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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 91 records · Page 5Linked to original sources

Function and distribution of beta3-adrenoceptors in rat, rabbit and human urinary bladder and external urethral sphincter.

1. Activation of beta-adrenoceptors causes relaxation of the urinary bladder and contraction of the external urethral sphincter, which consists of fast-contracting skeletal muscles. A beta2-adrenoceptor agonist, clenbuterol, recently has been developed as a therapeutic drug for the treatment of urinary incontinence, however beta2-adrenoceptor agonists have undesirable effects on cardiac and striated muscle function. 2. In this study, we compared the effects of the beta2-adrenoceptor agonist, clenbuterol and of a novel beta3-adrenoceptor agonist, GS332, on urinary bladder and external urethral sphincter function in rat, rabbit and human. We also determined the distribution of beta3-adrenoceptors in human urinary bladder and external urethral sphincter, using radioligand-binding techniques. 3. Clenbuterol induced marked relaxations in rat, rabbit and human urinary bladder smooth muscles and also induced marked contractions in rat periurethral striated muscles (external urethral sphincter), while GS332 induced marked relaxations in rat and human, but not in rabbit, urinary bladder smooth muscles and induced small contractions in rat periurethral striated muscles. 4. The radioligand binding studies showed presence of beta2- and beta3-adrenoceptors in human urinary bladder, external urethral sphincter and abdominal rectus muscles. The affinities of GS332 were the highest in urinary bladder and the lowest in the skeletal (abdominal rectus) muscles, while the affinities of clenbuterol were similar in urinary bladder, external urethral sphincter and the skeletal (abdominal rectus) muscles. 5. These results suggest that GS332 could, similarly clenbuterol, have a role in the treatment of urinary frequency and urinary incontinence.

Adrenergic beta-Agonists↗

[A case of common variable immunodeficiency with intractable diarrhea and the functional disorder of renal tubules].

We report a case of a 31-year-old woman with common variable immunodeficiency (CVID) complicated with intractable diarrhea and the functional disorder of renal tubules. The patient became hypogammaglobulinemic after she suffered from measles at 6 years of age. She also suffered from lupus-like syndrome at 7 years of age. The complete remission was obtained by glucocorticosteroid treatment. An intravenous immunoglobulin replacement therapy was introduced at 11 years of age, since then her general condition was stable for more than 20 years. When she was 29 years old, she suffered from generalized malaise, anorexia with body weight loss, and numbness of face. The intractable diarrhea as protein loosing syndrome, and the severe abnormality of electrolyte balance with metabolic acidosis as the functional disorder of renal tubules were found. Her condition was not improved by the electrolytes or alkali replacement therapy. She was admitted for further evaluation and treatment. The intractable diarrhea and the functional disorder of renal tubules were dramatically improved after absolute restriction of food intake under hyperalimentation. When she began to take food, the symptom and sign became worse again. The interstitial nephritis and nonspecific inflammation of intestine were found by the tissue biopsy. The most characteristic finding was the infiltration of lymphocytes (predominantly CD 8 + T lymphocytes) in both intestinal mucosa and renal interstitium. The introduction of glucocorticosteroids improved her general condition and biochemical findings. This CVID case is complicated with intractable diarrhea and the functional disorder of renal tubules which is associated with the infiltration of CD 8 + lymphocytes in intestine and kidney. We consider that such case is very rare and valuable to report.

Adult↗

Factors affecting the freeze-fracture morphology of in vivo polyhydroxyalkanoate granules.

Interesting morphologies were observed when Comamonas acidovorans containing polyhydroxyalkanoates (PHA) of various compositions was freeze-fractured at temperatures far below the glass transition temperatures of PHA. In vivo granules of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) comparatively showed the most ductility, and could be stretched extensively. Contrary to the uniform needle-type deformation shown by the poly(3-hydroxybutyrate) homopolymer when fractured at -110 degrees C, copolymers containing 3-hydroxyvalerate units showed various deformation structures. Similar observations were made when in vivo granules of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) were freeze-fractured, although the ductility of the latter was much reduced. In addition, it was found that fracturing at -160 degrees C resulted in decreased ductility of the PHA granules with the concomitant increase in the number of mushroom-type deformation structures. Our results suggest that PHA granules with higher resistance to freeze-fracture deformation show less ductility, and therefore produce the mushroom-type morphology. This is the first report on the freeze-fracture morphology of PHA copolymers containing short-chain-length monomers.

