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Biomedical subjects

H Fujii

Publications and source records attributed to H Fujii.

At least 505 records · Page 28Linked to original sources

Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.

We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.

Administration, Oral↗

Effects of brain (B-type) natriuretic peptide on coronary artery diameter and coronary hemodynamic variables in humans: comparison with effects on systemic hemodynamic variables.

OBJECTIVES: This study attempted to clarify the effects of human brain (B-type) natriuretic peptide on coronary artery diameter and coronary vascular resistance in humans. BACKGROUND: Brain natriuretic peptide induces vasodilation in systemic circulation by activating particulate guanylate cyclase of the vascular smooth muscle. METHODS: In 13 patients with normal coronary arteries and left ventricular function, brain natriuretic peptide was infused at 0.5 microgram/kg body weight per min for 4 min into the left main coronary artery (six patients, Group A) or into the pulmonary artery (seven patients, Group B). Systemic hemodynamic variables and coronary sinus blood flow were measured before and after the infusion. The lumen diameter of the left coronary artery was quantitatively measured. RESULTS: In both groups, brain natriuretic peptide significantly increased heart rate and decreased mean arterial pressure. Rate-pressure product remained unchanged in both groups. Brain natriuretic peptide decreased systemic vascular resistance index significantly in both groups (both p < 0.01 vs. baseline), and there was no difference in the effect between the groups. Brain natriuretic peptide decreased coronary vascular resistance in Group A (p < 0.01 vs. baseline) but did not affect coronary vascular resistance in Group B (p < 0.01 vs. Group A). The lumen diameters of the proximal and distal segments of the left coronary artery were increased significantly after brain natriuretic peptide in both groups. After infusion of brain natriuretic peptide, mean plasma level of brain natriuretic peptide in the coronary sinus increased from 36 to 130,411 pg/ml in Group A and from 64 to 12,329 pg/ml in Group B. CONCLUSIONS: Brain natriuretic peptide shows a vasodilator effect on the coronary artery system in humans. However, the effect does not appear uniformly but is seen preferentially in the epicardial coronary artery. The sensitivity of the coronary resistance vessels to brain natriuretic peptide is low compared with that of the resistance vessels of the systemic circulation.

Cardiac Catheterization↗

Intracellular distribution of Hg2+ applied to epidermis in mice. Analysis of subcellular fractions.

To analyze the permeation of Hg2+ in the epidermis as contact dermatitis allergen, the carrier substances from the HgCl2-treated epidermis were isolated. The peak amount of Hg2+ in the epidermis of mouse tail skin was observed at 12 h after the painting. Thereafter, it remained almost stationary. In the analysis of subcellular fractions, the nuclei fraction showed the highest Hg2+ incorporation, while the soluble protein fraction showed the lowest.

Animals↗

Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon.

A new apparatus has been developed using the laser speckle phenomenon for non-contact, two-dimensional analysis of tissue circulation in the choroid and optic nerve head (ONH). The fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB), which is a quantitative index of blood velocity. The results were displayed on color graphic monitors showing the two-dimensional variation of the NB level in the measurement field. In the rabbit, this apparatus was used to study the relationship between the results of NB measurement and the choroidal blood flow determined by the microsphere technique, the relationship between NB obtained from the ONH tissue free of visible surface vessels and the ocular perfusion pressure (OPP) after a lethal injection of pentobarital, and the effect of intraocular pressure (IOP) on the NB in the choroid or in the ONH. A stepwise reduction in the OPP was introduced by elevating the IOP manometrically. The relative decrease in the average NB over the field measured, NBav, in the choroid with the reduction in OPP showed a significant correlation with the relative change in the blood flow rate determined using the microsphere technique (r = 0.60, P < 0.001). NBav in the ONH had a good correlation with the OPP after a lethal injection of pentobarbital (r = 0.98, P < 0.001). NBav in the choroid decreased with reduction in the OPP. Although NBav in the ONH was little affected by OPP change when OPP was above 40 mmHg, at OPP levels below 40 mmHg, NBav in the ONH decreased along with a reduction in the OPP. These results suggest that by using the present apparatus, the blood velocity in the choroid or ONH under various conditions can be studied non-invasively in the living eye.

Animals↗

Post-radiation primary intranodal leiomyosarcoma.

An unusual case of post-radiation primary intranodal leiomyosarcoma of the cervical lymph node is presented. The patient was a 32-year-old white man who was treated in 1986 with hemiglossectomy and right neck dissection, followed by radiation therapy, for squamous cell carcinoma of the tongue. Six years later, he presented with an enlarged left cervical lymph node which on biopsy showed a high grade spindle cell malignant neoplasm. Immunohistochemistry and electron microscopic study verified the smooth muscle origin of the tumour. Extensive work-up for a second primary lesion was negative. Primary intranodal leiomyosarcoma is extremely rare. We briefly discuss the histological differential diagnosis of spindle cell lesions of lymph nodes, leiomyosarcoma of the vessel wall and radiation-associated sarcoma.

