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Biomedical subjects

W T Lee

Publications and source records attributed to W T Lee.

At least 73 records · Page 4Linked to original sources

Risk assessment of polymyositis/dermatomyositis after treatment with injectable bovine collagen implants.

BACKGROUND: Questions have been raised about a possible relation between injectable collagen and polymyositis and dermatomyositis (PM/DM). Predictions of the prevalence of PM/DM have been based on anecdotal estimates of the duration of follow-up for the collagen-treated population. OBJECTIVE: Our purpose was to study the duration of follow-up for a large sample of collagen-treated patients. METHODS: Physicians in North America who purchased collagen implants during fiscal year 1988 were categorized according to collagen practice size; one third were randomly invited to participate in the study. RESULTS: Review of 2622 patient records yielded an average duration of follow-up of 4 years. CONCLUSION: Five-year incidence rates were used to estimate the expected number of cases of PM/DM in the collagen-treated population. Through June 1993 the expected number was 30.2. The number of confirmed cases after treatment was seven, less than one fourth of the number of cases expected for a model of the collagen-treated population, matched for age, sex, and race.

Adolescent↗

A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children.

Recent calcium supplementation trials in children have confirmed a positive but moderate effect of calcium intake on bone mineral accretion. However, the lasting effect of a higher bone mineral mass after calcium-supplement withdrawal is not known. This is an 18-mo follow-up study conducted after an 18-mo controlled calcium supplementation trial to study the persistent effect of higher bone mineral mass in children. Radial bone mineral mass was determined by single-photon absorptiometry; lumbar spine and femoral neck bone mineral mass were evaluated by dual-energy X-ray absorptiometry in 84 healthy Hong Kong children at age 8.5 y and these evaluations were repeated at age 10 y. Pubertal status was determined by Tanner staging. At the end of the follow-up, the differences in percentage gains in lumbar spine bone mineral content (12.1 +/- 8.2% compared with 14.9 +/- 10.05%, P = 0.24) and lumbar spine area (8.6 +/- 5.1% compared with 9.4 +/- 5.5%, P = 0.47) between the study and control groups disappeared. Dietary calcium intakes during follow-up were similar for the two groups (555 and 640 mg/d, P = 0.23). In multiple-regression analyses, pubertal status was the strongest correlate of bone acquisition and linear growth in the study period. In conclusion, higher percentage gains in bone mineral mass in childhood by calcium supplementation for 18 mo were reversible. Our study showed that the benefits of calcium supplementation disappear after treatment is withdrawn. Longer-term calcium trials are necessary to determine whether peak bone mass can be modified through sustained supplementation so that appropriate calcium intakes can be determined.

Absorptiometry, Photon↗

Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture.

We have previously shown that somatostatin (SRIF) is synthesized in B and T lymphocytes of rat spleen and thymus and released into the medium of cultured lymphocytes. To determine the role of SRIF in the control of lymphocytes proliferation, the expression of SRIF in normal lymphocytes was inhibited using a 3'-terminal phosphorothioate-modified antisense oligonucleotide complementary to a sequence that includes the translation start site of the rat SRIF messenger RNA. Spleens were obtained from adult male rats, and their lymphocytes were cultured for 24 or 72 h to measure SRIF content and cell proliferation, respectively. For the proliferation studies, [3H]thymidine was incorporated during the final 18 h. The lymphocytes were incubated with 15-30 micrograms/ml SRIF antisense and control antisense. SRIF antisense (25 micrograms/ml) increased lymphocyte proliferation 15-fold (P < or = 0.001), reaching a plateau (25- to 30-fold increase) between 25-30 micrograms/ml SRIF antisense. SRIF was extracted from lymphocytes and measured by RIA. Levels of SRIF content were almost undetectable with 10 micrograms/ml antisense and were significantly lower (P < or = 0.01) with 25 micrograms/ml antisense. When RC 160 (10(-5) M), a SRIF agonist analog, was used in the incubation, the stimulation of cell proliferation exerted by the SRIF antisense was completely abolished. Control antisense had no effect on proliferation or SRIF content. These findings indicate that 1) lymphocytes in culture are able to incorporate SRIF antisense; and 2) SRIF antisense inhibits the expression of lymphocytic SRIF, which leads to lymphocyte proliferation. In conclusion, cell proliferation is dramatically increased by eliminating the expression of SRIF from the lymphocytes, which indicates that in vitro SRIF is acting in a paracrine and/or autocrine fashion to inhibit lymphocyte proliferation.

Animals↗

Cytochrome c oxidase deficiency in fibroblasts of a patient with mitochondrial encephalomyopathy.

