Biomedical subjects

S Takeshita

Publications and source records attributed to S Takeshita.

At least 19 recordsLinked to original sources

PubMed1992

Prognostic significance of histologic parameters of soft tissue sarcomas.

BACKGROUND AND METHODS: A univariate and multivariate analysis for the correlation between histomorphologic factors and prognosis was made using data from 1116 patients with soft tissue sarcoma, including 1005 cases available with complete histologic and follow-up data. RESULTS: The overall 5-year survival rate was 43.6%. The univariate analysis using Kaplan-Meier survival curves showed that tumor differentiation, cellularity, nuclear atypia, cellular pleomorphism, mitotic activity, amount of fibrous stroma, extent of myxoid areas, extent of tumor necrosis, and histologic grading (determined by the estimated range of malignancy for each type of sarcoma using a reported guideline) were all significant prognostic factors in the overall soft tissue sarcoma group. By a multivariate analysis using a procedure based on the Weibull model to failure data, the histologic grading and extent of tumor necrosis were proved to be prognostically significant in the overall sarcoma group. However, after additional analysis on each histologic type of sarcoma, it was determined that both tumor necrosis and histologic grading were applicable in only two types: malignant fibrous histiocytoma and leiomyosarcoma. Liposarcoma, synovial sarcoma, and malignant schwannoma each also showed some determinable factor of prognostic significance. CONCLUSIONS: It was concluded that there seemed to be no single universal prognostic parameter that could be applied to each soft tissue sarcoma type. These results suggest that the predictive significance of the various histologic parameters should be based on each specific type of sarcoma.

Adolescent↗

PubMed1992

Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.

The roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case-control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, Cl 5.9 to 32.5), whereas heavy drinkers experienced about a 2-fold risk increase compared with non-drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex-smokers (RR = 1.5, 95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non-smokers, but without evidence for a dose-response relationship in terms of pack-years. Analysis among HBsAg-negative subjects revealed similar non-significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7, 2.2 to 6.3) and familiar liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.

Adult↗

PubMed1992

Alleviation of intestinal lesions by combined treatment with a 5-fluoro-2'-deoxyuridine (FUDR) derivative and alpha-difluoromethylornithine (DFMO)[correction of DMFO] in tumor-bearing mice.

alpha-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced intestinal lesions in tumor-bearing mice caused by treatment with N3-(3-methylbenzoyl)-3',5'-diacetyl [corrected]-FUDR (FF-705), a derivative of 5-fluoro-2'-deoxyuridine (FUDR). FF-705 at 32 mg/kg (the effective dose) suppressed tumor growth to about 40% of the control level. At this dose, body weight gain was suppressed slightly when FF-705 was given alone, and this change was milder in the DFMO-supplemented group. Intestinal lesions were suppressed almost completely by concomitant treatment with DFMO. The gross lesion index in the combined treatment group was similar to that in the controls and significantly smaller than in the FF-705-alone group (0.3 and 1.9, respectively). The histological lesion index in the combined treatment group was also significantly smaller than in the FF-705-alone group (7.9 and 23.8, respectively). When FF-705 was given at 64 mg/kg, the intestinal mucosal lesions were more severe, but DFMO supplementation reduced them by approximately 50%. Moreover, maltase and diamine oxidase activities of intestinal epithelium remained higher with combined treatment than with FF-705 alone. With FF-705 at 256 mg/kg (a toxic dose), DFMO had little protective effect against intestinal damage.

Amine Oxidase (Copper-Containing)↗

PubMed1992

Anomalous origin of the left coronary artery from the pulmonary artery: direct assessment of anomalous and collateral coronary flow by pulsed Doppler echocardiography.

We directly assessed the anomalous and collateral coronary flow profiles of a 58 year-old-man with Bland-White-Garland syndrome using pulsed Doppler echocardiography. Doppler recordings in this patient document the utility of pulsed Doppler echocardiography in the assessment of a cardiac shunt associated with a congenital coronary anomaly in an adult.

Blood Flow Velocity↗

PubMed1992

Hydroxyl radical generation by red tide algae.

