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Biomedical subjects

I Ahmad

Publications and source records attributed to I Ahmad.

At least 19 recordsLinked to original sources
PubMed1998

Involvement of Mash1 in EGF-mediated regulation of differentiation in the vertebrate retina.

It is believed that signaling through the epidermal growth factor (EGF) receptor plays a critical role in the development of Drosophila eyes. In the present study we have analyzed the role that EGF-mediated signaling plays in vertebrate retinal development. We have observed that during late retinal neurogenesis EGF delays rod photoreceptor differentiation and that this effect of EGF involves the modulation of expression of a homologue of Drosophila proneural genes, Mash1. EGF causes a significant decrease in Mash1 expression and an increase in the proportion of proliferating cells in the retina in vitro. The decrease in Mash1 expression is accompanied by a concomitant decrease in opsin expression, a marker for overt rod photoreceptor differentiation. Withdrawal of EGF leads to an increase in both Mash1 and opsin expression; however, the onset of expression of Mash1 precedes that of opsin. Our study identifies a proliferative intermediate precursor, characterized by Mash1 expression, that is the target of EGF-mediated suppression of rod photoreceptor differentiation. Based on the evolutionarily conserved roles of EGF- and Notch-mediated signaling in the delay of differentiation in proliferating precursors we propose that these distinct signaling mechanisms act in concert to ensure the fidelity of the strict temporal and spatial nature of cell fate determination in the retina.

Animals↗
PubMed1998

In vitro and in vivo antifungal activity of amphotericin B lipid complex: are phospholipases important?

Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipids L-alpha-dimyristoylphosphatidylcholine (DMPC) and L-alpha-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active amphotericin B can be released from ABLC by exogenously added (snake venom, bacteria, or Candida-derived) phospholipases or by phospholipases derived from activated mammalian vascular tissue (rat arteries). Such extracellular phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of C. albicans that were resistant to ABLC but not AmB-d in vitro were deficient in extracellular phospholipase activity, as measured on egg yolk agar or as measured by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in the treatment of experimental murine infections produced by these mutants. Isolates of Aspergillus species, apparently resistant to ABLC in vitro (but susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that routine in vitro susceptibility tests with ABLC itself as the test material may not accurately predict the in vivo activity of ABLC and that the enhanced therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part, to the selective release of active amphotericin B from the complex at sites of fungal infection through the action of fungal or host cell-derived phospholipases.

Amphotericin B↗
PubMed1997

Metabotropic glutamate receptors prevent nitric oxide-induced programmed cell death.

Activation of metabotropic glutamate receptor (mGluR) subtypes can prevent neuronal injury through the signal transduction pathways of nitric oxide (NO). It is this link to NO free radical injury and subsequent DNA damage that is the most intriguing. We therefore examined whether neuronal protection through mGluR activation was dependent on the molecular mechanisms of programmed cell death (PCD). The NO generators sodium nitroprusside and 3-morpholino-sydnonimine were administered to induce NO toxicity in primary hippocampal neurons. PCD was documented by hematoxylin and eosin nuclear staining, DNA gel electrophoresis, transmission electron microscopy, and protein synthesis assays. Following NO exposure, PCD induction was rapid and robust in approximately 70% of the neuronal population. Activation of specific mGluR subtypes with 1S,3R-ACPD and L-AP4, agents that are neuroprotective against NO, significantly limited the progression of PCD. In contrast, antagonism of mGluRs with L-AP3 did not prevent the development of PCD. Induction of new protein synthesis, a common requisite for PCD, was evident following NO exposure, but did not appear to represent a principal pathway of modulation by the mGluR agonists. Our studies suggest that mGluR modulation of NO-induced PCD represents a primary molecular pathway responsible for neuronal survival. Further elucidation of the molecular mGluR signaling pathways may yield new insight into specific genetic regulatory mechanisms responsible for neuronal injury.

