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Biomedical subjects

S Seto

Publications and source records attributed to S Seto.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney.

It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR.

Animals↗
PubMed1985

Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes.

Deoxyadenosine has been implicated as the toxic metabolite causing profound lymphopenia in immunodeficient children with a genetic deficiency of adenosine deaminase (ADA), and in adults treated with the potent ADA inhibitor deoxycoformycin. However, the biochemical basis for deoxyadenosine toxicity toward lymphocytes remains controversial. The present experiments have examined in detail the sequential metabolic changes induced in nondividing human peripheral blood lymphocytes by incubation with deoxyadenosine plus deoxycoformycin, or with 2-chlorodeoxyadenosine (CdA), an ADA resistant deoxyadenosine congener with anti-leukemic and immunosuppressive properties. The lymphotoxic effect of deoxyadenosine and CdA required their phosphorylation, and was inhibited by deoxycytidine. As early as 4 h after exposure to the deoxynucleosides, strand breaks in lymphocyte DNA began to accumulate, and RNA synthesis decreased. These changes were followed by a significant fall in intracellular NAD levels at 8 h, a drop in ATP pools at 24 h, and cell death by 48 h. Incubation of the lymphocytes with 5 mM nicotinamide, a NAD precursor and an inhibitor of poly(ADP-ribose) synthetase, prevented NAD depletion. The nicotinamide treatment also rendered the lymphocytes highly resistant to deoxyadenosine and CdA toxicity, without altering dATP formation or the accumulation of DNA strand breaks. The poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide exerted a similar although less potent effect. These results suggest that NAD depletion, probably triggered by poly(ADP-ribose) formation, is the principle cause of death in normal resting human lymphocytes exposed to deoxyadenosine plus deoxycoformycin, or to CdA.

Adenosine Triphosphate↗
PubMed1985

Reconstitution of cell-mediated immunity in severe combined immunodeficiency following fetal liver transplantation.

A male infant X-linked, adenosine deaminase-positive severe combined immunodeficiency underwent partial immunological reconstitution by fetal liver transplantation at twenty months of age. Reconstitution of T lymphocytes was observed from sixteen weeks after transplantation, in the increase of T lymphocytes, positive delayed-type skin reaction and in vitro responsiveness to mitogens and allogeneic cells, sequentially. Chimerism was defined by chromosomal analysis and HLA typing, in which one haplotype seemed to be shared between the donor and the host by chance. However, defective immunoglobulin production has not yet been corrected. The assay on T-B lymphocyte interaction in vitro suggested that the failure might be attributed to an intrinsic defect of B lymphocytes, which were cells of donor origin after transplantation. Three years following transplantation, the patient is free of severe infections, although he requires regular injections of gamma globulin.

B-Lymphocytes↗
PubMed1984

Lack of evidence for the participation of tonin in the pathogenesis of one-kidney, one-clip renovascular hypertension.

It has been reported that immunization against tonin normalizes blood pressure, and that sialoadenectomy, during which the tonin-rich salivary glands are removed, decreases blood pressure in one-kidney, one-clip hypertension. To investigate the role of tonin on this form of hypertension further, we actively immunized one-kidney, one-clip hypertensive rabbits with tonin and measured both the blood pressure response and the titer of antibodies raised against tonin. In addition, because sialoadenectomy may alter food intake, we assessed the effect of sialoadenectomy on the blood pressure of one-kidney, one-clip hypertensive rats fed a liquid diet to facilitate eating. After immunization, all rabbits developed antitonin-antibody titers ranging from 1:300 to 1:56,000. However, in none of the rabbits did the blood pressure decrease significantly (114 +/- 3 mm Hg before immunization; 129 +/- 6 mm Hg at 16 weeks after immunization). In one-kidney, one-clip hypertensive rats, sialoadenectomy did not lower blood pressure (179 +/- 5 mm Hg before sialoadenectomy; 202 +/- 9 mm Hg 3 weeks after sialoadenectomy). Neither blood pressure nor body weight differed between sialoadenectomy and sham-sialoadenectomy one-kidney, one-clip hypertensive rats (n = 6). In conclusion, neither active immunization against tonin in one-kidney, one-clip hypertensive rabbits nor sialoadenectomy in one-kidney, one-clip hypertensive rats significantly reduced established hypertension. These results do not support the hypothesis that tonin is involved in the pathogenesis of one-kidney, one-clip hypertension in these animal models.

