Biomedical subjects

V Kumar

Publications and source records attributed to V Kumar.

At least 19 recordsLinked to original sources

PubMed2026

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction ≥0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗

PubMed2025

Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial cell state.

Epithelial cancers disrupt tissue architecture and are often driven by mutations in genes that play important roles in normal epithelial morphogenesis. The intrahepatic biliary system is an epithelial tubular network that forms within the developing liver via the de novo initiation and expansion of apical lumens. Intrahepatic biliary tumors (intrahepatic cholangiocarcinoma) commonly harbor activating genomic alterations in the FGFR2 receptor tyrosine kinase, which plays important roles in epithelial morphogenesis in other developmental settings. Using a physiologic and quantitative 3D model we demonstrate that FGFR signaling is important for biliary morphogenesis and that oncogenic FGFR2 fusions and in-frame deletions disrupt biliary architecture. Importantly, we show that the trafficking of and signaling from the FGFR2 mutants, as well as their phenotypic impacts, are governed by the epithelial state of the cell. Unexpectedly, we also found that distinct tumor-driving FGFR2 mutants disrupt biliary morphogenesis in completely different and clinically relevant ways, informing our understanding of morphogenesis and tumorigenesis and highlighting the importance of convergent studies of both.

Journal Article↗

PubMed2006

Processing of rayon waste effluent for the recovery of zinc and separation of calcium using thiophosphinic extractant.

Zinc is used in various metallurgical, chemical and textile industries. In textile industries, waste effluent containing zinc is generated during the manufacture of rayon yarn. Due to the strict environmental regulations and the presence of toxic metallic and other constituents, the discharge of effluents in sewage is restricted. In view of above a process has been developed for the recovery of zinc from rayon waste effluent following solvent extraction technique using thiophosphinic extractants Cyanex 272 and 302. Before recycling of zinc sulphate solution in spinning bath, solution must be free from calcium, which is deleterious to the process as gypsum precipitates and forms scale. The extractant Cyanex 302 has been found selective for the recovery of 99.99% of zinc in the form of [R(2)Zn](org) from the effluent above equilibrium pH 3.4 maintaining the O/A ratio of 1/30 leaving all the calcium in the raffinate. The zinc from the loaded Cyanex 302 can be stripped with 10% sulphuric acid at even O/A ratio of 10. The stripped solution thus obtained could be recycled in the spinning bath of the rayon plant and raffinate could be disposed safely without affecting environment.

Calcium↗

PubMed2006

A postulated role of testosterone for prevention of cisplatin gonadal toxicity.

Testicular cancer is the most common solid tumor in young men. It has become one of the most curable solid neoplasms by applying multidisciplinary treatment approaches and new chemotherapeutic drugs. Cisplatin based chemotherapy as the most efficient chemotherapy of germ cell tumors has severe deleterious effects on all stages of spermatogenesis by various direct and indirect mechanisms. By marked improvement in oncologic control, prognosis and survival of patients with testicular cancer, their fertility, as one of the essential aspects of quality of life, is a matter of great concern. Since the probability and severity of spermatogenesis impairment is quite unpredictable during a course of cisplatin based chemotherapy, protecting the spermatogenesis during that phase by administration of exogenous testosterone in order to reduce the proliferation rate of germ cells would seem to be beneficial.

Antitoxins↗

PubMed2006

Bilobalide prevents ischemia-induced edema formation in vitro and in vivo.

EGb761, a standardized extract of Ginkgo biloba, has neuroprotective properties in animal models of ischemia, an activity that is partially attributed to its constituent, bilobalide. EGb761 has also been reported to inhibit edema formation induced by toxins such as triethyltin. The goal of this study was to test the activity of pure bilobalide to prevent edema formation in models of ischemia. Oxygen-glucose deprivation (OGD) in rat hippocampal slices served as a model of in vitro-ischemia. OGD caused cellular edema formation as indicated by an increase of slice water contents in 30 min. Bilobalide (1-10 microM) reduced slice water contents in ischemic slices in a concentration-dependent manner. As a model of in vivo-ischemia, we performed middle cerebral artery occlusion (MCAO) in mice. Permanent MCAO caused cell death and swelling of the ischemic hemisphere within 24 h. Pretreatment of the mice with bilobalide (10 mg/kg i.p.) reduced infarct area by 43% (as judged by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining) and edema formation by 70% (as judged by hemispheric enlargement). In parallel experiments, pretreatment with bilobalide also reduced forebrain water contents in the ischemic hemisphere by 57%. As an alternative model of brain edema formation, we used water intoxication to increase brain water content; bilobalide, was, however, inactive in this model. We conclude that bilobalide strongly and specifically attenuates edema formation in models of brain ischemia in vitro and in vivo. Bilobalide may be therapeutically effective in brain edema which occurs secondarily to large hemispheric stroke and traumatic brain injury in humans.

