PubMed Health⌕ Search

Biomedical subjects

R Mahmood

Publications and source records attributed to R Mahmood.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effects of retinoid status on TGF beta expression during mouse embryogenesis.

In a previous study we investigated the effects of RA excess on TGF beta protein localization in early postimplantation stages of mouse development. Here we extend this investigation by comparing the effects of retinoid deficiency with those of excess, and by comparing the effects of altered retinoid status on TGF beta protein and RNA transcript distribution. In vitamin A-deficient embryos, TGF beta 1 RNA and protein distribution were both unaltered compared with controls; conversely, TGF beta 2 protein levels were reduced while RNA levels remained normal. In RA-treated embryos, the previous study showed that intracellular TGF beta 1 levels were decreased, while those of extracellular TFG beta 1 were initially decreased but subsequently increased; here we found that TGF beta 1 RNA transcript levels were reduced following exposure to RA excess. TGF beta 2 showed a clear disparity between the effects of RA excess on protein and RNA transcript levels: RNA transcript distribution was unchanged or showed a slight increase in RA-treated embryos, whereas the previous results showed greatly reduced protein levels. The new results provide further evidence for interaction between retinoids and TGF beta s during mouse development, and indicate that retinoids are capable of differentially regulating TGF beta isoforms through mechanisms involving different stages in the process of TGF beta synthesis and secretion. The long-term nature of the effects of transient exposure to RA excess suggests that the mechanisms of RA-TGF beta interaction may be indirect.

Animals↗
PubMed1995

Multiple roles for FGF-3 during cranial neural development in the chicken.

FGF-3 has been implicated in the development of the hindbrain and otocyst in vertebrate embryos. Since the chicken embryo offers a favourable system in which to study the development of these structures, we have isolated and characterised cDNAs for chicken Fgf-3 and determined its pattern of expression in chick embryos from stage 3 (primitive streak) to stage 25 (early organogenesis). Within the developing cranial neural tube, Fgf-3 exhibits dynamic spatial and temporal expression. During extension of the head process, RNA is detected in the midline of the developing neural plate. In neurulating embryos, transcripts are observed initially in rhombomeres 4 and 5 of the hindbrain and later, in rhombomere 6. During hindbrain development, expression is lost from these rhombomeres, but becomes restricted to rhombomere boundaries, providing an intracellular marker which distinguishes a population of cells within boundary regions. Fgf-3 expression is elevated in ventral and medial boundary regions and is greatly reduced in dorsal parts. Studies of regenerating rhombomere boundaries show that Fgf-3 expression is induced in reforming boundaries when even-numbered rhombomere tissue is grafted next to odd, but not when like is juxtaposed to like. Fgf-3 disappears from boundary regions just prior to the loss of the morphological boundaries suggesting a boundary-associated function. Other sites of expression have also been identified. At early stages of development Fgf-3 is expressed in the epiblast and mesendoderm of the primitive streak, in mesoderm lateral to the streak and in Hensen's node. In older embryos transcripts are detected in the endoderm of the pharyngeal pouches, the ectoderm of the second and third pharyngeal arches and the stomodeum. Expression was also detected in the segmental plate and in the posterior half of the three most-recently generated somites.

Amino Acid Sequence↗
PubMed1994

Geographical mapping of diabetic patients from the deprived inner city shows less insulin therapy and more hyperglycaemia.

To determine whether or not economic and social deprivation were associated with different diabetic treatment and metabolic control, data of patients from deprived inner city wards and prosperous wards were compared. A database was obtained for 1528 patients attending our hospital Diabetes Care Centre. Demographic data and postcodes were used to construct geographical maps of disease and deprivation. Blood glucose and glycated haemoglobin were measured. Inner city patients were less likely to be taking insulin, but if they were, they were more likely to have higher blood glucose values (p = 0.02) and higher glycated haemoglobin values (p = 0.02), compared to patients from prosperous wards. Insulin-treated patients from socially and economically deprived wards had worse diabetic control than patients from more prosperous wards. The study emphasizes the needs to target deprived patients for education and motivation to understand diabetes, and to optimize metabolic control.

Adult↗
PubMed1993

Inducible protective processes in animal systems: IV. Adaptation of mouse bone marrow cells to a low dose of ethyl methanesulfonate.

