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Biomedical subjects

K Uehara

Publications and source records attributed to K Uehara.

At least 37 records · Page 2Linked to original sources

Potential role of activin A in follicular development during the second half of pregnancy in the golden hamster: utero-placental source of activin A.

Numerous antral follicles develop during the second half of pregnancy in the golden hamster. However, mechanisms regulating follicular development during this period are unknown. Because inhibin and activin are related to follicular development, these hormones were studied to gain insight into any potential roles in follicular development. Plasma inhibin A and B suddenly increased from day 8 of pregnancy, reached peak levels on day 10 and gradually declined to term. Plasma activin A gradually increased from day 8 to day 15 of pregnancy, and this was followed by an abrupt decrease at day one of lactation. Ovariectomy on day 12 of pregnancy rapidly reduced plasma inhibin A and B, but not activin A levels. Hysterectomy or placentectomy on day 12 of pregnancy caused an abrupt decrease in the levels of plasma activin A and FSH, but not inhibin A and B at 6 h after surgery. Hysterectomy also induced atresia of large antral follicles at 24 h after surgery. These results indicate that antral follicles are the main source of circulating inhibin A and B, whereas uteri and placentae are the main source of circulating activin A. These results suggest that increased levels of activin A may be involved in folliculogenesis in the ovary during the second half of pregnancy in the golden hamster.

Activins↗

Secretory pattern of inhibin A, inhibin B and inhibin pro-alpha C during induced follicular atresia and subsequent follicular development in the golden hamster (Mesocricetus auratus).

The changes in plasma concentrations of inhibins A, B and pro-alpha C were determined in the cyclic golden hamster during follicular atresia induced with antiserum against luteinizing hormone releasing hormone (LHRH-AS) at 1100 h on day 4 (day 1=day of ovulation). Follicular status in the ovary was also studied by determining the number of follicles ovulating in response to human chorionic gonadotrophin (hCG) injection. The time-courses of changes in plasma concentrations of inhibins A, B and pro-alpha C were different from each other during induced follicular atresia and subsequent follicular development. Plasma concentrations of inhibin A decreased to 58.6% of initial values by 24 h after LHRH-AS treatment, and then remained relatively low until at least 60 h later. Plasma concentrations of inhibin B decreased to 64.2% of the initial values by 18 h after LHRH-AS treatment and remained at basal values for 36 h, but increased abruptly to greater than initial values at 42 h after the treatment. Plasma concentrations of inhibin pro-alpha C increased at 6 and 12 h, decreased suddenly to 21.9% of the initial values by 24 h after LHRH-AS treatment, and then gradually increased until 60 h after LHRH-AS. The number of follicles responding to hCG decreased gradually between 0 and 30 h after LHRH-AS, when no ovulations were observed, and then gradually increased until 60 h. The changes in follicular ovulatory responses to hCG correlated with the plasma profile of inhibin A throughout the experiment. These results suggest that inhibin A is mainly secreted by large antral follicles. In contrast, during the subsequent follicular development, the plasma concentration of inhibin B increased earlier than that of inhibin A. These results suggest that inhibin B is secreted by small and large antral follicles. Plasma concentrations of inhibin pro-alpha C were high at a time when plasma concentrations of oestradiol-17 beta had already decreased, indicating that inhibin pro-alpha C is secreted not only from healthy follicles but also from early atretic antral follicles.

Animals↗

Ankle arthrodesis and tibial lengthening for congenital sensory neuropathy with anhidrosis.

This report describes a patient with congenital sensory neuropathy with anhidrosis (CSNA) with destructive arthropathy of the left ankle joint that was treated with ankle arthrodesis and tibial lengthening, using an Ilizarov external fixator. The fusion at the ankle joint was successful, but, at the lengthening site, loosening of the apparatus occurred and formation and maturation of the distracted callus were delayed. Intramedullary nailing was used after the removal of the external fixator, and a low-intensity ultrasound device was employed, after which the distracted callus matured gradually. During the maturation period, the patient's dysplastic right hip joint was destroyed, without the occurrence of any severe symptoms. Distraction osteogenesis in patients with CSNA may lead to good results if rigid fixation, nonweight-bearing (i.e., adequate rest), and appropriate biological stimulation can be employed.

