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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 163 records · Page 9Linked to original sources

[Effect of growth hormone on fetal and placental growth of spontaneous dwarf rat].

The effect of growth hormone on fetal and placental growth was studied in the spontaneous dwarf rat (SDR). The SDR is a newly established experimental model for pituitary growth hormone (GH) deficient dwarfism with an autosomal recessive mode of inheritance. The growth of heterogenic fetuses which were made by crossing female SDRs with normal male rats was similar to that of homogenic SDR fetuses on day 16 of gestation (Day 16), but on Day 20 heterogenic fetuses which had GH in their serum were significantly heavier than homogenic fetuses. There was no significant difference between the two groups in placental weight. The daily infusion of ovine-GH into pregnant SDR caused a significant increase in placental weight on Day 20, but had no effect on fetal growth. These results suggest that fetal GH plays a role in the fetal growth without affecting placental growth, and that maternal GH affects placental growth without affecting fetal growth.

Animals

[Idiopathic dural arteriovenous fistula of the superior sagittal sinus associated with intracerebral hemorrhage: a case report].

A case was reported of a surgically removed idiopathic dural arteriovenous fistula of the superior sagittal sinus associated with intracerebral hemorrhage. Dural arteriovenous fistula of the superior sagittal sinus is said to be rare. Only 9 cases have been reported in detail so far. A 46-year-old male was referred to our clinic complaining of left motor weakness of sudden onset. He had no history of head injury. CT scan revealed subcortical hemorrhage in the right frontal lobe. enhanced CT scan showed string-like enhancement in the margin of the hemorrhage. Right internal carotid angiogram disclosed a dural arteriovenous fistula, of which the feeding artery was a meningeal branch of the posterior ethmoidal artery, draining the superior sagittal sinus and right frontal superficial cortical vein. The superior sagittal sinus was not obstructed. It was diagnosed as a rare idiopathic dural arteriovenous fistula in the superior sagittal sinus. Surgical obliteration of an arteriovenous fistula was performed preserving the superior sagittal sinus. Etiological aspects and surgical management of the rare lesion was discussed referring to previous reports.

Adult

[Studies on the combined effect of fosfomycin with sulbactam/cefoperazone on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa].

We studied the combined effect of fosfomycin (FOM) with sulbactam/cefoperazone (SBT/CPZ) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA, 246 strains) and Pseudomonas aeruginosa (190 strains) in vitro. In ratio of mixed serum concentration of antibiotics at three hours after intravenous administration, the combination of FOM with SBT/CPZ and alone of arbekacin showed over 90% in cumulative percentage of MIC against MRSA and P. aeruginosa. The effect of the combination of FOM and SBT/CPZ was observed in MRSA strains of > 16 micrograms/ml of SBT/CPZ MIC and > 256 micrograms/ml FOM MIC. As well as in P. aeruginosa strains, the effect of the combination of FOM and SBT/CPZ was observed in strains of > 16 micrograms/ml of SBT/CPZ MIC and < 256 micrograms/ml FOM MIC, but it was not remarkable in strains of > 256 micrograms/ml FOM MIC. These results suggests that the combination treatment of FOM and SBT/CPZ may be effective for mixed infection of MRSA and P. aeruginosa.

Cefoperazone

[Hypopituitarism associated with empty sella after steroid pulse therapy in a patient with SLE].

A case of systemic lupus erythematosus (SLE) complicated with hypopituitarism after steroid pulse therapy is reported. A 46-years-old-female with a history of SLE starting in 1975 was admitted to our hospital in February 1991 for lupus nephritis. Steroid pulse therapy, 1000 mg methyl-prednisolone for 3 successive days as one therapy unit, was administered. Proteinuria improved remarkably, however, general fatigue and headache appeared 2 weeks after initiation of therapy. Endocrinological examination revealed hypopituitarism including the levels of TSH, FSH, GH and ACTH. The secretion of FSH and LH gradually improved after replacement therapy of dried thyroid. MRI examination of the brain revealed an empty sella. It is known that pituitary tumor, cerebrovascular accident and autoimmune lymphocytic hypophysitis cause hypopituitarism. In this case, it is unlikely that the pulse therapy may be responsible for the infarction of the anterior pituitary artery furthermore, there has been no articles describing such incidence after steroid pulse therapy. This case may be indicative of a very rare case in which the empty sella might have been exacerbated by the pulse therapy in the causation of hypopituitarism.

