Biomedical subjects
Publications and source records attributed to M Kawamura.
A 23-year-old man underwent a tracheostomy. A massive hemorrhage from the tracheostomy site occurred 50 days later. An emergency operation was immediately performed and an erosion was noted on the innominate artery. The artery was divided and the hemorrhage was successfully stopped.
Two distinct infectious molecular clones of human immunodeficiency type 2 (HIV-2) were analyzed for their biological properties in six cell lines. Fourteen chimeric and ten mutant viruses were constructed from these two viral genomes to localize the genetic determinants responsible for the phenotypes. Growth property of the viruses in the cell lines, together with the biochemical data, showed that a major determinant for the viral tropism resides in the env gene. In addition, in some cell lines, the accessory genes vif and nef affected the efficiency of virus replication. Thus, like HIV-1, mutations in the auxiliary and env genes of HIV-2 contributed much to the differences in virological characteristics.
Neurotropin, a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug in Japan. Its analgesic effect has been demonstrated by reduced mechano-nociception in hyperalgesic rats exposed to SART-stress (a repeated cold stress) for 5 days. In order to clarify the mechanism of the analgesic effect of neurotropin at the spinal cord level, we examined the effects of several neurotransmitter receptor antagonists given by intrathecal (i.t.) injection on the antinociceptive effect of intraperitoneally (i.p.) injected neurotropin [100 and 200 Neurotropin Unit (NU)/kg]. The analgesic effect of neurotropin was significantly inhibited not only by methysergide (100 nmol/rat, i.t.), a non-selective antagonist against serotonin (5-HT), but also MDL 72222 (30 nmol/rat, i.t.), a selective 5-HT3 antagonist, but not influenced by ketanserin (100 nmol/rat, i.t.), a 5-HT2A antagonist. The antinociceptive effect of neurotropin (200 NU/kg, i. p.) was significantly inhibited also by yohimbine (30 nmol/rat, i.t.), a noradrenergic alpha2 antagonist. However, the analgesic effect of neurotropin (100 and 200 NU/kg, i.p.) was not influenced by naloxone (30 nmol/rat, i.t.), an opioid antagonist. These results suggest that the mechanism of the antinociceptive effect of neurotropin is via enhancement of endogenous descending pain inhibitory pathways of the serotonergic and noradrenergic systems, especially involving 5-HT3 and noradrenergic alpha2 receptors in spinal dorsal horn in which these neurons terminate. No influence of opioid receptors at the spinal cord level is indicated.
The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.
A series of (4S)-4-[(2S)-benzyl-3-mercaptopropionylamino]-4-(N-phenylcarbamoyl )-butyric acids has been identified as potent systemically active enkephalinase inhibitors. Structure-activity relationships (SAR) are discussed. Further chemical modification of the inhibitors was carried out in order to identify the inhibitors which are orally active in an animal model. Compounds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were evaluated.
Mutations were introduced into a genomic region encoding the C-terminal portion of Gag capsid protein of pathogenic simian immunodeficiency virus (SIVmac239). All the mutants generated were defective for virion production and were non-infectious for monkey cells. They all efficiently suppressed the replication of wild type SIVmac in monkey cells. These results were in good agreement with those obtained for human immunodeficiency virus type 1, showing the importance of SIV/monkey model system for studies on Gag.
OBJECTIVES: The main aim of this study was to investigate the relationship between mothers' gingival condition (an assumed indicator of their self-care level) and the prevalence and severity of dental caries of their children. SAMPLE AND METHODS: Subjects comprised 1471 pairs of mothers and their children who attended for the 3-year-old dental check-up at a community health centre in Hiroshima. The mothers' gingival condition was scored as 'excellent (+2)', 'good (+1)', 'questionable (0)', 'poor (-1)' or 'very poor (-2)' according to the criteria of the Oral Rating Index (ORI). Caries experience of the children was recorded using the WHO caries diagnostic criteria for dmft. RESULTS: The percentage of caries-free children was 51.3%, and the mean dmft score was 2.61. The percentages of caries-free were higher and the mean dmft level were lower in the children of mothers with better gingival condition compared to the children of mothers with worse gingival condition. CONCLUSIONS: Mothers' gingival condition was associated with the prevalence and severity of dental caries of their children.
