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Biomedical subjects

Y Karasawa

Publications and source records attributed to Y Karasawa.

At least 19 recordsLinked to original sources
PubMed1997

Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils.

TTC-909 (Clinprost), a chemically stable PGI2 analog, isocarbacyclin methyl ester (TEI-9090 or Clinprost) incorporated in lipid microspheres, when administered intravenously after brain ischemia, prevents ischemic neuronal damage possibly by modulating cerebral blood flow and platelet aggregation. However, the possibility exists that TEI-7165, which is the free acid form and a central metabolite of TEI-9090, has direct neurotrophic action in vivo, since TEI-7165 has been shown to block neuronal voltage-dependent Ca2+ channels in vitro, and a novel prostacyclin receptor showing high affinity with TEI-7165 has been detected in a variety of brain regions including the hippocampus. In the present study, we infused TEI-7165 for 7 days into the lateral ventricle of gerbils starting 2 h before or just after 3-min forebrain ischemia. TEI-7165 infusion prevented significantly the ischemia-induced shortening of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region, as well as synapses within the strata moleculare, radiatum and oriens of the region, were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. TEI-7165 infusion did not affect hippocampal blood flow or temperature. These findings, together with the previously depicted accumulation of centrally administered [3H]TEI-7165 around hippocampal neurons, suggest that TEI-7165 has a direct neuroprotective action in brain ischemia.

Animals↗
PubMed1997

Different sympathetic-parasympathetic interactions on sinus rate and atrioventricular conduction in dog hearts.

We investigated the sympathetic-parasympathetic interactions involved in SA nodal pacemaker activity and AV conductivity in the anesthetized dog heart. Stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAPS) and stimulation of the intracardiac parasympathetic nerves to the AV nodal region (AVPS) induced negative chronotropic and dromotropic responses, respectively. Cardiac sympathetic stimulation, aminophylline, 3-isobutyl-1-methylxanthine (IBMX, a relatively pure nonselective phosphodiesterase inhibitor) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-p iridine-5-carboxylate (Bay k 8644, a Ca2+ channel agonist) increased sinus rate and decreased AV conduction time. Sympathetic stimulation augmented the negative chronotropic response to SAPS but not the negative dromotropic response to AVPS, IBMX augmented both responses, Bay k 8644 augmented the chronotropic response and attenuated the dromotropic response, and aminophylline did not affect the chronotropic response to SAPS and inhibited the dromotropic response to AVPS. Additionally, when Bay k 8644 directly given via the AV node artery decreased AV conduction time, it attenuated the negative dromotropic response to AVPS and carbachol injected into the AV node artery. These results suggest that the differential sympathetic-parasympathetic interactions on sinus rate and AV conduction are at least partly induced by an interaction between changes in slow inward Ca2+ current or intracellular Ca2+ and the cardiac effects of acetylcholine in the heart in situ.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Ligation of caeca improves nitrogen utilisation and decreases urinary uric acid excretion in chickens fed on a low protein diet plus urea.

1. The effect of the ligation of the caeca on nitrogen utilisation and nitrogen excretion was examined in conventional chickens fed a diet containing 50 g protein/kg plus urea. 2. Ligation of the caeca significantly improved nitrogen balance and utilisation by up to more than 2 times as much as those of controls (P < 0.05). 3. The treatment significantly decreased uric acid excretion by 77 mg nitrogen/day (P < 0.01) and also total nitrogen excretion (P < 0.05): the former decrease almost explained the latter. 4. No effect of the ligation of caeca on urea and ammonia excretion was observed. 5. It is concluded that nitrogen metabolism in chickens is affected by possible changes in caecal fermentation by preventing entry into the caeca of substances from urine and digesta.

Ammonia↗
PubMed1996

Neuroprotective effect of 4'-(4-methylphenyl)-2,2':6',2-terpyridine trihydrochloride, a novel inducer of nerve growth factor.

We have identified 4'-(4-methylphenyl)-2,2':6',2-terpyridine: trihydrochloride (SS701), which belongs to a family of a small unique neuroprotective agents. SS701 accelerated the production of nerve growth factor (NGF) in cultured astroglial cells, dose- and time-dependently. In in vivo studies, SS701, when administered 30 min after induced cerebral ischemia, neuroprotective effects on delayed neuronal death in Mongolian gerbils were evident. The neuroprotective effects of SS701 against ischemia-induced delayed neuronal death are attributed to stimulation of the production of NGF.

