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Biomedical subjects

G M Chan

Publications and source records attributed to G M Chan.

At least 19 recordsLinked to original sources
PubMed2005

Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats.

Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations in IUGR cerebral transcriptional regulation, which may result from changes in chromatin structure. Candidate nutritional triggers for these changes include altered cerebral zinc and one-carbon metabolite levels. We hypothesized that IUGR affects cerebral chromatin structure in neonatal and postnatal rat brains. Rats were rendered IUGR by bilateral uterine artery ligation; controls (Con) underwent sham surgery. At day of life 0 (d0), we measured cerebral DNA methylation, histone acetylation, expression of chromatin-affecting enzymes, and cerebral levels of one-carbon metabolites and zinc. At day of life 21 (d21), we measured cerebral DNA methylation and histone acetylation, as well as the caloric content of Con and IUGR rat breast milk. At d0, IUGR significantly decreased genome-wide and CpG island methylation, as well as increased histone 3 lysine 9 (H3/K9) and histone 3 lysine 14 (H3/K14) acetylation in the hippocampus and periventricular white matter, respectively. IUGR also decreased expression of the chromatin-affecting enzymes DNA methyltransferase 1 (DNMT1), methyl-CpG binding protein 2 (MeCP2), and histone deacetylase (HDAC)1 in association with increased cerebral levels of zinc. In d21 female IUGR rats, cerebral CpG DNA methylation remained lower, whereas H3/K9 and H3/K14 hyperacetylation persisted in hippocampus and white matter, respectively. In d21 male rats, IUGR decreased acetylation of H3/K9 and H3/K14 in these respective regions compared with controls. Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific.

Acetylation↗
PubMed2004

Vietnamese centipede envenomation.

The Vietnamese centipede (Scolopendra subspinipes) is one of the largest and most aggressive tropical centipedes. It has become a popular pet among arthropod enthusiasts and the general public. Despite their reputation, few well-documented cases of envenomation are reported in the medical literature. A 53-yo man developed severe pain, swelling and erythema of his left hand and forearm after being bitten on the hand by his pet Vietnamese centipede. The neurological and vascular examination of the arm was normal. He was admitted to the hospital, treated with arm elevation, analgesics and parenteral antibiotics. His symptoms gradually resolved and he was discharged after 4 d with no neurological or cosmetic sequelae.

Animals↗
PubMed2001

Induction of apoptosis in mammary gland by a pure anti-estrogen ICI 182780.

The antiestrogen, ICI 182780 (ICI) proves to be clinically useful for the treatment of estrogen receptor positive breast tumours. We report the assessment of the in vivo and in vitro effects of ICI on apoptosis of breast epithelial cells. In vivo, administration of rats with ICI for 3 weeks resulted in a reduction in the size of the lobular structures with the rate of mammary epithelial apoptosis equivalent to 10, 35 and 45% on treatment with 1, 1.5 and 2 mg ICI per kg body weight, respectively. Concomitantly, these treatment led to a 2.0-, 2.2- and 2.5-fold increase in Bax. Similar elevations were also observed in Bad levels which increased 1.7-, 2.6- and 2.7-fold respectively in the ICI treatment as compared to controls. This also resulted in a dose dependent decrease in Bcl-2 and Bcl-xL protein expressions. Growth inhibition and induction of apoptosis were also observed in the MCF-7 cells following in vitro treatment with ICI. This is closely associated with [1] the down-regulation of Bcl-2 and Bcl-xL proteins and [2] upregulation of Bax and Bad, whose gene products are known to be involved the regulation of apoptosis in mammalian cells. Stable over-expression of Bcl-2 resulted in protection of MCF-7 cells from apoptosis and growth inhibitory effects of ICI. Conversely, reduction of Bcl-2 by antisense transfection make MCF-7 cells more sensitive to ICI-induced growth inhibition and apoptosis. These findings suggest that modulation of Bax, Bcl-xL, Bcl-2 and Bad proteins by ICI may be, in part, responsible for the anti-proliferative and apoptotic effect of ICI seen clinically and in animal models.

Animals↗
PubMed2001

Relation of forearm's bone and soft tissues to infant's body composition.