Cupriavidus necator↗

[Resected case of thymic cyst with primary lung cancer].

Thymic cyst is a rare and benign tumor of mediastinal tumor. A 77-year-old male was pointed out the tumor shadow on Chest X-ray film and diagnosed lung cancer. On admission some examination was performed and revealed mediastinal tumor accidentally. Primary lung cancer was completely resected and mediastinal tumor was extirpated. Pathological examination revealed lung cancer (poorly differentiated squamous cell carcinoma) and thymic cyst. Many methods of examination were tried for diagnosis of thymic cyst, but couldn't diagnose exactly before its resection. Some of the patients with thymic cyst was reported to develop SVC syndrome or change to malignant tumor. Therefore we think complete resection is the best treatment.

Aged↗

[Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis].

Eighteen cases (7 males and 11 females) of food-dependent exercise-induced anaphylaxis were observed for several years. The age of the patients at the first visit to our hospital ranged from 9 to 43 years (average 24.3 years). The offending foods were wheat in 9 cases, shrimp in 2 cases, shellfish in 1 case, fish in 1 case, and unknown foods in 5 cases. The inducing exercises were ball play games, running, riding a bicycle, swimming, kendo (Japanese fencing), walking, and so on. We advised these patients to avoid eating offending foods or taking exercises, or to take antiallergic medicine such as DSCG, and repirinast. We observed their clinical courses and laboratory data for 2 to 10 years. Only a few cases relapsed anaphylactoid reactions, but all cases have improved until now. In some cases, IgE RAST scores for wheat decreased. In other cases, the rate of histamine release on anti-IgE stimulation decreased after taking DSCG.

Adolescent↗

Newt prolactin and its involvement in reproduction.

The amino acid sequence of newt (Cynops pyrrhogaster) prolactin deduced from the nucleotide sequence of its cDNA showed a relatively high homology with sequences of chicken and sea turtle prolactins as well as with those of anuran prolactins. Cynops prolactin receptor transcripts were detected in various tissues and organs, suggesting that prolactin plays multiple roles in urodeles. Urodele prolactin was purified from the pituitaries of C. pyrrhogaster. Antiserum against this prolactin was used for radioimmunoassay of plasma prolactin and immunoneutralization experiments. Endogenous prolactin was shown to induce migration to water, courtship behavior, and cessation of spermatocytogenesis in the Cynops newt. The hormone was found to be involved in the development of cloacal glands such as the lateral and abdominal glands, growth of the tail and Mauthner neurons, secretion of oviducal jelly, and enhanced synthesis of a female attracting pheromone (sodefrin), and responsiveness of the olfactory epithelium to sodefrin. In most of these cases, prolactin was found to act synergistically or antagonistically with sex steroids. We also discovered that hypersecretion of prolactin in the newts subjected to cold temperature was induced by hypothalamic stimulation rather than release from hypothalamic inhibition.

Amino Acid Sequence↗

Time-resolved high-performance liquid chromatography fluorescence detector using a nanosecond pulsed light source for detecting lanthanide-chelated compounds.

We have constructed a time-resolved fluorescence detection (TRFD) system for the analysis of amino compounds with high-performance liquid chromatography (HPLC) using lanthanide ion chelates. In order to carry out time-resolved measurements, we have employed a nanosecond pulsed xenon-arc lamp as an excitation light source. Amino compounds derivatized by isothiocyanobenzyl-EDTA (IEDTA) with the lanthanide chelate are mixed with an enhancer solution in a post-column manner and detected by TRFD. Taking advantage of a property of the long fluorescence lifetime of the lanthanide chelates, high selectivity against background fluorescence was achieved. In order to demonstrate the usefulness of TRFD, fundamental performance tests were carried out. Details of the system are also described.

Chelating Agents↗

Molecular cloning of newt sex pheromone precursor cDNAs: evidence for the existence of species-specific forms of pheromones.

