Kazumi Kuriwaki

Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency.

We have reported the clinical and biochemical findings in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency. This paper is the first report about cardiomyopathy in jvs mice. Adult jvs mice (at the age of 2 3 months) show cardiac hypertrophy which is caused by enlargement of the cardiac muscle cell associated with increases of non‐collagen protein and DNA content. Carnitine administration (2 mg/head, twice a day, from 1 month of age) significantly suppresses the cardiac hypertrophy, showing that carnitine deficiency plays an important role in the development of the cardiac hypertrophy. The discovery of cardiac hypertrophy in carnitine‐deficient jvs mice will lead to clarification of the pathophysiology of cardiomyopathy in systemic carnitine deficiency in human beings.

Intramural hematoma of the thoracic aorta

OBJECTIVE This study was designed to clarify the optimal treatment mode of patients with intramural hematoma (IMH) of the thoracic aorta. METHODS From 1992 through 1997, 51 patients underwent surgical repair or medical treatment of IMH of the thoracic aorta. There were 36 male and 15 female patients, aged between 49 and 79 years with a mean of 67 years. The ascending aorta and/or aortic arch was involved in 18 patients (group I), whereas the descending thoracic aorta was affected in 33 (group II). The presence of intimal disruption in IMH was confirmed in 10 of group I and 13 of group II patients. RESULTS For group I patients 13 required aortic arch repairs and the remaining 5 underwent conservative therapy including anti-hypertensive medication. Primary indications for immediate surgery were: cardiac tamponade in 5 patients, aortic dissection superimposed on IMH in 2, and persistent pain with an aortic arch aneurysm in 1, respectively. Early elective operations were done for enlarged ulcer in 3 patients and aneurysmal dilatation in 2 of which 1 had a coexisting aortic arch aneurysm. The 2-year survival rate after diagnosis was 94% with an operation-free rate of 25%. Nine of the group II patients experienced surgical intervention of which 8 had intimal disruption, 4 patients received urgent replacement of the descending thoracic aorta for massive pleural effusion and 1 had the aortic arch replaced for a coexisting aneurysm with persistent pain. All other patients underwent conservative treatment and 4 of them had to be shifted to early surgery during the initial hospitalization because of an enlarged ulcer. The 5-year survival rate in group II patients was 63% with an operation-free survival rate of 66%. CONCLUSIONS On the basis of our experience early operation is recommended for almost all patients with ascending aortic IMH, and medical therapy for those with descending aortic involvement unless complication developed. However, the presence of intimal disruption may require early surgical treatment even in the patients with descending thoracic IMH.

Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-α) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status

In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF-α and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-α; positive EGF-R and TGF-α; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-α. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF-α correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF-α are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF-α may provide useful information for selecting the appropriate treatment.

Apocrine Adenocarcinoma of the Bilateral Axillae

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88 year old Japanese male who complained of a mass lesion and puslike discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP‐15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma. Acta Pathol Jpn 41: 927‐932, 1991.

Acute aortic dissection in a patient with osteogenesis imperfecta

A case of osteogenesis imperfecta complicated with acute type A aortic dissection is presented. Emergency graft replacement of the ascending aorta was performed successfully despite the anticipated difficulties with tissue friability. Therefore, such an operation is suggested to be worthy of consideration and feasible in patients with osteogenesis imperfecta.

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c‐erbB‐2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c‐erbB‐2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

Morphological characteristics of lipid accumulation in liver‐constituting cells of acid lipase deficiency rats (Wolman’s disease model rats)

