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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 1,405 records · Page 78Linked to original sources
PubMedDate not supplied

Cytokeratin intermediate filaments of rat hepatocytes: different cytoskeletal domains and their three-dimensional structure.

A new method of visualizing the three-dimensional architecture of the cytokeratin filaments of the intact rat hepatocyte in situ has been achieved. Frozen sections of liver cut 10 micron thick were serially extracted to remove all elements of the cells except the intermediate filaments. Parallel sections were stained with monoclonal antibodies to the two main cytokeratins found in bile duct and liver cells. Immunofluorescent antibody and immunogold electron microscopy techniques were used to identify the proteins morphologically. Several new observations resulted from these studies. The pericanalicular sheath of intermediate filaments was visualized using steropairs as an uninterrupted branching tubular structure composed of cytokeratins located in the cell cortex of adjacent hepatocytes. Intermediate filaments in the cell cortex formed a distinct sheet of matted filaments which enveloped the entire hepatocyte. The cortical intermediate filaments were in continuity with the pericanalicular sheath and the filaments located within the cytoplasm. The intermediate filaments are attached to the centrioles and appeared to tent the nuclear lamina-pore complex at points of contact. Monoclonal antibodies to rat liver intermediate filament cytokeratins (CK49 and CK55) each stained intermediate filaments located in the cell cortex, within the cytoplasm and at the nucleus. By immunogold staining, some of the intermediate filament filaments were shown to contain both cytokeratins. Filaments which did not stain were thought to be either actin at the cell periphery or nuclear lamins around the nucleus. It is concluded that the cytokeratins form a specialized framework for the cell cortex, canaliculus, centrioles and the nucleus of hepatocytes. The filaments run continuously throughout the cytoplasm without terminating.

Animals↗
PubMedDate not supplied

Endoscopic injection sclerotherapy for esophageal varices in the elderly.

A group of 1127 patients who underwent sclerotherapy for esophageal varices were compared for outcome in terms of age: over and under age 70 years. Esophageal varices were completely eradicated in 81 of 110 patients > 70 years (73.6%) and in 791 of 1017 patients < 70 years (77.8%). Gastrointestinal bleeding after sclerotherapy occurred in 9 patients > 70 years (8.2%) and in 84 of those < 70 years (8.3%). Complications occurred in 16 patients > 70 years (14.5%) and in 141 < 70 years (13.9%). Liver failure and hepatoma accounted for more than 80% of the causes of death in both groups (80.3% versus 83.8%). The 5-year cumulative survival rates in patients with bleeding esophageal varices (bleeders) without hepatoma were 21.8% in those > 70 years and 58.7% in those < 70 years (p < 0.01), the relative survivals being 25.3% versus 66.6%. Patients without hepatoma and treated by prophylactic sclerotherapy accounted for 66.2% of patients > 70 years and 61.7% of those < 70 years, the relative survivals being 75.9% versus 71.9%. As analyzed by the Cox proportional-hazards model, age > 70 years was a prognostic factor in the bleeders (p < 0.01) but not in the nonbleeders. We recommend that elderly patients with esophageal varices be given prophylactic sclerotherapy, as the outcome for these patients is poor once bleeding has occurred.

Aged↗
PubMedDate not supplied

Laparoscopic oversewing of a bleeding Mallory-Weiss tear under endoscopic guidance.

Continuous bleeding from a Mallory-Weiss tear required laparoscopic surgery to halt the bleeding. The oversewing of the laceration at the esophagogastric junction was readily performed under video control with endoscopic guidance and the bleeding ceased. To stop bleeding from such a tear, we prefer to use this modern approach.

Hemostasis, Endoscopic↗
PubMedDate not supplied

Serum lipids, lipoprotein lipids and coronary heart disease in patients with xanthelasma palpebrarum.

