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Biomedical subjects

M Takeichi

Publications and source records attributed to M Takeichi.

At least 217 records · Page 12Linked to original sources

Neurobiological studies of experimental diphenylhydantoin intoxication--III. Electron microscopic studies on development and disintegration mechanism of altered axon terminals and synaptic endings in rat cerebellum with chronic diphenylhydantoin intoxication.

The processes of development and disintegration of axonal spheroids were electron microscopically studied in the rat cerebellum with chronic diphenylhydantoin intoxication. According to the severity and character of membrane accumulation, the whole course ranging from development to disintegration of altered axon terminals and synaptic endings in the DPH-intoxicated rat cerebellum was classified into the following four stages--initial, moderate, advanced and terminal. The initial stage was characterized by the appearance of a small number of interconnected tubules 150 to 350 A in diameter in non-enlarged axon terminals and synaptic endings. Usually these tubular structures tended to congregate in a certain part of axoplasm so that there were no intimate relationships between them and ordinary cell organelles. The moderate stage was characterized by an increased number of interconnected tubules in slightly or moderately swollen axon terminals and synaptic endings. The advanced stage was characterized by an extraordinary number of interconnected tubules in extremely highly swollen axon terminals and synaptic endings. Membranous scrolls and/or membranous strands separated by a cleft-like space were also found in an association with interconnected tubules so that the morphological organization of spheroids in the rat cerebellum with chronic DPH intoxication was very analogous to those of infantile neuroaxonal dystrophy. The terminal stage was characterized by the following three axonal events, i.e., rarefaction and coagulation necroses, and phagocytosis of spheroids by glial elements, presumably astrocytic in origin. The formation and fate of such axonal spheroids have not as yet been shown and discussed by electron microscopists. Thus the present paper was the first to reveal the electron microscopic observations suggestive of the details of development and disintegration mechanisms of spheroids by means of animal experimentations.

Animals↗

Teratocarcinoma cell adhesion: identification of a cell-surface protein involved in calcium-dependent cell aggregation.

Teratocarcinoma cells have a Ca2+-dependent cell-cell adhesion site (t-CDS) that is unique in being inactivated with trypsin in the absence of CA2+ but not in the presence of Ca2+. Fab fragments of antibodies raised against teratocarcinoma F9 cells dissociated by treatment with trypsin and calcium (anti-TC-F9) inhibit the aggregation of teratocarcinoma cells mediated by t-CDS. This inhibitory effect of Fab is removed when anti-TC-F9 is absorbed with F9 cells treated with trypsin and calcium (TC-F9), but not when it is absorbed with F9 cells treated with trypsin and EGTA (TE-F9). Comparisons of cell-surface antigens reactive to anti-TC-F9 in TC-F9 cells with those in TE-F9 cells reveal that only one component, with an approximate molecular weight of 140,000 (p140), is detected specifically on the surface of TC-F9 cells. When TC-F9 cells are retrypsinized in the absence of CA2+, a substance with an approximate molecular weight of 34,000 (p34) is released that can neutralize the aggregation-inhibitory effect of the Fab. This p34 interferes with the immunoprecipitation of p140 with anti-TC-F9, suggesting that p34 is a tryptic fragment of p140. Anti-TC-F9 Fab causes the dissociation of the monolayers of teratocarcinoma cells. This effect is removed by absorption of the Fab with p34 as well as with TC-F9 cells, but not with TE-F9 cells. These results suggest that p140 is essential for the function of t-CDS, and that this is an actual cell-adhesion molecule active in the establishment of monolayers of teratocarcinoma cells.

Antigens, Surface↗

Nullipotent teratocarcinoma cells acquire the pluripotency for differentiation by fusion with somatic cells.

By fusion of nullipotent embryonal carcinoma F9 cells with certain somatic cells freshly collected from differentiated tissues such as thymus and lens, pluripotent hybrid cell lines were obtained. They exhibited a wide spectrum of differentiation, including neural tubes, cartilages, skeletal muscles, ciliated epithelia and others, in solid tumors formed after injection into syngeneic mice. Cells from these tumors differentiated into several cell types when cultured in vitro. A possibility of the introduction of genes to code the factors for regulating differentiation into F9 cells by fusion is suggested.

