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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 235 records · Page 13Linked to original sources
PubMed1999

High normal blood pressure, hypertension, and the risk of type 2 diabetes in Japanese men. The Osaka Health Survey.

OBJECTIVE: To investigate the relationship between high normal blood pressure or hypertension and the risk of developing type 2 diabetes in a large Japanese cohort. RESEARCH DESIGN AND METHODS: We enrolled 7,594 Japanese men aged 35-60 years who did not have diabetes or impaired fasting glucose at study entry. Type 2 diabetes was defined as a fasting plasma glucose level of > or = 126 mg/dl or a 2-h postload plasma glucose level of > or = 200 mg/dl. High normal blood pressure was defined as no history of hypertension and a systolic blood pressure of > or = 130 and < 140 mmHg or a diastolic blood pressure of > or = 85 and < 90 mmHg. Subjects were considered to have hypertension if they had a systolic blood pressure > or = 140 mmHg, if they had a diastolic blood pressure > or = 90 mmHg, or if they were taking anti-hypertensive medications. RESULTS: We confirmed 600 cases of type 2 diabetes during the 72,946 person-years of follow-up. Both high normal blood pressure and hypertension were associated with the risk of type 2 diabetes. Compared with normotensive men, men with high normal blood pressure had a multiple adjusted relative risk (RR) of 1.39 (95% CI 1.14-1.69), and men with hypertension had a multiple adjusted RR of 1.76 (1.43-2.16). Even among lean men (BMI < 22.7 kg/m2), men with high normal blood pressure had a multiple adjusted RR of 1.71 (1.20-2.42), and men with hypertension had a multiple adjusted RR of 2.02 (1.34-3.05) compared with normotensive men. CONCLUSIONS: High normal blood pressure and hypertension are associated with an increased risk of developing type 2 diabetes.

Adult↗
PubMed1999

Impaired fasting glucose and the risk of hypertension in Japanese men between the 1980s and the 1990s. The Osaka Health Survey.

OBJECTIVE: To determine whether impaired fasting glucose (IFG) increased the risk for hypertension in two large Japanese cohorts during the different time periods. RESEARCH DESIGN AND METHODS: We prospectively investigated two Japanese cohorts: a 1980s population, comprising 4,130 normotensive and nondiabetic men aged 35-60 years entered between 1981 and 1983, and a 1990s population, comprising 4,319 normotensive and nondiabetic men aged 35-60 years entered between 1991 and 1992. Data on lifestyle factors were obtained from questionnaires. IFG was defined as a fasting plasma glucose level > or = 110 and < 126 mg/dl. RESULTS: During the 4-year observation period, 708 cases of hypertension were confirmed in the 1980s and 848 cases were confirmed in the 1990s. In both the 1980s and 1990s populations, IFG was associated with the risk of hypertension. The frequency of IFG in men in the 1990s group was twice as high as that in the 1980s group. The multivariate-adjusted odds ratio (OR) of hypertension was 1.54 (95% CI, 1.01-2.34) for men with IFG in the 1980s population and 1.73 (1.31-2.29) in the 1990s population, compared with those without IFG in the two populations. In the 1990s population, among lean men with a BMI < or = 23 kg/m2, men with IFG had a multivariate-adjusted OR of hypertension of 2.31 (1.46-3.65) compared with those without IFG. CONCLUSIONS: This study demonstrated direct correlation between IFG and hypertension and greater incidence of this hypertension in the 1990s group than in the 1980s group.

Adult↗
PubMed1999

Daily alcohol consumption and the risk of type 2 diabetes in Japanese men: the Osaka Health Survey.

