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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 901 records · Page 50Linked to original sources
PubMed1994

Isolated hepatic caudate lobectomy.

BACKGROUND: Isolated caudate lobectomy is a challenging surgical procedure for which safe and reliable techniques have yet to be developed. METHODS: Isolated caudate lobectomy was performed by initial inflow control of the caudate lobe, full mobilization of the liver from the inferior vena cava by dividing all short hepatic veins, and parenchymal division dorsal to the major hepatic veins with a clockwise rotation of the liver while the liver was selectively devascularized by Pringle's maneuver and occlusion of the confluence of the major hepatic veins flush with the inferior vena cava. RESULTS: Two patients with cirrhosis underwent this procedure successfully without intraoperative hemodynamic instability or postoperative liver dysfunction. CONCLUSIONS: This technique allows safe and truly selective excision of the caudate lobe without the need for occlusion of the inferior vena cava or venovenous bypass.

Carcinoma, Hepatocellular↗
PubMed1994

[Low molecular weight heparin inhibits raised intraocular pressure following intracameral administration of sodium hyaluronate].

The effect of low molecular weight (LMW) heparin on increase of intraocular pressure following intracameral administration of sodium hyaluronate (HA) was investigated in rabbit eyes. In each case, the aqueous humor of one eye was replaced with HA and a balanced salt solution (BSS) containing 10.0 IU/ml of LMW heparin, and as a control the aqueous humor of the fellow eye was replaced with HA and BSS containing no LMW heparin. Intraocular pressure was measured for 24 hours following the replacement. As a result, significant increase of intraocular pressure was observed at 6 hours after the injection in the eyes administered HA and BSS. In comparison, no significant increase of intraocular pressure was observed in the eyes injected with HA and LMW heparin. When the concentration of LMW heparin was less than 2 IU/nl or the LMW heparin was heat-deactivated, the HA-induced increase of intraocular pressure was not inhibited. The results indicated that LMW heparin inhibits increase of intraocular pressure following intracameral administration of HA possibly by an inhibitory effect on intraocular fibrin exudation, and the increase of intraocular pressure is probably associated with interaction between fibrin and HA.

Animals↗
PubMed1994

[Immunohistochemical localization of blood-retinal barrier breakdown after argon laser photocoagulation in the monkey retina].

Retinal photocoagulation induces breakdown of the blood-retinal barrier (BRB), but the site of the breakdown is not precisely known. The breakdown and repair of BRB following argon laser photocoagulation were studied in the monkey retina by immunohistochemical localization of serum albumin. Argon laser photocoagulation was performed to obtain ordinary burns as in human use. 1, 3, and 7 days after photocoagulation, serum albumin was observed in the outer retina and retinal pigment epithelium, but not around the retinal blood vessels. The immunostaining disappeared within 14 and 28 days after photocoagulation. The results of this study suggest that photocoagulation induces local breakdown of the outer BRB and that the breakdown is repaired within 14 days.

Animals↗
PubMed1994

[A case of Borrmann type 4 gastric cancer responding to sequential methotrexate and 5-fluorouracil combined with CDDP].

A case of Borrmann type 4 gastric cancer responding to sequential methotrexate and 5-fluorouracil combined with cis-diamminedichloroplatinum (CDDP) is reported. A 57-year-old woman was admitted to our hospital complaining of abdominal fullness. Upper gastrointestinal series and gastrofiberscopy revealed almost the entire stomach was involved with Borrmann type 4 cancer. Gastrectomy could not be performed because of peritoneal dissemination. However, the patient responded to sequential methotrexate and 5-fluorouracil therapy and CDDP administration. She enjoyed more than one year of hospital-free survival period and survived for almost two years.

Adenocarcinoma↗
PubMed1993

Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice.

BACKGROUND: Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer. METHODS: Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (3H-thymidine incorporation). RESULTS: CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines. CONCLUSIONS: These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin-antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.

