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N Aziz

Publications and source records attributed to N Aziz.

72 records · Page 4Linked to original sources

Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by progressive enlargement of the kidneys due to numerous expanding cysts ultimately leading to renal failure. We have identified a gene, Ke 6, located within the H-2K/tw5 region on mouse chromosome 17, which is downregulated in two distinct murine models of heritable PKD. Ke 6 is a member of the short-chain alcohol dehydrogenase family and possess remarkable amino acid sequence conservation with several bacterial proteins with oxidoreductase function. The Ke 6 gene gives rise to two transcripts--a 1-kb Ke 6a mRNA which is abundant in kidney and liver tissue and a 1.4-kb Ke 6b mRNA which is found at a moderate level in spleen tissue. We report here the complete nucleotide sequence of Ke 6a cDNA and the expression of the Ke 6 gene in murine models of PKD. The Ke 6 gene may be intimately involved in the manifestation of these cystic kidney diseases.

Alcohol Dehydrogenase↗

Only the DNA binding and transactivation domains of c-Myb are required to block terminal differentiation of murine erythroleukemia cells.

The c-Myb protein is a transcription factor with an apparent but poorly defined role in hematopoietic cell growth and differentiation. The DNA binding and several transcriptional regulatory domains of the c-Myb protein have been defined by transient transfections into nonhematopoietic cell lines. Although the relationship between these domains and transformation has been studied, little is known about the function of these domains during hematopoietic maturation. Up-regulation of stably transfected c-myb in murine erythroleukemia (MEL) cells blocks terminal differentiation when MEL cells are induced to differentiate with N,N'-hexamethylene bisacetamide. To determine which functional domains of c-Myb are necessary and sufficient to block differentiation, mutated c-myb constructs under the control of a murine metallothionein promoter were transfected into C19 MEL cells, and stable clonal cell lines were established. The ability of Myb mutants to block differentiation paralleled their ability to transactivate transcription of a reporter gene containing Myb-responsive elements, by transient transfection into a lymphoid cell line. The smallest c-Myb mutant able to block differentiation consisted of the DNA binding domain juxtaposed to the transactivation domain. Therefore, the DNA binding domain and the transactivation domain are necessary and sufficient for c-Myb to block differentiation in MEL cells.

Acetamides↗

c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro.

The product of the c-myb proto-oncogene is a highly conserved transcription factor that has been shown to function as both a transactivator and repressor. The v-myb oncogenes of E26 leukemia virus and avian myeloblastosis virus (AMV) encode proteins truncated at both the amino and carboxy termini, deleting portions of the DNA-binding and negative regulatory domains present in c-Myb. Similar truncations of c-Myb alter its function, suggesting that the viral proteins lack important regulatory sequences. Interestingly, eight potential sites of phosphorylation by proline-directed protein kinases conserved between the avian, murine and human Myb proteins are clustered in or near the negative regulatory domain of c-Myb. The majority of these sites are deleted in both the E26 and AMV viral proteins. In this paper we show that one proline-directed protein kinase, p42mapk, phosphorylates bacterially synthesized avian and murine c-Myb but not AMV v-Myb in vitro. We find that p42mapk phosphorylates c-Myb on serine and threonine, but not on tyrosine. Furthermore, deletion analysis indicates that the sites of phosphorylation map to the C-terminal negative regulatory domain. We speculate that the inability of v-Myb to be phosphorylated by p42mapk may contribute to its oncogenic properties.

Animals↗

Transport in vitro fertilization--a novel scheme for community-based treatment.

OBJECTIVE: To provide an inexpensive and extensive in vitro fertilization (IVF) service for the Mersey Region, United Kingdom. DESIGN: Twenty-four transport IVF patients treated in two district general hospitals using the central university laboratory as co-ordination point for treatment schedule and embryology. Outcomes were compared with 26 control patients treated in the central unit. SETTING: Royal Liverpool University Hospital, a central IVF unit, and two district general hospitals in the Mersey Region. PATIENTS: Fifty patients under 35 years of age with irreversible tubal damage selected and treated by IVF, half in the central unit and the other half in two district general hospitals. MAIN OUTCOME MEASURES: Pregnancy rate (PR) in the different centers. RESULTS: A PR of 42.3% per cycle in the peripheral hospitals compared with 30.7% per cycle in the central unit. CONCLUSION: Transport IVF is an inexpensive and feasible alternative to standard IVF in a central unit for patients without access to central units.

Adult↗

Is follicular flushing necessary for oocyte retrieval? A randomized trial.

