Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 901 records · Page 50Linked to original sources

PubMed1998

Endothelin-converting enzyme-1 is expressed on human ovarian follicles and corpora lutea of menstrual cycle and early pregnancy.

We have previously reported that membrane-bound amino- and carboxypeptidases were expressed on the human follicles and corpora lutea (CL), and we proposed that these peptidases are involved in ovarian functions, probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme-1 (ECE-1) on human follicles and CL, which is a membrane-bound endopeptidase and is known to convert big endothelin-1 to endothelin-1. In the preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca interna cells and weakly on the granulosa cells. In the menstrual and pregnant CL, ECE-1 was highly expressed on both large and small luteal cells, indicating that ECE-1 expression increases during luteinization. Western blotting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly expressed on the CL in early and midluteal phases than the CL in late luteal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemically detected on their cell surface. The activity of ECE-1 was also detected on cultured luteinizing granulosa cells by measuring endothelin-1 production from its precursor. The activity of ECE-1 was significantly enhanced by the treatment of human CG (10 U/mL) and interleukin (IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alteration was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment. These results indicate that ECE-1 is a cell surface differentiation-related molecule of human granulosa and of theca interna cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines.

Adult↗

PubMed1998

Blue fluorescence generated during lipid oxidation of rat liver microsomes cannot be derived from malonaldehyde but can be from other aldehyde species.

Generation of blue fluorescence together with phospholipid hydroperoxides and aldehyde species in rat liver microsomes during oxidation with FeCl2-ADP-ascorbic acid was monitored, and the kind of lipid oxidation products participating in the formation of blue fluorescence was investigated. Contents of phospholipid hydroperoxides were increased in an early stage of oxidation, and were decreased in an advanced stage of oxidation. Contents of components that liberated malonaldehyde, 4-hydroxyalkenals and other unsaturated aldehydes under the acidic assay conditions were increased in the advanced stage of oxidation. Water-soluble blue fluorescence with a maximum at 440-450 nm determined after separation through gel filtration accumulated in the advanced stage of oxidation, and was characterized as resistant to borohydride treatment and to be little dependent on pH values of the solvent. Wavelength of the maximum fluorescence and characteristics of the fluorescence were similar to those of fluorescence with maxima at 440-450 nm formed by reaction of unoxidized microsomes, bovine serum albumin or methylamine with alkenals, and different from those of fluorescence with maxima at above 460 nm obtained by the reaction with a mixture containing malonaldehyde. Hence, blue fluorescence accumulated in oxidized microsomes cannot be derived from free malonaldehyde but can be from other aldehyde species including alkenals.

Aldehydes↗

PubMed1998

Ischemic change on electrocardiogram induced by hypoglycemia in a diabetic patient.

A 34-year-old female patient who presented to our hospital had been treated with insulin for diabetes since she was 25 year old. For the previous year she had experienced chest pain on exertion and during hypoglycemia. During both chest pain and exercise tests, ST depression and flattening of the T wave were recognized in leads II, III, aVF, and V2-V6 on the electrocardiogram, and thus ischemic heart disease was suspected. Cardiac catheterization was performed, but no organic stenosis or spasms were found. Hypoglycemia (41 mg/dl) was induced by intravenous injection of rapid insulin (total 18 U, 0.4 U/kg). However, no coronary change was seen, although she felt chest pain and the same ischemic electrocardiographic changes occurred. We hypothesized the causes of the ischemic change to be both the effects of insulin on the cardiovascular system and the physiologic stress induced by the existence of microvascular abnormality. Special care should therefore be taken with diabetic patients being treated with insulin or hypoglycemic agents.

Adult↗

PubMed1998

The relation between the pacing sites in the right ventricular outflow tract and QRS morphology in the 12-lead ECG.