Animals↗
PubMed1993

Escherichia coli aromatic amino acid aminotransferase: characterization and comparison with aspartate aminotransferase.

Aromatic amino acid aminotransferase (ArAT) from Escherichia coli was overexpressed in E. coli cells, purified, and characterized. The enzyme was similar to aspartate aminotransferase (AspAT) of E. coli in many aspects, such as gross protein structure and spectroscopic properties. The reactions of pyridoxal 5'-phosphate-form ArAT with amino acids and pyridoxamine 5'-phosphate-form ArAT with oxo acids were investigated using stopped-flow spectrophotometric techniques. The kinetic parameters for these "half" reactions could excellently explain the ArAT-catalyzed overall transamination reactions at pH 8.0. Reactions of ArAT with aspartate and tryptophan which had been deuterated at position 2 showed isotope effects of 2.5 and 6.0 in the kcat values of the half-reactions, showing that the proton-transfer step is at least partially rate-limiting for these reactions. ArAT and AspAT showed overlapping substrate specificity. Both ArAT and AspAT were active toward dicarboxylic substrates. ArAT showed, however, 10(3)-fold higher activity toward aromatic substrates than AspAT. This high activity toward aromatic substrates was in part ascribed to the active site hydrophobicity of ArAT, which was suggested to be about 1.4 times as large as that of AspAT. In addition to dicarboxylic substrate analogs, aromatic substrate analogs such as carboxylic acids, 2-methyl amino acids, and 3-hydroxy amino acids caused characteristic changes in the absorption spectra of ArAT, while these aromatic analogs did not significantly change the spectra of AspAT. In particular, the erythro-3-hydroxy analogs of phenylalanine and aspartate caused a prominent absorption of ArAT at around 500 nm, which is generally ascribed to the accumulation of quinonoid intermediates. The threo forms of these 3-hydroxy analogs acted as substrates for ArAT. The erythro and threo forms of 3-hydroxyaspartate reacted with AspAT similarly as they reacted with ArAT; however, both forms of 3-phenylserine were poor substrates for AspAT, although phenylalanine was a fairly good substrate for AspAT. The observations on the two erythro-3-hydroxy amino acids show the similar orientation of these analogs in the active site of ArAT, probably through a hydrogen-bonding network involving the hydroxy groups of the analogs and Tyr70, and suggest that the aromatic binding pocket is near or even overlaps the side-chain-carboxylate-binding site for dicarboxylic substrates.

Amino Acid Sequence↗
PubMed1993

CX-397, a novel recombinant hirudin analog having a hybrid sequence of hirudin variants-1 and -3.

To elucidate the differential roles of N- and C-terminal halves of hirudins in thrombin inhibition, we produced novel recombinant hirudin analogs, CX-397 and CX-397R, having a hybrid amino acid sequence of hirudin variants-1 (HV-1) and -3 (HV-3). CX-397 is composed of the N-terminal half of HV-1 (HV-11-36) combined with the C-terminal half of HV-3 (HV-337-66). CX-397R is the opposite combination. Their anti-thrombin activity was determined by a fluorogenic enzyme assay and compared with that of recombinant HV-1 (rHV-1) and rHV-3. The order of the magnitude of dissociation constants (Ki) of these four hirudin analogs in thrombin inhibition was as follows: CX-397R (0.294 pM) > rHV-1 (0.148 pM) > rHV-3 (0.0593 pM) > CX-397 (0.0433 pM), indicating that CX-397 is the strongest inhibitor among them.

Amino Acid Sequence↗
PubMed1993

5-HT3 receptor antagonists. 3. Quinoline derivatives which may be effective in the therapy of irritable bowel syndrome.

