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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 415 records · Page 23Linked to original sources

Antigen-induced tenosynovitis in hypersensitized rabbits: a model for rheumatoid tenosynovitis.

Rabbits were first immunized and later challenged with the same antigen (bovine serum albumin, or ferritin) by injection into the tibialis anterior tendon. Inflammatory changes of the tenosynovium and epitenon included infiltration by neutrophils (early) and mononuclear cells (later) over a 6-week course of tenosynovitis. A pattern of antigen entrapment in the tendon together with immunoglobulin was shown by use of radiolabelled antigen and immunochemical staining. Half-life of antigen in the tissues averaged 5 days over the 6-week period. Changes in the epitenon included cellular necrosis, appearance of phagocytic cells, and disruption of the collagen matrix. Tissues of control animals (challenged without prior immunization) showed minimal changes and significantly less retention of antigen (P greater than 0.005). The model is relevant to the mechanism of tendon damage associated with antigen-driven chronic inflammation, as may be the case in rheumatoid arthritis.

Animals↗

Down-regulation of macrophage Ia mRNA expression by interferon (IFN)-alpha and IFN-beta mediated by de novo synthesized protein.

We investigated the regulation of class I and class II major histocompatibility complex (MHC) antigen expression of murine peritoneal macrophages (M phi) by interferons (IFNs) at the mRNA level. Enhancement of class I antigen expression by IFNs (IFN-alpha, beta, and gamma), induction of class II antigen expression by IFN-gamma, and inhibition of class II antigen expression by IFN-alpha or IFN-beta all corresponded to steady-state levels of these MHC-specific mRNAs. Cycloheximide (CHX), a protein synthesis inhibitor, was used to elucidate whether IFN regulation of MHC mRNA expression depends on the newly synthesized proteins. CHX concentration was carefully chosen so that M phi viability was not decreased, total protein synthesis was considerably but not completely inhibited, and suppression of surface class II expression was virtually perfect. Under these conditions CHX did not affect the levels of either class I or class II mRNA, but it prevented IFN-beta from interfering with class II mRNA induction by IFN-gamma. These results indicate that the augmentation of induction and/or accumulation of MHC mRNA by IFNs is not dependent on the de novo synthesis of protein, but the down-regulation of class II mRNA level by IFN-beta is mediated by some newly synthesized protein(s).

Animals↗

Histopathological classification of malignant lymphomas in slaughtered swine.

A histological classification of 36 cases of malignant lymphoma in slaughtered swine is reported. All the lymphomas observed were diagnosed as diffuse types and were further classified into four types by their histological characteristics based on the classification of the Japanese Lymphoma Study Group (Suchi et al., 1979). The cases consisted of 16 of the Burkitt type, 2 of the immunoblastic type, 3 of the medium-sized cell type and 15 of the mixed cell type. The histological appearances of these lymphomas were compared with those of human lymphomas. All tumours closely resembled non-Hodgkin's diffuse type of B cell lymphoma and differed from tumours in other sites such as the liver and kidneys.

Animals↗

Evidence for uptake of 8-methoxypsoralen and 5-methoxypsoralen by cellular nuclei.

The fluorescent appearance of oral mucosa cells treated with 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) was observed by means of fluorescence microscopy. Fluorescence at the nuclei was weakened in 8-MOP-treated cells, while it was intensified in 5-MOP-treated cells. These findings were consistent with changes in the fluorescence intensities on association of the psoralen derivatives with DNA in aqueous solution. This intensity change of fluorescence and also the blue shift of the fluorescence maximum of the derivatives on association suggested that the environment around the psoralen molecules is as little polar as methanol. From the results of these fluorescence microscopic observations and spectroscopic analysis of fluorescence of derivatives interacting with DNA during equilibrium dialysis, we concluded that 8-MOP, as well as 5-MOP, is incorporated by nuclei of human cells.

5-Methoxypsoralen↗

Food intake suppression in rats by a substance isolated from human feces.

A substance which suppresses food intake was isolated from human feces. This substance was extracted and partially purified using Sephacryl S-200 column chromatography and a DEAE-Sephadex A-25 column chromatography. To assess the biological activity, rats were subjected to various applications. The intraperitoneal administration and the intracerebroventricular microinfusion of this substance suppresses short- and long-term food intake. The central infusion suppresses feeding with a potency over 1000 times that the peripheral administration. The central infusion of the heat-treated substance was without effect. These results suggest that a substance present in human feces (probably of a proteic nature) suppresses food intake in rats, at the level of the central nervous system.

