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Biomedical subjects

G K Kumar

Publications and source records attributed to G K Kumar.

52 records · Page 3Linked to original sources

Effect of mutations at Met-88 and Met-90 on the biotination of Lys-89 of the apo 1.3S subunit of transcarboxylase.

The apo 1.3S subunit of transcarboxylase contains the sequence Ala-87-Met-88-Lys-89-Met-90, and it is Lys-89 that is biotinated. This sequence is highly conserved in all the biotin enzymes that have been sequenced (with the exception of acetyl-CoA carboxylase from chicken liver, which has Val in place of Ala). The role of Met-88 and Met-90 in specifying Lys-89 for biotination by synthetase was examined by site-directed mutagenesis. Genes of the 1.3S subunit coding for Thr-88, Leu-88, or Leu-90 were generated by oligonucleotide-directed in vitro mutagenesis and expressed in Escherichia coli. The mutated apo 1.3S subunits were isolated and the biotination by homogeneous synthetase from Propionibacterium shermanii was compared with that of the apo wild-type subunit. The Vmax for the apo mutants was the same as that for the apo wild type, but when Leu was substituted for Met-88 or Met-90, the Km for the mutant was lower than that of the wild-type or mutant Thr-88. The activity of the synthetase of E. coli was determined by an in vivo assay. During the early log phase of growth, a smaller portion of mutants Thr-88 and Leu-90 was biotinated than with the wild-type or mutant Leu-88. When the cultures progressed to stationary phase, mutants and the wild type were biotinated to the same extent. The overall results show that Met-88 and Met-90 are not required for biotination of the apo 1.3S subunit by the synthetases.

Amino Acid Sequence↗

Cell to cell association in Zajdela ascitic hepatoma. An ultrastructural study.

Zajdela ascitic hepatoma cells exist as small islands of two or more cells in addition to single cells. It is now shown that the number of cells per island is directly proportional to the age of the tumor. The number of single cells is maximal 24 h after transplantation of the tumor. Various types of inter-cellular connections are seen between adjacent cells in the island. These junctions are predominant in the apical regions of the cells. The electron-dense material present at junctional sites disappears from several sites after treatment of the islands with chelating agents such as EDTA, EGTA and citrate; the latter being most effective. No appreciable effect on the removal of electron-dense material from the junctional sites is observed when the islands are treated with either collagenase or trypsin.

Animals↗

Evolution of chromosomal abnormalities in sequential cytogenetic studies of ataxia telangiectasia.

Sequential cytogenetic studies of four patients with ataxia telangiectasia showed the progressive development of lymphocyte clones, each marked with a rearranged chromosome 14. Initial studies had shown random chromosomal breaks and rearrangements. Later studies in all patients showed nonrandom rearrangement of chromosome 14 with a breakpoint at 14q12 and with the distal segment translocated to either chromosome 14 or 7. The proportion of circulating lymphocytes carrying the marker tended to increase with time, accounting for the majority of the lymphocytes eventually in one case. The marked lymphocyte clones evolved further, as a result of loss of the small centric portions of the rearranged chromosome 14 (14pter leads to 14q12). Perhaps the abnormal clones in ataxia telangiectasia escape immunologic surveillance and flourish in an immunologically impaired environment. Subsequent to the loss of the centric portion of the rearranged chromosome 14, the cells may acquire additional capabilities that enhance malignant transformation.

Adolescent↗

Massive colonic bleeding and oral contraceptive "pills".

Two patients on oral contraceptives who developed massive colonic bleeding have been presented. The clinical course and various studies suggest the mesenteric insufficiency syndrome as being a possible result of oral contraceptive effect on mesenteric vasculature. Although no definite histologic confirmation is available, the onset, course, and follow-up of these patients suggest contraceptive-induced massive colonic bleeding. The spectrum of oral contraceptive-induced colonic bleeding may vary from mucosal injury with massive colonic bleeding to transmural infarction. Only the clinical follow-up would determine the severity of the involvement and that would determine whether surgical intervention will be necessary.

Adult↗

Side effects of diazoxide.

Diazoxide given for hypertensive crises caused severe complications in two patients. Hypotension, anginal syndrome, cerebral ischemia, and right hemiplegia developed in one patient, and myocardial infarction in the other.

Acute Disease↗

Gastrocolic fistulae in benign peptic ulcer disease.

Occurence of gastroenteric fistulae in non-surgically treated peptic ulcer disease is rare as suggested by only 26 cases published in the literature so far. We had the opportunity to care for 3 patients with this problem in a period of one year. At our institution, a search of the medical records dating back to 1955 yielded one additional case. Most of our patients had a history of salicylate or corticosteroid intake. We present here the details of these cases and discuss the possible role of the location of the ulcer and ulcerogenic anti-inflammatory drug ingestion in the causation of gastroenteric fistula. We believe the incidence of this uncommon entity may rise significantly with the more common use of salicylates and corticosteroids.

Adult↗

Esophageal carcinoma with pseudohyperparathyroidism and hypercorticism.

