Low susceptibility of specific inbred colonies of rats to nickel tumorigenesis in soft tissue.

Nickel sarcomatogenesis induced by a single intramuscular injection of 10 mg of nickel subsulfide (NiSS) into the soft tissue of two different colonies of Wistar rats was studied. In spontaneously hypertensive rats (SHR), a specific inbred colony of rats derived from a certain Wistar strain, the sarcoma induction rate was lower than that in common closed colony rats of the same strain (CWR). Sarcomas were induced in only 7 of the 30 rats (23.3%) in the SHR group (15 female and 15 male) but in 21 of the 31 rats (67.7%) in the CWR group (15 female and 16 male) (P < 0.005). The incidence of sarcoma induction was lower in female rats than in male rats in both the SHR (female 13.3% < male 33.3%) and CWR (female 53.3% < male 81.4%) groups. Primary tumors in the SHR group exhibited a lower grade of metastasis to lymph nodes (P < 0.001) and lungs (P < 0.05) than in the CWR group. Our study demonstrated that rats in a certain specific inbred colony are less susceptible to nickel tumorigenesis in soft tissue than rats in a common closed colony.

Noradrenergic hyperinnervation may inhibit necrosis of coronary arterial smooth muscle cells in stroke-prone spontaneously hypertensive rats.

Noradrenergic (NA) nerve fibre distribution and vascular smooth muscle morphology were investigated in the coronary artery of stroke-prone spontaneously hypertensive rats (SHRSP). Fluorescent NA nerve fibres of SHRSP aged 10, 30, 60, 90 and 180 days were examined by the glyoxylic acid method and compared with those of age-matched normotensive Wistar Kyoto (WKY) rats. The distribution densities of NA nerve fibres were measured by quantitative image analysis using the Interactive Bildanalyse System. The densities of NA nerve fibres of the left coronary artery of SHRSP were significantly higher than those of WKY rats at all ages examined. NA hyperinnervation in the coronary artery of SHRSP may be caused by the hyperfunction of the stellate ganglia which innervate the coronary arteries. Scanning electron microscopy observations showed that the surface of smooth muscle cells of the left coronary artery in SHRSP was smooth and similar to that of WKY rats at 120 days of age, but was slightly modified by more invaginations and projections than that in WKY rats at 180 days of age. No necrotic cells, however, were found in SHRSP. By transmission electron microscopy the smooth muscle cells in SHRSP were shown to be irregular in profile with deep indentations of the plasma membrane and surrounded by many layers of basal laminalike material, but no necrotic cells were found. We suggest that NA hyperinnervation protects the vascular smooth muscle cells from necrosis in the coronary artery of SHRSP by a trophic effect mediated by NA nerve fibres.

Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats (SHRSP).

Noradrenergic (NA) nerve fiber density was investigated in the subepicardium and myocardium of ventricles in stroke-prone spontaneously hypertensive rats (SHRSP) and was compared with that of normotensive Wistar Kyoto (WKY) rats. Fluorescent NA nerve fibers in the subepicardium of the right and left ventricles of both strains at the ages of 10, 30, 60, 90, and 180 days were examined by the glyoxylic acid method. NA nerve fibers in the myocardium of the right and left ventricles and the ventricular septum of both strains at the ages of 30, 90, and 180 days were also examined in a similar manner. The density of NA nerve fibers was measured by quantitative image analysis. The distribution pattern of NA nerve fibers in the entire subepicardium of ventricles of both strains showed a meshwork pattern throughout the examination period. In sections of the myocardium, NA nerve fibers were distributed between heart muscle cells and around blood vessels in both strains at all ages examined. The densities of NA nerve fibers in the subepicardium of the ventricles of SHRSP were significantly higher than those of WKY rats at all ages examined except for the subepicardium of the left ventricle at 90 days of age. The densities in the myocardium of the right ventricle in 30- and 90-day-old SHRSP were significantly higher than those in WKY rats. The ratios of NA nerve fiber density of SHRSP to that of WKY rats were greater in the subepicardium of the right and left ventricles, except at 90 days of age, and in the myocardium of the right ventricle of younger animals as compared with older ones. NA hyperinnervation in the subepicardium and myocardium of the ventricles of SHRSP may be a primary change of the heart before the onset of hypertension and may be caused by hyperfunction of the stellate ganglia.

Immunoreactivity to neurohormonal polypeptide in colorectal carcinomas and tumor-neighboring mucosa, and its significance.

