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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 847 records · Page 47Linked to original sources

[Adenosine and adenosine receptors in the kidney].

In the kidney, adenosine plays important regulatory roles, including renal blood flow, glomerular filtration rate, renin secretion, tubuloglomerular feedback, tubular reabsorption of sodium and water, sympathetic neurotransmitter release, and erythropoietin secretion. These functions are mediated through adenosine 1 (A1)-receptors and adenosine 2 (A2)-receptors. These receptors couple to the inhibition and stimulation of adenylate cyclase, through Gi and Gs proteins, respectively. A variety of other effecter systems have been reported to be coupled to A1 receptors, including phospholipase C, phospholipase A2 and potassium, as well as Ca++ channels. Recently, A1 receptors, A2 receptors and novel A2 receptor have been cloned, sequenced and expressed. In association with the development of selective adenosine analogues, we are now ready to take up problems at the biochemical and molecular biological levels.

Adenosine↗

[Studies on the mechanism of late asthmatic response by Candida antigen inhalation using bronchoalveolar lavage].

To elucidate the mechanism of late asthmatic response (LAR), which is related to intractable asthma attack, the cellular and humoral components of LAR were examined in bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation tests with Candida allergen on Candida-sensitive asthma patients. BAL examination was carried out 2 hours after remission of LAR, and differential cell counts and measurements of leukotrienes (LTs) by high performance liquid chromatography were investigated in BALF and peripheral blood. The number of neutrophils and basophils in circulating blood showed a peak before LAR, and then decreased markedly at LAR. And an increase in the percentage of eosinophils (p less than 0.01) and neutrophils was evident in BALF after LAR compared with the level in the non-attack state. The percentage of basophil-mast cells, however, did not change in the same manner. The serum level of LTC4 increased significantly at LAR in comparison with its level in the phase before LAR. And the level of LTC4 was also significantly higher in BALF after LAR (p less than 0.01). However, LTD4 and LTB4 were at almost undetectable levels in BALF in the non-attack state and after LAR. The results indicate that neutrophils as well as eosinophils may accumulate and release several kinds of leukotrienes at local sites in late asthmatic response provoked by the inhalation of Candida antigen; this gives clues as to the mechanism of severe and intractable asthma attacks.

Adult↗

[Studies on IgG subclass antibodies in adult asthma. 2. Changes in serum antigen specific IgG subclass antibodies for aging and intractability in asthmatics].

To clarify the factors which induce intractable asthma, the level of serum IgG subclass antibodies to mite (Dermatophagoides farinae) and Candida antigens (Candida albicans) for aging and severity was investigated in 230 bronchial asthmatics (Male: 117, Female: 113) aged 6-81 years old (mean age = 40). Total IgE level and IgE antibodies to mite and Candida antigens were measured by radioimmunosorbent test (RIST) and radioallergosorbent test (RAST), respectively. The serum level of IgG and IgG1 antibodies to the antigens were measured by enzyme-linked immunosorbent assay (ELISA). The results were as follows: 1) The incidence of severe asthma in aged and late onset asthmatics, especially late onset intractable asthma (LOIA), was higher than that in young and early onset asthmatics. 2) The serum level of total IgE and IgE antibodies to mite in aged and late onset asthmatics was lower than that in young and early onset asthmatics. 3) The incidence of severe and intractable asthmatics in the group of low IgE levels (less than 300 IU/ml) was higher than that in the group of high IgE levels (over 500 IU/ml). The incidence of positive IgE (RAST) score to mite in severe and intractable asthmatics was lower than that in mild and moderate asthmatics. 4) Considering aging, the serum levels of IgG and IgG1 antibodies to mite and Candida in severe and intractable asthmatics was higher than those in mild asthmatics. These data indicate that the aged and late onset asthmatics may produce dominantly the IgG (IgG1) antibody to the antigens, and have severe asthma attacks caused by IgG (IgG1) rather than IgE antibody.

Adolescent↗

Papillary renal cell carcinoma. Report of two cases.

