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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 523 records · Page 29Linked to original sources
PubMed1993

Cytotoxic activity of spleen-derived T lymphocytes against autologous biliary epithelial cells in autopsy patients with primary biliary cirrhosis.

Autoimmunity against biliary epithelial cells is considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). However, cytotoxic activity of T lymphocytes against biliary epithelial cells has not previously been examined. This study has demonstrated that spleen-derived T lymphocytes were cytotoxic for autologous biliary epithelial cells in all of five patients with PBC, even though it was only detectable at high effector to target ratios. Such cytotoxicity was not found in non-PBC patients. CD8-positive T lymphocytes were shown to be responsible for the cytotoxicity by negative selection, and its inhibition was dependent on the ratio of cold to hot target cells. These observations may support a current hypothesis that the pathogenesis of PBC is partly due to T cell autoimmunity directed against the bile duct epithelium.

Aged↗
PubMed1993

[Case report of toxic shock-like syndrome due to group A streptococcal infection].

A case of streptococcal toxic shock like syndrome occurring in a 44-year-old previously healthy Japanese male is reported. He initially had a sore throat, low grade fever, diarrhea and mild pains in a lower extremities. Shortly thereafter, he rapidly developed a high fever, profound hypotension, multifocal epidermal necrosis, and sever purulent fasciitis and myositis in both lower extremities, which required above knee amputation of both legs. He later developed disseminated intravascular coagulopathy, adult respiratory distress syndrome, acute renal failure, coma and necrotizing inflammation of both arms and external genitalia despite treatment. He died on the 13th hospital day. Streptococcus pyogenes was isolated from the necrotic muscles and right knee joint. The organism was typed as M3, T3, was sensitive to penicillins, and was found to be producing streptococcal pyogenic exotoxin A in vitro. This is the first case report of streptococcal toxic shock like syndrome in Japan.

Adult↗
PubMed1993

Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin.

In a previous study (H. Shirataki, K. Kaibuchi, T. Yamaguchi, K. Wada, H. Horiuchi, and Y. Takai, J. Biol. Chem. 267:10946-10949, 1992), we highly purified from bovine brain crude membranes the putative target protein for smg p25A/rab3A p25, a ras p21-related small GTP-binding protein implicated in neurotransmitter release. In this study, we have isolated and sequenced the cDNA of this protein from a bovine brain cDNA library. The cDNA had an open reading frame encoding a protein of 704 amino acids with a calculated M(r) of 77,976. We tentatively refer to this protein as rabphilin-3A. Structural analysis of rabphilin-3A revealed the existence of two copies of an internal repeat that were homologous to the C2 domain of protein kinase C as described for synaptotagmin, which is known to be localized in the membrane of the synaptic vesicle and to bind to membrane phospholipid in a Ca(2+)-dependent manner. The isolated cDNA was expressed in COS7 cells, and the encoded protein was recognized with an anti-rabphilin-3A polyclonal antibody and was identical in size with rabphilin-3A purified from bovine brain by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Moreover, both rabphilin-3A purified from bovine brain and recombinant rabphilin-3A made a complex with the GTP gamma S-bound form of rab3A p25 but not with the GDP-bound form of rab3A p25. Immunoblot and Northern (RNA) blot analyses showed that rabphilin-3A was highly expressed in bovine and rat brains. These results indicate that rabphilin-3A is a novel protein that has C2 domains and selectively interacts with the GTP-bound form of rab3A p25.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats.

To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.

Actins↗
PubMed1993

Erythromycin increases gastric antral motility in human premature infants.

The aim of this study was to determine if erythromycin (EM), which is a potent motilin agonist, alters gastrointestinal motility in premature infants. Six infants who were born after 23-30 weeks gestation and weighed 825-1,408 g at birth were studied when 6-31 days old. Intraluminal pressure changes within the gastric antrum and proximal duodenum were recorded. We infused EM 0.75 mg/kg intravenously for 15 min and we compared gastric and duodenal contractions for 30 min between before and after the initiation of EM infusion. In these preterm infants the migrating complex was not present, and was not induced by EM. However, in all 6 infants EM increased nonpropagating antral clusters of contractions (p < 0.05). The antral motility index increased 4-fold (p < 0.05). We concluded that human premature infants have functioning motilin receptors.

