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Biomedical subjects

V Kapur

Publications and source records attributed to V Kapur.

At least 19 recordsLinked to original sources

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems.

Phosphodiesterase-5 (PDE-5) inhibitors selectively inhibit PDE-5 enzymes that are present in various tissues like penile tissue, platelets, vascular, and smooth muscle tissue. The drug's actions on these tissues have lead to the successful therapeutic use in patients suffering from conditions such as erectile dysfunction (ED) and pulmonary hypertension. PDE-5 inhibitors (PDE-5i) act on the erectile tissue causing penile smooth muscle relaxation and vasodilatation leading to penile erection. In addition, in particular when used in conjunction with prostaglandin inhibitors, PDE-5i cause vasodilatation in pulmonary vasculature hence decreasing both the pulmonary arterial pressure and resistance. PDE-5i have also shown to mildly decrease blood pressure, increase cardiac index, and increase coronary blood flow in experimental animals as well as in human studies. The Food and Drug Administration (FDA) has approved three PDE-5i for the treatment of ED: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) and one for pulmonary hypertension: sildenafil (Revatio). These agents are highly selective for PDE-5 enzymes as compared to other subclasses of PDE enzymes and have the almost identical pharmacological action but slightly different pharmacokinetics. Only little data exist about long-term use of PDE-5i and their effects on different organ system. This paper reviews the current information available on chronic PDE-5 inhibitor use.

3',5'-Cyclic-GMP Phosphodiesterases↗

A triplicate obturator foramen.

The obturator foramen is a large opening in the hip bone situated below and anterior to the acetabulum. The obturator foramen is enclosed by the obturator membrane, apart from the part above near the obturator groove, where the obturator vessels and nerve pass through. The present study reports multiple openings in the obturator foramen detected incidentally in a left hip bone specimen and discusses its clinical implications. To the best of our knowledge, the occurrence of multiple openings associated with the obturator foramen is rare and has not been reported in any standard textbook of anatomy or in any research study. Anatomical knowledge of the presence of such anomalies may be clinically important for radiologists interpreting skiagrams and surgeons performing operative procedures in the hip region.

Humans↗

An asymmetrical inferior articular process of a lumbar vertebra.

The present case report describes the topographical anatomy and radiological study of an asymmetrical inferior articular process of a lumbar vertebra, which was detected during routine osteology teaching of undergraduate medical students. The inferior articular process of the lumbar vertebra on the left side was rudimentary, while that on the right was normal in size. On the left side an additional bony projection was noted anterior to the rudimentary inferior articular process. The difference in height between the inferior articular processes of the two sides may play an important role in the kinematics of the particular joint. The orientation of the facets of the articular processes of the vertebrae are important for axial weight transmission and anomalies involving these can possibly alter the orientation of movements in that particular segment. An asymmetrical inferior articular process may be related to disc prolapse and may be a cause of back pain. In view of the paucity of research reports of anatomicoradiological study of the inferior articular process of a lumbar vertebra in relation to other parts of the vertebra, we, as anatomists, believe that knowledge of anomalies of the inferior articular process may be relevant for academic, anthropological and clinical purposes.

Cadaver↗

Transcriptional response of human microglial cells to interferon-gamma.

Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-gamma, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-gamma signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-gamma induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-gamma-a key to understanding cell-mediated immunity of the CNS.

Cells, Cultured↗

Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem.

Chronic heart failure (HF) is an increasingly common cardiovascular disorder. The goal of health-care providers is to optimize quality of life in this population, including sexual health. Up to 75% of patients with HF report erectile dysfunction (ED). As HF is a condition with distinct physiologic sequelae, some unique organic and psychological factors contributing to ED in this patient population have been identified, along with risk factors common to the development of coronary artery disease, HF and ED. This review describes contributing factors to ED in the setting of HF and highlights treatment considerations for this distinct patient population.

Adrenergic beta-Antagonists↗

A multidisciplinary approach to assess erectile dysfunction in high-risk cardiovascular patients.

Erectile dysfunction (ED) is increasingly considered as one manifestation of systemic vascular disease. Accordingly, ED and coronary artery disease share mutual risk factors and frequently coexist. Sexual health is an important aspect of our patients' lives, and ED is a common concern of the cardiovascular patient. Despite this, sexual function is under-addressed in the cardiac patient. Even when this topic is broached by the primary care physician or urologist, ED frequently remains untreated due to safety concerns involving cardiac disease and other comorbidities. This article describes our experience with this unique patient population, as well as our approach to building a multidisciplinary clinic designed to specifically address the important issue of ED in the cardiac patient.

