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Biomedical subjects

M Uehara

Publications and source records attributed to M Uehara.

At least 19 recordsLinked to original sources

Occlusive effects of lactic acid-glycolic acid copolymer membrane on gingival fibroblasts in vitro.

The cell occlusive effects on human gingival fibroblasts of degradable lactic acid-glycolic acid copolymer membranes (noncoated membranes) and membranes coated with a sucrose ester of fatty acid (coated membranes) were studied and compared with those of expanded polytetrafluoroethylene (e-PTFE) membranes. The membranes were immersed in a culture medium periodically for 21 days and interposed into a chemotaxis chamber, and the fibroblasts then were cultured in the chamber for another 7 days. The passage rate of cells through the membranes was calculated and the change in surface structure of each membrane after immersion for 28 days was observed by an environmental scanning electron microscope. The passage rate of coated membranes (3.4+/-2.2%) was significantly lower than that of noncoated (25.7+/-5.1%) at the 28th day whereas the passage rate of e-PTFE membranes was 0.8-1.5%. Many pores were observed on the noncoated membranes before immersion while the coating material covered most of the pores on the coated membranes. The average pore size of the noncoated membranes was larger than that of the coated membranes at day 28. The structure of the e-PTFE membranes underwent no change. The passage rate of the coated membranes was not different from the e-PTFE membranes, suggesting an effect that might be useful for a guided tissue regeneration procedure.

Fibroblasts

Dietary fructooligosaccharides prevent postgastrectomy anemia and osteopenia in rats.

Gastrectomized rats develop anemia and osteopenia, and ingestion of fructooligosaccharides leads to an increase in iron absorption and promotes recovery from anemia in iron-deficient rats. Laparotomized (sham-operated control) rats and totally gastrectomized (Billoth II) rats, in groups of 14 each, were fed a control diet without fructooligosaccharides or a diet containing fructooligosaccharides (75 g/kg of diet) for 6 wk. All rats received an intramuscular injection of vitamin B-12 every 2 wk. Tail blood was collected every week for determination of hematocrit and hemoglobin concentration. At the end of the experiment, the rats were killed and the femur and tibia were collected for measurement of bone mineral density (BMD). The hematocrit, hemoglobin concentration, hemoglobin regeneration efficiency, and BMD of both femurs and tibias were significantly lower in gastrectomized rats fed the control diet than in the other three groups. Dietary fructooligosaccharides prevented anemia and osteopenia in totally gastrectomized rats.

Anemia

Accidental transmission of HCV and treatment with interferon.

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunodeficiency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2-3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.

Accidents, Occupational

Assessment of growth potential by MIB-1 immunohistochemistry in ameloblastic fibroma and related lesions of the jaws compared with ameloblastic fibrosarcoma.

Specimens from two ameloblastic fibromas (including one recurrent case), two ameloblastic fibro-odontomas, and one ameloblastic fibrosarcoma were subjected to investigation by MIB-1 immunohistochemistry in order to elucidate the growth potential of these tumors. MIB-1 labeling indices in the epithelial component of these tumors ranged from 2.9 to 7.5%, whereas those in the mesenchymal component ranged from 1.5 to 13.5%. Of these, labeling indices in the mesenchymal component of the recurrent ameloblastic fibroma and ameloblastic fibrosarcoma were quite high. These findings suggest that evaluation of growth potential in ameloblastic fibroma and related lesions could be of help in understanding tumor aggressiveness and in selecting appropriate surgical procedures.

Adolescent

Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts.

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.

Animals

Analysis of the vasodilator nerve function by nicotine in isolated dog skin artery.

Mechanisms underlying the relaxation induced by nicotine were analyzed in cutaneous arterial strips isolated from dogs and with the endothelium removed. In the strips treated with prazosin and precontracted with prostaglandin F2 alpha, nicotine produced relaxations which were not influenced by atropine but abolished by hexamethonium. Relaxations induced by nicotine were partially inhibited by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the remaining relaxations were abolished by desensitization to calcitonin gene-related peptide (CGRP) or treatment with CGRP-(8-37), a CGRP receptor antagonist, or with capsaicin. Desensitization to vasoactive intestinal polypeptide (VIP) or a VIP receptor antagonist did not influence the nicotine-induced relaxation. In the strips densensitized to CGRP, the nicotine-induced relaxation was abolished by L-NA; the inhibitory effect was reversed by L-arginine. Perivascular nerves containing NADPH diaphorase and CGRP immunoreactivity were histochemically identified in the cutaneous artery. CGRP immunoreactivity was abolished by treatment with capsaicin. It is concluded that nicotine produces relaxation in dog cutaneous arterial strips, possibly mediated by NO and CGRP liberated from vasodilator nerves.