Adult↗

Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma.

BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.

Administration, Oral↗

High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis.

BACKGROUND AND AIMS: The aims of the present study were to determine the occurrence rate of hepatocellular carcinoma (HCC) and to assess the risk factors for the development of HCC in compensated viral liver cirrhosis. METHODS: Two hundred and thirty-nine cirrhotic patients (65 hepatitis B surface antigen (HBsAg) positive, 165 hepatitis C virus (HCV) antibody positive (anti-HCV), and nine with both HBsAg and anti-HCV positivity) were studied. The Kaplan-Meier method evaluated by a log-rank test was used to estimate the cumulative probability of HCC development. Independent predictors of HCC development were estimated by using the Cox proportional hazard regression analysis. RESULTS: Dual infection manifested as HBsAg and anti-HCV positive was the highest risk of HCC. Multivariate analysis indicated that anti-HCV positive, HBsAg positive, and lactate dehydrogenase were independent predictors of the development of HCC among individuals with viral cirrhosis. In the HBsAg-positive group, a high-titer of HBV-DNA (more than 3.7 log genome equivalents (LGE)/mL) was most predictive of HCC development. In the anti-HCV-positive group, male gender and a high-titer of HCV-RNA (more than 1.0 Meq/mL) were predictive factors for the development of HCC. CONCLUSIONS: Individuals with high viral loads should be monitored for the development of HCC. Clinical efforts at eradicating or reducing the viral load may reduce the risk for HCC.

Alanine Transaminase↗

Establishment and characterization of immortalized Schwann cells from murine model of Niemann-Pick disease type C (spm/spm).

Niemann-Pick disease type C (NPC) is characterized by an accumulation of unesterified cholesterol in the endosomal/lysosomal (E/L) system, resulting in progressive neurodegeneration and death during early childhood. To investigate the cellular pathomechanism of nervous system involvement in NPC, continuous neural cell lines are desirable. In this study, we obtained neuronal and Schwann cell cultures and established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of NPC model mouse (spm/spm). One of the cell lines, designated SPMS9, had distinct Schwann cell phenotypes and was maintained over 10 months without phenotypic alterations. The level of Npc1 mRNA was markedly decreased, and NPC1 protein was not detectable in SPMS9 cells. These cells contained intracytoplasmic granules positive for filipin cholesterol staining and immunoreactive for GM2 ganglioside. Electron-microscopically, intracytoplasmic polymorphous membranous inclusions and vacuoles were demonstrated in SPMS9 cells. The treatment with an inhibitor of ceramide-specific glucosyltransferase, N-butyldeoxynojirimysin (NB-DNJ) markedly reduced the intracytoplasmic granular immunofluorescence for GM2 ganglioside in SPMS9 cells, whereas the amount of filipin-positive granules remained unchanged. The SPMS9 cells retained vesicular fluorescence of cationic dye acriflavine 16-24 hours after loading, indicating the defect of transmembrane efflux pump activity of NPC1 in the E/L compartment in these cells. These immortalized Schwann cells can be useful in studies on the nervous system lesions in NPC.

Animals↗

Contribution of endogenous inhibin to the decline of the secondary surge of follicle-stimulating hormone in the rat.

The involvement of inhibin in the decline of the secondary surge of follicle-stimulating hormone (FSH) was investigated in the rat. After ovariectomy or treatment with inhibin antiserum conducted at 2300 hours during pro-oestrus, plasma concentrations of FSH were maintained at high levels compared with control rats. However, plasma FSH started to decline at 0500 hours during oestrus in both the groups. The same treatments conducted during metoestrus markedly increased plasma FSH after 24 h (twofold compared with the treatments during pro-oestrus), suggesting that the treatments sufficiently depleted circulating inhibin. To examine whether the decline of plasma FSH occurred through a transcriptional mechanism or through a translational mechanism, FSH-beta mRNA expression and the pituitary concentration of FSH were measured. Neither ovariectomy nor inhibin immunization conducted during the night of pro-oestrus, affected the pituitary concentration of FSH after 24 h, whereas a noticeable increase was observed after the treatments conducted during metoestrus. In both stages, both ovariectomy and inhibin immunization significantly increased FSH-beta mRNA expression compared with control rats. In contrast with the pituitary concentration of FSH, the effect of inhibin immunization on FSH-beta mRNA expression was not different between the stages. The present data demonstrate the involvement of inhibin in the decline of the secondary surge of FSH, and suggest that a factor or factors other than inhibin may also be responsible for the fall in FSH. Changes in the pituitary concentration of FSH and FSH-beta mRNA expression suggest that post-transcriptional mechanisms may be involved in the suppression of FSH secretion during oestrus.

