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Biomedical subjects

M Matsubara

Publications and source records attributed to M Matsubara.

At least 19 recordsLinked to original sources

Seroepidemiological survey for antibody to Borrelia burgdorferi in cows.

Antibody to Borrelia burgdorferi was examined in 380 healthy and 38 clinical cases of cows from Hokkaido and Shizuoka in Japan. In healthy animals, IgG and IgM antibody to B. burgdorferi HO14 strain were found in 44 cows (14.6%) and 24 cows (8.0%) from Hokkaido. In contrast, antibody-positive case was not observed except for only 1 case which was IgM positive (1/79: 1.3%) in cows from Shizuoka. Mean antibody levels of healthy animals in Hokkaido and Shizuoka were 0.651 and 0.263 (IgG antibody to HO14 strain), 0.642 and 0.169 (IgG to HP3 strain), 0.613 and 0.367 (IgM to HO14 strain) and 0.582 and 0.286 (IgM to HP3 strain). The differences of the antibody levels between cows from Hokkaido and Shizuoka were significant. Seasonal difference was found in seropositive cows from Hokkaido. The rate of seropositive cows was high in summer (23.4% in June and 11.8% in July) but low in winter (0% in January and February). The pattern was discussed to be associated with activation of ticks. One of 4 cows with arthritis showed significantly higher IgG antibody level than that of healthy cows and cows with some disease, although the serum was collected from Shizuoka where antibody-positive animals for B. burgdorferi were rare among healthy cows. This high IgG antibody may suggest that the arthritis of such cows was caused by infection with B. burgdorferi. Two of 7 cows with unclassified abortion showed positive antibody reaction in Hokkaido. These cases, however, may not be related to the B. burgdorferi infection because the positive rate was similar to those of healthy cows in the same season.

Animals

Collagenolytic/gelatinolytic enzymes in corneal wound healing.

We have documented changes in expression of collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in healing or ulcerating corneal wounds of rat or rabbit. Correlation of our findings with specific changes in the extracellular matrix of the repair tissue suggests two different roles for the enzymes, MMP-2 and MMP-9. MMP-2 is expressed in undamaged corneal stroma where it may degrade the occasional collagen molecule that becomes damaged. After corneal wounding, expression of this enzyme is increased and much of it appears in the active form. These changes persist for at least seven months, suggesting that MMP-2 is involved in the prolonged process of collagen remodelling in the stromal repair tissue. MMP-9 is expressed in the epithelial layer of repair tissue with a timing suggesting it might participate in controlling resynthesis of the basement membrane. MMP-9 also appears to be involved in degradation of the epithelial basement membrane that precedes corneal ulceration.

Animals

[The influence of paraquat on cell cycle--analysis of cell kinetics using DNA/BrdU staining].

We examined the in vitro and in vivo effects of paraquat on the cell cycle. After we exposed paraquat to the cultured cell (MDCK), we examined cell kinetics by flow cytometry with BrdU-PI double staining. And we administered paraquat intravenously to the rats, we collected and separated rat's liver and pulmonary cells, and we examined the cell kinetics by same method. Consequently our study found that the cells in the S-phase were noted to be abundant, and we suggested that paraquat apparently arrested the cell cycle at S time, and that DNA damage was importance in the mechanism of paraquat toxicity.

Animals

[Evaluation of cardiac functions in patients with progressive systemic sclerosis (PSS)].

Cardiac functions in 20 female patients with PSS were measured by ultrasound cardiography and compared with those of 10 healthy age-matched controls. The following results were obtained: 1) The patients with PSS showed the increases in left ventricular mass (LVmass), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW) more than those of controls. 2) Diastolic descent rate (DDR) of patients decreased significantly in comparison with the healthy controls. 3) Right ventricular dimension (RVD) of patients were demonstrated to dilate more than those of controls. Conclusively ultrasound cardiography (UCG) is an available method for detecting the cardiac lesion of PSS. Abnormal signs were recognized even though their clinical features were limited to the extremities.

Adult

Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics.

