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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 289 records · Page 16Linked to original sources
PubMed1993

Low temperature dependent IgG3 subclass antibody with low avidity to C100-3 antigen derived from hepatitis C virus in voluntary blood donors.

The presence of an antibody which reacts strongly at lower temperatures to C100-3 antigen derived from the hepatitis C virus (HCV) was demonstrated in blood donors' sera. These sera reacted with the antigen most strongly at 4 C and most weakly at 37 C and are termed 'cold antibody group'. The cold antibody group reaction was specifically inhibited with soluble C100-3 antigen. Cold antibody bound to C100-3 antigen at 4 C was dissociated at 37 C and was isolated in this manner. Low temperature-dependent anti C100-3 antibody was shown to be predominantly IgG3 subclass by ELISA using anti-human IgG subclass antibody. This IgG3 antibody was dissociated from antigen with 6M urea, demonstrating its low avidity. HCV-RNA was demonstrated in two of five samples. Therefore, to achieve more effective prevention of post-transfusion hepatitis C, we propose the incorporation of programs to detect low temperature-dependent low-avidity antibody against HCV-related antigen.

Antibody Affinity↗
PubMed1993

[Expression of proliferating cell nuclear antigen following filtration surgery in rabbits].

We evaluated cell replication in wound healing following experimental filtration surgery. Cell replication was measured via immunohistochemistry for proliferating cell nuclear antigen, which is a marker of cell proliferation. Trabeculectomy was performed on albino rabbit eyes, with the filtering site harvested on postoperative days 1, 4, 7, and 14. Samples were fixed with 10% buffered formalin and prepared for paraffin section, and proliferating cell nuclear antigen was detected in filtering site tissue using the labeled streptavidin-biotin method. The number of immunoreactive cells increased at days 4 to 7 and was markedly decreased at day 14; the filtering site was obstructed at days 7 to 14. These findings may have clinical implications for the administration of antiproliferative agents after filtration surgery. Evaluation of cell replication following filtration surgery by detecting proliferating cell nuclear antigen is a simpler technique than autoradiography.

Animals↗
PubMed1992

[Incidence of hepatitis C in chronic liver diseases following tattooing].

The seroprevalence of hepatitis C virus (HCV) was investigated in 16 tattooed men with chronic liver diseases using the Ortho-Chiron HCV antibody ELISA system. In 11 out of the 16 men, the result was positive, which was significantly higher as compared with that of presumably healthy blood donors in the Tokyo area, i. e., 1.14% of 2470 donors tested. These results suggest that HCV infection occurred at the time of tattooing in these 11 patients.

Adult↗
PubMed1992

Uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary culture: effects of alpha-globulin, temperature, and pH.

The mechanism of uptake of fractionated [3H]heparin in conjunction with the effect of alpha-globulin (the major binding protein of heparin) was investigated in primary cultures of rat parenchymal hepatocytes. The uptake clearances were estimated from the initial linear phase, up to 1 min, of the uptake-versus-time profile. The uptake clearance for fractionated [3H]heparin was 11.0 mL/min/g of liver at 7.5 nM fractionated [3H]heparin in the absence of alpha-globulin. This value decreased with increasing concentration of alpha-globulin in the incubation solution, a fact suggesting that the rate of uptake of alpha-globulin-bound, fractionated [3H]heparin is lower than that of unbound [3H]heparin, as generally assumed for hepatic drug elimination. However, the uptake clearance in the presence of alpha-globulin at 8 mg/mL, where free, fractionated [3H]heparin was supposed to be negligible according to the results of our in vitro study, was approximately 12% of that in the absence of alpha-globulin. These results suggest that alpha-globulin-bound, fractionated [3H]heparin also contributes to the uptake of fractionated [3H]heparin. This effect on uptake could be explained by the protein-mediated transport concept rather than the traditional assumption that protein-bound drugs are not transported. The uptake clearance was reduced significantly by reducing the incubation temperature from 37 to 4 degrees C. However, neither the pH of the incubation solution (6.4-8.4) nor several inhibitors of active transport had any clear effects on the uptake clearance.

