Biomedical subjects
Publications and source records attributed to T Tsujimura.
Signaling through the c-kit receptor tyrosine kinase (Kit) is essential for development and survival of mast cells but not of basophils. Moreover, we recently found an activation mutation of Kit in several tumor mast cell lines.
A 71-year-old female visited our outpatient unit with chief complaints of anorexia and a sense of abdominal distension. The abnormalities found after admission were conspicious increases in CA125 levels in serum and ascites as well as anemia, accelerated erythrocyte sedimentation and increased serum LDH. The patient underwent an emergency operation for ileus. The histological diagnosis was serous papillomatous cancer. Immunohistologic staining of the cancer tissue demonstrated the production of CA125. In this very rare the remnant of the Müllerian duct in the peritoneum is thought to have been cancerous.
Cytokines, interleukin (IL)-1alpha, IL-1beta, IL-3, IL-6, macrophage colony stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF-alpha) as well as parathyroid hormone-related protein (PTHrP) have been shown to enhance the osteoclast activity. To investigate mechanisms of the development of bone metastasis of prostatic cancers, expression of these cytokines and PTHrP was examined immunohistochemically in prostatic cancers of patients administered no prior therapy or endocrine therapy. All cytokines and PTHrP were stained in the cytoplasm of the epithelium of non-cancerous prostatic glands, and IL-3 and IL-6 were stained in the cytoplasm of smooth muscle cells besides epithelial cells of non-cancerous prostatic glands. Incidences of positivity of staining in prostate cancers of patients administered no prior therapy were 100% for IL-1alpha, IL-1beta, IL-6, M-CSF and TNF-alpha, 20% for IL-3, and 80% for PTHrP. Incidence of prostatic cancers stained positively for IL-1alpha and IL-1beta decreased significantly in patients administered endocrine therapy, but those for IL-3, IL-6, M-CSF, TNF-alpha and PTHrP did not change significantly. The present results suggest that prostatic cancers produce various cytokines, IL-1alpha, IL-1beta, IL-3, IL-6, M-CSF and TNF-alpha, as well as PTHrP, and that expression of these cytokines and PTHrP except IL-1alpha and IL-1beta is not under androgen control. Cytokines and PTHrP produced by prostatic cancers may play a role in the development of bone metastasis of prostatic cancers.
Three cases of benign pelvic tumors are presented (2 leiomyomas and 1 fibroma). All three tumors were suspected of being malignant neoplasms because they were visualized as heterogeneous high signal intensity on T2-weighted images, and thus they were difficult to diagnose preoperatively. One of the leiomyomas was located in the retroperitoneum and had been misdiagnosed as an ovarian tumor. All three tumors exhibited secondary myxoid changes, these changes may have been responsible for the high signal intensity on the T2-weighted MR images. Since benign tumors sometimes mimic malignant tumors on MR images, exploratory laparotomy is essential to make a definitive diagnosis.
Effects of interleukin (IL)-18 on experimental bone metastasis of human breast cancer cells, MDA-231 cells, in nude mice were investigated. In addition, effects of IL-18 on subcutaneous growth of MDA-231 cells were examined. Bone metastasis was produced by an intracardiac injection of MDA-231 cells. Twenty eight days after the cell injection, severe osteolytic bone metastasis was examined by X-ray radiography, and both non-osteolytic and osteolytic bone metastases were examined microscopically. IL-18 (1 microgram/mouse) was injected intraperitoneally according to protocols A and B. In protocol A, IL-18 was injected daily from day 7 after an intracardiac or subcutaneous injection of cells, and in protocol B, it was injected daily for 7 days each before and after the cell injection. In protocol A, IL-18 injections significantly suppressed both the incidence of osteolytic bone metastasis detected by X-ray radiography (about 80% vs. about 20% for the control group vs. the treatment group) and the number of its foci/mouse (1.6 vs. 1 for the control group vs. the treatment group). However, they did not cause significant effects on either the incidence of bone metastasis detected microscopically or the number of its foci/mouse. In protocol B, IL-18 injections caused no significant effects on either the incidence of osteolytic bone metastasis detected by X-ray radiography or the number of its foci/mouse. They caused no significant effects on the incidence of bone metastasis detected microscopically, but significantly decreased the number of its foci/mouse (about 2.0 vs. about 1 for the control group vs. the treatment group). In both protocols A and B, IL-18 injections produced no significant effect on the tumor take and subsequent growth of tumors after a subcutaneous injection of the cancer cells. Since in protocol A, IL-18 appears to have exerted its action after establishment of metastasis by cancer cells to the bone marrow, the effects of IL-18 found in Protocol A indicate that IL-18 inhibited osteolytic growth at bone metastatic sites of breast cancers. On the other hand, since in protocol B IL-18 is likely to have functioned around the time when lodging of cancer cells and early development of metastasis occur in the bone marrow, the effects of IL-18 found in Protocol B indicate that the cytokine also suppresses an early stage of bone metastasis of breast cancers, although, this effect was less apparent than the effect on osteolytic growth. Therefore, IL-18 may be useful for suppression of osteolytic bone metastasis which is a serious problem in patients of advanced breast cancers.
