Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 37 records · Page 2Linked to original sources

PubMed1992

Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients.

For further study of the correlation of L-myc restriction-fragment-length polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs at the time of surgery, L-myc RFLP was analyzed in 252 Japanese lung-cancer patients. A close correlation between L-myc RFLP and metastasis was confirmed in this large number of patients (p = 0.01). The correlation was particularly pronounced in cases of adenocarcinoma and squamous-cell carcinoma. Poor prognosis (additional metastases after surgery) was observed in lung-cancer patients with L-S (identified as long and short bands produced with EcoRI) and S-S type L-myc RFLP. In addition, the death rate of lung-cancer patients with the L-S and S-S types was greater than that of those with the L-L type. Lung-cancer patients of the L-S and S-S types had almost 4 times higher incidence of multiple cancer in the lung, pharynx and other organs than those with the L-L type. Our results indicate that, in patients with lung cancer, genetic disposition with respect to the L-myc gene influences the extent of metastasis, the incidence of multiple cancers and prognosis.

Combined Modality Therapy↗

PubMed1992

A muscarinic receptor agonist mobilizes Ca2+ from caffeine and inositol-1,4,5-trisphosphate-sensitive Ca2+ stores in cat adrenal chromaffin cells.

To gain some understanding of the characteristics of intracellular Ca2+ stores of cat adrenal chromaffin cells, we investigated the effects of ryanodine, a blocker of Ca(2+)-induced Ca2+ release channels in muscle, on both cytosolic Ca2+ concentration and catecholamine secretion induced by caffeine or methacholine. The results suggest that Ca2+ stores consist of at least two compartments, one which is sensitive to both caffeine and inositol-1,4,5-trisphosphate (IP3), and the other which is sensitive to IP3 alone.

Adrenal Glands↗

PubMed1992

8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions.

Mutations caused by oxidative DNA damage may contribute to human disease. A major product of that damage is 8-hydroxyguanine (oh8Gua). Because of differences in experimental design, the base pairing specificity of oh8G in vivo is not completely resolved. Here, oh8dGTP and DNA polymerase were used in two complementary bacteriophage plaque color assays to examine the mutagenic specificity of oh8Gua in vivo. The first is a reversion assay that detects all three single-base substitutions caused by misreading of guanine analogues inserted at a specific site. oh8Gua at that site gave a mutation frequency of 0.7%. Twenty-two of the 23 mutations were G----T substitutions. The second assay, a forward mutation assay, tests the mispairing potential of any altered nucleotide 1) during incorporation as substrate nucleotide, and 2) after multiple incorporations into a single-stranded DNA gap region of M13mp2. Substituting oh8dGTP for dGTP during polymerization produced 16% mutants; two classes of mutations were observed, both caused by pairing of oh8Gua with A. Seventy-six of 78 mutations were A----C substitutions, and two were G----T substitutions. These assays thus illustrate mutagenic replication of oh8Gua as template causing G----T substitutions and misincorporation of oh8Gua as substrate causing A----C substitutions, both caused by oh8Gua.A mispairs.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1992

Detection and serotyping of rotaviruses in stool specimens by using reverse transcription and polymerase chain reaction amplification.

Direct rotavirus serotyping (VP7, G type) in stool specimens was carried out by reverse transcription and polymerase chain reaction amplification (RT-PCR) and compared to serotyping by enzyme immunoassay with monoclonal antibodies (EIA-MAb). The methods used for double-stranded (ds) RNA extraction, RT-PCR amplification, and the primers used were modified from previous reports [Gouvea et al.: Journal of Clinical Microbiology 29:519-523, 1990; Gentsch et al.: Journal of Clinical Microbiology, 1992]. For samples that were positive by both methods, the serotypes obtained were identical, however RT-PCR typing was found to be considerably more sensitive (70.4% samples serotyped) than EIA-MAb (35.6% of samples serotyped). The overall sensitivities for detection of rotavirus in stool samples by latex agglutination, enzyme immunoassay, electron microscopy, polyacrylamide gel electrophoresis, and RT-PCR were essentially the same. The results confirm that RT-PCR typing (genotyping) is extremely valuable for G typing of samples which cannot be typed by EIA-MAb. We also developed a PCR confirmation technique for serotypes 1, 2, and 4.

