Biomedical subjects

M Furuta

Publications and source records attributed to M Furuta.

At least 91 records · Page 5Linked to original sources

PubMed1996

Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect possible mechanisms of recruitment and activation of downstream molecules.

We previously identified a gene, LckBP1, which encodes a protein that binds to the Lck SH3 domain and is identical to murine SH1. Using unstimulated T lymphocytes, we further demonstrated that Lck binds to HS1 in vivo and that HS1 is tyrosine phosphorylated upon TCR stimulation. In the present report, we analyzed the binding pattern of several src kinases and HS1 in greater detail. The Lck SH3 domain binds to HS1 constitutively, while the Lck SH2 domain associates with HS1 only upon TCR stimulation. A similar binding pattern was observed with Lyn and HS1, but not with Fyn and HS1, in which the Fyn SH2 region associates with HS1 upon TCR stimulation but the Fyn SH3 region does not associate with HS1 regardless of TCR stimulation. Such distinct binding patterns of the src kinase SH2 and SH3 domains to HS1 may represent a mechanism by which src family kinases select substrates and activate particular downstream signaling pathways.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older.

Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N1 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates wer 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36% respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expect a realistic probability of long-term survival with definitive radiation therapy.

Actuarial Analysis↗

PubMed1996

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy.

The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P = 0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P = 0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P = 0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P = 0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy.

Aged↗

PubMed1996

A new murine lymphocytotoxic monoclonal antibody recognizing HLA-A2, -A28 and -A9.

Monoclonal antibodies recognizing polymorphic as well as monomorphic epitopes on HLA antigens are important tools for understanding the immunobiology of HLA molecules. We immunized BALB/c mice with a HLA-A2 transfectant and screened for hybridomas which reacted with a HLA-A2 transfectant but not with a HLA-B75 transfectant. After subcloning by limiting dilution four times, a hybridoma secreting a monoclonal antibody (mAb) (IgG 2a, kappa) designated 1-145 was established. 1-145 reacted with Epstein-Barr virus transformed B lymphoblastoid cell lines (B cell lines) which expressed HLA-A2, -A28, -A23 and -A24. The titer of 1-145 in culture supernatant against HLA-A2 and -A28 antigens was similar and the titer against HLA-A23 was lower. 1-145 reacted with cells expressing HLA-A24 but the titer against HLA-A24 antigens was even lower than that against HLA-A23 antigens. The HLA-A24 antigens on the peripheral blood lymphocytes were not detected by 1-145 possibly due to the lower expression compared to the B cell lines. These differences of the titers were reflected to microlymphocytotoxicity assay in which 1-145 culture supernatant lysed all PBLs expressing HLA-A2,-A28 and -A23 but did not lyse PBLs expressing HLA-A24. Published deduced amino acid sequence data of HLA class 1 molecules indicate that Lys in position 127 may be critical for 1-145 binding.

Amino Acid Sequence↗

PubMed1996

High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1).

PURPOSE: To evaluate the usefulness of radiation therapy alternative to surgery for clinical N0-N1 non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From 1976 through 1989, 116 patients with NSCLC without mediastinal involvement were treated with definitive radiation therapy alone at Gunma University Hospital. All patients were treated with once-daily standard fractionation using 10 MV X-rays. The total dose ranged from 60 Gy to 80 Gy. RESULTS: The actuarial 2- and 5-year survival rates of the entire group were 43% and 20%, respectively with a median survival time of 19 months. The survival of 76 patients with stage T2 tumors was significantly better than that of 28 patients with T3 tumors (mean survival time 21 versus 15.5 months; p < 0.05). Sixty-two patients with tumors less than 5 cm in diameter had a 2-year progression rate of 20%, in comparison with 39% of 54 patients with tumors greater than 5 cm. The difference of survivals for these 2 groups was statistically significant. Twelve patients given a total dose of 80 Gy or more had only 17% local progression at the time of last follow-up, however, 5 of them developed severe stenosis of proximal bronchus after 6 to 15 months. CONCLUSIONS: These results should provide support for definitive radiation therapy using 60 to 70 Gy to manage the patients with medically inoperable NSCLC without mediastinal involvement.

Actuarial Analysis↗

PubMed1995

LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck.

