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Biomedical subjects

R Sakai

Publications and source records attributed to R Sakai.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Multiple chemical sensitivities: case definition, etiology and relations to allergy, poisoning, psychogenic illness etc].

Multiple Chemical Sensitivities (MCS) have been defined as an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects; no single widely accepted test of physiologic function can be shown to correlate with symptoms (Cullen MR, 1987). The etiology of MCS is hypothesized as a toxicant-induced loss of tolerance to multiple chemicals with subsequent manifestation of multiple-organ symptoms triggered by low-level exposure to such chemicals. The involvement of multiple organs might be attributed to a neurogenic switching mechanism. The final diagnosis of MCS is to rely on provocation of symptoms in a exposure chamber by a double-blind method. Relations of MCS to allergy, poisoning, psychogenic illness, chemical sensitivity, idiopathic environmental intolerances etc. are discussed in terms of case definition and etiology of these disorders.

Diagnosis, Differential↗
PubMed1999

[Economical evaluation for drug consultation at home].

We started drug consultation at patients' homes in October, 1998. The number of drug consultations are 2.65 per month per patient and the consulting time is 2.25 hours per patient. The fee for drug consultation is 550 points twice a month. We evaluate the fee for drug consultation. Our data suggest that this fee needs to be 550 points three times a month.

Aged↗
PubMed1998

Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation.

Proteins with SH2 and SH3 domains link tyrosine kinases to intracellular pathways. To investigate the biological functions of a mammalian SH2/SH3 adaptor, we have introduced a null mutation into the mouse gene for Grb2. Analysis of mutant embryonic stem cells, embryos, and chimeras reveals that Grb2 is required during embyrogenesis for the differentiation of endodermal cells and formation of the epiblast. Grb2 acts physiologically as an adaptor, since replacing the C terminus of the Ras activator Sos1 with the Grb2 SH2 domain yields a fusion protein that largely rescues the defects caused by the Grb2 mutation. Furthermore, Grb2 is rate limiting for mammary carcinomas induced by polyomavirus middle T antigen. These data provide genetic evidence for a mammalian Grb2-Ras signaling pathway, mediated by SH2/SH3 domain interactions, that has multiple functions in embryogenesis and cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Purification and characterization of Microcystis aeruginosa (freshwater cyanobacterium) lectin.

Microcystis aeruginosa, strain M228, a laboratory culture of freshwater cyanobacterium, showed hemagglutinating activity against rabbit, horse and human ABO erthrocytes. Crossed absorption tests revealed the presence of a single type of lectin in the extract of M228 strain cells. The lectin, termed MAL, was purified in combination with the affinity chromatography on acid-treated agarose gel and the gel permeation chromatography in an electrophoretically pure form. MAL was a glycoprotein containing 7.8% neutral sugars and was composed of a single polypeptide having a molecular weight of 57 kDa. Isoelectric point was estimated to be pH 6.4. Hemagglutinating activity of the lectin was inhibited effectively by N-acetyl-D-galactosamine and by glycoproteins. D-galactose and lactose also showed moderate inhibitory activity. The destruction of the hemagglutinating activity by a 2-mercaptoethanol treatment suggests the presence of intra-chain disulfide bond(s) essential for the activity in the molecule. The sequence of the amino-terminal region of MAL was determined as Val-Leu-Ala-Ser-Leu-Val-Ser-Thr-Ser-Gln-Ala-Gly-Ser-Leu-Glu-Leu-Leu- Ala [corrected].

ABO Blood-Group System↗
PubMed1998

Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas.

p130Cas (Cas), the protein encoded by the Crkas gene (also known as Cas), is an adaptor molecule with a unique structure that contains a Src homology (SH)-3 domain followed by multiple YXXP motifs and a proline-rich region. Cas was originally cloned as a highly tyrosine-phosphorylated protein in cells transformed by v-Src (refs 2,3) or v-Crk (ref. 4) and has subsequently been implicated in a variety of biological processes including cell adhesion, cell migration, growth factor stimulation, cytokine receptor engagement and bacterial infection. To determine its role in vivo, we generated mice lacking Cas. Cas-deficient embryos died in utero showing marked systemic congestion and growth retardation. Histologically, the heart was poorly developed and blood vessels were prominently dilated. Electron microscopic analysis of the heart revealed disorganization of myofibrils and disruption of Z-disks. In addition, actin stress fiber formation was severely impaired in Cas-deficient primary fibroblasts. Moreover, expression of activated Src in Cas-deficient primary fibroblasts did not induce a fully transformed phenotype, possibly owing to insufficient accumulation of actin cytoskeleton in podosomes. These findings have defined Cas function in cardiovascular development, actin filament assembly and Src-induced transformation.

Actin Cytoskeleton↗
PubMed1998

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Adolescent↗
PubMed1998

Coxiellosis in domestic and wild birds from Japan.

