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Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 595 records · Page 33Linked to original sources

Suppression of hepatic gluconeogenesis in long-term Troglitazone treated diabetic KK and C57BL/KsJ-db/db mice.

The orally effective antidiabetic agent Troglitazone (CS-045) exerts hypoglycemic effects in various insulin-resistant obese and/or diabetic animals. Since increased hepatic gluconeogenesis is a major cause of hyperglycemia in these diabetic animals, we evaluated the effect of long-term Troglitazone treatment on hepatic gluconeogenesis. Troglitazone was administered for 7 days to normal ddY mice, diabetic KK mice, diabetic C57BL/KsJ-db/db mice, and its heterozygote, db/+ mice, as a 0.1% or 0.2% food admixture. Troglitazone significantly decreased plasma glucose in diabetic KK and db/db mice, but not in normal ddY and db/+ mice. 14C incorporation into blood glucose from NaH14CO3 was measured to assess hepatic gluconeogenesis in diabetic KK and normal ddY mice. Hepatic gluconeogenesis was significantly increased in diabetic KK mice (P < .01) as compared with normal mice, and was significantly suppressed (P < .05) after 7 days of Troglitazone treatment (approximately 200 mg/kg/d). Glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) were significantly decreased but fructose-1,6-bisphosphate (FBP) was not significantly increased in the liver of diabetic db/db mice treated with Troglitazone for 7 days (approximately 80 mg/kg/d) as compared with control db/db mice. These changes in G6P, F6P, and FBP corresponded with the activity of fructose-1,6-bisphosphatase (Fru-1,6P2ase) and 6-phosphofructo-1-kinase (6-PF-1K), which determined the content of F6P and FBP. Namely, Fru-1,6P2ase was significantly decreased in Troglitazone-treated db/db mice as compared with control mice, whereas 6-PF-1K activity was not affected by Troglitazone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of intraarterial carboplatin and ACNU for the treatment of gliomas.

BACKGROUND: Intraarterial chemotherapy with carboplatin for malignant gliomas has been tried recently, but its therapeutic efficacy and toxicity have not yet been elucidated. METHODS: We treated patients with malignant glioma by intraarterial chemotherapy using carboplatin, and compared the efficacy as well as the side effects with intraarterial ACNU. RESULTS: Twenty patients were treated with carboplatin (300 mg/m2) and 22 patients were treated with ACNU (80-200 mg/m2). Response (complete remission+partial response) rate for carboplatin was 12.5% compared to 45% for ACNU. Despite higher response rate for ACNU, the difference in the survival curves of the two groups was not significant. Three patients who were treated with high dose (150-200 mg/m2) of ACNU developed hemiparesis and aphasia. Seven patients treated with carboplatin developed 10 incidences of neurotoxicities; two hemiparesis, one aphasia, one blindness, one visual field disturbance, three convulsions, and two developed incidences of disturbances of consciousness. CONCLUSIONS: Intraarterial carboplatin was not superior to intraarterial ACNU in achieving remissions, and showed much greater tendency to produce neurotoxicities.

Adolescent↗

Venticular expression of atrial and brain natriuretic peptides in patients with myocarditis.

We analyzed the ventricular expression of atrial and brain natriuretic peptides (ANP and BNP) in patients with myocarditis. Immunohistochemical analysis of endomyocardial biopsy specimens showed ANP and BNP immunoreactivity in the early myocarditis group (ANP in 4/10 and BNP in 3/10) and the late myocarditis group (ANP and BNP in 4/10), but not in the controls (0/8). Hemodynamic parameters, such as left ventricular volume indexes, pulmonary capillary wedge pressure, and left ventricular end-diastolic pressure, were higher and the cardiac index and ejection fraction were lower in the patients positive for ANP and/or BNP. Histological changes, including myocyte size, cellular necrosis, inflammatory infiltrates and fibrosis, were more severe in the immunohistochemically positive biopsy specimens. In the autopsy hearts, ANP- or BNP-positive myocytes were noted in the chronic myocarditis or postmyocarditis group, but not in acute fulminant myocarditis or in normal controls. Both ANP and BNP were predominantly localized in the residual myocytes edging the myocardial lesions, and also in the myocytes just beneath the left ventricular endocardium. This study demonstrated augmented ventricular ANP and BNP expressions in patients with myocarditis, and suggested that regional stress is important in the augmentation of these peptides as well as hemodynamic stress.

