Hypothalamic 11,12-epoxyeicosatrienoic acid attenuates fever induced by central interleukin-1beta in the rat

Inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that the metabolite of the enzyme is candidate of endogenous antipyretic. Cytochrome P-450 of arachidonic acid cascade leads to the formation of regioisomeric 5,6-, 8,9- 11,12- and 14,15-epoxyeicosatrienoic acid (EET). Various isomers of EET were administrated into the preoptic area and anterior hypothalamus (PO/AH) to test their influence on fever induced by interleukin-1β (IL-1β) administrated into the PO/AH in conscious rats. The IL-β-induced fever was attenuated in the 11,12-EET-pretreated rats, although 5,6-, 8,9- and 14,15-EET did not affect the fever. Intra-PO/AH injection of 11,12-EET did not alter normal body temperature. The results suggest that 11,12-EET acts in the hypothalamus as an endogenous antipyretic.     

Histological differences between sternal and iliac bone marrow in various hematological diseases

Even in normal state, hematopoietic activity is different in terms of the site of bone marrow as well as age. The activity may also differ with bone marrow site in various hematological diseases. We chose 32 cases with various hematological diseases and examined their bone marrow histologically at two different sites (sternum and posterior iliac crest) at almost the same time. We studied the histological differences in 5 cases of malignant lymphoma, 15 cases of aplastic anemia, 8 cases of myelodysplastic syndrome, 2 cases of myeloproliferative syndrome and 2 cases of acute leukemia. In malignant lymphoma, the iliac marrow was slightly hypoplastic compared with sternal marrow but there were no differences in the components of hematopoietic cells, that were thought to reflect normal hematopoietic activity for their respective ages. In 5 among 15 cases of aplastic anemia, nodular hyperplastic areas were observed in sternal marrow even though iliac marrow was severely hypoplastic. The presence of a nodular hyperplastic area is useful for differential diagnosis between aplastic anemia and refractory anemia, because such a histological change was not observed in the cases of refractory anemia. In myeloproliferative syndrome and acute leukemia, there were no differences between sternal and iliac marrow. They were hyperplastic and had almost the same hematopoietic components.     

THE ROLE OF ENDOTHELIAL CELLS IN THE PATHOGENESIS OF ATHEROSCLEROSIS

Using mainly rabbits and rats investigations on the endothelial permeability of the aorta, on relation between thrombus formation and endothelial damage, and on tissue culture of the endothelial cells of the rabbit aorta have been carried out.
The permeability of endothelial layer of rabbit aorta Increased by cholesterol-feeding. This seems to be derived from morphological and functional disorder of the endothelial cells. As a hemodynamic effect of blood flow, increased permeability of the endothelium of rat aorta was also found in experimental renal hypertension.
Accumulation of blood-plasma components (edema) was seen in the subendothellal area in cholesterol-fed rabbit aorta and in hypertensive rat aorta. Long-standing subendothellal edema is considered to be the cause of fibrous intlmal thickening (Grade I lesion/Nakashlma).
Endothelial defect of the aorta due to various damages is related to thrombus formation, and this seems to be accelerated by cholesterol feeding.
Morphological differences between normal endothelium and that of atherosclerotic lesion in human and in rabbit aortas can be seen.
Tissue culture of the endothelium was performed in vivo and in vitro, and some discussions were made on the characteristics of cultured endothelial cells.     

Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis

Hypervascularity is a characteristic synovial feature of rheumatoid arthritis (RA). We previously reported that Tie1 and Tie2, endothelium-specific tyrosine kinase receptors essential for angiogenesis, are expressed not only by vascular cells, but also by a subpopulation of synovial lining and stromal cells in the inflamed RA synovium. The present study used immunohistochemistry and in situ hybridization to examine whether angiopoietin-1 and -2 (Ang1 and Ang2), ligands for Tie2, are also expressed in the RA synovium. Ang1 and Ang2 were expressed in all of 15 RA synovial samples, and their distribution pattern was similar to that of Tie2. Intense staining was noted in synovial lining and stromal cells, as well as in small vessels in areas of papillary projection and high cell density. Double immunohistochemistry revealed coexpression of Ang1, Ang2, and Tie2 in synovial components exhibiting proliferating cell nuclear antigen immunoreactivity. In addition, Ang1 and Ang2 were preferentially expressed in vimentin-positive fibroblastic cells. To address the functional role of Ang/Tie signaling in RA pathophysiology, we carried out [(3)H]thymidine incorporation and transwell chemotaxis assays using cultured fibroblastic synoviocytes obtained from 2 RA patients. Incubation with various concentrations of recombinant Ang1 or Ang2 did not alter DNA synthesis, but the ligands enhanced chemotactic migration of RA fibroblastic synoviocytes. Our results suggest that the autocrine/paracrine signaling of the Ang/Tie2 system is important for the up-regulated angiogenesis in the RA synovium, as well as for synoviocyte behavior, by regulating chemotactic cell movement.     

Cell size and oxidative enzyme activity of different types of fibers in different regions of the rat plantaris and tibialis anterior muscles

The cross-sectional areas and succinate dehydrogenase activities of different types of fibers in different regions of the plantaris and tibialis anterior muscles in 10-week-old male rats were determined using quantitative histochemistry. The muscle fibers were classified as type I, type IIA, or type IIB according to their adenosine triphosphatase activities. There were no regional differences in either the mean cross-sectional area or the mean succinate dehydrogenase activity of type IIA fibers in both muscles. In contrast, type IIB fibers in the deep region of both muscles had smaller cross-sectional areas and higher succinate dehydrogenase activities than those in the superficial and middle regions. These data suggest the presence of regional differences in the cross-sectional area and succinate dehydrogenase activity of type IIB fibers in the muscle.     

Effects of leukocytic pyrogen and sodium salicylate on hypothalamic thermosensitive neurons in vitro

The membrane mechanisms associated with Cl- conductance activated by GABA in spinal and hippocampal neurons cultured from the embryonic mouse and rat have been studied with voltage- and patch-clamp techniques. The elementary mechanism underlying the conductance response is predominantly all-or-none with both similar and different kinetics in different assays. beta-Alanine and glycine also alter conductance via a similar mechanism, but the electrical properties associated with each transmitter are unique. Clinically important drugs modulate GABA-mediated responses by altering the kinetics of ion channel activity. Inhibitory synaptic currents whose time constant of decay coincides with the common, slower phase of channel kinetics in pharmacological experiments are altered in amplitude and/or time course by the same drugs. The results strongly suggest that the synaptic events reflect the activation of 1700 channels whose open-time distribution describes the time constant of decay.     

Acute renal injury by tetraethyl orthosilicate in mice: ultrastructure, histochemistry and X-ray microanalysis.

Tetraethyl orthosilicate (Si(OC2H5)4, or TEOS) is a silicon-containing compound which has widespread industrial applications and which has been documented as biohazardous. The histopathological features and mechanism of TEOS toxicity in the kidney of ICR mice were investigated in a light and electron microscopy study, which included energy dispersive X-ray microanalysis. TEOS was given to mice as intraperitoneal injection of approximately 1,670 mg/kg body weight in experiments based on a 24 h time-scale. Tissues were examined after sampling either immediately on death if this occurred within 24 h or, in the case of surviving animals, after sacrifice at 24 h. Renal injury was considered to be the most probable cause of death, on the basis of the following main findings: 1) acute tubular necrosis (glomerular lesions were absent); 2) a dense deposit of silicon over the microvilli of dead tubular epithelial cells; 3) an abundant aggregation of hydroxyapatite crystals containing calcium in the cytoplasm and mitochondria of the dead tubular epithelial cells; and 4) abundant myelinosomes and some hydroxyapatite crystals in the cytoplasm of viable proximal convoluted tubule epithelial cells. It was speculated that silicon compounds may bind to the plasma membranes of the proximal convoluted tubule epithelial cell microvilli and damage or interfere with membrane calcium channels. The resulting calcium ion imbalance may play a role in the subsequent progression of acute tubular necrosis by TEOS.     

