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S Haq

Publications and source records attributed to S Haq.

At least 19 recordsLinked to original sources
PubMed2005

The structure and crystallization of thin water films on Pt(111).

When water is adsorbed on Pt(111) above 135 K several different ice structures crystallize, depending on the thickness of the ice layer. At low coverage water forms extended islands of ice with a (square root(37) x square root(37))R25(o) unit cell, which compresses as the monolayer saturates to form a (square root(39) x square root(39))R16(o) structure. The square root(39) low-energy electron diffraction (LEED) pattern becomes more intense as the second layer grows, remaining bright for films up of 10-15 layers and then fading and disappearing for films more than ca. 40 layers thick. The ice multilayer consists of an ordered square root(39) wetting layer, on which ice grows as a crystalline film which progressively loses its registry to the wetting layer. Ice films more than ca. 50 layers thick develop a hexagonal LEED pattern, the entire film and wetting layer reorienting to form an incommensurate bulk ice. These changes are reflected in the vibrational spectra which show changes in line shape and intensity associated with the different ice structures. Thin amorphous solid water films crystallize to form the same phases observed during growth, implying that these structures are thermodynamically stable and not kinetic phases formed during growth. The change from a square root(39) registry to incommensurate bulk ice at ca. 50 layers is associated with a change in crystallization kinetics from nucleation at the Pt(111) interface in thin films to nucleation of incommensurate bulk ice in amorphous solid water films more than 50 layers thick.

Journal Article↗
PubMed2005

The structure of the mixed OH + H2O overlayer on Pt[111].

The structure of the mixed p(3 x 3)-(3OH + 3H2O) phase on Pt[111] has been investigated by low-energy electron diffraction-IV structure analysis. The OH + H2O overlayer consists of hexagonal rings of coplanar oxygen atoms interlinked by hydrogen bonds. Lateral shifts of the O atoms away from atop sites result in different O-O separations and hexagons with only large separations (2.81 and 3.02 angstroms) linked by hexagons with alternating separations of 2.49 and 2.813.02 angstroms. This unusual pattern is consistent with a hydrogen-bonded network in which water is adsorbed in cyclic rings separated by OH in a p(3 x 3) structure. The top-most two layers of the Pt atoms relax inwards with respect to the clean surface and both show vertical buckling of up to 0.06 angstroms. In addition, significant shifts away from the lateral bulk positions have been found for the second layer of Pt atoms.

Journal Article↗
PubMed2004

Hydrogen bonding in mixed OH+H2O overlayers on Pt(111).

The stability of OH on Pt(111) has been investigated to determine the role of hydrogen bonding in stabilizing the overlayer. We find that the optimal structure is a mixed (OH+H2O) phase, confirming recent density-functional theory predictions. The reaction O+3H(2)O forms a hexagonal (sqrt[3]xsqrt[3])R30 degrees -(OH+H2O) lattice with a weak (3x3) superstructure, caused by ordering of the hydrogen bonds. The mixed overlayer can accommodate a range of H(2)O/OH compositions but becomes less stable as the H2O content is reduced, causing defects in the hydrogen-bonding network that lift the (3 x 3) superstructure and destabilize the overlayer.

Journal Article↗
PubMed2001

Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure.

BACKGROUND: Left ventricular failure is commonly preceded by a period of hypertrophy. Intriguingly, many of the signaling pathways that have been implicated in the regulation of hypertrophy, including the 3 mitogen-activated protein kinases (MAPKs: extracellular signal-regulated kinase, stress-activated protein kinase, and p38), protein phosphatase, calcineurin, and the protein kinase Akt and its target glycogen synthase kinase-3 (GSK-3), also regulate the apoptotic response. METHODS AND RESULTS: To understand the mechanisms that might regulate the progression of heart failure, we analyzed the activity of these signaling pathways in the hearts of patients with advanced heart failure, patients with compensated cardiac hypertrophy, and normal subjects. In patients with hypertrophy, neither the MAPK nor the Akt/GSK-3 pathways were activated, and the dominant signaling pathway was calcineurin. In failing hearts, calcineurin activity was increased but less so than in the hypertrophied hearts, and all 3 MAPKs and Akt were activated (and, accordingly, GSK-3ss was inhibited), irrespective of whether the underlying diagnosis was ischemic or idiopathic cardiomyopathy. CONCLUSIONS: In the failing heart, there is a clear prohypertrophic activity profile, likely occurring in response to increased systolic wall stress and neurohormonal mediators. However, with the activation of these hypertrophic pathways, potent proapoptotic and antiapoptotic signals may also be generated. Therapies directed at altering the balance of activity of these signaling pathways could potentially alter the progression of heart failure.

Calcineurin↗
PubMed2001

Skull base involvement by a nasopharyngeal carcinoma shown by Tc-99m MDP SPECT but not by computed tomography.