Optimal pace mapping is a good predictor of the appropriate ablation site for idiopathic right ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). We studied the relationship between the RVOT pacing site and QRS morphology in the 12-lead ECG during pacing to find the optimal site more quickly. In 13 patients with idiopathic VT, pacing at 8 sites in the RVOT (free wall, septum, and anterior and posterior regions of upper and lower sites) was performed while 12-lead ECGs were recorded. The R-wave amplitude minus the S-wave amplitude in lead I (RI-SI) and aVF (RavF-SavF) and the transitional zone index (TZI) were compared in the different pacing sites; TZI was defined to examine the transitional zone as a value. The RI-SI was smaller in the anterior region than in the other regions, and the negative RI-SI predicted that the pacing site was in the upper or lower anterior regions. The RavF-SavF was larger in the septum and anterior regions than in the free wall and posterior regions. The TZI was larger in the free wall region than in the septum. From the results, we constructed a flow chart that differentiates the origin of the arrhythmia in the RVOT and a directional guide that indicates the direction from the current mapping site for optimal pace mapping. The results provided an ECG guide for locating the focus of VT originating from the RVOT. These findings may systematically improve the mapping procedure.

Adolescent↗

PubMed1998

Heart rate variability before spontaneous episodes of ventricular tachycardia originating from right ventricular outflow tract in patients without organic heart disease.

Ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT) has been reported to be induced by exercise or isoproterenol and is considered to be related to catecholamines. This study was designed to examine the role of autonomic tone in spontaneous episodes of VT originating from RVOT. High frequency (HF; peak power of 0.20-0.40 Hz) and low frequency (LF; peak power of 0.05-0.15 Hz) spectral components of heart rate variability were calculated from RR intervals in a 30-min period before 33 episodes of VT during 24-h Holter monitoring in 8 patients. One VT episode was sustained, 20 were incessant and 12 were nonsustained. The ratio of LF and HF power and heart rate increased significantly from 8 min before the onset of VT, whereas the HF power gradually decreased but this decrease did not reach the statistical significance. In conclusion, an increase of the ratio of LF and HF power preceding VT suggests that activation of sympathetic tone plays an important role in the occurrence of VT originating from the RVOT.

Adolescent↗

PubMed1998

A cysteine-dependent serine protease associated with the dormant spores of Bacillus cereus: purification of the protein and cloning of the corresponding gene.

Subtilisin-like serine protease, which is associated with the dormant spores of Bacillus cereus, was solubilized by washing the spores with 2 M KCl and purified to homogeneity by carbobenzoxy-D-phenylalanine-liganded affinity column chromatography and hydrophobic interaction column chromatography. Enzyme activity was completely inhibited by reagents for sulfhydryl groups such as HgCl2 as well as by conventional subtilisin inhibitors, suggesting the enzyme to be cysteine-dependent. The enzyme retained activity in 5 M urea at 4 degrees C for at least 2 months, and the specific activity was 50 times that of subtilisin BPN when measured for a common chromogenic substrate, carbobenzoxy-glycyl-glycyl-L-leucine p-nitroanilide. The gene encoding this protease was cloned in Escherichia coli, and its nucleotide sequence was analyzed. The deduced amino acid sequence suggested that the protease is produced as a precursor comprising three portions; a signal sequence (28 amino acid residues), a prosequence (80 amino acid residues) and a mature enzyme (289 amino acid residues). The mature region of the enzyme had high similarity with a thermitase from Thermoactinomyces vulgaris (72% identity) and a thermostable alkaline protease from Thermoactinomyces sp. E79 (66% identity), which have the N-terminal sequence showing scarcely noticeable similarity with corresponding stretches of subtilisins and mercuric ion-sensitive free cysteine in the equivalent position of the primary structure.

Amino Acid Sequence↗

PubMed1998

Diagnosis and sero-epizootiology of equine herpesvirus type 1 and type 4 infections in Japan using a type-specific ELISA.

Recently, a type-specific ELISA using equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4) glycoprotein Gs (gGs) was developed by Crabb and Studdert [1993]. To investigate the dissemination of EHV-1 and -4 among horses in Japan, we applied their ELISA as suitable for discriminating between EHV-1 and -4 infections serologically. Type-specificity of the ELISA was confirmed by using paired sera of infected horses with either EHV-1 or -4. Application of the ELISA to sera collected before and after the winter season of 1995-1996 from 80 racehorses revealed that 30 horses showed significant antibody responses against EHV-1 and 9 against EHV-4, respectively. The results indicated that this ELISA using paired sera is useful for a diagnosis and an epizootiological study on EHV-1 and -4 infections.