The unicellular marine phytoplankton Chattonella marina is known to have toxic effects against various living marine organisms, especially fishes. However, details of the mechanism of the toxicity of this plankton remain obscure. Here we demonstrate the generation of superoxide and hydroxyl radicals from a red tide unicellular organism, C. marina, by using ESR spectroscopy with the spin traps 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-t-butyl-alpha-phenylnitrone (PBN), and by using the luminol-enhanced chemiluminescence response. The spin-trapping assay revealed productions of spin adduct of superoxide anion (O2-) (DMPO-OOH) and that of hydroxyl radical (.OH) (DMPO-OH) in the algal suspension, which was not observed in the ultrasonic-ruptured suspension. The addition of superoxide dismutase (500 U/ml) almost completely inhibited the formation of both DMPO-OOH and DMPO-OH, and carbon-centered radicals were generated with the disappearance of DMPO-OH after addition of 5% dimethyl sulfoxide (Me2SO) and 5% ethanol. Furthermore, the generation of methyl and methoxyl radicals, which are thought to be produced by the reaction of hydroxyl radical and Me2SO under aerobic condition, was identified using spin trapping with a combination of PBN and Me2SO. Luminol-enhanced chemiluminescence assay also supported the above observations. These results clearly indicate that C. marina generates and releases the superoxide radical followed by the production of hydroxyl radical to the surrounding environment. The velocity of superoxide generation by C. marina was about 100 times faster than that by mammalian phagocytes per cell basis. The generation of oxygen radical is suggested to be a pathogenic principle in the toxication of red tide to susceptible aquaculture fishes and may be directly correlated with the coastal pollution by red tide.

Cyclic N-Oxides↗

PubMed1992

Diet and prognosis of breast cancer.

The relationship between the occurrence of breast cancer and dietary intake, in particular a high-fat diet, has attracted much attention in recent years. In addition, the prognosis of breast cancer patients on the basis of dietary intake is also an interesting subject. The present study utilized breast cancer patients whose dietary intake was carefully assessed about one decade previously in a case-control study to determine whether dietary intake was indeed related to the patients' prognosis. The study included 212 patients who underwent a surgical operation between 1975 and 1978. They were followed-up until 1987, and a total of 47 breast cancer deaths were certified. The 5- and 10-year relative survival rates were 78.5% and 75.3%, respectively. The older patients tended to ingest smaller amounts of all nutrients, except animal fat from fish. Height was significantly correlated with total animal protein intake, whereas there was no significant correlation between body mass index and intake of any nutrient. Although the age-adjusted mean values of the nutrient intakes, other than vegetable fat, decreased with advancing stage, the differences were statistically insignificant. The results of multivariate analyses, in which some confounding factors (e.g., clinical stage) were adjusted using a proportional hazards model, showed that all hazards ratios in each nutrient were close to unity, and no dose-response relationship was seen. The present investigation did not provide any support for the hypothesis that a high-fat diet is a survival determinant for breast cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

PubMed1992

Genomic organization of the mouse OSF-1 gene.

The mouse OSF-1 protein (also known as pleiotrophin, HB-GAM, HBGF-8, or HBNF) gene was isolated from a mouse genomic library and sequenced. OSF-1 is a 15-kD secreted protein specifically expressed in bone and brain, and is believed to play a role in brain development and osteogenesis. The mouse OSF-1 gene consists of at least 5 exons and 4 introns and spans > 32 kb. Computer analysis of approximately 4 kb of 5'-flanking sequence of the OSF-1 gene revealed two candidate promoter regions. One candidate promoter contains a thyroid hormone/retinoic acid-responsive element and the other contains two glucocorticoid-responsive elements. DNA sequence analysis of novel OSF-1 cDNA clones indicates that two promoters can be utilized in MC3T3-E1 osteoblastic cells. The overall organization of the mouse OSF-1 gene is similar and the locations of the three exon-intron junctions within the coding region are identical to the mouse gene encoding the differentiation-related factor midkine (MK). Based on this similarity and on the high degree of nucleotide sequence homology (approximately 55%) of mouse OSF-1 and mouse MK, we conclude that OSF-1 and MK are generated from a common ancestral gene and are members of a family of structurally and probably functionally related proteins.

Amino Acid Sequence↗

PubMed1992

Various factors associated with the manifestation of influenza-like illness.