Duodenum↗
PubMed1993

In vivo effect of lipopolysaccharide on alveolar and peritoneal macrophages of rats: superoxide anion generation and 5-lipoxygenase metabolism of arachidonic acid.

Influences of the intravenous administration of Escherichia coli lipopolysaccharide, 3 mg/kg, on the production of superoxide anion (O2-) and 5-lipoxygenase metabolites of arachidonic acid (AA) were evaluated in alveolar macrophages (AM) and peritoneal macrophages (PM) on days 1 and 3 after injection. The dose selected was that found to induce a significant leakage of [125I]bovine serum albumin in the pulmonary vasculature. AM obtained 1 day after LPS injection generated smaller amounts of O2- on stimulation with C5a but generated similar amounts with wheat germ lectin (WGA) or AA compared with control AM. This result suggested a prior complement activation. On day 3, on the contrary, their production of O2- significantly exceeded that by control AM with either of the three stimuli. PM collected on day 1 after LPS injection generated a significantly greater amount of O2- on stimulation with either WGA or AA than did control PM. The amount of O2-, however, decreased from day 1 to day 3. AM collected 1 day after the injection of LPS generated significantly more leukotriene B4 (LTB4) and 5-HETE on stimulation with A23187 alone and in combination with AA than did the cells from untreated rats. Such activities returned to the control levels in the AM collected on day 3. In contrast, the PM collected on day 1 produced amounts of LTB4 and 5-HETE similar to those of the control PM, but the cells on day 3 produced significantly more LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Brainstem and cerebellar vermis involvement in autistic children.

Recent reports have suggested functional abnormalities of the brain stem in autistic children, and structural abnormalities have also been reported. We obtained magnetic resonance imaging (MRI) scans for 21 autistic children and compared them with 21 control MRI scans. The areas of the brain stem and cerebellar vermis were measured using midsagittal images. The brain stem and cerebellar vermis lobules VIII to X were found to be significantly smaller in autistic children. A positive correlation between the size of the brain stem and cerebellar vermis was observed in the autistic children. This correlation was not observed in the control children. This suggests that the size of the brain stem and cerebellar vermis are anatomically altered in autistic children and that growth of the brain stem and cerebellar vermis in autistic children is different from normal children.

Autistic Disorder↗
PubMed1993

Pathophysiology of brain swelling after acute experimental brain compression and decompression.

Global ischemia was created by controlled expansion of an epidural balloon for 25 minutes in Group A (six cats) and for 5 minutes in Group B (six cats). The alterations of intracranial pressure, arteriovenous oxygen content difference, cerebral metabolic rate of oxygen, cerebral blood flow, and electroencephalogram were observed until brain death or 24 hours' survival with normal intracranial pressure. The animals were then killed for brain histological examination. In four other cats, a 2% solution of Evans blue dye (4 mg/kg) was injected intravenously--immediately after deflation--resulting in 25 minutes of global ischemia. Two other cats received 5 minutes of global ischemia. The cats were killed 1 hour later. Abrupt swelling occurred in Group A, and no swelling was found in Group B. A transient absolute hyperemia was found immediately after deflation in both groups. The cerebral blood flow and cerebral metabolic rate of oxygen decreased markedly with low arteriovenous oxygen content difference and flat electroencephalogram in Group A, compared with gradual recovery of cerebral blood flow and cerebral metabolic rate of oxygen with high arteriovenous oxygen content difference and reappearance of electroencephalogram activity in Group B. The extravasation of Evans blue was observed on the compressed cerebral hemisphere, thalamus, hypothalamus, and brain stem in swelling animals and only on the compressed hemisphere in nonswelling animals. Histologically, the damage and congestive dilation of capillary, degeneration, and necrosis of neuronal and glial cell were found prominently on the hypothalamus and brain stem in the swelling group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Establishment and characterization of a SV40 T-antigen immortalized epithelial-like cell line derived from the newborn rat colorectum and its malignant transformation by the ras oncogene.

