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Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 181 records · Page 10Linked to original sources

The effects of Hange-shashin-to on the content of prostaglandin E2 and water absorption in the large intestine of rats.

The effects of Hange-shashin-to (TJ-14) were examined regarding the amount of prostaglandin E2 (PGE2) and the water absorbing capacity in the large intestine of rats. Repeated oral administration of TJ-14 at doses of 125 to 1000 mg/kg revealed a significant decrease in PGE2 content in the colonic mucosa and also the promotion of colonic water absorption in a dose dependent manner. However, there was no remarkable influence on the concentrations of aldosterone and electrolytes in the serum, even at 1000 mg/kg. From these results, it was considered that some of the anti-diarrheal effects of TJ-14 might be based on a repression of the increase in the amount of PGE2 as well as promotion of the water absorbing capacity of the large intestine. Moreover, it was also suggested that it is possible, by the application of TJ-14, to prevent the loss of water content caused by diarrhea.

Aldosterone↗

Preventive effects of Hange-shashin-to on irinotecan hydrochloride-caused diarrhea and its relevance to the colonic prostaglandin E2 and water absorption in the rat.

The possible preventive effect of Kampo medicine Hange-shashin-to (TJ-14) on chronic diarrheal symptoms induced by the administration of the anticancer agent irinotecan hydrochloride (CPT-11) was investigated in the rat. Repeated oral administrations of TJ-14 at 125 and 500 mg/kg significantly prevented the reduction in body weight and the onset of chronic diarrheal symptoms due to CPT-11 in a dose-dependent manner, even though it failed to show a definite effect on acute diarrheal symptoms. In addition, treatment with TJ-14 accelerated the healing of the intestinal tract injured by repeated dosing of CPT-11 and inhibited significantly the increase of colonic prostaglandin E2 (PGE2) which is closely related to the onset of diarrhea. TJ-14 also improved colonic water absorption impaired by repeated dosing of CPT-11 in rats. These results demonstrate that TJ-14 is an effective medicine for the prevention and/or treatment of CPT-11-induced chronic diarrheal symptoms.

Animals↗

Effects of choreito consumption on urine variables of healthy cats fed a magnesium-supplemented commercial diet.

OBJECTIVE: To investigate the effect of choreito consumption (500 mg/kg of body weight/d) on struvite crystal formation and signs of lower urinary tract disease (LUTD) in cats consuming a commercial canned diet with 0.5% added inorganic magnesium. SAMPLE POPULATION: 6 male and 6 female adult cats, all considered to be clinically normal on the basis of physical examination findings; results of CBC, serum biochemical analyses, urinalyses, and urine cultures; and freedom from urolithiasis on the basis of urethrocystoscopic (females) or urethrocystographic (males) findings. PROCEDURE: Diets were fed for 12 weeks, or until appearance of signs of LUTD, including dysuria, hematuria, urine pH > 7.0, and severe struvite crystalluria. Presence of at least 2 of these signs was required for removal from study. Urine specimens were examined for electrolytes, struvite crystal content, and hematuria. RESULTS: Results for urine variables were compared between groups at 4 weeks, because of reduction in cat numbers attributable to removal from study. Struvite crystal content of 24-hour urine specimens was significantly lower for cats fed the choreito-containing diet. Moreover, frequency and severity of hematuria were significantly decreased in cats fed the choreito-containing diet. Correlation between hematuria and struvite crystal content was not observed in either group. Additionally, all 6 cats fed the diet without choreito had been removed from study by day 58 because of signs of LUTD. Of the 6 cats fed the choreito-containing diet, 2 completed the 12-week study. CLINICAL RELEVANCE: Choreito may be beneficial for relief of some signs of struvite-associated LUTD disease in cats.

Analysis of Variance↗

Effects of choreito and takushya consumption on in vitro and in vivo struvite solubility in cat urine.