Cytochrome c oxidase (CCO) deficiency is associated with various types of mitochondrial encephalomyopathy. The enzyme activities in different tissues and organs are varied. We report an 11-year-old girl with CCO deficiency, who presented with nystagmus, ptosis and optic atrophy. Her younger sister died of respiratory failure at 7 years of age and had the same initial clinical manifestations. Their parents were consanguineous. The girl had mild mental retardation and frequent premature ventricular contractions. Brain magnetic resonance imaging of the patient on admission revealed multiple lesions in both the gray and white matter. Except for arrhythmia and marked right axis deviation of the heart on electrocardiography, no other evidence of cardiac involvement was noted. Although a muscle biopsy was normal for both histochemical stains and electron microscopy, the enzyme assays in cultured skin fibroblasts revealed partial CCO deficiency, which may explain the clinical presentations.

Arrhythmias, Cardiac↗

Staphylococcal enterotoxin B induces the expression of activation markers on murine memory T cells in the absence of proliferation or lymphokine secretion.

Superantigens have been used to study peripheral tolerance in CD4+ T cells. The superantigen SEB induces T cell anergy by promoting the differentiation of SEB-activated virgin T cells into anergic memory T cells. Memory T cells from SEB or antigen-primed mice do not proliferate when they are cultured with SEB. The present studies were performed to determine whether memory T cells fail to interact with SEB antigen-presenting cells or whether SEB promotes incomplete or negative signals in memory T cells. When murine virgin and memory T cells were separated on the basis of CD45RB expression and cultured with SEB-pulsed B cells, SEB induced the expression of CD25, which then mediated proliferation when IL-2 was added to the cultures. In addition, SEB promoted the expression of the CD40L, which is required for T helper cell function. Finally, PMA induced a costimulatory signal leading to the proliferation of these cells. Surprisingly, the agents, i.e., IL-2 and PMA, which induced TM cell proliferation in conjunction with SEB failed to induce lymphokine secretion. However, in the presence of IL-4 plus IL-5, the T memory cells induced the SEB-pulsed B cells to secrete IgM and IgG. These results suggest that memory T cells are not simply unresponsive to SEB but are actively anergized.

Animals↗

Thenar hypoplasia in Klippel-Feil syndrome due to aberrant radial artery.

A 10-year-old boy with Klippel-Feil syndrome had progressive atrophy of the left thenar eminence and absence of left radial pulse. Neurophysiologic studies and angiography were normal. However, duplex sonography over the wrists revealed an aberrant left radial artery. We speculate that the thenar atrophy in this patient is congenital, which may be due to the anomaly of the left radial artery, and is further compromised by vascular compression in the thoracic outlet.

Child↗

Effects of double-blind controlled calcium supplementation on calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca).

A double-blind controlled Ca supplementation trial was conducted for 6 months in thirty-four 7-year-old Chinese children from Hongkong and Jiangmen, China. The children were randomly allocated to the study group (n 17) or control group (n 17), and a CaCO3 tablet (300 mg Ca) or a placebo tablet was taken daily. True fractional Ca absorption (TFCA) was evaluated before and after the trial using stable isotopes: 8 mg 44Ca mixed in 100 g chocolate milk was given after an intravenous injection of 0.75 mg 42Ca. There was no significant difference in baseline TFCA between the study group (60.6 (SD 11.4)%) and the controls (58.2 (SD 9.0)%; P = 0.55). Serum 25-hydroxycholecalciferol levels were comparable between the two groups (P = 0.71). After 6 months, TFCA of the study group (55.6 (SD 12.7)%) was significantly lower than that of the controls (64.3 (SD 10.7)%; P = 0.015). By comparing the individual changes in TFCA after the trial between the two groups there was a non-significant reduction in TFCA (5.03 (SD 12.4)%; P = 0.11, Wilcoxon signed-rank test) in the study group (60.6-55.6%), whereas a significant increase in TFCA (6.17 (SD 7.7)%; P = 0.004, Wilcoxon signed-rank test) was observed in the controls (58.2-64.3%). The differential in TFCA between the two groups after 6 months was significantly different (P = 0.001), and remained significant after adjustment for baseline dietary intakes, weight and height by multiple-regression analysis (P = 0.003). If the mechanism of TFCA from chocolate milk in response to the treatment effects is similar to that from the total diet, then our results suggest that children with adequate vitamin D status can adapt to a change in Ca intake by adjusting the efficiency of TFCA. In corollary, children on habitually-low Ca diets have a higher TFCA than the counterparts with higher Ca diets.

Calcium↗

A randomized double-blind controlled calcium supplementation trial, and bone and height acquisition in children.