Small portable units using the dual X-ray absorptiometry method (pDEXA) are becoming available to evaluate a localized region of the body such as the forearm. The purpose of this study was to evaluate the relationship between infant's forearm measurements of bone mineral, lean, and fat mass and total body composition. Twenty-two infants participated in this study. Mean age of the infants was 21 d with a weight range of 1-3.6 kg. All infants were stable and had their forearm and total body scanned on the same day. The long-term precision error for the pDEXA was 0.4%. The infant's total body was scanned by the XR-26 (Norland Medical Systems, Fort Atkinson,WI). Forearm bone mineral content, bone mineral density (BMD), fat mass, and lean mass correlated to total body mineral content (BMC) (r = 0.84, p < 0.001), total body BMD (r = 0.73, p < 0.001), total fat mass (r = 0.53, p < 0.05), and total body lean mass (r = 0.80, p < 0.001). Forearm BMC, lean, and fat mass correlated significantly with body weight and length (r = 0.73-0.94). In conclusion, forearm measurements of bone mineral, fat, and lean mass reflect total body bone mineral, fat, and lean mass in small infants.

Absorptiometry, Photon↗
PubMed2000

Bone mineral status in prepubertal children with cystic fibrosis.

OBJECTIVES: To determine whether osteopenia is evident in prepubertal children with cystic fibrosis (CF) and, if so, whether it is caused by a deficiency in bone formation or increased bone resorption. STUDY DESIGN: With the use of a prospective case control study design, we investigated 11 prepubertal children with CF between the ages of 8 and 12 years old and a non-CF control group matched by weight and sex. Bone density at the radius, ulnar, trochanter, femoral neck, and lumbar spine, biochemical markers of bone metabolism, calcium, vitamin D metabolites, and intact parathyroid hormone were measured in all subjects. Comparisons between the 2 groups were performed with Wilcoxon matched pairs and Fisher exact tests. RESULTS: Intake of total calories, calcium, phosphorus, and vitamin D was significantly greater in the CF group than in the control group. Serum 25(OH)vitamin D levels were significantly lower in the CF group: median 22 ng/mL for the CF group and 39 ng/mL for the control group (P =.02). 1,25(OH)(2) vitamin D levels were borderline or low in 7 subjects in the CF group and 2 members of the control group (P =.08, Fisher exact test). Intact parathyroid hormone levels were higher than the upper limit of normal in 4 subjects of the CF group and 1 member of the control group. Despite these biochemical abnormalities, we found no evidence of bone mineral deficiency in the CF group. CONCLUSIONS: Prepubertal children with CF do not have bone mineral deficit compared with a weight- and sex-matched control group; however, their lower vitamin D levels may portend problems with bone mineralization during adolescence and adulthood.

Bone Density↗
PubMed2000

Case-control study of factors associated with nutritional rickets in Nigerian children.

OBJECTIVE: Because the causes of nutritional rickets in tropical countries are poorly understood, we conducted a case-control study to determine factors associated with rickets in Nigerian children. STUDY DESIGN: We compared 123 Nigerian children who had rickets with matched control subjects. Dietary, demographic, anthropometric, and biochemical data were collected to assess factors related to calcium and vitamin D status, which might predispose children to rickets. RESULTS: Mean (+/- SD) daily dietary calcium intake was low in both children with rickets and control children (217 +/- 88 mg and 214 +/- 77 mg, respectively; P =.64). Children with rickets had a greater proportion of first-degree relatives with a history of rickets (14.6% vs 3.1%; P <.001), a shorter mean duration of breast-feeding (16.0 vs 17.3 months; P =.041), and a delayed age of walking (14 vs 12 months; P <.001). Among children with rickets, biochemical features suggestive of calcium deficiency included hypocalcemia, extremely low calcium excretion, and elevated 1, 25-dihydroxyvitamin D and parathyroid hormone values. Median 25-hydroxyvitamin D concentrations were 32 and 50 nmol/L (13 and 20 ng/mL) in children with rickets and control children, respectively (P <.0001). Only 46 subjects with rickets (37%) had 25-hydroxyvitamin D values <30 nmol/L (12 ng/mL). CONCLUSIONS: Vitamin D deficiency appears unlikely to be the primary etiologic factor of rickets in African children. Moreover, low dietary calcium intake alone does not account for rickets. Insufficient dietary calcium probably interacts with genetic, hormonal, and other nutritional factors to cause rickets in susceptible children.

