Biomedical subjects

M Dohi

Publications and source records attributed to M Dohi.

At least 37 records · Page 2Linked to original sources

PubMed1992

Pentamidine: a non-peptide GPIIb/IIIa antagonist--in vitro studies on platelets from humans and other species.

In this paper we show that the non-peptide anti-parasite agent pentamidine is a broad spectrum anti-platelet agent with an IC50 of 1.1 microM in ADP-induced platelet aggregation in human platelet rich plasma (PRP). It had similar activity when collagen, arachidonic acid, platelet activating factor, thrombin and epinephrine were used. It had no effect on platelet intracellular cAMP levels. It inhibited 125I-fibrinogen, 125I-fibronectin and 125I-von Willebrand factor binding to ADP-activated fixed platelets with IC50 values of 160, 160 and 60 nM respectively. Pentamidine showed a high degree of species selectivity with slightly less activity in monkey and dog PRP and little activity in guinea pig, rabbit, rat and mouse PRP compared with human. This was similar to the other RGD analogues tested. This species specificity was shown to be dependent on the species of platelets and independent of the species of fibrinogen. Thus, pentamidine is a potent non-peptide inhibitor of fibrinogen binding to GPIIb/IIIa.

Amino Acid Sequence↗

PubMed1992

Prolonged survival of MRL-lpr/lpr mice treated with Tripterygium Wilfordii Hook-F.

MRL-lpr/lpr mice were treated with Tripterygium Wilfordii Hook-F (TWHF), a Chinese herbal medicine successfully used for human rheumatoid arthritis. Dramatic prolongation of survival and the reduction of urinary protein were observed in mice treated with a high dose of TWHF (20 mg/kg, three times a week) compared to the control animals receiving solvent alone. A slight but significant reduction was also seen in the degree of lymphadenopathy and arthritis with the high dose treatment. Surprisingly, no significant difference was present in IgM rheumatoid factor and IgG anti-double-stranded DNA antibody levels or in the histopathology of lupus nephritis. These results indicate the dissociation of histopathological renal disease and the degree of proteinuria or the life span. Although further pharmacological analysis is required, TWHF might be potentially useful for diseases such as systemic lupus erythematosus or nephrotic syndrome.

Animals↗

PubMed1992

Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis.

T cell activation in the characteristic synovial lesions of rheumatoid arthritis may play a major role in the pathogenesis of this autoimmune disease. Analysis of T cell clonal diversity in these sites remains equivocal. Using the PCR and subsequent single-strand conformation polymorphism analysis it is possible to assess the degree of junctional diversity in the TCR with minimal selection bias. Concentrating on the beta-chain of the TCR, a paucity of clonotypic T cell expansion is demonstrated in the peripheral blood of healthy individuals. After polyclonal stimulation in vitro (with concanavalin A or phytohemagglutinin) this pattern does not change. In contrast, some T cell clonotypes appear following in vitro stimulation with purified protein derivative. Analysis of the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis indicated many dominant T cell clonotypes. These data argue for a clonally diverse T cell response in the affected tissues of rheumatoid arthritic subjects.

Arthritis, Rheumatoid↗

PubMed1992

Enantiomeric difference in percutaneous penetration of propranolol through rat excised skin.

The percutaneous penetration of R-(+)- and S-(-)-propranolol (PL) through rat excised skin was investigated in vitro. The flux of S-(-)-PL after application to normal skin was high compared with that of R-(+)-PL. On the other hand, in damaged rat skin, the flux of R-(+)-PL was almost equivalent to that of S-(-)-PL. It is suggested that there is an enantiomeric difference between S-(-)- and R-(+)-PL in terms of penetration through rat stratum corneum.

Animals↗

PubMed1992

[Percutaneous absorption of drug from alpha-olefin oligomer gel bases].

The percutaneous absorption of drug from the alpha-olefin oligomer (alpha-OL) gel base prepared by using palmitate of dextrin (Rheopearl KL) as a gelling agent was investigated by using the abdominal skin of rats in vivo. The 20, 30, 40 and 50 alpha-OLs with average molecular weights of 288, 380, 440 and 535, respectively were used in this study. The flurbiprofen (FP) was selected as a model drug. The percutaneous absorption of FP from the alpha-OL gel base was observed to be influenced by the molecular weight of alpha-OL. The percutaneous absorption profiles of FP from 40 and 50 alpha-OLs gel bases were almost the same. On the other hand, the absorption of FP from 30 alpha-OL gel base was significantly higher than those of 40 and 50 alpha-OLs gel bases. Furthermore, the percutaneous absorption of FP from 20 alpha-OL gel base was observed to be the highest in the test gel bases. In order to establish the reason for the differences in the percutaneous absorption of FP from 20, 30, 40 and 50 alpha-OLs gel bases, the apparent partition ratios of FP between water and four different alpha-OLs were determined as a parameter of the affinity of FP for the vehicle. Consequently, it has become apparent that the partition ratio exerts an influence on the percutaneous absorption of FP from the alpha-OL gel bases.