PURPOSE: Plain radiographs, computed tomography (CT), and more recently magnetic resonance imaging (MRI) are used routinely to stage carcinoma of the nasopharynx. Tc-99m methylene diphosphonate (MDP) SPECT is seldom used for local staging of the disease. MATERIALS AND METHODS: Plain radiographs and CT were used to stage squamous carcinoma of the nasopharynx in a 50-year-old man with a left XII nerve palsy. RESULTS: Findings of the plain radiographs were normal, whereas the CT scan revealed a nonhomogenous hyperdense mass in the nasopharynx but intact underlying bone. Given the symptoms, a Tc-99m MDP planar scan was ordered and showed no enhanced uptake, but SPECT images obtained at the same time revealed markedly increased focal radiotracer uptake in the region of the tumor, indicating osseous involvement. CONCLUSION: Possible bony invasion with a nasopharyngeal carcinoma may be better shown with MDP SPECT than with planar isotope bone scans, plain radiographs, or CT.

Adult↗
PubMed2000

Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy.

Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes. Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy. Herein, we report that glycogen synthase kinase-3beta (GSK-3beta), a protein kinase previously implicated in processes as diverse as development and tumorigenesis, is inactivated by hypertrophic stimuli via a phosphoinositide 3-kinase-dependent protein kinase that phosphorylates GSK-3beta on ser 9. Using adenovirus-mediated gene transfer of GSK-3beta containing a ser 9 to alanine mutation, which prevents inactivation by hypertrophic stimuli, we demonstrate that inactivation of GSK-3beta is required for cardiomyocytes to undergo hypertrophy. Furthermore, our data suggest that GSK-3beta regulates the hypertrophic response, at least in part, by modulating the nuclear/cytoplasmic partitioning of a member of the nuclear factor of activated T cells family of transcription factors. The identification of GSK-3beta as a transducer of antihypertrophic signals suggests that novel therapeutic strategies to treat hypertrophic diseases of the heart could be designed that target components of the GSK-3 pathway.

Animals↗
PubMed2000

Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways.

Multiple intracellular signaling pathways have been shown to regulate the hypertrophic growth of cardiomyocytes. Both necessary and sufficient roles have been described for the mitogen activated protein kinase(1) (MAPK) signaling pathway, specific protein kinase C (PKC) isoforms, and calcineurin. Here we investigate the interdependence between calcineurin, MAPK, and PKC isoforms in regulating cardiomyocyte hypertrophy using three separate approaches. Hearts from hypertrophic calcineurin transgenic mice were characterized for PKC and MAPK activation. Transgenic hearts demonstrated activation of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2), but not p38 MAPK factors. Calcineurin transgenic hearts demonstrated increased activation of PKCalpha, beta(1), and theta, but not of epsilon, beta(2), or lambda. In a second approach, cultured cardiomyocytes were infected with a calcineurin adenovirus to induce hypertrophy and the effects of pharmacologic inhibitors or co-infection with a dominant negative adenovirus were examined. Calcineurin-mediated hypertrophy was prevented with PKC inhibitors, Ca(2+) chelation, and attenuated with a dominant negative SEK-1 (MKK4) adenovirus, but inhibitors of ERK or p38 activation had no effect. In a third approach, we examined the activation of MAPK factors and PKC isoforms during the progression of load-induced hypertrophy in aortic banded rats with or without cyclosporine. We determined that inhibition of calcineurin activity with cyclosporine prevented PKCalpha, theta, and JNK activation, but did not affect PKCepsilon, beta, lambda, ERK1/2, or p38 activation. Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKCalpha, theta, and JNK in the heart, while PKCepsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy.

Animals↗
PubMed1999

Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH(2)-terminal kinases.

Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-1 in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload-induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure.

Adenoviridae↗
PubMed1998

Effect of subcutaneous injection of granulocyte-macrophage colony stimulating factor (GM-CSF) on healing of chronic refractory wounds.

OBJECTIVE: To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on healing of chronic wounds. DESIGN: Prospective open study. SETTING: 1 cancer hospital and 2 University hospitals, Pakistan. SUBJECTS: 35 patients with chronic wounds (duration 3 months or longer) that had not responded to standard treatment. Patients with malignant ulcers were excluded. INTERVENTION: GM-CSF 10 microg/cm2 was injected subcutaneously along the edges and base of the wound. The treatment was given only once and patients were followed weekly for a minimum of six weeks. MAIN OUTCOME MEASURES: Changes in size, shape, depth, edges and base of the wound, amount and quality of the granulation tissue, and type of discharge. RESULTS: Six patients were excluded from the analysis, 4 who died early of underlying disease and were not evaluable, and 2 who were excluded when histological examination of the wound showed that it was malignant. Although various types of wounds were studied, most (n = 10, 34%) were postoperative. 23 of the wounds were over 2 cm in diameter (mean 4.8 x 4.6 cm) with thin granulation tissue, and almost half were infected. Nine of the 29 wounds healed completely within six weeks while another 11 decreased in size by more than 50%; 7 patients responded slightly. Only two wounds showed no evidence of healing during the observation period. More than half of the 20 wounds that responded had healed by three weeks. Response did not correlate with any clinical variable including the presence of infection. Toxicity was negligible. CONCLUSIONS: We conclude that subcutaneous injection of a single dose of GM-CSF may induce healing in refractory chronic wounds. Trials are necessary to validate these initial observations and to decide the optimal dose and route, and whether any additional benefit may be derived from repeated injections.

