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Biomedical subjects

S Kajihara

Publications and source records attributed to S Kajihara.

At least 19 recordsLinked to original sources

Wiener filter-magnetoencephalography of visual cortical activity.

This paper reports a revised Wiener filter to resolve the inverse problem for magnetoencephalograms (MEGs) according to the structural and functional constraints based on magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI). Wiener filter-MEG imaging for half field stimulation with the chromatic stimulus resolved fast, slow and late responses in V1, V4 and the inferotemporal cortex, respectively. The time courses of these responses were roughly comparable with those reported by unit recording studies of the corresponding monkey visual cortical areas. Wiener filter-MEG imaging had comparable spatial resolution and better signal to noise ratio than fMRI. The background noise was robust in fMRI responses, but became virtually eliminated in Wiener filter responses. Wiener filter-MEG imaging with upper and lower quadrant field stimulation demonstrated V1 responses differentially distributed respectively in the lower and upper banks of the calcarine sulcus. These results demonstrate that responses in two cortical areas facing close to each other can be resolved by Wiener filter-MEG. The present method provides a way to image brain activities with millisecond- and millimeter-order spatiotemporal resolution.

Adult↗

Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS: To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS: The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol. CONCLUSIONS: These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.

Adult↗

Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.

BACKGROUND: CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. METHODS: We examined 831 adults undergoing health screening. The majority (780) was Pro90 homozygous for the CD36 gene product, but 51 displayed a CD36 mutation (2 homozygous and 49 heterozygous for Ser90). This is the major mutation site involved in CD36 deficiency in Japanese. RESULTS: Among parameters related to insulin resistance, there were no differences in body mass index (BMI), HDL cholesterol, total cholesterol, triglycerides, insulin and insulin resistance index (HOMA IR), or blood pressure between 91 normal subjects (45 male and 46 female) randomly selected from the 780 Pro90 homozygotes and the 51 (29 male and 22 females) CD36-deficient subjects (Ser90 homozygote and Pro90Ser heterozygote). Free fatty acid concentrations, however, were higher in Ser90 CD36 subjects than in Pro90 control subjects. CONCLUSIONS: The CD36Pro90Ser mutation is not necessarily related to the insulin resistance syndrome, but is associated with high free fatty acid concentrations in Japanese.

Adult↗

Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma.

Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.

Aged↗

Moving mesh method for reconstructing some spread sources in the brain.

The purpose of this paper is to propose a new algorithm for the analysis of biomagnetic field data obtained from magnetoencephalography (MEG) measurements. This new method overcomes two major problems faced by the current method of data analysis. The first problem is the need to determine the number of sites of brain activity before calculations can be performed. The second problem is inability of the analysis to provide any information regarding the volume of the brain activity. The new data analysis method, called the Moving Mesh Method (MMM), is capable of analyzing MEG data without the need to determine the number of sources beforehand. In addition, the MMM determines the location of brain activity as a three dimensional volume, instead of as a point source of activity. The MMM uses an iterative method of calculating the position of the sources to achieve greater accuracy, and a regularized g-inverse matrix to stabilize its solution. The feasibility of the MMM was examined by two methods. First, a computer simulation was used to confirm the MMM's capability to analyzing MEG data. In the second experiment, the MMM was applied to analyze somatosensory evoked fields obtained using a new imaging system (Shimadzu Biomagnetic Imaging System, Model-100). From the interpretation of the results, we have concluded that the MMM is a feasible method of biomagnetic data analysis.

Algorithms↗

Relationship between left atrial spontaneous echo contrast and the features of middle cerebral artery territory in nonvalvular atrial fibrillation.

We investigated the relationship between left atrial spontaneous echo contrast (SEC) and cerebrovascular features in nonvalvular atrial fibrillation (NVAF). Few reports have been published to compare cardiac and cerebrovascular imaging in patients with NVAF. Forty-four patients with NVAF were studied using transesophageal echocardiography and non-invasive imaging including magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and transcranial color Doppler imaging (TCD) in the middle cerebral artery (MCA) territory. The symptomatic severity was divided into asymptomatic, transient ischemic attack (TIA), and stroke. The severity of the MRI findings was divided into normal, small, and large infarcts. The severity of the MRA findings was divided into normal, attenuation, and occlusion. MCA was bilaterally scanned and a side-to-side asymmetry ratio of pulsatility index (PI) was measured. The severity of SEC was divided into normal, SEC, and thrombi. Five patients with other thromboembolic risk or poor results of TCD were excluded. SEC and thrombi were detected in 12 (30%) and in 3 patients (5%), respectively. TIA and stroke were detected in 8 (21%) and in 17 patients (44%), respectively. Small and large infarcts were detected in 9 (23%) and in 18 patients (46%), respectively, on MRI. Attenuation and occlusion were detected in 14 (36%) and in 8 patients (21%), respectively, on MRA. PI ratio was 1.21 +/- 0.25. SEC severity was highly associated with PI ratio and MRA severity in monovariate analysis (P < 0.005), P < 0.01, respectively). SEC severity was highly associated with PI ratio and MRA severity in stepwise multiple regression analysis (P = 0.0001, r = 0.630, n = 39). In patients with NVAF, left atrial SEC was highly related to attenuation or occlusion on MRA and imbalance of cerebral blood flow on TCD in the MCA territory.