Administration, Oral↗

Abnormal musculoaponeurotic tunnel in the arm: possible entrapment of the median nerve and brachial artery with high origin of nerve to pronator teres within the tunnel.

Median nerve and brachial artery in the arm are not usually overlapped by any structure. Connective tissue bands and muscular slips draping or enclosing this neurovascular bundle have been reported, however, which may produce clinical symptoms of nerve compression and vascular changes. We report an unusual musculoaponeurotic band that originates as the ligament of Struthers but terminates as the brachiofascialis muscle of Wood and in the process may have entrapped both the median nerve and brachial artery. The nerve to pronator teres originates from the median nerve within this tunnel. On histological examination the nerve was flattened and showed some perineurial thickening. In view of the flexor function of brachialis muscle, this anomalous musculoaponeurotic band may be considered a clinically important entity in the causation of idiopathic neurovasculopathy in the hand.

Brachial Artery↗

Management of community-acquired pneumonia in persons with spinal cord injury.

STUDY DESIGN: Retrospective case series. OBJECTIVES: Respiratory disorders are the leading cause of death in persons with spinal cord injury (SCI), but the epidemiology and medical management of pneumonia in persons with chronic SCI is not well characterized. We describe the clinical presentation of persons with SCI with community-acquired pneumonia (CAP), characterize its management and compare practice to recommendations for CAP in the general population. SETTING: Three United States Veterans Affairs Medical Centers with specialized SCI services. METHODS: Chart abstraction was performed for all persons with chronic SCI seen at participating centers for treatment of CAP during a 2-year period. Collected data included presenting signs and symptoms, laboratory and imaging results, initial antibiotic therapy, secretion mobilization techniques, in-patient vs outpatient management, length of stay, and mortality. RESULTS: In all, 41 persons with SCI received treatment for CAP during the study period. A total of 32 (78.0%) patients were admitted for treatment; two (4.8%) required intubation and mechanical ventilation. Initial antibiotic coverage met guideline recommendations for only half of inpatients and infrequently provided adequate antipseudomonal coverage. Microbiologic testing was performed on 26 cases (63.4%) and demonstrated a specific pathogen in only five cases (12.2% of total). Three cases (7.3%) died during treatment for CAP, and 16 (42.1%) of 38 CAP survivors died within a median follow-up of 3 years. CONCLUSION: The majority of chronic SCI patients who present to specialized SCI centers with CAP are admitted for treatment. Short-term mortality is comparable to CAP in the general population.

Adult↗

Partial genome sequencing of Rhodococcus equi ATCC 33701.

Preliminary analysis of a partial (30% coverage) genome sequence of Rhodococcus equi has revealed a number of important features. The most notable was the extent of the homology of genes identified with those of Mycobacterium tuberculosis. The similarities in the proportion of genes devoted to fatty acid degradation and to lipid biosynthesis was a striking but not surprising finding given the relatedness of these organisms and their success as intracellular pathogens. The rapid recent improvement in understanding of virulence in M. tuberculosis and other pathogenic mycobacteria has identified a large number of genes of putative or proven importance in virulence, homologs of many of which were also identified in R. equi. Although R. equi appears to have currently unique genes, and has important differences, its similarity to M. tuberculosis supports the need to understand the basis of virulence in this organism. The partial genome sequence will be a resource for workers interested in R. equi until such time as a full genome sequence has been characterized.

Aerobiosis↗

Development of a DNA marker by minisatellite associated sequence amplification (MASA) from the endangered Indian rhino (Rhinoceros unicornis).

Rhinoceroses are highly endangered species and their protection warrants immediate remedial measures. Development of DNA markers is envisaged to complement global efforts of the conservation of these extant animals. Minisatellite associated sequence amplification (MASA) of DNA from Indian rhinoceros (Rhinoceros unicornis) and three sub-species of South African black rhinoceros (Diceros bicornis) was carried out using a primer based on consensus sequence of the minisatellite repeat locus 33.15. Several bands in the range of 3.0 kilobases (kb) to 650 base pairs (bp) were identified that were useful for successful differentiation of R. unicornis from D. bicornis. Of these fragments, a 688 bp one, unique to R. unicornis was cloned and sequenced (Accession No. AF-296689). The band patterns uncovered by MASA and the species-specific hybridisation of pSG5 may be utilised as a tool for differentiating the R. unicornis genome from that of D. bicornis. This approach may also be adopted for the development of DNA-based genetic marker(s) useful for identification of other endangered species.

