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Biomedical subjects

M Ishihara

Publications and source records attributed to M Ishihara.

At least 145 records · Page 8Linked to original sources
PubMed1996

Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome 7, 7q36.

A Ras-related GTP-binding protein cDNA has been isolated from a human skin fibroblast cDNA library using a genomic subclone derived from a YAC clone as a probe. The polypeptide, consisting of 184 amino acids deduced from nucleotide sequences, contains five repeats of the Ras-related GTP-binding region and is highly homologous to the rat RHEB (Ras homologue enriched in brain) gene, which encodes a Ras-related growth factor- and synaptic activity-regulated protein, with 98.9% amino acid identity. Therefore, it is suggested to be a human homologue of the rat RHEB protein, and we have designated it human RHEB. Using fluorescence in situ hybridization, we concluded that this human RHEB gene was localized to band q36 on chromosome 7. Considering the chromosomal localization as well as the potential function of this protein, it will be very important to investigate whether it may play a role in the etiopathogenesis of holoprosencephaly type 3 or hereditary sacral agenesis, in which the disease susceptible locus is linked to the microsatellite marker, D7S22, in this chromosomal region, 7q36.

Amino Acid Sequence↗
PubMed1996

Structural characteristics of heparin-line domain required for interaction of midkine with embryonic neurons.

Midkine is a heparin binding growth/differentiation factor with neurite promoting activity. We examined inhibitory activities of various heparin derivatives toward interaction of midkine with neurons and elucidated the structural requirements of the heparin-like domain necessary for the interaction. All of the three sulfate groups in the heparin disaccharide unit (6-O-sulfate, 2-O-sulfate and N-sulfate) were necessary for full inhibitory activity. Among these, the N-sulfate group was critically important. The minimum size with inhibitory activity was approximately 7,000 Da. Thus, the highly sulfated region in cell surface heparan sulfate proteoglycan is required for neurons to interact with midkine.

Animals↗
PubMed1996

Detection of antibodies to Borrelia species among patients with confirmed sarcoidosis in a region where Lyme disease is nonendemic.

BACKGROUND: Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The purpose of this study was to evaluate the relationship between Lyme disease and sarcoidosis. METHODS: We examined the seroprevalence of antibody to Borellia species in patients with sarcoidosis. We performed the enzyme-linked immunosorbent assay, using three Japanese Borrelia species in addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific proteins in 38 patients with histopathologically confirmed sarcoidosis and 80 healthy controls. RESULTS: Two patients (5.3%) were positive for antibodies to Borrelia species according to one or both assays, and one (1.2%) healthy control was positive. In both patients it was suspected that Borrelia infection had developed prior to the development of sarcoidosis. CONCLUSION: Borrelia species were thought not to be responsible for the development of sarcoidosis in a nonendemic region in Japan. Since clinical manifestations of Lyme disease share certain similarities with those seen in sarcoidosis, ophthalmologists should be aware of the need to differentiate between the two diseases and the need for prompt treatment in each case.

Adult↗
PubMed1996

Genetic polymorphisms of the major histocompatibility complex-encoded antigen-processing genes TAP and LMP in sarcoidosis.

Sarcoidosis is a granulomatous disease showing a significant increase in the HLA-DR5, -DR6, and -DR8 associated alleles in Japanese. To investigate whether the class I antigen-processing genes, encoded within the MHC class II region between the HLA-DP and -DQ loci, are involved in determining the susceptibility to sarcoidosis, TAP1, TAP2, and LMP2 alleles were analyzed by the PCR-RFLP method in 85 Japanese patients with sarcoidosis and 91 healthy controls. There were no significant differences in the distribution of TAP1 and LMP2 alleles between the subgroups of the patients and controls positive or negative for DR5, DR6, and DR8. A significant decrease in the frequency of TAP2*0201 was found among the patients negative for DR5, DR6, and DR8 as compared to the DR-matched controls (p < 0.05), but this could be explained by its linkage disequilibrium to the negatively associated allele DR1. These findings suggest that the TAP or LMP2 gene is not primarily involved in the susceptibility to sarcoidosis. In the course of this study, a linkage disequilibrium was observed in the Japanese population between TAP1 and TAP2 alleles, TAP1*0201 and TAP2*0102.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Attenuation of the no-reflow phenomenon after coronary angioplasty for acute myocardial infarction with intracoronary papaverine.

The no-reflow phenomenon is observed as reduction of coronary blood flow on the angiograms (angiographic no-reflow) after immediate percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI). To assess whether a potent coronary microvascular dilator--papaverine--could attenuate the no-reflow phenomenon, nine patients with AMI who were found to have angiographic no-reflow after PTCA were studied. Angiographic no-reflow was defined as the Thrombolysis in Myocardial Infarction flow grade 1 or 2 without any mechanical obstructions in the epicardial artery. A bolus dose of 10 mg of intracoronary papaverine was administered, and the flow grade was again evaluated. Intracoronary papaverine caused a significant improvement of the flow grade (p= 0.0152). The number of cineframes that were required for the contrast medium to pass two selected landmarks on the angiograms also significantly decreased (41 +/- 17 frames to 18 +/- 8 frames, p= 0.0039). Thus intracoronary papaverine attenuated angiographic no-reflow that occurred after PTCA for AMI.