OBJECTIVE: To determine the effects of the takushya portion of choreito, a traditional Chinese treatment for urolithiasis, on urine and struvite crystal variables in cats fed diets containing takushya. SAMPLE POPULATION: 6 male and 6 female adult cats, all considered to be clinically normal on the basis of physical examination findings, results of CBC, serum biochemical analyses, urinalyses, and urine cultures; and freedom from urolithiasis on the basis of urethrocystoscopic (females) or urethrocystographic (males) findings. PROCEDURE: Cats were fed a commercial canned diet supplemented with 0.1-mg of takushya/kg of body weight, or with 0.5 mg of choreito/kg. Diets were fed, using a Latin-square design, to 3 groups of 4 cats (2 male, 2 female) each for 2 weeks, followed by blood and 24-hour urine sample collections. RESULTS: Consumption of takushya, which comprises 20% by weight of choreito, was not associated with adverse effects in cats at the amounts provided during the period of study. Moreover, takushya was responsible for most of the effect of choreito consumption on reduction of urine pH, and approximately half its ability to reduce struvite crystal formation in cat urine. CLINICAL RELEVANCE: Alternative treatments for struvite urolithiasis in cats may be feasible.

Analysis of Variance↗

[Acute subdural hemorrhage of arterial origin: report of three cases].

Three cases of acute subdural hematoma without head injury, but associated with bleeding from cortical artery are described. Case 1: a 74-year-old male had sudden headache during a bronchial asthma attack followed by deterioration of consciousness. He was deeply comatose on admission, and CT scans revealed a huge subdural hematoma. Evacuation of the large hematoma revealed a spurting cortical branch of the middle cerebral artery beneath it. Case 2: Four days before admission, a 69-year-old male developed headache during a fit of coughing. His CT scans on admission showed a thin subdural hematoma. Because it was increasing in volume, the hematoma was removed surgically. A spurting cortical branch of the middle cerebral artery was seen on the surface of the temporal lobe. Case 3: a 80-year-old male, who had had an operation for inguinal hernia under spinal anesthesia ten days before, suffered a sudden headache just after he stood up. CT scans revealed a thick subdural hematoma. As the clot was being removed a spurting artery was seen in the Sylvian region. In a review of 116 surgical cases of acute subdural hematoma at our institute, the incidence of acute spontaneous subdural hemorrhage was 2.6%. The etiology of nontraumatic hematoma is a matter of controversy. Our three cases suggested that the etiology might be the rupture of a cortical artery at the site of adhesion with the dura mater. This would predispose the artery to tearing with minor trauma. Hematoma evacuation by craniotomy and treatment of the ruptured cortical artery were necessary for favorable outcome.

Acute Disease↗

[Discharge program to facilitate home care of patients with respirator].

We have introduced a program to provide home care for the patient with an artificial respirator, and have used it for patients with amyotrophic lateral sclerosis (ALS). This program urges us to keep a good relationship with home care nurses, medical engineers and medical social workers, and also relieves the patient and patient's family from anxiety. It also tells us how to remove the patient's sputum, how to differentiate sterilized materials from non-sterilized, and so on. This program has been carried out successfully, resulting in the patient's early discharge from the hospital. The patient is now enjoying a comfortable life at home with the aid of an artificial respirator. We conclude that this program is useful for such a patient and his family through the smooth introduction of home care, will increase the quality of the patient's life, and will achieve an early discharge.

Aged↗

Further pharmacological study on Sho-seiryu-to as an antiallergic.

Examination was made of the pharmacological characteristics of Sho-seiryu-to, an antiallergic kampo medicine. Sho-seiryu-to suppressed histamine release from rat peritoneal mast cells, but failed to inhibit the binding of [3H]-mepyramine to histamine H1 receptors in guinea pig cerebral cortex and lung. Sho-seiryu-to had no effect on cutaneous reactions induced by serotonin, platelet-activating factor (PAF), leukotriene (LT) C4 or LTD4. Ketotifen prolonged electrically induced convulsions, while Sho-seiryu-to did not. Sho-seiryu-to did not affect salivation induced by pilocarpine. Sho-seiryu-to thus does not appear to inhibit histamine H1 receptors or inflammation induced by serotonin, PAF, LTC4 and LTD4, but suppresses mast cell activity. Sho-seiryu-to would thus have only a few side effects such as dry mouth and convulsions due mainly to the blockage of the action of muscarinic in salivary glands and histamine in the brain.

Animals↗

Preliminary studies for interaction of a cyclobutane thymine dimer region with its cognate antibody.