Drug Administration Schedule

Effects of treatment with bezafibrate on lipoprotein lipase activity and mass in patients with hypertriglyceridemia.

The activity and mass of lipoprotein lipase (LPL) in postheparin plasma (PHP) from patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance, hyperinsulinemia were investigated in order to clarify the cause of hypertriglyceridemia and the effects of bezafibrate (CAS 41859-67-0), a novel lipid lowering agent. Eight weeks of treatment with bezafibrate (200 mg/d) lowered plasma total cholesterol and triglyceride by 7 and 39%, respectively, and increased plasma high density lipoprotein (HDL) cholesterol by 23% in the patients (n = 15). The LPL activity and mass of PHP in the patients were found to be lower than in the normal controls. The LPL activity and mass of PHP in the patients before treatment with bezafibrate (n = 15) were 2.05 +/- 1.06 mumol/ml/h and 147 +/- 45 ng/ml, respectively, whereas after treatment with 200 mg/d of bezafibrate for 8 weeks, these values were 3.62 +/- 1.30 mumol/ml/h (p < 0.01) and 226 +/- 57 ng/ml (p < 0.05), respectively. The increases of LPL mass were positively correlated with the decrease of triglyceride levels during the same period. These results suggest that the expression of LPL enzyme protein is impaired in patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance and hyperinsulinemia, and the impaired expression of LPL recovers during treatment with bezafibrate, resulting in improvement of hypertriglyceridemia.

Adult

[Postoperative intravesical installation of tetrahydropyranyl-adriamycin (THP) and cytosine arabinoside (CA) for superficial bladder cancer: clinical results of prophylactic effects on recurrence].

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) and cytosine arabinoside (CA) was performed on 42 patients with superficial bladder cancer after transurethral resection (TUR) for the purpose of prophylaxis of recurrence. The instillation was carried out with 30 mg of THP dissolved in 30 ml of distilled water and 200 mg of CA (total 40 ml). These drugs were instilled 7 times for the initial 2 weeks after TUR, and then 7 times every two weeks, 8 times every month, and 4 times every three months. Cases eligible for evaluation of efficacy were 38 out of 42 patients. The cumulative non-recurrence rate at one, two and three years were 94%, 84% and 75%, respectively. These high non-recurrence rates were demonstrated regardless of the size, number and pathological grade of the tumors. Severe bladder irritability was demonstrated in 8 (19%) of 42 patients, but generalized side effects were not seen in any case. The reformed regimen with 20 mg of THP in 30 ml of physiological saline solution was then performed on trial in several patients and there were no severe symptoms. THP combined with CA seems to be remarkably effective for the prophylaxis of recurrence, while a high concentration of THP in distilled water may lead to severe bladder irritability.

Administration, Intravesical

[A multicentric glioma exhibiting three supratentorial lesions].

We reported a multicentric glioma having three separate lesions in the cerebrum. A 75-year old man was hospitalized with progressive disorientation. Computed tomography demonstrated two lesions in the left temporal lobe and the right frontal lobe. Magnetic resonance image disclosed one more lesion in the right occipital lobe. 2-staged operative procedures were performed for the left temporal and the right frontal tumors. It was histologically proven that one was glioblastoma and the other was anaplastic astrocytoma. The patient subsequently underwent radiotherapy and chemotherapy. Most multicentric gliomas are diagnosed in autopsy. Therefore it should be stressed that diagnosis is best made by biopsy or surgery. We discussed what therapy we should use for this fatal disease.

Aged

Effects of preoperative transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma. The relationship between postoperative course and tumor necrosis.