Aged↗

A splice mutation in the human canalicular multispecific organic anion transporter gene causes Dubin-Johnson syndrome.

The human Dubin Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by chronic conjugated hyperbilirubinemia and impaired hepatobiliary transport of non-bile salt organic anions. A highly homologous phenotype exists in the transport deficient (TR-) Wistar rat, which has a defective canalicular multispecific organic anion transporter (cMOAT). This protein mediates adenosine triphosphate-dependent transport of a broad range of endogenous and xenobiotic compounds across the (apical) canalicular membrane of the hepatocyte. The cDNA encoding rat cMOAT has recently been cloned, and this mutation in the TR- rat has been identified. Subsequently the human homologue of rat cMOAT localized in the liver was found to be the cause of DJS. In an individual with DJS, we have identified a single novel nucleotide substitution in the exon-intron junction of the cMOAT gene which generates liver cDNA with a 67bp exon deletion.

Anion Transport Proteins↗

Case report: a long-term survivor of jejunal leiomyosarcoma with liver metastasis: effective transcathetel arterial embolization for hepatic metastatic foci.

We report a case of jejunal leiomyosarcoma with liver metastases in a 52-year-old Japanese male. An echogram demonstrated multiple cystic liver masses in April 1991. The diagnosis of metastatic leiomyosarcoma was made on the basis of characteristic hepatic angiography images and liver biopsy findings. The jejunal leiomyosarcoma was resected and unresectable liver metastatic foci were treated repeatedly with transcathetel arterial embolization. Transcathetel arterial embolization was considered to be effective in this case as the patient survived 4 years and 9 months after the first treatment.

Catheterization↗

Differential expression of laminin receptors in human hepatocellular carcinoma.

BACKGROUND: Laminin receptors are involved in cell-extracellular matrix interactions in malignant cells that show invasion and metastasis. Hepatocellular carcinoma frequently shows early invasion into blood vessels, and intrahepatic and extrahepatic metastases. However, the role of laminin receptors in hepatocellular carcinoma is unknown. AIMS: To examine the expression of mRNA for laminin receptors and their isoforms in hepatocellular carcinoma. METHODS: The expression of several laminin receptors, including alpha1 integrin, alpha6 integrin and its isoforms alpha6A and alpha6B, beta1 integrin and its isoforms beta1A and beta1B, and 32kD/67kDa laminin binding protein was examined in human hepatocellular carcinomas and non-cancerous liver tissues using the reverse transcription polymerase chain reaction. RESULTS: Alpha6 Integrin, beta1 integrin, and laminin binding protein showed notably increased expression in hepatocellular carcinoma, compared with non-cancerous liver tissue, although the alpha1 integrin did not show a significant change. Furthermore, beta1B integrin, a splicing variant of beta1 integrin, was overexpressed in hepatocellular carcinoma while the beta1A integrin isoform did not show significant changes between hepatocellular carcinoma and surrounding non-cancerous liver tissue. CONCLUSIONS: The differential upregulation of laminin receptors and their splicing isoforms was shown in hepatocellular carcinoma, suggesting that certain laminin receptors and their isoforms may be involved in the development and progression of hepatocellular carcinoma.

Aged↗

Influence of head model in biomagnetic source localization.

We evaluated the influence of the head model on biomagnetic source localization by utilizing a computer simulation. We localized the source of a magnetic field that was calculated using a realistic head model, and then evaluated the localization errors. It was seen that the sphere model adequately localized the dipole in cases near the sensor, but not in cases where the dipole was deeply situated.

Brain↗

Phylogenetic tree-based epidemiological analysis of hepatitis C virus transmission in a region of Japan with a high prevalence of infection.

Local clustering of hepatitis C virus (HCV) infection has been demonstrated in various regions in Japan. HCV genotypes have now been compared between infected individuals from districts of Saga prefecture with either a high (H district) or low (L district) prevalence of HCV-seropositivity. The prevalence of HCV genotype 1b was significantly higher (P < 0.001) in the H district (45/50; 90%) than in the L district (19/36; 52.8%). A phylogenetic tree was constructed based on the genomic sequences of viral isolates from 20 patients infected with genotype 1b in the H district. Almost all these HCV strains clustered in the same regions of the tree. With regard to risk factors for HCV transmission, the percentage of patients with a history of surgery was significantly higher in the H district than in the L district (58 versus 33.3%; P < 0.05). Of 20 patients infected with similar strains of HCV in the H district, 16 (80%) had at least one parenteral risk factor associated with medical care. These results indicate an increased transmission of similar strains of HCV in the H district as a result of nosocomial infection.