Papillary renal cell carcinoma is an uncommon variant of renal cell carcinoma which has unique features including hypovascularity or avascularity, extensive stromal macrophage infiltration and better prognosis than that for nonpapillary renal cell carcinoma. Two cases of papillary renal cell carcinoma presenting hypovascular or avascular angiology are presented. Histologically, the two tumors had a purely papillary structure. Papillae were lined by a layer of epithelial cells which lacked prominent cellular atypia, and there were numerous macrophages in the stroma. In addition, in one patient, extensive calcification of the tumor capsule was present. Furthermore, our experience in the present study with imprint cytology indicates that it offers corroborative information for the intraoperative diagnosis made on the basis of frozen section examination.

Adult↗

[A case of portal-systemic encephalopathy presenting characteristic MR images in globus pallidus, hypothalamus, corpus callosum, pontine base, and middle cerebellar peduncle].

A 53-year-old woman developed symptoms of slow speech, mild dementia, increased deep tendon reflex, ataxic gait, flapping tremor, and dystonic posture during two years. She had liver cirrhosis and hyperammonemia, which suggested a diagnosis of portal-systemic encephalopathy. MR T1-weighted images showed increased signal intensity in globus pallidus, internal capsule, substantia innominata, and a part of hypothalamus. T2-weighted images revealed abnormal findings as follows: high intense area in middle cerebellar peduncle, and low signal intensity of corpus callosum and pontine base. This is the first report about MRI abnormalities in substantia innominata, corpus callosum, and pontine base in a patient with portal-systemic encephalopathy.

Brain↗

[XYY syndrome associated with motor neuropathy].

We described a case of XYY syndrome associated with motor neuropathy. The case was a 27-year-old male, who had 47-XYY chromosome karyotype. His symptoms were distal dominant muscle weakness and muscle atrophy in his lower extremities without objective sensory disturbance. He had no mental retardation or family history of neurologic diseases. The electrophysiological and pathological examinations revealed that his symptoms were due to peripheral motor neuropathy (neuronal type). His motor neuropathy may be of sporadic type. There may be some relation in the pathogenesis between XYY syndrome and motor neuropathy, although in the literature, XYY syndrome with motor neuropathy had not been reported so far.

Adult↗

Role of a thymic stromal cell clone in inducing the stage-specific differentiation of various subpopulations of double negative thymocytes.

The monolayer of a thymic stromal cell clone termed MRL104.8a induced the differentiation of adult double negative (DN) thymocytes (CD3-4-8-) through a CD3-4-8+ intermediate into CD3- (or dull) 4+8+ stages. DN thymocytes were separated into three subpopulations depending on their cell-surface expression of Pgp-1 and IL-2R, namely, Pgp-1+IL-2R-, Pgp-1-IL-2R+, and Pgp-1-IL-2R-. The present study investigated the requirements of the MRL104.8a monolayer for inducing the differentiation of these DN thymocyte subpopulations. The following were revealed: i) the MRL104.8a monolayer failed to induce the differentiation of a Pgp-1+IL-2R- subpopulation; ii) whereas a Pgp-1-IL-2R+ subpopulation did not express either CD4 or CD8 Ag when cultured in medium, culturing this subpopulation on the thymic stromal cell monolayers resulted in the expression of CD8 but not CD4 Ag; and iii) a Pgp-1-IL-2R- DN subpopulation obtained through less extensive treatments with anti-CD4 and anti-CD8 antibodies in the presence of C before sorting procedures spontaneously differentiated into double positive cells in medium. In contrast, most of DN cells with the same phenotype obtained through extensive anti-CD4 and -CD8 treatments before sorting failed to express CD4 and/or CD8 Ag in medium but could differentiate through a CD3-4-8+ into more mature stages only when they were cultured on the thymic stromal monolayer. These results indicate differential requirements of thymic stromal cells for the differentiation of various DN subpopulations with qualitatively distinct phenotypes and different magnitudes (very low vs almost zero levels) of CD4/CD8 expression.

Animals↗

Distinctive glycolipid patterns in Wilms' tumor and renal cell carcinoma.

