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Biomedical subjects

K Matsubara

Publications and source records attributed to K Matsubara.

At least 73 records · Page 4Linked to original sources
PubMed2000

The tissue distribution of lidocaine in acute death due to overdosing.

A 78-year-old woman committed double suicide with a bolus injection of 1 g of lidocaine hydrochloride. The tissue distribution of lidocaine in this fatal poisoning was investigated using an improved gas chromatographic method. The blood level was 42 microg/ml and the brain concentration was 70 miccro/g. Thus, the cause of death in this case was clearly diagnosed as lidocaine overdosing. The blood level of 42 microg/ml was higher than that calculated using the standard pharmacokinetic parameters. Lower blood/tissue ratios were also detected compared with the data described in the literature. These results indicated that the cardiac failure should have occurred immediately after the lidocaine injection. The present data show the distribution of lidocaine after acute death due to overdosing.

Journal Article↗
PubMed2000

Correlation between gene functions and developmental expression patterns in the mouse cerebellum.

Quantitative changes of 419 gene transcripts during postnatal mouse cerebellar development were accurately determined with a novel polymerase chain reaction (PCR)-based technique. About 70% of the genes showed differences in expression levels, and the magnitude of difference was relatively small. By hierarchic cluster analysis of developmental expression patterns, the genes were categorized into 19 clusters, which were subsequently assembled into four major groups: group 1, with elevation of gene expression throughout the time course; group 2, with relatively unchanged levels; group 3, with transiently high expression at approximately 12 days; and group 4, with highest expression at approximately 4 days. Genes related to brain functions were segregated into several clusters of group 1 and group 3: the same clusters in which cerebellum-specific genes were also segregated. Genes for protein synthesis belonged to group 4. Genes with housekeeping functions belonged to group 2. Western blotting analysis of representative protein products of each group revealed correlation with the mRNA level for those belonging to group 1 and group 4, but not necessarily in the other groups. The close correlation of algorithmically categorized temporal expression patterns of genes with their functions will be useful for estimating the functions of thousands of novel genes.

Animals↗
PubMed2000

Reproducibility and applicability of gallium replication as evaluated by biological specimen use.

Structures of biological surfaces pressed on to a pure liquid gallium surface were successfully traced on to the gallium surface by quick-freezing below the melting point (28.78 degrees C) in air or water for replication in scanning electron microscopy. Gallium's high surface tension (approximately 700 mN m(-1) at 30 degrees C) deteriorates the spatial resolution of replicas and destroys some types of specimens. Five different biological surfaces were replicated on to gallium surfaces to evaluate spatial resolution and specimen resistance, i.e. reproducibility and applicability. Gallium replication of jewel beetle wing and human hair demonstrated submicron spatial resolution in the horizontal direction at least. Trials of protozoa, bacteria, and culture cell replication showed that protozoa are suited to replication because the cell membrane has characteristic structures with sufficient resistance to the gallium surface.

Animals↗
PubMed2000

Urinary orotic acid levels in normal pregnancy and pregnancy-induced hypertension.

Our objective was to study the urinary levels of orotic acid in normal pregnancy and in pregnancy-induced hypertension. Such levels were measured using high-performance liquid chromatography with column-switching. The levels of urinary orotic acid (micromol/g creatinine) in normal pregnancy (n = 14) were 6.9 +/- 2.3 (first trimester), 10.1 +/- 2.4 (20 weeks) and 12.0 +/- 3.7 (30 weeks). In pregnancy-induced hypertension (n = 14), the corresponding levels were 6.5 +/- 1.7, 7.8 +/- 2.7 and 7.6 +/- 2.3, respectively. Normal pregnant subjects individually showed a significant elevation at 20 and 30 weeks of gestation as compared with those in the first trimester (p < 0.01). A high consumption of arginine in nitric oxide production during normal pregnancy may cause a physiological elevation of urinary orotic acid. The absence of an elevation in pregnancy-induced hypertension may be associated with a decrease in nitric oxide production.

Arginine↗
PubMed2000

Cardiogenic shock triggered by verapamil and atenolol: a case report of therapeutic experience with intravenous calcium.

