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Biomedical subjects

R Wada

Publications and source records attributed to R Wada.

At least 73 records · Page 4Linked to original sources

Venereal infection of mares by equine arteritis virus and use of killed vaccine against the infection.

Venereal infection with equine arteritis virus (EAV) was established in each of seven mares by inoculation via the cervix with 20 ml of viral suspension (> or = 8 x 10(6) plaque-forming units; PFU), following treatment with prostaglandin and oestradiol. A dose of < or = 8 x 10(5) PFU produced infection in only five of eight mares. Serum neutralizing antibody developed in mares manifesting clinical signs of equine viral arteritis (EVA), and a weak antibody was detectable in one apparently healthy mare inoculated with 8 x 10(5) PFU. Virus isolation was demonstrated not only in the buffy coat but also in nasal swabs of infected mares. EAV was isolated frequently from the body tissues of the mares (killed 10 to 34 days post-inoculation) up to day 12, but rarely from the reproductive tissues later than day 12. The virus persisted longest in the splenic and deep inguinal lymph nodes, followed by the spleen and internal iliac lymph nodes. Four mares immunized with a killed vaccine for EVA showed no clinical disease after venereal challenge with EAV; the virus was recovered from the buffy coat of three mares and from the nasal swab of one of them, but not from the remaining animal.

Animals↗

Suppressive effect of tetraprenylacetone on gastric atrophy induced by short-term administration of N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND: Several studies have been reported on the effects of various therapeutic agents in enhancing or suppressing the carcinogenic activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). However, it is still unknown whether a mucosal protective agent could suppress its carcinogenic activity. METHODS: Twenty-five Wistar male rats were divided into four groups: group 1, MNNG alone; group 2, MNNG + tetraprenylacetone; group 3, control; group 4, tetraprenlacetone alone. MNNG 100 mg/mL, was freely given to groups 1 and 2, and tetraprenylacetone (200 mg/kg intraperitoneal) was additionally administered every other day to the rats in groups 2 and 4. The animals were sacrificed at 10 weeks and the gastric mucosa examined. RESULTS: Atrophic changes were observed in the antrum after 8 weeks of oral administration of MNNG. Furthermore, using immunohistological analysis with 5-bromo-2'-deoxyuridine (BrdU), the proliferative zone was found to be enlarged and shifted upward, although the BrdU labelling index of the proliferative zone was unaltered. Intraperitoneal administration of tetraprenylacetone every other day suppressed the MNNG-induced atrophic change and the alterations proliferative markers. Tetraprenylacetone alone did not have an effect either on morphological or proliferative markers. CONCLUSION: These observations suggest that gastric mucosal defensive factors may play critical roles in suppressing atrophic change inducing carcinogenesis by an exogenic carcinogen.

Animals↗

Metastatic cancer involving pancreatic duct epithelium and its mimicry of primary pancreatic cancer.

We investigated 47 autopsy cases of metastatic cancer involving the pancreas. Metastatic disease in nine cases involved the pancreatic duct epithelium. In two cases, metastatic cancer cells showed Pagetoid features. In three cases, pancreatic metastatic disease showed solitary proliferation with focal in situ carcinoma-like lesions mimicking primary pancreatic cancers. Each of these three cases had primary lung adenocarcinomas. Serial sections revealed abrupt borders between the in situ carcinoma-like lesions and the non-cancerous epithelium. Primary pancreatic cancers did not show Pagetoid features or abrupt borders between the cancerous and non-cancerous epithelium. We conclude that the possible diagnosis of pancreatic metastasis should be carefully ruled out in the histological detection of latent primary pancreatic cancer.

Aged↗

Cellular proliferation and differentiation in rat atrophic gastric mucosa induced by N'-methyl-N'-nitro-N-nitrosoguanidine.

