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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 109 records · Page 6Linked to original sources

Analytical color fluorescence electron microscopy of adrenal cortex.

The analytical color fluorescence electron microscope (ACFEM) was employed to study rat adrenal gland. The lipid droplets of adrenocortical cells emitted cathodoluminescence (CL) and this spectrum had two peak wavelengths at 320 and 430 nm. Administration of hypocholesterolemic drugs, 17 alpha-ethinyl estradiol and 4-aminopyrazolo pyrimidine, significantly decreased the CL of 320 nm in all three zones of the adrenal cortex. Conversely, in hypophysectomized-rat adrenal cortices, the CL of 320 nm significantly increased and that of 430 nm diminished. In the ACTH-treated group, CL of 320 nm in the zonae fasciculata and reticularis faded up to 2 hours after injection, while that in the zona glomerulosa remained. These results suggest that the CL of 320 nm in adrenocortical cells is derived from cholesterol ester. The CL analysis by the ACFEM in combination with the cryo-scanning electron microscopy method can be an alternative to conventional histochemical technique in simplicity, specificity, and preservation of the ultrastructure.

Adrenal Cortex↗

DNA recognition by beta-sheets.

The modes of DNA recognition by beta-sheets are analyzed by using the known crystal and solution three-dimensional structures of DNA-protein complexes. Close fitting of the protein surface and the DNA surface determines the binding geometry. Interaction takes place so that essentially the N-to-C direction of the beta-strands either follows or crosses the DNA groove. Upon following the major groove a two-stranded antiparallel beta-sheet dives into the groove and contacts DNA bases with its convex side facing the DNA, while upon following the minor groove, it binds around the sugar-phosphate backbones, with its opposite concave side shielding the DNA. In order for the beta-strands crossing the minor groove to interact with the DNA, the dinucleotide steps need to almost totally helically untwist and roll around major groove. The beta-sheet, on the other hand, needs to adopt a concave curvature on the binding surface in the direction that follows the DNA minor groove, and a convex surface in the direction that bridges the sugar-phosphate backbones across the groove. The result is to produce a hyperbolic paraboloidal DNA-binding surface.

Amino Acid Sequence↗

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa. Thirty-six patients (33%) were responders, while the remaining 74 patients (67%) were nonresponders. Multivariate analysis showed that a high virus titer (assessed by serum core protein level, P = .0021) and the presence of more than two amino acid substitutions in the interferon sensitivity-determining region (ISDR) (P = .0036) correlated significantly with the response to interferon therapy. Because mutations analyzed by direct sequencing of polymerase chain reaction (PCR) products may reflect artifacts of direct sequencing, we further analyzed quasispecies of HCV in this region by cloning and sequencing. Although PCR-based analysis of responders with multiple amino acid substitutions in the ISDR showed the presence of a small amount of wild-type strain in their serum, the results obtained by direct sequencing and cloning were essentially the same. A longitudinal study of quasispecies in 2 patients who showed a dramatic change in the virus titer showed no conversion from wild type to mutant or vice versa. Our results indicate that amino acid substitutions and virus load are independent predictors of the response to interferon therapy. The ability of some patients with no mutation in the ISDR or high virus load to eliminate the virus suggests the presence of other unidentified factors, host or viral, that influence the response to interferon therapy.

Adult↗

Successful combined resection of carcinoma of the esophagus and adrenal metastasis: report of a case.

We report herein the case of a 56-year-old man who underwent successful combined resection of carcinoma of the esophagus and an adrenal metastasis. The patient presented with carcinoma of the thoracic esophagus, and an adrenal tumor was incidentally detected by computed tomography(CT). Complete removal of the carcinoma was accomplished along with a combined resection of the thoracic esophagus and left adrenal gland. Surgery was followed by the administration of anticancer chemotherapeutic agents. He is currently doing well with a grade 1 performance status and no signs of recurrence 22 months after his operation. To our knowledge, no previous report of the successful simultaneous resection of esophageal carcinoma and an adrenal metastasis has been documented in the literature.

Adrenal Gland Neoplasms↗

Anti-inflammatory effects of beraprost sodium, a stable analogue of PGI2, and its mechanisms.

