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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 289 records · Page 16Linked to original sources

Resistance training improves insulin sensitivity in NIDDM subjects without altering maximal oxygen uptake.

OBJECTIVE: To examine the effect of resistance training on insulin sensitivity in nonobese NIDDM patients. RESEARCH DESIGN AND METHODS: Previously sedentary nonobese NIDDM patients were enrolled in a resistance training group (RT; n = 9) or used as sedentary control subjects (SED; n = 8). SED subjects did not perform exercise training because of orthopedic disorders. The training program consisted of two sets of nine exercises with 10-20 repetitions. Subjects trained five times a week for 4-6 weeks. Insulin sensitivity, as assessed by the hyper-insulinemic-euglycemic clamp technique, HbAJc, and body composition, was measured before and after the training period. Maximal oxygen uptake (VO2max) and quadriceps strength were measured in the RT group. RESULTS: The two groups did not differ significantly on any variables before participation in the program. The glucose disposal rate during the hyperinsulinemic-euglycemic clamp increased 48% in the RT group (6.85 +/- 1.86 to 10.12 +/- 3.15 mg.kg-1 lean body mass.min-1; P < 0.05), but remained unchanged in the SED group (5.95 +/- 1.63 to 6.36 +/- 1.61 mg.kg-1 lean body mass.min-1). There was no significant change in body composition in either group. In the RT group, a 16% increase in quadriceps strength (191.1 +/- 45.8 to 216.9 +/- 42.8 Nm; P < 0.05) but no significant change (27.6 +/- 5.0 to 28.6 +/- 6.5 ml.kg-1.min-1) in VO2max was observed. CONCLUSIONS: Moderate-intensity, high-volume resistance training improves insulin sensitivity in nonobese NIDDM without altering VO2max.

Body Composition↗

In vivo nitric oxide detection in the septic rat brain by electron paramagnetic resonance.

To detect nitric oxide (NO) in the rat brain during lipopolysaccharide (LPS)-induced sepsis, electron paramagnetic resonance (EPR) was employed with the NO trapping technique, using an iron and N,N-diethyldithiocarbamate (DETC) complex. An X-band (about 9.5 GHz) EPR system detected a triplet signal (g = 2.038) derived from an NO-Fe-DETC complex being superimposed on the g(perpendicular) signal of Cu-DETC complex at liquid nitrogen temperature. The height of the triplet signal peaked seven hours after injection of 40 mg/kg of LPS, and over 25 x 10(4) U/kg of IFN-gamma enhanced the LPS-induced NO formation. Pretreatment with N(G)-monomethyl-L-arginine (NMMA), an NO synthase inhibitor, deleted only the triplet signal. A triplet signal (g(iso) = 2.040, aN = 1.28 mT) derived from the NO-Fe-DETC complex was also observed at ambient temperature. Then, a home-built 700 MHz EPR system was used to detect an NO signal in the septic rat brain in vivo. We successfully monitored the NO-Fe-DETC signal in the head region of a living rat under the condition that provided maximum height of the NO-Fe-DETC signal in the X-band EPR study. Pretreatment with NMMA again deleted the NO-Fe-DETC signal. This is the first EPR observation of endogenous NO in the brain of living rats.

Animals↗

Diminished fibrinolysis and thrombosis: clinical implications for accelerated atherosclerosis.