It has been demonstrated that mucosal cell proliferation in atrophic gastritis is significantly accelerated, although the dynamics of the cell proliferation and differentiation have not been well characterized. We sequentially analyzed the markers of proliferation and differentiation of rat atrophic gastritis induced by MNNG. Immunohistochemical staining by anti-BrdU, anti-PCNA, and anti-PDGF-BB antibodies demonstrated that cell proliferation in atrophic gastritis was accelerated not only in the parenchymal tissue but also in the mesenchymal tissue. Expression of a gap junction protein (connexin 32), which is a marker for differentiation of epithelial cells, was reduced during the progression of atrophy. Some apoptotic cells were observed in the lower to middle third of the atrophic mucosa, whereas apoptotic cells were rarely seen in normal mucosa, which suggests that apoptosis in these parts of the mucosa may be related to the occurrence of mucosal atrophy.

Animals↗

Gastric stump carcinosarcoma with rhabdomyosarcomatous differentiation.

Gastric carcinosarcoma is an unusual tumor and its occurrence in the gastric stump is extremely rare. A report is presented here of a unique case of gastric stump carcinosarcoma with rhabdomyosarcomatous differentiation in a 74-year-old man. The patient had undergone partial gastrectomy with gastrojejunostomy (Billroth II method) 30 years previously. The tumor had both adenocarcinoma and sarcoma components, and an immunohistochemical study suggested a focal transition between these components. The main sarcomatous components showed fibrosarcomatous features with a scattered distribution of rounded tumor cells, whose rhabdomyosarcomatous differentiation was immunohistochemically determined. Ultrastructural examination supported the rhabdomyosarcomatous natures. Experience with the present tumor indicates that carcinosarcoma with rhabdomyosarcomatous differentiation can occur in the gastric stump and that this disease is capable of aggressive behavior.

Aged↗

Emergence of rifampin-resistant Rhodococcus equi in an infected foal.

To investigate the emergence of rifampin resistance in Rhodococcus equi strains isolated from foals and their environment in Japan, we compared the in vitro antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals and 98 soil isolates from their horse-breeding farms. As a control, 39 human isolates from patients with and without AIDS were also tested for susceptibility to rifampin. All of the isolates showed rifampin sensitivity, except isolates from one infected foal and two patients with AIDS that showed rifampin resistance. To investigate the emergence of rifampin-resistant R. equi in the infected foal, which had received rifampin monotherapy for a month before euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the intestinal contents of the one foal with rifampin-resistant organisms were analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99 isolates from the lesions, all of which were virulent R. equi strains containing a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin resistant (MIC, > or = 12.5 microg/ml). On the other hand, of the 20 isolates from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC, > or = 25 microg/ml), and 5 of them were avirulent R. equi strains. Among these 101 rifampin-resistant R. equi isolates with and without virulence plasmids characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III, and 12 were type IV. These results demonstrated that at least eight different rifampin-resistant R. equi strains emerged concurrently and respectively from the different lesions and intestinal contents of the infected foal.

Actinomycetales Infections↗

Isolation of Streptococcus equi subsp. equi from thoroughbred horses in a racehorse-breeding area of Japan.

For determination whether strangles has invaded the Hidaka district of Hokkaido, the main racehorse-breeding area of Japan, a epizootiological survey with bacterial isolation was carried out during the breeding season in 1995. Streptococcus equi subsp. equi, which is the causative agent of strangles, was isolated from two Thoroughbred horses with submandibular lymphadenitis. Isolates were identified by serological grouping, biochemical tests and analysis of cell surface proteins by Western immunoblotting. Through this survey, it revealed that S. equi subsp. equi has invaded the Hidaka district and that strangles has become prevalent in racehorse-breeding farms in this area.

Animals↗

Secretory meningioma with severe perifocal edema--case report.

An 82-year-old male presented with a small parasagittal meningioma associated with disproportionately severe perifocal edema. Histological examination including immunohistochemical staining and electron microscopy resulted in a diagnosis of secretory meningioma. In addition to tumor size, the edema could not be explained by location, growth rate, vascular involvement, or other factors. We conclude that secretory meningiomas may possess an innate ability to cause brain edema.