OBJECTIVE: To clarify whether advanced colorectal carcinomas possess an amphocrine nature and produce both pancreatic and gut neurohormonal polypeptide and epithelial mucin in comparison with surrounding colorectal mucosa. DESIGN: Retrospective analysis of paraffin-embedded specimens from 100 cases of colorectal carcinoma (39 colonic and 61 rectal) and surrounding mucosa, with histochemical and immunohistochemical studies. RESULTS: The immunoreactivity of the carcinomas and surrounding mucosa by the labeled streptavidin-biotin complex method for polyclonal rabbit antibody against human vasoactive intestinal polypeptide, pancreatic polypeptide, and somatostatin was 61%, 59%, and 82% respectively; that of mucosa neighboring immunoreactive tumors was 87%, 85%, and 90%; and that of mucosa neighboring nonimmunoreactive tumors was 67%, 63% and 61%. Double staining for different types of neurohormonal polypeptide revealed that most carcinoma cells had a multiendocrine nature, and a number of neurohormonal polypeptide--positive and epithelial mucin-positive carcinoma cells (amphocrine cells) were found in almost every histological type of carcinoma by double staining for immunoreactivity and periodic acid-Schiff reaction or mucicarmin. CONCLUSION: Colorectal carcinomas exhibit not only multiendocrine characteristics, producing various types of neurohormonal polypeptide, but also amphocrine characteristics of different grades, and most tumor-neighboring crypt cells possess those characteristics, too. We concluded that these characteristics of colorectal carcinomas may be related to their origin as multipotential endodermal stem cells.

Coenzyme A-independent monoacylglycerol acyltransferase from rat intestinal mucosa.

Rat intestinal mucosa contains high diacylglycerol-synthesizing activity (monoacylglycerol acyltransferase (MGAT) activity) due to monoacylglycerol and fatty acid, independently of coenzyme A and ATP. MGAT activity was purified from rat intestinal mucosa by successive chromatography separations on DEAE-cellulose, CM- Sephadex, and anti-IgG-Sepharose against rat pancreatic lipase. The enzyme was electrophoretically homogeneous, and its molecular weight was 49,000, which is identical with that of rat pancreatic lipase. Immunoblotting analysis with antibody against rat pancreatic lipase showed one immunoreactive protein with an estimated molecular weight of 49,000. The activity of the purified enzyme was completely inhibited by addition of the antibody. Using immunocytochemical techniques, it was found that immunoreactive protein against rat pancreatic lipase was uniformly distributed within the absorptive cells of the intestine but was absent from the microvillar membrane. The MGAT activity of intestinal mucosal homogenate was inhibited by about 65% by addition of antibody against rat pancreatic lipase. Trioleoylglycerol- and dioleoylglycerol-hydrolyzing activities of the purified enzyme and pancreatic lipase were inhibited by addition of intestinal mucosa extract. These results suggest that pancreatic lipase is present in intestinal absorptive cells and that it may contribute to resynthesis of diacylglycerol from monoacylglycerol and fatty acids in these cells.

Characteristics of MHC antigen expression and tumor-infiltrating mononuclear cells in renal cell adenomas and carcinomas.

We compared the expression of major histocompatibility complex (MHC; HLA class I and II) antigens and the presence of tumor-infiltrating mononuclear cells presenting S100 protein (S100), CD68 antigen, or CD45RO antigen in formalin-fixed, paraffin-embedded tissue sections of 10 renal cell carcinomas and 9 renal cell adenomas using immunohistochemistry. The expression of beta 2-microglobulin (B2MG) as an HLA class I antigen in all 10 cases (100%) and that of HLA-DR/alpha as an HLA class II antigen in 7 of 10 cases (70%) of carcinoma was stronger than that in the adjacent proximal convoluted tubule, but was respectively not different to weaker in 8 of 9 cases and not different to markedly weaker in all cases of adenoma. Furthermore, there was comparatively dense infiltration by S100(+) antigen-presenting cells in the carcinomas, but almost none in the adenomas and generally dense infiltration by CD45RO(+) T cells and CD68(+) macrophages in the carcinomas, but little to none in the adenomas. We concluded that the generally enhanced expression of MHC antigens in carcinomas must be an immunophenotypic deviation from not only the adjacent proximal convoluted tubule but also adenomas, and that the predominant infiltration of antigen-presenting cells, T cells and macrophages in the carcinomas, but not in the adenomas, reflects the anti-cancer immune reaction.

Pericardial malignant mesothelioma: case report and discussion of immunohistochemical and histochemical findings.

