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A Nakano

Publications and source records attributed to A Nakano.

At least 163 records · Page 9Linked to original sources
PubMed1994

Gelatinase A and APP.

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Amyloid Precursor Protein Secretases↗
PubMed1994

The Saccharomyces cerevisiae MSI4 gene encodes the yeast counterpart of component A of Rab geranylgeranyltransferase.

We describe the isolation of MSI4 as a multicopy suppressor of ira1 (inhibitory regulator of Ras). We find it encodes a 66-kDa protein with three regions similar to component A of Rab geranylgeranyltransferase and Rab guanine nucleotide dissociation inhibitor. A gene disruption experiment showed that MSI4 is essential for cell growth. To investigate its functions further, we constructed a strain whose MSI4 is driven by the GAL1 promoter. This strain accumulated the endoplasmic reticulum precursor form of a vacuolar enzyme, carboxypeptidase Y, under the restrictive conditions. Moreover, we showed that the activity of geranylgeranyl-transferase for Ypt1p was very low in the mutant shifted to glucose medium. We propose that the MSI4 gene product is a yeast counterpart of component A of Rab geranylgeranyltransferase that is essential for Ypt1p to localize on membranes.

Adaptor Proteins, Signal Transducing↗
PubMed1994

A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae.

A staurosporine-sensitive mutation (stt1) in yeast has been found in the PKC1 gene that encodes a protein kinase C homologue (Yoshida, S., Ikeda, E., Uno, I., and Mitsuzawa, H. (1992) Mol. Gen. Genet. 231, 337-344). We report here another staurosporine-sensitive mutant, stt4, which shows very similar phenotypes to that of the stt1 mutant. The stt4 temperature-sensitive mutant arrests mostly in G2/M phase at 37 degrees C, and the stt4 deletion mutant shows an osmoremedial phenotype. Staurosporine sensitivity of the stt4 mutant was suppressed by overexpression of PKC1/STT1, indicating genetic interaction between stt4 and pkc1/stt1. The nucleotide sequence of STT4 predicts a hydrophilic protein composed of 1,900 amino acid residues, with 26% sequence identity to the yeast VPS34 gene product and 27% to the catalytic subunit of mammalian phosphatidylinositol (PI) 3-kinase, respectively. Cell homogenates of the stt4 deletion mutant show normal PI3-kinase activity but lack most of the PI4-kinase activity that is detected in the wild-type. We conclude that STT4 encodes a yeast PI4-kinase that functions in the PKC1 protein kinase pathway.

1-Phosphatidylinositol 4-Kinase↗
PubMed1994

Genetic interactions among genes involved in the STT4-PKC1 pathway of Saccharomyces cerevisiae.

Loss of yeast protein kinase C function results in three distinct phenotypes: staurosporine sensitivity, cell lysis and blockage of cell cycle progression at the G2/M boundary. Genetic analysis of the PKC1/STT1 protein kinase C gene and its interactions with STT4, encoding an upstream phosphatidylinositol 4-kinase, and BCK1, encoding a downstream protein kinase, reveal that they form part of a single pathway. However, the BCK1-20 mutation (a gain-of-function mutation of BCK1) or overexpression of PKC1 cannot suppress all of the phenotypes caused by the loss of STT4 function, strongly suggesting the existence of a branch point between STT4 and PKC1. We also describe the MSS4 gene, a multicopy suppressor of the temperature-sensitive stt4-1 mutation. MSS4 is predicted to encode a hydrophilic protein of 779 amino acid residues and is essential for cell growth. Based on genetic and biochemical data, we suggest that MSS4 acts downstream of STT4, but in a pathway that does not involve PKC1.

1-Phosphatidylinositol 4-Kinase↗
PubMed1994

Cerebrospinal fluid leakage from the nipple after ventriculoperitoneal shunt: case report.

A case of ventriculoperitoneal shunt malfunction is presented, in which cerebrospinal fluid was discharged from the nipple. A pseudocyst was found at the end of peritoneal catheter in the right subphrenic abdominal cavity. In addition, a fibrous tract was formed around the peritoneal catheter and communicated with the lactiferous duct probably injured incidentally during the subcutaneous insertion of catheter. Consequently, cerebrospinal fluid accumulated in the pseudocyst in the abdominal cavity and then flowed backward in the fibrous tract to the lactiferous duct during the respiration to discharge from the nipple.

Abdomen↗
PubMed1994

Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast.