Animals↗

PubMed1998

The preventive and interventional effects of raloxifene analog (LY117018 HCL) on osteopenia in ovariectomized rats.

The effects of LY117018 HCL (LY) treatment on bone metabolism, spine bone mineral density (BMD), bone mineral content (BMC), and serum cholesterol were studied in ovariectomized (OVX) rats. Experiment 1 was designed to observe the preventive effects of LY on bone loss due to ovariectomy (OVX; prevention study). The rats were divided into three groups: sham group, OVX + vehicle, and OVX + LY. LY was administrated at the same time of OVX. Experiment 2 was designed to investigate the interventional effects of LY on OVX rats with osteopenia (intervention study). The rats were divided into the sham and OVX groups, first. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into two groups: OVX + vehicle and OVX + LY. The longitudinal effects of LY on bone were studied by dual-energy X-ray absorptiometry and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. Urinary Pyr and Dpyr increased maximally at 6 weeks post-OVX, decreased at 12 and 18 weeks post-OVX, although the OVX rats had significantly higher levels of Pyr and Dpyr than the sham group during the experiment. LY was a very potent inhibitor of Pyr and Dpyr excretion while at the same time only partially reducing the bone loss in the high turnover phase at 6 weeks postovariectomy. However, at the later time points at 12 and 18 weeks, no further bone loss occurred in rats treated with LY, while the vehicle-treated group lost another 10% in spine BMD and BMC. LY also completely blocked further bone loss when used in an intervention protocol. LY significantly reduced serum cholesterol levels in OVX rats. The results suggest that LY is not fully protective during the early rapid bone loss phase, but the compound is fully protective during the later slow phase of bone loss in both the protocols.

Absorptiometry, Photon↗

PubMed1998

A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. The Alendronate Research Group.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption. The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored. A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18.2%, respectively. The most common adverse effects were gastrointestinal symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H and P groups, respectively (P < 0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration. Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Adult↗

PubMed1998

Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease.

We describe a family with Liddle's disease caused by a novel mutation of the beta subunit of the human epithelial sodium channel (ENaC). A 15-year-old Japanese female was referred to our outclinic because of hypertension. The physical examination showed no abnormal findings except mild hypertension, but the laboratory data revealed low levels of plasma renin activity, plasma aldosterone and serum potassium. A comprehensive analysis of steroid hormones showed only high levels of urinary free cortisol and 17-hydroxycorticosteroids. During loading tests, blood pressure and serum potassium responded well to triamterene and slightly to spironolactone, but did not respond to dexamethasone. In addition, the normal ratio of tetrahydrocortisol plus 5alpha-tetrahydrocortisol to tetrahydrocortisone in a 24 h urinary excretion test strongly suggested a diagnosis of Liddle's disease rather than apparent mineralocorticoid excess syndrome. DNA sequence analysis of members of this family revealed a single cytosine base insertion at Arg-597 of the beta human ENaC in the proband and her mother, leading to a loss of the last 34 amino acids from the normally encoded protein as the result of a frameshift. We conclude that a de novo cytosine insertion into the final exon of the C-terminus of the beta human ENaC is responsible for Liddle's disease in this Japanese family.

Adolescent↗

PubMed1998

Carbamazepine-induced sinus node dysfunction and atrioventricular block in elderly women.

