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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 37 records · Page 2Linked to original sources
PubMed1992

Conjugated 1 beta-hydroxycholic acid in the urine of newborns and pregnant women measured by radioimmunoassay using antisera raised against N-(1 beta-hydroxycholyl)-2-aminopropionic acid-bovine serum albumin conjugate.

Anti-tauro 1 beta-hydroxycholic acid antisera were prepared by immunizing rabbits with N-(1 beta,3 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholan-24-oyl)-2- aminopropionic acid-bovine serum albumin (BSA) conjugate. The antisera raised had high affinity (1.25-1.46 x 10(9) M-1) and specificity for conjugated 1 beta-hydroxycholic acid; cross-reactivity for glyco 1 beta-hydroxycholic acid was 100% and that for the glycine and taurine conjugates of other 1 beta-hydroxylated bile acids ranged from 11.30 to 0.23%. Urinary concentrations of conjugated 1 beta-hydroxycholic acid were determined by radioimmunoassay in newborns, 0-20 d after birth, in amounts ranging from 0.29 to 18.51 micrograms/ml and in women in late pregnancy (less than 1.13 micrograms/ml), as well as in normal women (less than 0.12 microgram/ml).

Animals↗
PubMed1992

Measurement of conjugated 1 beta-hydroxycholic acid in urine of newborns by specific radioimmunoassay.

Anti-tauro 1 beta-hydroxycholic acid antisera were prepared by immunizing rabbits with N-(1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholan-24-oyl)glycine bovine serum albumin conjugate. The immunoglobulin G fraction was obtained by ammonium sulfate precipitation, followed by diethylaminoethyl cellulose column chromatography. The antibody was characterized using [2-3H]tauro 1 beta-hydroxycholic acid which has a high affinity (Ka = 1.09 x 10(9) M-1) and reasonable specificity. Cross-reactivity for glyco 1 beta-hydroxycholic acid was 100% and those for other 1 beta-hydroxylated bile acids ranged from 4.32 to 29.6%. Concentrations of conjugated 1 beta-hydroxycholic acid in urine of newborns at 0-20 d after birth were determined by radioimmunoassay to be significant (0.2-11.1 micrograms/ml), exhibiting a tendency to increase during the 20 d after birth.

Animals↗
PubMed1992

Prophylactic use of ofloxacin in granulocytopenic patients with hematological malignancies during post-remission chemotherapy.

The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p less than 0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p less than 0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p less than 0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p less than 0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy.

Adolescent↗
PubMed1992

[Gadolinium-MRI findings of two adrenoleukodystrophy cases treated with gamma-globulin].

Two cases of adrenoleukodystrophy were reported. We treated them with intravenous gamma-globulin infusion. MRI with gadolinium enhancement was performed before and after the therapy to evaluate the effect of gamma-globulin. Case 1 was a 19-year-old boy, who noticed left hemianopsia when he was 18 years old. Case 2 was a 36-year-old man, who developed ataxic gait and character change when he was 33 years old. Very long chain fatty acids in plasma and RBC membrane were elevated in both cases. On T2-weighted image of MRI, high signal lesions were seen in the white matter of occipital lobe in case 1, cerebellum, internal capsule, and around the corpus callosum in case 2. On T1-weighted image, the rim of every lesion was enhanced by gadolinium infusion. After the gamma-globulin therapy, gadolinium enhancement of the rim remarkably reduced in case 1. No reduction was observed in case 2. MRI findings of case 1 indicate the possibility that gamma-globulin may suppress the inflammation of the adrenoleukodystrophy.

Adrenoleukodystrophy↗
PubMed1992

[Choice of left gastric vena caval shunt for esophageal varices--its rationale and clinical results].

