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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 127 records · Page 7Linked to original sources
PubMed1996

Mutations and oxidative DNA damage in phage M13mp2 exposed to N-nitrosomorpholine plus near-ultraviolet light.

Previously we reported that a direct-acting mutagen can be formed from N-nitrosomorpholine (NMOR) on exposure to near-ultraviolet light (UVA, 320-400 nm). We have now studied the spectrum of mutations caused by NMOR plus UVA. M13mp2 phages suspended in a sodium phosphate buffer were treated with NMOR under UVA irradiation and Escherichia coli NR9099 was then infected with the phage. Mutations induced in the phage DNA lacZ alpha region were analyzed. The majority (approximately 50%) of the induced sequence changes were G to T transversions. This suggested that modifications in guanine residues were responsible for these transversions. We explored the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) in the DNA. When the phage were treated with NMOR plus UVA, 8-oxodG/dG in DNA increased up to 12-fold over the value in untreated control. When a mutM-deficient mutant of E. coli CSH50 was used as the host, the mutation level was higher than that observed with CSH50. We conclude that 8-oxodG may be involved in mutations induced by NMOR plus UVA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (I) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (delta F1388) and (II) a previously described g-->a transition at position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a). Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. Extended haplotype analyses indicated that the delta F1388 mutation was associated with a single specific haplotype whereas the 3992-9g-->a mutation was primarily associated with a single haplotype but also occurred in the context of several other different haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly associated with mutations in the SUR1 gene and provide evidence for the existence of at least two founder HI chromosomes in this population.

Animals↗
PubMed1996

Endothelin-1 kinetics in plasma, urine, and blister fluid in burn patients.

Endothelin-1, a peptide isolated from vascular endothelial cells, facilitates the constriction of vascular smooth muscle and various pharmacological actions including vasodilation, the proliferation of smooth muscle cells and fibroblasts, and the stimulation of arachidonic acid metabolism. In this study, plasma, urine, and blister fluid endothelin-1 concentrations were determined in burn patients and changes in vasoactive substances derived from endothelial cells secondary to burns were investigated. Plasma endothelin-1 concentrations in burn patients were significantly lower than those in healthy individuals at rest. However, extremely high blister fluid endothelin-1 concentrations were observed within 30 hours of a burn. The amounts of endothelin-1 excreted in urine by burn patients over 24 hours also were higher than those in healthy individuals. The finding of high concentrations of endothelin-1 in blister fluids suggests that endothelin-1 is produced at wound regions in burn victims. Clinically, it appears that endothelin-1 is involved in circulation at the wound surface or in the healing of burns.

Adult↗
PubMed1996

Expression of MAGE genes in human colorectal carcinoma.

OBJECTIVE: The human genes MAGE-1 and -3 encode tumor-specific peptide antigens, which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by those genes may be useful for cancer immunotherapy. There is, however, little information on the expression of these genes in human colorectal carcinomas. METHOD: The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and corresponding normal tissue specimens of the colorectum was determined by means of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC). RESULTS: The expression of MAGE genes was not recognized in normal colorectal tissues at all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The expression was seen frequently in patients with liver metastasis (p < 0.01). Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4 negative cell lines, respectively. CONCLUSIONS: The MAGE genes were expressed exclusively in tumor tissues of one third of patients with colorectal carcinoma. The identification of such tumor rejection antigens is considered to uncover a new possibility for the specific immunotherapy of colorectal carcinoma. The demethylating agent may increase the number of patients who might be candidates for MAGE-specific immunotherapy.

Antigens, Neoplasm↗
PubMed1996

Vascular reconstruction in limb salvage operations for soft tissue tumors of the extremities.

Eight patients with vascular threatening soft tissue tumors underwent wide excision of the tumors followed by vascular reconstruction. Superficial femoral vessels were resected in 6 patients and popliteal vessels in 2 patients. Arterial reconstruction was performed with a synthetic graft in 4 and a reversed saphenous vein graft in 4. Venous reconstruction was performed with a synthetic graft in 5 and a saphenous vein graft in 2. Adjuvant multimodality treatment was used in 6 patients. After an average of 30 months, the revascularized vessels were found to be patent in 5 patients with arterial reconstruction and in 1 patient with venous reconstruction. Six patients maintained functional extremities. Two other patients had to have amputations, 1 because of a deep infection that involved the grafts and the other because of an acute occlusion of the reconstructed artery. Edema of the leg, which was treated successfully with an elastic support and elevation of the leg, has been observed in all patients after operation. No local recurrence has been observed with an average followup period of 42.5 months. Pulmonary metastasis developed in 2 patients, and 1 of them underwent a pulmonary metastasectomy. Limb salvage in vascular threatening soft tissue tumors using vascular reconstruction techniques is useful and preferable in some patients.