Adolescent↗
PubMed2000

Daily physical activity program increases bone mineralization and growth in preterm very low birth weight infants.

OBJECTIVE: A study of daily physical activity was performed with 32 preterm infants to evaluate changes in body weight and bone mineralization. STUDY DESIGN: Subjects were matched by birth weight and gestational age and randomly assigned to the physical activity (PA; n = 16) or to the control (C; n = 16) program. PA consisted of range of motion against passive resistance to all extremities for 5 to 10 minutes daily. Peripheral dual-energy x-ray of the right forearm (ulna and radius); biomarkers of bone formation (serum type I collagen C-terminal propeptide [PICP]) and resorption (urine pyridinoline cross-links of collagen [Pyd]); serum calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH), and 1, 25-(OH)(2) vitamin D; and urine levels of calcium, phosphate, and creatinine were obtained. All measurements were made at study entry and at 2.0 kg of body weight. RESULTS: Despite a similar nutrient intake at advised levels for preterm infants, gains in body weight (g) and forearm bone length (cm), bone area (BA; cm(2)), bone mineral content (BMC; mg), and fat-free mass (g) were greater in PA infants. Forearm bone mineral density and fat mass gains did not differ between groups. Serum PICP levels remained constant in PA infants but decreased in C infants suggesting a slower rate of bone formation. Urine Pyd or bone resorption activity was similar between groups. A higher level of serum PTH was observed in PA infants at 2. 0 kg of body weight; however, the change from study entry to completion did not differ between groups. All other serum and urine values were similar and within normal limits. CONCLUSION: A daily PA program promotes greater gains in body weight, forearm length, BA, BMC, and fat-free mass in premature infants.

Adipose Tissue↗
PubMed1999

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

Alkaline Phosphatase↗
PubMed1999

Cloning of delta12- and delta6-desaturases from Mortierella alpina and recombinant production of gamma-linolenic acid in Saccharomyces cerevisiae.

Two cDNA clones with homology to known desaturase genes were isolated from the fungus Mortierella alpina. The open reading frame in one clone encoded 399 amino acids and exhibited delta12-desaturase activity when expressed in Saccharomyces cerevisiae in the presence of endogenous fatty acid substrate oleic acid. The insert in another clone contained an open reading frame encoding 457 amino acids and exhibited delta6-desaturase activity in S. cerevisiae in the presence of exogenous fatty acid substrate linoleic acid. Expression of the delta12-desaturase gene under appropriate media and temperature conditions led to the production of linoleic acid at levels up to 25% of the total fatty acids in yeast. When linoleic acid was provided as an exogenous substrate to the yeast cultures expressing the delta6-desaturase activity, the level of gamma-linolenic acid reached 10% of the total yeast fatty acids. Co-expression of both the delta6- and delta12-desaturase cDNA resulted in the endogenous production of gamma-linolenic acid. The yields of gamma-linolenic acid reached as high as 8% of total fatty acids in yeast.

Amino Acid Sequence↗
PubMed1999

Postpartum body composition changes in lactating and non-lactating primiparas.