Animals↗
PubMed1984

[Fundamental and clinical studies on ceftazidime in the field of paediatrics].

Ceftazidime (CAZ), a new cephem antibiotic for injection, was used in the field of paediatrics, and the following results were obtained. Antibacterial activity of CAZ was high against Gram-negative rods including P. aeruginosa, but slightly low against Gram-positive cocci. Absorption and excretion of CAZ were rapid, and 90% or more was excreted at 6 hours after administration. The clinical efficacy was excellent or good in all the 4 cases treated with CAZ, and no side effects were observed.

Age Factors↗
PubMed1982

A study of a female with congenital sideroblastic anemia.

A female infant with congenital refractory sideroblastic anemia is described. A marked reduction of delta-aminolevulinic acid (ALA) synthetase activity of erythroblasts was noticed with and without treatment of pyridoxal phosphate. Mitochondrial neutral protease activity of erythroblasts, which inactivates specifically the apo form of ALA synthetase, was normal and the sensitivity of apo form of ALA synthetase to the neutral protease was also normal. It was speculated that the reduction of ALA synthetase activity is not due to the high speed of destruction, but rather due to the impairment in production of ALA synthetase, which could explain the unresponsiveness to pyridoxine therapy in this case.

5-Aminolevulinate Synthetase↗
PubMed1981

Correction of hypertension by partial nephrectomy in segmental renal artery stenosis and electron microscopic studies of renin.

An 18-year-old man had hypertension with hyperreninemia and marked difference in plasma renin activity between both renal veins after tilting. Selective renal arteriography revealed a stenotic lesion in a segmental artery to the upper pole of the left kidney with poststenotic dilatation. The upper pole of the kidney with abnormal arterial segment was resected and the blood pressure returned to normal. Electron microscopically, a large number of mature juxtaglomerular cell granules were associated with many protogranules in the epitheloid cell. These findings suggest that his hypertension was due to overproduction of renin from the upper pole.

Adolescent↗
PubMed1980

Heptaprenyl pyrophosphate synthetase from Bacillus subtilis.

Heptaprenyl pyrophosphate synthetase was detected in partially purified extracts of Bacillus subtilis. The enzyme catalyzed the synthesis of all-trans C35 prenyl pyrophosphate from isopentenyl pyrophosphate and farnesyl or geranylgeranyl pyrophosphate, but it did not catalyze a reaction between isopentenyl pyrophosphate and either dimethylallyl or geranyl pyrophosphate. The enzyme reaction proceeded with an elimination of 2-pro-R hydrogen of isopentenyl pyrophosphate without accumulation of any prenyl pyrophosphate shorter than C35. The molecular weight of the enzyme was estimated by gel filtration to be 45,000. Michaelis constants for isopentenyl, farnesyl, and geranylgeranyl pyrophosphate were 12.8, 13.3, and 8.3 microM, respectively.

Alkyl and Aryl Transferases↗
PubMed1980

Substrate specificity of squalene synthetase.

22 artificial homologues of farnesyl pyrophosphate were examined for the reactivity as substrate for squalene synthetase of pig liver microsomes. 16 of the homologues were found to be reactive to give corresponding squalene-like products. Extention of the omega-terminal of the carbon chain of farnesyl pyrophosphate is acceptable to the enzyme at least by two carbon atoms in either trans or cis direction (2E,6E)-3,7,11-Trimethyldodeca-2,6-dienyl- and (2E,6E)-3,7-dimethyldodeca-2,6-dienyl pyrophosphates are both good substrates, whereas (2E,6E)-3,7-dimethylundeca-2,6-dienyl-, (2E,6E)-3,7-dimethyl-trideca-2,6-dienyl-, (2E,6E)-3,7-dimethyltetradeca-2,6-dienyl-, (2E,6E)-3,7,10-trimethylundeca-2,6-dienyl-, and (2E,6E)-3,7,12-trimethyltrideca-2,6-dienyl pyrophosphates are poor substrates. These results indicate that the carbon chain length rather than 10,11-double bond is important for the reactivity as substrate. Replacement of 3-methyl of farnesyl pyrophosphate by an ethyl group or introduction of a methyl group at C-4 results in a complete loss of activity.

Animals↗