A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the place of an aromatic ring in their minimum-energy conformations. These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats. Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively). However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.000 10 mg/kg, i.v., respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po. On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2. The ID50 value of endo-8-methyl-8- azabicyclo[3.2.1]oct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4- quinolinecarboxylate 10e was 0.013 mg/kg, po. With respect to the selected compounds 6a and 10e, effects of 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined. These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor. Although 10e showed 800-fold decreased potency compared with 4 in the B-J reflex test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions. From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).

Animals↗
PubMed1993

[CT and MR imaging of post-aortic left brachiocephalic vein].

The usefulness of CT and MR imaging (MRI) for the diagnosis of post-aortic left brachiocephalic vein (PALBV) is discussed. The subjects of the present study consisted of five patients with PALBV, two males and three females, aged four months to sixty years. Chest CT and MRI were performed as a follow-up study of other intrathoracic lesions in two cases, and for further examination of congenital heart diseases in two infant cases. The other patient underwent both CT and MRI to evaluate sporadic chest pain. Therefore, all PALBV were found incidentally. PALBV passes below the aortic arch in front of the trachea, draining the superior vena cava behind the ascending aorta. This finding was particularly well documented on consecutive coronal sections on MRI. In patients with intrathoracic malignant or specific inflammatory lesion, differentiation between PALBV and lymphadenopathy is necessary for treatment. From our experience, marked enhancement on CT and no signal intensity on MRI in PALBV could differentiate this anomaly from mediastinal lymphadenopathy. In two infantile cases with congenital cardiovascular anomalies such as tetralogy of Fallot, right aortic arch and pulmonary arterial stenosis, MRI was found to be superior to CT in demonstrating these anomalies.

Adult↗
PubMed1993

The association between transfusion and cancer-free survival after curative resection for hepatocellular carcinoma.

BACKGROUND: In cases of surgery for hepatocellular carcinoma (HCC), postoperative intrahepatic recurrence is the main obstacle to long-term survival of patients. The association between perioperative transfusion and recurrence-free survival was studied in 126 patients with HCC who underwent hepatic resection between 1985 and 1990 and in whom complete follow-up information was available until 1992. METHODS: Patients who received neither whole blood nor packed erythrocytes during hospitalization formed the no transfusion group (n = 72), and the remaining patients who were given either whole blood or packed erythrocytes during hospitalization constituted the transfusion group (n = 54). RESULTS: The 1-year, 3-year, and 5-year recurrence-free survival rates of the nontransfused versus transfused groups were 80.6% versus 74.1%, 50.9% versus 33.4%, and 37.1% versus 26.2%, respectively (P = 0.1590). After adjustment for other covariates, the serum albumin level and histological intrahepatic metastasis (im) remained as significant variables for recurrence-free survival. Although there was no association between the erythrocyte transfusion and the recurrence-free survival of the patients with serum albumin levels either more than 3.5 g/dl or less than or equal to 3.5 g/dl, the 1-year, 3-year, and 5-year recurrence-free survival rates of the nontransfused versus transfused groups of the patients with im-negative HCC were 92.2% versus 80.0%, 62.6% versus 36.3%, and 47.4% versus 27.1%, respectively (P = 0.0254). CONCLUSIONS: The association between erythrocyte transfusion and the recurrence-free survival was recognized only in patients with im-negative HCC.

Adult↗
PubMed1993

Insulin-stimulated GLUT4 translocation is relevant to the phosphorylation of IRS-1 and the activity of PI3-kinase.

We examined the role of 185-kDa insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3-kinase) in the signaling pathway of insulin-stimulated GLUT4 translocation. We had already developed a novel cell line to detect GLUT4 on the cell surface, directly and sensitively (Kanai, F., Nishioka, Y., Hayashi, H., Kamohara, S., Todaka, M., and Ebina, Y. (1993) J. Biol. Chem. 268, 14523-14526). We stably expressed a mutant insulin receptor in which Tyr972 was replaced with phenylalanine. Insulin-stimulated tyrosyl phosphorylation of IRS-1 and GLUT4 translocation were decreased in cells expressing the mutant receptor, as compared to findings in cells expressing the normal receptor. Wortmannin, an inhibitor of PI3-kinase, inhibits the insulin-stimulated PI3-kinase activity and GLUT4 translocation at 50 nM, but not the NaF-stimulated GLUT4 translocation. These results suggest that the tyrosine phosphorylation of IRS-1 and activation of PI3-kinase may be involved in the signaling pathway of the insulin-stimulated GLUT4 translocation.

