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Biomedical subjects

J Shimizu

Publications and source records attributed to J Shimizu.

At least 91 records · Page 5Linked to original sources

Secretion and excretion of immunoglobulin A to cecum and feces differ with type of indigestible saccharides.

The study was conducted to elucidate the effects of orally administered indigestible saccharides (IDS) on immunoresponses of the intestinal tracts, especially secretion and excretion of immunoglobulin A (IgA). Male 4-week-old Sprague-Dawley rats were fed diets containing several kinds of IDS (cellulose, corn husk, glucomannan, curdlan and lactulose) at 5% for three weeks. The results indicated that the proportion of IgA-presenting lymphocytes in the cecal mucosa of the tested IDS groups increased significantly or tended to increase compared with that of the cellulose group. No significant differences among the experimental groups were observed in the CD4(+)- and CD8(+)-presenting lymphocytes and the CD4+/CD8+ ratios in the small intestine, cecum and mesenteric lymph nodes. IgA amounts in the cecal contents increased significantly in the glucomannan and curdlan groups as compared with that in the cellulose group. The inconsistent results were observed in the cecal IgA amounts of the lactulose group. Although IgA excretion into feces increased periodically in the cellulose, hardly any changes were observed in the glucomannan and curdlan groups. These results revealed that IgA secretion from cecal mucosa to contents was promoted, and its excretion to feces was decreased by the oral administration of highly fermentable IDS, respectively, while non- or low-fermentable IDS functioned adversely to IgA responses in the intestinal tract. It is suggested that the response of IgA in the intestinal immune system differs with the type of IDS ingested.

Administration, Oral↗

Curdlan and gellan gum, bacterial gel-forming polysaccharides, exhibit different effects on lipid metabolism, cecal fermentation and fecal bile acid excretion in rats.

The effects of curdlan (CD) and gellan gum (GG), bacteria-producing polysaccharides, on lipid concentrations of serum and liver, fecal bile acid composition and intestinal fermentation products were studied in rats fed diets containing cellulose powder (CP), CD or GG at 5% for 4 wk. The cecal weight of the CD group increased significantly as compared to that of the other two groups and the pH of its contents was significantly low. The gastrointestinal transit time in the GG group was significantly shorter than that in the CP and CD groups. No significant inter-group differences were observed in the serum concentrations of total cholesterol and HDL-cholesterol, but a significant decrease was observed in the hepatic total cholesterol concentration of the CD group as compared to that of the CP and GG groups. No significant difference in the total bile acid excretion in feces was observed among the groups, but significantly low values were observed in the proportion of secondary bile acids in the CD group as compared to those of the CP and GG groups. Amounts of short-chain fatty acids (acetic, propionic and butyric acid) and lactic acid in the cecal contents were significantly higher in the CD group than in the other two groups. These results reveal that dietary CD is easily degraded and fermented by intestinal bacteria in the cecum and lowers cholesterol concentration in the liver, while dietary GG shortens the gastrointestinal transit time, suggesting the promotion of evacuation.

Animals↗

[Randomized controlled trial for smoking cessation among city office employees].

To evaluate the effect of a smoking cessation program by health professionals, a randomized intervention study was carried out in the Omihachiman city office in 1993. Participants (n = 53), volunteers from current smokers in the city office, were randomly divided into intervention and control groups. The intervention group received intensive education for five months (i.e., the effect of smoking on health, the beneficial aspects of quitting smoking, how to stop smoking and how to deal with the withdrawal symptoms). Group lectures (two times) and individual counseling (three times) were used for health education. After five months, the control group was also given the same advice on smoking cessation. Comparison of smoking cessation rates between the two groups was performed at the end of the intervention period. Follow-up of all participants occurred at six and 12 months post intervention. After the five months of intervention, smoking cessation rate in the intervention group (19.2%) tended to be higher than that in the control group (7.4%), but was not significant (chi 2 = 1.62). Over all smoking cessation rates of all participants (n = 53) at the end of the 10 month intervention was 32.1% and at six months and 1 year after the end of the 10 month intervention were 24.5% and 13.2%, respectively. Comparison of participants who successfully stopped smoking and those who did not, it was revealed that younger age, lower expired air CO concentration (p < 0.01), and attitude for smoking cessation at the beginning were significantly related to smoking cessation. In our study, after five months, smoking cessation rate in the intervention group was about two times that of the control group, although the effectiveness of our smoking cessation program could not be validated due to small sample size. Taking into account the rate of smoking cessation after one year, We believe that programs by health professionals are effective for smoking cessation.

Adult↗

[Two cases of an intracranial large hemangiopericytoma associated with brain swelling in the early operative stage].