The objective of this study is to evaluate the postpartum body composition changes in lactating versus non-lactating or formula-feeding primiparas during the first 12 wk. Twenty primiparous females (age range 17-35 y) who decided to nurse or formula feed their infant were studied. The non-lactating mothers (n = 6) were younger (21 versus 29 y) and had a lower prepregnancy weight (55 kg versus 63 kg) than the lactating mothers (n = 14). Body weight, height, waist and hip measurements, 3-d dietary and activity records, skin-fold thickness from triceps, suprailiac, midthigh, and midupper arm circumference, and total body composition were evaluated at three time periods (at delivery, at 6 wk, and at 12 wk postpartum). Total body composition for bone mineral, lean, and fat mass was measured by dual energy x-ray absorptiometry. At delivery and 6 wk postpartum, the weights and heights were similar between the two groups. By 12 wk postpartum, the formula-feeding group had a weight loss that was different from delivery, 66 +/- 10 kg to 59 +/- 8 kg, P < 0.03. There was no significant weight change in the lactating group during the study. The weight loss consisted of more lean mass than fat mass. The total body bone mineral content did not differ between the two groups during the study. Both groups had reduction in their waist size from delivery to 12 wk postpartum. But only the non-lactating mothers had reductions in their hip and midthigh measurements. There were no changes between the two groups in the skin-fold measurements. Lactating mothers had a higher total daily calories (1974 +/- 318 versus 1464 +/- 178 calories, P < 0.002) and fat intake (63 +/- 14 versus 47 +/- 9 g, P < 0.02) than the non-lactating mothers. The energy expenditure was similar between both groups. In conclusion, during the first 12 wk postpartum, non-lactating mothers who were younger and weighed less prepregnancy lost body weight and had more waist, hip, and midthigh size reductions compared to lactating mothers.

Adolescent↗
PubMed1998

Identification of Delta5-desaturase from Mortierella alpina by heterologous expression in Bakers' yeast and canola.

A DNA fragment with homology to Delta6-desaturases from borage and cyanobacteria was isolated after polymerase chain reaction amplification of Mortierella alpina cDNA with oligonucleotide primers corresponding to the conserved regions of known Delta6-desaturase genes. This fragment was used as a probe to isolate a cDNA clone with an open reading frame encoding 446 amino acids from a M. alpina library. Expression of this open reading frame from an inducible promoter in Saccharomyces cerevisiae in the presence of various substrates revealed that the recombinant product had Delta5-desaturase activity. The effects of growth and induction conditions as well as host strain on activity of the recombinant Delta5-desaturase in S. cerevisiae were evaluated. Expression of the M. alpina Delta5-desaturase cDNA in transgenic canola seeds resulted in the production of taxoleic acid (Delta5,9-18:2) and pinolenic acid (Delta5,9,12-18:3), which are the Delta5-desaturation products of oleic and linoleic acids, respectively.

Amino Acid Sequence↗
PubMed1998

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Aged↗
PubMed1995

Effect of physical activity on bone mineralization in premature infants.

OBJECTIVE: A 4-week pilot study was done with 26 preterm infants to evaluate whether a physical activity program would result in greater bone mineralization. DESIGN: Subjects were matched by birth weight, gender, and gestational age, and randomly assigned to the physical activity program (group EX; n = 13) or to the control group (group C; n = 13). Physical activity consisted of range of motion with passive resistance to all extremities for 5 to 10 minutes daily. Baseline and 4-week values were determined for both bone mineral analyses and serum levels of calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25-hydroxy-vitamin D. RESULTS: Despite similar nutrient intake at advised levels for preterm infants, EX infants gained more weight than control subjects (17.8 vs 13.4 gm/kg body weight per day; p = 0.01). A difference in radial bone mass and density change as determined by single-beam photon absorptiometry (+/- 2% error) was found between groups (p = 0.006 by analysis of covariance). Changes in bone width and in bone mineral content and density were enhanced by physical activity. Group EX infants had 12%, 18%, and 34% gains in bone width and in bone mineral density and content, respectively; group C infants had only a 2% gain in bone width and 11% and 14% losses from baseline in bone mineral content and density, respectively, during the 4-week study. Serum biochemical values were similar in the groups except for lower alkaline phosphatase levels in group EX. There was a negative association between bone mineral content and parathyroid hormone values: r = -0.83, p = 0.01. CONCLUSIONS: A physical activity program may increase the effects of adequate nutrition in healthy preterm very low birth weight infants by promoting weight gain and bone mass and by decreasing the risk of osteopenia.

Absorptiometry, Photon↗
PubMed1995

Effects of dairy products on bone and body composition in pubertal girls.

