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Biomedical subjects

M Seishima

Publications and source records attributed to M Seishima.

At least 109 records · Page 6Linked to original sources

Alterations in intracellular calcium transients of fibroblasts from progressive systemic sclerotic patients: a digital imaging microscopic study.

Intracellular Ca2+ concentrations ([Ca2+]i) in cultured skin fibroblasts from normal subjects and progressive systemic sclerosis (PSS) patients were determined by using Fura-2 and fluorescent videomicroscopy. With the exception of fibroblasts from one PSS patient showing a higher [Ca2+]i, no significant difference was observed in resting [Ca2+]i between the two groups of fibroblasts. Bradykinin (BK) (10 microM) induced a transient [Ca2+]i increase in normal fibroblasts, whereas the BK-induced [Ca2+]i increase was reduced or not detectable in PSS fibroblasts. Removal of extracellular Ca2+ did not eliminate the BK-induced [Ca2+]i increase in normal fibroblasts. These findings suggest that BK stimulates Ca2+ release from intracellular stores in human fibroblasts, and also that the BK-mediated Ca2+ release is impaired in PSS fibroblasts.

Adult↗

[Serum lipid and apolipoprotein levels in patients with chronic pancreatitis].

Serum lipid and apolipoprotein (apo A-I, A-II, A-IV, B, C-II, C-III, E and H) levels were determined in 26 patients with chronic pancreatitis without complications such as liver disease or diabetes mellitus. These patients were divided into two groups, CP-I (n = 16) and CP-II (n = 10), according to the clinical criteria for chronic pancreatitis. HDL-cholesterol and apo A-I levels in CP-I and CP-II groups significantly decreased compared to those in sex- and age-matched healthy controls (p less than 0.05), whereas there were not significant differences in triglyceride and total cholesterol levels between these groups and controls. On the other hand, apo A-IV levels in CP-I and CP-II were 7.1 +/- 1.0 mg/dl and 8.3 +/- 1.5 mg/dl, respectively and these values were significantly lower than 11.2 +/- 1.8 mg/dl in controls (p less than 0.001). In this study, the serum lipids apparently showed normal levels in patients with chronic pancreatitis who had no severe complication, and the markedly low apo A-IV levels in these patients were considered to be mainly due to the decrease of lipid absorption from the intestine.

Adult↗

Regulation of hepatic apolipoprotein synthesis in the 17 alpha-ethinyl estradiol-treated rat.

Regulatory mechanisms of hepatic apolipoprotein synthesis were studied in groups of male Sprague-Dawley rats made severely hypolipidemic by treatment with pharmacological doses of 17 alpha-ethinyl estradiol. Treatment resulted in a marked reduction of plasma cholesterol and apolipoproteins B, A-I, and A-IV. Hepatic apoA-I mRNA and apoA-I synthesis were increased in the ethinyl estradiol-treated animals. Hepatic apoA-IV protein synthesis rates were unaltered; however, a reduction of the apoA-IV mRNA level was observed. Diet-control studies suggested the effects of 17 alpha-ethinyl estradiol on apoA-I, unlike those on apoA-IV, appeared to be related to the steroid and not to reduced caloric intake. Livers of control and ethinyl estradiol-treated rats synthesized both apoBH and apoBL. Total hepatic apoB (apoBL plus apoBH) synthesis and apoB mRNA levels in the ethinyl estradiol-treated rats were similar to ad libitum fed or diet-controls. In ad libitum fed and diet-control rats, 21% and 32%, respectively, of newly synthesized hepatic apoB was apoBH. In contrast, 47% of the newly synthesized apoB in the ethinyl estradiol-treated animal was apoBH. Nucleotide sequence analysis of hepatic apoB mRNA confirmed a marked decrease in the proportion of the apoBL mRNA in ethinyl estradiol-treated animals. After cessation of 17 alpha-ethinyl estradiol treatment, the hepatic apolipoprotein A-I synthesis rate, apolipoprotein A-I and A-IV mRNA levels, and the apoBH and apoBL synthesis rates, as well as plasma apolipoprotein and cholesterol levels, returned to normal. A major finding of the present study is that pharmacological doses of ethinyl estradiol do not affect total hepatic apoB synthesis, but increase the relative amount of apoBH synthesized.