Intracranial hemangiopericytomas are hypervascular tumors. Consequently, resection of these tumors must occasionally be stopped owing to profuse bleeding. We report two cases of large intracranial hemangiopericytoma whose resection had to be stopped owing not to bleeding but to brain swelling. These patients were treated with large doses of barbiturate until the intracranial pressure had normalized. After preoperative irradiation therapy, the residual tumors were easily removed without serious complications. We speculate that the brain tissue around a large hemangiopericytoma might be under ischemia because of long-standing compression and deviation of blood to the hypervascular tumor. A large amount of blood flowing into these brain tissues due to external and internal decompression inverts cerebral perfusion acutely from ischemia to hyperemia. The brain swelling in the early operative stage would be evoked by this "inverted cerebral hyperemia". We found that brain swelling is sometimes encountered during the resection of a large hemangiopericytoma even in the early operative stage. If swelling occurs, tumor resection should be stopped immediately and intracranial pressure should be controlled. The residual tumor can then be easily removed without complications after preoperative irradiation therapy.

Adult↗

[A case report of hepatocellular carcinoma with hepatic and portal venous tumor thrombus and multiple intrahepatic metastasis who survived over 1 year after the operation with combined locoregional chemotherapy].

Hepatocellular carcinoma (HCC) with vascular invasion and/or intrahepatic metastasis (IM) has a poor prognosis, so advanced HCC may be considered as a contraindication for hepatectomy. We experienced a case of HCC with hepatic venous and portal venous tumor thrombus and multiple IM who survived over 1 year after the operation with combined locoregional chemotherapy. (Case): A 67-year-old male patient was diagnosed with HCC with extracapsular invasion after transarterial embolization (TAE). CT scan revealed the HCC had a right portal venous tumor thrombus and multiple IM. Posterior lobectomy and thrombectomy of hepatic venous and portal venous tumor thrombus and placement of portal venous catheter ware performed. From the first day after operation the patient received continuous intravenous and intraportal 5-FU for 3 weeks. At the first month after operation, TAE and PEIT were given against residual IM. After discharge the patient received hepatic arterial infusion chemotherapy (MTX/CDDP/5-FU/Leucovorin). Fourteen months after operation, the patient is surviving in good physical condition.

Aged↗

Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma.

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), but little is known about the prognostic value of COX-2 in HCC or its associated nontumor liver tissue. We examined the expression of COX-2 protein by immunohistochemistry in 53 patients with HCCs whose corresponding nontumor tissues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrhosis (n = 32). Samples of nine histologically normal livers and eight precancerous dysplasias were also analyzed. The level of COX-2 increased from normal liver to chronic hepatitis to cirrhosis. The majority of cirrhotic livers (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%). In HCC, 17% of samples displayed a high COX-2 expression, and 37% of samples expressed COX-2 at a moderate level. Concordant results were obtained with reverse transcription-PCR and Western blot analyses. Clinicopathological survey indicated a significant correlation between COX-2 expression and differentiated carcinoma (P = 0.019). Although there was no correlation between COX-2 expression in HCC and prognosis, a striking difference was found between COX-2 expression in nontumor tissue and shorter disease-free survival (P = 0.0132). Moreover, high COX-2 expression in nontumor tissue was significantly correlated with the presence of active inflammation (P < 0.0001). The present findings suggest that COX-2 expression in nontumor tissue may play a positive role in relapse of HCC after surgery.

Blotting, Western↗

Ventricular pressure-volume area (PVA) accounts for cardiac energy consumption of work production and absorption.

We briefly review that ventricular systolic pressure-volume area (PVA) can predict changes in myocardial O2 consumption (VO2) associated with cardiac work production (positive work) and absorption (negative work). PVA represents the total mechanical energy of cardiac contraction as it is an integral of mechanical energy generated during systole in the cardiac chamber. We have shown that PVA linearly correlates with VO2 under varied pre- and afterload conditions in the left ventricle of the excised cross-circulated canine heart preparation as well as other heart preparations of different species. PVA is the sum of external mechanical work (EW) and mechanical potential energy (PE) which is almost fully convertible to mechanical work without affecting VO2. To compare the energetic effects of cardiac work production and absorption, we varied the timing of the servo pump motion relative to left ventricular (LV) contraction. When the pump fills the LV during diastole and sucks (allows ejection) during systole, cardiac work is produced by the heart, and hence EW > 0. When the pump fills the LV during systole and sucks during diastole, work is absorbed by the heart, and hence EW < 0. The pressure-volume loop rotates counterclockwise when EW > 0. It rotates clockwise when EW < 0. As the result, PVA (= PE + EW) > PE when EW > 0; PVA < PE when EW < 0. We found that VO2 always linearly correlated with PVA regardless of the polarity of EW. Therefore, PVA is the unique determinant of VO2 in a cardiac chamber in a stable contractility.

