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Biomedical subjects

N Aziz

Publications and source records attributed to N Aziz.

At least 55 records · Page 3Linked to original sources
PubMed1997

Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women.

Immunologic alterations occur during pregnancy, but the effect of pregnancy on HIV infection is controversial. We characterized some of the immunologic alterations with potential to influence HIV disease in 99 infected and 46 uninfected women during pregnancy and up to 6 months post-partum. Immunophenotyping to quantitate the major lymphocyte subsets and determine expression of activation and adhesion molecules on T cells was performed using 3-color staining and laser flow cytometry. Serum neopterin, beta 2-microglobulin, and tumor necrosis factor-alpha (TNF alpha) were quantitated using commercial immunoassays. HIV + pregnant women were compared to uninfected pregnant subjects and to reference ranges established on healthy, HIV-seronegative non-pregnant female controls. Both CD4 and CD8 T cell subsets were increased in HIV-negative pregnant women compared to non-pregnant controls. In HIV-infected pregnant women, CD4 T cells were low and CD8 cells were elevated compared to HIV-negative pregnant and non-pregnant women. Levels of subsets were stable during pregnancy and postpartum in both groups of women. Evidence of peripheral immune activation was found during the later stages of pregnancy. Increases in HLA-DR and CD38 activation antigens on CD8 cells, serum neopterin and beta-2-microglobulin were seen during pregnancy in HIV-negative women. These correlates of immune activation were increased in HIV-infected pregnant women and increased further during pregnancy, paralleling changes seen in uninfected pregnant women. These immunologic alterations may directly or indirectly enhance viral replication, impacting the long-term course of HIV disease.

Biopterins↗
PubMed1997

A radiation hybrid map of human chromosome 5 with integration of cytogenetic, genetic, and transcript maps.

One of the major goals of the human genome project is to establish a physical map of each human chromosome with a density of sequence-tagged site (STS) markers exceeding one every 100 kb. We report here the generation of a human chromosome 5-specific radiation hybrid (RH) map that includes 556 markers. Of these markers, 132 loci are ordered with a maximum likelihood ratio of >1000:1 compared with the next most likely order. An additional 113 loci were ordered relative to these backbone markers with a maximum likelihood ratio of >10:1 but <1000:1. Together, these 245 loci form an ordered framework map for the chromosome. Using this framework, >300 more markers were localized based on two-point analysis with the ordered set. On average, there are 50 markers in common with the RH map presented here and other chromosome 5 maps included in the current whole genome cytogenetic, genetic, and physical maps. The accuracy of all the maps is evident in that there are no more than two discrepancies between any one of them and these data. All of the maps encompassing chromosome 5 complement each other providing excellent STS coverage with >2200 loci combined. The chromosome 5-specific RH map contains 20% of these independent loci. In addition, our RH map contains STSs derived from clones suitable for fluorescent in situ hybridization, allowing alignment to the cytogenetic map. Together, these maps will assist in the assembly of sequence-ready contigs and will aid in the identification of disease loci on chromosome 5 by positional cloning and positional candidate approaches.

Centromere↗
PubMed1997

Distribution of HLA-DQ alpha and polymarker (LDLR, GC, GYPA, HBGG, and D7S8) alleles in Arab and Pakistani populations living in Abu Dhabi, United Arab Emirates.

Randomly collected blood samples from 100 Arabs and 100 Pakistanis residing in Abu Dhabi were analyzed using the HLA-DQ alpha and polymarker (LDLR, GC, GYPA, HBGG, D7S8) PCR based reverse dot blot systems. Allelic frequencies for each allele and observed heterozygosity for each locus were calculated. Departures from Hardy-Weinberg expectations (HWE) were determined using the unbiased estimate of the expected homozygote/ heterozygote frequencies, the likelihood ratio test and the exact test. No significant departures from HWE expectations were detected.

Blood Proteins↗
PubMed1996

Differential regulation of c-Myb-induced transcription activation by a phosphorylation site in the negative regulatory domain.

The c-myb protooncogene encodes a highly conserved 75-89-kDa transcription factor that contains three functional domains, an amino-terminal DNA binding domain (DBD), a central acidic transactivation domain, and a carboxyl-terminal negative regulatory domain (NRD). Two acute transforming retroviruses, avian myeloblastosis virus and the E26 leukemia virus, transduced portions of c-myb and encode Myb proteins that are truncated in both the DBD and the NRD. Several conserved potential sites for phosphorylation by proline-directed serine/threonine protein kinases reside in or near the NRD, suggesting that phosphorylation might play a role in regulating c-Myb. We have previously demonstrated that serine 528, located in the NRD, is a target for p42(mapk) in vitro. Serine 528 is phosphorylated in vivo in several cell lines, and substitution of serine 528 to alanine (S528A) resulted in an increased ability of Myb to transactivate a synthetic promoter containing five copies of the mim-1A Myb-responsive element and a minimal herpes tk promoter. We have tested the ability of S528A Myb to transactivate a series of cellular target promoters and report that the serine to alanine substitution increased the ability of Myb to activate transcription from the CD34 promoter but not the c-myc or mim-1 promoters. This suggests that phosphorylation of serine 528 may differentially regulate c-Myb activity at different promoters. The DNA binding and multimerization activities of c-Myb appear to be unaffected by the S528A substitution, suggesting that phosphorylation of serine 528 may mediate its effect on the transcription transactivating activity of c-Myb by regulating interactions with other proteins.