Androstadienes↗
PubMed1993

The inhibitory effect of substance P antagonist, CP-96,345, on the late discharges of nociceptive neurons in the rat superficial spinal dorsal horn.

The effects of local spinal applications of the substance P antagonist, CP-96,345, on the electrically-evoked discharges of nociceptive neurons were examined in the superficial spinal dorsal horn of adult rats anesthetized with sodium pentobarbital. Extracellular single-unit recordings were made from lumbar spinal dorsal horn neurons which were excited by noxious mechanical stimulation and had early and late discharges evoked by A- and C-fiber inputs, respectively, following transcutaneous electrical stimulation. CP-96,345 was applied directly onto the surface of the spinal cord close to the recording sites. A dose of 50 nmol of CP-96,345 drastically inhibited the late discharges of 80% of neurons, without affecting early discharges significantly. This study demonstrated the specific inhibitory effect of CP-96,345 on the late discharges of a restricted population of spinal dorsal horn neurons. These results illustrate the important role of substance P in nociceptive transmission mediated by primary afferent C-fibers in normal acute pain.

Animals↗
PubMed1993

Direct demonstration of insulin-induced GLUT4 translocation to the surface of intact cells by insertion of a c-myc epitope into an exofacial GLUT4 domain.

Stimulation of glucose transport is the main physiological effect of insulin in target tissues. This effect is linked to translocation of the GLUT4 glucose transporter from an intracellular pool to the cell surface. To elucidate the molecular mechanisms involved in this effect, we developed a simple direct sensitive method to detect GLUT4 immunologically on the cell surface. cDNA containing GLUT4 inserted by a c-myc epitope in the first ectodomain (GLUT4myc) was constructed without disrupting the functions of GLUT4 and was expressed in 3T3-L1 and Chinese hamster ovary fibroblast cells. In response to insulin, the GLUT4myc expressed in 3T3-L1 adipocytes was translocated to the cell surface from the intracellular pool, as shown by assays of exofacial antibody binding against the myc epitope and of the uptake of 2-deoxyglucose. Insulin, guanosine 5'-O-(3-thiotriphosphate), guanylyl imidodiphosphate, NaF, and phorbol 12-myristate 13-acetate also induced the translocation of GLUT4myc in Chinese hamster ovary cells coexpressing the human insulin receptor.

3T3 Cells↗
PubMed1993

Molecular characterization of the gene operon of heat shock proteins HSP60 and HSP10 in methicillin-resistant Staphylococcus aureus.

Methicillin-resistance of S.aureus (MRSA) was diminished or depressed at 44 degrees C. In order to investigate whether bacterial heat shock response is correlated with methicillin resistance, we examined the inducibility of the heat shock proteins (HSPs) in MRSA, and cloned and sequenced of their genes. A temperature shift from 37 degrees C to 46 degrees C enhanced the production of at least 8 kinds of cytoplasmic proteins as measured with two-dimensional PAGE. The induced protein profile was almost the same as methicillin sensitive S.aureus, and stress conditions due to ethanol, cadmium or low pH. Two of these proteins were HSP60 and HSP10. Their N-terminal amino acid sequences were 79%, and 83%, homologous with thermobacterium PS3, respectively. A positively hybridized 4.2 kbp DNA fragment encoding both proteins was isolated from the chromosomal DNA of MRSA. The resulting sequence revealed two reading frames and showed high homology to those of hsp60 (groEL) and hsp10 (groES) of bacteria (E.coli) and several other species. The genes of HSP60 and HSP10 in S.aureus comprised an operon as in E.coli. The relationship between those HSPs and PBP2' is currently under investigation.

