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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 703 records · Page 39Linked to original sources

Effect of thromboxane A2 synthetase inhibitor, OKY-046, on sputum in chronic bronchitis and diffuse panbronchiolitis.

The mechanisms of excessive sputum production are only partially understood. We speculated that a selective thromboxane (Tx) A2 synthetase inhibitor, OKY-046, now used in the treatment of asthma in Japan, could decrease excess sputum production in patients with chronic airways disease. To test this hypothesis, we carried out a double-blind, placebo-controlled study of the effects of OKY-046, administered orally at 400 mg.day-1, on the sputum of patients with chronic bronchitis and patients with diffuse panbronchiolitis. Patients treated with OKY-046 showed a significant decrease (22%) in sputum volume after 1 month, and a 39% decrease after 3 months. Although the rheological properties of the sputum and the concentrations of fucose and immunoglobulin (Ig) A in the sputum remained unchanged, significant decreases were observed in the concentrations of total protein, albumin, sialic acid and phospholipid. Since albumin and fucose are chemical markers of plasma exudation and mucus secretion, respectively, whilst sialic acid and phospholipid are derived both from serum and mucus, our results indicate that this TxA2 synthetase inhibitor reduced sputum volume by inhibiting microvascular leakage in the airway. OKY-046 may, therefore, be of value in the treatment of chronic bronchitis and diffuse panbronchiolitis.

Adult↗

Effects of serotonin1A agonists on anoxia-induced impairment of protein synthesis in rat brain slices.

Earlier in vivo experiments suggest that serotonin1A (5-HT1A) agonists are new tools for the treatment of experimental cerebral ischemia. The present study examined this idea in an in vitro system. Incubation of rat brain slices under anoxic conditions for 30 min decreased protein synthesis that was assayed in a normoxic medium by measuring the incorporation of [14C]lysine into trichloroacetic acid-insoluble tissue extracts. The 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino) tetralin (10-100 microM) and buspirone (50 microM) attenuated the anoxia-induced decrease in protein synthesis in the slices. Although the degree of the effect is small, it may be relevant to the neuroprotective effect in the in vivo experiments.

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

Novel benzodioxan derivative, 5-(3-[((2S)-1,4-benzodioxan-2- ylmethyl)amino]propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotonin1A receptors.

The present study characterizes the neurochemical profile of the newly synthesized compound 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-be nzodioxole HCl (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (Ki: 0.35 nM) and moderate affinity for alpha 1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotransmitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.

5-Hydroxytryptophan↗

Four rice seed cDNA clones belonging to the alpha-amylase/trypsin inhibitor gene family encode potential rice allergens.

Four rice seed proteins encoded by cDNAs belonging to the alpha-amylase/trypsin inhibitor gene family were overexpressed as TrpE-fusion proteins in E. coli. The expressed rice proteins were detected by SDS-PAGE as major proteins in bacterial cell lysates. Western blot analyses showed that all the recombinant proteins were immunologically reactive to rabbit polyclonal antibodies and to a mouse monoclonal antibody (25B9) specific for a previously isolated rice allergen of 16 kDa. Some truncated proteins from deletion mutants of the cDNAs retained their reactivity to the specific antibodies. These results suggest that the cDNAs encode potential rice allergens and that some epitopes of the recombinant proteins are still immunoreactive when they are expressed as their fragments.

Allergens↗

Isolation and culture of bovine mammary epithelial cells and establishment of gene transfection conditions in the cells.

Bovine mammary epithelial cells (BMEC) were isolated as acinous fragments from a mammary gland of a lactating cow. They grew well on plastic substratum, showed the characteristic cobblestone morphology of epithelial cells, and secreted alpha s1-, beta-, and kappa-caseins even when grown on plastic substratum. A plasmid containing the bacterial chloramphenicol acetyl transferase (CAT) gene was transfected to the isolated BMEC by calcium phosphate precipitation and electroporation methods. The transfection efficiency of BMEC by the calcium phosphate method was greatly improved by post-transfection osmotic shock with glycerol or polyethylene glycol. An about 700 bp DNA fragment containing 5'-flanking sequence of bovine alpha s1-casein gene showed promoter activity in the transfected BMEC. The primary culture of BMEC might be useful for studies on regulation of bovine milk-protein gene expression.

Animals↗

[Endotoxin-induced lung injury. The roles of leukocytes and oxidants, and the efficacies of steroids and antioxidants].

