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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 19 recordsLinked to original sources
PubMed1995

Uptake of fractionated 3H-heparin by isolated rat Kupffer cells.

PURPOSE AND METHODS: The uptake of fractionated 3H-heparin by isolated rat Kupffer cells was examined to determine the uptake mechanism. RESULTS: The association of fractionated 3H-heparin was concentration-dependent with a dissociation constant of 3.4 nM and a maximum association capacity of 1.3 pmol/10(6) cells, suggesting the involvement of a specialized mechanism. Although 2,4-dinitrophenol inhibited neither the association nor internalization of fractionated 3H-heparin, lowering the temperature from 37 degrees C to 4 degrees C reduced the internalization of fractionated 3H-heparin by 70% without affecting the association. CONCLUSIONS: It is suggested that the uptake mechanism may differ from receptor-mediated endocytosis of polypeptides and be mediated by scavenger receptors, because organic anions, and several ligands of scavenger receptors, as well as several heparin analogs, inhibit the binding of fractionated 3H-heparin to Kupffer cells, while phenylarsine oxide, which is known to inhibit the receptor-mediated or absorptive endocytosis of polypeptides, inhibits neither the association nor internalization of fractionated 3H-heparin.

2,4-Dinitrophenol↗
PubMed1995

Effects of ageing on the oral absorption of D-xylose in rats.

The effects of ageing on the oral absorption of D-xylose were investigated in rats. The pharmacokinetic analysis of D-xylose concentration in plasma after oral administration showed that the fraction absorbed was increased to 0.998 +/- 0.002 and 0.950 +/- 0.049, respectively, in old (52 weeks) and very old (102 weeks) rats, compared with 0.768 +/- 0.052 in young (9 weeks) rats, while the absorption rate constant was not significantly changed: 0.944 +/- 0.233, 0.844 +/- 0.143 and 0.725 +/- 0.004 h-1, respectively, in young, old and very old rats. The absorbed fractions estimated from faecal and urinary excretion were in agreement with those by the pharmacokinetic analysis. Thus, the present study demonstrated an increase in the extent of the oral absorption of D-xylose with ageing. The increase in the extent of absorption might be caused by a delay in the intestinal transit, because the absorption rate constant was unchanged. These results suggest potential increases with ageing in the fractions absorbed of hydrophilic drugs such as D-xylose where oral absorption is incomplete.

Administration, Oral↗
PubMed1995

Influence of anesthetic regimens on the intestinal absorption of 5-fluorouracil in rats.

We investigated the influence of anesthetic regimens on the intestinal absorption of 5-fluorouracil (5-FU), which is known to be absorbed by concurrent Na(+)-dependent, carrier-mediated transport and passive transport, in single-pass perfusion experiments in rats. Compared with the absorption in unanesthetized rats, the regular dose of urethane (1.13g/kg) reduced the maximum transport rate (Jmax), the Michaelis constant (Km) and the membrane permeability coefficient of passive transport (P m,d); a low dose of urethane (0.7g/kg) reduced Jmax and Kmax, but did not affect Pm,d; pentobarbital sodium (50 mg/kg) increased Jmax without affecting Km, and reduced Pm,d. The reductions in Jmax and Km were comparable for the regular and low doses of urethane. Thus, urethane and pentobarbital, which have been most commonly used in laboratory animal experiments, exerted qualitatively different effects on the carrier-mediated transport of 5-FU, although they similarly inhibited the passive transport. For urethane, the effect on the passive transport was avoided by reducing the dose, but the effect on the carrier-mediated transport was not. This influence of anesthetic regimens on intestinal drug absorption may not be easily scaled for normalizing absorption data. When compiling them for such purposes as establishing in situ-in vivo quantitative correlation, the absorption data in perfusion (in situ) should be categorized on the basis of anesthetic regimens, to avoid ending up with poor outcomes. We also examined the effect of urethane on the exsorption of Na+ in the intestinal loop where Na+-free buffer was introduced, and found a minimal effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1994

Absence of paravascular nerve projection and cross-innervation in interscapular brown adipose tissues of mice.

To determine whether a paravascular nerve projection or cross-innervation exists in the interscapular brown adipose tissue (BAT), the distribution of noradrenergic or peptidergic nerve fibers in intact or denervated interscapular BAT pads of mice was examined histochemically. Noradrenaline (NA) fibers were visualized by the glyoxylic acid condensation method, and neuropeptide Y (NPY) and substance P (SP) fibers were detected immunohistochemically. Numerous NA-positive fibers and a few NPY- or SP-positive fibers were observed around intralobular arterioles in intact BAT pads. Some NA-positive fibers and very few NPY- or SP-positive fibers were seen around interlobular arteries. NA- and NPY-positive fibers were also found around brown adipose cells in the parenchyme of BAT, whereas SP-positive fibers were absent around the cells. However, all sections cut from denervated BAT pads of unilaterally or bilaterally denervated animals showed a total absence of NA-, NPY- or SP-positive nerve fibers. Therefore, neither a paravascular projection of NA, NPY, and SP fibers to the BAT nor a cross-innervation of these nerve fibers between the left and right BAT pads exists in the mouse BAT.

