Immunoelectron microscopic localization of carcinoembryonic antigen in gastric adenocarcinoma cell lines

The distribution of carcinoembryonic antigen (CEA) in human gastric adenocarcinoma cell lines (HPE-GAC-3 cells and HPE-GAC-2 cells) was determined immunohistochemically by indirect peroxidase-labeled antibody method at the light and electron microscopic levels. In GAC-3 cells that proliferated as non-adherent single cells, CEA was located in the perinuclear spaces, the endoplasmic reticulum, Golgi apparatus, vesicles, multivesicular body (MVB) and entire plasma membrane. Membrane CEA was shown to be internalized into MVB in GAC-3 cells. In GAC-2 cells that form an acinus, CEA was predominantly present along the microvilli of the lumina) surface and in glycocalyceal bodies, the vesicles which bud from the microvilli into the lumen. These results suggest that in poorly differentiated cancer cells CEA is transported over the entire cell surface, retained on the membrane and accumulated Into the cell by way of the MVB, but in well differentiated cancer cells the newly synthesized CEA is rapidly and predominantly transported to the luminal surface and rapidly released from the membrane into the lumen by way of the glycocalyceal body.     

Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain

Background: We previously reported that the homozygous mutation of Otx2 gene, a mouse cognate of the Drosophila head gap gene orthodenticle , causes failure in the development of the rostral head anterior to rhombomere 3, which may correspond to earlier Otx2 expression in cells destined for the anterior mesoendoderm. At the same time, the Otx2 heterozygous mutation displayed a phenotype characterized as otocephaly, probably related to expression in the anterior neuroectoderm at the subsequent pharyngula stage. Defects were characteristic in the most anterior and posterior regions of Otx2 expression where Otx1 , another mouse cognate of orthodenticle , is not or weakly expressed. They were not found in the region where Otx1 is expressed.
Results: In the present work, Otx1 null mutant mice were generated by gene targeting in embryonic stem cells. No defects were apparent in the regionalization of the early embryonic rostral brain. The newborn brain defects were subtle and most likely related to later Otx1 -unique expression. Otx1 and Otx2 double heterozygous mutant brains, however, exhibited marked defects throughout the fore- and midbrains, where defects were not apparent with a single mutation alone.
Conclusions: Otx1 and Otx2 play synergistic roles in the development of the forebrain and midbrain where both genes are expressed.     

Protective role of heme oxygenase-1 in renal ischemia

Oxidative stress, which has been implicated in the pathogenesis of ischemic renal injury, degrades heme proteins, such as cytochrome P450, and causes the elevation in the level of cellular free heme, which can catalyze the formation of reactive oxygen species. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is induced not only by its substrate, heme, but also by oxidative stress. In various models of oxidative tissue injuries, the induction of HO-1 confers protection on tissues from further damages by removing the prooxidant heme, or by virtue of the antioxidative, antiinflammatory, and/or antiapoptotic actions of one or more of the three products, i.e., carbon monoxide, biliverdin IXalpha, and iron by HO reaction. In contrast, the abrogation of HO-1 induction, or chemical inhibition of HO activity, abolishes its beneficial effect on the protection of tissues from oxidative damages. In this article, we review the protective role of HO-1 in renal ischemic injury, and its potential therapeutic applications. In addition, we summarize recent findings in the regulatory mechanism of ho-1 gene expression.     

General Pathology Of Kawasaki Disease

Systemic pathological alterations were studied in thirty-seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct-adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.     

Malignant phyllodes tumour with a noninvasive ductal carcinoma component

 A malignant phyllodes tumour with a noninvasive ductal carcinoma component is reported. The patient was an 80-year-old Japanese woman with a breast tumour detected by routine physical examination. A simple mastectomy was performed. The excised tumour was 10.5×9.4×5.4 cm in size and bulged into the skin with ulceration. The macroscopic appearance was that of a phyllodes tumour. Histologically the tumour consisted mainly of stromal components with a leaf-like structure lined by atypical ductal epithelium. The epithelial component showed gradual evolution to intraductal papillary carcinoma in a few areas. The stromal component was composed mainly of fibrosarcoma with areas of osteosarcoma and rhabdomyosarcoma. Neither stromal invasion of intraductal carcinoma nor transition between the stromal and epithelial elements was seen. Three months after the operation, death occurred, with multiple pulmonary and subcutaneous metastases. This case probably represents malignant change in both the stromal and the epithelial components of a phyllodes tumour. Since the two elements were independent, the possibility that a phyllodes tumour may be one of the origins of true carcinosarcoma is raised. Received: 11 March 1997 / Accepted: 5 May 1997     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.     

NEURAL INVOLVEMENT IN KAWASAKI DISEASE

Neurological findings and histopathology of the nervous system were studied in 30 patients with Kawasaki disease.
As neurological manifestations, irritability, lethargy, meningeal signs such as nuchal rigidity, Kernig's sign, and opisthotonus, and facial nerve paralysis were present in 8 patients. In 9 out of 11 patients who had examination of cerebrospinal fluid, pleocytosis mainly consisting of lymphocytes and mononuclear cells was seen. Protein and glucose concentrations were within normal range.
On histopathological investigation, aseptic chorio and/or leptomeningitis were present in 7 out of 14 patients. Severe edema, edema necrosis and localized status spongiosus were frequently observed. Atrophy, nonspecific degeneration and loss of neurons were detected, but pathognomonic changes were not evident. Marginal gliosis in the subpendimal region and superficial cerebral cortex and glial nodule formation surrounding the degenerated neurons were occasionally seen. Vascular changes such as endoarteritis, periarteritis and perivascular cuffing were present in 5 out of 14 patients, though such lesions were geneally mild. Ganglionitis and neuritis in the various areas were seen in 13 patients.     

RETARDED MESANGIAL TRANSPORT AND ITS PATHOMORPHOLOGIC SEQUELAE IN HUMAN AND EXPERIMENTAL RENAL DISEASES

Human renal biopsy specimens (472 cases) from varied kidney diseases, especially minimal glomerular change group and other idiopathic glomerular diseases having nephrotic manifestation of mainly juvenile individuals, showed morphologic evidence of paraarterial deposits of afferent arterioles at the glomerular entrances in more than 50% of examined cases. Because these deposits were often accompanied with concomitant mesangial, intraarterial and subendothelial deposits of afferent arterioles, it was felt that retarded mesangial transport which is ordinarily associated with certain glomerular diseases might be an important factor to produce these particular paraarterial deposits. The referred deposits of minimal glomerular change group cases were thought to predispose the occurrence of focal sclerotic capillary lesions at the vascular poles of glomeruli. The experimental chronic nephrotic rats produced by daily administration of aminonucleoside of puromycin revealed mesangial dysfunction with increased uptake and retarded disposal of secondarily overloaded aggregated human gamma globulin at mesangial areas in glomeruli. Besides, the increased deposits of autologous serum proteins in mesangial areas and arteriolar walls were common findings in those rats, and these deposits were observed to be always preceded to the occurrence of segmental sclerotic changes of glomeruli, which were often associated in the later stage of this experiment. ACTA PATHOL. JPN. 33: 219∼236, 1983.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.