Alkenes↗

PubMed1992

[A case of asymptomatic endobronchial lipoma followed for 4 years].

Bronchoscopy was performed on a 68-year-old male patient with pulmonary tuberculosis, and revealed a yellow smooth polypoid tumor in the lumen of the left upper division bronchus. The histopathological diagnosis of the biopsy specimen was endobronchial lipoma. Since the patient did not have any symptoms due to the lipoma, we performed treatment for tuberculosis and continued careful observation of the tumor. During the subsequent 4 years, the patient developed no complications such as obstructive pneumonia, and the size of the tumor under bronchoscopic observation did not change. Endobronchial lipoma is a very rare benign tumor. Almost all reported cases have undergone operation or endoscopic surgery. This case is the first that was followed over 4 years without surgical procedure. The findings of follow-up bronchoscopic examination suggest that the growth rate of endobronchial lipoma is very slow. Furthermore, we reviewed 36 cases of endobronchial lipoma in the Japanese literature, including our case. Smoking seems to have a strong relation to the occurrence of the tumor. It is noteworthy that 6 cases had separate malignancies, but the direct relationship between endobronchial lipoma and such malignancies is unclear.

Aged↗

PubMed1991

Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases.

Eleven patients with food-dependent, exercise-induced anaphylaxis were studied. Seven patients experienced anaphylactic symptoms only after eating certain foods, such as shellfish, wheat, and grape before exercise. In the remaining four patients, no specific food could be identified, but the act of eating itself predisposed to anaphylaxis. Their anaphylactic symptoms were all clearly distinguished from cholinergic urticaria by history. Patients who developed anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or had atopic first-degree relatives. Six patients had increased serum IgE levels, and IgE antibodies against the causative food allergens were detected by the skin prick test or RAST in four cases. In contrast, patients who developed the symptoms after 30 years of age (N = 4) appeared to have a less atopic background, and IgE levels were within normal range except in one case. Three of four patients in the latter group developed symptoms after ingesting food made of wheat followed by exercise. All patients were sensitive to wheat as determined by the skin prick test. In six of 11 patients, a considerable rise in plasma histamine concentration was observed after exercise challenge with treadmill alone, and food intake followed by exercise induced a further increase in one patient.

Adolescent↗

PubMed1991

T-cell-dependent accumulation of eosinophils in the lung and its inhibition by monoclonal anti-interleukin-5.

The transnasal administration of an extract of the parasite Ascaris suum to C57BL/6 mice for 3 weeks produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. The oral administration of ciclosporin significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that the pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB x C57BL/6) F1-W/Wv (W/Wv) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of lung eosinophilia in this model. Monoclonal antimurine interleukin-5 injected intraperitoneally clearly inhibited the infiltration of eosinophils in the lung, suggesting that T-cell-derived interleukin-5 is essential.

Animals↗

PubMed1991

Inhibition of allergen-induced bronchoconstriction in sensitized guinea pigs by orally administered allergen.

Crude mite extract (CME) was orally administered to guinea pigs sensitized to CME. It was shown that such treatment reduces the bronchoconstrictive response upon allergen provocation. Isolated tracheae taken from guinea pigs orally administered CME allergen showed less contraction in response to CME as compared to those obtained from sensitized but not orally treated animals. The oral administration of allergens seemed to attenuate the bronchial hyperresponsiveness of sensitized animals to a non-specific chemical stimulus (histamine). IgE antibodies titrated by 8 days passive cutaneous anaphylaxis, and IgG1 and IgG2 antibodies measured by ELISA were comparable in the sera obtained from animals before and after CME treatment.

Administration, Oral↗

PubMed1991

Synthesis of biologically active recombinant Der f II.