Adult↗
PubMed1996

Transcatheter arterial renal and adrenal embolization with iohexol-ethanol solutions. Animal experimental study and clinical application.

RATIONALE AND OBJECTIVES: The authors compared the embolic effect of radiolucent absolute ethanol (AE) with that of a radiopaque iohexol-ethanol (IES) solution for renal ablation in dogs and for the destruction of human aldosteronomas by the technique of transcatheter arterial embolization (TAE) to test whether IES can be an alternative to AE. METHODS: The embolic agents were infused through a balloon catheter into the renal arteries of 17 dogs (9 infused with 0.3 mL/kg AE; 8 infused with IES). The immediate and parenchyma were compared between the two groups. Transcatheter arterial embolization with IES also was performed in three humans with unilateral aldosteronoma. RESULTS: The IES was visualized faintly under fluoroscopy in all dogs. There were no significant differences in embolic effects between the AE and IES. Three patients with aldosteronoma were treated successfully by TAE with IES. CONCLUSIONS: The IES can be used as a "visible ethanol" to improve the safety and ease of ethanol embolization.

Adrenal Cortex Neoplasms↗
PubMed1996

Seasonal variation of mood and behaviour in a healthy middle-aged population in Japan.

A population survey of seasonality in six representative cities in Japan was conducted using the Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). The questionnaires were given to 951 parents (male: female ratio 1:1 age range 34-59 years) of high-school students. Significant regional differences in seasonal variations of mood, length of sleep, and weight were observed; the proportion of individuals reporting high seasonality in the two northern cities was significantly higher than that in the other areas. These results provide evidence for a northern predominance in the prevalence of seasonal affective disorder in Japan.

Adult↗
PubMed1996

The effects of 5-hydroxydopamine on salivary flow rates and protein secretion by the submandibular and parotid glands of rats.

The secretory effects of 5-hydroxydopamine (5-OHDA) were tested in Nembutal-anaesthetized adult male Sprague-Dawley rats injected I.V. over a wide range of doses, with and without various autonomic antagonists and Ca2+ channel blockers. Polyacrylamide disc gel (15%) and iso-electric focusing (IEF) electrophoresis by the PhastSystem were used to separate and determine the types of protein in submandibular saliva. Amylase activity of parotid saliva was determined by the blue dextran method. Salivation by the submandibular glands following application of 5-OHDA was completely abolished by both prazosin and propranolol, whereas salivation by the parotid glands was completely abolished by propranolol alone. Following application of 5-OHDA, there was a dose-related increase in flow rates and total output of protein, but not in the protein concentration and amylase activity, from both salivary glands. The effect of 5-OHDA on submandibular saliva was significantly reduced by alpha-adrenoceptor blockers, but not by beta-adrenoceptor and cholinergic blockers, nor by any Ca2+ channel blocker. The effect of 5-OHDA on the parotid gland was not significantly altered by atropine and phentolamine. However, after pretreatment with reserpine, a 95% reduction was observed in the salivation from the submandibular gland. This implies that 5-OHDA is mostly acting indirectly via release of noradrenaline. The proteins in submandibular saliva following treatment with 5-OHDA alone or 5-OHDA in combination with beta-adrenoceptor blockers were mainly of the alpha-type, whereas after treatment with 5-OHDA in combination with alpha-adrenoceptor blockers they were of the beta-type. The alpha-type was found in saliva after treatment with each of three Ca2+ channel blockers.

Adrenergic alpha-Antagonists↗
PubMed1996

Characterization of spirochetes isolated from ticks (Ixodes tanuki, Ixodes turdus, and Ixodes columnae) and comparison of the sequences with those of Borrelia burgdorferi sensu lato strains.

Ixodes persulcatus serves as a tick vector for Borrelia garinii and Borrelia afzelii in Japan; however, unidentified spirochetes have been isolated from other species of ticks. In this study, 13 isolates from ticks (6 from Ixodes tanuki, 6 from Ixodes turdus, and 1 from Ixodes columnae) and 3 isolates from voles (Clethrionomys rufocanus) were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, rRNA gene restriction fragment length polymorphism, partial sequencing of the outer surface protein C (OspC) gene, whole DNA-DNA hybridization, and 16S rRNA gene sequence comparison. All of the results revealed that these Borrelia strains clearly represent at least two new species. A third is also likely, although additional strains have to be isolated and characterized before a separate species is designated. We designated all isolates of I. tanuki and C. rufocanus as group Hk501 and all isolates of I. turdus as group Ya501. Phylogenetic analysis based on 16S rRNA gene sequences distinguished these Borrelia strains from those belonging to hitherto known Borrelia species. Furthermore, the genomic groups, each with its own tick vectors with enzootic cycles, were quite different from each other and also from those of Lyme disease Borrelia species known to occur in Japan. The results of 16S rRNA gene sequence comparison suggest that the strain Am501 from I. columnae is related to group Hk501, although its level of DNA relatedness is less than 70%.

