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Biomedical subjects

G Kato

Publications and source records attributed to G Kato.

At least 19 recordsLinked to original sources

Novel phosphorylation at a mitotic site, serine 75, in human pp60c-src from unsynchronized human tumor cells having a spherical morphology.

Endogenous pp60c-src from Y79 unsynchronized human retinoblastoma cells is phosphorylated at an additional N-terminal serine residue relative to unsynchronized fibroblast pp60c-src. We confirmed that the novel phosphorylation site is Ser 75, which is the same as that phosphorylated in overexpressed human pp60c-src during NIH3T3 cell mitosis. We also showed that the Ser 75 phosphorylation pattern correlates with cell rounding in 14 various unsynchronized human tumor cell lines. Especially, pp60c-src from Lu135 having a spherical morphology similar to that of Y79 is phosphorylated as high as Y79 pp60c-src. Mitotic spherical cells of the epithelial-like HepG2 express pp60c-src phosphorylated on Ser 75. On the other hand, Y79 pp60c-src is phosphorylated on Ser 75 throughout the cell cycle. These data suggest that this phosphorylation may be important in spherical cell morphology.

3T3 Cells

Juvenile xanthogranuloma with cutaneous and cerebral manifestations in a young infant.

Juvenile xanthogranuloma is usually a self-limiting disease of the skin. Intracranial manifestations are extremely rare. We report the clinico-pathological features of an 8-month-old boy suffering from a gradually enlarging nodule of the chest wall and subsequent epileptic seizures. The subcutaneous tumor and a cerebral subcortical tumor of the left temporal lobe were resected. The histological appearance of both tumors corresponded to juvenile xanthogranuloma and included histiocytes, foamy cells, giant cells, inflammatory cells, and collagen-producing fibroblasts showing a storiform pattern. Immunohistochemical studies demonstrated positivity of the tumor cells for lysozyme, CD68 and myeloid-histiocytic antigen, but not S-100 protein, supporting mono-histiocytic differentiation. This case indicates that juvenile xanthogranuloma should be considered in the differential diagnosis of intracranial "xanthomatous" and histiocytic lesions.

Antibodies

A novel insight into the mechanism of the antithrombotic action of defibrotide.

Defibrotide is a polydeoxyribonucleotide sodium salt with antithrombotic properties. These properties have been attributed to its profibrinolytic activity [increase of tissue plasminogen activator (t-PA) activity, concomitant decrease of that of plasminogen activator inhibitor (PAI)], but there could conceivably be other factor(s). To look for these, we studied Defibrotide in a thrombosis model (pulmonary thromboembolism in mice) in which free radicals play a pivotal role. Defibrotide was found to be active after both intravenous and oral administration. Defibrotide behaved in vitro like a scavenger of H2O2 but not of O2.- in cell-free systems. Defibrotide added in vitro to cellular systems decreased the stimulated release of beta-glucuronidase from polymorphonuclear cells (PMNs), the luminol chemiluminescence induced by oxygen species generated by stimulated PMNs and the generation of O2.- from stimulated macrophages. We think that the antithrombotic activity of Defibrotide is based on other factor(s) in addition to profibrinolytic activity, i.e., some scavenger activity and desensitization of cells involved in thrombus formation must also be taken into account.

Animals

Alternative treatment of heartworm disease.

Conventional adulticidal therapy may cause acute death due to embolism in major pulmonary arteries resulting in severe infarction of the lung. To avoid this problem removing a significant number of worms with flexible alligator forceps prior to adulticidal therapy is recommended. Before surgery, an accurate diagnosis and critical evaluation of the patient is mandated for proper choice and sequence of treatment.

Animals

Novel serine phosphorylation occurs in the fibroblast form of pp60c-src from Y79 retinoblastoma cells.

Two-dimensional tryptic peptide analysis showed that pp60c-src from the human retinoblastoma cell line Y79 gave a unique phosphopeptide, which was not found in human fibroblast RT59. There was no significant difference in the extent of phosphorylation of other peptides between the two cell lines. Only phosphoserine was detected in this phosphopeptide. Both the fibroblast form and the neuronal form of pp60c-src from Y79 cells had this unique peptide phosphorylated to the same extent. The phosphorylation site was inferred to be serine 97 by comparing the tryptic map and the arginyl-endopeptidase map. The specific protein kinase activity of pp60c-src from Y79 cells was nearly equal to that of RT59 pp60c-src. This unique serine phosphorylation in the fibroblast form was discussed in relation to the oncogenic change of Y79 cells.

Cell Line

Amelioration of delayed neuronal death in the hippocampus by nerve growth factor.