An extremely rare case of malignant mesothelioma of the pericardium is reported. The tumor appeared to be the biphasic type of diffuse malignant mesothelioma which present many small to fine lipid droplets in the cytoplasm, particularly that of the epithelial cell, and a positive immunohistochemical reaction with antibodies to low molecular weight cytokeratin (45-50 kDa) in all of the tumor cells. The literature is also reviewed and the presence of lipid droplets and the importance of the immunohistochemical positivity to low molecular weight cytokeratin for differential diagnosis from other malignant tumors, such as invasive adenocarcinoma or primary sarcoma of the pleura, or soft tissue sarcoma involving the pleura is discussed.

Noradrenergic hyperinnervation in the caval vein of stroke-prone spontaneously hypertensive rats.

1. The distribution of fluorescent noradrenergic (NA) nerve fibres in the caval vein, which originate from the coeliac ganglion, was examined by glyoxylic acid method in stroke-prone spontaneously hypertensive rats (SHRSP) aged 10, 30, 60, 90 and 180 days. The results were compared with those in age-matched normotensive Wistar Kyoto (WKY) rats. 2. The distribution pattern of NA nerve fibres in the caval vein in both strains changed from a meshwork pattern at 10 days of age to a wavelike line arrangement after 30 days of age. 3. The densities of NA fibres of the caval veins in SHRSP were significantly higher (P < 0.01, Student's t-test, 6 d.f.) than those of WKY at all ages examined. The difference in NA fibre density between SHRSP and WKY showed double peaks at 10 and 90 days of age. 4. The present study suggests that hyperinnervation of the caval vein based on the hyperfunction of the coeliac ganglion is an important factor in the development of hypertension and also may participate in increasing cardiac output because the heart of SHR causes marked hypertrophy from 90 days of age.

Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats.

1. Noradrenergic (NA) nerve fibre distribution was investigated in the epicardium and myocardium of the heart in stroke-prone spontaneously hypertensive rats (SHRSP) and was compared to that in normotensive Wistar-Kyoto (WKY) rats. Fluorescent NA nerve fibres in the left and right epicardium of both strains aged 10, 30, 60, 90 and 180 days, and in the myocardium of left and right ventricles and the ventricular septum of both strains aged 30, 90 and 180 days were examined by the glyoxylic acid method. The distribution densities of NA nerve fibres were measured by quantitative image analysis. 2. The distribution pattern of NA nerve fibres in the epicardium of both strains showed a constant meshwork pattern throughout the entire examination period. 3. In the myocardium, NA nerve fibres were distributed irregularly between myocytes of both strains in all ages examined. 4. The densities of NA nerve fibres in the epicardium of SHRSP were significantly higher (P < 0.01 and 0.05; Student's t-test, 6 d.f.) than those of WKY at all ages examined except left epicardium at 90 days of age. 5. The densities in the right myocardium in 30 and 90 day old SHRSP were significantly higher (P < 0.05; Student's t-test, 6 d.f.) than those of WKY. 6. NA hyperinnervation in the epicardium and the myocardium of SHRSP may be assumed to be caused by the hyperfunction of the stellate ganglia which innervate the heart and may give rise to hypertrophy of the heart in SHRSP by a trophic effect of NA nerve fibre.

CA125-producing adenocarcinoma of the seminal vesicle.

A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. Immunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CA125, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin.

Effects on tumor induction, growth, metastasis and histology of concurrent administration of putrescine and its metabolizing inhibitor alpha-difluoromethylornithine in nickel tumorigenesis in soft tissue.

The effects of putrescine and the inhibitor of its biosynthesis alpha-difluoromethylornithine (DFMO) on nickel tumorigenesis in soft tissue was studied. Three groups of female F-344 rats were injected i.m. with 10 mg of nickel subsulfide (NiSS) in the right hind leg, after which one group was administered 200 mg/kg body wt of putrescine (i.p.) once a week, and one group was administered 0.2% DFMO in the drinking water for 32 weeks until termination. The DFMO-treated group exhibited longer tumor induction time, lower tumor growth rate and significantly lower metastatic rate, whereas the putrescine-treated group exhibited a temporarily higher tumor growth rate than the NiSS-only group. Histologically, the putrescine-treated group and especially the DFMO-treated group frequently exhibited differentiated sarcomas but the NiSS-only group exhibited anaplastic sarcomas. The present study demonstrated that long-term administration of DFMO has an inhibitory effect on tumors and metastasis, and induces differentiation of tumor cells from anaplastic round cells to well-differentiated pleomorphic cells in NiSS tumorigenesis in soft tissue.

Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum. A histochemical and immunohistochemical study.