BACKGROUND: The effects of preoperative transcatheter arterial chemoembolization (TAE) for hepatocellular carcinoma (HCC) remain a matter of controversy. METHODS: Seventy-two patients with HCC were entered in the study; the patients did not have the risk factors for disease recurrence of tumor larger than 5 cm in diameter, the presence of venous invasion, or intrahepatic metastasis. Only patients with 3 years of follow-up after curative resection were selected. Forty-six underwent TAE (Group I) and 26 did not undergo TAE (Group II). Group I was divided into three subgroups according to the degree of tumor necrosis: IA, complete necrosis; IB, partial necrosis; and IC, no necrosis. Group II was divided into two subgroups: IIB, partial necrosis; and IIC, no necrosis. RESULTS: Preoperative TAE did not improve the average disease-free survival rates of the group as a whole. For patients undergoing TAE, the survival rate of Group IB was significantly worse than that of Groups IA or IC. The survival rate of Group IB was worse than that of Group II, but the difference was not significant. In Group II, the survival of Group IIB was worse than that of Group IIC. Histologically, residual tumor cells lacking mutual contact were detected in some patients in Group IB. CONCLUSION: These results indicate that partial tumor necrosis caused by preoperative TAE or spontaneous tumor necrosis per se might facilitate postoperative disease recurrence. This may occur because in patients with partial necrosis, the remaining tumor cells are less firmly attached and more likely to be dislodged into the bloodstream during hepatic resection.

Adult

Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

CYP3 A4 is the adult-specific form of cytochrome P450 in human livers [Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. & Kamataki, T. (1990) Biochemistry 29, 4430-4433]. The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5'-flanking sequences between CYP3A4 and CYP3A7 genes was 91%, and that each 5'-flanking region had characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470-1475]. The BTE binding factor (BTEB) was present in both adult and fetal human livers. To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5'-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) specific element(s) which could bind with a factor(s) in livers was present in the 5'-flanking region of the CYP3A4 gene to show the transcriptional activity.

Adult

Proliferating cell nuclear antigen in hepatocellular carcinoma and small cell liver dysplasia.

BACKGROUND: Recently, proliferating cell nuclear antigen (PCNA) has been measured by using a monoclonal antibody in a variety of malignant neoplasms. METHODS: The authors evaluated cell proliferative activity by immunostaining for PCNA in 92 hepatocellular carcinoma nodules and 14 lesions of small cell liver dysplasia. RESULTS: The average PCNA labeling indices (LI) in Grades I, II, III, and IV were 12.2%, 17.5%, 53.7%, and 83.9%, respectively. There were statistically significant differences in the PCNA LI between all the histologic grades, except for Grades I and II. The less differentiated the histologic grade, the higher the PCNA LI became. This finding was also recognized in a hepatocellular carcinoma showing a "nodule in a nodule" appearance, in which the less-differentiated inner nodule had a higher PCNA LI than did the well-differentiated outer lesion. For an analysis of the disease-free survival in 74 patients with clinical follow-up data, 2 groups of patients with a PCNA LI higher and lower than the average level (32.0%) were compared. The disease-free survival rate after surgery was significantly higher (P < 0.005), and the venous invasion was significantly less frequent (P = 0.0003) in the low PCNA LI group than in the high PCNA LI group. The average PCNA LI in small cell liver dysplasia was 13.9%, which was almost equal to that of Grades I and II hepatocellular carcinoma. CONCLUSIONS: The PCNA LI of hepatocellular carcinoma showed a close correlation with both the histologic findings and the biologic behavior. Small cell liver dysplasia was a small round focus having proliferative activity similar to that of Grades I and II hepatocellular carcinoma.

Aged

The primary structure of two proteins from the small ribosomal subunit of rice.

We isolated two rice cDNAs which encode an open reading frame of 117 amino acids or 82 amino acids. Their deduced amino acid sequence correspond to the ribosomal proteins (r-protein). A comparison of the amino acid sequence shows that the deduced amino acid sequence of one cDNA is homologous to the rat r-protein S20 and Xenopus r-protein S22. Another encoded products with a high degree of homology to the rat r-protein S21 and the yeast r-protein YS25.

Amino Acid Sequence

Transitional cell carcinoma pattern in primary carcinoma of the fallopian tube.