OBJECTIVE: To investigate the relationship between daily alcohol consumption and the risk of type 2 diabetes in a large Japanese cohort. RESEARCH DESIGN AND METHODS: We enrolled 6,362 Japanese men aged 35-61 years who did not have diabetes, impaired fasting glucose, hypertension, or liver cirrhosis at study entry. Type 2 diabetes was defined as a fasting plasma glucose (FPG) level > or =126 mg/dl or was diagnosed by a physician. Data on alcohol consumption were obtained from questionnaires. We confirmed 456 cases of type 2 diabetes during the 62,016 person-years of follow-up. RESULTS: The relationship between daily alcohol consumption and the risk of type 2 diabetes among lean men and among men with a higher BMI was paradoxical. Among lean men (BMI < or =22.0 kg/m2), heavy drinking was associated with an increased risk of type 2 diabetes. Men who consumed > or =50.1 ml/day of alcohol had a relative risk (RR) of 2.48 (95% CI 1.31-4.71) compared with nondrinkers after adjusting for age, BMI, regular physical exercise, parental history of diabetes, smoking habits, and FPG level. However, among men with a BMI > or =22.1 kg/m2, moderate drinking (29.1-50.0 ml/day) was associated with a decreased risk of type 2 diabetes. Daily moderate drinkers had a multiple adjusted RR of 0.58 (0.39-0.87) compared with nondrinkers. CONCLUSIONS: Among men with a BMI > or =22.1 kg/m2, moderate alcohol consumption was associated with a reduced risk of type 2 diabetes, but among lean men (BMI < or =22.0 kg/m2), heavy alcohol consumption was associated with an increased risk of type 2 diabetes.

Adult↗
PubMed1999

[A case of hepatocellular carcinoma with tumor thrombus in the right atrium successfully treated by arterial administration of lipiodol-SMANCS].

In February, 1996, a 73-year-old male with liver dysfunction was admitted to our hospital for further examination and treatment of liver tumor. The liver tumor was revealed by imaging examination, which was mainly in the S4-S8 of liver with a thrombus growing from the right anterior branch to the right branch of the portal vein, and from the right hepatic vein to the inferior vena cava and right atrium. The serum AFP and PIVKA-II levels were elevated to 3.610 ng/ml and 54 AU/ml, respectively. The patient was diagnosed as having hepatocellular carcinoma, and was treated by arterial administration of anticancer drugs (epirubicin hydrochloride, mitomycin C and carboplatin) and TAE. Though the main tumor (S4-S8 of liver) was reduced by TAE, the portal and atrial tumor thrombus did not respond. One month after TAE (20 May, 1996), the first arterial administration of Lipiodol-SMANCS was given, followed by 4 successive procedures with an interval of about 1.5 months (total dose 15 mg), resulting in remarkable tumor thrombus shrinkage and reduction of AFP levels to 80 ng/ml. This case shows that arterial administration of SMANCS may be one of the effective treatments for hepatocellular carcinoma, even with tumor thrombus of hepatic vein, IVC and right atrium.

Aged↗
PubMed1999

[Effective treatment of AFP-producing lung cancer with UFT].

The main form of chemotherapy for non small cell lung cancer is a multiple combination therapy centered on cisplatin (CDDP). We herein report a case in which a favorable course was obtained for a patient with extremely rare AFP-producing lung cancer by single oral administrations of UFT, following extirpation of brain metastasis. The patient was an 80-year-old male whose main complaints were headache and aphasia. Following close examination, a diagnosis was made of moderately differentiated adenocarcinoma with the primary lesion in S6 of the right lung. A metastatic lesion was found in the left occipital lobe. Blood AFP was an abnormally high 17,000 ng/ml. No tumorous lesions were found in the liver. The brain metastasis were extirpated to alleviate cranial nerve symptoms, and the tissue was found to be the same as that of the primary lesion. AFP staining of the tumor tissue revealed positive cells. Because there was proliferation in the primary tumor following surgery, administration of UFT (300 mg/day Tegafur) was begun. Four weeks later the tumor had begun to shrink, and at 15 weeks was judged to be a partial response. A reduction in AFP was also seen. The patient showed absolutely no side effects from UFT, thus enabling outpatient treatment. Good results were obtained both in reducing the tumor and in maintaining the patient's quality of life.