Animals↗

PubMed2006

Introduction of community-based skin-to-skin care in rural Uttar Pradesh, India.

OBJECTIVE: Two-thirds of women globally give birth at home, yet little data are available on use of skin-to-skin care (STSC) in the community. We describe the acceptability of STSC in rural Uttar Pradesh, India, and measured maternal, newborn, and ambient temperature in the home in order to inform strategies for introduction of STSC in the community. STUDY DESIGN: Community-based workers in intervention clusters implemented a community mobilization and behavior change communication program that promoted birth preparedness and essential newborn care, including adoption of STSC, with pregnant mothers, their families, and key influential community members. Acceptance of STSC was assessed through in-depth interviews and focus groups, and temperature was measured during home visits on day of life 0 or 1. RESULTS: Incidence of hypothermia (<36.5 degrees C) was high in both low birth weight (LBW) and normal birth weight (NBW) infants (49.2%, (361/733) and 43% (418/971), respectively). Mean body temperature of newborns was lower (P<0.01) in ambient temperatures <20 degrees C (35.9+/-1.4 degrees C, n=225) compared to > or =20 degrees C (36.5+/-0.9 degrees C, n=1450). Among hypothermic newborns, 42% (331/787) of their mothers had a lower temperature (range -6.7 to 0.1 degrees C, mean difference 0.4+/-1.2 degrees C). Acceptance of STSC was nearly universal. No adverse events from STSC were reported. STSC was perceived to prevent newborn hypothermia, enhance mother's capability to protect her baby from evil spirits, and make the baby more content. CONCLUSION: STSC was highly acceptable in rural India when introduced through appropriate cultural paradigms. STSC may be of benefit for all newborns and for many mothers as well. New approaches are needed for introduction of STSC in the community compared to the hospital.

Body Temperature Regulation↗

PubMed2006

Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats.

The study was aimed to investigate the antioxidant activity of Cytisus scoparius L. (Family: Leguminosae) on CCl(4) (carbon tetrachloride) treated oxidative stress in Wistar albino rats. CCl(4) injection induced oxidative stress by a significant rise in serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transaminases (SGPT), lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) along with reduction of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and glutathione reductase (GRD). Pretreatment of rats with different doses of plant extract (250 and 500mg/kg) significantly lowered SGOT, SGPT, LDH and TBARS levels against CCl(4) treated rats. GSH and hepatic enzymes like SOD, CAT, GPx, GRD, and GST were significantly increased by treatment with the plant extract, against CCl(4) treated rats. The activity of extract at the dose of 500mg/kg was comparable to the standard drug, silymarin (25mg/kg). Based on these results, it was observed that Cytisus scoparius extract protects liver from oxidative stress induced by CCl(4) in rats and thus helps in evaluation of the traditional claim on this plant.

Alanine Transaminase↗

PubMed2006

The knee skyline radiograph: its usefulness in the diagnosis of patello-femoral osteoarthritis.

The aim of this study was to determine the usefulness of the skyline radiograph in the diagnosis of patellofemoral osteoarthritis. Additionally, we wanted to assess the usefulness of patello-femoral crepitus as a clinical sign of this condition. Seventy-seven patients scheduled to undergo knee surgery had standard antero-posterior, lateral and skyline X-rays of their affected knee. The presence of clinical patello-femoral crepitus was also documented preoperatively. At the operation, their patellofemoral joints were graded into two groups according to the presence or absence of osteoarthritis. The lateral and skyline view X-rays as well as patello-femoral crepitus were compared individually against the operative findings. The skyline view had a sensitivity of 79% and a specificity of 80%. The lateral view had a sensitivity of 82% and specificity of 65%. Patello-femoral crepitus as a sign had a sensitivity of 89% and a specificity of 82%. There was no statistically significant difference between the two radiological views in terms of sensitivity and specificity in the diagnosis of patellofemoral osteoarthritis. Hence, we cannot recommend the skyline view as a routine radiological investigation in all cases of suspected patellofemoral osteoarthritis.