A prospective randomized trial was performed to evaluate the necessity of follicular flushing during transvaginal, ultrasonically guided oocyte recovery under mild sedation. Patients with tubal damage as the sole cause of their infertility were randomized into one of two groups. Group one had their follicles aspirated only. Follicles of patients in Group 2 were aspirated and flushed with a total of 10 ml of flushing medium. There was no significant difference in the number of oocytes retrieved, fertilization rate or pregnancy rate in each group. There was, however, a significant shortening of operating time in the aspiration only group.

Adult↗

Pharmacokinetics of fentanyl administered by computer-controlled infusion pump.

Fentanyl was administered to 21 patients using a computer-controlled infusion pump (CCIP) based on a pharmacokinetic model. Eleven of the patients were dosed according to the pharmacokinetics described by McClain and Hug, and ten of the patients were dosed according to the pharmacokinetics described by Scott and Stanski. The authors measured the difference between the measured arterial fentanyl concentrations and the concentrations predicted by the CCIP for each pharmacokinetic parameter set. The median absolute performance error (MDAPE) in patients dosed according to McClain and Hug's parameters was 61%, and the MDAPE in patients dosed according to Scott and Stanski's parameters was 33%. The population pharmacokinetics in these 21 patients were analyzed using a pooled data technique. The pharmacokinetics of fentanyl in this population showed a smaller central compartment volume and a more rapid initial distribution half-life than previously estimated for fentanyl. The derived pharmacokinetic parameters described these patients well and also predicted the observed fentanyl concentrations from four previously published fentanyl studies with reasonable accuracy. Comparison of the parameters used by the authors with those of McClain and Hug demonstrated that dosing regimens designed from pharmacokinetic models can be fairly accurate at the times sampled in the original study but may not be accurate at time points not sampled in the original research. The authors concluded that although the pharmacokinetics of fentanyl administered by CCIP are the same as the pharmacokinetics of fentanyl administered by a bolus or constant rate infusion, a pharmacokinetic study using a CCIP may be particularly effective at characterizing the most rapid distribution pharmacokinetic parameters, and thus may provide parameters appropriate for subsequent use in a CCIP.

Adult↗

Determination of alfentanil in serum by radioimmunoassay or capillary column gas-liquid chromatography. A comparison of the assays.

In view of recent controversies about the specificity and accuracy of radioimmunoassays (RIA) for morphine and alfentanil, we assessed the validity of an RIA for alfentanil by comparing it with a novel capillary column gas-liquid chromatographic (GLC) assay. The coefficients of variation for eight determinations of alfentanil in plasma or serum were approximately 2% at 2, 20, and 400 ng/ml with both assays. The assay comparison was done using 85 serum samples from patients given intravenous alfentanil. There was an excellent correlation between the assay results obtained by RIA and by GLC in the range of 10-1 825 ng/ml. The two assays can therefore be used interchangeably in pharmacokinetic studies.

Alfentanil↗

Iron regulates ferritin mRNA translation through a segment of its 5' untranslated region.

In previous studies, we showed that acute administration of iron to intact rats or to rat hepatoma cells in culture induces synthesis of the iron-storage protein ferritin by activating translation of inactive cytoplasmic ferritin mRNAs for both the heavy (H) and the light (L) subunits. In the course of activation, these ferritin mRNAs are recruited onto polysomes. To elucidate the structural features of these mRNAs involved in the translational response to iron, a chimera was constructed from the 5' and 3' untranslated regions (UTRs) of ferritin L subunit mRNA fused to the reading frame of the mRNA of bacterial chloramphenicol acetyltransferase (CAT). This chimera and deletion constructs derived from it were introduced into a rat hepatoma cell line by retrovirus-mediated gene transfer. The complete chimera showed increased CAT activity in response to iron enrichment of the medium, whereas deletion of the first 67 nucleotides of the 5' UTR, which contain a highly conserved sequence, caused loss of regulation by iron. Whereas cis-acting sequences located in the 5' flanking regions of many genes have been repeatedly implicated in modulating their transcriptional expression, we report here a specific regulatory translational sequence found within the 5' UTR of a eukaryotic mRNA.

Animals↗

Oviposition and biting patterns of Aedes triseriatus in the flood plains of Fort Bend County, Texas.

Aedes triseriatus deposited eggs at all tree heights between ground level and 3.7 meters, from June through early August, 1985, in a flood plain area of Fort Bend County, TX. Percentage of eggs decreased with increasing oviposition heights and greater preferences were found for ground level and 1.2 meters. More eggs were deposited at all heights in June than in July and August. Weekly biting activity of the mosquito was recorded for a 24-hour period throughout the study. Biting occurred during the day with early morning and late afternoon peaks and continued into the crepuscular period.

