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Biomedical subjects

Y Takai

Publications and source records attributed to Y Takai.

At least 199 records · Page 11Linked to original sources
PubMed1997

Molecular cloning of mouse Doc2alpha and distribution of its mRNA in adult mouse brain.

We have previously isolated from a human brain cDNA library, a new protein having two C2-like domains which interact with Ca2+ and phospholipid, and named Doc2alpha. Doc2alpha is abundantly expressed in brain, where it is highly concentrated on the synaptic vesicle fraction, and is implicated in Ca2(+)-dependent exocytosis. We have isolated here a mouse Doc2alpha cDNA and determined the localization of its mRNA in adult mouse brain. The amino acid sequence of the mouse Doc2alpha cDNA is 92% identical with that of the human counterpart. Northern blot analysis and in situ hybridization on adult mouse brain sections have revealed that Doc2alpha is predominantly expressed in mouse brain, where it is expressed in neuronal cells, but not in non-neuronal cells. Doc2alpha is highly expressed in the olfactory bulb, cerebral cortex, hippocampus, amygdaloid complex, and ventromedial hypothalamus nucleus, but not in the cerebellum, caudate-putamen, or ventral thalamus. These results indicate that Doc2alpha is expressed heterogeneously in mouse brain, where it is predominantly expressed in neuronal cells, and suggest that Doc2alpha plays a specific role in the area where it is expressed.

Amino Acid Sequence↗
PubMed1997

DNA polymorphism analysis of a case of complete hydatidiform mole coexisting with a fetus.

A complete hydatidiform mole coexisting with a fetus is a rare condition. The diagnosis is often difficult because of the morphological similarity to a partial mole, but is crucial to management in the postmolar course. We present a case of molar pregnancy coexisting with a fetus in which DNA polymorphism analysis revealed a different genetic origin for the fetal and molar parts. This is the only known case of a complete mole in a twin pregnancy complicated by pre-eclampsia followed by maternal pulmonary oedema. During follow-up, the patient developed a clinically invasive mole which was successfully treated with chemotherapy. In this case, genetic analysis unequivocally diagnosed a twin pregnancy consisting of a complete hydatidiform mole and a fetus.

Adult↗
PubMed1997

Phosphorylation-dependent control of structures of intermediate filaments: a novel approach using site- and phosphorylation state-specific antibodies.

Site-specific phosphorylation of intermediate filament (IF) proteins on serine and threonine residues leads to dynamic alterations in filament structure. Site- and phosphorylation state-specific antibodies for IF proteins can visualize spatial and temporal distribution of site-specific IF protein phosphorylations in the cell. These antibodies are also useful to identity IF kinases involved in cellular events, including cell signaling and cell cycle.

Antibodies↗
PubMed1997

A novel function of the C-terminal lipid moieties of Rab3A small G protein implicated in Ca2+-dependent exocytosis--inhibition of interaction with GTP and reduction of this inhibition by phospholipid.

BACKGROUND: Rab3A small G protein is implicated in Ca2+-dependent exocytosis. It undergoes posttranslational lipid-modifications at its C-terminal region. These lipid moieties are important for the actions of the regulators of Rab3A, but not for the interaction with its downstream target. RESULTS: We have found another function of the C-terminal lipid moieties of Rab3A. GTP rapidly associates with the guanine nucleotide-free form of unmodified Rab3A, but not with the same form of modified Rab3A. Moreover, GTP rapidly dissociates from the GTP-bound form of modified Rab3A, but not from the same form of unmodified Rab3A. The association of GTP with the guanine nucleotide-free form of modified Rab3A is stimulated by the Rab3 GDP/GTP exchange protein (Rab3 GEP), and the dissociation of GTP from the GTP-bound form is markedly reduced by synaptic vesicle phospholipid. CONCLUSIONS: These results suggest that the interaction of the lipid moieties of Rab3A with Rab3 GEP or synaptic vesicles is required for the interaction of modified Rab3A with GTP. Moreover, these results - together with the fact that Rabphilin-3A associated with synaptic vesicles inhibits the activity of Rab3 GTPase-activating protein - suggest that the GTP-bound form of modified Rab3A is associated with synaptic vesicles through both Rabphilin-3A and the vesicle phospholipid.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Single dose radiocurability of four murine solid tumors and a predictive assay for the curability in situ.

Correlations between radiocurability and kinetic parameters were investigated in four transplantable tumor types in WHT/Ht mice. The radiation dose to achieve 50% tumor control at 120 days after irradiation, i.e., TCD50/120, was 30 Gy for squamous cell carcinoma H, 32 Gy for squamous cell carcinoma NOS, 46 Gy for rhabdomyosarcoma KAS, and 63 Gy for fibrosarcoma YAS. The tumor cell kinetic parameters investigated were specific growth delay, volume doubling time, 125I-iododeoxyuridine (IUdR) uptake rate, and specific cell loss rate. The specific cell loss rate was defined as the ratio of cell loss rate in non-irradiated tumors to the rate in irradiated tumors, and was obtained by measuring the retention rate of radioactivity in the tumors. No correlations were found between specific growth delay, volume doubling time, 125I-IUdR uptake rate, and TCD50. However, the specific cell loss rate correlated with the TCD50. Therefore, the 125I-IUdR labeling method may be useful as an in situ predictive assay for tumor radiocurability.

