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Biomedical subjects

Y Okuda

Publications and source records attributed to Y Okuda.

At least 307 records · Page 17Linked to original sources

Pathway and carbon sources for hepatic glycogen repletion in dogs.

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beta-adrenergic stimulation contributes to incretin effect in conscious dogs.

Oral glucose administration increases insulin secretion to a greater extent than peripheral glucose infusion (incretin effect). It also augments protal vein blood flow, hepatic uptake of glucose, and fractional hepatic extraction of insulin. The mechanisms for these various effects are not known but could involve both neurogenic stimuli and gut hormones. The present studies examined the effect of a non-nutrient drink, 1 g/kg body wt oral mannitol, on these parameters during an intravenous glucose infusion in conscious dogs. The dogs had chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, and femoral artery. After a 30-min control period, an infusion of atropine, propranolol, phentolamine, or propranolol and phentolamine was begun. Thirty minutes later, glucose (13 mg.kg-1.min-1) was then infused into a peripheral vein for 120 min with continuation of the atropine and adrenergic blockade. Water or mannitol (10% solution) was administered orally 50 min after the initiation of the glucose infusion. Mannitol, but not water, significantly enhanced the insulin response to intravenous glucose, as indicated by higher insulin concentrations in the portal vein as well as more rapid reduction of the plasma glucose. This incretin effect was significantly attenuated by infusion of propranolol but not by atropine or phentolamine. Mannitol did not increase portal vein blood flow or have any effect on the hepatic uptake of glucose or the fractional hepatic extraction of insulin. Thus absorption of nutrient is not necessary for the incretin effect but is for the increased portal vein blood flow and increased fractional extraction of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Double aortic arch associated with coarctation of both limbs: a case report.

A case of double aortic arch with coarctation of both limbs is described. The patient, a thirteen-year-old girl, demonstrated only the symptoms of coarctation and had no intracardiac anomalies. Discrete coarctation of bilateral limbs distal to the subclavian artery was shown by aortography. Although either double aortic arch or coarctation of the aorta is not so rare, the combination of these two anomalies is quite unusual. This is the third case in the world literature.

Abnormalities, Multiple↗

Ketone body utilization and its metabolic effect in resting muscles of normal and streptozotocin-diabetic rats.

By using an in situ rat hindquarter perfusion, we evaluated ketone body utilization and its metabolic effects in the resting muscle of 24 h fasted normal and streptozotocin (STZ)-diabetic rats. Under the perfusion with ketone body-supplementation (1 mM each of acetoacetic acid (AcAc) and 3-hydroxybutyric acid (3-OHB], the AcAc and 3-OHB uptake of STZ-diabetic rats was significantly (P less than 0.05) smaller than that of normal rats. This might be explained by the low enzyme activity of 3-oxoacid CoA transferase demonstrated in the hindlimb muscles of STZ-diabetic rats and this reduced ketone body uptake would be one of the causes of the development of diabetic ketoacidosis. The glucose uptake and the phosphofructokinase (PFK) activity of normal rats were significantly (P less than 0.05) higher than those of STZ-diabetic rats. In both normal and STZ-diabetic rats, the glucose utilization and PFK activity of the muscles in the ketone body-supplemented condition were significantly (P less than 0.05) lower than those in the non-supplemented condition. This inhibition of glucose utilization by ketone bodies should be due to the mechanism by which the oxidation of ketone bodies inhibits PFK in the muscle.

Animals↗

Oral insulin in diabetic dogs.

Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

Administration, Oral↗

[Diagnosis of male infertility].

The diagnostic methods for male infertility in our clinic are reviewed, and the following are emphasized. In azoospermia, examinations for obstructive azoospermia such as testicular biopsy should be made focussing on patients with 10 ml or higher testicular volume and with 20 mIU/ml or lower serum FSH level. In hypospermic patients, examination of post-ejaculated urine and ultrasonotomography examination of prostate are necessary for the diagnosis of incomplete retrograde ejaculation and obstruction or stenosis of the ejaculatory ducts.

Algorithms↗

Effect of oral glucose ingestion on hepatic non-esterified fatty acids and ketone body metabolism in normal dogs.