Obesity is associated with an increased risk of atherosclerotic coronary artery disease. Cytokines and oxygen-centered free radicals implicated in insulin resistance stimulate adipocyte and endothelial production of plasminogen activator inhibitor type-1 (PAI-1), the primary physiologic inhibitor of fibrinolysis, in vitro. In obese hyperinsulinemic animal models simulating insulin resistance, plasma PAI-1 activity is increased. As the cardiovascular risk profile in specific populations may differ, endogenous fibrinolysis in lean and obese subjects was characterized and the mechanisms underlying differences were identified. Obese subjects (body mass index > 26) exhibited increased blood levels of PAI-1 antigen compared with corresponding values in lean controls. Blood t-PA antigen differed as well, yet basal endogenous fibrinolytic activity was decreased because of the high PAI-1 activity. The increased PAI-1 level was associated with increased levels of immunoreactive insulin (IRI). In diabetic subjects, coronary atherectomy specimens exhibited strong positive PAI-1 immunostaining, suggesting that in the diabetic vascular wall, intramural fibrinolytic activity is diminished. Using the oral glucose tolerance test, patients with significant stenosis confirmed by coronary angiography exhibited increased sigmaIRI, sigmaBS, sigmaIRI/sigmaBS, and IRI at 120 min compared to subjects without significant stenosis. IRI at 120 min was closely correlated with the severity of coronary artery disease. These results indicate that adipocyte overproduction of PAI-1 by insulin induces decreased endogenous fibrinolytic activity and contributes to the accelerated coronary macroangiopathy in hyperinsulinemic obese subjects with insulin resistance.

Animals↗

[Sick sinus syndrome after chemotherapy for malignant lymphoma with right atrial tumor at initial presentation].

A 56-year-old man was admitted complaining of throat discomfort and dyspnea. He was given a diagnosis of diffuse large B-cell lymphoma on the basis of findings from tumor biopsy specimens of his left pharynx. MRI tomograms and ultrasonic cardiograms revealed a right atrial tumor causing tricuspid stenosis. Although chemotherapy rendered the cardiac tumor indistinct on MRI and UCG images, gallium-67 scintigraphy still demonstrated abnormal cardiac uptake. After 6 courses of CHOP therapy, sick sinus syndrome with syncope suddenly developed in the patient. A cardiac pacemaker was immediately implanted, and radiotherapy was started. The patient's sinus rhythm returned to normal shortly afterward, and the gallium-67 uptake eventually disappeared. In this case gallium-67 scintigraphy was the only diagnostic procedure capable of detecting evidence of residual disease.

Antineoplastic Combined Chemotherapy Protocols↗

Quantitative analysis of the cyclin expression in human esophageal cancer cell lines.

To study the altered mechanisms of cell cycle regulation in esophageal cancer, the expressions of cyclins involved in G1/S transition were analyzed in a series of 26 human esophageal cancer cell lines. To evaluate and compare the levels of cyclin expression, flow cytometric analysis was performed using human lymphocytes as control. Increased expressions of cyclin A, D1, D3 and E were found in 23.1% (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines, respectively. All cell lines studied expressed less cyclin D2 than lymphocytes and the majority of the cell lines expressed cyclin D3 at levels similar to those of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E. Expressions of cyclin D1 and E were significantly elevated as compared to those of cyclin A, D2 and D3. These results suggest that increased expressions of the positive cell cycle regulators cyclin D1 and E may play an important role in esophageal carcinogenesis.

Biomarkers, Tumor↗

[Clinicopathological study of multiple myeloma associated with hyperammonemia].

Of 5 multiple myeloma patients with hyperammonemia, autopsy was performed in 4 patients, while amino acid metabolism was examined in 3 patients. As a result they were classified into the following 3 types; A, liver dysfunction and severe liver infiltration of myeloma cells. B, severe liver infiltration without liver dysfunction. C, Neither liver dysfunction nor severe liver infiltration. In one type A patient, isoleucine decreased. In two patients without liver dysfunction (one type C patient and another patient in whom autopsy was not performed) valine, leucine and isoleucine decreased, and tyrosine decreased slightly. The Fischer ratio decreased in these 2 patients, while it decreased slightly in a type A patient. Clinically, in 4 patients hyperammonemia was observed during periods of poor general condition and when refractory to chemotherapy. In an aggressive type case, consciousness disturbance was developed rapidly and multiple myeloma was diagnosed. In all patients, consciousness disturbance was noted. Hyperammonemia might have been caused by hepatic failure or systemic-portal shunt in patients with liver infiltration. In those without liver infiltration, it was suggested that hyperammonemia was caused by myeloma related humoral factors that influence amino acid metabolism.

