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Biomedical subjects

M Hirokawa

Publications and source records attributed to M Hirokawa.

At least 109 records · Page 6Linked to original sources

Further investigation of phenanthroindolizidine alkaloids from Tylophora tanakae.

In addition to ten alkaloids previously described, we have isolated two alkaloid N-oxides from Tylophora tanakae MAXIM. (Asclepiadaceae). Further, the polar fraction of the leaves and caules of this plant cultivated in a farm afforded two new polar alkaloids. The structures of the four products were determined. The relation between the structure and cytotoxic activity of this group of alkaloids is discussed.

Alkaloids↗

Acute terminal pancreatitis occurring in jejunal heterotopic pancreas.

CONCLUSION: We report a unique case of acute terminal pancreatitis occurring in the jejunal heterotopic pancreas. Unlike previously reported cases, acute pancreatitis was not found histologically in the ordinary pancreas. BACKGROUND: Heterotopic pancreas may show the same inflammatory or neoplastic changes, such as acute pancreatitis and adenocarcinoma, as those that occur in the ordinary pancreas. However, histologically proven acute pancreatitis occurring in heterotopic pancreas is very rare and only three reports have been described. METHODS: A 53-yr-old Japanese man died of hepatic failure, and autopsy was performed. RESULTS: Autopsy incidentally revealed heterotopic pancreas of the jejunum. Microscopically, focal acute pancreatitis was observed in the jejunal heterotopic pancreas, whereas the pancreas of the normal location showed no abnormality. In addition, no clinical evidence of pancreatic disease was noted before death. Therefore, we diagnosed this case as acute terminal pancreatitis occurring in the jejunal heterotopic pancreas.

Acute Disease↗

[The efficacy of re-TUR after 3 weeks of initial TUR treatment for locally advanced bladder cancer].

BACKGROUND: Radical cystectomy was usually performed for the patient with advanced bladder cancer. The choice of surgical procedure whether bladder preserved therapy or radical cystectomy has sometime plagued us in bladder cancer treatment. Because we don't have clear guideline for the treatment of locally advanced bladder cancer (T2-T3a N0M0). We devised a radical treatment for the patients with locally advanced bladder cancer without radical cystectomy. PATIENTS AND METHODS: We performed re-TUR treatment after 3 weeks of initial TUR for 13 patients with grade 2 and locally advanced bladder cancer diagnosed with pelvic CT scan, transurethral ultrasonography or bimanual examination under the anesthesia. RESULTS: We could successfully preserve all cases of bladder with the use of this devised TUR (periods 9-45 months median 22 months). This method has significantly reduced the cystectomy rate in such locally advanced cases compared with the cystectomy rate prior to 1993 (p < 0.001). CONCLUSION: This method has significance on treatment for locally advanced papillary bladder cancer as bladder preserving therapy with careful observation.

Aged↗

[Prognosis in the cases with renal cell carcinoma according to clinical parameters].

BACKGROUND: The objects of this study is to evaluate the clinical prognostic factors in renal cell carcinoma. MATERIALS AND METHODS: During a 30-year period from January 1965 to December 1994, 1301 cases with renal cell carcinoma were treated at the Yokohama City University Hospital and its affiliated hospitals. In these cases, cause specific 679 cases from January 1965 to December 1990 were analyzed in a study undertaken to investigate long-term treatment results and clinical prognostic factors. RESULTS: 1. The cause specific 5-, 10-, 15-, and 20-year survival rates were 48.7%, 41.1%, 32.3%, and 26.5% respectively, indicating thus that a great number of cases had an ominous prognosis even 5 years or moreafter surgical treatment. 2. Among patients under 40 years of age (n = 29) none died more than 2 years after receiving operation, the prognosis for this particular group of cases being relatively good. 3. Female, incidentally detected cancer, small tumor size (< or = 4.0 cm), slow growing type and low stage were proven to be favourable prognostic factors in renal cell carcinoma. 4. The cause specific 5-year survival rate for the patients (n = 239) from 1965 to 1981 was 33.8%, while the rate for the patients (n = 440) from 1982 to 1990 was 56.5%. This improvement of survival rate was brought by the increase of the incidentally detected renal cell carcinoma. 5. In the incidentally detected renal cell carcinoma, the incidence of slow growing cases and the cases of less than 4.0 cm tumor size were higher than in the symptomatic renal cell carcinoma. 6. Multivariate analysis using Cox's proportional hazard model showed that stage was the most important prognostic factor. CONCLUSIONS: These results suggested that sex, age, symptom, tumor size, growing type, and stage were important prognostic factors in renal cell carcinoma.