Cloning of cDNA encoding a decapeptide pheromone (sodefrin) that attracts conspecific female newts was attempted. A cDNA clone encoding a protein consisting of 189 amino acid residues including a sodefrin sequence was isolated from a Cynops pyrrhogaster abdominal gland cDNA library. Likewise, a cDNA clone encoding a molecule comparable to the sodefrin precursor was obtained from a Cynops ensicauda abdominal gland cDNA library. This clone encoded a precursor protein of 192 amino acid residues, including a sodefrin-like peptide sequence with substitutions of two amino acid residues. This is the first report of a peptide pheromone precursor in vertebrates.

Abdomen↗

bFGF suppresses serum-deprivation-induced apoptosis in a human lens epithelial cell line.

There is increasing evidence that basic fibroblast growth factor (bFGF) plays an important role in cell proliferation, differentiation, and survival in various systems. In the eye, although a truncated, dominant negative bFGF receptor in transgenic mice induced defective lens development and caused lens fiber cells to display characteristics of apoptosis, there is little direct evidence of the effect of bFGF on lens epithelial cell apoptosis. Our study examines the effects of bFGF on programmed cell death induced by serum deprivation using a human lens epithelial cell line. Cells supplemented with 20% fetal bovine serum were used as normal controls. Over a period of 7 days, the addition of 100 ng/ml bFGF effectively suppressed serum-deprived apoptosis. The expression of gamma-crystallin and major intrinsic protein, which are markers of lens cell differentiation, was not detected. Also there was no significant difference in cell proliferation between serum-deprived cells with or without bFGF. ICE (caspase-1) was expressed under both the conditions, but the level of expression between the two groups was not substantially different. bcl-2 and c-myc were upregulated only in bFGF-treated cells. Thus we speculate that the inhibitory effect of bFGF on apoptosis is through the upregulation of the inhibitor of apoptosis, instead of downregulation of the initiator. This effect appears to be independent of lens cell differentiation and proliferation.

Animals↗

Osmotic response element is required for the induction of aldose reductase by tumor necrosis factor-alpha.

Induction of aldose reductase (AR) was observed in human cells treated with tumor necrosis factor-alpha (TNF-alpha). AR protein expression increased severalfold in human liver cells after 1 day of exposure to 100 units/ml TNF-alpha. An increase in AR transcripts was also observed in human liver cells after 3 h of TNF-alpha treatment, reaching a maximum level of 11-fold at 48 h. Among the three inflammatory cytokines: TNF-alpha, interleukin-1, and interferon-gamma, TNF-alpha (100 units/ml) gave the most induction of AR. Differences in the pattern of AR induction were observed in human liver, lens, and retinal pigment epithelial cells with increasing concentrations of TNF-alpha. A similar pattern of AR promoter response was observed between TNF-alpha and osmotically stressed human liver cells. The deletion of the osmotic response element (ORE) abolished the induction by TNF-alpha and osmotic stress. A point mutation that converts ORE to a nuclear factor-kappaB (NF-kappaB) sequence abolished the osmotic response but maintained the TNF-alpha response. Electrophoretic gel mobility shift assays showed two NF-kappaB proteins, p50 and p52, capable of binding ORE sequence, and gel shift Western assay detected NF-kappaB proteins p50 and p65 in the ORE complex. Inhibitors of NF-kappaB signaling, lactacystin, and MG132 abolished the AR promoter response to TNF-alpha.

Aldehyde Reductase↗

Identification of four novel mutations of the XLRS1 gene in Japanese patients with X-linked juvenile retinoschisis. Mutation in brief no. 234. Online.

The XLRS1 gene (HUGO-approved symbol, RS1) has been found to cause X-linked recessive retinoschisis (RS) which is characterized by splitting of the superficial layer of the retina. Recent mutation analysis of this gene revealed 82 different mutations in 214 patients with RS. We have now identified 10 mutations of the XLRS1 gene in 11 unrelated Japanese males with RS. Mutations found in these patients were; 1) a 20-kb deletion in exon 1 region; 2) mutations in the initiation sequence (M1V); 3) mutations in the splice donor site (IVS1 + 1 g-->a); 4) two nonsense mutations (Q88X, W163X); and 5) five missense mutations (E72K, Y89C, R182C, G109E, P203L). Four (M1V, Q88X, G109E, and W163X) of the 10 mutations were novel. The R182C mutation was identified in 2 unrelated patients. The 3 mutations found between exons 1 and 3 cause premature translation termination in the XLRS1 protein. The rest of the 7 mutations were clustered between exons 4 and 6. This region of the protein is homologous to the proteins implicated in cell-cell adhesion.

