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Biomedical subjects

S L Hsia

Publications and source records attributed to S L Hsia.

At least 19 recordsLinked to original sources
PubMed2000

A pilot study to evaluate the treatment of basal cell carcinoma with 5-fluorouracil using phosphatidyl choline as a transepidermal carrier.

BACKGROUND: In certain situations, successful topical therapy of basal cell carcinoma (BCC) without the inconvenience, risk, and expense of surgery would be of great value to patients. Placing 5-fluorouracil (FU) in an appropriate carrier may solve these problems. Phosphatidyl choline (PC) penetrates effectively throughout the epidermis of shaved rabbits and may be able to carry small water-soluble molecules such as nucleotides across lipid barriers when applied topically. OBJECTIVE: We propose that employing PC as a vehicle will facilitate the penetration of 5-FU and increase efficacy as compared to petrolatum-based 5-FU cream. METHODS: This pilot study is a double-blinded and randomized therapeutic trial. Thirteen patients with 17 biopsy-proven, moderate thickness BCCs were randomized to receive either cream A (5% 5-FU in a PC vehicle) or cream B (Efudex(R): 5% 5-FU in a petrolatum base). Patients applied cream A or cream B twice a day for 4 weeks. The patients underwent an excisional biopsy of the treated BCC site at week 16. RESULTS: There was a 90% cure rate (9/10) in those lesions treated with 5% 5-FU in PC cream and a 57% cure rate (4/7) in those treated with 5% 5-FU in a petrolatum-based cream. CONCLUSION: Although the study was unable to detect any statistically significant differences in outcome between the study groups, this small pilot study shows preliminary findings which may indicate an increase in the short-term eradication of BCC using a PC-based vehicle as compared to conventional petrolatum-based formulations.

Administration, Topical↗
PubMed1996

The hypocholesterolemic and antiatherogenic effects of topically applied phosphatidylcholine in rabbits with heritable hypercholesterolemia.

To test possible hypocholesterolemic and antiatherogenic effects of transdermally administered phosphatidylcholine (PC), we applied a 33% solution of PC in ethanol containing 0.01% butylated hydroxytoluene as antioxidant, to the shaved back of a strain of inbred rabbits which spontaneously developed hypercholesterolemia (serum cholesterol above 110 mg/dl) and severe atherosclerotic lesions especially in the aortic arch. After the topical application of PC, increases of choline-containing phospholipids in blood were observed, reaching a plateau in 24-48 hr. There were significant reductions in serum cholesterol and LDL cholesterol in the treated animals 2-3 weeks after the treatment. Atherosclerotic lesions in the aortic arch were clearly less severe in the animals repeatedly treated with topical PC. The hypocholesterolemic and antiatherogenic effects of topical PC could be the result of increased cholesterol efflux from extrahepatic tissues and enhanced reverse cholesterol transport.

Administration, Cutaneous↗
PubMed1993

A micro enzymic method for determination of choline-containing phospholipids in serum and high density lipoproteins.

A micro method is described for the assay of choline-containing phospholipids in serum and high density lipoproteins (HDL) using an automated microtiter plate reader. The method is adapted from the enzymic method of Takayama, Itoh, Nagasaki, and Tanimuzu (Clin. Chim. Acta 79, 93-98, 1977) using phospholipase D, choline oxidase, and peroxidase coupled with the color generating system phenol and 4-amino-antipyrine. The micro method requires 5 microL of serum or HDL sample, and 42 samples can be assayed in duplicate in one run using a 96-well flat-bottom microtiter plate. The reaction is linear up to 400 mg/dL and the lower limit of detection is 0.25 mg of choline-containing phospholipids per assay. The coefficient of variation within an assay is 0.86-0.79%, and day-to-day variation is 0.9-1.5%. Results obtained by the micro method are in excellent agreement with those obtained by the procedure of Takayama et al. (r = 0.997). The supernatant left after removal of low density lipoproteins and very low density lipoproteins from serum and precipitation with heparin/manganese chloride reagent can thus be conveniently used for the micro assay of choline phospholipids in HDL.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation.