We examined whether beraprost sodium (beraprost), a stable analogue of PGI2, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 micrograms/head) plus epinephrine (0.6 microgram/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 +/- 1.64 micrograms/lung, beraprost 10 micrograms/kg; 7.49 +/- 1.36 micrograms/lung, 30 micrograms/kg; 5.33 +/- 0.71 micrograms/lung, 100 micrograms/kg; 5.52 +/- 0.79 micrograms/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE1 (170 micrograms/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 +/- 0.01, control; 3.96 +/- 0.04) and right ventricular hypertrophy (normal; 28.2 +/- 0.9%, control; 32.3 +/- 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 micrograms/kg/day of beraprost, the effects were statistically significant (beraprost 30 micrograms/kg/day; 3.85 +/- 0.02 and 27.8 +/- 1.4%, 100 micrograms/kg/day; 3.85 +/- 0.02 and 27.3 +/- 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10(-13) mol/paw; 91.19 +/- 2.22%, 10(-12) mol/paw; 85.79 +/- 4.85%, 10(-11) mol/paw; 78.49 +/- 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (-)-isoproterenol (10(-12) mol/paw), but PGE1 (10(-11) mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo.

Alprostadil↗

Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors.

A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy-(E)-6-he ptenoate (3a, S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin.

Animals↗

Multiple pulmonary nodules after recovery from chickenpox in a patient with chronic lymphocytic leukaemia.

A 61-year-old woman with chronic lymphocytic leukaemia (CLL) was found to have multiple pulmonary nodules on an annual chest radiograph 4 months after recovery from chickenpox. To exclude the metastatic carcinoma, an open lung biopsy was performed. Histological examination disclosed isolated necrotic nodules surrounded by some lymphocytes and a few giant cells. These histological findings were compatible with healed varicella pneumonia and the DNA of varicella-zoster virus (VZV) was detected by polymerase chain reaction (PCR) method. We report a case of asymptomatic pulmonary involvement of VZV infection in a patient with CLL.

Antiviral Agents↗

PDGF-BB decreases systolic blood pressure through an increase in macrovascular compliance in rats.

The cardiovascular roles of platelet-derived growth factor (PDGF) were examined in anesthetized rats by monitoring blood pressure and in isolated blood vessels and heart preparations. Intravenous injection of PDGF-BB lowered blood pressure. The decrease in systolic pressure was greater than that in diastolic pressure, so the pulse pressure decreased. PDGF-AA and -AB, other isoforms of PDGF, did not have any effect on blood pressure. Pretreatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, shortened duration of the hypotensive effect of PDGF-BB. The administration of L-arginine with L-NAME partially prevented the effect of L-NAME. PDGF-BB relaxed aortic rings precontracted with phenylephrine with a 50% effective concentration of 3 ng/ml. In contrast, in isolated mesenteric vascular preparations, the vasodilating activity of PDGF-BB was observed only at a high concentration (>12.5 ng/ml). In isolated heart preparations, PDGF-BB had no effect on the beat rate or contractile activity. These results suggest a new role of PDGF-BB that may contribute to the regulation in circulation through the increase in macrovascular compliance mediated by NO.

Animals↗

Effects of angiotensin AT1 receptor antagonist on volume overload-induced cardiac gene expression in rats.

The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin AT1 receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin AT1 receptor antagonist, CS-866 (10 mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10 mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Ca(2+)-ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Ca(2+)-ATPase expression. Unlike the left ventricle, the significant downregulation of alpha-myosin heavy chain and transforming growth factor-beta 3 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-beta 3. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that AT1 receptor partially contributed to volume overload-induced changes in cardiac gene expression and that AT1 receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy.

Actins↗

[Wide resection and reconstruction of chest wall: usefulness of A-O metal plate].

A 53-year-old male was admitted to our department with a chest tumor due to infiltration of lung cancer. Right upper lobectomy and a wide en bloc excision of the right upper chest wall were performed, including the 2nd, 3rd, 4th, and 5th ribs with upper lobectomy of right lung. The defect was replaced with three A-O metal plates, which joined both stumps of the ribs, from the third to the fifth rib. These metal plates were very useful because it was easy to bent and twist them to fit the defect in operation. And curved metal plates preserved a cone from of chest cage. Postoperative course was favourable without mechanical ventilation and wound infection.

Carcinoma, Squamous Cell↗

Immunocytochemical localization of a full-length myotonin protein kinase in rat L6 myoblasts.

Expansion mutation of CTG-repeat motifs within myotonin protein kinase (MtPK) gene is responsible for pathological changes in myotonic dystrophy (DM). To explore its pathological role in skeletal muscle, a full-length human MtPK cDNA was transfected into rat L6 myogenic cell line. Recombinantly expressed human MtPK protein in L6 cell line has a predicted molecular mass of 70 kDa. We have raised a polyclonal antibody against a synthetic peptide in the deduced sequence of the C-terminal portion of MtPK. MtPK in L6 cell is localized to perinuclear region, that resembles with sarcoplasmic reticulum. The MtPK-transfected myoblast cells established in this study will allow us to elucidate the molecular pathomechanism of muscle manifestations in DM.

Animals↗

Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure-activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds.

A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H-tetrazol-5- ylbiphenyl-4-yl)-methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.