A monoclonal antibody (TDM-2) specific to a UV-induced cyclobutane pyrimidine dimer has previously been established. We investigated here the structural requirements of antigen recognition by the antibody using chemically synthesized antigen analogs. TDM-2 bound to the cis-syn, but not the trans-syn thymine dimer, and recognized not only the cyclobutane ring but also the 5'- or 3'-side phosphate groups flanking the cyclobutane dimer site. The antibody showed strong binding to photodimer-containing single stranded DNA but indicated little binding to double stranded DNA.

Antibodies, Monoclonal↗

GABAB receptors, monoamine receptors, and postsynaptic inositol trisphosphate-induced Ca2+ release are involved in the induction of long-term potentiation at visual cortical inhibitory synapses.

gamma-Aminobutyric acid (GABA)A receptor-mediated inhibitory synaptic transmission in visual cortex undergoes long-term potentiation (LTP), which is input-specific and associative. The present study, conducted under a blockade of ionotropic glutamate receptors, demonstrates an induction mechanism of LTP considerably different from those of associative LTP at excitatory synapses. Inhibitory responses of layer V cells evoked by layer IV stimulation were studied in developing rat visual cortex slices by using intracellular and whole-cell recording methods. LTP induction was prevented by the application of an antagonist for GABAB receptors but not for GABAA or metabotropic glutamate receptors. Inhibition of postsynaptic G-proteins, phospholipase C, inositol trisphosphate (IP3) receptors, or Ca2+ increase prevented the generation of LTP, as did the blockade of GABAB receptors. In rat cerebral cortex, GABAB receptor activation is not known to affect the IP3 level by itself. However, it facilitates IP3 formation induced by the activation of alpha 1 adrenoceptors, which are believed to be located postsynaptically. Accordingly, I examined the involvement of these and other amine receptors, including histamine H1, muscarinic acetylcholine, and serotonin 5-HT2 receptors, all of which are coupled to IP3 formation. Only the blockade of alpha 1 adrenoceptors or serotonin 5-HT2 receptors prevented LTP induction in most, but not all, of the cells. These results suggest that LTP induction requires the activation of postsynaptic GABAB receptors and that its effect is mediated at least partly by facilitation of the monoamine-induced IP3 formation, which then causes Ca2+ release from the internal stores in postsynaptic cells.

Animals↗

A highly expressed 81 kDa protein in immortalized mouse fibroblast: its proliferative function and identity with ezrin.

An 81 kDa protein was found to be highly expressed in spontaneously immortalized CD1-ICR mouse fibroblasts, RS-4, as compared to normal fibroblasts. RS-4 cells have a reduced serum requirement and exhibit multilayered growth in vitro but are not tumorigenic. The protein was purified from RS-4 cell extracts and used to obtain a polyclonal antibody that specifically immunoprecipitated an 81 kDa protein from cell lysates. Immunocloning of its cDNA and sequence analysis revealed its identity with ezrin, an F-actin binding protein that is a component of the cortical cytoskeleton. Microinjection of the purified IgG fraction of the anti-p81 antiserum into the cytoplasm of RS-4 cells blocked their entry into S phase suggesting that the protein has a proliferative function. Immunostaining of normal mouse tissues showed that the expression of p81/ezrin was highest in proliferating cell populations. Unlike RS-4, NIH3T3 cells exhibit contact inhibition and express levels of p81/ezrin similar to those of normal fibroblasts. When NIH3T3 cells were transfected with p81/ezrin cDNA they lost contact inhibition and thus resembled RS-4 cells. The study demonstrates a proliferative function of p81/ezrin and suggests its involvement in pathways that negatively regulate contact inhibition.

3T3 Cells↗

Enhanced folding of hairpin ribozymes with replaced domains.

Reversely joined ribozymes (Komatsu et al., 1995) have been proven to be active. Here we describe the construction of hairpin ribozymes with separated domains, but containing complementary arms for association of the two domains. Linker nucleotides were inserted between the arms and domains. These ribozymes were active under the standard conditions (12 mM MgCl2), depending on the length of the linker. When the complementary arms were covalently joined through a stable loop, these ribozymes showed cleavage activities. However, the K(m) value of the stem-loop ribozymes was found to be larger than that of the parent ribozyme, which can adopt both linear and bent conformations. Kinetic analyses of these modified hairpin ribozymes suggest a higher turnover of the hairpin ribozyme as compared to other small ribozymes. The present ribozymes provide insight into the nature of the domain interaction and are suitable for physicochemical studies on the tertiary structure of the hairpin ribozyme.