Adolescent↗

Helix formation of poly (L-glutamic acid) in the presence of alkaline earth metal cations in aqueous alcohol solutions.

Effects of divalent counterions (Mg2+, Ca2+, Sr2+, Ba2+) on the helix formation of poly(L-glutamic acid) are investigated in aqueous alcohol (MeOH, EtOH, 2PrOH, tBuOH) solutions. To observe helix formation inherent to the divalent counterions, the chlorides were added to a poly(L-glutamate) having an inert monovalent counterion, tetrabutylammonium cation. Marked counterion- and alcohol-specificities were observed for the dependence of helix content, theta, on the alcohol content. The theta values for most Mg2+ and Ca2+ systems decreased with increasing alcohol content in a higher alcohol region, while those for Sr2+ and Ba2+ systems were almost constant. A specific helix stabilization was observed for mixed divalent counterion systems. These results are self-consistently interpreted by taking into account contact ion-pair formation between the counterions and the polymer charges on the coil conformation.

Alcohols↗

Interleukin-8 and monocyte chemotactic activating factor responses to cardiopulmonary bypass.

Cardiac operations with cardiopulmonary bypass cause a systemic inflammatory response. Neutrophils and monocytes-macrophages play an important role in triggering the initiation of the inflammatory response. Recently, some kinds of cytokines that are powerful leukocyte chemotactic factors have been characterized concerning an inflammatory response: interleukin-8 has a potent chemoattractant activity for neutrophils, and monocyte chemoattractant factor has monocyte-macrophage chemotactic activity. To investigate the possible roles of the cytokines in the inflammatory response in cardiopulmonary bypass, 12 adult patients undergoing cardiopulmonary bypass were studied for measurement of interleukin-8 and monocyte chemoattractant factor. Systemic blood was collected before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 3, 12, 24, and 48 hours after cardiopulmonary bypass from the patients' radial arteries. Significant increases in levels of interleukin-8 and monocyte chemoattractant factor were detected with a peak level at 3 hours after bypass compared with levels before cardiopulmonary bypass (p < 0.05). This study demonstrated that interleukin-8 and monocyte chemoattractant factor are released into the circulation after adult hypothermic cardiopulmonary bypass and reach a maximum level 3 hours after bypass.

Aged↗

Effects of diclofenac sodium and indomethacin on proliferation and collagen synthesis of lens epithelial cells in vitro.

We investigated the effects of diclofenac sodium and indomethacin on the proliferation of and collagen synthesis by lens epithelial cells (LECs) of human cataracts in culture. The anterior capsule with attached LECs, obtained by anterior capsulotomy during cataract surgery, was cultured directly without cell dispersion. When the culture became almost confluent, diclofenac sodium or indomethacin at various concentrations was added to the incubation medium. The incorporation of 3H-thymidine and 3H-proline into the LECs was measured after the cells were labeled with these radioactive materials. Both drugs greatly suppressed the incorporation of 3H-thymidine and of 3H-proline, indicating that they inhibit cell division and collagen synthesis by LECs. Both drugs may help prevent posterior capsule opacification.

Anti-Inflammatory Agents, Non-Steroidal↗

Hepatocellular carcinoma metastatic to the mandible.

