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Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 973 records · Page 54Linked to original sources

Ocular fundus lesions in systemic lupus erythematosus model mice.

We investigated the ocular fundus of (NZWXBXSB) F1 mice, which are considered to be a good model for systemic lupus erythematosus (SLE) with antiphospholipid syndrome. The abnormal fundus findings were documented by fundus photography, and the chorioretinal lesions were studied histopathologically. The incidence of ocular fundus abnormalities and systemic signs in these F1 mice was significantly higher in males than in females, as with the systemic symptoms. This indicated an influence of the Yaa (Y chromosome-linked autoimmune acceleration) gene. Lesions in the fundus appeared as white spots, which increased in number during the course of the disease and developed into retinal detachment in some animals. This developmental course resembled the course of patients with multifocal posterior pigment epitheliopathy. Dilatation of the veins and narrowing of arteries were marked. Histopathological findings included: (1) destruction of the photoreceptor cell layer, (2) degeneration and loss of the retinal pigment epithelium, (3) thickening of the wall of the choroidal arterioles, and (4) narrowing and occlusion of the choriocapillaris associated with hyaline degeneration and thrombus formation. The study of the SLE mouse model should contribute to the understanding of the abnormalities in the fundus associated with collagen diseases.

Animals↗

Prevalence of antibody against non-A, non-B hepatitis virus in Japanese patients with hepatocellular carcinoma.

Antibodies against a possible causative agent of non-A, non-B hepatitis, hepatitis C virus (HCV), in Japanese patients with hepatocellular carcinoma were analyzed using the enzyme-linked immunosorbent assay (ELISA) system from Ortho Diagnostic Systems, Japan. Fifty of 58 cases of hepatitis B virus surface antigen (HBsAg)-negative hepatocellular carcinoma were positive for the antibody (86%) and 8 of 42 cases of HBsAg-positive hepatocellular carcinoma were positive (19%). Among patients with HBsAg-negative hepatocellular carcinoma, the prevalence of the antibody was greater among those who had received a blood transfusion (97%) than among those with no history of transfusion (70%). Only 3 of 54 patients with cancers other than hepatocellular carcinoma were found to be antibody-positive (5.6%) and all three patients had a history of blood transfusion. These results show a close relationship between the presence of anti-HCV antibody and HBsAg-negative hepatocellular carcinoma in Japan.

Carcinoma, Hepatocellular↗

Antiepileptic effects under steady state of phenytoin serum levels produced in acute experiments.

The antiepileptic effects of phenytoin (PHT) were examined during steady-state serum levels. Experiments were conducted on 69 adult male rabbits weighing 2.5-3.5 kg. A steady state of one or two different PHT serum levels per rabbit was produced with intravenous (i.v.) injections of loading and infusion doses. A train of focal and generalized seizure discharges (SDs) induced by electrical stimulation was compared before and after dosing with PHT. The results showed that PHT levels of 10-40 micrograms/ml induce inhibitory effects, shortening the duration of neocortical focal SDs. The inhibitory effects paralleled the PHT levels and were proportionally related to epileptogenicity in individual neocortical areas. At serum levels under approximately 5-10 micrograms/ml, the spread of secondarily generalized SDs originating from neocortical focal SDs was suppressed more than the shortening of the duration of the primary focus. On the other hand, PHT showed no effects or only slight inhibitory effects on hippocampal SDs, and the SDs spread from them even at levels of 15-40 micrograms/ml. Electroshock (ES)-induced generalized SDs were slightly suppressed in duration at levels of 20-30 micrograms/ml. Moreover, both the focal and the generalized SDs were greatly prolonged at high serum levels (greater than 40 micrograms/ml), although such facilitative effects were rare. The clinical contributions of these results to PHT treatment in human epilepsy are discussed.

Animals↗

Possible roles of transglutaminases in Alzheimer's disease.

The localizations of two transglutaminases [factor XIIIa and tissue transglutaminase (tTG)] and their mRNAs were examined in human brain tissues from neurologically normal and Alzheimer disease (AD) cases, using immunohistochemical and in situ hybridization methods. In all cases, meningeal macrophages and ependymal macrophage/microglia were positive for factor XIIIa. The mRNA encoding factor XIIIa was detected in macrophages and microglia. As reported previously, intense staining with the antibody to factor XIIIa of a subset of microglia was seen in the parietal cortex in AD brains. Few or no microglia were found associated with classical senile plaques. In contrast, many labeled microglia were associated with primitive plaques. Further-more, most of these cells were mainly seen in the subpial cortical layer but were very rare in the hippocampus. On the other hand, few factor-XIIIa-positive microglia were found in the parietal cortices from non-neurological cases, but moderate numbers were found in their hippocampal tissues. TG and its mRNA were localized in astrocytes in all the cases. In AD, a few neurofibrillary tangles were positive to tTG. These results suggest that the subsets of microglia which express factor XIIIa may play some roles in the early phase of AD pathology.

Aged↗

Complementary DNA sequences of renin. State-of-the-art review.

