Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 343 records · Page 19Linked to original sources

PubMed1992

Sarcomatoid carcinoma of the bladder: a case report.

We reported a case of sarcomatoid carcinoma of the bladder in a 78-year-old woman presenting with pollakisuria. She has remained well without any evidence of recurrence for 25 months after radical cystectomy. Microscopic examination revealed a composition almost exclusively of spindle and dedifferentiated cells, accompanied by only a few cells retaining epithelial features of differentiation. The latter cells were immunohistochemically positive for epithelial membrane antigen (EMA). A concomitant carcinoma in situ was present in the adjacent mucosa. Immunohistochemical exploration with EMA proved useful for reinforcing the conventional histological diagnosis.

Aged↗

PubMed1992

Constitutive expression of leukemia inhibitory factor (LIF) mRNA and production of LIF by a cloned murine thymic stromal cell line.

We have found that normal mouse thymus expressed mRNA for leukemia inhibitory factor (LIF), suggesting the presence of cell component(s) in the thymus that produces this cytokine. High levels of mRNA for LIF were observed to be constitutively expressed in the murine thymic stromal cell clone, MRL104.8a. This stromal cell clone produced potent magnitudes of LIF activity in its culture supernatant. These observations imply that LIF may also exert its growth/differentiation-regulating effect in the thymus. Thus, this thymic stromal cell clone provides a tool for investigating potential roles of LIF in the intrathymic T cell development.

Animals↗

PubMed1992

[A case of intractable hemoptysis due to malignant hemangioendothelioma].

A 65-year-old man who died of respiratory failure due to malignant hemangioendothelioma is reported. He was admitted to our hospital because of intractable hemoptysis. Chest roentgenogram revealed multiple patchy shadows in both lungs, but we could not make a diagnosis by usual clinical examinations including transbronchial lung biopsy. Since the patient's condition became critical, oxygen therapy, anticoagulants and antibiotics were started. In addition, corticosteroid therapy and double filtration plasmapheresis were performed since immunological disorder was suspected because of positive immunological examinations such as antinuclear antibodies and an increase in circulatory immune complexes. There was little response to the treatments and the patient finally died of respiratory failure. At autopsy, multiple tumor nodules were found throughout the lungs and the liver. Metastasis to mediastinal lymph nodes was also discovered. These findings made it impossible to confirm the primary lesion. Microscopy showed proliferation of anastomosing capillaries encasing tumor cells of unknown origin. Silver staining demonstrated capillaries encompassing the atypical cells, suggesting a vascular origin of the tumor. Furthermore, factor VIII related-antigen in the tumor cells was confirmed by the peroxidase-antiperoxidase (PAP) method. The final diagnosis of malignant hemangioendothelioma was made from these histological findings. Malignant hemangioendothelioma is rare, but is an important cause of intractable hemoptysis.

Aged↗

PubMed1991

2,5-Anhydro-D-mannitol: its unique central action on food intake and blood glucose in rats.

Peripheral administration of D-fructose has been reported to decrease food intake, and its 2-deoxy analogue, 2,5-anhydro-D-mannitol (2,5-AM), increased food intake and decreased blood glucose in rats. In the present study, 2,5-AM was selected for comparison with well-known 2-deoxy analogues of glucose. Infusion of 2,5-AM into the rat third cerebroventricle at 11.00 h induced feeding dose dependently (Y = 0.63 logX-1.20, r = 0.95, P less than 0.05). Rats treated with 2,5-AM at a maximal effective dose of 24 mumol/rat ate meals most persistently (P less than 0.05). No periprandial drinking was observed. Ambulatory activity increased concomitantly with feeding, but did not exceed the activity normally associated with a meal. Infusion of 24 mumol 2,5-AM into the third cerebroventricle induced no substantial change in plasma glucose or insulin in any 60-min experimental period. Unilateral microinfusion of 1.2 mumol 2,5-AM induced feeding in all 6 rats (P less than 0.01) when a cannula tip was located in the ventromedial hypothalamic nucleus (VMH), but not in the lateral hypothalamic area (LHA). These findings indicate that feeding elicitation may be due to disinhibition by 2,5-AM through the VMH. This is quite unique compared to the action mechanisms of hexose, pentose and their analogues, except 2,5-AM.