The time course of changes in hepatic lipid metabolism (non-esterified fatty acids (NEFA), ketone body) after ingestion of glucose was assessed in normal dogs. Glucose ingestion suppressed significantly (p less than 0.01) the amount of NEFA reaching the liver (12.4 +/- 1.0 to a nadir of 2.9 +/- 0.6 mumol/kg/min at 80 min) and increased significantly (p less than 0.05) net hepatic balance (-1.8 +/- 0.6 to 0.5 +/- 0.4 mumol/kg/min at 120 min). After glucose ingestion, the amount of total ketone body presented to the liver decreased significantly (p less than 0.05) to a nadir of 1.1 +/- 0.4 mumol/kg/min at 60 min and gradually increased after 120 min. These changes reflect the increased insulin secretion induced by glucose ingestion. The hyperinsulinemia would inhibit peripheral lipolysis and stimulate esterification of fatty acids. It would reduce ketone body concentration both by a direct effect on hepatic production as well as the consequence of diminished NEFA levels. In summary, the present study clearly demonstrated the time course changes in NEFA and ketone body level after oral glucose ingestion.

Animals↗

Effect of glucose and an aldose reductase inhibitor on myo-inositol uptake by cultured human endothelial cells.

The effects of an aldose reductase (AR) inhibitor, elevated glucose and other compounds were evaluated on in vitro 2-[3H] myo-inositol (MI) uptake in cultured human endothelial cells (ECs). Significant AR activity was present in ECs (1,373 +/- 170 mumol/mg.min: incubated with 28 mM glucose for 48 hr). Since Na(+)-deprivation and the addition of Ouabain (5 mM) significantly reduced MI uptake, MI incorporation into ECs might be dependent on an active transport system via Na(+)-K+ ATPase activity. MI uptake was reduced significantly (21 +/- 6, 39 +/- 7% reduction) in the presence of excess glucose (27.5, 55 mM). However, addition of the AR inhibitor (ONO-2235 100 microM) prevented the glucose mediated inhibition of MI uptake (15 +/- 5, 21 +/- 6% reduction). These results suggest that inhibition of AR might prevent glucose-mediated toxicity via an increment of MI uptake.

Aldehyde Reductase↗

Ascorbic acid prevents the inhibition of DNA synthesis induced by high glucose concentration in cultured human endothelial cells.

Effects of glucose and ascorbic acid on in vitro collagen and DNA synthesis were evaluated in human umbilical vein endothelial cells. Ascorbic acid significantly potentiated collagen synthesis. Incubation of cells with elevated glucose concentration for 24h significantly reduced [3H]-thymidine uptake (2h). However, the addition of ascorbic acid (0.1 mM) dramatically prevented the inhibition of thymidine uptake. Based on these data, it is suggested that ascorbic acid supplementation in diabetics may prevent or ameliorate diabetic angiopathy.

Ascorbic Acid↗

[A case of rheumatoid arthritis complicated with auranofin-induced acute interstitial pneumonitis].

A case of auranofin(AF)-induced acute interstitial pneumonitis in a patient with rheumatoid arthritis (RA) is reported and possible mechanism of the incidence is discussed. A 57 year-old woman with a history of RA starting in early April 1989, had been prescribed AF for seven days prior to her referral to this hospital. Because of the severity of her polyarthritis, AF was discontinued; therapy with gold sodium thiomalate (GST) instead was started on 23 June 1989. The patient responded quite favorably. At a total cumulative dose of 160mg of GST, however, she developed generalized exfoliative dermatitis and the drug was discontinued. On 29 Sept. 1989 when her skin lesions cleared up completely, she was put on AF again. Six days after resumption of AF therapy, she developed fever. Nonproductive cough and dyspnea on exertion was observed within the following three days. The chest X-ray film revealed diffuse reticular-linear infiltrates more prominently in both upper lobes. Arterial blood gas studies showed hypoxemia and a restrictive ventilatory defect was demonstrated by pulmonary function studies. AF was stopped. High dose pulse iv corticosteroid(CS) therapy combined with oral CS was instituted. Immediate improvement of both subjective and objective findings was observed. By using the patient's peripheral blood lymphocytes, delayed lymphocyte stimulation test(DLST) against the probable causative agents was performed before the bolus CS therapy. Stimulation Index(shown in percentage) was markedly elevated in AF(724%) as compared with GST(163%). The fiberoptic bronchoscopy with bronchoalveolar lavage(BAL) was performed. Analysis of BAL fluid revealed increased cellularity (9 x 10(5)/ml) with marked lymphocytosis of 79%.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

[Influence of stellate ganglion resection on intracranial pressure].

