Search PubMed⌕ Search

Biomedical subjects

S Kanai

Publications and source records attributed to S Kanai.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of pancreatic duct ligation and aging on acute taurocholate-induced pancreatitis. Experiments in the perfused pancreas in rats.

CONCLUSION: When taurocholate was injected into the common bile duct, high ductal pressure due to ligation of the pancreatic duct did not produce more damage in the pancreas of both old rats and young adult rats, and levels of pancreatic enzymes in portal venous effluent were lower in old rats than in younger rats. BACKGROUND: The effects of ligation of the pancreatic duct and aging on acute pancreatitis caused by taurocholate are still unclear. METHODS: Young adult and old male Wistar rats were used. Six hours after ligation of the common bile duct in both the duodenum and liver hilus, rats were killed and the pancreata were perfused. Taurocholate or normal saline was injected retrogradely into the common bile duct. The levels of amylase and lipase in the portal venous effluent were determined as markers of damage to the pancreas. The pancreas was also histologically examined after the perfusion experiments using an Image Analysis System. RESULTS: (1) A nonsignificant elevation of pancreatic enzymes was found in portal venous effluent by the retrograde injection of saline into the common bile duct. Injection of taurocholate caused a marked elevation of enzymes in the effluent for the first 30 min after injection, which then gradually decreased. (2) Basal levels of pancreatic enzymes were significantly higher in the ligation group than in the nonligation group. Injection of saline into the common bile duct had no apparent effect on enzymes in the effluent. In contrast, taurocholate injection into the common bile duct produced a marked increase in enzymes in the portal venous effluent. However, no significant difference was found between the ligation group and the nonligation group. (3) Similar findings were obtained when old rats were used. (4) Although basal levels of enzymes were almost the same in nonligated old and young adults rats, taurocholate injection into the pancreatic duct in old rats resulted in a significant depression of enzymes compared to that in young adult rats. In the ligation group, pancreatic enzymes in the portal venous effluent following taurocholate injection tended to be lower in old rats than in young adult rats. The results were histologically supported in that various degrees of fibrosis were found in the pancreata of old rats.

Acute Disease↗
PubMed1996

Long term treatment with (-)deprenyl reduces the optimal dose as well as the effective dose range for increasing antioxidant enzyme activities in old mouse brain.

C57BL mice of the male sex received different doses of (-)deprenyl (0.25, 0.5, 1.0 mg/kg per injection 3 times a week, s.c.) for 3 months beginning at the age of 26 months. At the age of 29 months, animals were sacrificed and superoxide dismutase (SOD) and catalase (CAT) activities were examined in several brain regions. The dose of 0.5 mg/kg (3 times a week) was most effective in increasing SOD and CAT activities in S. nigra, striatum and cerebral cortex but not in hippocampus or cerebellum. The dose of 0.25 mg/kg was also effective in increasing enzyme activities, but the effect was much lower than the dose of 0.5 mg/kg. The magnitudes of increase in enzyme activities with the dose of 0.5 mg/kg, however, were generally much lower than respective values we previously found in animals treated with (-)deprenyl for only 3 weeks. The highest dose of 1.0 mg/kg had negligible effect. Enzyme activities in all groups of animals that were examined 2 weeks after the last (-)deprenyl dose were practically the same as respective control values. Together with the results from our previous study with short term (-)deprenyl treatment in old mice, these results replicate our previous findings in old female rats. We showed that longer term treatment with (-)deprenyl reduces the optimal dose for increasing antioxidant enzyme activities by a factor of 5 to 10. The present study further indicates that longer term treatment with (-)deprenyl also reduces the effective dose range of (-)deprenyl as well as the magnitude of increase of enzyme activities. If the effect of (-)deprenyl for increasing these antioxidant enzyme activities in selective brain regions is causally related to its effect of increasing average life expectancies of animals, the selection of a proper dose of the drug may be a critical factor for life span studies in which the drug, is administered for more than one year.