Analysis of Variance↗
PubMed1997

Perinatal exposure to morphine disrupts brain norepinephrine, ovarian cyclicity, and sexual receptivity in rats.

The effect of perinatal exposure to morphine on the development of catecholaminergic and reproductive function in female rats was investigated. Adult rats received morphine intraperitoneally daily for 40 days. The dose of morphine was progressively increased at 10-day intervals from 5, 7.5, 10 to 15 mg/kg body weight until day 40. The rats were mated between days 38 and 45. Administration of morphine at dose rates of 20 and 30 mg/kg continued during pregnancy. The dose was increased to 40 mg/kg for 10 days postpartum. Results showed that morphine disrupted ovarian cyclicity in 52% of the females. Amongst the remaining females, 43% became pregnant when mated. In the female offspring born to such dams, sexual maturation was delayed and body weight was reduced until weaning. At adulthood, lordosis behavior was inhibited when the female offspring were tested against stimulus males. Plasma estradiol and ovarian estradiol and progesterone levels were reduced. Norepinephrine concentration in the hypothalamus was reduced, whereas it remained unchanged in the amygdala. Dopamine concentrations in both hypothalamus and amygdala were not influenced by perinatal morphine exposure. These results suggest that chronic morphine treatment during perinatal life selectively influences the development of noradrenergic mechanisms in the rat brain and this may in turn be responsible for reduced reproductive activity.

Amygdala↗
PubMed1997

A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis.

We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial.

Adult↗
PubMed1997

A prospective phase II trial to evaluate the efficacy and toxicity of hepatic arterial infusion of ifosfamide in patients with inoperable localized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common tumor in the developing countries. Most patients present with relatively advanced disease and have a poor survival. Due to lack of any effective therapy, there is an urgent need to investigate new drugs. We conducted a prospective trial to evaluate the efficacy and tolerability of ifosfamide (IFEX) in patients with histologically proved, inoperable, localized HCC. Eligibility criteria included World Health Organization (WHO) performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5 g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2) was given continuously over 96 hours. Mesna was given intravenously, in same doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple lesions involving both lobes of the liver. Mean size of ultrasonographically evident largest lesion was 11.0 cm. Three patients are inevaluable; one died early, one refused further therapy, and another was lost to follow-up. Among the 16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor response. An additional four (25%) patients had stable disease. Only two (12.5%) patients had progression of disease while on therapy. Overall response rate (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months and mean survival was 7.1 months. Subjective improvement in pain was observed in all but two patients and correlated well with the objective response. Chemotherapy-related side effects were predominantly grade III-IV anemia and alopecia. Three patients had catheter-related complications (one local infection, one bleeding, and one thrombosis). Two patients developed mild encephalopathy and two had hepatic decompensation as evidenced by worsening liver function tests. The results of this pilot study suggest that IFEX, given as a continuous hepatic arterial infusion, is an active drug in inoperable localized HCC. Toxicity is manageable. This drug deserves further trials to properly evaluate its therapeutic potential.

Adult↗
PubMed1996

Purification, characterization, and cDNA cloning of a galactose-specific C-type lectin from Drosophila melanogaster.

We purified a lectin from a pupal extract of Drosophila melanogaster. This lectin agglutinated trypsinized and glutaraldehyde-fixed bovine red blood cells in the presence of calcium or magnesium. The hapten sugar of this lectin was galactose. The molecular mass of the intact lectin was determined to be 41 kDa, and it comprised 14- and 17-kDa subunits. The 17-kDa subunit was shown to be a glycosylated form of the 14-kDa subunit. Analysis of the cDNA for this lectin revealed that the 14-kDa subunit consists of 163 amino acid residues and contains all residues conserved in various C-type lectins. It was suggested that the Drosophila lectin and Sarcophaga lectin share some properties and function similarly in defense and development, but probably they are not structural homologues.

Amino Acid Sequence↗
PubMed1995

Serum sialic acid as an indicator of change in coronary artery disease.

We measured serum levels of total sialic acid (TSA) by an enzymatic method in 74 men who completed the St Thomas' Atherosclerosis Regression Study (STARS). Coronary artery disease (CAD) was assessed as the change (delta) in mean absolute width of coronary segments (MAWS) over 3 years by a computerized technique. Delta TSA was significantly correlated with delta MAWS (r = -.50, P < .001) after adjusting for age, blood pressure, smoking status, and plasma low-density lipoprotein (LDL) cholesterol. The relative risk of progression of CAD for a delta TSA exceeding 10 mg/dL as compared with a delta TSA not exceeding 10 mg/dL was 4.6 (95% confidence interval, 2.4 to 8.7). We conclude that serial measurement of serum TSA levels may be a useful indicator of the progression of CAD.

Age Factors↗