Serum lipids and lipoprotein lipids were studied in 53 patients (21 males and 32 females) with xanthelasma palpebrarum and 40 age-matched normal controls (20 males and 20 females). Patients were subdivided into patients with normolipidemia, hyperlipidemia or familial hypercholesterolemia (FH). In both male and female patients with hyperlipidemia or FH, the serum cholesterol (Chol) levels were significantly higher than in normal controls. In both male and female patients with normolipidemia or hyperlipidemia, the VLDL-Chol levels were significantly higher than in normal controls. Male patients with FH showed significantly higher levels of VLDL-Chol than normal controls. Both male and female patients with normolipidemia, hyperlipidemia or FH showed significantly higher levels of LDL-Chol, lower HDL-Chol levels and lower HDL-Chol/LDL-Chol ratios than normal controls. In both male and female patients with hyperlipidemia and in male patients with FH, the serum triglyceride (TG) levels were significantly higher than in normal controls. Both male and female hyperlipidemic patients showed significantly higher levels of VLDL-TG than normal controls. In male patients with FH, the VLDL-TG levels were significantly above the control levels. In male patients with normolipidermia, the LDL-TG levels were significantly higher than in normal controls. In both male and female patients with hyperlipidemia or FH, the LDL-TG levels were significantly higher than in normal controls. The HDL-TG levels in patients with normolipidemia (males) or FH (females) were significantly lower than in normal controls. The prevalence of coronary heart disease in patients with normolipidemia, hyperlipidemia or FH was 29.4%, 24.0% and 45.4%, respectively.

Adult↗
PubMedDate not supplied

The effect of idebenone on the lateral mobility of proteins in hepatocyte plasma membrane of old rats as revealed by fluorescence recovery after photobleaching (FRAP) technique using an endogenous label.

The average lateral diffusion constant of proteins (D) in the cell membrane of hepatocytes has been measured in liver smears by fluorescence recovery after photobleaching (FRAP) based on the so-called peroxide-induced autofluorescence (PIAF) deriving from the oxidation of riboflavin bound to membrane proteins. It has been shown before that D displays a significant negative linear age-correlation. The in vivo effect of idebenone was tested on this parameter. Old (23.7 months at killing) male Fischer 344 rats received 50 mg of the drug per kg body weight per os through gastric tube, suspended in 5% gum arabic solution (Verum I group) or the same dose and form of idebenone completed by 80 mg centrophenoxine per kg body weight (Verum II group) for 35 days. D was measured on a double blind basis in hepatocyte plasma membrane of the Verum or Placebo (5% gum arabic, only) groups. A significant increase of D (29.6%) was induced by idebenone in the Verum I group; nevertheless, even the Placebo group displayed a moderate, but statistically significant increase of D (10.7%). The Verum II group showed a total of 39.6% increase in the value of D. The loss of body weight being characteristic for these animals at the age of around 2 years was between 0.87 and 1.06 g/day, whereas in other experiments higher values (1.77 g/day) were observed in the controls.

Journal Article↗
PubMedDate not supplied

Effect of leupeptin on the lateral mobility of proteins in the plasma membrane of hepatocytes of C57BL/6 mice: FRAP studies on liver smears.

Four groups of male C57BL/6 mice (ages 2, 3.8, 11.8-12.5 and 24 months) were administered leupeptin at 5 mg/100 g body weight/day via intraperitoneally implanted osmotic minipumps. Both untreated and saline-treated mice served as controls. The time and dose-dependence of the effects of leupeptin on the lateral mobility of proteins in hepatocyte surface membranes were analyzed first in mice treated for 2, 5, 8, 11 and 14 days, respectively, by using the fluorescence recovery after photobleaching (FRAP) technique. The age dependence of the response to this treatment was also studied after 14 days of treatment in mice of various ages. The average lateral diffusion constant (D) and the fractional recovery (FR) were measured, and D x FR calculated. Leupeptin treatment at a daily dose of 5 mg/100g for 2 weeks increased plasma glutamic-pyruvlc transaminase levels 2-fold in all age groups. Leupeptin treatment caused a linear increase of D and a decrease of FR with respect to the duration of the treatment in adult mice. In all age groups about 30% of the membrane proteins became immobile after 14 days of treatment, whereas the still mobile fraction displayed a large increase of D. The values of D x FR in the leupeptin-treated groups were slightly higher than those in the untreated mice until the age of 15 months but decreased after this age. The results are interpreted in terms of the known inhibitory effect of leupeptin on cytoplasmic and lysosomal thiol proteases, causing a general slowing down of the protein turnover and, specifically, of proteins in the hepatocyte membrane.