Previous work in our laboratory has shown the relation between leukocytes (WBC) and the generation of oxidants in endotoxin (LPS) shock. The purpose of this study was to find out if WBC-derived oxidants can produce acute lung injury in guinea pigs given LPS. We alos evaluated the efficacies of steroids and antioxidants against the initial changes in LPS-induced lung injury. One group of guinea pigs (200-250 g, male) received 0.7 mg/kg (LD50, 24 hrs.) of E. coli LPS in the peritoneal cavity (group I). The animals in group II received 30 mg/kg of methylprednisolone (MP), followed by intraperitoneal LPS. The animals in group III were given 30 mg/kg of 2-aminomethyl-4-tert-butyl-6-propionylphenol hydrochloride (ONO-3144), a known as antioxidant (OH radical scavenger), and then an injection of LPS. The animals were killed at following time course: 30, 60 or 180 minutes after the LPS injection. Hematological examinations (WBC counts), total cell counts and differential counts in bronchoalveolar lavage (BAL) fluid were done along with light microscopic studies. Superoxide dismutase (SOD) activity, catalase activity and malonaldehyde (MDA) produced as a result of lipid peroxidation in the lung were measured and correlated with histological changes. Survival ratios of the three groups were compared. The results obtained were: 1) Significant leukopenia occurred in all groups. 2) In group I, WBC, especially eosinophils, were recovered by BAL and the total cell number of the BAL fluid had increased by 180 minutes after LPS injection, but MP or ONO-3144 treatment inhibited the migration of WBC (eosinophils and neutrophils) into alveolar lumen after LPS injection. 3) Histologic examinations revealed diffuse edema, hemorrhage, and marked leukocyte infiltration in the alveoli in group I, but not in group II or III. 4) SOD activity in all group diminished below the control level. Catalase activity had significantly increased by 180 minutes after LPS injection in group I, but not in group II or III. MDA had increased remarkably by 60 minutes after injection of LPS in group I, but MP or ONO-3144 treatment prevented such increases. 5) Animals in group II and III survived significantly longer than those in the other group. In conclusion, these findings suggest that LPS provokes WBC-mediated vascular damage in the lung and steroids or antioxidants can minimize the injury and prevent edema formation. Steroids might be useful for achieving quantifiable changes in LPS-induced WBC chemotaxis to the lung and for decreasing oxidant-induced lung injury.

Animals↗

Jaundice associated with Pseudomonas aeruginosa bacteremia complicating acute leukemia.

Two adult patients with acute leukemia developed marked jaundice during Pseudomonas aeruginosa bacteremia. The progressive increase in serum conjugated bilirubin levels was disproportionate to the gradual decrease in serum alkaline phosphatase and transaminase activity to or below low normal. The production of coagulation factors decreased. Autopsy revealed periportal cholestasis with minimal liver-cell damage. These findings suggested decreased metabolic activity of liver cells associated with bacteremia, probably leading to impaired bilirubin excretion. Both patients died despite appropriate antibiotic therapy. Isolated hyperbilirubinemia, thus, seemed to be an ominous prognostic sign in severe infection.

Aged↗

Adult-onset Still's disease with submassive hepatic necrosis.

We present a 74-year old woman who was hospitalized because of typical spiking fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation of serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal laboratory findings were dramatically improved after treatment with prednisolone. The clinical course of this patient indicates that AOSD with severe hepatic necrosis can successfully be treated with early administration of corticosteroid, although it remains unknown whether the disease can remain in remission with no or minimal treatment.

Aged↗

Hyperlipidemia and hemostatic system.

The plasma levels of blood coagulation and fibrinolytic factors and the serum levels of lipids were measured in 62 subjects (22 normolipidemia and 40 hyperlipidemia) to investigate whether hyperlipidemia may affect the hemostatic system. Prothrombin, factors VII, IX and X were elevated in hyperlipidemic patients. The positive correlations were found between factors VII, IX and X, and triglyceride. The significant correlations were also found between VII and IX, and total cholesterol. Plasma levels of thrombin-antithrombin III complex (TAT), which reflects activation of coagulation system, were slightly but significantly higher in type IIb hyperlipidemia, although they were within normal range. Plasma levels of active plasminogen activator inhibitor (PAI) in type IIb and IV were significantly higher than in normals. A significant correlation was found between active PAI and triglyceride (r = 0.76, p < 0.0001). After the administration of fat emulsion to 18 patients with various diseases, which induced artificial hypertriglyceridemia, PAI levels as well as triglyceride levels significantly increased. These results suggest that hypertriglyceridemia may increase the synthesis and/or release of PAI, inducing a hypofibrinolytic condition, which could lead to thrombosis. It has been established that lipoprotein (a) [Lp(a)], which has a molecular structure homology to plasminogen, impairs fibrinolysis by its competitive inhibition of adsorption of plasminogen to vascular endothelial surface and/or fibrin. We assayed plasma levels of Lp(a) and parameters of blood coagulation and fibrinolysis in 168 patients with type II diabetes mellitus and 48 normal controls. In the diabetics, the levels of Lp(a) as well as levels of tissue-type plasminogen activator (t-PA) antigen and PAI activity were significantly higher than normal controls. Furthermore, it was shown that Lp(a) had a weakly negative correlation with t-PA antigen in the diabetics. These results suggest that an elevated level of Lp(a) may decrease release of t-PA, although the underlying mechanism remains unsolved.

