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Biomedical subjects

A C Roy

Publications and source records attributed to A C Roy.

At least 19 recordsLinked to original sources
PubMed2003

Over-expression and secretion of angiogenin in intrauterine growth retardation placenta.

Human angiogenin is a potent inducer of neovascularization. There is a strong evidence to suggest that it might be involved in morphological and angiogenic changes in the placenta, that are necessary for a successful fetal outcome during pregnancy. However, its precise role in the pathogenesis of abnormal pregnancies is yet unknown. Intrauterine growth retardation (IUGR), an abnormal pregnancy is not a specific disease entity per se, but rather a manifestation of many possible fetal and maternal disorders. In this study, we demonstrated, for the first time, that placental explants in vitro secrete significantly elevated levels of angiogenin in placental tissues from patients with IUGR. We also observed enhanced mRNA expression in placenta from these patients. In addition, using the immunohistochemical methods, we observed identical staining of angiogenin to villous syncytiotrophobalst and fetal endothelial cells in both IUGR and normal placenta. Functionally active placental explants were used to detect immunoreactive angiogenin in conditioned media of all the samples from IUGR placenta and normal term group. The mean levels of angiogenin secreted by IUGR placenta were 1.4-, 1.6-, and 1.3-fold higher (P < 0.01) than normal term samples at 24, 48, and 72 hr of culture, respectively. Expression profiles of angiogenin from term and IUGR cases are in agreement with its mRNA levels and immunoblot analysis. In conclusion, the significant elevated levels of angiogenin in IUGR placenta may provide a molecular mechanism for the abnormal placental development.

Female↗
PubMed2003

Visuo-motor control of the ipsilateral hand: evidence from right brain-damaged patients.

We investigated the extent to which the right hemisphere is involved in the control of the ipsilateral hand by analysing the kinematics of right-hand prehension in right brain-damaged (RBD) patients. We required patients to grasp one of five possible objects, equally-sized and distributed over a 40 degrees wide workspace. With the purpose of investigating the right hemisphere contribution to the on-line visuo-motor control, we also assessed patients' ability to correct their movement "in-flight", in response to a sudden change of object position. Patients' performance was compared to that of aged-matched controls. A Younger group of healthy subjects, matching the population classically tested on double-step paradigms, was also evaluated to fully assess whether patients' kinematics could be partially due to normal ageing. As a further aim, the possible influence of hemispatial neglect was evaluated by comparing the performances of right brain-damaged patients with and without neglect. In normal subjects, the results confirmed and extended the notion of (a). positional tuning of grip formation, and (b). fast reactions following a change in object position. In addition, subtle effects of ageing on visuo-motor behaviour were shown by less efficient movement correction in the Elderly group. Patients executing reach-to-grasp actions into the left contralesional hemispace were selectively affected in both temporal and spatial aspects of movements. While their performances were relatively well preserved in the right hemispace, patients did not show positional tuning of grip formation, nor fast corrections of their movements when acting in the left hemispace. Interestingly, similar deficits were found irrespective of the presence of neglect. These results show that the right hemisphere contributes to the processing of visuo-motor information that is necessary for executing actions with the ipsilateral hand in the contralateral space.

Adult↗
PubMed2003

Expression and secretion of the vascular cell adhesion molecule-1 in human placenta and its decrease in fetal growth restriction.

OBJECTIVE: The vascular cell adhesion molecule-1 (VCAM-1) is a member of the immunoglobulin gene superfamily and is expressed principally on endothelial cells. The present study was undertaken to compare the expression and secretion of VCAM-1 from normal pregnancies and those complicated by fetal growth restriction (FGR). METHODS: Placentas from first-trimester (FT) (n = 17), normal term (n = 19), and FGR (n = 16) patients were collected immediately after elective cesarean delivery. VCAM-1 mRNA expression profiles by reverse transcriptase polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay using explant culture in vitro, and its cellular localization by confocal microscopy were compared between FGR and normal placentas. RESULTS: Functionally active placental explants were used to detect immunoreactive VCAM-1 in conditioned media of all the samples from the three groups. The mean levels of VCAM-1 produced by FT villi were found to be 1.9-, 1.7-, and 1.5-fold higher (P <.02) than term villi at 24, 48, and 72 hours of culture, respectively. Conversely, the respective mean levels of VCAM-1 produced by FGR placental villi were 2.3-, 2.5-, and 2.0-fold lower than levels of the normal term placental villi (P <.05). The secretion profiles of VCAM-1 from FT, term, and FGR villi correlated well with the mRNA levels; the amount secreted in FT villi was twice that of term villi. Moreover, mRNA transcripts from FGR pregnancies showed significantly decreased expression, in conformity with explant results. CONCLUSIONS: The presence of VCAM-1 in placental villi and down-regulation of its production at term indicate that VCAM-1 production is specific to developmental stage. The decreased VCAM-1 expression in FGR pregnancy could be attributed to the uteroplacental deficiency that is characteristic of this condition.

