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Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 217 records · Page 12Linked to original sources
PubMed2001

An enhanced fibrinolysis prevents the development of multiple organ failure in disseminated intravascular coagulation in spite of much activation of blood coagulation.

OBJECTIVES: To investigate the relationship between fibrinolytic enhancement and the development of multiple organ failure (MOF) in disseminated intravascular coagulation (DIC). To detect the useful prognostic index for outcome in DIC. DESIGN: Case-control study. SETTING: A department of internal medicine in a university hospital, a clinical division for diagnosis and treatment, mainly of respiratory diseases, hematologic diseases, DIC, and other diseases requiring critical care medicine. PATIENTS: A total of 69 DIC patients, 31 with MOF. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The DIC patients with MOF had more elevated levels of tissue plasminogen activator antigen (t-PA) and plasminogen activator inhibitor antigen (PAI), and more depressed levels of plasmin-alpha2 plasmin inhibitor complex (PIC) and fibrin/fibrinogen degradation products than those without MOF, although no significant difference in thrombin-antithrombin complex (TAT) levels was observed. A fibrinolytic enhancement (shown by PIC) was parallel to an activation of blood coagulation (shown by TAT) in DIC patients without MOF, although no such fibrinolytic enhancement was provoked even by much activation of blood coagulation in DIC patients with MOF. Whereas all the patients without MOF were restored from DIC, 14 of 31 patients with MOF were unable to be restored from DIC and died. A significant increase in plasma levels of t-PA and PAI under the condition of sustained hemostatic activation was observed in the patients who died. CONCLUSION: Enhanced fibrinolysis was considered to be the important defense mechanism in preventing the development of MOF in DIC. The increases in plasma levels of t-PA and PAI were poor prognostic markers in DIC. Further careful study may be useful to clarify whether the fibrinolytic therapy is beneficial in clinical DIC patients with MOF.

Antifibrinolytic Agents↗
PubMed2001

Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects.

OBJECTIVE: Administration of leptin to animals increases sympathetic nerve activity and heart rate. We therefore tested the hypothesis that plasma leptin is linked independently to muscle sympathetic nerve activity (MSNA) and heart rate in healthy humans. METHODS: We measured plasma leptin, plasma insulin, body mass index (BMI), percent body fat, waist: hip ratio, MSNA, heart rate and blood pressure in 88 healthy individuals (50 men and 38 women). RESULTS: In men, plasma leptin concentration correlated significantly with BMI (r = 0.75, P < 0.001), percent body fat (r = 0.70, P< 0.001), waist: hip ratio (r = 0.69, P < 0.001), insulin (r = 0.37, P = 0.009), and age (r = 0.38, P = 0.006). Only BMI and waist: hip ratio were linked independently to plasma leptin concentration (r = 0.78, P < 0.001). Plasma leptin concentrations also correlated with heart rate (r = 0.39, P = 0.006) and mean arterial pressure (MAP; r = 0.38, P = 0.007), but not with MSNA (r = 0.17, P = 0.24). After adjustment for BMI and waist: hip ratio, plasma leptin concentration correlated significantly only with heart rate (r = 0.29, P = 0.04), and not with MAP (r = 0.21, P = 0.14). Individuals were divided into high-leptin and low-leptin subgroups on the basis of plasma leptin concentrations adjusted for BMI and waist: hip ratio. Those with high leptin concentrations had significantly faster heart rates than those with low leptin. MAP and MSNA were similar in both subgroups. No relationship between leptin and either heart rate or MSNA was evident in women. CONCLUSIONS: In normal men, heart rate, but not MSNA, is linked to plasma leptin concentration. This sex-specific relationship between heart rate and plasma leptin is independent of plasma insulin, BMI, waist:hip ratio and percentage body fat.

Adult↗
PubMed2001

Acute hypotension and bradycardia by medulla oblongata compression in spinal surgery.

A 71-year-old man was admitted to the hospital with subarachnoid hemorrhage caused by a cervical dural arteriovenous shunt. During surgery, the patient developed acute hypotension and bradycardia, probably caused by surgical compression of the medulla oblongata. During posterior fossa and upper cervical surgery, monitoring cardiovascular, respiratory, and evoked potential parameters is advocated. In the current case, only cardiovascular monitoring detected alteration of brain stem function. Anesthesiologists should be aware that surgical manipulation of the dorsal medulla might cause hemodynamic changes and expose patients to danger. Through close cardiovascular monitoring we can rapidly detect changes in vital signs, which allows prompt intervention to prevent irreversible neurologic deficits and potentially catastrophic patient outcome.

Aged↗
PubMed2001

Ectopic expression of MAFB gene in human myeloma cells carrying (14;20)(q32;q11) chromosomal translocations.

