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Biomedical subjects

T Gomi

Publications and source records attributed to T Gomi.

At least 109 records · Page 6Linked to original sources
PubMed1989

Captopril, an angiotensin I-converting enzyme inhibitor, decreases proteinuria in hypertensive patients with renal diseases.

A crossover study was planned in order to compare the effects of captopril and slow channel calcium entry blocker (Ca antagonist) on urinary protein excretion in 7 hypertensive patients with renal diseases, including 4 with IgA nephropathy, 2 with lupus nephritis and 1 with benign nephrosclerosis. Captopril decreased urinary protein excretion by 52% without any change in creatinine clearance, while Ca antagonist was having a slight effect on proteinuria even though the drug showed an equivalent antihypertensive effect as captopril. These results suggest that the attenuation of proteinuria induced by captopril may be related to an inhibition of angiotensin II formation and/or a direct action of this drug on protein permeability of glomerular basement membrane.

Adult↗
PubMed1989

Effect of sodium restriction on platelet function in patients with essential hypertension.

The effects of sodium intake on blood pressure and platelet function were evaluated in 19 subjects with essential hypertension (10 men and 9 women; mean age 49.7 years). The study was conducted under 3 conditions: (1) normal sodium diet (12 g/day of salt was used in cooking), (2) after 5 days of mild sodium restriction diet (6 g/day of salt was used in cooking) and (3) after moderate sodium restriction (no salt was used in cooking). Blood pressure was significantly reduced following sodium restriction without any change in heart rate. The ratio of the plasma level of beta-thromboglobulin to platelet factor IV, regarded as the most reliable index for platelet activation in vivo, increased significantly after mild sodium restriction; this change was maintained after moderate sodium restriction. Plasma thromboxane B2, a stable metabolite of thromboxane A2, increased significantly after sodium restriction; the level of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostacyclin, was unaffected. These results indicate that dietary sodium restriction induces both a reduction of blood pressure and an activation of platelet function in vivo. Thus, one must consider both antihypertensive effects and effects on platelet function as factors in adjusting the dietary sodium intake in the course of antihypertensive therapy.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of sodium intake on the hypotensive effect of calcium antagonists.

To clarify the influence of Na balance on the hypotensive effect of calcium antagonists, the changes of blood pressure and humoral factors after a single oral administration of 40 mg nicardipine were evaluated in 15 subjects with essential hypertension under high, normal, and low Na regimens (mean 24 hour urinary Na excretion: 320 +/- 24, 147 +/- 7, 27 +/- 6 mEq, respectively). Nicardipine induced a significant reduction of mean blood pressure and increase in heart rate. The change of mean blood pressure after nicardipine was negatively related to the pretreatment mean blood pressure under the three levels of Na intake (p less than 0.01). The slopes of the correlation lines for high, normal, and low Na regimens were -0.61, -0.69, and -0.52, respectively, without statistical significance. Nicardipine brought about significant increases in plasma renin activity and plasma norepinephrine, but no changes in plasma levels of epinephrine, 6-keto-prostaglandin F1 alpha, thromboxane B2 or serum aldosterone concentration. These results suggest that the magnitude of the untreated blood pressure and thereby the peripheral resistance are major determinants of the blood pressure fall caused by calcium antagonists, and that the failure to increase aldosterone and epinephrine in the face of peripheral vasodilation may be responsible in part for the hypotensive effect of this drug.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effects of guanfacine monotherapy on blood pressure, heart rate, plasma renin activity, aldosterone, and catecholamines in hypertensive patients with chronic glomerulonephritis.

Effects of guanfacine, a centrally acting antihypertensive, on blood pressure, heart rate, plasma renin activity, serum aldosterone, plasma norepinephrine, and renal function were evaluated in 16 patients with hypertension with biopsy-proved chronic glomerulonephritis. Guanfacine monotherapy with a daily dose of 1 to 2.5 mg at bedtime for 6 months brought about a significant reduction in blood pressure (171 +/- 2/110 +/- 2 to 144 +/- 2/89 +/- 1 mm Hg; P less than 0.01), with concurrent decreases in heart rate (78 +/- 2 to 70 +/- 2 bpm; P less than 0.01), plasma renin activity (1.96 +/- 0.12 to 1.21 +/- 0.19 ng/ml/hr; P less than 0.05), aldosterone (14.6 +/- 1.5 to 9.7 +/- 0.9 ng/dl; P less than 0.05), plasma norepinephrine (220.5 +/- 24.2 to 132.8 +/- 27.7 pg/ml; P less than 0.05). There was no change in serum creatinine, beta 2-microglobulin, or endogenous creatinine clearance during guanfacine monotherapy. Our data suggest that guanfacine exerts its antihypertensive effect via the inhibition of sympathetic outflow and in part the suppression of the reninangiotensin-aldosterone system and that guanfacine is suitable for the effective treatment of hypertension associated with chronic glomerulonephritis.