Aging↗
PubMed1996

Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor.

Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.

Animals↗
PubMed1996

Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a study in a new rat model without gene expression of the CCK-A receptor.

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of non-insulin-dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas. The CCK-A receptor is known to be involved in regulating pancreatic exocrine function and growth. We examined the growth of the pancreas in terms of wet weight, enzyme compositions, and protein and DNA contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats but was significantly lower in OLETF rats than in LETO rats. The total DNA contents in the whole pancreas (cell numbers) were comparable for both strains and increased significantly with age. However, the ratio of protein content to DNA content (the cell size) significantly increased with age in LETO rats, with no increase in OLETF rats. The changes in chymotrypsin, amylase, and insulin with respect to age were in the same direction in both strains: a decrease or no change in total and/or cellular contents of chymotrypsin and insulin and increases in amylase. These results suggest that the CCK-A receptor plays some role in the increase in cell size associated with normal growth of the pancreas from 5 to 25 weeks of age (after weaning).

Aging↗
PubMed1996

Age-related changes in alpha-adrenoceptor-mediated blood pressure in the rat: relationship between the potency for phenylephrine and the maximum number of binding sites.

To study the effects of aging on the blood pressure potency of phenylephrine, 6-, 10- and 40-week-old rats were used. In anesthetized rats, the potency (pD2 value) of phenylephrine on the blood pressure tended to increase with age from 6 to 10 weeks, but significantly decreased thereafter with age from 10 to 40 weeks. Similarly, in pithed rats, the potency of phenylephrine significantly increased, but decreased thereafter. In isolated rat thoracic aorta, the pD2 value of phenylephrine from the contractile responses significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. The change in the potency of phenylephrine on the blood pressure was proportional to the pD2 value of phenylephrine estimated in aortic preparations. The specific binding of [3H]prazosin to single smooth muscle cells of thoracic aorta from different aged rats was saturable. The maximum number of binding sites (Bmax) significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. However, the dissociation constant of [3H]prazosin (Kd) did not alter with age. The changes in the potencies (pD2 values) of phenylephrine on the pressure responses and on the contractile responses were proportional to the logarithm of the maximum number of binding sites. The present study suggests that age-related changes in blood pressure are due to changes in the maximum number of binding sites (receptor density) of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1996

[Age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated responses].

We studied age-related alteration of inhibitory effects of a Ca2+ channel antagonist, isradipine, on alpha 1-adrenoceptor mediated responses in 6-, 10-, and 40-week-old rats. Age-related changes were observed in the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions in the isolated thoracic aorta, the amplitude of the Ca(2+)-evoked increase of intracellular Ca2+ concentration and sustained contraction in fura-2-loaded preparations and the maximum number of binding sites (Bmax) of [3H] (+)-isradipine to aortic membranes. The dissociation constant (KD) of [3H] (+)-isradipine did not alter with age. In anesthetized rats, isradipine inhibited the dose-response curves of norepinephrine on the blood pressure in 6- and 40-week-old animals more effectively than those in 10-week-old animals. An inverse relationship between the potency of norepinephrine in the isolated thoracic aorta, the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions and the logarithm of Bmax obtained in the [3H] (+)-isradipine binding experiment were found. These results suggest that the age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated contractile responses and the increase of blood pressure are due to changes in the alpha 1-adrenoceptor density and the population of voltage-dependent L-type Ca2+ channels, rather than changes in the affinity of drug to the alpha 1-adrenoceptor or Ca(2+)-sensitivity of contractile elements of aortic smooth muscle.

Aging↗
PubMed1995

Somatostatin inhibits pancreatic exocrine secretion centrally via sympathetic nerves in conscious rats.