Base Sequence↗

Characterization of a barotolerant mutant of the yeast Saccharomyces cerevisiae: importance of trehalose content and membrane fluidity.

A barotolerant mutant of Saccharomyces cerevisiae and its parent were compared with respect to the barotolerance of each strain, intracellular content of trehalose, amounts of three major heat shock proteins (hsps), relative proportion of unsaturated and saturated fatty acids in membrane phospholipids, and membrane fluidity. Changes in the amount of trehalose, but not hsps, were associated with changes in the barotolerance of each strain during the different phases of growth and with the difference in barotolerance between the mutant and parent strain. The membrane fluidity in the case of the mutant was low, while that of the parent was high. These results suggest that accumulation of trehalose and the condition of the membrane are more important for barotolerance than accumulation of hsps.

Fatty Acids↗

C-type natriuretic peptide as an autocrine/paracrine regulator of osteoblast. Evidence for possible presence of bone natriuretic peptide system.

C-type natriuretic peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial natriuretic peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [3H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of "bone natriuretic peptide system."

3T3 Cells↗

Effect of heat stress on development in vitro and in vivo and on synthesis of heat shock proteins in porcine embryos.

The present study was conducted (1) to examine the effect of an acute increase in ambient temperature on the development of porcine day 6 embryos in culture and after transfer to recipient gilts, and (2) to analyze intracellular production of heat shock proteins (hsps). The viability of porcine day 6 embryos following a temporary acute elevation in ambient temperature (at 42 degrees-45.5 degrees C and for 10-180 min) was examined. Synthesis of 70 kDa hsp (hsp70) and 90 kDa hsp (hsp90) was determined by SDS-PAGE and Western blot analysis in porcine day 6 embryos subjected to heat stresses. Nonheat-stressed embryos were considered as control. Significantly higher numbers of viable nuclei were observed in treatment groups of 42 degrees C-10 min (236.6 +/- 71.4; P < 0.05) and 43 degrees C-30 min (276.8 +/- 89.4; P < 0.005) compared to control (173.9 +/- 53.9). The 42 degrees C-180 min group (158.0 +/- 27.1 microns) had a greater increase in diameter after 24 hr in culture following heat stress compared to control (82.5 +/- 47.3 microns), while heat stress with 43 degrees C for > or = 60 min, 44 degrees-44.5 degrees C for > or = 30 min, or 45 degrees-45.5 degrees C for > or = 10 min impaired their survival, as assessed by differences in number of viable nuclei. The embryos subjected to heat stresses under the conditions of 42 degrees C-180 min, 43 degrees C-10 min, 43 degrees C-30 min, 44 degrees C-10 min, or 45 degrees C-10 min developed to normal piglets after transfer to recipient gilts. Overall pregnancy rate was 75% (6/8), and farrowing rate 62.5% (5/8). Of heat-stressed embryos transferred, 59% (36/61) developed to normal piglets. Heat-stress conditions of 42 degrees C for 180 min, 43 degrees C for 30 min, 44 degrees C for 10 min, and 45 degrees C for 10 min were determined as critical with respect to the in vitro and in vivo survival of porcine embryos. Porcine day 6 embryos constitutively synthesized hsp70 even without heat stress, while hsp90 was detected only at trace level. Neither hsp70 nor hsp90 levels increased in the embryos subjected to heat stresses. In conclusion, porcine day 6 embryos could continue to develop in vivo or during in vitro culture after exposure to acute and temporary rise in temperature. However, no increase of hsp70 and hsp90 was observed in the heat-stressed porcine embryos, while hsp70 was detected in the nonheat-stressed porcine embryos. The precise mechanism of the thermotolerance was unclear.

Animals↗

Role of platelet-activating factor in pathogenesis of galactosamine-lipopolysaccharide-induced liver injury.

In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antagonist) on hepatic injury in vivo as well as on neutrophil adherence to hepatic endothelial cells in vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury. Although an enhanced serum TNF-alpha level after GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-alpha, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.

Animals↗

Role of macrophages in regeneration of liver.