Animals↗

PubMed1991

Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation.

Only 10-15% of unseparated thymocytes adhered to culture plates precoated with fibronectin (FN), but 60-70% of the CD4-8- (double-negative) thymocyte population did. This population bound to FN but not to collagen, laminin, or vitronectin. Its binding to FN was inhibited by anti-FN antibody or a mixture of synthetic peptides corresponding to two different sites of FN, termed the V10 sequence and the RGDS (Arg-Gly-Asp-Ser) sequence, which interact, respectively, with the VLA-4 and VLA-5 FN receptors expressed on T-lineage cells. CD4-8- thymocytes also adhered to a monolayer of a thymic stromal cell clone, MRL104.8a, that induces growth-maintenance and differentiation of such thymocytes. The involvement of FN-FN receptor interaction in this adhesion was demonstrated by the following lines of evidence: (i) the MRL104.8a cells expressed FN molecules on their surface and (ii) the adhesion of CD4-8- thymocytes to MRL104.8a monolayers was almost completely inhibited by simultaneous addition of anti-FN antibody and a mixture of peptides (V10 plus RGDS) capable of binding to anti-FN receptors (VLA-4 and -5). Most important, blocking the adhesion of CD4-8- thymocytes to the thymic stromal cell monolayer resulted in potent inhibition of the differentiation of these thymocytes, which was otherwise induced toward the expression of CD4 and/or CD8 molecules. These results indicate that immature CD4-8- thymocytes adhere to thymic stromal cells preferentially through FN-FN receptor interaction and that such adhesion has a critical role in inducing and/or supporting the differentiation of these thymocytes.

Animals↗

PubMed1991

Role of glycosaminoglycans in the regulation of T cell proliferation induced by thymic stroma-derived T cell growth factor.

The present study investigates the regulatory effects of glycosaminoglycans such as heparin and heparan sulfate on T cell proliferation induced by thymic stromal cell monolayer or its derived T cell growth factor (TCGF). A thymic stromal cell clone (MRL104.8a) supported the growth of Ag-specific, IL-2-dependent Th cell clone (9-16) in the absence of Ag and IL-2 by producing a unique TCGF designated as thymic stroma-derived T cell growth factor (TSTGF). The addition of heparin to cultures in which the growth of 9-16 Th cells was otherwise stimulated by the MRL104.8a monolayer or a semipurified sample of the TSTGF resulted in heparin dose-dependent inhibition of 9-16 Th proliferation. The dose of heparin required for inducing 50% reduction of TSTGF-induced proliferation of Th at a given cell number was found to be proportional to the magnitude of the TSTGF added to cultures, suggesting that heparin exerted its inhibitory effect by binding to the TSTGF rather than by acting on Th cells. A similar growth-inhibiting effect of heparin was observed in IL-7-dependent proliferation of pre-B cell line or Th, but not in IL-2-dependent T cell proliferation or IL-3-dependent myeloid cell proliferation. A strong affinity of TSTGF and IL-7 for heparin was confirmed by the fact that both TSTGF and IL-7 adhered to columns of heparin-agarose and were eluted by salt. When various glycosaminoglycans were tested for the heparin-like Th growth-regulatory capacity, heparan sulfate exhibited Th growth-inhibiting ability comparable to that observed for heparin. These results indicate that the activity of thymic and/or bone marrow stroma-derived lymphocyte growth factor (TSTGF/IL-7) but not of Th-producing TCGF (IL-2) is negatively regulated by heparin or heparan sulfate, which would represent major glycosaminoglycans in the extra-cellular matrix of stromal cells.

Administration, Topical↗

PubMed1991

Lack of bladder tumor promoting activity in rats fed sodium saccharin in AIN-76A diet.

