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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 955 records · Page 53Linked to original sources
PubMed1993

Comparison of survival curves of gastric cancer patients after surgery according to the UICC stage classification and the General Rules for Gastric Cancer Study by the Japanese Research Society for gastric cancer.

OBJECTIVE: This study compared the UICC classification with the General Rules for Gastric Cancer Study (GRGCS) of the Japanese Research Society by analyzing recent results of gastric cancer surgery in Japan. SUMMARY BACKGROUND DATA: The present UICC stage classification for gastric cancer was published in 1987 and the Japanese GRGCS were published in 1985. Both are based on the results of surveys conducted in the early 1970s. METHODS: The survival curves of 926 patients, who underwent gastric cancer surgery between 1982 and 1985 at Kyoto University Hospital and its 31 associated hospitals, were analyzed according to the UICC classification and the GRGCS using SAS computer software. RESULTS: There was no difference in survival rate between UICC stages IA and IB. GRGCS stage III was found to include UICC stages II, IIIA, and IIIB, and GRGCS stage IV included UICC stages IIIA, IIIB, and IV, with significantly different survival rates. In contrast, each UICC stage included different GRGCS stages with no significant differences in survival rates. The survival rate of stage IV patients of both classifications who underwent gastrectomy was significantly higher than that of stage IV patients receiving bypass or exploratory surgeries. CONCLUSIONS: The UICC classification is better than the GRGCS for classifying gastric cancer in Japan. However, UICC stage I does not need to be subdivided into stages IA and IB, and stage IV should be further subdivided into stages IVA and IVB according to the surgery performed: IVA, gastrectomy, and IVB, bypass or exploratory surgery.

Humans↗
PubMed1993

Chemical modification by polyethylene glycol of the anti-tumor enzyme arginine deiminase from Mycoplasma arginini.

Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in culture by depleting amino acids in the medium. Here we demonstrate that arginine deiminase (EC 3.5.3.6) from Mycoplasma arginini had stronger growth-inhibitory activity against all 4 kinds of tumor cell lines tested than L-asparaginase and arginase, which are well-known anti-tumor enzymes. Next, chemical modification of the arginine deiminase molecule with polyethylene glycol was shown to enhance its potency as an anti-tumor enzyme. The percentage of modified amino groups per molecule was estimated to be 51% of the total amino groups, and the average molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The enzymic activity of the modified enzyme was 25.5 units/mg protein, which was equivalent to 57% of that of the native enzyme. The modified enzyme strongly inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more than 10 ng/ml, showing almost the same dose-response curve as the native enzyme. When a bolus of 5 units of the modified enzyme was intravenously injected into male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and remained undetectable for more than 8 days. On the other hand, in the case of bolus injection of the same number of units of native enzyme, the plasma L-arginine level recovered up to 66% of the control level at 8 days. These results suggest that this modified enzyme has a longer plasma clearance time and may be more effective as a new anti-tumor agent than the native enzyme.

Animals↗
PubMed1993

Cytotoxicity of Porphyromonas gingivalis toward cultured human gingival fibroblasts.

Direct cytotoxicity of black-pigmented anaerobic rods was studied on the confluent monolayer of human gingival fibroblasts in vitro. Only strains of Porphyromonas gingivalis caused morphological alteration (cell-rounding) and notable depression of viability of fibroblasts. To determine the location of the cytotoxicity, bacterial surface components, i.e., outer membrane, lipopolysaccharide, fimbriae and outer membrane vesicles were prepared from P. gingivalis and their cytotoxicity was assessed. Among these preparations, only outer membrane vesicles are supposed to have high affinity to human gingival fibroblasts, and the cytotoxicity of outer membrane vesicles was found to be much stronger than that of the other constituents. This cytotoxic factor seemed to consist largely of protein and to be associated with the enzyme activity of outer membrane vesicles. The effects of some protease inhibitors and L-cysteine on the cytotoxicity of outer membrane vesicles suggest that the mechanism of cell-rounding is different from that of cell death.

Adolescent↗
PubMed1993

Participation of an arginyl residue of insulin chain B in the inhibition of hemagglutination by Porphyromonas gingivalis.