Animals↗
PubMed1997

Infrared Study of Substituted Acetophenones Adsorbed on Silica

Infrared spectra are reported of silica preheated at 873 K and exposed at 295 K to the vapors of four acetophenones (H, 4-Me, 4-OMe, and 4-NO2). Surface-adsorbate interactions involved hydrogen bonding between isolated silanol groups and carbonyl groups, the strength of the hydrogen bonds being related to the electronic effects of the acetophenone ring substituents. The 4-OMe compound also generated SiOH···OMe hydrogen bonds probably via a bridging structure involving two silanol groups perturbed simultaneously by each adsorbed molecule. The mode of adsorption of substituted benzene derivatives on silica is strongly dependent on the electronic effects of the substituents on each other and on the aromatic pi-electron charge density. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Stability of association of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine with liposomes is composition dependent.

The ether lipid, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), has anticancer activity, but it has serious side-effects, including hemolysis, which prevent its optimal use. We surmised if ET-18-OCH3 could be stably associated with liposomes, less free ET-18-OCH3 would be available for lytic interaction with red cells. Liposome composition variables investigated included acyl chain saturation, phospholipid head group and mole ratio of Chol and ET-18-OCH3. It was found that attenuation of hemolysis was strongly liposome composition dependent. Some ET-18-OCH3 liposome compositions were minimally hemolytic. For example, whereas the HI5 (drug concentration required to cause 5% human red cell lysis) was 5-6 microM for free ET-18-OCH3, it was approximately 250 microM for DOPC (dioleoylphosphatidylcholine):Chol (cholesterol):DOPE-GA (glutaric acid derivatized DOPE):ET-18-OCH3, (4:3:1:2) and 640 microM for DOPE (dioleyolphosphatidylethanolamine):Chol:DOPE-GA:ET-18-OCH3 (4:3:1:2) liposomes. Efflux of carboxyfluorescein (CF) from liposomes and Langmuir trough determinations of mean molecular area of lipids in monolayers (MMAM) were used as indicators of membrane packing and stability. Incorporation of ET-18-OCH3 in liposomes reduced the MMAM. Reduction in CF permeation was correlated with reduction in hemolysis. The most stable liposomes included components, such as cholesterol, DOPC and DOPE, which have complementary shapes to ET-18-OCH3.

Centrifugation, Density Gradient↗
PubMed1997

Enhanced therapeutic effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine.

The ether-lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) has anticancer activity, but systemic toxicity has restricted its therapeutic use. In this report "free" ET-18-OCH3 and a stable, well-characterized, liposome-based formulation of ET-18-OCH3 (ELL-12) were compared for in vivo toxicity in normal mice and for therapeutic efficacy in three mouse tumor model systems. The entrapment of ET-18-OCH3 in liposomes decreased the acute toxicity of ET-18-OCH3 after i.v. administration. The maximum tolerated dose for a single i.v. dose of free ET-18-OCH3 was found to be approximately 25 mg/kg, whereas the maximum tolerated dose for ELL-12 was approximately 200 mg/kg. ELL-12 was much less hemolytic in vivo than ET-18-OCH3. The therapeutic efficacy of free ET-18-OCH3 and ELL-12 was investigated against i.p. P388 leukemia, Lewis lung cancer lung metastases, and B16/F10 melanoma (lung tumor nodules) in mice. Although ET-18-OCH3 had some anticancer activity, it was found that ELL-12 was more effective than ET-18-OCH3 in all three tumor models at lower and nontoxic dose schedules. These results suggest that association of ET-18-OCH3 in stable, well-characterized liposomes transforms it into an effective antitumor agent.

Animals↗
PubMed1997

Delta-1 is a regulator of neurogenesis in the vertebrate retina.

In the retina, cell fate determination is thought to be regulated by a series of local cell-cell interactions. Evidence suggests that retinal precursors utilize Notch-mediated intercellular signaling to regulate their fates. However, the identity of the endogenous ligand and its role in the Notch-signaling pathway is not well understood. We have identified C-Delta-1 as the putative endogenous ligand for Notch, in the developing chick retina. C-Delta-1 is coexpressed spatially and temporally with C-Notch-1 and their expression is associated with the temporal aspects of cell birth in the developing retina. This suggests that Delta-Notch signaling is utilized to maintain progenitors in an uncommitted state and that a subtle fluctuation in this signaling helps to sort out competent cells during successive cell-fate determination. We have tested the latter possibility in the specification of the ganglion cells. In early stages of retinal development when ganglion cells are the predominant cells born, decreasing C-Delta-1 expression with antisense oligonucleotides increases the proportion of RA4 antigen-expressing ganglion cells which are recruited predominantly in the periphery. Conversely, use of exogenous Drosophila Delta leads to a decrease in the RA4 antigen-expressing ganglion cells. Our results suggest that C-Delta-1 activation of the Notch pathway regulates the specification of retinal neurons in general and of ganglion cells in particular.

