VARIOUS EPITHELIAL AND NON-EPITHELIAL TUMORS SPONTANEOUSLY OCCURRING IN LONG-LIVED MICE OF A/St, CBA, C57BL/6 AND THEIR HYBRID MICE

Various kinds of epithelial and non-epithelial tumors, and tumor-like lesions spontaeously developed in long-lived mice of strains A/St, C57BL/6 and CBA, and of (C57BL/6 x CBA) F₁, hybrids, all of which had been fed in the 2nd Department of Pathology, Gifu University School of Medicine.
Some tumors were successfully transplanted into the same strain of mice. An interesting tumor line showing phagocytic activity and growing only in the liver even when inoculated subcutaneously, which was obtained from a reticulum cell neoplasm, Type A by Dunn, originated in the liver of a (C57BL/6 X CBA) F₁ hybrid male mouse.     

IMMUNOPATHOLOGICAL STUDY OF GLOMERULAR IgA DEPOSITION IN ddY MICE

Serial renal biopsies were performed to observe in detail the age-related glomerular IgA deposition in ddY mice. Moreover, lymphocytes from spleens and Peyer's patches (PP) were immunologically examined in the mice at 10 months of age. The incidence of IgA deposition in the glomeruli was 0% at 3 months, 33% at 7 months, 60% at 10 months and 100% at 13 months, but IgA deposits were less intense than IgG and IgM deposits. Serum levels of IgA and polyclonal IgA responses of PP cells were significantly higher in the mice with glomerular IgA deposits. However, neither the Lyt-l+/Lyt-2+ cell ratio nor the polyclonal IgA responses of spleen cells were related to IgA deposition. Therefore, gut-associated lymphoreticular tissue (GALT) probably plays an important role in the pathogenesis of the high IgA response and glomerular IgA deposition observed in this strain. These results suggest that ddY mice would be valuable as a model of spontaneous glomerular IgA deposition, as well as being useful for studying the possible relationship between the mucosal immune system and glomerular IgA deposition. ACTA PATHOL JPN 38 : 1 -10, 1988.     

HUMAN TESTICULAR GERM CELL TUMORS IN VITRO and IN ATHYMIC NUDE MICE

Four cell lines derived from pure and mixed types of human testicular germ cell tumors in vitro and in nude mice were examined by light and electron microscopies. The NEC8 and NEC15 cell lines in vitro were composed of embryonal carcinoma cells with potentiality of trophoblastic differentiation. All of the tumors formed in nude mice by both cell lines were pure embryonal carcinomas. On the other hand, the NEC14 and ITO-II cell lines showed morphological differentiation from embryonal carcinoma cells to trophoblastic cells and to yolk sac tumor cells in vitro. In nude mice, these cell lines formed mixed tumors which consisted of embryonal carcinoma, yolk sac tumor, immature teratoma or trophoblastic cells. Our data suggest that some embryonal carcinomas have multipotentiality of morphological differentiation but that others have little such potentiality.     

SMALL MULTIPLE CARCINOID TUMORS OCCURRING IN THE ILEUM WITH A PSEUDOCYSTIC LIVER METASTASIS

A 49-year-old woman was admitted to the hospital with a palpable mass in the right hypochondrium. A laparotomy was performed under the clinical diagnosis of a solitary cyst of the liver. The cystic lesion of the liver was removed. Although the histological finding of the cyst wall showed a similarity to hepatocellular carcinoma of trabecular pattern, the tumor cells with uniform nuclei and little mitotic figure were positive for both argyrophil and argentaffin reaction. The pathological diagnosis was metastatic carcinoid tumor of the liver. There was no carcinoid syndrome nor the other clinical symptoms after the operation and various postoperative examinations could not reveal a primary site of the carcinoid tumor. The cystic lesion of the liver recurred ten months after the first operation and a second laparotomy was performed to reveal the primary site in the ileum: three submucosal tumors, 0.8, 0.7, and 0.3 cm. in diameter, two of them, however, extended into the muscle wall or subserosa and conclusively, the small lesion of the ileum metastasized into the liver as a large pseudocystic lesion.     

