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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 19 recordsLinked to original sources
PubMed1992

Neuroblastoma. Correlation of neuropeptide expression in tumor tissue with other prognostic factors.

BACKGROUND: The neuropeptide contents in neuroblastomas were quantified by radioimmunoassay (RIA) to assess their possible biologic significance. METHODS: Neuroblastoma tumor tissue was obtained from the primary tumor site before therapy in 16 patients with newly diagnosed neuroblastoma and in 7 patients with central nervous system medulloblastomas or gliomas. RESULTS: The tumor tissue was assayed for vasoactive intestinal peptide (VIP), somatostatin (SRIF), substance P, and neurotensin by both immunostaining and RIA techniques. Increased VIP levels of 1.2 pg/micrograms DNA or more correlated significantly with cellular differentiation (P = 0.003) and favorable disease stage (P = 0.002) in neuroblastomas. Increased SRIF contents (greater than 1.3 pg/micrograms DNA) correlated with differentiation of the tumor (P = 0.002). Increased VIP and SRIF content did not correlate with N-myc oncogene expression or ras oncogene protein immunostaining. No VIP was detectable in brain tumors, and other neuropeptides were variable in content. CONCLUSIONS: RIA of VIP and SRIF levels in primary tumor tissue may offer an independent objective assay of biologic behavior in neuroblastoma biopsy specimens.

Adolescent↗
PubMed1992

Detection of JC virus in the brains of aged patients without progressive multifocal leukoencephalopathy by the polymerase chain reaction and Southern hybridization analysis.

Ninety-one brain tissue sections taken at autopsy from 33 elderly patients (63-100 years old) without progressive multifocal leukoencephalopathy were examined for the presence of JC virus DNA by the polymerase chain reaction and Southern hybridization analysis after DNA extraction. JC virus DNA was detected in 15 sections from 10 patients. These results suggest that JC virus is frequently present in the brains of aged patients.

Aged↗
PubMed1992

Behavior of axons, Schwann cells and perineurial cells in nerve regeneration within transplanted nerve grafts: effects of anti-laminin and anti-fibronectin antisera.

Wistar rats (close cloned strain) were used to investigate the effect of endogenous laminin and fibronectin on axons, Schwann cells and perineurial cells in the regenerating peripheral nervous system (PNS). Sciatic nerve grafts obtained from donor rats were frozen, thawed and treated with rabbit anti-rat laminin or anti-fibronectin antiserum. Control grafts were treated with normal rabbit serum alone. One cm long portions of the sciatic nerve of the recipient rats were replaced with grafts. At 15 days after transplantation the number of regenerated axons in the laminin- and fibronectin-depleted grafts was half of that in the control. The growing axons in the laminin-depleted grafts did not recognize the basal lamina scaffolds (BLS) remaining in the basal lamina tubes, while in the control and fibronectin-depleted grafts 90% or more of axons grew inside the BLS. Elongation of axons always preceded migration of Schwann cells with the latter subsequently adhering to and wrapping around the former. Perineurium-forming fibroblastic cells recognized the combination of axons and Schwann cells and formed perineurial fasciculi around them. These fibroblastic cells did not recognize empty BLS but responded to them only when fibronectin was depleted. Macrophages sometimes closely faced the naked axons which elongated outside the BLS. These results suggest that in the early stages of nerve regeneration endogenous laminin and fibronectin not only regulate the growth of regenerating nerve fibers, but also exert a positive influence on perineurial cells and macrophages, both of which play important roles in nerve tissue injury and repair.

Animals↗
PubMed1992

Expression and transport into mitochondria of bovine cytochrome P-450(SCC) in insect cells using the baculovirus expression system.

Bovine cytochrome P-450(SCC) introduced with the baculovirus host vector system was found to be expressed in Spodoptera frugiperda cells. Cell fractionation analysis indicated that the P-450(SCC) expressed as the precursor form was transported into mitochondria and converted to a mature form. However, this form did not exhibit definite activity for cholesterol side chain cleavage. These findings suggest that most of the P-450(SCC) expressed by this system is an inactive protein within mitochondria that is not folded to the conformation of the active enzyme and/or does not incorporate heme appropriately.

