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Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 955 records · Page 53Linked to original sources

Changes in liver and spleen volume in alcoholic liver fibrosis of man.

Alcoholic liver fibrosis is a relatively common form of alcoholic liver disease in Japan. It is regarded by some investigators as a prodromal stage of alcoholic liver cirrhosis, but little is known about the volumes of the liver and spleen in this disease state. Therefore, liver and spleen volumes were measured by computed tomography in 32 patients with alcoholic liver fibrosis in comparison with 10 healthy volunteers. Patients with alcoholic liver fibrosis were divided into three subgroups (13 of Grade 1, 9 of Grade 2 and 10 of Grade 3) according to the severity of fibrosis. The volume was calculated from the sum of the area measurements of successive transverse sections of the two organs. The liver volume (mean +/- S.D.) in Grade 2 alcoholic liver fibrosis (1,281 +/- 112 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (1,017 +/- 73 cm3) and in Grade 1 (1,090 +/- 157 cm3), and the liver volume in Grade 3 (1,490 +/- 132 cm3) was larger than in Grade 2 (p less than 0.01). The mean volume of hepatocytes estimated by a two-dimensional image analysis system was significantly (p less than 0.05) larger in Grade 3 than in Grade 2, and that in Grade 2 was larger than in Grade 1. The spleen volume in Grade 3 (151 +/- 40 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (86 +/- 26 cm3), Grade 1 (89 +/- 38 cm3) and Grade 2 (68 +/- 19 cm3). The presumed reason for hepatic volume increase would be the ballooning of hepatocytes along with increased fibrotic component.

Humans↗

Monitoring of cortical blood flow during excision of arteriovenous malformation by thermal diffusion method.

The cortical blood flow adjacent to arteriovenous malformations was monitored in six patients before, during, and after excision of arteriovenous malformations using a thermal diffusion probe. In a large arteriovenous malformation, a progressive increase in cortical blood flow up to two times the preexcision value was noted with occlusion of the feeding arteries. Lowering arterial pressure to keep normal cortical blood flow during and after operation resulted in minimum brain edema and an excellent result. Direct measurement of cortical blood flow is of value in determining the precise level of hypotension to prevent brain edema and ischemia that may occur with excision of a large arteriovenous malformation.

Adult↗

Coronary flow velocity waveforms in aortic stenosis and the effects of valve replacement.

In 6 patients with pure aortic stenosis, the flow velocity waveforms in the left anterior descending coronary artery were studied using an 80-channel 20-MHz pulsed Doppler velocimeter before and immediately after aortic valve replacement. All patients showed normal coronary arteriograms. The left anterior descending coronary artery flow velocity waveform in aortic stenosis was characterized by a reverse flow in the first half of systole and a slowly increasing diastolic inflow. After aortic valve replacement, the reverse flow in the first half of systole disappeared in all patients, but an end-systolic reverse flow was discerned in 5 of 6 patients. The increasing rate of the diastolic inflow was augmented in all patients. After aortic valve replacement, the time from onset of diastole to the diastolic peak velocity was shortened from 176.8 +/- 28.8 to 90.5 +/- 18.8 ms (p less than 0.01), and the diastolic peak velocity increased from 90.5 +/- 28.0 to 122.5 +/- 17.2 cm/s (p less than 0.05). Blood pressure and heart rate, however, did not change significantly before and after valve replacement. These changes in the left coronary artery velocity waveforms after valve replacement suggest the beneficial effects of removal of aortic stenosis on human coronary artery inflow.

Aortic Valve↗

Microbial glycolipids: possible virulence factors that scavenge oxygen radicals.

Two important pathogens of developing countries, Mycobacterium leprae, the etiologic agent of leprosy, and Leishmania donovani, the protozoal parasite that causes kalaazar, persist in the human host primarily in mononuclear phagocytes. The mechanisms by which they survive in these otherwise highly cytocidal cells are presently unknown. Since the best understood cytocidal mechanism of these cells is the oxygen-dependent system that provides lethal oxidants including the superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH), and singlet oxygen (1O2), we sought specific microbial products of these organisms that might enable them to elude oxidative cytocidal mechanisms. Phenolic glycolipid I of M. leprae and lipophosphoglycan of L. donovani are unique cell-wall-associated glycolipids produced in large amounts by the organisms. In this study, phenolic glycolipid I derivatives and lipophosphoglycan were examined for their ability to scavenge potentially cytocidal oxygen metabolites in vitro. Electron spin resonance and spin-trapping indicate that phenolic glycolipid I derivatives and lipophosphoglycan are highly effective in scavenging hydroxyl radicals and superoxide anions. The results suggest that complex glycolipids and carbohydrates of intracellular pathogens that can scavenge oxygen radicals may contribute to their pathogenicity and virulence.

