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Biomedical subjects

K Yamada

Publications and source records attributed to K Yamada.

At least 253 records · Page 14Linked to original sources
PubMed2001

Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2.

Isolated strabismus affects 1-5% of the general population. Most forms of strabismus are multifactorial in origin; although there is probably an inherited component, the genetics of these disorders remain unclear. The congenital fibrosis syndromes (CFS) represent a subset of monogenic isolated strabismic disorders that are characterized by restrictive ophthalmoplegia, and include congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DURS). Neuropathologic studies indicate that these disorders may result from the maldevelopment of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. To date, five CFS loci have been mapped (FEOM1, FEOM2, FEOM3, DURS1 and DURS2), but no genes have been identified. Here, we report three mutations in ARIX (also known as PHOX2A) in four CFEOM2 pedigrees. ARIX encodes a homeodomain transcription factor protein previously shown to be required for nIII/nIV development in mouse and zebrafish. Two of the mutations are predicted to disrupt splicing, whereas the third alters an amino acid within the conserved brachyury-like domain. These findings confirm the hypothesis that CFEOM2 results from the abnormal development of nIII/nIV (ref. 7) and emphasize a critical role for ARIX in the development of these midbrain motor nuclei.

Amino Acid Sequence↗
PubMed2001

Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor.

In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. Mice, which received morphine (10 mg kg(-1) s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg(-1) i.p.) on the 6th day. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg(-1) i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. In naïve mice, acute morphine treatment (10 mg kg(-1) s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg(-1) i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples.

In our search for candidate genes for affective disorder on the short arm of chromosome 18, we cloned IMPA2, a previously unreported myo-inositol monophosphatase gene, that maps to 18p11.2. We determined its genomic structure and detected three new single nucleotide polymorphisms (SNPs). In the present study, we screened the gene further to search for additional polymorphisms in Japanese samples and identified seven other SNPs, including a novel missense mutation. These polymorphisms clustered into three regions of the gene. Three relatively informative SNPs, 58G>A, IVS1--15G>A and 800C>T from clusters 1, 2 and 3, respectively, were selected for association tests using a case-control design. The Japanese cohort included 302 schizophrenics, 205 patients with affective disorder and 308 controls. Genotyping was done either by melting curve analysis on the LightCycler or by sequencing. All three SNPs showed significant genotypic association (nominal P = 0.031--0.0001) with schizophrenia, but not with affective disorder. These findings increase the relevance of 18p11.2 to schizophrenia susceptibility because GNAL, which has been shown previously to be implicated in schizophrenia in an independent study, is in close physical proximity to IMPA2. Our findings suggest that IMPA2 or a gene nearby may contribute to the overall genetic risk for schizophrenia among Japanese.

Adult↗
PubMed2001

Identification of a compound short tandem repeat stretch in the 5'-upstream region of the cholecystokinin gene, and its association with panic disorder but not with schizophrenia.

The cholecystokinin gene (CCK) is thought to play a role in the pathogenesis of both panic disorder and schizophrenia. In this study, we have extended the 5'-upstream sequence of the CCK gene, and identified a compound short tandem repeat (STR), located approximately -2.2 to -1.8 kb from the cap site. This STR was found to be polymorphic with ten different allele lengths. Case-control studies using 73 panic patients, 305 schizophrenics and 252 controls showed a significant allelic association with panic disorder (P = 0.025), but not with schizophrenia. Dividing the STR alleles into three classes according to length, Long (L), Medium (M) and Short (S), produced strong genotypic (MM) (nominal P = 0.0014) and allelic (M) (nominal P = 0.0079) associations with panic disorder. screening the newly extended promoter region detected not only the previously identified -36c>t and -188a>g single nucleotide polymorphisms (SNPs) but a new rare snp, -345g>C. Neither of the former two SNPs showed significant association with either panic disorder or schizophrenia. Haplotypic distributions of the STR and SNPs -188 and -36 were significantly different between panic samples and controls (P = 0.0003). These findings suggest that the novel STR or a nearby variant may confer susceptibility to the development of panic disorder.

5' Untranslated Regions↗
PubMed2001

Patterns of pelvic invasion are prognostic in the treatment of locally recurrent rectal cancer.