Animals

Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis.

The density and fine structure of the peripheral nerve system in various skin lesions of 64 patients with atopic dermatitis (AD) was quantitatively analyzed by immunohistochemical staining with antibodies directed against protein gene product (PGP) and substance P (SP). The density of PGP-positive peripheral nerves was 2.5 x 10(3) microns2/delta s (delta s = 0.24 mm2 selected area) in early acute lesions, 3.8 x 10(3) microns2/delta s in subacute lesions, 4.9 x 10(3) microns2/delta s in lichenified lesions and 7.1 x 10(3) microns2/delta s in prurigo lesions of AD. The density of nerve fibers in subacute, lichenified and prurigo lesions was significantly higher than in uninvolved skin of AD patients (2.0 x 10(3) microns2/delta s). Electron microscopically, bulging of axons with many mitochondria and a loss of their surrounding sheath of Schwann cells suggests that the free nerve endings in skin lesions of AD are in an active state of excitation. Many pinocytotic vesicles in the periphery of basal keratinocytes facing nerve endings which contained many neurovesicles suggests reciprocal effects between keratinocytes and nerve endings. The number of SP-positive nerve fibers in AD lesions was far less than one-tenth of the number of PGP-positive nerve fibers.

Adolescent

A 15-year follow-up study of patients with non-insulin-dependent diabetes mellitus (NIDDM) in Osaka, Japan. Factors predictive of the prognosis of diabetic patients.

Risk factors related to the prognosis of diabetic patients were studied in a follow-up study of 1939 patients with non-insulin-dependent diabetes mellitus (NIDDM) for a mean observation period of 15 years at our institute. Age at entry into the study was the most powerful risk factor related to the survival of diabetic patients in this study. Moreover, the risk of death, computed in relation to baseline factors, was significantly increased in male patients; in patients with fasting plasma glucose (FPG) levels greater than 140 mg/dl, with hypertension, with diabetic retinopathy or with proteinuria; and in patients treated with an oral hypoglycemic agent of insulin at baseline, even after correction for age. The baseline factors were compared between the groups of patients who were alive and who had died at the end of the follow-up study. Greater age at onset of NIDDM and at entry into the study, higher FPG level, higher systolic and diastolic blood pressure, as well as an increase in the proportion of male patients and in patients with ischemic ECG changes, with diabetic retinopathy, with proteinuria, and with treatment with an oral hypoglycemic agent of insulin, were observed in the group of deceased patients. Furthermore, multiple logistic analysis indicated a significant relationship of age at entry, FPG, hypertension, retinopathy, proteinuria and therapeutic regimen to prognosis. We also found that the baseline factors predictive of prognosis were very different in each age group.

Adult

Morphological and morphometric features of the deformed cervical and caudal vertebrae in a new mutant knotty-tail (knt/knt) mouse.

Morphological and morphometric examinations were conducted on skeletons of knotty-tail (knt/knt) mouse, a new autosomal recessive mutant. The knt/knt mice have short and knotty tails. The number of caudal vertebrae is reduced and their deformed caudal vertebrae show no parallelism between the epiphyseal planes and no osseous fusions. Morphological changes, except for the caudal vertebrae, are confined to the neural arches of the axis in knt/knt mice. As for the tail anomaly, the knt gene seems to have the same action as the tk gene, but knt/knt mice differ from other strains with respect to cervical morphology. The morphometry of the caudal vertebrae revealed that knt/knt mice have a discontinuous and lower ratio of width to length after their 6th caudal vertebra. The morphometry also revealed that knt/knt mice have 1) broadened cervical vertebrae in the transverse direction, 2) thickened ventral lamina of the 6th cervical vertebra and 3) shortened and broadened ventral tuberculum of the atlas. From these results, the knt/knt mouse was considered to be a new pleomorphic mutant.

Animals

Epitope analysis of birch pollen allergen in Japanese subjects.