Alpha-Globulins↗
PubMed1992

Cloning and characterization of a repetitive sequence from Pneumocystis carinii.

Four repetitive sequence clones measuring 10.9-23.4 kb in length were isolated from the genomic library of Pneumocystis carinii. Restriction enzymes mapping and cross-hybridization studies revealed that these clones are interrelated and that they derive from the common repeat unit, which is specific for P. carinii. Dot-blot analysis suggested that the copy number of the repeat sequence is about 100, assuming that the genome size is 1.5 x 10(7) bp. Interestingly, the repetition unit extended over at least 23.4 kb and included long, 5.2-kb inverted repeats, for example, A-B-A'-C, in which A' is the inversion of A.

Blotting, Southern↗
PubMed1992

Postnatal changes in sublobular distribution of NADPH-cytochrome P-450 reductase in rat liver.

Immunohistochemical distribution of NADPH-cytochrome P-450 reductase (NADPH-ferrihaemoprotein reductase; EC 1.6.2.4.) in the liver lobule was examined during development of the rat. From the 19th day of gestation to 4 days after birth, the enzyme was distributed uniformly throughout the lobule. The immunostaining for the enzyme was weak before birth, and became slightly stronger after birth. A slightly uneven distribution of immunoreactivity, stronger in perivenular zones, appeared at 5 days after birth. Then, the staining intensity in perivenular zones became progressively stronger with age, except for a slight increase between 10 and 20 days of age. The intensity in periportal zones also increased gradually, although it remained weaker than that in perivenular zones. Around 30 days of age, the distribution of the immunostaining, stronger in perivenular than in periportal zones, was similar to that seen in the lobules of adult animals. Thus, heterogeneity among hepatocytes with respect to the enzyme content is not present in fetal and newborn rats but develops gradually during postnatal development; the postnatal growth of the liver is accompanied by a change in the pattern of the distribution of this enzyme within the lobule.

Age Factors↗
PubMed1992

Low prevalence of gastric metaplasia in the duodenal mucosa in Peru.

We compared the prevalence of gastric metaplasia of the duodenal mucosa (GM) and its characteristics in 204 Peruvian patients from a low socioeconomic level with the corresponding prevalence reported in dyspeptic patients from a developed country, the United Kingdom. Gastric metaplasia was significantly less prevalent in the Peruvian than in the United Kingdom series. However, when present, GM was not significantly different in extent or frequency of colonization by Helicobacter pylori or association with active duodenitis, despite a higher prevalence of H. pylori-associated gastritis. Hypochlorhydria was markedly more frequent in the Peruvian than in the United Kingdom series. The finding of a low prevalence of H. pylori-colonized GM in patients with previously reported low prevalence of duodenal ulcer gives further support to a pathogenic link between both conditions.

Adolescent↗
PubMed1992

High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes.

Lung cancer is closely associated with cigarette smoking. Aromatic hydrocarbons in smoke, including benzo[a]pyrene, first require metabolic activation by Phase I enzymes, cytochrome P450, to their ultimate forms, and these activated forms are then subjected to detoxification by Phase II enzymes, especially glutathione S-transferases. Thus, genetically determined susceptibility to lung cancer may depend on the metabolic balance between Phase I and Phase II enzymes. In this study, we identified individuals genetically at high risk of lung cancer in terms of polymorphisms of the P450IA1 gene and GST1 gene. The relative risk of individuals with a combination of the genotypes of both a homozygous rare allele of the P450IA1 gene and the nulled GST1 gene was remarkably high at 5.8 for lung cancer and 9.1 for squamous cell carcinoma compared with other combinations of genotypes.

Adenocarcinoma↗
PubMed1992

Regulation of Drosophila neural development by a putative secreted protein.