Aged↗

Differential expression of nitric oxide synthase isoforms in form-deprived chick eyes.

PURPOSE: To clarify whether nitric oxide synthase (NOS) is involved in development of myopia, we examined the influence of form deprivation on the expressions of NOS isoform mRNA. METHODS: NOS isoform cDNAs were amplified from total RNA extracted from control and 7-day-form-deprived chick retina-RPE (retinal pigment epithelium)-choroid, using competitive RT-PCR (reverse-transcription polymerase chain reaction). Each NOS isoform protein was also analyzed by Western blotting and immunohistochemistry. RESULT: Expression of inducible NOS (iNOS) mRNA was highest in the control chick retina-RPE-choroid, followed by the expression of brain NOS (bNOS) mRNA. Expression of endothelial NOS (eNOS) mRNA was faint. The iNOS protein level, however, was only slightly higher than the levels of the bNOS and eNOS proteins and was found mainly in the outer part of the photoreceptor layer and inner and outer parts of RPE and choroid. bNOS alone was found in the outer nuclear layer. Although form deprivation reduced the iNOS and bNOS mRNA expressions, only the iNOS protein showed significant reduction. CONCLUSION: All three NOS isoforms were expressed in chick retina-RPE-choroid. Predominant expression of iNOS, instead of bNOS and eNOS, suggested the existence of ocular tissue-specific regulation of the iNOS gene. In addition to differences in expression level, bNOS displayed regional differential expression. Moreover, only iNOS was reduced in response to form deprivation. It is suggested that NOS isoforms may be differentially involved in the mechanisms regulating the posterior eye tissues, including myopic eye growth.

Animals↗

Reduced expression of calponin h1 in leiomyosarcoma of the uterus.

To determine the genetic differences between various smooth muscle tumors of the uterus, the expression of calponin h1 (cytoskeletal protein) was examined in normal myometrium and in smooth muscle tumors of the uterus (leiomyosarcoma, smooth muscle tumors of uncertain malignant potential, cellular leiomyoma, bizarre leiomyoma, and ordinary leiomyoma) using immunohistochemistry and Western blotting. Analysis of calponin h1 transcripts using the reverse-transcription-PCR was also performed. Immunohistochemically, calponin h1 was expressed in normal myometrium and in all leiomyomas; however, its expression was markedly weaker in leiomyosarcoma. The results of both Western blotting and the analysis of calponin h1 transcripts were compatible with the immunohistochemical results. It is suggested that reduced expression of calponin h1 is associated with leiomyosarcoma of the uterus, and that calponin h1 expression may serve as a valuable molecular maker in the differential diagnosis of smooth muscle tumors of the uterus.

Adult↗

Microsatellite instability in breast cancers with special reference to patients' age and bilaterality.

We examined breast cancers from 67 female patients to ascertain the possible correlation between RER or LOH status, age and bilaterality using eight microsatellite markers on chromosomes 2p, 3p, 16q, 17p and 17q. The frequencies of RER in young patients (25-35 years old), patients with double primary disease (43-77 years old) and patients with contralateral metastases (46-72 years old) were 35%, 63%, and 80%, respectively, while that in elderly patients (60-81 years old) was 0%. In contrast, there were no statistically significant differences in the frequency of LOH between these groups. Our results suggest that RER might play an important role in the occurrence of breast cancer at a younger age and in bilateral breast cancer.

Adult↗

[Rare intra-abdominal complications of a ventriculoperitoneal shunt: report of three cases].

