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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 649 records · Page 36Linked to original sources
PubMed1987

Synthesis and antiinflammatory activity of N-substituted-dihydropyridylacetic acids, esters, and amides.

A group of N-substituted-1,4-dihydropyridylacetic acids (13-16), esters (4-12), and amides (17-23) were synthesized in order to investigate the effect of 4-substituents (R2 = Ph, n-Bu or Me) and alpha-substituents (R3 = H, Me) on antiinflammatory activity. In the acetic ester class of compounds, the relative activities (R2-substituents) were Ph greater than n-Bu greater than Me. The presence of an R3 methyl substituent enhanced activity. Increasing the length of the alkyl ester substituent enhanced activity, since the tri-ester (7) was more active than the bis-ester (6), and the bis-ester (11) was more active than the mono-ester (10). The relative order of antiinflammatory potency was generally ester greater than amide greater than acid. Methyl 2-methyl-2-(-1-[4-phenyl-3-(4,4-dimethyloxazolin-2-yl)-1,4-dihy dropyridyl]) acetate (9) was the most active antiinflammatory agent in the series, reducing inflammation 73.9% at 3 hr after a 100 mg/kg po dose.

Acetates↗
PubMed1986

Sequence of human DNA polymerase beta mRNA obtained through cDNA cloning.

A cDNA library from polyA+ RNA of a human teratocarcinoma cell line in phage lambda gt11 was screened with a fragment of the rat beta-polymerase cDNA, lambda pol beta-10, as probe. Five positive phage were identified and plaque purified. The cDNA of one positive clone selected for detailed study was 1257 bp. This insert was sequenced and found to contain the coding region for beta-polymerase, as well as 163 bp and 137 bp from the 5' and 3' untranslated regions, respectively. The primary structure of human beta-polymerase (318 amino acids, Mr = 36, 133) deduced from the cDNA was similar to rat beta-polymerase (95% matched residues). The greatest difference between the sequences of the human and rat cDNAs was in the 3' untranslated regions (64% matched base residues). These results provide necessary sequence information for study of the human beta-polymerase gene.

Amino Acid Sequence↗
PubMed1986

Rheumatoid- and osteo-arthritis: quantitation of ultrastructural features of capillary endothelial cells.

Joint tissues from patients with rheumatoid arthritis (3), osteoarthritis (3) and normal healthy individuals (2) were examined in the transmission electron microscope and the morphological features of capillaries within 2 mm of the synovial membrane were quantified. Weibel-Palade bodies (WPB) were significantly increased in capillary endothelial cells in rheumatoid and osteoarthritis compared with normal controls, when quantified by three different methods. WPB were positively correlated with both projections of the luminal plasmalemma and pinocytic vesicles in normal joint and some patients with rheumatoid and osteoarthritis. Pinocytic vesicles and projections were also positively correlated.

Arthritis, Rheumatoid↗
PubMed1986

Antianxiety effect of cannabis: involvement of central benzodiazepine receptors.

The present work, involving clinical, behavioral, and biochemical studies, was undertaken to elucidate the probable mechanism of the observed antianxiety effects of cannabis. The population for the clinical study consisted of 50 male chronic cannabis users who were otherwise healthy and 50 matched controls. When evaluated on Taylor's Manifest Anxiety Scale (TMA), these subjects had low anxiety scores as compared with the controls. To explore the possible interaction of cannabis with the benzodiazepine receptors, behavioral and biochemical studies in mice were devised, involving acute and chronic cannabis administration. Behavioral study revealed that mice under chronic cannabis treatment scored significantly higher on foot shock-induced aggression, but this was significantly blocked by benzodiazepine receptor antagonist. Furthermore, chronic cannabis treatment significantly (p less than 0.001) increased the frequency of licking response periodically punished by shocks. This confirms the antianxiety effect of cannabis, which also appears to be mediated through a benzodiazepine receptor, as it was reduced significantly (p less than 0.001) by a benzodiazepine receptor blocker. Specific 3H-diazepam binding was carried out in frontal cortex to assess both the population and affinity of benzodiazepine receptors. Our results indicate that acute cannabis treatment has no significant effect, whereas chronic cannabis treatment significantly increased 3H-diazepam binding as compared with controls. Scatchard analysis further reveals that increased affinity is responsible for increased binding to these receptors. It is therefore our contention that the antianxiety effect of cannabis is mediated through central benzodiazepine receptors.