In an attempt to clarify the role of macrophages and their mediators during regeneration of the liver, the difference of liver regeneration among C3H/HeN (LPS-responsive strain) and C3H/HeJ (LPS-resistant strain) mice was investigated. After a 67% partial hepatectomy, an increase in the weight of regenerating liver was significantly delayed in the C3H/HeJ mice, as compared with C3H/HeN mice. The number of hepatocytes labeled with antibody against PCNA reached maximum levels 48 hr after partial hepatectomy, but the PCNA labeling index in C3H/HeJ mice was 20% less than that for C3H/HeN mice. In addition, TNF-alpha activities in serum were enhanced shortly after partial hepatectomy in C3H/HeN strain mice, but were not increased in C3H/HeJ strain mice. Serum IL-6 levels were markedly enhanced in both C3H/HeN and C3H/HeJ mice, but a bimodial peak (14 and 48 hr after partial hepatectomy) was demonstrated in C3H/HeN mice, in contrast to a single peak (at 24 hr) in C3H/HeJ mice. Suppression of Kupffer cells by previous administration of gadolinium chloride in C3H/HeN mice reduced the increase in both serum TNF-alpha and IL-6 concentrations, reduced PCNA labeling index of hepatocytes by 20%, and disturbed the regeneration of the liver. Previous administration of antibody against TNF-alpha reduced the PCNA labeling index of hepatocytes by 20% after partial hepatectomy in C3H/HeN strain mice. These results suggest that LPS-responsive macrophages in the liver and their mediators, especially TNF-alpha, could partly play a role in liver regeneration.

Animals↗

Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease.

BACKGROUND & AIMS: We and others have previously shown that the mutation of K-ras codon 12 was found in the majority of pancreatic adenocarcinomas. The mutation has also been identified in the pancreatic duct with mucous cell hyperplasia in association with chronic pancreatitis. Ductal hyperplasia is also frequently found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The aim of this study was to assess the incidence and types of mutations in hyperplastic foci in these cases. METHODS: The nucleotide sequence of the K-ras gene at codon 12 of the DNA extracted from microdissected hyperplastic epithelium of the pancreatic duct obtained at autopsy in patients without pancreatic adenocarcinoma or chronic pancreatitis was analyzed. RESULTS: Of 38 patients with 79 hyperplastic foci, 12 patients (with 19 hyperplastic foci) had mutations. None of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which were not found in 30 cases of adenocarcinoma. CONCLUSIONS: These results suggest that the ras gene mutation occurs frequently in multifocal hyperplastic foci of pancreatic duct and that the mutations may not have direct relevance to the carcinogenesis of pancreatic cancer.

Adult↗

Cytokine-induced neutrophil chemoattractant release from hepatocytes is modulated by Kupffer cells.

To clarify the role of intercellular communication in the liver during accumulation of neutrophils, the release of cytokine-induced neutrophil chemoattractant (CINC) (interleukin-8 [IL-8] related protein in rodents) by hepatocytes was investigated in the presence of Kupffer cell-conditioned medium in vitro. Kupffer cells were prepared by perfusion of rat liver with collagenase followed by centrifugation on a metrizamide gradient and were cultured in the presence or absence of lipopolysacharide (LPS). The conditioned medium was collected after 24 hours, and rat hepatocytes were cultured in the presence or absence of Kupffer cell-conditioned medium. An amount of CINC in the culture supernatant was measured by western blotting analysis and enzyme-linked immunosorbent assay (ELISA), and expression of its messenger RNA (mRNA) was assessed by the polymerase chain reaction. LPS-stimulated Kupffer cell-conditioned medium enhanced an expression of CINC mRNA in hepatocytes and increased the production of CINC by hepatocytes. Enhanced production of CINC was not shown when the Kupffer cell-conditioned medium was pretreated with heat (56 degrees C, 30 minutes). The production of CINC by hepatocytes in the presence of the LPS-stimulated Kupffer cell-conditioned medium was reduced by an antibody against interleukin 1 beta (IL-1 beta), but not by antibodies against tumor necrosis factor alpha (TNF-alpha) or LPS. These results suggest that production of CINC by hepatocytes could be regulated by IL-1 beta released from Kupffer cells, leading to neutrophil accumulation during liver injury, because this protein is a strong chemoattractant for neutrophils.

Animals↗