The uteri of mice up to 20 days after birth show estrogen-independent growth, although their growth is accelerated by estrogen, while the growth of the uteri of mice after 20 days completely depends on estrogen. In the present study, we compared the sensitivities of uterine cells in their proliferation responding to epidermal growth factor (EGF) and diethylstilbestrol (DES) between 5-day-old and 25-day-old ovariectomized mice. A single subcutaneous injection of EGF at doses of 0.25 and over 0.25 microgram/g body weight (BW) increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase in the 3H-thymidine uptake was attained at a dose of 1 microgram/g BW of EGF in both mice. A single subcutaneous injection of DES at 0.001 and over 0.001 microgram/g BW increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase was attained at 0.004 microgram/g BW of DES in both mice. EGF and DES increased labeling indices of both the epithelium and stroma in both 25-day-old and 5-day-old mice. The present results suggest that sensitivities of uterine cells of neonatal mice in their proliferation responding to EGF and DES are similar to those of postneonatal mice.
The role of the Fas ligand-Fas system in castration-induced apoptosis in the epithelia of the ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG) and epididymis (Ep) was investigated using lpr/lpr, and gld/gld mutant mice which are deficient in Fas and Fas ligand, respectively. The degree of apoptosis in the epithelium was quantitatively estimated by an apoptotic index (a percentage of apoptotic cells). The weights (mg/10 g body weight) of the VP, SV, CG and Ep of lpr/lpr and gld/gld mice were similar to those of normal +/+ mice and castration decreased the weights of the VP, SV, CG and Ep in these three kinds of mice to similar levels. Castration also increased the apoptotic indices in these organs reaching maximum on days 2-6 after castration. There was no significant difference in the apoptotic index of these organs among +/+, lpr/lpr and gld/gld mice on days 0-8 after castration. Agarose gel electrophoresis of DNAs extracted from the VP, SV, CG and Ep of +/+, lpr/lpr and gld/gld mice on day 4 after castration showed a ladder pattern. The present results suggest that the Fas ligand-Fas system plays little role in castration-induced apoptosis in the mouse male accessory sex organs such as the VP, SV, CG and Ep.
The intravenous (i.v.) administration of Lyt-1dull T cells into syngeneic (C57BL/6 x C3H/He)F1 T cell-depleted B cell mice resulted in the induction of typical thyroiditis exhibiting massive cellular infiltration. The present study investigated which types of lymphoid cells infiltrate in the thyroiditis lesion and whether immunohistologic change takes place on epithelial cells of thyroid follicles. Both L3T4+ and Lyt-2+ T cells were found in the lesion, although the frequency of infiltration was higher in the former than in the latter. Thyroiditis was also induced by injection of Lyt-1dull L3T4+ but not of Lyt-1dull Lyt2+ T cells, indicating the critical role of a part of L3T4+ T cell subset (Lyt-1dull L3T4+ T cell subpopulation) in inducing thyroiditis. Only rare Lyt-2+ T cells were seen in such a thyroiditis lesion. Infiltrating T cells were predominantly of L3T4+, and these L3T4+ T cells formed cellular infiltrating lesion together with moderate number of B cells and relatively small number of macrophages. Importantly, class II MHC antigens were detected on epithelial cells of thyroid follicles. Such class II MHC expression was observed in coincidence with the area of cellular infiltration in the thyroid. These results demonstrate that: (1) a part of L3T4+ T cells which is required for the induction of thyroiditis by adoptive cell transfer infiltrates into the inflammatory lesion, (2) the induction of the thyroiditis lesion is formed by these L3T4+ T cells as well as B cells and macrophages, but does not necessarily depend on the participation of Lyt-2+ T cell subset, and (3) the aberrant expression of class II MHC antigens on thyroid epithelial cells coincides with cellular infiltration.