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and bradycardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

Adrenergic beta-Antagonists↗
PubMed2000

Everyday breath hydrogen excretion profile in Japanese young female students.

A breath hydrogen test has been used widely as a noninvasive and simple method of detecting carbohydrate malabsorption as well as estimation of the small intestinal and orocecal transit time. By means of this method, we have examined the change in breath hydrogen concentration of young female students in their everyday life in order to reveal the breath hydrogen excretion profile under normal circumstances. In this survey, we have asked them to collect their own breath samples every one-hour as regularly as possible during one day from awakening until bedtime. We also asked them to complete the questionnaire concerning their dietary habit, dietary record and physical activities. Among the 43 subjects who gave the breath hydrogen records, 37 subjects excreted detectable hydrogen into their alveolar air. By comparing the changes in breath hydrogen concentration during the time of day, breath hydrogen excretions could be classified into two distinct patterns; more than half of the total hydrogen excretion occurred in the first half of the waking hours (designated as "pattern A", 18 cases) and in the latter half (designated as "pattern B", 19 cases). Taking into consideration the subjects' records of diets and physical activities, the early-pronounced breath hydrogen excretion observed among 18 "pattern A" students was probably resulted from the malabsorption of the dietary carbohydrate in the breakfast meals.

Adult↗
PubMed2000

Peroneal mononeuropathy in pediatric Hodgkin's disease.

A 12-year-old boy with Hodgkin's disease developed left peroneal nerve palsy during combination therapy with chemotherapy and low-dose irradiation. The palsy occurred twice; around 1-2 weeks after the second administration of vincristine in the second and third COPP (cyclophosphamide, vincristine, prednisolone, and procarbazine) regimens. Without any treatment, the peroneal neuropathy completely resolved clinically three months and electromyographically six months after the onset. He used to play television games for more than 6 hours a day with the legs crossed while sitting on the bedside. Compared to adult patients, little is known about the relationship between peroneal neuropathy and systemic malignant diseases in pediatric patients. This case shows for the first time that habitual leg crossing during potentially neurotoxic chemotherapy could induce peroneal mononeuropathy in a pediatric cancer patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases.

Peroxynitrite can nitrate tyrosine residues of proteins. We examined nitrotyrosine-containing proteins in cerebrospinal fluid of 66 patients with neurogenic disease by immunoblot analysis. Nitrated tyrosine residue-containing protein was observed in the cerebrospinal fluid and was concluded to be manganese superoxide dismutase (Mn-SOD). The nitrated Mn-SOD level was strikingly elevated in amyotrophic lateral sclerosis patients and was slightly increased in Alzheimer's and Parkinson's disease patients, whereas an elevated Mn-SOD level was observed only in progressive supranuclear palsy group.

Adult↗
PubMed2000

Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA.

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.

Base Sequence↗
PubMed1999

A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas.

Certain human DNA regions are strikingly undermethylated at CpG sites in sperm compared to adult somatic tissues. These sperm-specific hypomethylation sequences are thought to function early in embryogenesis or gametogenesis. By using the restriction landmark genomic scanning (RLGS) cloning method, we have isolated a novel sperm-specific hypomethylation sequence, the status of which changes during spermatogenesis, embryonal growth and differentiation. This sequence is a part of a new 'NotI repeat' consisting of a 1.4 kb repetitive unit sequence named DE-1. The sequence is GC-rich and has high homology to a CpG DNA clone that was isolated by a methyl CpG protein binding column, indicating that it was normally highly methylated. We investigated the methylation status of this sequence. In the normal genome the sequence was methylated, but in the human hepatocellular carcinoma (HCC) genome, the target sequence was demethylated at the cytosine residue of the CpG dinucleotides with high frequency (75% in the previous study). These data suggest that this regional DNA hypomethylation may play a role in both cell differentiation and hepatocarcinogenesis.

Animals↗
PubMed1999

Isolation of NotI clusters hypomethylated in HBV-integrated hepatocellular carcinomas by two-dimensional electrophoresis.