Alanine↗
PubMed1996

The sperm deformity index: a reliable predictor of the outcome of oocyte fertilization in vitro.

OBJECTIVE: To evaluate a novel expression of sperm morphological parameters, the sperm deformity index, as a predictor of fertilization in vitro. DESIGN: Prospective blind clinical trial. SETTING: Academic tertiary referral center. INTERVENTION(S): Detailed sperm morphological assessment applying strict morphological criteria and a multiple entry technique for an unselected male population undergoing IVF. The sperm deformity index, defined as the average number of deformities per sperm assessed, was calculated. PATIENT(S): One hundred fifty-eight patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy. RESULT(S): Seventy-three percent of patients achieved fertilization. Patients achieving fertilization had a significantly higher median proportion of normal forms and a significantly lower median sperm deformity index than the nonfertilizers. The receiver operator characteristic (ROC) curves identified cutoff points that maximized the sum of sensitivity and specificity at sperm deformity index 1.6 and normal forms 4%. The sperm deformity index had a greater sensitivity (96%), specificity (72%), positive predictive value (90%), and negative predictive value (86%) than the proportion of normal sperm morphology (87%, 69%, 89%, 66%, respectively) at the optimal cutoff points. The area under the ROC curve was greater for the sperm deformity index (0.875) than for the proportion of normal sperm morphology (0.622). Achieving pregnancy did not correlated with sperm morphology. CONCLUSION(S): The sperm deformity index is a more reliable predictor of the outcome of fertilization in vitro than the proportion of normal sperm morphology and can assist to identify patients who require techniques such as intracytoplasmic sperm injection.

Adult↗
PubMed1996

Aberrant 11beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: implications for regulation by the Ke 6 gene.

Glucocorticoids have been used to create experimental polycystic kidney disease in rodents and to induce cysts in embryonic kidneys cultures. In addition, the plasma corticosterone levels are higher in a heritable murine model of polycystic kidney disease, cpk mice, in the first postnatal week. Previously, we had shown that the 11beta-hydroxysteroid dehydrogenase-1 (11betaHSD-1) gene is down-regulated in the cpk mice in a coordinated pattern with the Ke 6 gene. In this study, we measured the level of 11betaHSD-1 activity in kidney and liver tissues of cpk homozygote mice and found a reduction in its activity only in the kidney, not in the liver. The activity of the 11betaHSD-1 enzyme appears to be tightly correlated to the level of Ke 6 protein in these tissues. We discuss the possibility that the activity of the 11betaHSD-1 enzyme may be regulated by the Ke 6 enzyme. Ke 6 gene expression has been located to the outer stripe region of rodent kidneys, which is the same region of expression as that for the 11betaHSD-1 gene. These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11betaHSD-1 activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Ke 6 gene. Sequence and organization and aberrant regulation in murine polycystic kidney disease.

Ke 6 gene is a newly identified gene located in the major histocompatibility complex and is a candidate steroid dehydrogenase gene because of structural homology and regulatory similarities with mammalian steroid dehydrogenases. We report here the complete nucleotide sequence and intron-exon organization of the Ke 6 gene and cloning of the alternatively spliced Ke 6b transcript. We find that Ke 6 gene expression is down-regulated in pcy mice which is a murine model of polycystic kidney disease (PKD). Thus far, Ke 6 gene expression is down-regulated in all murine models of PKD we have examined. Abnormal steroid metabolism as a possible cause of PKD is discussed.

Amino Acid Sequence↗
PubMed1995

Modulation of c-Myb-induced transcription activation by a phosphorylation site near the negative regulatory domain.

The c-myb protooncogene encodes a highly conserved transcription factor that functions as both an activator and a repressor of transcription. The v-myb oncogenes of E26 leukemia virus and avian myeloblastosis virus encode proteins that are truncated at both the amino and the carboxyl terminus, deleting portions of the c-Myb DNA-binding and negative regulatory domains. This has led to speculation that the deleted regions contain important regulatory sequences. We previously reported that the 42-kDa mitogen-activated protein kinase (p42mapk) phosphorylates chicken and murine c-Myb at multiple sites in the negative regulatory domain in vitro, suggesting that phosphorylation might provide a mechanism to regulate c-Myb function. We now report that three tryptic phosphopeptides derived from in vitro phosphorylated c-Myb comigrate with three tryptic phosphopeptides derived from metabolically labeled c-Myb immunoprecipitated from murine erythroleukemia cells. At least two of these peptides are phosphorylated on serine-528. Replacement of serine-528 with alanine results in a 2- to 7-fold increase in the ability of c-Myb to transactivate a Myb-responsive promoter/reporter gene construct. These findings suggest that phosphorylation serves to regulate c-Myb activity and that loss of this phosphorylation site from the v-Myb proteins may contribute to their transforming potential.