Animals↗

Integration of mini-retroviral DNA: a cell-free reaction for biochemical analysis of retroviral integration.

After retroviral infection of a permissive cell, the viral RNA is reverse-transcribed to make a DNA copy of the viral genome. Integration of this DNA copy into the host genome is a necessary step for efficient viral replication. We have developed a cell-free system for integration of exogenous mini-retroviral DNA. The termini of this linear mini-Moloney murine leukemia virus (MoMLV) DNA are designed to mimic the ends of authentic unintegrated MoMLV DNA. The viral proteins required for integration can be provided either as a cytoplasmic extract of MoMLV-infected NIH 3T3 cells or as disrupted MoMLV particles. Phage lambda DNA serves as the target for integration. Genetic markers present on the mini-MoMLV DNA enable integration events to be detected, and the recombinants recovered, by selection in Escherichia coli. Integration, which occurs at heterogeneous locations in the target DNA, is absolutely dependent on the presence of a source of viral proteins and a divalent cation in the reaction mixture. The fidelity of the integration reaction was confirmed by sequencing the junctions between the integrated MoMLV DNA and adjacent lambda DNA sequence. In each case, as expected for authentic MoMLV DNA integration, a 4-base-pair duplication of target DNA sequence flanked the integrated MoMLV DNA.

Animals↗

Purification and properties of Halobacterium halobium "cytochrome aa3" which lacks CuA and CuB.

An a-type cytochrome was purified from Halobacterium halobium. The cytochrome showed an absorption spectrum similar to that of cytochrome aa3; it showed absorption peaks at 420 and 598 nm in the resting state, peaks at 441 and 602 nm in the reduced form, and its CO compound showed peaks at 430 and 600 nm. The cytochrome molecule was composed of only one kind of polypeptide with the molecular weight of 40,000. The cytochrome contained two heme a molecules in the molecule but no copper. The cytochrome did not show cytochrome c oxidase activity. Midpoint redox potential at pH 8.0 of the cytochrome was determined to be +0.31 V. The amino acid composition of the cytochrome resembled that of subunit I of mitochondrial cytochrome aa3. While two molecules of heme a were reduced with sodium dithionite, only one of two heme a molecules was reduced with ascorbate plus TMPD. The heme a reduced with ascorbate plus TMPD did not react with molecular oxygen or carbon monoxide, while one of two heme a molecules reduced with sodium dithionite was oxidized by molecular oxygen and combined with carbon monoxide.

Amino Acids↗

Purification and characterization of cytochromes P-450 from liver microsomes of 3-methylcholanthrene-treated crab-eating monkeys.

Two forms of cytochrome P-450 (P-450MC1 and P-450MC2) were purified from liver microsomes of crab-eating monkeys (Macaca irus) treated with 3-methylcholanthrene (MC). Monkey P-450MC1 preparation had a specific content of 14.0 nmol/mg protein and showed a main protein band with a minimum molecular weight of 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Monkey P-450MC2 preparation had a specific content of 12.1 nmol/mg protein and a minimum molecular weight of 54,000. The carbon monoxide-reduced difference spectral peaks of monkey P-450MC1 and P-450MC2 were at 448 and 447 nm, respectively. In the reconstituted system, monkey P-450MC2 had high activities for benzo[a]pyrene 3-hydroxylation and 7-ethoxycoumarin O-deethylation. Monkey P-450MC1 had low activities toward these two substrates and a high activity for benzphetamine N-demethylation. Monkey P-450MC1 and P-450MC2 were detected by immunoblotting using an antibody prepared against rat cytochrome P-450c, which is a major form of cytochrome P-450 in liver microsomes of MC-treated rats. These results suggested that the molecular properties of cytochrome P-450 in liver microsomes of crab-eating monkeys treated with MC are similar to those in rats.

