Isao Okayasu

Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo

In a previous study, we demonstrated that retinoic acid or a synthetic retinoid, Ch 55 ((E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid), significantly affects in vivo angiogenesis, on the basis of our working hypothesis that a cell differentiation modulator could also exhibit anti-angiogenic activity. In the present study, three novel synthetic retinoids, Re 80 (4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl- 2- naphthalenyl)-1-propenyl]benzoic acid), Am 580 (4-[(5,6,7,8-tetrahydro- 5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid) and Am 80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid), whose cell differentiation-modulating effects are roughly comparable to or more potent than that of Ch 55, which was the most effective angiostatic retinoid identified previously, were examined. Their anti-angiogenic effects were tested in an in vivo assay system involving chorioallantoic membranes of growing chick embryos. They were all found to exert dose-dependent anti-angiogenic effects in the picomolar range. Their rank order for inhibitory potency was Re 80 > Am 580 > Am 80, the ID50 values being 6.3, 23 and 28 pmol/egg, respectively. These results indicate that treatment involving these three novel synthetic retinoids might have potential therapeutic efficacy in various angiogenesis-dependent disorders, including solid tumors, psoriasis, rheumatoid arthritis and diabetic retinopathy.

Detection of Helicobacter pylori infection in early stage gastric cancer : a comparison between intestinal- and diffuse-type gastric adenocarcinomas

Background. Helicobacter pylori (H pylori) infection has been suggested to be a risk factor for gastric carcinogenesis. However, those previous studies have been concerned with advanced cancer cases. To the authors knowledge, no detailed investigation on the prevalence of H pylori in early stage gastric cancer tissue has been performed. The relationship between early stage gastric cancer and the prevalence of H pylori was studied by a immunohistochemical staining analysis.

Changes in Bacterial Phagocytosis of Macrophages in Experimental Ulcerative Colitis

We previously reported that numerous macrophages which phagocytosed dextran sulfate sodium were observed to have accumulated in the mucosal lesions and in the spleen in experimental ulcerative colitis induced in mice with dextran sulfate sodium. In this paper, we investigated the bacterial phagocytic ability of macrophages which were isolated from spleens of mice treated with 3% dextran sulfate sodium for 6 months. In this model, the number of phagocytosed bacteria (Listeria monocytogenes) and the phagocytic index were significantly decreased. The phagocytic ability of splenic macrophages obtained from nontreated mice was also evaluated by incubating with dextran sulfate sodium in vitro, and adding bacteria. The number of phagocytosed bacteria and the phagocytic index were also significantly decreased. These observations suggest that the decrease in bacterial phagocytosis in this model by macrophages that phagocytosed dextran sulfate sodium indicates a decline of the mucosal defense system to bacteria.

Transfer of experimental autoimmune thyroiditis to normal syngeneic mice by injection of mouse thyroglobulin-sensitized T lymphocytes after activation with concanavalin A

Induction of autoimmune thyroiditis in normal syngeneic CBA/J mice was achieved by injection of 72-hr concanavalin A (Con A)-induced lymphoblasts from donor mice which had been immunized with mouse thyroglobulin (MTg) emulsified with complete Freunds adjuvant (CFA). Injection of lymph node or spleen cells, or frequent injection of serum taken from mice with autoimmune thyroiditis failed to transfer appreciable thyroiditis to recipient mice. Selection by treatment of incubated cells with monoclonal antibody and complement revealed that effector cells in Con A-induced lymphoblast populations for the transfer of autoimmune thyroiditis were Thy-1.2+, Lyt-1.1+, and Lyt-2.1- lymphocytes. These results demonstrate that experimental autoimmune thyroiditis can be adoptively transferred into naive mice by activated Thy-1+, Lyt-2- lymphoblasts.

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine‐orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.

Cancer in collagen disease. A statistical analysis by reviewing the Annual of Pathological Autopsy Cases (Nippon Boken Shuho) in Japan.

Cases of systemic lupus erythematosus, systemic sclerosis, periarteritis nodosa, and dermato‐ and polymyositis autopsied in Japan during a recent, 7‐year period (1972–1978) were studied to assess the incidence of cancer as a complication. In comparison with the other three groups, cases of dermato‐ and polymyositis (DP) showed quite a high incidence of malignancy: 53 of 99 for males (53.5%) and 36 of 139 for females (25.9%). In patients older than 50 years of age cancer was recognized in the autopsies of 65.7% of males and 38.2% of females with DP. The stomach was both the primary site and had the highest incidence of cancers in DP (62.3% males, 27.8% females). It was concluded that DP has a strong association with the development of cancer, particularly gastric carcinoma, in Japan.

