihood or Bayesian models are usually more consistent. Third, many methods utilize case-specific data, such as sampling times or infection exposure intervals. This impedes study of persistent infections in vulnerable groups, where such information has a limited use. Finally, most methods implicitly assume that transmission events are independent, while common source outbreaks violate this assumption. We propose a maximum likelihood framework SOPHIE (SOcial and PHilogenetic Investigation of Epidemics) based on integration of phylogenetic and random graph models. It infers transmission networks from viral phylogenies and expected properties of inter-host social networks modelled as random graphs with given expected degree distributions. SOPHIE is scalable, accounts for intra-host diversity and accurately infers transmissions without case-specific epidemiological data.
Fertility and Sterility, Sep 1, 2002
Results: VEGF was localized in various components of the growing follicles, which were at differe... more Results: VEGF was localized in various components of the growing follicles, which were at different stages of folliculogenesis. Granulosa cells and oocytes of primordial follicles were immunonegative. In early primary follicles, VEGF was present in the oocyte but its immunoreactivity was weak, while newly developing zona pellucida of primary follicles was not positive for VEGF. Subsequently, with the commencement of antral spaces between granulosa cells of the secondary follicle, zona pellucida of some of the secondary follicles became strongly positive for VEGF, forming a continuous ring around the oocyte. In preovulatory mature follicles, neither the oocyte nor the zona pellucida were stained positively for VEGF, except for a weak immunoreactivity in granulosa cells and theca interna cells. Western blot analyses have also demonstrated that 26 kDa VEGF protein was present in the follicles. Moreover, in an ovulated cumulus-oocyte complex we have observed a halo immunoreaction of VEGF around the fully mature oocyte, with a negative cumulus cell mass. In contrast, the zona pellucida of growing follicles were not positive for KDR and Flt-1 receptors. The positive immunoreactivity in these follicules was mostly limited to granulosa and theca interna cells. Conclusions: This is the first study that reports the presence of VEGF protein in the zona pellucida. Interestingly, its presence in the zona pellucida of some secondary follicles is very striking. Accordingly, the possibility that VEGF may be an important regulatory molecule for the dominant follicle selection or atresia should be considered. Supported by: AKD-20.01.0103.14.
Open Forum Infectious Diseases, 2017
Background. Early recognition of tuberculosis (TB) cases is critical to prevent spread. Infants a... more Background. Early recognition of tuberculosis (TB) cases is critical to prevent spread. Infants are at high risk for TB acquisition after exposure. A TB case went unrecognized despite seeking medical attention in December 2016 for a cough and suspicious radiographic and laboratory testing. During a two week period in November and December 2016 the case visited an infant in a Neonatal Intensive Care Unit (NICU) almost daily for extended periods of time. The NICU was housed in a local community hospital, but staffed by personnel from a separate local children's hospital. On January 3, 2017, Summit County Public Health was notified of the case and after ascertaining the potential NICU TB exposure began a collaborative contact investigation with the community hospital and the children's hospital staff, newborns and visitors to the NICU. Methods. This observational study describes a TB contact investigation of potentially exposed persons in a NICU. The three institutions jointly developed a plan whereby the children's hospital notified families of the potentially exposed babies, provided prophylactic anti-tubercular medication and follow-up screening. The hospitals' Infection Preventionists notified and tested the potentially exposed staff. The health department screened the case's family, personal contacts, and any identified or concerned NICU visitors. At the onset of the investigation the three institutions held a joint press conference. The investigation began in early January 2017 and ended late April 2017. Results. Total Infants potentially exposed 68 Families contacted 68 Infants evaluated 62 Infants put on INH prophylaxis 31 Infants tested at 10-12 weeks 47 Infants tested positive 0 Employees tested 183 Employees tested positive 0 Conclusion. An after-action review revealed strengths, weaknesses and lessons learned. One successful decision was the planned press conference that provided media and public with transparent, consistent messages. A weakness was the inability to identify visitors since there was no NICU visitor log. Therefore visitors other than parents could not be individually contacted about exposure and screening. This investigation successfully involved three different community institutions and was conducted with minimal disruption and public concern. Disclosures. All authors: No reported disclosures.