Birch pollen is a very common cause of nasal allergy (pollinosis) not only in Scandinavia, Europe, Canada, and the northern part of the United States but also in Hokkaido, Japan. We have previously reported a positive association between the HLA-DR9 phenotype and the development of birch pollen allergy in Japanese subjects. However, there is little information about T cell epitopes of birch pollen which are presented by HLA class II molecules other than HLA-DR9. Therefore, we analyzed the difference in T cell epitope usage in patients who had HLA-DR9 versus those who did not. Seven Japanese patients with birch pollinosis were studied. Some groups of peptides representing T cell epitopes (Betula verrucosa; Bet VI peptides, p7-33, p23-46, p138-160) appeared to be shared by the majority, while another peptide (Bet VI p72-95) was recognized predominantly by patients who expressed HLA-DR9 and/or HLA-DQ3 molecules. Moreover, seven T cell clones and eight T cell lines were generated from two patients who did not have HLA-DR9 or HLA-DQ3. Using some of these T cell clones/lines, we investigated the relationship between HLA class II molecules and antigenic peptides. One of these T cell clones recognized antigenic peptides in the context of the HLA-DQ1 molecule. To our knowledge, this is the first indication that the epitope on Bet VI can be presented by the HLA-DQ molecule.

Allergens

Calcium and silicon from bioactive glass concerned with formation of nodules in periodontal-ligament fibroblasts in vitro.

Previously, the authors reported that bioactive glass promoted formation of nodules in cultured periodontal-ligament fibroblasts and high concentrations of calcium and silicon were detected in the culture medium. Herein, the effects of bioactive glass, calcium alone and calcium and silicon for formation of nodules on the periodontal-ligament fibroblasts are examined. The cells were cultured with bioactive glass, without bioactive glass, calcium and silicon, with calcium alone and with calcium and silicon. The cell growth, alkaline-phosphatase activity, amount of pro-collagen type I and the number of nodules were measured periodically until the 21st day. The cell growth rate with calcium and silicon was the highest, however the rate with bioactive glass and calcium alone were similar to that without them. The alkaline-phosphatase activity and the amount of pro-collagen showed peaks at the 11th day. At the peak, the alkaline-phosphatase activity with bioactive glass or calcium and silicon, and the pro-collagen with bioactive glass was higher than without them. The number of nodules with bioactive glass, calcium alone or calcium and silicon was greater than without them. These findings suggested that the combination of calcium and silicon released from bioactive glass was concerned with the formation of nodules on the periodontal-ligament cells.

Alkaline Phosphatase

Random amplification of polymorphic DNA is useful for the differentiation of several anthropophilic dermatophytes.

The efficacy of random amplification of polymorphic DNA (RAPD) analysis, a polymerase chain reaction (PCR)-based technology, as a tool for differentiation of several anthropophilic dermatophytes, that is, Trichophyton mentagrophytes var. interdigitale, T. rubrum and Epidermophyton floccosum, was examined. Total cellular DNA extracted by a mini-preparation method were used as template DNAs and PCRs were performed using five primers, all of which were synthesized 10-mers. All of the primers generated PCR products and their electrophoresed profiles were characteristic for each of the species. Since these anthropophilic dermatophyte species could be differentiated clearly by the RAPD analysis, this method may be useful for identification of these species. Minimal intraspecies polymorphisms were observed between the isolates of T. mentagrophytes var. interdigitale. The banding patterns were reproducible using template DNAs prepared at different times from each of stock cultures.

Arthrodermataceae

Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan.

We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4 kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[-1]) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from 5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/-1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36 pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho 0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.

Administration, Oral

Prevalence of infantile and early childhood eczema in a Japanese population: comparison with the disease frequency examined 20 years ago.

To investigate the prevalence of infantile and early childhood eczema in a Japanese population, we clinically inspected the entire bodies of 4-month-old infants (341 cases), 10-month-old infants (339 cases) and 3-year-old children (341 cases). The examination was performed in spring, when exacerbations of infantile and childhood eczema most frequently occur in Japan. Eczema was observed in 30-31% of the infants, and in 20% of the 3-year-old children. The prevalence was almost the same as in similar age groups that we examined 20 years ago.

Child, Preschool

High phosphorus diet rapidly induces nephrocalcinosis and proximal tubular injury in rats.

