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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 505 records · Page 28Linked to original sources

Pathogenesis of cerebellar deformity in experimental Chiari type I malformation caused by mumps virus.

We sought to elucidate the pathogenesis of Chiari type I malformation using an experimental model of hydrocephalus produced by inoculating hamsters with mumps virus. Dilatation of the lateral ventricules was detected in all brains inoculated at 2, 10, and 25 days of age. The cerebellum in hamsters inoculated at 2 and 10 days of age showed elongation and flattening of the vermis and protrusion or notching of the uvula. All layers, i.e., the molecular, Purkinje cell, and granular layers, and the white matter were preserved, but had become narrow. Purkinje cells remained normal. Hamsters inoculated at 25 days of age did not develop the cerebellar deformity. Mumps virus antigen was detected in all ependymal cells and in some epithelial cells of the choroid plexus in all hamsters that had been inoculated at 2, 10, or 25 days of age. Results suggest that Chiari type I malformation is caused by two main factors occurring simultaneously, i.e., increasing intracranial pressure and rapid histogenesis of the cerebellar cortex.

Animals↗

Histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse, a model of Menkes kinky hair disease.

The cerebellar Purkinje cells in the hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria.

Animals↗

The significance of tissue-type plasminogen activator for pretransplant assessment of liver graft viability: analysis of effluent from the graft in rats.

We studied the significance of tissue-type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4 degrees C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4 degrees C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80 +/- 0.23 ng/ml vs 0.42 +/- 0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134 +/- 13 mg/dl vs 120 +/- 2 mg/dl, 0.34 +/- 0.40 mg/dl vs 0.09 +/- 0.01 mg/dl, and 183 +/- 79 micrograms/dl vs 102 +/- 40 micrograms/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of trypan blue-stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold-preserved liver grafts in rats.

Animals↗

Initiation of a fibrinolytic system in hepatic resection: the roles of tissue-type plasminogen activator and plasminogen activator inhibitor-1.

The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the alpha 2-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values of alpha 2-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress.

Aged↗

Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation.

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.

Animals↗

Occult lymph node metastasis in gastric cancer with submucosal invasion.

To evaluate more precisely the incidence of lymph node metastasis in patients with submucosally invaded (sm) gastric cancer, three additional sections were made from the remaining half of 1,794 lymph nodes taken from 57 patients, for a detailed reexamination. Lymph node metastasis was demonstrated in 19 nodes from 11 patients by the initial routine examination; however, the detailed reexamination showed cancer involvement in a further nine lymph nodes from eight patients. Of these eight patients, metastasis had not been detected in any lymph nodes by routine examination in six. Macroscopically, the lesion was of the depressed or mixed type in six of the eight patients. From the intranodal location and growth pattern of the cancer foci, lymph nodes with occult metastasis were divided into the marginal sinus type, the medullary sinus type, and the mixed type, with the marginal type being found most frequently. The overall incidence of lymph node metastasis in patients with sm gastric cancer was as high as 29.8% (17/57) in this series. Moreover, a follow-up study revealed that two patients with occult metastasis died of cancer recurrence postoperatively. Accordingly, systematic regional lymph node dissection should be carried out at the time of surgery for sm gastric cancer.

Adenocarcinoma↗

Hepatic regeneration following right lobectomy: estimation of regenerative capacity.

