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Biomedical subjects

H Tachikawa

Publications and source records attributed to H Tachikawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Parental representation in eating disorder patients with suicide.

OBJECTIVE: We examined parental, personality, and symptomatological characteristics in relation to suicide attempts among eating disorder patients. METHODS: Fifty-one eating disorder inpatients, divided into two groups according to lifetime suicide attempts, and 107 non-psychiatric subjects were compared on the following variables: Parental Bonding Instrument (PBI), Global Clinical Score (GCS), Eating Disorder Inventory-91 (EDI-91), Eating Attitudes Test-26 (EAT), clinical and personality characteristics, and family backgrounds. RESULTS: Suicidal patients reported significantly higher overprotection by both parents than non-suicidal patients and non-psychiatric subjects. Suicidal patients had a more prevalent history of child abuse, affective instability, unstable self-image, avoidance of abandonment, maladaptive perfectionism, personality disorder, and mood disorder. There were no differences in symptomatological factors or the severity of the eating disorders. CONCLUSION: The results suggest that high overprotection is associated with suicidal behaviour in eating disorder patients. The association between overprotective parenting and personality characteristics, and methods of suicide prevention are discussed briefly.

Adolescent↗
PubMed2000

Tardive dystonia provoked by concomitantly administered risperidone.

Two cases of tardive dystonia are reported. The first case was an 18-year-old schizophrenic woman suffering from parkinsonism and hypotension induced by antipsychotic drugs. Risperidone (4 mg/day) was added to her drug regimen and after increasing the dosage to 6 mg/day, she began to exhibit retrocollis. The second case was a 61-year-old woman who had schizophrenia and tardive dyskinesia. After replacing chlorpromazine (75 mg/day) with risperidone (4 mg/day), she began to exhibit retrocollis. The retrocollis in both cases was considered to be tardive dystonia provoked by risperidone administered concomitantly with other antipsychotics. Risperidone is reported to produce few extrapyramidal symptoms, but these cases suggested that changing from other drugs to risperidone, or rapidly increasing risperidone dosage, may provoke tardive syndrome.

Adolescent↗
PubMed2000

[A study of recovery factor about drug addiction recovery center "DARC"].

This study examines the effectiveness of the 'DARC' (Drug Addiction Rehabilitation Center) and its program in treating patients with drug dependence. DARC is the only rehabilitation facility group managed by recovered drug users in Japan. It uses the 'Twelve Step Program' as part of its recovery regime. Through structured questionnaires, the changes of participants' and ex-participants' everyday behavior, their acceptance of spirituality, attitude toward drugs, self-esteem, their coping skills and loneliness were examined. The results revealed: a.. Negative partial correlation between loneliness and everyday behavior. b.. Negative partial correlation between loneliness and positive/effective coping skills. c.. Positive partial correlation between acceptance of 'spirituality' and attitude toward drugs. d.. Positive partial correlation between acceptance of 'spirituality' and positive/effective coping skills. These results suggest that the acceptance of 'spirituality' and decreasing loneliness are important factors in the recovery from drug dependence.

Adaptation, Psychological↗
PubMed1999

Novel polymorphism in the promoter and coding regions of the human cholecystokinin B receptor gene: an association analysis with schizophrenia.

Genetic variations in the 5'-untranslated region and the coding region of the CCK-B receptor (CCK-BR) gene were investigated in healthy controls. Novel variants (-215 C-->A, Leu37Phe, Arg319Glu) were found in addition to the mutations (Val125Iso, His207His, Arg215His, 2491 C-->A) reported previously. In the present study, association analysis was carried out for these variants between 80 unrelated schizophrenic patients and 100 healthy controls. The genotype frequency of the -215 C-->A nucleotide substitution in the 5'-untranslated region of CCK-BR gene was significantly higher in the schizophrenic patients than in the controls (6.25%, P = 0.037). However, the difference was not significant after Bonferroni correction for multiple comparisons. Moreover, no association was found between the clinical characteristics of the patients and the genotype frequencies of the variants. These results suggest that the CCK-BR gene polymorphisms have no association with schizophrenia nor its clinical heterogeneity. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:700-704, 1999.