A survey enrolling 814 schoolchildren was conducted immediately after a peak epidemic in the 1988-1989 influenza season and then a case-control study for influenza-like illness (ILI) was carried out using information concerning illness onset and usual lifestyle. Based on the analysis of the correlations among symptoms and actions taken due to symptoms, cases were defined as those with fever greater than or equal to 38 degrees C and subsequent absenteeism and medical consultation during peak epidemic; within this, mild-ILI (MILI) was defined as fever greater than or equal to 38 degrees C and less than 39 degrees C, and severe-ILI (SILI) as fever greater than or equal to 39 degrees C. Controls were defined as those with no symptoms (NS) during that period. Adjusted odds ratios (OR) were obtained through an unconditional logistic regression model between the MILI (80) or SILI (48) and NS (196) groups from among respondents (803). For MILI, increased risks were observed for easily-inflamed tonsils (OR = 3.0, 95% CI: 1.7-5.4); and larger family size (1.9, 1.1-3.4); with decreased risks for higher school grades (0.4, 0.2-0.9); frequent intake of vegetables or fruits other than green/yellow vegetables (0.5, 0.3-1.0); and larger room space per capita (0.4, 0.2-0.9). For SILI, there were increased risks for easily-inflamed tonsils (3.8, 1.8-8.1) and history of doctor-diagnosed asthma (2.9, 1.2-6.7); and decreased risks for higher grades (0.2, 0.1-0.6), frequent intake of milk or dairy products (0.3, 0.1-0.6) and vaccination (0.3, 0.1-0.8).

Case-Control Studies↗

PubMed1992

Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.

The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.

Angiography↗

PubMed1992

Individual and environmental characteristics related to influenza-like illness among children: a school-based case-control study.

To investigate individual and environmental characteristics associated with the manifestation of influenza-like illness (ILI), a survey enrolling 509 schoolchildren was conducted after an epidemic peak in the 1988/89 season, and then a case-control study was designed according to the information concerning illness onset and usual life-style. Case series were defined as those with fever greater than or equal to 38 degrees C due to acute respiratory illness, subsequent absenteeism and medical consultation during the epidemic peak; mild-ILI (MILI; fever greater than or equal to 38 degrees C and less than 39 degrees C) and severe-ILI (SILI; fever greater than or equal to 39 degrees C). Control series were defined as those with no symptoms (NS) during the same period. An adjusted odds ratio (OR) was obtained using an unconditional logistic regression model for MILI (55) or SILI (33) and NS (204) groups among respondents (508). For MILI, increased risk was observed for easily inflamed tonsils (OR, 3.2; 95% CI, 1.6-6.4), with decreased risks for higher school grade (0.4, 0.2-0.8) and frequent intake of milk or dairy products (0.5, 0.3-1.0), but no significant association was determined for vaccination (0.6, 0.3-1.2). For SILI, there was an increased risk for easily inflamed tonsils (3.3, 1.4-7.9); and decreased risks for the higher grades (0.1, 0.1-0.3); use of a kerosene or gas heater with indoor exhaust (0.4, 0.2-0.9); and vaccination (0.3, 0.1-0.7). The OR of vaccinees for SILI constantly decreased regardless of grade and easily inflamed tonsils.

Age Factors↗

PubMed1992

Novel TCR gene rearrangements and expression in radiation-induced thymic lymphomas.

Using the intrathymic (i.t.) injection assay with a B10.Thy 1 congenic donor-host combination, we previously demonstrated that the pre-neoplastic cells (thymic prelymphoma cells) exist in immature T cell subpopulations; mainly in CD4-CD8- double negative (DN) and CD4-CD8+ single positive (SP) thymocytes and to some extent in CD4+CD8+ double positive (DP) thymocytes. Most thymic lymphomas that developed from these prelymphoma cells showed concomitant TCR alpha, beta and gamma gene rearrangements and expression. In this lymphomas, two lymphomas also showed TCR delta gene rearrangements. This represents the intermediate stages of TCR gene rearrangement. Every lymphoma, however, expressed CD3-associated alpha beta TCR on the cell surface, but not gamma delta TCR. Novel rearrangements of V gamma 4 and J gamma 4-C gamma 4 segments with non-gamma elements were found respectively in a concerted and symmetrical fashion. Recombinase-mediated inter-chromosomal exchanges characteristic of thymic lymphomas may function in radiation-induced lymphomagenesis.