Adult↗
PubMed1986

High dose therapy and autologous marrow transplantation as salvage treatment for patients with diffuse large cell lymphoma.

Twenty-nine patients with diffuse large cell lymphoma who failed traditional chemotherapy were treated with high dose chemotherapy with or without total body irradiation followed by infusion of cryopreserved autologous marrow. Complete response was achieved in 11/29 patients (38%), partial response in 13/29 patients (45%) and 5/29 patients (17%) had no response. Six complete responders remain well and free of disease for 5+, 6+, 9+, 10+, 18+ and 25+ months, 3 relapsed at 2, 3 and 8 months after marrow infusion, and 2 died from infectious complications. Complete response was seen more frequently with the absence of bulky tumor (70 vs 21%, P = 0.03), a total body irradiation containing regimen (52 vs 0%, P = 0.03), a history of complete remission with initial chemotherapy (55% vs. 9%, P = 0.03), and a performance status greater than or equal to 80 (56 vs 15%, P = 0.06). High dose therapy had a high response rate (83%) in resistant diffuse large cell lymphoma and yielded durable complete responses in a minority of these patients.

Adolescent↗
PubMed1986

Structure of rat DNA polymerase beta revealed by partial amino acid sequencing and cDNA cloning.

A cDNA library of newborn rat brain poly(A)+ RNA in phage lambda gt11 was screened with a polyclonal antibody against chicken DNA polymerase beta. One positive phage was isolated and purified after testing 2 X 10(7) recombinants. This phage, designated lambda pol beta-10, contained an 1197-base-pair cDNA insert that corresponded to a mRNA with a poly(A) sequence at the 3' terminus and a single, long open-reading frame of 957 bases. The open-reading frame, starting 44 residues from the 5' end of the cDNA, predicted a 36,375-Da protein of 318 amino acids. Comparison of this deduced amino acid sequence with the partial sequence obtained with purified polymerase beta revealed a match of six tryptic peptides, involving a total of 47 amino acid residues. This confirmed the identity of the cDNA. Blot-hybridization analysis of newborn rat brain poly(A)+ RNA revealed a mRNA species of approximately the same size as the cDNA insert; in addition, a second mRNA species approximately equal to 4000 bases long was detected. Computer-derived secondary structure analysis of the enzyme predicted seven regions of alpha-helix distributed throughout and three regions of beta-sheet.

Amino Acid Sequence↗
PubMed1986

3H-spiperone binding in platelet membranes: a possible biological marker for schizophrenia.

High-affinity-specific 3H-spiperone binding to platelet membranes was carried out in 30 schizophrenic patients, without prior antipsychotic medication, fulfilling the Research Diagnostic Criteria, and in 30 matched control subjects. The psychosis was rated on the Modified Brief Psychiatric Rating Scale. Compared with healthy subjects, schizophrenic patients had significantly higher 3H-spiperone binding due to a lower dissociation constant (38%), i.e. increased affinity. No significant difference was observed in the maximum number of binding sites (Bmax) between the two groups. It is our contention that 3H-spiperone binding to platelets may be a biological marker for schizophrenia.

Adolescent↗
PubMed1986

Differential effects of pH on calcium activation of myofilaments of adult and perinatal dog hearts. Evidence for developmental differences in thin filament regulation.