Animals↗

Kinetic evaluation of 11C-1-aminocyclopentane carboxylic acid in rabbits bearing VX-2 tumors using positron emission tomography.

Tumor detection with 11C-1-aminocyclopentane carboxylic acid (11C-ACPC) showed that this amino acid has a high affinity for malignant tumors. We studied the kinetics of intravenously injected 11C-ACPC in the rabbit VX-2 tumor using positron emission tomography. Three female rabbits bearing VX-2 tumor in the thighs were used. High uptake of 11C-ACPC was seen in the tumor and liver. 11C-ACPC in plasma decreased rapidly after injection and its activity in the tumor increased with time. The kinetic evaluation of ACPC uptake into the tumor was performed using the unidirectional transport model. The average values of the transfer constant of 11C-ACPC for VX-2 tumor were 0.030 +/- 0.002 ml/min/g. This preliminary result may form the basis for a quantitative analysis of the in vivo distribution of 11C-labeled ACPC in tumors.

Amino Acids↗

Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]methionine.

For the evaluation of tumor imaging with L-[methyl-11C]methionine (11C-Met), a basic study on the differentiation of tumor from inflammation with 11C-Met and a comparison of the diagnostic value of the image with that obtained using 67Ga citrate, a conventional scintigraphic agent, are important. 11C-Met accumulations into inflammatory lesions, AH109A tumor and normal tissues of rats were examined by means of a tissue distribution study. Aseptic inflammatory lesions on the back of Donryu rats induced by croton oil and 1.5% carrageenan showed significantly lower accumulations of 11C-Met than the AH109A tumor. Histologically, croton oil induced granulomatous inflammation and carrageenan, acute exudative inflammation. Whole-body autoradiography with 14C-Met, a substitute for 11C-Met, was negative in the carrageenan lesion and showed a slightly increased activity at the periphery of the croton oil lesion, in contrast with the high tumor activity. Whole-body autoradiography with 67Ga citrate was performed to compare the imaging ability with that of 14C-Met; it showed high activities in the tumor, bone, and intestine, and a broad increased activity at the periphery of the croton oil lesion, but was negative in the carrageenan lesion. 11C-Met accumulations in the inflammations were very low and clinical application with positron emission tomography, should be useful for the differential diagnosis of tumor from inflammation.

Animals↗

Insulin secretion in childhood obesity.

In 132 severely obese children (72 boys and 60 girls) who underwent institutional therapy, oral glucose tolerance tests were carried out on admission, and these children were divided into groups with normal and high insulin levels, in terms of the sigma IRI values obtained, on the basis of the reference value + 2SD calculated by Maruhama et al. From these children, those who had diabetes mellitus (DM) and those in whom DM was suspected were distinguished according to the diagnostic criteria of USPHS (Drash et al). The insulin levels were normal in 58 children and high in 64. Ten children were found to have DM, and 19 were suspected to have DM. Metabolism of the glucose load occurred at both normal and high insulin levels in some children. There was also a group of children in whom glucose metabolism was incomplete at high insulin levels and a group of children in whom glucose metabolism was not possible even at high insulin levels, showing an obvious DM reaction. These findings suggest that there is a difference in the sensitivity of the insulin receptors in these children. Age, severe obesity and a family history of DM were considered to be risk factors for DM. Although there was a moderate, positive correlation between sigma IRI and the obesity index and between sigma IRI and age, it seems that the level of insulin secretion varies considerably in obese children.

Adolescent↗

Effects of guanosine nucleotides on skinned smooth muscle tissue of the rabbit mesenteric artery.