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.

Age Factors↗
PubMed1989

Increased androgen binding capacity in sebaceous glands in scalp of male-pattern baldness.

Sebaceous glands were isolated by manual dissection under a microscope from surgical specimens of scalp skin with male pattern baldness and skin specimens of hairy and bald scalp obtained at autopsy. The 800 X g pellet (nuclear fraction) and the 164,000 X g supernatant fraction (cytosol) of homogenates of the sebaceous glands were used for measurements of androgen binding characteristics, using dextran-coated charcoal and sucrose gradient methods. Scatchard plots showed high affinity binding for [3H]dihydrotestosterone (DHT) and [3H]methyltrienolone (R1881). Nuclei prepared from bald scalp contained greater total androgen binding capacity than nuclei of hairy scalp, although Kd values of type I binding were similar (0.68 vs 0.56 nM, respectively). On sucrose gradient, the binding protein from cytosol was found in the 7 to 8S density range. Androgen binding by cytosol of sebaceous glands of hairy scalp had Kd of 1.89 +/- .79 and 2.05 +/- .56 nM for DHT and R1881, respectively, and Bmax of 18.7 +/- 4.4 and 20.0 +/- 4.6 fmol/mg protein for DHT and R1881, respectively. Cytosol from sebaceous glands of bald scalp had Kd values approximately half those of hairy scalp, and Bmax values 50%-100% higher. The bound 3H labeled DHT and R1881 could be partially displaced by testosterone (40-50%), moxestrol (28-32%), promegestone (19-26%), and delta 4-androstenedione (6-12%), but not by dehydroepiandrosterone. These data demonstrate the presence of specific androgen binding protein in sebaceous glands, and that sebaceous glands of bald scalp have greater binding affinity and capacity for androgens than those in hairy scalp. This difference may explain the greater androgenic response in androgenic alopecia.

Adult↗
PubMed1989

Effect of dialysate composition on the lipid response to L-carnitine supplementation.

Cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response in hyperlipidemia. We have compared in a double-blind, cross-over study the effect of dialysate buffer composition (acetate or bicarbonate) on the serum lipid response to L-carnitine supplementation during hemodialysis. We studied nine patients (mean age, 19 years; range, 14 to 23) with hyperlipidemia undergoing maintenance hemodialysis. Plasma levels of carnitines and lipids, including total and HDL cholesterol (HDL-C) and triglycerides (TG), were measured at baseline and monthly intervals after receiving 2 grams of L-carnitine or placebo added to dialysis bath for three months. One month of carnitine supplementation in acetate hemodialysis significantly reduced plasma TG (230 +/- 95 to 136 +/- 20 mg/dl; P less than 0.05) and elevated HDL-C (50 +/- 12 to 71 +/- 26 mg/dl; P less than 0.05). However, this effect was no longer observed at the end of three months of supplementation. Bicarbonate hemodialysis had lower baseline TG values, but carnitine supplementation did not modify plasma lipids (TG:144 +/- 87 to 158 +/- 115 mg/dl; HDL-C:50 +/- 23 to 50 +/- 19 mg/dl). Both groups had a significant increase in plasma carnitine levels after carnitine supplementation. These results suggest that bicarbonate hemodialysis may add a protective effect in hyperlipidemia by reducing requirements of carnitine supplementation. On the other hand, carnitine supplementation should be considered in patients with hyperlipidemia undergoing acetate hemodialysis. The observed difference in response between acetate and bicarbonate hemodialysis may be due to enhanced formation of acetyl-CoA and fatty acid synthesis during acetate hemodialysis.

Acetates↗
PubMed1988

Interaction of rabbit lipoproteins and red blood cells with liposomes of egg yolk phospholipids.