2,2'-Dipyridyl↗
PubMed1996

Effects of superoxide dismutase and catalase on growth of retinal pigment epithelial cells in vitro following addition of linoleic acid or linoleic acid hydroperoxide.

The rod outer segments of the retina that are phagocytized by retinal pigment epithelial (RPE) cells are susceptible to lipid peroxidation because of their high content of polyunsaturated fatty acids. Linoleic hydroperoxides (LHP), synthesized by peroxidation of linoleic acids (LA), produce greater damage to retinal function than does LA. We compared the effects of LHP and LA on the growth of cultured chick embryonic RPE cells and analyzed a model of data sets using multiple linear regression for the number of cells as a function of time. The spectrum of LA had a sharp peak at 205 nm and a broad spectrum at 235 nm, while LHP had only a broad spectrum at 235 nm. Exposure to LA and LHP caused dose-dependent damage of chick embryonic RPE cells: they were significantly more affected by the addition of LHP than LA. The antioxidative enzymes catalase and superoxide dismutase minimized damage to the RPE cells caused by LHP in proportion to the enzyme concentration. However, RPE cells incubated with LA were more affected by the enzymes than when no enzymes were added.

Animals↗
PubMed1996

[Natural process of wound healing of photocoagulated retinal pigment epithelium in culture--observation of DNA synthesis by BrDu incorporation].

We examined the proliferation of retinal pigment epithelial (RPE) cells after krypton laser photocoagulation in culture. A pigmented monolayer of chick embryonic RPE cells was cultured on a collagen membrane placed on collagen gel. RPE cells were labeled with bromodeoxyuridine (BrDu) every 12 hours until 7 1/2 days after the photocoagulation and stained immunocytochemically with anti BrDu antibody. Immediately after the photocoagulation, RPE cells became detached at the burned lesion and the collagen membrane beneath the RPE layer was exposed. Some cells adjacent to the burned lesion showed DNA synthesis and subsequent mitosis between 12 to 24 hours after the photocoagulation. Cells with labeled nuclei migrated into the denuded burned area after 24 hours and covered the whole burned area within three days after the photocoagulation. DNA synthesis continued in these on the burned lesion after complete coverage of the lesion but stopped temporarily 3 1/2 to 4 1/2 days after the photocoagulation. Thereafter DNA synthesis increased again and continued until the end of the experiment. Such use of the cultured RPE cells might be useful in studying cellular reaction after photocoagulation.

Animals↗
PubMed1995

In situ degradation and absorption of [15N]urea in chicken ceca.

[15N]Urea was introduced (in situ) into a ligated cecal pouch of chickens to determine if it is degraded therein and absorbed into the blood as ammonia during the following 60 min. A mean of 49% of the introduced urea-15N was recovered from the blood of the mesenteric vein draining the cecal pouch and 26% was recovered from the cecal lumen fluid. Of the urea-15N introduced into the pouch, 4%, 2%, 15% and 5% were detected as urea, ammonia and non-protein fractions, except urea and ammonia, and proteins in the lumen fluid, respectively. Non-protein-15N, except urea and ammonia, protein-15N, urea-15N and ammonia-15N values recovered in the cecal venous blood were 10%, 19%, 18% and 2% of the introduced 15N, respectively. Urea concentration in the cecal venous blood increased from 0.71 mg to 3.13 mg per 100 ml for the first 15 min after introduction of urea-15N (P < 0.01) then decreased until 60 min. No significant change was found in blood ammonia concentration, however, despite a small increase during the period 15-45 min after urea-15N introduction. Ammonia-15N increased in the caecal venous blood for the first 30 min then decreased to a plateau level of 43% of the peak level. The rates of increase of urea-15N and non-protein-15N concentrations attained maxima in the blood as early as 15 min, then decreased linearly (P < 0.05). It is concluded that, although urea is actively degraded to ammonia in the ceca, it is mostly absorbed from the ceca, not in the form of ammonia, but as protein, urea and amino acids.

Absorption↗
PubMed1995

Effect of colostomy on the occurrence of dietary [15N]urea in intestinal contents, blood, urine and tissues in chickens fed a low protein diet plus urea.