Acute Disease↗

PubMed1992

Guanine-nucleotide binding activity, interaction with GTPase-activating protein and solution conformation of the human c-Ha-Ras protein catalytic domain are retained upon deletion of C-terminal 18 amino acid residues.

A truncated human c-Ha-Ras protein that lacks the C-terminal 18 amino acid residues and the truncated Ras protein with the amino acid substitution Gly-->Val in position 12 were prepared by an E. coli overexpression system. The truncated Ras protein showed the same guanine-nucleotide binding activity and GTPase activity as those of the full-length Ras protein. Further, the same extent of GTPase activity enhancement due to GTPase-activating protein was observed for the truncated and full-length Ras proteins. In fact, two-dimensional proton NMR analyses indicated that the tertiary structure of the truncated Ras protein (GDP-bound or GMPPNP-bound) was nearly the same as that of the corresponding catalytic domain of the full-length Ras protein. Moreover, a conformational change around the effector region upon GDP-->GMPPNP exchange occurred in the same manner for both proteins. These observations indicate that the C-terminal flanking region (18 amino acid residues) of the Ras protein does not appreciably interact with the catalytic domain. Therefore, the truncated Ras protein is suitable for studying the molecular mechanism involved in the GTPase activity and the interaction with the GTPase-activating protein. On the other hand, an active form of the truncated Ras protein, unlike that of the full-length Ras protein, did not induce neurite outgrowth of rat pheochromocytoma PC12 cells. Thus, membrane anchoring of the Ras protein through its C-terminal four residues is not required for the interaction of Ras and GAP, but may be essential for the following binding of the Ras-GAP complex with the putative downstream target.

Animals↗

PubMed1992

A 1H-15N NMR study of human c-Ha-ras protein: biosynthetic incorporation of 15N-labeled amino acids.

A 1H-15N NMR study was performed on the GDP-bound form of a truncated human c-Ha-ras oncogene product (171 amino acid residues). Resonance cross peaks of the backbone amide 1H-15N nuclei of a uniformly 15N-labeled protein were observed with heteronuclear single-quantum coherence spectroscopy (HSQC). In order to resolve overlapping cross peaks, selective 15N-labeling of one or two types of amino acid residues (Ala, Arg, Asx, Glx, Gly, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Tyr and/or Val) was carried out using appropriate E. coli mutant strains. By this procedure, all the backbone 1H-15N cross peaks were classified into amino acid types.

Amino Acids↗

PubMed1992

Effects of epidermal growth factor and transforming growth factor-beta on insulin-induced differentiation in rat dental pulp cells.

An established pulp cell line (RPC-C2A) was used to study the regulatory effect of insulin on dentinogenesis. Insulin increased alkaline phosphatase activity and the incorporation of [2,3-3H]-proline into collagenase-digestible protein, whereas [3H]-thymidine incorporation by the cells was inhibited by insulin. The enhancing effect of insulin on alkaline phosphatase activity was inhibited by epidermal growth factor (EGF) or transforming growth factor-beta (TGF-beta). The stimulatory effect of insulin on collagen synthesis was also inhibited when insulin was combined with EGF, but was accelerated by the addition of TGF-beta. Inhibitory effects of insulin on the [3H]-thymidine incorporation were potentiated by EGF, though EGF alone strongly increased the effect; whereas the addition of TGF-beta had no significant effect on the insulin action. These findings suggest that insulin may be concerned with the differentiation of pulp cells in dentinogenesis and that EGF or TGF-beta regulate the insulin effects.

Alkaline Phosphatase↗

PubMed1992

Lack of effect of islet amyloid polypeptide on hepatic glucose output in the in situ-perfused rat liver.