BACKGROUND: A broad papillary proliferation resembling that in transitional cell carcinoma (TCC) of the urinary bladder was seen in 12 of 21 primary carcinomas of the Fallopian tube (PCFT). METHODS: According to their predominant histologic pattern (more than 50%), PCFT were classified into 9 TCC-predominant and 12 non-TCC-predominant tumors. The two groups were compared by clinicopathologic, histochemical, and immunohistochemical means. RESULTS: TCC-predominant tumors were grossly solid and microscopically demonstrated more frequent tumor necrosis and spindled tumor cells than non-TCC-predominant tumors. Mucin histochemistry revealed a correlation between TCC-predominant tumor and sulfomucin-predominant secretion and between non-TCC-predominant tumor and sialomucin-predominant secretion. Immunohistochemical studies for cytokeratins, vimentin, epithelial membrane antigen (EMA), Leu-M1, carcinoembryonic antigen (CEA), and CA 125 were not useful for discrimination between the two groups. Both groups showed similar features in patient age, clinical stage, cytology of ascites or peritoneal washing, and serum CA 125 level. Despite the similarity in treatment (surgery and postoperative chemotherapy) between the two groups, TCC-predominant tumors tended to relapse later (mean, 31.2 months after diagnosis) than non-TCC-predominant tumors (mean, 14.4 months after diagnosis), resulting in a significant difference in the 2-year disease-free survival rate. CONCLUSIONS: TCC pattern and non-TCC pattern are considered to be worthy of distinction in PCFT.

Adult

High-risk human papillomavirus infections and overexpression of p53 protein as prognostic indicators in transitional cell carcinoma of the urinary bladder.

Ninety Japanese patients with transitional cell carcinoma of the urinary bladder were investigated for tumor incorporation of DNA for high-risk human papillomavirus (HPV) types 16, 18, and 33 by in situ hybridization with biotinylated DNA probes. In addition, immunohistochemical analysis of p53 protein expression was performed with an antibody to p53 protein. Twenty-eight tumors were positive for HPV DNA, and multiple HPV infection was detected in 17 cases. Positive nuclear staining of cancer cells by the antibody to p53 protein was detected in 32 cases. DNA for HPV 16, 18, and/or 33 and the overexpression of p53 protein were simultaneously observed in 6 tumors by using a mirror section method. The overexpression of p53 protein was frequently detected in invasive and nonpapillary tumors (P < 0.05) and in high grade tumors (P < 0.05). In contrast, HPV infection was more common in noninvasive and papillary tumors (P < 0.01). The patients with tumors positive for HPV DNA and/or p53 antibody had a significantly worse survival rate (P < 0.05). These results suggest that HPV infection or overexpression of p53 protein may be related to tumor behavior and may indicate a relatively poor prognosis in patients with transitional cell carcinoma.

Aged

X-ray absorption spectroscopic studies of a transient intermediate in the reaction of cyanide metmyoglobin with dithionite by using rapid freezing.

The reaction of cyanide metmyoglobin (Mb+CN-) with dithionite produces a transient intermediate, supposed to be cyanide-ligated ferrous myoglobin. The Fe K-edge X-ray absorption spectrum of the intermediate has been measured by using rapid freezing and compared with those of Mb+CN- and deoxymyoglobin (deoxyMb). The shapes of the XANES (X-ray Absorption Near Edge Structure) spectra of Mb+CN- and the intermediate are very similar, including the intensity ratios of the peak C1 to D. This indicates that CN- remains bound with a linear Fe-C-N configuration in the intermediate. The absorption edge of the intermediate is shifted to 1.2 eV lower energy than that of Mb+CN-, reflecting a valence change in the heme iron. The EXAFS (Extended X-ray Absorption Fine Structure) spectrum of the intermediate closely resembles that of Mb+CN- but significantly differs from that of deoxyMb. Analysis shows that the average iron-nearest neighbor atom distance is 1.99 +/- 0.01 A for both Mb+CN- and the intermediate and 2.05 +/- 0.01 A for deoxyMb. These results imply that the local structure around the heme iron of Mb+CN- does not change upon reduction until the cyanide ligand is released.

Animals

Characterization of inhibitory activities and binding mode of synthetic 6'-modified methyl N-acetyl-beta-lactosaminide toward rat liver CMP-D-Neu5Ac: D-galactoside-(2-->6)-alpha-D-sialyltransferase.

6'-Deoxy (12), 6'-thio (13), and 6'-O-tetrahydropyranosyl (14) analogues of methyl N-acetyl-beta-lactosaminide (3), were synthesized from lactose. NOE experiments proved that they adopt the same conformation as that of 3. Inhibition studies using these synthetic analogues, including the disulfide dimer 15, toward (2-->6)-alpha-sialytransferase (EC 2.4.99.1) revealed that the 6'-deoxy analogue 12 had remarkable inhibitory activity as the first acceptor-analogue inhibitor for this enzyme. It is noteworthy that the disulfide 15 also behaves as an inhibitor. The results indicated that chemical modification at the 6'-position of 3 did not cause much decrease in the binding affinity to the sialytransferase. Further, a novel possibility that the acceptor and the acceptor-analogue inhibitor can bind simultaneously to the sialytransferase was proposed based on the inhibition studies with 12 and CMP.