Adult↗
PubMed1996

LMP7 polymorphism in Japanese patients with sarcoidosis and Behçet's disease.

To evaluate the influence of the MHC-linked LMP7 gene on disease susceptibility in HLA class I and class II-associated diseases, the distribution of LMP7 alleles was determined using the PCR-RFLP method in 69 Japanese patients with Behçet's disease, 65 patients with sarcoidosis, and 100 unrelated healthy controls. No differences were found between either of the patient groups and the healthy control group, indicating that LMP7 allelic variation may not contribute to the pathogenesis of either Behçet's disease or sarcoidosis. We also analyzed linkage disequilibria between LMP7 and HLA class II alleles in Japanese populations.

Alleles↗
PubMed1996

F-wave in patients with hemifacial spasm: observations during microvascular decompression operations.

In patients with hemifacial spasm (HFS), the spasm is due to cross compression of the facial nerve by a blood vessel. There are currently two hypotheses how the cross compression can cause HFS: 1. the spasm is caused by ephaptic transmission and hyperexcitability at the site of compression; and 2. the spasm is caused by hyperexcitability in the facial motonucleus. In peripheral nerves, F-waves, which result from the backfiring of antidromically activated anterior horn cells, have been proposed as indices of anterior horn cell excitability. Enhancement of the F-waves in facial muscles also indicates increased excitability of the facial motonucleus. On the other hand, abnormal muscle response (AMR), which can be elicited by stimulating one branch of the facial nerve and recording electromyographically from muscles innervated by other branches of the facial nerve, is specific for patients with HFS. We have therefore measured the AMRs and the F-waves in the facial muscle of HFS patients under anesthesia in order to investigate the excitability of the facial motonucleus. We obtained facial nerve evoked electromyograms from 14 HFS patients during microvascular decompression (MVD) operation. The F-waves, obtained with surface electrodes from the mentalis muscle, were defined as the second response after the M-wave. The F-waves in facial muscles cannot usually be elicited during surgical anesthesia using inhalation anesthetics. However, the F-waves were elicited on the spasm side in 10 out of 14 patients with HFS and the F-waves disappeared after MVD under anesthesia, as the early responses (R1) of the blink reflex were elicited on the spasm side before MVD under anesthesia. The F-waves elicited during anesthesia were suppressed significantly, compared with those before MVD. These results suggest that excitability in facial motonucleus increased on the spasm side.

Electric Stimulation↗
PubMed1996

Analysis on allelic variation of the HLA-DMB gene in Japanese by PCR-RFLP as well as direct DNA sequencing and identification of a new DMB allele, DMB*0105.

In the HLA-D region, one of the class II genes, DMA and DMB have been identified between the DQ and DP genes, and four allelic polymorphisms in each of the DMA (DMA*0101 approximately 0104) and DMB (DMB*0101 approximately 0104) genes have been so far recognized. Several recent studies suggested that the DM molecule is required for class II antigen presentation pathway especially by promoting the binding of antigenic peptides to the classical HLA class II molecule. In this study, we have analyzed genetic polymorphism and allelic variation of the DMB gene in a Japanese population by the direct DNA sequencing technique and also by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and could recognize DMB*0101 (49.3%), DMB*0102 (23.2%), DMB*0103 (23.2%), and DMB*0104 (0.4%). Further, a new DMB allele, DMB*0105 characterized by the presence of Val and Ile at two polymorphic sites, codons 144 and 179, respectively was identified. Strong linkage disequilibria were found between DMB*0101 and DRB1*0101, DPB1*0402 and DRB1*1502, and also between DMB*0103 and DRB1*1501 and DQB1*0602. HLA-DMB genotyping using the PCR-RFLP method established here will provide accurate evaluation of the effects of sequence allelism in the DMB gene on the HLA class II disease associations.

Alleles↗
PubMed1996

Genetic polymorphisms in the keratin-like S gene within the human major histocompatibility complex and association analysis on the susceptibility to psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. However, it has not yet been clarified if the HLA-Cw6 and Cw7 genes themselves are the susceptible gene related to this disease or if it is some other non-HLA gene in a linkage disequilibrium with these HLA-C alleles. The S gene, recently identified in the HLA class I region 160 kb telomeric of HLA-C, encodes a keratin-like protein and is expressed specifically in the granular layer of the epidermis. Therefore, it is tempting to speculate that the S gene is one of the strong candidate genes responsible for the pathogenesis of psoriasis vulgaris. Direct sequencing of the first and second exon of the S gene after polymerase chain reaction (PCR) amplification has allowed the identification of two diallelic polymorphic sites in exon I and seven diallelic polymorphic sites in exon 2, three among which result in amino acid exchanges, a Ser-Phe substitution at amino acid position 186, a Gly-Val substitution at position 393 and a Ser-Leu substitution at position 394. No significant difference in the dimorphic distributions of the S gene was observed between the patients with psoriasis vulgaris and healthy controls, suggesting that the susceptible gene for psoriasis is not the S gene itself.