Somatostatin is known to be a potent inhibitor of pancreatic exocrine secretion, but the mechanism of its effect is not fully understood. The mechanism of the inhibition by centrally administered somatostatin was examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately, and with a duodenal cannula, an extrajugular vein cannula and a cerebroventricular cannula. Somatostatin was injected into the left lateral ventricle, and the inhibitory mechanism was examined using vagotomized rats and various drugs that affect sympathetic neurons. Intracerebroventricular administration of somatostatin significantly inhibited pancreatic exocrine secretion stimulated by bile-pancreatic juice diversion. The inhibitory effect was not abolished by vagotomy, pretreatment with propranolol, but was abolished by pretreatment with hexamethonium or phentolamine. The plasma level of somatostatin after its intracerebroventricular administration increased 3-fold, but its intravenous infusion at a rate giving a similar plasma somatostatin level to that produced by its intracerebroventricular injection, had no significant effect on pancreatic secretion. These results suggest that somatostatin inhibits pancreatic exocrine secretion centrally via sympathetic efferent nerves and that alpha-adrenergic receptors have an important role in its inhibitory action.

Animals↗
PubMed1995

Partial sequence of ribulose-1,5-bisphosphate carboxylase/oxygenase and the phylogeny of Prochloron and Prochlorococcus (Prochlorales).

The prochlorophytes, oxygenic photosynthetic prokaryotes having no phycobiliprotein but possessing chlorophylls a and b, have been proposed to have a common ancestry with green chloroplasts, yet this is still controversal. We report here that partial sequence comparisons of the large subunit of ribulose-1,5'-bisphosphate carboxylase/oxygenase, including sequence data from two prochlorophytes, Prochlorococcus and Prochloron, indicate that Prochlorococcus is more closely related to a photosynthetic bacterium, Chromatium vinosum (gamma-purple bacteria), than to cyanobacteria, while Prochloron is closely related to the prochlorophyte Prochlorothrix and to cyanobacteria. The molecular phylogenetic tree indicates that a common ancestor of Prochlorococcus and gamma-purple bacteria branched off from the land plant lineage earlier than Prochloron, Prochlorothrix, and cyanobacteria.

Amino Acid Sequence↗
PubMed1995

Biochemical characterization of a Ca(2+)-dependent lectin from the hemolymph of a photosymbiotic marine bivalve, Tridacna derasa (Röding).

A Ca(2+)-dependent lectin was purified from the hemolymph of a photosymbiotic bivalve, Tridacna derasa. An electrophoretically homogeneous form was obtained by using affinity chromatography with Sepharose 4B. More than 80% of the hemolymph protein was accounted for by this lectin. The apparent molecular mass of the lectin, in its native form exhibiting hemagglutinating activity, was estimated by gel filtration analysis to be approximately 480 kDa. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in the absence of reductants, it migrated as a single band corresponding to a very large size, while in the presence of 2-mercaptoethanol, it migrated as two distinct bands of 23 and 46 kDa. These results indicate that the subunits were linked by disulfide bridges to form the native protein. After reducing pyridylethylation, each of the 23- and 46-kDa polypeptides was isolated by gel filtration in a mobile phase containing guanidine-HCl. The two polypeptides had the same amino-terminal sequence and a similar amino-acid composition, and in the presence of 2-mercaptoethanol gave a single band on isoelectric focusing at a pH of 6.0. The results suggested that the 46-kDa peptide is a homodimer of 23-kDa subunits held together by a covalent bond other than a disulfide linkage. This lectin required calcium ions for its activity. By ultraviolet spectrophotometry the association constant for the calcium ion was determined to be 0.88 mM. The hemagglutinating activity decreased dramatically below pH 6.5, but re-increased to the original level when the solution was neutralized. Such a pH-dependent alteration of the ligand-binding activity was similar to that found in vertebrate asialoglycoprotein receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Decline in glucose metabolism in the brain in neuronal ceroid lipofuscinosis (NCL) in English setter--evidence by positron emission tomography (PET).