Insulin chain B, containing each one arginyl and lysyl residue in its peptide chain, inhibited hemagglutination by Porphyromonas gingivalis. To determine the further inhibitory profile, chain B was digested into 4 fragments by protease, which was contained in the preparation of hemagglutinin from P. gingivalis. Identification of each fragment by the amino acid analysis revealed that the chain was cleaved at the carboxyl site of arginyl and/or lysyl residues, but one fragment contained citrulline instead of arginine at its carboxyl terminal. This citrulline might have originated from arginine by an arginine deiminase-like enzyme of P. gingivalis. Only one fragment that contained the arginyl residue exhibited inhibitory activity on hemagglutination, but it was considerably weakened compared with that of the intact chain B. The difference in the inhibitory activity seemed to depend on the position of an arginyl residue in the peptide; this was also confirmed using several derivatives of bradykinin. The present result suggests that the internal arginyl residue in a peptide chain may be critical for the inhibition of the hemagglutination by P. gingivalis.

Amino Acid Sequence↗
PubMed1993

Effects of right ventricular pacing on QRST isointegral maps in patients with and without myocardial infarction: body surface distribution of significant changes in QRST area compared to supraventricular complex.

To assess the effects of right ventricular (RV) pacing on body surface QRST distributions, we recorded QRST isointegral maps (I-maps) during sinus rhythm and RV pacing in 25 patients with anterior myocardial infarction (MI), 19 with inferior MI, and 14 without MI. The QRST values at each lead point recorded during sinus rhythm and RV pacing with an 87-lead system were analyzed with a paired t-test in each patient. An abnormal decrease in the QRST value of the I-map was assessed by the difference map, which indicated a "-2SD area," where the QRST integral value was less than the normal range (mean - 2SD) calculated from 608 normal individuals. The I-maps were similar during the two activation sequences in patients with and without MI. However, during RV pacing, QRST values significantly decreased over the upper right anterior chest and increased over the lower left anterior chest and back. The sigma DMs (sum of QRST integral values below the normal range) for both activation sequences were strongly correlated in patients with anterior MI and with inferior MI (r = 0.91 and r = 0.92, respectively; P < 0.001). Although small but significant changes in QRST values were detected, the distribution of the "-2SD area" and the sigma DM were similar during both activation sequences in patients with prior MI. Thus, these findings demonstrate that an altered activation sequence produces small but significant changes in QRST values but that I-maps still provide information that is useful for the diagnosis of MI during RV pacing.

Adult↗
PubMed1993

The mutation of codon 249 in the p53 gene is not specific in Japanese hepatocellular carcinoma.

Hepatocellular carcinoma samples obtained from 59 patients at surgical resection were examined for mutations of the third base at codon 249 of the p53 gene, using the polymerase chain reaction and oligonucleotide hybridization techniques. This point mutation, which is frequently observed in HCC cases from Southern Africa and Quidong in China, was not recognized in either 60 hepatocellular carcinomas or 53 noncancerous liver tissue samples from Japan. Thirty-four of 45 patients (75.6%) were positive for the hepatitis C virus, which was a higher rate than that for hepatitis B virus infection (9 of 55; 16.4%). The exposure to aflatoxin B1 was not considered to be remarkable. These results suggest that the point mutation of the third base at codon 249 is not common in Japanese patients, and it is suggested that numerous other factors affect the mutation of the p53 gene and the development of hepatocellular carcinoma.

Adult↗
PubMed1993

Circadian motile activity of erythrophores in the red abdominal skin of tetra fishes and its possible significance in chromatic adaptation.

The red abdominal skin of the neon tetra Paracheirodon innesi and the cardinal tetra P. axelrodi was found to blanch at night or in the dark. Melatonin added to the bathing medium caused blanching of the red skin. Microscopic observations of the erythrophores indicated that the erythrosomes aggregated in response to norepinephrine, melanin-concentrating hormone (MCH), and melatonin. Of these compounds, melatonin was the most effective. By contrast, many erythrophores were refractory to MCH. Alpha-melanophore-stimulating hormone, isoproterenol, adenosine, and ATP each caused dispersal of the pigment to some extent. Isoproterenol dispersed the pigment only when an alpha-adrenergic blocker, tolazoline, was present. It appears that the change in color of the abdominal skin is primarily due to increased secretion during the night of the pineal hormone melatonin, while other hormonal and nervous factors may modify the distribution of the pigment in the erythrophores.

Adaptation, Physiological↗
PubMed1993

Muscarinic cholinoceptors that mediate pigment aggregation are present in the melanophores of cyprinids (Zacco spp.).