An unusual case of multicentric ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum was studied, with special attention given to the histogenesis of these neoplasms. A total of six ileal carcinoids, the largest of which was located in the wall of Meckel's diverticulum, were macroscopically and microscopically confirmed to be multicentric and revealed no visceral metastases. The histochemical and immunohistochemical profiles of the ileal carcinoids and the appendiceal carcinoma differed considerably: the former resembled subepithelial neuroendocrine cells and the latter resembled epithelial nonmucous cells and Paneth cells. The appendiceal carcinoma exhibited signs of endocrine differentiation, expressing somatostatin and vasoactive intestinal polypeptide, and secreted mucus. The tumor had metastasized to various organs. The carcinoids exhibited signs of neuroendocrine and glandular differentiation, expressing neuron-specific enolase, serotonin, chromogranin A, and endocrine granule constituent, and secreted little mucus. The data suggest different tumor cell origins or different grades of differentiation of the two types of intestinal endocrine cell tumor.

Adenoendocrine cell carcinoma of the gallbladder: a histochemical and immunohistochemical study.

A case of adenoendocrine cell carcinoma of the gallbladder with adenomucous cells and neuroendocrine cells is reported. A histochemical and immunohistochemical study revealed that the primary tumor in the gallbladder was composed of mucus-secreting and/or argyrophil cells. Furthermore, the tumor showed a positive reaction to carcinoembryonic antigen (CEA) in all tumor cells, to chromogranin A and cytokeratin in many tumor cells, to endocrine granule constituent (EGC) in some tumor cells, and to serotonin and somatostatin in a few tumor cells. In addition, a few mucous cells showed argyrophilia and EGC-positivity in their cytoplasms. This case suggests that the adenoendocrine cell tumor is derived from endodermal stem cells as a result of bidirectional (exocrine and endocrine) differentiation.

Sympathetic hyperinnervation protects vascular smooth muscle cells from necrosis in stroke-prone spontaneously hypertensive rats.

Sympathetic nerve fiber distribution and vascular smooth muscle morphology were investigated in the ophthalmic artery of stroke-prone spontaneously hypertensive rats (SHRSP) and were compared with those of normotensive Wistar Kyoto (WKY) rats at the age of 120 days. The distribution of fluorescent noradrenergic (NA) nerve fibers was examined by the glyoxylic acid method. The ophthalmic artery was divided into two portions according to the size of the outer diameter, that is into a proximal portion (above 100 microns) and a distal portion (30-70 microns). The distribution densities of noradrenergic nerve fibers were measured by quantitative image analysis using the Interactive Bild-Analyse System (IBAS). The distribution densities of NA nerve fibers in both portions of the ophthalmic artery were significantly higher (p < 0.01) in SHRSP than that in WKY rats. The difference in the density of NA fibers of the ophthalmic arteries between SHRSP and WKY rats was 1.9 times in the proximal portion and 1.5 times in the distal portion. The vascular smooth muscle cells of the ophthalmic arteries in SHRSP were observed by scanning electron microscope to examine the trophic effect of NA nerve fibers on the vascular smooth muscle cells. The smooth muscle cells of both portions of the ophthalmic arteries in SHRSP showed a smooth surface texture and no necrosis, and were very similar to those of WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Warthin's tumor as a hamartomatous dysplastic lesion: a histochemical and immunohistochemical study.

The etiology of Warthin's tumor was sought by histochemical and immunohistochemical methods using 7 surgically extirpated samples and normal salivary glands as a control for the epithelial component. All the samples exhibited a variety of amyloid deposition in the interfollicular area of the lymphoid component. The interfollicular lymphoid cells were both T-cells and cells of B-cell lineage with an almost 1 to 2 population ratio. Most antigen-positive B-cells were plasma cells that exhibited polyclonality of immunoglobulin. B-cells were also present in the lymphoid mantles and a few were found in the germinal centres. The epithelial component exhibited mucinous and proteinaceous fluid in the lumen and varied immunohistological reactions; being particularly positive to carcinoembryonic antigen, S-100 protein, and B-cell antigen; quite similar to that of normal salivary duct cells. The results suggest that Warthin's tumor may not be a hamartomatous neoplasm at all but a hamartomatous dysplastic lesion.

Increased density of fluorescent adrenergic fibers around the middle cerebral arteries of stroke-prone spontaneously hypertensive rats.