Adenocarcinoma↗
PubMed1999

[Lung cancer detected in a patient under age 40 treated for pneumothorax].

We report a case of lung cancer in a relatively young patient who presented pneumothorax. A 31-year-old man complaining of pressure in his left chest was admitted with left pneumothorax disclosed on X-ray film. Although pleural drainage was performed for a week, the left lung did not expand well, and surgical treatment was required. During surgery, a tumor (1.5 x 1.0 cm in size) was discovered in the upper lobe of the left lung (S3). Histopathological examination revealed that it was a large cell carcinoma. People under the age of 40 account for only a small fraction of the entire lung cancer patient population. Pneumothorax occurs together with lung cancer, especially in people under age 40. We reasoned that lung cancer should be considered a possible complication in patients under 40 who experience recurrent or prolonged bouts of pneumothorax.

Adult↗
PubMed1999

Abnormal expression of sex steroid receptors and cell cycle-related molecules in adenocarcinoma in situ of the uterine cervix.

It was recently reported that cervical adenocarcinoma showed an abnormal expression of estrogen receptor (ER) and cell cycle-related molecules (cyclin E, p53, p16, p21, and p27). To investigate whether similar alterations exist in glandular intraepithelial lesions, the expression of ER, progesterone receptor (PR), Ki-67, and the above cell cycle-related molecules was examined in 15 cases of glandular dysplasia (GD) and 10 cases of adenocarcinoma in situ (AIS), using the immunohistochemical technique. An expression of ER and PR was often decreased or missing in GD and, especially, in AIS. The Ki-67 labeling index was significantly higher in AIS than in GD or normal glandular cells. In GD, expression of all the cell cycle-related molecules was not recognized (except for a few p27-positive cases), a situation comparable to normal glands. In contrast, an abnormal expression of all the cell cycle-related molecules examined was demonstrated in AIS. There was a significant positive correlation, in terms of the extent of staining, between cyclin E and p21 in AIS. These results suggest that an altered expression of these molecules occurs in AIS as it does in invasive adenocarcinoma, and provide additional evidence supporting AIS as a precursor of cervical adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Granular cell tumor of the breast: report of a case.

A case of granular cell tumor of the breast in a 43-year-old woman is described. The patient presented with a painless mass in the upper-outer quadrant of her right breast. Mammography showed a spiculated tumor and ultrasonography demonstrated a hypoechoic mass with an irregular border. Magnetic resonance (MR) mammography revealed a homogeneous enhanced mass in T1-weighted images using Gd-DTPA and a ringed high-intensity area around the mass in T2-weighted images. Fine-needle aspiration cytology failed to show any malignant cells. A partial resection of the breast was performed and histological examination revealed a granular cell tumor. Granular cell tumors are generally always benign, but they may be misdiagnosed as malignant tumors because of their mammographic and ultrasonographic findings. MR mammography did not reveal a typical breast cancer in either T1- or T2-weighted images in the present case. This case illustrates the need for care in preoperative examinations in order to avoid overdiagnosis of breast cancer.

Adult↗
PubMed1999

Characterization of T-cell receptor beta chain mRNA expression in IFN-alpha-responsive chronic myelogenous leukaemia patients.

Interferon-alpha (IFN-alpha) has shown promise in the treatment of chronic phase of chronic myelogenous leukaemia (CML). IFN-alpha has also been found to indirectly up-regulate the expression of major histocompatibility (MHC) antigens, and to directly increase the activity of lymphocytes against tumour cells. To elucidate whether IFN-alpha induces anti-leukaemic activity of the autologous T cells in CML patients, we analysed the accumulation of T-cell receptor (TCR) in each Vbeta family using the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by single-strand conformation (SSCP) analysis. We found the predominant expression of the Vbeta 10, 12, and 14 families in the peripheral blood (PB) of CML patients, in contrast to healthy donors. Especially, in IFN-alpha-responsive patients, we observed an enhancement of the accumulation of the Vbeta 9 and 20 families, suggesting that T cells enhanced by IFN-alpha may react with a discrete set of antigens on the surface of malignant cells. These findings may demonstrate that CML cells possess the heterogenous antigens and the clonal expansion of Vbeta 9+ and Vbeta 20+ T cells may be a prognostic indicator of the immune responsiveness to IFN-alpha.