Aedes↗

Both subunits of rat liver ferritin are regulated at a translational level by iron induction.

A few hours after administering iron to rats, liver ferritin synthesis increases several fold. However, Northern blot analysis with cDNA probes for ferritin light (L) and heavy (H) subunit mRNAs failed to show an increase in total population of either messenger. Cytoplasmic distribution of ferritin messages was therefore investigated in control and iron administered rats killed at 3.5 hours. The liver post-mitochondrial supernatant was fractionated on a sucrose gradient to separate polyribosomes, monosomes, ribosomal subunits and cell sap. RNA extracted from each fraction and analyzed using Northern blotting showed that 65% of the total mRNA population for each subunit was present in the cell sap of control rats, presumably as mRNP particles since ribosomal RNA was absent from this fraction. After iron administration, these reserves of free mRNA were recruited onto the polysomes, reducing the free mRNA pool to 15% of the total. We interpret this to be due to activation of blocked ferritin messages on entry of iron into the cell.

Animals↗

Downbeat nystagmus as a side effect of lithium carbonate: case report.

In this case study, lithium carbonate, used to control bipolar disorders, is postulated to be the cause of downbeat nystagmus; the degree of nystagmus could be correlated with the dosage and serum level of the drug. All tests for anatomic lesion were negative, including metrizamide cisternography.

Basal Ganglia Diseases↗

Conservation in rat liver of light and heavy subunit sequences of mammalian ferritin. Presence of unique octopeptide in the light subunit.

Ferritin, an iron-storage protein found in all life forms examined, is composed of varying proportions of two subunits of different molecular weight, heavy (H) and light (L). Using cDNA clones, we have determined the nucleotide sequence corresponding to the mRNA of the L-subunit of rat liver ferritin. The coding region of 546 nucleotides (182 amino acids) is flanked by 5'- and 3' -untranslated regions of approximately 130 and 150 nucleotides, respectively. The rat liver L-subunit amino acid sequence derived from the reading frame of the cDNA showed 88% and 82% homology, respectively, with the amino acid sequences of horse spleen ferritin (Heusterspreute, M., and Crichton, R. R. (1981) FEBS Lett. 129, 322-327), and human spleen ferritin (Wustefeld, C., and Crichton, R. R. (1982) FEBS Lett. 150, 43-48), thus demonstrating evolutionary conservation of the L-subunit sequence. However, a major difference between the rat and the horse and human sequences is the insertion of an octopeptide near the COOH-terminus of the rat protein resulting in a slightly longer peptide chain in this species. The reading frame and parts of the derived amino acid sequence including the octopeptide sequence were confirmed by direct amino acid sequencing of cyanogen bromide peptides from rat liver ferritin. Minor fragments of rat liver ferritin, presumably derived from the H-subunit, were also isolated after cyanogen bromide treatment. On sequencing, these H-peptides showed limited homology with regions of the L-sequence but extensive homology with published H-sequences from human liver and spleen. The H-subunit sequence did not contain the octopeptide found as part of the L-subunit sequence.

Amino Acid Sequence↗

Effect of melatonin alone or in combination with human chorionic gonadotropin or ovine luteinizing hormone on the in vitro secretion of estrogens or progesterone by granulosa cells of rats.

This work was undertaken to learn what effect, if any, melatonin might have on estrogen and progesterone production in vitro. Granulosa cells (10(6)/tube) were harvested from immature Sprague-Dawley rats, previously primed with diethylstilbestrol. Such cells were incubated for 90 min in medium only or in medium to which hCG (10 or 100 IU) or melatonin (3, 30, or 300 pg) had been added separately and in combination. Melatonin alone had no significant effect on the amount of estrogen produced, but in combination with hCG, a significant increase in estrogen followed (P less than 0.05). Estrogen was measured by RIA. More mature granulosa cells from rats primed with both diethylstilbestrol and porcine FSH were similarly collected and incubated in medium alone or in medium containing ovine LH (oLH; 0.3 or 3 ng) and/or melatonin (23 or 23 X 10(2) pg). The progesterone produced was measured by a competitive protein-binding method. A significant increase (P less than 0.05) in progesterone followed the addition of either melatonin or oLH alone, but a substantially greater increase was seen when oLH and melatonin were combined. These results show that, at least over a short period (90 min), melatonin is progonadal, in that it augments gonadotropic stimulation of granulosa cells and leads to increased synthesis of estrogen or progesterone. Melatonin may also independently stimulate granulosa cell production of progesterone.

Animals↗