The SAR1 gene product (Sar1p), a 21-kD GTPase, is a key component of the ER-to-Golgi transport in the budding yeast. We previously reported that the in vitro reconstitution of protein transport from the ER to the Golgi was dependent on Sar1p and Sec12p (Oka, T., S. Nishikawa, and A. Nakano. 1991. J. Cell Biol. 114:671-679). Sec12p is an integral membrane protein in the ER and is essential for the Sar1 function. In this paper, we show that Sar1p can remedy the temperature-sensitive defect of the sec12 mutant membranes, which is in the formation of ER-to-Golgi transport vesicles. The addition of Sar1p promotes vesicle formation from the ER irrespective of the GTP- or GTP gamma S-bound form, indicating that the active form of Sar1p but not the hydrolysis of GTP is required for this process. The inhibition of GTP hydrolysis blocks transport of vesicles to the Golgi and thus causes their accumulation. The accumulating vesicles, which carry Sar1p on them, can be separated from other membranes, and, after an appropriate wash that removes Sar1p, are capable of delivering the content to the Golgi when added back to fresh membranes. Thus we have established a new method for isolation of functional intermediate vesicles in the ER-to-Golgi transport. The sec23 mutant is defective in activation of Sar1 GTPase (Yoshihisa, T., C. Barlowe, and R. Schekman. 1993. Science (Wash. DC). 259:1466-1468). The membranes and cytosol from the sec23 mutant show only a partial defect in vesicle formation and this defect is also suppressed by the increase of Sar1p. Again GTP hydrolysis is not needed for the suppression of the defect in vesicle formation. Based on these results, we propose a model in which Sar1p in the GTP-bound form is required for the formation of transport vesicles from the ER and the GTP hydrolysis by Sar1p is essential for entering the next step of vesicular transport to the Golgi apparatus.

Biological Transport↗
PubMed1994

Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies.

Immunofluorescence staining of yeast cells with anti-binding protein (BiP) antibodies shows uniform staining of the endoplasmic reticulum (ER). We have found that overproduction of Sec12p, an ER membrane protein, causes a change of BiP distribution within the cell. Upon induction of Sec12p by the GAL1 promoter, the staining pattern of BiP turns into bright dots scattering in the cell, whereas the staining of Sec12p remains to be the typical ER figure. Overproduction of other ER membrane proteins, HMG-CoA reductase or Sed4 protein, does not induce such relocalization of BiP. Pulse-chase experiments and electron microscopy have revealed that the overproduction of Sec12p inhibits protein transport from the ER to the Golgi apparatus. When the transport is arrested by one of the sec mutations that block the ER-to-Golgi step at the restrictive temperature, the BiP staining also changes into the punctate pattern. In contrast, the sec mutants that block later or earlier steps of the secretory pathway do not induce such change of BiP localization. These observations indicate that relocalization of BiP is caused by the inhibition of ER-to-Golgi transport. Using immunoelectron microscopy, we have found that the punctate staining is because of the accumulation of BiP in the restricted region of the ER, which we propose to call the "BiP body." This implicates existence of ER subdomains in yeast. A vacuolar protein, proteinase A, appears to colocalize in the BiP body when the ER-to-Golgi transport is blocked, suggesting that the BiP body may have a role as the site of accumulation of cargo molecules before exit from the ER.

Base Sequence↗
PubMed1994

Mutational analysis of the Sar1 protein, a small GTPase which is essential for vesicular transport from the endoplasmic reticulum.

SAR1 encodes a 21-kDa GTPase, which is required for vesicle formation from the endoplasmic reticulum in yeast. Although it belongs to the expanding small GTPase superfamily, there are interesting structural features that are unique to the Sar1 protein. We performed a site-directed mutational study to identify the amino acid residues that are essential for the Sar1p function. Among seven mutants we constructed, four are functionless by themselves, while two confer temperature sensitivity to cells. When the mutant proteins are overproduced in wild-type cells, all of these six show a dominant negative effect on cell growth. The replacement by serine of the only cysteine residue present in Sar1p caused no significant change in the growth phenotype. These findings are not only important for analyzing the mechanism of the Sar1p action in yeast, but will also be very useful for studying the function of Sar1p counterparts in higher eukaryotes.

Amino Acid Sequence↗
PubMed1994

Protective capacity of L-form Salmonella typhimurium against murine typhoid in C3H/HeJ mice.