OBJECTIVE: To study the effect of calcium supplementation with dairy products on the bone and body composition of pubertal girls. DESIGN: Randomized control study with 12-month follow-up. SETTING: General community. SUBJECTS: Forty-eight white girls whose mean age was 11 years and sexual development at Tanner stage 2. INTERVENTION: One group's diet was supplemented with dairy products to the recommended dietary allowance of 1200 mg calcium daily. The other group ate their usual diet. MAIN OUTCOME MEASURES: Bone mineral content and density were measured at the radius, femoral neck, lumbar spine, and total body bone mineral by single-photon and dual-energy x-ray absorptiometry at the start of the study and after 3, 6, 9, and 12 months. Body composition (lean body mass and body fat) was measured by dual-energy x-ray absorptiometry at the same intervals. Serum calcium, phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, alkaline phosphatase, magnesium, and albumin concentrations were determined at the start and end of the study. The urinary calcium/creatinine ratio and hydroxyproline concentration were also determined. RESULTS: The dairy group had higher intakes of calcium, phosphate, vitamin D, and protein than control subjects. The dairy group had significantly greater increases during the 1-year study in bone mineral density at the lumbar spine bones (22.8% +/- 6.9% vs 12.9% +/- 8.3%) and in total body bone mineral (14.2% +/- 7.0% vs 7.6% +/- 6.0%) than control subjects. Dietary calcium, phosphate, vitamin D, and protein intakes were associated with the lumbar bone density and total body bone calcium. There were no differences in serum or urinary biochemical values between the two groups at the start or end of the study. CONCLUSIONS: Young girls whose dietary calcium intake was provided primarily by dairy products at or above the recommended dietary allowances had an increased rate of bone mineralization. Increased intake of dairy foods did not increase overall total or saturated fat intake and was not associated with excessive weight gain or increased body fat.

Body Composition↗
PubMed1994

Effects of human milk or formula feeding on the growth, behavior, and protein status of preterm infants discharged from the newborn intensive care unit.

The growth, behavior, and protein status of 59 healthy preterm (mean gestational age 30 wk) infants fed either human milk or one of three infant formulas were studied post-discharge from the hospital. Formula-fed infants received either a standard term formula, a standard preterm formula, or an experimental preterm formula from discharge to 8 wk of age. From 8 to 16 wk, all formula-fed infants received the standard term formula. At 2, 8, and 16 wk, anthropometric, dietary intake, blood biochemistry, amino acid, and Brazelton Neonatal Behavioral Assessment measurements were evaluated. Weights, lengths, and head circumferences were similar for all feeding groups at discharge. After discharge all formula-fed infants were heavier than human milk-fed infants. Length and head circumference values and plasma urea nitrogen and retinol-binding protein concentrations were not different among dietary groups. Formula-fed infants had higher plasma concentrations of numerous amino acids compared with those of human milk-fed infants during the first 8 wk but not at 16 wk. There were no differences among the feeding groups in the Brazelton assessment. This study found little effect on the growth or behavioral or protein status of preterm infants discharged from the hospital who were fed either human milk or formulas designed for term or preterm infants.

Amino Acids↗
PubMed1993

Alterations in vitamin D and calcium metabolism with magnesium sulfate treatment of preeclampsia.

OBJECTIVE: Our purpose was to determine the effects of magnesium sulfate therapy on preeclamptic women and their fetuses with regard to the hormones and ions involved with calcium homeostasis, including 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, parathyroid hormone, and calcium. STUDY DESIGN: The study group comprised 15 preeclamptic women at term treated with magnesium sulfate during labor. Controls were seven normal women in term labor. The hormones and ions were measured in maternal blood obtained at the onset of labor and at delivery and in umbilical venous (fetal) blood. RESULTS: Baseline maternal levels of 25-hydroxyvitamin D and parathyroid hormone were lower in preeclamptics than in controls. Magnesium infusion led to significant elevations in magnesium, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone levels and lowered calcium concentrations. Fetuses of treated subjects demonstrated reductions in serum total and ionized calcium and elevations of 1,25-dihydroxyvitamin D and parathyroid hormone. CONCLUSION: Magnesium sulfate infusion causes reductions in both maternal and fetal calcium levels. Both mother and fetus respond with increased 1,25-dihydroxyvitamin D and parathyroid hormone levels, which may prevent more severe maternal, fetal, and neonatal hypocalcemia.

Calcitriol↗