Amino Acid Sequence↗
PubMed1995

Animal models of polycystic kidney disease.

Polycystic kidney disease (PKD) is one of the most prevalent causes of heritable renal failure. The disease is characterized by the occurrence of numerous fluid-filled cysts within the parenchyma of kidney. The cysts are epithelial in origin and expand in size, leading to crowding of normal kidney tissue. Ultimately, there is gross enlargement of the kidneys with loss of normal functions, and death usually occurs because of complications related to renal failure. Animal models of polycystic kidney disease are proving to be extremely useful for studying the molecular basis of renal cyst formation and for the isolation of genes carrying the mutations. This article describes the various animal models of polycystic kidney disease, spontaneously and experimentally derived, that have recently been identified.

Animals↗
PubMed1995

Association between brain indole levels and severity of posthypoxic myoclonus in rats.

We have previously reported the presence of posthypoxic, audiogenic myoclonus in rats after cardiac arrest and the ability of the 5-HT precursor, 5-HTP, to attenuate these muscle jerks. In addition, we have recently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of myoclonus in these animals, suggesting a deficiency in serotonergic neurotransmission. In the present study, the levels of 5-HTP, 5-HT, and 5-HIAA were measured in seven regions of the brain in myoclonic and normal rats to identify the areas of the brain in which a serotonergic dysfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation from cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in indole levels in the following areas of the brain: cortical 5-HIAA, striatal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, myelencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebellar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesencephalic 5-HIAA appear most relevant to the pathophysiology of posthypoxic myoclonus because regression analyses showed significant correlations between the myoclonus scores of the animals and the levels of these indoles. Based on the observed pattern of results, we postulate a dysfunction in serotonergic lateral (cortical) and far lateral (extrapyramidal) ascending pathways in posthypoxic myoclonus.

5-Hydroxytryptophan↗
PubMed1994

Zidovudine and dideoxycytidine differ in their effects on human immunodeficiency virus-induced pathologic activation of the immune system. AIDS Clinical Trial Research Group 047.

When zidovudine and dideoxycytidine (ddC) were given on schedules of 1 week on drug and 1 week off, results differed substantially in effects on HIV (human immunodeficiency virus type 1)-induced immune activation. Zidovudine (200 mg every 4 h) caused marked lowering toward normal of serum neopterin and beta 2-microglobulin within 1 week. This effect was lost within 1 week off zidovudine. Intermittent ddC (0.03 mg/kg every 4 h) had a smaller 1-week effect but had a delayed cumulative suppressive effect on HIV-associated immune activation that was not seen with intermittent zidovudine therapy. Zidovudine and ddC given in alternating weeks had synergistic effects in the first 10 weeks (e.g., early and rapid reduction followed by cumulatively greater effects on immune cell activation). The identical sawtooth effect of intermittent zidovudine was also evident in serum HIV p24 antigen levels. This is consistent with the hypothesis that the increased serum levels of the immune activation markers seen in HIV infection reflect stimulatory effects of HIV viral components on immune system cells.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Coordinate regulation of 11 beta-HSD and Ke 6 genes in cpk mouse: implications for steroid metabolic defect in PKD.

Polycystic kidney disease (PKD) is characterized by multiple renal cysts, which ultimately result in renal failure. We have reported the identification of a new gene, Ke 6, within the major histocompatibility complex, which is downregulated in two different mouse models of heritable PKD (N. Aziz, M. Maxwell, B. St.-Jacques, and B.M. Brenner. Mol. Cell. Biol. 13: 1847-1853, 1993). The Ke 6 gene gives rise to two transcripts, Ke 6a and Ke 6b. Ke 6a protein has significant homology to several mammalian and bacterial steroid dehydrogenases. The homology of Ke 6a protein to specific functional domains of the human and rat 11 beta-hydroxysteroid dehydrogenase enzyme (11 beta-HSD), which inactivates glucocorticoids, is substantial. We report here that the Ke 6 gene and the 11 beta-HSD gene are regulated in the same aberrant pattern in the cpk mouse. The strong evidence for a critical role of steroids in cystogenesis leads us to propose that a possible elevation of intrahepatic and intrarenal steroid levels occurs in the cpk mouse as a result of repression of steroid metabolic enzymes, which ultimately leads to development of cysts.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Effect of aspirating needle calibre on outcome of in-vitro fertilization.

Thirty patients with intact ovaries undergoing ultrasound-guided transvaginal oocyte retrieval for in-vitro fertilization treatment had their ovaries randomized for follicular aspiration with small and large aspiration needles while under mild sedation. Collections using smaller diameter needles had no significant effect upon the number of oocytes collected per follicle aspirated, or on the subsequent fertilizing capacity of those oocytes. There was significant reduction in pain perceived by the patient when the smaller needle was used during the collection.

Adult↗