Islet amyloid polypeptide (IAPP), a novel peptide isolated from islet amyloid deposits in patients with insulinoma and non-insulin-dependent diabetes mellitus (NIDDM), has been reported to be cosecreted with insulin from pancreatic beta cells and to inhibit glucose uptake and glycogen synthesis in muscle tissue in vitro. We investigated the effects of the synthesized, rat-amidated form of IAPP on hepatic glucose output, and IAPP extraction, using an in situ flow-through perfusion system in rats to elucidate the actions of IAPP on the liver. The IAPP (10(-8) mol/L) alone had no effects on the hepatic glucose release. Infusion of 6 x 10(-11) mol/L glucagon alone resulted in an expected elevation in glucose production (30.0 +/- 1.7 mumol/35 min/g liver). Insulin (3 x 10(-10) mol/L) submaximally decreased the glucagon-stimulated glucose production to 73% (from 30.0 +/- 1.7 to 22.0 +/- 1.4 mumol/35 min/g liver; n = 7, P less than .01). A simultaneous infusion of 10(-8) mol/L IAPP did not influence the glucagon-stimulated glucose production (27.6 +/- 1.2 mumol/35 min/g liver) or the insulin-dependent inhibition of glucagon-stimulated glucose production (22.6 +/- 1.3 mumol/35 min/g liver). IAPP extraction by the liver in a single passage was minimal, in contrast to approximately 50% hepatic insulin extraction. These results indicate that IAPP does not play any important role in modulating glycogen metabolism in the liver.

Amyloid↗

PubMed1992

Giant basal prolactinoma extending into the nasal cavity.

An unusual case of a giant prolactinoma extending to the nasopharynx and nasal cavity is presented. A 35-year-old man admitted for nasal obstruction and visual disturbances was found to have bilateral anosmia, right homonymous hemianopsia, and a right hemiparesis. The serum prolactin level was 13,300 ng/mL. Radiological examination revealed a large mass invading the skull base and extending into the suprasellar region and the left frontal lobe superiorly and into the nasopharynx inferiorly. Subtotal removal was done through a bilateral orbitofrontal craniotomy, which was followed by radiotherapy and bromocriptine administration. Immunohistochemical analysis confirmed a prolactinoma. The rarity of such a tumor, its location and extension, and the usefulness of magnetic resonance imaging and immunohistochemistry are stressed. Pertinent literature is reviewed.

Adult↗

PubMed1992

Architectural distortion of subcutaneous fascial layer in breast tumors: ultrasonographic evaluation.

To develop a criterion to evaluate architectural changes of the subcutaneous tissue layer around the breast, 120 patients with histologically proven tumors were studied as to ultrasonographical delineation of the superficial layer (SL) of the superficial fascia. Breast ultrasonography was performed using an electronic-linear scanner with a 5.0 MHz probe. When SL was identified over the tumor, it was classified into 3 types: flat, disrupted, and convergent types. SL was identified in 106 patients (88%). Forty-six were evaluated to be flat type, and 41 (89%) of them had benign tumors. The remaining 60 were subdivided into either disrupted (n = 44) or convergent type (n = 16); 53 (88%) of these 60 cases had cancerous lesions. Histologically, inward retraction of SL was the most common pattern in breast cancer. Thus, the ultrasonographic pattern of SL reflects the histological findings and can be a useful clue to differentiate benign lesions from cancerous ones.

Adult↗

PubMed1992

Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial.

OBJECTIVES: The study was designed to compare pharmacologic and exercise stress during thallium-201 single-photon tomography in a multicenter prospective crossover trial. BACKGROUND: Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients. METHODS: The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thallium tomographic tests performed 30 days apart, one during intravenous administration of adenosine (140 micrograms/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics. RESULTS: Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p less than 0.0001) and 11.1 (p less than 0.00001), respectively. The agreement by computer quantification was 86% with kappa and Z statistics of 0.709 (p less than 0.0001) and 12.2 (p less than 0.00001), respectively. Agreement on localization of the perfusion defect to a specific coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p less than 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p less than 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued. CONCLUSIONS: Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine.