Animals↗
PubMed1992

Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II isoforms.

The 5' regions of the human phosphoribosylpyrophosphate synthetase subunit I and II genes (PRPS1 and PRPS2, respectively) were isolated and sequenced. A comparison of the nucleotide sequences between human and rat PRPS1 genes revealed that the sequences around the transcription initiation sites were conserved over 56 nucleotides, and that a TATA-like sequence, a CCAAT box and three putative Sp1 binding sites were present at almost the same positions in the GC-rich sequences. Two major transcription initiation sites were localized in the human PRPS1, one of the two was located 27 nucleotides downstream from the TATA-like sequence, while the upstream initiation site was in the TATA-like sequence. The promoter region of the human PRPS2 gene was also GC-rich and contained a TATA-like sequence, four Sp1 binding sites and a homopyrimidine stretch. The initiation sites were localized at 90 nucleotides upstream from the ATG initiation codon. Chloramphenicol acetyltransferase (CAT)/promoter fusion assays showed that a 2.0 kb region (human PRPS1) and a 1.1 kb region (human PRPS2) possessed the promoter activities in four cell lines. The CAT activities in the three human cell lines tended to correlate with the steady-state mRNA levels of the PRPS1 and PRPS2 genes. These results suggest that the 5' flanking regions cloned contribute to the cell-differential expression of these two genes.

Amino Acid Sequence↗
PubMed1992

Chemical structures critical for the induction of FMN-dependent NADH-quinone reductase in Escherichia coli.

An FMN-dependent NADH-quinone reductase is induced in Escherichia coli by growing the cells in the presence of menadione (2-methyl-1,4-naphthoquinone). Since the properties of induced enzyme are very similar to those of NAD(P)H: (quinone-acceptor) oxidoreductase (EC 1.6.99.2), known as DT-diaphorase, from animal cells, structural requirements of quinone derivatives as an inducer of NADH-quinone reductase in E. coli were examined. Among quinone derivatives examined, it was found that 2-alkyl-1,4-quinone structure with C-3 unsubstituted or substituted with Br is critical as a common inductive signal. Michael reaction acceptors which have been reported to be strong inducers of DT-diaphorase in mouse hepatoma cells were not always effective inducers in E. coli. However, several compounds, such as 2-methylene-4-butyrolactone, methylacrylate and methyl vinyl ketone, showed a slight inductive activity. The efficient inducers of NADH-quinone reductase in E. coli contain 1,4-quinone structure as a part of the inductive signal. These compounds belong to Michael acceptors and are likely to conjugate with thiol compounds such as glutathione.

Benzoquinones↗
PubMed1992

Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.

The balance between levels of metalloproteinases and their corresponding inhibitors is a critical factor in tumor invasion and metastasis. Down-regulation of the activity of these proteases was achieved by transfection of invasive and metastatic rat cells with the complementary DNA for metalloproteinase inhibitor/tissue inhibitor of metalloproteinase 2 (MI/TIMP-2), a novel inhibitor of metalloproteinases recently described. (Y. A. DeClerck et al., J. Biol. Chem., 264: 17445-17453, 1989; W. G. Stetler-Stevenson et al., J. Biol. Chem., 264: 17374-17378, 1989). Secretion of functional MI/TIMP-2 protein in stably transfected cells resulted in a marked decrease in metalloproteinase activity. Partial suppression of the formation of lung colonies after i.v. injection in nude mice was observed in a transfected clone expressing high levels of MI/TIMP-2. Production of MI/TIMP-2 in four clones markedly reduced tumor growth rate in vivo after s.c. injection and completely suppressed local tissue invasion. Thus, down-regulation of metalloproteinase activity has a striking effect on local invasion and partially suppresses hematogenous metastasis.

Animals↗
PubMed1992

The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts.

