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Biomedical subjects

Hiroshi Kato

Publications and source records attributed to Hiroshi Kato.

At least 19 recordsLinked to original sources
PubMed2006

Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors.

Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.

Analysis of Variance↗
PubMed2006

Detection and quantification of specific IgE antibodies against eight Malassezia species in sera of patients with atopic dermatitis by using an enzyme-linked immunosorbent assay.

The lipophilic yeast Malassezia, a member of the cutaneous microflora, is an exacerbating factor in atopic dermatitis (AD). Of the 11 currently recognized species, M. globosa and M. restricta are found to frequently colonize the skin of AD patients. In this study, we attempted to quantify specific IgE antibodies against eight Malassezia species, namely, M. dermatitis, M. furfur, M. globosa, M. obtusa, M. pachydermatis, M. slooffiae, M. sympodialis, and M. restricta, in sera from AD patients by using an enzyme-linked immunosorbent assay (ELISA). The specific IgE value against M. restricta was greater than those against other Malassezia species. Competitive ELISA inhibition tests revealed that M. restricta contained species specific as well as shared antigens. Therefore, M. restricta could be considered as a candidate diagnostic antigen for detecting anti-Malassezia IgE in sera from AD patients.

Adolescent↗
PubMed2006

Reliability and validity of the Bangla version of WHOQOL-BREF in an adult population in Dhaka, Bangladesh.

The aim of the present study was to evaluate the validity and reliability of the Bangla version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in an adult population in Bangladesh. Approximately 200 adults in the Dhaka district were interviewed using a questionnaire containing the Bangla version of the WHOQOL-BREF, as well as questions related to sociodemographic data. To assess the reliability of WHOQOL-BREF, Cronbach's alpha was calculated, and test-retest reliability was evaluated using intraclass correlation coefficient (ICC) of the first and second administrations. For comparison, approximately 200 leprosy patients were also interviewed with the questionnaire to examine the discriminant validity between groups. On the whole, sufficient validity was observed, and the Bangla version of the WHOQOL-BREF was deemed to be valid and reliable in assessing the quality of life of an adult population in Bangladesh.

Adult↗
PubMed2006

Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.

Animals↗
PubMed2006

[Tear eosinophil cationic protein measurement in patients with seasonal allergic conjunctivitis].

PURPOSE: In the patients with seasonal allergy conjunctivitis (SAC), we investigated the concentration of tear eosinophil cationic protein (ECP) levels, the diagnosis of SAC and the usefulness of studying the disease states. SUBJECTS AND METHODS: The subjects were patients suffering from conjunctivitis seasonal allergy caused by cedar pollen and a healthy control group, and the study period was three years from 2001 to 2003. We divided the allergy group into 27 eyes of 27 patients that we measured before the pollen season and 44 SAC eyes of 44 patients that we measured during the pollen season. The healthy control group was 23 eyes of 23 healthy adults. Tears were collected by the schirmer I method. The ECP value of specimens was measured by enzyme-linked immunosorbent assay (ELISA) using samples which we eluted in buffer (0.5 M NaCl + 0.5% tris buffer saline with Tween 20) from Schirmer test paper. RESULTS: The measurement range of ELISA was 3.6-180 microg/l. The mean ECP value above the lower limit of ELISA in tears was 5.06 +/- 3.39 microg/l (n = 7) (mean +/- standard deviation) for the healthy control group, 9.32 +/- 6 .68 (n = 11) for the preseason group, and 54.90 +/- 117.74 (n = 29) for the pollen season group. The difference between the healthy group and the seasonal group was highly significant (p < 0.005), but there was no significant difference between the healthy group and the preseason group. We set the cut-off point at the 95th percentile (11.1 microg/l) of the healthy group and considered any value above cut-off as positive. The ECP value was positive in 2.5% (3 eyes out of 27) in the preseason group and 40.9% (18 of 44) in the seasonal group, and there was a significant difference (p < 0.01) between the seasonal group and the healthy group. When the seasonal group was divided into patients who had started treatment before the pollen season and those who began treatment during the season, we found a small ECP difference, but it was not statistically significant. CONCLUSION: Measurement of the ECP value in seasonal pollen allergy sufferers may be useful for pathological ascertainment, but it dose not provide adequate diagnosis because of the large number of false negative cases.