The Drosophila strawberry (sty) locus was isolated by P-element insertion mutagenesis in a screen for mutations affecting eye development. Analysis of the mutant phenotype and the putative expression pattern of the sty gene suggested that it has multiple functions. Mutations in the sty gene lead to irregular spacing of ommatidia, an increase in the number of photoreceptor cells, as well as abnormal axonal projections to the lamina and disrupted structure of the optic lobes in the adult fly. The sty mutation also causes abnormal head involution, a change in a number of sensilla in the antennomaxillary complex in the embryonic stage and abnormal morphogenesis of the maxillary palp and wings in later stages. We examined the presumptive expression of the sty gene during development by histochemical staining for lacZ expression from enhancer trap elements inserted within the sty gene. During embryogenesis, expression of lacZ showed a segmental pattern in the ectoderm and in the nervous system. In the eye imaginal discs, lacZ was expressed in photoreceptor cells beginning a few rows posterior to the morphogenetic furrow. The lacZ was also expressed in the wing disc. In the adult, lacZ was expressed in the retina and lamina. We cloned the sty gene by P-element tagging and found that it encodes a putative secreted protein containing a cysteine-rich region similar to the epidermal growth factor (EGF) repeat. On the basis of the loss of functional phenotype, the expression pattern and the predicted structure of its product, we propose that sty encodes a diffusible protein acting as a signal involved in lateral inhibition within the developing nervous system and also as a factor involved either directly or indirectly in axonal guidance and optic lobe development.

Animals↗
PubMed1992

Pathomorphologic study of pale bodies in hepatocellular carcinoma.

Pathomorphological and immunohistochemical studies were conducted on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was seen in 6 (5.7%) of 106 consecutively resected HCC cases. It was of interest that varying degrees of sclerotic change were found in 4 of the 6 cases and a certain correlation between PBs and sclerotic change of HCC tissue was suggested. Histologically, PBs were identified as a pale amorphous substance with a distinct margin and most of PBs occupied the entire cytoplasm of the cancer cells. PBs were practically negative for periodic-acid Schiff, and were also negative for phosphotungstic acid hematoxylin and orcein stains. Ultrastructurally, PBs were found to be a mass of granular or fibrillar materials having a single-layered limiting membrane, and dilated rough endoplasmic reticular (rER) were also found in the vicinity of PBs, suggesting the presence of a close relationship between rough endoplasmic reticula and PBs. Most PBs were found to be strongly positive for anti-fibrinogen antibody and some of them were weakly positive for anti-albumin, but were solely negative for other antibodies such as anti-HBs antigen, anti-alpha-1-antitrypsin, and anti-ferritin. According to those findings, PBs were thought to be fibrinogens accumulating in cystic rER due to a defective intracellular transport or an excretion disturbance.

Aged↗
PubMed1992

Long-term results of anterior chamber tube shunt to an encircling band in the treatment of refractory glaucomas.

We performed the anterior chamber tube shunt to an encircling band procedure in 34 patients (36 eyes) with refractory glaucoma, and evaluated the long-term outcome. The preoperative mean intraocular pressure (IOP) was 36.8 +/- 9.6 mmHg, the postoperative mean IOP was 21.6 +/- 13.6 mmHg, a statistically significant (p < 0.01) reduction of IOP following this procedure. The final postoperative IOP was under 21 mmHg in 23 (63.9%) of the 36 eyes. The success rate of IOP control 36 months after the operation without any elevation of post-operative IOP was 30.3% (life-table method). Complications of this procedure included flattening of the anterior chamber (61.1%), damage to the corneal endothelium (25%), hyphema (25%), and a transient IOP elevation (25%). As filtering surgery with 5-fluorouracil is more effective and simple to perform, we conclude that the anterior chamber tube shunt to an encircling band procedure should be reserved for those with refractory glaucoma who have had multiple surgical interventions.

Adolescent↗
PubMed1992

Idiopathic pulmonary fibrosis and high prevalence of serum antibodies to hepatitis C virus.