Adenosine↗

PubMed1992

Effects of acute, transient coronary occlusion on global and regional right ventricular function in humans.

OBJECTIVES: The aim of this study was to investigate the changes in right ventricular function during acute coronary occlusion produced by inflating a coronary angioplasty balloon catheter. BACKGROUND: Alterations in right ventricular function are well known to occur in patients with acute myocardial infarction or ischemic cardiomyopathy. However, the changes in right ventricular function resulting from acute, transient coronary occlusion of each of the major coronary arteries have been scantily studied, perhaps because of serious limitations of currently available technology. METHODS: A newly designed, mobile, multiwire gamma camera, in combination with generator-produced tantalum-178, affords high count rate first-pass radionuclide angiography and is thus ideal for studying right ventricular function at the bedside. Accordingly, 46 patients underwent first-pass radionuclide angiography at baseline and during transient coronary occlusion induced by a coronary angioplasty balloon catheter. RESULTS: A significant, albeit modest, decrease in global right ventricular ejection fraction occurred during occlusion of the left anterior descending (from 42.9 +/- 9.3% to 39 +/- 8.7%, p < 0.05) and left circumflex (from 44 +/- 9.1% to 38.8 +/- 7.9%, p = 0.03) coronary arteries, but diagonal artery occlusion caused no significant change in right ventricular ejection fraction. Occlusion of the right coronary artery proximal (but not distal) to the acute marginal branch caused a significant decrease in right ventricular ejection fraction (from 42.6 +/- 4.7% to 35.7 +/- 7.2%, p < 0.01). Although occlusion of the left anterior descending, left circumflex and proximal right coronary arteries all caused significant deterioration in regional right ventricular function, only proximal right coronary occlusion caused right ventricular dilation (p < 0.005). CONCLUSIONS: Significant impairment of right ventricular function occurs during transient occlusion of the left anterior descending, left circumflex and proximal right coronary arteries, but only occlusion of the latter causes acute right ventricular dilation, probably as a result of ischemia.

Adult↗

PubMed1992

Quantification of left ventricular performance during transient coronary occlusion at various anatomic sites in humans: a study using tantalum-178 and a multiwire gamma camera.

To study the functional significance of transient coronary occlusion on systolic and diastolic left ventricular function relative to the anatomic site of occlusion, first-pass radionuclide angiography with a mobile multiwire gamma camera using tantalum-178 (dose activity less than or equal to 84 mCi/elution) was performed in 46 patients undergoing balloon coronary angioplasty. First-pass images were acquired immediately before angioplasty and during the last 30 s of a 60-s balloon inflation in 23 left anterior descending arteries, 18 right coronary arteries, 8 circumflex arteries and 3 diagonal coronary arteries. Occlusion of the left anterior descending artery resulted in significant decreases in left ventricular ejection fraction (54.6 +/- 12.7% to 32.3 +/- 10.6%, p = 0.0001) and peak filling rate (2.48 +/- 0.68 to 1.75 +/- 0.64 end-diastolic volumes/s, p = 0.0001), accompanied by severe abnormalities in regional function and left ventricular dilation. Right coronary artery occlusion caused inferior hypokinesia, but did not significantly change left ventricular ejection fraction (48.5 +/- 12.4% vs. 45.8 +/- 12.5%, p = NS) or peak filling rate (2.05 +/- 0.81 vs. 2.09 +/- 0.81 end-diastolic volumes/s, p = NS). Circumflex artery occlusion resulted in mild wall motion deterioration and a borderline decrease in ejection fraction (54.7 +/- 11.4% to 50.5 +/- 12%, p = 0.057). Diagonal artery occlusion did not cause significant changes in left ventricular ejection fraction or filling rate. The decrease in left ventricular ejection fraction during coronary occlusion was 9 +/- 25% and 27 +/- 22%, respectively, in those arteries with and without collateral supply (p = 0.052). These data provide strong evidence for the critical importance of the left anterior descending artery and the secondary role of the other coronary arteries in maintaining global systolic and diastolic left ventricular function and suggest a protective role of collateral vessels during coronary occlusion.