Adult↗
PubMed2002

Functional characterization of a natural variant of luteinizing hormone.

Luteinizing hormone (LH) plays an important role in the gametogenesis in both sexes by promoting the production of sex steroid hormones in the testes and ovaries. We previously described a genetic variant (V) of LH resulted from a mutation (G1502A) in the LH beta-subunit gene, causing the glycine102serine change in the protein hormone. This variant was subsequently found to be associated with both male and female infertility. In this study, we determined the functional aspect of this LH variant in vitro. Site-directed mutagenesis was employed to construct the V-LH beta-subunit gene. Bioactivities of V-LH expressed in Chinese hamster ovary (CHO) cells cotransfected with the V-beta-subunit and native alpha-subunit genes were compared to those of wild-type (WT) LH. The amino acid replacement did not result in the change of efficacy of alpha- and beta-subunit dimerization of the hormone. However, V-LH had significantly lower receptor-binding activity (P<0.001) and lower biopotency for progesterone production (P<0.001) than WT-LH at the higher concentrations of LH. Considering the latter and its known association with both male and female infertility, it is suggested that the V-LH may be a contributing factor to the pathogenesis of infertility in the carriers of this variant.

Animals↗
PubMed2002

Expression and localization of angiogenin in placenta: enhanced levels at term over first trimester villi.

Human angiogenin, a 14-kDa non-glycosylated polypeptide with both angiogenic and ribonucleolytic activities, is implicated in angiogenesis, a complex process of proliferation and formation of new capillary blood vessels from existing blood vessels. Placental growth requires extensive angiogenesis, which develops its vascular structure in both fetal chorionic villi and maternal deciduas. In this study, we investigated the expression profiles of angiogenin in placental villi from early and late gestation at both mRNA and protein levels using explant cultures in vitro followed by RT-PCR, immunoblot, and immunohistochemical analyses. From functionally active placental explants, angiogenin was detected in conditioned media of all the samples from first trimester and term group. The mean levels of angiogenin produced by term villi were found to be 2.6-, 2.1-, and 2.2-fold higher (P < 0.01) than first trimester villi at 24, 48, and 72 hr of culture, respectively. Expression profiles of angiogenin from term and first trimester villi seem to agree with its mRNA levels and immunoblot analysis; the expression in term villi was twice that in first trimester villi. The presence of angiogenin in placental villi and upregulation of its production towards term indicate that angiogenin production by the placenta is specific to the developmental stage. In conclusion, the observed changes in the localization and mRNA expression of angiogenin during placental development raise the possibility that it is involved in morphological and angiogenic changes in this endocrine organ vital to the successful fetal outcome during pregnancy.

Adult↗
PubMed2001

Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome.

Normal gonadal function is critically dependent on the integrity of pituitary-gonadal axis, where follicle-stimulating hormone (FSH) plays a key role. In the female, FSH is required for follicular growth, estrogen production and oocyte maturation. Its function is mediated by its specific receptor (FSHR), and defective FSHR has been shown to affect folliculogenesis and ovarian function. In this study, we screened the entire coding region of FSHR gene for pathogenic mutations in women with premature ovarian failure (POF) (n = 16) and polycystic ovary syndrome (PCOS) (n = 124) and found no mutations in these patients. Two known polymorphisms, Thr307Ala and Ser680Asn showed similar distributions of the allelic variations and protein isoforms in PCOS and normal control subjects (n = 236). It appears from this study that mutations in the coding regions of FSHR gene are not a causative factor of the above clinical manifestations in Chinese Singapore women.

Adolescent↗
PubMed2001

Expression profiles of interleukin-15 in early and late gestational human placenta and in pre-eclamptic placenta.