Cell Adhesion↗

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine.

A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.

Adolescent↗

Enhanced theophylline metabolism in patients with bronchial asthma at age 4 and under.

The plasma levels of theophylline (TP) and its metabolites were measured in patients with bronchial asthma who were treated with a slow-release preparation of TP. The ratios of the plasma levels of these metabolites to TP levels in the group aged 1-4 years were larger than those in the group aged 5 years and older, suggesting enhanced activity of drug-metabolizing enzymes during infancy.

Adolescent↗

Etoposide enhances the lethal effect of radiation on breast cancer cells with less damage to mammary gland cells.

PURPOSE: In the present study, the cytotoxic effects of anticancer drug treatment plus radiation on breast cancer and normal mammary gland cells were investigated in vitro. METHODS: Breast cancer and adjacent mammary gland tissue was obtained from surgically resected specimens from 13 premenopausal female patients, and was cultured. Cultured cells were treated with radiation and etoposide, and sensitivities were evaluated using an MTT assay. RESULTS: In breast cancer cells, radiation alone had a cytotoxic effect. When etoposide was added, synergistic effects were achieved which were independent of the radiation dose. The cytotoxicity of etoposide against normal gland cells, however, was much the same as that against cancer cells, and no synergistic effects were observed in normal cells even when radiation was added. CONCLUSIONS: Radiation combined with etoposide showed lethal effects against breast cancer cells with less damage to normal mammary gland cells.

Breast↗

Localization and ultrastructure of pulmonary dendritic cells during delayed-type hypersensitivity reactions in mice.

Dendritic cells (DCs) are widely distributed in the airways and can serve as potent antigen-presenting cells. To clarify their involvement in the cell-mediated immune responses of the lung, we immunohistochemically investigated their distribution and kinetics during pulmonary delayed-type hypersensitivity (DTH) reactions induced in sensitized mice by intratracheal instillation of hapten. Cellular infiltrate appeared around the bronchiole and its accompanying blood vessel at 12 h after elicitation and progressively expanded by 48 h. As quantitated by computer-assisted morphometry, I-A(+) DCs and CD4(+) Th cells significantly increased in number around the bronchiole to a maximum at 24 h, whereas F4/80(+) macrophages were predominantly accumulated around the accompanying vessel with a peak at 48 h. Serial-section analysis revealed that DCs were colocalized with Th cells in the inflamed peribronchiolar tissue. Immunoelectron microscopy demonstrated that DCs found inside and around the capillaries and venules of peribronchiolar interstitium displayed round forms, indicating their emigration from here, while those situated far from the microvessels were elongated, often in close apposition to the lymphocytes. Mitosis of DCs was rarely seen. The present results suggest that peribronchiolar accumulation of DCs resulting from accelerated influx of blood-borne immature DCs and the interaction with T cells at the application site may play inducing roles in the development of pulmonary DTH reactions by enhancing the recruitment of macrophages.

Animals↗

Dietary conjugated linoleic acid reciprocally modifies ketogenesis and lipid secretion by the rat liver.

The effects of dietary conjugated linoleic acid (CLA) and linoleic acid (LA) on ketone body production and lipid secretion were compared in isolated perfused rat liver. After feeding the 1% CLA diet for 2 wk, the concentration of post-perfused liver cholesterol was significantly reduced by CLA feeding, whereas that of triacylglycerol remained unchanged. Livers from CLA-fed rats produced significantly more ketone bodies; and the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to be consistently higher in the liver perfusate. Conversely, cumulative secretions of triacylglycerol and cholesterol were consistently lower in the livers of rats fed CLA, and the reduction in the latter was statistically significant. Thus dietary CLA appeared to exert its hypolipidemic effect at least in part through an enhanced beta-oxidation of fatty acids at the expense of esterification of fatty acid in the liver.

Animals↗