5' Untranslated Regions↗
PubMed1999

Theoretical evaluation of a model of the catalytic triads of serine and cysteine proteases by ab initio molecular orbital calculation.

Serine and cysteine proteases are structurally distinct families of proteolytic enzymes that exert analogous catalytic reactions. It is known that serine, histidine, and aspartate residues are involved in a putative catalytic triad of serine proteases whereas cysteine, histidine and aspartate (or asparagine) are involved in that of cysteine proteases. Although the overall three-dimensional structures of the two classes of proteases are quite different, a similar feature of the catalytic mechanism can be observed. We carried out a theoretical study in the gas phase on their two catalytic steps using ab initio molecular orbital calculation to evaluate the efficiency of each proteolytic activity. To examine the key aspects of the catalytic processes in their active sites, we employed simple molecular models, in which serine and histidine were substituted for by CH3OH and CH3SH, respectively, and aspartate by CH3CO2-. Molecular geometries of the two models were fully optimized by an energy-gradient method. The activation energies for proton transfer in the proteolytic steps and the total energies of each molecule in the intermediate states were calculated. These results revealed that the activation energy for proton transfer in the CH3SH-His-CH3CO2-system was smaller by 11 kcal mol-1than that of the CH3OH-His-CH3CO2-system. The calculated potential energy surface and the relative magnitudes of all steps in these reaction paths with regard to double proton transfer supported the above results. Taken together, these results indicated that the Cys-His-Asp proteolytic system might work more efficiently than the Ser-His Asp system.

Animals↗
PubMed1999

Novel variants in the promoter region of the CREB gene in schizophrenic patients.

Cyclic AMP-responsive element-binding protein (CREB) is one of the messenger molecules involved in intracellular signal transduction pathways used by most dopamine and serotonin receptor subtypes. In addition, CREB stimulates the expression of a number of genes, alterations in the expression of which may be associated with schizophrenia. The promoter region of the human CREB gene was therefore analyzed to identify genetic variants that may lead to the modification of CREB expression and contribute to schizophrenia. Eighty unrelated schizophrenics and 100 healthy controls were screened for genetic variants of the CREB gene by SSCP analysis, followed by direct sequencing of PCR products. Two novel variants (-933T-->C and -413G-->A) were found only in schizophrenics. A patient with the -933T-->C variant had unusual clinical characteristics in addition to typical schizophrenic symptoms.

Cyclic AMP Response Element-Binding Protein↗
PubMed1998

Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia.

Dysfunction of serotonin systems has been implicated in schizophrenia. In the present study, the human 5-HT1A receptor gene containing the 5' untranslated region was screened in order to detect genetic variations, through which alteration of protein function or level of expression might contribute to schizophrenia. Genomic DNAs were isolated from whole-blood samples of 61 unrelated schizophrenic patients and 100 healthy controls. Genetic variations were screened systematically by single-strand conformational polymorphism (SSCP) analysis, followed by direct sequencing of polymerase chain reaction (PCR) product as well as restriction fragment-length polymorphism (RFLP). The novel mutations (-51T --> C, -152C --> G, -321G --> C, -480delA, and -581C --> A) were found in the 5' untranslated region. Furthermore, we found a novel missense mutation (Gly272Asp) in the coding region in addition to the mutations (Pro16Leu, 294G --> A, and 549C --> T) reported previously. No significant differences in genotype frequencies as well as allele frequencies were found between patients and controls. Our data provided no evidence of association between schizophrenia and the variants in the 5' untranslated region as well as the coding region of the human 5-HT1A receptor gene.

Genetic Markers↗
PubMed1998

Molecular cloning and characterization of mouse ficolin-A.