Animals↗

Modulation of neuronal histamine in control of food intake.

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.

Animals↗

Environmental mycological studies on the causative agent of summer-type hypersensitivity pneumonitis.

Environmental mycological studies were carried out in 22 homes of patients with summer-type hypersensitivity pneumonitis and in 195 homes of control subjects. In 10 patients' homes, indoor sampling was performed by open-plate culture, house dust culture, and swab culture (group 1), but in the other 12 patients' homes, sampling was only by house dust culture (group 2). We isolated 302 strains of yeasts from the 22 patients' homes and 962 strains of yeasts from the homes of control subjects. The incidence of yeasts, except genera Trichosporon, was not significantly different between homes of patients and control subjects when homes were assessed by three culture methods. T. cutaneum was isolated from seven of 10 patients' homes in group 1, and their colonizing places were revealed by the swab culture method. In group 2, the cells were isolated from four of 12 patients' homes. No T. cutaneum, however, was isolated from the control subjects' homes. Among the isolated yeasts from patients' homes, 23 strains were reactive to the patients' sera at 1:128 or higher in indirect fluorescent antibody titers; 10 yeasts were T. cutaneum, isolated from 10 homes of 14 patients, but the other 13 yeasts were each a different species isolated from 10 different homes. Furthermore, inhalation challenge with the culture-filtrate antigen prepared from T. cutaneum was performed on the nine patients of six homes in group 1 and the two asymptomatic family members. Of the nine patients, six were positive, one was probable, and two patients were negative. Neither of the two asymptomatic family members responded. These results suggest that T. cutaneum is a major causative agent of summer-type hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗

Uracil-induced calculi and proliferative lesions of the mouse urinary bladder.

Uracil fed as 3% of the diet to rats produces urinary calculi and consequent proliferative lesions of the bladder epithelium, including papillomatosis. We evaluated the effects of dietary uracil in two strains of mice and compared the results in males and females. Uracil was fed as 3 or 1% of the diet to male and female Swiss and C3H mice for up to 20 weeks. The 3% dose produced marked proliferative changes in the bladder epithelium by 10 weeks of administration, the earliest time at which the animals were processed for microscopic evaluation. These lesions progressed to severe nodular and papillary hyperplasia so that all of the animals fed 3% uracil had to be killed by the end of the 15th week. These animals had uracil-formed calculi. In contrast, mice fed 1% uracil rarely developed uracil calculi, and also rarely developed proliferative changes in the bladder epithelium as observed by light microscopy. Also, the labeling index was determined and showed quantitatively the degree of cell proliferation similar to that qualitatively observed by light microscopic examination. At 10 weeks of administration, there was an increased labeling index in the males compared to females in both strains of mice fed 3% uracil, but this difference was not significant at 15 weeks. Similarly, the males tended to have more severe histologic changes than the females. The results of feeding high doses of uracil are similar in mice to those previously observed in rats.

Animals↗

Characterization of L1210 S cells with low sensitivity to mouse interferon-gamma.

A mouse leukemic cell line L1210 Sg with a low sensitivity to interferon-gamma (IFN-gamma) was described. On the nature of the antiviral action and binding of IFN, L1210 Sg cells were compared with L1210 m cell line which is sensitive to IFN-gamma. For a half reduction of the vesicular stomatitis virus-RNA synthesis, L1210 Sg cells required 500-fold more IFN-gamma than L1210 m cells did. However, both cell lines were induced to the antiviral state to the same extent with IFN-alpha or -beta. L1210 Sg and L1210 m cells were sensitive to the anti-proliferative action of IFN-alpha and -beta, but insensitive to IFN-gamma. (2'-5')Oligoadenylate synthetase was induced in these cell lines by IFN-beta, but not by IFN-gamma, which suggests that the induction of this synthetase may not be responsible for the antiviral action of IFN-gamma. No substantial difference between L1210 Sg and L1210 m cells was found in IFN receptors for IFN-gamma and IFN-beta either in number per cell or in their affinity to corresponding IFN type. However, differences were noted in time course profiles of cell-associated IFN-gamma at 37 C: in L1210 m cells, a rise-and-decay profile of IFN-gamma bound to cells was observed at 37 C, but in L1210 Sg cells, rise and slight decay was observed. On the other hand, a similar rise-and-decay curve of IFN-beta bound to these cells was observed. These results indicated that the low sensitivity of L1210 Sg cells to IFN-gamma may be due to this slight decay of receptor-bound IFN-gamma.