We retrospectively investigated the incidence and prognosis of and risk factors for cerebrovascular events in 1,064 patients with chronic uremia who received maintenance hemodialysis (HD) for more than 3 months during 24 years in our dialysis units in Miyazaki, Japan. Cerebrovascular events developed in 98 patients (9.2%). The confirmed incidences of cerebral hemorrhage (CH) and infarction were 8.7 and 3.7 per 1,000 patient-years, respectively. Of the 56 patients with CH, 40 (71.4%) died within 3 months of the onset of CH. Ganglio-thalamic lesion was observed in 32 (80.0%) of 40 patients with CH confirmed by a brain computed tomography. The incidence of polycystic kidney disease was higher in the CH group than in the overall HD population (12.5% v 3.9%, P < 0.01). Of the 13 patients with diabetes mellitus and nephrosclerosis, nine (69.2%) developed CH within 36 months of the initiation of HD; 11 (78.6%) of 14 patients with chronic glomerulonephritis developed CH after 36 months. CH developed in six patients (15.0%) within 6 hours of a previous HD session. We compared laboratory values, the supine blood pressure, and electrocardiographic (ECG) findings in 35 patients with CH and a control group (66 patients) matched in age, sex, basal renal disease, age at the initiation of HD, and the duration of HD. Data were obtained before and after HD 3 to 4 months before the first attack of CH. The systolic and diastolic blood pressure (SBP, DBP) before and after HD were significantly higher in the CH group than in the control group (pre-HD SBP: 171 +/- 22.5 v 154 +/- 19.3 mm Hg, P < 0.001; pre-HD DBP: 89 +/- 13.6 v 81 +/- 9.6 mm Hg, P < 0.001). The incidence of left ventricular hypertrophy was higher, and the Kt/V was significantly lower (1.23 +/- 0.26 v 1.38 +/- 0.34, P < 0.05) in the CH group than in the control group. However, there were no significant differences in the serum levels of albumin and cholesterol or the total dose of heparin during HD sessions between groups. In conclusion, the incidence of CH was high, and its prognosis was poor, in patients undergoing maintenance HD. Reversible risk factors include hypertension and possibly the amount of HD prescribed, but not anticoagulation with heparin.
A case of primary adrenal insufficiency with bilateral adrenal masses and meningitis due to disseminated cryptococcosis in a patient with mild non-insulin-dependent diabetes is presented. The diagnosis was made by fine-needle aspiration biopsy cytology. Although the meningitis responded to antifungal therapy, the bilateral adrenal gland enlargement did not change. Reflecting this, cryptococcal antigen titers became negative in CSF, but fell to 1:8 in serum. Although antifungal therapy continued, cryptococcal antigen titer increased both in CSF and serum for 50 days. Because the adrenal glands were the apparent focus for the persistent fungemia, bilateral adrenalectomy was performed. Antifungal therapy for an additional 15 months was needed to achieve negative serum cryptococcal antigen titers. Although adrenal insufficiency due to disseminated cryptococcosis is rare in healthy hosts, it should be included in differential diagnosis of unilateral and bilateral adrenal masses.
The growth kinetics of wild-type and nef mutant viruses of human immunodeficiency virus type 1 were comparatively analysed in several human CD4+ cell lines. Delayed replication of nef mutant virus was observed in all cell lines examined. To determine the stage in the virus replication cycle that is affected by Nef, a single-round replication assay was performed. Initially, the expression of marker genes in transfected cells was examined in order to study the role of Nef in the late phase of infection. The results obtained indicated that Nef is dispensable during the transcription to virion production stage. Next, the effect of Nef on the early phase was investigated with a single-round infection. It was demonstrated that Nef is required in the early phase of the virus replication cycle, from virion adsorption to integration. Finally, the infectivity of virus stocks prepared from four cell lines was determined. The relative infectivity of the nef mutant from the four cell lines differed. Taken together, we conclude that Nef acts via modulation of viral particles to enhance virus infectivity in a cell-dependent manner.
