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Biomedical subjects

H Yamauchi

Publications and source records attributed to H Yamauchi.

At least 19 recordsLinked to original sources
PubMed1992

Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist.

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.

Administration, Inhalation↗
PubMed1992

Cauliflower mosaic virus reverse transcriptase. Activation by proteolytic processing and functional alteration by terminal deletion.

We have previously expressed the cauliflower mosaic virus (CaMV) reverse transcriptase (RTase) gene, the ORFV gene, in yeast in an active form (RTase-Y). An activity gel analysis revealed that the molecular size of RTase-Y as well as an RTase associated with the CaMV particles (RTase-V) is 60 kDa. This size is about 18 kDa smaller than that of the inactive form previously expressed in Escherichia coli (RTase-E) (78 kDa), which corresponds to the coding capacity estimated for the ORFV gene. To investigate the possible involvement of proteolytic processing in the de novo synthesis of CaMV RTase, we constructed a series of deletions from either terminus or both termini of the ORFV coding sequence and expressed them in E. coli. Among the various truncated RTases, those (denoted delta N) that lack N-terminal peptide fragments 143-185 amino acids long were active on the synthetic RNA template-primer, poly(rC)-oligo(dG). Those RTases (denoted delta C) lacking C-terminal peptide fragments 50-102 amino acids long and those lacking both termini (denoted delta NC) were also active on this template. However, only the delta N RTases showed enzyme properties indistinguishable from the RTase-Y in that they transcribed natural RNA into DNA and required either Mg2+ or Mn2+ for their activity. The length of the deletion corresponded approximately to the difference of the molecular weights between RTase-Y and RTase-E. These results suggest that CaMV RTase is translated in an inactive precursor form and then converted to an active form by proteolytic processing during de novo synthesis. We have also demonstrated that C-terminal deletions cause a loss of activity on a natural RNA template accompanied by an alteration in metal ion requirement. The inability to incorporate dTTP accounts for the loss of activity on the natural RNA template. However, the affinities for dTTP and the corresponding template, poly(rA)-oligo(dT), were found to be unaltered.

Binding Sites↗
PubMed1992

Metabolism of subcutaneous administered indium arsenide in the hamster.

Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, but the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues.

Animals↗
PubMed1992

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. CASE DESCRIPTION: We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. CONCLUSIONS: This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.

Brain↗
PubMed1992

Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion.

BACKGROUND AND PURPOSE: The pathophysiology of crossed cerebellar diaschisis remains to be elucidated. The mechanism responsible appears to be deafferentation through the corticopontocerebellar tract, which terminates in the cerebellar gray matter. However, few studies have demonstrated the hemodynamic and metabolic changes in the cerebellar gray matter and pons in crossed cerebellar diaschisis. METHODS: Using positron emission tomography in 24 patients with unilateral supratentorial stroke, we evaluated regional blood flow, metabolic rate of oxygen, oxygen extraction fraction, and blood volume in the cerebellar cortex and pons. Sixteen patients with significant cerebellar blood flow asymmetry, defined as a percentage difference in blood flow beyond the upper 95% confidence limit defined in eight normal subjects, were selected as the group with crossed cerebellar hypoperfusion. RESULTS: In patients with crossed cerebellar hypoperfusion, the metabolic rate of oxygen was significantly decreased in the cerebellar cortex contralateral to the supratentorial stroke, compared with that in the ipsilateral cerebellar cortex; this decrease was less than the decrease in cerebellar blood flow. The degrees of cerebellar asymmetry in these two parameters were negatively correlated with the metabolic rate of oxygen in the pons. The oxygen extraction fraction was slightly, but significantly, increased. In contrast to the ischemic state, however, the cerebellar blood volume was decreased, with no difference in the ratio of cerebellar blood flow to blood volume. CONCLUSIONS: These findings support interruption of the corticopontocerebellar tract as the mechanism of crossed cerebellar hypoperfusion. Our results also suggest a mild elevation in the oxygen extraction fraction in this state, with a mechanism distinct from ischemia.