BACKGROUND: Local recurrence of rectal cancer after curative resection remains a difficult clinical problem. The aim of this study was to elucidate prognostic risk factors after resection of recurrent cancer. METHODS: Between January 1983 and December 1999, 83 patients with locally recurrent rectal cancer were studied retrospectively for survival benefit by re-resection. Sixty patients underwent resection for recurrent cancer, including total pelvic exenteration in 30 patients and sacrectomy in 23 patients. The extent of locally recurrent tumour was classified by the pattern of pelvic invasion as follows: localized, sacral invasion and lateral invasion. RESULTS: Multivariate analysis showed that the pattern of pelvic invasion was a significant prognostic factor which independently influenced survival after resection of recurrent cancer (P < 0.001). The 5-year survival rates were 38 per cent in the localized type (n = 27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral invasive type (n = 17). CONCLUSION: Resection for locally recurrent rectal cancer is potentially curative in patients with localized or sacral invasive patterns of recurrence. Alternatives should be explored in patients with recurrence involving the lateral pelvic wall.

Adult↗
PubMed2001

Expression of opsin molecule in cultured murine melanocyte.

Recently, we demonstrated the expression of rhodopsin in the tail fin of the Xenopus tadpole, in which photosensitive melanophores exist (Miyashita et al, The photoreceptor molecules in Xenopus tadpole tail fin, in which melanophores exist. Zool Sci 18:671-674, 2001). The presence of opsin molecules in pigment cells of lower vertebrates raises the possibility that pigment cells in animal skin function as photosensors generally. To explore this possibility in higher vertebrates, we tried to detect photoreception molecules in mammalian melanocytes. We extracted total RNA from Melan a2, a cell line of immortal murine melanocyte, which is derived from C57BL mice. The DNA sequence obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was homologous to the corresponding portion of the sequence of ocular rhodopsin of mice. Western blotting and fluorescent immunocytochemistry showed the existence of the opsin protein in the melanocytes. Another cell line, EL4, which is derived from lymphoma of C57BL/6N, scarcely expresses opsin mRNA, as judged by RT-PCR. Thus expression of the opsin gene is not ubiquitous among immortal cell lines. Detection of rhodopsin mRNA in murine tissues of C57BL/6N by RT-PCR showed its presence in the eye and skin but not in the liver. The role of the opsin molecule in melanocyte is not known at present, but this will provide additional insight into photoreception systems in animal skin.

Animals↗
PubMed2001

NMDA receptor subunits GluRepsilon1, GluRepsilon3 and GluRzeta1 are enriched at the mossy fibre-granule cell synapse in the adult mouse cerebellum.

Cerebellar N-methyl-D-aspartate (NMDA) receptors are concentrated in the granular layer and are involved in motor coordination and the induction of long-term potentiation at mossy fibre-granule cell synapses. In the present study, we used immunohistochemistry to examine the distribution of NMDA receptor subunits in the adult mouse cerebellum. We found that appropriate pepsin pretreatment of sections greatly enhanced the sensitivity and specificity of immunohistochemical detection. As a result, intense immunolabelling for GluRepsilon1 (NR2A), GluRepsilon3 (NR2C), and GluRzeta1 (NR1) all appeared in synaptic glomeruli of the granular layer. Double immunofluorescence showed that these subunits were colocalized in individual synaptic glomeruli. Within the glomerulus, NMDA receptor subunits were located between centrally-located huge mossy fibre terminals and peripherally-located tiny Golgi axon terminals. By immunoelectron microscopy, all three subunits were detected at the postsynaptic junction in granule cell dendrites, forming synapses with mossy fibre terminals. Consistent with the known functional localization, GluRepsilon1, GluRepsilon3, and GluRzeta1 are, thus, anatomically concentrated at the mossy fibre-granule cell synapse. By contrast, immunohistochemical signals were very low in Purkinje cell somata and dendrites in the molecular layer. The lack of GluRzeta1 immunolabelling in Purkinje cells was unexpected because the cells express GluRzeta1 mRNA at high levels and high levels of GluRzeta1 protein in the molecular layer were revealed by immunoblot. As Purkinje cells are exceptionally lacking GluRepsilon expression, the discrepant result may provide in vivo evidence suggesting the importance of accompanying GluRepsilon subunits in synaptic localization of GluRzeta1.

Animals↗
PubMed2001

Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator.

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A-induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.

Androstadienes↗
PubMed2001

Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator.

Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation-inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation-inducing activity was more potent than those of all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.

Acute Disease↗
PubMed2001

Two types of HKT transporters with different properties of Na+ and K+ transport in Oryza sativa.

