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Biomedical subjects

Y Yanagawa

Publications and source records attributed to Y Yanagawa.

At least 91 records · Page 5Linked to original sources
PubMed1995

Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred.

The X-chromosome-linked phosphoglycerate kinase (PGK) deficiency associated with severe chronic and acute haemolytic anaemia and mental disorders was first described in a large Chinese kindred in 1969. The molecular abnormality of this original variant remained to be identified. The red cell PGK activity was only about 5%, but the activity of the patients' lymphoblastoid cells was about 15% of normal. The PGK mRNA content of the patients' lymphoblastoid cells were normal. Analysis of the patients' mRNA showed the existence of a nucleotide transversion A-->T at position 491 (counting from adenine of the initiation codon). The mutation should cause an amino acid substitution Asp-->Val at position 163 of the enzyme. The replacement of the acidic aspartic acid by a hydrophobic valine is expected to induce drastic structural instability resulting in severe enzyme deficiency in the patients' tissues. The genotypes of two affected males, their mothers and 22 females of the family were identified by the PCR-mediated method using their genomic DNA samples. 13/24 females examined were found to be variant heterozygous. In this large family, affected males over three generations have died at a pre-adult age. Post- and pre-natal genotyping of the family members may prevent future problems.

Anemia, Hemolytic, Congenital↗
PubMed1995

Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism.

The objectives of this study were to elucidate the structural organization of the gene for human deoxyribonuclease I (DNase I) and to identify the mutation site underlying its classical genetic polymorphism. In order to determine the organization of this gene, we utilized a combination of direct polymerase chain reaction (PCR)-amplification of human genomic DNA and isolation of the overlapping clones from a cosmid human genomic library. Restriction endonuclease mapping, Southern blotting and DNA sequencing showed that the DNase I gene was approximately 3.2 kilobases long, it comprised 9 (I-IX) exons separated by eight introns and its complete sequence was determined. The first exon contained only the non-translated sequences of mRNA. In addition to several putative regulatory elements, TATA-like and CAAT-like sequences were observed in the region upstream of the translation initiation codon. These results provide information that will help to understand the expression and regulation of DNase I. The isoelectric focusing patterns of human DNase I showed that it exhibits classical genetic polymorphism (Kishi et al. 1989, 1990). A comparison of the entire translated sequences of the DNase I gene from two pairs of individuals with common DNase I phenotypes 1 and 2 revealed only one nucleotide residue difference in exon VIII, A for phenotype 1 and G for phenotype 2, thus producing Gln and Arg amino acid substitutions respectively at position 222 from the NH2-terminus of the mature enzyme. The predicted charge changes attributable to these amino acid substitutions are entirely consistent with the isoelectric focusing profiles of these two DNase I isozymes. We conclude that this substitution is solely responsible for the classical polymorphism of DNase I protein.

Adult↗
PubMed1995

[A case of radiation optic neuropathy after resection of a pituitary adenoma].

A case of optic neuropathy after postoperative radiation therapy is reported. A 69-year-old woman had a partial resection of a pituitary adenoma in 1990 and was treated with 45Gy of irradiation to the postoperative pituitary lesion for one month. Seven months later she had sudden right visual field loss. Goldmann perimetry examination revealed remarked visual field defect in her right eye with visual acuity of 1.0. The right relative afferent pupillary defect was positive. The value of critical flicker fusion for her right eye was reduced and the amplitude of steady-state pattern-reversal visually evoked cortical potential was significantly less for the right monocular stimulation than that for the fellow eye stimulation, but Ganzfeld electroretinograms were normal for both eyes. Magnetic resonance imaging using Gadolinium-diethylene triaminepenta-acetic acid revealed enhancement on the right optic nerve, which had not been recognized immediately after the radiation therapy, without any suggestion of right optic nerve compression by the residual pituitary adenoma.