The present study was conducted on 8 patients with advanced diabetic nephropathy who showed a significant reduction of proteinuria through ACE inhibition. Camostat mesilate, one of the most potent protease inhibitors developed for oral use, was administered to these patients at a daily dose of 600 mg starting after 4 weeks of ACE inhibitor administration. Laboratory data were obtained 1) just before the ACE inhibition, 2) after 4 weeks of the ACE inhibitor single treatment, and 3) after another 4 weeks of the additional treatment with camostat mesilate. The urinary protein excretion decreased from 1) 10.1 +/- 1.3 to 2) 7.3 +/- 1.1, and 3) 4.6 +/- 0.9 g/day [mean +/- SEM; significance of difference 1)-2), p less than 0.05; 2)-3), p less than 0.01], and the serum total protein values increased from 1) 5.0 +/- 0.3 to 2) 5.2 +/- 0.2, and 3) 5.4 +/- 0.3 g/dl [1)-3), p less than 0.05]. The plasma levels of fibrinogen, and of E fragment and D-dimer of FDP changed from 1) 476 +/- 43 to 2) 477 +/- 41, and 3) 374 +/- 33 mg/dl [2)-3), p less than 0.01], from 1) 125 +/- 19 to 2) 147 +/- 27, and 3) 104 +/- 30 ng/ml [2)-3), p less than 0.05], and from 1) 261 +/- 60 to 2) 272 +/- 86, and 3) 185 +/- 56 ng/ml [2)-3), p less than 0.05], respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The role of xanthine oxidase in paraquat intoxication.

The role of xanthine oxidase in the mechanism of paraquat toxicity was assessed by in vitro and in vivo experiments. Paraquat stimulated the reduction of cytochrome c by xanthine-xanthine oxidase system in vitro. Paraquat, when added in vitro, stimulated hypoxanthine-dependent superoxide production in the cytosol of rat lung. Tungsten-feeding inhibits xanthine oxidase activity in a variety of tissues in experimental animals. Its therapeutic effect on paraquat intoxication was studied in this paper. In rats fed a tungsten-enriched diet for 5 weeks prior to intraperitoneal injection of 50 mg/kg paraquat dichloride, the mortality decreased significantly compared with rats fed a standard diet. Pretreatment with oxypurinol (1000 mg/kg, s.c.) also ameliorated the paraquat toxicity in rats. We conclude that xanthine oxidase plays an important role in paraquat toxicity and that xanthine oxidase inhibitors may become antidotes for paraquat intoxication.

Animals

Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling cornea.

We have documented changes in collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in remodelling rabbit cornea. MMP-2 (65 kDa gelatinase) in the proenzyme form is synthesized by the cells of the normal corneal stroma. After keratectomy the level of MMP-2 is increased in the stroma and enzyme appears in both pro- and activated forms. In addition, corneal cells synthesize MMP-9 (92 kDa gelatinase) in the proenzyme form after keratectomy; expression occurs in both the epithelial as well as stromal corneal layers. Changes in expression of both enzymes are precisely localized to the repairing portion of cornea, but demonstrate important differences in timing that correlate with the timing of specific events of matrix remodelling. Our data suggest that each of the gelatinases plays a different role in tissue remodelling after injury. We hypothesize that MMP-2 performs a surveillance function in normal cornea, catalyzing degradation of collagen molecules that occasionally become damaged. After wounding, this enzyme appears to participate in the prolonged process of collagen remodelling in the corneal stroma that eventually results in functional regeneration of the tissue. MMP-9 expression does not correlate with stromal remodelling, but we suggest that the enzyme might play a part in controlling resynthesis of the epithelial basement membrane.

Animals

A case report of EMO syndrome showing localized hyperhidrosis in pretibial myxedema.

We describe here a case of EMO syndrome, which is defined as a combination of exophthalmos, pretibial or localized myxedema, and hypertrophic osteoarthropathy. A 34-year-old Japanese man with Graves' disease developed the characteristic eye changes. He showed 22 mm protrusion of both eyes and hypertrophy of the right lateral rectus muscle as well as both superior rectus muscles by computerized tomography. He subsequently developed lightly erythematous, indurated, nonpitting, peau d'orange plaques and nodules on his lower legs. Finally, he developed Graves' acropathy with hypertrophic osteoarthropathy in the metacarpal bones. Histological examination of myxedematous skin showed typical deposition of mucin accompanied by changes in the amount and distribution of elastic fibers. In addition, the lesional skin showed localized hyperhidrosis, a rarely reported complication of pretibial myxedema. We speculate that this hyperhidrosis of the lesional skin was brought about by stimulation of peripheral sympathetic nerves by surrounding mucin deposition, in the setting of poorly controlled hyperthyroidism.

Adult

Passive smoking by pregnant women and fetal growth.