Positron emission tomography scans were performed on brains of homozygous and heterozygous English setters with neuronal ceroid-lipofuscinosis (NCL) from 13 months of age to 24-25 months of age for homozygous dogs and to 38 months for heterozygous dogs, respectively. After iv injection of 18F-fluorodeoxyglucose (FDG), 7 coronal brain scans as well as sequential arterial blood samplings were performed for 45 min under pentobarbital anesthesia. From these data, three different functional images (DAR (standardized uptake value), FDG uptake (fractional uptake) and glucose uptake) were reconstructed and quantitatively analysed. In the age range from 13 to 15 months, glucose images were comparable for both homozygous and heterozygous dogs, so that no differentiation was possible between healthy and diseased dogs on the basis of PET findings. Between 18 and 24 months of age, a drastic decline in glucose metabolism was observed in homozygous dogs, while the decline in glucose utilization was very mild in this period for heterozygous dogs. Furthermore, in PET scans, cerebral atrophy and ventricular enlargement were clearly shown in homozygous dogs. Consequently at the age from 20 to 24 months, a clear differential diagnosis between healthy (heterozygous) and diseased (homozygous) dogs became possible even if the clinical symptoms were still not clear in the latter. We conclude that the biochemical alterations in the brain in canine NCL occurs and progresses very rapidly in the last quarter of their lives.

Aging↗
PubMed1994

Lack of satiety effect of cholecystokinin (CCK) in a new rat model not expressing the CCK-A receptor gene.

This work expands recent observations that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no pancreatic expression of the cholecystokinin (CCK)-A receptor gene. We examined whether the CCK-A and -B receptor genes were expressed in the brain (hypothalamus) of OLETF rats in comparison with control (Long-Evans Tokushima Otsuka = LETO) rats. CCK-A receptor mRNA was detected in the hypothalamus of LETO rats but not OLETF rats. The CCK-B receptor gene was expressed in the hypothalamus in both strains. Cerebroventricular administration of CCK-8 sulfate inhibited daily food intake in LETO rats, but not in OLETF rats. These results show that in OLETF rats the absence of CCK-A receptor gene expression in the hypothalamus results in hyperphagia because of lack of satiety.

Animals↗
PubMed1994

(-)Deprenyl increases the life span as well as activities of superoxide dismutase and catalase but not of glutathione peroxidase in selective brain regions in Fischer rats.

(-)Deprenyl, a MAO-B inhibitor that is also known to be effective for symptoms of Parkinson's disease, when injected subcutaneously (sc) in male Fischer-344 rats at a dose of 0.5 mg/kg per day (3 times a week) from 18 months of age, significantly increased the remaining life expectancy. The average life span after 24 months was 34% greater in treated rats than in saline-treated control animals. Furthermore, a short-term (3 wk) continuous sc infusion of deprenyl significantly increased activities of superoxide dismutase and catalase but not of glutathione peroxidase in selective brain regions such as s. nigra, striatum, and cerebral cortex, but not in hippocampus or cerebellum, or the liver. The optimal dose for increasing these activities, however, differed greatly depending on the sex and age of animals, with a 10-fold lower value for young female than male rats. Interestingly, aging caused an increase and a decrease in the optimal dose in female and male rats, respectively. In addition, treatment for a longer term tended to reduce the optimal dosage in the same animal group. The results clearly demonstrate that deprenyl increases antioxidant enzyme activities in selective brain regions. If this effect of deprenyl is causally related to its life-prolonging effect, the dosage to be used for any life span study would be a critical factor, with the dosage differing widely depending on sex, age of animal, and mode and duration of drug administration.

Animals↗
PubMed1994

The effect of a long term (6 months) treatment with (-)deprenyl on antioxidant enzyme activities in selective brain regions in old female Fischer 344 rats.

