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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 325 records · Page 18Linked to original sources
PubMed1991

Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose.

Cytochrome P450IA1 is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke; an association of lung cancer with DNA polymorphisms of P450IA1 gene was shown in our previous study. In this paper, we investigated the interindividual difference of genetically determined susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. We first compared the total amounts of cigarettes consumed over the lifetime of patients and showed that the patients with a "susceptible" P450IA1 gene genotype contracted carcinoma after fewer cigarettes [mean +/- SD, 31.3 +/- 12.8 x 10(4) cigarettes (n = 12)] than those with other genotypes [42.5 +/- 18.2 x 10(4) (n = 33)], with a statistical significance of P less than 0.05. Next, we carried out a case-control study to estimate the odds ratios of susceptible to nonsusceptible individuals in relation to the cumulated cigarette dose. We thus showed that the individuals with the susceptible genotype were at remarkably high risk with an odds ratio of 7.31 (95% confidence interval, 2.13 to 25.12) at a low dose level of cigarette smoking and that the difference in susceptibility between genotypes was reduced at high dose levels.

Adenocarcinoma↗
PubMed1991

Excitation-contraction uncoupling during ischemia in the blood perfused dog heart.

The bioluminescent of Ca(2+)-indicator, aequorin, was loaded into the left ventricular apex of blood-perfused hearts from 13 dogs for simultaneous recording of left ventricular pressure and intracellular calcium levels. During a 2 minute period of ischemia, systolic and diastolic pressures significantly decreased. In contrast, these pressure changes were associated with an increase in both systolic and diastolic calcium reaching a maximum diastolic value of 0.59 microM and a systolic value of 1.11 microM. This apparent dissociation between pressure and [Ca2+]i supports the hypothesis that changes in myofilament Ca2+ responsiveness are of major importance in modulating contractility during ischemia in large mammalian hearts.

Aequorin↗
PubMed1991

A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan.

In Japan, hepatocellular carcinoma (HCC) is one of the most prevalent cancers, with a reported fatality rate showing a consistent and significant increase in the last decade. At most, only 25% of HCC cases are positive for the hepatitis B surface antigen (HBsAg). To investigate a potential role for hepatitis C virus (HCV) in the development of HCC, sera from 105 HBsAg-negative HCC patients were collected from five districts of Japan and assayed for antibody to HCV antigen (HCVAb). A large number of these patients (76.2%) were found to be positive for the HCVAb in comparison with the reported prevalence in sera from blood donors (1.1%). A history of blood transfusion was found in 39.6% of the cases positive for HCVAb, which was significantly different to the lower rate (4.7%) observed in HCC patients who were both positive for HBsAg and negative for HCVAb (P less than 0.001).

Blood Transfusion↗
PubMed1991

Seroepidemiology of HCV and HBV infection in northern China.

The HCVAb positive rate in normal population in Beijing was 2.1% and HBsAg positive rate was 2.5%. There is an increasing tendency in the aged group. Plasmapheresis might have been the major cause of HCV transmission in blood donors in the Hebei area. There was a high prevalence of HCVAb and HBsAg in chronic liver diseases in the Beijing area and the HCVAb-positive rate significantly increased corresponding to disease progression.

Adolescent↗
PubMed1991

Immunomodulator, LZ-8, prevents antibody production in mice.

LZ-8, a new and recently discovered immunomodulator from Ganoderma lucidum, has been shown to have immunosuppressive activity in vivo and to be a member of the immunoglobulin superfamily. In this paper we examined the in vivo effect of LZ-8 on antibody production using the hepatitis B surface antigen (HBs Ag) in mice. LZ-8 had mitogenic activity in vitro towards spleen cells of C57BL/10 (B10) and C57BL/10BR (B10BR) as previously shown towards those of DBA/2 mice. B10 and B10BR mice produced anti-HBs Ag antibody by the twice sensitization of the antigen while intraperitoneal administration of LZ-8 twice weekly into the mice (8 and 12 mg/kg) greatly prevented the production of antibody to HBs Ag (83.3-96.8% inhibition). We further examined the effect of LZ-8 administration on mitogen responsibility of spleen cells and on the T-cell subset population in both the spleen and lymph node but no significant differences were observed between the LZ-8 treated and untreated mice. These results suggest that the immunosuppressive activities of LZ-8, previously shown, such as the prevention of systemic anaphylaxis and the Arthus reactions, were caused by the blocking of antigen-specific antibody production.