Adult↗

[Methotrexate and salazosulfapyridine in the long-term treatment of rheumatoid arthritis].

Long term treatment of 190 cases of rheumatoid arthritis with either methotrexate or salazosulfapyridine was analyzed for their efficacy and adverse effects. Both treatment groups showed improvement of clinical symptoms, erythrocyte sedimentation rate, and CRP after 1 month of treatment, while RAHA titers decreased significantly after several months. Erythrocyte sedimentation rate and CRP of salazo-sulfapyridine group, once improved, deteriorated again after 12 months of treatment, while methotrexate group showed sustained improvement for 48 months. Radiologic progression estimated according to JF Fries was significantly less in MTX group than in SASP group. Life table analysis showed that the overall probability of continuing methotrexate or salazosulfapyridine at 4 years was 63% and 55%, respectively. The main reason of treatment termination in methotrexate group was adverse effects, while that in salazo-sulfapyridine group was inefficacy.

Adult↗

Quality of hematologic recovery in patients with aplastic anemia following cyclosporine therapy.

To evaluate quality of hematologic recovery in aplastic anemia (AA) patients treated with cyclosporine A (CyA), we examined polymorphonuclear leukocytes (PMNCL) from 25 AA patients for clonality and glycosyl-phosphatidylinositol (GPI)-anchored membrane protein expression. Using three different X-linked gene probes, we failed to detect clonal hematopoiesis in seven CyA-responsive female patients. Clonal hematopoiesis was detected in two of six female patients refractory to CyA therapy, although one of these two patients had shown monoclonality before therapy. Flow-cytometric analysis revealed a normal expression of GPI-linked membrane proteins, including CD55, CD59, and CD16 on PMN in all patients treated with CyA, irrespective of response, except for one patient who had a small proportion of GPI-anchored membrane protein-negative cells before therapy. The proportion remained unchanged 41 months after hematologic recovery following CyA therapy. These findings suggest that successful therapy of AA with CyA may not be associated with a significant risk of developing late clonal complications, such as paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplasia.

Adolescent↗

[Clinical efficacy of the Porges Urospiral, a reversible intraprostatic spiral stent, in patients with benign prostatic hypertrophy].

The Porges Urospiral, a urethral spiral stent made of stainless steel wire, is designed for patients with benign prostatic hypertrophy. To evaluate the safety and efficacy of the stent, a prospective uncontrolled study was performed on 60 patients who complained of urinary retention (48 patients) or severe dysuria (12 patients) due to prostatic hypertrophy. Four patients had neurogenic disorders resulting in bladder dysfunction. The average age of the patients was 77.4 years old, ranging from 61 to 91 years old. In 48 patients, the stent was used instead of transurethral resection of the prostate (TUR-P) because of the patients poor general conditions, while in 12 patients the stent was transiently used until TUR-P. Subjective symptoms, according to an original scoring system, and objective signs, uroflowmetry measurements and residual urine volume, before and 3 months after stent insertion were compared. The stent was indwelt for more than 3 months in 40 of the 57 patients in whom the stent could be inserted. Out of 37 evaluable patients, subjective symptoms improved in all the patients and objective symptoms improved in 26 patients (70.3%). Complications included urinary incontinence, urination pain, urethral pain, gross hematuria or migration of the stent. Although these complications disappeared in a few days after the insertion of the stent in a majority of the patients, the stent was removed in 17 patients due to complications within 3 months after insertion. The overall clinical efficacy of this stent was 56% in 50 evaluable patients who had no neurogenic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Inhibitory effect of terfenadine, a selective H1 histamine antagonist, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