To examine genetic and epigenetic alterations associated with HBV integration in hepatocarcinogenesis, we compared genomic DNA profiles of primary hepatocellular carcinomas (HCCs) and cell lines that either contained or did not contain integrated HBV. To accomplish this, we carried out Restriction Landmark Genomic Scanning (RLGS), a two-dimensional system that displays 2000-3000 Not I landmark sites in a single gel electrophoresis experiment. We identified one Not I landmark spot that showed high signal intensity in HBV-integrated cell lines or in primary HCCs, but not in HCCs or tumor-cell lines free of HBV integration. Cloning of this spot revealed that it consisted of a Not I cluster sequence enriched with CpG dinucleotides. This sequence, hypomethylated in association with HBV integration, was found in the peri-centromeric region of human acrochromosomes. The results demonstrate that epigenetic changes at specific sequences in the genome occur in association with HBV integration during the process of hepatocarcinogenesis.

Base Sequence↗
PubMed1999

Identification of a cis-acting regulatory sequence responsible for the repression of brnQ in Salmonella typhimurium.

brnQ is the gene encoding the LIV-II transport system for branched-chain amino acids in Salmonella typhimurium. The expression of the gene is transcriptionally repressed by an excess of glycyl-l-leucine added to the bacterial culture. To investigate the mechanism of regulation, we constructed brnQ-lacZ translational fusions with various deletions upstream from the promoter of brnQ, and examined the effects of the deletions on the regulation. We found a cis-acting region, 5'-GTGTTTTA-3', for the repression of brnQ expression, which was located 94 base pairs upstream from the transcription start site. Removal of the sequence resulted in derepression of brnQ. Two homologous sequences were found 45 base pairs downstream and 42 base pairs upstream from the sequence. We designated these sequences as O1, O2, and O3, in the order from the sequence proximal to the promoter to that distal to the promoter, respectively. The gleR1 mutation, which we reported previously to be a regulatory mutation enhancing transcription of brnQ, was a G-to-T transversion in the O1 sequence 50 base pairs upstream from the transcription start site. Insertion of five nucleotides between O1 and O2 resulted in derepression of brnQ. Further insertion of five nucleotides did not restore the original regulation of brnQ, indicating the importance of the proper spacing of these sequences. We also showed that the protein product of livS, the gene responsible for regulation of the LIV-I transport system, may bind to the O2 sequence. Furthermore, LivS was shown to be an allele of Lrp based on complementation experiments.

Artificial Gene Fusion↗
PubMed1999

Stereoselective analyses of selegiline metabolites: possible urinary markers for selegiline therapy.

The stereoselective analysis of selegiline metabolites in human urine and plasma by gas chromatography using the chiral column with the non-chiral reagent was investigated for the differentiation of selegiline therapy from the methamphetamine (MA) abuse. This method gave clear separations of MA and amphetamine (AM) isomers without any artifactual optical-opposite peaks due to the reagent. After the administration of selegiline tablets, desmethylselegiline (DMS), MA and AM were observed as (-)-isomers in the urine and plasma. Within the first 48 h after dosing, approximately 40% of selegiline administered was excreted in urine as these three metabolites. The parent drug, selegiline, was not detected in any urine or plasma samples. On the other hand, MA and AM were observed only as (+)-isomers in the urine of MA abusers. For the distinction of selegiline users from street MA abusers in urinalysis, (-)-DMS, a specific metabolite of selegiline, was not a suitable marker. (-)-DMS rapidly disappeared from urine and was excreted only 1% of the given dose. By the moment analysis with the trapezoidal integration, the mean residence times of (-)-DMS in plasma and urine were 2.7 and 3.8 h, respectively, which were 5-20 times shorter than those of (-)-MA or (-)-AM. The values of AM/MA in the urine increased from 0.24 to 0.67 (r = 0.857) along with time after the selegiline administration. This ratio was not a sufficient marker to differentiate selegiline users from MA abusers, although the values of AM/MA in 74% of MA abusers were less than 0.24. The present GC technique improved the chiral analyses of MA and AM. This chiral analysis is the most useful technique to avoid the misinterpretation in the discrimination between clinical selegiline therapy and illicit MA use.

Adult↗