Ethyl methanesulfonate (EMS), a monofunctional alkylating agent, was used in the present investigations to investigate the induction of adaptive response (inducible protective processes) in mitotic cells of Swiss albino mouse. When a low (conditioning) dose of 80 mg/kg body wt was challenged with a subsequent high (challenging) dose of 240 mg/kg body wt, after different time lags, the yield of chromosomal aberrations in bone marrow cells was found to be significantly reduced compared with that of the challenge dose. It appears, therefore, that a low dose of EMS offered resistance to the mitotic cells against further clastogenic effect of any challenge dose of EMS employed. It is clear from the results that the phenomenon of adaptive response can also be encountered in mammalian in vivo systems.

Adaptation, Physiological↗
PubMed1993

Necrobiosis lipoidica diabeticorum: association with background retinopathy, smoking, and proteinuria. A case controlled study.

In order to evaluate patients with necrobiosis lipoidica diabeticorum and to compare them with age, sex, and duration of diabetes matched controls, 15 patients with necrobiosis were each matched with 5 control subjects with diabetes mellitus. Complications of diabetes, glycaemic control, and proteinuria were measured. Patients with necrobiosis (mean age 40, range 18-74 years) had a mean duration of diabetes of 14 (range 3-36) years; 8 patients were male, and 7 were female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p = 0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003) were all more common with necrobiosis. There were no significant differences between patients with necrobiosis and control patients in the prevalence of vascular disease and neuropathy. Glycosylated haemoglobin concentrations were higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were similar in both groups. We conclude that smoking, proteinuria, and retinopathy were more prevalent in diabetic patients with necrobiosis; the skin lesion may therefore share common aetiological factors which affect the microvascular circulation, leading to damage to basement membranes and vascular endothelial cells.

Adult↗
PubMed1992

Inducible protective processes in animal systems. III. Adaptive response of meiotic cells of the grasshopper, Poecilocerus pictus, to a low dose of ethyl methanesulfonate.

Meiotic cells of Poecilocerus pictus exposed to a low dose of 0.03 M of ethyl methanesulfonate (EMS) were found to be resistant to the induction of chromosomal anomalies by a subsequent challenge dose (0.12 M) of the same mutagen as compared to cells that were not pre-exposed. They responded with a significantly reduced incidence of chromosomal anomalies in metaphase I and II and anaphase I and II. These results indicate the presence of an inducible chromosomal repair mechanism in meiotic cells of P. pictus. The incidence of chromosome damage was found to be less when the time lag between the conditioning and challenging doses was reduced, suggesting that under the conditions tested, the efficacy of repair enzymes gradually decreases as the time between the two doses increases.

Adaptation, Biological↗
PubMed1992

Interactions between retinoids and TGF beta s in mouse morphogenesis.

Using immunocytochemical methods we describe the distribution of different TGF beta isoforms and the effects of excess retinoic acid on their expression during early mouse embryogenesis (8 1/2 - 10 1/2 days of development). In normal embryos at 9 days, intracellular TGF beta 1 is expressed most intensely in neuroepithelium and cardiac myocardium whereas extracellular TGF beta 1 is expressed in mesenchymal cells and in the endocardium of the heart. At later stages, intracellular TGF beta 1 becomes very restricted to the myocardium and to a limited number of head mesenchymal cells; extracellular TGF beta 1 continues to be expressed widely in cells of mesenchymal origin, particularly in head and trunk mesenchyme, and also in endocardium. TGF beta 2 is widely expressed at all stages investigated while TGF beta 3 is not expressed strongly in any tissue at the stages examined. Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF beta 1 and TGF beta 2 proteins but had no effect on TGF beta 3. Intracellular TGF beta 1 expression was reduced in all tissues except in the myocardium, while extracellular TGF beta 1 was specifically reduced in neuroepithelium and cranial neural crest cells at early stages. TGF beta 2 was reduced in all embryonic tissues. The down-regulation of intracellular TGF beta 1 was observed up to 48 hours after initial exposure to retinoic acid while some down-regulation of TGF beta 2 was still seen up to 60 hours after initial exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

An in vitro coupled transcription-translation system from Staphylococcus aureus.

We have developed a Staphylococcus aureus cell-free system that is capable of directing DNA-dependent synthesis of proteins. The staphylococcal plasmids pE194 and pSK265 were used to characterize this system. The in vitro system was found to direct the synthesis of the appropriate proteins predicted from the nucleotide sequence of the plasmids. As is the case in vivo, low levels of the inducer, erythromycin, promoted the synthesis of the pE194-encoded ribosomal RNA methyltransferase in the in vitro system.

