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Biomedical subjects

S A Tan

Publications and source records attributed to S A Tan.

At least 19 recordsLinked to original sources
PubMed1995

Polymer encapsulated cell lines genetically engineered to release ciliary neurotrophic factor can slow down progressive motor neuronopathy in the mouse.

Ciliary neurotrophic factor (CNTF) has recently generated great interest due to its potential as a therapeutic agent for the treatment of human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Because the systemic half-life of CNTF is only in the order of a few minutes, continuous delivery of this trophic factor could be attractive or even necessary in the therapy of these diseases. One promising technique involves the polymer encapsulation of cells which have been genetically modified to secrete neurotrophic factors. The polymer capsules can be implanted into animals and effect the slow release of the protein for several months. The encapsulation technique immuno-isolates the foreign cells from host immune cells and at the same time prevents tumour formation by the transplanted cells. In this study, we have used progressive motoneuronopathy (pmn) mice to determine the extent to which encapsulated cell lines secreting CNTF could alter the course of the disease. pmn/pmn homozygotes present severe loss of myelinated motor fibres and a significant reduction of facial motoneuron cell bodies. The mice develop weakness of the hindlimbs and die during the sixth week after birth. We found that CNTF delayed the disease progression by increasing the survival time by 40% and by improving motor function as assessed by three behavioural tests. Moreover, histological counts of the phrenic nerve myelinated axons and facial nucleus motoneurons indicated a significant reduction of motoneuron loss. These results suggest that polymer-encapsulated cells releasing neurotrophic factors may provide a potential delivery system for treating neurodegenerative diseases such as ALS.

Animals↗
PubMed1995

Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease.

Bcl-2 and its analogs protect different classes of neurons from apoptosis in several experimental situations. These proteins may therefore provide a means for treatment of neurodegenerative diseases. We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn). Pmn/pmn mice lose motoneurons and myelinated axons, and die at 6 weeks of age. When these mice were crossed with transgenic mice that overexpress human Bcl-2, there was a rescue of the facial motoneurons with a concomitant restoration of their normal soma size and expression of choline acetyltransferase. However, Bcl-2 overexpression did not prevent degeneration of myelinated axons in the facial and phrenic motor nerves and it did not increase the life span of the animals. Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself be sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.

Animals↗
PubMed1994

Glial cell line-derived neurotrophic factor (GDNF), a new neurotrophic factor for motoneurones.

Glial cell line-derived neurotrophic factor (GDNF) has been postulated to be a specific dopaminergic neurotrophic factor since it selectively enhances the survival of dopaminergic neurones in vitro. We report here that GDNF can also act as a neurotrophic factor for motoneurones. GDNF released by GDNF-transfected BHK cells increases the activity of choline acetyltransferase (ChAT) in cultures from embryonic rat ventral mesencephalon containing cholinergic neurones from cranial motor nuclei and in cultured spinal motoneurones. Furthermore, local application of polymer-encapsulated BHK cells releasing GDNF to transected facial nerve in newborn rats diminishes the death of motoneurones normally occurring after axotomy in the neonatal period. The present results indicate that GDNF may have a therapeutic potential in human motoneurone diseases such as amyotrophic lateral sclerosis.

Animals↗
PubMed1994

Birth defects--the state of awareness amongst mothers.

Birth defects have in recent years become the major cause of perinatal morbidity and mortality. The incidence of birth defects is between 2% to 6% of all live births. However, from a survey carried out in Singapore General Hospital (SGH), the majority of mothers enter pregnancy without realising the risks that they or their offspring may face. Only 20% to 25% of mothers were aware of the actual incidence of birth defects, and only 2.5%-10% knew that the risk of Down Syndrome (DS) increases with maternal age. However, the use of ultrasound is now well accepted and is considered a necessary investigation by 90% of the mothers surveyed.

Congenital Abnormalities↗
PubMed1992

The diagnostic value and patient acceptability of outpatient endometrial sampling with Gynoscann.

Endometrial sampling with Gynoscann was performed in the outpatient department in 70 women with abnormal vaginal bleeding prior to dilatation and curettage (D&C). Successful endometrial sampling was achieved in 62 (89%) patients; Of the samples obtained 44 (71.0%) were adequate for cytological assessment and 46 (74.2%) for histological assessment, compared to 80% of D&C samples being adequate for histological examination. In those patients in whom outpatient endometrial sampling was adequate, both the cytological and histological diagnosis agreed with the D&C. The outpatient endometrial sampling was well tolerated by the patients since the majority (89%) experienced either no or little pain. Vaginal bleeding following the procedure was minimal in all except 1 patient. Endometrial sampling with Gynoscann may be useful for endometrial assessment prior to commencement of hormonal therapy and hysterectomy. It is a potentially useful screening test for early detection of endometrial cancer in patients at risk.

