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Biomedical subjects

G Isshiki

Publications and source records attributed to G Isshiki.

At least 73 records · Page 4Linked to original sources

Interactions between steroid hormones and insulin-like growth factor-I in rabbit chondrocytes.

The mechanism of action of steroid hormones on skeletal growth is not understood in detail. We examined the interactions of steroid hormones and insulin-like growth factor-I (IGF-I) during DNA and sulfated proteoglycan synthesis in rabbit costal chondrocytes. Progesterone at 0.05 nM stimulated the incorporation of [3H]thymidine into DNA by 30% above the control level in confluent cultures, but neither testosterone nor 17 beta-estradiol stimulated DNA synthesis. None of the hormones affected [3H]thymidine incorporation stimulated by IGF-I when chondrocytes were incubated with one of the hormones and IGF-I simultaneously. In contrast, when confluent cultures were incubated with one of the sex steroids for 24 h before the addition of IGF-I, stimulation of DNA synthesis by the growth factor was enhanced about 45% above the control value by 0.5 nM progesterone, 50% by 0.5 nM testosterone, and 80% by 50 nM 17 beta-estradiol. The effects of IGF-I on proteoglycan synthesis, as judged by the incorporation of [35S]sulfate, were stimulated by treatment with progesterone or testosterone. Dexamethasone at physiological concentrations inhibited chondrocyte DNA synthesis in confluent cultures to 10% of the control level. At 50 nM, dexamethasone suppressed IGF-I induction of DNA synthesis by 60%. This suppression was greater when dexamethasone was added before IGF-I than when the additions were simultaneous. When chondrocytes were treated with hydrocortisone or dexamethasone for 24 h before the addition of IGF-I, the glucocorticoids synergistically accelerated proteoglycan synthesis mediated by IGF-I. These findings suggest that steroid hormones have priming effects on the biological action of IGF-I in cartilage metabolism.

Animals↗

Variation of lysosomal enzyme activity with gestational age in chorionic villi.

The activities of 14 lysosomal enzymes in chorionic villi at gestational ages of 6-12 weeks were assayed. Arylsulphatases A and B, alpha-glucosidase and beta-glucuronidase activities increased with advancing gestational age. When compared with the activity in cultured amniotic fluid cells, arylsulphatase A, beta-galactosidase, alpha-glucosidase, heparan N-sulphatase, alpha-L-iduronidase, alpha-mannosidase, neuraminidase, and sphingomyelinase showed significant differences. All except beta-glucuronidase showed lower activity in chorionic villi than in cultured amniotic fluid cells. Prenatal diagnosis using chorionic villi was possible except for alpha-L-iduronidase. Storage at -20 degrees C up to 42 days did not significantly affect activity. The results emphasize the importance of using fresh or frozen age-matched control tissue for diagnosis.

Amniotic Fluid↗

Heterogeneity of human islet cell antibodies in terms of cross-species reactivity.

There has been no consistent view about the cross-species reactivity of islet cell antibodies (ICA), and no report about their target antigens in the pancreatic islet cells of different species. Therefore, we examined the cross-reactivity of human ICA against rodent pancreatic islet cells, and found at least two types of ICA, one having a comparatively strong cross-reactivity and the other lacking it. Furthermore, using human as well as some rodent pancreatic tissues that had been modified chemically, we came to suspect that the target antigens of ICA were sialic acid residues of glycolipids. Therefore, we suggest that there are at least two types of ICA recognizing sialic acid residues of glycolipids, one reacting with antigen(s) commonly present in human and rat islets, and the other with antigen(s) only present in human islets.

Animals↗

HLA-DQ antigens and DQ beta amino acid 57 of Japanese patients with insulin-dependent diabetes mellitus: detection of a DRw8DQw8 haplotype.

DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. Ala) at residue 57 of the DQ beta chain (non-Asp-57). Most Caucasoid IDDM patients are homozygous non-Asp-57. We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). Their DQB1 alleles and the aa encoded by their DQB1 codons 57 were identified, using 11 different sequence-specific oligonucleotide probes. Secondly, they were examined with DQw8 specific T lymphocyte clones and with anti-DQ monoclonal antibodies. The DQB1 genes on their DR4 and DRw9 haplotypes in all cases encoded Asp-57. Two patients were Asp-57 homozygous, the rest were Asp-57/non-Asp-57 heterozygous. The DR4 haplotypes all carried DQw4 (rather than DQw8), and the DRw9 haplotypes all carried DQw9. Furthermore, five of six DRw8 positive patients carried a previously undetected DRw8DQw8 haplotype, where both the DQA1 and DQB1 genes were similar to those usually found on the DR4DQw8 haplotype. Thus, the DR/DQ allele combinations and aa residue 57 of the DQ beta chain of Caucasoid and Japanese IDDM patients are largely different.

Antibodies, Monoclonal↗

Prevention of vertical transmission of hepatitis B virus by yeast recombinant hepatitis B vaccine.

