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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 253 records · Page 14Linked to original sources
PubMed1997

Sertraline in coexisting major depression and diabetes mellitus.

As many as 25 percent of patients with diabetes mellitus may also have depressive symptoms. Tricyclic antidepressants (TCAs) may produce increased appetite and weight gain with adverse consequences for diabetes. The selective serotonin reuptake inhibitors (SSRIs), however, may improve fasting blood sugar in laboratory studies. In an initial application, sertraline was administered at a dose of 50 mg/day in a 10-week open study to 28 non-insulin-dependent diabetes mellitus (NIDDM) patients with DSM-III-R major depression after a 2-week single-blind placebo washout period with a minimum 17-Item Hamilton Rating Scale for Depression (HAM-D) score of 18. The patient group included 16 males and 12 females with a mean age of 54.2 +/- 8.8 years. Results indicated (1) significant improvement in mean HAM-D (22.6 +/- 3.4 to 4.9 +/- 5.9, p < .001) and in mean Beck Depression Inventory (BDI) scores (21.9 +/- 10.5 to 12.7 +/- 8.3, p < .001); (2) fall in platelet serotonin (5-HT) content (79.7 +/- 22.5 to 13.6 +/- 12.7 ng/10(8) platelets, p < .001); (3) correlation of baseline platelet 5-HT content with response to sertraline by BDI scores (r = 0.51, p < .05); (4) improved dietary compliance for those with baseline value below 70 percent (59.7% to 69.1%, p < .005); and (5) 13 of 17 patients with baseline glycosylated hemoglobin A (HbA1c) levels greater than 8.0, showed a reduction (p = .018). Sertraline may be an effective antidepressant in patients with diabetes mellitus and response may be predictable by higher baseline platelet 5-HT content, with the potential to improve dietary compliance and reduce HbA1c measures. As with all open studies, replication is essential.

1-Naphthylamine↗
PubMed1997

Arteriovenous fistula combined with basal external penile compression: a new cure for male impotence.

We describe here a new procedure designed to enable reproducible sustained erection in a canine model. In 10 dogs, an end-to-side arteriovenous fistula was created between the inferior epigastric artery and deep dorsal vein. A chronic skin tunnel was created at the penile base. Blood flow, intracavernosal pressure and intraspongiosal pressure and blood gases were measured initially and 3 months later. Cuff application for 30 minutes was used daily. At 3 months, animals were sacrificed and biopsies obtained. Physiologic and histological parameters of erectile structures remained unchanged. Intracavernosal and intraspongiosal pressures increased to 33.7 +/- 6.7 mm Hg and 25.3 +/- 12.2 mm Hg (from 8.0 +/- 2.9 and 6.0 +/- 3.6 mm Hg) after cuff application. We conclude that sustained erections are feasible. This procedure appears safe for human trials.

Anastomosis, Surgical↗
PubMed1997

Intestinal strongyloidiasis--a rare opportunistic infection.

We describe the features of intestinal strongyloidiasis in six patients; five of them were immunosuppressed (four on corticosteroids, one with chronic renal failure). Vomiting and diarrhea were the predominant symptoms. Duodenal mucosa on endoscopy varied from normal to severe ulceration. Albendazole 400 mg/day for two weeks was effective. This condition should be considered in immunosuppressed individuals with gastrointestinal symptoms, especially since these symptoms may be mistakenly attributed to the underlying disease.

Adult↗
PubMed1997

Presenilin-1 is associated with Alzheimer's disease amyloid.