The regenerative capacity of the liver was assessed using a volumetric method on computed tomography in 21 adults: 16 underwent a standard right hepatic lobectomy for hepatocellular carcinoma, there were hepatic metastases in 3 others, and 2 suffered from other diseases. The patients' ages ranged from 33 to 68 years with a mean age of 57.0 years. The regeneration rate was expressed as the rate of the volume increase of the remnant left lobe compared with the preoperative volume of the left lobe. A univariate regression analysis showed that the portal pressure had a highly inverse correlation with the regeneration rate of the liver (r = -0.4753, P = 0.0397), while a multiple regression analysis demonstrated the correlation between the portal pressure, age, and the regeneration rate (multiple r = 0.5640). The regeneration rate of the normal liver (97.6 +/- 53.5%) was significantly higher than that of the chronic hepatitic (43.0 +/- 40.7%), and also tended to be higher than that of the cirrhotic liver (51.5 +/- 13.2%). However, there were no differences between chronic hepatitic and cirrhotic livers. The portal pressure before hepatectomy of the normal liver (149 +/- 19 mmH2O) was significantly lower than those of chronic hepatitic (188 +/- 38 mmH2O) and cirrhotic (245 +/- 78 mmH2O) livers. We thus conclude that the regenerative capacity of the liver following a right hepatic lobectomy could be estimated on the basis of both portal pressure and age. The regenerative capacity was also influenced by underlying liver diseases.

Adult↗

The prediction of portal pressure: a multivariate analysis of clinical data and intraoperative portal pressure.

Portal pressures were estimated non-invasively in 100 patients who underwent hepatic resection and completely fulfilled the 21 variables evaluated. Ten variables were selected from among all those in the univariate analysis, and a stepwise discriminant analysis revealed four independent significant variables, namely: The indocyanine green dye retention test at 15 min (ICGR15); the prothrombin time index; the platelet count; and the globulin fraction. An equation to estimate the portal pressure was made using the coefficients in the analysis, the reliability of which was confirmed (r = 0.70484, P = 0.0001). The univariate analysis revealed ten significant variables to discriminate portal hypertension, defined as a portal pressure of over 200 mmH2O. A multiple logistic regression analysis of these variables revealed two independent variables, being ICGR15 and the platelet count. Thus, we consider that our equation for estimating portal pressure is potentially useful, and that the platelet count and ICGR15 are the most significant parameters in discriminating between the presence or absence of portal hypertension. Moreover, a platelet count of less than 120 x 10(3)/mm3 and an ICGR15 value of more than 15% correlated well with portal hypertension.

Adult↗

Laparoscopic splenectomy.

A technique for laparoscopic splenectomy is described. The patient is placed in the right semidecubitus position and pneumoperitoneum is prepared. The splenic artery and vein are exposed near the hilum, using a laparoscopic ultrasonic dissector. The larger vessels are doubly ligated, and the spleen is resected and maneuvered into a nylon surgical sack; the sack is removed through a 2-cm incision along the midaxillary line. This procedure has been used for four patients requiring splenectomy for benign disease, and the outcome has been entirely satisfactory for all concerned.

Adult↗

Estimation of risk of major complications after hepatic resection.

To identify the risk factors predicting major postoperative complications from among preoperative and intraoperative variables, an extensive retrospective analysis of 209 patients who underwent hepatic resections was performed using multivariate logistic regression. The major complications were defined as liver failure, intractable ascites and pleural effusion, intraperitoneal infection, intra-abdominal hemorrhage requiring reoperation, major bile leakage, and gastrointestinal tract bleeding. First, detailed pre- and intraoperative data including medical history, laboratory data, portion and extent of hepatectomy, operative time, and amount of blood loss were univariately analyzed. Next, any significant variables were multivariately analyzed using the logistic regression method. Diabetes, increased intraoperative blood loss, resection of segment 8, and an increased serum blood urea nitrogen level were independent and significant variables predicting major postoperative complications. A higher level of serum cholesterol and a procedure involving a portion of left lateral segment were found to decrease the risk. Both more careful operative procedures and intensive management of DM and renal dysfunction in the perioperative period could result in a better quality of life after hepatic resection.

Blood Loss, Surgical↗

Elevated serum and urinary thrombomodulin levels in patients with non-insulin-dependent diabetes mellitus.