Animals↗
PubMed1997

cDNA cloning and expression analysis of NeuroD mRNA in human retina.

We have shown that bHLH proteins are involved in mammalian retinal development. Here we report the identification and analysis of the expression of a neurogenic differentiation gene, NeuroD, in human retina. In situ hybridization and immunocytochemical analyses of adult retina showed that NeuroD transcripts and NeuroD immunoreactivity are predominantly localized to the outer nuclear layer which contains the photoreceptors. Southern analysis of PCR-amplified cDNA revealed that NeuroD mRNA is also expressed in fetal human retina. Fetal monkey retina was used to analyse the spatial distribution of NeuroD in the developing retina. Both NeuroD transcripts and immunoreactivity are largely detected in the outer neuroblastic layer. Therefore, NeuroD may be involved in the differentiation as well as maintenance of the differentiated properties of photoreceptors.

Adult↗
PubMed1997

Effect of kerosene and its soot on the chrysotile-mediated toxicity to the rat alveolar macrophages.

In order to examine the pulmonary toxicity of kerosene oil and its combustion product (soot) in asbestos-exposed rats, various biochemical and chemical parameters were assayed. Treatment of rats with a single intratracheal dose of chrysotile asbestos (5 mg) and kerosene (50 microliters) or its soot (5 mg) in combination led to an increased number of pulmonary alveolar macrophages (PAM), elevated levels of hydrogen peroxide, and thiobarbituric acid-reacting substances, alterations in the activities of primary (glutathione peroxidase and catalase) and secondary (glutathione reductase and glucose-6-phosphate dehydrogenase) endogenous antioxidant enzymes, and depletion in the levels of glutathione in PAM compared to the chrysotile, kerosene, or soot alone. These changes may indicate the generation of oxidative stress in the macrophages. The resulting oxidative stress may be subsequently critical in collapsing the cellular membrane, which may change the cell membrane permeability and may also damage the phagolysosomal membrane, thereby releasing the membrane bound enzymes as indicated by an increased leakage of intracellular acid phosphatase and lactate dehydrogenase. The injury to macrophages may trigger events that lead to lung fibrosis and/or malignancies in the exposed animals. This study may be helpful in understanding the etiology of certain clinical and pathological disorders in the population exposed simultaneously to both asbestos and kerosene or its combustion products.

Animals↗
PubMed1997

Growth inhibitory effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine.

The growth inhibitory effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) and various liposome compositions of ET-18-OCH3 were compared in a standardized growth inhibition assay utilizing a diverse tumor cell line panel including cell lines expressing multidrug resistance. ET-18-OCH3 and ELL-12 (4:3:1:2, dioleoylphosphatidylcholine/ cholesterol/dioleoylphosphatidylethanolamine-glutaric acid/ET-18-OCH3), an optimal liposomal ET-18-OCH3 formulation, inhibited growth in the micromolar range in drug-sensitive and -resistant cells. In general, ET-18-OCH3-liposomes were about twofold less growth inhibitory than ET-18-OCH3. However, the known hemolytic effects of ET-18-OCH3 were greatly reduced, up to 20 or more times, by liposome association. The effects of ET-18-OCH3 and ELL-12 were compared in intracellular [Ca2+] modulation and DNA fragmentation assays. ET-18-OCH3 elicited both concentration- and serum-dependent transient and permanent increases in intracellular [Ca2+]. In contrast, ELL-12 did not modulate intracellular [Ca2+]. ET-18-OCH3 and ELL-12 similarly affected DNA fragmentation, which may be indicative of apoptosis. The results suggest that, although the specific growth inhibitory effects of ET-18-OCH3 and ELL-12 are similar, associating ET-18-OCH3 with stable well-characterized liposomes eliminates nonspecific cell membrane-associated lytic effects.