Serological evidence of infection with Coxiella burnetii was found in 41 (2%) of 1,951 domestic birds and in 167 (19%) of 863 wild birds from 17 and 5 prefectures in Japan, respectively, by microagglutination (MA) test. The bacteriological evidence of the infection was found in 17 (41%) of 41 domestic birds and 37 (22%) of 167 wild birds by the nested polymerase chain reaction (PCR). In addition, C. burnetii was isolated from five each of serum, spleen and fecal specimens from five jungle crows (Corvus macrorhynchos) (whose sera were positive by both the MA test and PCR) by inoculating laboratory mice. Domestic quail (Coturnix coturnix japonica) (3%), domestic muscovy ducks (Cairina moschata) (3%), domestic chickens (2%), domestic mallards (Anas platyrhynchos domesticus) (2%), carrion crows (Corvus corone) (37%), jungle crows (35%), and wild rock doves (Columba livia) (6%) showed serologic evidence of experience with C. burnetii. There was a tendency for a high prevalence among birds living and/or feeding in close proximity to infected livestock. This suggests that these birds are one of the less important links in maintaining the whole cycle of C. burnetii infection.

Agglutination Tests↗
PubMed1998

[Chronic myelogenous leukemia with long-term hypoplasia induced by alpha-interferon and hydroxyurea].

A 48-year-old woman was admitted with chronic myelogenous leukemia in November, 1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC 404,000/microliter. On January 29, 1997, administration of HU was stopped, and treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day. However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU was reduced to 500 mg on February 27, and the IFN administration was reduced to 3 times a week from April 4, because the WBC count was less than 10,000/microliter. Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated marked hypoplastic changes, and chromosome analysis of bone marrow cells showed Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7 months, but hematologic parameters did not recover. There were 9 cases reported in detail with bone marrow hypoplasia induced by IFN. One patient received IFN alone and 8 patients received anti-cancer drugs before treatment of IFN. We concluded that great care must be taken for IFN treatment of CML.

Antineoplastic Agents↗
PubMed1997

Characterization of the kinase activity essential for tyrosine phosphorylation of p130Cas in fibroblasts.

The cellular transformation by v-Src or v-Crk induces tyrosine phosphorylation of a common substrate molecule, p130Cas (Cas), which tightly binds these oncoproteins in vivo. From its structure, Cas is deduced to be an ideal substrate for Src family kinases and Abl kinase. The tyrosine kinase activity associated with Cas was analysed using mouse variant fibroblasts lacking at least one of tyrosine kinases. In normal fibroblasts, Cas is associated with a significant level of tyrosine kinase activity which efficiently phosphorylates Cas in vitro. The Cas-associated tyrosine kinase activity was remarkably elevated in Csk-/- cells, which resulted in hyperphosphorylation of cellular Cas. The associated kinase activity was slightly increased in Src-/- cells whereas not significantly changed in Abl-/- nor Fak-/- cells. On the contrary, the Cas-associated kinase activity was remarkably decreased in Fyn-/- cells. At the same time, association of Cas with Fyn kinase in vitro was most obviously detected in normal fibroblasts as well as Csk-/- cells. Transient expression of v-Crk induced elevation of the Cas-associated kinase activity in all of these cell lines except the primary culture of Fyn-/- fibroblasts. These results indicate that Fyn kinase plays an essential role in v-Crk-mediated phosphorylation of Cas.

3T3 Cells↗
PubMed1997

Effect of sublethal total body irradiation on acute graft-versus-host disease and graft-versus-leukemia effect in SCID mice.

SCID mice were transplanted with H-2-incompatible C3H/He splenocytes with or without previous TBI with 2Gy to evaluate the influence of sublethal TBI on GVHD and on the graft-versus-leukemia (GVL) effect. Transplantation immediately after TBI induced lethal GVHD, but delayed donor leukocyte infusion (DLI) 5 days after TBI reduced the severity of the GVHD. SCID mice inoculated with L1210 cells after TBI received a DLI 5 days after TBI to induce the GVL effect. Survival of these mice was longer than that of control nonirradiated mice. Serum levels of tumor necrosis factor-alpha, IL-1alpha, IL-6, IL-2 and IFN-gamma were significantly elevated, and they reached maximum levels at 5 days post-transplantation. Except for IFN-gamma, all cytokine levels were higher in irradiated mice than those in nonconditioned mice. Cytotoxicity against L1210 cells mediated by splenocytes from irradiated recipients was greater than that mediated by effector cells from nonirradiated mice. All the irradiated mice survived more than 120 days after L1210 rechallenge, while all nonirradiated mice died of leukemia within 5 weeks. In conclusion, compared with control mice infused with donor splenocytes without previous TBI, SCID mice which received sublethal TBI and DLI showed superior cytotoxicity against L1210 cells and survived longer without severe GVHD.