STUDY OBJECTIVE: The aim was to investigate the effect of passive smoke exposure during pregnancy on fetal growth in the Japanese population. DESIGN: The study comprised a community based interview and clinical survey of pregnant women in Aichi Prefecture, Japan. SETTING: Participants attended for delivery at 146 private and public practices and hospital clinics in the Prefecture. SUBJECTS: Participants were 6831 women who delivered a live singleton without malformation during the three consecutive months from June 1987, and comprised about 34% of total deliveries in the Prefecture during the period. MEASUREMENTS AND MAIN RESULTS: 35% of the women had been exposed passively to cigarette smoke for 2 h or more per day at home, in the work place, or in other places during pregnancy. At this level of passive exposure among non-smoking women with term deliveries (greater than or equal to 37 weeks), a small effect on fetal growth was observed; mean birth weight was reduced by 10.8 g, and the relative risk of growth retardation (less than 2500 g birth weight) was 1.0 (95% CI: 0.7-1.5), after adjusting age, parity, height, alcohol drinking, occupation, and gestation. CONCLUSIONS: The results suggest that the reduction of fetal growth associated with passive smoke exposure during pregnancy may be small in Japanese population.

Adolescent

Changes in gastric mucosal content of adenosine, xanthine and hypoxanthine induced by restrained water immersion stress: antiulcer effects of tetraprenylacetone.

The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5'-triphosphate (ATP), adenine-5'-diphosphate (ADP), adenine-5'-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP + AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides

Transforming growth factor-beta and interleukin-1 modulate metalloproteinase expression by corneal stromal cells.

The enzyme collagenase participates in remodeling the extracellular matrix of corneal stroma during normal wound healing and mediates the degradation of extracellular matrix that occurs in many corneal pathologic states. Because this enzyme is synthesized and secreted by corneal cells, therapy of degradative disorders might be geared toward control of enzyme expression. The effects of two cytokines, transforming growth factor-beta (TGF-beta) and interleukin-1 (IL-1), on the expression of collagenase by cultured corneal stromal cells are reported. In addition, the concomitant effects of these cytokines on expression of three additional members of the matrix metalloproteinase (MMP) family--stromelysin, 72-kilodalton (kD) gelatinase, and 92-kD gelatinase--were investigated. When stromal cells are situated in the normal corneal stroma, they produce only a single MMP, 72-kD gelatinase. This pattern of expression was reproduced by stromal cells freshly plated in primary culture. However after passage in culture, the cells also began to secrete collagenase and stromelysin. Treatment of primary cultures with recombinant human IL-1 also induced collagenase and stromelysin expression. In addition, 92-kD gelatinase expression was induced and 72-kD gelatinase expression was increased further by IL-1 treatment. Treatment of passaged cultures or IL-1-treated primary cultures with recombinant human TGF-beta reverted the pattern of enzyme expression toward that exhibited by primary, untreated cultures, ie, expression of collagenase and stromelysin was repressed while expression of 72-kD gelatinase was increased. These results suggest that TGF-beta and IL-1 may be important agents for controlling MMP expression in healthy and diseased corneas.

Animals

Mechanism of basement membrane dissolution preceding corneal ulceration.

In animal models for corneal ulceration, the degradation of extracellular matrix components of the stroma does not occur until after the basement membrane underlying the corneal epithelium has disappeared. Using a thermal-burn model, it was demonstrated that epithelial basement membrane is degraded actively by products of corneal cells in a process that does not require the participation of polymorphonuclear leukocytes. A new gelatinolytic metalloproteinase, preliminarily identified as the matrix metalloproteinase, MMP-9, is synthesized and secreted by corneal cells with a timing appropriate for a role in basement membrane degradation. During healing of ulcers, when new matrix is being deposited actively in the burned tissue, a second new gelatinase appears in the cornea, preliminarily identified as a stable activated form of the matrix metalloproteinase, MMP-2. The timing of expression suggests a role for this enzyme in appropriate deposition and remodeling of new matrix in the regenerating corneal tissue.

Animals

[A case of renal failure due to primary cholesterol atheroembolism].