Adult↗
PubMed2006

[Clinical evaluation of a measurement method for secretory IgA in tears].

PURPOSE: To evaluate the efficacy of measurement of secretory IgA (sIgA) in tears with tear sampling methods using filter paper, and to review sIgA measurement method for clinical application. SUBJECTS AND METHODS: Subjects were divided into the following 4 groups: a healthy control group, 29 eyes of 29 subjects; a contact lens group, 15 eyes of 15 subjects; a dry eye group, 13 eyes of 13 subjects; and a herpes group, 6 eyes of 6 subjects. In all subjects the sIgA value in tears was measured. In addition, in eighteen eyes of 18 healthy control individuals, the tear sIgA value was measured three times, morning, noon, and night in one day, and the variation of tear sIgA value was checked. The tears were sampled by the Schirmer 1 method. Schirmer papers were eluted in 200 microl of 0.5 M NaCl and 0.5% Tween 20 in 0.05 M phosphate-buffered solution (pH 7.2). Tear sIgA value was measured by ELISA (enzyme-linked immunosorbent assay). RESULTS: Tear sIgA value was 1249.0+/-1025.0 microg/ ml in the healthy control group; 1057.4+/-1583.3 microg /ml in the contact len groups; 197.8+/-91.3 microg/ml in the dry eye group; and 759.7+/-467.8 microg/ml in the herpes group. There was no significant difference between the healthy control group and the contact lens group, or the control group and the herpes group. There was a significantly (p<0.0001) low value in the dry eye group in comparison with the healthy control group. In the 18 healthy control individuals, there was a tendency for the tear sIgA value collected at noon to be higher. CONCLUSION: Measurment of the changes in tear sIgA values caused by inflammation of the lacrimal gland is useful as a clinical test of lacrimal gland function.

Adult↗
PubMed2006

Different expression patterns of intact forms of squamous cell carcinoma antigens between normal and malignant cervical squamous epithelial tissues: nondenaturing polyacrylamide gel electrophoretic analysis.

Squamous cell carcinoma antigen (SCCA), a 45-kDa tumor-associated serpin, mainly consists of two highly homologous molecules, SCCA1 and SCCA2, which possess unique proteinase inhibitory properties. Importantly, our previous study demonstrated that an intact structure of SCCAs, and not a cleaved form yielded by interacting with target proteinase, is essential for their function as a serpin. The aim of this study is therefore, to develop a simple method of analyzing expression patterns of intact forms of SCCAs (functional SCCAs) in cervical squamous epithelial tissues and to investigate whether there are any differences in the expression of intact forms of SCCAs between normal and malignant cervical squamous epithelial tissues. We used nondenaturing polyacrylamide gel electrophoresis (PAGE) with immunoblotting. The newly generated antibody, Pab Y2, recognizes only intact form of SCCAs, while the conventional antibody, Mab 27, reacts with the cleaved form of SCCA1 as well as intact forms of SCCAs. Nondenaturing PAGE using Pab Y2 showed that an intact form of SCCAs in the heat-treated tissue extract at 60 degrees C for 2 h was separated into at least five bands, termed as bands A-E from cathode to anode. By comparison with two-dimensional electrophoresis patterns of SCCAs, it was found that the first three bands, i.e. bands A-C, are derived from the intact form of SCCA1, while the other two bands, i.e. band D and E are from the intact form of SCCA2. Specifically, band E, but not band D, of SCCA2 is apparently increased in squamous cell carcinomas compared with normal squamous epithelium. In conclusion, this novel analytical approach will be useful for investigating the different expression patterns of functional SCCAs between normal and malignant cervical squamous epithelial tissues.