We report on four elderly women in whom carbamazepine was suspected of inducing sinus node dysfunction (3 patients) and atrioventricular block (1 patient). Patients were treated with carbamazepine, 200 to 600 mg a day, for trigeminal neuralgia (n = 3) or epilepsy (n = 1). After 1 to 16 months of carbamazepine therapy, these patients were admitted to our emergency room because of bradyarrhythmia. Their conduction disturbances on electrocardiographic monitoring disappeared immediately after the cessation of carbamazepine intake. Provocation tests were performed on three patients. Because of renal insufficiency, one patient could not undergo the provocation test. Her carbamazepine clearance was markedly decreased. Carbamazepine induced sinus arrest in two patients within 48 hours after intake, but did not induce atrioventricular block in the remaining patient. In two patients, computer simulation of carbamazepine pharmacokinetics was performed and disclosed a clear-cut relationship between the plasma concentration of carbamazepine and the frequency of sinus arrest. During the test, the maximum plasma carbamazepine concentration in these two patients did not exceed the therapeutic range. However, it did exceed the range in the one with a negative test. Our results suggest that careful monitoring of ECG and plasma drug concentration is required with carbamazepine therapy, especially in elderly women.

Aged↗

PubMed1998

Effects of corticotropin-releasing factor on feeding and pancreatic polypeptide response in the dog.

We have previously reported that corticotropin-releasing factor (CRF) is a potent stimulator of adrenocorticotropic hormone and cortisol secretion in the dog. Therefore, in the present study, we investigated the extrahypophysiotropic actions of CRF in this species. When CRF was injected into the third cerebral ventricle, it failed to inhibit food intake significantly at doses of 1.19, 3.57, and 11.9 nmol. This is in sharp contrast with the results in rodents. At the 3.57 and 11.9 nmol doses, CRF markedly stimulated the secretion of pancreatic polypeptide (PP), a hormone under vagal control, and at the highest dose CRF increased plasma glucose levels. These results suggest species differences in the feeding response to CRF and activation of the parasympathetic nervous system in the dog.

Animals↗

PubMed1998

Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients.

Patients with chronic renal failure often show accumulation of intermediate-density lipoprotein (IDL). Because recent studies have emphasized the atherogenicity of IDL in the general population, we evaluated the relationship between this lipoprotein and aortic atherosclerosis in uremic patients treated with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL. Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay. Aortic PWV was significantly higher in the hemodialysis patients than in the control subjects. The hemodialysis group showed a significant increase in VLDL and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the control levels. Lp(a) levels did not differ between the two groups. In the hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not. Multiple regression analyses indicated that plasma triglycerides, independent of HDL cholesterol, had a significant association with aortic PWV in the hemodialysis patients but not in the control subjects. Further analyses revealed that aortic PWV in the hemodialysis patients had a significant and independent association with IDL cholesterol, whereas aortic PWV in the control subjects had significant and independent associations with HDL cholesterol and Lp(a). These results demonstrate that IDL is the lipoprotein fraction most closely associated with aortic PWV in the hemodialysis patients.

Adult↗

PubMed1998

An immunocytochemical study for lysosomal cathepsins B and D related to the intracellular degradation of titanium at the bone-titanium interface.

The morphological relationship between titanium and lysosomal proteinases, cathepsins B and D, at the bone-titanium interface using titanium-coated plastic implants placed for 28 days in the tibiae of 6-week-old rats was immunocytochemically investigated by the colloidal immunogold-silver method. Under light microscopy the titanium layer appeared to make direct contact with the bone and one or a few layers of slender cells were interposed between the bone and titanium. Ultrastructurally, the titanium came in contact with the bone or the slender cell layer through a 20 to 40 nm thin amorphous zone. The slender cells at the bone-titanium interface consisted of two types; one was an osteoblast type with glycogen granules which was found along the newly-formed bone facing titanium layer. The other was a fibroblast type which came in contact with the titanium layer and occasionally endocytosed the detached titanium fragments. In addition, some of the slender cells also showed degenerative changes. Immunocytochemically, cathepsins B and/or D were sometimes colocalized in some phagolysosomes with titanium fragments. These findings suggested that the fibroblast types at the bone-titanium interface may act as scavengers to remove both cell debris and titanium by means of some endocytotic ability, and lysosomal cathepsins also developed in response to the endocytosed titanium. The osteoblast type also appears to show a high degree of osteogenic activity around the titanium-coated plastic implants.

Animals↗

PubMed1998

Toxicity study of a rubber antioxidant, 2-mercaptobenzimidazole, by repeated oral administration to rats.