Mutations in presenilin (PS)-1 and -2, located on chromosome 14 and 1 respectively, are the major association with early-onset familial Alzheimer's disease (FAD). FAD has also been linked to mutations in the amyloid beta precursor protein (beta PP), and the presence of the apolipoprotein E4 allele is a risk factor for late-onset AD. The role of PS in FAD and in sporadic AD is unclear. We previously reported the presence of a PS-1 carboxyl-terminal epitope in neuritic plaques (Wisniewski T, Palha JA, Ghiso J, Frangione B: S182 protein in Alzheimer's disease neuritic plaques. Lancet 1995, 346:1366). In the present study, we examined a number of biochemically different cerebral and systemic amyloidoses, finding the PS-1 carboxy epitope only in association with amyloid beta (A beta) lesions. We confirm the presence of this epitope ultrastructurally in neuritic plaques. In addition, biochemical and amino acid sequence data are presented for an association of the 18-kd carboxy fragment of PS-1 with neuritic plaques with a start at residue 300. Three of the proteins with linkage to AD have now been found as components of neuritic plaques. It remains to be determined whether all of these proteins are involved in the same or different pathological pathway(s) and which of these proteins is the most important for the common, late-onset form of AD.

Adult↗
PubMed1997

Quantitative estimation of ultrasonographic attenuation in the myocardium using conventional echocardiographic instrumentation.

Through the careful and judicious use of the time gain controls in conventional echocardiographic instrumentation, we have found that it is possible to obtain quantitative estimates of the attenuation of ultrasound beams even in vivo. These estimates are based on the quantitative comparison of the amplitude of the echo waveforms at different depths. Here, we report on such attenuation measurements using both a tissue phantom and the interventricular septum of the myocardium in vivo. The in vitro estimates of attenuation with this method are in agreement with independent laboratory measurements of the same parameter. In vivo measurements on the myocardium indicate oscillations in the magnitude of the attenuation over the heart cycle and suggest methods for the quantitative assessment of a variety of pathologic conditions in the myocardium noninvasively using conventional ultrasound scanners.

Diastole↗
PubMed1997

Nodular pulmonary immunoglobulin light chain deposits with coexistent amyloid and nonamyloid features in an HIV-infected patient.

Isolated nodular pulmonary amyloidosis is a rare condition characterized by localized deposits of immunoglobulin (Ig) light chain amyloid. Nonamyloid nodular light chain deposits in lungs can occur in systemic light chain deposition disease. Both amyloid and nonamyloid light chain deposits have been described at separate sites in the same or different organs but rarely in lungs. We report the clinical, radiologic, and pathologic findings in a drug user infected with the human immunodeficiency virus who had multinodular pulmonary Ig light chain deposits consisting of both amyloid and nonamyloid granular morphologic features. The deposits, closely associated with numerous plasma cells, had a unique histochemical and ultrastructural profile, with intermixed Congo red-positive fibrillar amyloid and Congo red-negative granular nonamyloid components. Immunohistochemical and immunoelectron microscopic studies showed reactivity of both the fibrillar and granular deposits for kappa and lambda light chains but not heavy chains. There was no evidence of restricted clonality of local or bone marrow plasma cells, serum or urine monoclonal protein, or secondary causes of amyloidosis. The amyloid deposits (but not the nonamyloid deposits) were reactive with antibody to amyloid rho component. There was no staining for other types of amyloid, i.e., amyloid A or transthyretin. The relationship between pulmonary amyloidosis, infection with the human immunodeficiency virus, and illicit drug use is unknown. We conclude that the nodular pulmonary light chain deposits with both amyloid and nonamyloid morphologic features are related to local plasma cell proliferation and that the fibrillar and nonfibrillar components most likely result from different conformations of the Ig light chains.

Adult↗
PubMed1997

Phorbol ester-induced low density lipoprotein receptor gene expression in HepG2 cells involves protein kinase C-mediated p42/44 MAP kinase activation.