Adenoma↗
PubMed1994

Stable expression of human CYP1A2 and N-acetyltransferases in Chinese hamster CHL cells: mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

In order to investigate the metabolic activation pathway of food-derived heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), cultured cell lines which stably expressed human cytochrome P4501A2 (CYP1A2) and N-acetyltransferases (NATs) were developed by the method of complementary DNA (cDNA) transfection. First, a cell line expressing CYP1A2, designated A2R-5, was established from the cell line CR-68, which was previously established by introducing NADPH-cytochrome P-450 reductase cDNA into Chinese hamster CHL cells. The expression of CYP1A2 in the transfected cells was confirmed by determining sensitivity to aflatoxin B1. As the next step, the A2R-5 as well as CR-68 cells were further transfected with human monomorphic NAT (NAT1) or polymorphic NAT (NAT2) cDNAs. The expression of NAT in the transfected cells was confirmed using p-aminobenzoic acid and sulfamethazine as substrates, while no activity was seen in parental CR-68 and A2R-5 cells. The cell line, ANP-25, which expressed both CYP1A2 and NAT2, was approximately 370- and 100-fold more sensitive to IQ and MeIQx, respectively, than parental CR-68 cells in cytotoxicity assays. There were no clear differences in sensitivity to both compounds among CR-68, A2R-5, and the cell lines which expressed NAT1 alone, NAT2 alone, and CYP1A2 plus NAT1. Mutagenicity of IQ and MeIQx at the hypoxanthine-guanine phosphoribosyltransferase locus was also detectable only in ANP-25 cells but not in A2R-5 or the cell line expressing CYP1A2 plus NAT1. From these results, it is proposed that both CYP1A2 and NAT2 (but not NAT1) are required for mutagenic activation of these compounds, implying that acetylator polymorphism may be an important risk factor in the carcinogenicity of these compounds.

Acetyltransferases↗
PubMed1994

Circadian rhythm of the autonomic nervous system in long QT syndrome.

The circadian changes in the activity of the autonomic nervous system in a group showing long QT duration in electrocardiogram (ECG) were studied in order to differentiate symptomatic congenital long QT syndrome from asymptomatic. The asymptomatic group presented only long QT duration (QTc > 0.46). Seven girls and two boys, including two subjects experiencing syncope of non-neurological origins, were examined by using heart rate (HR) power spectrum analysis. In three subjects, the peak of the high frequency band, indicating the parasympathetic activity, disappeared during night-time (sleep), which means the possibility of a high risk of sudden cardiac death. In two of three subjects, moreover, the averaged sympathetic activity during daytime was significantly increased compared to that during night-time, in addition to the abrupt increase of sympathetic activity in the morning. These two subjects, in which one boy had a family history of Romano-Ward syndrome, were the same people experiencing the syncope attack. We succeeded in objectively elucidating that congenital long QT syndrome is adrenergic-dependent, and suggest that HR power spectrum analysis may be of value in distinguishing symptomatic congenital long QT syndrome from asymptomatic showing only long QT duration.

Autonomic Nervous System↗
PubMed1994

[The role of flagella of Campylobacter jejuni in colonization in the intestinal tract in mice and the cultured-cell infectivity].

For analyzing the role of the bacterial flagella in colonization in the intestinal tract of mice and adhering to or invading the Intestine 407 cell, a nonflagellated, nonmotile mutant was induced by ultraviolet irradiation of a flagellated, motile wild-type strain of Campylobacter jejuni CF84-340. There was no great difference in the cellular infectivity to the Intestine 407 cells between the wild-type and the mutant strains. Cellular adherence and invasiveness were then compared by fluorescent antibody staining, and an obvious difference was found in the latter. While 21.4% of the organisms of the wied-type strain invaded the cells, only 6.1% of those of the flagella-defective mutant did so. In the experiments in mice involving oral administration, cellular invasiveness was not found with the flagella-defective mutant and no organisms were detected from the blood, although bacteremia is one of the characteristics of infection with C. jejuni. Moreover, no intestinal adherence of the mutant was detected, suggesting early elimination of the organism administered. These results indicate that the bacterial flagella are concerned in not only the cellular adherence and intestinal deposit, but also the intracellular invasiveness and invasion into the blood stream from the intestinal wall in the infected mice.