Animals↗

Transcriptional analysis of the response of poultry species to respiratory pathogens.

Respiratory tract diseases are the single most important cause of economic loss due to infections among poultry populations worldwide. However, the molecular mechanisms of the host response to infections remain unknown. Here, we review the literature and describe the adoption of a conceptually simple approach to understand the genetic and biochemical responses of host cells during infection with respiratory pathogens, such as avian pneumovirus (APV). The strategy that we have adopted integrates the powerful techniques of cDNA subtraction hybridization and microarray analysis for global transcriptional profiling. The results of our investigations identify the specific transcriptional alterations in host-cell gene expression that result from an attempt by the host to combat and limit the spread of the pathogen or by the pathogen to enhance its own survival and ability to reproduce. Our studies suggest that a molecular description of host-pathogen interactions in terms of differential gene expression will provide key insights on the molecular basis of disease pathogenesis, pathogen virulence, and host immunity. In addition, the results suggest that the identification of genes and pathways with a role in host response to infection has considerable practical implications for the future design and development of effective immunomodulators and vaccines.

Animals↗

Sequence analysis of the nucleocapsid and phosphoprotein genes of avian pneumoviruses circulating in the US.

Avian pneumovirus (APV) has recently been described as the cause of a new respiratory syndrome in turkey flocks in the United States. We here describe the complete sequence of the nucleocapsid (N) and phosphoprotein (P) genes of this emerging APV (APV/US). Our results show 59 and 61% nucleotide sequence identity of the APV/US N gene with N genes of previously described European APV subgroups A and B, respectively. The P gene of APV/US showed only 53% nucleotide sequence identity with the ortholog from APV subgroup A. Phylogenetic analyses of both N and P genes clearly demonstrate that the APV/US lineage is evolutionarily related but distinct from European APVs. Moreover, sequence analysis of the N and P genes from two laboratory adapted isolates of APV/US (APV/MN-1a and APV/MN-1b) and from ten clinical samples from APV-infected turkeys suggests only modest level of amino acid divergence in the N (0-0.3%) and P (0-1.4%) proteins. Taken together, the results of this study indicate support that APV/US represents a new subgroup (subgroup C) of APV and show that there is limited heterogeneity in the N and P genes of APV/US isolates.

Amino Acid Sequence↗

Complete genomic sequence of Pasteurella multocida, Pm70.

We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged approximately 270 million years ago and the gamma subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for approximately 1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and whole-genome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen.

Base Sequence↗

Factors associated with sleep apnea in men with spinal cord injury: a population-based case-control study.

OBJECTIVE: To characterize a population of spinal cord injury (SCI) patients with sleep apnea, and to determine associated factors and comorbidities. STUDY DESIGN: Population-based retrospective case-control study. SUBJECTS: 584 male patients served by a Veterans Affairs SCI service. MEASURES: Medical records were reviewed for sleep apnea diagnosis, demographic information, neurologic characteristics, and treatments received. Sleep study reports were not available to determine the nature of abnormal respiratory events (ie central, obstructive, hypoventilation). For each case with tetraplegia, a control tetraplegic subject without sleep apnea diagnosis was selected. RESULTS: We identified 53 subjects with diagnosed sleep apnea: 42 tetraplegic, 11 paraplegic. This represented 14.9% of all tetraplegic and 3.7% of all paraplegic patients in the population (P<0.0001 for comparison of tetraplegic and paraplegic proportions). In tetraplegic subjects, sleep apnea was associated with obesity and more rostral motor level, but not with ASIA Impairment Scale. Medical comorbidities associated with sleep apnea in non-SCI patients, such as hypertension, were more common in case subjects. Less than half of case subjects were receiving some form of treatment. For motor-complete tetraplegics, long-term positive airway pressure treatment was less common with motor level C5 and above compared to C6 and below. CONCLUSION: In this population, sleep apnea has been frequently diagnosed, particularly in tetraplegic subjects. The true prevalence is likely to be considerably higher, since this study considered only previously diagnosed cases. Sleep apnea was associated with obesity and higher neurologic level, but not ASIA Impairment Scale. Medical comorbidities were more frequent in this group, and treatment acceptance was poor with higher level motor-complete injuries. Since the type of sleep apnea (central or obstructive) was not distinguished, we cannot comment on the prevalence and associations based on specific types of sleep apnea.