Animals↗
PubMed1997

[Radiation therapy for low-grade astrocytomas: survival and QOL].

From 1980 to 1994, 59 patients with a diagnosis of lowgrade astrocytoma were treated in our hospital. We analyzed survival, prognostic factors and quality of life (QOL) in survivors who had been recurrence free for at least 2 years. The overall 2-, 5- and 10-year survival rates were 75, 65 and 49 % respectively. The major prognostic factors were field size (the smaller, the better) and age (the younger, the better) according to Cox regression analysis. Quality of life was evaluated in the 20 patients who had survived at least 2 years without tumor regrowth. Performance status was good in most of the patients, and 17(85%) patients were intellectually and physically normal. Headache, fatigue and memory difficulties were the major clinical complaints of these patients and were observed in 7(35%), 6(30%) and 7(35%) of the patients, respectively, although severe symptoms were rare.

Adolescent↗
PubMed1997

[Effects of combination chemoradiotherapy with daily low-dose CDDP for esophageal cancer--results of a randomized trial].

Between 1994 and 1996, 24 patients with esophageal carcinoma were entered in a randomized clinical trial comparing radiotherapy (RT) only (arm A) versus RT and a daily low dose of CDDP (5 mg/m2) (arm B). For arm B group, CDDP was injected within 30 min after irradiation. All patients were irradiated with a total dose of 60 Gy /30fr. at first, and some patients were boosted. An overall response rate of 75.0% (complete response rate of 25.0%) was observed in arm A and 91.7% (complete response rate of 16.7%) in arm B, respectively. The survival rate at 1 year was 23.8% in arm A and 40.0% in arm B. Median survival time was 7 months in arm A and 9 months in arm B. Toxicity was acceptable and no significant difference was noted between arm A and arm B.

Aged↗
PubMed1997

[Nutritional support in terminal patients--evaluation of 109 cases receiving home parenteral nutrition].

For end-stage patients with malignant disease, home parenteral nutrition (HPN) is an effective and useful treatment in terms of pain control and nutritional support. Therefore, these patients are able to spend their final days at home with their family. In 1990, we started the treatment and have been experienced 109 cases. In this report, we evaluate these cases and which condition or circumstance are necessary to perform HPN for the terminal patients.

Adult↗
PubMed1997

[Binocular functions in amblyopia and strabismus].

Regarding the changing trends in the concept, definition, etiological classification, and criteria for diagnosis of amblyopia, we reviewed a total of 4,693 cases of amblyopia seen during the past 37 years. The amblyopia was divided into four types: strabismic, anisometropic, ametropic, and form vision deprivative. There was a definite trend for the incidence to decrease and for the diagnosis to be made during earlier age in recent years. Although favorable recovery of visual acuity is obtained after treatment of amblyopia and strabismus, there are difficulties in obtaining good binocular functions in early-onset amblyopia and strabismus. This feature was evaluated in regard to motion perception asymmetry (MPA) and binocular depth from motion (DFM). Many cases of early-onset amblyopia and strabismus showed no disparity stereopsis, or position stereopsis, in spite of the presence of DFM. The MPA appeared to be closely related to early-onset esotropia regardless of age, while it disappeared and motion perception became symmetric 4 to 5 months after birth in normal infants. The DFM seemed to play an important role in maintaining good motor alignment for several years after surgery. I developed a checkerboard pattern stimulator in 1978. This method proved to be useful in developing binocular functions and motor alignment by applying simultaneous bifoveolar stimulation and anti-suppression. Extensive exposure to the stimulation was essential for therapeutic success.

Adolescent↗
PubMed1996

Interaction of both the C2A and C2B domains of rabphilin3 with Ca2+ and phospholipid.

Rabphilin3, a downstream target molecule of the Rab3 subfamily small G proteins, has two C2 domains (the C2A and C2B domains) at its C-terminal region and is implicated in Ca(2+)-dependent neurotransmitter release. Rabphilin3 interacts with Ca2+ and phospholipid at its C2 domain, but it remains to be clarified which domain, the C2A or C2B domain, interacts with these compounds. We have found here that both the C2A and C2B domains interact with Ca2+ with similar kinetics but interact with phospholipid with slightly different kinetics.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Physical and functional interaction of rabphilin-3A with alpha-actinin.