Aged↗

A dislocated and enlarged proliferative zone in human gastric intestinal metaplasia.

There are many published reports suggesting a close relationship between intestinal metaplasia and gastric carcinogenesis, but there are few studies that examine the cellular kinetics of these tissues in humans. Thus, we sought to characterize the proliferative zone of intestinal metaplasia of the human stomach and correlate this with its known malignant potential. We examined the incorporation of bromodeoxyuridine into 228 human endoscopic biopsy specimens from duodenal mucosa (n=35) and non-intestinalized antral mucosa (n=127) as well as antral mucosa with intestinal metaplasia (n = 66). The proliferative zone in specimens with intestinal metaplasia was deeper when compared to non-intestinalized antral mucosa, but was more superficial than that of duodenal mucosa. Although the labeling index of intestinalized mucosa was similar to that of non-intestinalized antral mucosa, the size of the proliferative zone was significantly increased in intestinal metaplasia. The dislocation of the proliferative zone with an increase in its size in intestinal metaplasia is considered to be a hallmark of gastric intestinal metaplasia.

Bromodeoxyuridine↗

Histopathological studies of superficial-type early colorectal carcinoma.

BACKGROUND: Superficial-type early colorectal carcinoma (SCa) is presently not a rare finding and is very important in discussions regarding the development of large bowel cancers, although the histologic characteristics of SCa remain obscure. METHODS: Using 54 SCa lesions (34 intramucosal adenocarcinomas (SCa-m) and 20 adenocarcinomas with invasion to the submucosa (SCa-sm)), the largest dimension of the depressed region of the lesion and the greatest dimension of the entire lesion were measured by the computed image analyzer, and the expression of p53 and ras of SCa were examined immunohistochemically. RESULTS: The percent of depressed regions in SCa lesions measuring less than 5 mm in greatest extent was larger than in those measuring more than 6 mm, and the percent of depressed regions in SCa-sm with deeper carcinoma invasion was lower than that of SCa-sm with shallower invasion. There was a positive correlation between the depth of invasion and the maximum dimension of the carcinoma. The frequency of association with adenoma in all SCa-m was 21% and was 32% in SCa-m that were more than 6 mm in greatest extent, although all minute SCa-m lesions less than 5 mm were pure carcinomas without any adenomatous component. Positive expression of ras was noted in 41% of SCa-m and 36% of SCa-sm, respectively, while positive expression of p53 was noted in 63% of SCa-m and 88% of SCa-sm, respectively. CONCLUSIONS: These results suggested that 70% to 80% of SCa developed via a de novo carcinoma theory and showed the depression form in the initial histologic stage and thereafter in the flat-protrusion form, while 20% to 30% of SCa arose from the preexisting flat adenoma via the adenoma-carcinoma sequence theory. The results also suggested that p53 was related to the enlargement and deeper invasion of SCa, regardless of the sequence of development of colorectal cancer.

Adenocarcinoma↗

P53 protein expression in pancreatic tumors and its relationship to clinicopathological factors and prognosis.

We examined the expression of p53 protein by immunohistochemical method in a series of pancreatic tumors and evaluated its relationships to the clinicopathological factors and prognosis. The study involved 108 cases of pancreatic tumors (79 ductal carcinomas, 1 acinar cell carcinoma, 14 endocrine tumors, 6 solid cystic tumors, 8 benign ductal tumors) and 8 chronic pancreatitides. Thirty-nine cases of pancreatic ductal carcinoma (49.4%) were positive for p53 protein. Analysis of the Cox hazards model identified p53 positivity and stage at the initial operation as an independent prognostic factor. Patients with p53 positive ductal carcinomas had a greater risk of death compared to p53 negative cases (P < 0.05). There was, however, no statistically significant correlation between p53 protein expression and other clinicopathological factors. Cases of stage III and IVb with positive p53 showed a bleak prognosis compared to p53 negative cases (P < 0.05). Our results suggest that p53 expression is common in invasive pancreatic ductal carcinomas and may have a prognostic value.

