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Biomedical subjects

H Okamoto

Publications and source records attributed to H Okamoto.

At least 199 records · Page 11Linked to original sources
PubMed2000

The clinical and photobiological characteristics of solar urticaria in 40 patients.

Forty patients with solar urticaria, 16 male and 24 female, were examined personally during the past 25 years. The median age at onset of symptoms was 32 years, ranging from 13 to 76 years. Most commonly (45%) solar urticaria first appeared during the third decade. The mean duration of the disease was 3.6 years at presentation. The action spectrum was found in the visible light range in 24 patients (60%), in the ultraviolet (UV) A range in four, in the UVB in four, from the UVA to UVB in three, from the UVA to visible light in one and in a broad range from UVB to visible light in four patients. An inhibition spectrum was detected in 13 of 19 patients (68%), occurring at longer wavelengths than the action spectrum in 12 of these cases. The augmentation spectrum was found in only four of 14 patients (29%) examined. Twenty-four of 31 patients (77%) developed an urticarial reaction to autologous serum, which had been previously irradiated in vitro at the action spectrum for that patient. In a single patient, solar urticaria was caused by a drug, namely chlorpromazine. In two patients, polymorphic light eruption occurred in association with solar urticaria. No single modality of treatment was satisfactory, but combined use of antihistamines, sunbathing, psoralen UVA photochemotherapy and/or sunscreening agents partially suppressed the symptoms.

Adolescent↗
PubMed2000

Genetic divergence between Atlantic and Indo-Pacific stocks of bigeye tuna (Thunnus obesus) and admixture around South Africa.

Two mitochondrial DNA segments of the bigeye tuna (Thunnus obesus) were amplified by polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLP) analyses of these segments were used for the genetic stock study. The variation in a segment flanking the ATPase and COIII genes was low; only two genotypes (alpha and beta) were detected by RsaI digestion. Yet a large difference in the genotype distribution was observed between ocean basin samples. The alpha type predominated in four Atlantic samples, where 178 of 244 individuals were the alpha type. In contrast, only one of 195 individuals collected in the Indo-Pacific was the alpha type? The frequency of the alpha type varied considerably from 0 to 80% among seven samples collected off the Cape of Good Hope. The variation found in the other segment, containing the D-loop region, was much higher; two endonucleases (DpnII and RsaI) detected five genotypes each and 15 composite genotypes. A highly significant difference in genotype frequencies was observed between the Atlantic and Indo-Pacific samples, but no heterogeneity was observed among the four Atlantic or among four Indo-Pacific samples. These results clearly indicate that not only gene flow, but also fish migration, between the Atlantic and Indian Oceans are severely restricted, and that fishes from these distinct stocks are intermingling around South Africa. The simple and diagnostic genetic marker found in this study can be used to estimate mixing ratios between Atlantic and Indian stocks around South Africa.

Animals↗
PubMed2000

Efficient insertion mutagenesis of Arabidopsis by tissue culture-induced activation of the tobacco retrotransposon Tto1.

The tobacco retrotransposon Tto1 is one of a few active retrotransposons in plants. Its transposition is activated by tissue culture and is primarily regulated at the transcriptional level. Here we demonstrate that Tto1 introduced in Arabidopsis is also activated by tissue culture. Transcription of Tto1 was induced by tissue culture and driven by its LTR promoter. Transposed copies of Tto1 were observed in almost all of the plants regenerated from the explants cultured for only 1 week. A total of 255 independent regenerated lines have been produced, and the average copy number of transposed Tto1 in these lines is estimated to be 3.2. Sequences flanking Tto1 were amplified by thermal asymmetric interlaced (TAIL)-PCR. Of 165 independent amplified products, 123 showed significant homology to known genes or hypothetical protein genes. The insertion sites of Tto1 are spread over all chromosomes and the target site sequence shows moderate consensus. Taken together, these results indicate that Tto1 can be used as a tool for efficient insertion mutagenesis of Arabidopsis which is especially suitable as a reverse genetics system.

Arabidopsis↗
PubMed2000

Mother-to-infant transmission of GB virus type C/HGV.

