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Biomedical subjects

F Hashimoto

Publications and source records attributed to F Hashimoto.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibition of cholesterol synthesis from mevalonate by aminotriazole treatment in vivo.

3-Amino-1,2,4-triazole (aminotriazole) is an irreversible inhibitor of catalase which is a marker enzyme of peroxisomes. We studied the effect of aminotriazole treatment on biosyntheses of cholesterol and bile acid in vivo. When catalase activity of peroxisomes of rat liver was inhibited by aminotriazole treatment, bile acid content in the bile was significantly decreased to about 70% of the control, but that in the liver was not changed. Cholesterol content in the bile was significantly decreased to about 80% of the control, while in liver and serum the content was not significantly changed. When [2-14C]mevalonate was administered to rats, radioactivities of cholesterol in the liver, serum and bile were all drastically decreased by aminotriazole treatment, and an unidentified radioactive product was detected. Radioactivity of bile acid in the bile was also greatly decreased. In a similar experiment with [4-14C]cholesterol, aminotriazole treatment had no effect on the radioactivity of either cholesterol or bile acid in the liver, serum and bile. In this case, the unidentified product could not be detected. These results indicate that when catalase activity of liver peroxisomes is suppressed by aminotriazole treatment, biosynthesis of bile acid from exogenous cholesterol is not inhibited, but a step in the pathway of biosynthesis of endogenous cholesterol from mevalonate is inhibited.

Amitrole↗
PubMed1989

Changes in polyamine-oxidizing capacity of peroxisomes under various physiological conditions in rats.

Rat liver peroxisomal polyamine oxidase activity was determined under various physiological conditions by using the peroxidase method with phenol and 4-aminoantipyrine. N1-Acetylpolyamines such as N1-acetylspermine and N1-acetylspermidine were better substrates than the free polyamines. The polyamine oxidase activity in rat peroxisomes increased significantly when cell proliferation was high. The activity began to appear in fetal liver at the 16th approximately 18th day of pregnancy and peaked in neonatal liver on the first day (approx. 1.7-times higher than in adult liver). In regenerating rat liver, only polyamine oxidase activity among the peroxisomal enzymes tested was increased considerably 12 h after partial hepatectomy (approx. 2.8-fold over the control liver). Finally, the enzyme activity was significantly increased by administration of clofibrate, a peroxisome proliferator, which also causes hepatomegaly. In all cases, the increase in polyamine oxidase activity was not more than 3-fold. Since the level of polyamine oxidase activity in the normal liver is more than adequate in relation to the level of the substrates, the slight but significant increase under conditions of cell proliferation may have a role in modulating levels of polyamines in the proliferating liver tissue.

Animals↗
PubMed1989

Radioimmunoassay of glycated serum protein using monoclonal antibody to glucitollysine and coomassie-brilliant-blue-coated polystyrene beads.

A radioimmunoassay for glycated serum protein (GSP) was developed using monoclonal antibody to glucitollysine and polystyrene beads coated with Coomassie-Brilliant-Blue (CBB) as adsorbent for serum protein. The monoclonal antibody was raised by immunizing BALB/c mice with reduced glycated LDL and fusing their spleen cells with mouse myeloma cells. CBB-coated polystyrene beads were introduced to absorb a constant amount of serum protein. The protein adsorbed on the CBB-coated beads was reduced by NaHB4, and after treatment with radiolabeled antibody, the radioactivity of each bead was counted with an automatic gamma-counter. The standard glycated protein used was reduced glycated human serum albumin, in which 8 of 59 lysine residues were glycated. The intra- and interassay coefficients of variation of GSP were 4.8-6.5% and 1.6-6.0%, respectively. The GSP level of diabetic patients was significantly higher than that of normal controls (1.97 +/- 1.23 vs. 0.47 +/- 0.21 nmol/mg-protein; mean +/- SD, p less than 0.001). The GSP levels of patients with insulin-dependent and non-insulin-dependent diabetes mellitus were 3.03 +/- 1.05 and 1.51 +/- 1.00 nmol/mg-protein, respectively. A good correlation was found between the levels of GSP and hemoglobin A1c (HbA1c) (r = 0.85, p less than 0.001). In patients admitted to the hospital for diabetes education and glycemic control, the GSP level decreased 43 +/- 12% with the decrease in the fasting plasma glucose level (39 +/- 13%) and the mean daily plasma glucose level (MPG, 47 +/- 15%) in a four week period after admission, whereas the HbA1c level decreased only 13 +/- 6% during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Specific radioimmunoassay of glucitol-lysine--application to lens proteins in streptozotocin-diabetic rats.