Like melanophores of many teleosts, those of the dark chub, Zacco temmincki, and the common minnow, Z. platypus (Cyprinidae, Cypriniformes) responded to norepinephrine (NE) by the aggregation of pigment. It was further found that some melanophores were responsive to acetylcholine (ACh) in the same way. The response to NE was blocked by an alpha-adrenergic blocker, phentolamine, whereas the response to ACh was not. By contrast, two muscarinic cholinoceptor antagonists, namely, atropine and scopolamine, effectively blocked the action of ACh. The pigment aggregation due to the liberated sympathetic neurotransmitter was blocked by phentolamine but not by cholinergic blockers. These results suggest that, although the melanophores of these species are controlled in an orthodox manner by the sympathetic nervous system, some of them possess extra muscarinic cholinoceptors that also mediate the aggregation of pigment. The present report is the first to describe the presence of cholinoceptors on the chromatophores in species of fish other than those that belong to the order Siluriformes. The evolutionary implications of these findings are discussed.

Acetylcholine↗
PubMed1993

In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine.

Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in target CD4+ ATH8 cells, the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively. Both agents completely blocked the replication of 3'-azido-2',3'-dideoxythymidine-sensitive and -insensitive clinical HIV-1 isolates at 0.08 microM as tested in target phytohemagglutinin-activated peripheral blood mononuclear cells. The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI-272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells. Both compounds blocked the posttranslational cleavage of the p55 precursor protein to generate the mature p24 Gag protein in stably HIV-1-infected cells. The n-octanol-water partition coefficients of KNI-227 and KNI-272 were high, with log Po/w values of 3.79 and 3.56, respectively. Degradation of KNI-227 and KNI-272 in the presence of pepsin (1 mg/ml, pH 2.2) at 37 degrees C for 24 h was negligible. Current data warrant further careful investigations toward possible clinical application of these two novel compounds.

Antiviral Agents↗
PubMed1993

Glomerulonephritis with various crystalline deposits.

A 60-year-old Japanese male was admitted with nephrotic syndrome complaining of facial and pedal edema. Renal biopsy revealed mesangial and endocapillary proliferation with massive mesangial and subendothelial deposits. Deposits of IgA, IgG, IgM, C3 and fibrinogen were identified by immunofluorescence technique in both mesangial and subendothelial areas. Deposits of kappa and lambda light chains were also recognized in similar patterns. Electron microscopy revealed crystalline structures of various appearance in these deposits. A large deposit consisted of various small triangular, quadrilateral and polygonal shapes of deposits with crystalline structures. These crystalline structures exhibited lattice or parallel lamellar lines with different periodic distances. Although a disease producing paraproteinemia was suspected, no immunoglobulin disorder or light chain abnormality could be detected on clinical and laboratory examinations. On the second biopsy, a faint reaction for cryoglobulin was recognized. However, the crystalline deposits observed in this case were absolutely different from the tubular structures seen in cryoglobulinemic nephropathy. This was a very rare and unclassified case.

Crystallization↗
PubMed1993

Body surface distribution of abnormally low QRST areas in patients with Wolff-Parkinson-White syndrome. Evidence for continuation of repolarization abnormalities before and after catheter ablation.

BACKGROUND: Whether the Wolff-Parkinson-White syndrome (WPW) is associated with repolarization abnormalities is controversial. The QRST isointegral map (I-map) is theoretically independent of the activation sequence and dependent on repolarization properties. There have been no reports concerning the effects of radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization properties analyzed by I-mapping. METHODS AND RESULTS: I-maps were constructed from data recorded in 38 patients with WPW to investigate repolarization properties and their body surface distribution in a physiological state, without pharmacological influences, and in 13 ablated patients to elucidate the effects of RF ablation on repolarization properties. Patients were divided into three groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10 patients with type B (right-sided AP); and group C, 13 patients who were successfully ablated. Group C consisted of three subgroups: subgroup CA, 7 patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I-maps of WPW were highly (r = .87) correlated with the mean normal I-map, the location of the minimum in groups A and B differed significantly from that in normals. The minimum was located over the upper right anterior chest in normal subjects, over the back in 82% of 22 patients with type A WPW including ablated patients (groups A+CA), and over the mid to lower right anterior chest in 62% of 13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA and B+CB had an abnormally low QRST area ("-2SD area") over the back and right anterior chest, respectively. The abnormally located minimum and the "-2SD area" were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After RF ablation, the distribution of the minimum, initially abnormal, became normal over a period of days or weeks, and the "-2SD area" disappeared over 1 week in all 7 patients. Correlation coefficients between I-maps and the mean normal I-map increased after RF ablation. CONCLUSIONS: (1) WPW is often associated with abnormalities in repolarization properties. (2) Repolarization abnormalities were located over the back in type A WPW and over the right mid to lower chest in type B WPW: (3) The abnormalities remain immediately after RF ablation and gradually normalize. These findings support the concept that ST-T abnormalities in 12-lead ECGs following RF ablation are attributable to "cardiac memory."