Animals↗

Identification of essential amino acids in the Azorhizobium caulinodans fucosyltransferase NodZ.

The nodZ gene, which is present in various rhizobial species, is involved in the addition of a fucose residue in an alpha 1-6 linkage to the reducing N-acetylglucosamine residue of lipo-chitin oligosaccharide signal molecules, the so-called Nod factors. Fucosylation of Nod factors is known to affect nodulation efficiency and host specificity. Despite a lack of overall sequence identity, NodZ proteins share conserved peptide motifs with mammalian and plant fucosyltransferases that participate in the biosynthesis of complex glycans and polysaccharides. These peptide motifs are thought to play important roles in catalysis. NodZ was expressed as an active and soluble form in Escherichia coli and was subjected to site-directed mutagenesis to investigate the role of the most conserved residues. Enzyme assays demonstrate that the replacement of the invariant Arg-182 by either alanine, lysine, or aspartate results in products with no detectable activity. A similar result is obtained with the replacement of the conserved acidic position (Asp-275) into its corresponding amide form. The residues His-183 and Asn-185 appear to fulfill functions that are more specific to the NodZ subfamily. Secondary structure predictions and threading analyses suggest the presence of a "Rossmann-type" nucleotide binding domain in the half C-terminal part of the catalytic domain of fucosyltransferases. Site-directed mutagenesis combined with theoretical approaches have shed light on the possible nucleotide donor recognition mode for NodZ and related fucosyltransferases.

Amino Acid Sequence↗

Stage- and tissue-specific expression of a beta-1,4-galactosyltransferase in the embryonic epidermis.

Changes in oligosaccharide structures of glycoconjugates have been observed, and are postulated to have key roles in embryonic development and differentiation. N-Acetylglucosamine (GlcNAc) beta-1,4-galactosyltransferase (beta4GalT) AKI showed different expression patterns in time and space, and different enzymatic activity from the other known family members. The epidermis of mouse embryo included a high level of AKI activities, which transferred galactose (Gal) to endogenous glycoprotein (molecular weight 130 kDa) (GP130). The maximum activity was for 13.5-d postcoitum embryos. Specific antibody against AKI inhibited 81% of GlcNAc betaGalT activities, which indicates that AKI represents the major part of the embryonic epidermis enzymes. AKI shows 2.2 times higher galactosyltransferase activity toward Gal-acceptor glucose with alpha-lactalbumin (alpha-LA) than toward GlcNAc without alpha-LA. AKI is also expressed in mouse melanoma and leukemia cell lines and in human basal cell carcinoma specimens. The GP130 Gal acceptor once galactosylated by AKI may be directly involved in epidermal differentiation and oncogenesis.

Aged↗

Characterization of isotype-specific regions of five classes of canine beta-tubulin and their expression in several tissues and cell culture.

The structure of isotype-specific regions of classes 1, II, III, IVa and IVb of canine beta-tubulin was characterized by 3'-RACE and the expression of these isotypes in canine tissues was examined by ribonuclease protection assay (RPA). Furthermore, a malignant mammary tumor-derived osteosarcoma-like cell line was established and the altered expression of beta-tubulin isotypes in taxol-resistant sublines was analyzed. The deduced amino acid sequences in isotype-specific regions corresponding to classes I, II and IVb were identical to those of humans and mice, but those in classes III and IVa showed slight differences among species. RPA revealed that classes I and IVb were widely distributed, but classes II, III and IVa were restricted to the brain. Because RPA could clearly distinguish the expression of class IVa from that of class IVb, it was thought to be more useful than northern blot for analysis of beta-tubulin isotype expression. In vitro, taxol-resistant sublines displayed a significant increase in class IVa as compared with taxol-sensitive cells, suggesting that altered expression of class IVa was associated with taxol resistance in these cell lines.