A novel ficolin-related gene was isolated from the mouse liver lambda ZAPII cDNA library. The protein encoded by this gene consists of both collagen- and fibrinogen-like domains, which are common features of the ficolin family, and was named mouse ficolin-A. The amino acid sequence of mouse ficolin-A is 60.2, 59.8, 59.8, and 59.6% identical to those of porcine ficolin-alpha, -beta, human ficolin-1, and EBP-37/P35, respectively. Northern blot analysis showed that mRNA of mouse ficolin-A is highly expressed in liver and spleen. Immunoblot analysis using an anti-mouse ficolin-A antiserum showed that mouse ficolin-A is a plasma protein with binding activity to elastin and GlcNAc.

Acetylglucosamine↗
PubMed1998

Role of oxidant stress and antioxidant protection in acephate-induced renal tubular cytotoxicity.

Acephate (AT) is an organophosphate (OP) insecticide. Due to their reputation for low environmental persistence, OP pesticides are often used indiscriminately resulting in detrimental exposure to humans and other nontarget species. Although the toxicity of OP compounds is primarily through blockade of neural transmission via inhibition of acetylcholinesterase, studies have revealed histopathological alterations in the renal proximal tubules, suggesting a role for additional mechanisms in renal toxicity. It is our hypothesis that Reactive Oxygen Species (ROS) may play a role in OP-induced renal tubular injury for the following reasoning. Renal tubular cells concentrate many nephrotoxic chemicals including OPs, and renal injury from many of these compounds has been shown to arise from excessive ROS production. Furthermore, it has been established that many phosphorothiolates, which are sulfur-containing OPs and constitute the class of OP compounds to which AT belongs, are S-oxidized to highly reactive intermediates within cells and tissues. Because of these considerations, we examined whether ROS play a role in OP-induced renal tubular epithelial cell (LLC-PK1) toxicity using AT as a prototype. AT produced a concentration- and time-dependent increase in cell damage in LLC-PK1 cells, measured by lactate dehydrogenase (LDH, % of total) leakage. The cytotoxicity (LDH) induced by 2500 ppm of AT over 72 h was significantly suppressed by antioxidants 2-methylaminochroman (2-MAC) and desferrioxamine (DFO). H2O2 levels were significantly elevated following exposure of LLC-PK1 cells to 2500 ppm of AT. Malondialdehyde (MDA) formation was also significantly increased in AT-exposed cells compared to the control cells, indicating the occurrence of enhanced lipid peroxidation. 2-MAC and DFO, in addition to providing cytoprotection, inhibited AT-induced MDA generation in a significant and concentration-dependent manner. Results from this study, which is the first to explore the toxic effects of AT on renal tubular cells, demonstrate that toxic action of AT on kidney cells is partly through an ROS-mediated mechanism. Based on these direct in vitro findings, we further hypothesize that oxidant stress may play a role in the pathogenesis of AT-induced acute tubular necrosis and renal dysfunction observed in cases of AT overdoses.

Animals↗
PubMed1998

Familial hemiplegic migraine with irreversible brain damage.

Familial hemiplegic migraine (FHM) is an autosomal dominant syndrome characterized by recurrent episodes of varying degrees of hemiparesis associated with migraine. The aura including hemiparesis may be prolonged and in severe attacks may often be associated with confusion or coma. We describe a case of FHM whose aura was atypically prolonged and resulted in irreversible brain deficit which on magnetic resonance imaging (MRI) was suggestive of cortical hyperperfusion. A subsequent MRI showed left brain atrophy.

Adult↗
PubMed1997

Overproduction of Mpd2p suppresses the lethality of protein disulfide isomerase depletion in a CXXC sequence dependent manner.