The primary structure of human renin precursor was deduced from its complementary DNA (cDNA) sequence. The predicted sequence consists of 406 amino acids with a pre- and a prosegment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology, especially in the catalytically important region, was found upon comparison of the mouse and human renins. An overall homology, including presequence between the two renins, is 68.7%. Close similarities were also observed in the primary structure of renins and other aspartyl proteinases with defined three-dimensional structures, suggesting a tertiary structure for renin that is similar to the other enzymes. A bilobal model of the tertiary structure of human renin with two approximately equal domains separated by a cleft was constructed using the homology of amino acid sequence of renins and other aspartyl proteinases. These results indicate that human kidney renin is homologous with mouse submandibular renin in primary and tertiary structures, proteolytic processing, and catalytic apparatus with small differences. The major structural difference distinguishing the two renins was the presence of the two possible glycosylation sites in human kidney renin, which was not observed in mouse submandibular gland renin.

Amino Acid Sequence↗

Angiotensinogen-producing hepatocellular carcinoma.

This paper describes the first case of an angiotensinogen-producing tumor. The tumor obtained from a hypertensive patient was examined for its renin and angiotensinogen contents. Renin activity was undetectable; however, the angiotensinogen level was extremely high compared with the levels in the tissue surrounding the hepatoma. The presence of angiotensinogen immunoreactivity in the tumor cells was demonstrated by immunohistochemical staining with an angiotensinogen anti-serum. The plasma level of angiotensinogen was also markedly elevated. These results strongly suggest that the hepatoma was an angiotensinogen-producing tumor.

Adult↗

Three-dimensional structure of human renin.

A three-dimensional model of human renin has been constructed based on the assumption that the overall folding of the aspartyl proteases is very similar. As a reference, we used penicillopepsin, the structure of which has been reported at a resolution of 1.8 A, and its main chain was traced to build a model of renin. The resulting structure seems to be stable from the hydrophobic and hydrophilic viewpoints. Comparison of the tertiary structure of human renin with that of penicillopepsin and mouse renin suggests the existence of a high structural homology as well as differences in the molecular geometry of the active sites that may influence the substrate specificity. The asparagine side chains in the glycosidation signal of Asn-X-Thr are exposed on the surface. Moreover, the site in human renin that corresponds to the proteolytic cleavage site in mouse renin also appears to be exposed on the surface so as to be easily scissored during the maturation process. The insertions and deletions of amino acid residues were found to arise on the surface, and in some places they occurred in complementary manners. Models of molecular complexes between human renin and renin inhibitor were constructed to understand the interacting modes that indicate how new renin inhibitors develop. Inhibitor-binding sites were directly assigned based on the models of the inhibitor-enzyme complex.

Amino Acid Sequence↗

Anemia and neutropenia due to copper deficiency in enteral nutrition.

Copper deficiency has been regarded a rare complication of total parenteral nutrition. This report describes the first known case of anemia and neutropenia caused by copper deficiency in a patient receiving long-term enteral nutrition. A 34-year-old man presented with bulbar palsy and tetraplegia after an operation for cerebellar hemorrhage on June 7, 1989. Nasopharyngeal tube feeding with a defined-formula diet (Besvion) was instituted on June 19, 1989. He developed normocytic anemia and neutropenia approximately 19 months after the initiation of the tube feeding. Serum copper and ceruloplasmin levels were markedly below normal. There were anisocytosis and erythrocyte deformities in the peripheral blood smear. Bone marrow aspirates revealed a hypocellular marrow with numerous myeloid and erythroid cells with cytoplasmic vacuoles. Because the amount of copper administered was estimated to be 2.6 to 5.1 mumol/d during the tube feeding, copper deficiency was suspected to be the cause of the hematologic disorders. The patient's daily oral copper intake was increased to 34 mumol/d. His serum copper and ceruloplasmin concentrations reached a normal level after 16 days and 23 days of copper supplementation, respectively. A marked reticulocytosis occurred after 10 days of copper supplementation, and his anemia gradually improved over the next 3 months. His blood neutrophil count also returned to normal within 2 weeks.

Adult↗

Computer simulation of optimum personnel assignment in hospital pharmacy using a work-sampling method.

A computer simulation of the dispensing work performed in a hospital pharmacy was undertaken, based on analysis data from a work-sampling method and utilizing a personal computer. As a result it was found to be possible to estimate the complete work volume of a day based on the number of prescriptions in the day, and hence to predict fairly precisely the number of pharmacists required to complete that work. The method also enables the users to assign the optimum number of staff for dispensing duties according to the estimated number of prescriptions and the optimum waiting time of patients. A correlation has been noted between the total residence time of prescriptions and the mean waiting time of patients. Using this simple and effective technique to efficiently assign personnel makes it possible to cope with an increasing workload and limited number of staff.

Computer Simulation↗

Levels of proelafin peptides in the sera of the patients with generalized pustular psoriasis and pustulosis palmoplantaris.