Animals↗
PubMed1997

In vivo protective role of Koflet (an ayurvedic preparation) against cellular toxicity caused by CCl4 and flyash.

Swiss albino rats were treated in groups with CCl4, and flyash to induce cellular toxicity in the lungs and trachea. Animal groups received treatment of Koflet (K) with CCl4 (7 days) and with flyash (30 days); their general health and biochemical parameters were studied and used as an indication of cellular injuries. A significant loss was observed in body weight and food consumption in animals given only CCl4 or flyash, while simultaneous treatment with K resulted in a non significant alteration from normal control groups. Enzyme (alkaline phosphatase, Ca2+ -Mg2+ -ATPase, glutamic-oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) activities were estimated in tissue homogenate preparation of lung, trachea and serum, which showed no significant change except for GPT activity as compared to control animals which received CCl4 or flyash with K. Similarly lung, trachea and serum contents of carbohydrate, protein, sialic acid, serum protein, serum cholesterol were estimated and it was found that alteration caused by CCl4, or flyash becomes almost non-significant compared to that of the control after the treatment of K, except for carbohydrate and serum cholesterol values. The animal group which was only treated with K did not show any significant alteration in their biochemical markers or injuries, except for cholesterol.

Animals↗
PubMed1997

High performance liquid chromatographic determination of folic acid and its photodegradation products in the presence of riboflavin.

A high performance liquid chromatographic procedure was developed to determine folic acid and its photodegradation products, p-aminobenzoic acid, pterine-6-carboxylic acid, p-aminobenzoyl-L-glutamic acid, and pteroic acid in the presence of riboflavin. The method involves reversed phase, paired-ion chromatography on mu-BondaPak C18 column using a UV detector (254 nm), and isocratic solvent system (at ambient temperature) comprising 0.017 M monobasic potassium phosphate, tetrabutyl ammonium hydroxide solution (20%, aqueous) and methanol (870:15:250, v/v). The range of quantitation for the individual compounds was found to be: p-aminobenzoic acid, 0.01 - 1.25 x 10(-5) M; pterine-6-carboxylic acid, 0.01-2.0 x 10(-5) M; p-aminobenzoyl-L-glutamic acid, 0.02-2.0 x 10(-5) M; pteroic acid, 0.02-2.5 x 10(-5) M; folic acid, 1.0-5.0 x 10(-5) M; riboflavin, 1.0-5.0 x 10(-5) M. Linear regression analysis of the data demonstrates adequate performance of the method in terms of accuracy and precision (R. S. D. 3%). The method is specific, rapid and convenient and has been applied to photodegradation studies of folic acid in the presence and absence of riboflavin.

4-Aminobenzoic Acid↗
PubMed1997

Kinetic and regulatory properties of rat liver phosphoribosylpyrophosphate synthetase complex are partly distinct from those of isolated recombinant component catalytic subunits.

Rat liver phosphoribosylpyrophosphate (PRPP) synthetase exists as complex aggregates composed of two catalytic subunits (PRS I and II, in a ratio of approximately 4:1) and two catalytically inactive PRPP synthetase-associated proteins. To better understand the significance of the complex structure, the properties of the native liver enzyme were compared with those of homologous aggregates of recombinant PRS I and PRS II (rPRS I and rPRS II). (1) The specific activity per catalytic subunits of the liver enzyme was about 2.5 times lower than that of rPRS I over a wide pH range. Km values for substrates and Ka values for Pi and Mg2+ of the three enzymes were similar. (2) Specific activity of the liver enzyme for the reverse reaction was about 2 times lower than those of rPRSs. Km values for substrates of the three enzymes were comparable. (3) The liver enzyme was more stable than were rPRSs when incubated at a high temperature or in the absence of stabilizing agents. (4) The liver enzyme was markedly less sensitive to inhibition by nucleotides compared to rPRS I. GDP at 1 mM inhibited the liver enzyme and rPRS I by 32 and 93%, respectively. This effect is not ascribable to molecular interaction between rPRS I and II, as reconstitution of the two did not alter the sensitivity to nucleotide inhibition. (5) Our observations suggest that complex aggregation states of the native enzyme not only suppress the activities but also stabilize the catalytic subunits and the associated proteins and remarkably reduce the sensitivity to inhibition by nucleotides.