1. Effects of guanosine triphosphate (GTP) and guanosine 5'-o-(3-thio)triphosphate (GTP gamma S) on mechanical properties of skinned smooth muscle tissues of the rabbit mesenteric artery were investigated. 2. In skinned muscle tissues prepared by saponin, GTP (above 100 microM) and GTP gamma S (above 1 microM) enhanced the Ca2+-induced contraction (0.3 microM-Ca2+ buffered with 2 mM-EGTA) in the presence of 1 microM-ionomycin, a depletor of stored Ca2+. The concentration-response (pCa-tension) relationship observed in the presence of 10 microM-GTP gamma S shifted to the left with no change in the maximum response evoked by 10 microM-Ca2+. The action of GTP was reversible but that of GTP gamma S was not. 3. The enhancement of the Ca2+-induced contraction by GTP gamma S occurred with increases in the phosphorylation of myosin light chain and in the shortening velocity as measured with the slack test. 4. GTP gamma S had no effect on the Ca2+-independent contraction of skinned muscle tissues evoked by MgATP in Ca2+-free solution (4 mM-EGTA), following treatment with rigor solution containing adenosine 5'-o-(3-thio)triphosphate (ATP gamma S). 5. The present results indicate that GTP and GTP gamma S enhance the Ca2+-induced contraction in skinned muscle tissues due to increase in the Ca2+ sensitivity of contractile proteins. These enhancing actions of guanosine nucleotides on contractile proteins are discussed in comparison to those of protein kinase C.

Animals↗

Dynamic distribution of the Golgi marker thiamine pyrophosphatase is modulated by brefeldin A in rat hepatoma cells.

Cytochemical electron microscopy of cultured rat hepatoma cells (AH-130) demonstrated that thiamine pyrophosphatase (TPPase) activity was localized in the Golgi complex. When the cells were treated with brefeldin A (BFA, 2.5 micrograms/ml) for 10 min, the characteristic structure of the Golgi stack was no longer observed, and TPPase was cytochemically stained in the vesicular and tubular structures scattered in the cytoplasm. A longer exposure of the cells to the drug (20 min to 1 h) resulted in the distribution of the TPPase activity in the endoplasmic reticulum (ER) and nuclear envelope. Such an unusual distribution of the enzyme activity, however, was reversible even in the presence of BFA. At 2 h after the exposure, the TPPase activity disappeared from the ER and was concentrated again in the vesicular and tubular structures. The enzyme activity was finally localized in the Golgi complex which was reassembled by 4 h after the exposure. The reversible effect of BFA may be due to a possible metabolism of the drug into an inert form during the incubation. Taken together, these results indicate that BFA causes a rapid disassembly of the Golgi complex and redistribution of the marker enzyme TPPase into the ER including the nuclear envelope. The spontaneous reversibility of the drug effect also favors a dynamic recycling of the Golgi marker between the ER and the Golgi complex under the conditions used.

Animals↗

Actions of a newly synthesized nitro-compound, E-4701, on rabbit vascular smooth muscles.

The effects of a newly synthesized water soluble and light resistant nitro-compound, E-4701, on the electrical and mechanical properties of smooth muscle cells of rabbit mesenteric and coronary arteries were investigated. In the endothelium-denuded rabbit mesenteric artery, E-4701 relaxed the tissue pre-contracted by noradrenaline (IC50 = 40 microM) to a greater extent than that contracted by high K, but to a lesser extent than that contracted by acetylcholine (ACh) or high K in endothelium-denuded rabbit coronary artery (the IC50 was 20 nM or 60 nM, respectively). Nitroglycerin showed much the same relaxing action on the above tissue (IC50 for the ACh- or K-induced contraction was 20 nM or 65 nM, respectively). Relaxing actions of E-4701 or nitroglycerin were prevented by 10 microM methylene blue. In muscle cells of the porcine coronary artery, E-4701 or nitroglycerin inhibited the Ca-transient provoked by ACh, as examined using fura-2. Both drugs had no effect on the Ca-induced contraction in skinned muscle strips. ACh produced a transient hyperpolarization with subsequent depolarization, but in the endothelium-denuded tissues. ACh only depolarized the membrane. E-4701 inhibited the ACh-induced depolarization, but nitroglycerin did not. We concluded from our observations that E-4701 has the typical characteristics of a nitrocompound with an inhibitory action on the agonist-induced membrane depolarization.

Acetylcholine↗

Effects of tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate on morphology and anchorage-independent growth of normal and established chick embryo cells.

The effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the organization of cytoskeleton and growth of normal and established chick embryo cells (CEC) were studied. The cytoskeleton of normal CEC formed stress fibers, while that of the CEC lines established in our laboratory formed no stress fibers. TPA treatment of normal CEC resulted in disorganization of the stress fibers into amorphous structure, while that of the established CEC lines induced no reorganization of the cytoskeleton. TPA had no promotional effect in vitro or in vivo on tumor growth in normal or the established CEC.

Animals↗

Rescue of infectious virus from nonproducer Rous cells by chick cellular DNA.

The rescue of infectious virus from nonproducer BH RSV(-) cells by chick cellular DNA was attempted in order to investigate the functional state of endogenous and exogenous retroviral genes integrated within the cellular DNA. No infectious virus was rescued by transfection with DNAs of chick helper factor (chf)-negative chick embryo cells (CEC), chf-positive CEC or uninfected CEC producing endogenous Rous associated virus (RAV-0). On the other hand, infectious Rous viruses with the phenotype of RAV-0 and RAV-1 were rescued by transfection with DNAs of CEC which had been infected with RAV-0 and RAV-1. From these results, it seems that exogenous retroviral genes integrated in the cellular DNA are expressed rather easily by transfection while those present endogenously are not.

Animals↗

[Long-term follow-up of the f wave amplitude in chronic atrial fibrillation].

Long-term follow-up of the amplitude of fibrillatory waves (f waves) on the standard electrocardiograms 0.6 +/- 3.3 yr, up to 20 yrs) was performed in 45 patients with chronic stable atrial fibrillation (24 men and 21 women, average age 60.2 +/- 11.5 yrs). The patients were divided into three groups on the basis of the underlying heart disease. Seventeen patients with mitral stenosis were classified as the MS group, 11 with hypertensive heart disease, old myocardial infarction, and aortic insufficiency as the HD group, and 17 without apparent heart diseases as the no heart disease (NHD) group. The f wave amplitude was measured at lead V1 according to the technique employed by Peter. The initial f wave amplitudes of the MS group (0.24 +/- 0.12 mV, mean +/- SD) and of the HD group (0.19 +/- 0.08 mV) were significantly larger than that of the NHD group (0.13 +/- 0.08 mV, p less than 0.05). The f wave amplitudes were significantly decreased during the observation period in each group, and the terminal f wave amplitudes (expressed as the percent of the initial f wave amplitude) were 61 +/- 34% in MS group, 59 +/- 26% in the HD group and 67 +/- 34% in the NHD group. In the NHD group, there was no significant difference in the terminal f wave amplitude between the cases with (n = 10) and without (n = 7) maintenance dose of digitalis. These results showed the apparent reduction of the f wave amplitude with perpetuation of this arrhythmia, and suggested that maintenance doses of digitalis had little effect on this process.

Aged↗

[Double tracer whole body autoradiography using a short-lived positron emitter and a long-lived beta emitter].

We investigated glucose and amino acid metabolism in tumors and other organs using whole body autoradiography with a short-lived positron emitter and a long-lived beta emitter. The radioactive compounds used were 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) with a half life of 109.8 min and L-[methyl-14C]-methionine (14C-MET) with a half life of 5,730 years. A Donryu rat weighing about 150 g was subcutaneously inoculated at the back with experimental tumors of AH109A and AH272. 74 MBq (2 mCi) of 18F-FDG and 740 kBq (20 microCi) of 14C-MET was administered and after 30 min, the rat was sacrificed. Whole body frozen sections were obtained using autocryotome. For the 18F-FDG autoradiogram, the frozen sections were exposed to an X-ray film for 6 h. After seven days, these frozen sections were again exposed to 14C-MET for a week. Cross-contamination was minimized by adjusting the exposure time, the interval of exposures and the administered dose. The accumulation of the tracers was represented as the optical density ratio of the tissue of interest to the muscle. The tumor ratios were 12.5 for 18F-FDG and 8.6 for 14C-MET showing the highest accumulation in the whole body autoradiogram. In contrast the inflammatory tissue ratios were 1.27 for 18F-FDG and 0.77 for 14C-MET showing very low amino acid metabolism. With the present double tracer whole body autoradiogram, 18F-FDG accumulation was seen in the brain and the heart but not to the liver as against 14C-MET accumulation which was seen to the liver but not to the brain and the heart.

Animals↗