A radioimmunoassay using antibody against glucitol-lysine was developed to quantitate glycated proteins in the lens of diabetic rats. The amount of glycated protein was expressed as molar equivalents of reduced glycated hippuryl lysine (GlcRED-Hip-Lysine). Significant differences (p less than 0.01) were found in the amounts of glycated protein in the lenses of rats with streptozotocin-induced diabetes (3.92 +/- 0.59 nmol/mg protein, n = 5), those with streptozotocin-induced diabetes treated with insulin (2.94 +/- 0.36 nmol/mg protein, n = 4) and normal rats (1.23 +/- 0.22 nmol/mg protein, n = 5). There was a significant correlation between the concentration of glycated protein in the lens and the HbA1c level at the end of the 12 week experiment (r = 0.957, p less than 0.001). These results indicate that glycation of lens protein is parallel with the severity of diabetes in rats.

Animals↗
PubMed1988

Time-dependent changes of collagen crosslinks in the socket after tooth extraction in rabbits.

Time-dependent changes of the reducible collagen crosslinks in the healing tissue of rabbit tooth extraction wounds were analyzed chromatographically. The ratio of dihydroxylysinonorleucine to hydroxylysinonorleucine in the collagen from normal alveolar bone was 4.4. This value increased about four times, on the 10th day after tooth extraction, coinciding with the phase of active woven bone formation, and then decreased rapidly toward a normal value on the 14th day after tooth extraction. The data suggest that active biosynthesis and fibrillogenesis of bone collagen precede the morphological completion of lamellar bone formation.

Alveolar Process↗
PubMed1988

Physician acceptance of the hepatitis B vaccine at a university medical center.

To examine how physicians at different training levels accepted the hepatitis B vaccine (Heptavax), we mailed questionnaires to all medical students, residents, and faculty at our university medical center. Eighty-one per cent responded; 57 per cent of those had been vaccinated. Attitudes of vaccine safety and efficacy and the perception of increased risk of getting hepatitis B were associated with having been vaccinated. The associations were strongest for the faculty and weak or negative for the medical students.

Academic Medical Centers↗
PubMed1988

Metabolic disposition of 14C-muroctasin in laboratory animals.

1. The absorption, distribution, metabolism and excretion of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a novel compound having an immunomodulator action, have been studied in mice, rats, rabbits and monkeys. 2. MDP-Lys(L18) was well transferred in the body from the administered site after subcutaneous infection of various doses in all animals. 3. Species differences were observed in the whole blood elimination half-life, the longest being in rabbits with ca. 3 h. The values of other species were less than 2 h. On the other hand, the AUC value was the highest in rabbits followed in decreasing order by monkeys, rats and mice. 4. After the subcutaneous infection of 14C-MDP-Lys(L18) (1 mg/head) to mice, the most organ levels of the radioactivity reached the maximum within 2 h. The level was the highest in liver. Tissue distribution pattern in rats was identical to that in mice. 5. The route of excretion of radioactivity was mainly via expired CO2 in all animals. The values were 40-50% of dose, irrespective of animal species. Excretion rate of the radioactivity in the urine was the highest in rabbits followed in decreasing order by rats, monkeys and mice. The fecal excretion of radioactivity varied from 1-12% of dose among the species. 6. The major urinary and fecal metabolites were lactic acid and MDP-Lys(L18), respectively. It was revealed that MDP-Lys(L18) was rapidly biotransformed to N-acetylmuramic acid, lactic acid and carbon dioxide, successively.

Absorption↗
PubMed1987

Radioimmunoassay of glycosylated albumin with monoclonal antibody to glucitol-lysine.

