Biomedical subjects

A K Sandhu

Publications and source records attributed to A K Sandhu.

17 recordsLinked to original sources

PubMed2001

Risk factors of uterine rupture.

OBJECTIVE: To determine the incidence of uterine rupture in Ministry of Health Hospitals in Bahrain and to find the risk factors associated with this obstetrical tragedy. METHODS: A case control study was conducted on all the cases of uterine rupture in Ministry of Health Hospitals in Bahrain during the period 1st of January 1990 until 31st of December 1999. The following risk factors which, were studied, included parity, gestational age, previous cesarean delivery, previous cesarean section for cephalopelvic disproportion, previous evacuation of the uterus, induction and or augmentation of labor, malpresentation, duration of the labor, type of the delivery and birth weight. RESULTS: Forty-five uterine ruptures were reported during the study period with an incidence of 1 in 2213 deliveries. Previous cesarean delivery, prior cesarean section for cephalopelvic disproportion, malpresentation, induction and augmentation of labor were found to be significant risk factors for uterine rupture. While high parity, previous evacuation of the uterus, duration of labor, type of the delivery, birth and weight were not associated with uterine rupture. CONCLUSION: An Obstetrician should be careful in monitoring the progress of labor in women with previous cesarean delivery to avoid the occurrence of a ruptured uterus. Oxytocin or prostaglandin or both should be used judiciously to prevent catastrophic uterine rupture.

Adult↗

PubMed2000

Effects of human papillomavirus-associated cells on human immunodeficiency virus gene expression.

OBJECTIVE: To examine the effects of soluble factors secreted by human papillomavirus (HPV)-associated cells on human immunodeficiency virus (HIV) expression. METHODS: Supernatants collected from cultured cervical biopsies and cervical cancer cell lines, and HPV-immortalized and normal keratinocytes were tested for the ability to induce HIV p24 production in two cell lines that contained latent HIV (the U1 monocytic line and the ACH-2 T cell line). Levels of HIV p24 were measured by enzyme-linked immunosorbent assay (ELISA). Culture supernatants were also assayed for the inflammatory cytokines interleukin 6, tumor necrosis factor, and interleukin 1 beta by ELISA. RESULTS: Supernatants from all epithelial cells tested upregulated HIV p24 expression in the U1 line but not in the ACH-2 cells. Only differentiated normal keratinocytes induced p24 production by ACH-2 cells. Neutralization of the cytokines, particularly interleukin 6, partially reduced the level of HIV-inducing activity in the culture supernatants. Additionally, cervical biopsies from HIV-infected women cultured in vitro also were able to induce HIV in U1 cells but not ACH-2 cells. CONCLUSIONS: Our results suggest that HPV infection of the cervix might influence HIV pathogenesis by inducing the production of immune and inflammatory factors that enhance HIV expression.

Cervix Uteri↗

PubMed1999

Identification of a gene at 16q24.3 that restores cellular senescence in immortal mammary tumor cells.

We have mapped a cellular senescence gene, SEN16, within a genetic distance of 3 - 7 cM, at 16q24.3. Microcell mediated transfer of a normal human chromosome 16, 16q22-qter or 16q23-qter restored cellular senescence in four immortal cell lines, derived from human and rat mammary tumors. The resumption of indefinite cell proliferation, concordant with the segregation of the donor chromosome, confirmed the presence of a senescence gene at 16q23-qter. While microcell hybrids were maintained in selection medium to retain the donor chromosome, sporadic immortal revertant clones arose among senescent cells. Reversion to immortal growth could occur due to inactivation of the senescence gene either by a mutation or a deletion. The analysis for chromosome 16 specific DNA markers, in revertant clones of senescent microcell hybrids, revealed a consensus deletion, spanning a genetic interval of approximately 3 - 7 cM at 16q24.3.

Adenocarcinoma↗

PubMed1997

Colocalization of P2Y2 and P2Y6 receptor genes at human chromosome 11q13.3-14.1.