Adult↗
PubMed1999

[Vitamin B1 deficiency polyneuropathy presenting homolateral imitative synkinesia].

We report a 56-year-old woman with vitamin B1 polyneuropathy, showing bilateral homolateral imitative synkinesia. Needle electromyogram revealed neurogenic changes, and the amplitude of muscle action potential was low. Sural nerve biopsy showed a marked loss of myelinated fibers, and severe axonal degeneration was diagnosed. Spinal and brain MRI revealed no abnormalities. In the literature, these synkinesias were observed in patients with parietal, thalamic, and basal ganglia lesions and with chorea. We suggest that this synkinesia is the release phenomenon in the circuit of the motor programming system due to the disturbance of peripheral nerve or funiculus posterior.

Electromyography↗
PubMed1998

Design and synthesis of new secretory phospholipase A2 inhibitor of a phospholipid analog.

All stereoisomers of N-acyl-4,5-disubstituted oxazolidinone phospholipid analogs were synthesized by regio and stereoselective epoxide ring opening accompanied by introduction of an amino group. The (4R,5S)-derivative showed stronger inhibitory activity toward type II phospholipase A2 than the 4-substituted oxazolidinone phospholipid analog previously reported.

Drug Design↗
PubMed1998

Mg2+ binding and catalytic function of sphingomyelinase from Bacillus cereus.

The modes of Mg2+ binding to SMase from Bacillus cereus were studied on the basis of the changes in the tryptophyl fluorescence intensity. This enzyme was shown to possess at least two binding sites for Mg2+ with low and high affinities. The effects of Mg2+ binding on the enzymatic activity and structural stability of the enzyme molecule were also studied. The results indicated that the binding of Mg2+ to the low-affinity site was essential for the catalysis, but was independent of the substrate binding to the enzyme. It was also indicated that the alkaline denaturation of the enzyme was partly prevented by the Mg2+ binding, whereas no significant protective effect was observed against the denaturation by urea. The pH dependence of the kinetic parameters for the hydrolysis of micellar HNP and mixed micellar SM with Triton X-100 (1:10), catalyzed by SMase from B. cereus, was studied in the presence of a large amount of Mg2+ to saturate both the low- and high-affinity sites. The pH dependence curves of the logarithm of 1/Km for these two kinds of substrates were similar in shape to each other, and showed a single transition. On the other hand, the shapes of the pH dependence curves of the logarithm of kcat for these two kinds of substrates were different from each other. The pH dependence curve for micellar HNP showed three transitions and, counting from the acidic end of the pH region, the first and third transitions having tangent lines with slopes of +1 and -1, respectively. On the other hand, the curve for mixed micellar SM with Triton X-100 showed one large transition with a slope of +1 (the first transition) and a very small transition (the third transition). On the basis of the present results and the three-dimensional structure of bovine pancreatic DNase I, which has a primary structure similar to that of B. cereus SMase, we proposed a catalytic mechanism for B. cereus SMase based on general-base catalysis.

Animals↗
PubMed1998

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.

The contribution of hydrogen bonds to the conformational stability of human lysozyme was investigated by the combination of calorimetric and X-ray analyses of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0 to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB), considering factors affected by substitutions, was evaluated on the basis of X-ray structures of the mutant proteins. In the present study, one of six mutant proteins was suitable for evaluating the strength of the hydrogen bond. Delta Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5 kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule, contribute to the stabilization of the human lysozyme.