Fertility and Sterility, Apr 1, 2000
Objective: We previously reported an antipeptide antibody to human glycodelin that recognizes gly... more Objective: We previously reported an antipeptide antibody to human glycodelin that recognizes glycodelin in amniotic fluid and epithelial glands of the endometrium. The objective of this study was to determine the presence of glycodelin in human umbilical cord. Design: Controlled clinical study.
Proceedings of the National Academy of Sciences of the United States of America, Jul 17, 2001
Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-respo... more Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (Gp) might promote angiogenic response by examining the migration and tube formation in human umbilical cord vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this increase was blocked by antibody to Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting that the angiogenic effects of glycodelin might be mediated by VEGF. The results also showed that Gp significantly increased the release of VEGF protein and mRNA expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin might play an important role in neovascularization during embryogenesis and tumor development.
Clinical Cancer Research, Jan 15, 2004
Purpose: The purpose of this study is to develop a high-throughput approach to detect protein exp... more Purpose: The purpose of this study is to develop a high-throughput approach to detect protein expression from hundreds and thousands of samples and to apply this technology to profile circulating angiogenic factor protein levels in patients with gynecological tumors. Experimental Design: Analytes containing a mixture of protein are immobilized onto antibody-coated surface of support in array format. The presence of protein in analytes is detected with biotin-labeled antibody coupled with an enhanced chemiluminescence or fluorescence detection system. The exact amount of protein can be quantitatively measured. The expression levels of five angiogenic factors (angiogenin, interleukin 8, vascular endothelial growth factor, platelet-derived growth factor, and epidermal growth factor) from 157 samples were quantitatively measured using this novel protein array technology and were statistically analyzed. The expression patterns of angiogenic factors were analyzed using two-way hierarchical cluster analysis approach. Results: A novel protein array technology, which can simultaneously and quantitatively measure few protein levels from hundreds and thousands of samples was developed. Only minute amounts of sample are required for the assay. This approach also features high sensitivity and specificity. Using this novel protein array approach, we analyzed the plasma expression levels of five angiogenic factors in 137 patients diagnosed with a tumor and 20 controls. Statistical analysis reveals different expression levels of angiogenic factors between patients and controls. Cluster analysis suggests a possible classification of normal subjects from patients. Conclusions: Enhanced protein profiling arrays provide a high-throughput and sensitive system to detect one or few protein from hundreds and thousands of samples. Such an approach should have broad application in biomedical discovery.
Morbidity and Mortality Weekly Report, Sep 30, 2022
states has been reduced from 37 to 13 (2). Increased hepatitis A vaccination coverage, particular... more states has been reduced from 37 to 13 (2). Increased hepatitis A vaccination coverage, particularly through implementation of successful, nontraditional vaccination strategies among disproportionately affected populations (5), is needed to continue progress in halting current outbreaks and preventing similar outbreaks in the future. Health departments investigated HAV infections among persons who met the Council of State and Territorial Epidemiologists' hepatitis A case definition † using statespecific case investigation forms. Deidentified demographic, risk factor, and clinical outcome data were requested from all states reporting outbreaks for all outbreak-associated cases during
Free Radical Biology and Medicine, Apr 1, 2003
Glycodelin is a glycoprotein that has immunosuppressive activity. We have shown that K562 cells, ... more Glycodelin is a glycoprotein that has immunosuppressive activity. We have shown that K562 cells, hematopoitic progenitor cells, are capable of synthesizing glycodelin peptide (Gp) and, perhaps, contribute to Gp in tissues. In addition, several reproductive and nonreproductive tissues themselves are capable of synthesis of glycodelin. In this study, we report that lipid peroxides induce the synthesis of Gp. Antioxidants vitamin E and pyrrolidine dithiocarbamate (PDTC) and antioxidizing enzymes catalase and superoxide dismutase (SOD) effectively blocked phorbol myristate acetate-(PMA-) and lyso phosphatidic acid-(LPA-) induced synthesis of Gp. Dioctanoin (a mimic of diacylglycerol) activated Gp synthesis, and an inhibitor of protein kinase C (PKC) downregulated the response. Based on these observations, we postulate that oxidants by way of PKC might potentiate the angiogenic process.