Acute Disease↗
PubMed1997

Requirements for localization of p130cas to focal adhesions.

p130cas (Cas) is an adapter protein that has an SH3 domain followed by multiple SH2 binding motifs in the substrate domain. It also contains a tyrosine residue and a proline-rich sequence near the C terminus, which are the binding sites for the SH2 and SH3 domains of Src kinase, respectively. Cas was originally identified as a major tyrosine-phosphorylated protein in v-Crk- and v-Src-transformed cells. Subsequently, Cas was shown to be inducibly tyrosine phosphorylated upon integrin stimulation; it is therefore regarded as one of the focal adhesion proteins. Using an immunofluorescence study, we examined the subcellular localization of Cas and determined the regions required for its localization to focal adhesions. In nontransformed cells, Cas was localized predominantly to the cytoplasm and partially to focal adhesions. However, in 527F-c-Src-transformed cells, Cas was localized mainly to podosomes, where the focal adhesion proteins are assembled. The localization of Cas to focal adhesions was also observed in cells expressing the kinase-negative 527F/295M-c-Src. A series of analyses with deletion mutants expressed in various cells revealed that the SH3 domain of Cas is necessary for its localization to focal adhesions in nontransformed cells while both the SH3 domain and the C-terminal Src binding domain of Cas are required in 527F-c-Src-transformed cells and fibronectin-stimulated cells. In addition, the localization of Cas to focal adhesions was abolished in Src-negative cells. These results demonstrate that the SH3 domain of Cas and the association of Cas with Src kinase play a pivotal role in the localization of Cas to focal adhesions.

3T3 Cells↗
PubMed1997

Multiple brain gas embolism after ingestion of concentrated hydrogen peroxide.

We present a 63-year-old man who developed multiple brain infarction after ingesting a 35% hydrogen peroxide solution. Neurologic examination revealed left hemiparesis, primarily affecting the lower limb, and mild weakness of the right lower limb. Gadolinium-enhanced MRI revealed patchy bilateral brain lesions. Oxygen gas embolization is the likely cause of the brain infarctions.

Accidents↗
PubMed1997

Isolation and molecular characterization of four arginine/glutamate rich polypeptides from the seeds of sponge gourd (Luffa cylindrica).

Four arginine/glutamate rich polypeptides referred to as 5 k-, 6.5 k-, 12.5 k-, and 14 k-AGRPs were purified to homogeneity by gel filtration on Sephadex G-75 followed by CM-cellulose, butyl-Toyopearl 650 M, and reverse-phase HPLC from the seed of sponge gourd (Luffa cylindrica). Tricine SDS-PAGE indicated that 5 k- and 6.5 k-AGRPs are single polypeptides, but 12.5 k- and 14 k-AGRPs consist of two polypeptide chains, which are linked by disulfide bond(s). The N-terminal amino acid sequences of four AGRPs were analyzed by a gas-phase sequencer, and the result indicated that they are distinct molecules. Comparison of the sequences with those of proteins in the protein data base demonstrates that 5 k- and 6.5 k-AGRPs have a significant homology with a basic peptide from pumpkin seeds and with cocoa seed vicilin, respectively, and that 12.5 k- and 14 k-AGRPs are related to 2S seed storage proteins. Furthermore, it was assumed that the four AGRPs might occur in the protein bodies within cells of the seed.

Amino Acid Sequence↗
PubMed1997

Primary structure of 6.5k-arginine/glutamate-rich polypeptide from the seeds of sponge gourd (Luffa cylindrica).

The amino acid sequence of 6.5k-arginine/glutamate rich polypeptide (6.5k-AGRP) from the seeds of sponge gourd (Luffa cylindrica) has been determined. The 6.5k-AGRP consists of a 47-residue polypeptide chain containing two disulfide bonds, and a molecular mass calculated to be 5695 Da, which fully coincides with a value of [M+H]+ = m/zeta 5693.39 obtained by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The mass spectrometric evidence indicated that 6.5k-AGRP is also present partially truncated at the C-terminus. In our preparations, approximately half of the polypeptide molecules have the C-terminal sequence Arg-Arg-Glu-Val-Asp; the other half lack Val-Asp and end with the glutamic acid, making a total of 45 residues in the polypeptide chain. The two disulfide bonds connect Cys12 to Cys33 and Cys16 to Cys29. Comparison of the amino acid sequence of 6.5k-AGRP with those of the other known proteins included in the PIR protein sequence database showed that it is related to the amino acid sequence of the N-terminal region encoded by the first exon of the cocoa (Theobroma cacao) and cotton seeds vicilin genes, sharing a characteristic two Cys-Xaa-Xaa-Xaa-Cys motif.

Amino Acid Sequence↗