Animals↗

PubMed1992

[Percutaneous transluminal coronary angioplasty and coronary bypass grafting for refractory angina in chronic dialysis patients].

Between June 1983 and July 1989, 25 consecutive chronic dialysis patients with medically refractory angina pectoris underwent revascularization, either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) (21 males and 4 females, mean age of 57 +/- 10 years, and mean duration of dialysis of 3.7 +/- 5.0 years). Patients with single-vessel disease and/or mildly calcified lesions received PTCA (n = 15), while those with multi-vessel disease and/or severely calcified lesions received CABG (n = 10). As controls for PTCA-treated dialysis patients, 208 non-dialysis patients who received initial PTCA in 1988 were used. The mean number of diseased vessels was 2.7 +/- 0.7 for CABG group, and 1.5 +/- 0.8 for PTCA group (p < 0.01). In both groups, 80% of patients were successfully revascularized. In CABG group, however, 7 of 10 patients had major complications including 2 hospital deaths, while no complications occurred in the PTCA group. During the follow-up period after CABG (35 +/- 30 months), recurrent angina developed in one patient, who was successfully treated with PTCA. In the PTCA group, angiographic success was initially obtained in 16 of 21 lesions (76%), which was significantly lower than that in the control group (92%, p < 0.05). Follow-up angiography revealed restenosis in 6 of 16 lesions with successful PTCA (38%), similar to that observed in the control group (32%, p = ns). A second PTCA was successful in 5 of 6 patients with restenosis, however, 4/5 patients developed recurrent angina. Three of 4 patients with a second episode of restenosis underwent a third PTCA, and angina recurred in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Conserved V(D)J junctional sequence of cross-reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution.

A dominant T cell population bearing the cross-reactive idiotype of T cell antigen receptor (TcR) has been obtained using an anti-TcR monoclonal antibody (mAb) developed in syngeneic mice. Forty-four cytotoxic T cell (CTL) clones with reactivity to a mAb (N9-127) were selected out of 396 H-2Db-restricted CTL clones specific for FBL-3 tumor antigen from C57BL/6 mice. These CTL clones were divided into two groups according to the blocking pattern of cytotoxic activities with mAb N9-127. All eight CTL clones chosen from both groups expressed TcR with a specific combination of alpha and beta chains (V alpha 1J alpha 112-2/V beta 10D beta 2.1J beta 2.7), and the difference in the blocking susceptibility resided in a single amino acid substitution (Gly to Asp) in the D-J joint of beta chain. This provides direct evidence for the molecular basis of cross-reactive idiotypes of TcR recognized by mAb.

Amino Acid Sequence↗

PubMed1991

Structure of extrachromosomal circular DNAs generated by immunoglobulin light chain gene rearrangements.

Recombination at the immunoglobulin kappa or lambda light chain locus generates extrachromosomal circular DNAs. We have isolated circular DNAs from adult mouse spleen cells and prepared a circular DNA clone library. We characterized four J kappa-positive and one J lambda 1-positive clones. The J kappa-clones contained both coding and signal joints of V kappa-J kappa joining, and the J lambda 1-clone contained a signal joint of V lambda 1-J lambda 1 joining. Genomic organization of the V kappa gene families used in these joints suggested the excision of circular DNA preceded by inversion. A specific dinucleotide (P) insertion in the coding joint was observed in two clones. Three coding joints were out of frame and one clone had an in-frame coding joint, although possibly combined with a pseudo-V kappa gene. These kappa-positive circular DNAs are possibly excised from the chromosome by secondary recombinations which replace non-productive primary rearrangements.

Amino Acid Sequence↗

PubMed1991

Effect of an acute maternal stress on the fetal hypothalamo-pituitary-adrenal system in late gestational life of the rat.