Adjuvants, Immunologic↗
PubMed1991

Neuronal activity in visual, auditory and polysensory areas in the monkey temporal cortex during visual fixation task.

The activity of 252 neurons in the inferotemporal visual area TEO, the superior temporal auditory area (AA), and the superior temporal polysensory area (STP) during the performance of a visual spot-fixation task and two variations, blink and tone tests, was examined in two behaving monkeys. A considerable number of not only TEO cells (45%) but also AA (29%) and STP (34%) cells were activated during the spot-fixation task, but unresponsive to the blanking of the spot during the fixation stage in the blink test. In addition, it was found that the activity of a third of the TEO, AA and STP cells which fired during the task-start stage in the spot-fixation task was modulated by cross-interaction between spot and tone simultaneously presented in the tone test: among these, the spot-induced activity of all TEO cells was enhanced by the tone, whereas the spot-induced activity of all AA and STP cells was suppressed by the tone. These findings are discussed in relation to the process of attending selectively to a fixation-spot.

Acoustic Stimulation↗
PubMed1991

Xenobiotic responsive element in the 5'-upstream region of the human P-450c gene.

The nucleotide sequence of the 5'-upstream region up to about -4.1 kb of the human P-450c gene was determined. Two kinds of repetitive sequences were located; one was the Alu sequence which was inserted at three positions (-3127 to -3038, -3017 to -2770, and -2167 to -1851), and the other was the SINE-R element located just upstream of the most distal Alu sequences. The region other than the two repeated sequences showed an overall similarity of 70% to that of the rat P-450c gene. Survey of XRE or its homologues, responsible for the inducible expression of the rat P-450c gene, revealed eight XRE core sequences in this region of the human P-450c gene. Three of them were carried in the Alu sequences. A fusion gene which was constructed by ligating the upstream region of the human P-450c gene to the chloramphenicol acetyltransferase (CAT) gene expressed the CAT activity in response to the inducer, methylcholanthrene, when transfected into Hepa-1 cells. Stepwise decrease in CAT activity in three regions was observed as the 5'-upstream sequence containing XRE motifs was removed. However, the XRE core sequence in the Alu sequences seemed inactive, because elimination of the three elements in the Alu sequences did not affect the expressed CAT activity. In accordance with this observation, competition experiments using gel mobility shift assay showed that XRE core sequences in the Alu sequences could not compete with the XRE sequence for the inducer-bound receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene.

Individuals with high genetic risk of lung cancer had previously been identified by MspI polymorphisms of the cytochrome P450IA1 gene. In the present study we analyzed the structures of individual P450IA1 genes by PCR direct sequencing of genomic DNA of each genotype raised by the MspI polymorphisms, which were ascribed to a single point mutation in the 3'-flanking region. We then found a novel point mutation in the coding region of the gene which results in the substitution of Ile for Val at residue 462 in the heme binding region. We further analyzed the genetic association between this amino acid replacement and MspI polymorphisms in the general population, using a new method to detect polymorphisms not recognized by restriction enzymes. The results showed that there are at least two forms of human P450IA1 protein with different primary structures and that one of the forms is closely linked with the lung cancer-susceptible genotype of MspI polymorphisms. Thus MspI polymorphisms, which are associated with increased risk of lung cancer, are linked to at least one amino acid substitution, which gives an important clue, at the molecular level, toward elucidation of increased susceptibility to lung cancer.