Adult↗
PubMed1992

Elevated plasma glucagon in amyotrophic lateral sclerosis.

This study shown an abnormality in glucagon levels that may explain the glucose intolerance, abnormal insulin reactions, and abnormal plasma amino acid levels seen in amyotrophic lateral sclerosis (ALS). We randomly administered two test meals, differing only in protein source (soy versus casein) at least 1 week apart and measured fasting and postprandial bloods for glucagon, insulin, and glucose levels in 11 ALS patients. With the soy test meal, glucagon levels were elevated in all ALS patients compared with controls: at fasting (237 +/- 111 versus 108 +/- 46 pg/ml, p less than 0.01) and 1/2 hour (389 +/- 94 versus 133 +/- 68 pg/ml, p less than 0.001), and 2 hours postprandial (379 +/- 75 versus 108 +/- 53 pg/ml, p less than 0.001). Glucagon levels after the casein test meal were also significantly elevated. Insulin was elevated by both test meals. Casein produced significant glucose intolerance.

Adult↗
PubMed1992

Placental chorioangioma: a case report and review.

Placental Chorioangioma occurs in 1% of pregnancies and are generally asymptomatic. However, they are known to cause a number of complications which are detrimental to the mother, fetus or the neonate. A typical case where acute polyhydramnios precipitated premature labour and delivery of the fetus as a result of a large placental chorioangioma is presented. A brief review of the other possible complications are also included.

Adult↗
PubMed1991

Effects of exogenous monoiodotyrosine on the serum levels of anterior pituitary hormones.

Monoiodotyrosine is a tyrosine hydroxylase inhibitor. Ingestion of one gram monoiodotyrosine caused a 10,000-fold increase of serum monoiodotyrosine from basal levels of 0.69 +/- 0.20 nmol/l to a peak of 10.6 +/- 1.7 mumol/l in women and 7.1 +/- 2.3 mumol/l in men 30 min later, and the t1/2 was 45 min. Monoiodotyrosine stimulated PRL to a peak of 170 +/- 51 micrograms/l in women and 90 +/- 6 micrograms/l in men 30 min after the monoiodotyrosine peak, or 60 min after the ingestion. Other anterior pituitary hormones were unchanged. Dopamine infusion or L-dopa pretreatment attenuated the monoiodotyrosine effect. TRH exaggerated the PRL peak, and chlorpromazine did not increase but prolonged the hyperprolactinemia. These results suggest that dopamine synthesis inhibition may be the mechanism of PRL stimulation.

Adult↗
PubMed1990

Modulation of the renin-aldosterone system by iodotyrosines as tyrosine hydroxylase inhibitors.

This study shows that MIT and DIT stimulate aldosterone secretion. This may be due to their tyrosine hydroxylase inhibitory property. Dopamine abolishes the stimulation. Prolonged MIT administration enhances the stimulation of aldosterone secretion and can cause hypokalemia. Volume expansion reverses the hyperaldosteronism. PRA and blood pressure do not change, even after prolonged MIT intake.

Adult↗
PubMed1990

Hyperiodotyrosinemia-induced hyperprolactinemia and hyperaldosteronism.

A 21-year-old goitrous hypothyroid Chinese woman had elevated serum iodotyrosines with a monoiodotyrosine level of 85.9 nmol/l (normal 0.49-0.89 nmol/l) and a diiodotyrosine level of 25.3 nmol/l (normal 0.023-0.53 nmol/l). She was amenorrheic with low luteinizing hormone and follicle-stimulating hormone levels at 5.8 and 2.8 U/l, respectively. The hypogonadotropic hypogonadism was due to an elevated prolactin level of 8.8 nmol/l. She also had a low potassium level of 3.2 mmol/l, and a high urinary aldosterone level of 158 nmol/day. The hyperprolactinemia, hypogonadotropic hypogonadism, hyperaldosteronism and hypokalemia subsided with the administration of bromocriptine 5 mg/day. However, bromocriptine accentuated the hyperiodotyrosinemia, and the patient remained hypothyroid. Levothyroxine therapy lowered the monoiodotyrosine and diiodotyrosine levels, ameliorated all her endocrinopathies, started her periods, and shrank the goiter. She probably had a deiodinase defect which permitted the discharge of accumulated iodotyrosines from the thyroid gland. Since iodotyrosines are tyrosine hydroxylase inhibitors, the hyperiodotyrosinemia causes dopamine synthesis inhibition, and induces the hyperprolactinemia and hyperaldosteronism.

