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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,027 records · Page 57Linked to original sources
PubMed1997

Up-regulation of the Nedd2 gene encoding an ICE/Ced-3-like cysteine protease in the gerbil brain after transient global ischemia.

We assessed the expression of several genes encoding pro-apoptotic cysteine proteases similar to interleukin-1 beta converting enzyme (ICE) and nematode Ced-3 in association with delayed neuronal death (DND) after transient forebrain ischemia in Mongolian gerbil. The levels of the two species of Nedd2 mRNA concomitantly increased about two-fold in the whole forebrain at 3-6 h after 10-min ischemia and declined to the basal level by 24 h. In situ hybridization revealed that the Nedd2 gene was up-regulated in some neuronal populations in CA1 and CA3 regions of the hippocampus. In contrast, expression of ICE, CPP32/Yama/Apopain, and TX/ICErelll did not change within 48 h. These observations raise the possibility that up-regulation of Nedd2 in the vulnerable neurons may contribute to the proteolytic processes preceding the manifestation of apoptosis and/or necrosis after ischemic insult.

Animals↗
PubMed1997

Conscious sedation with high-dose midazolam for pediatric gastrointestinal endoscopy.

BACKGROUND: Midazolam is used frequently to sedate children for gastrointestinal endoscopy. The sedative dosage of intravenous midazolam commonly reported in children is up to 0.3 mg/kg. We hypothesized that larger doses of midazolam could be used for pediatric endoscopy. METHODS: We retrospectively reviewed the medical records of 116 pediatric patients (aged 1 year to 18 years) who had endoscopy. The efficacy and side effects of sedation in 45 patients who received midazolam doses of > or = 0.3 mg/kg were compared with the same effects in 71 children who received < 0.3 mg/kg. RESULTS: All patients received approximately 1 mg/kg meperidine (up to 50 mg) intravenously. The blood pressure, pulse rate, respiratory rate, oxygen saturation, degree and duration of sedation, and incidence of side effects such as hypotension, hypoxia, or vomiting were similar in both groups. CONCLUSIONS: Intravenous doses of midazolam > 0.3 mg/kg can be used for conscious sedation in children.

Adolescent↗
PubMed1997

Mapping epitopes to distinct regions of the extracellular domain of endoglin using bacterially expressed recombinant fragments.

Endoglin (CD105) is a homodimeric cell surface component of the TGF-beta 1 receptor complex, which is expressed at high levels on vascular endothelium and at lower levels on activated monocytes. It is also the target gene for the dominantly inherited vascular disorder hereditary hemorrhagic telangiectasia type 1. To date, each family has a distinct endoglin mutation, most of which generate premature stop codons. The purpose of the current study was to identify monoclonal antibodies capable of binding to normal and mutated forms of the protein. We generated stable transfectants of full-length human endoglin in murine fibroblasts and engineered and expressed in bacteria several fragments of the extracellular domain. Relatively pure polypeptides were recovered with good yield from inclusion bodies and were tested by ELISA and Western blot; 11 monoclonal antibodies were shown to react specifically with the endoglin transfectants. Ten of these monoclonal antibodies reacted with the bacterial fragments, and their epitopes were assigned to 3 distinct regions of endoglin. Monoclonal antibodies P3D1, TEC4 and GRE reacted with the N-terminal region of 204 amino acids encoded by exons 1 to 5. Monoclonal antibodies P4A4, 44G4, E-9, MAEND3 and PN-E2 all bound to a region of 54 amino acids encoded mostly by exon 7. Monoclonal antibodies CLE4 and RMAC8 reacted with the C-terminal region of the extracellular domain, coded for by exons 8 to 12. Knowing the localization of these epitopes will facilitate the structural and functional analysis of normal and mutated forms of endoglin.

3T3 Cells↗
PubMed1997

Partial purification and characterization of a murine malaria parasite, Plasmodium berghei specific aldolase.

Cell-free P. berghei contains 26.1 times more aldolase activity as compared to normal mouse erythrocytes. Subcellular fractionation of cell-free parasite showed maximum enzyme activity in the soluble fraction. The parasite enzyme was active in a narrow pH range of 7.8-8.0. Of the enzyme activity 90% was lost within 2 weeks at 4 degrees C. Slight inhibition was observed with specific inhibitors ATP, pyrophosphate (PPi) and PEP. The F1, 6DP Km was 0.025 mM.

Animals↗
PubMed1997

Comparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoelii.