Amino Acid Sequence↗
PubMed1993

Human myelomonocytic cell line THP-1 produces a novel growth-promoting factor with a wide target cell spectrum.

Conditioned medium from a human myelomonocytic cell line THP-1 promoted the growth of a wide variety of cell types, i.e., human and mouse myeloid cells (HL-60, U937, K562, and M1), mouse T-cells (EL-4), human B cells (Daudi and Raji), mouse mastocytoma cells (IC-2), human melanoma cells (A375-C6), mouse transformed fibroblast cells (L929), human lung fibroblast cells (TIG-1), and mouse bone marrow fibroblast/stromal-like cells. The growth-promoting activity was acid-labile. The activity was resistant to 50 degrees C for 5 min but completely lost in 5 min at 70 degrees C. The activity was resistant to treatment with trypsin but sensitive to chymotrypsin alpha, Pronase E, and proteinase K, indicating the proteinous nature of this activity. The activity was lost by dithiothreitol and 2-mercaptoethanol. Molecular weight (M(r) 50,000-70,000) was estimated by gel filtration-high performance liquid chromatography. After the sequential anion exchange, hydrophobic, and hydroxylapatite high performance liquid chromatography, the partially purified factor exhibited the same target cell spectrum as the conditioned medium.

Animals↗
PubMed1993

The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor.

We have shown previously that insulin stimulated the tyrosine phosphorylation of the alpha-type 85-kDa subunit (p85) of phosphatidylinositol (PI) 3-kinase in vitro and in vivo. In the present work, we identified the major tyrosine phosphorylation sites of the alpha-type p85 by the insulin receptor. [32P]Phosphopeptides obtained from lysylendopeptidase digestion of phosphorylated alpha-type p85 in intact cells after insulin treatment were analyzed using reverse-phase high performance liquid chromatography and thin layer electrophoresis. The tyrosine phosphorylation sites of alpha-type p85 in vivo were assigned to three major phosphopeptides, designated p1, p2, and p3. Highly purified insulin receptor also phosphorylated the purified p85 of PI 3-kinase from the bovine thymus at p1. The purified glutathione S-transferase (GST)-p85 (alpha-type) fusion protein and its truncated proteins from Escherichia coli were also phosphorylated by the purified insulin receptor at p1, p2, and p3 in vitro. Analysis of [32P]phosphopeptide of the truncated GST-p85 (alpha-type) fusion proteins and radiosequence analysis revealed that the p1, p2, and p3 phosphopeptides were phosphorylated at tyrosines 607, 580, and 368, respectively. In addition, phenylalanine substitutions at tyrosine 607 and 580 reduced the p1 and p2 phosphopeptides in vivo, respectively. We conclude that the alpha-type p85 of PI 3-kinase was phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor in vivo.

Amino Acid Sequence↗
PubMed1993

Heat shock promoter of thermophilic chaperonin operon.

The translation of a heat shock protein (HSP), TGroEL, of thermophilic bacterium PS3 increased within 10 minutes when the culture temperature was raised from 60 degrees C to 70 degrees C. In contrast to hyperthermophilic HSPs such as Pyrodictium ATPase, TGroEL is homologous to GroEL of E. coli (Tamada et al. (1991) Biochem. Biophys. Res. Commun. 197, 565-571). The promoter of the thermophilic heat shock gene (tgrE) was sequenced to analyze the heat shock response. The sequences of the promoter were CCTACTTGCA (-35 region) and GTTCATTAATA (-10 region), which are more heat labile than those of the sigma 32 recognition sites of GroEL. The expression of this homologous tgrE in E. coli may be lethal to the cells. The ATPase alpha subunit of this thermophile is also homologous to TGroEL.

Amino Acid Sequence↗