We have surgically treated esophageal varices, particularly by left gastric vena caval shunt (LGCS) as the first choice in patients with good liver function (n = 40). The correlation between clinical outcomes and preoperative splanchnic hemodynamics, and therapeutical plans were evaluated: 1) Operative mortality was nil with recurrence rate of 15.0% and rebleeding noted in only one case. 2) The liver function according to Child's classification showed no significant changes before and after operation. Survival rate was more than 70% with good rehabilitation rate (over 90%). 3) The presence of hyperdynamic splanchnic circulation (left gastric venous flow and gastric wall microcirculation) lead to successful clinical results. 4) Combined use of sclerotherapy was efficacious in case of persistent and recurrent varices. We conclude that LGCS is successful in treating esophageal varices in the setting of hyperdynamic portal circulation with acceptable liver function.

Anastomosis, Surgical↗
PubMed1992

[Myoclonus epilepsy associated with ragged-red fibers--report of a patient with negative myoclonus].

A 21-year-old woman, who had no particular familial history, was admitted to our hospital because of hand tremor and gait disturbance. On neurological examination, she showed muscle weakness in the proximal extremities. There was an ataxia on heel-to-shin testing. Action and postural myoclonus involving the extremities were also noted. In addition, with dorsiflexion of the hands, asterixis-like movement was manifested. Pyruvate was 1.0 mg/dl and lactate was 24.1 mg/dl in cerebrospinal fluid. Brain CT scan revealed mild cerebellar atrophy. EEG showed synchronous diffuse slow wave. Median nerve SEPs showed a large N20-P25 component (20 microV). Median nerve C-reflex was not evoked. With dorsiflexion of the hands, the asterixis-like movement was induced with brief cessation of surface EMG activity in the forearm muscles, as shown by the accelerometer trace. Biopsy specimens of the biceps brachii muscle revealed numerous ragged-red fibers. By PCR-RFLP method with use of a mismatched primer, we analyzed mitochondrial DNA extracted from peripheral leukocytes. The A to G mutation at nucleotide position 8,344 in a tRNA(Lys) gene of a mitochondrial genome was detected. In this patient, clonazepam was effective on the asterixis-like movements. From existence of positive myoclonus, giant SEPs and efficacy of clonazepam, we considered this movement to be negative myoclonus. Our study indicated the possibility that such an involuntary movement could be induced by certain posture in patients with MERRF.

Adult↗
PubMed1992

[Urinary 11-dehydrothromboxane B2 and 6-keto-prostaglandin F1 alpha in normal pregnant women and in women complicated with pregnancy-induced hypertension].

In normal pregnancy, increased production of platelet thromboxane A2(TXA2) parallels increased biosynthesis of vascular prostacyclin (PGI2). An imbalance in the formation of these prostaglandins is believed to be associated with the pathogenesis of pregnancy-induced hypertension (PIH). Recent evidence suggested that aspirin in low doses was effective in reducing the incidence of PIH, by selective inhibition of platelet-derived TXA2 biosynthesis. In this communication, we determined the urinary 11-dehydro TXB2 and 6-keto-PGF1 alpha, which are major metabolites of TXA2 and PGI2, respectively, from early to late pregnancy of normal pregnant women and of women complicated with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha decreased significantly from as early as 10wks of gestation when compared with that in non-pregnant controls (1.43 +/- 0.15 vs 1.99 +/- 0.13: Mean +/- SEM, p less than 0.05), and increased in later pregnancy to the control values at term. No significant difference was found in the excretion of 11-dehydro TXB2 between normal pregnant women and women with PIH. In contrast, urinary excretion of 6-keto-PGF1 alpha decreased in women with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha increased significantly as compared with that of pregnant controls. These results demonstrated that disturbed production of vascular PGI2 may be the primary cause of PIH, and affect the vascular responsiveness to pressor inducers such as angiotensin II.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

[Increased red-cell sodium-lithium countertransport activity and urinary 11-dehydrothromboxane B2 during pregnancy].