After intravenous injection of liposomes prepared from egg yolk phospholipids into rabbits, the phospholipids were readily assimilated by the lipoproteins, and there were increases in the circulating levels of cholesterol and phospholipids. The increases in cholesterol level were mainly due to increases of free cholesterol. Gradient ultracentrifugation showed that the lipoproteins decreased in density, and gel filtration chromatography showed that they increased in particle size. Upon electrophoresis, they exhibited slower mobility. Liposomes recovered from rabbits 3 hr after the injection contained free cholesterol, apolipoproteins A-I, E and traces of C. The apolipoprotein may target the liposomes for uptake by hepatocytes. Incubation of the liposomes with rabbit red blood cell membranes in vitro caused a decrease in cholesterol content of the membranes. However, the cholesterol/phosphate ratio in red blood cells isolated from the rabbits after the injection of liposomes did not change significantly, suggesting rapid replenishment of red blood cell cholesterol in vivo, possibly by equilibration with lipoprotein cholesterol or tissue cholesterol. These results suggest that the injection of phospholipid liposomes may have an antiatherogenic effect by the removal of tissue cholesterol and enhancing hepatic disposal of cholesterol through the reverse cholesterol transport mechanism.

Animals↗
PubMed1988

delta 5-3 beta-hydroxysteroid dehydrogenase activity in sebaceous glands of scalp in male-pattern baldness.

Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenates of the isolated glands exhibited activities of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 17 beta-hydroxysteroid dehydrogenase, and testosterone 5 alpha-reductase by the conversion of [3H]dehydroepiandrosterone (DHA) to 3H-delta 4-androstenedione (AD), [3H]testosterone, and [3H]dihydrotestosterone. Homogenates of glands from bald (B) scalp had greater 3 beta HSD activity than homogenates of glands from hairy (H) scalp. After differential centrifugation, 3 beta HSD activity was found mainly in the microsomal and 105,000 X g supernatant fractions. Specific activity of the enzyme based on protein mass was highest in the microsomal fraction; however, the total 3 beta HSD activity in the 105,000 X g supernatent of B glands was significantly (p less than .01) greater than that of H glands. 3 beta HSD activity in sebaceous glands isolated from autopsy specimens did not differ from that of glands isolated from surgical specimens in apparent Km (0.13-0.14 microM), pH optima (8.0), or coenzyme requirement for NAD. Since substantial 3 beta HSD activity was present in the cytosol, and cytosol of B glands showed increased 3 beta HSD activity, the increased conversion of DHA to AD may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.

3-Hydroxysteroid Dehydrogenases↗
PubMed1988

Oestrogen and progesterone receptors in lentigo maligna.

We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextran-coated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non-specific binding for oestrogen and progesterone. The presence of steroid hormone receptors in LM suggests the possibility that hormone responsiveness may be relevant in the transformation of a lentigo maligna into malignant melanoma.

Aged↗
PubMed1988

Defect in cholesteryl ester transport in serum of patients with uremia receiving maintenance hemodialysis: increased inhibitor activity for cholesteryl ester transfer.

The rate of cholesterol transfer (RCT) from high-density lipoproteins (HDLs) to very low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) was previously found to be lower in the serum of patients with uremia receiving maintenance hemodialysis than in the serum of control subjects, and the defect was associated with the serum density greater than 1.063 gm/ml fraction (Hsia et al. J LAB CLIN MED 1985;106:53). The present study shows that cholesterol transfer from HDLs to VLDLs and LDLs could be increased when the lipoprotein-deficient fraction of control serum was substituted for the patients' fraction. Cholesteryl ester transfer protein (CETP) activity in patient serum was assayed and found to be below that in the serum of control subjects. CETP and CETP inhibitor activities in patient and control sera were separated by hydrophobic chromatography on phenyl-Sepharose. Recovery of CETP activity from patient samples was 214% +/- 62%, and that from controls was 112% +/- 15%. The data indicate that the low RCT of patients was caused by increased levels of an inhibitor to CETP activity in their serum.

Adult↗
PubMed1987

Lipid and lipoprotein levels in undialyzed patients with chronic renal failure.