Selective neuronal death in the CA1 sector of the hippocampus [delayed neuronal death (DND)] develops several days after transient global cerebral ischemia in rodents. Because NGF plays a potential role in neuronal survival, it was decided to study its effect in DND. We report here that intraventricular injection of NGF either before or after 5 min forebrain ischemia in the Mongolian gerbil significantly reduced the occurrence of DND. The tissue content of NGF in the hippocampus was decreased 2 d after ischemia and recovered to the preischemic level by 1 week. By the Golgi staining technique, changes first began in the dendrites of affected neurons as early as 3 hr. Such changes could be ameliorated by NGF treatment. Although previous knowledge of NGF is limited to the survival of cholinergic neurons in the CNS, it is assumed that other mechanisms must be operating in the hippocampus, for example, postsynaptic modification at dendrites or aberrant expression of NGF receptors possibly at the initial excitation period by glutamate. Furthermore, because previous work has shown that inhibition of protein synthesis reduces the occurrence of DND, a program leading to cell death might also be operating via de novo synthesis of certain protein(s), collectively termed "killer protein," because of a lack of NGF.

Animals

Reduction of delayed neuronal death by inhibition of protein synthesis.

Brief forebrain ischemia in rodents causes delayed neuronal death selectively in the CA1 pyramidal cells of hippocampus. Treatment with a reversible protein synthesis inhibitor, anisomycin, significantly reduced the occurrence of delayed neuronal death in the Mongolian gerbil. This result indicates that de novo synthesis of certain protein(s), collectively termed 'killer protein' is required, possibly due to deprivation of nerve growth factor or other trophic factors.

Animals

Cell-cell contact promotes specific activity of pp60c-src protein kinase in human retinoblastoma cells.

Tyrosine-specific protein kinase activity of pp60c-src was examined in human Y79 retinoblastoma cells cultured in monolayers after clusters in suspension culture had been dissociated. The activity increased five- to six-fold between Days 1 and 7 in the monolayer cultures, with a concomitant increase in numbers of cellular contacts per cell. There was no effect of conditioned medium from high-density cultures in suspension on the activity of cultures with a low degree of contacts. The level of c-src protein in cell lysates was nearly constant irrespective of the degree of cellular contacts. These results suggest that the specific activity of pp60c-src is regulated by cell-cell contact.

Cell Communication

Effect of polylysine-bound laminin on human retinoblastoma cell lines.

We have studied the responses of three human retinoblastoma cell lines (GM1232, Y79, and WERI-Rb1) to substratum-bound laminin (LN), fibronectin (FN), or collagen (CN) in serum-containing medium. About 95% of the cells attached to poly-D-lysine (PN)-pretreated plastic surfaces either unbound or protein-bound within 1 h after plating. With PN-bound LN, GM1232 cells showed an outgrowth of processes and cell spread within 1 d, but very little was seen on PN-bound FN, CN, or unbound PN even by Day 4. Both the percentage of cells with processes and the number of processes/cell were dependent on the amount of LN bound to the surfaces at Day 4. On LN surfaces without PN pretreatment, by Day 2 most cells had formed floating aggregates and were not attached to the surfaces. By Day 4 only a part of the peripheral cells of attached aggregates displayed process outgrowth and cell spreading. Dibutyryl cyclic AMP (dbcAMP) maintained these effects of PN-bound LN, and promoted process branching, cell spreading, and elongation with concomitant inhibition of cell growth. The percentage of cells with processes was 83%. Y79 and WERI-Rb1 cells, passed for several years, showed little and weak response to PN-bound LN either in the absence or presence of dbcAMP. These results indicate that the morphologic differentiation of GM1232 cells is elicited specifically by PN-bound LN, and that dbcAMP maintains and promotes this differentiated status.

Bucladesine

Neurochemical profile of tianeptine, a new antidepressant drug.

Tianeptine is a new effective antidepressant drug. However, its neurochemical profile in animals differs from that of tricyclic or atypical antidepressants. In the present study, we compared the ex vivo effects of tianeptine on platelet serotonin uptake to those of clomipramine. Ex vivo, after subchronic (15 days, washout 24 h) treatment (10 mg/kg/day i.p.) in rats, tianeptine induced an increase (30%) in [14C]serotonin uptake at a [14C]serotonin concentration of 500 nM while clomipramine induced a decrease (40%) in [14C]serotonin uptake. Stimulation of uptake affected mainly Vmax but not Km. Tianeptine did not inhibit monoamine oxidase (MAO), MAOA or MAOB activity. In vitro, there was no binding of tianeptine to any of the various receptors examined: alpha- and beta-adrenergic, dopamine, serotonin, imipramine, GABA, glutamate, benzodiazepine, muscarinic, histamine, Ca2+ channels. After chronic administration (10 mg/kg/day for 15 days) tianeptine did not alter the concentration (Bmax) or the affinity (Kd) of alpha-2, beta-1, serotonin-1, serotonin-2, imipramine, benzodiazepine, or GABAB receptors. The major effect of tianeptine in rat platelets and synaptosomes is a small increase in 5-HT uptake after subchronic administration.