Adult↗

Two-dimensional analysis of hemodynamic changes in axial and random pattern flaps.

The present study was performed to evaluate the time course of hemodynamic change in axial and random pattern flaps two-dimensionally. The axial pattern flap, including the central auricular artery and vein, and the random pattern flap without these vessels were created in the auricles of the rabbit. The blood flow of these flaps was investigated and assessed using laserflowgraphy, which provides a two-dimensional analysis of microcirculation. In the axial pattern flap, a gradient of blood flow toward the short axis of the flap and decreased blood flow in the surrounding area were noticed immediately after operation. The hemodynamic changes became less marked with time. In the random pattern flap, a gradient of blood flow toward the long axis of the flap was noticed around 6 hr after operation and the blood flow in the surrounding area increased throughout the investigations.

Animals↗

Branched-chain alpha-keto acid dehydrogenase complex in rat skeletal muscle: regulation of the activity and gene expression by nutrition and physical exercise.

Branched-chain alpha-keto acid dehydrogenase complex is the rate-limiting enzyme in the catabolism of branched-chain amino acids in skeletal muscle. It is suggested that activation of this enzyme in the muscle during exercise plays an important role in the increased oxidation of branched-chain amino acids in the muscle. Evidence suggests that branched-chain alpha-keto acids, the substrates for the enzyme, regulate the activity state of the enzyme in the muscle during exercise through phosphorylation/dephosphorylation cycle of the enzyme protein. We propose a model for the mechanism of enzyme activation by exercise. In addition to this acute effect of exercise, we present evidence suggesting that exercise training modulates the enzyme activity and gene expression for the enzyme. Increases in the total activity as well as enzyme proteins by exercise training are suggested to be associated with mitochondrial biogenesis in the muscle.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Pharmacological correlation between total drug concentration and lactones of CPT-11 and SN-38 in patients treated with CPT-11.

The pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were examined to establish the pharmacokinetic variability of the active lactones of CPT-11 and SN-38 in comparison with that of the total (lactone and carboxylates) plasma CPT-11 and SN-38. Twelve patients with malignancies were entered in the study. All received 100 mg/m2 of CPT-11 by intravenous drip infusion over 90 min. Blood was sampled at 10 time points in heparin-containing syringes. Analysis by high-performance liquid chromatography showed that the ratio of CPT-11 lactone to total CPT-11 concentration was highest (66%) just after the end of infusion and gradually decreased to 30% at 24 h. Almost 70% of SN-38 lactone was detected after the end of infusion and this decreased to 50% within 24 h. The standard errors of percent lactone of CPT-11 of SN-38 to total drug concentration at each sampling point were less than 12%. The area under the concentration-time curve (AUC) of total CPT-11 and that of total SN-38 were significantly correlated with the AUCs of the lactone CPT-11 and those of lactone SN-38, respectively. We conclude that, for practical purposes, monitoring of total CPT-11 and SN-38 has essentially the same clinical significance as monitoring of lactone CPT-11 and SN-38.

Adult↗

A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38.

The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10-hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT-11 administration. The model was developed with a training set consisting of pharmacokinetic studies in 36 patients who received a 90-min i.v. infusion of CPT-11 at a dose of 100 mg/m2. A multiple regression analysis of CPT-11 or SN-38 concentrations observed at each time point in the training set was used to predict the AUC of CPT-11 or SN-38. The final sampling models using only two time points were: AUCCPT-11 = 3.7891*C2.5 + 14.0479*C13.5 + 1.5463 AUCSN-38 = 0.5319*C2.5 + 19.1468*C13.5 + 72.7349 where C2.5 and C13.5 are the plasma concentration of CPT-11 (micrograms/ml) or SN-38 (ng/ml) at 2.5 and 13.5 h after the initiation of CPT-11 infusion, respectively. The models were validated prospectively on a separate test data set of 12 patients receiving the same dose of CPT-11 investigated in a previous study. Validation of the final LSM on the test data set gave values of root mean square error (RMSE) of 12.72% and 5.97% for the AUC of CPT-11 and that of SN-38, respectively. The model can be used to monitor the AUCs of both CPT-11 and SN-38 for the early prediction of toxicities and to establish a pharmacokinetically based dose modification strategy for safe administration of CPT-11.

Adult↗

Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara.