Antigens, Neoplasm↗
PubMed2006

Suppression of SCC antigen promotes cancer cell invasion and migration through the decrease in E-cadherin expression.

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. Recent studies have shown that SCCA can influence the behavior of cancer cells. It is well known that cell-cell adhesion is an important factor for the progression of cancer. The present study, therefore, was undertaken to investigate the effect of SCCA2 on the cell adhesion related molecule, E-cadherin, and cancer cell behavior. For this purpose, antisense SCCA2 cDNA was transfected into human uterine cancer cell lines, SKG IIIa and SiHa, which express SCCA2. Suppression of SCCA2 expression by antisense SCCA2 cDNA transfection decreased E-cadherin expression and promoted cell migration and invasion as well as the blockage of E-cadherin function by anti-E-cadherin antibody administration. In conclusion, SCCA2 regulates cell migration and invasion via E-cadherin expression, suggesting that SCCA2 may be involved in cancer behavior such as invasion or metastasis.

Antigens, Neoplasm↗
PubMed2005

Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma.

AIM: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. METHODS: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. RESULTS: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. CONCLUSION: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

Analysis of Variance↗
PubMed2005

Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal CA1 neurons.

The role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) in long-term potentiation (LTP) and long-term depression (LTD) was studied in CA1 neurons in guinea pig hippocampal slices. In standard solution, short tetanic stimulation consisting of 15 pulses at 100 Hz induced LTP, while three short trains of low-frequency stimulation (LFS; 200 pulses at 1 Hz) at 18-min intervals or one long train of LFS (1000 pulses at 1 Hz) induced stable LTD in both the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS). Bath application of 2-aminoethoxydiphenyl borate (2-APB), an IP3R antagonist, or of alpha-methyl-4-carboxyphenylglycine (MCPG), a wide-spectrum metabotropic glutamate receptor antagonist, during weak tetanic stimulation significantly increased the magnitude of the LTP in both the S-EPSP and A-PS. Three short trains of LFS or one long train of LFS delivered in the presence of 2-APB or MCPG did not induce LTD, but elicited LTP. Based on these results, we conclude that, in hippocampal CA1 neurons, IP3Rs play an important role in synaptic plasticity by attenuating LTP and facilitating LTD.

Animals↗
PubMed2005

The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy.

LDL-apheresis is now commonly used as the only practical treatment for homozygous familial hypercholestreolemia (homozygous FH). However, even when applying apheresis therapy, the use of a drug or drugs is recommended to suppress the rapid rebound of cholesterol, which usually takes place after each apheresis procedure, and keep the LDL-cholesterol level within or near the optimal range for as long as possible. In this study, the usefulness of ezetimibe, a novel cholesterol-lowering drug, in enhancing the efficacy of apheresis therapy was evaluated in six Japanese patients with homozygous FH undergoing LDL-apheresis in combination with atorvastatin or simvastatin. With the exception of one patient, significant decreases in LDL-cholesterol at 2 weeks after each apheresis procedure were obtained during the period from 4 to 12 weeks of treatment, with an average reduction rate of 9.0% and a range of 4.3-12.6%. This corresponds to a suppression of rebound by approximately 36 mg/dl, from 391 to 355 mg/dl on average, in LDL-cholesterol values. Although the effect is not very strong, ezetimibe nevertheless appears to be a useful drug in combination with statins for those with homozygous FH undergoing LDL-apheresis.

Adult↗
PubMed2005

Promoter analyses of SCC antigen genes.