Food and Environmental Virology
MMWR. Morbidity and Mortality Weekly Report, 2019
Infection Control & Hospital Epidemiology, 2020
Background: Hepatitis C virus (HCV) transmission at outpatient hemodialysis clinics is well docum... more Background: Hepatitis C virus (HCV) transmission at outpatient hemodialysis clinics is well documented, but little is known about HCV transmission risks in long-term care facilities (LTCFs) providing hemodialysis services. LTCFs can provide onsite hemodialysis for residents by contracting with a licensed hemodialysis clinic to either provide its staff to the LTCF or to train LTCF staff as caregivers. In August 2019, the Georgia Department of Public Health (DPH) was notified about an HCV seroconversion in patient A at a LTCF providing onsite hemodialysis. Methods: Three residents (including patient A) were receiving hemodialysis at the LTCF in August 2019; patients B and C had chronic HCV infection upon admission. Records were reviewed for medical history, behavioral risk factors, and healthcare exposures. We conducted onsite infection control assessments and interviewed staff. Serum specimens were collected for all 3 patients in August 2019 and HCV tested for genetic similarity usin...
The Journal of Infectious Diseases, 2020
Background Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID... more Background Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). Methods We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. Results There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 ...
American Journal of Transplantation, 2019
Prior to the availability of current therapy, hepatitis B virus (HBV) infection was associated wi... more Prior to the availability of current therapy, hepatitis B virus (HBV) infection was associated with high rates of cirrhosis, graft failure, and death in solid organ transplant recipients. 1-3 With current antiviral agents including tenofovir and entecavir, solid organ transplant recipients with HBV infection have similar outcomes to transplant patients without HBV infection. 4 For organ recipients acquiring hepatitis C virus (HCV) infection, some authors report decreased patient and graft survival 4-6 while others describe comparable survival in HCV-infected and uninfected patients after correcting for comorbidities. 7,8 HCV infection in solid organ transplant recipients has been associated with accelerated rates of hepatic fibrosis. 9,10 Fortunately, new direct acting antiviral agents (DAA) are effective in eliminating HCV when administered before or after transplantation and regimens are available for patients with kidney failure or hepatic decompensation. 4,11 Patients with preexisting chronic HCV infection have been successfully treated posttransplant with high rates
Cellular and molecular gastroenterology and hepatology, Sep 1, 2016
Hepatitis C virus infection strongly affects mitochondrial DNA genetic diversity, which can be us... more Hepatitis C virus infection strongly affects mitochondrial DNA genetic diversity, which can be used to discriminate recent from past infections. BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing. RESULTS: Results were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days. CONCLUSIONS: HCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission.
One set of genes sufficient for transformation of primary human cells uses the combination of Ha-... more One set of genes sufficient for transformation of primary human cells uses the combination of Ha-Ras-V12, the telomerase catalytic subunit hTERT, SV40 large tumor antigen (LT), and SV40 small tumor antigen (ST). Whereas SV40 LT inactivates the retinoblastoma protein and p53, the contribution of ST is poorly understood. The essential helper function of ST requires a functional interaction with protein phosphatase 2A (PP2A). Here we have identified changes in gene expression induced by ST and show that ST mediates these changes through both PP2A-dependent and PP2A-independent mechanisms. Knockdown of PP2A B56γ subunit can substitute for ST expression to fully transform cells expressing LT, hTERT, and Ras-V12. We also identify those genes affected similarly in two cell lines that have been fully transformed from a common parental line by two alternative mechanisms, namely ST expression or PP2A B56γ subunit knockdown. ST altered expression of genes involved in proliferation, apoptosis, ...
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Papers by Sumathi Ramachandran