Amino Acid Sequence↗

[A case of elderly onset Parkinson's disease complicated by dropped head syndrome].

An 86-year old man presented with a 7-year history of gait disturbance. He was admitted to our hospital on April 2000 because he was experiencing difficulty eating due to progression of dropped head syndrome. Upon standing and sitting, remarkable dropped head and kyphosis were observed. When lying, the patient was able to stretch his neck, and he could stand and walk with the aid of a walker. Rigidity and resting tremor were present predominantly in the lower limbs. Parkinson's disease was diagnosed therefore L-dopa and Cabergoline were administered. Parkinsonism and dropped head syndrome improved in response to treatment. Cases involving dropped head syndrome due to Parkinson's disease are reportedly improved by L-dopa, but exasperated by dopamine agonists. The mechanism of dropped head is thought to be an imbalance in the tonus of the anterior and posterior neck muscles. Dropped head in the present case may have been a complication of Parkinson's disease since it improved in response to L-dopa.

Aged↗

[Myasthenia gravis is improved temporarily at postburn period].

A 62-year-old woman with a 25-year history of myasthenia gravis (MG) was admitted to our hospital due to burn injury over 20-25% of the total body surface area. Five months before admission, the serum concentration of acetylcholine receptor (AchR) antibodies was 80.9 nmol.l-1 (normal range < 0.3 nmol.l-1). Anticholinesterase agents had been administered for MG, but were discontinued six days after admission due to muscarinic side effects, but no symptoms of MG appeared. Thirteen days after admission, the AchR antibody titer was 21.2 nmol.l-1. Free skin grafting was performed under general anesthesia without any event. About 80 days after admission, weakness of extraocular muscles appeared. Positive tensilon test and the characteristic electromyographic findings revealed deterioration of MG, and anticholinesterase agents were resumed. Ten months after admission, the AchR antibody titer was 50.4 nmol.l-1. The mechanism of the temporary improvement of MG symptoms does not appear to be explained by the diffuse immunosuppression after burn. At a postburn period, nicotinic AchRs at the neuromuscular junction are known to be temporarily induced. This up-regulation may have caused the temporary improvement in this patient.

Burns↗

A case of papillary muscle rupture caused by acute myocardial infarction.

A 63-year-old female was admitted because of cardiogenic shock due to complete rupture of the posterior papillary muscle. The diagnosis was made by echocardiography. She was treated successfully by an emergency replacement of the mitral valve. Early diagnosis and surgical treatment are mandatory and life-saving in the case of complete papillary muscle rupture.

Coronary Angiography↗

Structural principles and amorphouslike thermal conductivity of Na-doped Si clathrates

The postulated low thermal conductivity and the possibility of altering the electronic conductivity of metal-doped clathrates with semiconducting host elements have stimulated great interest in exploring these compounds as promising thermoelectric materials. The electronic and thermal properties of the prototypical Na xSi (46) system are studied in detail here. It is shown that, despite the fact that the Na/Si clathrate is metallic, its thermal conductivity resembles that of an amorphous solid. A theoretical model is developed to rationalize the structural stability of the peculiar structural topology, and a general scheme for rational design of high efficiency thermoelectric materials is presented.

Journal Article↗

Intrathecal morphine suppresses NK cell activity following abdominal surgery.

PURPOSE: The effects of morphine on natural killer (NK) cell activity were investigated in patients who underwent hysterectomy. METHODS: Forty patients were divided into four groups of ten. The groups received intrathecal 0.5 mg morphine (Group IT0.5), intrathecal 0.1 mg morphine (Group IT0.1) or 10 mg morphine i.v. (Group IV). The remaining ten patients served as controls and received inhalation anesthesia alone (Group C). Blood samples were withdrawn before and two hours after surgery and on postoperative days one and two to determine the blood NK cell activity using a chromium release assay with K562 cells as targets, plasma catecholamines and cortisol levels. The postoperative pain score and side effects were studied in the four groups. RESULTS: In Group IT0.5, the NK cell activity was lower on postoperative day 1 (23.9 +/- 8.4%) than the baseline level (45.7 +/- 13%) before surgery, and recovered on postoperative day 2. In Groups IT0.1, C and IV, the NK cell activities showed no significant changes. In all four groups, neither plasma adrenaline nor noradrenaline concentrations changed. In all four groups, the plasma cortisol levels increased after surgery, on postoperative days 1 and 2. The pain score was lower two hours after surgery and on postoperative day 1 in Group IT0.5 than in the other groups. CONCLUSION: These results suggest that long-lasting analgesic effects of intrathecal 0.5 mg morphine suppress the immune response following abdominal surgery.