Amino Acid Sequence↗
PubMed1991

Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene.

We identified genetic polymorphisms in the 5'-flanking region of the human cytochrome P450IIE1 gene and investigated the effect of these polymorphisms on the transcriptional regulation of the gene. PCR direct sequencing of the two homozygous alleles [types A (c1/c1) and C (c2/c2)] revealed the existence of several point mutations in the distal 5'-flanking region of the gene, but no differences in the proximal promoter region. The DNA segment (-1372 to -960) placed upstream of SV40 promoter and the chloramphenicol acetyltransferase (CAT) gene enhanced the expression of the gene, and the enhancement of expression by type C DNA was about 10 times that by its type A counterpart. DNase I footprinting analysis showed at least one protected region in which one of the polymorphic loci (RsaI polymorphism) was located. The DNase I sensitivities and protection profiles of the two genotypes were different. The protected region had high homology to the consensus sequence of the binding region of liver specific transcription factor HNF1 (LF-B1), and this was confirmed by gel retardation assay. These results indicate that genetic polymorphisms in the 5'-flanking region of the human P450IIE1 gene affect its binding of trans-acting factor and change its transcriptional regulation. This may lead to inter-individual differences of microsomal drug oxidation activity.

Amino Acid Sequence↗
PubMed1991

Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan.

In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.

Enzyme-Linked Immunosorbent Assay↗
PubMed1991

Trabeculectomy with 5-fluorouracil.

The effect of subconjunctival injection of 5-fluorouracil (5-FU) after trabeculectomy was studied retrospectively in 205 eyes of 168 patients. A life table analysis of the surgical outcome was based on the type of glaucoma and age related differences, and a comparison was made with patients who had trabeculectomy without subconjunctival 5-FU. The success rate at 30 months after trabeculectomy with 5-FU therapy was considerably higher in primary open-angle glaucoma at 93.6% (72.7%), secondary glaucoma at 88.9% (72.4%), and refractory glaucoma at 72.2% (32.5%) with (or without) the use of ocular hypotensive drops when compared with historical control groups treated without 5-FU (60.0% (41.7%), 35.5% (24.0%), and 18.0% (8.0%), respectively). In patients aged over 70 years, no statistically significant improvement could be demonstrated with the use of 5-FU after trabeculectomy in primary open-angle glaucoma. Our study may provide data on the appropriate dosage and indications for the use of this drug after glaucoma surgery.

Aged↗
PubMed1991

Measurement of NADPH-ferrihemoprotein reductase content in sections of liver.

We developed a method for measuring the content of NADPH-ferrihemoprotein reductase in sections of liver. First, reductase in sections of rat liver was detected with the indirect immunoperoxidase reaction. Subsequently, specific absorbances were measured in the stained sections by microphotometry. Then, the resulting specific absorbances were converted into the reductase content in the sections using an apparent extinction coefficient obtained from a nitrocellulose binding assay. The average of the reductase content in hepatocytes in periportal, intermediate, and perivenous zones thus measured was consistent with the value in liver homogenates estimated by enzyme-linked immunosorbent assay. Therefore, the present method gave accurate measurement of the reductase content in the sections. Perivenous hepatocytes contained 1.5 times as much reductase (1.15 nmol/g liver, mean for five animals) as that in periportal hepatocytes (0.74 nmol/g liver). The reductase content in hepatocytes in the intermediate zone (0.93 nmol/g liver) was intermediate between values of the periportal and perivenous hepatocytes.

Animals↗
PubMed1991

An improved microphotometry system for measurement of cytochrome P-450 in hepatocyte cytoplasm.