Rabphilin-3A is a downstream target molecule of Rab3A small GTP-binding protein and implicated in Ca2+-dependent neurotransmitter release. Here we have isolated a rabphilin-3A-interacting molecule from a human brain cDNA library by the yeast two-hybrid method and identified it to be alpha-actinin, known to cross-link actin filaments into a bundle. alpha-Actinin interacts with the N-terminal region of rabphilin-3A, with which GTP-Rab3A interacts, and this interaction stimulates the activity of alpha-actinin to cross-link actin filaments into a bundle. The interaction of rabphilin-3A with alpha-actinin is inhibited by guanosine 5'-(3-O-thio)triphosphate-Rab3A. These results suggest that the Rab3A-rabphilin-3A system regulates the alpha-actinin-regulated reorganization of actin filaments. It has been shown that reorganization of actin filaments is also involved in Ca2+-dependent exocytosis. Therefore, rabphilin-3A may serve as a linker for Rab3A and cytoskeleton.

Actinin↗
PubMed1996

Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae.

The RHO1 gene encodes a homolog of mammalian RhoA small GTP binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth sites, including the bud tip and the cytokinesis site, and is required for bud formation. We have recently shown that Pkc1p, a yeast homolog of mammalian protein kinase C, and glucan synthase are targets of Rho1p. Using the two-hybrid screening system, we cloned a gene encoding a protein which interacted with the GTP-bound form of Rho1p. This gene was identified as BNI1, known to be implicated in cytokinesis or establishment of cell polarity in S.cerevisiae. Bni1p shares homologous domains (FH1 and FH2 domains) with proteins involved in cytokinesis or establishment of cell polarity, including formin of mouse, capu and dia of Drosophila and FigA of Aspergillus. A temperature-sensitive mutation in which the RHO1 gene was replaced by the mammalian RhoA gene showed a synthetically lethal interaction with the bni1 mutation and the RhoA bni1 mutant accumulated cells with a deficiency in cytokinesis. Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase. These results suggest that Rho1p regulates cytoskeletal reorganization at least through Bni1p and Pkc1p.

Base Sequence↗
PubMed1996

Interaction of Rabphilin3 with synaptic vesicles through multiple regions.

Rabphilin3 is a downstream target protein of Rab3A small G protein, implicated in neurotransmitter release. We have previously reported that about 4 molecules of Rabphilin3 are associated with one synaptic vesicle through a vesicle anchoring protein(s). We have shown here that Rabphilin3 interacts with rat synaptic vesicles through at least three regions: the N-terminal region (1-280 amino acids (aa)), the C-terminal region containing the two C2 domains (440-704 aa), and an unidentified region. A model for the interaction of Rabphilin3 with the vesicles is discussed.

Adaptor Proteins, Signal Transducing↗
PubMed1996

SMAP, an Smg GDS-associating protein having arm repeats and phosphorylated by Src tyrosine kinase.

Smg GDS is a regulator having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. Structurally, it has 11 Arm repeats, a protein interaction motif, found in the Drosophila Armadillo protein, a homolog of mammalian beta-catenin. We have isolated here an Smg GDS-interacting protein from a human brain cDNA library by use of the yeast two-hybrid method and named it SMAP (Smg GDS-associated protein). SMAP was a protein with a Mr of 91,189 and 792 amino acids. SMAP had 9 Arm repeats. Recombinant SMAP interacted with recombinant Smg GDS but did not affect the two activities of Smg GDS on RhoA. SMAP was tyrosine phosphorylated by v-Src, and this phosphorylation reduced the affinity of SMAP for Smg GDS. Tissue and subcellular distribution analyses indicated that SMAP was ubiquitously expressed and highly concentrated at the endoplasmic reticulum area. Searches for sequence homology to SMAP revealed that SMAP was significantly homologous to sea urchin SpKAP115, suggesting that SMAP is a mammalian counterpart of SpKAP115 or its related protein. SpKAP115 is an accessory subunit of sea urchin kinesin II, an ATPase motor that transports vesicles along microtubules. These results suggest that SMAP serves as an adaptor for both Smg GDS and kinesin II or its related protein and links them with both the Smg GDS-regulated small G protein and Src tyrosine kinase signalings.

Amino Acid Sequence↗
PubMed1996

Interaction of the Rho family small G proteins with kinectin, an anchoring protein of kinesin motor.

The Rho family small G proteins are implicated in various cell functions, such as cell morphological change, cell motility, and cytokinesis. However, their modes of action in regulating these cell functions remain to be clarified. In the present study, we have isolated a cDNA encoding a protein which interacts with the GTP-bound form, but not with the GDP-bound form, of the Rho family members, including RhoA, Racl, and Cdc42, by the yeast two-hybrid method. This protein is kinectin, known to be a vesicle membrane anchoring protein of kinesin, which is an ATPase motor transporting vesicles along microtubules.

Binding Sites↗