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Biomedical subjects

A Kojima

Publications and source records attributed to A Kojima.

At least 325 records · Page 18Linked to original sources

Immunogenicity of lysozyme derivatives lipid-conjugated to various degrees in mice treated with and without cyclophosphamide: dissociation of delayed-type hypersensitivity and helper function.

Lysozyme and a series of its lipid-conjugated derivatives without adjuvant were examined in mice for their abilities to induce delayed-type hypersensitivity (DTH), helper T-cell activity, and antibody formation. In addition, the effect of cyclophosphamide (CY) on the immune responses was assessed in mice immunized with these lysozyme derivatives. Precipitated lysozyme without lipid conjugation was a good inducer of both antibody and DTH responses. Lipid conjugation to lysozyme to intermediate degrees readily caused the failure only in inducing the antibody response. As lysozyme was lipid-conjugated more heavily, DTH response was also reduced and finally abolished. In contrast, the helper activity was little affected by any degree of lipid conjugation. These results indicate that the helper T-cell activity was dissociated from the both DTH response and the antibody production. CY pretreatment extensively enhanced DTH response induced by such lipid-conjugated derivatives that failed to induce antibody response. Furthermore, CY pretreatment in doses in a wide range enhanced not only DTH response but also antibody formation. It is, therefore, concluded that the enhancement of DTH response by CY does not necessarily entail suppression of antibody formation.

Animals↗

An increase of liver uptake of thyroxine, an initial step of an increased fecal loss of thyroxine in response to propylthiouracil in rats.

Propylthiouracil augmented fecal loss of thyroxine (T4), but methimazole was without effect in this respect in rats. In vitro uptake of labeled T4 by the liver was significantly enhanced by a small amount of propylthiouracil in the presence of dilute rat plasma. Methimazole was without effect under comparable conditions. In contrast, propylthiouracil and methimazole failed to affect in vitro uptake of labeled T4 by the kidney and diaphragm in the presence of dilute rat plasma. Since deiodination of T4 does not occur in the presence of dilute rat plasma, it is suggested that propylthiouracil specifically stimulates liver uptake of T4 as an initial step of an increase of biliary-fecal excretion of T4 in rats.

Animals↗

Pathogenicity for chicks of line cells from lymphoma of Marek's disease.

Pathogenicity for chicks of the MSB-1 line, a cell line derived from the tumorous tissue of a chick with Marek's disease (MD) and established by Akiyama & Kato, was studied. Five groups, including a control one, of 20 chicks each were inoculated with 1 X 10(3), 1 X 10(4), 1 X 10(5), 1 X 10(6) and no cells of a 180-day culture of the cell line at one day of age. They were housed all together in an isolation unit. An attempt was first made successfully to isolate MD virus (MDV) directly in culture of kidney cells 3 weeks after inoculation. Horizontal infection was first detected 4 weeks after inoculation. From 3 weeks after inoculation on, the disease with almost the same clinical and pathological pictures as the infection with a virulent strain of MDV showed a high incidence. Morbidity was closely related to the number of MSB-1 line cells inoculated. Parenchymal destruction was conspicuous in the central lymphoid organs of four chicks given the largest number of MSB-1 line cells and sacrificed in extremis about 4 weeks after inoculation. Establishment of MD in chicks inoculated with MSB-1 line cells carrying MDV genome seemed to be initiated under the circumstances where the line cells which had come into contact with susceptible cells in the peritoneal cavity released virulent MDV per se. Then host chicks might be infected with MDV and suffer from MD at a high rate. There was no great difference in oncogenic potential between MSB-1 line cells cultivated in vitro for 180 days and virulent MDV serially passaged through one-day-old chicks.

Animals↗

Fine structure of epithelial cells of Lieberkühn's crypts in feline panleukopenia.