Adult↗
PubMed1988

Relationship between transient DNA hypomethylation and erythroid differentiation of murine erythroleukemia cells.

The state of DNA methylation in mouse erythroleukemia (MEL) cells has been analyzed in relation to commitment to differentiation in response to treatment with hexamethylenebisacetamide (HMBA). Previous experiments have shown that induction by HMBA involves transient genome-wide hypomethylation of DNA that is achieved by replacement of 5-methylcytosine with cytosine residues. The experiments described in the present communication revealed that hypomethylation is a very early event in the process of differentiation. Exposure of the cells to 3-deazaadenosine, an adenosine analog, in combination with homocysteine, resulted in the intracellular accumulation of 3-deazaadenosylhomocysteine, which caused an inhibition of HMBA-induced hypomethylation that was correlated with a comparable inhibition of differentiation. While these experiments suggest that hypomethylation is a necessary step in the process of differentiation, other experiments reported here indicate that hypomethylation of DNA may be necessary but not sufficient to trigger the whole program of differentiation in MEL cells. We found, for example that exposure of the cells to cycloheximide during the first 24 hr of induction by HMBA resulted in complete inhibition of differentiation without significant effect on the HMBA-induced hypomethylation. This result also indicates that the enzymatic machinery required for the hypomethylation of DNA is present in uninduced cells.

Acetamides↗
PubMed1988

Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver.

Five cDNA clones encoding rat liver guanidinoacetate methyltransferase (S-adenosyl-L-methionine: guanidinoacetate N-methyltransferase, EC 2.1.1.2) were isolated from a lambda gt11 cDNA library by use of a polyclonal antibody to the purified enzyme. Sequence analysis of the longest cDNA indicated that it consisted of 711 base pairs (bp) of coding region, 51 bp of 5' noncoding region, and 162 bp of 3' noncoding region excluding the poly(A) tail. The amino acid sequence deduced from the cDNA contained the sequences of NH2-terminal and three tryptic peptides. The predicted amino acid composition and molecular weight were in excellent agreement with those obtained with the purified enzyme. Introduction of the cDNA into plasmid pUC118 having the lac promoter resulted in a production in Escherichia coli of a Mr 26,000 polypeptide in the presence of isopropyl beta-D-thiogalactopyranoside. This protein represented as much as 5% of the bacterial soluble protein and showed the guanidinoacetate methyltransferase activity. Sequence analysis and tryptic peptide mapping indicated that the enzyme obtained by the recombinant DNA procedures was structurally identical to the liver enzyme, except for the absence of the NH2-terminal blocking group. Also, the enzyme showed kinetic properties indistinguishable from those of the liver enzyme.

Amino Acid Sequence↗
PubMed1988

Plasma beta-thromboglobulin to platelet factor 4 ratios as indices of vascular complications in essential hypertension.

The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.

Blood Platelets↗
PubMed1987

Amino acid sequence of S-adenosyl-L-homocysteine hydrolase from rat liver as derived from the cDNA sequence.

Rat liver cDNA libraries constructed in lambda gt11 were screened for reactivity with polyclonal antibodies to native S-adenosyl-L-homocysteine (AdoHcy) hydrolase (adenosylhomocysteinase; EC 3.3.1.1). Five clones were isolated and sequenced. The amino acid sequence, deduced from the cDNA sequence, contained the sequence of eight peptides obtained by tryptic and cyanogen bromide fragmentation of rat liver AdoHcy hydrolase. Identification of the amino- and carboxyl-terminal peptides in the amino acid sequence showed that the complete sequence was obtained. A "fingerprint" sequence was found that is characteristic of dinucleotide-binding domains of many proteins. For AdoHcy hydrolase, this region from the lysine at position 213 to the aspartate at position 244, containing the sequence Gly-Xaa-Gly-Xaa-Xaa-Gly at positions 219-224, is presumably the site of binding for NAD+, which is required for the activity of the enzyme.

Adenosylhomocysteinase↗
PubMed1986

S-adenosylhomocysteinase from rat liver. Amino acid sequences of the peptides containing active site cysteine residues modified by treatment with 5'-p-fluorosulfonylbenzoyladenosine.

5'-p-Fluorosulfonylbenzoyladenosine (FSBA) inactivates rat liver S-adenosylhomocysteinase exhibiting characteristics of an active site-directed reagent. The inactivation is not associated with the covalent binding of the reagent, but is correlated with the loss of 2 sulfhydryl groups/enzyme subunit (Takata, Y., and Fujioka, M. (1984) Biochemistry 23, 4357-4362). Treatment of the FSBA-inactivated enzyme with iodoacetate in the absence of reducing agent and then with [14C] iodoacetate after reduction with 2-mercaptoethanol yielded the enzyme containing approximately 2 mol of radiolabeled S-carboxymethylcysteine/mol of subunit. Analysis of tryptic peptides showed that the radioactivity was associated with 2 carboxymethylcysteine-containing peptides whose amino acid sequences were: Trp-Ser-Ser-Cys(Cm)-Asn-Ile-Phe-Ser-Thr-Gln-Asp-His-Ala-Ala-Ala-Ala-Ile- Ala-Lys and Gly-Glu-Thr-Asp-Glu-Glu-Tyr-Leu-Trp-Cys(Cm)-Ile-Glu-Gln-Thr-Leu-His-Phe- Lys, respectively. These results indicate that the inactivation of S-adenosylhomocysteinase by FSBA is the consequence of formation of a disulfide between two specific cysteine residues on each of the four identical subunits.