HISTOPATHOLOGICAL AND MORPHOMETRICAL STUDY OF THE HUMAN EPIDIDYMIS AND TESTIS

Histopathological and morphometrical observations of the epididymis and testis were performed on 159 autopsy cases and 3 surgical materials of orchiectomy. The serum values of testosterone, FSH, LH, and values of intratesticular testosterone were measured in a certain number of the cases. Concerning the epididymis, increasing arteriosclerotic change was observed in the older epididymis. A high incidence of hyalinization of small arteries and arterioles was found in the younger epididymis. Eosinophilic microbodies were seen in the epithelial nuclei of the ductus epididymidis with high incidence in the older age groups. They were thought to be a catabolic compound containing phospholipids and protein resulting from cell degeneration of the mucosal epithelium. The diameter of the ductus epididymidis decreased with age. Inflammatory changes and ensued periductal sclerosis were found in the efferent duct area with an extremely high incidence. Serum values of testosterone correlated with both the age and morphological scoring calculated on the basis of either clusters or individual Leydig cells. Furthermore, testicular volume was inversely correlated with age. ACTA PATHOL. JPN. 34: 1327–1342, 1984.

The difference of susceptibility of target thyroid gland to autoimmune thyroiditis induced by a combination of implantation of thyroid gland and injection of lipopolysaccharide.

Autoimmune thyroiditis was induced in CBA/J mice by a newly developed method consisting of a combination of implantation of one whole syngeneic thyroid gland under the capsule of the kidney and subsequent injection of lipopolysaccharide (LPS) intravenously 6 hr after implantation. This procedure was repeated once, a week later. With this method the implanted thyroid gland, after becoming necrotic due to circulatory disturbance and regenerating, also developed definite thyroiditis, quite similar to that of the intact thyroid gland on Day 49. With respect to the H-2 haplotype of the mice, both intact and implanted thyroid glands of CBA/J (H-2k) and C3H/He (H-2k) mice showed severe thyroiditis, whereas those of BALB/c (H-2d) and C57BL/6 (H-2b) mice developed mild inflammation. With a combination of implantation of thyroid glands derived from parental good (CBA/J) or poor responder (BALB/c) mice and subsequent injection of LPS into (good X poor responder) (CBA/J X BALB/c)F1 hybrid mice, it was found that the genetic background of the target thyroid tissue itself has a strong influence on susceptibility.

ABNORMAL INTRACRANIAL VASCULAR NETWORKS (“MOYAMOYA” DISEASE), POSSIBLY DUE TO OCCLUSION OF BILATERAL INTERNAL CAROTID ARTERIES — A CASE REPORT WITH HISTOMETRICAL ANALYSIS —

An autopsy case of abnormal Intracranial vascular networks at the base of the brain corresponding to so‐called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year‐old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long‐stading obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro‐vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time.

A combination of necrosis of autologous thyroid gland and injection of lipopolysaccharide induces autoimmune thyroiditis.

Autoimmune thyroiditis was induced in CBA/J female mice by a newly developed method consisting of intraperitoneal implantation of one whole syngeneic thyroid gland with subsequent intravenous injection of lipopolysaccharide (LPS). The best timing for intravenous injection of LPS after intraperitoneal implantation of the thyroid tissue was 6 hr. Intraperitoneal injection of serum (but not spleen cells) taken from the mice which received implantation of one whole syngeneic thyroid gland alone, with simultaneous intravenous injection of LPS, induced autoimmune thyroiditis in the normal syngeneic mice. Furthermore, intraperitoneal injection of the medium in which one whole syngeneic thyroid gland was incubated at 37 degrees C for 10 hr, with simultaneous intravenous injection of LPS, also induced autoimmune thyroiditis in the normal syngeneic mice. Instead of intraperitoneal implantation of one whole syngeneic thyroid gland, implantation of either one lobe of autologous thyroid under the capsule of the kidney, with subsequent intravenous injection of LPS induced autoimmune thyroiditis in both intact and implanted thyroids. It is suggested that combined effects of leakage of tissue antigen originating from the necrotized tissue into the circulation and polyclonal activation by subsequent injection of LPS induced an autoimmune response.