Regeneration of the sciatic nerve in transplanted nerve grafts in which laminin was inactivated was examined electron microscopically. Nerve grafts for transplantation were obtained from close cloned donor Wistar rats; 1-cm nerve segments of the sciatic nerve were frozen and thawed to kill the Schwann cells. Control recipient rats received grafts treated with normal rabbit serum to repair the artificially-made complete defect of the right sciatic nerve, and the experimental group of rats received grafts doubly treated with normal serum and rabbit anti-laminin antiserum. In the control grafts regenerating axons grew almost completely through the inside of the basal lamina scaffolds (92%) and adhered to the structure, while in the anti-laminin antiserum treated grafts the axons were present outside (52%) and inside (48%) the scaffolds simultaneously. In this case, the adhesion of axons to the scaffolds was obscure. Axons were associated with and without Schwann cells both inside and outside the basal lamina scaffolds. No unassociated Schwann cells were observed. The maximal number of axons in a 2 mm portion of the antiserum-treated grafts was approximately 250 axons per 100 x 100 microns square and 520 in the control at 15 days. At 30 days, almost the same number of axons was found at the distal (8 mm) portion of both groups. The growth in the former was delayed for 3 days. These results indicate that regenerating peripheral nerve axons may enter the basal lamina scaffolds and grow well because of the neurotrophic function of laminin present at the inner side of Schwann cell basal lamina.

Animals↗
PubMed1992

Postoperative complications and survival after pancreatoduodenectomy in patients aged over 70 years.

An analysis of postoperative complications and survival was conducted in 31 patients undergoing pancreatoduodenectomy (PD) for carcinoma of the pancreas or periampullary carcinoma. Of them, 11 were over 70 years of age and 20 were under 70. Anastomotic leakage was the most common complication after PD. Definite pancreatic leakage was found in one patient in the over 70 group, and one case each of pancreatic, biliary, and gastric leakage were found in the under 70 group. All complications were treated conservatively without any further operative intervention. The overall morbidity rate was 41.9% (13/31), being 45.5% (5/11) in the over 70 group and 40.0% (8/20) in the under 70 group, and no operative deaths occurred within 30 days after surgery. The cumulative survival rate of the patients aged over 70 years with carcinoma of the pancreas or periampullary carcinoma did not differ significantly from the rate of those under 70. It was thus concluded that PD achieves an adequate prognosis and survival in patients over 70 years of age.

Adult↗
PubMed1992

Dementia in cerebral amyloid angiopathy: a clinicopathological study.

Dementia is in addition to cerebral haemorrhage major symptom of cerebral amyloid angiopathy (CAa). In order to explore the pathological basis for dementia in CAa-related conditions, we made a clinicopathological analysis of CAa, with special attention to dementia. Among 150 patients (mean age 78.6 years) with autopsy-proven intracranial haemorrhage in Tokyo Metropolitan Geriatric Medical Center, CAa with cerebral haemorrhage accounted for 8.0% (12 cases), associated with hypertension and metastatic brain tumour. Among 38 patients with lobar haemorrhage, CAa represented the second most common cause (21.1%) of intracranial haemorrhage after hypertension. A total of 20 patients with CAa (mean age 82.5 years) were studies clinically and pathologically. Hypertension was present in 50%. Thirteen had a history of stroke and others had either ill-defined or no strokes. The average number of strokes 2.9. Fifteen patients (75%) had dementia. Based on the clinicopathological grounds for dementia, CAa-related conditions could be divided into three subtypes: "haemorrhagic", "dementia-haemorrhagic" and "dementia" type. Haemorrhagic type (30%, 6 cases) showed multiple recurrent lobar haemorrhages caused by CAa. Hypertension was present in only 1 patient. The incidence of senile plaques and neurofibrillary tangles was generally correlated with age. Only 1 patient had dementia. The dementia-haemorrhagic type (40%, 8 patients) had recurrent strokes with cerebral haemorrhage after preceding dementia. There were two different neuropathological subsets: CAa with atypical senile dementia of Alzheimer type (SDAT) and CAa with diffuse leucoencephalopathy. Patients with CAa with atypical SDAT had multiple cerebral haemorrhages caused by CAa combined with atypical Alzheimer-type pathology. Patients with CAa with diffuse leucoencephalopathy had cerebral haemorrhages in combination with diffuse white matter damage like Binswanger's subcortical vascular encephalopathy (BSVE). The incidence of senile changes correlated with age. Patients with the dementia type (30%, 6 patients) showed progressive dementia with or without haemorrhage. All had hypertension. They had a combined condition of Alzheimer-type pathology with conspicuous CAa with BSVE. Dementia in CAa-related conditions may be responsible for multiple factors including not Alzheimer-type degeneration, but also diffuse leucoencephalopathy like Binswanger's disease. We also found an asymptomatic type, an ischaemic type, a vasculitis type and an hereditary type in this condition.