Animals↗
PubMed1994

[Werner's syndrome associated with meningioma and a cerebrovascular disorder].

We present a case of Werner's syndrome associated with intracranial meningioma and a cerebrovascular disorder. A 49-year-old male was transferred to this hospital with a head injury as a result of a car accident, and a CT scan revealed a traumatic intracerebral hemorrhage. The patient displayed the characteristic clinical features of Werner's syndrome, including premature senility, juvenile cataract, atrophic skin, and a tendency to ward familial occurrence was present. MRI and cerebral angiography revealed multiple intracerebral hemorrhages, perhaps due to amyloid angiopathy, multiple lacunar infarctions and parasagittal meningioma. This is the first report on the MRI findings in the brain of a patient with Werner's syndrome. We suspect that of Werner's syndrome also shows evidence of premature aging on MR images.

Cerebral Angiography↗
PubMed1993

[An outbreak of gastroenteritis due to group C rotavirus in Tokyo].

In April 1991, an outbreak of acute gastroenteritis due to group C rotavirus occurred at an elementary school in Tokyo. Fifty-one (13%) of 393 students became ill. The main clinical symptoms were diarrhea (100%), abdominal pain (68%) and vomiting (56%). No enteropathogenic bacteria were found in the fecal specimens. However, the virus particles morphologically indistinguishable from conventional rotavirus were detected in 6 of 11 fecal specimens by electron microscopy. Immune electron microscopy showed that these virions aggregated with anti-group C rotavirus serum. The RNA pattern of the virus particles involved in this outbreak showed a pattern similar to that of typical group C rotavirus on polyacrylamide gel electrophoresis.

Child↗
PubMed1992

[Pharmacokinetics and toxicological study on the intraperitoneal administration of cisplatin and etoposide in gynecological malignancies].

We administered cisplatin and etoposide into the peritoneal cavity of 13 postoperative patients with gynecological malignancies, and studied the pharmacokinetics and toxicity in the combination of both drugs. Cisplatin 100 mg/body and etoposide 200 mg-400 mg/body were mixed together in 500 ml or 1,500 ml of normal saline and administered intraperitoneally on the day of operation and two or three weeks later. The peritoneal peak level of free cisplatin, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. However, there was no difference in the peritoneal and plasma AUC. The peritoneal level and AUC of etoposide, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. Among the groups of 1,500 ml, peritoneal and plasma levels and AUC were almost proportional to the doses. Nausea and vomiting were experienced in all patients. With the increase of etoposide, more marrow suppression was observed. However, we encountered no other significant side effects. In conclusion, intraperitoneal administration of cisplatin and etoposide in this setting can be used safely with minimum side effects, and the dilution of 1,500 ml seems to be better.

Adult↗
PubMed1991

Stimulation of DNA synthesis in Jurkat cells by synergistic action between adenine and guanine nucleotides.

P2-purinoceptor agonists stimulated the DNA synthesis of Jurkat cells via a pathway independent of cAMP and intracellular free calcium. The response was greatly enhanced by the synergistic action between adenine and guanine nucleotides, suggesting that binding sites of these nucleotides are different from each other, and the proliferation is stimulated by a novel interaction between adenine and guanine nucleotide receptors. The stimulatory effects of P2-agonists on proliferation was completely abolished by cholera toxin and attenuated by pertussis toxin, which suggests that substrates for cholera toxin and pertussis toxin are involved in the proliferative pathways associated with P2-purinoceptors.

Adenine Nucleotides↗
PubMed1991

Tertiary structure of conotoxin GIIIA in aqueous solution.