We investigated in this study the response of the fetal hypothalamo-pituitary-adrenal (HPA) system during an acute maternal stress in rats, in order to find out a possible role of developing fetal hypothalamus and to correlate its function to the androgen unbalance during the critical period of sex-specific brain differentiation. Pregnant rats of days 18-22 of gestation were subjected to an acute forced immobilization, and plasma levels of corticosterone (B) and ACTH were measured in mothers and fetuses. Hypothalamic contents of CRH and beta-endorphin (EP), pituitary content of ACTH, and plasma levels of B and ACTH were measured in mothers and fetuses under the maternal stress on day 20 of gestation. By an acute exposure to the 20 minutes' stress, plasma levels of B and ACTH elevated significantly in mothers on each day of gestation. A significant increase of fetal plasma ACTH was detected from day 18 in males, and from day 20 in females. During the maternal stress on day 20 of gestation, hypothalamic contents of CRH and EP decreased significantly in male and female fetuses, when plasma levels of B and ACTH elevated significantly. These results indicate that fetal HPA axis seems to actually respond to the maternal stress during the late gestational period. Further, a release of CRH under the stress together with an activation of EP system in the fetal hypothalamus suggests a possible mechanism regulating the androgen secretion by the fetal hypothalamus via changes of the LH levels.

Adrenocorticotropic Hormone↗

PubMed1991

Ontogeny of the response of the hypothalamo-pituitary-adrenal axis to maternal immobilization stress in rats.

In this study we investigated the response of the rat fetal hypothalamo-pituitary-adrenal (HPA) axis to an acute maternal stress in late gestation. On day 20 of gestation, pregnant rats were exposed to forced immobilization stress for up to 60 min. In mothers, a significant increase in plasma ACTH and corticosterone(B) was observed at 20 and 60 min. The ACTH content in the maternal pituitary decreased significantly at 60 min. Fetal blood pH was decreased by the maternal stress, showing a hypoxic condition of the fetus. Fetal plasma ACTH increased transiently at 20 min. Fetal plasma B increased at 20 and 60 min. ACTH in the fetal pituitary and the placenta did not show marked changes due to the maternal stress. Pregnant rats on day 18-21 of gestation were subjected to a 20 min maternal stress. In the basal condition without stress, fetal plasma ACTH and B showed parallel ontogenic patterns, having a peak value on day 19 of gestation. Fetal plasma ACTH as well as plasma B were increased significantly by the maternal stress at all points evaluated. These results indicate that fetal hypoxia is important in stress transmission to the fetal HPA axis in this type of maternal stress, and the fetal HPA axis responds to the stress as early as day 18 of gestation.

Adrenocorticotropic Hormone↗

PubMed1991

The effect of an acute stress in late pregnancy on hypothalamic catecholamines of the rat fetus.

Prenatal stress in the last trimester of pregnancy induces permanent disorders in sex-specific differentiation of the brain in rats. In order to determine the neuroendocrine response of the fetal hypothalamus to the maternal stress, we investigated the temporal change in fetal hypothalamic catecholamines when their mothers were exposed to an acute stress. On day 20 of gestation, pregnant rats were subjected to forced immobilization and sacrificed at 0, 30, 60, 120 and 180 minutes. Plasma corticosterone reached a peak at 60 minutes of stress in mothers and fetuses. Hypothalamic norepinephrine and epinephrine decreased at 120 and 180 minutes of stress in mothers, whereas in fetuses, hypothalamic norepinephrine decreased at 120 and 180 minutes of stress, and dopamine also showed a tendency to decrease. These results suggest that maternal stress in late pregnancy decreases fetal hypothalamic norepinephrine which is involved in androgen-dependent sex differentiation of the brain.

Androgens↗

PubMed1990

Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues.

Using the differential hybridization screening method between osteoblastic and fibroblastic cells, a cDNA clone coding for an osteoblast specific protein, named OSF-1, consisting of 168 amino acid residues including a possible 32 amino acid long leader sequence, was isolated from murine osteoblastic cell line MC3T3-E1. The OSF-1 gene was shown by Northern blotting analysis to be expressed in mouse calvarial osteoblast-enriched cells and in mouse brain tissues, but not in thymus, spleen, kidney, liver, lung, testis or heart. The human counterpart was also found in cDNA libraries from human osteosarcoma cell line MG63 and normal brain tissues. DNA sequence analysis revealed four amino acid sequence differences between the mouse and human, of which only one is located in the mature protein. This extremely high sequence conservation suggests that OSF-1 plays a fundamental role in bone and brain functions.

Animals↗