Animals↗

Transient changes of serum lipoprotein(a) as an acute phase protein.

Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antitrypsin and haptoglobin, increased rapidly and markedly after the episodes. Initial values of serum Lp(a) concentrations were almost the same in both groups. Increases in serum Lp(a) levels were also observed during the first few days, with a return to the initial levels after more than 1 month. The periods for reaching maximal levels of acute phase proteins were similar in both groups of patients. On the contrary, the period required for Lp(a) to reach the maximal level in the myocardial infarction group was significantly longer than in the post-operative group. The present study suggests that Lp(a) has the characteristics of an acute phase reactant and may play an important role in recovery from tissue damage.

Acute-Phase Proteins↗

[A case of psoriasis vulgaris whose lipoprotein lipase activity decreased during treatment with etretinate].

Treatment with etretinate is known to be effective for patients with psoriasis. However, it has been reported that the administration of etretinate often generates side effects which disturb lipoprotein metabolism. In this study, 5 patients with psoriasis vulgaris were treated with etretinate (1 mg/kg/day), and the changes in serum lipids, apolipoprotein levels, and lipoprotein lipase (LPL) activity were observed. In 4 out of the 5 cases, the above determinations were within the normal range throughout the course. However, in the case of one 35-year old man, LPL activity markedly decreased on day 28 after the administration of etretinate and was restored when the administration was suspended. Furthermore, LPL activity decreased again when the administration was resumed. Therefore, it appeared that the decrease of LPL activity in this case was mainly due to the administration of etretinate.

Adult↗

[Role of singlet oxygen in pathogenesis of liver injury in rats treated with D-galactosamine].

A study was conducted to elucidate the possible role of singlet oxygen in pathogenesis of D-galactosamine-induced liver injury. Tissue and plasma levels of singlet oxygen were determined with chemiluminescence analysis. Following results were obtained: 1) Chemiluminescence as well as malondialdehyde, which is regarded as one of terminal products of lipid peroxidation, significantly increased in the liver and plasma of rats treated with D-galactosamine. 2) Elevation of plasma GPT and total bilirubin was also observed in rats with D-galactosamine-induced liver injury. Histological examination of the liver revealed submassive hepatic necrosis. 3) Administration of vitamin E, a radical scavenger of singlet oxygen, significantly inhibited the increases of chemiluminescence and MDA in the liver and plasma as well as the elevations of GPT and total bilirubin in the plasma. Histological changes of the liver were also found to improve significantly by vitamin E administration. In conclusion, singlet oxygen seems to be definitely involved, at least in part, in pathogenesis of liver damage induced by D-galactosamine. In addition, inhibition of the liver injury is possible, to some extent, by administration of vitamin E, one of the potent radical scavengers of singlet oxygen.

Animals↗

Defective formation of inositol 1,4,5-trisphosphate in bradykinin-stimulated fibroblasts from progressive systemic sclerotic patients.

The effect of bradykinin on inositol 1,4,5-trisphosphate (1,4,5-IP3) formation was investigated in fibroblasts from normal subjects and patients with progressive systemic sclerosis (PSS). 1,4,5-IP3 in both PSS and normal fibroblasts reached peak levels at 15 sec after stimulation with bradykinin, though this level was significantly lower in PSS fibroblasts than in normal cells. There was no difference in 1,4,5-IP3 content between islet-activating protein (IAP)-treated and untreated cells in either PSS or normal fibroblasts. These findings suggest that bradykinin stimulates phosphoinositide hydrolysis by phospholipase C in human fibroblasts via IAP-insensitive pathway, and that PSS fibroblasts appear to be defective in the pathway.

Bradykinin↗

Enzyme-linked immunosorbent assay of lipoprotein(a) in serum and cord blood.