Lipid and lipoprotein levels were measured in undialyzed uremic men and compared with levels of healthy control subjects. The patients had lower high-density lipoprotein (HDL) cholesterol (mean +/- SD, 46.3 +/- 14.8 vs 54.1 +/- 18.2 mg/dl) and increased serum triglycerides (197 +/- 151 vs 142 +/- 87.7 mg/dl). When compared with patients maintained on dialysis, the undialyzed patients had higher HDL cholesterol (46.3 +/- 14.8 vs 30.3 +/- 13.3 mg/dl), serum cholesterol (226 +/- 81 vs 151 +/- 42 mg/dl), and triglycerides (197 +/- 151 vs 146 +/- 105 mg/dl). The low-density lipoprotein (LDL): high-density lipoprotein cholesterol ratios were 3.78, 3.24, and 2.84 in the dialyzed, undialyzed, and control groups, respectively. Lecithin: cholesterol acyl transferase activity of undialyzed patients was similar to controls when measured by an endogenous substrate assay (148 +/- 112 vs 112 +/- 28 nmol/ml/hr), but were significantly lower when assayed using exogenous substrate (73.3 +/- 25.6 vs 112.8 +/- 7 nmol/ml/hr). The rate of cholesterol transfer (RCT) from HDL to very low density lipoprotein and LDL was in the following order: dialyzed patients (1.85 +/- 1.29 mg/dl/hr) less than undialyzed patients (2.41 +/- 1.57 mg/dl/hr) less than control subjects (4.83 +/- 3.13 mg/dl/hr). Within the undialyzed patient group, black patients had lower serum cholesterol and triglycerides and higher HDL and HDL3 cholesterol than white patients. Apoprotein A-I levels were higher and apoprotein B levels were lower in the black patients. There was a strong correlation (r = 0.9501) between apoprotein A-I and HDL levels in the black patients, but not in the white patients (r = -0.148).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

A fluorometric method for the determination of triglycerides in nanomolar quantities.

A fluorometric assay for triglycerides in nanomole quantities is described. Glycerol is liberated from triglycerides with lipase from Chromobacter viscosum, then converted by glycerol kinase to glycerol-3-phosphate, which is oxidized by glycerol-3-phosphate oxidase, producing H2O2. The H2O2 ultimately forms a peroxidase-catalyzed fluorogen with p-hydroxyphenylacetic acid. The excitation and emission wavelengths of the fluorogen are 325 and 415 nm, respectively. The assay is linear in the range 0.05-35 nmol of triglycerides using triolein as standard.

Chromatography, Liquid↗
PubMed1986

High-density lipoprotein and glycosylated hemoglobin in nondiabetic individuals.

We investigated associations of high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I, and triglyceride levels with hemoglobin A1 (HbA1) and insulin levels in nondiabetic subjects (137 women and 111 men). In women, HDL cholesterol, apolipoprotein A-I, and log-triglyceride values were significantly correlated with those of HbA1 and log-fasting insulin. These univariate associations persisted when age and Quetelet's index were included as covariates in multiple regression analyses. Conversely, univariate associations of HDL cholesterol and log-triglyceride levels with Quetelet's index were diminished by the addition of insulin values to multivariate models. Insulin levels and Quetelet's index were highly correlated. Although there were weaker associations in men, apolipoprotein A-I and HbA1 values were inversely related. These data suggest that HDL cholesterol and apolipoprotein A-I levels are closely linked to glucose metabolism in nondiabetic individuals.

Adult↗
PubMed1985

Defect in cholesterol transport in patients receiving maintenance hemodialysis.

