Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 217 records · Page 12Linked to original sources

PubMed2001

KT3-671, an angiotensin AT1 receptor antagonist, attenuates vascular but not cardiac responses to sympathetic nerve stimulation in pithed rats.

Effects of KT3-671 on vascular and cardiac sympathetic neurotransmission were investigated in pithed rats. The pressor response to spinal stimulation (5 Hz) of the pithed rat without the adrenals was approximately 75% of that with the adrenals. Guanethidine (8 mg/kg, i.v.) decreased by about 76% the pressor response to sympathetic stimulation in the pithed rat with intact adrenals and the guanethidine-resistant response was almost completely abolished by bilateral adrenalectomy. Therefore, the following experiments were done using the pithed rat without the adrenals. KT3-671 (1-10 mg/kg, i.v.) as well as losartan (1-10 mg/kg, i.v.) inhibited dose-dependently the pressor response to sympathetic stimulation. KT3-671 was approximately four times more potent than losartan in inhibiting the pressor response. The two angiotensin II subtype 1 receptor antagonists (10 mg/kg, i.v.) did not affect the pressor response to exogenously administered norepinephrine. Neither KT3-671 nor losartan influenced the tachycardia induced by spinal stimulation and isoprenaline. Intravenous infusion of angiotensin II (100 ng/kg/min) did not affect both pressor and tachycardic responses to sympathetic stimulation. In conclusion, KT3-671 as well as losartan inhibits vascular but not cardiac sympathetic neurotransmission of the pithed rats, which may contribute to its overall antihypertensive efficacy.

Adrenalectomy↗

PubMed2001

Colonisation and transmission of Clostridium difficile in healthy individuals examined by PCR ribotyping and pulsed-field gel electrophoresis.

Healthy adults who had not been exposed to antimicrobial agents for the preceding 4 weeks were examined for intestinal carriage of Clostridium difficile. The 1234 individuals examined were composed of seven groups: three classes of university students, hospital workers at two hospitals, employees of a company and self-defence force personnel at a local station. Overall, 94 (7.6%) individuals were positive for C. difficile by faecal culture but carriage rates among the study groups ranged from 4.2% to 15.3%. Typing by PCR ribotyping and pulsed-field gel electrophoresis demonstrated clusters of carriers colonised by a single type in each of three groups, indicating that cross-transmission of C. difficile can occur in community settings. Follow-up culture was performed on 38 C. difficile-positive individuals and C. difficile was isolated again from 12 (32%) of them 5-7 months after the initial culture; six (50%) of these 12 individuals had a new strain on repeat culture. Two or more family members were C. difficile-positive in five of 22 families examined. C. difficile with an identical type was isolated from persons within a family in only one family. These results suggest that intestinal carriage by healthy adults may play a role as a reservoir for community-acquired C. difficile-associated diarrhoea, but that cross-transmission of C. difficile does not occur frequently among family members at home.

Adolescent↗

PubMed2001

Molecular evolution of human echovirus 9 isolated from patients with aseptic meningitis in northern Kyushu during the summer of 1997.

An epidemic of aseptic meningitis caused by human echovirus 9 (E-9) occurred in the summer of 1997 in northern Kyushu, Japan. Sequences of genome position 2504-3358, which encoded a part of VP1, of the nine isolated viruses were determined. An RGD motif and B-C loop were found in all. They were almost identical and closely related to the virulent strain Barty.

Amino Acid Sequence↗

PubMed2001

Anti-angiogenic treatment for peritoneal dissemination of pancreas adenocarcinoma: a study using TNP-470.

We established peritoneal dissemination-prone subcultures (PCI-43p3) using nude mice by a repetitive in vivo selection of intraperitoneally inoculated PCI-43, a pancreas adenocarcinoma cell line. The subcultures showed upregulated expression of matrix metalloproteinase (MMP)-9, but not MMP-2 in culture supernatants. They also produced increased amounts of vascular endothelial growth factor (VEGF), which was not associated with alterations in isoforms of VEGF mRNA. PCI-43p3 cells attached to cultured mesothelial cell monolayers more readily than did the parent PCI-43 cells. The angiogenesis inhibiting agent, TNP-470, at 30 mg / kg was administered to the model mice, resulting in a prominent suppression of the establishment of peritoneal nodules. The suppression was dependent on the duration of TNP-470 treatment. TNP-470 treatment significantly suppressed proliferation of tumor cells in disseminated nodules, assessed in terms of immunostaining for proliferating cell nuclear antigen (PCNA). TNP-470 did not affect the in vitro attachment between PCI-43p3 and mesothelial cells. The combined data show that anti-angiogenic treatment profoundly suppresses the in vivo process of peritoneal dissemination.

