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Biomedical subjects

H Sudo

Publications and source records attributed to H Sudo.

At least 55 records · Page 3Linked to original sources

[Two-dimensional echocardiographic recognition of dilated cardiomyopathy: comparison with postmortem studies].

To elucidate the pathophysiology of dilated cardiomyopathy (DCM), the relationship of two-dimensional echocardiographic wall motion abnormalities (asynergy) to histopathological findings was evaluated in autopsied patients including seven with DCM, five with old myocardial infarction (OMI) and three with the normal heart. The DCM cases were classified morphologically in two groups, namely four of type I and II and three of type III, according to Shozawa's classification. Three short-axis views of the left ventricle were divided into 19 segments; the wall motion was assessed visually and classified as normal motion, hypokinesis, akinesis and dyskinesis. The postmortem specimens were immersed in 10% formalin; transverse sections and wall divisions were prepared corresponding to the two-dimensional echocardiographic views, and the area of each segment was determined by a computer planimetry excluding the papillary muscles and trabeculae. Fibrosis (%) was measured histologically by the point counting method with light microscopy. The results were as follows: In DCM, fibrosis (%) increased with increasing severity of asynergy: 17.1% fibrosis in normal motion; 28.7% in hypokinesis; 40.7% in akinesis and dyskinesis. In OMI, fibrosis (%) also increased with increasing severity of asynergy. On comparison of DCM with OMI, no difference was established relating to fibrosis (%) in the asynergic segments; moreover, in both groups, asynergy was detected more frequently in the segments in which fibrosis (%) exceeded 21%. On comparison of type I+II DCM with type III DCM, fibrosis (%) of type III was significantly less than that of type I+II in the same degree of asynergic segments. Moreover, fibrosis (%) of type I+II tended to be greater in the outer layer than in the inner layer, while fibrosis (%) of type III was evenly distributed throughout the myocardium, or greater in the inner layer than in the outer layer. In type I+II, wall thinning was marked with increasing severity of asynergy; in contrast, these correlations were not observed in type III. In type I+II, a higher fibrotic rate was observed in the left ventricular free wall and an abnormal Q wave appeared frequently on ECG. This tendency was not found in type III. These findings indicate that fibrosis is one of the most important factors in decreasing cardiac muscular contractility in DCM, and suggest that there is a different pathogenesis between type I+II and type III fibrosis.

Adolescent↗

In vitro hemopoiesis within a microenvironment created by MC3T3-G2/PA6 preadipocytes.

The clonal preadipose cell line, MC3T3-G2/PA6, has the capacity to differentiate into adipocytes in response to glucocorticoids and to support in vitro growth of hemopoietic stem cells (CFU-S). To study the relationship between these capacities, we precultured the MC3T3-G2/PA6 cells for varying days in the presence or absence of dexamethasone and then cocultured them with mouse bone marrow cells. Logarithmically growing cultures contained no detectable adipocytes and showed the highest growth-supporting activity for CFU-S, whereas cultures containing the largest number of adipocytes showed the lowest activity. When bone marrow cells were seeded onto 3-day-old MC3T3-G2/PA6 preadipocyte layers at 1 X 10(5) cells/35-mm dish, day 12 CFU-S grew with a population doubling time of about 37 hr, and at least 75% of them were associated with the cell layer between days 2 and 7. In the absence of the preadipocytes, CFU-S were not detected in the adherent cell fraction and decreased with a half-life of about 18 hr. More than 80% of CFU-C were also found to be associated with the preadipocyte layer, and they increased about 24-fold in number during 7 days in culture. Morphologically, hemopoietic cells developing into mature granulocytes and macrophages were distributed between the layers of preadipocytes. Dendritic processes of preadipocytes were frequently in close alignment with the hemopoietic cells. However, adipocytes failed to show such an intimate association with hemopoietic cells. These results indicate that MC3T3-G2/PA6 cells in the preadipocyte stage, but not in the adipocyte stage, have the capacity to support CFU-S growth, and that hemopoiesis in our cocultivation system proceed within the microenvironmental milieu provided by MC3T3-G2/PA6 preadipocytes.

Adipose Tissue↗

Combined drug therapy--cholestyramine and compactin--for familial hypercholesterolemia.

Combined drug therapy with cholestyramine and compactin was found to be extremely effective against heterozygous cases of familial hypercholesterolemia. With a single drug regimen, compactin at a dosage of 15 mg/day produced a cholesterol reduction of 23% (70 mg/dl) in cases of combined hyperlipidemia, while twice the dosage (30 mg/day) was needed to produce a comparable effect with heterozygous familial hypercholesterolemia. When compaction was combined with cholestyramine (in a 4 g dose three times a day), the cholesterol-lowering effect of compactin was strongly improved with heterozygous familial hypercholesterolemia; half the dosage of compactin was enough to produce the additive effect compared with the effect produced by each single drug regimen.

Anticholesteremic Agents↗

In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria.