Intimal sarcoma of the pulmonary artery: report of an autopsy case

Primary pulmonary artery sarcomas (PASs) are rare and lethal tumors. They are easily misdiagnosed as chronic pulmonary embolism, mediastinal mass or tumor emboli, which delay a proper treatment. Although the advanced technologies are now increasingly being used, their diagnosis is usually hard to establish preoperatively at the present time. We report here a case of a 68-year-old female with PAS with lung metastases, who firstly presented with symptoms of common cold and anemia. Although a PAS had been suspected, the final diagnosis of pulmonary intimal sarcoma was made only postoperatively by histological and immunohistochemical examination. The patient died 8 months after the operation because of tumor growth progression, despite adjuvant chemotherapy and radiation therapy. Although pulmonary intimal sarcomas are usually of poorly differentiated mesenchymal malignancy, most reported cases are immunohistochemically positive for vimentin, alpha-smooth muscle actin (SMA), and/or desmin, therefore resembling leiomyosarcomas. However, the diagnosis of leiomyosarcoma should not be made on the basis of immunostains in the absence of typical morphologic features, and PAS, like the present case, should be more appropriately classified as intimal sarcoma according to the new WHO Classification of Tumours of Soft Tissue and Bone published in 2002.     

Immunohistochemical studies of DMBA-induced rat mammary tumors

In order to clarify the biological characteristics of rat mammary tumors induced by 7,12-dimethylbenz-[a]-anthracene (DMBA), histochemical and immunohistochemical studies were performed. Two types of luminal spaces were observed within the tumor. In one type, the lumen was surrounded by eosinophilic columnar cells which were strongly reactive for soybean agglutinin (SBA) but weakly stained with keratin antibodies. In the luminal spaces, substances positive for PAS, dialyzed iron ferrocyanide or alcian blue and resistant to mucopolysaccharidase were occasionally observed. Ultrastructurally, the luminal surface was characterized by the presence of microvilli and tight junctions. In the other type, the lumen was often found in highly cellular foci and surrounded by pale, polygonal or elongated cells which were weakly stained with keratin antibodies but not SBA. The luminal spaces presented a peculiar structure filled mainly with mucoid substances sensitive to hyaluronidase, chondroitinase ABC and heparitinase, and the inner surface of the spaces was surrounded by basement membrane components: laminin, fibronectin and type IV collagen. The results of the present study therefore showed that DMBA-induced mammary tumor consists, partly, of a structure resembling human adenoid cystic carcinoma.     

Small cell carcinoma of the endometrium: report of a case with analysis of Wnt/beta-catenin pathway

Small cell carcinoma of the endometrium (SCCE) is extremely rare. Previous reports indicate that SCCE frequently shows systemic spread and has a poor prognosis. Beta-catenin has been shown to be a key downstream effector of the Wnt signaling pathway, which regulates cell growth and survival. Decreased membranous expression of beta-catenin in cancers correlates with poor prognosis and is associated with dissemination of tumor cells and the formation of metastases. Recently, some different investigators demonstrated aberrant beta-catenin accumulation in neuroendocrine tumors arising in different organs, suggesting a role for the Wnt/beta-catenin signaling pathway during neuroendocrine tumorigenesis. Here, we report a new case of SCCE associated with peritoneal spreading and aggressive course; the patient died one month after surgery. This study also aimed at assessing the involvement of the Wnt signaling pathway in this rare neuroendocrine tumor. Interestingly, both intense nuclear beta-catenin accumulation and cyclin D1 immunoreactivity were restricted to carcinoma cells invading lymphatic vessels. However, mutation analysis failed to demonstrate any mutation in exon 3 of the beta-catenin gene or exon 15 of the APC gene in the present case. Although the mechanism of nuclear accumulation of beta-catenin is still unknown, the heterotopic nuclear localization of beta-catenin may play a role in the tumor invasion process and, subsequently, may be associated with the aggressive behavior of SCCE.