1. The occurrence of 15N was examined in excreta for 10 h, and in intestinal contents, blood and tissues at 10 h after [15N]urea was fed to conventional and colostomised cockerels. 2. Total-15N excretion and 15N-balance in control chickens were 18.88 and 44.79 mg/kg body weight/10 h), respectively. The former was increased and the latter was decreased by colostomy by 10.75 mg (P < 0.01). 3. Amounts of [15N]urea, [15N]ammonia and [15N]uric acid excreted by control birds were 13.78, 3.90 and 0.18 mg/kg body weight/10 h or 0.73, 0.21 and 0.01 of the total-15N excreted respectively. 4. The [15N]urea, [15N]uric acid and total-15N excreted were all increased after colostomy but [15N]ammonia was decreased (uric acid P < 0.05, others P < 0.01). The increase in total-15N was mostly accounted for by [15N]urea. 5. Colostomy resulted in significantly less total-15N in the contents of the whole intestine (P < 0.01), less total-15N, [15N]ammonia and [15N]urea in the contents of the colo-rectum (P < 0.01) and less total-15N and [15N]urea in the contents of the upper intestine (P < 0.05); it did not affect any in caecal contents. 6. [15N]Urea in blood, liver and kidney (blood P < 0.01, others P < 0.05), and [15N]glutamine amide (P < 0.05) and [15N]uric acid (P < 0.01) in blood were significantly decreased after colostomy. 7. The results support the hypothesis that most of the dietary urea is utilised as the result of a back-flow of ureteral urea into the caeca where it is rapidly converted into ammonia which is then metabolised to other compounds.

Animal Feed↗
PubMed1995

Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydro-beta-carboline derivatives.

A series of 1,2,3,4-tetrahydro-beta-carbolines has been synthesized and evaluated for cerebral protecting effects against lipid peroxidation and potassium cyanide intoxication in mice. Most of the compounds synthesized had potent effects against lipid peroxidation. Among them, 1-(3,5-dimethoxyphenyl)-2-propyl-1,2,3,4-tetrahydro-beta-carboline (22) was found to have a combination of potent effects against both lipid peroxidation and potassium cyanide intoxication. Structure-activity relationships are discussed.

Animals↗
PubMed1995

Effects of cecal ligation and colostomy on motility of the rectum, ileum, and cecum in turkeys.

Motilities of the rectum, ileum, and ceca were examined in surgically prepared turkeys by using strain gauge transducers implanted on these sites after cecal ligation or colostomy. All birds were provided ad libitum access to feed and water throughout the study. Cecal ligation increased the frequency of small anti-peristaltic contractions in the proximal (P < .01) and distal (P < .05) rectum and the frequency of defecations (P < .05) compared with intact controls. Cecal ligation decreased the frequency of single contractions in the proximal ileum (P < .05) and that of all contractions in the distal ileum (P < .05), and ligation (P < .01) and colostomy (P < .05) increased the frequency of single contractions in the distal site. However, major and minor cecal contractions were not affected by colostomy in the proximal and distal cecum. The results suggest that the effects on contractile activities of the hindgut must be considered when interpreting responses to cecal ligation and colostomy.

Animals↗
PubMed1995

Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis.

The CA1 pyramidal neurons in the hippocampus are selectively vulnerable to transient ischemic damage. In experimental animals, the CA1 pyramidal neurons undergo cell death several days after brief forebrain ischemia. It remains, however, unknown whether this delayed neuronal death is necrosis or apoptosis. To investigate the degenerating processes of the CA1 pyramidal neurons in gerbil hippocampus after brief ischemia, lysosomal and nuclear alterations in the cells were examined using immunocytochemistry, in situ nick-end labeling, and Southern blotting. By light and electron microscopy, immunoreactivity for cathepsins B, H, and L, representative lysosomal cysteine proteinases, increased in the CA1 pyramidal neurons 3 d after ischemic insult, which showed cell shrinkage. By morphometric analysis, the volume density of cathepsin B-positive lysosomes markedly increased 3 d after ischemic insult, while that of autophagic vacuole-like structures also increased at this stage, suggesting that cathepsin B-immunopositive lysosomes increasing in the neurons after ischemic insult are mostly autolysosomes. Nuclei of the CA1 neurons were nick-end labeled by biotinylated dUTP mediated by terminal deoxytransferase 3 and 4 d after ischemic insult, but not in the prior stages. Simultaneously, dense chromatin masses appeared in nuclei of the neurons. By Southern blotting, laddering of DNA occurred only in CA1 hippocampal tissues obtained 4 d after ischemic insult. Confocal laser scanning microscopy demonstrated that the fragmented DNA in the CA1 pyramidal layer was phagocytosed by microglial cells. The results suggest that delayed death of the CA1 pyramidal neurons after brief ischemia is not necrotic but apoptotic.

Animals↗
PubMed1995

[The effects of dopa and oxygen on RNA concentrations in cultured chick embryonal retinal pigment epithelial cells].