It is thought that Na+ and K+ homeostasis is crucial for salt-tolerance in plants. To better understand the Na+ and K+ homeostasis in important crop rice (Oryza sativa L.), a cDNA homologous to the wheat HKT1 encoding K+-Na+ symporter was isolated from japonica rice, cv Nipponbare (Ni-OsHKT1). We also isolated two cDNAs homologous to Ni-OsHKT1 from salt-tolerant indica rice, cv Pokkali (Po-OsHKT1, Po-OsHKT2). The predicted amino acid sequence of Ni-OsHKT1 shares 100% identity with Po-OsHKT1 and 91% identity with Po-OsHKT2, and they are 66-67% identical to wheat HKT1. Low-K+ conditions (less than 3 mM) induced the expression of all three OsHKT genes in roots, but mRNA accumulation was inhibited by the presence of 30 mM Na+. We further characterized the ion-transport properties of OsHKT1 and OsHKT2 using an expression system in the heterologous cells, yeast and Xenopus oocytes. OsHKT2 was capable of completely rescuing a K+-uptake deficiency mutation in yeast, whereas OsHKT1 was not under K+-limiting conditions. When OsHKTs were expressed in Na+-sensitive yeast, OsHKT1 rendered the cells more Na+-sensitive than did OsHKT2 in high NaCl conditions. The electrophysiological experiments for OsHKT1 expressed in Xenopus oocytes revealed that external Na+, but not K+, shifted the reversal potential toward depolarization. In contrast, for OsHKT2 either Na+ or K+ in the external solution shifted the reversal potential toward depolarization under the mixed Na+ and K+ containing solutions. These results suggest that two isoforms of HKT transporters, a Na+ transporter (OsHKT1) and a Na+- and K+-coupled transporter (OsHKT2), may act harmoniously in the salt tolerant indica rice.

Amino Acid Sequence↗
PubMed2001

Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.

BACKGROUND: Clusterin is a soluble complement regulatory protein that binds to C5b-7 and inhibits generation of membrane attack complex, C5b-9. Glomerular deposition of clusterin has been observed in human and experimental membranous nephropathy in association with C5b-9 and immune deposits. However, it is controversial as to whether clusterin observed in glomeruli is synthesized by the resident glomerular cells or is derived from the circulation. We examined whether clusterin is expressed by resident glomerular cells exposed to complement-mediated injury. METHODS: In vitro, cultured mesangial cells were exposed to antithymocyte serum immunoglobulin G and 5% normal rat serum as a complement source. In vivo, we induced anti-Thy1 nephritis in rats and examined the kidneys on days 8 and 29. RESULTS: We observed increased expression of clusterin in cultured rat glomerular mesangial cells stimulated by sublytic complement attack. We also demonstrated that in comparison with control rats, both a marked increase in clusterin mRNA in the glomeruli and marked deposition of clusterin protein in the mesangial area occurred in the OX-7-treated rats on day 8 in association with C5b-9 deposition and on day 29. CONCLUSION: Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack.

Animals↗
PubMed2001

Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression.

BACKGROUND: The angiotensin-converting enzyme (ACE) I/D genotype affects serum ACE levels and the onset and progression of renal disease, but little is known about the mechanism. We investigated a possible association between the ACE I/D genotype and renal ACE mRNA levels in healthy subjects. METHODS: Renal biopsy samples were obtained from 50 healthy kidney donors. The ACE I/D genotype was determined by polymerase chain reaction (PCR). Renal ACE mRNA quantification was performed by competitive RNA-PCR. In situ hybridization (ISH) for ACE mRNA on renal biopsy specimens was also performed. RESULTS: The number of ACE transcripts in 100 ng of total RNA was significantly (P < 0.01) lower in subjects with II genotype (5.6 +/- 5.3 x 10(5), N = 20) compared with those with the ID (17.9 +/- 13.6 x 10(5), N = 23) or the DD genotype (36.9 +/- 14.6 x 10(5), N = 7) in healthy donors. The ISH studies showed that both tubular and glomerular ACE mRNA expressions were weak in subjects with the II genotype, intermediate in subjects with ID genotype, and strong in subjects with DD genotype. CONCLUSIONS: It is suggested that renal ACE gene expression is associated with the ACE I/D genotype in healthy Japanese subjects.

Biopsy↗
PubMed2001

Insulin secretion to glucose as well as nonglucose stimuli is impaired in spontaneously diabetic Nagoya-Shibata-Yasuda mice.