INDUCTION OF INTRACRANIAL TUMORS IN MICE BY HUMAN ADENOVIRUS TYPE 12

C₃Hf/Bi mice inoculated intracranially with human adenovirus type 12 were studied by fluorescent antibody technique and light microscopy.
The cells with fluorescent T antigens were present in the wall of the ventricles and in the epithelium of the choroid plexuses. Tumors were induced in 21 of 45 mice and the predilection sites were the olfactory bulb, the floor of the fourth ventricle and the tapetum which was in contact with the hippocampus.
The relationship between production of the T antigen and tumor development as well as histological features of the tumors was discussed.     

PROGRESSION OF PULMONARY TUMOR IN MICE 1. HISTOLOGICAL STUDIES OF PRIMARY AND TRANSPLANTED PULMONARY TUMORS*

Histological and biological observations were carried out on pulmonary tumors in mice which arose in the following four series of experiments: 1) pulmonary tumors in A/Jax and DD strain of mice which developed spontaneously or were induced by a single injection of 3-methylcholanthrene or 4-nitroquinoline-n-oxide, 2) transplanted pulmonary tumors in the first and second transfer generations, 3) tumorous growth which developed in subcutaneously transplanted lung tissues, and 4) serially transplanted pulmonary tumors in five established lines. The pulmonary tumor in mice was considered as a progressive tumor and the varieties of histology were classified into five or eight types on the basis of relationship between the histological features and the biological activities. The idea of the progression from benign to malignant stage was presented in the pulmonary tumors in mice by the author for the first time.     

MYOFIBROBLASTS IN FIBROUS TUMORS AND FIBROSIS IN VARIOUS ORGANS

The morphology and population of myofibroblasts detected by electron microscopy in fibrous tumors and fibrosis in various organs have been examined. The myofibroblast was identified by characteristic features of the indented nucleus, bundles of abundant microfilaments with dense bodies, focal basal lamina and well-developed rough endoplasmic reticulum. It has been observed that myofibroblasts in a variety of fibrous tumors and fibrosis appeared predominantly in fibromatosis and reparative process of deep fibrous tissues and organs particularly in the lesions involving the fascia and subcutaneous tissue. It was suggested that myofibroblasts would be modified fibroblasts to which fibroblasts in the fascia and deeply situated fibrous tissue transformed during proliferation and differentiation.     

EMBRYONAL RHABDOMYOSARCOMA IN NUDE MICE AND IN VITRO

A transplantable tumor strain desiǵnated YNnu and a cultured cell line desiǵnated YN were established from the human paratesticular rhabdomyosarcoma of a 15-year-old boy. In vitro the cells showed ultrastructural features of immature mesenchymal cells, and a few cells were labeled by antibodies to myoǵlobin and/or desmin. In nude mice, the cells became to contain numerous myofibrils with Z-bands, and considerable number of cells reacted with anti-myoglobin and/or anti-desmin antibodies. We conclude that spindle-shaped or small round cells are the most immature rhabdomyoblast with multiplicity for cellular differentiation. ACTA PATHOL. JPN. 36: 1495-1505, 1986.     

孤儿肽在自发性高血压大鼠和家兔心血管系统的分布

目的 研究孤儿肽（ｏｒｐｈａｎｉｎ ＦＱ,ＯＲＱ）在自发性高血压大鼠和家兔心血管系统的分布。方法 采用反转录－聚合酶链反应（ＲＴ－ＰＣＲ０法和免疫组织化学方法。结果 ＲＴ－ＰＣＲ的结果显示,ＯＦＱ的前体ｍＲＮＡ在自发性高血压大鼠的主动脉,肺动脉,肾动静脉均有较高的表达,其表达水平与脑组织表达水平相似,心房组织也有弱的表达,但在心室组织未见ＯＦＱ前体ｍＲＮＡ的表达。     

PERIARTERITIS NODOSA IN SPONTANEOUSLY HYPERTENSIVE RATS - INCIDENCE AND DISTRIBUTION—

SHR rats (Nihon Rat Inc.) were used to study spontaneous arterial lesions morphologically resembling human periarteritis nodosa (PN). Male SHR rats (159) developed PN in 76.1%, whereas females (39) in 10.3% during a period of 2 to 15 months of age. The frequency of PN in male SHR rats tended to increase with ageing and reached 100% at 9 months of age. PN lesions were widely distributed with only the lungs, brain and aorta being spared. PN in females was restricted to the tongue, parametrium and mesenterium, Male SHR rats with hypertension of more than 180 mm Hg showed PN in 81.7%, whereas in females with the same hypertension PN was found in only 17.4%. Although there was apparent sex difference in the incidence and background of hypertension, male SHR rats might be a useful animal model of human PN.     