The chemical structure of 2-mercaptobenzimidazole (2-MBI), which is widely used as a rubber antioxidant, is partially similar to those of thiourea (TU) and ethylenethiourea (ETU), both potent thyrotoxic compounds. In order to determine the oral toxicity of 2-MBI, a 28-day repeated dose toxicity study in Wistar rats followed by observation over a 14-day recovery period was conducted at dose levels of 2, 10 and 50 mg/kg 2-MBI administered by gavage. No toxic deaths occurred due to 2-MBI treatment. Decreases of body weight gain and food consumption in the 50 mg/kg dose group were observed during the second half of the treatment period. In addition, hematological examination and serum biochemical tests revealed decreased white blood cells and hemoglobin and increased serum urea nitrogen, cholesterol, phospholipid, gamma-glutamyl transpeptidase and the Na+/K+ ratio in the 50 mg/kg dose group. Marked thyroid enlargement (to 10 fold the control weight), histopathologically associated with diffuse hyperplasia of follicles with decreased colloid and thickening of the fibrous capsule, was found. Reduction in thymus weight was also observed in a dose-dependent manner, without significant histopathological alteration. The non-observed effect level (NOEL) of 2-MBI in this gavage study was found to be less than 2 mg/kg/day based on the significant decrease in thymus weight in the 2 mg/kg 2-MBI treatment group. In an ancillary study, measurement of serum levels of T3, T4 and TSH, and thyroid weight after gavage treatment with 0.15 and 0.3 mmol/kg of three antithyroid compounds for 14 days revealed a more potent antithyroid effect for 2-MBI than for TU or ETU.

Administration, Oral↗

PubMed1998

Peliosis hepatis associated with idiopathic restrictive cardiomyopathy.

A rare case of peliosis hepatis associated with idiopathic restrictive cardiomyopathy is reported. A 75-year-old man was admitted for evaluation of marked edema and jaundice. Serum total bilirubin was elevated above 20 mg/dl. The liver biopsy under laparoscopy revealed marked sinusoidal dilatation and retention of red blood cells, which was consistent with a diagnosis of peliosis hepatis. Cardiac catheterization revealed right ventricular filling disturbance without specific findings on endomyocardial biopsy, suggesting idiopathic restrictive cardiomyopathy. The level of serum total bilirubin decreased in association with improvement of edema after drip infusion of furosemide therapy.

Aged↗

PubMed1998

Aneurysm of the gastroduodenal artery.

We report a case of gastroduodenal arterial aneurysm incidentally discovered by abdominal ultrasonogram, in which three-dimensional computed tomography (3D-CT) was useful for diagnosis. An 85-year-old man was hospitalized because of fever and liver dysfunction. Carcinoma of the papilla of Vater was diagnosed by endoscopic retrograde cholangio-pancreatography, while abdominal ultrasonogram and CT scan revealed a round mass measuring 6.2x4.1 cm on the ventral side of the pancreatic head. Three-dimensional CT demonstrated that the mass arose from a branch of the common hepatic artery and projected downward, indicating a gastroduodenal arterial aneurysm. During pancreatoduodenectomy and aneurysmectomy, it was confirmed that this aneurysm arose from the gastroduodenal artery.

Adult↗

PubMed1998

Multiple remote brain hemorrhages after removal of a giant colloid cyst of the third ventricle--case report.

A 59-year-old male presented with progressive gait and memory disturbance. Computed tomography (CT) showed a huge high density mass, of about 45 mm maximum diameter, in the third ventricle with marked hydrocephalus. Magnetic resonance imaging showed the mass as mixed iso- to hypointensity on T2-weighted imaging and high intensity on T1-weighted imaging. Bifrontal craniotomy was carried out. The histological diagnosis was colloid cyst. Six hours after the operation, a large quantity of cerebrospinal fluid (CSF) was discharged via an epidural drainage, accompanied by generalized convulsion. CT showed multiple brain hemorrhages and subarachnoid hemorrhage remote from the operative field. The cause of hemorrhages is obscure, but postoperative overdrainage of CSF through epidural drainage over a short time following excessive intraoperative CSF aspiration may have contributed to this rare complication.

Brain Diseases↗