Increased plasma levels of soluble thrombomodulin have been reported in several disorders as a marker for vascular endothelial damage. Serum and urinary thrombomodulin levels were measured in 79 patients with non-insulin-dependent diabetes mellitus. Both levels were significantly higher (23.5 +/- 6.1 ng/ml and 146.6 +/- 64.9 ng/ml, respectively) than those of normal healthy controls (18.8 +/- 3.1 ng/ml, P < 0.001, and 96.8 +/- 60.3 ng/ml, P < 0.01). Serum thrombomodulin levels increased in keeping with urinary albumin levels. In urine thrombomodulin was lower in the macroalbuminuria group than in the microalbuminuria group, suggesting two mechanisms: intravascular overproduction and impaired renal clearance. Both serum and urinary thrombomodulin levels in diabetic patients might be predictors for very early nephropathy.

Adult↗

Dextran sulfate, a competitive inhibitor for scavenger receptor, prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Dextran sulfate competes with binding of modified LDL to the scavenger receptor in macrophages. To elucidate the role of dextran sulfate in the atherosclerotic process, 100 mg of dextran sulfate in drinking water was given to 5 Watanabe heritable hyperlipidemic (WHHL) rabbits for 12 months starting at age 4 months. During the experimental period, there were no significant differences in plasma cholesterol levels between dextran sulfate-treated and untreated rabbits. After 12 months' treatment, accumulation of cholesterol ester in total aorta was significantly suppressed in dextran sulfate-treated rabbits as compared with untreated rabbits (71.4 +/- 22.3 vs. 42.7 +/- 16.5 mg/g dry weight, P < 0.05). Furthermore, lesion area with atherosclerotic plaques in treated rabbits was significantly less than that in untreated rabbits (59.7 +/- 24.5 vs. 30.4 +/- 14.4%, P < 0.05). These results indicate that dextran sulfate might prevent the progression of atherosclerosis by competitively inhibiting the binding of modified LDL to scavenger receptors.

Animals↗

Plasma lipid abnormalities and risk factors for coronary artery disease in Japanese subjects with diabetes mellitus and glucose intolerance.

We evaluated the plasma lipid levels of 3163 subjects including subjects with non-insulin-dependent diabetes mellitus (NIDDM), insulin-dependent diabetes mellitus (IDDM), impaired glucose tolerance (IGT), and normal glucose tolerance. Furthermore, we performed 100 g oral glucose tolerance tests on 2113 subjects, and analyzed the relationships of risk factors for coronary artery disease to glucose intolerance. Mean plasma cholesterol and triglyceride levels were highest in NIDDM (213 mg/dl and 148 mg/dl), and plasma HDL-cholesterol level was lowest in IGT and NIDDM (42 mg/dl), as compared to those in normal subjects (cholesterol, 200 mg/dl; triglycerides, 109 mg/dl; HDL-cholesterol, 52 mg/dl). Multiple regression analysis demonstrated a significant relationship of either blood pressure, plasma triglyceride or HDL cholesterol level to plasma insulin and glucose response after glucose loading.

Adult↗

Ipsilateral motor control of the forelimb in the congenitally acallosal mouse.

The corticospinal projections of mice with callosal agenesis were investigated using electro-physiological and horseradish peroxidase techniques. In the normal mouse, intracortical stimulation of the motor area with the microelectrode resulted in contralateral contraction of the forelimb, whereas ipsilateral contraction was observed in the acallosal mouse. Hence, mice with congenital absence of the corpus callosum show physiologically ipsilateral motor control. Furthermore, latency of the forelimb contraction elicited by electrical stimulation of the acallosal mouse was slightly shorter than that of the normal mouse. On the other hand, it was confirmed by a horseradish peroxidase technique that the corticospinal tract and peripheral motor neurons in the spinal cord of the acallosal mouse were identical to those of the normal mouse.

Agenesis of Corpus Callosum↗

The role of prostaglandins in hepatic resection.