The Lck tyrosine kinase molecule plays an essential role in T cell activation and T cell development. Using the expression cloning technique, we have isolated a gene that encodes a molecule, LckBP1, able to associate with murine Lck. Analysis of full-length LckBP1 cDNA indicates at least four potentially important segments: a four tandem 37 amino acid repeat motif with a potential helix-turn-helix DNA binding motif; a proline-rich region; a proline-glutamate repeat; and an SH3 domain. These four regions are very similar to the human haematopoietic-specific protein 1 (HS1). Deletion mutant analysis of LckBP1 revealed two proline-rich regions that permit association with Lck SH3. One region contains prolines conserved among HS1 and cortactin, and the other region contains a potential MAP kinase recognition site. In vivo association between Lck and LckBP1 was confirmed by immunoprecipitation of lysates from a pre-T cell line and adult thymocytes using antibodies specific for Lck and LckBP1. LckBP1 is tyrosine phosphorylated after T-cell receptor stimulation. The SH3 domain and the potential helix-turn-helix motif in LckBP1 suggest that this molecule may associate with various molecules and function as a DNA binding molecule. The data also suggest that LckBP1 mediates intracellular signalling through Lck in T cells.

3T3 Cells↗

PubMed1995

Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: the subtilisin-like proprotein convertases.

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2 (SPC2) and PC1/PC3 (SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member--furin/PACE (SPC1)--is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation of the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.

Animals↗

PubMed1995

Effects of cilostazol on development of experimental diabetic neuropathy: functional and structural studies, and Na+ -K+ -ATPase acidity in peripheral nerve in rats with streptozotocin-induced diabetes.

We studied the ability of cilostazol (CL), an antithrombotic and vasodilating agent, to prevent functional, structural and biochemical abnormalities including delayed motor nerve conduction velocity (MNCV), morphological changes in myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the tail nerve, and morphometric analysis of the sural nerves revealed that this dose of cilostazol had a significant effect on reduction of average size of myelinated fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase activity of peripheral nerve were each significantly less than in normal control rats. Cilostazol (30 mg/kg/day) prevented reduction of Na(+)-K(+)-ATPase activity. Decrease in cyclic AMP content was completely prevented with both doses of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may have beneficial effects in the treatment of diabetic neuropathy, possibly via improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content. Cilostazol may thus be a potent drug for the clinical treatment of diabetic neuropathy.

Animals↗

PubMed1995

Establishment and characterization of a new human lung poorly differentiated adenocarcinoma cell line, GLL-1, producing carcinoembryonic antigen (CEA) and CA19-9.

A new human lung poorly differentiated adenocarcinoma cell line producing carcinoembryonic antigen (CEA) and CA19-9, designated GLL-1, was established from a serial xenograft established in our laboratory. In this paper, we investigated the characteristics of GLL-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of GLL-1 cells during exponential growth was approximately 28 h in RPMI-1640 with 10% fetal calf serum. Positive reactions for CEA and for CA19-9 were seen within the cytoplasm of GLL-1 cells by immunohistochemical staining. In log phase, the fractions for G0/G1, S and G2/M were 76.2%, 20.0% and 3.8%, respectively. Chromosome analysis revealed that GLL-1 cells contained the modal number of 72 chromosomes (range 66-97). GLL-1 cells exhibited numerous numerical and structural abnormalities. The Do value for radiation sensitivity, calculated by taking the reciprocals of the slope of the radiation dose response curve, was 109 cGy. The extrapolation number (n) for the radiation response curve was 1.57. Tumor take was observed in nude mice inoculated subcutaneously in the back with 2 x 10(6) GLL-1 cells. The histopathological features of the tumor induced by inoculation of GLL-1 cells were also the same as the original lung cancer.

Adenocarcinoma↗

PubMed1995

Clinical implication of symptoms in patients with non-small cell lung cancer treated with definitive radiation therapy.

To clarify clinical significance of symptoms presented at the beginning of treatment, we analyzed the symptoms in 240 patients with non-small cell lung cancer treated with definitive radiation therapy. Symptoms were classified into four groups: no symptom (Grade 0), cough, sputum/hemosputum and fever up (Grade 1), chest pain and breathlessness (Grade 2), appetite loss, body weight loss, SVC syndrome, hoarseness, and pain in the upper limb/shoulder (superior sulcus tumor) (Grade 3), and their therapeutic outcomes were examined. The 2- and 5-year overall actuarial survival rates for patients with squamous cell carcinoma were 38.5% and 15.4% for Grade 0, 40.5% and 20.1% for Grade 1, 17.9% and 2.6% for Grade 2, and 15.8% and 5.3% for Grade 3. A statistical difference was noted in survival between Grades 0-1 and Grades 2-3 (P < 0.01), but was not seen between Grades 0 and 1, or between Grades 2 and 3. As for patients with stage III disease alone, the difference in survival was still significant between Grades 0-1 and 2-3 (P < 0.05). In patients with adenocarcinoma/large cell carcinoma, however, no obvious relationship was found between symptoms and prognosis, except for body weight/appetite loss. In conclusion, though the symptoms closely related to clinical stage and performance status and not an independent prognostic factor, chest pain and breathlessness correlated with poor therapeutic outcome as well as body weight loss and T3-4 related symptoms, while cough, sputum (hemosputum), and fever were favorable symptoms in patients with squamous cell carcinoma who received definitive radiation therapy.