Our results show that calcium activation of myofilament preparations of dog heart in the perinatal period is unaffected by a reduction in pH from 7.0 to 6.5, which, in adult heart myofilaments, induces a 0.4 pCa unit (-log molar free calcium concentration) rightward shift in the relation between pCa and myofibrillar adenosine triphosphatase activity. Acidic pH also had no effect on calcium binding to myofibrillar troponin C of perinatal hearts. The stoichiometry of troponin C bound calcium at full myofilament activation (about 3 mol calcium/mol troponin C) was the same for adult and perinatal heart myofibrils, as was their myofibrillar troponin C content. Moreover, there were no differences in isoelectric pH of troponin C from adult and perinatal hearts. We tested whether variants of myofilament proteins other than troponin C could account for the differential effects of acidic pH. In adult and perinatal dog heart preparations, myosin heavy chain isoenzymes appeared the same as measured, using native pyrophosphate gel electrophoresis. No evidence for thick filament-related calcium regulation in the perinatal heart myofilaments was obtained, when tested in studies in which native thin filaments were displaced with a 10-fold molar excess of pure actin. In preparations in which native thick filaments were displaced with a 10-fold molar excess of pure skeletal muscle myosin, the effects of acidic pH on calcium activation were the same as in native adult and perinatal preparations. Our major conclusion from these results in that the perinatal heart myofilaments are likely to possess variations in thin filament activity and structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1986

Interaction of polyglutamyl derivatives of methotrexate, 10-deazaaminopterin, and dihydrofolate with dihydrofolate reductase.

Polyglutamyl derivatives of methotrexate (MTX) and 10-deazaaminopterin (10-DAM) containing a total of one through six glutamate residues (Glu residues) were tested as inhibitors of dihydrofolate reductase (DHFR) derived from sheep, chicken, and beef liver. The ability of dihydropteroylpentaglutamate to antagonize the inhibitory activity of these analogues was also studied. The most striking effects were seen with sheep liver DHFR, where polyglutamylation of MTX causes stepwise decreases in the concentration required for 50% inhibition (IC50) with each additional Glu residue until MTX with a total of six Glu residues has an IC50 value 1/3 that of MTX. With 10-DAM the pattern is more complex. The IC50 values increase with addition of Glu residues until a maximum is reached with 10-DAM having a total of three Glu residues which has a value twice that of 10-DAM. 10-DAM with a total of four Glu residues and 10-DAM with a total of five Glu residues have progressively lower IC50 values, the latter being equipotent with 10-DAM. With dihydropteroylpentaglutamate as substrate instead of dihydrofolate, the IC50 values are increased 2- to 5-fold for both MTX and 10-DAM derivatives. The results obtained with chicken liver and beef liver DHFR are generally similar to those described for the sheep liver enzyme, but the effects of polyglutamylation are less pronounced. The addition of 0.2 M KCl to the assay system reduces the differences in inhibitory potency of the polyglutamyl derivatives with all three enzymes tested. We conclude that polyglutamylation can alter the interaction of folate analogues and dihydrofolate with DHFR.

Aminopterin↗
PubMed1986

Radionuclide bone imaging in patients with low back pain presenting to the orthopaedic surgeon.

This study looks retrospectively at 113 patients with low back pain referred by orthopaedic surgeons for bone scanning. 79 scans (70%) were reported normal and 34 scans (30%) abnormal. 61 out of the 79 patients with normal scans were diagnosed and managed as "chronic back strain". Negative bone scans were also encountered in 3 patients with degenerative disease, 3 with prolapsed intervertebral disc and one with spondylolysis. In those patients with positive scans, a varied range of diagnoses was encountered, the main ones being bone metastases, previous trauma, osteomyelitis and degenerative disease. The scan was shown to be helpful in deciding on the presence or absence of pathology, and in identifying the sites of involvement, but not the nature of the disease. A higher likelihood of positivity is seen in the more elderly patients as well as those below 20 years of age. In interpreting the scan, the clinical context is important e.g. a history of trauma, previous surgery or of malignant disease. The bone scan may be normal in disc prolapse and in degenerative disease of the spine.

Adolescent↗