The presence of interleukin-15 (IL-15) mRNA in human placenta has been demonstrated previously. The present study was undertaken to investigate the expression profiles of IL-15 mRNA and protein in early and late gestational placental tissues, and also the effect of labour on its production. Levels of placental IL-15 expression were also determined in patients presenting with pre-eclampsia. An explant culture system was used to study the release of immunoreactive IL-15 by the placental tissues. Enzyme-linked immunosorbent assays were employed to quantify concentrations in the culture medium. The results showed that placental tissues from all groups released immunoreactive IL-15 into the culture medium. Moreover, the level of secretion by the term placental tissues was much higher than that by first trimester tissues. The presence of labour at term resulted in a further increase in placental IL-15 production. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the expression of IL-15 mRNA in these tissues. The results confirmed the expression of IL-15 in placenta from all the groups and the mRNA levels in the samples was highly correlated with the respective protein concentrations. Levels of both IL-15 mRNA and protein were significantly reduced in the pre-eclamptic placental tissue compared with the normal controls. The present study suggests an important role for this novel cytokine in human pregnancy.

Culture Media↗
PubMed2001

Hemostatic and fibrinolytic status in patients with ovarian cancer and benign ovarian cysts: could D-dimer and antithrombin III levels be included as prognostic markers for survival outcome?

We determined the hemostatic and fibrinolytic status in 60 patients with ovarian cancer and benign ovarian cysts. Hypercoagulation, increased platelets, and enhanced fibrinolysis were seen in patients with preoperative ovarian cancer compared to patients with benign ovarian cysts. Enhanced thrombin generation, evidenced by increased F1+2 and decreased antithrombin III (ATIII) levels with further enhanced fibrinolysis by elevated D-dimer, was seen in advanced cancer. Ten ovarian cancer patients died within 13 months after diagnosis and another died at 24 months, all from advanced stage of cancer, except one from stage IC cancer who died at 11 months. The survival rates from the disease at 13 months and 24 months were 66.7% and 45%, respectively. Most of the patients had gone through the complete course of chemotherapy, and those patients still alive have been disease free between 13 and 42 months. No statistical relationships for the hemostatic parameters studied in ovarian cancer patients could be found between those who died and those still living 13 and 24 months after diagnosis, except for ATIII and D-dimer levels. Elevated D-dimer levels were associated with those who died within 13 and 24 months from the disease, and the decreased ATIII levels only reached statistical significance by 24 months. It could be suggested that these two parameters might be useful as systemic prognostic markers in survival outcome from the disease for the first 24 months in advanced ovarian cancer, in addition to the known correlation with the International Federation of Gynecology and Obstetrics stage.

Adolescent↗
PubMed2001

Association between estrogen receptor-beta gene polymorphisms and ovulatory dysfunctions in patients with menstrual disorders.

Estrogen plays a significant role in human ovulation. It acts as an important positive regulator of the preovulatory gonadotropin surge necessary to initiate the cascade of events leading to ovulation. The steroid hormone exerts its physiological responses through the estrogen receptor (ER), of which two subtypes, ERalpha and ERbeta, are known. ERbeta messenger ribonucleic acid occurs maximally in the ovaries and granulosa cells; thus, ERbeta may be essential for normal ovulation. In a recent gene knockout study, it has been shown that ERbeta gene null female mice develop normal reproductive tract and ovaries during pre- and neonatal periods, but have an abnormal frequency of spontaneous ovulation in adulthood. In the present case-control study, we explored the association of two recently described ERbeta gene polymorphisms, RSAI and ALUI, with ovulatory dysfunctions. The respective frequencies of these polymorphisms were significantly higher in patients than in controls (P= 0.009 and P= 0.059). The polymorphisms were significantly associated with ovulatory dysfunctions, especially in patients homozygous for the polymorphisms (P = 0.016 and P = 0.038, respectively). The compound homozygosity of the polymorphisms was seen only in patients (n = 5) and not controls (P = 0.009). The serum levels of LH, FSH, and progesterone were lower in the homozygous and compound homozygous than in the respective nonpolymorphic patients. All five compound homozygous patients had ovulatory dysfunctions with no etiological pathology. Our results suggest that ERbeta gene RSA:I and ALU:I polymorphisms may be associated with ovulatory defects in some patients, especially those with unknown causes.

Adolescent↗
PubMed2001

Balloon endometrial thermoablation--an alternative management of adenomyosis with menorrhagia and dysmenorrhoea.

A 45 years old Chinese housewife presented with menorrhagia and dysmenorrhoea due to adenomyosis failed to respond to various medical treatments. She was treated with balloon thermoablation. The total menstrual blood loss (MBL) decreased from 96.94 ml before to 37.57 ml, six months after thermoablation. The pictorial blood loss chart (PBLC) showed similar decrease in blood loss. Dysmenorrhoea was also cured. At three year follow up, there was no recurrence. This is the first report which shows thermoablation decreases MBL objectively and can be tried to treat adenomyosis.