An unusual case of bihormonal activity by squamous cell carcinoma of the esophagus is presented. It is a rare presentation of esophagus carcinoma because of the following reasons: 1. Synthesis of cortisteroids by esophageal carcinoma. 2. Pseudohyperparathyroidism caused by the same tumor. 3. Presentation of hypokalemic alkalosis as the initial manifestation and lack of specific gastrointestinal symptomatology of esophageal carcinoma.

Carcinoma, Squamous Cell↗

Comparison of some permeability properties of rat liver slices, liver cells in suspension, and in vivo-produced aggregates of dispersed liver cells.

It has been reported earlier that when rat liver is dispersed to a single cell suspension, the parenchymal cells lose the ability to take up pyrimidine bases but acquire the ability to take up RNAase and macromolecular nucleic acids. It is now shown that these changes are largely reversed on intraperitoneal reaggregation of the parenchymal cells and that, in these respects, the aggregates behave more like the organized tissue than like the dispersed cells.

Animals↗

Effect of cell concentration on the uptake of amino acids by rat liver parenchymal cells in suspension.

The accumulation of several amino acids in the acid-soluble fraction and their incorporation into protein in rat liver parenchymal cell suspensions, has been shown to depend on the concentration of cells in the incubation medium; the uptake, both in the acid-soluble and the acid-insoluble fractions, decreased as the cell concentration increased from 0.03 X 10(6) cells/ml upwards, reaching a plateau at high cell concentrations (3-5 X 10(6) cells/ml). The uptake values at high cell concentrations were the same as those obtained in liver slices in which a similar effect was not observed. Evidence is presented which suggests that this phenomenon is mediated by a material released from the cells in suspension, which is inhibitory to enhancement of the uptake of amino acids by these cells over and above the value obtained in normal, adult liver slices.

Amino Acids↗

Postgastrectomy bezoars.

Sixteen cases of postgastrectomy bezoars were diagnosed and treated in the period of five years. Various mechanisms of their information, symptomatology and therapy are discussed. We believe postgastrectomy bezoars are relatively frequent but often missed entities. Considering the relative frequency of this entity and ease of therapy, this condition should not be missed if one is aware of its existence.

Adult↗

Substance P and mitochondrial oxygen consumption: evidence for a direct intracellular role for the peptide.

Substance P (SP), a member of the tachykinin group of peptides, has been shown to augment the sensory discharge of the carotid body, an oxygen sensing chemoreceptor. In this study we present evidence that the excitatory effect of SP, in part, could arise from a direct effect of the peptide on mitochondrial oxidative phosphorylation. Measurement of the partition coefficient of SP showed that the peptide has a relatively high apolar partition, which could be consistent with its distribution across lipid bilayers and in intracellular organelles. In addition, the effects of three concentrations of SP were tested on oxygen consumption of mitochondria isolated from rat hearts. The results showed that while the lower concentration of the peptide (0.5 microM) did not affect O2 consumption, higher concentrations, i.e., 1 and 2 microM, enhanced the rate of state 4 respiration by 52 and 64%, respectively. The rate of state 3 respiration, on the other hand, was unaltered with 0.5 and 1 microM, and was only slightly decreased with 2 microM of the peptide. The ADP:O ratio was unaffected by any concentrations of SP tested. The peptide-induced effect on state 4 respiration was even more pronounced with glutamate as a respiratory substrate and in presence of K+ in the medium. These results indicate that SP, in addition to its more accepted role as a neurotransmitter or modulator in the carotid body, may elicit intracellular response by interfering directly with oxidative phosphorylation.

Adenosine Diphosphate↗

Hageman factor deficiency in ataxia telangiectasia.

Ataxia-telangiectasia is clinically characterized by the presence of cerebellar ataxia, choreoathetosis, and oculocutaneous telangiectasia. Humorocellular immune deficiency may be associated with the disease. So far, no coagulation abnormalities have been reported in patients with ataxia-telangiectasia. Presence of Hageman factor deficiency in our patient could merely be a coincidental occurrence of two rare independent disease states. Since this coagulation abnormality in Hageman factor deficiency is rather subtle and not usually associated with clinically significant bleeding, this defect can be easily overlooked.

Adult↗

G proteins in carotid body chemoreception.

G proteins are signal coupling molecules that play major roles in mediating the effects of transmitters as well as certain sensory signals. In the present study we examined whether oxygen chemoreception in the carotid body is coupled to G proteins. Experiments were performed on carotid bodies isolated from anesthetized cats. Presence of G proteins was examined with ADP-ribosylation of the carotid body membranes. Pertussis toxin (PTX), which inactivates G proteins in neuronal tissues, ADP-ribosylated a single band of carotid body protein with a molecular mass of 41 kDa. With cholera toxin (CTX) only a faint band of protein corresponding to approximately 45 kDa was evident. Perfusing the isolated carotid bodies with PTX (2.5 micrograms/min; 60 min) attenuated the sensory response to hypoxia by 52% of the controls. Perfusion with CTX (50 micrograms/min; for 60 min), on the other hand, increased baseline activity and potentiated the hypoxic response by 125% of controls. Heat-inactivated toxins, however, had no influence on the carotid body sensory response to hypoxia. These results suggest that G proteins are present in the chemoreceptor tissue and they seem to be coupled to the transduction and/or to the transmission of the hypoxic stimulus.

Animals↗