Calorimetry, Differential Scanning↗
PubMed1998

Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible immunohistochemical marker of a favorable prognosis.

BACKGROUND: The purpose of this study was to assess the prognostic significance of the expression of estrogen receptor and cell cycle regulatory gene products in cervical adenocarcinoma. METHODS: In 40 cases of adenocarcinoma of the uterine cervix and 10 normal cervices, expression of estrogen receptor and cell cycle regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was studied using immunohistochemical techniques. The survival of the patients was analyzed in terms of such variables as the expression of these molecules in the tumor and conventional clinicopathologic features, and the Cox proportional hazards model was used to predict the survival of patients with cervical adenocarcinoma. RESULTS: Expression of estrogen receptor was consistently observed in normal cervical glands, but in cervical adenocarcinoma it was lost (in 28 cases) or significantly diminished (in 12 cases). Normal cervical glandular cells were usually negative for the cell cycle regulatory gene products, whereas 47.5-85% of cervical adenocarcinomas were positive for these molecules. When the expression of these molecules was analyzed, significant positive correlations were found between p16 and p27, cyclin E and p27, and cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the presence of parametrial invasion, the presence of lymph node metastasis, negative staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all correlated significantly with a poor prognosis. In a stepwise regression analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the best predictors of a favorable prognosis. CONCLUSIONS: Expression of p21WAF1/CIP1 correlated with a favorable prognosis for patients with cervical adenocarcinoma and may serve as a useful marker of survival in cases of this disease.

Adenocarcinoma↗
PubMed1998

Induction of plasminogen activator inhibitor type 1 and type 1 collagen expression in rat cardiac microvascular endothelial cells by interleukin-1 and its dependence on oxygen-centered free radicals.

BACKGROUND: Ischemia with or without reperfusion induces the release of diverse products from monocytes, including cytokines such as interleukin-1 (IL-1). To determine whether these phenomena modulate fibrinolysis and potentially exacerbate impairment of the macrocirculation, microcirculation, or both, we characterized the effects of IL-1 on the expression of fibrinolytic system and matrix proteins in rat cardiac microvascular endothelial cells (CMECs). METHODS AND RESULTS: Confluent CMECs were exposed to IL-1 in serum-free medium for 24 hours, and cell-conditioned medium was assayed for plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of plasminogen activators, and for type 1 collagen with Western blotting. IL-1 (2 ng/mL) specifically increased the accumulation of PAI-1 (4.4 +/- 0.6-fold; mean +/- SD; n = 9) without affecting tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) levels, which remained unchanged. IL-1 increased the accumulation of collagen in conditioned media by 3.5 +/- 0.7-fold (n = 6). Conversely, the accumulation of both PAI-1 and collagen induced by IL-1 was inhibited with an IL-1 receptor antagonist (200 ng/mL; n = 6) and with cycloheximide (10 micrograms/mL; n = 6), implying that protein synthesis was a requirement for the effect. To determine whether the IL-1 effect was mediated by induction of oxygen-centered free radical production, known to be induced by IL-1, we exposed the cells to the hydroxyl radical scavenger tetramethylthiourea (10 mmol/L) and observed abolition of the IL-1-induced increase in the expression of PAI-1 and collagen (n = 6). Conversely, superoxides (generated with 10 mU/mL xanthine oxidase plus 0.6 mmol/L hypoxanthine, and 100 mumol/L hydrogen peroxide) induced the accumulation of PAI-1 and collagen (n = 6). IL-1 (1 microgram/kg body wt) and lipopolysaccharide (50 micrograms/kg body wt) administered in vivo increased PAI-1 protein in rat hearts as detected with Western blotting and PAI-1 immunostaining of rat heart microvessels, indicating the effects delineated in vitro were paralleled by effects in vivo. CONCLUSIONS: These results indicate that IL-1-induced oxygen-centered free radicals stimulate elaboration of PAI-1 and collagen by CMECs. Accordingly, microvascularly mediated inhibition of fibrinolysis may predispose to the persistence of microvascular thrombi, thereby contributing to impaired microcirculatory function, the no-reflow phenomenon, and cardiac dysfunction after ischemia and reperfusion.