The three-dimensional structure of conotoxin GIIIA, an important constituent of the venom from the marine hunting snail Conus geographus L., was determined in aqueous solution by two-dimensional proton nuclear magnetic resonance and simulated annealing based methods. On the basis of 162 assigned nuclear Overhauser effect (NOE) connectivities obtained at the medium field strength frequency of 400 MHz, 74 final distance constraints of sequential and tertiary ones were derived and used together with 18 torsion angle (phi, chi 1) constraints and 9 distance constraints derived from disulfide bridges. A total of 32 converged structures were obtained from 200 runs of calculations. The atomic root-mean-square (RMS) difference about the mean coordinate positions (excluding the terminal residues 1 and 22) is 0.8 A for backbone atoms (N, C alpha, C). Conotoxin GIIIA is characterized by a particular folding of the 22 amino acid peptidic chain, which is stabilized by three disulfide bridges arranged in cage at the center of a discoidal structure of approximately 20-A diameter. The seven cationic side chains of lysine and arginine residues project radially into the solvent and form potential sites of interaction with the skeletal muscle sodium channel for which the toxin is a strong inhibitor. The present results provide a molecular basis to elucidate the remarkable physiological properties of this neurotoxin.

Amino Acid Sequence↗
PubMed1991

p53 gene mutations in colorectal tumors from patients with familial polyposis coli.

The p53 gene has been elucidated as a tumor suppressor gene, and inactivation of this gene caused by deletion or point mutations may play a crucial role in the development of human malignancies. In colorectal carcinomas with an allelic deletion of the p53 gene, the remaining p53 gene was mutated with considerable frequency. It is most difficult to detect point mutations or small deletions of the gene because the mutations occur in diverse regions, although four hot spots have been observed [J.M. Nigro et al., Nature (Lond.), 342: 705-708, 1989]. The polymerase chain reaction and denaturing gradient gel electrophoresis facilitate detection of mutations in the hot spots of the p53 gene. Using these methods, we detected mutations in three adenomatous polyps and one carcinoma from familial polyposis coli patients and three carcinomas of sporadic cases. The DNA sequence analysis confirmed mutations of the p53 gene in 2 adenomas (13 base-pair deletions in one and a point mutation in the other) and 1 carcinoma (point mutation) from familial polyposis coli patients. These results suggest that the p53 gene mutations may be involved in the formation not only of carcinomas but also of adenomas which occur in familial polyposis coli patients.

Adenomatous Polyposis Coli↗
PubMed1991

[Diagnosis of colorectal cancer from DNA level].

The inherited cancer-inducing disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanisms in general oncogenesis. This paper reviewed recent remarkable progresses of molecular mechanisms in colorectal tumorigenesis. This is concerned with the various kinds of genetic alterations that accumulate in the development from normal mucosa to adenoma, and then to adenocarcinoma in comparison with FPC and sporadic cases. This review included also information on the localization of FPC major gene. These observations indicate that in cases of colorectal tumorigenesis several genetic alterations may be involved, including activation of K-ras gene, deregulated expression of c-myc gene or c-fos gene and inactivation of tumor suppressor genes such as p53 and DCC genes, as well as the loss of heterozygosity. The observation suggest that adenomas will have undergone several gene or chromosome mutations before reaching to the fully malignant state. Therefore, DNA diagnosis for colorectal tumors in the clinical level may contribute to more accurate prognosis and better results for further therapy.

Adenoma↗
PubMed1990

Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice.