There is limited information relating Ca intake to bone and height acquisition among Oriental children who consume little or even no milk. The present controlled study investigated the acquisition of bone mass and height of Chinese children with an initial Ca intake of approximately 567 mg/d who were supplemented to about 800 mg/d. Eighty-four 7-year-old Hong Kong Chinese children underwent an 18-month randomized, double-blind, controlled Ca-supplementation trial. The children were randomized to receive either 300 mg elemental Ca or a placebo tablet daily. Bone mass of the distal one-third radius was measured by single-photon absorptiometry, lumbar spine and femoral neck were determined using dual-energy X-ray absorptiometry. Measurements were repeated 6-monthly. Baseline serum 25-hydroxycholecalciferol concentration and physical activity were also assessed. Baseline Ca intakes of the study group and controls were respectively 571 (SD 326) and 563 (SD 337) mg/d. There were no significant differences in baseline serum 25-hydroxycholecalciferol concentration (P = 0.71) and physical activity (P = 0.36) between the study and control groups. After 18 months the study group had significantly greater increases in lumbar-spinal bone mineral content (20.9 v. 16.34%; P = 0.035), lumbar-spinal area (11.16 v. 8.71%; P = 0.049), and a moderately greater increment in areal bone mineral density of the radius (7.74 v. 6.00%; P = 0.081) when compared with the controls. The results confirm a positive effect of Ca on bone mass of the spine and radius but no effects on femoral-neck and height increase. A longer trial is warranted to confirm a positive Ca effect during childhood that may modify future peak bone mass.

Absorptiometry, Photon↗

Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload.

Slow Continuous ultrafiltration (SCUF) was first used in 1980 as an alternative mode of fluid removal for patients with oliguric acute renal dysfunction from whatever causes. The advantage of this treatment is that haemodynamic parameters remain stable in the presence of significant removal of fluid. We are describing our experience in 7 patients [age: 57 +/- 9 years; 4 male, 3 female] with cardiac failure and fluid overload who had undergone 8 sessions of SCUF. All of them had renal impairment and were resistant to diuretics. Blood lines were attached to a Kawasumi Renak-E dialyser (Cuprophane membrane) in series using Gambro AK10 dialysis blood pump. The following parameters were monitored: Blood pump (Qb): 175 +/- 26 ml/min, time (T): 393 +/- minutes. Venous pressure averaged a55 +/- 24 mmHg. We achieved ultrafiltration of 2,189 +/- 699 ml/session or 5.5 +/- 1.7 ml/hr. There was no significant change in blood pressure [systolic pre: 143 +/- 14, post: 136 +/- 13 mmHg, not significant; diastolic pre: 87 +/- 10, post: 83 + 10 mmHg, not significant and pulse rate [pre: 87 +/- 9 vs post: 84 +/- 2 per minute, not significant. Heparin dosage averaged 274 +/- 26 IU/hr during the SCUF. We conclude that SCUF is beneficial to diuretic resistant patients with cardiac failure and fluid overload in whom dialysis treatment is not required.

Adult↗

Growth-dependent regulation of cellular ceramides in human T-cells.

The role of ceramide, a putative lipid second messenger in the regulation of cell growth, was investigated in T-lymphocytes. An inverse relationship between the cellular concentrations of ceramide and the proliferative capacity of human T-lymphocytes was observed for cells treated with either interleukin-2 or phorbol ester plus ionomycin. The same relationship between cellular ceramide concentrations and DNA synthesis also was observed for cells derived from a cultured T-cell line, the Jurkat T-cells. Alternative approaches for modulating the cellular ceramide concentrations were employed to determine the relationship between sphingolipids and cell growth. Treatment of normal T-lymphocyte cultures with exogenous cell-permeable ceramide analogues or sphingosine stereoisomers decreased DNA synthesis. A similar effect was seen with stearylamine. Cells treated with D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of UDP-glucosyl:ceramide transferase, accumulated cellular ceramide concentrations and had decreased DNA synthesis. These results define a correlation between the concentration of cellular ceramides and the capacity of T-lymphocytes to proliferate. However, the addition of bacterial sphingomyelinase to the T-cell medium caused an increase in ceramide concentrations (presumably at the plasma membrane), which did not affect cell growth. These results support the hypothesis that functionally distinct pools of ceramide may reside within the T-cell.

Cell Division↗

True fractional calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca).