This study was designed to investigate the influence of stellate ganglion resection on intracranial pressure and blood flow through common carotid and vertebral arteries in 10 mongrel dogs. Following anesthesia with diazepam and pancuronium, each dog was intubated and ventilated to maintain normocapnia. Intracranial pressure was measured with a subdural catheter (Nihon Koden) inserted through right and left temporal burr holes. The right and left common carotid and vertebral arteries were surgically identified, and blood flow estimated with an ultrasonic probe (Transonic T201). After baseline measurement, the stellate ganglion was resected on the right side in 5 dogs, and on the left in the remaining animals. There were no significant change in intracranial pressure. After stellate ganglion resection, there was a significant increase in blood flow through the ipsilateral common carotid and vertebral arteries, but there were significant decreases in flow through the contralateral vessels.

Animals↗

Idiotype-specific T helper clones recognize a variable H chain determinant.

Previously we described a Th clone specific for a regulatory idiotype on 3A4, an anti-Id mAb that mimics a murine L1210/GZL tumor-associated Ag. In our studies, we determined the molecular target on the stimulating anti-Id antibody that is recognized by the Th clone. The Th clone responds with proliferation to the H chain of 3A4 but not to the L chain. Furthermore, the 3A4 chain stimulates this Th clone more efficiently than either the intact 3A4 or the Fab fragments, and the presentation by APC of the H chain is more resistant to chloroquine treatment than the presentation of the intact 3A4 molecule. These results suggest that regulatory T cells "see" their target idiotopes as linear sequence determinants present on isolated Ig chains, and show that this might have biologic advantages with respect to the mechanism of Ag presentation.

Animals↗

Basophil histamine release by platelet-activating factor in aspirin-sensitive subjects with asthma.

Histamine release induced by platelet-activating factor (PAF) from leukocytes of aspirin-sensitive subjects with asthma was higher than that from normal control subjects, despite the similarity of anti-IgE-induced histamine release. Moreover, basophils of some aspirin-sensitive subjects with asthma released histamine by PAF stimulation in the absence of cytochalasin B that affects histamine release and is required in PAF-induced histamine release from leukocytes of atopic subjects with asthma and normal control subjects. In addition to temperature dependency and inhibition by ethylenediaminetetraacetic acid reported previously, PAF-induced histamine release was enhanced by cytochalasin B and indomethacin and inhibited by dexamethasone. These features are common with IgE-mediated histamine release and suggest the existence of the common pathway to PAF-induced histamine release and IgE-mediated histamine release. The results in the present study indicate the pathophysiologic significance of PAF-induced histamine release and that activation of basophils by PAF may be relevant to the pathogenesis in some aspirin-sensitive subjects with asthma.

Adult↗

Characterization of two polysaccharides having activity on the reticuloendothelial system from the root of Glycyrrhiza uralensis.

Two polysaccharides, called glycyrrhizans UA and UB, were isolated from the root of Glycyrrhiza uralensis Fischer. They were homogeneous on electrophoresis and gel chromatography, and showed reticuloendothelial system-potentiating activity in a carbon clearance test. Glycyrrhizan UA is composed of L-arabinose: D-galactose: L-rhamnose: D-galacturonic acid in the molar ratio of 20:14:1:3, and glycyrrhizan UB is composed of L-arabinose: D-galactose: D-glucose: L-rhamnose: D-galacturonic acid in the molar ratio of 12:10:1:10:20, in addition to small amounts of O-acetyl groups and peptide moiety, respectively. About 10% (glycyrrhizan UA) and 35% (glycyrrhizan UB) of the D-galacturonic acid residues exist as the methyl esters. Methylation analysis, carbon-13 nuclear magnetic resonance and periodate oxidation studies indicated their structural features.