SCC antigen (SCCA) has been used as a tumor marker for squamous cell carcinoma. Analyses of the SCCA1 and SCCA2 genes, which are almost identical, and their promoters have been reported. Recently it was found that both SCCAs were stimulated by interleukin (IL)-4 and IL-13. Here we analyzed the promoter activity of both SCCAs in the 5'-flanking region, exon 1, and intron 1 to evaluate a putative STAT6 binding site. The addition of intron 1 to the luciferase assay constructs including the 5'-flanking region significantly augmented the promoter activity of both SCCA1 and SCCA2. Furthermore, deletion analyses of intron 1 revealed that a 50-bp fragment of intron 1 that includes putative STAT6 binding site was responsible for the increased promoter activity. Although the sequences of SCCA1 and SCCA2 are very similar in the 5'-flanking region, the analysis of the -337 single nucleotide polymorphism of SCCA2 indicated that this polymorphism may underlie the difference in promoter activity between SCCA1 and SCCA2.

Amino Acid Sequence↗
PubMed2005

Differential functional expression of cation-Cl- cotransporter mRNAs (KCC1, KCC2, and NKCC1) in rat trigeminal nervous system.

GABA is the main inhibitory neurotransmitter in the adult brain, which causes Cl- influx into the cell via GABAA receptors. The direction of Cl- inflow is dependent on the Cl- gradient across the membrane. Cation-Cl- cotransporters have been considered to play pivotal roles in controlling intracellular Cl- concentration ([Cl-]i) of neurons; hence, they modulate the GABAergic function. To elucidate how these cotransporters are distributed in the trigeminal nuclei, we investigated the expressions of K+-Cl- cotransporters (KCC1 and KCC2) and Na+-K+-2Cl- cotransporter (NKCC1) mRNAs by using in situ hybridization histochemistry. KCC2 mRNA was expressed in the motor trigeminal nucleus (Mo5), the principal trigeminal nucleus (Pr5), and the spinal trigeminal nucleus (Sp5), but not in the trigeminal ganglion (TG) and the mesencephalic trigeminal nucleus (Me5). On the other hand, KCC1 and NKCC1 mRNAs were expressed in all the trigeminal nuclei. The resting [Cl-]i of Me5 neurons was significantly higher than that of Mo5 neurons. Thus, in primary sensory neurons such as the TG and the Me5, [Cl-]i would be higher than those in the other trigeminal nuclei because of the lack of KCC2 mRNA expression. Since Me5 neurons, but not Mo5 neurons, responded to GABA by depolarization, GABA would have differential physiological functions among trigeminal nuclei and TG.

Animals↗
PubMed2005

Discovery of a novel and potent human and rat beta3-adrenergic receptor agonist, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid.

In search for potent and selective beta3-adrenergic receptor (beta3-AR) agonists as potential drugs for the treatment of type II diabetes and obesity, a novel series of 1-(3-chlorophenyl)-2-aminoethanol derivatives were prepared and evaluated for their biological activity at human beta1-, beta2-, and beta3-ARs and rat beta3-AR expressed in Chinese hamster ovary (CHO) cells. Replacement of the right-hand side (RHS, benzene ring) in the 'first generation' beta3-AR agonists BRL 37344 and CL 316243 with a 1H-indole ring gave compound 31 with unique pharmacological properties among beta3-AR agonists. Initial in vitro assays showed that 31 possesses modest rat and human beta3-ARs agonistic activity. Introduction of various substituent into the indole nucleus of 31 afforded a number of compounds with good beta3-ARs agonistic activity. In particular, 90 having a carboxylic acid functionality at the 7-position of the indole nucleus showed the most potent human beta3-AR agonistic activity. Finally, optical resolution of 90 led to the identification of the most promising compound, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid (96, AJ-9677). This compound exhibited potent human beta3-AR agonistic activity (EC50=0.062 nM, IA=116%) with 210- and 103-fold selectivity over human beta2-AR and beta1-AR, respectively. Compound 96 also exhibited potent rat beta3-AR agonistic activity (EC50=0.016 nM, IA=110%). Moreover, repeated oral administration of 96 inhibited body weight gain and significantly decreased glucose, insulin, free fatty acid, and triglyceride concentrations in plasma in KK-Ay/Ta mice. On the basis of this pharmacological profile, 96 entered clinical development as a drug for the treatment of type II diabetes and obesity.

Acetates↗