Adolescent↗

[A case of multiple organ failure with massive intestinal bleeding caused by methicillin-resistant Staphylococcus aureus in a postcystectomy patient--efficacy of mask continuous positive airway pressure training and intraarterial embolization].

A 51-year-old man underwent radical cystectomy with tubeless cutaneous ureterostomy. Methicillin-resistant Staphylococcus aureus (MRSA) enteritis developed postoperatively. MRSA caused critical infections such as pneumonia and sepsis, which subsequently progressed to adult respiratory distress syndrome, massive melena and multiple organ failure. The patient was rescued by intensive management including mask continuous positive airway pressure, systemic vancomycin administration and intraarterial embolization to stop jejunal bleeding.

Carcinoma, Transitional Cell↗

Multicentric Castleman's disease with an increased serum level of macrophage colony-stimulating factor.

We describe a 74-year-old patient with multicentric Castleman's disease (MCD) whose serum macrophage colony-stimulating factor level was elevated. Serum levels of tumor necrosis factor-alpha and interleukin 6 were also elevated at presentation, and they returned to normal levels after chemotherapy. Although the total serum cholesterol level was below normal on admission, it increased after chemotherapy. These results suggest that the activation of monocytes or macrophages may be involved in certain pathological phenomena in MCD.

Aged↗

Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial cells.

Effects of intraluminal pressure on cultured intestinal epithelial cells were assessed by measuring cell proliferation and DNA synthesis after exposure to various pressures. Pressures of 40 to 120 mm Hg promoted cell proliferation and DNA synthesis. Pressure-induced DNA synthesis was further enhanced by the addition of interleukin-2, suggesting the regulation of intestinal epithelial growth by pressure in coordination with cytokines. Pretreatment with either a phospholipase C inhibitor or protein kinase C inhibitor significantly inhibited DNA synthesis promoted by pressure and interleukin-2. This study demonstrates a novel mechanism whereby pressure regulates cell growth in intestinal epithelial cells, possibly via activation of phospholipase C and protein kinase C.

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

The immunoregulatory effects of NK cells: the role of TGF-beta and implications for autoimmunity.

The cytotoxic activities of natural killer (NK) cells--important in innate immunity--have received considerable attention, but NK cells also regulate T- and B-cell functions as well as hematopoiesis. Here, David Horwitz and colleagues focus on the capacity of NK cells to regulate antibody production positively and negatively, and in particular on the role of NK-cell transforming growth factor beta (TGF-beta) in downregulation of B-cell activity.

Animals↗

Heterotopic salivary gland adenocarcinoma in the cervical region.

A case of heterotopic salivary gland adenocarcinoma (HSGA) in the right cervical region is presented. The carcinoma cells were positive for alpha-amylase, carcinoembryonic antigen, epithelial membrane antigen, cytokeratin as well as for expression of human salivary alpha-amylase messenger ribonucleic acid. The possibility of HSGA should be considered when an adenocarcinoma producing human salivary alpha-amylase is diagnosed away from sites where major and minor salivary glands normally are found.

Adenocarcinoma↗

Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease.