Catheterization↗
PubMed2000

Hand kinematics during reaching and grasping in the macaque monkey.

In this paper, we develop an animal model of prehension movements by examining the kinematics of reaching and grasping in monkeys and by comparing the results to published data on humans. Hand movements were recorded in three dimensions in monkeys who were trained to either point at visual targets under unperturbed and perturbed conditions, or to reach and grasp 3-D objects. The results revealed the following three similarities in the hand kinematics of monkey and man. (1) Pointing movements showed an asymmetry depending on target location relative to the hand used; in particular, movements to an ipsilateral target took longer than those to a contralateral one. (2) Perturbation of target location decreased the magnitude of the velocity peak and increased the duration of pointing movements. (3) Reaching to grasp movements displayed a bell-shaped wrist velocity profile and the maximum grip aperture was correlated with object size. These similarities indicate that the macaque monkey can be a useful model for understanding human motor control.

Animals↗
PubMed2000

Association of AccI polymorphism in the follicle-stimulating hormone beta gene with polycystic ovary syndrome.

OBJECTIVE: To search for FSH beta-subunit gene mutations in patients with polycystic ovary syndrome (PCOS) and determine the association between the mutations and the syndrome. DESIGN: Clinical and molecular studies. SETTING: Clinics and laboratories of the National University Hospital Obstetrics and Gynecology Department in Singapore. PATIENT(S): One hundred thirty-five patients with PCOS and 105 normal control subjects. INTERVENTION(S): Exons two and three were screened for mutations by single-stranded conformational polymorphism and DNA sequencing. MAIN OUTCOME MEASURE(S): Polymerase chain reaction followed by restriction enzyme analysis. RESULT(S): No missense mutation was found in the functional units of the FSHbeta gene in patients with PCOS, but a thymine-cytosine substitution in exon 3 (codon 76, TAT to TAC) was identified. The nucleotide change led to creation of an AccI digestion site. The distribution pattern of AccI polymorphism in the patients was significantly different from that in the control group, and the occurrence of homozygous carriers was significantly higher in patients (12.6%) than in the control group (3.8%). The frequency of polymorphism and prevalence of homozygosity were significantly higher in patients with PCOS with obesity (0.50% and 31.0%, respectively) than in those with menstrual disorders only (0.366% and 8.5%, respectively), which correlated with significantly higher androgen levels in the obese patients. CONCLUSION(S): The AccI polymorphism in FSHbeta gene may be associated with PCOS in some women, especially those with obesity.

Acne Vulgaris↗
PubMed2000

Mitochondrial gene mutations in gestational diabetes mellitus.

Mitochondrial DNA mutations have been implicated in many diseases including diabetes mellitus. Although gestational diabetes mellitus (GDM) has been suggested to have genetic determinant and to be etiologically indistinct with non-insulin-dependent diabetes mellitus (NIDDM), its association with mitochondrial gene mutations is still unknown. In this study, 137 patients with GDM and 292 non-diabetic pregnant controls were examined for mitochondrial DNA mutations from the nucleotide 3130-4260 encompassing tRNA-Leu gene and adjacent NADH dehydrogenase 1 gene by polymerase chain reaction, single-stranded conformation polymorphism, restriction fragment length polymorphism and DNA sequencing. One heteroplasmic mutation at the position of 3398 (T-C), which changed a highly conserved methionine to threonine in NADH dehydrogenase subunit 1, was identified in 2.9% GDM patients but not in the controls, indicating its association with GDM (P = 0.01). Two novel mutations, a heteroplasmic C3254A and a homoplasmic A3399T, were also found in GDM subjects, the functional meaning of which merits further investigation. G3316A and T3394C mutations implicated in NIDDM, were seen at higher frequencies in patients with GDM than the controls. Our results suggest that mitochondrial DNA mutations may contribute to the development of GDM in some patients.

Adult↗
PubMed2000

Increased expression of interleukin 6 in term compared to the first trimester human placental villi.