Animals↗

Neurobiological studies of experimental diphenylhydantoin intoxication. II. Electrophysiological and electron microscopic studies of the rat cerebellum with chronic diphenylhydantoin intoxication.

The oral administration of diphenylhydantoin (DPH) for a period of more than nine months produced ataxia and muscle weakness in rats. The cerebellum of rats which were fed food containing DPH for a period of 12 months was studied electrophysiologically and morphologically. In the DPH-administered rats, little facilitation of Purkinje cell responses was elicited by the stimulation of the inferior olive, and a low frequency and a short duration of after-discharges on the cessation of tetani were observed as compared with that of the control rats. The value of the chronaxie of Purkinje cell axons was smaller in the DPH-administered rats than that in the control rats. Withdrawal of an overdose of DPH from the body returned these phenomena to those observed under normal condition, leaving the degeneration of synaptic boutons and some myelinated axons in the cerebellum. The electrophysiological results were well supported by the electron microscopic findings of degenerative presynaptic terminals and the depletion of synaptic vesicles.

Animals↗

Neurobiological studies of experimental diphenylhydantoin intoxication. - I. Electron microscopic investigations of the rat cerebellum with chronic diphenylhydantoin intoxication.

The effect of chronic administration of diphenylhydantoin on the fine structures of the rat cerebellum was ultrastructurally investigated. Materials from nine control rats and 16 experimental rats to which 200 to 300 mg/kg b.wt. of diphenylhydantoin was administered orally for 12 months were studied with the light and electron microscopes. The most striking changes were observed in the presynaptic boutons located predominantly in the molecular layer and the neuropil of deep cerebellar nuclei and sometimes in the granule cell layer. The changes consisted of the proliferation of either interconnected tubules 150 to 350 A in diameter associated with membranous scrolls and/or membranous strands separated by a cleft-like space, or parallel tubules about 600 A in diameter with a honeycomb-like architecture in the cross section, and hypertrophy of the boutons. Other alterations were a generalized increase in the density of the axoplasmic matrix, the accumulation of mitochondria, vesicular structures and dense bodies, an increased number of neurofilaments and a decreased number of synaptic vesicles. The axon displayed morphological abnormalities similar to those found in the terminal boutons. Along with the synaptic and axonic changes mentioned above, the perikaryal alterations in the Purkinje cell and in granule cell layers and deep cerebellar nuclei were also found, but they were generally not so prominent so that they were considered to reflect a non-specific reaction to synapto-axonic changes rather than a primary degenerative change. However, in contrast to the neuronal changes, no indication of damage of the glial elements was found, nor were the vascular changes.

Animals↗

Analysis of the cell adhesion mechanism using somatic cell hybrids. I. Aggregation of hybrid cells between adhesive V79 and non-adhesive Ehrlich's ascites tumour cells.

V79 Chinese hamster cells dissociated with 1 nm EDTA retain 2 kinds of cell adhesion mechanisms, one dependent on Ca2+ and the other independent of Ca2+. Ehrlich's ascites tumour (EAT) cells are provided with neither Ca2+-dependent nor CA2+-independent mechanisms. Studies on the aggregation of cells of 25 different hybrid clones obtained by fusing these 2 lined cells revealed the following points with regard to adhesive properties of hybrid cells. (1) The activity of the Ca2+-independent mechanism was lower in most hybrid clones than in parental V79 cells. (2) There were a few hybrid clones whose Ca2+-dependent mechanism activity was lower than in V79 cells. In these clones, the Ca2+-independent mechanism was also less active than the parental cells. (3) A hybrid clone with reduced Ca2+-dependent mechanism activity only was not found. (4) All the hybrid clones have at least one set of chromosomes derived from V79. (5) The number of chromosomes derived from EAT cells tended to be less in hybrid clones with lower aggregative ability. These results can be explained by assuming that the activity of the Ca2+-independent and Ca2+-dependent mechanisms of V79 cells may be differently inhibited by genes contained in EAT cells.

Animals↗

Huge lipomatous pseudohypertrophy of the pancreas.

A rare case of lipomatous pseudohypertrophy of the pancreas associated with multiple cysts in an adult is presented. Endoscopic retrograde pancreatography showed a long, willow-like main pancreatic duct. Resected body and tail of the pancreas weighed 1,200 gm.

Adult↗