Adult↗

Cilostazol, a selective type III phosphodiesterase inhibitor, decreases triglyceride and increases HDL cholesterol levels by increasing lipoprotein lipase activity in rats.

Cilostazol, a selective type III phosphodiesterase inhibitor, has antiplatelet and vasodilating effects. In this study, the effects of cilostazol on lipid metabolism and lipoprotein lipase (LPL) activity were studied in rats. Cilostazol was administered orally at doses of 30 or 100 mg/kg twice a day for 1-2 weeks to rats. Cilostazol decreased the serum triglyceride level in normolipidemic rats. The serum triglyceride level was reduced and HDL cholesterol level was increased by cilostazol in streptozotocin (STZ)-induced diabetic rats. The disappearance of exogenous triglyceride was accelerated by cilostazol in normolipidemic rats. Cilostazol increased post-heparin plasma LPL activity but had no effect on hepatic triglyceride lipase activity in STZ-induced diabetic rats. Cilostazol also increased LPL activity in the heart in STZ-induced diabetic rats. These findings suggest that an increase in LPL activity is responsible for the serum triglyceride lowering and HDL cholesterol elevating effects of cilostazol in rats.

Animals↗

Contamination of passenger trains with Dermatophagoides (Acari: Pyroglyphidae) mite antigen in Japan.

Passenger trains were surveyed for contamination with Dermatophagoides farinae Hughes and Dermatophagoides pteronyssinus (Trouesart) mites in Japan. A total of 492 dust samples were collected from upholstered seats in six commuter trains, one long-distance express train and three night trains in October, 1996 and January, April, and July, 1997. Mite antigen levels contained in fine dust fractions of these samples were measured by an enzyme-linked immunosorbent assay. Most samples obtained from commuter trains showed relatively high mite antigen levels of > 10 microgm(-2) (corresponding to > 100 mites). Express and night trains showed lower antigen levels per square meter, but higher mite antigen levels per gram of fine dust than commuter trains, indicating relatively high mite antigen densities. Seasonal comparisons indicated that commuter trains showed the highest mean antigen level per square meter in winter (January), whereas the highest antigen level per gram of fine dust was observed in summer (July) in express and night trains.

Animals↗

Liposome-encapsulated OK-432 specifically and sustainedly induces hepatic natural killer cells and intermediate T cell receptor cells.

BACKGROUND: OK-432 is a biological response modifier used in Japan to augment host immunity and is known to increase the host antitumour response. By using liposomes, which are vesicles made from phospholipids that have a structure resembling the cell membrane, we encapsulated OK-432. METHODS AND RESULTS: Encapsulated OK-432 was injected into the tail veins of mice, and its effect was compared with that of unencapsulated OK-432 given intravenously. In mice that received either form of OK-432, both the number of natural killer (NK) and intermediate T cell receptor (intTCR) cells (intrahepatic T cells generated by extrathymic differentiation) increased markedly in the liver, with the peak level occurring 3 days after administration. Both forms of OK-432 also increased cytotoxic activity against Yac-1 cells. The increase in numbers of cells and in cytotoxic activity in the liver persisted for longer in mice that received encapsulated OK-432 than in animals that received unencapsulated OK-432. CONCLUSIONS: Because it has been shown that both NK and intTCR cells play an important role in tumour immunity, an increase in the number of such cells can be considered likely to have an increased antitumour effect. Encapsulated OK-432 elicited liver-specific augmentation of cytotoxic activity and the effect was more persistent than that produced by OK-432 given in the conventional form; therefore, it may be useful for the treatment of tumours, particularly those arising in the liver.

Animals↗