Sodium saccharin (NaSac) fed as 5% of Prolab diet promotes bladder tumor carcinogenesis in male F344 rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed as 0.2% of the diet for 4 weeks. NaSac also increases urothelial proliferation if fed for short periods in Prolab diet, but no increased proliferation is seen if it is fed for up to 10 weeks in AIN-76A semisynthetic diet, even at levels as high as 7.5% of the diet. To determine whether NaSac as part of an AIN-76A diet has promoting activity, groups of approximately 30 male, 5-week-old F344 rats were fed AIN-76A diet containing (a) 0.2% FANFT for 4 weeks followed by 5% NaSac for 100 weeks; (b) 0.2% FANFT followed by control diet; or (c) control diet followed by 5% NaSac. Bladder tumor incidences were 10, 23, and 0%, respectively. When fed in Prolab diet, 0.2% FANFT for 4 weeks followed by NaSac or control diet for 100 weeks resulted in bladder tumor incidences of 40 and 17%, respectively. Groups of rats fed 0.1 or 0.2% FANFT for 1 or 2 weeks followed by 5% NaSac or control diet for 100 weeks had bladder tumor incidences of 0 to 7%. These data demonstrate that NaSac does not promote bladder cancer in male rats if fed in AIN-76A diet. Other studies suggest that this is due to the low urinary pH in rats fed AIN-76A diet.

Animals↗

PubMed1991

Glucocorticoid treatment reduces prostacyclin synthesis in response to limited stimuli.

Dexamethasone 21-acetate (DMS 21-A) time- and dose-dependently suppressed bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells. The suppression was more prominent in the presence of pertussis toxin, which by itself could enhance bradykinin-induced prostacyclin synthesis. The DMS 21-A treatment diminished prostacyclin synthesis also in response to vasopressin. In contrast, it did not affect prostacyclin synthesis in response to arachidonic acid or A23187. Melittin-induced prostacyclin synthesis was reduced only at low doses (1-7 x 10(-7) M). The suppression of bradykinin-induced prostacyclin synthesis by DMS 21-A was completely blocked by cycloheximide. DMS 21-A had no effect on the cellular level of lipocortin I protein, but increased the anti-phospholipase A2 activity in EDTA extracts of the cells. These results suggest that the DMS 21-A treatment induces phospholipase A2 inhibitor protein(s) other than lipocortin I and reduces prostacyclin production in response to limited stimuli.

Animals↗

PubMed1991

Murine thymic nurse cell clone supports the growth of fetal thymocytes in the presence of interleukin 2.

To investigate the role of thymic nurse cells (TNC) in activation and differentiation of fetal CD4-CD8- (double-negative) thymocytes, we have co-cultured murine fetal thymocytes (14-15 days of gestation) with an established murine TNC clone. We show here that TNC induced the growth of the fetal double-negative thymocytes in the presence of recombinant interleukin 2 (rIL2). Activated fetal thymocytes markedly formed lymphocyte-TNC complexes and proliferated extensively after 5 days in the co-culture. The activated fetal thymocytes in this co-culture condition remained double negative after 10 days in culture. None of them gave rise to phenotypically and functionally competent lymphocytes during this period. TNC alone and the supernatant of TNC had no effect on activation. The presence of both TNC and rIL2 was necessary for the growth of fetal thymocytes in our system. The proliferation of fetal thymocytes was inhibited by a monoclonal antibody against mouse IL2 receptors (IL2R). The fetal thymocytes could be maintained further in this co-culture condition. The prolonged cultivation of fetal thymocytes resulted in the establishment of the fetal thymocyte line and its several clones. CD4 single-positive cells of activated fetal thymocytes first appeared 14 days after the onset of culture and their number increased, whereas CD8+ cells or CD4CD8 double-positive cells were not observed. These results indicate that fetal CD4-CD8- thymocytes underwent phenotypic change after long periods of culture. All established clones of fetal thymocytes are CD4 single positive showing lymphocyte-TNC interactions but do not express CD3 complex. Northern blot analysis detected mRNA for the gamma T cell receptor, but no messages for the delta, alpha or beta T cell receptor. Chemical cross-linking of 125I-labelled IL2 revealed that the 90-kDa band (presumably considered to be the IL2R beta chain) was clearly present in IL2-responsive fetal clones, whereas freshly isolated day 14-15 fetal thymocytes lacked the band. Taken together, TNC might be involved in the differentiation and/or expansion of murine fetal thymocytes by inducing IL2R beta chain, which forms the functional IL2R together with IL2R alpha chain and CD4, one of the T cell accessory molecules, on the cell surface through direct cell-cell interaction.

Animals↗

PubMed1991

Production of granulocyte-macrophage colony-stimulating factor or GM-CSF-like growth factor by rat thymic epithelial cell line.

An epithelial cell line, IT-45R1, has been established from a thymus of normal Wistar rat and was found to produce growth factor which stimulated the proliferation of bone marrow cells. This growth factor induced the formation of colonies composed of macrophages, granulocytes, or both, in semi-solid medium and stimulated the proliferation of an interleukin 3 (IL3)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent clone. Neither IL3-dependent clone nor IL6-dependent clone responded to IT-45R1 factor. Additionally, IT-45R1 factor acted on both rat and mouse bone marrow cells but not on human bone marrow cells. Molecular weight of IT-45R1 factor was 30 kD and its isoelectric point was 4.5. To determine whether IT-45R1 factor is GM-CSF or not, Northern blot analysis and neutralization with anti-mouse GM-CSF antibody were carried out. IT-45R1 expressed GM-CSF mRNA, but neither M-CSF nor IL6 transcripts. However, antiserum specific for mouse GM-CSF did not neutralize IT-45R1 factor. Taken together, a rat thymic epithelial cell line, IT-45R1, constitutively produces GM-CSF or GM-CSF-like growth factor.

Animals↗

PubMed1991

Hypothalamic neuronal histamine modulates energy balance in rats.

Effects of hypothalamic histamine on food intake and adaptive behavior to altered ambient temperature were assessed in rats by manipulating histamine endogenously. Infusion of a-fluoromethylhistidine (FMH) into the third cerebroventricle elicited meals dose dependently (p less than 0.01), when hypothalamic histamine was normally high. The effect of FMH was attenuated, and thioperamide conversely suppressed food intake (p less than 0.05), when the probes were performed during the minimum histamine content. The ventromedial hypothalamus and the paraventricular nucleus were identified as the active target loci. Hypothalamic histamine level was lowered at 4 degrees C and raised at 31 degrees C ambient temperature. FMH attenuated both the elevated histamine level and adaptive behavior at 31 degrees C. Neuronal histamine may play a physiological role in feeding suppression through those hypothalamic nuclei, and also in adaptive behavior in abnormal ambient temperature.

Adaptation, Physiological↗

PubMed1991

Benign mixed mesenchymal tumor of the spermatic cord.

We report a case of benign mixed mesenchymal tumor consisting of spindle cells and an area involving osseous elements. Immunohistochemical investigation revealed the spindle tumor cells to express vimentin and the alpha-subunit of S100 protein, but no staining for other specific antigens. The findings thus suggest that the spindle tumor cells are undifferentiated in nature and derived from mesenchyma, the osseous component being interpreted as evidence of a specific differentiation.

Antigens, Neoplasm↗

PubMed1991

Lowered responsiveness of bronchoalveolar lavage T lymphocytes in hypersensitivity pneumonitis.

We previously reported that Trichosporon cutaneum was the major causative antigen of summer-type hypersensitivity pneumonitis (HP) in Japan. In summer-type HP patients, we noticed that the proliferative responses of bronchoalveolar lavage (BAL) lymphocytes to phytohemagglutinin (PHA) and concanavalin A were significantly lower than those of the peripheral blood lymphocytes of the same patients. It was shown in this study that the low response of BAL lymphocytes was due to an intrinsic lowering of the responsiveness of the T cells. Results of the mixed culture experiments, in which the responses to mitogens of BAL and peripheral blood T cells mixed with either alveolar macrophages or blood monocytes were compared, indicated that the decreased proliferative response was due neither to the suppressive effect nor to defects in accessory function of the alveolar macrophages. BAL T cells did not act as suppressor cells when they were added to the culture of peripheral T cells. The decreased proliferative response was not due to the dominance of CD8+ T cells frequently seen in BAL cells of HP patients, because both CD4+ and CD8+ T cells separated from BAL cells of HP patients showed lower responsiveness than those of peripheral blood T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Molecular structure of extraordinarily stable RNA: model building and X-ray analysis.