To clarify the mechanisms of impaired insulin secretion in Nagoya-Shibata-Yasuda (NSY) mice, an inbred strain of mice with spontaneous development of type 2 (non-insulin-dependent) diabetes mellitus, the insulin response to glucose (5.5 to 27.8 mmol/L) and nonglucose stimuli (glibenclamide, arginine, and BayK8644, a Ca-channel opener) was studied in vitro using isolated islets from male NSY and control C3H/He mice at 36 weeks of age by the batch incubation method. Insulin response to 5.5 mmol/L glucose was not significantly different between NSY and C3H/He mice, but insulin response to a high concentration of glucose (> or = 11.1 mmol/L) was significantly smaller in NSY mice than in control C3H/He mice. The dose-response curve of insulin secretion showed a markedly reduced maximum response, but almost normal glucose sensitivity in NSY islets. Insulin responses to glibenclamide (1 mmol/L), arginine (20 mmol/L), and BayK8644 (0.1 mmol/L) were also significantly smaller in NSY mice than in C3H/He mice. Insulin content of islets, in contrast, was significantly higher in NSY mice than in C3H/He mice. The impaired insulin response to glucose and nonglucose stimuli together with higher insulin content in islets in the NSY mouse suggest that a defect in voltage-dependent Ca(2+)-channel or thereafter in the cascade of insulin secretion may be responsible for impaired insulin secretion in NSY mice. NSY mice, therefore, could be a novel animal model of type 2 diabetes with a defect in insulin secretion at a different site from that in previously known animal models.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Comparison between 1-hour and 24-hour drain clamping using diluted epinephrine solution after total knee arthroplasty.

A prospective study was conducted to determine the optimal clamping time in the drain-clamping method after total knee arthroplasty. In a randomized trial, 44 primary total knee arthroplasties were studied after the drain-clamping method using diluted epinephrine solution was applied for 1 hour or 24 hours. The mean blood loss into the drains was less in the 24-hour group compared with the 1-hour group (35 mL in the 24-hour group and 247 mL in the 1-hour group). No statistically significant difference was found in hemoglobin or hematocrit levels between the 2 groups after surgery. Only 1 patient (4.5%) in the 1-hour group and 2 patients (9.1%) in the 24-hour group received blood transfusion. There were significantly more complications in the 24-hour group (P <.05). Two patients (9.1%) in this group required additional surgery. One-hour clamping is preferable to 24-hour clamping in the drain-clamping method for minimizing complications.

Aged↗
PubMed2001

Dietary gamma-linolenic acid dose-dependently modifies fatty acid composition and immune parameters in rats.

gamma-linolenic acid (GLA) has been reported to improve several inflammatory disorders through regulation of eicosanoid production. However, since GLA is a precursor of arachidonic acid, it may bring about increasing tissue arachidonic acid levels with subsequent pro-inflammatory events. To explore this possibility, we examined the effect of high-dose GLA acid on the fatty acid profile of immune cells, leukotriene B4 production by peritoneal exudate cells and immunoglobulin productivity of mesenteric lymph node lymphocytes of Sprague-Dawley rats. Male rats were fed 10% fat diets containing graded levels, 0, 20, 40 and 60% of GLA for 3 weeks. The results showed the distinction in activity of metabolizing GLA between immune cells and liver. Thus, in immune cells such as mesenteric lymph node and spleen lymphocytes and peritoneal exudate cells, more dihomo-gamma-linolenic acid was found than in the liver. Leukotriene B4 production by peritoneal exudate cells was significantly suppressed when fed the highest level of GLA suggesting a lower risk of allergic reaction. Moreover, immunoglobulin productivity in mesenteric lymph node lymphocytes was promoted by dietary GLA. The present study indicates that a high dose of GLA may exert anti-inflammatory effects through suppression of leukotriene B4 release and strengthening of gut immune system, thus ameliorating allergic reaction.

Animals↗
PubMed2001

Neurinoma of the greater superficial petrosal nerve developed acute facial palsy: case report and review of the literature.

The authors report on a patient with a greater superficial petrosal nerve neurinoma. The patient developed severe acute facial palsy and the palsy improved soon after removal of the tumor. We review of the literature and describe its rarity and surgical treatment with regard to other facial nerve neurinomas originating from the main trunk of the facial nerve.

Case Reports↗
PubMed2001

Condylar bony change, disk displacement, and signs and symptoms of TMJ disorders in orthognathic surgery patients.

OBJECTIVE: We sought to investigate the relationship between condylar bony change and disk displacement with respect to the signs and symptoms of temporomandibular joint (TMJ) disorders in patients undergoing orthognathic surgery. STUDY DESIGN: We performed a cross-sectional retrospective study of the pretreatment helical computed tomography scans of 129 orthognathic surgery patients. RESULTS: Condylar bony change, unilaterally or bilaterally, was found in 35.7% of the subjects and 24.4% of the joints. Disk displacement, unilaterally or bilaterally, was seen in 41.4% of the subjects and 29.5% of the joints. The type of craniofacial deformity was significantly associated with condylar bony change and disk displacement. No association of clinical symptoms with respect to craniofacial deformity, condylar bony change, or disk displacement was found except in the case of TMJ sounds. CONCLUSION: The results suggested that craniofacial deformity might be related to TMJ disorders, but the only clinical symptom associated with types of craniofacial deformity was TMJ sounds.

Adolescent↗