Toshio Nishide

Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen

PURPOSE To establish a new index of regional fat distribution using ultrasonography for assessment of the ratio of the visceral fat area (V) to the subcutaneous fat area (S) (V/S ratio). SUBJECTS AND METHODS The subjects examined were 62 patients (23 males and 39 females); 51 patients had hyperlipidemia and 11 patients had glucose intolerance. The mean body mass indices ranged from 20.3 to 42.9. The mean age of the patients was 44 +/- 13 years. The thicknesses of the preperitoneal fat layer (P) and subcutaneous fat layer (S) in the abdomen were measured by ultrasonography and the P/S ratio was calculated. The V/S ratio was obtained with radiographic computed tomography. RESULTS Of the various P/S ratios examined, the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat was most closely correlated with the V/S ratio (r = 0.746, p < 0.0001). This ratio was termed the abdominal wall fat index (AFI). AFI was positively correlated with serum triglyceride levels and negatively correlated with high-density lipoprotein cholesterol (r = -0.312, p < 0.05), whereas the V/S ratio was correlated with triglyceride levels. AFI was positively correlated with basal insulin levels in both men and women. CONCLUSION These results suggest that AFI measured by ultrasonography may be a new indicator of visceral fat deposition, and may reflect metabolic disorders such as lipid metabolism and glucose metabolism disorders.

Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS)

Twenty-five heterozygous familial hypercholesterolemic patients treated with LDL-apheresis and drugs and 11 patients treated with drugs underwent follow-up angiography 2.3 years later. One-hundred thirteen lesions were measured by quantitative angiography. Mean LDL-cholesterol levels during the trial were 140 +/- 34 mg/dl in the apheresis group and 170 +/- 58 mg/dl (P < 0.05) in the control group. The mean changes in minimal lumen diameter of lesions were +0.19 +/- 0.30 mm (improved) in the apheresis group (n = 76) and -0.44 +/- 0.40 mm (worsened) in the control group (n = 37) (P < 0.0001). When progression and regression were defined as a change in minimal lumen diameter of +/- 0.67 mm, in the apheresis group, two (8%) patients had progression, 19 (76%) stayed unchanged and four (16%) had regression, but in the control group seven (64%) patients had progression and four (36%) stayed unchanged. The frequency of regression or no change was significantly higher in the apheresis group than in the control group (P < 0.004). Intensive cholesterol lowering therapy with LDL-apheresis and lipid lowering drugs can achieve a substantial decrease in LDL-cholesterol levels to induce regression of coronary lesions in familial hypercholesterolemic patients with advanced coronary artery disease.

Adsorption of lipoprotein containing apolipoprotein-B through plasma separation for treatment of familial hypercholesterolemia.

For the treatment of familial hypercholesterolemia, Liposorber LA-40 was clinically applied. The Liposorber is a commercially developed affinity adsorbent for plasma perfusion which selectivily adsorbs low density lipoproteins and very low density lipoproteins and is specially designed for plasmapheretic treatment of hypercholesterolemia. The Liposorber column, containing activated cellulose beads having an affinity for liporpotein containing apolipoprotein-B, has an excellent adsorption capacity, excellent selectivity, minimum albumin loss. This new apheresis system was applied to 2 clinical cases. After seven months of trial perfusion every 2 weeks, patient condition was good, with a level of total cholesterol under 300 mg/dl. No replacement fluids were given during or after treatment. In this paper, clinical results of these patients were shown and the mechanism of adsorption of this specific adsorbent was discussed.

A familial hyperalphalipoproteinemia with low uptake of high density lipoproteins into peripheral lymphocytes

A patient with an extremely high level of high density lipoprotein (HDL)-cholesterol and HDLc-like particles in the serum is discussed. The patient was a 46-year-old female with a serum total cholesterol concentration of 382 mg/dl and HDL-cholesterol level of 214 mg/dl. The HDL-cholesterol levels of her mother, brother, sister and 2 of her daughters were 82 mg/dl, 82 mg/dl, 74 mg/dl, 82 mg/dl and 82 mg/dl, respectively (mean HDL-cholesterol levels of control subjects: 52 +/- 6 mg/dl in males and 55 +/- 8 mg/dl in females). Her serum apolipoprotein A-I and E levels were elevated. Zonal ultracentrifugal analysis of her serum lipoproteins showed that the increased level of HDL-cholesterol was mainly due to HDL2; HDLc-like particles were also recognized between the LDL and HDL fractions. The incorporation of the patients HDL and HDLc-like particles into cultured HepG2 cells was almost the same as that of HDL (1.063 less than d less than 1.21) from normal control serum. The incorporation of normal control HDL into the patients peripheral blood lymphocytes was markedly less than that into lymphocytes from normal controls. These findings are discussed in terms of the reason for hyperalphalipoproteinemia in this patient.

Long Term Result of Ldl Selective Plasma Adsorption Therapy on Familial Hypercholesterolemia

A newly developed low density lipoprotein (LDL) selective adsorption column from the separated plasma was applied to one patient of heterozygous familial hypercholesterolemia for 20 months at intervals of two weeks. LDL selective adsorption column, Liposorber LA-40, contains 400 ml of swollen dextran sulfate cellulose beads. The long-term, 20 month results of treatment with LDL selective plasma adsorption therapy are reported. LDL selective plasma adsorption therapy by Liposorber is useful in decreasing LDL-cholesterol of familial hypercholesterolemia and is more specific and produces a smaller loss of useful components of the serum than the double filtration plasmapheresis treatment. This treatment is effective in improving clinical conditions of familial hypercholesterolemia. In spite of our lengthy treatment with this therapy, no blood transfusion and no replacement of fluids was done in 20 months.