The activity of Na-Li countertransport (CT), a marker of the risk of essential hypertension, was determined in 55 primigravid women during pregnancy, together with urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) as a marker of thromboxane A2 synthesis. The mean Na-Li CT (mean +/- SEM) value was increased significantly at 20 weeks gestation and thereafter, and reached higher levels in late pregnancy than in non-pregnant controls (0.31 +/- 0.02 vs. 0.21 +/- 0.01mmol per hr per liter RBC, p less than 0.05). Fifty five primigravid women could be divided into two groups, depending upon Na-Li CT activity either higher or lower than the value of 0.25mmol per hr per liter RBC at any time in the pregnancy up to term. At 20 weeks gestation all but one of 13 women in the lower-activity group had Na-Li CT activity less than 0.20 mmol per hr per liter RBC, and none developed PIH, whereas out of 42 women in the higher-activity group, all but one had Na-Li CT activity more than this value, and 8 developed PIH. Urinary 11-dehydro-TXB2 increased as pregnancy progressed, maximum levels being attained in women at term, about 3 times higher than in controls (4.19 +/- 0.35 vs. 1.36 +/- 0.10 ng per mg creatinine, p less than 0.05). Although the formation of thromboxane A2 was reported to be higher in pregnancy complicated by hypertension, no significant difference existed in the levels of 11-dehydro-TXB2 between women with PIH and women with uncomplicated pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1992

Effects of a thromboxane synthetase inhibitor (OKY-046) on vascular reactivity to angiotensin II after stricture of the abdominal aorta in pregnant rabbits.

The abdominal aorta of 20 pregnant rabbits was surgically constricted below the renal arteries on the 21st day of pregnancy, producing a stricture that decreased the blood flow by 60%. Four pregnant rabbits underwent sham operation and served as control. The pressor response to angiotensin II (A-II) was assessed by measuring the systolic blood pressure in the ear of rabbits. We intravenously administered 20 mg/kg of OKY-046, a thromboxane A2 (TXA2) synthetase inhibitor (OKY group: n = 13) or saline (n = 7) daily from the 23rd day of pregnancy until the day of delivery. After stricture of the abdominal aorta, the "effective pressor dose" (EPD:nanograms of A-II/kg/min necessary to cause a 20 mmHg rise in systolic pressure) was significantly lower in the saline group than in the control group. On the 27th and 29th day of pregnancy, the EPD in the OKY group was significantly higher than that in the control group. The plasma thromboxane B2 (TXB2) level in the OKY group was significantly lower than that in the saline group on the 27th day. The fetal birth weight in the saline group was significantly lower than that in the control group. These finding suggest that OKY-046 restores the vascular refractoriness induced by A II and suppresses TXA2 synthesis in pregnant rabbits with aortic constriction.

Angiotensin II↗
PubMed1992

Proteasomes: protein and gene structures.

Proteasomes are ring- or cylinder-shaped particles that have a sedimentation coefficient of 20S and are composed of a characteristic set of small polypeptides. These particles have a latent multicatalytic proteinase activity. Recently, proteasomes were found to combine reversibly with multiple protein components to form 26S proteolytic complexes that catalyze ATP-dependent, selective breakdown of proteins ligated with ubiquitin. This suggests that the 26S complexes are a new type of ATP-requiring protease in eukaryotic cells. We have studied the structures of various eukaryotic proteasomes at the molecular level by physicochemical and recombinant DNA techniques and have proposed that the gross structures of proteasomes, such as their size and shape, have been highly conserved during evolution. Proteasome subunits appear to be encoded by a family of homologous genes named the "proteasome gene family," which may have evolved from a common ancestral gene. Evidence obtained by genetic analyses in yeast and studies on the levels of proteasome expression in various eukaryotic cells indicates that proteasomes have essential roles in the cell. In this review, we summarize available information on the protein and gene structures of proteasomes and discuss the biological functions of proteasomes.

Amino Acid Sequence↗
PubMed1992

[A population based survey of attendance at screenings in urban areas].

