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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 91 records · Page 5Linked to original sources
PubMed1991

Two cases of steroid sulfatase deficiency with complex phenotype due to contiguous gene deletions.

We report contiguous gene deletions in the distal short arm of the X chromosome in two patients with ichthyosis, due to steroid sulfatase deficiency, and other complex phenotypes. One patient had chondrodysplasia punctata (CDP) and ichthyosis with a normal chromosome constitution. Another patient had a CDP-like phenotype, ichthyosis, and hypogonadism. His karyotype was 46, -X,Y, +der(X)t(X;Y)(p22;q11). DNA from the two patients was analyzed by Southern blotting using cloned fragments mapped in the Xp21-Xpter region to investigate gene deletions. DNA from the patient with CDP showed a gene deletion of the STS, DXS31, and DXS89 loci, and DNA from the patient with X-Y translocation lacked fragments of the STS, DXS31, DXS89, and DXS143 loci. These findings suggest that the common deleted region involving the STS locus might have caused the similar phenotypes in both patients.

Abnormalities, Multiple↗
PubMed1991

An endonuclease activity in human polymorphonuclear neutrophils that removes 8-hydroxyguanine residues from DNA+.

An endonuclease that specifically removes 8-hydroxyguanine (oh8Gua) from DNA has been isolated from Escherichia coli. As the amount of oh8Gua produced in DNA of X-ray-irradiated mice is known to decrease with time after irradiation, an attempt was made to find a similar activity in human polymorphonuclear neutrophils (PMNs) using a synthetic dsDNA containing oh8Gua as a substrate. The PMN enzyme was isolated free of other DNases, and found to cleave the substrate DNA simultaneously at 2 sites, the phosphodiester bonds 5' and 3' to oh8Gua, producing free hydroxyl and phosphate groups, respectively. The enzyme showed almost no activity on DNAs containing other kinds of modified base tested or mismatched DNA. Thus human cells also contain an endonuclease that specifically removes oh8Gua residues from DNA.

Base Sequence↗
PubMed1991

8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

Substrate specificities of FPG protein (also known as formamidopyrimidine DNA glycosylase) and 8-hydroxyguanine endonuclease were compared by using defined duplex oligodeoxynucleotides containing single residues of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxodA), and 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine (Me-Fapy). Duplexes containing 8-oxodG positioned opposite dC, dG, or dT were cleaved, whereas single-stranded DNA and duplexes containing 8-oxodG.dA or 8-oxodA positioned opposite any of the four DNA bases were relatively resistant. Both enzymes cut duplexes containing 8-oxoG.dC 3' and 5' to the modified base but failed to cleave duplex DNA containing synthetic abasic sites, mismatches containing dG, or unmodified DNA. 8-Oxoguanine, identified by HPLC-electrochemical detection techniques, was released during the enzymatic reaction. Apparent Km values for FPG protein acting on duplex substrates containing a single Me-Fapy or 8-oxodG residue positioned opposite dC were 41 and 8 nM, respectively, and those for 8-hydroxyguanine endonuclease were 30 and 13 nM, respectively. Comparison of the properties of the two enzyme activities suggest that they are identical. In view of the widespread distribution of 8-oxodG in cellular DNA, the demonstrated miscoding and mutagenic properties of this lesion, and the existence of a bacterial gene coding for FPG protein, we propose that 8-oxodG DNA is the primary physiological substrate for a constituent glycosylase found in bacteria and mammalian cells.

Base Sequence↗
PubMed1991

NMR studies of a DNA containing 8-hydroxydeoxyguanosine.

The effects of hydroxylation at the C8 of a deoxyguanosine residue in DNA were studied by NMR analysis of a self-complementary dodecanucleotide, d(C1-G2-C3-oh8G4-A5-A6-T7-T8-C9-G10-C11-G12), which has an 8-hydroxy-2'-deoxyguanosine (oh8dG) residue at the 4th position. NMR data indicate that the 8-hydroxyguanine (oh8G) base takes a 6,8-diketo tautomeric form and is base-paired to C with Watson-Crick type hydrogen bonds in a B-form structure. The thermal stability of the duplex is reduced, but the overall structure is much the same as that of the unmodified d(CGCGAATTCGCG) duplex. The structural changes caused by 8-hydroxylation of the deoxyguanosine, if any, are localized near the modification site.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Receptor types mediating the rise in the cytosolic free calcium concentration by L-aspartate and L-glutamate in immature cerebellar neurons with N-methyl-D-aspartate receptors.