To measure cytochrome P-450 (P-450) content in hepatocyte cytoplasm, we developed a dual monochromator-equipped microphotometry system (KWSP-1). Simultaneous measurements of absorbance at 450 and 490 nm with narrow band width (0.5 nm) and small spot size (2 microns) were accomplished by this system. Corresponding fields in serial sections could be easily and rapidly identified under the Nomarski imaging mode of KWSP-1. Photometric accuracy and repeatability of wavelength setting of KWSP-1 were also satisfactory for measurement of P-450. With this system, it is thus possible to measure the extinction of P-450 from many small measuring areas and to precisely determine P-450 content in the cytoplasm of rat hepatocytes. A microphotometric method was developed using cuvette slides and two serial 10-microns thick sections (mapping method). The intracellular distribution of P-450 in individual hepatocytes could be visualized by the mapping method with KWSP-1. However, this method was not applicable to tissue sections containing hemoglobin larger than 4 microM.

Animals↗
PubMed1991

High glucose-6-phosphatase activity in non-pigmented epithelial cells of rabbit ciliary body.

For study of the origin of glucose in the aqueous humor, glucose-6-phosphatase (G6Pase) and hexokinase activities, and glycogen, were cytochemically examined in the ciliary body (CB) of rabbit. G6Pase activity was also assayed biochemically. The staining reaction for G6Pase activity was strong in the non-pigmented epithelium (NPE) in the pars plana and tips of ciliary processes in the region containing large ciliary pockets within the pars plicata. NPE cells contained abundant reaction product for G6Pase activity in the endoplasmic reticulum (ER) and nuclear envelope. However, NPE in other regions of the CB and pigmented epithelium (PE) of CB, and other areas surrounding the anterior and (PE) of CB, and other areas surrounding the anterior and posterior chambers, showed weak or no G6Pase staining reaction. Biochemical G6Pase activity in the whole ciliary body was relatively high. Both NPE and PE in the pars plana and the tips showed strong staining reaction for hexokinase activity but no staining for glycogen. Furthermore, NPE cells in the tips bore large aggregates of smooth ER and many Golgi apparati. These suggest that the high G6Pase activity in NPE cells in the pars plana and the tips is related to glucose release into the aqueous humor.

Animals↗
PubMed1991

The opioid activity and receptor selectivity of fluorinated Leu5 enkephalin analogues in vitro and in vivo.

The opioid activity and the selectivity for opioid receptor (subtypes) of newly synthesized fluorinated enkephalin (Enk) analogues, [2R, 4R], [2R, 4S], [2S, 4S] and [2S, 4R] trifluoro-Leu5-Enk (KKF-31, 32, 33 and 34) were investigated. The inhibitory effect of KKF-compounds on the electrically induced contractions of guinea-pig ileum (GPI) and mouse vas deferens (MVD) were dose-dependent but relatively lower than that of L-Leu5-Enk, except that KKF-34 was rather slightly more potent than L-Leu5-Enk in MVD preparations. In GPI preparations, the pA2 values of naloxone for these compounds were higher than those of naltrindole while the values of naltrindole for KKF-compound were higher than those of naloxone in MVD preparations. Intracerebroventricular KKF-31 and KKF-32 at doses of 20 and 10 nmol/mouse, respectively, produced analgesia comparable to 0.1 nmol Tyr-D-Arg-Phe-Lys-NH2 and 100 nmol Tyr-D-Thr-Gly-Phe-Leu-Thr; however, neither KKF-33 nor 34 produced analgesia up to the doses of 100 nmol/mouse. Both naloxone, 1 mg/kg, i.p., and naltrindole, 10 mg/kg, i.p., antagonized KKF-31- and KKF-32-induced analgesia. The results suggest that the introduction of trifluoromethyl group in Leu5 results in the alternation of the opioid activity and receptor selectivity. Although KKF-33 and KKF-34 possessed a more potent in vitro inhibitory effect than KKF-31 and KKF-32, mediated through mu- and delta-opioid receptors in both preparations, they did not show any appreciable analgesic effect. KKF-31 and KKF-32 produce naloxone- and naltrindole-reversible analgesia irrespective of in vitro mu- and delta-opioid activity.

Analgesics↗