Vaccination with native full-length merozoite surface protein 1 (MSP1) or with recombinant C-terminal peptides protects mice against lethal challenge with virulent malaria parasites. To determine whether other regions of MSP1 can also induce protection, Plasmodium yoelii MSP1 was divided into four separate regions. Each was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The N-terminal fragment began after the cleavage site for the signal sequence and ended in the region comparable to the cleavage site for the C terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein was 30 kDa smaller than the predicted peptide. One peptide from the middle region was produced, and the C terminus consisted of a 42-kDa fragment corresponding to the analogous peptide of P. falciparum and a 19-kDa fragment that extended 37 amino acids in the amino-terminal direction beyond the probable cleavage site. To test protection of mice against lethal P. yoelii challenge, three mouse strains (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant proteins of MSP1. Mice vaccinated with the C-terminal 19-kDa protein were highly protected (described previously), as were those vaccinated with the 42-kDa protein that contained the 19-kDa fragment. The N-terminally expressed fragment of P. yoelii was not full length because of proteolytic cleavage in E. coli. The GST-82-kDa partial fragments induced some immunity, but the surviving mice still had high parasitemias. Vaccination with the peptide from the middle region of MSP1 gave minimal to no protection. Therefore, in addition to the C-terminal 19- and 42-kDa proteins, the only other fragment to give protection was the 82-kDa protein. The protection induced by the truncated 82-kDa protein was minimal compared with that of the C-terminal fragments.

Animals↗
PubMed1997

Tempo and mode of nucleotide substitutions in gag and env gene fragments in human immunodeficiency virus type 1 populations with a known transmission history.

The complex evolutionary process of human immunodeficiency virus type 1 (HIV-1) is marked by a high level of genetic variation. It has been shown that the HIV-1 genome is characterized by variable and more constant regions, unequal nucleotide frequencies, and preference for G-to-A substitutions. However, this knowledge has largely been neglected in phylogenetic analyses of HIV-1 nucleotide sequences, even though these analyses are applied to a number of important biological questions. The purpose of this study was to identify a realistic model of HIV-1 evolution and to statistically test if the application of such a model significantly improves the accuracy of phylogenetic analyses. A unique and recently reported HIV-1 transmission cluster consisting of nine infected individuals, for whom the direction and time for each transmission were exactly known, formed the basis for the analyses which were performed under a general model of nucleotide substitution using population sequences from the env V3 and p17gag regions of the HIV-1 genome. Examination of seven different substitution models by maximum-likelihood methods revealed that the fit of the general reversible (REV) model was significantly better than that of simpler models, indicating that it is important to account for the asymmetric substitution pattern of HIV-1 and that the nucleotide substitution rate varied significantly across sites. The shape parameter alpha, which describes the variation across sites by a gamma distribution, was estimated to be 0.38 and 0.25 for env V3 and p17gag, respectively. In env V3, the estimated average transition/transversion rate ratio was 1.42. Thus, the REV model with variable rates across sites (described by a gamma distribution) provides the best description of HIV-1 evolution, whereas simple models are unrealistic and inaccurate. It is likely that the accuracy of phylogenetic studies of HIV-1 and many other viruses would improve substantially by the use of more realistic nucleotide substitution models. This is especially true when attempts are made to estimate the age of distant viral ancestors from contemporary viral sequences.

Base Sequence↗
PubMed1997

Management of varicella zoster virus retinitis in AIDS.

AIMS/BACKGROUND: Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS. METHODS: A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out. RESULTS: Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051). CONCLUSIONS: This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Seasonal cyclothymia to seasonal bipolar affective disorder: a double switch after stroke.

The appearance of bipolar affective disorder after stroke depends on the presence of two factors: a predisposing factor of either genetic loading or subcortical atrophy, and a lesion of specific corticolimbic pathways involving the right hemisphere. Whether cyclothymia and seasonal affective disorder further predispose to poststroke affective disorder is not clear. A case is described which highlights these issues. The aetiological factors, pathophysiology, and diagnosis are discussed.

Aged↗
PubMed1997

Sensitization to the locomotor stimulant activity of cocaine is associated with increases in nitric oxide synthase activity in brain regions and spinal cord of mice.