Three cases of rare intra-abdominal complications of ventriculoperitoneal shunt (VPS) surgery are reported. Case 1 was a 32-year-old male who had undergone VPS surgery for hydrocephalus following meningitis on July 10, 1980. Two weeks later he developed fever and a cystic mass about 10 cm in diameter in the right hypochondrium. Shuntography and a barium enema study demonstrated a pseudocyst at the distal end of the shunt. The cyst wall was excised, the peritoneal tube removed, and VPS converted to a ventriculoatrial route following which the pseudocyst resolved. Case 2 was a 49-year-old female who developed hydrocephalus following subarachnoid hemorrhage, and VPS surgery was performed on March 10, 1989. Two weeks later, she developed fever and right upper abdominal pain. Abdominal x-ray and CT scan revealed a right subdiaphragmatic abscess. The abscess was drained and the shunt system was removed on April 4. VPS was placed again on April 21 without further complications. She was symptom free for the next 7 years. Case 3 was a 57-year-old female who presented in a semicomatose state after falling from bed on May 5, 1995. CT scan showed left-sided acute subdural hematoma (ASDH) for which surgery was performed. Her neurological status improved postoperatively. She eventually developed hydrocephalus and left-sided subdural effusion for which right VPS and left subduroperitoneal shunt (SPS) surgery was performed on January 25, 1996. The peritoneal end of the tube of the SPS protruded out of the anus one and a half year after shunt placement. The entire SPS system was removed as there was no more collection in the subdural space. We reviewed the literature and discussed the pathophysiology involved in the development of intraabdominal complications following VPS.

Abdominal Injuries↗

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗

Immunohistochemical analysis of the expression of cdk4 and p16INK4 in human endometrioid-type endometrial carcinoma.

BACKGROUND: Abnormalities in G1 cell cycle regulation have been associated with the malignant transformation of cells. To obtain further information about the role of factors regulating the G1 cell cycle in the development of endometrial carcinoma, the authors analyzed the expression of cdk4 (cyclin-dependent kinase) and p16INK4 (an inhibitor of cdk4). METHODS: Immunohistochemical staining was performed on 20 specimens of normal endometria and 41 specimens of endometrioid-type endometrial carcinoma using antibodies against cdk4 and p16INK4. RESULTS: In the glandular epithelia of the normal endometria, cytoplasmic staining of cdk4 and p16INK4 was observed only in the proliferative phase, but nuclear staining of these agents was negligible. In endometrial carcinomas, 8 (19.5%) and 14 (34.2%) were positive for cdk4 and p16INK4 in the nucleus, respectively. Topographically, the nuclear cdk4 positive tumor cells were negative for p16INK4 and the nuclear p16INK4 positive tumor cells were found in areas without nuclear cdk4 expression, suggesting an inverse correlation between the two agents. In addition, the poorly differentiated carcinomas were more frequently positive for nuclear cdk4 than were the highly differentiated carcinomas (P = 0.03). CONCLUSIONS: These data suggest that increased expression of nuclear cdk4 associated with loss of p16INK4 expression could be involved in the carcinogenesis of a subset of endometrial carcinomas.

Carcinoma, Endometrioid↗

Contribution of water molecules in the interior of a protein to the conformational stability.

Water molecules frequently occur in the interior of globular proteins. To elucidate the contribution of buried water molecules to the conformational stability of a protein, we examined the crystal structures and the thermodynamic parameters of denaturation of six Ile to Ala/Gly mutant human lysozymes, in which a cavity is created at each mutation site by the substitution of a smaller side-chain for a larger one. One or two ordered water molecules were found in the cavities created in some mutants (I106A, I59A and I59G). The cavity volumes for these three mutants were bigger than those that remained empty in the other mutants. The stability of the mutant proteins with the newly introduced water molecules was about 8 kJ/mol higher than that expected from the change in hydrophobic surface area (DeltaDeltaASAHP) exposed upon denaturation. It was concluded that a water molecule in a cavity created in the interior of a protein contributes favorably to the stability.

Amino Acid Substitution↗

Analysis of bovine selenoprotein P-like protein gene and availability of metal responsive element (MRE) located in its promoter.