Base Sequence↗

Serum lipoprotein(a) levels before and after subtotal thyroidectomy in subjects with hyperthyroidism.

Lipoprotein(a) [Lp(a)], a lipoprotein that structurally resembles low-density lipoprotein (LDL), contains apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apo B). There exists a close inverse correlation between serum concentrations of LDL or apo B and concentrations of thyroid hormone in patients with thyroid disease, probably due to a change in LDL receptor activity. To clarify the relations between thyroid hormone and Lp(a), we measured serum Lp(a) levels in 13 hyperthyroid subjects before treatment (stage H), during the euthyroid stage induced immediately before performing a subtotal thyroidectomy (stage E), and during the hypothyroid stage observed transiently after the operation (stage L). The mean serum concentration of Lp(a) increased significantly (P = .01) from 9.4 mg/dL in stage H to 26.8 in stage L through the level of 15.5 mg/dL in stage E. There was no significant difference between the mean serum concentration of Lp(a) in these patients in stage E and healthy controls (14.2 mg/dL). There was a low but statistically significant negative correlation between the Lp(a) level and the serum free thyroxine (fT4) concentration (r = .31, P < .05). The results suggest that thyroid hormone is a potent modulator of Lp(a) metabolism.

Adult↗

Copy-dependent and position-independent expression of rat aldolase A gene.

In order to understand the molecular mechanisms of the temporal and spatial differences of gene expression in higher organisms, rat aldolase A gene carrying two distinct promoters was introduced into fertilized eggs and the resulting transgenic mice were analyzed. The transgene expression is tissue-specific and is developmentally regulated. In addition, the expression is regulated in a copy-dependent manner irrespective of where the transgene is integrated, suggesting that a mechanism excluding the effect of the integration site exists within the transgene itself. To explore the conformational change of this gene in the genome, the DNase I hypersensitive sites of the gene were examined. Three sites (DHS-1,2, and 3) were identified upstream and downstream of the gene and these sites were retained in the transgene as well as in the gene observed endogenously.

Animals↗

Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.

Adult↗

Position-independent, high-level, and correct regional expression of the rat aldolase C gene in the central nervous system of transgenic mice.

Aldolase C is mainly expressed in the central nervous system (CNS). To clarify the regulatory mechanisms for the CNS-specific expression, transgenic mice were created using two constructs of the rat aldolase C gene. A fusion gene comprising the 5' regulatory region of the aldolase C gene was expressed in a CNS-specific manner. However, the expression levels and the cellular localization of the gene varied among transgenic mice. The other construct, including both 5' and 3' regulatory regions of the gene, showed position-independent and high-level expression as well as the correct regional distribution in the CNS. These results indicate that the 13-kb sequence of the rat aldolase C gene contains sufficient information for faithful expression of the gene.

Animals↗

[Clinical investigation of HCV antibodies positive cases in the district with high mortality rate of liver diseases in Saga Prefecture].

The mortality and morbidity rates of chronic liver disease (CLD) have been extremely high for several years at Saga prefecture in Japan. Epidemiological studied revealed districts with high mortality rate of CLD (H-district). We measured C 100-3Ab and HCVCoreAb (CoreAb) in the H-district and observed high discrepancy between C100-3 and CoreAb. In order to examine pathogenesis of this discrepancy, we determined serum HCVRNA in these cases. The positive cases of HCV-Ab among 459 subjects were 33.6% (159). 59 subject were positive for both, 88 were only positive for CoreAb, 7 were only positive for C100-3Ab. Serum HCVRNA was detected in 92% (22/24) of both positive cases, in 67% (6/9) of only CoreAb positive cases, in 43% (3/7) of only C100-3Ab positive cases. These results suggested the cases positive for C-100-3 and CoreAb have chronic liver injury due to HCV infection, while the cases positive for only CoreAb involves healthy carrier or the memory state of HCV infection without liver injury.

Aged↗

Hereditary fructose intolerance caused by a nonsense mutation of the aldolase B gene.

The nucleotide sequence of a patient's aldolase B gene was determined and showed a substitution of a single nucleotide (C----A) at position 720 in the coding region, which resulted in the 240th amino acid, a cysteine, being changed to a stop codon (TGC----TGA). By an allele-specific oligonucleotide probe and polymerase chain reaction, the patient was shown to be homozygous for the mutation. To examine whether this mutation causes functional defect of the enzyme, the activity of the aldolase B from the patient, expressed in Escherichia coli by using expression plasmid, was measured. No activity was observed, and the predicted product was recovered from E. coli expression plasmid, indicating that this nonsense mutation was the cause of aldolase B deficiency.

Base Sequence↗