We investigated the capacity of a clonal osteogenic cell line MC3T3-E1, established from newborn mouse calvaria and selected on the basis of high alkaline phosphatase (ALP) activity in the confluent state, to differentiate into osteoblasts and mineralize in vitro. The cells in the growing state showed a fibroblastic morphology and grew to form multiple layers. On day 21, clusters of cells exhibiting typical osteoblastic morphology were found in osmiophilic nodular regions. Such nodules increased in number and size with incubation time and became easily identifiable with the naked eye by day 40-50. In the central part of well-developed nodules, osteocytes were embedded in heavily mineralized bone matrix. Osteoblasts were arranged at the periphery of the bone spicules and were surrounded by lysosome-rich cells and a fibroblastic cell layer. Numerous matrix vesicles were scattered around the osteoblasts and young osteocytes. Matrix vesicles and plasma membranes of osteoblasts, young osteocytes, and lysosome-rich cells showed strong reaction to cytochemical stainings for ALP activity and calcium ions. Minerals were initially localized in the matrix vesicles and then deposited on well-banded collagen fibrils. Deposited minerals consisted exclusively of calcium and phosphorus, and some of the crystals had matured into hydroxyapatite crystals. These results indicate that MC3T3-E1 cells have the capacity to differentiate into osteoblasts and osteocytes and to form calcified bone tissue in vitro.

Alkaline Phosphatase↗

Effect of dibutyryl cyclic AMP on collagen synthesis in a clonal osteoblast-like cell line derived from newborn mouse calvaria.

The effects of dibutyryl cyclic AMP (DBcAMP) and related compounds on collagen synthesis in a clonal osteoblast-like cell line, MC3T3-E1, were investigated. The addition of DBcAMP to cultures increased the hydroxyproline content of the cells. It also enhanced the incorporation of labeled proline into collagen and elevated the activity of prolyl hydroxylase, an enzyme involved in collagen synthesis. These effects were observed at concentrations of 0.1 to 2 mM DBcAMP. 8-Bromo cyclic AMP also increased the hydroxyproline content of the cells, while sodium butyrate and dibutyryl cyclic GMP had no such effect. These results suggest that the intracellular accumulation of cyclic AMP in osteoblasts leads to their active production of collagen, a major component of the organic matrix of bone.

Animals↗

Adipose conversion of mouse bone marrow fibroblasts in vitro: their alkaline phosphatase activity.

By an in vitro colony assay and cytochemical staining, we investigated the capacity of mouse bone marrow fibroblasts to differentiate into adipocytes and to express alkaline phosphatase (ALP) activity. Glucocorticoids enhanced colony formation of the fibroblasts, and stimulated their adipose conversion (55-65% of the colonies became adipocyte-positive), but they did not affect ALP activity. The fibroblasts became heterogeneous in size and morphology after growing in vitro then differentiated into adipocytes. All the cell types had ALP activity, and more than 95% of the colonies contained ALP-positive cells. ALP staining was strongest in cells in the early stage of adipose conversion, gradually decreasing with maturation. Our results indicate that the majority of the mouse bone marrow fibroblasts that formed colonies under our culture conditions are preadipocytes. We conclude that these fibroblasts originate from adventitial reticular cells present in bone marrow stroma because reticular cells have been reported to possess high ALP activity and have been suggested to differentiate into adipocytes.

Adipose Tissue↗

Serum lipoprotein profile in Japanese obese children.

The analysis of serum lipoprotein was performed in school children in suburban areas in Japan. Serum lipid levels and lipoprotein profiles of obese children were compared to those of controls with normal body weight. Obese children with body weight more than 20 per cent above ideal body weight comprised approximately 6 per cent of the children. There was little difference in concentration of total cholesterol and triglycerides between the obese and the non-obese children. However, in obese children, the level of HDL-cholesterol was significantly lower and the level of (VLDL + LDL)-cholesterol was higher, so that the ratio of (VLDL + LDL)-cholesterol to HDL-cholesterol was substantially higher than in non-obese children. In the obese children, a linear correlation was obtained between total serum cholesterol and the ratio of (VLDL + LDL)-cholesterol to HDL-cholesterol level, which showed the increase of HDL-cholesterol was not accompanied with the increase of total cholesterol, while in the non-obese children, total serum cholesterol was not parallel with the ratio of (VLDL + LDL)-cholesterol to HDL-cholesterol level, suggesting a co-increase of HDL-cholesterol with LDL-cholesterol. As the changes in lipoprotein profiles characterized by the increase in LDL and the decrease in HDL is one of the major risk factors of atherosclerosis, the prevention of obesity during school life seems to be important to prevent atherosclerotic diseases even in normolipidemic children.

Adolescent↗

Therapeutic effects of ML-236B in primary hypercholesterolemia.

ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, was administered to 11 patients with primary hypercholesterolemia. After 4--8 weeks of drug treatment at doses of 50--150 mg/day, serum cholesterol levels were reduced by 11--37% (27% on average) in cases of heterozygous familial hypercholesterolemia and combined hyperlipidemia. A marked reduction in tuberous xanthomas was noticed in a homozygous case of familial hypercholesterolemia, but here the drug was less effective in reducing the serum cholesterol level and a higher dose was required for treatment. Softening of Achilles tendon xantomas was observed in a case of combined hyperlipidemia.

Adult↗

Specific modification of hepatic triglyceride lipase activity by ultracentrifugally separated serum lipoprotein fractions.

Hepatic triglyceride lipase (H-TGL) obtained from postheparin plasma is first stimulated and than progressively inhibited by addition of an increasing amount of serum. To solve the mechanism of this modification, serum fractions isolated by ultracentrifugation were added to the assay mixture and their effects on H-TGL activity were determined. We demonstrated that the addition of the d=1.21 bottom fraction together with HDL almost fully reproduces the effect of the whole serum.

Heparin↗