A cDNA library corresponding to mite protein was screened employing anti-Der f II antibody. Two possible clones containing plasmids pFL1 and pFL11 were obtained. The two plasmids had insertions of about 500 basepairs. The DNA sequences of the two insertions were determined, from which the amino acid sequences were deduced. The amino acid sequence of the purified native Der f II protein could be determined to 45 residues from the N terminus. As a result of comparison, we concluded that the cDNAs prepared from live Dermatophagoides farinae mite corresponded to the mite allergen Der f II. The recombinant Der f II was biologically active.

Allergens↗

PubMed1991

Interleukin-4 gene expression in human peripheral blood mononuclear cells.

Interleukin-4 (IL-4) mRNA was detected in normal human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A by Northern blot analysis. The signal was undetectable in PBMC before the stimulation, but became detectable 3 hrs after the stimulation and reached a maximum in 3-6 h and disappeared gradually thereafter. Immunosuppressive drugs such as ciclosporin, hydrocortisone and prednisolone inhibited the IL-4 mRNA expression dose dependently. Interferon-gamma did not show any inhibitory effect on IL-4 gene expression.

Blotting, Northern↗

PubMed1990

Bronchial responsiveness to mite allergen in atopic dermatitis without asthma.

Eight patients with atopic dermatitis (AD) without a history of asthmatic episodes and 8 patients with mite-allergic bronchial asthma (BA) were subjected to bronchial inhalation challenge with a nonspecific stimulus (acetylcholine) and an immunologically specific stimulus (house dust mite allergen). AD patients had a significantly greater concentration of IgE (p less than 0.01) and antimite IgE antibody (p less than 0.05) than BA patients. Nonspecific bronchial hyperreactivities of AD patients distributed from normal to asthmatic range. After allergen challenge, all 8 AD patients and all 8 BA patients showed an immediate asthmatic response (IAR). The mite extract concentration to induce an IAR was significantly (p less than 0.01) greater in AD patients than in BA patients. A late asthmatic response was observed in 6 out of 8 BA patients, whereas it was not observed in any AD patient. Our results showed that AD patients are less reactive to a specific mite allergen than BA patients in spite of greater concentrations of antimite IgE antibody. They suggest that this difference in the bronchial reactivity to the allergen concerns the difference in the onset of clinical symptoms and that a certain level of bronchial hyperreactivity to the allergen is a prerequisite for the development of asthmatic symptoms.

Adolescent↗

PubMed1990

Percutaneous absorption of indomethacin from mixtures of fatty alcohol and propylene glycol (FAPG bases) through rat skin: effects of oleic acid added to FAPG base.

The effects of oleic acid (OA) added to mixtures of fatty alcohol and propylene glycol (FAPG bases) on the percutaneous absorption of indomethacin (ID) were investigated by using the abdominal skin of rats in vivo. The percutaneous absorption of propylene glycol (PG) from FAPG base was simultaneously examined. The percutaneous absorption of ID from FAPG bases in the absence of OA was poor as compared with that from FAPG bases containing OA. It was observed that when OA was added to the vehicles in the range of 5 to 30%, the percutaneous absorption of ID from the vehicles was increased. In particular, the maximal enhancement of percutaneous absorption of ID was achieved at 5% OA. However, the enhancing effect of percutaneous absorption of ID diminished when the OA content in the vehicle exceeded 50%. PG was readily absorbed through the rat skin from FAPG bases and its percutaneous absorption profiles were similar to those of ID. It can be presumed that PG and ID penetrate together through the skin. In addition, it was confirmed that the percutaneous absorption of ID and PG from FAPG bases was not affected by the viscosity of the vehicle. If FAPG base is to be used as a vehicle for the purpose of percutaneous absorption of ID, OA is considered to be a useful additive.

Animals↗

PubMed1990

Enhancing effects of myristyl lactate and lauryl lactate on percutaneous absorption of indomethacin in rats.

The enhancing effects of myristyl lactate (ML) and lauryl lactate (LL) on the percutaneous absorption of indomethacin (ID) from test solutions in propylene glycol (PG) were investigated in rats. ID absorption was observed to be markedly enhanced by the addition of ML or LL to PG as compared with the control (PG alone). The marked enhancing effects were observed at concentrations greater than 3% ML and 3% LL in PG. In particular, the maximal enhancement of percutaneous absorption of ID was achieved at 5% ML and LL. To elucidate the mode of action of ML as an enhancer, the percutaneous absorption of ID through the skin pretreated with ML alone was investigated. It was suggested that ML acts on the stratum corneum to produce its effect.