An immunoassay specific for glycosylated albumin was developed by the use of beads coated with antibody to human serum albumin (beads) and 125I-labelled monoclonal antibody to reduced bovine glucosylated low density lipoprotein. One bead was capable of binding 100 ng of serum albumin which had been treated with sodium borohydride (NaBH4) to reduce the Schiff base in the protein. The monoclonal antibody reaction with glucitol-lysine epitopes on the reduced glucosylated proteins and amino acids studied, including human serum albumin (HSA), bovine serum albumin and hippuryl-L-lysine. The detection limit of this assay was 100 pmol/mg HSA, which was sensitive enough for clinical use. The mean serum reduced glycosylated albumin concentration measured by this new method was significantly higher in diabetic patients (2.63 +/- 0.35 nmol/mg HSA, n = 32) than in healthy subjects (0.53 +/- 0.05 nmol/mg HSA, n = 38). The serum reduced glycosylated albumin concentration correlated with both hemoglobin A1c (r = 0.69, p less than 0.005) and the fasting blood glucose level (r = 0.51, p less than 0.005) in diabetic patients.

Aged↗
PubMed1987

Significance of catalase in peroxisomal fatty acyl-CoA beta-oxidation.

Catalase activity was inhibited by aminotriazole administration to rats in order to evaluate the influence of catalase on the peroxisomal fatty acyl-CoA beta-oxidation system. 2 h after the administration of aminotriazole, peroxisomes were prepared from rat liver, and the activities of catalase, the beta-oxidation system and individual enzymes of beta-oxidation (fatty acyl-CoA oxidase, crotonase, beta-hydroxybutyryl-CoA dehydrogenase and thiolase) were determined. Catalase activity was decreased to about 2% of the control. Among the individual enzymes of the beta-oxidation system, thiolase activity was decreased to 67%, but the activities of fatty acyl-CoA oxidase, crotonase and beta-hydroxybutyryl-CoA dehydrogenase were almost unchanged. The activity of the peroxisomal beta-oxidation system was assayed by measuring palmitoyl-CoA-dependent NADH formation, and the activity of the purified peroxisome preparation was found to be almost unaffected by the administration of aminotriazole. The activity of the system in the aminotriazole-treated preparation was, however, significantly decreased to 55% by addition of 0.1 mM H2O2 to the incubation mixture. Hydrogen peroxide (0.1 mM) reduced the thiolase activity of the aminotriazole-treated peroxisomes to approx. 40%, but did not affect the other activities of the system. Thiolase activity of the control preparation was decreased to 70% by addition of hydrogen peroxide (0.1 mM). The half-life of 0.1 mM H2O2 added to the thiolase assay mixture was 2.8 min in the case of aminotriazole-treated peroxisomes, and 4 s in control peroxisomes. The ultraviolet spectrum of acetoacetyl-CoA (substrate of thiolase) was clearly changed by addition of 0.1 mM H2O2 to the thiolase assay mixture without the enzyme preparation; the absorption bands at around 233 nm (possibly due to the thioester bond of acetoacetyl-CoA) and at around 303 nm (due to formation of the enolate ion) were both significantly decreased. These results suggest that H2O2 accumulated in peroxisomes after aminotriazole treatment may modify both thiolase and its substrate, and consequently suppress the fatty acyl-CoA beta-oxidation. Therefore, catalase may protect thiolase and its substrate, 3-ketoacyl-CoA, by removing H2O2, which is abundantly produced during peroxisomal enzyme reactions.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1987

Structure and formation of a stable histidine-based trifunctional cross-link in skin collagen.