We report the case of a 2-year-old Japanese boy with acute favism who was treated with human haptoglobin products. He had been exhibiting chronic nonspherocytic haemolytic anaemia until the diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency when 14 months old. He suffered a favic crisis at 24 months of age, when the administration of haptoglobin was effective for relieving bilirubinaemia and haemoglobinuria. Serum-free Hb rapidly decreased to normal levels despite the sustained level of serum lactate dehydrogenase. His G6PD gene was G6PD Guadalajara. This is the first application of haptoglobin therapy for acute favism and the first reported case of Japanese G6PD deficiency with typical favic crisis. Haptoglobin treatment might be helpful for managing the haemolytic crisis in the disease.

Child, Preschool↗

A case of infantile febrile psoriasiform dermatitis.

An infant suffered from psoriasiform dermatitis complicated by severe constitutional symptoms. During his 12 months of hospitalization, the symptoms exacerbated periodically despite numerous therapeutic trials. Histologic findings revealed lichenoid psoriasiform dermatitis with striking eosinophilic necrosis of epidermal cells and satellite cell necrosis. Immunohistochemically, CD1+ Langerhans cells had almost disappeared, and CD8+ cytotoxic-suppressor T cells were predominant over CD4+ helper-inducer T cells in the epidermis. These findings in the skin biopsy specimens suggested some similarity to graft-versus-host disease but no known cause of that disorder was proved. Finally, methotrexate was effective. The patient became afebrile, and his skin lesions improved, leaving almost no scarring. This patient seems to have had specific clinical features that do not correspond with any of the known dermatitis. Clinical, histologic, and laboratory findings did not uncover any etiologic factors.

Dermatitis↗

Methylation patterns of I epsilon region in B cells stimulated with interleukin 4 and Epstein-Barr virus in patients with a high level of serum IgE.

Human IgE synthesis requires the presence of both interleukin 4 (IL-4) and T-cells. However, it is not clear what role IL-4 and T-cells play in the induction of IgE synthesis at the level of gene regulation. B cells that were obtained from patients with a high level of serum IgE and from healthy donors were immortalized by Epstein-Barr virus. We examined IgE production of these B cells stimulated with IL-4. Supernatant IgE levels of patient's B cells cultured with or without IL-4 were higher than those of healthy donor's B cells. Our results indicated that B cells stimulated with IL-4 from patients produced IgE, germline C epsilon transcript, and S mu S epsilon recombination. The germline C epsilon transcript was dose-dependently induced in the presence of IL-4 and related to the supernatant IgE level. In B cell stimulated with IL-4 that were obtained from patients, (some of the) DNA near or within the I epsilon region was (already partly) unmethylated, unlike those from healthy donors, and there was a loss of methyl groups of the DNA upon the addition of IL-4 in B cells from both patients and normal donors. IgE synthesis of B cells stimulated with IL-4 in patients with a high level of serum IgE is due to an accessibility in the immunoglobulin heavy-chain isotype switch, and this may reflect the accessibility in synthesis of germline C epsilon transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I epsilon region.

Asthma↗

[A clinical study of six cases of toxic shock-like syndrome by group A Streptococcus].

We have encountered six cases with toxic shock-like syndrome (TSLS) by Group A Streptococcus since 1978. Every patient had from the onset flu-like symptoms or high fever and immediately developed some of the following clinical signs: hypotension, acute renal failure, disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS). Three of the six patients died with rapid clinical courses and three survived. As for the surviving patients, early administration of antibiotics and anti-DIC therapy were effective. Streptococcus pyogenes were isolated from the blood in five of the patients, ascites from another, and necrotizing tissue in one patient. The serovars of the isolated strains were typed as T1/M1 in three, T8 in one, and T28 in another. The toxin-type of the strains were typed as B in four and B + C in one. Though there have been few reports of TSLS before 1992 in Japan, it is supposed that many TSLS cases may have potentially occurred.

Aged↗

Intestinal fatty acid binding protein is available for diagnosis of intestinal ischaemia: immunochemical analysis of two patients with ischaemic intestinal diseases.

Mesenteric infarction and other acute ischaemic intestinal diseases are still a challenging diagnostic problem. Based on animal experiments, intestinal fatty acid binding protein (I-FABP), which is uniquely localised to the bowel, has recently been proposed as a new serum marker for intestinal ischaemia. This paper reports on two cases with acute intestinal ischaemic diseases, and the measurement of serum I-FABP by western blot analysis. The concentrations of ordinary serum markers were normal and the bowel necrosis was not diagnosed until surgical exploration. Immunochemical analysis showed that the I-FABP concentrations in the patients' serum samples were high at the time of admission, and that I-FABP was undetectable in the samples obtained after bowel resection and in healthy control subjects. This paper suggests that I-FABP is released into the circulation in the acute phase of intestinal ischaemia and that I-FABP can be used in establishing the diagnosis of ischaemic intestinal diseases.

Acute Disease↗

Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.