L forms of Salmonella typhimurium LT2 conferred strong protection to a lethal challenge with its parental bacterium on innately hypersusceptible C3H/HeJ mice, and its minimal protective dose was approximately 150 L-forming units. Although L-form S. typhimurium was avirulent for C3H/HeJ mice, it multiplied slowly in both the liver and spleen with the maximal growth 2-3 weeks after immunization and thereafter it persisted in the liver until 24 weeks. Protective immunity began to work between 4 and 6 weeks after immunization, and it remained active as long as the L forms colonized the liver (until 24 weeks after immunization). Vaccination with the L form induced a population of T cells responding to L-form whole-cell lysate (WCL), while delayed-type hypersensitivity (DTH) to the extract of S. typhimurium was induced after the establishment of solid immunity. Moreover, neither T-cell responses nor DTH to heat-killed S. typhimurium was generated. In addition, antibody responses were elicited to WCL but not to heat-killed S. typhimurium. These results indicate that protection conferred by the L forms is attributable to the persistent colonization of the L forms rather than the presence of DTH, and also that Salmonella cytoplasmic antigens are involved in induction of immunological responses by vaccination with the L forms.

Animals↗
PubMed1994

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia.

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease in the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypoplastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1994

Effect of tyrphostin on cell growth and tyrosine kinase activity of epidermal growth factor receptor in human gliomas.

The effects of tyrphostin, a selective protein tyrosine kinase inhibitor, on epidermal growth factor (EGF)-stimulated cell growth and EGF-receptor tyrosine kinase activity were studied in four human glioma cell lines. Stimulation by EGF induced variable enhancements of cell growth as well as tyrosine phosphorylation of EGF receptor and intracellular target proteins in all glioma cell lines. The level of immunoreactive EGF receptor detected with antibodies against extra- and intracellular domains was moderate in all four glioma cell lines, but markedly decreased with the latter antibody in two glioma cell lines. This variation was associated with considerable reduction of the EGF-stimulated tyrosine autophosphorylation level. Tyrphostin inhibited dose-dependently the EGF-stimulated cell growth and tyrosine autophosphorylation in all glioma cell lines, and the optimum time for the maximum inhibitory effect on tyrosine autophosphorylation was 12 to 18 hours after treatment with tyrphostin. The antiproliferative activity of tyrphostin nearly correlated quantitatively with its potency as an inhibitor of the EGF-stimulated EGF receptor tyrosine kinase activity. Tyrphostin had no significant effect on the immunoreactive EGF receptor levels, on the affinity constants and numbers of EGF receptor, or on the down-regulation and specific internalization of EGF receptor in any glioma cell line, suggesting that the effects of tyrphostin are not likely to be the results of reduction in EGF receptor and EGF binding capacity. In addition, the serum-stimulated cell growth was also inhibited dose-dependently by higher concentrations of tyrphostin in all glioma cell lines. It might be suggested, therefore, that tyrphostin inhibits EGF-stimulated cell growth by a specific suppression of EGF receptor tyrosine kinase activity, and at higher concentrations there appears to be some degree of either nonspecific inhibition or inhibition of serum-stimulated protein tyrosine kinase activity to induce the cell growth inhibition of gliomas.

Catechols↗
PubMed1994

[The relationship between the family system and the family coping among families with a chronically ill child].

The purposes of this study were to identify the family coping strategies among families with chronically ill children and to explore the relationship between the family system (variables), the family burden and the family coping. One hundred fifty-two families with chronically ill children were studied. The Japanese version of Family Adaptability and Cohesion Evaluation Scales II and the Family Coping Behavior Inventory II were used. The result were 1) the family cohesion and adaptability in families with a chronically ill child tended to be lower than normal families; 2) the integration coping pattern was positively related with family cohesion and the family burden; 3) the problem solving coping pattern was positively related with the family burden; 4) the normalization coping pattern was negatively related with the family burden and positively related with the family cohesion; 5) the crisis response coping pattern was positively related with the family burden and negatively related with the family cohesion.

Adaptation, Psychological↗
PubMed1994

OK-432 chemical pleurodesis for the treatment of persistent chylothorax.

A 52-year-old woman with thoracic esophageal carcinoma was admitted to our hospital. Standard radical esophagectomy was carried out via a right posterolateral thoracotomy and laparotomy. A drainage tube was removed from the right side of the chest on the 9th postoperative day. Three days later a chest roentgenogram showed massive left pleural effusion, and a tube was inserted into the left pleural cavity. The volume of the effusion was 900 ml/day and chylothorax was diagnosed. Conservative therapy was applied for 30 days, but chyle leakage persisted. Intra-pleural infusion of OK-432, a Su-strain of Streptococcus pyogenes, and doxycycline hydrochloride was carried out to seal the leakage point. The effusion stopped immediately after the procedure. There were no major side effects. This procedure should be considered the treatment of choice for patients with persistent chylothorax not responding to initial conservative management.

Chronic Disease↗