Electron microscopic observation was carried out on epithelial cells of Lieberkühn's crypts of cats naturally affected with feline panleukopenia. The most important change was the replication of feline panleukopenia. The most important change was the replication of feline panleukopenia virus in the nucleus with associated alterations in the lining epithelial cells of the crypts. In these cells in the early stage of infection, virus particles 20 nm in average diameter were found either singly or in small regularly arrayed clusters everywhere in the markedly swollen nucleus. In the course of infection, the nucleus of infected cells became rather atrophic with a marked margination of chromatin granules. Its major portion was occupied with masses of fine fibrillar substance. It was a "viral matrix area" in which appeared a large compact aggregate of virus particles showing a crystalline array. At the same time, the outer membrane of the nuclear envelope partially extended and disrupted. Membranous elements related to it in the cytoplasm were regularly distributed almost always with particles indistinguishable from the virus particles in the nucleus. From these results it was suggested that the major portion of the infected nucleus, or the site of viral replication, might correspond to the amphophilic intranuclear inclusion body revealed by light microscopy.

Animals↗

Prevention of postthymectomy autoimmune thyroiditis in mice.

Several immunologic procedures are described, by which the postthymectomy autoimmune thyroiditis in (C3H/HeMs X 129/J)F1 female mice was clearly prevented. These include the grafting of a neonatal thymus or a cell injection from adult thymus, spleen, and lymph nodes, but not from bone marrow. Their preventive effects, however, depended on the timing of treatments. In general, the earlier the treatment was given, the better the effect was. Thymus cells from 7-day-old mice were effective, whereas spleen cells from the same donors and neonatal thymus cells were ineffective. Neonatal thymectomy or 500-rad irradiation decreased the number of effective cells in the spleen. All of these data suggest that the cells responsible for the prevention of postthymectomy thyroiditis are T-cells, and that ontogenetically these cells first acquire their preventive ability in the thymus after birth and then migrate to the peripheral lymphoid tissues. The minimal effective dose of adult spleen cells was 15 X 10(4). Although 10(7) spleen cells from the mice thymectomized 3 days after birth failed to prevent the disease, the same dose of cells from those thymectomized at 7 days clearly prevented it. This suggests that qualitative rather than quantitative differences exist in peripheral T-cells of mice thymectomized 3 days after birth and those of normal mice or mice thymectomized at 7 days when the animals get to adulthood.

Animals↗

Spontaneous development of autoimmune thyroiditis in neonatally thymectomized mice.

An experimental mouse model of autoimmune thyroiditis induced by neonatal thymectomy (between 2 and 4 days of age) is described. Thymectomy within 24 hours after birth or thymectomy after 5 days of age failed to induce the disease. This type of thyroiditis occurred spontaneously a few months after the operation, lasted until approximately 12 months of age, and appeared to subside with aging. Hybrid mice of (C3H/He X 129)F1 are so far the most susceptible to neonatal thymectomy and the incidence in females (25 per cent) is significantly higher than that in males (6 per cent). Mice with thyroid lesions usually had circulating antibodies to mouse thyroid extract. Histologically, lymphocytes and plasma cells were the main cellular types of infiltrates and lymphoid follicles were seen in some cases. Interestingly, adenoma-like nodular hyperplasia of thyroid epithelium was observed in several thymectomized mice, with or without lymphoid infiltration. Besides those observed in the thyroid gland, lymphoid infiltrations were often observed in such organs as the ovary, the stomach, and the coagulating gland of thymectomized mice. These characteristics are compared with those of Hashimoto's thyroiditis and with those of its other animal models, and possible mechanisms which may be involved in the present disease are discussed.

Aging↗

Pituitary unresponsiveness to thyrotropin-releasing hormone in thyrotoxic patients during chronic anti-thyroid drug therapy and in rats previously treated with excess thyroid hormone.

In an attempt to study pituitary-thyroid feedback control in thyrotoxic patients, TRH tests were performed in 10 thyrotoxic patients who were treated for varying intervals with propylthiouracil. Plasma TSH was undetectable before and after administration of 500 mug TRH in 7 patients (euthyroid or hypothyroid) after therapy for 1 to 4 months. Also, plasma TSH was undetectable before and after TRH in 3 patients who had been euthyroid for at least 6 months. To explore this abnormality, rats were made thyrotoxic by administering large doses of thyroxine or desiccated thyroid for 3 to 28 days. Discontinuation of thyroid hormone administration was followed by a significant but temporary fall of plasma thyroxine and triiodothyronine concentration below control levels. Duration of the low plasma thyroxine and triiodothyronine concentration was longer with the prolonged administration of thyroid hormone. Despite low plasma thyroxine and triiodothyronine concentrations, plasma TSH was below normal before and after administration of TRH. This unresponsiveness of the pituitary to TRH may be comparable to that found in thyrotoxic patients receiving antithyroid drugs for a certain period. Since this pituitary unresponsiveness to TRH in rats is due to a depletion of pituitary TSH content, it is suggested that depletion of pituitary TSH in thyrotoxic patients during antithyroid therapy is the cause of pituitary unresponsiveness to TRH.