Extracellular nucleotides mediate a number of physiological responses through either ligand gated P2X or G protein-coupled P2Y receptors. To date, six P2Y receptor subtypes, P2Y1-P2Y6, have been cloned. We mapped the human P2Y6 receptor gene to chromosome 11q13.3-13.5. Oligonucleotide primers complementary to a part of the human P2Y6 receptor cDNA were used to amplify a region from genomic DNA from a panel of mouse/human somatic cell hybrid cell lines, each containing a single human chromosome. A PCR product of the expected size (714 bp) resulted from a single hybrid cell line containing human chromosome 11. The gene was further localized to a region of chromosome 11 using a subchromosomal hybrid panel containing different segments of chromosome 11. Based on the specific PCR product obtained and its Southern hybridization to the P2Y6 receptor cDNA, the human P2Y6 receptor gene was localized to chromosome 11q13.3-13.5. Previously, we have localized the P2Y2 receptor gene to human chromosome 11q13.5-14.1. This is the first report of the clustering of the P2 receptor genes. The clustering of these two P2Y receptor subtypes suggests a relatively recent expansion of the gene family by gene duplication.

Animals↗

PubMed1996

Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells.

Screening of a human erythroleukemia cell cDNA library with radiolabeled chicken P2Y3 cDNA at low stringency revealed a cDNA clone encoding a novel G protein-coupled receptor with homology to P2 purinoceptors. This receptor, designated P2Y7, has 352 amino acids and shares 23-30% amino acid identity with the P2Y1-P2Y6 purinoceptors. The P2Y7 cDNA was transiently expressed in COS-7 cells: binding studies thereon showed a very high affinity for ATP (37 +/- 6 nM), much less for UTP and ADP (approximately 1300 nM), and a novel rank order of affinities in the binding series studied of 8 nucleotides and suramin. The P2Y7 receptor sequence appears to denote a different subfamily from that of all the other known P2Y purinoceptors, with only a few of their characteristic sequence motifs shared. The P2Y7 receptor mRNA is abundantly present in the human heart and the skeletal muscle, moderately in the brain and liver, but not in the other tissues tested. The P2Y7 receptor mRNA was also abundantly present in the rat heart and cultured neonatal rat cardiomyocytes. The P2Y7 receptor is functionally coupled to phospholipase C in COS-7 cells transiently expressing this receptor. The P2Y7 gene was shown to be localized to human chromosome 14. We have thus cloned a unique member of the P2Y purinoceptor family which probably plays a role in the regulation of cardiac muscle contraction.

Amino Acid Sequence↗

PubMed1996

Cloning and chromosomal localization of the human P2Y1 purinoceptor.

We have isolated two types of human P2Y1 cDNA clones from the human erythro leukemia cell cDNA library. The sequence of both clones codes for the same 373 amino acid polypeptide and these clones differ only in the length of the 3' untranslated region. The long form of the cDNA has 1165 nt 3' untranslated region while the 3' untranslated region in the short form is only 258 nt. Both forms are, however, polyadenylated. A multiple human tissue northern blot indicated two transcripts of approximately 4.4 kb and 7.0 kb. The 4.4 kb mRNA is present in all the eight tissues, while the approximately 7.0 kb transcript is expressed only in placenta, skeletal muscle, and pancreas. Using oligonucleotide primers specific for the human P2Y1 purinergic receptor to amplify a region from genomic DNA from a panel of mouse/human somatic cell hybrid cell lines, we have localized the P2Y1 gene to human chromosome 3.

Amino Acid Sequence↗

PubMed1996

A gene on 6q 14-21 restores senescence to immortal ovarian tumor cells.

We have identified a gene on 6q14-21 which restores senescence to immortal ovarian tumor cells. Single gpt tagged human chromosomes, present in mouse/human monochromosomal hybrids, were introduced into immortal human and rat ovarian tumor cells via microcell fusion. Analysis of chromosome transfer clones for cell morphology and growth properties revealed that chromosome 6 or 6q restored senescence to both human and rat ovarian tumor cells while chromosomes 10 or 14 did not affect the proliferative potential of these cells. Reversion to immortal growth concordant with loss of the donor chromosome confirmed the presence of a senescence gene on 6q. During continuous maintenance of microcell hybrids in MX medium, rare immortal revertant clones grew out of the human and rat senescent cell populations. Analysis of independent revertant clones of rat cells, for chromosome 6 markers, revealed a common deletion of chromosomal region 6q14-21 in all revertants. Restoration of senescence following introduction of a gpt tagged chromosome segment 6q13-21 into human and rat ovarian tumor cells confirmed the location of a senescence gene in this region. In contrast, introduction of a chromosome 6 lacking the region 6q14-21 did not impart senescence in these cells. Based on these results we assigned the senescence gene (SEN 6A) to region 6q14-21.