A defect in cholesterol transport was detected in patients with uremia who were receiving long-term hemodialysis when the rate of cholesterol transfer (RCT) from high-density lipoprotein (HDL) to very low-density (VLDL) and low-density lipoproteins (LDL) was compared with that in controls. The RCT (mean +/- SD) in 29 men with uremia (1.85 +/- 1.29 mg/hr/100 ml) and 11 women with uremia (1.84 +/- 1.00 mg/hr/100 ml) was significantly lower (P less than 0.001) than values in 55 healthy men (4.50 +/- 2.61 mg/hr/100 ml) and 23 healthy women (3.72 +/- 1.92 mg/hr/100 ml), respectively. Six patients, but none of the controls, totally lacked the ability for cholesterol transfer. The decreased RCT of the patients could not be completely accounted for by their decreased HDL cholesterol levels, because patients matched with controls for HDL cholesterol within 1 mg/100 ml also had lower RCT (P less than 0.0025). Recombination and crossover of serum fractions of patients and controls separated by ultracentrifugation revealed that the defect in cholesterol transfer of the patients was in the d greater than 1.063 gm/ml fraction (containing HDL and other serum proteins), which not only contained less HDL cholesterol, but was also qualitatively inferior as donor for cholesterol transfer. In one of four patients studied, the d less than 1.063 gm/ml fraction (VLDL and LDL) also had deficient ability to accept cholesteryl esters in the transfer. These in vitro data indicate a defect in cholesterol transport in the patients who are undergoing hemodialysis. Whether this defect exists in vivo and creates the risk of accelerated atherosclerosis warrants further study.

Adult↗
PubMed1984

Persistence of serum lipid abnormalities in children with idiopathic nephrotic syndrome.

We investigated the severity and duration of hyperlipidemia in 59 nephrotic children during relapse and remission. Serum total cholesterol and triglyceride values were greater than or equal to 95th percentile for age and sex in all patients with minimal change nephrotic syndrome in relapse and in patients with non-MCNS and persistent proteinuria. Most of these patients also had a significant elevation of low- and very-low-density lipoproteins. A significant number of children with MCNS during prolonged remission had elevated serum concentrations of total cholesterol (46%), triglycerides (42%), LDL (29%), and VLDL (40%). Persistence and severity of lipid changes correlated well with duration of disease and frequency of relapses. Significantly decreased HDL and HDL/LDL were found in patients with non-MCNS and persistent proteinuria. Our results suggest that nephrotic children may have prolonged periods of hyperlipidemia even after clinical remission. In addition, some of these children with significantly decreased HDL/LDL may be at increased risk of developing premature atherosclerosis.

Adolescent↗
PubMed1984

delta 5-3 beta-Hydroxysteroid dehydrogenase delta 4-5-isomerase activity and metabolism of dehydroepiandrosterone in rat preputial gland.

After intracardial injection of [1,2-3H]dehydroepiandrosterone ([3H]DHA) into female rats, [3H]DHA was found to accumulate and was metabolized in the preputial gland, but not in the diaphragm. The identified metabolites of [3H]DHA in the preputial gland were delta 4-androstenedione-3 alpha, 17 beta-diol. Cells were isolated from the preputial gland after treatment with trypsin and collagenase III, and centrifugation in Ficoll gradients. Activity of the enzyme complex delta 5-3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (3 beta-HSD) responsible for transforming DHA into delta 4-androstenedione was found mainly in the 105,000 g pellet (microsomal fraction) of homogenates of the isolated cells. It used preferentially NAD over NADP as a coenzyme, with a pH optimum at 8.5. The apparent Km for DHA was 5.5 X 10(-5) M, and the Vmax was 1.72 nmol/min/mg microsomal protein. These findings indicate that DHA is preferentially taken up by the preputial gland where it undergoes metabolism to form more potent androgens, and suggest that DHA may have important androgenic influence on the preputial gland.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Cord blood serum in newborns of diabetic mothers.

Serum cholesterol, triglycerides and lipoprotein cholesterol were measured in cord bloods from 117 newborns. Group I consisted of 39 infants of diabetic mothers and Group II (control) consisted of 78 newborns of non-diabetic mothers. The most significant difference in serum lipids between the two groups was the higher levels of LDL cholesterol and lower levels of HDL cholesterol in the newborns of diabetic mothers. Cord blood serum cholesterol was slightly, but not significantly, higher in children born of diabetic mothers. Serum triglycerides were also not significantly different between the groups. While it remains to be established whether elevated levels of LDL cholesterol and decreased levels of HDL cholesterol at birth in these infants represent a transient phenomenon, this study suggests that newborns of diabetic mothers may be predisposed early in life to LDL hypercholesterolemia and thus may be at a greater risk of developing coronary heart disease later in life.

Cholesterol↗