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Biomedical subjects

F Goto

Publications and source records attributed to F Goto.

At least 145 records · Page 8Linked to original sources
PubMed1987

S-mephenytoin 4-hydroxylase is inherited as an autosomal-recessive trait in Japanese families.

The 4-hydroxylation of S-mephenytoin exhibits polymorphism in both whites and Japanese such that the populations can be divided into extensive and poor metabolizers. To determine whether genetic constitution is a primary determinant in the expression of such metabolism, four extended Japanese families containing 13 sets of parent/offspring relationships were phenotyped for their mephenytoin 4-hydroxylation activity using the 8-hour urinary ratio of unchanged R- and S-mephenytoin as the trait measurement. The incidence of the poor metabolizer phenotype in these families was 2.2 times greater than that in an unrelated Japanese population. In three families in which both parents were poor metabolizers of mephenytoin, all six children also exhibited the poor metabolizer trait. The phenotype distribution for each family studied was consistent with the hypothesis that mephenytoin 4-hydroxylation activity is under diallelic, monogenic control, with the poor metabolizer phenotype being the autosomal recessive homozygous genotype and the extensive metabolizer phenotype including both the autosomal dominant and heterozygous genotypes.

Alleles↗
PubMed1987

[Mechanism of the renin-angiotensin system and thromboxane A2 on the maintenance of GFR during reduced renal perfusion pressure in dogs].

The interaction between the renin-angiotensin (RA) system and thromboxane A2 (TXA2) was examined in dogs, before and during the renal artery pressure (RAP) was decreased. Intrarenal arterial administration of a small dose of angiotensin II (AII) reduced renal blood flow (RBF) and glomerular filtration rate (GFR) in non-treated dogs when RAP was maintained at the normal level. When mean RAP was decreased to 60 mmHg by means of an aortic clamp, AII reduced RBF, but increased GFR up to 122% of the control value. In dogs pretreated by captopril, GFR decreased when RAP was reduced to 60 mmHg, while RBF was well maintained. However, with the administration of AII, RBF decreased markedly. By indomethacin pretreatment, GFR and RBF decreased during reduced RAP, and their reduction rates were accelerated with the administration of AII into the renal artery. By pretreatment with the thromboxane A2 synthetase inhibitor UK38485, the changes of RBF and GFR following AII infusion were similar to nontreated dogs at normal RAP, but during reduced RAP, AII infusion into the renal artery decreased GFR to 80% of the control value. The thromboxane B2 (TXB2) production by the renal cortex during reduced RAP increased to 2.7-fold that at normal RAP, but TXB2 production did not increase during reduced RAP in captopril pretreated dogs. These results suggest that the RA system and prostanoids, especially TXA2, are important factors for maintaining GFR at low RAP.

Angiotensin II↗
PubMed1987

Effect of cyclooxygenase and thromboxane synthase inhibition on the response to angiotensin II in the hypoperfused canine kidney.

The potential for endogenous prostaglandin production to modulate the renal vascular response to intrarenal infusions of angiotensin II (AII) was investigated in the canine kidney at varying renal perfusion pressures (RPP), using suprarenal aortic constriction to vary RPP. AII, infused to achieve increments in renal arterial plasma concentrations of 300 pg/ml, induced reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) when RPP was 80 mm Hg or above. When RPP was reduced to 60 mm Hg, AII decreased RBF, but GFR failed to change. The vasoconstrictor response to AII was enhanced by indomethacin (8 mg/kg) at all perfusion pressures, but was not modified by the thromboxane (Tx) A2 synthase inhibitor, UK 38,485 (1 mg/kg). In contrast, the lack of change in GFR in response to AII at a RPP of 60 mm Hg was converted to a significant reduction by both indomethacin and UK 38,485. These observations are consistent with the hypothesis that the effect of AII on RBF is attenuated by renal release of vasodilator prostaglandins at all RPP. However, at low RPP, AII infusion also induces the release a factor that increases GFR. As this response can be prevented by both TxA2 synthase and cyclooxygenase inhibition, it is possible that this factor is TxA2.

Angiotensin II↗
PubMed1986

Production of pyrogen by polymorphonuclear leukocytes during the course of casein-induced peritonitis in rabbits.