Animals↗

[Ginsenoside-Rb1 as a suppressor in central modulation of feeding in the rat].

Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb1 on feeding behavior and endogenous chemical substances. Rb1 infusion into the rat third cerebroventricle was started at 1930 hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000 hr. Rb1 at doses of 0.05, 0.10 and 0.20 mumol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 mumol. Ambulatory activity was not affected in the doses tested. Infusion of Rb1 increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 mumol Rb1 into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb1 was found to have a suppressive effect on feeding partly through the VMH.

Animals↗

C1q and C3 in bronchoalveolar lavage fluid from patients with summer-type hypersensitivity pneumonitis.

Immune complexes have been thought to participate in the pathogenesis of hypersensitivity pneumonitis, but the role of complement components is not defined. In our study of nine patients with summer-type hypersensitivity pneumonitis (summer-type HP), C1q in bronchoalveolar lavage fluid (BALF) was strikingly increased (mean 3.7, range 0.4 to 10 micrograms/ml). The value of C1q/albumin was several to 20 times greater in BALF than in serum samples from individual patients. In contrast, BALF samples from control subjects (ten patients with sarcoidosis and nine normal subjects) contained an undetectable amount (less than 0.02 micrograms/ml) of C1q. C3 in BALF also increased in the summer-type HP patients. Furthermore, C1q (as well as specific IgG and IgA antibody activities to Trichosporon cutaneum antigen) in BALF correlated with clinical symptoms and diffusing capacity (DCO), while the BAL lymphocytosis or the change of OKT4/OKT8 ratio did not. These findings are indicative of local secretion or concentration mechanism of C1q and C3, supporting the involvement of immune complexes in the respiratory tract of the patients.

Alveolitis, Extrinsic Allergic↗

Depression of intestinal epithelial cell production rate by hindgut bypass in rats.

Influence of hindgut bypass on the epithelial cell production rates of the small and large intestine was tested in rats. Hindgut bypass decreased cryptal cell production rates of the jejunum, ileum, cecum, and distal colon by 40-65%. These results suggest that the entrance of ileal effluent into the hindgut and, presumably, the resultant microbial production of short-chain fatty acids are required to maintain the normal epithelial cell proliferation not only in the hindgut but also in the small intestine.

Animals↗

Differential mechanisms of feeding modulation induced by amino sugars in rats.

The present study examined and compared the effects of N-acetylglucosamine and 1-deoxy-N-acetylglucosamine on feeding behavior with those of glucosamine and 1-deoxyglucosamine. Infusion of 12 mu mole N-acetylglucosamine and 24 mu mole 1-deoxy-N-acetylglucosamine into the rat third cerebroventricle did not affect the feeding behavior. However, oral administration of 1200 mumol N-acetylglucosamine elicited feeding and 2400 mumol 1-deoxy-N-acetylglucosamine markedly suppressed feeding. These effects were abolished by truncal vagotomy. Both glucosamine and 1-deoxyglucosamine affected feeding by intra-third cerebroventricular and oral administration. These findings indicate that N-acetyl amino sugars modulate feeding behavior peripherally through the vagal afferent nerve.

Acetylglucosamine↗

Experimental hypersensitivity pneumonitis in rabbits induced by Trichosporon cutaneum: role of local cellular and humoral immune responses.