Adenosine↗
PubMed1985

S-Adenosylhomocysteinase from rat liver. Evidence for structurally identical and catalytically equivalent subunits.

Lines of evidence are presented which indicate that rat liver S-adenosylhomocysteinase consists of four identical or nearly identical subunits. Cross-linking of the enzyme with dimethyl suberimidate followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis yields four distinct protein bands with molecular weights of 47,000, 93,000, 145,000, and 190,000. The molecular weight of the largest protein is in excellent agreement with that of the native enzyme. Carboxypeptidase A liberates 4 mol of COOH-terminal tyrosine/mol of enzyme, and the number of arginine-containing peptides in a tryptic digest of the enzyme is one-fourth of that arginine residues present in the enzyme. The enzyme reversibly binds 4 mol of the substrate adenosine in a noninteracting manner, and the binding is associated with the reduction of 3.2 mol of enzyme-bound NAD+. However, in the presence of dithiothreitol, the same compound causes a time-dependent irreversible loss of enzyme activity concomitant with the formation of 3.6 mol of enzyme-bound NADH/mol of enzyme. Studies with adenine-labeled adenosine shows that radioactivity corresponding to 3.8 mol of substrate is tightly bound to the inactivated enzyme. Since the inactivation is apparently the consequence of reaction of dithiothreitol with an enzyme-bound intermediate as revealed by the kinetics of inactivation, these results support the conclusion that the four subunits of rat liver S-adenosylhomocysteinase are functionally equivalent.

Adenosine↗
PubMed1985

Acute and subacute toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1 ,4-dihydropyridine (PP-1466).

The acute and subacute oral toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1,4 -dihydropyridine (PP-1466) was investigated in several animal species in comparison with nifedipine and nicardipine. A clear species difference in LD50 values was found in acute toxicity of PP-1466, and rabbits were the most sensitive between animal species used, then dogs, mice and rats in order. Prominent acute circulatory failure and associated secondary changes were noticed in toxic signs and autopsy findings. PP-1466 as well as nifedipine was apparently less toxic than nicardipine. In the subacute toxicity studies in rats, deaths occurred only in the 2000 mg/kg/d treated groups of both sexes of PP-1466 and nifedipine. Major changes in various observations and examinations were focussed on the cardiovascular system and liver. On the cardiovascular system, it was revealed as congestion and hemorrhage in the various organs and tissues on autopsy finding in dead rats during the test period. A dose-dependent increase in heart weight was observed in rats sacrificed at the termination of the test period. On the liver, it was revealed as a dose-dependent increase in liver weight, changes in liver lipid levels, changes in several serum biochemistry parameters, such as GOT, GPT and ALP (alkaline phosphatase) activities and lipid levels measured at the termination of the test period. These changes were toxicologically mild and functional except the autopsy findings in dead rats. Female rats were slightly more sensitive than males, and PP-1466 was slightly less toxic than nifedipine on subacute oral toxicity in rats.

Administration, Oral↗
PubMed1984

Molecular cloning of cDNA for rat glycine methyltransferase.

Using a highly purified preparation of glycine methyltransferase mRNA, double-stranded cDNA was synthesized and inserted into the PstI site of pBR322. The resulting recombinant DNA was used to transform E. coli X 1776 by conventional methods. Among tetracycline-resistant transformants, a number of colonies were found to contain cDNA sequence for glycine methyltransferase as examined by hybrid-selected translation. A restriction endonuclease cleavage map was constructed covering about 720 base pairs. With the cDNA as the probe, the content of the glycine methyltransferase mRNA was quantitated in various rat tissues and was found to be proportional to the specific enzyme activity.

Animals↗
PubMed1984

Spectrophotometric studies of the interaction of S-adenosylhomocysteinase with adenosine, adenine and cordycepin.

The spectral changes observed on interaction of S-adenosylhomocysteinase with adenine and cordycepin are approximated by the addition of dimethylsulfoxide to the aqueous solutions of these compounds, but not by protonation of the compounds. Although adenosine when bound to the enzyme undergoes partial reactions, it gives a spectral change similar to those obtained with adenine and cordycepin, except for the occurrence of a peak at 327 nm due to the reduction of the enzyme-bound NAD. From these results, it is suggested that S-adenosylhomocysteinase binds the nucleoside substrates mainly through hydrophobic interactions.

Adenine↗