Calcium↗
PubMed1990

Role of upstream sequences in the expression of the staphylococcal enterotoxin B gene.

The staphylococcal enterotoxin B gene (seb) is positively regulated at the transcriptional level (Gaskill, M. E., and Khan, S. A. (1988) J. Biol. Chem. 263, 6276-6280). The sequences involved in the regulation of transcription of the seb gene have been studied by deletion analysis. A multicopy Staphylococcus aureus plasmid carrying the cloned seb gene was used to generate a series of mutants that are deleted in the upstream region of this gene. The levels of enterotoxin B protein and mRNA produced by the deletion mutants were analyzed. A region between 59 and 93 nucleotides upstream of the transcription initiation site was found to be required for transcription and expression of the seb gene. Deletion of this sequence greatly reduced or eliminated transcription of the seb gene. DNA-protein binding experiments showed that cell-free extracts made from an staphylococcal enterotoxin B-producing strain contain protein(s) that specifically bind to the upstream region. This protein may be involved in the transcriptional activation of the seb gene.

Base Sequence↗
PubMed1989

Serine-324 of myosin's heavy chain is photoaffinity-labeled by 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate.

A portion of the active site of rabbit skeletal myosin near the ribose ring of ATP can be labeled by the photoaffinity analogue 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate (Bz2ATP). The specificity of the photolabeling was assured by first trapping [14C]Bz2ATP at the active site by use of thiol cross-linking agents [Mahmood, R., Cremo, C., Nakamaye, K., & Yount, R. (1987) J. Biol. Chem. 262, 14479-14486]. Five radioactive peptides were isolated by high-performance liquid chromatography after extensive trypsin and subtilisin digestion of photolabeled myosin subfragment 1. Four of these peptides were sequenced by Edman techniques, and all originated from a region with the sequence Gly-Glu-Ile-Thr-Val-Pro-Ser-Ile-Asp-Asp-Gln, which corresponds to rabbit myosin heavy chain residues 318-328. The fifth labeled peptide had an amino acid composition appropriate for residues 312-328. Amino acid composition, radiochemical analysis, and sequence data indicate that Ser-324 is the major amino acid residue photolabeled by Bz2ATP. Spectrophotometric evidence indicates that the benzophenone carbonyl group has inserted into a C-H bond from either the alpha- or beta-carbon of serine. These results place Ser-324 at a distance of 6-7 A from the 3'(2') ribose oxygens of ATP bound at the active site of myosin.

Adenosine Triphosphate↗
PubMed1987

The interaction and photolabeling of myosin subfragment 1 with 3'(2')-O-(4-benzoyl)benzoyladenosine 5'-triphosphate.

The photoprobe 3'(2')-O-(4-benzoyl)benzoyladenosine 5'-triphosphate (Bz2ATP) was used to characterize the nucleotide-binding site of myosin subfragment 1 (SF1). Improved synthesis and purification of Bz2ATP are reported. 1H NMR and ultraviolet spectroscopy show that Bz2ATP is a 60:40 mixture of the 3'(2')-ribose isomers and that the epsilon M261 is 41,000 M-1 cm-1. Bz2ATP is hydrolyzed by SF1 comparably to ATP in the presence of actin or K+, NH4+, or Mg2+ ions; and the product, Bz2ADP, has a single binding site on SF1 (K'a = 3.0 X 10(5) M-1). [3H]Bz2ATP was photoincorporated into SF1 with concomitant loss of K+-EDTA-ATPase activity. Analysis of photolabeled SF1 showed that the three major tryptic peptides (23, 50, and 20 kDa) of the heavy chain fragment and the alkali light chains were labeled. The presence of ATP during irradiation protected only the 50-kDa peptide, indicating that the other peptides were nonspecifically labeled. If Bz2ATP was first trapped on SF1 by cross-linking the reactive thiols, SH1 and SH2, with p-phenylenedimaleimide, only the 50-kDa tryptic peptide was labeled. These results confirm and extend previous observations that [3H]Bz2ATP trapped on SF1 by cobalt(III) phenanthroline photolabeled the same 50-kDa peptide (Mahmood, R., and Yount, R.G. (1984) J. Biol. Chem. 259, 12956-12959). Thus, the 50-kDa peptide is labeled with or without thiol cross-linking, indicating that the relative position of SH1 and SH2 does not affect the labeling pattern.

Adenosine Triphosphatases↗