DISTRIBUTION OF KERATIN PROTEIN IN NORMAL PROSTATE AND PROSTATIC TUMORS

Fifty cases (20 cases of benign hyperplasia, 30 cases of adenocarcinoma) of prostatic tissues were studied for expression of keratin. The basal cells were strongly and continuously positive in normal prostatic glands and in benign prostatic hyperplasia. The secretory cells and carcinoma cells were negative. The basal cells remained partially in intra-ductal carcinoma, revealing keratin positive cells in a spotty pattern. These findings may be useful in differential diagnosis between benign prostatic hyperplasia and carcinoma of the prostate.     

CYTOPLASMIC INCLUSIONS AND VIRUS-LIKE PARTICLES IN BLAST CELLS IN ACUTE LYMPHOBLASTIC LEUKEMIA

Cytoplasmic inclusions and virus-like particles are described in blast cells of peripheral blood from a 16-year-old female with acute lymphoblastic leukemia. Three kinds of inclusions were identified on electron microscopy. The first type of inclusion was single membrane-bounded vacuoles, some of which contained virus-like particles, the second was lysosome-like structures, and the third appeared to be of mitochondrial origin. Virus-like particles were round in shape and had a diameter of 26 to 58 nm. They consisted of an electrondense outer membrane and an electron-lucent core. At the present time the exact nature and significance of these virus-like particles still remain unclear.     

PATHOLOGICAL, HISTOCHEMICAL AND ULTRASTRUCTURAL STUDIES ON SEA-BLUE HISTIOCYTES AND GAUCHER-LIKE CELLS IN ACQUIRED LIPIDOSIS OCCURRING IN LEUKEMIA

Smears of bone marrow aspiration from 82 patients with leukemia and major hematopoietic organs, such as bone marrow, spleen, liver and lymph nodes, obtained from 97 autopsy cases of the disease, were light-microscopically examined. As the results, occurrence of either sea-blue histiocytes or Gaucher-like cells, or of both, was observed in bone marrow smears of 23 patients and in the hematopoietic tissues of 44 out of the examined cases, particularly marked in those of chronic myelogenous leukemia. In acute myelogenous leukemia, these lipid storage cells were also confirmed though less in frequency or degree. Histochemically, the sea-blue histiocytes were substantiated to contain ceroid-like pigments in their cytoplasm, while the lipid materials stored in the Gaucher-like cells were presumed to be glycolipids. Ultrastructural morphology of the inclusions in the sea-blue histiocytes was almost consistent with that of ceroid previously reported, but showed more marked variegated and heterogeneous features. Intracytoplasmic inclusions of the Gaucher-like cells differed from those of Gaucher cells seen in Gaucher's disease and were dominated by fibrillar or linear deposits. Transitions from phagocytized leukemic cells to the inclusions characteristic of each type of the cells were traced. ACTA PATH. JAP. 27: 775-797, 1977.     

PRODUCTION OF ALPHA-FETOPROTEIN BY HUMAN GERM CELL TUMORS IN VIVO AND IN VITRO

The production of alpha-fetoprotein (AFP) by human germ cell tumors was studied in surgical specimens, cultured cells and transplanted tumors in nude mice. AFP was detected most frequently in yolk sac (endodermal sinus) tumors, and it was also detected, though only occasionally, in embryonal carcinomas and in teratomas. AFP-positive cells in teratomas presented a glandular or hepatoid appearanece. Our experimental data suggest that AFP production in embryonal carcinomas is due to the functional expression of yolk sac differentiation preceding its morphologic expression. Although the transplanted tumors maintained the productivity of AFP, the cultured cells were not successful in maintaing a continuous AFP production.