Adult↗
PubMed1992

Effects of massive small bowel resection on metabolism of bile acids and vitamin D3 and gastrin release in dogs.

The effects of ursodeoxycholic acid (UDCA) and 1 alpha-hydroxyvitamin D3 on pathophysiological changes following massive resection of the distal small bowel (75%) were investigated by using adult beagle dogs. After surgery, body weight decreased, watery diarrhea occurred, and the transit time of the alimentary tract shortened. These undesirable consequences lessened markedly after oral administration of UDCA, though 1 alpha-hydroxyvitamin D3 was not effective. Plasma levels of both 25-hydroxyvitamin D3 and 24, 25-dihydroxyvitamin D3 decreased after surgery, while plasma 1 alpha, 25-dihydroxyvitamin D3 concentrations remained unchanged during the observation period of six months. Although fasting plasma concentrations of total bile acid were not reduced, the integrated response to a meal decreased significantly after surgery in spite of the administration of UDCA. The concentration of UDCA in the gallbladder bile increased markedly in dogs which received UDCA. Taurine-conjugated bile acids accounted for more than 90% of the gallbladder bile. Postprandial hypergastrinemia occurred following the massive small bowel resection in the control group and in the group which received 1 alpha-hydroxyvitamin D3 alone, while it did not occur in the group given UDCA together with 1 alpha-hydroxyvitamin D3. These results indicate that administration of UDCA after massive resection of the small intestine is effective in maintaining good nutritional state.

Administration, Oral↗
PubMed1992

Synthesis and structure-activity relationships of a new series of cephalosporins, E1040 and related compounds.

The synthesis and in vitro antibacterial activity of a series of 7-[(Z)-2-aminoaryl-2-oxyiminoacetamido]-3-ammoniomethyl++ +-3-cephems are described. Variation of an oxyimino moiety with aminoaryl at the C-7 side chain and a quaternary ammonium moiety at the C-3 side chain were examined and structure-activity relationships were studied. E1040, the 3-(4-carbamoylquinuclidinio)methyl derivative of the 7-alpha-methoxyimino series of aminothiadiazolyl cephalosporins, exhibited excellent activity against both Gram-positive and Gram-negative bacteria, particularly against Pseudomonas aeruginosa, and possessed high stability to beta-lactamases.

Bacteria↗
PubMed1992

[Portal blood levels of mitomycin C after intraperitoneal administration].

Portal blood levels of mitomycin C (MMC) were measured after intraperitoneal administration of 10 or 20 mg of mitomycin C following pancreatoduodenectomy. The portal concentration of MMC increased rapidly to the maximum concentration of 826 +/- 364 ng/ml at 5 minutes after administration, when the dosage was 20 mg (four cases). The peripheral blood levels followed the portal levels and the maximum concentration was 397 +/- 123 ng/ml at 15 minutes. Then the MMC levels of both portal and peripheral blood decreased gradually, but concentration higher than 100 ng/ml was maintained for 90 minutes after administration. In four patients given 10 mg of MMC, the patterns of the blood levels were similar, but the concentration was lower than in the group given 20 mg. In both groups, the AUC values were higher in portal than in peripheral blood. MMC administered intraperitoneally was absorbed rapidly through portal circulation and a high MMC level of portal blood was obtained. Therefore, it would prevent the dissemination of cancer cells into the liver which may well occur during operation for pancreatic carcinoma.

Humans↗
PubMed1992

[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].

The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.

Adenocarcinoma↗
PubMed1992

[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.

Adult↗
PubMed1992

[Clinicopathological and immunohistochemical studies on carcinoma of the papilla of Vater].