BACKGROUND: The potentially hepatotropic flavivirus-like virus, GB virus type C (GBV-C)/HGV, has been detected in a few patients with acute and chronic hepatitis and in a certain proportion of blood donors and recipients of blood or blood components. STUDY DESIGN AND METHODS: Sera from 2979 pregnant Japanese women were examined for the presence of GBV-C/HGV RNA by nested RT-PCR. Mothers who were positive for viral RNA and their 34 infants were followed and tested for infection. RESULTS: Of the 2979 women, 32 (1.1%) were positive for GBV-C/HGV RNA. Twenty-six (76.5%) of 34 babies born to these women were positive for the virus when first tested. A significantly higher titer of viral RNA was observed in mothers whose infants were infected than in those whose infants were uninfected (mean +/- SD, 10(6.3 +/- 0.9) vs. 10(4.6 +/- 0.9)/mL; p<0.001). Twenty-three (96%) of 24 babies born to mothers whose serum viral titers were 10(6) mL or more were infected with the virus. Infants delivered by elective caesarean section had a lower risk (OR, 0.13; 95% CI, 0.02-0.82) than those delivered vaginally or by emergency caesarean section. No other risk factors for mother-to-infant transmission were confirmed. CONCLUSIONS: GBV-C/HGV is frequently transmitted from mothers to infants in the general population. The most critical factor is the titer of viral RNA in the maternal serum. By the use of elective caesarean section in women with high titers of viral RNA, vertical transmission of the virus may be lessened.

Carrier State↗
PubMed2000

Neutrophil chemoattractant 2 beta regulates expression of the Reg gene in injured gastric mucosa in rats.

BACKGROUND & AIMS: Regenerating (Reg) protein has a trophic effect on gastric mucosal cells. We have shown that Reg gene expression is increased in enterochromaffin-like (ECL) cells during the healing of damaged gastric mucosa around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage. METHODS: Time course changes of the expression of genes for various proinflammatory cytokines and Reg were investigated after induction of gastric mucosal lesions in rats. The direct effect of proinflammatory cytokines on Reg gene expression and Reg protein production were investigated in vitro using counterflow elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain reaction. Reg gene expression was also investigated in rats treated by the neutralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 beta). RESULTS: During healing, the gene expression of several proinflammatory cytokines and Reg was markedly augmented. Among the proinflammatory cytokines, CINC-2 beta is the only cytokine in which augmented expression preceded the increase of Reg gene expression. In rats treated with CINC-2 beta neutralizing antibody, the augmentation of Reg gene expression was significantly inhibited. When ECL cells were incubated with these proinflammatory cytokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg protein in ECL cells. CXCR-2 was identified in isolated ECL cells. CONCLUSIONS: CINC-2 beta, expressed in damaged gastric mucosa, stimulates the production of Reg protein in ECL cells via CXCR-2 and may be involved in the accelerated healing of injured gastric mucosa.

Animals↗
PubMed2000

Comparative in vitro activity of telithromycin (HMR 3647), three macrolides, amoxycillin, cefdinir and levofloxacin against gram-positive clinical isolates in Japan.

The in vitro activities (MIC and MBC) of telithromycin (HMR 3647) against clinical isolates in Japan were investigated in comparison with those of erythromycin A, clarithromycin, azithromycin, amoxycillin, cefdinir and levofloxacin. Telithromycin was more potent than the reference compounds against erythromycin A-susceptible or resistant Streptococcus pneumoniae isolates possessing either mef (mefA or mefE) genes or the ermB gene. Against erythromycin A-susceptible or inducibly resistant Staphylococcus aureus and erythromycin A-susceptible and intermediate Enterococcus faecalis, telithromycin was highly active.

Amoxicillin↗
PubMed2000

Cytopathology of pregnancy-induced cell patterns in cervicovaginal smears.

Considerable interest has been devoted to cytology in pregnancy, especially the morphologic changes that may cause problems in differential diagnosis. It is surprising that the published discussion of the cytologic appearance of smears from pregnant women has been so limited. This review emphasizes that retained trophoblastic tissue may be a source of highly atypical appearing cells in the cervicovaginal cytology obtained under various clinical conditions. Distinguishing between Arias-Stella cells and cells of glandular abnormalities can be problematic, since the morphologic characterization of the former is poor. This review also emphasizes that a full awareness of the morphology of pregnancy as well as of the patient's clinical history are needed for greater precision in diagnosing cell patterns as pregnancy-related and not malignant.