Cytokines and their specific receptors expressed at the feto-maternal interface are known to play a critical role in regulating various placental functions. Interleukin 6 (IL-6) has been shown to be produced by both decidua and the trophoblast cells of the placenta. The aim of the present study was to examine the expression profile of placental IL-6 protein and mRNA at early and late stages of gestation. Placental villi were obtained from women undergoing first trimester pregnancy termination or elective Cesarean section at term. Functionally active placental explant culture system was used to study the release of IL-6 by these tissues. IL-6 was detected in placental conditioned media of all the samples from first trimester and term group. The mean levels of IL-6 produced by term villi were found to be 5.5, 7.5 and 5-fold higher at term when compared with the first trimester at 24 h, 48 h and 72 h of culture, respectively. Expression of IL-6 mRNA was demonstrated by RT-PCR performed on total RNA isolated from these tissues. IL-6 mRNA expression was detected in both early and late gestational placental tissues. Moreover, the level of IL-6 mRNA was found to be approximately 4-fold higher at term compared with first trimester. These data are consistent with the hypothesis that levels of IL-6 production by the placenta are developmental stage-specific and suggest that expression of IL-6 in the placenta could be subjected to transcriptional regulation.

Cells, Cultured↗
PubMed2000

Association of molecular variants of luteinizing hormone with male infertility.

Luteinizing hormone (LH) stimulates the interstitial Leydig cells to produce testosterone, which is essential for spermatogenesis. Abnormalities in the function of LH may affect the process of spermatogenesis and thus result in infertility. The aim of this study was to determine the association of three known variants of LH (Gln54Arg [Trp8Arg; Ile15Thr] and Gly102Ser) with male infertility. A total of 145 infertile men and 200 healthy fertile men were recruited and screened for the presence of these three LH variants. The Gln54Arg variant could not be detected in either of the groups studied. Twelve infertile (8.2%) and 15 fertile (7.5%) men were found to carry the [Trp8Ile; I15Thr] variant, but its occurrence did not show any significant difference between the patient and control groups. The Gly102Ser variant was detected in five patients with infertility (3.4%), but not in the control subjects (P = 0.013). This study showed that the Gln54Arg and [Trp8Ile; I15Thr] variants in the LHbeta gene were not associated with male infertility, whereas the Gly102Ser variant might be implicated in infertility in some Singapore Chinese men.

Adult↗
PubMed2000

Preliminary investigation of follistatin gene mutations in women with polycystic ovary syndrome.

Strong evidence for a link between the follistatin gene and polycystic ovary syndrome (PCOS) has recently been found in a well-designed large-scale study. Follistatin binds to activin and affects its functions, e.g. stimulation of FSH synthesis and secretion. Thus, it may play a role in the functional impairment of the FSH-granulosa cell axis in PCOS. In this study, we screened 64 Chinese patients with PCOS for mutations in the entire coding region (including the region encoding alternative carboxy-terminals) of the follistatin gene using polymerase chain reaction (PCR)-based single-stranded conformational polymorphism (SSCP) and DNA sequencing. However, we could not identify a single mutation of either the activating or inhibiting type, using these techniques. Therefore, it would appear that PCOS in the local Chinese population is not caused by mutations in the coding regions of the follistatin gene.

Adult↗
PubMed2000

Effect of T-helper 1 cytokines on secretion of T-helper 2 cytokines by term trophoblast cells in culture.

A successful pregnancy has been postulated to be the result of a discrete balance between T-helper 1 (Th1) and T-helper 2 (Th2) type cytokines involved in growth and development of the conceptus. The aim of the present study was to examine the effect of Th1 cytokines (interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha)) on the release of Th2 cytokines including IL-6 and IL-10 by trophoblast cells obtained from term placenta. Trophoblast cells isolated by enzymatic disaggregation and Percoll gradient fractionation were cultured in supplemented medium alone or with varying concentrations of the selected recombinant cytokines. After 48 h of incubation, samples of the culture supernatant were analyzed for the Th2 cytokines IL-6 and IL-10 using specific ELISA assays. Both IL-1 beta and TNF alpha had no effect on the cell number and viability as determined by MTT assay. IL-1 beta significantly stimulated trophoblast release of IL-6 in a dose-dependent manner (3.3-, 5.5-, 10.3- and 22.4-fold higher compared to the control at 10, 50, 100, 500 U IL-1 beta/ml respectively, p < 0.05). TNF alpha also stimulated release of IL-6 by these cells. However, the stimulation at lower concentrations was not very high and a significant (p < 0.05) stimulation was observed only at higher concentrations (1.1-, 1.3-, 2.6- and 5.9-fold higher at 500, 1000, 1500, 2000 U TNF alpha/ml respectively). In contrast, neither IL-1 beta or TNF alpha exerted any significant effect on IL-10 release by term trophoblast cells (p > 0.05). The results of this study provide evidence that production of Th2 cytokines might be under the control of different regulatory pathways.

Cells, Cultured↗