The familial occurrence of allergic diseases was studied in 478 individuals and their family members. The results showed that there was pronounced familial clustering. Total serum IgE concentrations of atopic patients and their parents were well correlated. Moreover, the concentration of specific IgE of the patients and their parents was also well correlated, suggesting that IgE production was genetically determined. To determine if major structural abnormalities of IGHE, IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2 genes in all 55 leukocyte DNAs. We could not find any large deletions or duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high serum IgE concentrations.

Adolescent↗

Comparison of therapeutic efficacies of type A and F botulinum toxins for blepharospasm: a double-blind, controlled study.

Type F botulinum toxin can be used for treating patients with dystonia who become refractory to type A toxin injection due to antibody development. We compared the therapeutic efficacy of type F botulinum toxin to that of type A toxin in a self-controlled, double-blind clinical trial. In nine patients with blepharospasm, we injected type A toxin on one side and the same units of type F toxin on the other side. Although the onset of clinical effect, maximal benefit, and adverse reactions were similar between type A and F toxins, the duration of the clinical effect was significantly shorter on the side injected with type F toxin. Although type F toxin proved its promise as an alternative to type A toxin, its usefulness is limited by the shorter duration of action.

Aged↗

Antimetastatic activities of synthetic Arg-Gly-Asp-Ser (RGDS) and Arg-Leu-Asp-Ser (RLDS) peptide analogues and their inhibitory mechanisms.

We have investigated the inhibitory effect of the N-terminal modified Arg-Gly-Asp-Ser (RGDS) analogues, AcDRGDS and AcDRLDS, on tumor cell adhesion to the components of extracellular matrix and basement membrane, and also tested the antimetastatic effect of their conjugates with trimesic acid, Ar(DRGDS)3 and Ar(DRLDS)3. AcDRGDS significantly inhibited tumor cell adhesion to fibronectin, vitronectin and RGDS substrates, but not to CS1 substrate which is a ligand for the alpha 4 beta 1 tumor surface integrin receptor. In contrast, AcDRLDS variant peptide significantly inhibited tumor cell adhesion to laminin, in addition to RGDS-mediated adhesion to fibronectin and vitronectin. AcDRLDS also inhibited tumor cell adhesion to CS1 as well as the RGDS sequence within the fibronectin molecule in a concentration-dependent manner, although the inhibitory effect was less than that of the CS1 (EILDV) peptide. Ar(DRLDS)3 inhibited the laminin- and fibronectin-mediated invasion and migration of tumor cells, whereas Ar(DRGDS)3 selectively inhibited fibronectin-mediated invasion and migration. Ar(DRGDS)3 and Ar(DRLDS)3 were much more effective in inhibiting experimental lung or liver metastases of various types of murine and human tumors than the original RGDS-containing peptides or Ar(COONa)3. Multiple administrations of Ar(DRGDS)3 or Ar(DRLDS)3 potently inhibited spontaneous lung metastasis produced by intra-footpad injection of B16-BL6 cells without affecting the primary tumor size at the time of surgical excision, as compared with RGDS peptide or untreated control. Thus, Ar(DRGDS)3 and Ar(DRLDS)3 substantially increased the exhibiting any antimetastatic effect of the peptides without direct cytotoxicity.

Amino Acid Sequence↗

Efficacy of subcutaneous application of live infectious bursal disease vaccine in young chickens with maternally derived antibody.

The infectivity of neutralized IBDV by normal chicken serum (NCS) was detected in day-old and 3-week-old chicken spleen adherent (CSA) cells, and that of neutralized IBDV by maternal antibody (MN-Ab) was detected in 3-week-old CSA cells. Moreover, CSA cells from day-old chickens had complement receptor (CR), and CSA cells from 1-week-old had both CR and Fc receptor (FcR). However, the infectivity of neutralized IBDV by MN-Ab was confirmed on CSA cells which were blocked for FcR on CSA cells by heat-aggregated NCS (56 degrees C, 60 min). These results indicated that infection of neutralized IBDV by NCS on CSA cells occurred via CR, and neutralized IBDV by MN-Ab was infected via FcR. In day-old specific pathogen free (SPF) chickens, the antibody level in NCS treated and non-treated IBD live vaccine subcutaneously inoculated groups was higher than the levels in the MN-Ab-treated IBDV inoculated group, and detected until 28 days old. Moreover, subcutaneously inoculated chickens were protected against the challenge of wild IBDV at 21 days old, whereas subcutaneously inoculated chickens were infected with MN-Ab-treated IBD live vaccine. In commercial layers which had MN-Ab, antibody levels of subcutaneously vaccinated group were higher than both the non-vaccinated and orally vaccinated groups, and virus isolation and viral antigen were positive with high detection rates on peripheral lymphocytes of each subcutaneously vaccinated group of SPF and commercial chickens.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