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay (ELISA) in 66 patients (46 male and 20 female; mean age +/- SEM, 61.5 +/- 10.1 yr) with idiopathic pulmonary fibrosis (IPF). Nineteen (28.8%) were positive for this test. The frequency of HCV positiveness was significantly higher in the patients with IPF than in the 9,464 control subjects, whose ages were comparable with those of the patients (3.66%, p less than 0.05). Importantly, 12 of the 19 patients with IPF and positive ELISA results (63.2%) had positive results on the Chiron recombinant immunoblotting assay (RIBA), which is known to be more specific for HCV. We judged the 12 perceptible reactions as eight reactive and four indeterminate. When we examined liver function retrospectively, only two of eight patients who tested positive for the HCV had liver dysfunction, suggesting that anti-HCV positivity in IPF was not observed as a result of liver disease. These results lead us to speculate that HCV infection may play an important role in the pathogenesis of IPF, or that the sera of patients with IPF may contain some antibody against an unknown epitope and cross-react with the anti-HCV assay.

Aged↗
PubMed1992

Relation between cytochrome P-450 increase and endoplasmic reticulum proliferation in hepatocytes of mice treated with phenobarbital: a microphotometric and morphometric study.

To obtain detailed information on phenobarbital (PB)-induced cytochrome P-450 (P-450) increase and endoplasmic reticulum (ER) proliferation in hepatocytes, we estimated microphotometrically the amount of P-450 per unit cytoplasmic volume and morphometrically the area of ER per unit cytoplasmic volume in hepatocytes adjacent to the portal area or central venule (1 periportal or 1 perivenular cells) and in the second and third layers from the portal area or central venule (2, 3 periportal or 2, 3 perivenular cells) from mice injected with 35, 50, 100, or 150 mg/kg PB once a day for 3 days. By dividing the P-450 amount by the ER area, the number of P-450 molecules per unit ER area was also calculated. In 1 and 2, 3 perivenular cells, except for 2, 3 perivenular cells after injection of 150 mg/kg PB, the amount of P-450 increased with ER proliferation and the number of P-450 molecules in ER remained unchanged after injection of 50, 100, or 150 mg/kg PB. In 2, 3 periportal cells, however, the P-450 amount and the number of P-450 molecules in ER increased markedly without or with some ER proliferation after injection of 50, 100, or 150 mg/kg PB; the P-450 increase appears to be generally independent of ER proliferation. The 1 periportal cells are probably exceptional hepatocytes that usually did not respond to PB stimulation.

Animals↗
PubMed1992

Macromolecule-macromolecule interaction in drug distribution. II. Effect of alpha-globulin on saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary culture.

The uptake of fractionated [3H]heparin was investigated in rat parenchymal hepatocytes in primary culture. The initial uptake of fractionated [3H]heparin was found to be saturable with the maximum uptake velocity (Vmax) of 10.1 +/- 1.46 pmol/min/mg protein and the Michaelis constant (Km) of 284 +/- 47.9 nM. The effect of alpha-globulin, the major protein binding to fractionated [3H]heparin, on the saturable uptake profile of fractionated [3H]heparin was also investigated. The uptake clearance was reduced, depending on the concentration of fractionated [3H]heparin, by the addition of 1 mg/ml alpha-globulin. We assumed that fractionated 3H-heparin bound to alpha-globulin was not available for uptake and that the reduction in the uptake clearance was solely attributable to the saturable binding of fractionated [3H]heparin to alpha-globulin. The uptake clearance versus concentration profile was analyzed to obtain the dissociation constant (Kd) of 31.8 nM and the capacity (n) of 0.047 for the binding of fractionated [3H]heparin to alpha-globulin. The saturable binding of fractionated [3H]heparin to alpha-globulin was supported by in vitro binding experiments using gel chromatography, in which bound fractionated [3H]heparin decreased with the concentration of fractionated [3H]heparin in the presence of alpha-globulin. In conclusion, the present study demonstrated the saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes and the saturable binding of fractionated [3H]heparin to alpha-globulin. The saturable uptake may suggest the involvement of a specific transport system such as receptor-mediated endocytosis.

