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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 1,063 records · Page 59Linked to original sources

Comparison of bone and total alkaline phosphatase activity on bone turnover during menopause and in patients with established osteoporosis.

OBJECTIVE: Recently, a bone alkaline phosphatase (AP) enzyme immunoassay (EIA) was developed for measurement of bone AP activity with a monoclonal antibody. We compared the clinical performance of bone AP (bAP) measured by EIA and total AP (tAP) to examine if bAP is preferable to tAP as a bone formation marker in the post-menopause and established osteoporosis. DESIGN AND PATIENTS: Serum was obtained from 50 pre- and 93 post-menopausal healthy women, and 54 osteoporotic patients with vertebral fractures and 57 patients with hip fracture. MEASUREMENTS: Total AP was measured spectrophotometrically with p-nitrophenyl phosphate as substrate. The intra- and inter-assay coefficients of variation were 0.7-1.8% and 0.6-1.1%, respectively. Bone AP activity (bAP) was measured by EIA kit, ALKPHASE-B (Metra Biosystems, Inc.) using a monoclonal antibody against human bone AP. The intra- and inter-assay CVs were 4.0-8.3% and 6.2-7.9%, respectively. RESULTS: The percentage mean increase of bAP (54.9%) in post-menopausal subjects over premenopausal subjects was higher than that of tAP (40.1%). In age-matched comparison, % mean increases were 57.5% for bAP and 35.3% for tAP. Z-score for bAP in post-menopausal subjects was significantly higher than that for tAP. However, there was no significant difference in Z-scores between tAP and bAP in osteoporotic patients with vertebral fractures or with hip fracture. The correlation coefficient of bAP with age (r = 0.316) was similar to that of tAP with age (r = 0.319). In post-menopausal subjects, there was no difference in the concentrations of tAP nor bAP among the groups in whom times since the menopause was 0-9 years, 10-19 years and more than 20 years. Bone AP was highly correlated to tAP in the normal subjects, the patients and the total study group. CONCLUSION: Preference can be given to bone AP by enzymatic immunoassay over total AP based on their clinical utility during the menopause; however, no preference can be given to bone AP over total AP in established osteoporosis.

Adult↗

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan.

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non-A through -E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV-C by reverse transcription-polymerase chain reaction with nested primers deduced from the 5'-noncoding region. RESULTS: HGV/GBV-C RNA was detected in 23 (7.4%) of the 361 donors with anti-HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti-HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV-C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV-C would deserve consideration.

Adult↗

Relation of disease activity during chronic hepatitis C infection to complexity of hypervariable region 1 quasispecies.

We studied the heterogeneity in the E2/NS1 hypervariable region 1 of the hepatitis C virus (HCV) genome in relation to the natural course after infection. The subjects were composed of 38 chronic hepatitis C carriers who had been followed for 9 to 218 months after the onset of non-A, non-B (type C) hepatitis, being tested monthly for serum alanine aminotransferase levels. The complexity of the sequence heterogeneity was assessed by single-strand conformation polymorphism analysis. The quasispecies complexity had no relation to the route of infection, the time from infection and the duration of aminotransferase elevation after the onset. However, it had a significant relationship with the degree of aminotransferase elevation in the course of the disease. The quasispecies complexity was directly correlated with the first peak of serum aminotransferase at the onset (r = .48, P < .01) and the mean aminotransferase levels during the period of persistent aminotransferase elevation (r = .58, P < .01). Twenty-three of the 38 patients were further followed for 24 months with biweekly alanine transaminase (ALT) tests. Their aminotransferase levels remained within the normal range during follow-up, and no significant change was seen in the quasispecies complexity after this asymptomatic period. However among the 23 patients, the quasispecies complexity increased in six cases (26%) and decreased in five (22%). A significant direct relation was seen between changes in the quasispecies complexity and the mean aminotransferase levels during the asymptomatic period (r = .55, P = .01). These findings suggest that the development of the HCV quasispecies nature may be related to the severity of the hepatitis in the course of infection.

Adult↗

A thymoma associated with hyperparathyroidism.

A 50-year-old woman sustaining a noninvasive thymoma accompanied by hyperparathyroidism is presented. Although this is the third case report to date in the literature of the combination of these two diseases, the patient did not evidence the myasthenia gravis cited in the two previous reports. In the two years following concomitant extended thymectomy and resection of the right superior parathyroid gland, including the adenoma, the patient has been following a favorable course without recurrence.

Adenoma↗

Continuous brachial plexus infusion of butorphanol-mepivacaine mixtures for analgesia after upper extremity surgery.