Adult↗

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Acetylcysteine↗

Histopathological and immunofluorescent studies on transplacental infection in experimentally induced abortion by equine arteritis virus.

Five pregnant mares, at between 6 and 8 months gestation, were experimentally infected with the Bucyrus strain of equine arteritis virus (EAV). Of the five mares, four aborted and one died. The pathogenesis of the abortions was studied, using histopathologic techniques, tissue immunofluorescence and virus isolation. Common microscopic lesions in the maternal reproductive organs indicated myometritis with a degeneration of the myocytes and an infiltration of the mononuclear cells. Epithelial cells of the endometrial gland showed sporadic degeneration. Lesions in the fetal tissue included an atrophy of the lymphoid follicles in the spleen and lymph nodes with degenerated lymphocytes. The placentae were oedematous and degenerated fibroblasts were observed in the subvillous layers. Immunofluorescence detected EAV antigen in the myometrium and the endometrial gland in the dams, in the subvillous layer of the placentae, and in the aborted fetuses. EAV was recovered from the maternal uteri, placentae and fetuses. The placentae yielded the greatest amounts of the virus. Transplacental infection of the fetus was clearly demonstrated in the EAV infection.

Abortion, Veterinary↗

New biodegradable oligoesters for pharmaceutical application.

Tartaric acid, malic acid, and glyceric acid were copolycondensed with glycolic acid at various molar ratios in feed to quickly synthesize biodegradable oligoesters. They were likely to have a moderately cross-linked structure with relatively low molecular weights and hydrophilic groups on the chains. In addition to macroscopic gels which were insoluble in any solvents, we could obtain the oligoesters which were insoluble in water but soluble in N,N-dimethylformamide. The degradation rate of the oligoesters was higher than that of lactic acid (LA) oligomers having molecular weights of a few thousands. On the contrary, their glass transition and flow temperatures were much higher than those of LA oligomers, indicating that their handling during the preparation of drug delivery dosage forms was much improved. The formulation of microspheres containing drugs from the oligoesters revealed that they were useful as biodegradable matrices having high degradation rates.

Antineoplastic Agents↗

Biodegradability of oxidized poly(vinyl alcohol).

Poly(vinyl alcohol) dehydrogenase (PVADH) purified from Pseudomonas sp. 113P3 catalyzed an oxidation of poly(vinyl alcohol) (PVA) in the presence of pyrroloquinoline quinone (PQQ) to give a beta-diketone structure on PVA. Although PVADH oxidized not only enzymatically oxidized PVA but also chemically oxidized PVA, PVA-degrading microorganisms, Pseudomonas sp. 113P3 and Arthrobacter tumescens sp. 52-1 grew on the enzymatically oxidized PVA, but not on the chemically oxidized PVA. This suggests that the growth of PVA-degrading microorganisms is affected by the structure of oxidized PVA.

Alcohol Oxidoreductases↗

Galactosemic neuropathy in transgenic mice for human aldose reductase.

We studied the functional consequences of an enhanced polyol pathway activity, elicited with galactose feeding, on the peripheral nerve of transgenic mice expressing human aldose reductase. Nontransgenic littermate mice were used as controls. With a quantitative immunoassay, the expression level of human aldose reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about 25% of that in human sural nerve. When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10-fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a significant and progressive decrease in motor nerve conduction velocity in transgenic mice to 80% of the level of galactose-fed littermate mice, which was not significantly different from that of galactose-free littermate mice. A morphometric analysis of sciatic nerve detected > 10% reduction of mean myelinated fiber size but no alterations of myelinated fiber density in galactose-fed transgenic mice compared with other groups. The functional and structural changes that develop in galactose-fed transgenic mice are similar to those previously reported in diabetic animals. The results of these studies suggest that transgenic mice expressing human aldose reductase may be a useful model not only for defining the role of the polyol pathway in diabetic neuropathy but also for identifying and characterizing effective inhibitors specific for human aldose reductase.

Aldehyde Reductase↗