Epithelial-like cells from the colorectum of one-day-old newborn rats were immortalized by transfection with the simian virus 40 (SV40) T-antigen gene, and a cell line OUMS-25 was established. The cells were positive for the SV40 T-antigen, and immunoreactive to a colonic epithelial cell monoclonal antibody and a keratin-18 monoclonal antibody. Ultrastructural studies revealed the presence of microvilli on the cell surface and desmosomes between the adjacent cells. Karyotypic analysis showed that OUMS-25 cells were aneuploid. Cloning efficiency of the cells was 0.01% in soft agar. However, the cells were not tumorigenic in the syngeneic newborn rats. The cells were further transformed by transfection with the cloned activated c-Ha-ras oncogene containing a point mutation within codon 61. Characteristics of the activated-c-Ha-ras transfected cells (OUMS-25/RAS) were different in some respects from those of the parent cells (OUMS-25). OUMS-25/RAS cells demonstrated more malignant morphology, elevated cloning efficiency in soft agar, and tumorigenicity. This is the first report on the immortalization and malignant transformation of colorectal epithelial-like cells by transfection with a combination of SV40 T-antigen gene and cloned activated c-Ha-ras oncogene.

Animals↗
PubMed1993

Simultaneous determination of methamphetamine and its metabolites in the urine samples of abusers by high performance liquid chromatography with chemiluminescence detection.

A HPLC determination method for methamphetamine (MA) and its metabolites in the urine samples of abusers has been developed. MA, amphetamine (AP), norephedrine (NE), p-hydroxymethamphetamine (pOHMA), p-hydroxyamphetamine (pOHAP) and an internal standard, namely beta-phenylethylamine (PEA) were derivatized with dansyl chloride. They were separated on a reversed phase column with gradient elution using an acetonitrile/tetrahydrofuran/imidazole buffer mobile phase and chemilumigenically determined using bis(2,4,6-trichlorophenyl)-oxalate/hydrogen peroxide as post column reagents. The lower determination limits were as low as 1 x 10(-14)-3 x 10(-14) mol. AP, NE, pOHAP and PEA were derivatized with naphthalene-2,3-dicarboxaldehyde, and were separated on a reversed phase column using an acetonitrile/imidazole buffer mobile phase and chemilumigenically determined. The lower determination limits were 3 x 10(-16)-1.5 x 10(-15) mol. Enzymatic hydrolysis of glucuronides of pOHMA (pOHMAG) and pOHAP (pOHAPG) allowed them to be determined as pOHMA and pOHAP, respectively. After adjusting the pH of the urine samples to 10.5 and adding PEA, all metabolites except glucuronides were extracted quantitatively into chloroform-isopropanol (3:1). Utilizing the two methods, MA and all metabolites were determined in urine samples of MA abusers. The tendency, in order of decreasing concentration was: [MA] > [A] > [pOHMAG] > [pOHMA] > [NE] > [pOHAPG] > [pOHAP]. Although ephedrine (EP) was was detected in several samples, it was not considered to be a metabolite of MA but rather a component derived from cough medicine.

Adolescent↗
PubMed1993

Determination of auranofin, a chrysotherapy agent, in urine by HPLC with a postcolumn reaction and visible detection.

Auranofin [(2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S) (triethylphosphine)gold(I): AF] is a unique orally active chrysotherapy agent. A HPLC method has been developed for determining AF in urine. The proposed method comprises initial chromatographic separation of AF followed by on-line decomposition by potassium iodide with a released mercapto group undergoing a color-developing reaction with 5,5'-dithiobis(2-nitrobenzoic acid). An aliquot (100 microliters) of a urine sample was chromatographed on a YMC AM-302 octadecylsilica column (4.6 mm i.d. x 15 cm, ambient) with a water-methanol (35:65) eluent delivered at a flow rate of 1 ml/min. A reagent solution for a postcolumn reaction comprised of 50 microM 5,5'-dithiobis(2-nitrobenzoic acid), 0.3 M potassium iodide and a 50 mM phosphate buffer (pH 7.4), was delivered at a flow rate of 0.5 ml/min. The postcolumn reactor consisted of a poly(tetrafluoroethylene) tube (0.5 mm i.d. x 5 m) at 60 degrees C. Detection wavelength was 412 nm. The identity of the AF peak was confirmed by a 3-dimensional chromatogram as well as by atomic absorption spectrophotometric analysis of gold in the column effluent. Under the conditions described above, a linear relationship was obtained between peak height and AF concentration in the range 0.1 to 10 microM, with a correlation coefficient of 0.999. The detection limit was 50 nM (S/N = 3 at 0.005 AUFS) and the reproducibility was within 4% for 5 determinations. The AF concentrations in the urine of a rabbit given AF intraperitoneally were determined.