L-Aspartate (Asp) and L-glutamate (Glu) increased the cytosolic free calcium concentration ([Ca]in) in medium-sized cerebellar neurons having N-methyl-D-aspartate (NMDA) receptors. The sustained rise in [Ca]in induced by Asp, but not by Glu, was reduced by the addition of NMDA antagonists, which consistently suppressed the rise in [Ca]in induced by a low concentration of Asp or Glu in combination with glycine. The results suggest that Asp is a more preferential agonist of NMDA receptors than Glu, although Glu can also be an agonist in the presence of glycine.

2-Amino-5-phosphonovalerate↗
PubMed1991

Plasma islet amyloid polypeptide (Amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients.

Fasting plasma islet amyloid polypeptide concentrations and their responses to an oral glucose load were determined in non-diabetic control subjects and patients with abnormal glucose tolerance in relation to the responses of insulin or C-peptide. Plasma islet amyloid polypeptide was measured by radioimmunoassay. In the non-diabetic control subjects, fasting plasma islet amyloid polypeptide was 6.4 +/- 0.5 fmol/ml (mean +/- SEM) and was about 1/7 less in molar basis than in insulin. The fasting islet amyloid polypeptide level rose in obese patients and fell in patients with Type 1 (insulin-dependent) diabetes mellitus. In non-obese patients with impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetic patients without insulin therapy, the level was equal to that of the control subjects, but a low concentration of islet amyloid polypeptide relative to insulin or C-peptide was observed in the non-obese Type 2 diabetic group. The patterns of plasma islet amyloid polypeptide responses after oral glucose were similar to those of insulin or C-peptide. However, compared to non-obese patients, a hyper-response of islet amyloid polypeptide relative to C-peptide was noted in obese patients who had a hyper-response of insulin relative to C-peptide. This study suggests that basal hypo-secretion of islet amyloid polypeptide relative to insulin exists in non-obese Type 2 diabetes and that circulating islet amyloid polypeptide may act physiologically with insulin to modulate the glucose metabolism.

Adult↗
PubMed1991

Detection of Epstein-Barr virus and human herpes virus type 6 in saliva from patients with lymphoproliferative diseases by the polymerase chain reaction.

Direct detection of these viruses was made by using the PCR for amplifying viral DNA. In virtually all adults low levels of the herpesvirus can be detected. Therefore it is necessary to quantitate the amount of viral DNA, and a method to compare the plasmid containing the cloned target gene was used here. After 35 cycles of amplification, 10 copies of the viral DNA per 100 microliters saliva were detected. The PCR was used to detect increased levels of EBV and HHV-6 in saliva from patients with lymphoproliferative diseases, suggesting that these viruses may play a part in their pathogenesis. Viral detection by such highly sensitive methods as PCR may allow better monitoring of medication, as well as early detection of EBV- and HHV-6 related diseases that may arise in these patients. The great sensitivity of PCR and its ability to analyse very small samples make this technique most suitable for clinical diagnosis.

Adult↗
PubMed1991

Serum and urinary human heart fatty acid-binding protein in acute myocardial infarction.

A competitive enzyme immunoassay (C-EIA) was developed for the measurement of serum and urinary levels of human heart fatty acid-binding protein (hh-FABP), and the appearance and time-course changes of hh-FABP levels were evaluated in patients with acute myocardial infarction (AMI). Control serum and urinary hh-FABP levels, which were determined in 86 serum and 42 urine samples from 86 patients without AMI, were found to range between 0 and 2.8 ng/mL. Serial determinations performed on 11 patients with AMI demonstrated that hh-FABP levels were significantly elevated in the first serum and urine samples obtained within 14 h of the onset of clinical symptoms. Two serum and 2 urine samples obtained only 1.5 h after the onset of symptoms already showed elevated hh-FABP levels, while in the same serum samples the activity of the myocardial-specific isoenzyme of creatine kinase (CK-MB) was still normal. Maximal serum and urinary hh-FABP levels appeared between 5 and 10 h after symptoms developed, and fell sharply towards normal thereafter. The hh-FABP levels in serum and urine both peaked earlier than the elevation of CK-MB activity in serum. The presence of hh-FABP in serum and/or urine seems to be a marker for myocardial damage and could be used as a useful tool for the early diagnosis of AMI.