Disease Susceptibility↗
PubMed1996

Syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives.

The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple method without chromatography from the leaves of Alpinia speciosa K. SCHUM. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents. Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl]phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii.

Animals↗
PubMed1996

Synthesis and antifungal activity of cinnamic acid esters.

Cinnamic, p-coumaric and ferulic acids were isolated from pineapple stems (Ananas comosus var. Cayenne). Twenty-four kinds of esters were prepared from these acids, alcohols and the components of Alpinia. Isopropyl 4-hydroxycinnamate (11) and butyl 4-hydroxycinnamate (12) were found to have almost the same effectiveness in antifungal activity against Pythium sp. at 10 ppm as that of the commercial fungicide iprobenfos (kitazin P).

Anti-Infective Agents↗
PubMed1996

[A photoallergenicity study of prulifloxacin (NM441) in guinea pigs].

Photoallergenicity of prulifloxacin, a new antibacterial agent, was examined using guinea pigs compared with those of the other quinolone antibacterial drugs, ofloxacin (OFLX), lomefloxacin (LFLX), ciprofloxacin (CPFX), enoxacin (ENX) and nalidixic acid (NA). Prulifloxacin and other drugs were orally administered at minimal phototoxic doses 1 hr before UVA (18 J/cm2) irradiation. This photosensitization procedure was daily repeated for 5 days. On 16 days after the final sensitization, the animals were challenged with UVA (18 J/cm2) after the administration of correspondent substances at maximal non-phototoxic doses. Photoallergic reactions were induced by OFLX (40 mg/kg), LFLX (3 mg/kg), CPFX (170 mg/kg) and ENX (80 mg/kg), but were not observed in prulifloxacin (170 mg/kg) and NA (30 mg/kg). These results show that photoallergenicity of prulifloxacin were less severe than those of the other quinolone antibacterial drugs under the conditions of this study.

Animals↗
PubMed1996

[Multiple primary malignant neoplasms associated with genitourinary cancer].

Between October 1980 and December 1994, we treated 392 patients with malignant neoplasms associated with genitourinary organs. We made a statistical study on 42 patients (10.6%) with multiple malignant neoplasms. The average age of 42 patients was 72.2 years and 83% of the patients were male. Malignant neoplasms originating from bladder, prostate or kidney were observed in 19 cases (35%), 19 cases (35%) or 10 cases (11%), respectively. The incidence of prostatic cancer was higher than that in other single primary malignant neoplasms associated with genitourinary organs. The other organs having malignant neoplasms accompanying genitourinary organs were the stomach (39%), lungs (12%), esophagus (9%), and pancreas (9%). Only 16 patients (35%) had synchronous multiple malignant neoplasms. However, 35 cases (75%) including these cases had second primary malignant neoplasms within 5 years of the first. In conclusion, the incidence of multiple malignant neoplasms with genitourinary cancer was as high as 10.6% and the prognosis of these patients was poor. These findings suggest the necessity of careful follow-up on patients with genitourinary cancer.

Adult↗
PubMed1996

HLA serological and class II genotyping in sarcoidosis patients in Japan.

To investigate the HLA alleles that contribute to the genetic susceptibility to sarcoidosis, HLA serological typing was performed in 75 patients with sarcoidosis and 150 controls using the standard complement-dependent microcytotoxicity method. The genomic DNAs of the 75 patients and 130 of the 150 controls were used to analyze HLA-DRB1, -DQA1, -DQB1 and -DPB1 alleles, utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serological typing showed that the frequencies of HLA-DR52, -DR5, -DR6 and -DR8 were significantly increased in the patients compared to the controls. In PCR-RFLP genotyping, the frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*14), DRB1*08, DQA1*0501 and DQB1*0301 were significantly increased in the patients compared to the controls. The frequencies of the DRB1*12 alleles were also increased among the patients, but this increase was not significant. The frequencies of DRB1*0101, DQB1*0501, and DPB*0402 were significantly lower in the patients than in the controls. The significant increases in the frequencies of DQA1*0501 and DQB1*0301 could be due to the linkage disequilibrium between the DR52-associated DRB1 alleles and DQA1*0501 and DQB1*0301 alleles among the Japanese. The significantly increased frequency of the DR8 (DRB1*08) haplotype, which lacks the DRB3 gene encoding DR52 antigen, suggested that the DR5 (DRB1*11), DR6 (DRB1*14) and DR8 (DRB1*08) of the DRB1 alleles may determine the susceptibility to sarcoidosis among the Japanese.

Adolescent↗