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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 307 records · Page 17Linked to original sources

Segregation of bovine viral diarrhea virus isolated in Japan into genotypes.

It was suggested that 3 strains of bovine viral diarrhea virus (BVDV) isolated from persistently infected calves in Tochigi prefecture in Japan belonged to BVDV type II. It was recognized lack of PstI site on the 5'-untranslated region of genome of them as well as BVDV type II reported previously. Inoculated with the 3 strains, the calves showed the mild decrease of platelet counts which was specific clinical sign of BVDV type II. We should report that the 3 strains were the first BVDV type II isolated in Japan. Neutralizing antibody titers of the antisera against the 3 strains using laboratory strains as neutralizing virus were lower than those of them using homologous strains. Therefore, it was indicated that the difference between BVDV type I and BVDV type II in the antigenicity.

Animals↗

Long term follow-up of a 46,XY phenotypic girl with 17alpha-hydroxylase deficiency treated with alternate-day dexamethasone.

We report an 18-year-old 46,XY phenotypic girl who has been on alternate-day dexamethasone therapy for 10 years. The patient was seen at our hospital for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue, and the karyotype of the peripheral lymphocytes was 46,XY. The diagnosis of 17alpha-hydroxylase deficiency was established by the evaluation of adrenal steroidogenesis at the age of 6.1 years when hypertension was clearly recognized, and was confirmed later by the gene analysis of CYP17 which disclosed a compound heterozygote. The growth rate was suppressed during the initial treatment with daily administration of 0.25-0.5 mg dexamethasone. Switching to alternate-day regimen of dexamethasone 0.5 mg/dose improved height velocity. Subsequent addition of low-dose estrogen therapy induced pubertal growth spurt. The blood pressure and adrenal hormone levels remained almost within the normal range throughout the course. Adrenal function was evaluated at the age of 15 years. Plasma ACTH and corticosterone levels were high only just before the next administration, when the plasma dexamethasone concentration should be at the nadir. Since corticosterone possesses glucocorticoid activity and can work as a glucocorticoid reserve, it is assumed that this mode of dexamethasone administration can be a safe treatment for this disorder. We conclude that the patient with childhood 17alpha-hydroxylase deficiency can be safely and effectively treated with alternate-day dexamethasone without interfering with linear growth.

Adolescent↗

Timing for discontinuation of treatment with a long-acting gonadotropin-releasing hormone analog in girls with central precocious puberty. TAP-144SR CPP Study Group.

The optimal timing for discontinuing treatment with a long-acting gonadotropin-releasing hormone (GnRH) analog (TAP-144SR) was investigated in patients with central precocious puberty (CPP). Thirty-five girls with CPP (21 with idiopathic disease and 14 with organic disease) were treated with the analog for 3 to 5 years. No significant differences were seen between the idiopathic and the organic CPP in the suppressive effect of bone maturation. Advancement of bone maturation was noticeably suppressed during the period between bone ages (BA) of 11.0 and 11.9. The height standard deviation score (Ht-SDS) for BA was consistently improved from 10 to 11.5 years of BA, and patients reached peak Ht-SDS at a BA of 11.5 years. The deltaHt-SDS (annual change in Ht-SDS) was noticeably decreased at BA over 12 years in spite of prolongation of the treatment. In the eight patients who have reached final height, the average Ht-SDS was -0.49 at end of the treatment (BA 11.7 years) and the final Ht-SDS was - 1.1 SD, respectively. Predicted adult height at the end of the treatment was significantly higher than the actual final height (P<0.01). The results suggest that a fall in Ht-SDS for BA which usually occurs at approximately 12 years of BA, is an indication for cessation of the treatment with TAP-144SR, and residual growth potential judged solely from BA may be decreased in girls with CPP after discontinuation of the treatment.

Age Determination by Skeleton↗

Differences of antagonism for a selective alpha1D-adrenoceptor antagonist BMY 7378 in the rabbit thoracic aorta and iliac artery.

Based on the affinity of alpha1D adrenoceptor subtype for a selective antagonist BMY 7378, we studied its functional role in rabbit thoracic aorta and iliac artery, and evaluated the subtypes of the alpha1-adrenoceptors that are activated by phenylephrine (a full agonist) and tizanidine (a partial agonist). In thoracic aorta, the concentration response curves of phenylephrine and tizanidine were antagonized by BMY 7378 with low potency (pA2 values 6.68+/-0.06 and 6.67+/-0.06, slopes of Schild plot 1.06+/-0.04 and 1.01+/-0.04, respectively). On the other hand, in iliac artery concentration response curves for phenylephrine were potently antagonized by a low concentration of BMY 7378, and the slope (0.75+/-0.02) of the Schild plot was significantly different from unity. In iliac artery, a concentration response curve of tizanidine was antagonized by BMY 7378 with low potency (pA2 value 6.64+/-0.08, slope of Schild plot 1.01+/-0.05). These results suggest that an alpha1D-adrenoceptor subtype contributes to alpha1-adrenoceptor mediating muscle contraction in iliac artery, but not in thoracic aorta of rabbit, and that it is activated by a full agonist phenylephrine but not by a partial agonist tizanidine.

