Development of neurochemical separation of ON and OFF channels at retinal ganglion cells

Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development.     

Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.     

Accumulation of prion protein in muscle fibers of experimental chloroquine myopathy: in vivo model for deposition of prion protein in non-neuronal tissues

Prion protein (PrP) is known to accumulate in some non-neuronal tissues under conditions unrelated to prion diseases. The biochemical and biological nature of such accumulated PrP molecules, however, has not been fully evaluated. In this study, we established experimental myopathy in hamsters by long-term administration of chloroquine, and we examined the nature of the PrP molecules that accumulated. PrP accumulation was immunohistochemically demonstrated in autophagic vacuoles in degenerated muscle fibers, and this was accompanied by the accumulation of other molecules related to the neuropathogenesis of prion diseases such as clathrin, cathepsin B, heparan sulfate, and apolipoprotein J. Accumulated PrP molecules were partially insoluble in detergent solution and were slightly less sensitive to proteinase K digestion than normal cellular PrP. Muscle homogenates containing these PrP molecules did not cause disease in inoculated hamsters. The findings indicate that the PrP molecules that accumulated in muscle fibers have distinct biochemical and biological properties. Therefore, experimental chloroquine myopathy is a novel and useful model to investigate the mechanism of deposition of PrP in non-neuronal tissues and might provide new insights in the pathogenesis of prion diseases.     

DNA analysis of a patient with two different marker chromosomes using Y-specific DNA probes

A female patient with unilateral gonadal dysgenesis was a mosaic for three cell lines, 45,X/46,X, + marI/46,X, + marII, including two different marker chromosomes. DNA analysis using 17 Y-specific DNA probes revealed that each marker consists of different segments of the Y chromosome.     

IMMUNOHISTOCHEMICAL STUDY ON THE DISTRIBUTION AND SIGNIFICANCE OF MONONUCLEAR CELLS IN HUMAN BREAST CARCINOMA

Lymphocyte subsets in the tumor nests of breast carcinoma were immunohistochemically investigated and a quantitative analysis was added. The majority of cases showed predominance of T cell and suppressor T cell (T8). A decrease in number of lymphocyte subsets and the helper T (T4)/T8 ratio in the stroma of tumor nests correlated well with the progression of clinical stage and the presence of metastasis. This correlation could not be found in the peripheral region of the tumor nests. Macrophages and NK cells were infrequently observed only in the peripheral region of ductal carcinoma. T cell infiltration was prominent in medullary carcinoma with lymphocyte infiltration (MC), and macrophages, NK cells, and T zone histiocytes were frequently encountered. For the purpose of knowing the activity of T cells, IL-2 receptor (Tac) and transferrin receptor were examined irnmunohistochemically. The fact that a few activated T cells were found only in the peripheral region of tumor nest suggested the local immune response in ductal carcinoma not to be so active as to reject the tumor cells. Since numerous activated T cells were recognized in the tumor nests of MC, this type of breast carcinoma was thought to have a higher immune reactivity. There was little evidence indicating NK cells to play a role for natural cytotoxicity in breast carcinoma. ACTA PATHOL. JPN. 36 1455-1468, 1968     

大鼠肺表面活性物质磷脂在急性肺泡损伤时的变化

以6mg/kg体重皮下注射N-亚硝基-N-氨基甲酸乙酯诱发大鼠急性肺泡损伤,在注射后第2天,肺泡灌洗液(即肺泡空间成份)表面活性物质磷脂含量明显减少,而蛋白质含量明显增加。细胞内层状体和微粒体中磷脂及蛋白质含量未见明显改变。与此同时,各肺成份中磷脂的组成也发生了变化,即PG/PI的比率明显降低。分子种的检测显示,两种酸性磷脂(Po和PI)的分子种构成不同,其主要分子种在急性肺泡损伤时有所改变。     

Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice

We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6,12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.     

MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF A CASE OF MUCOPOLYSACCHARIDOSIS II (HUNTER'S SYNDROME)

An autopsy case of a 19-year-old boy who had shown typical gargoyle features, strictly consistent with mucopolysaccharidosis type II (Hunter's syndrome) was reported. Histologically, cytoplasmic vacuolar change was found In hepatocytes, sinusoidal epithelium of spleen, follicular cells of thyroid, Sertoli cells of testis, chromophobe cell of pituitary and generalized fibroblast-like cells including meninges, cardiac valve and periosteum. The vacuoles consisting of membrane-bound structures with flocculus protein-like material and occasional electron dense bodies on electron microscopy, were considered to be the site of mucopolysaccharide deposition by histochemical analysis. Deposition of lipid material consistent with so-called membranous cytoplasmic body was observed in the neurons of central, peripheral and autonomic nervous system. Hepatosplenomegaly could be explained by cytoplasmic deposition, but the cause of cardiomegaly remained further to be studied. Biochemically hepatic mucopolysaccharide was identified as heparan sulfate, while in the kidney dermatan sulfate and heparan sulfate were detected. The correlation between morphology and biochemistry, and between deposition and degeneration was discussed.     

CORRELATION BETWEEN GLYCOCONJUGATE EXPRESSION AND FUCOSYLTRANSFERASE ACTIVITY IN HUMAN COLORECTAL CARCINOMA

Using the surgically extirpated specimens from 9 patients with colorectal carcinoma, fucosyltransferase activities in the carcinoma tissue and the normal mucosa were measured and were compared with the hlstochemical findings of glycoconjugates which were shown by staining with lectins reacting with blood group antigens and related substances. The fucosyltransferase activities of the carcinoma tissue were well correlated with the overall findings of lectin stainings after neuraminidase treatment. The more intense the carcinoma tissue was stained, the higher the fucosyltransferase activity was shown. However, there were marked differences in the fucosyltransferase activities by the portions measured, depending upon the relative amount of carcinoma tissue and Interstitial tissue; in the invasive portion with less carcinoma tissue, the activity was generally low in comparison with that in the surface area where carcinoma tissue was rather abundant. Thus, the morphological and lectin hlstochemical finding are of paramount importance for the eveluation of glycosyltransferase activity in human colorectal carcinoma.