Adult↗
PubMed1990

Extrathyroidal physiology of monoiodotyrosine in humans.

Normal serum monoiodotyrosine (MIT) levels (n = 152) were 0.69 +/- 0.20 nmol/l. There was wide variation of MIT levels in a 24-hour period without diurnal pattern, and there was no change throughout the menstrual cycle. MIT levels declined upon aging, but levels in hypo- and hyperthyroidism were not significantly different. MIT levels were detected in athyrotic patients (0.32 +/- 0.08 nmol/l). Desiccated thyroid raised the athyrotic MIT levels to the normal range, while levothyroxine did not. Diiodotyrosine (DIT) infusion caused an MIT rise which paralleled but lagged 1 h behind the DIT rise. These data suggest thyroidal as well as nonthyroidal sources of MIT, one of which is deiodination of DIT. Ingestion of 1 g MIT increased serum MIT to 10.6 +/- 1.7 mumol/l in women, and 7.1 +/- 2.3 mumol/l in men 30 min after ingestion; the serum half-life was 45 min.

Adult↗
PubMed1990

The effect of long endurance running on natural killer cells in marathoners.

Ten experienced marathoners were exercised 3 h in the laboratory. Blood samples were collected at 0 h baseline, 1 h exercise, and 5 min, 1.5 h, 6 h, and 21 h recovery and were analyzed for total number of lymphocytes expressing membrane antigens found on natural killer (NK) cells. NK activity was also measured. Four of the seven subpopulations of lymphocytes studied, Leu-11+19+, Leu-11+19-, Leu-11+7-, and Leu-19+11-, showed significant within-subject effects over time, using repeated measures ANOVA. Simple contrasts with baseline values showed that, at 1.5 h and 21 h recovery, total number of lymphocytes bearing three different combinations of NK markers, Leu-11+19+, Leu-11+19-, and Leu-11+7-, were significantly decreased when compared with baseline values. At 1.5 h recovery, NK activity was significantly decreased below baseline levels for four of the six effector NK cell/target K562 myelogenous leukemia cell (E:T) ratios tested. At 6 h recovery, NK activity was still decreased significantly with the 12.5:1 and 3:1 E:T ratios. By 21 h recovery, NK activity did not differ significantly from baseline levels. Cortisol levels at 5 min post-exercise were negatively correlated with NK activity at 1.5 h recovery (r = -0.62, P = 0.05, 50:1 E:T ratio; r = -0.66, P = 0.04, 25:1 E:T ratio). Further research is needed to elucidate the effect these changes have on host immunosurveillance and immunoresponsiveness in vivo.

Epinephrine↗
PubMed1989

Complement and immunoglobulin levels in athletes and sedentary controls.

Eleven marathon runners (42.7 +/- 2.1 yrs, 54.2 +/- 1.8 ml.kg-1.min-1) and nine sedentary controls (44.2 +/- 1.2 yrs, 33.3 +/- 1.1 ml.kg-1.min-1) were studied during 30 min of rest, a graded maximal treadmill test using the Balke protocol, and 45 min of recovery to determine the effects of training and acute exercise on complement and immunoglobulin levels. Three baseline and five recovery blood samples were obtained in addition to repeated 5-min samples during exercise. Data for the exercise period were analyzed using a multiple regression approach to repeated measures ANOVA to allow comparison between groups on a percent VO2max basis. Groups did not differ during any of the three phases for IgG, IgA, or IgM. Resting levels of complement C3 (0.89 +/- 0.05 vs 1.27 +/- 0.10 g/L, P less than 0.001) and C4 (0.19 +/- 0.02 vs 0.29 +/- 0.03 g/L, P less than 0.001) were significantly lower in athletes than in controls. Exercise complement C3 [F(1,18) = 14.1, P = 0.001] and C4 [F(1,18) = 7.6, P = 0.013], and recovery complement [F(1,18) = 19.4, P less than 0.001] and C4 [F(1,18) = 13.5, P = 0.002] were also lower in the athletes than in sedentary controls. Acute increases during exercise were not associated with changes in catecholamines or cortisol. These data suggest that blood concentrations of C3 and C4, but not IgG, IgA, or IgM, are decreased during rest, graded maximal exercise, and recovery in marathon runners in comparison with sedentary controls.

Adult↗
PubMed1989

Effects of long-endurance running on immune system parameters and lymphocyte function in experienced marathoners.