Adipose Tissue, Brown↗
PubMed1994

Interindividual difference in expression of human Ah receptor and related P450 genes.

The genomic clones of human aryl hydrocarbon receptor (Ahr) and Ahr nuclear translocator (Arnt) were isolated, and the structures of exon-intron junctions of these genes were partially determined. Based on the sequence information, a quantitative RT-PCR analysis was developed, and the expression of these genes was studied in various human tissues. mRNAs for Ahr and Arnt were widely expressed in human tissues and abundantly in lung. Individual difference in expression levels of Ahr and Arnt mRNA was observed in liver, lung and blood. In order to examine whether expression levels of Ahr and Arnt were associated with those of CYP1A1, we studied the expression of these mRNAs in blood among 20 healthy subjects, taking account of individuals' cigarette smoking habits. We found that the expression levels of CYP1A1 appeared to associate with those of Ahr and Arnt mRNAs (P < 0.06), and also that the expression of Ahr and Arnt was influenced by cigarette smoking. The expression of human Ahr and Arnt is reported here for the first time, providing a quantitative RT-PCR analysis as a useful tool for further studies.

Adult↗
PubMed1994

Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region.

The effects of two genetically associated polymorphisms [c1 allele: PstI -, RsaI +; c2 allele: PstI +, RsaI -] in the 5'-flanking region on the regulation and expression of the human CYP2E1 gene were investigated. DNase I footprinting and CAT activity analyses using various deletion mutants constructed with DNA segments from genotype A (c1/c1) or C (c2/c2) and SV40 or an endogenous promoter showed that the RsaI polymorphism affects the binding of a transcription factor and the transcriptional activation of CYP2E1, while the PstI polymorphism has little effect. The correlation between the genotypes and expression levels of CYP2E1 mRNA were examined in peripheral lymphocytes of 86 individuals by RT-PCR, the alcohol consumption by the subjects being taken into account. In non-drinkers, the mean ratio of the expression of CYP2E1 mRNA to that of GAPDH mRNA in genotype B (c1/c2) was 1.7-fold higher than that in genotype A (0.05 < p < 0.10). As compared to non-drinkers with genotype A, subjects with genotype B who drank alcohol on a daily basis expressed about 2.0-fold higher levels of CYP2E1 mRNA (p < 0.01). These results indicate that a RsaI polymorphism in the 5'-flanking region of CYP2E1 may lead to inter-individual differences in CYP2E1-mediated microsomal drug oxidation activities, including oxidation of N-nitrosamines.

Alleles↗
PubMed1994

[Semi-radical transurethral resection of the prostate for small benign prostatic hyperplasia].

The conventional method of transurethral resection of the prostate (TUR-P) is often not beneficial for small benign prostatic hyperplasia (BPH) because of a high frequency of postoperative bladder neck contracture (BNC). Herein, we examined the usefulness of semi-radical transurethral resection of the prostate (semi-radical TUR-P) from the view points of improvement of peak flow rate, the frequency of postoperative BNC and incidental carcinoma of the prostate in 79 cases of small BPH (group A) and 101 cases (group B) of large BPH in which less than 10 g for more than 10 g of the internal glands was resected, respectively. The bladder neck was resected carefully to avoid over resection which may cause BNC in small BPH cases. Satisfactory results were obtained in both groups, that is, the improvement of the peak flow rate from 7.03 +/- 3.79 ml/sec to 13.9 +/- 7.32ml/sec and from 4.96 +/- 2.88 ml/sec to 15.2 +/- 8.30 ml/sec, and the frequency of BNC were 2.53% (2/79) and 1.98% (2/101) in groups A and B, respectively. The frequency of incidental carcinoma of the prostate were 15.2% (12/79) and 17.8% (18/101) in groups A and B. We conclude that semi-radical TUR-P is a favorable maneuver for small BPH because of satisfactory improvement in peak flow rate with low frequency of postoperative BNC and its superiority in screening test for incidental carcinoma of the prostate.

Aged↗
PubMed1993

Predictive value of screening tests for persistent hepatitis C virus infection evidenced by viraemia. Japanese experience.

In November 1989, Japanese Red Cross Blood Centres started screening for hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with > or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
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↗