Animals

[Reifenstein's syndrome: case report of two siblings].

Two cases of penoscrotal hypospadias and gynecomastias in a 14-year-old and 16-year-old, who were siblings are reported. These cases, with rather small testes and 46, XY karyotypes, were classified as familial incomplete male pseudohermaphroditism, type 1, so called Reifenstein's syndrome. Their serum testosterone and estrogen levels were high, but the luteinizing hormone (LH) and follicle-stimulating hormone levels were within normal limits. LH-releasing hormone tests revealed good response of LH. Urethrographies showed no prostatic utricles. They had urethroplasties at the ages of 5 and 6. Anti-estrogen therapy had some effect on the gynecomastias.

Adolescent

[Studies on para-aortic metastatic lymph nodes in gastric cancer after endoscopic injection of activated carbon particles].

When activated carbon particles are injected into the tissues, they are absorbed into the lymphatic capillary and reach to the regional lymph nodes. Utilising this property of the activated carbon, we injected small sized carbon particles (CH-44) around the gastric cancer using endoscope to examine para-aortic lymph node metastasis. Sixty eight patients with gastric cancer existing serosal invasion were subjected to extended radical gastrectomy dissecting para-aortic lymph nodes as well as regional lymph nodes. Twenty patients (29.4%) had para-aortic lymph node metastasis. Cumulative 5-year survival rate of these patients after surgery was 20.0 per cent. High incidence of metastasis in para-aortic lymph nodes was found in the lymph nodes larger than 4mm in diameter, but 15.9 per cent of lymph nodes less than 2mm in diameter had metastasis. Large lymph nodes occupied almost wholly by cancer cells were stained scarcely by activated carbon particles, but lymph nodes with moderate or slight metastasis were stained black well and this method was very useful for lymph node dissection, even for micro-lymph nodes which seemed to escape from naked eye at surgery.

Aorta

Neurons of the dorsal lateral geniculate nucleus of the hereditary microphthalmic rat: a Golgi study.

Neurons of the dorsal lateral geniculate nucleus (LGNd) in the microphthalmic rat were examined by the Golgi-Cox method. LGNd neurons in the microphthalmic rat were classified into the multipolar (I) and bipolar (II) types as in the normal rat. The multipolar type was further divided into two subclasses (Ia and Ib) on the basis of their dendritic patterns. The proximal portion of their primary dendrites was thinner than in normal LGNd neurons. The Ia cells had 6-7 primary dendrites extending radially, while the Ib cells had 3-4 primary dendrites spreading primarily parallel to the optic tract. Type II cells had two or three primary dendrites emerging from the cell bodies. In both types, primary dendrites were shorter in length or less branched than usual. These results suggested that LGNd neurons in the microphthalmic rat had smaller dendritic fields than those in the normal rat.

Animals

Membrane-bound N-acetyl-beta-glucosaminidase. Different binding specificity in control and I-cell disease livers.

Several lysosomal enzymes solubilized at pH 4 from saponin-treated membranes showed markedly variable affinities to the bovine liver phosphomannosyl receptor in both bovine and human livers. The enzymes from I-cell disease liver did not bind the receptor in spite of normal intracellular activities. N-Acetyl-beta-glucosaminidase was effectively released from the membrane preparation of a control liver by mannose 6-phosphate, and other sugars showed little effect in this experiment. However, in the I-cell disease liver, dissociation occurred not by mannose 6-phosphate but by other sugars, such as fucose, mannose and N-acetyl-D-glucosamine. These results indicate the presence of an alternate transport system other than the pathway mediated by the mannose 6-phosphate receptor, and the role of other sugar-binding proteins is discussed in intracellular processing and transport of newly synthesized enzymes.

Acetylglucosaminidase

Neurotransmitters and receptors: clinical implications.

With the advent of new techniques such as the radioreceptor binding assay, significant advances have been made in the field of psychopharmacology during the past seven years. In this paper we discuss some of these contributions regarding our understanding about the nature of different psychopathological conditions such as anxiety, depression and schizophrenia.

Anxiety