Animals↗
PubMed1998

pH dependence of the reaction rate of p-bromophenacyl bromide and of the binding constants of Ca2+ and an amide-type substrate analog to bovine pancreatic phospholipase A2.

pH dependence of the chemical reaction rates of p-bromophenacyl bromide (BPB) and of the binding constants of Ca2+ to bovine pancreatic active- and pro-phospholipases A2 (PLA2s) was studied at 25 degrees C and ionic strength 0.2. The pH dependence curves of the reaction rates of BPB with both enzymes were biphasic. The amino acid residues participating in the two transitions were ascribed to His 48 and the N-terminal alpha-amino group for the active enzyme and to His 48 and Arg -1 for the proenzyme. The pH dependence curve of Ca2+ binding to the active enzyme was interpreted in terms of participation of Asp 49, His 48, and the alpha-amino group. On the other hand, the curve for the proenzyme was interpreted in terms of participation of Asp 49, His 48, and Arg -1. The Ca2+ and pH dependence of the binding constant of a potent competitive inhibitor, monodispersed (R)-2-dodecanoylamino-1-hexanol-phosphocholine (amide-PC), to bovine pancreatic active-PLA2 was also studied. The binding of amide-PC was markedly facilitated by Ca2+ binding to the enzyme, whereas that of a genuine substrate, monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC), was independent of Ca2+ binding. The pH dependence curve of the binding constant of the amide-PC showed one transition, and this was interpreted in terms of participation of His 48, whereas the binding of the diC6PC was independent of the ionization state of His 48. The difference in the Ca2+ dependence for the bindings of the diC6PC and amide-PC was considered to arise from the fact that the amide group of amide-PC can form a hydrogen bond with His 48, whereas the genuine substrate cannot form such a hydrogen bond.

Acetophenones↗
PubMed1998

Immunohistochemical detection of sex steroid receptors, cyclins, and cyclin-dependent kinases in the normal and neoplastic squamous epithelia of the uterine cervix.

BACKGROUND: Malignant transformation of sex steroid-dependent tissues has been reported to be associated with abnormal expression of sex steroid receptors. In addition, abnormalities of cell cycle-related molecules have been demonstrated in various malignancies. However, expression of steroid receptors and cell cycle-related molecules in the process of malignant transformation of the ectocervical squamous epithelium, which also is a sex steroid-dependent tissue, has not been elucidated fully. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous epithelia (30 cases), cervical intraepithelial neoplasia (CIN) (21 cases), and invasive squamous carcinoma (SCC) (33 cases), using antibodies against estrogen receptors (ER), progesterone receptors (PR), cyclins (E, A, and B1), cyclin-dependent kinases (cdk2 and cdc2), and p53 protein. In addition, growth activity of SCC was evaluated by Ki-67 labeling. RESULTS: In the normal epithelia, diffuse proportionate to regional expression of ER/PR and sporadic expression of cyclins/cdks were observed mainly in the parabasal cells irrespective of the menstrual cycle. In the neoplastic lesions, the expression of ER markedly decreased; however, the expression of PR increased. The expression of cyclins, cdks, and p53 was increased in a considerable number of these neoplastic cases. In addition, cyclin A positive SCC had elevated Ki-67 labeling, whereas cyclin E positive SCC cases had lower Ki-67 labeling. CONCLUSIONS: These findings suggest that malignant transformation of ectocervical epithelia is associated with loss of normal growth control by steroid hormones as well as with the acquisition of abnormal cell cycle regulatory mechanisms.

Adult↗