Humans↗

PubMed2006

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

BACKGROUND: Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). METHODS: We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. RESULTS: Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. CONCLUSIONS: Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

Arylamine N-Acetyltransferase↗

PubMed2006

Tectal plate cyst in adults.

Tectal plate cysts are very rare. We report two adult patients with benign tectal plate cyst and secondary hydrocephalus. The first patient had an unusual eye movement disorder with bilateral upper eyelid retraction (Collier's sign), limited upgaze, severe upgaze evoked nystagmus and retraction nystagmus. The second patient presented with ataxia and failure of upward gaze. Endoscopic fenestration of the tectal plate cyst and endoscopic third ventriculostomy in both cases result in neurological improvement. To the best of our knowledge, similar lesions at this site have not been reported in adults. The differential diagnosis with arachnoid cysts of the quadrigeminal CSF cistern is discussed.

Adult↗

PubMed2006

Role of computerised tomography in management of intra-articular fractures of the os calcis.

This study aimed to look at the role played by the CT scan in decision making in the management of intra-articular fractures of the calcaneum. Twenty-four patients with intra-articular fractures of the calcaneum were included. Their initial radiographs and CT films were blinded and assessed by three independent observers. Based on this they were selected for operative or non-operative management. The actual management was also recorded. The data were then subjected to statistical analysis to look at the association between the decision from radiograph, that from the CT scan and the actual management undertaken. Non-parametric tests for related samples were performed to look at the association between the actual management and the decisions made by assessing the radiographs and the CT scans. For all three observers, there was no significant difference between the actual management and decisions made by assessing the plain radiographs or the CT scan. There was also no significant difference between the radiograph-based and the CT-based decisions. However, the Cochran Q test showed that there was significant variation among the three observers for the CT-based assessment. Our results, show that the CT scan should only be done when a definite decision is made to operate on a patient, based on plain radiographs. Calcaneal fractures which are selected for non-operative management, based on X rays, should not have a CT scan as a routine as it provides no valuable additional information affecting the management decision.

Calcaneus↗

PubMed2006

Fabrication and evaluation of porous 2,3-dialdehydecellulose membrane as a potential biodegradable tissue-engineering scaffold.

A simple, novel method to produce porous 2,3-dialdehydecellulose (DAC) membranes as a potential tissue-engineering scaffold has been developed from methylolcellulose by the simultaneous water-induced phase separation and sodium chloride salt leaching techniques, followed by oxidation with sodium periodate in water. Membrane pores increased in size with increasing weight or particle size of the sodium chloride salt. The porosity of the membrane was not affected by the salt particle size, but it increased with an increase in the salt weight to 60%. At higher salt weight percentages, no significant change in the membrane porosity was observed. The oxidation step had no effect on the membrane porosity or pore size. All membranes with a porosity value ranging between 87 and 93% showed interconnected porous structures. The use of these membranes as a potential tissue-engineering scaffold was evaluated with the use of human neonatal skin fibroblast cells. Confocal microscopy showed cell attachment and spreading on these membranes. Immunohistochemical tests revealed the presence of collagen type III and fibronectin, indicating that the cells were viable and formed the extracellular matrix. In conclusion, the DAC membrane supports cell adhesion and proliferation and hence shows potential to be used as a tissue-engineering scaffold.

Absorbable Implants↗

PubMed2006

The CD2 family of natural killer cell receptors.