Rabbits with casein-induced peritonitis were febrile only during the early stage (1.5 to 12 hours) of inflammation. At that stage, peritoneal exudate cells (PEC) had preformed endogenous pyrogen (EP), while blood leukocytes and leukocytes obtained at the later stage of the inflammatory process did not. Early PEC consisted of 99% polymorphonuclear leukocytes (PMN). As early PEC and highly purified PMN (almost 100% pure) released almost identical amounts of EP, we concluded that PMN were the EP-producing cells in the early PEC. EP from PMN of rabbits was composed of three factors with similar molecular weight (8,000 to 18,000) but different pI values (pI 7.2, 5.4, and 4.5). EP in the three fractions could not be separated from thymocyte comitogenic factor (TMF) in terms of m.w. and pI values. About 60% of EP activity and 92% of TMF activity in the culture supernatant were present in the pI 7.2 fraction. The pI 7.2 factor was weaker in EP activity and stronger in TMF activity than the other acidic fractions (pI 5.4 and 4.5). After high purification, 42 ng of the pI 7.2 factor had one unit of EP activity: one unit of TMF activity was present in 126 pg of highly purified pI 7.2 factor.

Animals↗
PubMed1985

Antihypertensive activity and metabolic rate of prostaglandin E1 in surgical patients under general anesthesia.

Plasma immunoreactive prostaglandin E (iPGE) levels during PGE1 infusion for controlling systemic blood pressure were investigated. Differences in systemic blood pressure changes between halothane-nitrous oxide-oxygen (GOF) anesthesia groups and a neuroleptanesthesia (NLA) group during infusion in hypertensive surgical patients were compared. Plasma iPGE concentration increased from 200 +/- 30 pg/ml to 408 +/- 55 pg/ml within 5 minutes at the beginning of PGE1 infusion. After the cessation of PGE1 infusion, iPGE levels quickly returned to pre-infusion levels, but blood pressure had not recovered to pre-infusion levels within 30 minutes. Blood pressure was well controlled with PGE1 infusion, but the pressure changes in GOF anesthesia group were significantly larger than those in the NLA group. The results suggest that the long anti-hypertensive action of PGE1 could be effective to control blood pressure in hypertensive surgical patients during and after surgery.

Alprostadil↗
PubMed1985

Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations.

Interethnic differences in debrisoquin and mephenytoin hydroxylation have been compared between normal white (n = 183) and Japanese (n = 100) subjects with the 8-hour urinary metabolic ratio of debrisoquin and the urinary S/R enantiomeric ratio of mephenytoin to identify extensive (EM) and poor (PM) metabolizers. In white subjects the frequency of PMs was 8.7% and 2.7% for debrisoquin and mephenytoin, respectively. In contrast, in Japanese subjects no PMs of debrisoquin were identified, while the incidence of PMs of mephenytoin was 18%. These substantial differences (P less than 0.001) in polymorphic distributions of oxidative drug metabolizing ability have implications for interethnic efficacy and toxicity of drugs and other xenobiotics that are metabolized by the involved cytochrome P-450 isozymes.

Administration, Oral↗
PubMed1984

The effect of surgical stress on plasma 6-keto-PGF1 alpha concentrations in laparotomized patients under general anesthesia.

Plasma concentrations of a stable metabolite of prostacyclin, 6-Keto-PGF1 alpha, were measured in twenty-three adult patients who received abdominal surgery. Comparisons were made of plasma 6-Keto-PGF1 alpha levels and blood pressure between younger (under 35 years old) and senior (over 65 years old) patients. In the preanesthetic and anesthetic period before surgery, the undetectable levels in plasma 6-Keto-PGF1 alpha were unchanged in both groups. Plasma 6-Keto-PGF1 alpha concentration increased significantly to the same levels in both groups at the beginning of surgery. It remained at a high level through the surgery period in the younger group, but decreased to the preanesthetic period level in the senior group. Systolic blood pressure increased significantly during surgery in the senior group but not in the younger group. There is no doubt that surgical stress is a potent stimulus for prostacyclin formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Generation of an interleukin-I-like lymphocyte-stimulating factor at inflammatory sites: correlation with the infiltration of polymorphonuclear leucocytes.

Using a mouse thymocyte co-stimulation assay, we demonstrated thymocyte-stimulating activity in murine peritoneal fluid obtained from the early stage (3 to 9 h) of casein-induced inflammation. This early inflammatory stage coincided with the time at which an influx of polymorphonuclear leucocytes (PMN) into the inflamed site was observed. Similar thymocyte-stimulating activity was produced in vitro by PMN purified from 4-h peritoneal exudate but not by purified PMN obtained at a later stage (24 h) of the inflammation. The inflammatory factor was interleukin (IL)-I-like; it was devoid of IL-2 activity when tested with IL-2-dependent cells. It could stimulate murine thymocytes to produce IL-2. On a Sephadex G-75 column, the factor was eluted between the molecular sizes of 10 000 and 30 000; its peak activity was at 21 000. The factor mainly consisted of two (pI 6.5 and pI 5.0) iso-electrophoretically different factors.

Animals↗