It is postulated that an enhanced production of nitric oxide by inflamed intestine plays a role in the pathophysiology of active inflammatory bowel disease. In this study, systemic NOx concentrations and colonic nitric oxide synthase activity were determined in patients with ulcerative colitis or Crohn's disease. The relationship between these two parameters and disease activity, as well as differences in nitric oxide synthase activity between ulcerative colitis and Crohn's disease, were areas of specific focus. Patients with active ulcerative colitis and Crohn's disease had significantly elevated plasma NOx concentrations; a positive correlation was found between NOx values and inducible nitric oxide synthase activities in the active mucosa of these patients. In active ulcerative colitis, levels of inducible nitric oxide synthase were significantly elevated in both normal and inflamed mucosa, although inducible nitric oxide synthase activity was higher in the latter. These colonic inducible nitric oxide synthase activities correlated well with the results of endoscopic and histologic grading of inflammation. There was no increase in constitutive nitric oxide synthase activity in patients with active ulcerative colitis. However, constitutive nitric oxide synthase activity was significantly increased in the inflamed mucosa in patients with Crohn's disease. In Crohn's disease, elevated inducible nitric oxide synthase activity was found in both normal and inflamed mucosa, with no significant difference between the tissues. Such differences in nitric oxide production in the colonic mucosa possibly reflect the significant differences in the pathophysiology and characteristic clinical features between ulcerative colitis and Crohn's disease.

Adult↗

Regulation of BCL-6 gene expression in human myeloid/monocytoid leukemic cells.

We demonstrated in the present study that the BCL-6 transcripts were detectable not only in B cells, but also in circulating granulocytes and monocytes from normal individuals, and in human acute nonlymphocytic leukemia cells of certain subtypes (M3, M4, M5). Then, with an assumption that the BCL-6 gene expression may be related to the differentiation of myeloid cells, we analyzed the inducibility of BCL-6 gene expression along monocytic lineage differentiation in HL-60 and U-937 cells by treating them with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although the expression of BCL-6 transcripts was very low or undetectable in untreated HL-60 or U-937 cells, treatment of these cells with TPA to induce monocytic differentiation resulted in an apparent increase of BCL-6 mRNA, suggesting that BCL-6 gene expression is not limited to B cells and it is closely associated with monocytic lineage differentiation. The BCL-6 transcripts in TPA-treated U-937 cells were superinduced by the treatment with cycloheximide (CHX) and the half-life of the BCL-6 mRNA was apparently prolonged when TPA-treated U-937 cells were exposed to CHX in the presence of actinomycin D (ACD). Furthermore, the nuclear run-on assay revealed that the BCL-6 transcription signals were enhanced by TPA treatment. These results suggest that the increase of BCL-6 mRNA in U-937 cells stimulated with TPA to induce monocytic lineage differentiation is mediated by both transcriptional and post-transcriptional regulation.

Adult↗

Oxidative stress-mediated apoptosis of hepatocytes exposed to acute ethanol intoxication.

The present study was designed to investigate whether acute ethanol intoxication increases the production of active oxidants, and subsequently promotes apoptosis of hepatocytes. Hepatocytes were isolated from male Wistar rats, and cultured in the presence or absence of ethanol. The fluorescence in situ nick end labeling method and an enzyme-linked immunosorbent assay (ELISA) system to quantify fragmented DNA were used to estimate apoptotic change in hepatocytes. Nuclear morphological alterations and membrane barrier dysfunction of hepatocytes were assessed by staining with Hoechst 33342 and propidium iodide (PI). Intracellular glutathione level was determined as the fluorescence of monochlorobimane (MCLB), which forms conjugate with glutathione to become fluorescent. Ethanol (100 mmol/L) increased the amount of fragmented DNA and the number of apoptotic hepatocytes in vivo as well as in vitro. These ethanol-induced alterations in hepatocytes were attenuated by simultaneous incubation with either 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, or dimethylthiourea, an intracellular oxidant scavenger. Diethyl maleic acid (DMA), a glutathione depletor, enhanced the induction of apoptotic change, and decreased membrane barrier function in ethanol-treated hepatocytes, whereas ethanol per se did not increase the number of PI-positive hepatocytes. Furthermore, combination of ethanol and DMA but not ethanol alone decreased the hepatocyte MCLB fluorescence. Taken together, the present study suggests that active oxidants produced during ethanol metabolism mediate fragmentation of DNA in hepatocytes, and that intracellular antioxidants such as glutathione play a critical role in the cytoprotective mechanisms of hepatocyte against lethal cell death, ie, apoptosis, induced by ethanol.