Animals↗

Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: the role of systematic nodal dissection.

OBJECTIVE: To determine the extent of lymph node metastasis in clinical stage I non-small-cell lung cancer (NSCLC). METHODS: We performed a retrospective review of 524 patients with clinical stage I NSCLC who underwent lobectomy with systematic nodal dissection. RESULTS: The nodal status was N0 in 409 patients (78%), N1 in 44 (8%), N2 in 67 (13%), and N3 in four (0.8%). Thirty-six patients had single-level mediastinal nodal metastases and 35 had multi-level metastases. The incidence of N2/3 disease in patients with adenocarcinoma/squamous cell carcinoma/other histologic types according to tumor size was 0/0/0%, respectively, in tumors < or = 10 mm in diameter, 12/0/0% in tumors 11-20 mm in diameter, 14/4/23% in tumors 21-30 mm in diameter, and 26/14/20% in tumors >30 mm in diameter. Nodal metastases to the upper mediastinum from middle or lower lobe lesions were frequently observed in 51 N2 adenocarcinomas, whereas those to the lower mediastinum from upper lobe lesions were rare. Of 10 N2 squamous cell carcinomas, seven had regional and three had non-regional nodal metastases. The 5-year survival rate was 68, 43, and 30% in N0, N1, and N2, respectively (P<0.01, N0 versus N1, N0 and N2). CONCLUSIONS: Systematic mediastinal nodal dissection should be routinely performed for clinical stage I lung cancer to ensure the correct nodal status, but it might be dispensable in the patients with peripheral squamous cell carcinoma < or = 20 mm in diameter, with central squamous cell carcinoma < or = 30 mm, and with adenocarcinoma < or = 10 mm. When systematic nodal dissection cannot be performed, the incidence and extent of nodal metastases should be taken account with respect to histologic type, size, and location of the tumor.

Carcinoma, Non-Small-Cell Lung↗

Dried green leaf powders of Jew's mellow (Corchorus), persimmon (Diosphyros kaki) and sweet potato (Ipomoea batatas poir) lower hepatic cholesterol concentration and increase fecal bile acid excretion in rats fed a cholesterol-free diet.

A cholesterol-free diet containing dried powder of Jew's mellow leaves, persimmon leaves or sweet potato leaves respectively at 5% level as dietary fiber was fed to male Sprague-Dawley rats for about one month. The experiment was conducted twice except for sweet potato leaves. In the groups fed the diet mixed with powders of any of the three different dried green leaves, the hepatic cholesterol concentration significantly decreased. Such lowering was not observed in serum cholesterol concentration compared with the control (cellulose) group. A significant increase in fecal weight was observed in all the groups fed the green leaf samples. All the dried green leaves increased fecal excretion of bile acids per gram or per day compared with the control group in both experiments, but only the dried Jew's mellow leaves showed an increased excretion of neutral sterols. These results suggest that lowering of hepatic cholesterol by powdered green leaves is not necessarily due to the same factor, but to the increased fecal excretion of bile acids due to inhibited enterohepatic circulation in animals given these samples.

Animals↗

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗

Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats.

We investigated the effects of the dietary n-3-to-n-6 polyunsaturated fatty acid (PUFA) ratio (n-3/n-6 ratio) on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats by feeding them several types of dietary fat with a fixed PUFA-to-saturated fatty acid ratio. Dietary fat was fed to the rats as 10% of the total feed weight, starting two weeks before the initiation. An increase in the n-3/n-6 ratio did not suppress the incidence or reduce the latency of mammary tumor development. The number and weight of mammary tumors per tumor-bearing rat tended to be large in the group with an n-3/n-6 ratio of 7.84 compared with those in the other groups. As the n-3/n-6 ratios were elevated, the total number and weight of tumors increased gradually. The prostaglandin E2 (PGE2) concentration in mammary tumor tissue was markedly low in the group with an n-3/n-6 ratio of 1.03 compared with the group with an n-3/n-6 ratio of 0.01. In addition, PGE2 concentrations were almost constant when n-3/n-6 ratios were > 1.03. These results suggested that the increase in the n-3/n-6 ratio of dietary fat with the fixed PUFA-to-saturated fatty acid ratio cannot suppress the mammary carcinogenesis but can promote development of tumors, despite reduced PGE2 concentration in the tumor.

9,10-Dimethyl-1,2-benzanthracene↗

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state.