A stable nonreducible trifunctional cross-linking amino acid has been isolated from mature bovine skin collagen fibrils. Previous cross-link peptide isolations and amino acid analyses indicate the compound has properties identical with those of hydroxyaldolhistidine. Its newly proposed structure was verified using fast atom bombardment mass spectrometry, and 1H and 13C nuclear magnetic resonance. The data indicated that the cross-link consists of the prosthetic groups from one residue each of histidine, hydroxylysine, and lysine. The 1H and 13C nuclear magnetic resonance data indicated that imidazole C-2 of histidine is linked to C-6 of norleucine (epsilon-deaminated lysine residue) which in turn is linked to the C-6 amino group of hydroxylysine. Based on the trivial names for other cross-linking residues found in collagen and elastin it was given the name histidinohydroxylysinonorleucine. In vitro incubation studies for up to 24 weeks, in aqueous solution at physiological pH and ionic strength, using 6-month-old bovine embryo skin demonstrated a one-to-one stoichiometric relationship between the disappearance of the labile reducible bifunctional cross-link dehydrohydroxylysinonorleucine and the appearance of histidinohydroxylsinonorleucine. These results can partially explain the previously observed disappearance of dehydrohydroxylysinonorleucine with chronological age.

Amino Acids↗
PubMed1987

A computer simulation program to facilitate budgeting and staffing decisions in an intensive care unit.

ICUs have unique problems in choosing their best staffing levels for direct patient care because each unit's total patient needs per shift, quantitated in acuity points, vary widely. We devised a computer program to simulate our 12-bed medical/cardiac ICU workload and staffing system. Nursing staffing policies, costs, and availabilities, and a table of past patient acuities per shift were input; total overstaffing, understaffing, and cost per year for full-time nursing equivalents (FTEs) for direct patient care were output for different staffing levels. Using the model, we considered financial concerns, quality of care issues, and staff working preferences and determined that our best staffing level would be based on 5.5 direct FTEs per shift. The stimulation analysis is straightforward, flexible, adaptable, and easy to update and use.

Budgets↗
PubMed1987

Upper respiratory tract infections increase self-rated hostility and distress.

The authors administered a personality inventory, the Eysenck Personality Inventory and a distress scale, the Symptom Questionnaire, to all patients in a walk-in clinic of a general hospital during an influenza epidemic. Hostility, depression, anxiety and somatic symptoms were significantly higher in patients with upper respiratory tract infections (p less than .005); the majority scored in the range of psychiatric patients, regardless of whether patients had clinically classical influenza or merely symptoms and signs of another respiratory tract infection. There were no differences in the personality traits of extraversion or neuroticism between any of the groups, suggesting that hostility and distress were consequences of the viral infections and were largely unaffected by preexisting personality traits.

Adult↗
PubMed1987

Nifedipine GITS and hydrochlorothiazide in essential hypertension.

Twenty-nine subjects with mild to moderate essential hypertension completed this 13 week randomized, double-blind, placebo-controlled study comparing the antihypertensive effects of nifedipine GITS (N) (30-60 mg/day), hydrochlorothiazide (H) (25-50 mg/day) and placebo (P). Nifedipine GITS is a new formulation designed for once daily administration. N lowered blood pressure 15/10 mmHg (p less than 0.0005/p less than 0.0001), H 15/8 mmHg (p less than 0.0005/p 0.05), and P 4/0 mmHg (p = NS). All patients required the larger dose of active drug to control BP. No drug affected the heart rate. For N, but not H, there was a positive correlation between age and the magnitude in reduction of SBP (r = 0.79; p less than 0.005), but not for DPB. N drug levels did not correlate with its antihypertensive effect. Epinephrine, norepinephrine, aldosterone, and plasma renin activity were not affected by N. No patients on N experienced immediate vasodilator side effects. N is a well tolerated and effective antihypertensive drug that can be given once daily. It does not cause reflex stimulation of the sympathetic nervous system.

Adult↗
PubMed1986

Free peroneal flap coverage of the great toe defect resulting from a wrap-around flap transfer.

In thumb reconstruction, the wrap-around free flap from the great toe with distal terminal phalanx attached gives a better replica of a thumb esthetically and functionally and has many advantages. However, there are problems in the great toe, such as delayed wound healing, pain caused by long-time walking, ulceration, and skin erosion. We closed the skin defect of the great toe with a free peroneal flap in seven cases. In all cases of both the wrap-around flap and peroneal flap complete healing was obtained after the operation without trouble. The donor great toe causes no significant morbidity.

Adult↗