Animals↗

Beta 2 microglobulin haemodialysis related amyloidosis: distinctive gross features of gastrointestinal involvement.

Two cases of beta 2 microglobulin amyloidosis following long term haemodialysis found during necropsy are reported. The patients were 59 and 65 year old Japanese men, respectively. In both cases, systemic distribution of beta 2 microglobulin amyloid deposits was observed. The gastrointestinal tract including the stomach, small intestine, and colon showed the distinctive gross feature of rippled appearance, which was characterised by serosal wrinkles along the muscle layer arrangement. These areas were confirmed to contain deposits of beta 2 microglobulin in the muscularis propria. Although the outline of the muscle layers was preserved, most muscle fibres, encircled by the amyloid deposits, were atrophic or had disappeared microscopically. In neither case could a definite diagnosis of amyloidosis be made while the patient was alive. Interestingly, the oesophagus presented less involvement compared to the remainder of the gastrointestinal tract. In comparison with the AA or AL type of amyloidosis, beta 2 microglobulin haemodialysis related amyloidosis showed a rippled appearance of the serosal rather than mucosal changes, which may explain the difficulty in diagnosing amyloid deposits using biopsies of the gastrointestinal tract.

Aged↗

Lithium associated autoimmune thyroiditis.

A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration. Some areas showed a moderate degree of stromal fibrosis and atrophic thyroid follicles. Lymphoid follicles with germinal centres, disrupted thyroid follicles with lymphocytic infiltration, and Hürthle cells were also observed. The differential diagnosis in patients presenting with these histological features includes painless (silent) thyroiditis, autoimmune thyroiditis and lithium associated autoimmune thyroiditis. A detailed clinical history is essential if the correct diagnosis is to be reached.

Adult↗

Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches of rat small intestine.

Although vasoactive intestinal peptide (VIP) has been postulated to function in modulation of T cell trafficking, the exact mechanism has not been elucidated in vivo. In the present study, the effects of VIP on T lymphocyte migration were examined in rat Peyer's patches. T lymphocytes collected from intestinal lymph of rats were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein. Peyer's patches of the recipient rats were observed with intravital fluorescence microscopy. In vivo intra-arterial infusion of or in vitro incubation with VIP did not affect the initial lymphocyte interaction with postcapillary venules of Peyer's patches. However, these treatments with VIP significantly inhibited transendothelial migration and also significantly blocked the interstitial migration of T cells and inhibited their subsequent appearance in the interfollicular lymphatics. Treatment with adenosine 3',5'-cyclic monophosphate (cAMP)-inducing agents resulted in similar inhibitory effect on T lymphocyte migration in Peyer's patches. In conclusion, VIP has significant inhibitory effects on T lymphocyte migration in Peyer's patches, possibly mediated by elevation of the intracellular cAMP concentrations.

Animals↗

A case of gross hematuria arising during embolization for renal arteriovenous malformation.

A cirsoid type of arteriovenous malformation was treated successfully by superselective embolization using a platinum micro coil and absorbable gelatin sponge. During the procedure, as soon as the arteriovenous shunt had disappeared, an arteriopelvic shunt appeared. The pyelogram showed that the high pressure arterial blood flow drained directly into the pelvic cavity. Massive gross hematuria occurred immediately accompanied by a sudden blood pressure drop to 60 mm Hg, necessitating blood transfusion. Fortunately this complication was managed successfully. To our knowledge, there are only a few reported cases that make reference to gross hematuria occurring on embolization. We discuss the possible causes of this complication and the mechanism of occurrence of gross hematuria in renal arteriovenous malformation.

Arteriovenous Fistula↗