Adenocarcinoma↗

PubMed2001

Vaccination effect of interleukin-6-producing pancreatic cancer cells in nude mice: a model of tumor prevention and treatment in immune-compromised patients.

In an effort to explore properties important in hematogenous metastasis of pancreatic adenocarcinoma, we previously demonstrated that tumor-derived interleukin (IL)-6 is a crucial factor that conveys resistance to liver metastasis. Here we extend the study to examine a possible vaccination effect of tumor-derived IL-6 in T-cell-deficient nude mice, as a model for predicting the effect in immune-compromised patients. We used a pair of IL-6-nonproducing and highly producing pancreatic adenocarcinoma cell lines, PCI-43 and PCI-43h, respectively. The reaction intensity of anti-PCI IgG antibodies in host nude mice was maximal 28 days after inoculation of PCI-43h cells, and remained high thereafter. A fraction of the pancreatic carcinoma cell lines, namely, PCI-6, -10, and -43, expressed surface antigenic determinant(s) reactive with the IgG; but the others, PCI-19, -24, -55, -64, -66, -68, -72, and -79, did not. Inoculation of PCI-43h but not PCI-43 suppressed growth of simultaneously inoculated PCI-43, but not PCI-24 xenografts. In addition, administration of PCI-43h, but not PCI-43 suppressed the growth of PCI-43 that was xenografted 4 weeks later, thus revealing a vaccination effect of IL-6-producing PCI-43h, but not IL-6-nonproducing PCI-43. These data, obtained from T-cell-deficient nude mice, suggest an in vivo role for IL-6 in inducing IgG-mediated, pancreatic carcinoma-specific vaccination against a thymus-independent antigen.

Animals↗

PubMed2001

Simultaneous double or triple coil technique for closure of moderate sized (> or = 3.0 mm) patent ductus arteriosus.

One important complication of coil occlusion of patent ductus arteriosus using the conventional Gianturco coil is migration of coils into peripheral vessels. Especially in patients having relatively larger size ductus, the risk for such complication could be increased. In this regard, a detachable coil may have some technical benefits in performing coil occlusion and reducing the incidence of complications such as migration of coil. Based on our clinical experiences, we describe the clinical efficacy of a simultaneous double or triple coil occlusion technique using the Cook detachable coil system to close the ductus arteriosus, especially in patients whose ductus diameter more than 3.0 mm.

Adolescent↗

PubMed2001

Biological properties of lipid A isolated from Flavobacterium meningosepticum.

The biological properties of the lipid A from Flavobacterium meningosepticum, which we recently isolated and whose complete chemical structure has been determined (H. Kato, T. Iida, Y. Haishima, A. Tanaka, and K. Tanamoto. J. Bacteriol. 180:3891--3899, 1998), were studied. The lipid A exhibited generally moderate activity compared to Salmonella enterica subsp. enterica serovar abortus equi lipopolysaccharide (LPS) used as a control in the assay systems tested; lethal toxicity in galactosamine-sensitized mice, mitogenicity in mouse spleen cells, induction of tumor necrosis factor alpha (TNF-alpha) release from mouse peritoneal macrophages and J774-1 mouse macrophage-like and human THP-1 line cells, nitric oxide induction activity from J774-1 cells, and Limulus gelation activity. The moderate activity of the F. meningosepticum lipid A may be explained by its unique fatty acid composition and the lack of a phosphate group in position 4'. It is noteworthy that the lipid A apparently induced TNF-alpha release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice and that the activation was suppressed by the LPS-specific antagonist, succinylated lipid A precursor. Significant splenocyte mitogenicity in C3H/HeJ mice was also observed with the lipid A. Taken together with the previous results concerning Porphyromonas gingivalis lipid A, which has a high level of structural similarity to the lipid A of F. meningosepticum, and the induction of TNF-alpha release in macrophages from C3H/HeJ mice, the lipid A of F. meningosepticum, which has novel fatty acids, may possibly play an role for the activation of C3H/HeJ macrophages.