To clarify the present situation of screenings in urban areas, a population based survey on attendance at screenings was conducted in Kitakyushu City. Self-administered mailed questionnaires were sent to three thousand randomly selected subjects 40 years of age or over living in Kitakyushu City. The results are summarized as follows: 1. Considerable differences were observed in the number of people who were offered screenings at work sites for those between the ages of 40-59 compared to those 60 years of age or over, and between full-time employees and part-time or self-employed workers. 2. Among people who obtained stomach examinations, middle age men mainly received cancer screenings at work sites, while women or older men were mainly examined when they went to clinics or hospitals when abdominal discomforts occurred. Among women who received uterine examinations, all age groups mainly received cancer screenings at city administered screenings at clinics or hospitals, and rates decreased as age increased. 3. Among people who did not obtain stomach examinations, many middle age people wanted to be examined for stomach cancer but were unable to, while older people did not think it necessary. In the case of uterine cancer screening, middle age women did not want to receive it, while older women did not think it necessary. 4. For those people who are not offered cancer screenings at workplaces, it is assumed that those who have a positive attitude toward screening will obtain it, if offered, at sites conducted by the local government.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Sequence of critical events involved in fusion of phospholipid vesicles induced by clathrin.

Membrane fusion induced by clathrin is accompanied by several events such as conformational change, membrane binding and association of clathrin, and membrane aggregation (Maezawa et al. (1989) Biochemistry 28, 1422-1428; Maezawa and Yoshimura (1990) Biochem. Biophys. Res. Commun. 173, 134-140). To clarify the sequence of these events, we examined their time-courses by reducing the pH of the medium from 7.4 to a given pH in the range of 3.5-5.0 at 25 degrees C or 10 degrees C. Large unilamellar vesicles composed of phosphatidylserine and phosphatidylcholine were used in most experiments. The half-time for conformational change of clathrin was less than those for membrane binding and association of clathrin. The half-times and the initial rates of membrane binding and association of clathrin were similar order of magnitude, although the pH-profiles of the initial rates of the two events were somewhat different. Membrane aggregation started after membrane binding of clathrin. A lag phase was observed in the time-course of membrane fusion, whereas there was no lag phase in membrane binding and association of clathrin and membrane aggregation. Moreover, the lag time before fusion was independent of the clathrin concentration, although the initial rates of these three events were dependent on it, suggesting that the three reactions are not responsible for the lag phase before fusion, and that there is some other event(s) in the lag time. On the other hand, there was a threshould-pH in the pH profile of the lag-time and the threshold-pH coincided with the critical pH at which the final associated state of clathrin was apparently reversed in the presence and absence of liposomes, suggesting that the event(s) in the lag phase may be related to this final associated state of clathrin molecules on the liposome membranes. These results indicate that clathrin-induced fusion of liposomes is initiated through the following sequential events: conformational change of clathrin, membrane binding and association of clathrin, which occur simultaneously but independently, membrane aggregation, an event(s) in the lag phase, and actual fusion.

Clathrin↗
PubMed1991

Role of free radical scavengers in pancreatic carcinomas of hamsters.

The involvement of free radicals in the carcinogenic mechanism has been suggested, however, little is known about the role of free radicals in the pancreatic cancer. In this study, the effects of active oxygen on the carcinogenesis of the tumor were examined by measuring the levels of scavengers in pancreatic cancer of Syrian golden hamsters. Pancreatic cancer was induced by di-iso-propanol nitrosamine (500 mg/kg body weight/week x 24 weeks). Activities of superoxide dismutase (SOD), catalase, glutathion peroxide (GSH-Px) and malon dialdehyde (MDA) in the tumor and border zone were compared with those in the non-tumor region and control normal tissue. Activities of SOD and catalase in the tumor and border zone were significantly lowered than those in non-tumor region and normal tissue. GSH-Px levels were significantly higher in the tumor than those in the non-tumor region and normal tissue. MDA levels also tended to be high in the tumor. These results suggest that the development of cancer in pancreatic tissue is related to a reduction of SOD and catalase. GSH-Px and MDA are suggested to be involved in the reactions of free radicals.

Animals↗
PubMed1991

[Effect of synthetic protease inhibitor on the oncogenesis of pancreatic cancer in hamsters: study on pancreatic endocrine cells and free radicals].