The development of nephrocalcinosis and the time course of changes in kidney function, especially proximal tubular function, were studied in young male rats fed a high-phosphorus diet. The animals were fed a purified diet with a phosphorus content of either 0.5% (normal phosphorus diet) or 1.5% (high-phosphorus diet). In the group fed the high-phosphorus diet, nephrocalcinosis was found in 4 of 42 rats after 1 d of feeding and in all rats of this group at 3 d. The degree of nephrocalcinosis gradually increased with time. Upon histological observation by electron microscopy, vacuoles, lysosomes and swelling of microvilli in the proximal tubules were observed in rats fed the high-phosphorus diet after 1 d of feeding. Giant lysosomes with deposition of calcium and deposition of hydroxyapatite in mitochondria were observed in the proximal tubules of rats fed the high-phosphorus diet at 3 d. Albumin concentration in the urine of these rats was significantly increased at 3 d. The activity of N-acetyl-beta-D-glucosaminidase in the urine was also significantly increased after 1 d of feeding the high-phosphorus diet, and then reached a plateau. The beta 2-microglobulin concentration in the urine of rats fed the high-phosphorus diet was significantly increased at 14 d, and increased more toward 21 d. We concluded that nephrocalcinosis and injury to the proximal tubules are rapidly induced in rats fed a high-phosphorus diet.

Animals

[Analysis of T cell epitopes on birch pollen allergen].

Allergy to birch pollen is common in the Northern Europe, North America, and in Japan, mainly in Hokkaido Island. Previously, we have reported the positive association of birch pollen allergy in HLA-DR9 antigen. We also have identified the recognition sites in 17kDa protein (Bet v1), known as the major allergen of birch pollen, by using T cell proliferation assay against the trypsin digested materials of the 17kDa protein. In this study, overlapping synthetic peptides correspond to the Bet v1 sequences were used to investigate the specificity of T cell responses in two HLA-DR9 positive patients. Three of the epitopes, residues 35-52, 75-92, and 102-119, were recognized by T cells from both patients. These three epitopes include HLA-DR9 binding motifs. Then we established T cell clone specific to p75-92 residue. 78-89 peptide was the core sequence of the epitope for the T cell clone contained the anchor residues characteristic to HLA-DR9. Within the core sequence, five residues were identified as critical for recognition on the basis of inhibition of the T cell proliferative response against singly substituted analogue peptides.

Allergens

[Where is a leak point detected by "the low flow leak test" of anesthetic machines?].

"The low flow leak test" is recommended for pre-anesthetic inspection of anesthetic machines. We carried out anesthesia compression tests as a standard. Even in that case, often the low flow leak test does not meet the standard. We investigated the point where there is a leak in the anesthetic machine. Observing the leak that fluctuates each time there is detachment or attachment of the canister, the primary cause of the leak is thought to be related to the canister. It is important to carry out an inspection of the canister if the low flow leak test does not meet the standard.

Anesthesiology

Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analog for long-term clinical application of a wearable artificial endocrine pancreas.

Considering the management and safety of the insulin delivery route when a wearable artificial endocrine pancreas is applied to ambulatory diabetic patients on a long-term basis, we developed a s.c. insulin infusion algorithm by analyzing the dynamics of a s.c. injected short-acting insulin analog (Insulin Lispro) by a three-compartment model. Principally the insulin infusion algorithm was developed as a transfer function with the first-order delay in both proportional and derivative actions to blood glucose concentrations. The parameters for this algorithm were calculated to simulate a physiological plasma insulin profile as closely as possible. By applying this algorithm with regular insulin, diabetic patients showed a 2 h postprandial hyperglycemia and a delayed hyperinsulinemia, followed by hypoglycemic episodes 4-5 h after oral glucose load, just as observed in the computer simulation study. However, using Insulin Lispro, a near-physiological glycemic control (postprandial blood glucose of 153.1 +/- 8.3 mg/100 ml at 60 min and 90.3 +/- 7.1 mg/100 ml at 180 min, respectively) could be achieved without showing any delayed hyperinsulinemia or hypoglycemia. Daily glycemic excursions were also controlled near-physiologically and although the daily insulin requirement (731.7 +/- 160.5 mU/kg/day) was slightly higher, it was not significantly different from that with i.v. insulin infusion (622.3 +/- 142.6 mU/kg/day). These results indicate that the application of s.c. insulin infusion algorithm with Insulin Lispro is feasible for long-term glycemic control with a wearable artificial endocrine pancreas in ambulatory diabetic patients.

Adult