We have recently reported that continuous administration of butorphanol into the brachial plexus neurovascular sheath provided superior analgesia compared with that obtained with continuous i.v. administration. Furthermore, we found that analgesia was most pronounced when a mixture of mepivacaine and butorphanol was given and that butorphanol alone ranked next. In this study, we increased the dose of butorphanol, compared with that used in our previous reports, and an initial bolus dose of butorphanol was administered into the brachial plexus neurovascular sheath just after surgery had ended. Thereafter, postoperative pain relief was estimated. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, group A received a bolus of 1 ml of physiological saline with 1.5% mepivacaine, 10 ml into the brachial plexus sheath followed by a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/ 72 h. Group B was given a bolus of butorphanol 1 mg (1 ml) with 1.5% mepivacaine, 10 ml into the brachial plexus sheath and a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/72 h. After operation, VAS scores did not differ between the two groups. The time to first use of supplementary analgesia did not differ significantly between the two groups and there were no significant differences in the number of patients who required supplementary analgesia. These results indicate that continuous butorphanol 2 mg day-1 with 0.5% mepivacaine provided sufficient postoperative analgesia after upper limb surgery.

Analgesia↗

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Aged↗

Amelioration of systemic autoimmune disease by the stimulation of apoptosis-promoting receptor Fas with anti-Fas mAb.

Fas antigen (Fas) is a cell surface receptor molecule that mediates apoptosis-inducing signals into activated and/or autoreactive peripheral T and B cells by stimulation with Fas ligand or agonistic anti-Fas mAb. The i.p. administration of the hamster anti-mouse Fas mAb RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given another hamster anti-mouse Fas mAb Jo2 rapidly die of fulminant hepatitis with hemorrhage. Here, we report that MRL-gld/gld mice thoroughly recovered and/or were prevented from glomerulonephritis, arthritis, sialadenitis, vasculitis and lymphoadenopathy after receiving a single administration of the agonistic anti-mouse Fas mAb RK-8. The serum levels of autoantibodies were decreased after the administration. All the therapeutic effects of RK-8 persisted for >6 months. These findings suggest that the systemic administration of agonistic anti-Fas mAb without fulminant hepatitis-inducing activity is a useful therapeutic strategy for treating systemic autoimmune disease.

Animals↗

In vivo analysis of Fas antigen-mediated apoptosis: effects of agonistic anti-mouse Fas mAb on thymus, spleen and liver.

Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates apoptosis-inducing signals. To analyze the function of Fas in vivo, we examined the effects of agonistic anti-Fas antibodies in mice. The i.p. administration of the hamster anti-mouse Fas mAb, RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given the another hamster anti-mouse Fas mAb, Jo2, rapidly died of fulminant hepatitis with hemorrhage. Histological analyses of mice given RK-8 indicated severe damage of the thymus, and moderate damage of the spleen and liver. Most of the thymocytes and some hepatocytes underwent apoptosis within 1 day of administration. Flow cytometry revealed that CD4+ T cells were more sensitive to Fas-mediated apoptosis than CD8+ T cells. At day 7 after administration, the thymus was atrophied. These in vivo effects of RK-8 were transient; the thymus was regenerated, and the liver and spleen were apparently normal 1 month after injection. The administration of RK-8 into newborn mice caused severe damage of the liver and thymus. Most of the hepatocytes died and jaundice was induced. The newborn mice died within 1 week. Most hepatocytes of newborn mice may be more sensitive to apoptosis-inducing signals through Fas than those of adult mice. These results indicated that functional Fas, which introduces the death signal in vivo, is expressed on thymocytes, CD4+ splenocytes, and some adult and most newborn mouse hepatocytes.

Animals↗

Enhanced gene expression of scavenger receptor in peripheral blood monocytes from patients on cuprophane haemodialysis.

BACKGROUND: Macrophage scavenger receptor (SR) is implicated in playing a key role in macrophage-derived foam cell formation by taking up a large amount of modified low-density lipoproteins (LDL). It has also been postulated that alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2MG/LRP) is involved in the development of foam cells by taking up apo E-enriched chylomicrons and VLDL remnants, and lipoprotein lipase-triglyceride-rich lipoprotein complexes. Accumulation of these lipid-loaded monocyte/ macrophages in the subendothelial space is considered to be an early event of atherogenesis. Since atherogenesis is considered to be accelerated in dialysis patients, we attempted to investigate whether gene expression of SR and alpha 2MG/LRP are altered in peripheral blood monocytes from patients on haemodialysis with a cuprophane (Cu) or polymethylmethacrylate (PMMA) membranes. METHODS: Peripheral blood monocytes (PBM) were prepared from patients undergoing haemodialysis with a Cu membrane (n = 9), patients undergoing haemodialysis with a PMMA membrane (n = 9), and healthy controls (n = 7). In a separate experiment we examined SR gene expression in uraemic patients (n = 12) and healthy controls (n = 9). SR and alpha 2MG/LRP mRNA were semiquantitated using reverse-transcription polymerase chain reaction (RT-PCR) assay followed by Southern blotting. RESULTS: SR mRNA expression in PBM from patients on chronic haemodialysis with a Cu membrane was about twofold higher than that in PBM from patients on chronic haemodialysis with a PMMA membrane or the controls (P < 0.05). alpha 2MG/LRP mRNA expression in PBM showed no difference among these, three groups. SR gene expression in monocytes from uraemic patients was not increased compared with that in the controls. CONCLUSION: PBM from patients under Cu membrane dialysis showed higher gene expression of SR than patients under PMMA membrane dialysis, uraemic patients, or healthy controls. This increased gene expression of SR in monocytes may be associated with the pathogenesis of accelerated atherosclerosis in patients on dialysis with a Cu membrane.