The distribution of fluorescent adrenergic nerve fibers in the proximal portion (horizontal segment, Hs) and the three distal portions (major branches) of the middle cerebral arteries (MCA) was examined in stroke-prone spontaneously hypertensive rats (SHRSP) aged 10, 30, 60, 90, and 180 days, by the glyoxylic acid method. The results were compared with those in age-matched normotensive Wistar Kyoto (WKY) rats. While the distribution pattern of fluorescent nerve fibers in the proximal portion of WKY rats changed from a straight linear arrangement at 10 and 30 days of age to a network-like arrangement after 60 days, those from SHRSP showed a constant meshwork pattern throughout the entire examination period. In the distal portions of the MCA of both SHRSP and WKY rats at all ages examined, fluorescent nerve fibers formed a coarse network. The distribution densities of adrenergic nerve fibers in the proximal and distal portions of the MCA of SHRSP were significantly higher (P less than 0.01 and 0.05) than those of WKY rats at all ages examined, except in the proximal portion at 90 and 180 days of age. The difference in nerve fiber density between SHRSP and WKY rats reached a peak at 30 days of age in both proximal and distal portions, and then gradually decreased with age. The present study suggests that sympathetic hyperinnervation is an important factor in the development of hypertension, and is involved in its maintenance in SHRSP.

The role of bone fracture at the site of carcinogen exposure on nickel carcinogenesis in the soft tissue.

The influence upon nickel subsulfide (alpha-Ni3S2; Ni-SS)-induced carcinogenesis in the soft tissue of bone fracture at the site of Ni-SS exposure was studied using female Fischer rats. During the one year of the experiment, the group subjected to bone fracture exhibited the shortest tumor induction time and survival time, and a significantly higher metastatic rate. The present study may suggest a model for the metastasis of human soft tissue tumors.

Interleukin-2 receptor antigen, leukocyte common antigen, and Ki-1 antigen-expressing gastric plasmacytoma. A case report with an immunohistochemical study.

A case of primary gastric plasmacytoma expressing various surface and cytoplasmic antigens is reported. With the use of formalin-fixed and deparaffinized sections, 13 different antibodies were applied. Neoplastic plasma cells revealed monoclonal IgG and kappa light chain in the cytoplasm, and expressed epithelial membrane antigen, Ki 67 antigen, cytokeratin, CD 22 antigen, interleukin-2 receptor antigen, leukocyte common antigen and Ki-1 (CD 30) antigen. However, tumor cells were devoid of HLA-DR antigen. These data suggest that the neoplastic plasma cells are at the plasmoblastic stage of maturation and express various surface and cytoplasmic phenotypes.

Morphometric study of the superior cervical and stellate ganglia of spontaneously hypertensive rats during the prehypertensive stage.

To compare the functional state of the superior cervical (SCG) and stellate sympathetic ganglia (SG) of spontaneously hypertensive rats (SHR) with those of age-matched normotensive Wistar Kyoto rats (WKY), ganglion cell volume and area occupied by ganglion cells relative to each whole ganglionic area were morphometrically examined using the Texture Analyse System (TAS) in rats at 0, 10 and 30 days of age. The weight of each ganglion relative to animal weight was also measured. The ganglion cell volume and the relative area of ganglionic cells in both ganglia of SHR were significantly larger (P less than 0.05) than those of age-matched WKY at ages 0 and 10 days after birth. The relative ganglionic weights of SHR were significantly larger (P less than 0.01) compared with those of WKY at all ages examined, except for SG at 0 days after birth. These results show that the relative volume of sympathetic ganglion cells is greater in both SCG and SG of SHR than that of WKY, suggesting that hyperfunction of sympathetic ganglia occurs at the prehypertensive stage as a primary factor in the development of hypertension in SHR.

Morphological changes in cerebral vascular smooth muscle cells in stroke-prone spontaneously hypertensive rats (SHRSP). A scanning and transmission electron microscopic study.

The ultrastructure of the vascular smooth muscle cells of the middle cerebral artery in 6-month-old male stroke-prone spontaneously hypertensive rats (SHRSP) was studied by scanning (SEM) and transmission electron microscopy (TEM) and compared with that of age-matched normotensive Wistar Kyoto rats (WKY). Although the smooth muscle cells of WKY rats by SEM had a typical spindle shape and smooth surface texture, those of SHRSP were structurally modified by numerous surface invaginations and projections, bearing some structural resemblance to the myotendinous junction of skeletal muscle. Structural modifications affected more than half the surface of medial smooth muscle cells in SHRSP, but less than 0.6% of the surface of these cells in WKY rats. About 10% of medial smooth muscle cells were necrotic in SHRSP, but no necrotic cells were identified in WKY rats. By TEM, smooth muscle cells in SHRSP were shown to be irregular in profile with deep indentations of the plasma membrane and were surrounded by many layers of basal lamina-like material. The present study suggests that most smooth muscle cells in the middle cerebral artery of SHRSP may be modified to adapt to chronic hypertension by increasing the junctional area between muscle cells and connective tissue and that some cells may undergo necrosis.