We evaluated the immunopathologic properties of Trichosporon cutaneum, an important etiologic agent of summer-type hypersensitivity pneumonitis in Japan. Rabbits were sensitized and challenged by either a culture-filtrate antigen or a particulate antigen prepared from a TIMM 1318 strain of the fungus. Group 1 animals received repetitive intratracheal injections of a particulate T. cutaneum antigen without use of any adjuvant. Group 2 animals were sensitized by foot-pad injections of particulate antigen followed by an intratracheal challenge with the same antigen. Group 3 animals were sensitized by a culture-filtrate antigen emulsified in Freund's incomplete adjuvant followed by a challenge with the intratracheal injection of the same antigen. In group 1, we observed interstitial pneumonitis with prominent granulomatous reactions which resembled those in human hypersensitivity pneumonitis. Group 2 animals also showed granulomatous inflammation in a some minor extent, but they were accompanied with excessive infiltration of neutrophils. In contrast, group 3 showed mild alveolitis in a cell population consisting predominantly of macrophages. Lymphocytes from mediastinal nodes responded to the antigen in groups 1 and 2 but not in group 3. Interestingly, the specific IgA antibody activity in the bronchoalveolar lavage fluids (BALF) of group 1 was significantly higher than those of group 2, despite the IgG antibody activity was the same. The ratio of IgA/IgG antibody activity in individual BALF sample in these two groups correlated inversely with the grade of neutrophil infiltration. Thus, the presence of IgA antibody in the respiratory tract affects the pathological outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

Synthesis and application of a new phosphorylating agent: S-(N-monomethoxytritylaminoethyl)-O-(o-chlorophenyl)phosphorothi oate.

A new phosphorylating agent, S-(N-monomethoxytritylaminoethyl)-O-(O-chlorophenyl) phosphorothioate, was prepared and reacted with a 5'-hydroxyl group of an oligonucleotide using 1-mesitylene-sulfonyl-3-nitrotriazole (MSNT) as a condensing agent. After base labile protecting groups were removed, the partially deprotected oligonucleotide was separated on a reversed phase column and converted to the oligonucleotide with an aminoethyl or a phosphoryl group at the 5'-end by treatment with 80% acetic acid or iodine-water, respectively. The syntheses of ppT, pppT, A5'pp5'T and A5'ppp5'T were also performed by treatment of 5'-O-(N-monomethoxytritylaminoethylthiophosphoryl) thymidine with tri-n-octylammonium salt of phosphoric acid, pyrophosphoric acid, pA and ppA, respectively.

Indicators and Reagents↗

Disruption of light-dark cycle of feeding and drinking behavior, and ambulatory activity induced by development of obesity in the Zucker rat.

To clarify the contribution of abnormalities and disruption of the light-dark cycle of feeding behavior during obesity progression in Zucker rats, feeding, drinking and ambulation were measured at four different stages of obesity. In the obese rats, the nocturnal pattern of feeding, drinking and ambulation shifted gradually into the light period with the progression of obesity. The lean rats however were unaffected. In the analysis of meal parameters, nocturnal dominance of meal size in the obese disappeared by 12 weeks of age and that of meal frequency was lost by 30 weeks of age. This disruption of the light-dark cycle in meal parameters appeared uneven at different stages indicating that synergistic impairment of meal size and meal frequency might contribute to the impairment of the nocturnal feeding pattern, which leads, in part, to the development of obesity.

Age Factors↗

Ultrastructural characteristics of the fetal and neonatal rat urinary bladder.

The embryologic and neonatal development of the normal rat urinary bladder was investigated in Sprague-Dawley rats by light, transmission, and scanning electron microscopy from day 11 of gestation through 21 days of age. The epithelium at day 11 of gestation is composed of small, loosely-connected, rounded cells with occasional short microvilli on their surfaces. The large polygonal cells characteristic of the adult bladder begin to appear by day 15, but the microridges are not apparent until day 17. By day 20, the epithelium appears morphologically similar to the adult bladder. Several morphological features are observed at different times of gestation which are not seen in the normal adult bladder, but they have been found in bladder tumors. During days 12-15 of gestation, most of the luminal lining cells of the bladder epithelium have a single central cilium. Cilia are also occasionally seen at days 11, 16, and 17 of gestation. Occasional cells with long tentacles are present from days 13-16 of gestation. Cells that appear to form bridges between cells are also seen from day 14 of gestation and continue to be observed through day 11 after birth. No cells with distinctive pleomorphic microvilli, a feature of rapidly proliferating bladder epithelial cells in the hyperplastic or tumorous epithelium of the adult, were seen at any time during gestation or after birth. Small foci of superficial layer sloughing occurred at the time of birth, but were rapidly replaced by one day after birth. It is apparent from this study that the bladder epithelium is a rapidly changing, proliferating tissue in utero and continuing for a brief period after birth.

Animals↗