Adult↗

Effect of butyldiiodohydroxybenzoate on pituitary-thyroid interplay.

The effect of BHDB, an analogue of thyroxine, on the pituitary-thyroid system was studied in the rat. BHDB produced low plasma T4 and T3 concentrations similar to those produced by methimazole, but failed to elevate plasma TSH and to produce goiter because of displacement of T4 from the binding protein. Low plasma thyroid hormone concentrations were due to an increase of fecal loss of thyroid hormones. By releasing excess iodide, BHDB blocked the development of goiter produced by methimazole.

Animals↗

An elevation of plasma ISH concentration in spontaneously hypertensive rats (SHR).

Thyroid activity was tested in two substrains of SHR. Plasma level and pituitary content of TSH increased significantly in both substrains of SHR. As a result, the thyroid weight and thyroidal radioiodine uptake increased significantly. Plasma T3 concentration was decreased in Kyoto substrain but was normal in NN substrain, while plasma T4 concentration decreased significantly in both substrains. Since the pituitary content and plasma level of TSH were significantly higher in spite of the normal concentration of plasma T3, it is concluded that the pituitary "hormostat" is set at a higher level at least in the NN substrain of SHR.

Adrenal Glands↗

Congenital abnormality of pituitary-thyroid axis in spontaneously hypertensive rats (SHR) and stroke-prone rats (SPR).

In an attempt to study whether TSH abnormality was genetically determined in SHR and SPR, plasma T4, T3, TSH and prolactin concentrations were measured in the animals with intervals of 1 to 3 months. Hypertension was found in 6-month-old SHR and SPR, but it was not found in younger animals. In contrast, a decrease of plasma T3 and an increase of plasma TSH were found in 15-day-old SHR. Also, an increase of TSH was found in 1-month-old SPR in spite of normal plasma T3 concentration. These abnormalities in SHR and SPR increased progressively with age. It is suggested that thyroid-pituitary abnormality was genetically determined in SHR and SPR.

Age Factors↗

Cell-mediated and humoral immunity in mice: cross reaction between lysozyme and S-carboxymethylated lysozyme studied by a modified footpad test.

The mouse sensitized by subcutaneous (sc) injection of lysozyme in emulsion of Freund's complete adjuvant (FCA) was shown by a modified footpad test to develop three kinds of hypersensitivities. Injecting lysozyme in 2.5-mul emulsion of Freund's incomplete adjuvant (FIA) into the footpad elicited strong footpad swelling in 30 min (anaphylactic reaction), in 3 hr (Arthus-type reaction) and in 24 hr (delayed-type hypersensitivity; DTH). The mice showing anaphylactic reaction in the footpad test manifested severe active systemic anaphylaxis, and the sera of these animals showed high IgG1 antibody titers with only sparingly detectable or no IgE antibody titers. In the sensitizing system with the use of FCA, the antigenicity of S-carboxymethylated lysozyme (CM-lysozyme) devoid of the three-dimensional conformation of lysozyme was compared with that of the native molecule. CM-lysozyme and lysozyme completely cross-reacted to each other in DTH, but not at all in the anaphylactic or Arthus-type reaction or in IgG1 antibody production. CM-lysozyme was shown also to have the ability to bestow immunological memory for the induction of humoral immunity against lysozyme; intravenous (iv) injection of lysozyme in saline or sc injection of CM-lysozyme-FCA alone failed to induce immediate hypersensitivities and IgG1 antibody production against lysozyme, but pre-sensitization by sc injection of CM-lysozyme-FCA enabled the animal to induce these responses to significant levels when iv injection of lysozyme in saline was given as a booster.

Anaphylaxis↗