Electrophoresis, Polyacrylamide Gel↗

Successful treatment of a metastatic hormone-producing adrenal cancer by a combination of mitotane, tegafur and surgical resection.

A 34-year-old man had a huge hormone-producing adrenal cancer with multiple lung metastases, direct liver invasion and a tumor thrombus in the inferior vena cava. Initial treatment was mitotane alone. The dose of mitotane was 2 g/day initially and gradually increased to 15 g/day in combination with 600 mg of tegafur per day. During the initial phase of chemotherapy, the serum mitotane level was relatively low (2.9-4.6 micrograms/ml) and the pulmonary metastases tended to grow in size in spite of a gradual decline in urinary 17-KS and 17-OHCS and a regression of the primary tumor. A seemingly marked increase in serum mitotane (20.5-34.5 micrograms/ml) was coincident with the addition of tegafur. Rapid and consistent regression of the primary tumor occurred. This excellent response to the chemotherapy made the primary tumor with liver invasion and the metastases resectable. The adverse effect of mitotane, central nervous toxicity, appeared to be serum mitotane level dependent. The present results, together with previous reports in the literature, seem to recommend the following therapeutic approaches to advanced adrenal cancer: monitoring of the serum level may be useful in predicting the efficacy as well as the occurrence of side effects of mitotane, surgical treatment of the lesions should be performed whenever possible, even though it may be only palliative, and the combination of mitotane and tegafur is a choice of chemotherapy which should be evaluated in future studies.

17-alpha-Hydroxypregnenolone↗

Identical embryopathogenesis for exencephaly and myeloschisis: an experimental study.

Extensive histological and immunohistochemical studies were performed to elucidate the histopathogenesis of exencephaly induced in chick embryo as an experimental model. The findings were compared with those identified in a chick myeloschisis experimental model and in human autopsy cases. The experimental model of exencephaly in chick embryos was developed by induction with various teratogens including ethylnitrosourea, salicylate, and phenytoin. None of the cases of exencephaly was exposed to a teratogen prior to or within Hamburger and Hamilton stage 12 (45 to 49 hours postincubation), when the anterior neuropore closes. The process of overgrowth in development of exencephaly was identical to that of myeloschisis, and the results suggested neuronal overmaturation in the histological and immunohistochemical studies. Although the late-stage degenerative change with neovascularization over the exposed neural tissue (placode) was more severe in human exencephaly, the present experimental study may suggest a possible common embryopathogenesis of dysraphism. Exencephaly should be regarded as the most severe form of cranium bifidum, as myeloschisis is in spina bifida.

Animals↗

[Two cases of rheumatoid arthritis complicated with vasculitis-induced ischemic enterocolitis].

Episodes of catastrophic entero-colitis associated with mesenteric vascular insufficiency in patients with rheumatoid arthritis(RA) have rarely been recorded thus far. We herein report two cases of RA complicated with severe attacks of entero-colitis presumably due to mesenteric vasculitis. Surgical intervention was necessary in the first case, while the second patient recovered well only through conservative therapy. Case 1: A 74-year-old man with history of RA since 1985 started to complain of abdominal discomfort and nausea early in February, 1989. On February 12, Episodes of tarry stool developed. Rapid down-hill clinical course prompted laparotomy under the clinical diagnosis of peritonitis. Ischemic changes were observed at the ileum end, the entire length of which was 120 cm orally from the cecum. The site was resected. Multiple linear and aphthoid ulcer lesions were discovered throughout the entire lumen. Histopathologically, evidence of necrotizing vasculitis such as fibrinoid necrosis and mural thrombi was demonstrated in small arteries of the submucosal layer underlying the ulcer lesion. Case 2: A 63-year-old woman who had been suffering from RA since 1980 noticed the onset of nausea, abdominal pain and bloody diarrhea in July, 1989. Colonoscopy examination revealed multiple linear and aphthoid ulcers in the sigmoid colon which was presumed to be due to ischemia. Laboratory evaluation at that time demonstrated hypocomplementemia, positive circulating immune complex and high titer of anti-DNA antibody. Corticosteroid therapy with moderate dose was successful in alleviation of all the abnormal findings and the patient fully recovered three months after her initial GI episode.

Aged↗