A case of hepatocellular carcinoma metastatic to the mandible is described. The patient reported swelling, pain, and trismus after a pathologic fracture. After a systematic examination with the use of 99mTc-methylene diphosphonate, 67Ga-citrate, and 99mTc-pyridoxyl-5-methyl triptophan scintigraphy the primary focus was discovered in the right lobe of the liver. The focus was confirmed by computed tomography and magnetic resonance imaging. The histopathologic diagnosis of hepatocellular carcinoma was made from a biopsy specimen of the mandibular lesion.

Carcinoma, Hepatocellular↗

Genetic instability occurs in the majority of young patients with colorectal cancer.

Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, p < 0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.

Adult↗

Triangular flap repair of the congenital earlobe cleft.

Repair of a congenital earlobe cleft was performed on 16 patients using a new surgical technique derived from the Tennison-Randall triangular flap operation for cheiloplasty. There were no complications. This method was applied because the deformities and desired outcomes in the congenital earlobe cleft are similar to those of the cleft lip. Many papers have described surgery for congenital and acquired clefts; the former differs from the latter in some respects. The techniques described for the repair of acquired clefts are not always appropriate for congenital clefts. In addition, some operations specifically designed for congenital clefts require more complicated techniques. Using our technique to correct lobule deformities with a triangular flap in proportion to the angle and extent of the cleft, a superior cosmetic result was obtained in the repair of longitudinal earlobe clefts.

Congenital Abnormalities↗

Augmented responses to 5-HT2-receptor-mediated vasoconstrictions in atherosclerotic rabbit common carotid arteries.

The vascular responses of isolated and perfused atherosclerotic rabbit common carotid arteries to 5-HT were investigated. Atherosclerotic lesions were produced by positioning a hollow silicone collar around the common carotid arteries of rabbits fed with an atherogenic diet for 4 weeks. After the period, we removed the vessels from operated and sham-operated rabbits fed with either the atherogenic diet or a normal diet for 4 weeks. The removed vessels were divided into four groups: a control group, a cuffed normal-diet-fed group, a sham-operated, cholesterol fed group, and a cuffed cholesterol-fed group. Vascular effects of 5-HT and its analogs (5-CT, a 5-HT1-like receptor agonist; alpha-methyl-5-HT, a 5-HT2 agonist; 8-OH-DPAT and TFMPP, 5-HT1 agonists) were investigated in each group. The vasoconstrictor responses to 5-HT, 5-CT and alpha-methyl-5-HT were enhanced in atherosclerotic vessels. Removal of the endothelium did not affect the vascular responses to 5-HT and its analogs. Because the responses were not enhanced in vessel from a cuffed normal-diet-fed group, we did not show the data of this group in figures and did not examine antagonism studies. Vasoconstrictor responses to these agonists were markedly inhibited in other three groups by ketanserin and spiperone (5-HT2 receptor antagonists), and methysergide (a 5-HT1 and 5-HT2 receptor antagonist). 5-HT and its analogs did not show any vasodilatory action on phenylephrine-preconstricted preparations, which suggested that there were few functional 5-HT1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Desmoyokin/AHNAK protein localizes to the non-desmosomal keratinocyte cell surface of human epidermis.

Desmoyokin, a high-molecular-weight protein of 680 kD with a 170-nm-long dumbbell shape, was originally thought to be localized to the desmosomal attachment plaque and to work as a kind of stabilizer of desmosomes. Recently, desmoyokin was shown to be widely detected in many types of cells that do not possess desmosomes. The purpose of the present study was to elucidate the precise localization and possible function of desmoyokin in human epidermis. In 0.2-micron ultrathin cryosections of human skin for immunofluorescence, anti-desmoyokin antibody showed a ladder-like staining pattern along the cell surface, whereas anti-desmocollin and anti-desmoplakin antibodies as controls showed a discontinuous dotted staining pattern, indicating their distinct localization. Post-embedding immunoelectron microscopy with cryofixation and cryosubstitution revealed that desmoyokin was localized mainly along the non-desmosomal and non-hemidesmosomal plasma membrane, but not to the desmosomes and hemidesmosomes themselves. This localization was further confirmed by double-labeling immunoelectron microscopy with antibodies against desmocollin, desmoplakin, or bullous pemphigoid antigen. Results indicate that desmoyokin was not localized to the desmosomes themselves as previously considered. Desmoyokin was localized to the non-desmosomal and non-hemidesmosomal epidermal keratinocyte cell surface as a plasma membrane-associated protein, and might play a role in cell adhesion that is not directly associated with desmosomes or hemidesmosomes.