The CD2 family of receptors is evolutionarily conserved and widely expressed on cells within the hematopoietic compartment. In recent years several new members have been identified with important roles in the immune system. CD2 family members regulate natural killer (NK) cell lytic activity and inflammatory cytokine production when engaged by ligands on tumor cells. Furthermore, a subfamily of CD2 receptors, the CD 150-like molecules, has been implicated in the pathogenesis of X-linked lymphoproliferative disease (XLP). Many of these receptors have now been shown to bind homophilically or heterophilically to other molecules within the family. With these discoveries a novel mechanism for lymphocyte regulation has emerged: CD2 family members on NK cells engage ligands on neighboring NK cells, leading to NK cell stimulation. Moreover, heterotypic stimulatory interactions between NK cells and other leukocytes also occur. In this manner, CD2 family members may provide interlymphocyte communication that maintains organization within the hematopoietic compartment and amplifies immune responses. This review discusses these multiple roles for CD2 family members, focusing specifically on the regulation of NK cells.

Animals↗

PubMed2006

An unusual progression of benign thoracic spinal cord teratoma in pregnancy: a hormonally-mediated pathway?

Intradural spinal cord teratoma is a very rare tumour that can be associated with dysraphism. The relationship of this lesion to pregnancy is unknown and its occurrence during pregnancy in the thoracic spine has not been previously reported. We report a 19-year-old pregnant woman with spinal dysraphism, who presented with a new onset thoracic myelopathy. The MRI scan showed an intradural, extramedullary lesion with solid and cystic component in the thoracic spine at the level of T5-T6. A thoracic laminectomy and excision of this lesion was followed by significant improvement of her lower limb function. Histopathology confirmed a benign mature teratoma. The rapid progression of this lesion during pregnancy suggests a hormonal mediated pathway for the tumour growth. Further analysis from the resected specimen confirmed that the tumour was oestrogen and progesterone receptors positive.

Adult↗

PubMed2006

Role of natural killer cell subsets in cardiac allograft rejection.

To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.

Animals↗

PubMed2006

A new locus for autosomal dominant posterior polar cataract in Moroccan Jews maps to chromosome 14q22-23.

BACKGROUND: Posterior polar cataract is a clinically distinctive opacity located at the back of the lens. It is commonly acquired in age related cataract, and may infrequently occur in pedigrees with congenital cataract. To date, five loci for autosomal dominant congenital posterior polar cataract have been identified. These include two genes, CRYAB and PITX3, on chromosomes 11q and 10q respectively, and three loci with as yet unknown genes on chromosomes 1p, 16q and 20p. PURPOSE: To find the chromosomal location of a gene causing autosomal dominant congenital posterior polar cataract in three Moroccan Jewish families. METHODS: A whole genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. For fine mapping, five additional microsatellite markers were genotyped. Two-point lod scores were calculated using MLINK software, from the LINKAGE program package. After linkage was established, several positional candidate genes were assessed by PCR based DNA sequencing. RESULTS: The new cataract locus was mapped to an 11.3 cM interval between D14S980 and D14S1069 on chromosome 14q22-23. A maximum two point lod score of 5.19 at theta = 0 was obtained with the markersD14S274. The positional and functional candidate genes SIX1, SIX4, SIX6, OTX2, and ARHJ were excluded as the cause of cataract in these families. CONCLUSION: An as yet unidentified gene associated with posterior polar cataract maps to the long arm of chromosome 14q22-23.

Adult↗

PubMed2006

Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programmes.

OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1-6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7-13 and 14-27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period.

Adolescent↗

PubMed2006

Knowing what to sell, when, and to whom.

Despite an abundance of data, most companies do a poor job of predicting the behavior of their customers. In fact, the authors' research suggests that even companies that take the greatest trouble over their predictions about whether a particular customer will buy a particular product are correct only around 55% of the time--a result that hardly justifies the costs of having a CRM system in the first place. Businesses usually conclude from studies like this that it's impossible to use the past to predict the future, so they revert to the timeworn marketing practice of inundating their customers with offers. But as the authors explain, the reason for the poor predictions is not any basic limitation of CRM systems or the predictive power of past behavior, but rather of the mathematical methods that companies use to interpret the data. The authors have developed a new way of predicting customer behavior, based on the work of the Nobel Prize-winning economist Daniel McFadden, that delivers vastly improved results. Indeed, the methodology increases the odds of successfully predicting a specific purchase by a specific customer at a specific time to about 85%, a number that will have a major impact on any company's marketing ROI. What's more, using this methodology, companies can increase revenues while reducing their frequency of customer contact-evidence that overcommunication with customers may actually damage a company's sales.

Commerce↗