The levels of proelafin peptides in the sera of patients with pustulosis palmoplantaris, a unique type of localized pustular psoriasis, and generalized pustular psoriasis were determined by competitive enzyme-linked immunosorbent assays using antibodies against synthetic proelafin polypeptides corresponding to the elastase inhibitor (elafin) and transglutaminase substrate domains. The sera of patients with pustulosis palmoplantaris (9 cases) exhibited a normal range of proelafin peptide levels. The sera of patients with generalized pustular psoriasis (3 cases) showed high titres of proelafin peptide. There were no large differences in the titres between the 2 antibodies. The antibodies for 2 different domains of proelafin showed a similar immunoreactivity for the non-pustular region of the epidermis in all pustulosis palmoplantaris tested. The results indicate that serum proelafin peptides in pustular psoriasis may depend on the extent of the involved area, and that proelafin peptide level in pustulosis palmoplantaris remains normal despite enhanced local expression in the lesional skin. Since the skin lesions of patients with pustulosis palmoplantaris are limited to the palms and soles, enhanced expression of proelafin in the lesional skin may not lead to elevation of proelafin peptides in the serum.

Adult↗

Gene expression of human squamous cell carcinoma antigens 1 and 2 in human cell lines.

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. Little is known concerning how expression of the SCCA1 and SCCA2 genes is regulated in human cell lines. The purpose of this study was to determine whether the SCCA1 gene or SCCA2 gene is more strongly expressed in human cell lines. Squamous cell carcinoma cell lines secreted respectively 4 times and 50 times as much SCCA proteins into medium as normal human keratinocyte and non-squamous cell carcinoma cell lines, as measured by enzyme-linked immunosorbent assay. Quantitative RT-PCR ELISA digoxigenin-labeling assay demonstrated that SCCA1 mRNA expression in squamous cell carcinoma cell lines was respectively 2.8 times and 42 times that in keratinocyte and non-squamous cell carcinoma cell lines. The ratio of SCCA1 to SCCA2 mRNA expression differed distinctly among squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines (2.8, squamous; 24.1, keratinocyte; 11.0, non-squamous). These findings suggest that SCCA1 is mainly expressed in squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines and that the ratio of SCCA1 to SCCA2 expression might be a novel marker for the detection of squamous cell carcinoma.

Adenocarcinoma↗

Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats.

Clarithromycin and its metabolites have been examined for their abilities to induce specific form(s) of cytochrome P-450 and metabolite complex formation in rats. Pretreatment of rats with clarithromycin,N-demethyl clarithromycin, clarithromycin N-oxide, and decladinosyl clarithromycin resulted in 48-75% decreases in the amount of 2C11 and 100-600% increases in the amount of 3A1. Clarithromycin and N-demethyl clarithromycin, but not decladinosyl clarithromycin, produced a metabolite complex with cytochrome P-450 in vivo. Activities of testosterone 2 beta- and 6 beta-hydroxylases were increased by administration of clarithromycin and N-demethyl clarithromycin when these activities were measured in the presence of ferricyanide, but not significant induction was observed when measured in the absence of ferricyanide. Clarithromycin N-oxide treatment resulted in the increase in hydroxylation of testosterone not only at the 2 beta- and 6 beta-positions (430 and 190%, respectively), but also at 7 alpha-position (60%), regardless of the presence or absence of ferricyanide. In vitro experiments with hepatic microsomes of dexamethasone-pretreated rats indicated that the metabolites that were modified at the tertiary amino group more efficiently produced the metabolite complex with cytochrome P-450 compared with the parent compound. In contrast, decladinosyl and hydroxylated metabolites had similar or lower capacities for metabolite complex formation than did the parent compound. Clarithromycin and its N-modified metabolites were able to induce 3A1 and form a metabolite complex with cytochrome P-450 in vivo in varying extents. Decladinosyl clarithromycin has a weak inducibility of 3A1 and did not form a metabolite complex with cytochrome P-450 in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinicopathological features of gastric cancer in the remnant stomach.

BACKGROUND/AIMS: The clinicopathological features of 34 cases of gastric cancer in the remnant stomach were examined. PATIENTS AND METHODS: Twenty-three patients who underwent primary gastrectomy for benign gastric disease (Group I) and 11 patients who received gastrectomy because of primary gastric cancer (Group II) were studied. RESULTS: The median age at diagnosis of gastric remnant cancer was 62.2 years in Group I and 63.7 years in Group II. The median time interval between the primary operation and the appearance of gastric cancer was 12.6 years in Group I and 6.5 years in Group II. Almost all patients were symptomatic; presenting epigastralgia and constriction. The first diagnostic procedure for these patients was barium examination of the remnant stomach except one patient diagnosed by emergency gastroscopy for hematemesis. Seventy percent of patients in Group I had advanced gastric cancer, most of which were invasive to seromuscular layers, whereas in Group II early gastric cancer was dominant (55%). The prognostic evaluation after the second surgery showed that patients with early stages of cancer had longer survival in both Groups. CONCLUSIONS: These results suggest that early detection of gastric cancer in the remnant stomach by periodical follow up is important and that the application of aggressive surgery for this disease will provide better patient survival.

Adult↗