Animals↗

PubMed2001

Analysis of Clostridium difficile isolates from nosocomial outbreaks at three hospitals in diverse areas of Japan.

Clostridium difficile isolates recovered from patients with C. difficile-associated diarrhea (CDAD) at three hospitals located in diverse areas of Japan were analyzed by three typing systems, PCR ribotyping, pulsed-field gel electrophoresis (PFGE), and Western immunoblotting. At the three hospitals examined, a single PCR ribotype strain (type smz) was predominant and accounted for 22 (65%) of 34, 18 (64%) of 28, and 11 (44%) of 25 isolates, respectively. All of the 51 isolates that represented PCR ribotype smz were nontypeable by PFGE because of DNA degradation. Since the type smz strain did not react with any of the antisera against 10 different serogroups (A, B, C, D, F, G, H, I, K, and X), we prepared a new antiserum against a type smz isolate. All 51 type smz isolates presented identical banding patterns, reacting with the newly prepared antiserum (designated subserogroup JP-0 of serogroup JP). These results were compared with those of a strain from a hospital outbreak that occurred in New York, which has been identified as type J9 by restriction enzyme analysis and type 01/A by arbitrarily primed PCR but was nontypeable by PFGE because of DNA degradation. This strain was reported to be epidemic at multiple hospitals in the United States. The J9 strain represented a PCR ribotype pattern different from that of a type smz strain and was typed as subserogroup G-1 of serogroup G by immunoblot analysis. A single outbreak type causing nosocomial CDAD in Japan was found to be different from the strain causing multiple outbreaks in the United States, even though the outbreak strains from the two countries were nontypeable by PFGE because of DNA degradation.

Bacterial Typing Techniques↗

PubMed2001

Differential regulation of IGFBP-2 and IGFBP-5 gene expression by vitamin A status in Japanese quail.

To investigate the involvement of the insulin-like growth factor (IGF) system in vitamin A (VA)-supported growth, we examined the effects of VA status on IGF binding protein (IGFBP)-2 and -5 gene expression in Japanese quail. VA deficiency caused a reduction in IGFBP-2 mRNA only in lung, without effect in other tissues. However, the expression of IGFBP-5 mRNA was more sensitive to the change of VA status. IGFBP-5 mRNA levels were significantly reduced by VA depletion in a tissue-specific manner, which preceded the decrease in body weight. A single injection of retinoic acid or retinol to VA-deficient quail did not affect the levels of IGFBP-2 mRNA, but it rapidly induced the expression of IGFBP-5 mRNAs in some tissues. These results are the first to show that gene expression of some IGFBPs in vivo are under the control of VA status and suggest a possible involvement of the IGF system in mediating the physiological actions of VA in the growth of Japanese quail.

Aging↗

PubMed2001

Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants.

To elucidate the urinary concentration of total bile acids after birth and the profile of the usual and unusual urinary bile acids, especially 3beta-hydroxy-5-cholen-24-oic acid (Delta(5)-3beta-ol), we measured the concentrations of 13 bile acids in the urine from preterm infants vs. full-term controls by gas chromatography-mass spectrometry. The urinary concentration of total bile acids in early preterm infants below 32 weeks of gestational age significantly exceeded that of the late preterm and full-term infants (p < 0.0005). The major urinary bile acids in early preterm infants were cholic acid, 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acid and Delta(5)-3beta-ol. In conclusion, the high urinary concentrations of total bile acids in preterm infants may be due to an overproduction, or more likely to a low hepatic bile acid clearance. An alternative fetal pathway, the acidic pathway, may be a major route of bile acid biosynthesis in preterm infants.

Bile Acids and Salts↗

PubMed2001

Prenatal influence of ischemia-hypoxia-induced intrauterine growth retardation on brain development and behavioral activity in rats.