We measured RNA and DNA concentrations in cultured chick embryonal retinal pigment epithelial cells to investigate the effects of dopa and oxygen on DNA and RNA synthesis. RNA/DNA ratios were decreased by addition of 250 microM dopa. Decrease of RNA/DNA ratios was suppressed when the oxygen concentrations were reduced from 20% to 10%. Incubation with medium containing 100 microM dopa increased RNA/DNA ratios in 10% oxygen. Exposure of retinal pigment epithelial cells to 250 microM dopa caused the decrease of RNA concentrations in the retinal pigment epithelial cells, which was ameliorated by lowering oxygen concentrations. However, the addition of 100 microM dopa in 10% oxygen stimulated retinal pigment epithelial cells and seemed to increase RNA concentrations.

Animals↗
PubMed1995

[Multiple endocrine neoplasia type I].

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of primary hyperparathyroidism, pancreatic endocrine tumors, and neoplasms of the anterior pituitary gland. The disease is inherited as an autosomal dominant disorder with a high penetrance. Although many investigators have localized the causative genes to chromosome 11q3 by linkage analysis, the MEN1 gene remains unidentified. The use of molecular genetic markers in family linkage studies, however, have made it possible to identify gene carriers. Repetitive screening combined with the assignment of gene-carrier status will provide possibilities for therapeutic or prophylactic intervention earlier in the development of each of the manifestations of this syndrome, such as gastrointestinal bleeding secondary to ulcers or malignant transformation.

DNA↗
PubMed1994

The effect of FK506 on warm ischemia and reperfusion injury in the rat liver.

The protective effect of FK506 on hepatocytes against ischemia and reperfusion injury was examined by evaluating the following: the high energy phosphorus metabolism obtained using 31P magnetic resonance spectroscopy (31P-MRS) and the tissue blood flow of the liver in ischemia and the reperfusion process, mitochondrial glutamic oxaloacetic transaminase (m-GOT) and glutamic pyruvic transaminase (GPT), the survival rates of the animals, a histological study and immunohistological staining for intercellular adhesion molecule-1 (ICAM-1) in the liver after ischemia. The rats were treated with FK506 1 mg/kg/day i.m. for 4 days before testing. Ischemia was induced by clamping the hepatoduodenal ligament for 30 min. In 31P-MRS, the recovery of the hepatic energy status after ischemia, evaluated by beta-ATP/inorganic phosphate (Pi), was significantly better in the FK506 group. It also coincided with the recovery of tissue blood flow monitored with a laser Doppler flowmeter. In the histological examination, the congestion observed in the periportal region of the control group was mild, while there was less induction of ICAM-1 in the endothelial cells of the portal veins and hepatic veins in the FK506 group. From these findings, we concluded that FK506 had a protective effect on hepatocytes against warm ischemia and reperfusion injury, and the mechanism for this could partially be attributed to improved tissue blood flow after ischemia by the modulation of immunological events.

Alanine Transaminase↗
PubMed1994

Evaluation of tumor-associated antigen (2H6 antigen) in detecting early stages of gastric cancer.

A sandwich enzymed-linked immunosorbent assay (ELISA) was developed by using monoclonal antibody 2H6 (2H6 MoAb). MoAb 2H6 could be used to detect the 2H6 antigen in the sera of several cancers, showing positive rates of 65.4%, 66.7%, 47.4%, 80.0%, 45.2% and 16.7% in gastric cancer, hepatocellular carcinoma, cancers of the colon, esophagus, breast and pancreas, respectively. On the other hand, the positive rates in benign diseases or healthy donors were 3.4%, 3.4%, 4.2%, 8.3%, 6.9%, and 1.2% in myasthenia gravis, polymyositis, gastritis, gastric ulcer, other benign diseases and normal healthy donors, respectively. Fifty-two patients with gastric cancer were investigated in detail. The positive rates of serum 2H6 antigen, CEA, AFP, CA19-9 and CA125 in patients with gastric cancer were 65.4%, 9.6%, 2.3%, 25.0% and 8.1%, respectively. Among these tumor markers, serum 2H6 antigen levels alone were significantly elevated in patients with early stage (I and II) gastric cancer. Furthermore, combining the measurement for serum 2H6 with CA19-9 increased the percentage of gastric cancer slightly. No correlation between 2H6 antigen and these other tumor markers was observed. The serum levels of 2H6 antigen were monitored post-surgically in 11 patients for 12 weeks and they were found to diminish gradually. The findings suggest that the measurement of serum 2H6 antigen may be a useful marker for an early stage of gastric cancer.

Adolescent↗