Acetylation↗

Effects of beraprost sodium, a prostacyclin analogue, on tail flick response in two models of diabetic-neuropathy in rats and its mechanism.

The effects of beraprost sodium (BPS), a stable prostacyclin analogue, on the tail flick (TF) latency were investigated in streptozotocin-induced (STZ;55mg/kg, i.p.) diabetic male Sprague-Dawley (SD) rats and in spontaneously diabetic WBN/Kob rats. The SD rats were divided into 5 groups, i.e., (I) normal, (II) diabetic control, diabetic treated with (III) BPS (10 micrograms/kg/day), (IV) BPS (30 micrograms/kg/ day), and (V) aldose reductase inhibitor (ARI; epalrestat, 50 micrograms/kg/day). The drugs were administered orally. At 12 weeks, TF latency was significantly longer in untreated diabetic rats than in normal rats. After 4 weeks treatment, BPS significantly improved the abnormality in TF latency dose-dependently. But ARI did not normalize the response. The 45 weeks male WBN/Kob rats were divided into 2 groups: diabetic control and diabetic treated with BPS at 30 micrograms/kg/day, p.o., respectively. Untreated, age-matched wistar rats were served as the normal group. At 61 weeks, TF latency was significantly longer in control WBN/Kob rats than in normal wistar rats in time-dependent manner. After 16 weeks treatment, BPS significantly normalized the prolongation in TF latency. In in vivo experiments, BPS significantly increased the cyclic AMP (cAMP) content in sciatic nerves from normal rats dose-dependently. In STZ-induced diabetic rats, cAMP content in sciatic nerves were significantly reduced, and 4 weeks treatment of BPS significantly restored this reduced cAMP content. It was suggested that BPS may be effective on diabetic neuropathy by, at least in part, maintenance of cAMP contents in the nerves.

Animals↗

Role of P-selectin in the early stage of the Arthus reaction.

P-selectin is rapidly translocated to the surface of endothelial cells and platelets following exposure to chemical mediators such as histamine, thrombin and complement factors. The Arthus reaction is caused by vascular injury which is initiated by the local deposition of the immune complex followed by the activation of complement and release of chemical mediators. In this report, the role of P-selectin in the early stage of reverse passive Arthus reaction in rat using monoclonal antibodies (mAbs) against rat P-selectin will be investigated. Intravenous administration of the mAb ARP2-4 significantly attenuated paw edema 1 h after challenging it with antigen by 31.5% (1 mg/kg) and 44.7% (3 mg/kg), respectively. Edema formation was also reduced by sulfatide (73.1%, 50 mg/kg) and inositol hexakisphosphate (InsP6) (72.9%, 30 mg/kg), which have been reported to block P-selectin-mediated neutrophil adhesion. Moreover, neutrophil accumulation into the inflammatory site in the Arthus reaction was inhibited by anti-P-selectin mAb. P-selectin expression was detected along vessel walls prior to neutrophil accumulation, as determined by immunohistochemical staining using the antibody. In addition, the expression of P-selectin mRNA was induced 4 h after deposition of immune complex. From these results, we concluded that P-selectin plays an important role in the pathogenesis of the Arthus reaction especially in the early stage by recruiting neutrophils into sites of inflammation.

Animals↗

AstroNewt: early development of newt in space.

AstroNewt experiment explores the effects of earth gravity on the early development of Japanese red-bellied newt, Cynops pyrrhogaster. Since female newts keep spermatophore in cloaca, fertilized eggs could be obtained without mating. Fertilization of newt's egg occurs just prior to spawning, so that gonadotrophic cues applied to females in orbit leads to laying eggs fertilized just in space. A property of newt being kept in hibernation at low temperature may be of great help for the space experiment carried out with much limited resources. A general outline of the AstroNewt project is shown here in addition to some technical advances for the development of the project. Experimental schemes of two space experiments (IML-2 in summer 1994 and unmanned SFU at the beginning of 1995) are also shown.

Animals↗

Effects of beraprost sodium and prostaglandin E1 on skin blood flow in diabetic rats and normal dogs.

1. The present study was undertaken to compare the effects of beraprost sodium (BPS), a stable prostaglandin I2 analog, with prostaglandin E1 (PGE1) on the skin blood flow in anesthesized diabetic rats and anesthetized dogs. 2. In anesthetized diabetic rats, BPS, but not PGE1, caused a dose-dependent and significant increase in femoral skin blood flow. 3. In anesthetized dogs, PGE1 significantly increased femoral arterial blood flow than BPS. However, BPS significantly increased in-step skin blood flow than PGE1. 4. The above data suggest that BPS may be clinically useful for the treatment of circulatory insufficiency of lower extremities in diabetic patients.

Alprostadil↗