One hundred and two dentate patients with type II diabetes mellitus and 98 non-diabetic subjects were examined for oral conditions and metabolic state. Self-reported health behaviour was analysed. From factor analysis four factors emerged: general health behaviour (GHB), perceived fatigue (PF), diet control (DC) and regular diet (RD). In diabetics PF, DC and RD were significantly higher than that in non-diabetics. Patients with diabetes were more likely to control their disease through a programme of decreased kilojoule intake leading to weight management. However, they tended to tire. The mean gingivitis index was significantly higher (p < 0.01) among diabetics (2.39) than among non-diabetics (1.99). The number of missing teeth was significantly higher (p < 0.01) for diabetics (6.7) when compared with non-diabetics (4.3). On the other hand, aetiological factors (plaque, calculus) and the level of dental health behaviour as expressed in the HU-DBI scores were similar. Probing pocket depth did not differ statistically between groups. The increasing number of missing teeth in diabetics may primarily result from severe periodontitis with tooth mobility or deep pockets. Findings in this study suggest that the difference in the severity of periodontitis between diabetics and non-diabetics was significant although aetiological factors and the level of dental health behaviour were similar.
Overseas investigations have reported the amount and variety of dental services provided. An understanding of the current service-mix in private general practice is important in the anticipation of the future practice of dentistry. The main purpose of this study was to describe the service-mix of private general practitioners in Japan, which was recorded using the Australian Dental Association Dental Procedure Code. Some comparisons with previous studies were offered. The youngest age group and adolescents formed only a small percentage of the total patients, while the greatest percentage of patients occurred in the 45-64 year age group. The services provided were mainly restorative, diagnostic advanced restorative and endodontic services. Preventive services represented a minority of dental activity, especially for young patients. Periodontic and orthodontic services were also remarkable for their low percentage in all age groups. In comparison with an Australian study, the percentage of preventive services was considerably lower. Movement toward a preventive emphasis in Japanese dentistry requires a change in the clinical model, de-emphasizing biomedical and aetiological approaches and placing greater emphasis on the patient and factors affecting dental practice.
Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma.
BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing. METHODS: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested. RESULTS: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice. CONCLUSION: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.
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Various gag mutants of human immunodeficiency virus type 1 (HIV-1) generated in vitro were evaluated for their potentials to suppress the replication of wild-type (wt) virus. A single-round of wt virus replication in the presence of various mutant proteins was quantitatively monitored by transfection and infection experiments. Out of 38 mutants examined, 15 were demonstrated to interfere with the replication of wt HIV-1 at early and/or late viral replication phase. Some of these mutants were also effective against the replication of wt HIV-2. In this review, we focus on the mutants, which are able to act against a wide variety of HIV, and are very useful for future gene therapy against AIDS.
We experienced the safe and easy insertion method with the J-shaped left ventricular vent catheter. The catheter tip (about 15 cm) was vended in the J shape with the inner stainless steel introducer. This J-shaped catheter was inserted into the left atrium through the right upper pulmonary vein. Then this catheter was held vertically and only the outer silicone catheter was pushed into the left ventricle. In this method the catheter tip is turned to the front in the left atrium and inserted easily into the left ventricle along the anterior wall of the left atrium through the anterior margin of the mitral valve orifice.
201Tl-Chloride scintigraphy (early and delayed images) was performed in 40 patients with suspected metastatic bone lesions. The sensitivity and specificity of 201Tl scanning for detecting metastatic bone lesions were 66.7% and 77.4%, respectively. The uptake ratio of 201Tl per voxel of the lesions to the normal site was significantly different between the metastatic bone lesion and benign lesions. In 20 sites of 15 patients, 201Tl-Chloride scintigraphy was performed before and after radio- or radiothermotherapy. There was a significant difference in the mean uptake ratios in the early and delayed scans between before and after therapy. The mechanism of intracellular uptake of 201Tl is considered to be one of active transport, which might make 201Tl an accurate indicator of the viability of tumor cells and metabolic activity as long as there is sufficient blood flow to prompty transport 201Tl to tumor cells. Thus it would seem that decreased uptake of 201Tl and change in retention index after therapy depends partially on tumor blood flow. In conclusion, 201Tl-Chloride scintigraphy is very useful not only for clinically detecting metastatic bone lesions but also for assessing the therapeutic effects.