Actuarial Analysis↗

PubMed1995

Sonographic--histopathologic correlation on human tumor in nude mice treated with percutaneous ethanol injection therapy and radiation therapy.

OBJECTIVE: To clarify the relation between ultrasonography and histopathologic findings on tumor treated with percutaneous ethanol injection therapy (PEIT) and radiation therapy. MATERIALS AND METHODS: Ultrasound-histopathologic correlation was examined in animal models of PEIT and radiation therapy using human tumor xenografts. RESULTS: The detectability of intratumoral necrosis was correlated with size, distribution, and histologic features of necrosis. Echogenicity of necrosis induced by PEIT varied: coagulation necrosis with few basophilic degenerated nuclei was hyperechoic to viable tumor and easily recognized 7 to 14 days after PEIT. Necrosis, including abundant basophilic nuclei, showed similar echogenicity to viable tumor and was poorly identified. Six hours after radiation therapy, shrunken cells appeared scattered throughout the tumor, but they were not detected by ultrasound. CONCLUSION: To evaluate the effectiveness of a treatment with ultrasound through changes of internal echoes, the pattern of cell death also should be considered, which influences echogenicity of treated tumor tissue.

Animals↗

PubMed1995

Hyperfractionated and hypofractionated radiation therapy for human malignant glioma xenograft in nude mice.

Xenografts of a human malignant glioma subcutaneously transplanted into nude mice were irradiated with graded single doses (2, 5, 10 or 20 Gy) or five types of fractionation schedules in two weeks: conventional [20 Gy in 10 fractions (fr)], hyperfractionated [24 Gy in 20 fr (two fractions per day)], and hypofractionated-1, 2, 3 [20 Gy, 18 Gy, 16 Gy in 4 fr]. All of the fractionated irradiation groups showed tumor regression. The hypofractionation-1 group (20 Gy in 4 fr) demonstrated the most prominent tumor regression, while the hyperfractionation group (24 Gy in 20 fr) showed the least effect. The hypofractionation-2 group (18 Gy in 4 fr) showed similar regression to the conventional fractionation group (20 Gy in 10 fr). Histologically, tumors in the control groups consisted of a homogenous population of small anaplastic cells, and only a small number of tumor cells were glial fibrillary acidic protein (GFAP)-positive. Following irradiation, the population of small anaplastic cells decreased and the percentage of GFAP-positive cells increased. Cellular pleomorphism became much more prominent after irradiation in all of the fractionated irradiation groups as compared with the graded single dose irradiation groups. In this study, hyperfractionation was not effective against human glioma xenografts compared with conventional fractionation and hypofractionation. This indicates that care is needed in applying hyperfractionation regimens to human malignant gliomas.

Aged↗

PubMed1995

A matched-pair longitudinal study on the relationship between maternal smoking and head circumference of newborns.

The relationship between maternal smoking and the head circumference of newborns were analyzed using a matched-pair longitudinal method. For the study, data was collected from Japanese primiparas in Aichi, Japan. Forty-seven smoking and nonsmoking mothers were matched using multivariate caliper matching for birth weight and gender for their newborns, and gestational period and age for the gravidas. Significantly smaller head circumferences of the newborns from the smoking mothers were observed.

Birth Weight↗

PubMed1995

Association of the prohormone convertase 2 gene (PCSK2) on chromosome 20 with NIDDM in Japanese subjects.

Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3. PC2 is a type II proinsulin-processing enzyme, and it cleaves the proinsulin molecule on the COOH-terminal side of dibasic peptide, Lys64-Arg65, which joins the C-peptide and the A-chain domains. We have previously cloned and characterized the exon-intron organization of the human PC2 gene (gene symbol PCSK2), localized this gene to human chromosome 20 band p11.2 by fluorescence in situ hybridization, and identified a simple tandem-repeat DNA polymorphism (STRP) in intron 2 of the form (CA)n, suitable for genetic studies. Since non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased secretion of proinsulin and proinsulin-like molecules, we conducted a case-control study to determine whether a genetic variation in PCSK2 might contribute to the development of NIDDM. The study population consisted of 152 Japanese NIDDM subjects and 102 normal healthy nondiabetic control subjects matched for age and body mass index. The subjects were genotyped at the STRP in intron 2, and the results indicated a significant difference (P = 0.004) in the overall allele frequency distribution between the two groups. The A1 allele was found more frequently in NIDDM than in nondiabetic subjects (11 vs. 4%, P = 0.0068). The NIDDM patients were divided into two subgroups according to the presence or absence of the A1 allele.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1995

Geographic differences in seasonal variation of mean birth weight in Japan.

Seasonal variation of mean birth weight (MBW), mean gestational period (MGP), and MBW at 40 weeks of gestation (MBW40) in the 15 different prefectures of Japan were analyzed using vital statistics from 1974 to 1983. MBW generally shows a bimodal pattern with two peaks in spring and autumn and two troughs in summer and winter. Seasonality exhibits a general geographic trend: The autumn peak loses its height and the spring peak increases its amplitude as one moves from north to south. This trend suggests that environmental factors are associated with the creation of seasonality in MBW. For MGP the pattern is relatively unimodal with a deep trough in winter; however, a late summer small dip is observed in most cases. According to an analysis of coincidence between the two time series (MBW and MGP) and correlation analysis, the seasonal variation in birth weight basically depends on the gestational period. For MBW40, which represents the fetal growth rate, the seasonality shows a pattern similar to that of MBW. A statistically significant coincidence and a correlation are observed between the time series of MBW and MBW40. These results suggest that the two processes of fetal growth (gestational period and fetal growth rate) are associated with the creation of seasonality in MBW.

Birth Weight↗

PubMed1995

[Quick-freeze, deep-etch study of monkey lamina cribrosa].

Quick-freeze, deep-etch method was used to study the ultrastructure of normal monkey optic nerve lamina cribrosa. Glial cell somata were located beside collagen fibril bundles in the lamina cribrosa. Glial intermediate filaments, which were the main cytoskeletal proteins of 10-12 nm in diameter, were loosely packed in the somata and were tightly stacked in the processes. The glial plasma membrane directly abutted onto the myelin sheath of the optic nerve axon. The main component of the extracellular matrix (ECM) in the lamina cribrosa was interstitial collagen fibers of 30-60 nm in diameter, which were bridged by processes 5 nm in diameter and 20-30 nm in length and by 5 nm wide mesh-like structures. Small vessels running in the laminar beams were totally surrounded by basement membranes, laminar ECM, and glial cell components and thus were separated from optic nerve axons. The basement membrane which surrounded the laminar ECM was a fine fibrillar structure of 5 nm in diameter and also had numerous fibrils anchoring it to plasma membranes of vascular pericytes and glial cells.

Animals↗

PubMed1995

[Immunohistochemical study of radiation-induced apoptosis and oncogenes].

Relationships between radiation-induced apoptosis and oncogenes or suppressor genes (p53, MDM2, c-myc, p21ras and bcl-2) were immunohistochemically studied in 7 human tumors transplanted to nude mice. The most radiosensitive ependymoblastoma was negative for p53 and c-myc, however, the other 6 tumors were positive for them. Following irradiation, the ependymoblastoma became p53 positive, and showed the highest incidence of apoptosis among the 7 tumors. In addition, bcl-2 expression in this tumor was slightly different from that in the others.

Animals↗

PubMed1994

[Main household occupation and mean birth weight in Japan 1984].

By using the 1984 vital statistics released on magnet tapes by the Japanese government, we observed in the present study how the mean birth weight (MBW) varies from one group of mothers who fall under the same category of "main household job" to another. In so doing, we compared the MBWs among different job categories in terms of mother's age, baby's sex, and parity. The obtained results are summarized as follows: 1) The MBW of primiparae and male babies was found to be significantly different among the job categories in the age range of 20-39. In the group of multiparae and male babies, however, all the age ranges older that twenty showed significant differences in the MBW among the job categories. In the group of female babies, the significant difference was found in the age range of 20-39 and all the ranges older than twenty for primiparae and multiparae, respectively. 2) The above results were considered to be caused mainly by the low MBW in the category of "other" for primiparae, and by the high MBW in "part-time farming" and the low MBW in "other" for multiparae.

Adolescent↗