The signaling pathway involved in low density lipoprotein (LDL) receptor gene expression induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated in the human hepatoma HepG2 cell line. Treatment of HepG2 cells with 100 nM TPA resulted in an approximately 20-fold increase in LDL receptor mRNA level, as determined by RT-PCR, which peaked at 2-4 h of treatment and subsequently declined. The protein kinase C (PKC) inhibitors calphostin C and staurosporine prevented TPA-mediated LDL receptor mRNA induction. In contrast, TPA did not affect squalene synthase mRNA expression. Immunoblotting of cell extracts with isozyme-specific PKC antibodies revealed that HepG2 cells expressed PKC alpha, which was mainly cytosolic, and PKC beta, PK epsilon, and PKC zeta, all of which were present in both the cytosolic and particulate fractions. Treatment of HepG2 cells with 100 nM TPA resulted in translocation of cytosolic PKC alpha to the particulate fraction, with a maximum at 30 min-2 h of treatment, but was without effect on the subcellular distribution of the other isozymes. TPA treatment also led to activation of the mitogen-activated protein kinase (MAPK) ERK cascade. The specific MAPK pathway inhibitor PD98059 blocked TPA-induced ERK activation. Furthermore, pretreatment of cells with PD98059 inhibited TPA-induced LDL receptor mRNA induction. Moreover, pretreatment of cells with calphostin C inhibited TPA-mediated ERK activation and LDL receptor mRNA induction in a dose-dependent fashion. Based on a close kinetic correlation between PKC alpha translocation and ERK activation, and the effects of specific inhibitors, these findings suggest that translocation/activation of PKC alpha, and subsequent activation of the Raf-1/MEK/ERK MAPK cascade, represent key events in the transcriptional induction of LDL receptor gene by TPA in HepG2 cells.

Blotting, Northern↗
PubMed1997

Cardiovascular responses to treadmill exercise testing in anemia.

OBJECTIVE: To study exercise performance on a treadmill in anemic children. DESIGN: Prospective case control study. SETTING: Department of Pediatrics and Intensive Care Unit, Department of Medicine, King George's Medical College, Lucknow. SUBJECTS: The study population consisted of 41 cases of anemia (10 mild, 21 moderate and 10 severe) and 11 normal age and height matched children aged between 7-12 years. METHODS: These subjects were exercise tested on Quinton Model Q5000 treadmill using Modified Naughton Q5000 protocol. Heart rate, systolic blood pressure, double product, ECG changes, exercise duration and metabolic equivalents achieved during peak exercise were studied. Statistical analysis was performed using analysis of variance (ANOVA) test. RESULTS: No significant difference was observed in values of resting heart rate, heart rate at peak exercise, recovery heart rate, blood pressure response, resting double product, double product at peak exercise, recovery double product and ECG changes in any of the study groups (p > 0.05). However, the gain in heart rate at peak exercise compared to basal value, and double product, total exercise duration and metabolic equivalent (MET) values at peak exercise were significantly low in anemic children on comparison to normal controls (p < 0.001). CONCLUSIONS: Cardiovascular responses are blunted in anemia, mainly because of depleted cardiac reserve.

Analysis of Variance↗
PubMed1997

The evolution of Ty1-copia group retrotransposons in eukaryote genomes.

The Ty1-copia group of LTR retrotransposons has been studied extensively in yeast and Drosophila, the organisms in which they were first discovered, and more recently in higher plant and vertebrate species. Their properties, such as copy number, sequence homogeneity, transcriptional and transpositional activity vary greatly between these different hosts. We will try to resolve these apparent discrepancies between these properties, explain any fundamental differences in the biology of the Ty1-copia group between hosts, and propose a general model for LTR retrotransposon evolution.

Base Sequence↗
PubMed1997

The chromosomal distributions of Ty1-copia group retrotransposable elements in higher plants and their implications for genome evolution.