Lecithinized superoxide dismutase treatment improves steroid-refractory interstitial pneumonia.

Pulmonary fibrosis associated with amyopathic dermatomyositis is known to have a generally aggressive course and is ultimately fatal. We report the case of a 50‐year‐old patient with amyopathic dermatomyositis, who developed progressive interstitial pneumonia that was unresponsive to corticosteroids and multiple immunosuppressive agents, including cyclosporine and tacrolimus hydrate. Five courses of lecithinized superoxide dismutase were administered without adverse effects. Improvements in physiological parameters, such as pulmonary function and exercise tolerance, as well as the serum Krebs von den Lungen 6 level, were observed. This is the first report of a case of steroid‐refractory interstitial pneumonia treated with lecithinized superoxide dismutase.

Effect of 5-year administration of probucol on development of myocardial infarction in heterozygous familial hypercholesterolemia

Abstract This study was carried out to determine whether the decrease in plasma cholesterol produced by 5-year probucol administration would prevent development of myocardial infarction in patients with heterozygous familial hypercholesterolemia. Treated and untreated (control) groups included 39 and 91 patients, respectively. There were no differences in initial levels of total cholesterol (TC), low-density-lipoprotein (LDL)-cholesterol or high-density-lipoprotein (HDL)-cholesterol between groups. There were also no differences in age or incidence of risk factors at the beginning of the study. Probucol decreased levels of TC, LDL-cholesterol, and HDL-cholesterol by 23%, 24%, and 21%, respectively. Mean Achilles tendon thickening decreased from a median of 10.0 mm (range, 5.0 to 25.0 mm) to a median of 8.0 mm (range, 4.0 to 15.0 mm) over 5 years. Master double tolerance tests changed from positive to negative in five of 39 patients, and no patient experienced deterioration. There was no new episode of myocardial infarction in the treated group. Three cases of myocardial infarction were observed in the control group during the study. Results suggest that probucol administration might prevent development of myocardial infarction in patients with familial hypercholesterolemia.

Effects of chloroquine on the metabolism of phosphatidylcholine associated with low density lipoprotein in arterial smooth muscle cells

Phospholipid associated with LDL (LDL-phospholipid) has been suggested to affect metabolism of LDL in arterial smooth muscle cells. However, the metabolism of LDL-phosphatidylcholine in these cells has not been well clarified. We compared the metabolic pathway of LDL-phosphatidylcholine with that of cholesteryl ester associated with LDL (LDL-cholesteryl ester) in rabbit arterial smooth muscle cells by incubating the cells in the absence or presence of chloroquine, an inhibitor of lysosomal function. When the cells were incubated with LDL-[3H]cholesterol linoleate in the absence of chloroquine, 26.6 and 51.4% of incorporated radioactivity was found as cholesteryl ester in the lysosome-rich and microsome-rich fractions, respectively. When the cells were incubated in the presence of 50 microM chloroquine, the radioactivity found as cholesteryl ester in the lysosome-rich fraction increased to 45.5% while that in microsome-rich fraction decreased to 21.4%, indicating that LDL-cholesteryl ester accumulated in lysosomes as a consequence of inhibition of lysosomal function. When the cells were incubated with LDL-[14C]linoleoyl phosphatidylcholine in the absence of chloroquine, 25.1% of incorporated radioactivity was found as phosphatidylcholine in the lysosome-rich fraction and 24.8% in the cytosol-rich fraction. When the cells were incubated in the presence of chloroquine, phosphatidylcholine-associated radioactivity found in the lysosome-rich and cytosol-rich fractions changed only to 28.8% and 26.1%, respectively, showing that LDL-phosphatidylcholine did not accumulate in lysosomes when lysosomal function was inhibited. In conclusion, these data indicate that LDL-phosphatidylcholine, in contrast to LDL-cholesteryl ester, is not only hydrolyzed in lysosomes, but also at other subcellular sites.

Effect of conditioning of β-migrating very low-density lipoprotein with macrophages on the accumulation of cholesteryl esters in smooth muscle cells

The mechanism of cholesteryl ester accumulation in smooth muscle cells was investigated. Incubation of smooth muscle cells with β-migrating very low-density lipoprotein (β-VLDL, d < 1.006) for 24 h did not result in accumulation of oil red O-stained particles in the cells. However, incubation of smooth muscle cells with β-VLDL in the presence of rat peritoneal macrophages induced accumulation of oil red O-stained granules in smooth muscle cells. Medium containing [3H]-cholesteryl linoleate-labelled β-VLDL ([3H]β-VLDL) that was conditioned with rat peritoneal macrophages increased the incorporation of [3H]-cholesterol and the cholesteryl ester content in smooth muscle cells, whereas unconditioned [3H]β-VLDL did not. On zonal ultracentrifugation of conditioned medium containing [3H]β-VLDL with macrophages, radioactivity was found at two peaks of density 1.150 and < 1.006. This new fraction with d = 1.150 (peak II) migrated at β-positions, the same as that of low-density lipoprotein (LDL) on agarose gel elec...