Alpha-Globulins↗
PubMed1992

Effect of glucose on Na, K-ATPase activity in cultured bovine aortic endothelial cells.

The effect of high concentrations of glucose on Na, K-ATPase activity and the polyol pathway was studied using cultured bovine aortic endothelial cells. Na, K-ATPase activity was expressed as ouabain-sensitive K+ uptake. A significant decrease in Na, K-ATPase activity with an intracellular accumulation of sorbitol was found in confluent endothelial cells incubated with 400 mg/dl glucose for 96 h. However, there was no significant change in the Na, K-ATPase activity or sorbitol content of the cells incubated with 100 mg/dl glucose plus 300 mg/dl mannitol. The decrease in Na, K-ATPase induced by the high glucose concentration was restored by the simultaneous addition of 10(-4) M ponalrestat (ICI 128,436; Statil), an aldose reductase inhibitor. The addition of this agent also significantly reduced the increase in sorbitol induced by high glucose levels. These results suggest that the decrease in Na, K-ATPase activity induced in cultured aortic endothelial cells by high concentrations of glucose may be caused in part by the accumulation of sorbitol.

Aldehyde Reductase↗
PubMed1992

Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus.

In 43 patients with non-insulin dependent diabetes mellitus (NIDDM) associated with hypercholesterolemia, the effect of pravastatin, a potent HMG CoA-reductase inhibitor, on serum lipids, apolipoproteins and lipoprotein (a) was examined. After 1 to 3 months administration of 10 mg per day of pravastatin, the serum levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, while the serum level of high density lipoprotein cholesterol (HDL-C) was significantly increased in patients with NIDDM. The levels of apolipoproteins B (apo B) and E were significantly decreased, while apolipoprotein AI (apo A-I) was not changed by the administration of pravastatin. The atherogenic indices (LDL-C/HDL-C and apo B/apo A-I) were significantly decreased by the administration of this drug. The serum lipoprotein (a), which was increased in the diabetic patients, was not affected by the pravastatin treatment. Plasma glucose and hemoglobin A1c levels were not affected by the treatment. We concluded that pravastatin is a potentially useful agent in the treatment of hypercholesterolemia in patients with NIDDM.

Apolipoproteins↗
PubMed1992

[Isolated splenic tuberculosis].

A case of splenic tuberculosis is reported. The patient was a 79-year-old man who was admitted to the Tokyo Metropolitan Geriatric Hospital because of high fever and loss of body weight. Several finger-tip sized superficial lymph nodes were palpable in bilateral inguinal regions. The intermediate PPD skin test was positive. However, there was no evidences of active tuberculosis on the chest roentgenogram. The computed tomogram of the abdomen showed moderate enlargement of the spleen with multiple low density areas and several swollen lymph nodes in the para-aortic region. Although a lymph node of the inguinal region was resected for the pathologic examination, it showed no specific changes. In order to obtain a final diagnosis, laparotomy was performed. The spleen was markedly enlarged and nodular in appearance. No abnormal findings were observed in the other abdominal organs. Splenectomy was carried out. Numerous yellowish nodules, varying from 0.1 to 5 cm in diameter, were observed on the cut surface of the resected spleen (20 x 20 x 8 cm, 700 g). The bacteriologic examination revealed acid-fast bacilli. The fever subsided after splenectomy and following antituberculous therapy. Recently, isolated tuberculosis of the spleen has become very rare. Since 1965, only six cases in five reports can be found in the English, French and German literature. The present case is considered to be one such very rare cases of tuberculosis. Although splenic tuberculosis is rare at the present time, splenic tuberculosis should be included in the differential diagnosis of fever of unknown origin with splenomegaly.

Aged↗