The extent and duration of changes in leukocyte subsets, lymphocyte subpopulations, spontaneous blastogenesis, cortisol, and catecholamines were measured in ten experienced marathoners, who ran 3 h to exhaustion in a laboratory setting. Blood samples were taken at baseline, 1 h of exercise, and 5 min, 1.5 h, 6 h, and 21 h of recovery. The 3-h endurance run was associated with significant leukocytosis, granulocytosis, neutrophilia, monocytosis, and eosinopenia during recovery. All of these parameters except for eosinophils returned to normal by 21 h of recovery. Total lymphocyte count increased 31% at 1 h of exercise, then decreased 19% at 1.5 h of recovery when compared with baseline values. T cell count showed no significant changes, but B cell lymphocytosis was measured at 5 min and 6 h of recovery. T helper/T suppressor ratio (H/S) was significantly elevated 39% at both 1.5 h and 21 h of recovery due to the decrease in number of T suppressor cells. Spontaneous blastogenesis was significantly increased 52% by 1 h of exercise and remained elevated throughout recovery. The increase in cortisol from baseline to 1.5 h of recovery correlated positively with the increase in both total leukocyte count (r = 0.78, P = 0.008) and granulocyte count (r = 0.81, P = 0.005). Our results suggest that exhaustive endurance exercise in marathon runners is associated with many significant perturbations in immune system parameters, most of which return to normal levels at 21 h of recovery.

Adult↗
PubMed1989

Neuroendocrine and stress hormone changes during mirthful laughter.

Positive emotional activities have been suggested as modifiers of neuroendocrine hormones involved in the classical stress response. To detect changes in these components during a mirthful laughter experience, the authors studied 10 healthy male subjects. Five experimental subjects viewed a 60 minute humor video and five control subjects did not. Serial blood samples were measured for corticotropin (ACTH), cortisol, beta-endorphin, 3,4-dihydrophenylacetic acid (dopac)--the major serum neuronal catabolite of dopamine, epinephrine, norepinephrine, growth hormone, and prolactin. Repeated measures analysis of variance showed that cortisol and dopac in the experimental group decreased more rapidly from baseline than the control group (p = 0.011, p = 0.025, respectively). Epinephrine levels in the experimental group were significantly lower than the control at all time points (p = 0.017). Growth hormone levels in the experimental group significantly increased during baseline (p = 0.027) and then decreased with laughter intervention (p less than 0.0005), whereas, the controls did not change over time (p = 0.787). ACTH, beta-endorphin, prolactin, and norepinephrine levels did not significantly increase. The mirthful laughter experience appears to reduce serum levels of cortisol, dopac, epinephrine, and growth hormone. These biochemical changes have implications for the reversal of the neuroendocrine and classical stress hormone response.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Distribution of ciliatine (2-aminoethylphosphonic acid) and phosphonoalanine (2-amino-3-phosphonopropionic acid) in human tissues.

Ciliatine (2-aminoethylphosphonic acid) was detected in the human brain, heart, kidney, liver, intestine, spleen, adrenal glands, and aorta. Phosphonoalanine (2-amino-3-phosphonopropionic acid) was found in the human liver, intestine and spleen. Tissue homogenates were extracted with trichloroacetic acid and a chloroform-methanol mixture. After hydrolysis, each fraction was subfractionated by ion-exchange chromatography and examined by paper chromatography and electrophoresis using a specific ninhydrin-molybdate staining procedure to detect the phosphonic acids. The acids were found bound either to lipid or to protein; no free phosphonic acid was detected.

Adrenal Glands↗
PubMed1988

Determinants of morbidity and mortality due to acute respiratory infections: implications for intervention.

Acute respiratory infections (ARI) were monitored every two weeks in an urban community in Metro Manila, Philippines, to determine the incidence and risk factors for ARI morbidity. Hospitalized children with acute lower-respiratory-tract infection (ALRI) were studied to determine case-fatality rates (CFR) and predictors for mortality. Incidence rates were highest in infants, 3.2-4.0 per person, followed by children one to four years of age, with corresponding rates of 3.0-3.4 per person. The risk factors for ARI morbidity were low socioeconomic status and age less than one year. A CFR of 5% in children with ALRI was observed. Malnutrition and a positive culture of blood were significant risk factors for mortality. These identified risk factors underscore the value of primary health care interventions, such as the standard ARI case management, immunization, health education, promotion of breast-feeding, and vitamin A supplementation, as strategies for reducing ARI mortality in developing countries.

Acute Disease↗