In an attempt to obtain direct evidence for the critical role of HLA class II molecules in regulating the immune response, genomic genes for alpha- and beta-chains of HLA-DQw6 from HLA-Dw12 haplotype were introduced into the C57BL/6 (B6) strain of mouse and a line of HLA-DQw6 transgenic mouse was obtained. Tissue specificity of the expression of the transgenes was much the same as that of murine I-Ab genes. DQw6 molecules were expressed on B cells and macrophages in spleen cells and about 30 to 40% of the I-Ab+ spleen cells were positive for DQw6. The HLA-DQw6 transgenic B6 mouse became tolerant to the DQw6 molecules, as evidenced by the MLR and antibody production specific to the DQw6 molecules. The HLA-DQw6 transgenic B6 mouse showed a strong immune response to streptococcal cell wall antigen (SCW), whereas the B6 mouse was a low responder to SCW. The SCW-specific T cell line was established from the transgenic mouse and this T cell line recognized SCW in the context of HLA-DQw6 molecules expressed on the mouse L cell transfectant or on human monocytes. The proliferative response to SCW of primed lymph node T cells and the SCW-specific T cell line derived from the transgenic mice was inhibited by anti-HLA-DQ mAb. Thus, it is clear that the HLA-DQw6 genes acted as major histocompatibility genes in these transgenic mice.

Animals↗
PubMed1990

Conotoxin GIIIA: selective inhibition of 22Na influx via voltage-dependent Na channels in adrenal medullary cells.

Conotoxin GIIIA and GIIIB from the marine snail Conus geographus have been reported to inhibit voltage-dependent Na channels in skeletal muscle and postganglionic sympathetic neuron, but have no effect on Na channels in brain, giant axon and heart. In eel electroplax, conotoxins were also shown to share the common binding sites with saxitoxin (see review Gray et al. 1988). In bovine adrenal medullary cells, conotoxin GIIIA inhibited veratridine-induced influx of 22Na, 45Ca and secretion of catecholamines with an IC50 of 6 mumols/l while saxitoxin suppressed veratridine-induced responses with an IC50 of 6.3 nmol/l. [3H]Saxitoxin binding to the cells was inhibited by unlabeled saxitoxin with an IC50 of 5.1 nmol/l, but was slightly reduced by 10 mumols/l conotoxin GIIIA. Conotoxin GIIIA, at 10 mumols/l, did not alter carbachol-induced influx of 22Na, 45CA and secretion of catecholamines as well as high K-induced 45Ca influx and catecholamine secretion. These results indicate that conotoxin GIIIA, at concentrations 950 fold higher than saxitoxin, inhibits Na influx via voltage-dependent Na channels, but has no effect on the nicotinic receptor-ion channel complex or the voltage-dependent Ca channels. Conotoxin GIIIA seems to bind at the sites which are distinct from saxitoxin, but are functionally linked to the voltage-dependent Na channels. Conotoxins may be useful for the classification of Na channels in excitable cell membranes.

Adrenal Medulla↗
PubMed1990

[The serotype distribution of Campylobacter jejuni strains among gastroenteritis in hospitals over 7 year period in Tokyo].

Campylobacter jejuni strains isolated from gastroenteritis at 4 general hospitals of Tokyo Metropolitan during the period from 1981 to 1987 were serotype according to the slide agglutination test (TCK system) developed by the Tokyo Metropolitan Research Laboratory of Public Health. Two thousand four hundred seventy-nine strains isolated from sporadic cases among infants and children, 1,962 (78.5%) were typed by 33 typing sera numbered TCK 1 through TCK 33 and leaving 537 strains (21.5%) untypable. Out of the typable strains, 1,643 strains reacted with only single serum, while 319 strains reacted with 2 or more antisera. The most common serogroups included TCK 21, 20, 7, 1, 4, 23, 24, 10, 30 and 12. Out of the 1,250 strains isolated from sporadic cases among adults, 974 strains (77.9%) were typed and 276 strains were untypable. The most common serogroups were similar to those of infants and children. Serogroups TCK 1, 7, 4 and 21 were consistently the common serogroups every year during the 7 year study. Isolation frequency of serogroup TCK 30 have increased remarkably since 1986, while TCK 23, 14 and 9 have decreased.

Adult↗