True fractional Ca absorption (TFCA) was compared in children with different habitual Ca intakes using a double-label stable-isotope technique. Chinese children aged 7 years from Hongkong (n22) and Jiangmen (n12) participated in the study. An oral administration of 8 mg 44Ca in 100 g chocolate milk was given shortly after an intravenous injection of 0.75 mg 42Ca. Ca isotopic ratios were determined in urine samples collected 24 h later using thermal-ionization mass spectrometry. There was no significant difference in TFCA between Jiangmen and Hongkong children (P = 0.16). TFCA of a lower-Ca-intake group (Ca < or = 500 mg/d, n19) with mean Ca intake 359 mg/d was 63.1 (SD 10.7)% and that of a higher-Ca-intake group (Ca > 500 mg/d, n15) with mean Ca intake 862 mg/d was 54.8 (SD 7.3)%; the difference in TFCA was significant (P = 0.016). Serum levels of 25-hydroxycholecalciferol of the children were adequate (33.7 (SD 7.7) ng/ml). The present study indicates that growing children accustomed to a low-Ca diet appear to be able to enhance their absorptive capacity. If it is assumed that dietary Ca absorption by Chinese children resembles their TFCA from a single meal of chocolate milk, then the recommended dietary allowance (RDA) for Ca for Chinese children would be lower than the US RDA (800 mg/d), which is based on an estimated 40% Ca absorption as reported for Caucasian children. A comparative absorption study is necessary to determine whether there is any difference in TFCA between Caucasian and Chinese children.

Body Height↗

Cytotoxic T lymphocyte and antibody responses generated in rhesus monkeys immunized with retroviral vector-transduced fibroblasts expressing human immunodeficiency virus type-1 IIIB ENV/REV proteins.

The immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1-infected individuals. Genetic immunization using retroviral vectors provides an effective means of introducing antigens into the antigen presentation pathways for T cell stimulation. A nonreplicating, amphotropic murine retroviral vector containing the HIV-1 IIIB env gene has been used to transduce primary rhesus monkey fibroblasts for the expression of HIV-1 antigenic determinants. Rhesus monkeys were immunized with four doses of either vector-transduced autologous fibroblasts (VTAF) expressing the HIV-1 IIIB ENV/REV proteins or nontransduced autologous fibroblasts (NTAF) administered at 2-week intervals. The animals were evaluated for both the induction of HIV-1-specific immune responses and potential toxicity associated with this ex vivo treatment. The VTAF-immunized monkeys generated CTL responses specific for HIV-1 ENV/REV expressing autologous target cells, whereas, NTAF-immunized monkeys showed negligible CTL activity. The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC)-restricted CTL. In addition, antibody responses directed against the HIV-1 gp120 protein were also detected in the sera of VTAF-immunized monkeys. Clinical and histopathological evaluation of immunized monkeys showed no evidence of significant adverse events. Several animals that received either VTAF or NTAF had detectable anti-cytoplasmic antibodies, but were not positive for anti-nuclear antibodies or rheumatoid factor. Subsequent evaluation of renal, synovial, and hepatic tissue samples from these monkeys revealed no autoimmune disease-associated lesions. This study demonstrates the safety and ability of autologous retroviral vector-transduced cells expressing HIV-1 IIIB ENV/REV proteins to stimulate immune responses in a non-human primate model, and provides a basis for this form of genetic immunization in HIV-infected humans.

AIDS Vaccines↗

Double-blind, controlled calcium supplementation and bone mineral accretion in children accustomed to a low-calcium diet.

A randomized, double-blind, controlled calcium supplementation trial was conducted for 18 mo to determine its effects on bone acquisition and height increment in 162 7-y-old Chinese children (87 boys and 75 girls) with habitually low calcium intakes (280 mg/d). Distal one-third radial bone mineral content (BMC), area bone density (BMC/bone width), and height were evaluated every 6 mo. Baseline dietary intakes, serum 25-hydroxycholecalciferol, and physical activity were determined. The study group received 300 mg Ca/d as calcium carbonate; control subjects received placebo tablets. After 18 mo the study group had significantly greater gains in BMC (16.5% vs 13.97%; P = 0.02) and BMC/bone width (9.45% vs 6.31%; P = 0.0008) than the control subjects. The findings confirm a positive effect of calcium intake on bone acquisition but no effect on height increment. Whether a higher bone mass attained at age 8-9 y would be maintained and beneficial to future peak bone mass requires longitudinal investigation. Further study is warranted to determine calcium requirements for Chinese children.

Body Height↗

A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism.

The i.v. bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism. However, few of the published studies of this mode of treatment have been adequately controlled, and recent reports have suggested that p.o. bolus administration may be just as effective. In this study, 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned, after a 4-wk run-in period, to receive a 6-wk course of either thrice-weekly i.v. or p.o. alfacalcidol (initial dose, 4 micrograms). Then, after a further control period, they received a second 6-wk course, with either p.o. or i.v. alfacalcidol (whichever was not given in the first treatment period). Plasma parathyroid hormone (PTH) was measured weekly by the use of an intact hormone assay. Both routes of therapy resulted in a significant suppression of plasma PTH (P = 0.005) and an elevation in plasma ionized calcium (P = 0.01). The magnitude of the responses was similar for the two treatment phases, as was the relationship between the increment in calcium and the decrement in PTH. The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium. The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases. Oral bolus therapy and i.v. bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism. The postulated advantages of i.v. over p.o. therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies.

Administration, Oral↗