Adult↗

Satellite-tagged transcribing sequences in Bubalus bubalis genome undergo programmed modulation in meiocytes: possible implications for transcriptional inactivation.

We cloned and sequenced a 1378 bp BamHI satellite DNA fraction from the water buffalo Bubalus bubalis and have studied its expression in different tissues. The GC-rich sequences of the resultant contig pDS5 crosshybridize only with bovid DNA and are not conserved evolutionarily. Typing of buffalo genomic DNA using pDS5 with several restriction enzymes revealed multilocus monomorphic bands. Similar typing of cattle, buffalo, goat, sheep, and gaur genomic DNA revealed variations in copy number and allele length giving rise to species-specific band patterns. Expression study of pDS5 in bubaline samples by RNA slot-blot, Northern blot, and RT-PCR showed various levels of signal in all the somatic tissues and germline cells except heart. A GenBank database search revealed homology of pDS5 sequences in the 5' region from nt 1-1261 with collagen gene. An AluI typing analysis of DNA from bubaline semen samples showed consistent loss of two bands. The presence of corresponding bands in somatic tissues suggests a sequence modulation within the pDS5 array in meiocytes during spermatogenesis, which is restored in the somatic cells after fertilization. Modulation of the satellite-tagged transcribing sequence in the meiocytes may be a mechanism of its inactivation.

Animals↗

Pasteurella multocida gene expression in response to iron limitation.

Pasteurella multocida is the causative agent of a wide range of diseases in avian and mammalian hosts. Gene expression in response to low iron conditions was analyzed in P. multocida using whole-genome microarrays. The analysis shows that the expression of genes involved in energy metabolism and electron transport generally decreased 2.1- to 6-fold while that of genes used for iron binding and transport increased 2.1- to 7.7-fold in P. multocida during the first 2 h of growth under iron-limiting conditions compared with controls. Notably, 27% of the genes with significantly altered expression had no known function, illustrating the limitations of using publicly available databases to identify genes involved in microbial metabolism and pathogenesis. Taken together, the results of our investigations demonstrate the utility of whole-genome microarray analyses for the identification of genes with altered expression profiles during varying growth conditions and provide a framework for the detailed analysis of the molecular mechanisms of iron acquisition and metabolism in P. multocida and other gram-negative bacteria.

Animals↗

Detection of antibodies to U.S. isolates of avian pneumovirus by a recombinant nucleocapsid protein-based sandwich enzyme-linked immunosorbent assay.

The nucleocapsid (N) protein of subgroup C (United States-specific) avian pneumovirus (APV/US) was expressed in Escherichia coli, and antibodies to the recombinant N protein were shown to specifically recognize the approximately 47-kDa N protein of APV/US by Western immunoblot analysis. The recombinant APV/US N protein was used in a sandwich-capture enzyme-linked immunosorbent assay (ELISA), and the resulting assay was found to be more sensitive and specific than the routine indirect ELISA for the detection of APV/US antibodies in turkey sera.

Animals↗

PCR-based detection of an emerging avian pneumovirus in US turkey flocks.

Avian pneumovirus (APV) or turkey rhinotracheitis virus (TRTV) is an important respiratory pathogen of domesticated poultry in many countries in Europe, Africa, and Asia. Until recently, the United States was considered free of APV. In late 1996, an atypical upper respiratory tract infection appeared in turkey flocks in Colorado and shortly thereafter in turkey flocks in Minnesota. An avian pneumovirus (APV-US) that was serologically distinct from the previously described TRTV was isolated as the primary cause of the new syndrome. The nucleotide sequence of a fragment of the APV-US fusion gene was determined and used to develop a polymerase chain reaction-based assay that specifically detects APV-US viral nucleic acid sequences in RNA extracts of tracheal swabs and turbinate homogenates. The assay is highly sensitive in that it can detect <0.01 TCID50 of APV. The availability of this assay enables the rapid and accurate determination of APV-US in infected poultry flocks.

Animals↗