Animals↗

PubMed1996

Mapping of the P2U purinergic receptor gene to human chromosome 11q 13.5-14.1.

We mapped a human P2U purinergic receptor gene to chromosome 11q13.5-14.1. Oligonucleotide primers complementary to a part of the human P2U purinergic receptor cDNA were used to amplify a region from genomic DNAs from a panel of mouse/human somatic cell hybrid cell lines, each containing a single human chromosome. A PCR product of the expected size (378 bp) resulted from a single hybrid cell line containing human chromosome 11. The gene was further localized to a region of chromosome 11 using a sub-chromosomal hybrid panel containing different segments of chromosome 11. Based on the specific PCR product obtained and its Southern hybridization to the P2U receptor cDNA, the human P2U receptor gene was localized to chromosome 11q13.5-14.1.

Animals↗

PubMed1995

Gene expression in response to retinoic acid in novel human chromosome 21 monochromosomal cell hybrids.

To access a wide a variety of expressed sequence from human chromosome 21 we have placed this chromosome into undifferentiated P19 mouse embryonic carcinoma cells. Cell lines resulting from these experiments have a range of morphologies and a wide variety of karyotypes. We have studied the retinoic acid response of five cell lines, compared to P19 cells, by observing three markers of retinoic acid induced P19 differentiation--cell morphology, RAR alpha and Wnt1 transcription. We see an 'early' retinoic acid response effect, however this response breaks down by the time the 'late' gene. Wnt1 would be transcribed in P19 cells. A highly responsive cell line will be useful for cloning expressed sequences from human chromosome 21 which are produced by early genes in retinoic acid inducible pathways, such as those involved in neurogenesis.

Animals↗

PubMed1995

Chromosomal localization and expressed sequence tag generation of clones from a normalized human adult thymus cDNA library.

Expressed sequence tags (ESTs) from 298 clones have been generated from a randomly primed, normalized human adult thymus cDNA library. We describe the chromosomal localization of 136 of these ESTs by PCR-based mapping to a human monochromosomal somatic cell hybrid panel. Data base similarities to known genes are also described. A subset (n = 18) of these randomly primed ESTs extended the sequence of ESTs from other tissues currently in dbEST. Of the nonrepetitive human adult thymus ESTs generated in this study, 237 (79.5%) have no similarity to current data base entries. This would suggest that our collection contains approximately 100 new coding regions from thymus tissue, a large proportion of which likely will represent the middle regions of genes. The mapped ESTs should prove useful as new gene-based markers for mapping and candidate gene hunting, particularly when anchored to a well-developed physical map of the human genome.

Chromosome Mapping↗

PubMed1994

Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6.

In these studies we show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed limited potential for cell division and morphological characteristics of senescent cells. The loss of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by the analysis for DNA sequences specific for the donor chromosome. Our results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results we propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.

Animals↗

PubMed1994

Complementation of V(D)J recombination defect and X-ray sensitivity of scid mouse cells by human chromosome 8.

Cells derived from mice homozygous for the severe combined immune deficiency (scid) mutation exhibit hypersensitivity to ionizing radiation, and defects in DNA double-strand break repair and V(D)J recombination. Using the technique of microcell-mediated chromosome transfer, we have introduced a number of dominantly marked human chromosomes into scid cells to localize the human homolog of the murine scid gene. Analysis of human-scid hybrid clones revealed that the presence of human chromosome 8 partially restored accurate V(D)J recombination and radioresistance to scid cells. Subsequent loss of the human chromosome 8 from human-scid hybrid clones rendered these cells sensitive to gamma-radiation and impaired their ability to catalyse V(D)J recombination. Introduction of chromosomes 2, 14, 16 and 19 that encode other repair genes did not result in the correction of these two scid defects. These observations demonstrate that the human homolog of the mouse scid gene resides on human chromosome 8.

Animals↗

PubMed1993

A hamster-human subchromosomal hybrid cell panel for chromosome 2.