Adolescent↗
PubMed1993

Discrete cortical infarction with prominent impairment of thumb flexion.

BACKGROUND: Intracortical efferent zones in the primary motor cortex for thumb movements, namely thumb flexion, extension, adduction, and abduction, have been described in Macaca mulatta monkeys but not in humans. Even recent cortical mapping based on intraoperative monitoring does not provide information about intracortical efferent zones as it is not ethically possible to search the human motor cortex extensively by punctate electrodes. CASE DESCRIPTION: A 78-year-old man with discrete cortical embolism over the left central sulcus is described. Only a mild weakness of his right thumb was observed. Thumb flexion was affected to a greater degree than thumb extension, adduction, and abduction. The lesion ran along the bottom of the central sulcus and affected part of the precentral and postcentral gyri on both sides of it. Animal studies in Macaca mulatta monkeys have shown that the intracortical efferent zones for thumb movement, especially for thumb flexion, are located in the part of the motor cortex just adjoining the central sulcus that folds down from the "bank" to the depth of the central sulcus. It was possible to explain the prominent weakness of thumb flexion if we applied the results of the animal studies. CONCLUSIONS: Our case suggests that the same arrangement of intracortical efferent zones found in monkeys may also exist in human beings.

Aged↗
PubMed1993

Effect of thyroid hormone on epidermal growth factor gene expression in mouse submandibular gland.

Epidermal growth factor (EGF) in mouse submandibular gland (SMG) is synthesized in the granular convoluted tubular (GCT) cells. The synthesis of EGF in SMG has been shown to be increased by thyroid hormone. This increase was attributed to the increase in EGF mRNA. Not known is how thyroid hormone increases the mRNA level. In the present study the effect of thyroid hormone administration on EGF gene expression in SMG was studied in hypothyroid mice. Hypothyroidism was induced by treating the mice with propylthiouracil. The amount of SMG EGF mRNA was markedly decreased in hypothyroid mice. Administration of T3 increased the mRNA in a dose-dependent manner. The increase in EGF mRNA by T3 was evident as early as 6 h after T3 administration. A nuclear run-off assay indicated that the induction of EGF gene expression by T3 is at a transcriptional level. Bromodeoxyuridine incorporation into GCT cells was not affected by T3 administration, suggesting that T3 does not cause the proliferation of these cells. In situ hybridization revealed that T3 increases EGF mRNA in GCT cells at a single cell level. These results suggest that thyroid hormone increases EGF gene transcription without affecting cellular proliferation.

Animals↗
PubMed1993

Purification and characterization of a 3,5,3'-L-triiodothyronine-specific binding protein from bullfrog tadpole plasma: a homolog of mammalian transthyretin.

We analyzed the nature of the thyroid hormone-binding proteins in bullfrog plasma using N-bromoacetyl-[125I]T3 as an affinity labeling probe. Polyacrylamide gel electrophoresis under nondenaturing conditions of the bullfrog N-bromoacetyl-[125I]T3-labeled plasma proteins revealed two proteins with specific binding to T3. A labeled protein that migrated faster than albumin (T-T3BP) was detected only in plasma obtained from tadpoles at stages earlier than, but not at the end of, metamorphic climax. Another protein that migrated more slowly than albumin appeared in the plasma at the late climax stage and was present in the adult stage. To study the function of T-T3BP during metamorphosis, it was purified from tadpole plasma to the single protein. The molecular mass of this protein was estimated to be 56 kilodaltons by gel filtration, but only 16 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which indicates that the molecule comprised four identical subunits. The amino acid composition of T-T3BP and the amino acid sequence of its N-terminal portion were highly homologous with those of mammalian transthyretins. These molecular features indicate that T-T3BP is a homolog of mammalian transthyretins. However, in contrast to mammalian transthyretins, the affinity of bullfrog transthyretin for T3 was 360 times higher than that for T4. Scatchard analysis revealed that T-T3BP possessed a single class of T3-binding site, with a Kd of 0.67 nM at 0 C. These results suggest that bullfrog transthyretin may play an important role in transporting T3 in the blood during metamorphosis.