The immunoreactivity of tenascin, an extra cellular matrix glycoprotein, spatially and temporarily expressed in a site restricted manner during embryogenesis, wound healing and various benign and malignant tumours, was evaluated in 24 cases of adenoid basal cell carcinoma of the skin. The expression of tenascin showed three distinct patterns: firstly, the expression was confined to the stroma surrounding the tumour cells, secondly, to the stromal tissues of epithelial tumour foci and lumens of cribriform or cyst-like epithelial structures, and finally, a mixed pattern of these two was seen. It is suggested that in addition to the stromal reactivity, epithelial tumour cells may produce tenascin to deposit into the cribriform cystic lumens in the adenoid basal cell carcinoma in the skin.
Estrogen or prolactin suppresses mouse hepatocellular tumorigenesis induced by carcinogens through inhibition of the growth of preneoplastic hepatocytes. In the present study, we investigated whether estrogen or prolactin inhibits proliferation of normal hepatocytes as well as preneoplastic hepatocytes in mice. The proliferation of mouse hepatocytes was induced by partial hepatectomy, and DNA synthesis of the liver was evaluated by measurement of 5-[125I]iododeoxyuridine ([125I]IdUrd) uptake/mg liver DNA after an injection of [125I]IdUrd into mice. For acute treatment with estrogen or prolactin, estradiol-17 beta (E2) (1 micrograms) or ovine prolactin (140 micrograms) was injected into ovariectomized mice twice a day from the day of partial hepatectomy. For chronic treatment with estrogen, ovariectomized mice received implants of E2 pellets containing 100 micrograms E2 40 days before partial hepatectomy, and for chronic treatment with prolactin, hyperprolactinemia was induced by pituitary graft under the renal capsule of ovariectomized mice 40 days before partial hepatectomy or by daily injections of perphenazine (150 micrograms/day) beginning 40 days before partial hepatectomy. The acute treatment with either estrogen or prolactin did not affect the hepatocyte proliferation induced by partial hepatectomy. Chronic hyperprolactinemia induced by the pituitary graft or by injections of perphenazine, and the chronic treatment with E2 pellets did not suppress either basal or partial hepatectomy-induced proliferation of hepatocytes. The present results show that acute and chronic treatments with estrogen or prolactin do not inhibit proliferation of mouse normal hepatocytes, and suggest that the effects of estrogen and prolactin on proliferation of mouse hepatocytes are different from those on proliferation of preneoplastic hepatocytes.
The Fas-Fas ligand system plays a crucial role in the production of a signal for apoptosis in the immune system. In the present study, expression of Fas and Fas ligand in the testes and testicular germ cell tumors was examined immunohistochemically. Expression of both Fas and Fas ligand was found on Leydig cells, Sertoli cells, and germ cells in the testis, and on epithelial cells in the epidydimal duct. Expression of both Fas and Fas ligand was also found in all 23 seminomas, 8 embryonal carcinomas, and 3 yolk sac tumors which were examined in this study. Western blot analysis after sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under a reducing condition with tissues of the thymus, the testis, and a seminoma showed a single major band bound to the antibody for Fas or Fas ligand at the position of molecular weight slightly more than 47.5 kilodalton. Since both Fas and Fas ligand are expressed on normal testicular cells, and on cells of testicular germ cell tumors, the Fas-Fas ligand system in these cells seems to play a role other than producing a signal for apoptosis.
We report a case of histologically proved acute interstitial pneumonia (AIP) with subacute onset whose high-resolution CT (HRCT) findings were indistinguishable from those of bronchiolitis obliterans organizing pneumonia (BOOP)/cryptogenic organizing pneumonia (COP). The HRCT findings were air-space consolidation with air-bronchiologram associated with little ground-glass attenuation, and nodules. Some cases of AIP present HRCT findings indistinguishable from those of BOOP/COP.