We report a patient presenting rapid deterioration of renal function due to primary cholesterol atheroembolism. The patient was 75-year-old hypertensive male and was admitted to a hospital because of rt. hemiplegia which developed 2 weeks earlier. On admission, his blood pressure was 200/100 mmHg and serum creatinine level was 2.9 mg/dl with urinalysis 1+ both for protein and hematuria. 2 weeks later, an angiotensin converting enzyme inhibitor (ACE inhibitor, delapril 15 mg/day) was given to control high blood pressure. Immediately after this medication, his renal failure rapidly progressed with a fall in blood pressure (110/60 mmHg) and oliguria (100 ml/day). Although he was transferred to our hospital and was treated with hemodialysis, he died of an attack of acute myocardial infarction in a week. At post-mortem examination, microscopic findings of the kidney disclosed numerous occlusions of medium-sized artery by cholesterol emboli. These emboli were also observed in other organs, but not so prominent as in the kidney. The coronary arteries exhibited severe sclerosis. In this presented case, acute deterioration of renal function was caused by ACE-inhibitor, although which was administered in a volume depleted condition. Therefore, further study would be necessary whether or not ACE-inhibitors predispose the patients with this disease to acute renal failure.

Acute Kidney Injury

[A case of cerebral infarction with circulating anticoagulant to Fletcher factor].

A 44-year-old woman with a history of cerebral infarction and hypertension developed sudden onset of speech and visual disturbance. On admission, her general physical examinations showed high blood pressure of 210/120 mmHg and Raynaud's phenomena. The neurological examinations revealed right upper quadratic hemianopsia, left oculomotor nerve paresis and left hyperreflexia. Laboratory findings showed that antinuclear and anti-DNA antibodies were positive. The activity of Fletcher factor was reduced to 50%, and the activated partial thromboplastin time (APTT) was prolonged to 82.6 seconds. And a 1:1 dilution with normal plasma failed to correct the prolonged APTT, indicative of circulating anticoagulant to Fletcher factor. Plasma fibrinogen increased to 500 mg/dl but FDP was normal. The CT scan demonstrated the recurrently developed cerebral infarction in the left occipital lobe. Cerebral angiogram revealed mild atherosclerosis of basilar and bilateral posterior cerebral arteries, but any occlusive lesions were not found. Although she had a history of hypertension, this case suggests the possibility that the disturbance in fibrinolytic system may have been caused by the circulating anticoagulant to Fletcher factor, and contributed to her cerebral infarctions.

Adult

[Changes in cardiopulmonary functional reserve after thoracic surgery assessed by treadmill exercise test].

The authors evaluated the effect of thoracic surgery on cardiopulmonary functional reserve using a three-minute incremental test on treadmill before and after operation in 148 patients undergoing thoracic surgery. Patients were divided into two groups according to the presence or absence of respiratory symptoms during the exercise test. In all patients, the number of cases with hypoxemia induced by exercise test increased postoperatively including all cases with pneumonectomy. The number of patients who halted the test because of respiratory symptoms (Group A) increased after operation (45 cases before (30.4%), 82 cases after (55.4%)). Most of them showed at least 10 Torr lower PaO2 levels than their basal levels during exercise. Before operation, patients in Group A (n = 45) showed significantly lower FEV1.0% than those who halted the test because of other symptoms (Group B, n = 103) (68.0 +/- 12.5% vs 76.0 +/- 9.7%, mean +/- S.E. p less than 0.05, Student's t-test). After operation, patients in Group A (n = 82) showed a significantly lower %DLco than those in Group B (n = 66) (71.4 +/- 14.3% vs 88.6 +/- 16.8%, p less than 0.05). Preoperative %DLco did not differ between the two groups. Consequently, postoperative decrease in %DLco was characteristic for patients with respiratory symptoms, suggesting that hypoxemia during exercise induced by reduction in diffusion capacity may be responsible for their respiratory symptoms. The anaerobic threshold (AT), and index of aerobic capacity, and symptomlimited maximal oxygen consumption (VO2 max (s.l)), VO2 at the end of exercise, fell to 78.4% and 79.1% of preoperative levels respectively one month after operation. Both indices recovered to 85% of preoperative levels at six months after operation. AT and VO2 max (s.l) values were expressed as a percent of predicted maximal VO2 values for age, body weight and sex (%AT, %VO2 (s.l)). The %VO2 max (s.l) was significantly lower in patients with pneumonectomy (n = 8) as compared with that in patients with lobectomy (n = 55) (51.1 +/- 6.4% vs 60.6 +/- 11.4%, p less than 0.05). Patients with thoracotomy (n = 35) only showed significantly higher %VO2 max (s.l) values (70.5 +/- 12.1%) than those of patients with lobectomy (p less than 0.05). The %AT did not show significant differences among different operative procedure groups. Despite a good preoperative correlation (r = 0.725) between %VO2 max (s.l) and %AT in all patients, there was no correlation between the indices postoperatively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult