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J Kobayashi

Publications and source records attributed to J Kobayashi.

At least 307 records · Page 17Linked to original sources
PubMed1994

Serum-induced vascular smooth muscle cell elastolytic activity through tyrosine kinase intracellular signalling.

In previous studies, we related increased elastolytic activity in pulmonary arteries (PA) with endothelial injury to the later development of PA hypertension in rats. As the mechanism causing the increased PA elastase was unknown, we hypothesized that serum factors which are accessible to vascular smooth muscle cells (SMC) following endothelial injury stimulate their elastolytic activity. To test this, we developed an in vitro assay in which we added [3H]-elastin to cultured vascular SMC after 24 h serum starvation and monitored elastolysis following a further 24 h incubation with fetal bovine serum (FBS). We observed that serum induced increased elastolytic activity in both PA and aorta-derived SMC but not in endothelial cells or SMC with low basal levels of elastolytic activity. Maximum stimulation of SMC elastolytic activity occurred with a concentration as low as 1% FBS and despite elastase inhibitors in serum, suggesting that the activity is confined to the immediate pericellular region where enzyme concentration is high. Serum-stimulated elastolytic activity was not reproduced by growth factors or cytokines known to be associated with vascular disease or to induce release of elastases in other cells. The serum inducing elastolytic activity was heat and acid labile. It was associated with increased elastin adhesion to the 67 kD elastin binding protein on SMC surfaces and was prevented by tyrosine kinase inhibitors but not protein kinase C or A inhibitors. Our studies therefore suggest a mechanism whereby serum induction of SMC elastase requires signalling through the elastin binding protein and activation of tyrosine kinase.

Animals↗
PubMed1994

Application of enzyme immunoassay for postchemotherapy evaluation of human strongyloidiasis.

Posttherapy evaluation of strongyloidiasis is frequently difficult because coprologic examination is not sensitive enough for diagnosis of chronic infection. In the present study, anti-Strongyloides enzyme-linked immunosorbent assay antibodies were monitored before and after treatment with thiabendazole and pyrvinium pamoate in 199 patients with chronic strongyloidiasis in Okinawa, Japan. A significant decrease in antibody levels was observed in patients who became negative for fecal larvae after the treatment, whereas the antibody levels did not show a significant change after the treatment in patients who were still harboring the parasite. In the group coprologically negative in the follow-up examination, however, many individuals did not show a significant fall in antibody titers after treatment, which suggests that these cases were equivocal for complete cure. By the subsequent fecal reexamination performed on the equivocal cases, approximately 20% were additionally found to be still harboring the parasite. These results indicate that serologic testing is useful to check whether a real cure has been achieved among the patients in whose fecal samples the presence of larvae has not been demonstrated after treatment.

Adult↗
PubMed1994

Diabetic control and progression of retinopathy in elderly patients: five-year follow-up study.

OBJECTIVE: To assess whether control of diabetes mellitus is as important in the elderly as in young and middle-aged diabetic patients in terms of progression of retinopathy. DESIGN: A 5-year longitudinal cohort study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred fourteen non-insulin-dependent diabetic patients (30 males, 84 females) > or = 60 years of age. MEASUREMENTS: Retinopathy was checked at the beginning and end of the follow-up period. During the 5-year follow-up period, demographic variables, body mass index, HbA1c, blood pressure, and plasma lipids were monitored. Retinopathy was classified as follows: grade 0, no lesion; grade 1, non-proliferative retinopathy; grade 2, pre-proliferative retinopathy; grade 3, proliferative retinopathy. Progression of retinopathy during the 5-year follow-up was defined as an increase in its grade. RESULTS: At the start of the study, 13% of the patients already had retinopathy, all of grade 1. The 5-year follow-up study showed that progression of retinopathy was 23.6% in all cases, 22.2% in those with grade 0 initially, and 33.3% in those with grade 1 initially. The progression rates of retinopathy as a function of the mean HbA1c during the follow-up were as follows: lower than 7%, 2%; 7-8%, 20%; 8-9%, 40%; more than 9%, 61%. Multiple logistic regression analysis showed that, of the parameters examined, only HbA1c was a significant risk factor for progression of retinopathy. CONCLUSIONS: Control of diabetes mellitus is the most important factor associated with prevention of progression of retinopathy in elderly patients.

Aged↗
PubMed1994

Lipoprotein(a) is a risk factor for diabetic retinopathy in the elderly.

OBJECTIVE: To assess whether serum lipoprotein(a) is a risk factor for diabetic retinopathy in the elderly. DESIGN: A cross-sectional study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred four noninsulin-dependent diabetic patients (35 males, 69 females). Twenty-three were less than 60 years of age (middle-aged), and 81 were 60 years or older (elderly). MEASUREMENT: Levels of lipoprotein(a) (Lp(a)) and lipids were measured in fasting serum. HbA1c was also measured as an indicator of diabetic control. Other indicators possibly related to retinopathy were also checked. Retinopathy was estimated by photographs of fundi. RESULTS: Significantly higher indicators in the group with retinopathy than in the group without were: HbA1c, Lp(a), duration of diabetes, and systolic blood pressure (BP) in the total cases; HbA1c, duration of diabetes, and Lp(a) in the middle-aged; HbA1c, systolic BP, and Lp(a) in the elderly. Multiple logistic regression analysis showed that only HbA1c and Lp(a) were independent risk factors for retinopathy in all cases and in the elderly. The incidence of retinopathy was positively correlated to serum Lp(a) levels. CONCLUSION: Lp(a) is an independent risk factor for diabetic retinopathy.

Aged↗
PubMed1994

Properties of the binding sites of [3H]9-methyl-7-bromoeudistomin D in bovine aortic smooth muscle microsomes.

[3H]9-Methyl-7-bromoeudistomin D ([3H]MBED), a powerful caffeine-like Ca2+ releaser, binds to the caffeine binding site of terminal cisternae of skeletal muscle sarcoplasmic reticulum and activates Ca(2+)-induced Ca2+ release. Properties of the binding site of [3H]MBED were investigated in aortic smooth muscle. The specific activity was higher in microsomes than in other fractions. [3H]MBED binding sites in smooth muscle microsomes were of a single class with a high affinity (KD 50nM), comparable with that in skeletal muscle sarcoplasmic reticulum. Caffeine competitively inhibited [3H]MBED binding, indicating MBED shares the same binding site with caffeine. Solubilization and fractionation of the microsomes gave two fractions of [3H]MBED binding activities. These results suggest that, in smooth muscle, there are multiple binding sites of [3H]MBED and caffeine, which might correspond to different pharmacological actions of caffeine on smooth muscle. Therefore, [3H]MBED, which binds to the different binding sites of caffeine, is useful as a probe for investigation of the actions of caffeine at the molecular level.

Animals↗
PubMed1994

The endogenous vascular elastase that governs development and progression of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme related to the serine proteinase adipsin.

We showed previously a cause and effect relationship between increased activity of an endogenous vascular elastase (EVE) and experimentally induced pulmonary hypertension in rats. We now report the isolation and characterization of EVE. Degenerate oligonucleotides synthesized to homologous sequences in serine elastases were used in a PCR with rat pulmonary artery (PA) cDNA. The PCR product hybridized to a 1.2-kb mRNA and the intensity of hybridization was threefold increased in RNA from rat hypertensive PA at a timepoint when EVE activity was increased. The PCR product was used to screen a cDNA library and sequences obtained encoded rat adipsin. We then used immunoaffinity to purify EVE. An antibody to the elastin-binding protein was used to remove this competitor of elastase from the PA extract and the elastolytic activity increased 100-fold. The enzyme was purified using an antibody that recognizes NH2-terminal sequences of serine proteinases and the eluate was further purified using an antibody raised against recombinant adipsin. A single band at 20 kD immunoreactive with the adipsin antibody was resolved as an active enzyme on an elastin substrate gel. Immunogold labeling with an antibody to an adipsin peptide sequence localized EVE to PA smooth muscle cells. This is the first isolation of EVE; it appears to be a novel enzyme related to the serine proteinase adipsin originally found in adipose tissue.

Amino Acid Sequence↗
PubMed1994

[52-week oral toxicity study of lactitol (NS-4) in rats followed by 9-week recovery test].

Twenty five male and 25 female Slc:SD rats were given orally lactitol, a hepatic encephalopathy drug, for 52 weeks at doses of 0, 0.4, 2 or 10 g/kg/day. A 9 week recovery test was conducted after the discontinuation of the drug treatment. Treatment related death, soft stool, diarrhea, decreased body weight gain and food intake and increased water consumption were observed in the 10 g/kg group. Urinalysis showed increased Ca excretion in the 2 and 10 g/kg groups. In the 10 g/kg group, there were increased Ca++ excretion and urine specific gravity and decreased K+ and Na+ excretion and urine volume. Hematologic examination showed decreased platelet count in the 10 g/kg group. Biochemical examination revealed higher A/G ratio in the 2 and 10 g/kg groups. In the 10 g/kg group, there were lowered level of total cholesterol, triglyceride, phospholipid, Na+, Cl- and total protein. Distention of the cecum with increased organ weight was seen pathologically in the 2 and 10 g/kg groups. In the 10 g/kg group, cecal mucosa was hyperplasic. The adrenal gland was hypertrophic in the zona glomerulosa in the 2 and 10 g/kg groups. In the 10 g/kg group, the adrenal weight was increased. Dilatation of renal tubules was also found in the 10 g/kg group. The above mentioned changes were satisfactorily reversible except for the increased cecum weight in the 10 g/kg group. Based on the results obtained, the NOAEL of this study was suggested to be 0.4 g/kg/day.

Administration, Oral↗
PubMed1994

[Hepatic triglyceride lipase].

Human hepatic triglyceride lipase (HTGL) is a 476 residue glycoprotein that hydrolyzes triglyceride rich lipoproteins and high density lipoproteins. Comparison of the HTGL, LPL and PL gene structures established them as members of a lipase gene family. Familial HTGL deficiency is a rare disorder that is characterized by premature atherosclerosis and abnormal circulating lipoproteins. In HTGL transgenic mice, plasma HDL cholesterol and total cholesterol levels were found to be low and were correlated with decrease in the accumulation of aortic cholesterol. These results suggest that HTGL may have a protective effect against formation of atherosclerosis.

Animals↗
PubMed1994

[A case of recurrent breast cancer responding to combination therapy with mitoxantrone (MIT), 5'-deoxy-5-fluorouridine (5'-DFUR) and medroxyprogesterone acetate (MPA)].

The patient was a 50-year-old woman who had undergone left standard radical mastectomy who had undergone left standard radical mastectomy on June 1, 1986. She showed multiple liver metastases with elevation of CEA level in July, 1991, and 5'-DFUR plus MPA combination therapy was started. The daily dosages were: 800 mg/body and 1,200 mg/body, respectively. After intra-arterial infusion of pirarubicin and Lipiodol, bilateral oophorectomy was performed and an implantable reservoir for intra-arterial infusion chemotherapy was implanted via the proper hepatic artery. Then she was treated by arterial-infusion of mitoxantrone 10mg/body intermittently every two weeks. The metastatic foci responded to this therapy and her CEA level decreased.

Adenocarcinoma↗
PubMed1994

Production by a baculovirus expression system of the APO-protein of L-gulono-gamma-lactone oxidase, a flavoenzyme possessing a covalently-bound FAD.

L-Gulono-gamma-lactone oxidase, an enzyme functioning in L-ascorbic acid biosynthesis in higher animals, possesses a covalently-bound FAD as the prosthetic group. Catalytically-active enzyme was expressed in silkworm cells by a recombinant baculovirus encoding rat L-gulono-gamma-lactone oxidase. When recombinant enzyme was expressed under riboflavin-deficient conditions, most of it was found to be the apoprotein, as evidenced by an increase in enzymic activity upon addition of FAD to the assay mixture. Interestingly, the observed enzymic activity is thought to have been provoked by a noncovalent interaction between FAD and the apoprotein, since the covalent attachment of FAD was not demonstrated by a fluorometric gel-scanning experiment.

Animals↗
PubMed1994

[Reoperation and balloon dilatation for stenosed xenograft valved conduits].

Follow-up has been achieved in 41 hospital survivals who received xenograft valved conduits in the pulmonary position. The interval after operation ranged 6 months to 13 years (average 5.2 +/- 3.7 years) (+/- standard deviation). There has been 8 late deaths, 3 of which were sudden. Of the 11 reoperations, 7 underwent graft replacement with no operative death. The actuarial reoperation free survival rate was 73% at 5 years, and 54% at 10 years. There was a significant correlation between the interval after operation (x years) and the pressure gradient across the conduits (y mmHg). (y = 20.7 + 9.7x, r = 0.74, p < 0.001). Balloon dilatation of the conduits was performed in 15 patients. The mean conduit gradient was significantly (p < 0.001) reduced from 85 +/- 29 to 54 +/- 22 mmHg. However, the effect was not satisfactory enough and 4 patients received graft replacement after the balloon dilatation. These results warrant the avoidance of xenograft valved conduits in the pulmonary position, the safety of the graft replacement, and the limitation of the balloon dilatation for the stenosed conduits.

Adolescent↗
PubMed1994

Effects of treatment with bezafibrate on lipoprotein lipase activity and mass in patients with hypertriglyceridemia.

The activity and mass of lipoprotein lipase (LPL) in postheparin plasma (PHP) from patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance, hyperinsulinemia were investigated in order to clarify the cause of hypertriglyceridemia and the effects of bezafibrate (CAS 41859-67-0), a novel lipid lowering agent. Eight weeks of treatment with bezafibrate (200 mg/d) lowered plasma total cholesterol and triglyceride by 7 and 39%, respectively, and increased plasma high density lipoprotein (HDL) cholesterol by 23% in the patients (n = 15). The LPL activity and mass of PHP in the patients were found to be lower than in the normal controls. The LPL activity and mass of PHP in the patients before treatment with bezafibrate (n = 15) were 2.05 +/- 1.06 mumol/ml/h and 147 +/- 45 ng/ml, respectively, whereas after treatment with 200 mg/d of bezafibrate for 8 weeks, these values were 3.62 +/- 1.30 mumol/ml/h (p < 0.01) and 226 +/- 57 ng/ml (p < 0.05), respectively. The increases of LPL mass were positively correlated with the decrease of triglyceride levels during the same period. These results suggest that the expression of LPL enzyme protein is impaired in patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance and hyperinsulinemia, and the impaired expression of LPL recovers during treatment with bezafibrate, resulting in improvement of hypertriglyceridemia.

Adult↗
PubMed1994

[Bronchiolitis].

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Bronchiolitis↗
PubMed1993

C fiber generates a slow Na+ spike in the frog sciatic nerve.

The present study was carried out to examine the properties of A and C fibers in the bullfrog sciatic nerves by applying several agents through perfusing solutions between stimulating and recording electrodes. The compound action potentials (CAPs) of A beta and A delta fibers were tetrodotoxin (TTX)-sensitive and were abolished in Na(+)-free solution. However, C fiber CAP was TTX-insensitive although CAP disappeared in Na(+)-free solution. Moreover, C fiber CAP was not blocked by Ca2+ channel blockers and its chronaxy (2 ms) and conduction velocity (0.70 m/s) indicate that the time constant of C fiber CAP is relatively large (2.88 ms). These suggest that a slow Na+ channel, which is TTX-resistant, contributes to C fiber action potentials.

Action Potentials↗