Chromosome 14q +, which represents a chromosomal rearrangement involving the immunoglobulin heavy chain gene (IgH) locus, is a genetic hallmark of human multiple myeloma (MM). Here, we report the identification of (14;20)(q32;q11) chromosomal translocations found in MM cells. Double color fluorescence in situ hybridization analyses pinpointed the breakpoints at the 20q11 locus in two MM cell lines within a length of at most 680 kb between the KIAA0823 and MAFB gene loci. Among the transcribed sequences in the vicinity of the breakpoints, an ectopic expression of the MAFB gene, which is located at 450 - 680 kb telomeric to one of the breakpoints and encodes a member of the MAF family basic region / leucine zipper transcription factor, was demonstrated to be associated with t(14;20). This finding, together with that of a previous study describing its transforming activity, suggests that the MAFB gene may be one of the targets deregulated by regulatory elements of the IgH gene as a result of t(14;20).

Avian Proteins↗
PubMed2001

DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant clinical Helicobacter pylori isolates.

We previously reported that inactivation of rdxA and/or frxA converted Helicobacter pylori from metronidazole sensitive to metronidazole resistant. To examine the individual roles of rdxA and frxA in the development of metronidazole resistance in H. pylori, we examined the status of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant H. pylori isolates obtained following unsuccessful therapy containing metronidazole. Arbitrary primed fingerprinting analyses revealed that the genotypes of 11 sensitive and resistant pairs of strains were essentially identical. Amino acid sequence identities of RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from 92 to 98% and 95 to 98%, respectively, compared to that of H. pylori J99 (MIC, 1 microg/ml). All strains with high-level metronidazole resistance (MICs, 128 microg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs, 32 to 64 microg/ml) contained a single premature truncation and/or altered RdxA and FrxA caused by nonsense, frameshift, and unique missense mutations. The low-level metronidazole-resistant strains (MICs, 8 microg/ml) contained unique missense mutations in FrxA but no specific changes in RdxA. The results demonstrate that alterations in both the rdxA and frxA genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-H. pylori therapy containing metronidazole is most likely to involve a single sensitive strain infection rather than a coinfection with a metronidazole-resistant strain.

Amino Acid Sequence↗
PubMed2001

Clinical relevance of the babA2 genotype of Helicobacter pylori in Japanese clinical isolates.

Genotypic variation of Helicobacter pylori is speculated to associate with different clinical outcomes. In Western countries, the gene encoding blood group antigen-binding adhesin (BabA), babA2, is of high clinical relevance and is a useful marker to identify patients who are at higher risk for peptic ulceration and gastric adenocarcinoma, as are vacA and cagA. We investigated the presence of babA2 and cagA in 179 Japanese clinical isolates by PCR and Southern blot analysis and looked for correlations with various clinical outcomes (nonulcer dyspepsia, duodenal ulcers, gastric ulcers gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma). The prevalence of the babA2 genotype was 84.9% and that of the cagA genotype was 96.1%. There was no correlation between the babA2 and cagA genotypes, and there was no association between the babA2 or cagA status and clinical outcome. These results indicate that babA2 status is not of high clinical relevance in Japan and that Japanese strains are different from those infecting Western populations.

Adhesins, Bacterial↗
PubMed2001

Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.

Axin acts as a negative regulator in Wnt signaling through interaction with various molecules involved in this pathway, including beta-catenin, adenomatous polyposis coli, and glycogen synthase kinase 3beta. We show here that Axin also regulates the effects of Smad3 on the transforming growth factor beta (TGF-beta) signaling pathway. In the absence of activated TGF-beta receptors. Axin physically interacted with Smad3 through its C-terminal region located between the beta-catenin binding site and Dishevelled-homologous domain. An Axin homologue, Axil (also called conductin), also interacted with Smad3. In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo. Upon receptor activation, Smad3 was strongly phosphorylated by TGF-beta type I receptor (TbetaR-I) in the presence of Axin, and dissociated from TbetaR-I and Axin. Moreover, the transcriptional activity of TGF-beta was enhanced by Axin and repressed by an Axin mutant which is able to bind to Smad3. Axin may thus function as an adapter of Smad3, facilitating its activation by TGF-beta receptors for efficient TGF-beta signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Magnesium causes nitric oxide independent coronary artery vasodilation in humans.

OBJECTIVE: To determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium. DESIGN: Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries. SETTING: Hiroshima University Hospital a tertiary cardiology centre. PATIENTS: 17 patients with angiographically normal coronary arteries. INTERVENTIONS: Magnesium sulfate (MgSO(4)) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA. MAIN OUTCOME MEASURES: Diameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow. RESULTS: At a dose of 0.02 mmol/min, MgSO(4) did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO(4) caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 v baseline for all). MgSO(4) increased the changes in these parameters after the infusion of L-NMMA (p < 0.001 v baseline). CONCLUSIONS: Magnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.

Adult↗
PubMed2001

Acetylcholine increases intracellular Ca2+ in the rat pituitary folliculostellate cells in primary culture.

Pituitary folliculostellate cells (FSCs) are thought to partially inhibit pituitary hormone secretion through a paracrine mechanism. In this process, one of the important questions is what factors regulate the function of FSCs. Because ACh is synthesized in and possibly released from the corticotrophs and lactotrophs, we examined whether FSCs respond to ACh by the method of Ca2+ imaging in primary cultured FSCs from male Wistar rats. ACh (30 nM-3 microM) increased intracellular calcium concentration ([Ca2+](i)) of FSCs in a concentration-dependent manner, with an initial rapid rise followed by a relatively sustained increase. The complete block of the response by atropine and pirenzepine suggests involvement of muscarinic receptors. Depletion of the stored Ca2+ by thapsigargin blocked the response completely. Blockers of phospholipase C, U-73122 and neomycin, suppressed significantly the rise of [Ca2+](i). These results suggest that ACh increases [Ca2+](i) in FSCs by activating phospholipase C, presumably through activation of M(1) receptors. The rise in [Ca2+](i) could trigger a variety of Ca2+-dependent cellular processes, including the synthesis and release of bioactive substances, which in turn act on endocrine cells.

Acetylcholine↗
PubMed2001

Processing of shape defined by disparity in monkey inferior temporal cortex.

Neurons in the monkey inferior temporal cortex (IT) have been shown to respond to shapes defined by luminance, texture, or motion. In the present study, we determined whether IT neurons respond to shapes defined solely by binocular disparity, and if so, whether signals of disparity and other visual cues to define shape converge on single IT neurons. We recorded extracellular activity from IT neurons while monkeys performed a fixation task. Among the neurons that responded to at least one of eight random-dot stereograms (RDSs) containing different disparity-defined shapes, 21% varied their responses to different RDSs. Responses of most of the neurons were positively correlated between two sets of RDSs, which consisted of different dot patterns but defined the same set of eight shapes, whereas responses to RDSs and their monocular images were not correlated. This indicates that the response modulation for the eight RDSs reflects selectivity for shapes (or their component contours) defined by disparity, although responses were also affected by dot patterns per se. Among the neurons that showed selectivity for shapes defined by luminance or disparity, 44% were activated by both cues. Responses of these neurons to luminance-defined shapes and those to disparity-defined shapes were often positively correlated to each other. Furthermore the stimulus rank, which was determined by the magnitude of responses to shapes, generally matched between these cues. The same held true between disparity and texture cues. The results suggest that the signals of disparity, luminance, and texture cues to define the shapes converge on a population of single IT neurons to produce the selectivity for shapes.

Animals↗
PubMed2001

Elevated type IV collagen in bronchoalveolar lavage fluid from infants with bronchopulmonary dysplasia.

We measured the levels of type IV collagen and lipid peroxides in bronchoalveolar lavage fluid (BALF) from infants with respiratory distress syndrome (RDS) to determine the relationship to the development of bronchopulmonary dysplasia (BPD). We analyzed their levels between two groups, RDS infants who developed BPD (n = 8, BPD group) and those who did not (n = 11, RDS group). The levels of the type IV collagen in the BPD group were significantly higher than those in the RDS group at 3 and 7 days of age (p = 0.0024). In the BPD group, persistently increased levels of the type IV collagen were observed during the period up to 14 days of age. There was a positive relationship between the type IV collagen levels and polymorphonuclear leukocyte counts, and thiobarbituric acid-reactive substance levels in BALF. These results suggest that the increased type IV collagen levels in BALF of BPD infants may reflect pulmonary basement membrane damage and the involvement of oxygen metabolites in its process.

Birth Weight↗
PubMed2001

Sera from patients with Kawasaki disease induce intercellular adhesion molecule-1 but not Fas in human endothelial cells.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of unknown etiology occurring in childhood, characterized by abnormalities of the immune system including elevations of proinflammatory cytokines in the serum. We investigated the effect of serum from patients with KD on the expression of intercellular adhesion molecule-1 (ICAM-1) and Fas by human umbilical vein endothelial cells (HUVEC). METHODS: Confluent monolayers of HUVEC were incubated with sera from patients in the acute or convalescent phase of KD. Expression of ICAM-1 and Fas by HUVEC was assessed by flow cytometry. Concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in sera from patients with KD were measured by an immunoradiometric assay and an enzyme-linked immunosorbent assay, respectively. RESULTS: Sera from patients in the acute phase of KD produced significantly greater ICAM-1 expression by HUVEC than sera from patients in the convalescent phase. In contrast, KD sera did not induce Fas expression. While the mean serum concentration of TNF-alpha in patients in the acute phase of KD was significantly higher than in those in the convalescent phase, IL-1beta concentrations did not differ between the acute and convalescent phases. Exposure of HUVEC to recombinant human TNF-alpha increased the expression of both ICAM-1 and Fas, but a much lower concentration was required for an effect upon ICAM-1. Exogenous TNF-alpha did not induce apoptosis in HUVEC. CONCLUSIONS: These results suggest that increased expression of ICAM-1 by endothelial cells might be involved in the pathogenesis of acute KD, and that TNF-alpha might induce ICAM-1 expression.

Acute Disease↗
PubMed2001

Eosinophil infiltration and degranulation in normal human tissues: evidence for eosinophil degranulation in normal gastrointestinal tract.

Eosinophils play an important role in the pathogenesis of inflammatory diseases such as bronchial asthma and host immunity to parasitic infections. Deposition of eosinophil granule proteins and concomitant tissue damage have been documented in various diseases. Here, we review and summarize results of our immunofluorescence studies of eosinophil infiltration and degranulation in various normal human tissues. Furthermore, because eosinophil infiltration and degranulation are not normally present in healthy tissues, we examine whether eosinophil infiltration and degranulation normally occur in the small intestine and whether tissue procurement methods affect the extent of eosinophil infiltration and degranulation there. Hematopoietic and lymphatic tissues, including the thymus, showed eosinophil infiltration, but the only organ showing remarkable eosinophil infiltration and degranulation was the gastrointestinal (GI) tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel. These results suggest that tissue procurement methods affect the degree of eosinophil degranulation in the GI tract and that, among normal human body organs, both eosinophil infiltration and degranulation only occur in the GI tract.

Adult↗
PubMed2001

Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin, astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the rabbit.

Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles. However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated. We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular block was assessed by mechanical response with single twitch stimulation. Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated. The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.

Aminoglycosides↗
PubMed2001

Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes.

Since the pharmacological profiles of various non-steroidal anti-inflammatory drugs (NSAIDs) might depend on their differing selectivity for cyclooxygenase 1 (COX-1) and 2 (COX-2), we developed a new screening method using human peripheral monocytes. Monocytes from healthy volunteers were separated, and the cells were incubated with or without lipopolysaccharide (LPS). Monocytes without LPS stimulation exclusively expressed COX-1 on Western blotting analysis, whereas LPS stimulation induced COX-2 expression. Unstimulated monocytes (COX-1) and LPS-stimulated monocytes (COX-2) were then used to determinethe COX selectivity of various NSAIDs. The respective mean IC50 values for COX-1 and COX-2 IC50 (microM), and the COX-1/COX-2 ratio of each NSAID were as follows: celecoxib, 82, 6.8, 12; diclofenac, 0.076, 0.026, 2.9; etodolac, > 100, 53, > 1.9; ibuprofen, 12, 80, 0.15; indometacin, 0.0090, 0.31, 0.029; meloxicam, 37, 6.1, 6.1; 6-MNA (the active metabolite of nabumetone), 149, 230, 0.65; NS-398, 125, 5.6, 22; piroxicam, 47, 25, 1.9; rofecoxib, > 100, 25, > 4.0; S-2474, > 100, 8.9, > 11; SC-560, 0.0048, 1.4, 0.0034. The percentage inhibition of COX-1 activity at the IC50 of COX-2 also showed a wide variation among these NSAIDs. The bioassay system using human monocytes to assess the inhibitory effects of various NSAIDs on COX-1 and COX-2 may become a clinically useful screening method.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily, which regulate the differentiation of osteoprogenitor cells. Here we show that among members of the BMP family, BMP-4 and growth/differentiation factor 5 (GDF-5) induce osteoblast differentiation through the activation of three receptor-regulated Smads (i.e. Smad1, Smad5 and Smad8). By contrast, BMP-6 and BMP-7 induce alkaline phosphatase activity through Smad1 and Smad5, but not through Smad8. Consistent with these findings, BMP-4 induced phosphorylation and nuclear translocation of Smad1, Smad5 and Smad8, but BMP-6 activated only Smad1 and Smad5. BMP-4 and GDF-5 are known to bind to activin receptor-like kinase 3 (ALK-3) and/or ALK-6 (also termed BMP type IA and type IB receptors, respectively), whereas BMP-6 and BMP-7 preferentially bind to ALK-2. Compared with the effects induced by only one of the type I receptors, the combination of constitutively active forms of ALK-2 and ALK-3 (or ALK-6) more strongly induced alkaline phosphatase activity in C2C12 cells. Moreover, addition of BMP-4 and BMP-6 to C2C12 cells resulted in higher alkaline phosphatase activity than that of only one of these BMPs. The combination of ALK-2 and ALK-3 also induced higher transcriptional activity than either receptor alone. Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways.

Activin Receptors↗