We have developed a new sensitive method for quantifying lipoprotein(a) (Lp(a] in human serum, using a 'sandwich' type noncompetitive enzyme-linked immunosorbent assay (ELISA). The solid-phase used was a polystyrene plate. The anti-Lp(a) antibody-enzyme conjugate was labelled by linking Fab' fragments to peroxidase (EC 1.11.1.7) by the maleimide method. The minimum detectable concentration was 0.5 ng/well. Routinely, the assay was carried out with 1,000-fold diluted serum, and Lp(a) was quantified between 4.0 and 500 mg/l. Within-run coefficients of variation (CVs) ranged from 3.5% to 10.4% and between-run CVs from 5.0% to 11.1%. Results by the ELISA were in good agreement with those by radial immunodiffusion (r = 0.955). The distribution of Lp(a) in serum from 820 healthy donors was highly skewed: mean 141.1 mg/l, medium 97.9 mg/l. In cord blood, the mean and median were 15.6 and 9.8 mg/l, respectively. This ELISA for Lp(a) has the advantages of being highly sensitive and specific, simple to perform, and does not use radioisotopes.

Adolescent↗

Changes of serum apolipoprotein levels after oral administration of fat in human subjects.

Changes of serum apolipoprotein levels were studied every hour for 6 h after the administration of 55 g butter to 8 healthy male subjects. The mean serum apo A-IV level was significantly increased at 4 h (P less than 0.05) after fat ingestion compared to the mean initial level, although no significant changes of levels in other apolipoproteins (apo A-I, A-II, B, C-II, C-III, and E) were observed. The mean apo A-IV level in the triglyceride-rich lipoprotein (TRL) fraction (d less than 1.006) increased progressively over 6 h. In all 8 subjects, the time of peak concentration of apo A-IV in TRL fraction was delayed by 1-2 h compared to that in whole serum. On the other hand, the mean apo B-48 level in the fraction reached a peak at 4 h. These results raise the possibilities that some apo A-IV, newly synthesized or already existing in intestinal cells, may be directly secreted into the venous circulation and that apo A-IV and apo B-48 may distribute differently in different sizes of chylomicron. Alternatively, the amount of each apolipoprotein synthesized may depend upon the content of ingested fat. It is suggested that apo A-IV production by intestinal cells does not appear to be regulated by the rate of fat transport, and that apo A-IV does not play an important role in chylomicron formation compared to apo B-48.

Administration, Oral↗

Increased protein kinase C activity in fibroblast membranes from psoriatic patients.

The activity of phospholipid/Ca2+-dependent protein kinase (PKc) was measured in the membrane and cytosolic fractions of normal and psoriatic human fibroblasts. The psoriatic fibroblasts displayed higher membrane-associated PKc activity than normal cells. In contrast, no significant difference in PKc activities was observed in cytosolic fractions from normal and psoriatic fibroblasts. These data suggest that PKc is preferentially associated with the membrane in psoriatic fibroblasts and that such elevated PKc activity in membranes may play a role in the pathogenesis of this disease.

Cell Membrane↗

An increased apo A-IV serum concentration of patients with chronic renal failure on hemodialysis.

Serum apolipoprotein (apo) A-IV concentration was determined in 20 patients with chronic renal failure on hemodialysis. The mean value of apo A-IV was 33.5 +/- 6.3 mg/dl, that was increased by approximately 3 times compared with that in healthy controls (11.1 +/- 2.7 mg/dl, n = 23). No significant correlation of apo A-IV was observed with the other apolipoproteins (apo A-I, A-II, B, C-II, C-III, and E) levels, serum lipids (TC, TG, and HDL-C) levels, and lipoprotein concentrations in both the patients and the controls. However, apo A-IV was significantly correlated with serum creatinine, BUN, and beta 2-microglobulin levels (p less than 0.05) in the patients. On the other hand, in patients with nephrotic syndrome and in that of a patient with Fanconi's syndrome, apo A-IV was detected in their urine. These results, in turn, suggest from their well-known pathogenesis that apo A-IV can readily transverse the glomerular filter due to its small molecular mass size and that it is also probably taken up and catabolized by renal tubular cells in the same fashion as other low molecular mass proteins. These observations suggest that a decreased glomerular filtration and/or reduced catabolism of apo A-IV by tubular cells may be one of the important causes of the increase in the serum apo A-IV level in patients with chronic renal failure besides a decreased catabolism of chylomicron remnants containing apo A-IV.

Adult↗