Adrenergic alpha-1 Receptor Antagonists↗

Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease.

Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistant to steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.

Aged↗

Rheumatoid arthritis associated with renal amyloidosis and crescentic glomerulonephritis.

A 43-year-old woman with rheumatoid arthritis (RA), renal amyloidosis and crescentic glomerulonephritis had severe abdominal pain, melena and progressive renal failure. Autopsy findings revealed vasculitis of small and middle size of vessels and there was a deposition of amyloid in the small intestines. Although there were no findings of vasculitis in the kidney, amyloid deposition was noticed and 70-80% of glomeruli showed a crescentic formation. No immunological abnormality was found in glomeruli. Although the immunological mechanisms of crescentic glomerulonephritis were not necessarily eliminated, amyloid deposition may play a role in crescent formation.

Acute Kidney Injury↗

Influence of sustained hypoxia on the sensation of dyspnea.

We assessed the effect of sustained isocapnic hypoxia (PCO2 = 40 Torr, SaO2 = 80%) on the sensation of dyspnea in 16 normal healthy males. Subjects rated the sensation of dyspnea (c) on 15 cm visual analog scales during 20 min of sustained hypoxia. Following this hypoxic period, 8 subjects undertook mild exercise (10-50 W on a bicycle ergometer for 3 min) under the continuation of hypoxia. During sustained hypoxia, psi increased initially with ventilation from 0.6 +/- 0.2 (n = 16, mean +/- SE) to 2.9 +/- 0.6 at peak ventilation, but it decreased with ventilatory depression to 1.6 +/- 0.4. Dyspnea intensity during hypoxic exercise was significantly smaller than that at peak ventilation in the resting hypoxic period (2.3 +/- 0.7 vs. 3.9 +/- 1.0), although the ventilation was greater during exercise (24.0 +/- 3.0 vs. 19.7 +/- 1.4 l/min). These results indicate that sustained hypoxia has a biphasic, i.e., initial stimulatory and delayed depressant, effect on dyspnea and on ventilation. It is suggested that the dyspnea sensing mechanism is suppressed during mild exercise under sustained hypoxia.

Adult↗

Multiple scalp aneurysms caused by atypical temporal arteritis--case report.

A 55-year-old male suffered sudden onset of dysarthria and mild left hemiparesis due to a right intracerebral small hemorrhage. On admission, six subcutaneous elastic hard lumps were found on the scalp with painless and regular pulsation. The lumps were located along the course of the bilateral superficial temporal arteries (5 locations) and the occipital artery. The patient did not have symptoms of headache or blurred vision associated with temporal arteritis. The largest lump was removed for cosmetic reasons and definitive diagnosis. Histological examination demonstrated many infiltrating inflammatory cells along the entire vascular wall but without giant or fibrinoid necrosis. These multiple scalp aneurysms were probably caused by atypical temporal arteritis.

Aneurysm↗

Characterization of recombinant precursor proteins of the human seminal plasma sperm motility inhibitor synthesized in insect cells.

Human seminal plasma sperm motility inhibitor (SPMI) proteins which are exclusively secreted from seminal vesicles, inhibit sperm motility. It is secreted as biologically active 52 kDa and a mixture of 71 and 76 kDa precursor forms, which are identical to semenogelin-I and II (Sg-I and Sg-II), respectively. To understand the molecular mechanism underlying the inhibition of sperm motility by SPMI proteins, we expressed human Sg-I and Sg-II genes in insect cells using a baculovirus system. The baculoviruses expressing full-size Sg-I and Sg-II proteins that were N-terminally-tagged with a hexahistidine were selected, and were infected with Sf 21 cells. The Sg-I and Sg-II proteins were purified from infected cells by column chromatography using Ni-NTA resin 48 h after infection. The full-size Sg-I and Sg-II proteins were obtained in soluble forms. However, they tended to aggregate to form a gel, as expected from naturally occurring semenogelin. Both the purified recombinant Sg-I and Sg-II proteins showed strong SPMI activities with a complete inhibition of sperm motility at 60 units/mg, equivalent to the natural proteins. This production system that permits the generation of purified Sg-I and Sg-II proteins, as well as mutant derivatives, will be helpful for further study on male infertility.

Animals↗

[Experimental study on the therapeutic effects of SMS201-995 on bile-induced acute pancreatitis in the dog].