The effects of intrauterine growth retardation (IUGR) on brain histological or functional development were examined in rats. IUGR was induced by ligating the bilateral uterine arteries at day 17 of pregnancy. On day 22 of pregnancy, cesarean section was performed, and pups with a birth weight of <2 SD of the mean birth weight of control pups were regarded as IUGR rats. Morphological changes of the brain were studied by Nissl's staining at different timepoints during prenatal and postnatal periods. For behavioral study, an open-field test was performed at 5, 7 and 10 weeks after birth. Histological studies showed the migration disorder of the neurons in the cerebral cortex from embryonic day 17 to postnatal day (PD) 49. The open-field test revealed locomotor disturbance at PD49 in male IUGR rats, but not in female IUGR rats or control rats. It is concluded that IUGR due to antenatal ischemia-hypoxia causes morphological changes in the central nervous system, and induces behavioral impairment, particularly in male rats.

Animals↗

PubMed2001

Risk factors and seroprevalence of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection in uzbekistan.

OBJECTIVES: The aim of this study was to elucidate the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection in Uzbekistan and to explore whether there is a correlation between those blood-borne agents and socioeconomic risk factors. METHODS: One thousand nine hundred and eighteen subjects were studied. The subjects were divided into a low-risk group, a high-risk group and a patient group. Sera were tested for HBV surface antigen (HBsAg), anti-HCV, and anti-HIV. RESULTS: The seroprevalence of HBsAg, anti-HCV, and anti-HIV in the general population was 13.3, 13.1 and 0%, respectively. The anti-HCV infection rate was significantly higher in intravenous drug users (62.7%) than in prostitutes (9.2%), homosexuals (11.1%), and medical laboratory employees (12.5%) (p < 0.01). In the low-risk group, positivity for anti-HCV increased with age from 2.2% in the 15- to 20-year-olds up to the highest rate of 17.6% in the 31- to 40-year-olds; the positivity then decreased to 0% in the group over 60 years of age. In the high-risk group, the positivity for anti-HCV in the age groups under 40 years was approximately 30% and significantly higher than in the low-risk group (p < 0.01). Risk factors for transmission of HCV were medical treatment in the low-risk group, drug abuse in the high-risk group, and both in the patient group. CONCLUSIONS: This study demonstrates that the seroprevalence of HBV and HCV infection is high, whereas HIV infection is yet uncommon in Uzbekistan.

Adolescent↗

PubMed2001

Ischemic pre-conditioning affects the subcellular distribution of protein kinase C and calcium/calmodulin-dependent protein kinase II in the gerbil hippocampal CA1 neurons.

Brief ischemic episode, which in itself is not lethal, confers tolerance to subsequent ischemic insults. Since intracellular signal transduction system has been implicated in ischemic cell death, we studied the effect of pre-conditioning on the changes in the subcellular distribution of protein kinase Cgamma (PKCgamma) as well as CaM kinase II (CaMKII). Gerbils were pre-conditioned by a sublethal 2 min cerebral ischemia 24 h prior to lethal 5 min ischemia. The pre-conditioning generally downregulated PKCgamma and CaMKII in the CA1 hippocampus. Especially at the starting point of the second lethal ischemia, the cytosolic PKCgamma level was about 40% lower in the pre-conditioned group. Also, the crude synaptosomal CaMKII level at 24 h reperfusion following the second ischemia was significantly lower in the pre-conditioned group, showing enhanced recovery of CaMKII translocation. Present results suggest that ischemic pre-conditioning may downregulate calcium-mediated cell signaling system, enhancing normalization of calcium homeostasis, perturbed by the second ischemia of lethal duration.

Animals↗

PubMed2001

Up-regulation of upstream stimulatory factors by protein malnutrition and its possible role in regulation of the IGF-binding protein-1 gene.

Protein malnutrition drastically induces the expression of the IGF-binding protein-1 (IGFBP-1) gene. We have previously shown that the region between -77 and -112 bp upstream of the rat IGFBP-1 gene contributes to the response of this gene to amino acid limitation. In an attempt to elucidate the basis of the responsiveness of this putative amino acid response unit (AARU), we searched the nucleus of the rat liver for a trans-acting factor whose binding to AARU was dependent on protein nutrition. Liver nuclear extracts of rats fed a protein-free diet and of those fed a control diet were compared by EMSA using the AARU as probe. One of the protein-probe complexes underwent a drastic increase after dietary protein deprivation. Assays using specific antibodies and several competitor oligonucleotides led to identification of the protein composing the complex as upstream stimulatory factor-1 (USF) and USF-2. The binding site of the USF proteins in the AARU turned out to be a CACGGG sequence that was homologous to the consensus USF-binding sequence (E box; CANNTG). Further, Western blot analyses showed that a protein-free diet caused significant increases in USF-1 and USF-2 levels. Thus, elevated expression of the IGFBP-1 gene under protein malnutrition can be attributable to increased binding of USF to its promoter, which results from increased USF levels. The data suggest that the changes in these ubiquitously distributed transcription factors play an important role in the nutritional regulation of expression of mammalian genes.

Animals↗

PubMed2001

Hemopexins suppress phorbol ester-induced necrosis of polymorphonuclear leucocytes.

It was recently reported that intravenous administration of phorbol 12-myristate 13-acetate (PMA) showed a therapeutic effect in myelocytic leukemia patients. However, we previously observed that, in serum-free conditions, polymorphonuclear leucocytes (PMNs) were killed rapidly by exposure to PMA, suggesting the possibility of serious side effects. In this study, we found that PMA-induced necrosis of PMNs was prevented by serum, suggesting the existence of a "necrosis-suppressing factor". Next we tried to identify the serum factor. The hemopexins we purified were found to suppress necrosis of PMNs in a dose-dependent fashion. Hemopexins alone could not suppress necrosis, however, as it required the coexistence of another macromolecule such as albumin. Albumin promoted the suppressive activity of hemopexins in a dose-dependent fashion. These results strongly suggest that serum hemopexins may rescue mature PMNs from necrosis in the PMA-administered leukemia patient as previously reported, resulting in avoidance of serious side effects.

Animals↗

PubMed2001

Racemization kinetics of meluadrine tartrate in aqueous solution.

The kinetics of racemization of meluadrine tartrate in aqueous solution was investigated by HPLC, over the pH range of 1.2 to 12 at 40, 60 and 80 degrees C. The racemization was followed by measuring both the residual (R)-enantiomer and formed (S)-enantiomer of meluadrine. The pH-racemization rate profile of meluadrine showed a minimum racemization rate constant between pH 4 and 6, and the rate constant increased rapidly with decreasing pH below pH 3. In the basic region, the racemization rate constant showed a maximum at around pH 9. Four pathways of racemization of meluadrine are proposed, depending on the dissociation state of the phenolic and amino groups. The calculated racemization rate-pH profile agreed well with the observations. The values of activation energy (95-115 kJ/mol) suggest that a similar quinoid intermediate is involved throughout the pH range examined. The objective of this study is to clarify the racemization mechanism of benzylalcohol derivative with phenoric group. This study offers fundamental knowledge for the other benzylalcohol derivatives, which have similar moiety structure.

Adrenergic beta-2 Receptor Agonists↗

PubMed2001

Studies on macrolide antibiotics I. Synthesis and antibacterial activity of erythromycin A 9-O-substituted oxime ether derivatives against Mycobacterium avium complex.

A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics.

Anti-Bacterial Agents↗

PubMed2001

Synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives with amphoteric side chains.

Novel benzamide derivatives (19-24, 32a-c, 43d-f), each possessing a cycloaminoalkanecarboxylic acid side chain, were synthesized and their gastrointestinal prokinetic and dopamine D2 receptor antagonist activities were evaluated. 4-[(4-Amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetic acid (19) exhibited the most potent gastro- and colon-prokinetic activities, through intravenous administration to conscious dogs, and also showed the reduced dopamine D2 receptor antagonistic activity. However, 19 showed only weak gastrointestinal prokinetic activity after oral administration. Several ester prodrugs (44-62) of 19 were tested for pharmacological activities as well as physicochemical and metabolic stability; the butyl ester (46) was consequently selected as a promising gastrointestinal prokinetic agent with reduced side effects.

Animals↗