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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 595 records · Page 33Linked to original sources
PubMed1992

An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins.

1. To examine the role of epithelium in the responsiveness of tracheal smooth muscle in rabbit, we measured the contractile responses to acetylcholine (ACh), KCl, 5-hydroxytryptamine (5-HT), histamine, substance P (SP), neurokinin A (NKA), and electrical field stimulation EFS) in intact and epithelium-denuded preparations. 2. Removal of epithelium did not alter the contractile response to any agonist examined, except SP. 3. Removal of epithelium enhances the contractile response to SP. In the presence of phosphoramidon, the contractile response to SP was not significantly different in either group. The results suggest that the effect of epithelium is largely due to degradation of SP by enzymes in the epithelium. 4. Arachidonic acid metabolites did not seem to be related to the responses induced by contractile agonists or EFS. 5. In the presence of SP, the contractile responses and [3H]-choline outflow evoked by EFS were dose-dependently enhanced. Contractile responses to EFS and [3H]-choline outflow evoked by EFS were enhanced by SP significantly more than by NKA. Both were abolished by atropine or tetrodotoxin. 6. These results suggest that rabbit tracheal epithelium may modulate SP-induced contractions, both direct and indirect, by inactivation of SP. This phenomenon is widespread in mammals. The rabbit may be a useful model to examine airway cholinergic functions.

Animals↗
PubMed1992

Directed mutagenesis in an asporogenous methylotrophic yeast: cloning, sequencing, and one-step gene disruption of the 3-isopropylmalate dehydrogenase gene (LEU2) of Candida boidinii to derive doubly auxotrophic marker strains.

A model system for one-step gene disruption for an asporogenous methylotrophic yeast, Candida boidinii, is described. In this system, the 3-isopropylmalate dehydrogenase gene (C. boidinii LEU2) was selected as the target gene for disruption to derive new host strains for transformation. First, the C. boidinii LEU2 gene was cloned, and its complete nucleotide sequence was determined. Next, the LEU2 disruption vectors, which had the C. boidinii URA3 gene as the selectable marker, were constructed. Of the Ura+ transformants obtained with these plasmids, more than half showed a Leu- phenotype. Finally, the double-marker strains of C. boidinii were derived. When vectors with repeated flanking sequences of the C. boidinii URA3 gene were used for gene disruption, Leu- Ura+ transformants changed spontaneously to a Leu- Ura- phenotype ca. 100 times more frequently than they did when plasmids without the repeated sequences were used. Southern analysis showed that these events included a one-step gene disruption and a subsequent popping out of the C. boidinii URA3 sequence from the transformant chromosome.

3-Isopropylmalate Dehydrogenase↗
PubMed1992

Effects of secondary organ failure on compensation of acute heart failure in patients with myocardial infarct and dilated cardiomyopathy.

Compensation for heart failure can be influenced by cardiac loads due to organ failure. This investigation studied the effect of secondary organ failure on the hemodynamics of acute heart failure. Of 106 patients with acute heart failure due to myocardial infarction or dilated cardiomyopathy, 49 (46%) patients had secondary organ failure, either kidney, liver, brain or blood. Their acute heart failure was sustained for significantly longer than that of 57 patients without organ failure. A transient but severe decompensation induced secondary organ failure, although the left ventricular ejection fraction was not different from that of the control without heart failure. Hypervolemia in cases of renal failure, bradycardia in loss of consciousness, hyperdynamic state in anemia and low blood pressure in liver dysfunction caused the sustained acute heart failure. These results suggested that secondary organ failure might occur in 46% of patients with acute heart failure, and might disrupt compensation by different kinds of hemodynamic loads in low cardiac function.

Acute Disease↗
PubMed1992

[Evaluation of enzyme-linked immunosorbent assay for serodiagnosis of Bordetella bronchiseptica infection in guinea pigs].

An enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of Bordetella bronchiseptica (B. bronchiseptica) infection in guinea pigs was evaluated. An isolate of B. bronchiseptica from lung lesion of a guinea pig was used as antigen after ultrasonication. In the experimental infection, specific pathogen-free guinea pigs inoculated with the bacterium intranasally were examined every 5 or 10 days. The organism was recovered from all animals between 5 and 30 days post-inoculation (p.i.). Only one animal was sero-positive by agglutination test 30 and 50 days p.i.; whereas, by ELISA, one animal was positive 5 days p.i., and all the animals showed strong reaction 20 to 50 (end of experiment) days p.i. Field samples obtained from 1983 to 1989 were tested by ELISA. The results corresponded to those of macroscopic observations and bacterial isolation. The ELISA proved to be useful method for detection of B. bronchiseptica infection in guinea pigs.