In order to prevent vertical transmission of hepatitis B virus (HBV), yeast recombinant HB vaccine at a dose of either 5 mcg or 10 mcg was administered to 185 infants born to mothers who were positive for HBs antigen (HBsAg). All of them developed antibody to HBsAg (anti-HBs) after three vaccinations. Generally, the cut-off index (COI) of anti-HBs by radioimmunoassay (RIA) was higher in the 10 mcg dosage group than in the 5 mcg dosage group. The geometric mean titer (GMT) of anti-HBs, as measured by quantitative RIA, in the former group was 2.4 times that in the latter one month after the third vaccination. The incidence of clinical reactions was only 4% in a total of 561 injections, and none of the reactions were severe. It is concluded that recombinant HB vaccine is safe and has excellent immunogenicity for infants requiring prevention of HBV vertical transmission. It is also suggested that 10 mcg doses of the recombinant HB vaccine can provide more solid protection to high-risk infants without serious adverse reactions.

Carrier State↗

Plasma fructosamine assay in children with insulin-dependent diabetes mellitus.

Plasma concentrations of fructosamine, an indicator of glycated plasma proteins, were measured in non-diabetic children and children with insulin-dependent diabetes mellitus (IDDM) to see if they also correlate with glycemic control in children as well as in adults. Non-diabetic children aged less than 4 yr had significantly lower plasma fructosamine than non-diabetic children aged 4 or more. Total plasma protein in these children was slightly lower or close to that of older children. There was no difference in fructosamine between non-diabetic children aged 4 or more and healthy adult subjects. Plasma fructosamine in children with IDDM was twofold that of age-matched controls. In children with IDDM, correlations between fructosamine and HbAI (r = 0.799) or HbAIc (r = 0.841) were high. The measurement of plasma fructosamine, which is practical in children because of the small sample volume needed and no influence of HbF, is useful in the management of children with IDDM.

Adolescent↗

Efficacy of kan-baku-taiso-to (TJ-72) on breath-holding spells in children.

When Kan-baku-taiso-to (TJ-72) (0.1-0.25 g/kg/day) was given to 12 children with breath-holding spells (BHS) of the cyanotic type, the attacks were lessened starting in the second week of administration. There were no side effects even when administration was continued for more than one year. We think that the drug should be given primarily for BHS when the frequency of severe attacks is high and also to patients who did not respond to other medication.

Apnea↗

Complementation studies with clinical and biochemical characterizations of a new variant of multiple sulphatase deficiency.

A patient with a new variant of multiple sulphatase deficiency (MSDv) is reported. Unlike the usual type, onset was late and progress was slow. The phenotypic changes were those usually seen in multiple sulphatase deficiency but much milder. Cytoplasmic accumulations were found in skin fibroblasts, and urinary mucopolysaccharides and sulphatides were high. Arylsulphatases A, B and C (ASA, B and C), heparan N-sulphatase sulphoiduronate sulphatase, and N-acetylgalactosamine 6-sulphatase all had low activity in lymphocytes and cultured skin fibroblasts. Complementation for ASA activity was found in hybrids between MSDv and metachromatic leukodystrophy (MLD) as well as between multiple sulphatase deficiency (MSD) and MLD. Complementation for ASC activity was also seen in hybrids between MSDv and X-linked ichthyosis (XLI), and between MSD and XLI. However, neither ASA nor ASC activity increased in hybrid cells of MSDv and MSD. These results suggested that the mutations of MSDv and of MSD were allelic, although of different phenotypes.

Adult↗

Serial magnetic resonance imaging in subacute sclerosing panencephalitis.

Magnetic resonance (MR) imaging of a 17-year-old girl with subacute sclerosing panencephalitis (SSPE) was done several times to monitor the morphological changes and clinical course of the disease by comparison with computed tomographic (CT) scans. The MR image showed lesions that corresponded to the clinical symptoms in the early stages where no abnormalities appeared on the CT scans. The MR images delineated the extent of abnormal areas more clearly than the CT scans. However, the course of neurological manifestations did not always correspond to the MR findings. Serial MR imaging was useful in the detection and observation of the stages and clinical progress of SSPE.

Adolescent↗

Effects of phenylalanine loading on protein synthesis in the fetal heart and brain of rat: an experimental approach to maternal phenylketonuria.

Pregnant rats were loaded with L-phenylalanine, and the distributions of [14C]leucine and [14C]urea into fetal plasma and tissues were examined. Uptake of [14C]leucine into the supernatant and protein fractions of fetal plasma and tissues was low in the rats loaded with phenylalanine. In contrast, [14C]urea was distributed identically in both groups, indicating that maternal hyperphenylalaninemia did not affect blood flow across the placenta. Administration of phenylalanine and p-chlorophenylalanine produced amino acid imbalance in fetal tissues. Along with these changes, polysomes of the affected fetal heart and brain disaggregated without changes in the ribonuclease activity. These results indicate that high phenylalanine levels in maternal plasma disturb the active transport of amino acids across the placenta, causing an amino acid imbalance and disaggregation of polysomes in fetal heart and brain. These changes may contribute to the congenital heart disease and mental retardation of maternal phenylketonuria.

Animals↗