Amino Acid Sequence↗
PubMed1996

Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease.

In addition to NS3 protease, the NS4A protein is required for efficient cleavage of the nonstructural protein region of the hepatitis C virus polyprotein. To investigate the function and the sequence of NS4A required for the enhancement of NS3 protease activity, we developed an in vitro NS3 protease assay system consisting of three purified viral elements: (i) a recombinant NS3 protease which was expressed in Escherichia coli as a maltose-binding protein-NS3 fusion protein (MBP-NS3), (ii) synthetic NS4A fragments, and (iii) a synthetic peptide substrate which mimics the NS5A/5B junction. We showed that the NS3 protease activity of MBP-NS3 was enhanced in a dose-dependent manner by 4A18-40, which is a peptide composed of amino acid residues 18 to 40 of NS4A. The optimal activity was observed at a 10-fold molar excess of 4A18-40 over MBP-NS3. The coefficient for proteolytic efficiency, kcat/Km, of NS3 protease was increased by about 40 times by the addition of a 10-fold molar excess of 4A18-40. Using a series of truncations of 4A18-40, we estimated that amino acid residues 22 to 31 in NS4A (SVVIVGRIIL) constituted the core sequence for the effector activity. Single-substitution experiments with 4A21-34, a peptide composed of amino acid residues 21 to 34 of NS4A, suggested the importance of several residues (Val-23, Ile-25, Gly-27, Arg-28, Ile-29, and Leu-31) for its activity. In addition, we found that some single-amino-acid substitutions in 4A21-34 were able to inhibit the enhancement of NS3 protease activity by 4A18-40. This approach has potential as a novel strategy for inhibiting the NS3 protease activity important for hepatitis C virus proliferation.

Amino Acid Sequence↗
PubMed1996

Elongation factor 1 gamma mRNA expression in oesophageal carcinoma.

Elongation factor 1 gamma (EF1 gamma) is known to be a subunit of EF1, one of the G proteins that mediate the transport of aminoacyl tRNA to 80S ribosomes during translation. As little is known regarding the expression of EF1 gamma in human oesophageal carcinoma, this study looked at its expression using a northern blot analysis. Thirty six cases of oesophageal carcinoma and 15 oesophageal carcinoma cell lines were studied. The EF1 gamma mRNA overexpression at a level of twofold or more was seen in five (14%) of 36 carcinomatous tissues compared with the normal counterparts. All five overexpressed cases showed severe lymph node metastases compared with the non-overexpressed cases, and the difference was significant (p = 0.028). The stage of the disease of these five cases was far advanced compared with the nonoverexpressed cases (p = 0.012). All 15 oesophageal carcinoma cells expressed EF1 gamma mRNA relatively lower than the gastric or pancreatic carcinoma cell lines, in which EF1 gamma was originally isolated. As the expression of EF1 gamma mRNA could be detected even in the biopsy specimens, its overexpression in tumour tissue may provide preoperative useful information for predicting the aggressiveness of tumours.

Adult↗
PubMed1996

Leukotriene C4 inhibits ciliary activity in the presence of gamma-glutamyl transpeptidase.

We incubated human paranasal sinus mucosa in tissue culture with each of leukotrienes C4, D4, and E4 (LTC4, LTD4, and LTE4). Ciliary beat frequency (CBF) was measured photoelectrically, and the concentrations of leukotrienes in the incubation medium were determined over time. LTC4 significantly decreased CBF with 2-h, 4-h, and 8-h exposures to 10(-6) M, 10(-8) M, and 10(-10) M, respectively. Moreover, LTC4 dose dependently reduced CBF to 81.4% of the initial value after 6-h exposure to 10(-6) M, to 82.5% after 8-h exposure to 10(-8) M, and to 89.7% after 12-h exposure to 10(-10) M. LTD4 also exhibited progressive ciliary inhibition, while LTE4 had a minimal effect on CBF. In the medium, LTC4 was changed to LTD4 and further to LTE4. gamma-Glutamyl transpeptidase (gamma-GTP), an enzyme that converts LTC4 to LTD4, was detected in the mucosa. Serine-borate complex, an inhibitor of gamma-GTP, blocked the inhibitory effect of LTC4 on CBF. These findings suggest that LTC4 may induce ciliary inhibition indirectly by conversion to LTD4.