Effects of multiple administrations of cocaine and subsequent cocaine withdrawal on the activity of nitric oxide synthase (NOS) in brain regions and spinal cord of male Swiss-Webster mice were determined. Chronic administration of cocaine resulted in the development of sensitization to its locomotor activity in the mouse. Chronic administration of cocaine was associated with increases in NOS activity in cerebral cortex, cerebellum, midbrain, hypothalamus, hippocampus, amygdala and spinal cord, but NOS activity was unaffected in pons/medulla and corpus striatum. Forty-eight hours after withdrawal from cocaine, NOS activity was increased only in the cerebral cortex. Recent studies have shown that cocaine-induced sensitization to behavioral effects can be inhibited by NOS inhibitors. The present studies provide the first evidence that chronic treatment with cocaine alters NOS activity in brain regions and spinal cord, and are consistent with behavioral studies with cocaine and NOS inhibitors.

Amygdala↗
PubMed1997

A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans.

BACKGROUND AND PURPOSE: Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reported that transforming growth factor-beta1 (TGF-beta1) might be involved in angiogenesis after ischemic stroke in humans; here we present data of an extensive study on platelet-derived growth factor (PDGF) and its receptors. METHODS: We studied brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding PDGF-A, PDGF-B, and PDGF receptors (PDGF-R). Proteins were examined by Western blotting and immunohistochemistry using the antibodies to PDGF-AB, PDGF-BB, PDGF-R alpha, and PDGF-R beta. RESULTS: At the mRNA level, PDGF-A and PDGF-B were expressed mainly in neurons in penumbra. PDGF-R mRNA was strongly expressed in some astrocytes but mainly in type III/IV neurons in infarct and penumbra. The least expression was seen in the contralateral hemisphere (P<.001). In contrast, both PDGF-AB and PDGF-BB immunoreactive products were present in most cell types: PDGF-R alpha and PDGF-R beta mainly on neurons, and PDGF-R beta on some endothelial cells, with less staining of all the isoforms in the contralateral hemisphere. On Western blots, PDGF-AB and -BB were expressed more within white matter than gray matter of infarct/penumbra, whereas both isoforms of receptor were expressed mainly in gray matter compared with contralateral hemisphere. There was no or very weak expression of the receptor in white matter. CONCLUSIONS: PDGF proteins are highly expressed in white matter, suggesting that PDGF may exert its function in white matter participating either in regeneration of damaged axons or in glial scar formation. PDGF-BB and its receptor expressed on microvessel endothelial cells might be involved in angiogenesis after stroke. Thus, PDGF is likely to be angiogenic and neuroprotective in stroke.

Aged↗
PubMed1997

Addressing issues of face validity in the application of a clinical guideline.

In 1995, a statewide project to improve the practice of electroconvulsive therapy (ECT) in the Medicare population was started in Louisiana. A retrospective baseline study found high concurrent utilization of lithium and benzodiazepines, medications considered detrimental to ECT by the second American Psychiatric Association Task Force on ECT. Resistance to a clinical guideline because of lack of face validity by clinicians was used as an opportunity to involve clinicians in using data to evaluate their clinical practices. Results of the first two quarters of the project demonstrated that the strategy was successful.

Clinical Trials as Topic↗
PubMed1997

Epidemiology of juvenile low back pain: a review.

Studies show that the cumulative prevalence of low back pain (LBP) in juveniles was close to 30%. The majority of the LBP was mild. Of those with LBP approximately 8% sought medical treatment. Chronic or recurrent LBP averaged 8.1% of the adolescent populations studied. The cumulative prevalence of LBP increased with age. One study showed a cumulative prevalence of LBP of over 70% by age 15. A potential link between the adolescent growth spurt and the increased prevalence of LBP was proposed. Asynchronous bone growth resulting in skeletal malalignment was proposed as a possible cause of LBP. Immaturity of the vertebral bony structures was thought to increase the risk of pars defects. Correlations between anthropometric measurements of height and weight were inconclusive. The role of decreased muscle flexibility in LBP was also inconclusive. Some researchers found a correlation between age, gender, height and LBP. Disc degeneration and spondylolytic symptoms were also noted as sources of LBP. However, not all cases of disc degeneration (DD) or spondylolysis were symptomatic of LBP. It was noted that the prevalence of DD was rare in adolescents. Disc protrusions were more common in LBP groups than in non-LBP groups, and females with LBP had more disc protrusions than males with LBP. Risk factors for spondylolysis and spondylolisthesis included genetics, the growth spurt, repetitive stresses and sports participation. Within competitive sports, age and training more than 15 hours/week correlated with the incidence of spondylolytic changes. Participation in sports as a risk factor for LBP was reported. A familial tendency for LBP was noted in one study in which the child had an increased incidence of reported LBP if one or both parents had a history of LBP.