Lysosomal acid lipase is a hydrolase essential for the intracellular degradation of cholesteryl esters and triglycerides. In the laboratory, rats with congenital deficiency of lysosomal acid lipase and marked accumulation of cholesteryl ester, cholesterol free and triglyceride in livers (Wolman’s disease rat or Yoshida rat) that corresponded to human Wolman’s disease were found and maintained. The morphological characteristics of accumulated lipids in the livers of affected rats were examined also. Many small lipid droplets and lipid crystals were found in the cytoplasms of hepatocytes and ED1‐positive and ED2‐positive foamy Kupffer’s cells, respectively. Electron microscopically, many electron‐lucent lipid droplets with limiting membrane were found in hepatocytes. Foamy Kupffer’s cells had many multivesicular bodies with limiting membrane, which contained crivilinear bodies, lipid droplets and crystal clefts. At areas of aggregation of foamy Kupffer’s cells forming islets, there were many desmin‐positive Ito cells. Small lipid droplets with limiting membrane were also found in the cytoplasm of Ito cells and endothelial cells. These findings, which were obtained by morphological methods, indicated that triglyceride and both cholesteryl ester and free cholesterol accumulated in lipolysosomes mainly in hepatocytes and Kupffer’s cells, respectively, and suggest that lysosomal acid lipase could participate in dissolution of the membrane.

Induction of Sarcomas by a Single Subcutaneous Injection of 7,12-Dimethylbenz[a]anthracene into Neonatal Male Sprague–Dawley Rats: Histopathological and Immunohistochemical Analyses

Animal experiments have shown that carcinogenicity of chemicals is higher in fetal or neonatal periods than adult. We investigated sensitivities to a carcinogen in peri-neonatal rats with a model of sarcomas-induction by a subcutaneous injection of chemo-carcinogen that has rarely done in neonatal rats. Neonatal male SD rats were injected with 7,12-DMBA 10, 100, and 500 μg, which resulted in sarcomas-induction in 0, 62, and 94% of rats. Male SD rats were injected with DMBA 500 μg at 0, 3, 7, 14, and 21 days, which resulted in sarcomas-induction in 94, 70, 64, 50, and 44% of rats. Although the induced sarcomas were occasionally in mixed morphological feature as previous reports for sarcomas of rat, each was immunohistochemically in almost monotonous pattern, and classification was feasible. The incidence of rhabdomyosarcomas was higher in rats neonatally injected with a higher dose of DMBA than a lower dose, and in rats injected at peri-neonatal periods than later periods. In histological observations for the site of injection before overt sarcomas develop, clusters of atypical mesenchymal cells emerged as previous studies, but also those were immunohistochemically differentiated into rhabdomyocytes and other mesenchymal cells. We consider these findings may contribute a little to elucidation of process of sarcomas-induction in rats.

Primary malignant melanoma of the male urethra

We report a case of primary malignant melanoma of the male urethra in a patient whose penile shaft was successfully preserved, but who proceeded to acute renal failure (ARF) after interferon (IFN)‐β adjuvant immunotherapy. Primary malignant melanoma of the male urethra is rare and usually shows highly malignant potential. Therefore, urologists must often perform phallectomy, which impacts on the patient both sexually and mentally. A 64‐year‐old man presented at Saiseikai Sendai Hospital with asymptomatic gross hematuria and was diagnosed as distal urethral tumor. We predicted the highly malignant potential of this tumor from the urethroscopic finding and from urinary cytological examination. We did not select trans‐urethral resection (TUR), but selected partial urethrectomy.

Sharp increase in the incidence of mammary Carcinoma in Kagoshima prefecture, Japan

Between 1986 and 1990, among a female population of about 0.95 million, 1184 women living in Kagoshima Prefecture were diagnosed pathologically as having mammary carcinoma. The number of patients with mammary carcinoma, the crude incidence rate per 100 000 women and age-standardized mammary carcinoma incidence rates were 205, 21.29 and 19.42 in 1986, 212, 22.04 and 19.48 in 1987, 238, 24.74 and 21.8 in 1988, 245, 25.47 and 22.33 in 1989 and 284, 29.57 and 25.69 in 1990, respectively. The number of patients with this disease increased annually. The increase in the age-specific incidence rate of this type of cancer between 1986 and 1990 was 1.38-fold in women between 40 and 49 years of age, 1.46-fold in women between 50 and 59, 1.37-fold in the 60–69 age group, 1.48-fold in the 70–79 age group and 1.91-fold in women over 80. In both the urban and rural areas, the incidence increased annually during the course of this study. In 1990, the age-standardized mammary carcinoma incidence rate in urban area was 1.17 times that in rural area.