The third multicopy suppressor gene of the PDI1 deletion from Saccharomyces cerevisiae, MPD2, was isolated and characterized. The MPD2 gene encodes a protein with a putative signal sequence, ER retention signal, and a disulfide isomerase active site like sequence. The amino acid sequence around the active site like sequence is similar to the thioredoxin-like domains of PDI and PDI related proteins, although the similarity is comparatively low. A delta-pdi1 strain over-producing Mpd2p showed slow growth and was sensitive to 1 mM dithiothreitol. Mpd2p can be detected in wild type cells and is a glycoprotein. Although the MPD2 gene was not essential for growth, overexpression of the gene partially restored the maturation defect of carboxypeptidase Y caused by the PDI1 deletion. Mutagenesis analysis revealed that Mpd2p can compensate for the loss of PDI with its CXXC sequence.

Amino Acid Sequence↗
PubMed1997

Theoretical study on the interaction between dopamine and its receptor by ab initio molecular orbital calculation.

Dopamine has been implicated in the function of a diverse set of central nervous system and peripheral functions. We theoretically evaluated the chemistry of interaction between dopamine and its receptor using ab initio molecular orbital calculation. First, we calculated the total energy of dopamine on either a protonated or deprotonated molecule at the meta- or para-position hydroxy group of the catechol ring, and then evaluated the hydrogen bond effect in these hydroxy groups. These results suggested that the meta-position hydroxy group was liable to be protonated, and subsequently deprotonated by a negatively charged receptor site. It was considered that proton flopping, which occurred within the receptor site via the meta-position hydroxy group, appeared to be essential for exerting the biological action of dopamine. On the other hand, the para-position hydroxy group of the catechol ring contributed to stabilization of a dopamine molecule at the receptor site through a hydrogen bond. Second, we showed that the side-chain amino group of dopamine was readily protonated and bound a negatively charged receptor site by coulomb interaction. Third, we calculated the highest occupied molecular orbital and lowest unoccupied molecular orbital to elucidate chemical reactivities of these functional groups on the electron level. From the molecular orbital contour maps, it was suggested that frontier orbital interaction was involved in the dopamine-receptor interaction, in which the meta- and para-position hydroxy groups may function as a proton acceptor and a proton donor, respectively. Considering these theoretical results together, we hereby propose a model of the dopamine-receptor interaction: (1) a protonation-deprotonation at the meta-position hydroxy group takes place, (2) the protonated side-chain amino group of dopamine binds to a negatively charged receptor site by an ionic bond, and (3) the para-position hydroxy group not only contributes to stabilization for dopamine binding but may also enhance the protonation-deprotonation at the meta-position through bond interaction along the pi-bond between OH and the benzene ring.

Dopamine↗
PubMed1997

Analysis of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects.

Bile acids are believed to play a role in the etiology of colorectal cancer. To examine the relationship between bile acids and colorectal neoplasia, bile acids in colon residual liquid or fecal material were analyzed in 18 patients with colorectal adenoma, 12 patients with colorectal cancer, and 18 healthy control subjects. High-performance liquid chromatography combined with immobilized 3 alpha-hydroxysteroid dehydrogenase in column form showed a significant elevation in the proportion of deoxycholic acid (P < 0.05), lithocholic acid (P < 0.05), secondary bile acids (deoxycholic acid plus lithocholic acid) (P < 0.02), and the chenodeoxycholic acid-lithocholic acid family (chenodeoxycholic acid plus lithocholic acid) (P < 0.05) in the colon residual liquid or fecal material of the patients with colorectal adenoma compared with proportions in the control subjects. A similar trend was noted in the patients with colorectal cancer compared to the control subjects. These findings suggested that an increase in the proportion of secondary bile acids, in particular, of lithocholic acid, was closely related to the pathogenesis of colorectal neoplasia.

Adenoma↗
PubMed1997

Significance of serum iron and ferritin in patients with colorectal adenomas.