The role of prostaglandins (PGs) and the efficacy of PGE1 were investigated in hepatic resection. Patients who underwent hepatic resection were randomly assigned to two groups consisting of a control (n = 5) and a PGE1 treatment group (n = 6). Then the amount of 6-keto PF1 alpha, thromboxane B2 and (TXB2) and PGE2 were serially measured both before and after hepatic resection. Regarding changes in the PGs, a remarkable increase in TXB2 during hepatectomy was demonstrated in both groups. In the control group, both 6-keto PF1 alpha and PGE2 showed only a slight increase both during and after the operation. Regarding the efficacy of PGE1 on liver damage, no significant difference in postoperative liver function was found, however the lipoperoxide level at postoperative day 3 in the PGE1 treatment group (1.9 +/- 0.4 nmol/ml) was significantly lower than that in the control (2.6 +/- 0.5 nmol/ml: P < 0.05). Judging from the remarkable increase of TXB2, a stable metabolite of TXA2 during hepatectomy, it may be suggested that TXA2 plays an important role in the development of liver damage during hepatic resection.

6-Ketoprostaglandin F1 alpha↗

Insulin-binding sites in the mouse deferent duct.

In vivo light microscopic autoradiography was used to demonstrate the presence of specific insulin-binding sites in the mouse deferent duct three min after intravenous injection of 125I-insulin with or without excess of unlabeled insulin. The studies showed high specific insulin binding in the endothelial cells of capillaries and certain fibroblasts of the lamina propria. In the epithelium, although the tall columnar cells were free of specific insulin binding, the basal cells had relatively high specific insulin binding. Because the deferent duct has been considered to exert certain effects on sperms, the presence of high specific insulin binding at these sites may provide further support for this concept.

Animals↗

A comprehensive multi-institutional study of empiric therapy with flomoxef in surgical infections of the digestive organs. The Kyushu Research Group for Surgical Infection.

The effect of flomoxef as empiric therapy for surgical infections of the digestive organs was analyzed in 103 patients, most of whom (94.2%) had intra-abdominal infections. Surgical procedures were performed on 73 patients contemporaneously with the flomoxef therapy. Flomoxef is an oxacephem and has a potent and broad bactericidal spectrum against aerobes and anaerobes. It provokes fewer adverse reactions than latamoxef such as vitamin K deficiency and platelet dysfunction. Flomoxef was administered intravenously at a dose 1-4g/day for more than 3 days without any other antimicrobial agent. The clinical response was classified into 3 groups; cured, improved and failed, and both the cured and improved responses were defined as satisfactory. A satisfactory response was obtained in 99 patients (96.1%). Regarding bacteriological response, the overall eradication rate was 81.3%. Adverse reactions including abnormal laboratory data occurred in only two patients. One had abdominal pain, and the other had a mild elevation of transaminases, and both were mild and easily reversible. Therefore, flomoxef is considered to have the potential of becoming one of the most effective agents in empiric therapy for surgical infections of the digestive organs.

Adolescent↗

Physiological expression of the 2',5'-oligoadenylate synthetase gene in mouse intestine.

2',5'-Oligoadenylate synthetase (2-5A synthetase) is an enzyme induced by interferon (IFN) that is considered to play an important role in IFN action. The normal mouse, not treated exogenously with any IFN or IFN inducers, has been shown to have an enhanced level of 2-5A synthetase activity, which is distributed among several lymphoid tissues. In the present report, we investigated the expression of the 42-kD 2-5A synthetase mRNA in the organs of normal mice using RNA blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). Among the organs tested, intestinal tissues had the highest levels of this mRNA. Furthermore, the 42-kD 2-5A synthetase mRNA was expressed in intestines from germ-free mice and fetuses. Immunoblotting analysis using a monoclonal antibody against the 42-kD 2-5A synthetase revealed that the 42-kD enzyme as well as a cross-reactive protein of 30 kD were produced in the organs of the normal mouse.

2',5'-Oligoadenylate Synthetase↗