We wanted to evaluate the effect of terfenadine, a selective H1-receptor antagonist, on alcoholic beverage-induced bronchoconstriction. Eight patients with alcohol-induced asthma received terfenadine (60 mg, twice on the test day) or placebo, with the last dosing 2 h before the test in a double-blind, randomized, cross-over manner. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese saké), and bronchoconstriction was assessed as change in peak expiratory flow (PEF) over 120 min postchallenge. Inhalation challenges were performed with the same alcoholic beverage with which they had been orally challenged. The mean (SEM) percentage fall in PEF 15, 30, 45, 60, 90 and 120 min after the oral alcohol challenge was significantly reduced from 12.0 (3.1), 17.0 (1.7), 15.8 (2.3), 15.2 (3.4), 16.6 (4.8) and 14.7 (5.2)%, to 2.6 (1.8), 2.1 (1.6), 3.9 (1.2), 5.7 (2.2), 6.5 (2.6), 5.1 (1.6)%, respectively, by terfenadine. No significant bronchoconstriction was observed after the inhalation challenge. We conclude that the release of histamine makes a major contribution to alcoholic beverage-induced bronchoconstriction in Japanese asthmatic patients, and that histamine H1 antagonists may be effective in preventing alcoholic beverage-induced bronchoconstriction.

Adult↗

[Successful treatment of recurrent chronic myelogenous leukemia in allogeneic marrow transplant recipient with the donor leukocyte transfusion, without induction of acute graft-versus-host disease].

A 45-year-old female developed cytogenetic relapse of chronic myelogenous leukemia 4 years after allogeneic bone marrow transplantation. To induce a graft-versus-leukemia effect, peripheral blood buffy-coat cells were collected from the original marrow donor during 5 rounds of leukapheresis over 3 weeks, and 2.47 x 10(8) cells/kg were infused into the patient. Acute graft-versus-host disease (GVHD) did not develop even after an interval of 50 days from the last donor leukocyte transfusion (DLT). However, karyotypic analysis of bone marrow cells performed on the same day showed an apparent decrease in the proportion of Ph1 chromosome-positive cells (1/20) among all dividing cells, compared with the proportion (13/20) observed before DLT. At the same time, the proportion of red blood cells (RBCs) of donor origin among the peripheral RBCs of the patient, which was less than 10% before DLT, began to rise and reached 100% at 4 months after DLT. The karyotype of bone marrow cells obtained on day 90 after DLT was completely normal. Although chronic GVHD of the buccal mucosa and liver developed in association with pancytopenia on day 71 after DLT, this improved rapidly with oral administration of cyclosporine. The clinical course of this patient suggests that acute GVHD is not a prerequisite for elimination of Ph1-positive cells by DLT.

Acute Disease↗

[Secondary myeloid/natural killer cell acute leukemia appeared in multiple myeloma treated with melphalan].

A 67-year-old woman was treated with MP-P therapy and combination chemotherapy for multiple myeloma IgG-lambda type. After the therapy for about three years, pancytopenia developed. Bone marrow aspiration study revealed a few of myeloma cell and many atypical cells showing promyelocytic feature. Chromosomal abnormality was 46, X, -X, +8, -13, +mar. CD33 and CD56 were positive, but CD16 and HLA-DR were negative. We diagnosed as multiple myeloma complicated with secondary myeloid/natural killer (NK) cell acute leukemia. After she had been treated with low dose etoposide for leukemia, she obtained complete remission. But since myeloma progressed and the amount of M protein was increased, she was treated with dexamethasone and low dose etoposide, resulting in a decrease in the amount of M protein. After that, because of leukemic cell re-proliferation, she was treated with etoposide. However, she died of sepsis due to severe myelosuppression. This case was interesting one in coexist of multiple myeloma and secondary myeloid/NK cell acute leukemia, and those affecting her clinical course each other.

Aged↗

[A case of Legionella pneumonia successfully treated with roxithromycin].

A 56-year-old man was admitted to our hospital because of a high fever. An abnormal shadow was seen on his chest X-ray film. He was treated with piperacillin, isepamycin, and minocycline, but his fever remained and the abnormal shadow got worse. Because he had proteinuria, a severe headache, hyponatremia, and hypophosphatemia, Legionella pneumonia was suspected. A skin test for erythromycin was positive, so roxithromycin was given orally. By the next day the fever had remitted, the appearance of the chest X-ray film had improved, and his symptoms were promptly relieved. This case suggests that roxithromycin can be effective against Legionella pneumonia.

Administration, Oral↗