Aged↗
PubMed1992

Malignant lymphoma of the liver. Report of five cases and review of the literature.

Primary hepatic lymphoma is a rare disease. We report five cases here and summarize clinical and pathologic features of our own and reported cases from Western countries and Japan. The total number of cases was 68. The age of patients ranged from 7 to 87 years (median 55) with a male-to-female ratio of 3.1:1. Chronic hepatitis or cirrhosis before onset of hepatic lymphoma was noted in 44% of Japanese cases and 9.6% of Western cases. Macroscopically, the liver was occupied by solitary mass (60%), multiple masses (35%), or a diffuse lesion without nodule formation (5%). Histologically all cases were non-Hodgkin's lymphoma with the diffuse large cell type being most common. Three cases (4.4%) were follicular lymphoma. Immunohistochemically about 80% of the cases were B-cell type. Follow-up study showed that hepatic lymphoma had a relatively favorable prognosis when early detection of the disease was possible.

Female↗
PubMed1992

Isolation of cDNAs for LCE and HCE, two constituent proteases of the hatching enzyme of Oryzias latipes, and concurrent expression of their mRNAs during development.

The hatching enzyme of medaka consists of two types of proteases (HCE, LCE). cDNA clones for LCE and HCE were isolated from a lambda gt11 cDNA library constructed with poly(A)+ RNA of Day 3 embryos. LCE cDNA is 936 bp long and contains an 813-bp open reading frame encoding a preproenzyme with a 20-amino-acid signal sequence, a 51-amino-acid propeptide, and a 200-amino-acid mature enzyme. For HCE, two distinct cDNAs (HCE21, HCE23) having nucleotide sequences with 92.8% similarity were obtained. These cDNAs contain open reading frames encoding preproenzymes of 279 and 270 amino acids, respectively. The mature enzyme forms of both consist of 200 amino acids, the similarity between them being 95.5%. On Northern blotting analysis, the transcripts of LCE and HCE genes were first detected coincidentally in Day 2 embryos shortly before the production of LCE and HCE, accumulated thereafter in parallel, and dramatically decreased after hatching. The amino acid sequence, the HExxH motif, which is known to constitute an active site in some Zn proteases, is also found in LCE and HCE. However, the sequence analyses strongly suggest that both the enzymes belong to the astacin (protease) family, being distinct from sea urchin hatching enzyme, which is reportedly similar to collagenase.

Amino Acid Sequence↗
PubMed1992

Neuropathological background of twenty-seven centenarian brains.

The neuropathological features of 27 centenarian brains were investigated. They were found to have no fundamental differences from the brains of younger elderly individuals. It was noted that 3 centenarian brains showed no apparent senile changes or ischemic lesions and this group was designated "supernormal" centenarians. In contrast, there were 6 centenarian brains with numerous senile plaques in the cerebral cortex, a finding resembling that seen in senile dementia of the Alzheimer type (SDAT). However, these brains had only a few neurofibrillary tangles mainly in the hippocampus and the medial temporal lobe, and therefore were not affected by SDAT. These subjects were not truly demented. It was considered that these brains showed the upper limit of normal ageing, while the "supernormal" centenarians showed the lower limit. In addition, idiopathic Parkinson's disease was diagnosed pathologically in 4 subjects who did not show any clinical symptoms of this disease. Finally, 2 out of 5 cases with dementia developed it secondary to subdural haematoma.

Aged↗
PubMed1992

Effects of dithiocarbamates on testicular toxicity in rats caused by acute exposure to cadmium.