We studied the effects of SMS201-995, a long-acting somatostatin analogue, on bile-induced acute pancreatitis in the dog. According to morphometrical study, parenchymal necrotic ratio, zymogen granules area and zymogen granules occupied ratio of acinus were significantly decreased in SMS-treated pancreatitis. These results suggests that SMS-treated pancreatitis showed less damage than non-treated ones and decreased secretion of pancreatic enzyme. On the other hand, pancreatic blood flow showed a stronger decrease in SMS-treated dogs than in non-treated ones, and a significant difference was observed at 15 minutes and 1 hour after induction of pancreatitis. Many clinical and experimental evidences suggest that pancreatic ischemia causes acute pancreatitis. Pancreatitis may be worsened by an early phase treatment with SMS201-995, because this substance reduces pancreatic tissue blood flow. The harmful effect of this substance on pancreatic tissue blood flow must be kept in mind when SMS201-995 is used for therapeutic purpose of acute pancreatitis.

Acute Disease↗

Expression of interleukin-8 in human glomerulonephritis.

Interleukin-8 (IL-8) is a cytokine, which possesses both chemotactic and activating properties for neutrophils, lymphocytes and basophils. Various evidence has indicated IL-8 to be implicated in the pathophysiology of immune-mediated renal diseases. We thus examined the expression of IL-8 in renal diseases. We detected the expression of IL-8 both in mRNA and the protein levels in renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis. A significant correlation was found between the expression of IL-8 mRNA and the number of neutrophils in the glomerulus. We also found a negative correlation between the expression of IL-8 mRNA and creatinine clearance. Our study thus suggested IL-8 to be involved in the pathophysiology of proliferative glomerulonephritis.

Adolescent↗

Immunohistochemical detection of MUC2 mucin core protein in ulcerative colitis.

MUC2 mucin is predominantly expressed in the colon and is considered to play an important role in the protection of that organ. Recent findings suggested that MUC2 protein levels are significantly decreased in active ulcerative colitis (UC). We therefore performed an immunohistochemical study to reveal if the expression of MUC2 protein is altered in UC. Seventy-nine biopsy tissue specimens from 31 UC patients, along with normal colon tissues, were immunostained with anti-MUC2 mucin core protein monoclonal antibody (MoAb) CCP58 (IgG1). UC tissue specimens were divided into two groups based on the histological severity of inflammation, i.e., 64 with active inflammation (grades 2-5) and 15 without (grade 1). In the former group, 52 out of 64 (81.3%) tissue specimens contained sections of glands with a few cells positive for MoAb CCP58. These glands were small and consisted of MUC2 negative-short cells and a few positive cells without apparent mucus formation, considered to be immature regenerative glands. In contrast, the staining pattern was almost the same as that of the normal colon and no immature glands were seen in the group without active inflammation. The sections of immature regenerative glands with a few MUC2-positive cells were exclusively found in the UC tissues with active inflammation, but not in those without it, suggesting that the expression of MUC2 protein may be decreased in active UC.

Adolescent↗

Effects of YF476, a potent and selective gastrin/cholecystokinin-B receptor antagonist, on gastric acid secretion in beagle dogs with gastric fistula.

The antisecretory effects of the gastrin/cholecystokinin-B (CCK-B) receptor antagonist YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl) 1H-1,4-benzodiazepin-3-yl]-3-(3-methylaminophenyl)-urea, CAS 155488-25-8) on secretagogue- and peptone-induced gastric acid secretion in beagle dogs with chronic gastric fistula were examined. Plasma gastrin concentrations were evaluated following introduction of peptone into the stomach. Intravenous administration of YF476 dose-dependently inhibited pentagastrin (1 microgram/kg/h)-induced gastric acid secretion, with an ED50 value of 0.0023 mumol/kg. In contrast, intravenous administration of YF476 (0.3 mumol/kg) did not affect histamine (15 micrograms/kg/ h)-induced gastric acid secretion. Oral administration of YF476, famotidine and omeprazole dose-dependently inhibited peptone (8%, 200 ml)-induced gastric acid secretion with ED50 values of 0.11, 0.76 and 4.28 mumol/kg, respectively. The antisecretory effect of YF476 was about 7 and 40 times more potent than that of famotidine and omeprazole, respectively. Plasma gastrin concentrations were increased by introduction of peptone. These results suggest that YF476 is an extremely potent and selective antisecretory drug and the endogenous gastrin plays an important role in peptone-induced gastric acid secretion in dogs.

Animals↗

Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production: a case report with ultrastructural and immunohistochemical studies.