Selenoprotein P-like protein, similar to selenoprotein P, uses multiple TGAs for incorporation of selenocysteines but not as stop codons. It is also characterized by having a His-Pro-rich domain and a regionally differential expression pattern. Hence, in addition to selenium metabolism, this protein is considered to have a developmental function. In the present study, the structure of the selenoprotein P-like protein gene was analyzed. The gene consisted of five exons, and the 5'-flanking region contained a TATA box, TCF-1-CS, bHLH-CS, gamma-IRE-CS, c-Myb-CS, C/EBP-CS, HNF-5-CS, MRE2-CS, etc. The presence of motifs like TCF-1-CS, c-Myb-CS, etc. supports the suggestion that this protein is involved in cellular maturation. Since the presence of MRE2-CS suggests that this protein is related to the antidote effect of selenium against heavy metal intoxication, the availability of this motif was examined using bovine kidney cell lines, CKT-1 and MDBK. Metallothionein mRNA markedly increased 6 h after administration of 10(-6) M CdCl2 and ZnCl2 in both cell lines. No significant alteration was observed in selenoprotein P-like protein mRNA, whereas its basal expression was high, indicating that this protein is constitutively expressed. Thus, it is still possible that this protein acts as an antidote, even though it is not inducible by heavy metals.

Animals↗

Effect of temperature on the role of Hsp104 and trehalose in barotolerance of Saccharomyces cerevisiae.

We have studied the effect of temperature on the contribution of Hsp104 and trehalose to barotolerance using mutants deficient in Hsp104 and trehalose synthesis. When compared with a corresponding wild type strain, mutants of Hsp104 did not show temperature dependent barotolerance when the incubation temperature during the hydrostatic pressure treatment was increased. However, a mutant deficient in trehalose synthesis showed features similar to a wild type strain. Furthermore, the Hsp104 level was low in the insoluble fraction of the wild type strain after pressure treatment at 35 degrees C but not at 4 degrees C, and the protein profiles in the insoluble fraction were different between 35 degrees C and 4 degrees C. In contrast to the Hsp104 deficient mutants, the protein profile of the wild type after pressure treatment at 35 degrees C favors the role of Hsp104 as a disaggregator of proteins during hydrostatic pressure stress. These results suggest that the role of Hsp104 in barotolerance is temperature dependent in contrast to trehalose.

Adaptation, Physiological↗

The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitivity to neutralization by soluble CD4 and cellular tropism.

A primary isolate (KMT) of human immunodeficiency virus type 1 (HIV-1) resistant to recombinant soluble CD4 (rsCD4) was isolated from an HIV-1-infected individual and grown in a T lymphoid cell line. KMT isolate passaged on CEM cells (KMT/CEM) was still resistant to rsCD4. The V1/V2 and V3 regions of the viral envelope glycoprotein are thought to be involved in various biological phenotypes. To determine the exact envelope region of the KMT isolate responsible for sensitivity to rsCD4 and cellular tropism, we performed sequence analysis of KMT and KMT/CEM isolates. Sequence analysis of the KMT isolate showed that the sequence of the V3 region was relatively homogeneous, whereas a considerable heterogeneity of the V1/V2 region was noted. In contrast, the sequences of the V1 to V3 regions were homogeneous in KMT/CEM isolates. Analysis of NL4-3-based recombinant viruses with amplified sequences of the V1 to V3 regions from KMT and KMT/CEM isolates showed that the V1/V2 region modulated the sensitivity to rsCD4. A change in resistance to rsCD4 by the V1/V2 region was associated with the ability of the isolate to replicate in macrophages and efficiently replicate in T lymphoid cell lines. A change to an isolate sensitive to rsCD4 was associated with reduced replication efficiency in T lymphoid cell lines. Our results suggest that the V1/V2 region is involved in modulating the sensitivity to rsCD4, macrophage tropism, and replication efficiency in T lymphoid cell lines.

Amino Acid Sequence↗