Affinity Labels↗
PubMed1993

1,4:3,6-Dianhydrohexitol nitrate derivatives. I. Synthesis and antianginal activity of alkylpiperazine derivatives.

A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds with the aryl-heteroatom (O,S, or N)-propyl group. Among them, the phenylthiopropyl-substituted compound 13 exhibited the most potent activity. Furthermore, intraduodenal administration (i.d.) of 13 tended to decrease left ventricular end-diastolic pressure (LVEDP) in a propranolol-induced heart failure model (dogs) and showed a potent protective effect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is under further study as an orally active nitrate.

Administration, Oral↗
PubMed1993

1,4:3,6-Dianhydrohexitol nitrate derivatives. II. Synthesis and antianginal activity of aryl- or arylcarbonylpiperazine derivatives.

A series of 5-(4-aryl- or 4-arylcarbonylpiperazin-1-yl)-5-deoxy-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared in order to obtain orally active, nitrate-type vasodilators with reduced side effects. Our drug design was based on a small reduction in the lipophilicity compared to that of 5-deoxy-5-[4-(3-phenylthiopropyl)piperazin-1-yl]-1,4: 3,6-dianhydro-L-iditol 2-nitrate (1, KF14124). Compounds 4h (aryl = benzimidazol-2-yl), 4i (arylcarbonyl = nicotinoyl), and 4w (arylcarbonyl = 3-furoyl) showed potent anti-ischemic activity in a lysine-vasopressin-induced angina pectoris model (rats), and their structure-activity relationships are discussed. Compound 4i exhibited potent vasodilation of the coronary artery in anesthetized dogs and also exhibited potent preload reduction in a heart failure model (dogs) as compared with isosorbide dinitrate (2), nicorandil (3), and KF14124 (1). Furthermore, 4i showed much weaker acute lethal toxicity and less central nervous system depression than 1 in mice. Thus, 4i (KW-3196) is under development as a vasodilator and a drug for treating angina pectoris.

Angina Pectoris↗
PubMed1993

Effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein in rat heart.

This study was undertaken to examine the effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein (Gs), and coupling in the beta-adrenergic receptor-Gs-adenylate cyclase system in rat heart, in vitro. Cardiac membranes were preincubated with various concentrations (0.1, 1, and 10 mM) of hydrogen peroxide at 30 degrees C for 5, 10, 30 and 60 min. Although the assay of beta-adrenergic receptors involving [3H]-dihydroalprenolol ([3H]-DHA) binding revealed that the maximal number of binding sites (Bmax) was not altered, the dissociation constant (Kd) for [3H]-DHA was increased in the presence of 1 mM and 10 mM hydrogen peroxide (control 0.68 +/- 0.16 nM, vs 1 mM H2O2 1.13 +/- 0.16, 10 mM H2O2 1.01 +/- 0.12). Conversely, no significant changes in Gs activities were observed in hydrogen peroxide-treated groups. Adenylate cyclase activity (stimulated by forskolin) was significantly reduced by 10 mM hydrogen peroxide after a 5 min preincubation period (control 277.1 +/- 19.2 pmol cAMP/mg protein/min, H2O2 230.3 +/- 14.9). The amounts of cyclic AMP produced by the stimulation of membranes with GTP, GTP+(l)-isoproterenol, guanylimidodiphosphate (Gpp(NH)p) or Gpp(NH)p+(l)-isoproterenol were significantly lower in 10 mM hydrogen peroxide-treated groups than those in controls (GTP: control 57.6 +/- 5.6 pmol cAMP/mg protein/min vs H2O2 46.4 +/- 6.9, GTP+(l)-isoproterenol: control 83.9 +/- 10.2 vs H2O2 67.7 +/- 10.3, Gpp(NH)p: control 77.5 +/- 8.8 vs H2O2 61.0 +/- 8.6, Gpp(NH)p+(l)-isoproterenol: control 105.0 +/- 13.1 vs H2O2 83.9 +/- 12.2, forskolin: control 223.2 +/- 13.8 vs H2O2 182.8 +/- 18.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