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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,675 records · Page 93Linked to original sources
PubMed1988

The effect of polymerised fibrin on the catalytic activities of one-chain tissue-type plasminogen activator as revealed by an analogue resistant to plasmin cleavage.

A one-chain recombinant tissue-type plasminogen activator (EC 2.4.31.-) (tPA) analogue was constructed in which Arg-275 of the activation site was changed to Gly by site-directed mutagenesis. This analogue, tPA-Gly275, was very resistant to plasmin (EC 2.4.21.5) cleavage. It has been used to gain information about the activity of the uncleaved one-chain tPA form, also when plasmin is generated as a result of a plasminogen activation reaction. The amidolytic activity of tPA-Gly275 with less than Glu-Gly-Arg-pNA was investigated and compared to that of one-chain and two-chain wild-type recombinant tPA. A small but significant intrinsic amidolytic activity was observed with the analogue as well as the wild-type one-chain tPA form. However, it was much lower than that of two-chain tPA. Polymerised fibrin enhanced the amidolytic activity of both one-chain tPA forms but not of two-chain tPA. Measurements of the plasminogen activation kinetics in the absence of fibrin revealed that tPA-Gly275 possessed a significant intrinsic activity. However, it was 30-fold lower than that of two-chain tPA. Addition of polymerised fibrin profoundly enhanced the plasminogen activation rate of both tPA-Gly275 and wild-type one- and two-chain tPA to approximately the same maximal level. The results were interpreted to mean that fibrin binding can induce an activated state of the intact tPA one-chain form.

Biopolymers↗
PubMed1988

Differential enzymatic accessibilities of the 5' and 3' splice sites of beta-globin pre-messenger RNA in splicing competent HeLa cell nuclear extract.

Inhibition of oligonucleotide-directed cleavage of pre-mRNA using exogenously added E. coli RNase H has been utilized as a probe for mRNA-protein interaction. We now show that such an RNase H-like activity is present in splicing competent Hela cell nuclear extract. Using this extract and in vitro transcribed beta-globin pre-mRNA, we have demonstrated that synthetic oligonucleotides, complementary to the splice site sequences, direct preferential cleavage of the 5' splice site. Thus, these experiments using complementary oligonucleotide-directed, endogenous RNase H-like cleavage of pre-mRNA, suggest a useful probe for studying the mRNA-protein complex in vitro.

Base Sequence↗
PubMed1988

Identification of nonprotein ligands to the metal ions bound to glutamine synthetase.

Electron paramagnetic resonance (EPR) was used to study the environment of Mn2+ bound to the tight (n1) metal ion binding site of glutamine synthetase in the presence of analogues of the tetrahedral adduct, L-methionine (S)-sulfoximine [Met(O)(NH)-S] and L-methionine (R)-sulfoximine [Met(O)(NH)-R]. The Mn2+ EPR spectrum in the presence of Met(O)(NH)-S is identical with the previously published spectrum obtained from a mixture of isomers [Met(O)(NH)-RS] [Villafranca, J. J., Ash, D. E., & Wedler, F. C. (1976) Biochemistry 15, 544] and is characteristic of a highly octahedral metal ion environment with a small zero field splitting. The presence of Met(O)(NH)-R produces an EPR spectrum that appears characteristic of a more distorted metal ion environment, with a larger zero field splitting. These data demonstrate that the two isomers interact differently with the enzyme-bound Mn2+. Broadening of the Mn2+ EPR spectrum in the presence of Met(O)(NH) is observed in 17O-enriched water due to superhyperfine coupling of water to the metal ion. Deconvolution of the spectrum demonstrates the presence of at least a single water molecule in the inner coordination sphere of the metal ion. Superhyperfine coupling due to the 14N nucleus of the imine nitrogen of the sulfoximine moiety of Met(O)(NH)-S but not of Met(O)(NH)-R has been detected by electron spin-echo envelope modulation spectroscopy. Two intense peaks are evident in the presence of Met(O)(NH)-S with frequencies at 1.7 and 3.3 MHz. These peaks are absent when [15N]imine-labeled Met(O)(NH) is used, indicating the presence of the sulfoximine nitrogen of Met(O)(NH)-S in the inner coordination sphere of the metal ion.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1988

Hydrocephalus in asphyxiating thoracic dystrophy.

We document four patients, including two sibs, with asphyxiating thoracic dystrophy and mild congenital hydrocephalus. All infants were males; three had postaxial polydactyly. The CT scan of brain showed moderate dilatation of the lateral ventricles in all cases. This appears to be the first documentation of apparent hydrocephalus in this condition.

Asphyxia↗
PubMed1988

Motor vehicle crashes in dementia of the Alzheimer type.

To assess the occurrence and related features of motor vehicle crashes in patients with dementia of the Alzheimer type (DAT) we studied 30 patients who had been followed longitudinally and 20 healthy age-matched control subjects. Data were gathered from first-degree relatives who had lived with the subjects for the previous 5 years or more. Forty-seven percent of the DAT patients incurred at least one crash while they were driving, whereas only 10% of the control subjects had had a crash in the previous 5 years. The odds ratio for crashes in the DAT group was 7.9 (p less than 0.01). Moreover, in 77% of DAT patients, a deterioration in driving performance was noted, and 63% of the patients had stopped driving. However, only 42% of the DAT patients who stopped driving did so before a crash occurred. Mean illness duration was 4.0 (+/- 1.8) years, and the mean Mini-Mental Status Examination score was 19.9 (+/- 6.3) at the time of the first crash in the DAT group. The occurrence of crashes was not significantly correlated with dementia severity or with disease duration. These data suggest that the occurrence of driving crashes in patients with DAT is an important public health problem.