Arteriosclerosis↗

Identification of the nucleotides in the A-rich bulge of the Tetrahymena ribozyme responsible for an efficient self-splicing reaction.

P5abc is a large extension of the P5 element characteristic of subclasses IC1 and IC2 of group I introns. It has a conserved region termed the A-rich bulge, that is responsible for activation of the Tetrahymena self-splicing intron. By employing a modified color-colony assay system, we identified four adenosines in the bulge that are responsible for an efficient splicing reaction. On comparison with the X-ray crystal structure of the P4-5-6 domains of the Tetrahymena intron, three adenosines at positions 183, 184, and 186 were found to be identical to those significantly contributing to the formation of its tertiary structure. However, our results show that an adenosine at 187 is involved in the formation of a Watson-Crick base pair with U135, although it forms a Hoogsteen base pair in the crystal structure.

Animals↗

Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis.

Pentosidine is one of the advanced glycation end-products and is formed by glycosylation and oxidation. The aim of this study is to investigate the relationship between serum and urinary pentosidine levels and the activity of rheumatoid arthritis (RA). Using HPLC with column switching, we measured pentosidine in serum and urine from 77 patients with RA and 62 normal control subjects. The clinical features, blood biochemistry and activity of inflammation were examined in RA patients. Serum and urinary pentosidine in RA were significantly higher than in controls. Pentosidine significantly correlated with age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor, joint score and Lansbury Index in RA. The levels of pentosidine were higher in patients with active RA than in those with inactive RA. Serum and urine levels of pentosidine correlated with the activity of RA, and serum and urinary pentosidine may be a significant and novel marker for evaluating the disease status and the activity of RA.

Adult↗

Monoclonal antibody against phosphatidylserine inhibits in vitro human trophoblastic hormone production and invasion.

Naturally occurring antiphospholipid (aPL) antibodies against cardiolipin (CL)- and phosphatidylserine (PS)-dependent antigens are associated with placental dysfunction and unsuccessful pregnancy. Murine monoclonal aPL antibodies react with placental trophoblast and may interfere with normal trophoblastic function. In this study, we evaluated the expression of phospholipid-dependent antigens during trophoblast differentiation and measured the effects of monoclonal aPL antibodies on two in vitro aspects of trophoblast differentiation: hormone production and invasion into filters coated with extracellular matrix. Murine monoclonal IgM aPL antibodies that differentiated between PS and CL were used: 3SB9b reacted only with PS (CL-/PS+), D11A4 reacted only with CL (CL+/PS-), and BA3B5C4 reacted with both CL and PS (CL+/PS+). Isolated trophoblasts were cultured for 4 days, and reactivity with monoclonal aPL antibodies was evaluated daily. BA3B5C4 (CL+/PS+) reacted strongly with most trophoblasts that were freshly isolated (Day 0) and through 2 days of culture, after which time the percentage of cells reactive with BA3B5C4 decreased steadily. 3SB9b (CL-/PS+) reactivity increased during incubation; about 8% of cells reacted initially, but after 1 day of incubation 100% reacted, and this percentage remained stable throughout the 4-day incubation. D11A4 (CL+/PS-) reacted only minimally and at the level of the negative control monoclonal antibody (mAb) with 1- and 2-day cultures. Both mAbs that reacted with PS-dependent antigens completely prevented invasion of matrigel-coated filters by isolated trophoblasts. These mAbs also inhibited trophoblastic hCG and human PL production by more than 45%. Thus, as trophoblasts undergo differentiation, they are reactive with mAbs against PS. These antibodies are inhibitory in vitro to trophoblastic hormone production and invasion.

Antibodies, Monoclonal↗

Impaired left ventricular diastolic filling occurs in diabetic patients without atherosclerotic coronary artery disease.