In order to study the effect of synthetic trypsin inhibitor on the oncogenesis of pancreatic cancer, the histology, the kinetics of the B, A and D cells in the islets of Langerhans and activities of free radical scavengers, superoxide dismutase (SOD), glutathion peroxide (GSH-Px) and malon dialdehyde (MDA) in the tumor bearing tissues were measured in hamsters with pancreatic cancer induced by di-iso-propanol nitrosamine (DIPN) with or without camostat (FOY-305). In DIPN group (DIPN alone), the tubular adenocarcinoma was found in 80%, however, in FOY group (DIPN+FOY-305), papillary adenocarcinoma was found in 91%. In both DIPN and FOY groups, the number of B cells was decreased at 8 weeks and the number of A and D cells was decreased at 16 weeks. Activities of SOD in the tumor and borderzone in DIPN group were significantly lower than those in non-tumor region and normal tissue. However, activities of SOD in the tumor and borderzone in FOY group were higher than those in DIPN group. GSH-Px and MDH levels were significantly higher in FOY group suggesting the involvement in the reaction of free radicals. These results suggest that trypsin inhibitors have a prophylactic effect on the development of pancreatic cancer.

Animals↗
PubMed1991

Production and characterization of mouse monoclonal antibodies against human monocyte chemoattractant protein-1.

We developed five different hybridoma cell lines that produced mAb against human monocyte chemoattractant protein-1 (MCP-1). The subclass of all five antibodies was IgG1. All five mAb formed complexes with metabolically labeled MCP-1 that could be demonstrated by immunoprecipitation. The antibodies were specific for MCP-1. They did not cross-react by immunoprecipitation with structurally related host defense cytokines present in metabolically labeled PHA- or LPS-stimulated mononuclear cell culture fluids, nor did they cross-react in a direct ELISA with neutrophil attractant/activation protein-1, with crude platelet lysate proteins, or with pure platelet proteins that have amino acids sequences similar to that of MCP-1. The mAb also reacted with rMCP-1 expressed in Escherichia coli, suggesting that they recognize protein structure rather than the glycosylated portion of human MCP-1. When the mAb were mixed with MCP-1, the monocyte chemotactic response to MCP-1 was inhibited. A sandwich ELISA was developed to detect MCP-1 in biologic fluids containing relatively high concentrations of other proteins. The sensitivity was 300 pg/ml, or 30 pg/ELISA well. An anti-MCP-1 mAb column was used in an improved method of MCP-1 purification. Approximately 240 micrograms of MCP-1 were purified from 5 liters of FCS-containing U-105MG cell culture supernatant. The yield was at least 60%. In addition to two forms of MCP-1 reported previously by us, two more forms of MCP-1 were found in a mixture of culture supernatants of PHA- and LPS-stimulated human PBMC.

Animals↗
PubMed1991

Thermostable alanine racemase of Bacillus stearothermophilus. Construction and expression of active fragmentary enzyme.

Limited proteolysis studies on alanine racemase suggested that the enzyme subunit is composed of two domains (Galakatos, N. G., and Walsh, C. T. (1987) Biochemistry 26, 8475-8480). We have constructed a mutant gene that tandemly encodes the two polypeptides of the Bacillus stearothermophilus enzyme subunit cleaved at the position corresponding to the predicted hinge region. The mutant gene product purified was shown to be composed of two sets of the two polypeptide fragments and was immunologically identical to the wild-type enzyme. The mutant enzyme, i.e. the fragmentary alanine racemase, was active in both directions of the racemization of alanine. The maximum velocity (Vmax) was about half that of the wild-type enzyme, and the Km value was about double. Absorption and circular dichroism spectra of the fragmentary enzyme were similar to those of the wild-type enzyme. An attempt was made to separately express in Escherichia coli a single polypeptide corresponding to each domain, but no protein reactive with the antibody against the wild-type alanine racemase was produced. Therefore, it is suggested that the two polypeptide fragments can fold into an active structure only when they are co-translated and that they correspond to structural folding units in the parental polypeptide chain.

Alanine Racemase↗