Adolescent↗
PubMed1991

Effects of volatile anesthetics on bacteriorhodopsin in purple membrane, Halobacterium halobium cells and reconstituted vesicles.

In this study, we have investigated effects of volatile anesthetics on absorption spectra, proton pumping activity and decay of photointermediate M of bacteriorhodopsin (bR) in differently aggregated states. Anesthetics used in this study are ether-type general anesthetics; enflurane and sevoflurane. The observed effects on bR depend not only on variety or concentration of anesthetics but also strongly on the aggregation state of bR molecules in the membrane. In purple membrane (PM), bR having maximum light absorption at 567 nm (bR567) is formed in the presence of sevoflurane or a small amount of enflurane, while a species absorbing maximally at 480 nm (bR480) is formed upon the addition of large amounts of enflurane. X-ray diffraction studies show that the former species maintains crystallinity of PM, but the latter does not. In reconstituted vesicles where bR molecules exist as monomer, even sevoflurane forms bR480. Flash photolysis experiments show that bR567 contains a shorter-lived M intermediate absorbing maximally at 412 nm in the photoreaction cycle than bR does and that bR480 contains at least two long-lived M intermediates which seem to absorb maximally near and at lower than 380 nm. The measurements of light-induced pH changes of the whole cells and of the reconstituted vesicles in the presence of the anesthetics indicate that bR567 has a enhanced proton pumping efficiency, while bR480 has a quite low or no activity. No significant difference was observed in the anesthetic action between two inversely pumping vesicles. These observations suggest that on the formation of bR480, anesthetics enter into the membrane and affect the protein-lipid interaction.

Anesthetics↗
PubMed1991

Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease.

Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease.

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement.

Adenosine↗
PubMed1991

An endonuclease activity of Escherichia coli that specifically removes 8-hydroxyguanine residues from DNA.

An enzyme that specifically removes an 8-hydroxyguanine (8-OH-Gua) residue in DNA has been purified from Escherichia coli. To assay the enzymatic activity, a synthetic double-stranded DNA (dsDNA) containing 8-OH-Gua at a defined position was used as a substrate. The substrate DNA was simultaneously cleaved at 2 sites, i.e., the phosphodiester bonds 5' and 3' to 8-OH-Gua, leaving a phosphate at each of the neighboring deoxynucleosides. The cleavage was observed only in dsDNA, but not with single-stranded DNA containing 8-OH-Gua. This enzyme showed almost no activity on DNAs containing other kinds of modified bases such as 8-hydroxyadenine, O6-methylguanine and N7-methylguanine. Also DNAs containing mismatches (A/G or C/T) were not cleaved. Studies on several other properties of this enzyme indicate that it differs from endonucleases previously isolated from E. coli, indicating that it is likely to be an endonuclease which specifically recognizes 8-OH-Gua in dsDNA.

Base Composition↗
PubMed1991

Solution conformation of endothelin determined by means of 1H-NMR spectroscopy and distance geometry calculations.

The structure of endothelin-1 (ET-1), an endothelial cell-derived peptide with vasoconstricting activity, was determined in an aqueous solution by means of a combination of NMR and distance geometry calculations. The resulting structure is characterized by an alpha-helical conformation in the sequence region, Lys9-Cys15. Furthermore, an extended structure and a turn structure exist in the Cys1-Ser4 and Ser5-Asp8 regions respectively, and no preferred conformation was found for the C-terminal part of the peptide which was not uniquely constrained by the NMR data. These structural elements, the alpha-helical structure in the sequence portion, Cys-X-X-X-Cys, and the extended structure in Cys-X-Cys, are homologous to those found commonly in several neurotoxic peptides.