Antibody Specificity↗

Targeting of chrolamphenicol acetyltransferase to human immunodeficiency virus particles via Vpr and Vpx.

Vpr and Vpx are the auxiliary proteins of human immunodeficiency viruses (HIVs) selectively incorporated into mature viral particles. We showed that the bacterial chloramphenicol acetyltransferase (CAT) fused to the N-terminus of HIV-1 Vpr, HIV-2 Vpr, or HIV-2 Vpx was incorporated into mature virions in a type-selective manner. By using chimeric proteins between HIV-1 Vpr and HIV-2 Vpx, we found that the N-terminal side of these proteins was mainly important for type-selective virion incorporation. The C-terminal arginine-rich region of HIV-1 Vpr was also found to transport CAT fusion proteins into virions but without any type selectivity. Furthermore, the corresponding regions of HIV-2 Vpr and HIV-2 Vpx had no such activity. This region of HIV-1 Vpr may interact nonspecifically with viral genomic RNA. Collectively, Vpr and Vpx may provide a means to introduce foreign proteins and other molecules into HIV virions for therapeutic purposes.

Amino Acid Sequence↗

Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats.

1. Noradrenergic (NA) nerve fibre distribution was investigated in the epicardium and myocardium of the heart in stroke-prone spontaneously hypertensive rats (SHRSP) and was compared to that in normotensive Wistar-Kyoto (WKY) rats. Fluorescent NA nerve fibres in the left and right epicardium of both strains aged 10, 30, 60, 90 and 180 days, and in the myocardium of left and right ventricles and the ventricular septum of both strains aged 30, 90 and 180 days were examined by the glyoxylic acid method. The distribution densities of NA nerve fibres were measured by quantitative image analysis. 2. The distribution pattern of NA nerve fibres in the epicardium of both strains showed a constant meshwork pattern throughout the entire examination period. 3. In the myocardium, NA nerve fibres were distributed irregularly between myocytes of both strains in all ages examined. 4. The densities of NA nerve fibres in the epicardium of SHRSP were significantly higher (P < 0.01 and 0.05; Student's t-test, 6 d.f.) than those of WKY at all ages examined except left epicardium at 90 days of age. 5. The densities in the right myocardium in 30 and 90 day old SHRSP were significantly higher (P < 0.05; Student's t-test, 6 d.f.) than those of WKY. 6. NA hyperinnervation in the epicardium and the myocardium of SHRSP may be assumed to be caused by the hyperfunction of the stellate ganglia which innervate the heart and may give rise to hypertrophy of the heart in SHRSP by a trophic effect of NA nerve fibre.

Adrenergic Fibers↗

Application of a new perchloric acid treatment method to measure endotoxin by an endotoxin-specific chromogenic Limulus test in neonatal septicemia.

The endotoxin in blood was measured to establish both the cut-off value and to detect Gram-negative septicemia. We employed a new perchloric acid treatment method using an endotoxin-specific chromogenic Limulus test (Endospecy test). The cut-off value of endotoxin in blood was 11.2 pg/mL. All cases of septicemia (n = 7) showed high values of endotoxin. Three cases were Group B streptococci, and two cases were Escherichia coli. The others were showed to be negative in blood cultures. The paired values of endotoxin titers during a 48 h interval were useful to evaluate the effectiveness of antibiotics.

Bacteremia↗