Glycolipid patterns were analysed chromatographically in Wilms' tumor and renal cell carcinoma tissues and compared with those of uninvolved tissue. Ganglioside GM3 was found to be increased in both cancer tissues, whereas sulfatides accumulated only in renal cell carcinoma, as reported earlier. Neolactotetraosylceramide was detected in both cancer tissues, but not in the uninvolved kidney tissues. In four cases of Wilms' tumors, only a low level of sulfotransferase towards galactosylceramide was found in one case, while no activity was detected in the three other cases. Present results show that the increased sulfatide(s) in the renal cell carcinoma and the deficiency of the sulfatides in Wilms' tumors appear to be biochemical characteristics of histologically different carcinomas.

Carcinoma, Renal Cell↗

Sympathetic inhibition and attenuation of spontaneous hypertension by PVN lesions in rats.

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Animals↗

A correlation between GM-CSF gene expression and metastases in murine tumors.

Using 14 transplantable murine tumors, we investigated a possible correlation between their ability to produce the cytokine GM-CSF and the spontaneous metastatic potential when mice were subcutaneously inoculated. The following results were obtained: (1) seven tumors, which produced severe pulmonary metastases and metastatic swelling of lymph nodes, exhibited the ability to produce GM-CSF activity in culture. The cell population analysis revealed that the cells producing GM-CSF were tumor cells themselves, but that contaminating macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for GM-CSF was also found in all of these highly metastatic tumors tested. In mice inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in lungs; (2) in 3 other tumors, which produced histological but not macroscopical pulmonary metastases, no GM-CSF activity could be detected in the culture fluids. GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA-stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells of this type were transcribing GM-CSF gene, and secreting it in undetectable levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors, neither CSF activity nor GM-CSF mRNA could be detected even in the presence of cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our results indicate that there may be a correlation between GM-CSF gene expression in tumor cells and spontaneous metastases.

Animals↗

Expression of the GABAB receptor in Xenopus oocytes and inhibition of the response by activation of protein kinase C.

The functional GABAB receptor was expressed in Xenopus oocytes by injecting mRNA obtained from the cerebellum of the rat. Application of GABA in the presence of bicuculline induced a hyperpolarization under current-clamp conditions and an outward current under voltage-clamp conditions. Baclofen mimicked the effect of GABA in the presence of bicuculline, and the effect of baclofen was antagonized by phaclofen. The GABA-induced outward current was slightly inhibited by treatment with GDP-beta-S and was completely inhibited by treatment with GTP-gamma-S. The activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA), but not 4 alpha-phorbol-12,13-didecanoate, suppressed the GABAB receptor-mediated hyperpolarization, and the effect of TPA was antagonized by sphingosine. Thus, activation of protein kinase C inhibits the expressed GABAB receptor-mediated response.

Animals↗

New degradation product of des-Gly10-NH2-LH-RH-ethylamide (fertirelin) in aqueous solution.

A new degradation product was found in an ampule preparation of des-Gly10-NH2-LH-RH-ethylamide (fertirelin) stored at room temperatures. The same product, produced at a higher temperature, was identified to be a diastereomeric mixture of cyclo(His-Trp) by proton nuclear magnetic resonance spectroscopy, mass spectrometry, and comparison with authentic samples. Preferred conformations regarding substituents on the diketopiperazine ring of cyclo(His-Trp) were calculated using coupling constants between vicinal protons.

Amino Acid Sequence↗

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Animals↗

Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency.

The variant thyroxine-binding globulin in a family from Montreal (TBG-M) has a reduced affinity for thyroxine, shows a slight cathodal shift on isoelectric focusing, and has an increased susceptibility to inactivation by heat and acid. We present the molecular basis for TBG-M, deduced by sequencing the entire 1245-bp coding regions and intron/exon junctions of the TBG gene of an affected hemizygous male. A single nucleotide substitution in the codon for amino acid 113 of the mature protein (GCC to CCC) was found, resulting in the replacement of alanine by proline. The mutation was confirmed by allele-specific amplification of genomic DNA from the propositus and three other affected family members. Since point mutations throughout the molecule have been shown to alter the properties of variant TBGs, and because amino acid substitutions with proline are known to impair stability and function of proteins, the replacement of alanine 113 by proline provides a logical explanation for the observed properties of TBG-M.

Amino Acid Sequence↗