Journal Article↗
PubMedDate not supplied

Effect of long-term exercise under restricted-feeding on intestinal content of cholecystokinin and on the pancreas in aging rats.

The effects of exercise (5000 m/day running from 100 to 600 days of age) on the cholecystokinin (CCK) content in the proximal intestine, and the enzyme and insulin contents of the pancreas were examined in food-restricted rats. Food restriction decreased the body weight and the wet weights of the pancreas and proximal intestine but not the wet weight of the stomach. Food restriction also decreased the chymotrypsin content of the pancreas but not its amylase content. The contents of enzymes in the pancreas were not affected by exercise. The insulin content of the pancreas was lower in lean rats produced by food restriction and/or exercise than in controls. Exercise increased the wet weight of the proximal intestine and the CCK content of the intestine. The increase in the CCK content may be due to compensational change in the efficiency of digestion of luminal nutrients induced by exercise.

Journal Article↗
PubMedDate not supplied

Gene expressions of cholecystokinin (CCK) and CCK receptors, and its satiety effect in young and old male rats.

Cholecystokinin (CCK), one of the first discovered gastrointestinal hormones, which stimulates pancreatic enzyme secretion and induces gallbladder contraction, is one of the most abundant neurotransmitter peptides in the brain and is implicated in satiety via CCK-A receptors. We compared the suppressive effect of central administration of CCK on food intake in young and old rats. The suppressive effect on food intake was enhanced in old rats. To examine the mechanism of this enhanced suppression, we measured the mRNA levels of CCK, CCK-A and CCK-B receptors in the cerebral cortex and the hypothalamus of young and old male rats. The mRNA level of CCK-A receptors in the hypothalamus decreased with age, whereas the mRNA levels of CCK-B receptors in the hypothalamus and cerebral cortex did not. The mRNA level of CCK in the cerebral cortex decreased significantly in old rats, although the decrease in the hypothalamus was not significant. Therefore, the enhanced sensitivity to CCK of old rats could not be explained by changes in gene expressions of CCK and CCK receptors. Moreover, the effects of aging on the gene expressions of CCK-A and CCK-B receptors were different.

Journal Article↗
PubMedDate not supplied

Sex difference in gene expressions of cholecystokinin (CCK) and CCK receptor in young and old rats.

The gene expressions of cholecystokinin (CCK) in the proximal small intestinal mucosa and CCK-A receptor in the pancreas were examined in male and female young (4-8 months old) and old (26-29 months old) rats. Their concentrations of CCK in the intestine were also compared. In males, but not in females, the mRNA levels of CCK in the intestine and those of the CCK-A receptor in the pancreas were significantly lower in old than young rats. In females, but not in males, the tissue content of CCK in the proximal intestinal mucosa was significantly higher in old rats. The pancreatic wet weight and trypsin activity in the proximal lumen were similar in young and old rats of both sexes. Therefore, changes in the regulations of gene expressions of CCK and the CCK receptor with age differ in male and female rats.

Journal Article↗
PubMedDate not supplied

Monosynaptic facilitatory pathway from the hypothalamic ventromedial nucleus to the frontal cortex in the rat.

Stimulation of the ventromedial nucleus (VMH) evoked a short latency negative wave with two peaks (cN1 and cN2) followed by a small positive wave (cP) at the ipsilateral dorsal frontal cortex (area 10) in the rat. The maximum response was observed from the lateral edge of the frontal pole. From the depth profiles of recordings, cN1 changed polarity at a depth of about 4 mm and the cN1-cN2 changed into a large compound action potential at the medioventral part of the frontal pole at a depth of about 6 mm. Since the surface evoked potential and the compound action potential followed high frequency stimulation, these respective potentials are concluded to be due to antidromic and monosynaptic activation of the cortical neurons. This was verified by unit recording experiments. The cP was concluded to be produced by the initial rise of the monosynaptic EPSP.