Angioplasty, Balloon, Coronary↗

PubMed1992

Protection of DNA damage by dietary restriction.

Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats.

Animals↗

PubMed1992

Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex.

We investigated the effect of zonisamide, a new antiepileptic drug, on voltage-dependent Ca2+ currents in cultured neurons of rat cerebral cortex. Whole-cell voltage-clamp recordings demonstrated at least two distinct voltage-dependent Ca2+ currents: (1) a low-threshold, rapidly inactivating component, T-type Ca2+ current, which is sensitive to 100 microM Ni2+, and (2) a high-threshold, slowly inactivating (long-lasting) component, L-type Ca2+ current. Zonisamide, a new anticonvulsant effective against maximal electroshock (MES) seizures in mice reduced T-type Ca2+ current in a dose-dependent manner. The mean percentage of reduction was 59.5 +/- 7.2% at 500 microM, but zonisamide had no effect on L-type Ca2+ current. A methylated analog of zonisamide, which is ineffective against MES seizures in mice, was tested at a concentration of 500 microM, and reduced neither T-type nor L-type Ca2+ current. These findings suggest that the effects of zonisamide against MES seizures might occur through the reduction of T-type Ca2+ current. Because drugs that are effective against MES seizures are thought to prevent seizure discharge spread, T-type Ca2+ channels could underlie a cellular mechanism of spreading activity in epileptic seizures.

Action Potentials↗

PubMed1992

Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system.

Point mutations in the transmembrane domain of c-erbB-2 gene in human brain tumours were studied by DNA amplification with the polymerase chain reaction method. Amplified gene fragments in M13 phage vector were cloned, and subsequent nucleotide sequences were determined. Studied specimens were 10 human malignant and 3 human benign tumours of the central nervous system, and a normal human placenta. In malignant tissues, Val-to-Glu mutation that induces transforming activity of c-erbB-2 did not appear to codon 659 of c-erbB-2. In malignant tissues, many other types of mutations appeared in low frequency, either at codon 659 or other positions of the transmembrane domain of c-erbB-2. The ratio of mutated genes to normal genes was very low in all specimens of malignant tumours. The point mutations were not observed in benign brain tumour or normal human placental tissues. The transmembrane domain of c-erbB-2 may have several highly mutable hot spots, where brain tumour tissues show a predilection for point mutation.

Amino Acid Sequence↗

PubMed1992

1H-NMR assignment and secondary structure of human insulin-like growth factor-I (IGF-I) in solution.

Human insulin-like growth factor-I (IGF-I) was studied by two-dimensional 1H-NMR spectroscopy. Resonance assignments were obtained for all the backbone protons and almost all of the sidechain protons of the total 70 amino acid residues, using sequence-specific assignment procedures. The secondary structure elements of human IGF-I were identified by investigation of the sequential and medium range NOEs as a preliminary step in determining the three-dimensional structure of this protein by means of distance geometry calculations. The typical NOEs of d alpha beta(i,i + 3) and d alpha N(i,i + 3), as well as the successive strong NOEs of dNN connectivities and slowly exchanging amide protons confirmed the presence of three helical segments corresponding to the sequence regions, Ala8-Cys18, Gly42-Cys48, and Leu54-Cys61, and the existence of a beta-turn in the Gly19-Gly22 region. Our results definitely indicate that the secondary structure of human IGF-I in solution is consistent with that of insulin in the crystalline state.

Amino Acid Sequence↗

PubMed1992

Clinical application of an active electrode using an operational amplifier.

An active electrode (d10 mm, t6 mm) is presented, that functions as an impedance transformer (an input impedance > 10 G omega, an output impedance < 1 omega) by means of which we can derive surface EMG without any skin preparation and paste. This electrode was compared with a conventional one, and it was ascertained that the electrode could be replaced with the conventional one, and, moreover, it was preferable because it required less preparation time, and was less affected by environmental noise.

Amplifiers, Electronic↗