Retrotransposons make up a major fraction--sometimes more than 40%--of all plant genomes investigated so far. We have isolated the reverse transcriptase domains of the Ty1-copia group elements from several species, ranging in genome size from some 100 Mbp to 23,000 Mbp, and determined the distribution patterns of these retrotransposons on metaphase chromosomes and within interphase nuclei by DNA:DNA in situ hybridization. With some exceptions, the reverse transcriptase domains were distributed over the length of the chromosomes. Exclusion from rDNA sites and some centromeres (e.g., slash pine, 23,000 Mbp, or barley, 5500 Mbp) is frequent, whereas many species exclude retrotransposons from other sites of heterochromatin (e.g., intercalary and centromeric sites in broad bean). In contrast, in the plant Arabidopsis thaliana, widely used for plant molecular genetic studies because of its small genome (c. 100 Mbp), the Ty1-copia group reverse transcriptase gene domains are concentrated in the centromeric regions, colocalizing with the 180 bp satellite sequence pAL1. Unlike the pAL1 sequence, however, the Ty1-copia signal is also detectable as weaker, diffuse hybridization along the lengths of the chromosomes. Possible mechanisms for evolution of the contrasting distributions are discussed. Understanding the physical distribution of retrotransposons and comparisons of the distribution between species is critical to understanding their evolution and the significance for generation of the new patterns of variability and in speciation.

Chromosome Mapping↗
PubMed1997

The Ty1-copia group of retrotransposons in plants: genomic organisation, evolution, and use as molecular markers.

The genomic organisation and diversity of the Ty1-copia group retrotransposons has been investigated in several crop plants and their relatives from both dicotyledonous and monocotyledonous families, including potato (Solanum tuberosum), faba beans (Vicia faba), Vicia melanops, Vicia sativa, barley (Hordeum vulgare), rye (Secale cereale), and onion (Allium cepa). Extreme heterogeneity in the sequence of the Ty1-copia retrotransposons from all these plants was revealed following sequence analysis of reverse transcriptase fragments. The estimated copy numbers of the Ty1-copia group retrotransposons for the genomes of S. tuberosum, L. esculentum, A. cepa, S. cereale, and V. faba is highly variable, ranging from a few hundred to approximately a million copies per genome. In situ hybridisation data from metaphase and prophase chromosomes of V. faba, S. cereale, and H. vulgare suggest that retrotransposon sequences are dispersed throughout the euchromatic regions of the genome but are almost undetectable in most heterochromatic regions. In contrast, similar data from metaphase chromosomes of A. cepa suggests that although retrotransposon sequences are dispersed throughout the euchromatic regions of the genome, they are predominantly concentrated in the terminal heterochromatin. These results are discussed in the context of the role played by the Ty1-copia group retrotransposons in the evolution of the plant genome. Lastly, the application of retrotransposon sequences as genetic markers for mapping genomes and for studying genetic biodiversity in plants is presented.

Chromosome Mapping↗
PubMed1997

Interleukin-6 receptor-interleukin-6 fusion proteins with enhanced interleukin-6 type pleiotropic activities.

An sIL-6R/IL-6 chimera, directly fusing the natural forms of soluble IL-6 receptor and IL-6, as found in human body fluids, was produced in transfected human cells. The secreted p85 glycoprotein was active at a concentration of 120 pM to produce growth-arrest and spindleoid differentiation of murine melanoma F10.9 cells, which do not respond to IL-6 alone. This fusion protein was as active as the yeast-produced p56 fusion protein containing a shortened sIL-6R, linked through a flexible peptide chain to IL-6 (Hyper IL-6). The concentration of Hyper IL-6 needed to arrest the growth of F10.9 cells was much lower than that needed of a combination of IL-6 and sIL-6R, added separately. Hyper IL-6 was also more active than IL-6 in stimulating growth of murine plasmacytoma T1165 cells, the half maximal stimulation being obtained at 2 pM Hyper IL-6 versus 23 pM for IL-6. In order to evaluate the effect of the fused sIL-6R/IL-6 proteins on human hematopoietic primitive progenitor cells, they were added to suspension cultures of CD34+ cells from human cord blood in addition to both flt3/flk2 ligand (FL) and stem cell factor (SCF). Fused sIL-6R/IL-6 produced a marked stimulation of cell expansion and a marked increase in the number of colony forming units when subsequently plated in semi-solid medium with IL-3, GM-CSF, SCF and erythropoietin. Ex-vivo maintenance and expansion of early progenitor cells in bone marrow transplantation protocols may be a potential application for the sIL-6R/IL-6 chimeric glycoproteins.

Animals↗