Adult↗
PubMed2000

Endotoxin augments cerebral hyperemic response to halothane by inducing nitric oxide synthase and cyclooxygenase.

We examined the cerebral hyperemic response to halothane after treatment with bacterial lipopolysaccharide (LPS). To determine the involvement of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), we tested whether the effect of LPS on halothane-induced hyperemia was altered by pretreatment with the selective iNOS inhibitor, aminoguanidine (100 mg/kg), COX-2 inhibitor, NS-398 (5 mg/kg), or enzyme expression inhibitor, dexamethasone (4 mg/kg). Further, we examined whether the administration of a nitric oxide donor, diethylamine NONOate, would change the cerebral hyperemic response of halothane. Sprague-Dawley rats were anesthetized with 0.5 minimum alveolar anesthetic concentration of halothane and artificially ventilated. Regional cerebrocortical blood flow (rCBF) was assessed by laser-Doppler flowmetry. LPS (1 mg/kg) was administered intracerebroventricularly; artificial cerebrospinal fluid was used in controls. Four hours after LPS infusion, iNOS and COX-2 messenger ribonucleic acid (mRNA) levels (reverse transcription-polymerase chain reaction) and enzyme activities (arginine-citrulline conversion and prostaglandin E(2) enzyme immunoassay) were significantly increased. LPS enhanced halothane-induced 3.9 and 1.6-fold increases in rCBF at 1.0 and 1.5 minimum alveolar concentration, respectively. Co-treatment with NS-398 attenuated, but aminoguanidine or dexamethasone abolished the effect of LPS on halothane-induced rCBF increase. Diethylamine NONOate mimicked the enhanced rCBF response to halothane. These results suggest that LPS augmented halothane-induced cerebrocortical hyperemia by induction of iNOS and COX-2.

Anesthetics, Inhalation↗
PubMed2000

Neuronal and astroglial injuries in patients undergoing coronary artery bypass grafting and aortic arch replacement during hypothermic cardiopulmonary bypass.

UNLABELLED: More than 50% of patients suffer neuropsychologic impairment after cardiac surgery. We measured neuron-specific enolase (NSE) and S-100 protein (S-100) in patients' serum as putative markers of neuronal and astroglial cell injury, respectively. Group I (n = 13) underwent coronary artery bypass grafting (CABG) with mild hypothermic cardiopulmonary bypass (CPB); Group II (n = 6) underwent aortic arch replacement with deep hypothermic CPB; Group III (n = 8) underwent CABG under normothermia without CPB. During and after the operation, serum levels of NSE and S-100 were significantly increased only in Groups I and II (during CPB), NSE still being increased 12 h after surgery in Group II. This suggests that neuronal and astroglial cell injuries are more likely in patients undergoing CABG with mild hypothermic CPB or aortic arch replacement with deep hypothermic CPB than in those undergoing CABG under normothermia without CPB. However, these increases of NSE and S-100 failed to reflect clinical brain damage. Rather, an electroencephalogram, was only capable of detecting neurologic complications after surgery. IMPLICATIONS: Neuronal and astroglial cell injuries are likely to occur during coronary artery bypass grafting with mild hypothermic cardiopulmonary bypass (CPB) or aortic arch replacement with deep hypothermic CPB. Conversely, patients undergoing coronary artery bypass grafting without CPB under normothermic conditions may be less likely to suffer brain cell injury.

Aged↗
PubMed2000

Silencing of retrotransposons in arabidopsis and reactivation by the ddm1 mutation.

Gene silencing associated with repeated DNA sequences has been reported for many eukaryotes, including plants. However, its biological significance remains to be determined. One important function that has been proposed is the suppression of transposons. Here, we address transposon suppression by examining the behavior of the tobacco retrotransposon Tto1 and endogenous retrotransposons in Arabidopsis. After an initial increase in copy number because of active transposition in the Arabidopsis genome, Tto1 became silent. The amount of transcript was reduced, and the inactivated Tto1 became methylated. This silencing correlated with an increase in copy number. These phenomena mimic repeat-induced gene silencing. The homozygous ddm1 (for decrease in DNA methylation) mutation of Arabidopsis results in genomic DNA hypomethylation and the release of silencing in repeated genes. To investigate the role of DNA methylation and the gene-silencing machinery in the suppression of Tto1, we introduced the ddm1 mutation into an Arabidopsis line carrying inactivated Tto1 copies. In the homozygous ddm1 background, Tto1 became hypomethylated and transcriptionally and transpositionally active. In addition, one of the newly isolated endogenous Arabidopsis retrotransposon families, named Tar17, also became hypomethylated and transcriptionally active in the ddm1 mutant background. Our results suggest that the inactivation of retrotransposons and the silencing of repeated genes have mechanisms in common.