Using left ventriculography, left ventricular diastolic function was studied in 24 diabetic patients who had angina pectoris without atherosclerotic large-vessel coronary artery diseases (group A, 14 patients with exercise-induced ischemic ST-T changes as seen during electrocardiogram; group B, 10 patients without such changes). In groups A and B, the global peak filling rate was significantly less than that in control patients without diabetes or cardiac diseases. The ratio of the global time to the peak filling rate to the diastolic time was higher in both groups A and B than in the control groups. However, the total of time differences, defined as the sum of the time differences between global time to the peak filling rate and each of the three regional time to the peak filling rate, was greater in group A than in either group B or the control patients. Total time difference was similar in group B and the controls. Left ventricular diastolic filling was impaired in diabetic patients without large-vessel coronary artery disease. Impaired diastolic filling was present regionally in patients with ischemic ST-T change but globally in those without such change.

Adult↗

Drug conjugate of doxorubicin with glutathione is a potent reverser of multidrug resistance in rat hepatoma cells.

A recent study has suggested that degraded adducts smaller than 2 kDa in molecular weight of bovine serum albumin (BSA)-conjugated doxorubicin (DXR) (BSA-DXR) might exhibit cytotoxicity against multidrug resistant (MDR) cells. To investigate this notion further, intracellular accumulation and cytotoxicity of DXR coupled to several small peptides, such as glycylglycine (diGly), glycylglycylglycine (triGly), reduced glutathione (GSH) and oxidized glutathione (GSSG), were investigated using DXR-sensitive (AH66P) and DXR-resistant (AH66DR) rat hepatoma cell lines. Against both AH66P and AH66DR cells, diGly-conjugated DXR (diGly-DXR) and triGly-conjugated DXR (triGly-DXR) demonstrated the same cytotoxic activity as DXR, and the accumulation of both conjugates in the two cell lines was almost similar to that of DXR. After treatment of AH66DR cells with 5 microM verapamil [an inhibitor of P-glycoprotein (Pgp)], the intracellular levels of diGly-DXR and triGly-DXR were markedly increased and consequent cytotoxicity was improved. On the other hand, GSH-conjugated DXR (GSH-DXR) showed 9- and 7.5-fold more cytotoxic activity than BSA-DXR against AH66P and AH66DR cells, respectively. GSH-DXR accumulated rapidly in AH66DR cells, probably by the same mechanism as in AH66P cells, because the treatment of AH66DR cells with verapamil did not cause a significant increase in the intracellular drug level as compared with that in cells treated without verapamil. The levels of cytotoxicity and accumulation of GSSG-DXR were the same as those of BSA-DXR for both cell lines. These results indicate that GSH-DXR exerts potent cytotoxicity against both cell lines among the peptide DXR conjugates examined because of the rapid uptake and high accumulation of GSH-DXR similar to that of DXR without efflux.

Animals↗

Neuropathic arthropathy caused by paraneoplastic sensory neuropathy. A case report.

Neuropathic arthropathy of both knees after paraneoplastic sensory neuropathy developed in a 64-year-old woman. The patient was found to have small cell lung cancer 2 months after the onset of a sensory neuropathy that was diagnosed as paraneoplastic sensory neuropathy, a nonmetastatic neurologic complication in patients with malignancy. The onset of paraneoplastic sensory neuropathy was followed by the gradual onset of neuropathic arthropathy. This is the first well documented report on neuropathic arthropathy in a patient with paraneoplastic sensory neuropathy.

Carcinoma, Small Cell↗

Histopathological aspects of dural arteriovenous fistulas in the transverse-sigmoid sinus region in nine patients.

OBJECTIVE: In recent years, dural arteriovenous fistulas (DAVFs) have been primarily thought to be acquired lesions, formed after sinus thrombosis. The pathogenesis of DAVF, however, is still controversial. We have studied histopathological aspects of DAVFs in resected specimens obtained from nine patients, to obtain clues to the pathogenesis of DAVFs. METHODS: Histological comparison was made among nine DAVF cases and five control cases without venous sinus disease. In addition, the relationship between the clinical course and histological aspects was investigated. RESULTS: The essential abnormality found was a connection between the dural arteries and the dural veins within the venous sinus wall, through small vessels averaging approximately 30 microns in diameter. By using several staining methods, we confirmed that the vessels were part of the venous system; we named these dilated venules "crack-like vessels." CONCLUSIONS: The development of abnormal communications between dural arteries and dural veins (crack-like vessels) is regarded as the essential part of the pathogenesis of DAVFs, and sinus thrombus is not thought to be an essential lesion of DAVFs. It might be postulated that sinus hypertension caused by stenocclusive disease of the venous sinuses triggers the development of fistulous connections between arteries and veins in the dural wall, which may result in increasingly dilated venules and the formation of DAVFs.

Adult↗