Algorithms↗
PubMed1991

Inappropriate secretion of antidiuretic hormone in isolated adrenocorticotropin deficiency.

A 62-year-old man was admitted because of nausea and vomiting. Severe hyponatremia with renal sodium loss was found. Endocrinological studies revealed that the patient had isolated adrenocorticotropin (ACTH) deficiency and secondary adrenocortical insufficiency. Furthermore, an inappropriate secretion of antidiuretic hormone (ADH) in relation to the low plasma osmolality was observed at an early stage of hyponatremia. Hydrocortisone therapy effectively corrected his hyponatremia. Following the correction of hyponatremia, the value of free water clearance increased and the level of the plasma ADH decreased. Thus, the present case indicates that ACTH deficiency can cause the syndrome of inappropriate secretion of ADH.

Adrenocorticotropic Hormone↗
PubMed1991

Production and effect of infectious Dane particles in transgenic mice.

We have demonstrated by immunoelectron microscopy that 42-nm particles with double-shelled structures characteristic of Dane particles are present in the serum of transgenic mice, 1.2HB-BS 10, carrying partly duplicated hepatitis B virus (HBV) genome. Furthermore, these particles were shown to infect primary human fetal hepatocytes as demonstrated by the elevation of HBV surface antigen (HBsAg) in the culture medium. HBV DNA is known to be expressed in a liver- and kidney-specific manner in the adult mouse, so we examined the developmental expression of viral antigens. In the liver, viral antigens (HBsAg and HBV e antigen) began to be expressed before birth and the level of expression showed a sharp rise after birth. On the other hand, in the kidney, viral antigens began to be expressed after birth. Serum levels of viral antigens were roughly proportional to the levels of expression in the liver, suggesting that the liver is the main source for viral antigens in the serum. None of these transgenic mice produced anti-HBs or anti-HBV core response or showed biochemical or pathological change up to at least 24 months of age. All these results suggest that infectious viral particles can be produced in transgenic mice, and that expression and replication of HBV DNA are not toxic in vivo.

Aging↗
PubMed1991

Transforming activity of a synthetic c-Ha-ras gene containing O6-methylguanine in codon 12.

A mutagenic DNA-adduct, O6-methylguanine, was introduced into codon 12 of the synthetic c-Ha-ras gene by cassette mutagenesis. Transfection of this modified ras gene into normal NIH3T3 cells by the calcium phosphate procedure resulted in significant induction of focus formation. The ras gene inserted into the transformed cells was found to have a G to A transition at the position of the modified base. These results indicate that an O6-methylguanine residue in DNA may lead to a mutation and be one cause of activation of the ras gene.

3T3 Cells↗
PubMed1991

Internal Ca2+ mobilization by muscarinic stimulation increases secretion from adrenal chromaffin cells only in the presence of Ca2+ influx.

The cytosolic free Ca2+ concentration ([Ca2+]in) in single cat and bovine adrenal chromaffin cells was measured to determine whether or not there was any correlation between the [Ca2+]in and the catecholamine (CA) secretion caused by muscarinic receptor stimulation. In cat chromaffin cells, methacholine (MCh), a muscarinic agonist, raised [Ca2+]in by activating both Ca2+ influx and intracellular Ca2+ mobilization with an accompanying CA secretion. In bovine cells, MCh elevated [Ca2+]in by mobilizing intracellular Ca2+ but did not cause CA secretion. The MCh-induced rise in [Ca2+]in in cat cells was much higher than that in bovine cells, but when Ca2+ influx was blocked, the rise was reduced, with a concomitant loss of secretion, to a level comparable to that in bovine cells. Intracellular Ca2+ mobilization due to muscarinic stimulation substantially increased secretion from depolarized bovine and cat cells, where a [Ca2+]in elevated above basal values was maintained by a continuous Ca2+ influx. These results show that Ca2+ released from internal stores is not effective in triggering secretion unless Ca2+ continues to enter across the plasma membrane, a conclusion suggesting that secretion depends on [Ca2+]in in a particular region of the cell.

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