The non-invasive adenomatous component (nac) was observed in 44% of 32 resected specimens of carcinoma of the papilla of Vater. Incidence of the "nac" positive carcinoma declined with cancer staging, but there was no significant relationship between the "nac" and tumor size. The "nac" positive rates in "tumor forming", "ulcerating" and "mixed" types were 65, 0 and 38%, respectively. The "nac" negative carcinoma metastasized more frequently to the lymph nodes, duodenum, pancreas and veins. The five year survival rates of the patients with the "nac" positive and negative carcinoma were 78 and 22%, respectively. Immunohistochemically, the "nac" positive carcinoma mostly showed partial distribution of CA19-9, while the "nac" negative carcinoma, carcinoma of the pancreas and bile duct mostly showed diffuse distribution. The intact mucosa of the common channel and orifice of the papilla almost showed partial distribution, and duodenal mucosa showed negative distribution. The pancreatic and bile duct almost indicated diffuse distribution. The "nac" may be precancerous condition and the "nac" positive carcinoma may arise from the common channel or the orifice of the papilla or the duodenum. But the "nac" negative carcinoma may belong primarily to carcinoma of the pancreas and bile duct as de-novo carcinoma.

Adenoma↗
PubMed1992

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.

Adult↗
PubMed1992

[Preoperative administration of 5-FU emulsion for lymph nodes metastasis of pancreatic carcinoma].

5-FU oil emulsion (n = 5) or 5-FU dry syrup (n = 4), at a daily dose of 332mg for 7 days, was administered preoperatively to patient with periampullary carcinoma to evaluate the uptake of 5-FU to regional lymph nodes. In the group given 5-FU oil emulsion, the mean concentration of 5-FU was 293 +/- 97 ng/ml (mean +/- S.E.D), and that of the group given dry syrup was 72 +/- 20 ng/ml. Although no statistically significant difference was found, 5-FU seemed to reach the regional lymph nodes as an emulsion rather than as an aqueous solution. Preoperative administration of 5-FU emulsion might have some favorable effect on lymph node metastasis and lymph invasion of pancreatic carcinoma.

Administration, Oral↗
PubMed1991

High-intensity area in the deep white matter indicating hemodynamic compromise in internal carotid artery occlusive disorders.

We used positron emission tomography and magnetic resonance imaging to evaluate 16 patients with transient ischemic attacks or minor strokes and unilateral internal carotid occlusive disease, five with stenosis, and 11 with occlusion. Cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, cerebral blood volume, and T2-weighted magnetic resonance images obtained at 1.5-T were analyzed. Irrespective of vascular disease, patients with a confluent high-intensity area in the middle centrum semiovale had substantially decreased cerebral blood flow and ratio of cerebral blood flow to blood volume in the middle cerebral artery distribution of the cortex, with a substantially increased oxygen extraction fraction. We concluded that the confluent high-intensity area in the deep white matter region indicates hemodynamic compromise in the affected hemisphere in internal carotid artery occlusive disease.

Aged↗
PubMed1991

Coronal reconstruction images of glucose metabolism in Alzheimer's disease.

Coronal images of position emission tomography (PET) by 18F-labelled deoxyglucose reconstructed from interpolated scan in Alzheimer's disease clearly indicated suppression of glucose metabolism in the parietal lobe and lateral part of the temporal lobes, compared to normal controls. The medial part of the temporal lobes in Alzheimer's disease did show a mildly lower glucose metabolic rate than that in normal controls; therefore it is suggested that the parietal and lateral parts of the temporal lobes are primary affected regions in Alzheimer's disease, not the medial part of the temporal lobe, including the hippocampus.

Adult↗
PubMed1991

Cardiovascular characterization of SD-3211, a novel benzothiazine calcium channel blocker, in isolated rabbit hearts.

The cardiovascular effects of SD-3211, a novel benzothiazine Ca++ channel blocker, were compared with those of diltiazem and nicardipine in Langendorff-perfused rabbit hearts. SD-3211 was more potent in increasing coronary artery flow than in depressing cardiac function (i.e., contractile force, heart rate and conduction time). The relative specificity of SD-3211 for coronary vasodilation to cardiodepression was clearly greater than that of diltiazem, but less than that of nicardipine. Thus, the present study demonstrates that SD-3211, despite a non-dihydropyridine type of Ca++ channel blocker, can be characterized as a potent coronary vasodilator with a little effect on cardiac function.

Animals↗