Borates↗
PubMed1996

Dimethyl sulfoxide decreases interleukin-8-mediated neutrophil recruitment in the airways.

In this study, we investigated the role of dimethyl sulfoxide (DMSO) in inhibiting interleukin-8 (IL-8)-mediated neutrophil recruitment induced by Pseudomonas aeruginosa (PA) bacterial supernatant. First, we tested whether DMSO could inhibit IL-8 production induced by PA in human bronchial epithelial (16-HBE) cells in vitro. In these cells, exposure to PA or H2O2 induced IL-8 production dose dependently, an effect that was inhibited by 1% DMSO at both the protein and RNA level. Second, we tested whether DMSO could block the recruitment of neutrophils induced by PA in a bypassed segment of dog trachea in vivo. PA supernatant was placed in the tracheal segment for 6 h in four dogs, and neutrophil recruitment and IL-8 concentrations were measured in the superfusate. DMSO prevented the recruitment of neutrophils and IL-8 production induced by PA time dependently. The results suggest that DMSO may play an anti-inflammatory role in the airway by inhibiting IL-8 production in epithelial cells.

Animals↗
PubMed1996

Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation.

We investigated the role of neurogenic inflammation and the subsequent mechanisms in cigarette smoke-induced airway hyperresponsiveness in guinea pigs. Exposure to cigarette smoke was carried out at tidal volume for 3 min. Airway responsiveness to histamine was determined before and after smoke exposure followed by bronchoalveolar lavage (BAL). Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. Cigarette smoke produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. FK-224 (10 mg/kg i.v.), a tachykinin antagonist at NK1 and NK2 receptors, significantly inhibited these changes. The thromboxane (Tx) B2 concentration was increased in BAL fluid after smoke exposure and was significantly inhibited by FK-224. OKY-046 (10 mg/kg i.v.), a Tx synthase inhibitor, significantly inhibited airway hyperresponsiveness but had no effect on neutrophil influx or plasma extravasation. The results suggest that neurogenic inflammation and the subsequent generation of Tx in the airway are important in the development of the airway hyperresponsiveness induced by cigarette smoke.

Animals↗
PubMed1996

Radiobiological effects of gamma knife radiosurgery on brain tumors studied in autopsy and surgical specimens.

To elucidate the radiobiological effect of Gamma Knife radiosurgery on brain tumors, we performed a histological study on nine cases. In two, the material was obtained at autopsy and in seven following surgery. In the central region of the radiation field, destructive changes occurred both in tumor cells and in vessels. In the peripheral area, destructive and proliferative vascular changes were intermingled with residual tumor tissue. Immunohistochemical staining of surgical specimens showed that the vascular proliferative changes consisted of pericytic proliferation with or without endothelial proliferation. These characteristic changes might suppress tumor growth, at least in the short-term.

Adolescent↗
PubMed1996

Gamma thalamotomy for parkinsonian and other kinds of tremor.

On the basis of our experiences with selective ventralis intermedius thalamotomy with microrecording, certain cases of tremor with Parkinson's disease (PD, six cases), intentional tremor (one case) and essential tremor (one case) were treated by Gamma Knife. In all cases, 140-150 Gy were irradiated using 4-mm collimators. Three different strategies were used. (1) Gamma thalamotomy as the primary surgical treatment. (2) As a secondary treatment, irradiation of the symmetric point of the contralateral selective thalamotomy. (3) Extension of the previous thalamotomy. For the first three cases (all PD), a special plug pattern (100 plugs) was used, but was not employed for the later cases. No acute untoward effects were noted, and overall there appeared to be a reduction in tremor. The time course of tremor reduction varied from case to case, from about 5-6 months to 1 year.

Adult↗
PubMed1996

Gamma Knife radiosurgery for acoustic schwannoma: effects of low radiation dose and functional prognosis.

The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma were evaluated in 29 patients followed over 2 years after treatment. The mean dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic resonance signal intensity in the tumor center appeared in 69% and signs of tumor shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases, and 2 cases developed hydrocephalus. The percentage of pure-tone hearing preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18 months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma Knife radiosurgery was effective in suppressing tumor growth, with preservation of hearing.

Adult↗