Animals↗
PubMedDate not supplied

Inhibitory pathway from the frontal cortex to the hypothalamic ventromedial nucleus in the rat.

Stimulation of the dorsal frontal cortex (area 10, FCtx) evoked two negative waves with short latencies (N1 and N2) followed by a large, longlasting positive wave (P) in the ventromedial nucleus (VMH) as well as in the more dorsal structures in the hypothalamus and the ventral thalamus. Since the N1 followed high frequency stimulation, it was concluded to be due to antidromic activity. Double or triple pulse stimulation summated the P, and reduced the amplitude of the negative waves of the second and the third responses. VMH neuronal discharges were also decreased during the time course of the P. Therefore, the P was concluded to be composed of the IPSPs. VMH neuronal discharges were frequently superimposed on the N2, indicating the origin of this wave to be EPSPs. Strychnine reduced or blocked the inhibition of the VMH neurons caused by not only FCtx stimulation but also glycine application. The results indicate that the VMH receives both excitatory and inhibitory projections from the FCtx, and the inhibition may be transmitted by glycine.

Animals↗
PubMedDate not supplied

Effects of endoscopic injection sclerotherapy on portal hypertensive gastropathy: a prospective study.

The effect of endoscopic injection sclerotherapy (EIS) for esophageal varices on portal hypertensive gastropathy (PHG) was investigated in 137 patients who underwent EIS from July 1987 to March 1990. Two groups, PHG(+) (N = 35) and PHG(-) (N = 102) were distinguished by endoscopic findings obtained before EIS. PHG was classified into four grades by endoscopy scored as 0, 1, 2, or 3. The PHG score significantly worsened after EIS (p < 0.01), and PHG became worse 6 to 9 months after the eradication of varices followed by gradual improvement. Recurrent small veins, which required additional EIS, appeared more frequently in the PHG(+) group (p < 0.05). New gastric varices appeared or gastric varices enlarged after EIS more frequently in the PHG(+) group (7 patients, 20.0%) than in the PHG(-) group (12 patients, 11.8%), but this was not statistically significant. Thus, frequent endoscopy after EIS is needed with special attention directed to development of PHG and gastric varices, especially for patients with PHG prior to treatment.

Esophageal and Gastric Varices↗
PubMedDate not supplied

Endoscopic ligation of esophageal varices compared with injection sclerotherapy: a prospective randomized trial.

Fifty cirrhotic patients with esophageal varices underwent endoscopic treatment in a prospective randomized trial carried out to compare variceal ligation with injection sclerotherapy, with respect to safety, efficacy, and complications in the initial session. Twenty-five patients each were treated using endoscopic variceal ligation or endoscopic injection sclerotherapy in the initial session and then only endoscopic injection sclerotherapy for all following sessions. Ligations numbered 4.1 at the initial session. The total number of sessions of endoscopic injection sclerotherapy was 4.0 +/- 1.3 in the endoscopic injection sclerotherapy group compared with 3.6 +/- 1.4 in the endoscopic variceal ligation group. The total volume of the sclerosant used by the end of all the sessions was 23.9 +/- 10.3 ml in the endoscopic variceal ligation group and 39.0 +/- 11.5 ml in the endoscopic injection sclerotherapy group (p < 0.0001). In all patients, complete eradication of the varices was achieved, and at 7 to 15 months follow-up no evidence of recurrence was seen. Adverse effects such as pyrexia, chest pain, and pleural effusion after the initial session were significantly lower in the endoscopic variceal ligation group (p < 0.05), and total bilirubin, serum creatinine, lactate dehydrogenase, and urinary beta 2-microglobulin were significantly increased and PaO2 decreased after endoscopic injection sclerotherapy (p < 0.05). This study shows that endoscopic variceal ligation significantly decreased the adverse effects associated with endoscopic injection sclerotherapy in the initial session, and it is recommended as an alternative to sclerotherapy.

Aged↗
PubMedDate not supplied

Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration.

Aluminum Hydroxide↗