Animals↗
PubMed1992

[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].

Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of calmodulin inhibitors on amylase secretion from rat pancreatic acini.

To investigate the role of calmodulin in stimulus-secretion coupling in pancreatic acinar cells, we studied the effects of W-7, a calmodulin inhibitor, and KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM kinase II), on amylase secretion from rat pancreatic acini. Calmodulin inhibitor (W-7, 100 microM) and Ca2+/CaM kinase II inhibitor (KN-62, 10 microM) reduced amylase secretion stimulated by cholecystokinin (CCK) or carbachol. W-7 and KN-62 also inhibited amylase secretion stimulated by both calcium ionophore (A23187) and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA). To clarify the role of calmodulin in the interaction of intracellular mediators, pancreatic acini were permeabilized with streptolysin O. Following permeabilization, amylase secretion was stimulated by submicromolar free Ca2+, and this Ca(2+)-dependent amylase secretion was enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), TPA or cyclic adenosine 3',5'-monophosphate (cAMP). W-7 and KN-62 had no effects on amylase secretion stimulated by Ca2+ alone, but inhibited the enhancement in Ca(2+)-dependent amylase secretion by GTP gamma S, TPA or cAMP. These data suggest that calmodulin plays an important role in Ca(2+)-dependent amylase secretion from pancreatic acinar cells and in the interaction between Ca2+ and other intracellular messengers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

[Left ventricular filling disturbances in cardiac amyloidosis: a study of atrial sound and diastolic inflow velocities].

Cardiac amyloidosis is characterized by left ventricular filling disturbances in a relatively early stage. To investigate such disturbances more precisely, we studied atrial sound and left ventricular inflow velocity patterns. Twelve cases diagnosed as cardiac amyloidosis according to the clinical criteria including rectal biopsies and serum amyloid proteins or at autopsy were reviewed and analyzed. Their mean age was 60.9 +/- 12.5 years. Twelve age-matched cases with hypertrophic cardiomyopathy (HCM) served as the controls. We measured the amplitude of atrial sound by low-frequency phonocardiograms and the ratio of the heights of the A wave of apexcardiograms (ACG) to the total amplitude of the ACG. The mitral inflow velocity patterns were recorded using pulsed Doppler echocardiography. The rapid filling wave (R), atrial filling wave (A) and the ratio of A to R (A/R) were measured. In the amyloidosis group, atrial sound moderately increased in 2 cases, it was faint in 9 and not manifest in the remaining one. The A wave in the amyloidosis group was significantly smaller than that in the HCM group (p < 0.001) (12.4 +/- 3.9 vs 22.4 +/- 5.6%). In the left ventricular inflow velocity patterns, the R in amyloidosis was smaller than that in HCM (41.7 +/- 16.0 vs 56.4 +/- 12.1 cm/sec) (p < 0.02). The A in amyloidosis was also smaller than that in HCM (40.5 +/- 13.4 vs 58.1 +/- 13.0 cm/sec) (p < 0.006). The A/R was 1.0 +/- 0.34 in amyloidosis and 1.1 +/- 0.32 in HCM (N.S.). Both A and R were significantly less in amyloidosis than those in HCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Iron deficiency anemia and hypoproteinemia induced by fresh cow's milk].

We reported two patients who developed severe iron deficiency anemia and hypoproteinemia which were induced by excessive drinking cow's milk. Case 1, a 23-month-old girl, had started drinking 800-1,000ml of cow's milk everyday since the age of 9 months. She developed generalized edema at the age of 23 months and visited Saga Medical School for Treatment. Case 2, a 14-month-old girl began to drink cow's milk at the age of 6 months. She drank 1,500ml cow's milk every day at the age of 14 months. She was, referred to our hospital by her physician because of severe anemia. Hypoproteinemia and severe iron deficiency anemia in both of these patients were improved by oral iron intake and prohibiting of cow's milk. Although many children at their age usually drink more than 500ml cow's milk every day, manifestations of symptoms such as iron deficiency anemia and hypoproteinemia do not occur frequently. Thus some investigations suggest that genetic defects as well as other factors related to this disease may be important factors.

Anemia, Hypochromic↗
PubMed1992

[Effects of preoperative transcatheter portal embolization (TPE) on prevention of hepatic failure after massive hepatectomy].