Administration, Topical↗

PubMed1990

[Procoagulant activity of alveolar macrophages in bleomycin-induced lung fibrosis in rats].

Interstitial and intraalveolar fibrin deposition is a prominent feature in adult respiratory distress syndrome and is also observed in the inflammatory phase of interstitial lung disease (ILD). It is suggested that the coagulation abnormality in these disorders may be implicated in the pathogenesis of subsequent fibrosis of the lung. In this study, we examined the procoagulant activity (PCA) of alveolar macrophages during the development of bleomycin-induced lung fibrosis in rats. The PCA of alveolar macrophages was significantly increased at 2, 7 and 14 days after the intratracheal administration of bleomycin compared with that of control rats. The greatest PCA was observed at 7 days after the bleomycin injection, the inflammatory phase in the development of lung fibrosis. Increased PCA returned to the normal value at 21 days, while the fibrotic process advanced and the collagen content increased in the lung. Alveolar macrophages at 7 days after the administration of bleomycin or saline were separated into five density fractions on discontinuous Percoll gradients. The increase in the percentage of low-density macrophages was observed in bleomycin-injected rats. The greatest PCA was demonstrated in the lowest-density fraction (specific gravity less than 1.030), while reduced activities were observed in the higher-density fractions, in each group. The increased PCA of alveolar macrophages during lung injury was due in part to the increase of low-density subpopulation, which had greater PCA, although the fibrin deposition in the development of lung fibrosis remained to be defined, the increase of coagulation pathways may contribute to the progression of interstitial fibrotic lung diseases.

Animals↗

PubMed1990

Basophil histamine release and airway response to mite allergen in atopic dermatitis.

Twelve patients with atopic dermatitis (AD) were subjected to in vitro histamine release from peripheral blood leukocytes (basophils) and in vivo bronchial inhalation challenge using house dust mite (Dermatophagoides farinae) allergen. Not only seven patients with asthmatic history but also five patients without asthma responded to both the in vitro and the in vivo challenges. A significant correlation was observed between HR30 (a mite concentration producing a 30% release of total cellular histamine) and PC20 allergen (a mite concentration producing a 20% fall in FEV1). There was also a significant correlation between MHR (maximal histamine release) and the maximal fall in FEV1. The relationship held for both AD patients with asthma and without asthma. These results suggest that histamine release induced by the house dust mite allergen is a good in vitro test for predicting the bronchial response to this allergen. They also suggest that these tests are not disease specific, but are valuable in evaluating the degree of atopic state in a subject.

Allergens↗

PubMed1990

[3 cases of food-dependent exercise-induced anaphylaxis in which aspirin intake exacerbated anaphylactic symptoms].

Exercise-induced anaphylaxis (EIAn) is a distinct form of physical allergy. As one of the predisposing factors of EIAn, food intake is often cited, and such cases are classified as food-dependent EIAn. Another factor reported is the administration of drugs. Recently we had 3 patients with food-dependent EIAn who showed more severe symptoms when they took aspirin orally. None of them had shown symptoms when they took aspirin alone. Symptoms were provoked only when they took aspirin for common cold, headache or toothache followed by certain foods and exercise. Two out of the 3 patients had experienced food-dependent EIAn before. However, after taking aspirin, their anaphylactic symptoms were more severe with more slight degree of exercise. Results of exercise challenge by treadmill showed that exercise alone induced an increase in plasma histamine concentrations in 2 out of the 3 patients 5 to 15 minutes after the challenge. These data suggest the possibility that our patients have an increased histamine releasability from mast cells responding to exercise, and that aspirin intake might enhance the process.

Adult↗

PubMed1990

[Bronchial responsiveness to methacholine in the mouse tested by a new apparatus measuring respiratory resistance].

We developed a new apparatus for the measurement of mouse respiratory resistance (Rrs) by an oscillation method. Bronchial responsiveness to methacholine was studied in mice sensitized or not with egg albumin using this apparatus. All of the sensitized mice showed clearly increased bronchial reactivity upon nasal challenge with methacholine compared to normal control mice. The lung obtained from a sensitized mouse showed remarkable contraction of the bronchial smooth muscle, submucosal edema and cell infiltration around the bronchi. These results indicate that mouse Rrs is successfully measured by our newly developed apparatus and suggested that repeated sensitization of mice with allergen render their airway hyperreactive to methacholine.

Animals↗