We report a case of medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production. Macroscopically, a rectangular black area within a gray-white background was seen on the cut surface of the tumor. Histologically, the tumor was found to have a trabecular or nestlike architecture with many pigmented dendritic cells, resembling the "sustentacular cells" of paraganglioma, scattered among nonpigmented polygonal tumor cells. Fontana-Masson staining and bleaching with potassium permanganate and oxalic acid revealed that this pigment was melanin, which was also confirmed by electron microscopy. Immunohistochemically, pigmented dendritic cells were positive for calcitonin, as were the surrounding typical medullary thyroid carcinoma cells. These cells were also positive for S100 protein but not for HMB-45, compatible with sustentacular cells. These findings suggest that this tumor could be considered to bridge the gap between two variants of medullary thyroid carcinoma, the melanin-producing (pigmented) type and the paraganglioma-like type.

Aged↗

Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice.

Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10-135 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 microgram site-1 = 100 nmol site-1) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1 W/Wv) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK1 receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects. SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK1 receptors, and mast cells may not be key factors in SP-induced itching.

Animals↗

Protective effect of bismuth nitrate against injury to the bone marrow by gamma-irradiation in mice: possible involvement of induction of metallothionein synthesis.

The effects of bismuth nitrate (BN) on the lethal effect of and injury to bone marrow by gamma-irradiation were examined. Mice were given daily s.c. injections of BN for 2 days and were exposed to whole-body irradiation (137Cs; 8 grays) 24 hr after the second injection of BN. All mice exposed to gamma-irradiation without treatment with BN died within 30 days, but the lethal effect of gamma-irradiation was markedly reduced in mice given BN before irradiation. Irradiation (3 grays) significantly reduced the total number of leukocytes 1 day after irradiation but the number of leukocytes subsequently increased in both nontreated and BN-treated irradiated mice. However, the rate of recovery of the total number of leukocytes, as monitored from 5 days after irradiation, was significantly higher in BN-treated mice than in the nontreated mice. Reductions in the viability of hematopoietic stem cells (determined by monitoring the number of colony-forming units in the spleen) that were induced by gamma-irradiation (3 grays) were considerably diminished by the treatment of mice with BN before irradiation. BN significantly increased the concentration of metallothionein in the bone marrow cells of mice, but levels of other cellular antioxidants, such as catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione, were unchanged. These results suggest that BN protects bone marrow cells against the toxic effects of gamma-irradiation by inducing the synthesis of metallothionein in the bone marrow. Metallothionein might play an important role in determining the sensitivity of animals to gamma-irradiation.

Animals↗

Hypertrophic obstructive cardiomyopathy due to a novel T-to-A transition at codon 624 in the beta-myosin heavy chain (beta-MHC) gene possibly related to the sudden death.

Many missense mutations in the beta-myosin heavy chain have been reported in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, the controversy is present whether the mutation accompanying the change of electric charge is related with poorer prognosis. The proband, a 48-year-old female, of the family was diagnosed clinically as HOCM, and a structural analysis of the cardiac beta-MHC gene showed that the proband and her junior daughter had a novel mutation with T to A transition in codon 624 replacing tyrosine with asparagine, which was not present in her husband, elder daughter and son. The proband's husband, son and two daughters were healthy except that the ECG of junior daughter (15-year-old) showed complete right bundle branch block. Proband's mother died suddenly after the delivery of the proband and the proband also collapsed suddenly. The occurrence of sudden death in proband and her mother suggested that HOCM with this novel mutation might be associated with a high risk of sudden death irrespective of the absence of charge alteration.

Amyl Nitrite↗

Human endothelin receptors ET(A) and ET(B) expressed in baculovirus-infected insect cells--direct application for signal transduction analysis.

We expressed human endothelin receptors, ET(A) and ET(B), in insect Sf9 cells infected by recombinant baculoviruses that contained the respective cDNAs. Ligand-binding experiments showed that the two expressed receptors have the same affinities as observed for the receptors in mammalian cells, i.e. the ET(A) receptor showed an affinity order of ET-1 > or = ET-2 >> ET-3, and the ET(B) receptor remained nonselective for three isopeptide ligands. The ET(B) receptor was purified by affinity chromatography with K9-biotinyl-ET-1 without losing the ligand-binding activity from the membrane of infected Sf9 cells. Protein chemical analysis of the purified ET(B) receptor showed that it is glycosylated, and that the N-terminal 38-amino-acid peptide is susceptible to proteolytic digestion, resulting in a small 35-kDa receptor like that found in the human placenta. Surprisingly, the infected and unlysed cells showed a strong intracellular Ca2+ concentration increase ([Ca2+]i), which was generated by a unique signal-transduction pathway consisting of the insect GTP-binding protein and human endothelin receptors expressed in the late phase of virus infection. Due mainly to an efficient expression (over 200,000 receptors/cell), to a low background owing to no endogenous homolog receptor in insect Sf9 cells, and to a sensitive fluorescent reagent Fura-2, this insect Sf9 cell system can detect the [Ca2+]i induced by picomolar levels of endothelin-receptor. We propose that this highly sensitive system be used to screen for potential antagonists/agonists of endothelin receptors.

Amino Acid Sequence↗