We have constructed hamster-human hybrid cell lines containing fragments of human chromosome 2 as their only source of human DNA. Microcell-mediated chromosome transfer was used to transfer human chromosome 2 from a monochromosomal mouse-human hybrid line to a radiation-sensitive hamster mutant (XR-V15B) defective in double-strand break rejoining. The human chromosome 2 carried the Ecogpt gene and hybrids were selected using this marker. The transferred human chromosome was frequently broken, and the resulting microcell hybrids contained different sized segments of the q arm of chromosome 2. Two microcell hybrids were irradiated and fused to XR-V15B to generate additional hybrids bearing reduced amounts of human DNA. All hybrids were analyzed by PCR using primers specific for 27 human genes located on chromosome 2. From these data we have localized the integrated gpt gene on the human chromosome 2 to the region q36-37 and present a gene order for chromosome 2 markers.

Animals↗

PubMed1992

Pregnancy in sickle cell disease in Bahrain.

OBJECTIVE: To review the maternal and fetal complications in pregnant women with sickle cell disease and to compare their pregnancy outcome with those of controls. DESIGN: A case-control study. SETTING: Ministry of Health hospitals in Bahrain. SUBJECTS: 147 pregnancies in 140 women with sickle cell disease and 294 controls matched for age and parity. MAIN OUTCOME MEASURES: The characteristics of women who had crises, the frequency of the crises, hypertensive disorders of pregnancy, infection, diabetes, perinatal mortality and the delivery statistics in the index and control women. RESULTS: Maternal mortality was 1.4% and perinatal mortality was 73.3/1000 total births in women with sickle cell disease, there were no maternal deaths and the perinatal mortality was 6.8/1000 births in the control group. Anaemia was treated by blood transfusion in 47% of women with sickle cell disease and, of these, 39% had a crisis that appeared to have been precipitated by the transfusion in the absence of any other predisposing factors. The presence of raised HbF did not decrease the number of crises but reduced their severity. CONCLUSION: Pregnancy in women with sickle cell disease should be monitored very closely as it constitutes a high risk to both the mother and the baby.

Adult↗

PubMed1988

Maternal mortality in Bahrain with special reference to sickle cell disease.

The maternal mortality in Bahrain during the 10-year period, 1977-1986, was 33.9 per 100,000 livebirths; the second 5-year period showed a significant reduction (26.9) compared to the first 5-year period (42.3). Haemorrhage, pulmonary embolism, hypertensive diseases of pregnancy and infection were the main causes of maternal mortality. Sickle cell disease was found to be an underlying cause in about one third of the maternal deaths. Avoidable factors were present in 38% of the cases, the majority being due to the failure of the patients to seek medical care or follow medical advice. Health education, premarital counselling and family planning were identified as significant factors in reducing the maternal mortality rate.

Anemia, Sickle Cell↗

PubMed1988

Perinatal mortality in Bahrain.

A review of 583 perinatal deaths at the Ministry of Health hospitals in Bahrain, during the years 1985-1987 revealed a perinatal mortality rate of 19.6 per 1,000 total births. Lethal congenital malformations accounted for 145 (24.9%) deaths. Of the 438 normally formed infants there were 42.2% antepartum, 115 (26.3%) intrapartum and 138 (31.5%) early neonatal deaths; in 82.7% of cases the death was considered to be unavoidable. The population of Bahrain for 1986 according to the Central Statistics Organization (1) was 435,065, the majority of which was served by the Ministry of Health Maternity Service with approximately 10,000 deliveries per annum. The Ministry of Health provides maternity services through one main maternity hospital and 2 peripheral hospitals with consultant obstetric care. In addition to these, there are 3 maternity units run by midwives. High risk cases are usually delivered in the main hospital as there is a neonatal intensive care unit attached to it. The latter also acts as a referral centre for all sick babies in Bahrain. An analysis of the causes of perinatal deaths is an effective way of assessing the efficiency of maternity services. The objective of this study was to identify and improve the various factors influencing perinatal mortality in Bahrain.

Bahrain↗

PubMed1986

Congenital malformations and consanguinity.

In this study in Bahrain increased maternal age, high parity, consanguinity and a history of 2 or more previous abortions were found to increase the risk of congenital malformation.

Abortion, Spontaneous↗