Animals↗
PubMed1997

Stress and psychiatric disorder in rural Punjab. A community survey.

BACKGROUND: The prevalence of psychiatric disorders in rural Punjab is unknown. Previous studies in rural areas elsewhere in the Indian subcontinent have yielded widely differing estimates. METHOD: First-stage screening of a village near Gujar Khan used the Bradford Somatic Inventory and Self Reporting Questionnaire. Psychiatric interviews were conducted with stratified samples using the ICD-10 Diagnostic Criteria for Research. RESULTS: It is estimated that 66% of women and 25% of men suffered from anxiety and depressive disorders. Levels of emotional distress increased with age in both genders. Women living in unitary households reported more distress than those living in extended or joint families. With younger men and women, lower levels of education were associated with greater risk of psychiatric disorders. Social disadvantage was associated with more emotional distress. CONCLUSIONS: This study in rural Punjab confirms that findings of a previous study in Chitral, northern Pakistan, of high levels of emotional distress and psychiatric morbidity among women in rural areas of Pakistan.

Adolescent↗
PubMed1997

Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome critical region of human chromosome 21q22.2.

The new gene, DCRR1, from the proximal part of the Down's syndrome critical region (DCR) was identified by the GRAIL analysis of the 97-kb nucleotide sequence of two P1 DNAs and the cDNA for DCRR1 gene was cloned. A 7.36-kb cDNA encodes the imcompleted open reading frame composed of 1941 amino acid residues (220.2 kDa). The deduced amino acid sequence contains the conserved domain for protein phosphatases at the N-terminus. The domain encoding the rod-like tail of a myosin heavy chain was also found near the C-terminal region besides the signature for an actin binding protein, profilin, suggesting its possible role as a microtuble-associated protein. Two different sizes (7.9 and 9.0 kb) of mRNAs were detected in the poly(A)+ RNA from abundant tissues by the Northern analysis. The smaller transcript was only transcribed at a high level in the testis. The imbalance of the DCRR1 gene dosage may contibute to the pathogenesis of Down's syndrome.

Amino Acid Sequence↗
PubMed1997

Evaluation of diarrhoea management of health professionals trained at the Diarrhoea Training Unit of Rawalpindi General Hospital.

To promote the use of oral rehydration therapy (ORT), a training programme was launched by The Pakistan National Programme for Control of Diarrhoeal Disease (CDD) by establishing the Diarrhoea Training Units (DTUs). Physicians trained at DTU were designated to establish functioning oral rehydration therapy (ORT) corners at their health centres and train health workers in delivery of facilities on standard diarrhoea case management. The study was designed to evaluate the functioning of ORT corners three years after their establishment. The study revealed that ORT corners have failed to achieve the main objectives of DTU programme. Twenty-four out of 49 ORT corners were non-functional after three years of their establishment, mainly due to frequent transfers of trained staff. In 22 ORT corners evaluated, performance of health professionals was far from satisfactory, 19 out of 22 doctors were found to have inadequate performance in diarrhoea management and only 3 out of 7 LHVs performed adequately. LHVs could not consistently deliver health education messages to mothers. There seems to be a lack of interest and willingness to participate actively, as more than 50% of both doctors and LHVs did not consider ORT work as their job. We conclude that the ultimate objectives of improved and appropriate diarrhoea case management through ORT corners have not been achieved.

Antidiarrheals↗
PubMed1997

Technique for realistic anterior crowns using the IPS Empress porcelain system.

In dentistry, the concept of realism can be applied to the creation of an artificial prosthesis that is not perfect, but real. If prosthesis are made to a flawless perfection, they will appear artificial. Ultimately, the clinician and ceramist should strive for realism. The IPS Empress System (Ivoclar Williams, Amherst, NY) is an all-ceramic restorative alternative utilizing a pressable leucite-reinforced glass ceramic for a variety of indications (e.g., crowns, inlays/onlays, veneers). The resulting tooth-colored and metal-free restorations combine strength and aesthetics approaching those of natural teeth. This article describes the technique and procedures required to achieve realistic anterior crowns with this all-ceramic system.

Aged↗