The effect of long term treatment with (-)deprenyl (s.c. injection three times a week for 6 months) on superoxide dismutase (SOD) and catalase (CAT) in selective brain regions was examined in old (22 months) female Fischer 344 rats. The three doses of deprenyl used (0.1, 0.25 and 0.5 mg/kg/day) increased the activities of both enzymes in substantia nigra, striatum and cerebral cortices essentially in a dose dependent manner. However, for CAT activities in cerebral cortices, the smallest dose of 0.1 mg/kg/day was most effective, while the highest dose (0.5 mg/kg/day) had no effect. In contrast to these brain regions, there were no significant differences in enzyme activities between control and deprenyl-treated groups in the hippocampus and cerebellum. If the effect of deprenyl on the life span of female F-344 rats is causally related to its effect on antioxidant enzyme activities in selective brain regions as shown in this study, then a dose of 0.25 or 0.5 mg/kg/day appears to be most appropriate. Since this dose is much lower than the dose suggested by our previous short term (3 week) experiments, an even longer term experiment is necessary to determine the optimal dose of deprenyl to increase free radical scavenging and thus possibly extend lifespan.

Aging↗
PubMed1994

Tauro alpha-muricholate has a biliary transport maximum (Tm) value equivalent to that for tauroursodeoxycholate and tauro beta-muricholate in the rat.

Our previous studies have shown that Tm values for tauroursodeoxycholate (TUDC) and tauro beta-muricholate (T beta-MC) are more than two-fold higher than that for taurocholate (TC) in the rat. The present study attempted to clarify whether tauro alpha-muricholate (T alpha-MC) also has such an unusually large Tm value in the rat. Under nembutal anesthesia, male Wistar derived rats (body weight 280-300 g, 13 wks in age) were continuously infused with T alpha-MC solution. The infusion rate was raised stepwise every 20 min, until the bile flow began to decline. Bile was collected every 10 min and bile salt excretion rate was determined. The average of the highest three excretion values was assumed to be the Tm in each animal. The Tm value of T alpha-MC was found to be 2.86 +/- 0.36 mumol/min/100 g (mean +/- SD, n = 4), which was even greater than Tm values for TUDC (2.59 +/- 0.39 mumol/min/100 g, n = 4) and T beta-MC (1.93 +/- 0.31 mumol/min/100 g, n = 4) as we reported previously. The relationship between the bile flow rate (microliter/min/100 g, Y axis) and bile salt excretion rate (mumol/min/100 g, X axis) was highly linear [Y = (6.00 +/- 0.29) x +(6.60 +/- 1.88), P < 0.001, r = 0.95, n = 54]. The slope value for T alpha-MC (6.00 +/- 0.29 microliters/mumol) was significantly higher than that for TUDC (4.76 +/- 0.71 microliters/mumol) and was comparable to that for T beta-MC as we previously found for these bile salts in this rat strain. The results suggest that T alpha-MC has a very efficient transport system in this species as was observed for the other two bile salts that have a 7 beta-hydroxy group (TUDC and T beta-MC). This efficient transport system thus appears to be shared not only by bile salts specifically having a 7 beta-hydroxy group, but also by other bile salts such as T alpha-MC that have a 6 beta-hydroxy group but not a 7 beta-hydroxy group.

Animals↗
PubMed1994

(-)deprenyl increases activities of superoxide dismutase and catalase in certain brain regions in old male mice.

A subcutaneous continuous infusion of (-)deprenyl for 3 weeks in old C57BL male mice increased superoxide dismutase (SOD) and catalase (CAT) activities in s. nigra, striatum and cerebral cortex but not in hippocampus, cerebellum or liver. The doses of 0.5 and 1.0 mg/kg/day were most effective, while with a higher dose (2.0 mg/kg/day), deprenyl tended to lose its effect slightly and with a lower dose (0.25 mg/kg/day) deprenyl was clearly less effective. The results suggest that deprenyl can increase antioxidant enzyme activities in certain brain regions in mice as was previously demonstrated in rats of both sexes and different ages; this raises the possibility that deprenyl has this particular effect in animal species other than rats.

Aging↗