BACKGROUND: Colorectal adenomas are often detected on mass screening, although detection rates with fecal occult blood tests are low. The relationship between colorectal adenomas and the resulting blood loss was examined indirectly, using serum iron and ferritin levels. METHODS: Serum iron and ferritin concentrations were measured in 184 men with colorectal adenomas (> or = 1 cm in 92; < 1 cm in 92) and in 92 healthy male controls. Values in the three groups were compared. In the patients with adenomas > or = 1 cm, serum iron and ferritin levels were compared on the basis of the site, number, histology, and degree of dysplasia of the adenoma. RESULTS: The mean serum iron level was significantly lower in patients with adenomas > or = 1 cm than in controls (P < 0.05), although this level did not differ significantly between those with adenomas < 1 cm and controls. The mean serum ferritin level also was significantly lower in patients with adenomas > or = 1 cm than in those with adenomas < 1 cm and controls (P < 0.05, P < 0.01, respectively), although this level did not differ between those with adenomas < 1 cm and controls. There was no difference in mean serum iron or ferritin levels on the basis of the site, number, histology, or degree of dysplasia of the adenoma. CONCLUSIONS: We conclude that decreased serum iron and ferritin levels are related only to adenoma size and that adenomas > or = 1 cm may bleed steadily, resulting in iron deficiency. However, low dietary intake of iron and fiber may be one of the causes of low serum iron and ferritin.

Adenoma↗
PubMed1997

[Steroid responsive chronic brainstem encephalitis featuring mental symptoms, abnormal eye movement and cerebellar ataxia].

A 53-year-old man presented with progressive ataxia two and a half years prior to admission. Initially he was treated in a local hospital for 4 months with a diagnosis of spinocerebellar degeneration. Subsequently he developed psychomotor excitement with hallucination and was admitted to a mental hospital for 7 months with a diagnosis of Wernicke's encephalopathy. After a year of partial remission, he presented with increasing difficulty in thinking and walking. On admission he developed mental agitation and excitement, ocular flutter and opsoclonus, and prominent cerebellar ataxia. A lymphocytic pleocytosis in the CSF and a high-intensity lesion in the superior cerebellar peduncle of the upper brainstem revealed on a T2-weighted MRI led to a diagnosis of brainstem encephalitis. Treatment with steroid (two series of 3 days of 1,000mg methylprednisolone DIV, followed by 60mg oral prednisolone) brought about a dramatic improvement in mental and ocular symptoms corresponding with the CSF findings. He was left with mild cerebellar ataxia and returned to work on a small dose of steroids. Differential diagnoses including Bickerstaff's encephalitis and pathomechanism were discussed.

Brain Stem↗
PubMed1996

The defective secretion of a naturally occurring alpha-1-antichymotrypsin variant with a frameshift mutation.

A newly found variant alpha-1-antichymotrypsin (ACT), ACT Isehara-2, has a deletion of two bases (AA) at codon 391 near the carboxyl terminus. This frameshift mutation caused a change in the amino acid sequence and generated 10 extra amino acids (408 amino acids total) [Tsuda, M., Sei, Y., Matsumoto, M., Kamiguchi, H., Yamamoto, Y., Shinohara, Y., Igarashi, T. & Yamamura, M. (1992) Hum. Genet. 91. 467-468]. The serum ACT levels in three unrelated heterozygotes with this mutant ACT gene were 37% 49% and 54% that of the normal individuals. To examine the reduced serum levels, the normal ACT and the mutant ACT created by site-directed mutagenesis were transfected into COS-7 cells for comparison. The value for the retention rate (intracellular ACT/total ACT) was apparently higher in the cells expressing mutant ACT Isehara-2 than those bearing the normal gene. In the pulse-chase experiments, the secretion of the synthesized mutant ACT into the medium was not observed, whereas the normal ACT was mostly secreted as a 64-kDa form. The endoglycosidase H digestion and an electron microscopic analysis indicated that the retained mutant ACT was present in the endoplasmic reticulum. These results provide the biochemical basis for the decreased serum ACT level of individuals with ACT Isehara-2, and suggest the importance of the carboxyl-terminal region for its secretion.

Amino Acid Sequence↗