A tridecaribonucleotide, rUGAGCUUCGGCUC which adopts the extraordinarily thermally stable hairpin structure, was chemically synthesized. The crystallographic study of this RNA molecule was done. Crystals grew as plates belonging to space group C2 with a = 38.49A b = 32.30A c = 38.76A and beta = 117.56. and one molecule per asymmetric unit. Intensity data were collected at a resolution 2.1A. Structure determination using molecular replacement method has been underway. The favorable three-dimensional model of hairpin was built by molecular dynamics and molecular mechanics calculations.

Base Sequence↗

PubMed1991

The deterioration of visual acuity by exercise under a mesopic vision environment.

Visual acuity deteriorated following 15-minute bicycle ergometer pedaling under the condition of a mesopic vision environment. Visual acuity decreased sharply as the load increased. The visual functions which changed significantly after the exercise in the mesopic vision environment were visual acuity (deterioration) and accommodative near point distance (extension).

Accommodation, Ocular↗

PubMed1991

Grade 3 bladder cancer with lamina propria invasion (pT1): characteristics of tumor and clinical course.

To determine the clinical characteristics of grade 3 tumors with lamina propria invasion (pT1), we reviewed the data of 217 patients with superficial bladder cancer who had initially been treated by transurethral resection (193 patients) and fulguration (4), supravesical resection (13) or partial cystectomy (7). We classified the patients into four groups according to histological grade and stage of disease: group 1) grade 0 or 1, pTa tumors (n = 58); group 2) grade 2, pTa tumors (n = 106); group 3) grade 2, pT1 tumors (n = 30); and group 4a) grade 3, pT1 tumors (n = 23). Grade 3, pT1 tumors were significantly related to nonpapillary growth (p = 0.0002), multiple tumors (p = 0.005) and irritative bladder symptoms (p = 0.01). The 5-year progression rates were 0% for group 1, 5% for group 2, 8% for group 3, and 18% for group 4a. The respective 5-year survival rates were 97%, 91%, 83% and 79%. All five patients with grade 3, pT1 tumors who had originally undergone total cystectomy (group 4b) remained alive free of disease for a median follow-up 57 months, establishing a far better survival rate than that for group 4a. These findings show that patients with grade 3, pT1 tumors face a high probability of progression and poor chance of survival. Immediate radical treatment is indicated when tumors recur after initial transurethral resection.

Aged↗

PubMed1991

[Statistical analysis of tumors of the renal pelvis and the ureter--determinants of prognostic significance].

Sixty-two patients with epithelial tumors of the renal pelvis and the ureter were studied with respect to 16 clinicopathological factors and their relationship to the patients survival. The cumulative survival curves are depicted by the Kaplan-Meier method and the statistical difference in the survival rates were detected in 11 factors, age, tumor number, multicentricity, tumor size, histological tumor type, stage, grade, growth pattern, infiltration pattern, lymphatic invasion and venous invasion. Cox's proportional hazard model was applied to evaluate the contribution of these 11 factors to survival. With the univariate analysis, lymphatic invasion showed the greatest hazard ratio followed by growth pattern, stage, venous invasion, age, and grade in this order. Stepwise selection of these factors based on the relative magnitude of their contribution to the survival with Cox's proportional hazard model revealed the most important factor for survival as the lymphatic invasion (hazard ratio 5.29), followed by growth pattern (hazard ratio 2.89). In conclusion, patients with tumor lymphatic invasion and tumor of non-papillary growth pattern showed poor prognosis, and adjuvant chemotherapy should be performed on them to improve their survival.

Adult↗

PubMed1991

Newly detected endogenous substances: their physiological implications on food intake.

Feeding behavior in mammals is regulated by reciprocal interaction of the LHA and VMH in association with neural macrocircuits including the extrapyramidal, limbic, motor cortex, association cortex and other systems. Some chemoneurons in discrete hypothalamic loci that are related to feeding respond to chemical substances carried mainly in the blood. Among those chemicals, structurally different, endogenous organic acid y lactones, in addition to blood-born glucose analogues and hypothalamic neuronal histamine, are important in feeding modulation by conveying intrinsic satiety and hunger signals with different potency to the neurons in the hypothalamus.

Animals↗