N-Benzyl-D-glucamine dithiocarbamate (BGD), N-p-isopropylbenzyl-D-glucamine dithiocarbamate (PBGD), and diethyl-dithiocarbamate (DED) were compared for their protective effects against the testicular toxicity in rats induced by acute exposure to cadmium. Rats were injected subcutaneously with 109CdCl2 (3 mg Cd and 74 kBq of 109Cd/kg) and 30 min later, they were injected intraperitoneally with the chelating agents (0.4 or 3 mmol/kg). Cadmium injection increased lipid peroxidation and concentrations of hemoglobin and Ca in the testes, decreased the testicular weight, and caused sterility. The treatment with BGD (0.4 mmol/kg) did not satisfactorily protect against the testicular toxicity of cadmium. The administration of PBGD or DED at a dose of 3 mmol/kg significantly prevented the increase in the lipid peroxidation and hemoglobin concentration in the testes, the decrease in the testicular weight, and the sterility caused by cadmium. PBGD and DED significantly decreased the cadmium concentration in the testes, but DED increased the cadmium concentration in the kidney and brain. Only DED significantly prevented the increase in the testicular Ca concentration after cadmium. These results indicate that PBGD and DED protect against the sterility caused by cadmium in rats and that the effect of DED to increase the brain level of cadmium is more dangerous than the lack of effect of PBGD to prevent the increase in the testicular Ca level. The protective effects of PBGD and DED against the cadmium-induced testicular toxicity presumably result from a decrease in the cadmium concentration in the testes.

Animals↗
PubMed1992

Processing of the prepropeptide portions of the Bacillus amyloliquefaciens neutral protease fused to Bacillus subtilis alpha-amylase and human growth hormone during secretion in Bacillus subtilis.

A set of nested 3'-terminal deletions of the prepropeptide of the Bacillus amyloliquefaciens neutral protease gene was constructed. Alpha-amylase and human growth hormone were secreted using these truncated genes in Bacillus subtilis. The level of the secreted alpha-amylase varied with the region for the truncated prepropeptide contained in the fusion gene but was independent of its length. Even though length of the prepropeptide varied, the mobilities of secreted alpha-amylases were the same as that of the control alpha-amylase derived from the alpha-amylase clone, pTUB4 (Yamazaki et al., 1983). Analyses of the secreted N-terminal amino acid sequences confirmed that they were all identical to that of the authentic one. Precursor proteins of the alpha-amylase were found in the cell-associated fraction, suggesting that the prepropeptide portion was processed during secretion. On the other hand, the N-terminus of hGH secreted using one of these prepropeptide portions varied by 1 to 4 additional N-terminal amino acid residues derived from the junction sequence between the sequence for propeptide portion and mature hGH or from C-terminal region of the propeptide portion. These results suggest that the prepropeptide portion can be generally processed even in the heterogeneous fusion. A probable mechanism of processing and maturation of the fusion gene products is also discussed.

Amino Acid Sequence↗
PubMed1992

Nephrotoxicity of a new cephalosporin, DQ-2556, in rats.

A single intravenous administration of a new cephalosporin, DQ-2556, at 1200 mg/kg to Sprague-Dawley rats induced proximal tubular necrosis. The histological lesions were not closely correlated with renal cortical concentrations of DQ-2556. Development of renal injuries was examined histologically. The arcuate and cortical radial arteries of the kidneys were constricted immediately after the injection, but then became dilated and showed histological changes: penetration by erythrocytes, edematous thickening, and necrosis in the media. In addition to congestion in the outer medulla, the proximal convoluted and straight tubules exhibited the earliest changes 30 min after the injection, namely, enlargement and rounding of the mitochondria and swelling and irregular arrangement of the microvilli in the epithelial cells. Small necrotic foci of epithelium were observed from 4 hr. They were mainly distributed in the outer cortex and the outer stripe of the outer medulla 24 hr later. In the examination of hemodynamics, DQ-2556 significantly decreased the blood flow with increased vascular resistance in the renal artery during and after a single injection. These changes had disappeared wholly or partially 60 min after dosing commenced. Furthermore, Ca2+ channel blockers markedly inhibited increases in the serum urea nitrogen and creatinine concentrations and development of the tubular necrosis and the lesions of the arterial walls, which were induced by DQ-2556. These results suggest a possible contribution of the constriction of renal artery to the tubular necrosis.

Animals↗