Arabidopsis↗
PubMed2000

The role of osteopontin in the development of granulomatous lesions in lung.

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression may be a common factor involved in formation of granulomas of various origin.

Adenoviridae↗
PubMed2000

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗
PubMed2000

Circular double-stranded forms of TT virus DNA in the liver.

TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.

Base Sequence↗
PubMed2000

Species-specific TT viruses and cross-species infection in nonhuman primates.

Viruses resembling human TT virus (TTV) were searched for in sera from nonhuman primates by PCR with primers deduced from well-conserved areas in the untranslated region. TTV DNA was detected in 102 (98%) of 104 chimpanzees, 9 (90%) of 10 Japanese macaques, 4 (100%) of 4 red-bellied tamarins, 5 (83%) of 6 cotton-top tamarins, and 5 (100%) of 5 douroucoulis tested. Analysis of the amplification products of 90 to 106 nucleotides revealed TTV DNA sequences specific for each species, with a decreasing similarity to human TTV in the order of chimpanzee, Japanese macaque, and tamarin/douroucouli TTVs. Full-length viral sequences were amplified by PCR with inverted nested primers deduced from the untranslated region of TTV DNA from each species. All animal TTVs were found to be circular with a genomic length at 3.5 to 3.8 kb, which was comparable to or slightly shorter than human TTV. Sequences closely similar to human TTV were determined by PCR with primers deduced from a coding region (N22 region) and were detected in 49 (47%) of the 104 chimpanzees; they were not found in any animals of the other species. Sequence analysis of the N22 region (222 to 225 nucleotides) of chimpanzee TTV DNAs disclosed four genetic groups that differed by 36.1 to 50.2% from one another; they were 35.0 to 52.8% divergent from any of the 16 genotypes of human TTV. Of the 104 chimpanzees, only 1 was viremic with human TTV of genotype 1a. It was among the 53 chimpanzees which had been used in transmission experiments with human hepatitis viruses. Antibody to TTV of genotype 1a was detected significantly more frequently in the chimpanzees that had been used in transmission experiments than in those that had not (8 of 28 [29%] and 3 of 35 [9%], respectively; P = 0.038). These results indicate that species-specific TTVs are prevalent in nonhuman primates and that human TTV can cross-infect chimpanzees.

Animals↗
PubMed2000

Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase- and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N(17)-Cdc42, but not N(19)-RhoA, suppressed S1P- and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling.

3T3 Cells↗
PubMed2000

Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells.

In smooth muscle, a Rho-regulated system of myosin phosphatase exists; however, it has yet to be established whether Rho kinase, one of the downstream effectors of Rho, mediates the regulation of myosin phosphatase activity in vivo. In the present study, we demonstrate in permeabilized vascular smooth muscle cells (SMCs) that the vasodilator 1-(5-isoquinolinesulfonyl)-homopiperazine (HA-1077), which we show to be a potent inhibitor of Rho kinase, dose dependently inhibits Rho-mediated enhancement of Ca(2+)-induced 20-kDa myosin light chain (MLC(20)) phosphorylation due to abrogating Rho-mediated inhibition of MLC(20) dephosphorylation. By an immune complex phosphatase assay, we found that guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) stimulation of permeabilized SMCs caused a decrease in myosin phosphatase activity with an increase in the extent of phosphorylation of the 130-kDa myosin-binding regulatory subunit (MBS) of myosin phosphatase in a Rho-dependent manner. HA-1077 abolished both of the Rho-mediated events. Moreover, we observed that the pleckstrin homology/cystein-rich domain protein of Rho kinase, a dominant negative inhibitor of Rho kinase, inhibited GTPgammaS-induced phosphorylation of MBS. These results provide direct in vivo evidence that Rho kinase mediates inhibition of myosin phosphatase activity with resultant enhancement of MLC(20) phosphorylation in smooth muscle and reveal the usefulness of HA-1077 as a Rho kinase inhibitor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