Effects of TPE on prevention of hepatic failure after massive hepatectomy were studied experimentally using dogs. A 70% or 85% hepatectomy (Hx) was performed two weeks after TPE. All of the 70%Hx groups with(+)/without(-) TPE were alive for over two weeks after hepatectomy. While all of the 85%Hx group without TPE died, eight of ten in the 85%Hx group with TPE survived. Without TPE, total bilirubin levels in sera were elevated markedly in the 85%Hx group and moderately in the 70%Hx group after hepatectomy. The levels of escaped enzymes in sera, such as GOT or GPT, were also elevated remarkably in the TPE(-) groups. Although the levels of these enzymes were also high in the 85%Hx.TPE(+) group, these values were as same as those of 70%Hx.TPE(-) group. In the 85%Hx.TPE(-) group, critical diminution of functional hepatic cell mass and severe portal hypertension occurred after hepatectomy and coagulopathy and death followed to these phenomena. TPE might prevent the onset of these critical phenomena, and diminish the damage caused by massive hepatectomy. These results suggest that TPE is useful for prevention of postoperative hepatic failure so that we could perform massive hepatectomy safely, and extend the operative indication.

Alanine Transaminase↗
PubMed1992

Isolation and some biochemical properties of porcine pancreas mitochondria.

Morphologically and functionally intact mitochondria were isolated from the porcine pancreas using a conventional, differential centrifugation method. The homogenate of the porcine pancreas made in a medium containing 0.25 M sucrose, 10 mM Tris-Cl, pH 7.4, 0.5% bovine serum albumin and 1 mM EDTA, in the presence or in the absence of dibucaine and trypsin inhibitor, was centrifuged for 10 min at 700xg. The supernatant was centrifuged for 10 min at 7000xg, and the pellet was washed three times. Trypsin activity of mitochondria isolated in the absence of dibucaine and trypsin inhibitor was as low as that of mitochondria isolated in the presence of dibucaine and trypsin inhibitor, and a major part of the activity remained inactivated. Phospholipase A2 activity of the former mitochondria was as low as that of the latter, and remained unchanged up to 8-10 hr at 4 degrees C. The presence of bovine serum albumin and EDTA in the respiration medium was absolutely required to obtain good respiratory controls of those mitochondria. These data suggest that well-coupled mitochondria can be obtained from the pancreas by a conventional isolation procedure without activating the major part of trypsin.

Animals↗
PubMed1992

[A phase I study of DWA2114R].

Phase I study of DWA2114R, a new platinum analogue, was conducted in 39 patients with various tumor types by a group of 13 institutions. Of the 39 patients entered in this study, 35 were evaluable. The starting dose was 40 mg/m2 (1N) and the drug was administered i.v. for 20-30 min, escalating stepwisely up to 1,000 mg/m2 (25 N). The dose limiting factor (DLF) was leukocytopenia, especially neutrocytopenia, and the maximum tolerated dose (MTD) was more than 1,000 mg/m2. Major clinical toxicity was gastrointestinal. Hepatotoxicity and nephrotoxicity were mild. Following administration of the drug, plasma concentrations of total and filterable platinum (Pt) showed a triphasic and biphasic decays. Excretion into urine within 24 hours was in the range of 54.2% to 92.2% of the administered platinum. The recommended dose of phase II study was 800-1,000 mg/m2, repeating every 3-4 weeks.

Adult↗
PubMed1991

Oscillatory muscarinic acetylcholine responses of Xenopus oocytes are desensitized by protein kinase C and sensitized by protein phosphatase 2B.

The oscillatory current response to acetylcholine (ACh) in Xenopus laevis oocytes, mediated by endogenous muscarinic ACh receptors, is known to be mildly desensitized by repetitive ACh applications. Pretreatment of oocytes with staurosporine (an inhibitor of protein kinases) was found not only to abolish this desensitization but also to positively and progressively potentiate oscillatory ACh responses. This sensitization by staurosporine was suppressed by 12-O-tetradecanoylphorbol 13-acetate (an activator of protein kinase C). In staurosporine-untreated (control) oocytes, intracellularly injected calcineurin (an isozyme of Ca2+/calmodulin-dependent protein phosphatase 2B) or Ca2+ enhanced oscillatory ACh responses, while trifluoperazine (a calmodulin inhibitor) suppressed the ACh responses but did not affect oscillatory responses to intracellularly injected inositol 1,4,5-trisphosphate. These results suggest that, as far as short-term changes in receptor responsiveness are concerned, endogenous muscarinic ACh receptors in Xenopus oocytes are desensitized by phosphorylation by protein kinase C and sensitized by dephosphorylation by Ca2+/calmodulin-dependent protein phosphatase 2B.

Acetylcholine↗