Amino Sugars

Different functional forms of G-protein beta gamma-subunits, beta gamma-I and beta gamma-II, in bovine brain.

Heterotrimeric GTP binding regulatory proteins (G proteins) are involved in the signal transduction process in cells. We have previously demonstrated that G protein (Gi/o) in bovine brain contains two subspecies of the beta gamma-subunit, beta gamma-I and beta gamma-II, with distinct gamma subunits, i.e., gamma-I and gamma-II, but identical beta-subunit. We found that gamma-I agreed with the gamma-subunit reported elsewhere, while gamma-II was a novel gamma-subunit. In the present study we separated the fractions containing G-protein isoforms, Go*, Gi1, Go and Gi2, with a Mono Q column and they were subjected to 15% polyacrylamide gel electrophoresis. All isoforms were shown to possess both gamma subunits, gamma-I and gamma-II. The molar ratio of the two gamma-subunit isoforms was one to one, based on the relative intensity of Coomassie blue-stained bands. Differences in biological activity between G proteins composed of beta gamma-I and beta gamma-II were investigated. The amount of GTP gamma S bound to the alpha-subunit was larger in alpha beta gamma-I than in alpha beta gamma-II. The pertussis toxin-catalyzed ADP-ribosylation on alpha-subunit was enhanced by either beta gamma-subunit subspecies, but the effect was larger with beta gamma-I than with beta gamma-II. From gel filtration with a Sephacryl S 300, it appeared that all alpha- and either beta gamma-subunit, i.e., beta gamma-I or beta gamma-II, formed a trimer complex. These findings suggest the possible existence of two different functional forms in each G-protein isoform depending on the beta gamma-subunit subspecies.

Animals

Lipoprotein lipase mass and activity in severe hypertriglyceridemia.

To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LPL mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was 2,960 +/- 1,057 nmol/ml/h. The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were 25 +/- 5 ng/ml and 224 +/- 60 ng/ml, respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 mumol FFA released/h/microgram LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than -2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than -2 S.D. despite the fact that LPL masses were not less than -2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.

Adult

The prognostic value of immunohistochemical staining for proliferating cell nuclear antigen in synovial sarcoma.

BACKGROUND: The biologic behavior of synovial sarcoma remains a matter of controversy. Some investigators considered proliferative activity to be an important prognostic factor in this tumor. METHODS: Fifty-six patients with synovial sarcoma were immunohistochemically studied with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA). The percentage of nuclear areas with positive staining for PCNA (PCNA score), quantified by using an image analyzer, was compared with nuclear atypia, tumor necrosis, mitoses, and survival. Fifty-one patients were available for survival analysis. DNA flow cytometry was performed on 30 patients and compared with PCNA score and survival. The prognostic variables were analyzed with a multivariate technique using the Cox hazard model. RESULTS: Nuclear atypia (mild, 14; moderate, 23; severe, 14), mitosis (low, 34; high, 17), and tumor necrosis (< 50%, 37; > 50%, 14) were found to highly affect survival in the log-rank test (P < 0.01). Sixteen patients with a high (> or = 12.5) PCNA score had a worse survival (P < 0.01) than did the 35 patients with a low (< 12.5) PCNA score. In patients in whom DNA flow cytometry was performed, the S+G2M-phase fraction showed no correlation with the clinical outcome. However, there was a significant relationship between the extent of PCNA staining and S+G2M fraction (correlation coefficient [CC] = 0.54; P = 0.002), although the CC between PCNA staining and the mitotic count was only 0.38. However, the ploidy pattern was not related to PCNA scores or prognosis. In a multivariate analysis, a high PCNA score (P = 0.017) and severe nuclear atypia (P = 0.0003) were strong prognostic factors. CONCLUSIONS: The results suggest that a high PCNA score is one of the poor prognostic factors in synovial sarcoma.

Adolescent