Adolescent↗
PubMed1997

Prevalence of low back pain among physical therapists in Edmonton, Canada.

Questionnaires were sent to 462 physical therapists in Edmonton, Canada, to determine the prevalence of work-related low back pain (LBP) and to characterize those who reported pain. Of the 311 (67.3%) valid questionnaires returned. 49.2% reported back pain due to work. The occurrence rates of work-related LBP among physical therapists in Edmonton was higher than that of the general population reported in Canada (27%), Great Britain (27%), and the United States (26-29%). There was no significant difference (p < or = 0.05) between those with and without work-related LBP. The initial onset of work-related LBP frequently occurred within the first 5 years of practice as a physical therapist, and before the age of 30. Hospitals and private practices were the most prevalent work settings in which injury occurred. Patient handling, bending, stooping, lifting, carrying, pushing, and pulling were the commonly described activities causing precipitation of injury. The severity of back discomfort had been sufficient to require 13.7% of therapists to stop their work. Despite LBP, 35.3% of the pain sufferers continued to work. Over half (55.4%) of the respondents with current work-related LBP demonstrated little or no disability.

Adult↗
PubMed1997

Posteroanterior spinal mobilization: state of the art review and discussion.

Posteroanterior spinal mobilization is a commonly used technique among physical therapists to diagnose and treat lower back pain patients. Human subjects and instruments have been used to test for the reliability of physical therapists' ability to detect intervertebral motion, but studies confirm unreliable testing. Despite documented efficacy of manual treatment the mechanical response to posteroanterior spinal mobilization is not well understood, and this has been emphasized in recent studies. Various modes of instrumental methodology have been used for objective measurements of force application and joint displacement. Some instruments serve to mobilize the spine others serve as measurement tools for mobilization. The literature does not provide a gold standard for the ideal magnitude of force applied or joint displacement. The terminology used in the field of manual therapy is often confusing, and terms need to be defined. A review and discussion is presented here to highlight the issues and gaps.

Biomechanical Phenomena↗
PubMed1997

Molecular divergence of lysozymes and alpha-lactalbumin.

The vast number of proteins that sustain the currently living organisms have been generated from a relatively small number of ancestral genes that has involved a variety of processes. Lysozyme is an ancient protein whose origin goes back an estimated 400 to 600 million years. This protein was originally a bacteriolytic defensive agent and has been adapted to serve a digestive function on at least two occasions, separated by nearly 40 million years. The origins of the related goose type and T4 phage lysozyme that are distinct from the more common C type are obscure. They share no discernable amino acid sequence identity and yet they possess common secondary and tertiary structures. Lysozyme C gene also gave rise, after gene duplication 300 to 400 million years ago, to a gene that currently codes for alpha-lactalbumin, a protein expressed only in the lactating mammary gland of all but a few species of mammals. It is required for the synthesis of lactose, the sugar secreted in milk. alpha-Lactalbumin shares only 40% identity in amino acid sequence with lysozyme C, but it has a closer spatial structure and gene organization. Although structurally similar, functionally they are quite distinct. Specific amino acid substitutions in alpha-lactalbumin account for the loss of the enzyme activity of lysozyme and the acquisition of the features necessary for its role in lactose synthesis. Evolutionary implications are as yet unclear but are being unraveled in many laboratories.

Amino Acid Sequence↗
PubMed1997

Human papillomavirus DNA and virus-encoded antigens in cervical carcinoma.

The present study was undertaken to evaluate the prevalence of HPV in formalin-fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non-radioactive Southern hybridization with type-specific oligonucleotides for HPV 16 and 18. In addition, the tissue sections were immunohistochemically screened with two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both DNA hybridization and immunohistochemistry were in agreement for the majority of the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV with cervical carcinoma in Malaysia, the implementation of routine diagnosis for the virus in cervical biopsies would be clinically useful.

Antigens, Viral↗
PubMed1997

Isolation of Salmonella senftenberg bacteriophages.

A total of 61 bacteriophages were isolated from 100 strains of Salmonella senftenberg. Six bacteriophages were selected for typing purposes which were specific for S. senftenberg. Five phages, SasL1 to SasL5 were morphologically similar; phage SasL6 was morphologically different from the others. These phages fall into two morphological groups none of which correspond to the known tailed enterobacterial phage species. Hence, two new phage species represented by SasL1 and SasL6 are proposed.

Lysogeny↗