Elimination of CD25+ T cells, which constitute 5-10% of peripheral CD4+ T cells in normal naive mice, leads to spontaneous development of various autoimmune diseases. These immunoregulatory CD25+CD4+ T cells are naturally unresponsive (anergic) in vitro to TCR stimulation, and, upon stimulation, suppress proliferation of CD25-CD4+ T cells and CD8+ T cells. The antigen concentration required for stimulating CD25+CD4+ T cells to exert suppression is much lower than that required for stimulating CD25-CD4+ T cells to proliferate. The suppression, which results in reduced IL-2 production by CD25-CD4+ T cells, is dependent on cellular interactions on antigen-presenting cells (and not mediated by far-reaching or long-lasting humoral factors or apoptosis-inducing signals) and antigen non-specific in its effector phase. Addition of high doses of IL-2 or anti-CD28 antibody to the in vitro T cell stimulation culture not only breaks the anergic state of CD25+CD4+ T cells, but also abrogates their suppressive activity simultaneously. Importantly, the anergic/suppressive state of CD25+CD4+ T cells appeared to be their basal default condition, since removal of IL-2 or anti-CD28 antibody from the culture milieu allows them to revert to the original anergic/suppressive state. Furthermore, transfer of such anergy/suppression-broken T cells from normal mice produces various autoimmune diseases in syngeneic athymic nude mice. These results taken together indicate that one aspect of immunologic self-tolerance is maintained by this unique CD25+CD4+ naturally anergic/suppressive T cell population and its functional abnormality directly leads to the development of autoimmune disease.

Animals↗

A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts.

Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (VO2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+ handling VO2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling VO2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from approximately 60 micromol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

Animals↗

Effects of Ca2+ and epinephrine on Ca2+ recirculation fraction and total Ca2+ handling in canine left ventricles.

We investigated the effects of intracoronary Ca2+ and epinephrine on the intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the left ventricle (LV) of the excised cross-circulated canine heart preparation. We analyzed LV postextrasystolic potentiation (PESP) following a spontaneous extrasystole that occurred sporadically under constant atrial pacing. All PESPs decayed in alternans and none decayed monotonically. We extracted an exponential decay component from the alternans PESP, determined its beat constant (taue), and calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased taue and RF, but epinephrine did not change them, although both agents enhanced LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal decay of the alternans PESP. These results indicate that RF via the sarcoplasmic reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110 micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the control and enhanced contractile states. These results indicate that this new LV-level approach seems to better the understanding of the Ca2+ mass dynamics responsible for the mechanoenergetics enhanced by inotropic interventions.

Animals↗

Effect of indigestible saccharides on B lymphocyte response of intestinal mucosa and cecal fermentation in rats.

The effects of water-soluble and -insoluble indigestible saccharides (IDS) on immune responses of the intestinal tract were studied. Male 4-week-old Sprague Dawley rats were fed for three weeks on diets containing several kinds of IDS at 5%. The results revealed that the proportion of kappa-light chain and IgA-presenting lymphocytes in small intestinal and cecal mucosa differed in increased number depending on the type of IDS. The response of colonic mucosa was not pronounced. The amounts of short-chain fatty acid (SCFA) and lactic acid in the cecal contents of the other test groups except the celfur group tended to be higher than those in the cellulose group, particularly in the lactulose group where many acids showed significant increases. The correlation between the proportion of kappa-light chain and IgA-presenting lymphocytes in the cecal mucosa and lactic acid in the cecal contents was significant, but that between the proportion of both lymphocytes and SCFA was not. Based on the above, we concluded that the oral administration of IDS induces the proliferation of kappa-light chain and IgA-producing B lymphocytes in small intestinal and cecal mucosa, but the degree of response differs depending on the type of IDS. It is thus suggested that IDS are involved in the intestinal immune system of rats.

Animals↗

Changes in platelet aggregation and lipid metabolism in rats given dietary lipids containing different n-3 polyunsaturated fatty acids.

We compared the effects of different n-3 polyunsaturated fatty acids (PUFA) on platelet aggregation and lipid metabolism in rats. alpha-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used as n-3 PUFA sources. The rats were fed diets containing 10% lipids (polyunsaturated/saturated fatty acid (P/S) ratio = 1.0; n-3/n-6 = 0.02 for the control group, 0.2 for the test groups) for two weeks. The platelet counts, platelet aggregation, and production of thromboxane A2 (TXA2), plasma total cholesterol (TC) and triacylglycerols (TG) were not different between the ALA group and the control group, but showed a decreasing tendency for the EPA group and significant decreases for the DHA group. The production of prostacyclin in the aorta was significantly decreased in all of the n-3 PUFA groups when compared with that in the control group. Liver TC and TG concentrations were significantly decreased in the DHA group when compared with those in the control group. Based on the above, it is assumed that the physiological action exerted by n-3 PUFA differs by type and that DHA is a more effective n-3 PUFA, both for suppressing platelet aggregation and for modulating lipid metabolism in the plasma and liver of rats.

Animals↗