Itsuro Hayashi

Suppression of STAT5 Functions in Liver, Mammary Glands, and T Cells in Cytokine-Inducible SH2-Containing Protein 1 Transgenic Mice

ABSTRACT Various cytokines utilize Janus kinase (JAK) and the STAT (signal transducers and activators of transcription) family of transcription factors to carry out their biological functions. Among STATs, two highly related proteins, STAT5a and STAT5b, are activated by various cytokines, including prolactin, growth hormone, erythropoietin, interleukin 2 (IL-2), and IL-3. We have cloned a STAT5-dependent immediate-early cytokine-responsive gene, CIS1 (encoding cytokine-inducible SH2-containing protein 1). In this study, we created CIS1 transgenic mice under the control of a β-actin promoter. The transgenic mice developed normally; however, their body weight was lower than that of the wild-type mice, suggesting a defect in growth hormone signaling. Female transgenic mice failed to lactate after parturition because of a failure in terminal differentiation of the mammary glands, suggesting a defect in prolactin signaling. The IL-2-dependent upregulation of the IL-2 receptor α chain and proliferation were partially suppressed in the T cells of transgenic mice. These phenotypes remarkably resembled those found in STAT5a and/or STAT5b knockout mice. Indeed, STAT5 tyrosine phosphorylation was suppressed in mammary glands and the liver. Furthermore, the IL-2-induced activation of STAT5 was markedly inhibited in T cells in transgenic mice, while leukemia inhibitory factor-induced STAT3 phosphorylation was not affected. We also found that the numbers of γδ T cells, as well as those of natural killer (NK) cells and NKT cells, were dramatically decreased and that Th1/Th2 differentiation was altered in transgenic mice. These data suggest that CIS1 functions as a specific negative regulator of STAT5 in vivo and plays an important regulatory role in the liver, mammary glands, and T cells.

The policy of surgery for small carcinoid tumors of the rectum

In this report, we discuss the current policy of surgery for small carcinoid tumors of the rectum, with reference to our own cases and also to those reported in the literature. Ten cases of rectal carcinoid tumors were surgically treated at the National Kyushu Cancer Center over a period of sixteen years and three months. The tumors ranged in size from 0.2 to 1.0 cm, with an average of 0.5 cm, and all were confined to the submucosa. The lesions were treated by local excision in eight patients and by low anterior resection in the other two cases, where transanal or transsacral excision was considered difficult. No lymph node involvement was found in these two cases. All patients are alive and well without recurrence, after a average follow-up time of three years and six months. According to the literature, the incidence of metastasis from rectal carcinoid tumors smaller than 1 cm is very low, ranging between 1.7 to 3.4 per cent, and it therefore seems that most such lesions can be treated by local excision alone. If, however, any muscle invasion or lymphatic vessel invasion is demonstrated, then radical surgery is recommended.

Tubular adenoma with focal squamous metaplasia of the ascending colon

A case of tubular adenoma with focal squamous metaplasia of the ascending colon in a 66‐year‐old male is reported. The tumor was a pedunculated polyp with a size of 1.5 × 1.4 × 0.9 cm. Histologically, the tumor showed tubular adenoma with moderate to severe atypia, was accompanied by focal squamous metaplasia. It is thought that squamous epithelial polyp may be derived from colonic adenoma with squamous metaplasia, and that the malignant change of colonic adenoma with squamous metaplasia may lead to squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. Only seven cases of colonic adenoma with squamous metaplasia have been reported previously in the literature, and it is yet necessary to discuss the histogenesis, significance, and natural history of colonic adenoma with squamous metaplasia. ACTA PATHOL. JPN. 35 : 507–515, 1985.

Noonan Syndrome with Hypertrophic Obstructive Cardiomyopathy

A case of a 20 years old female who had Noonan syndrome associated with obstructive cardiomyopathy was presented. It is well known that Noonan syndrome is frequently complicated with cardiac anomaly, and although no autopsies were performed two cases have been diagnosed clinically as Noonan syndrome accompanied with idiopathic cardiomyopathy in our country. The present case would be the first autopsied case in Japan of Noonan syndrome associated with idiopathic obstructive cardiomyopathy.

Gastric stromal tumor of the uncommitted type treated by repeated removal of recurrent tumors : case report with immunohistochemical and ultrastructural observations

Abstract A gastric stromal tumor was found in a 61-year-old man. The patient was treated by total gastrectomy, but the tumor recurred, 26 months after surgery, in the peritoneal cavity at the anastomotic site of the esophagojejunostomy, with metastases to mesenteric lymph nodes. This second tumor was removed surgically, but, 7 years after the gastrectomy, multiple recurrent tumors were found in the peritoneal cavity; once again the tumors were removed. Although the recurrent tumors were surgically removed twice, the patient died of the disease 8 years after the initial surgery. Histologically, the gastric tumor consisted of spindle-shaped neoplastic cells arranged in interlacing tumor bundles with frequent mitotic figures (four mitoses per ten high-power fields). Although the recurrent tumors also consisted of spindle-shaped neoplastic cells, myxoid changes were prominent. Immunohistochemically, the neoplastic cells gave diffuse positive reactions only with antibodies CD34 and vimentin among a variety of antibodies tested. Ultrastructural analysis failed to provide conclusive evidence for the neural or muscular origin of the tumor. The gastric tumor was therefore considered to be gastric stromal tumor of uncommitted type with malignant behavior. The patient survived for a long-term period after the gastrectomy, followed repeated removal of the recurrent tumors.

Frequency of Thrombus on Non-Pathologic and Atherosclerotic Intima of Human Aorta — Thrombosis as a Pathogenesis of Atherosclerosis

Forty-four aortas dissected from human subjects were sliced into 30-50 se rial sections and studied morphologically for the presence of thrombi. A total of 569 thrombi were found histologically in 1,400 sections. The frequency of thrombosis was 7% for subjects under 30 years-old. However, with increasing age, the frequency rose to 8% in the third decade, 9% in the fourth decade, 13.5% in the fifth decade, 10.5% in sixth decade, 25.5% in the seventh decade and 33.5% for subjects over 80 years-old. Thrombi were morphologically classified into three types: (1) microthrombi (2) membranous thrombi, and (3) large massive thrombi. The latter were rarely found on the intima, and no sclerotic lesions were observed. The frequency of thrombosis on non-pathologic areas was 11 %, and almost all of them were microthrombi. The thrombi on the areas of cloudy thickening was 47% with 6% of them being classified as membranous thrombi or large massive thrombi. The thrombi on atherosclerotic lesions was 42%, unusually high compared with the other categories and 32 % of them were membranous or large massive thrombi. In each region of thoracic and abdominal aorta, thrombi were apt to be more on abdominal aorta than that on thoracic aorta.