Animals↗
PubMed1993

Marked species-difference in the vascular angiotensin II-forming pathways: humans versus rodents.

Using isolated arteries, we demonstrated a marked difference in the angiotensin II-forming systems between human and rodent vessels. In human arteries, only 30-40% of the conversion of angiotensin I to angiotensin II depended on the angiotensin-converting enzyme (ACE), and the rest of the angiotensin II formation was ascribed to chymostatin-sensitive angiotensin II-generating enzyme (CAGE). On the contrary, angiotensin II formation in rodent arteries totally depended upon ACE, without any sign of CAGE involvement. Such a marked species-difference can be relevant to the reported difference between humans and rodents in the ACE inhibitor effects on the myointimal hyperplasia after intimal balloon injury.

Adult↗
PubMed1993

In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177.

E4177, 3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine, was characterized by in vitro autoradiography and by examining functional antagonism upon angiotensin II (Ang II)-induced contraction of isolated vessels. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. In contrast, E4177 and losartan had little effect on the binding to rat adrenal medulla where AT2-receptors predominate. These results indicate that E4177 is AT1-specific as is losartan. E4177 and losartan competitively antagonized the Ang II-induced contraction of human and rabbit arterial strips without any agonistic action. The obtained IC50 values indicated that E4177 was twice as potent as losartan in human arteries and three times more so in rabbit aortic strips. Responses to norepinephrine, serotonin, histamine or KCl were not affected by E4177. In addition, E4177 (10(-5) M) had no effect on angiotensin-converting enzyme activity. These data indicate that E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.

Adrenal Cortex↗
PubMed1993

KRI-1314: an orally effective inhibitor of human renin.

Biochemical and pharmacological properties of KRI-1314, a newly synthesized, low molecular weight (M.W.: 690) renin inhibitor, were investigated in vitro and in vivo. The novel amino acid norstatine, which is shorter in chain length than the well-known statine, was incorporated into KRI-1314 as a tetrahedral transition-state analogue for the Leu10-Val11 scissile peptide in the renin substrate. KRI-1314 more strongly inhibited plasma renins from primates than those from dogs, rabbits, guinea pigs and rats. KRI-1314 competitively inhibited highly-purified human renin with a Ki value of 9.9 x 10(-10) M. KRI-1314 strongly inhibited the tissue renin-like activities of various organs from Japanese monkeys, with IC50 values on the order of 10(-8) M. KRI-1314 was also very stable in various tissue homogenates from Japanese monkeys. Both intravenous (from 0.25 to 3 mg/kg) and oral (10 and 30 mg/kg) administration of KRI-1314 to anesthetized and conscious sodium-depleted Japanese monkeys, respectively, significantly lowered the blood pressure and plasma renin activity without affecting the heart rate. In Japanese monkeys, KRI-1314 was continuously detected in the plasma up to at least 7 hr after oral administration of 10 and 30 mg/kg. These results demonstrate that KRI-1314 is a highly potent, primate-selective and long-lasting oral renin inhibitor with a blood pressure lowering effect.

Administration, Oral↗
PubMed1993

Distinct responses of interleukin-6 and other laboratory parameters to treatment in a patient with Wegener's granulomatosis.

We describe a patient with Wegener's granulomatosis in whom the serum levels of interleukin-6 (IL-6) and other laboratory parameters were monitored. The IL-6 and CRP levels, which were extremely high before treatment, declined rapidly with corticosteroid and cyclophosphamide. IgG, leukocyte count and platelet count declined more gradually. Thus, determination of the serum IL-6 level might be useful in diagnosing and monitoring Wegener's granulomatosis.

Biomarkers↗
PubMed1993

Hepatitis in an adult with rubella.

Rubella was accompanied by hepatic dysfunction in a 28-year-old male. Serum aminotransferase levels were moderately elevated and LDH markedly increased, especially LDH isoenzyme 5, whereas total bilirubin and ALP remained almost normal. GOT, GPT and LDH levels were completely normalized by the 21st hospital day. Paired antibody titers of viruses which may cause hepatitis, other than rubella, were of no significance. Laparoscopy showed enlarged, red liver. Histologic and electron microscopic findings of the liver were consistent with acute hepatitis. Hepatic damage with rubella is rare, and it is possible that the hepatic dysfunction seen in adult rubella may be mediated by an immunopathologic mechanism.

Acute Disease↗