Accidents, Traffic↗
PubMed1988

Angiotensinogen gene expression in neuronal and glial cells in primary cultures of rat brain.

Neuronal and glial cells in primary culture prepared from the hypothalamic-brain stem areas of one-day-old rat brains were analyzed for the presence of angiotensinogen messenger RNA (mRNA) to further confirm our previous conclusion that the brain contains an exclusive angiotensin system. Angiotensinogen mRNA was quantitated by Northern analysis using nick-translated angiotensinogen cDNA as the hybridization probe (Kunapuli and Kumar, 1987). Angiotensinogen mRNA sequences were present in the RNA isolated from both neuronal and glial cultures. Quantitative measurements of the mRNA using dot-blot analysis revealed that the level of angiotensinogen mRNA was three times higher in neuronal cultures compared with glial cultures. These observations provide the first evidence for the synthesis of angiotensinogen in neuronal as well as in glial cells form the brain.

Angiotensinogen↗
PubMed1988

Relative induction of molecular forms of cytochrome P-450 in gamma-hexachlorocyclohexane exposed rat liver microsomes.

The effect of gamma-hexachlorocyclohexane (HCH), (25 mg/kg body weight, i.p., administered for 4 consecutive days) on the induction of types of cytochrome P-450 in rat liver microsomes was studied. Induced proteins were characterized by "Western" blot analysis, using anticytochrome P-450 antibodies. It was observed that HCH is a "mixed-type" inducer and mediates induction of cytochrome P-450 b/e forms by several fold and of cytochrome P-450 c and d forms by nearly three fold.

Animals↗
PubMed1988

Pycnodysostosis. Case report.

The clinical and radiographic features of pycnodysostosis in a 17 year old Tanzanian man are described.

Abnormalities, Multiple↗
PubMed1988

Nonradioactive labeling of synthetic oligonucleotide probes with terminal deoxynucleotidyl transferase.

Synthetic oligonucleotides were tailed at the 3' end using terminal deoxynucleotidyl transferase. Nucleotide triphosphates with free primary amines at the end of side chains were compared for their tailing efficiency and/or detection sensitivity, using biotin-11-dUTP as a reference. Free primary amines were tagged with activated biotin or fluorescein isothiocyanate. The probes were then detected with either streptavidin-alkaline phosphatase complex or anti-fluorescein antibodies and alkaline phosphatase-conjugated secondary antibodies. Tailing conditions were optimized and the probes were tested for detection of Escherichia coli ST1a enterotoxin DNA and rotavirus RNA.

Affinity Labels↗
PubMed1988

Management of vesico-uterine fistulae: a report of six cases.

Six cases of vesico-uterine fistulae caused by cesarean section in four and pelvic trauma in two cases were treated during the past 15 years. Both the cases of vesico-uterine fistulae due to pelvic trauma and one case of vesico-uterine fistula due to cesarean section in whom the fistula was detected in the early post-operative period, could be managed successfully by suprapubic urinary diversion and control of infection. Two patients who were seen more than 1 year after the cesarean section, were cured by trans-abdominal closure of the fistula with omental interposition. One patient who reported 3 months after the cesarean section was managed by estrogen and progesterone-induced amenorrhea. The management protocol for vesico-uterine fistula should thus be individualised taking into consideration the etiology, and time interval between its occurrence and institution of treatment regimen.

Cesarean Section↗
PubMed1988

Synthesis, spectroscopic, and antitumor activity of metal chelates of S-methyl-N-(l-isoquinolyl)-methylendithiocarbazate.

Complexes of Mn(III), Fe(III), Fe(II), Co(III), Ni(II), Cu(II), Zn(II), and Pt(II) with S-methyl-N-(l-isoquinolyl) methylendithiocarbazate (N-N-SH) were isolated and characterized by elemental analysis, conductance measurement, magnetic susceptibilities, and spectroscopic studies. On the basis of these studies, a highly distorted, high-spin, chloro-bridged, polymeric octahedral structure for [Mn(N-N-S)Cl2]; a distorted, low-spin, monomeric octahedral structure for [Fe(N-N-S)2]; a distorted, high-spin, octahedral structure for [Ni(N-N-S)2]; and a square-planar structure for [M(N-N-S)X] (M = Ni, Cu, Pt or Zn and X = Cl- or -OAc) are suggested. With Fe(III), the complex [Fe(N-N-S)2][FeCl4] was isolated while the Co(II) was oxidized to yield the Co(III) ion as [Co(N-N-S)2]2[CoCl4]. All these complexes were screened for their antitumor activity against P 388 lymphocytic leukemia test system in mice. Except for Mn(III), Fe(III), and Co(III) complexes, all were found to possess significant activity; the Cu(II) and Zn(II) complexes showed a T/C% value of 160 and 195, respectively, at their optimum dosages.

Animals↗
PubMed1988

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones.

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and Mössbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.

Animals↗
PubMed1988

Glycated albumin and glycated hemoglobin levels in normal pregnancy.

Glycated albumin levels showed a progressive increase during normal pregnancy. The mean values (mole hexose/mole protein) were 1.68 +/- 0.27 (n = 15) in nonpregnant women, 1.83 +/- 0.21 (n = 11) in first trimester, 2.00 +/- 0.41 (n = 13) in second trimester, and 2.42 +/- 0.49 (n = 15) in third trimester. Glycated hemoglobin levels indicated a biphase pattern with low values at midpregnancy (controls 0.29 +/- 0.05, first trimester 0.30 +/- 0.04, second trimester 0.27 +/- 0.05, and third trimester 0.33 +/- 0.04). The data suggest that glycated albumin reflects the decreased glucose tolerance in pregnancy better that glycated hemoglobin levels. The reasons for the differing pattern of the two glycated proteins are discussed.

Adult↗