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Biomedical subjects

F Ahmad

Publications and source records attributed to F Ahmad.

At least 19 recordsLinked to original sources

Sentinel laboratory surveillance of hepatitis C antibody testing in England: understanding the epidemiology of HCV infection.

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.

Acute Disease↗

Unroofed coronary sinus and persistent left superior vena cava.

This report describes a case of unroofed coronary sinus and persistent left superior vena cava discovered during an echocardiographic investigation for dilated pulmonary artery. An unroofed coronary sinus is a rare interatrial shunt that is commonly associated with a persistent left superior vena cava. The latter is a usual cause of a dilated coronary sinus. The detection of a dilated coronary sinus should therefore prompt the search for abnormal coronary sinus drainage and other cardiac abnormalities. The treatment of unroofed coronary sinus and persistent left superior vena cava is undertaken only after assessing the pre- and post-treatment haemodynamics of all co-existing abnormalities.

Aged↗

Diminishing of aggregation for bovine liver catalase through acidic residues modification.

The tendency of proteins to aggregate is an important problem in biotechnology and the pharmaceutical industry. Because proteins in the aggregated state generally do not have the same biological activity as proteins in the native state. In order to prevent aggregation, it is essential to know the effective parameters in anti-aggregation mechanism. Using a chemical protein modification approach, UV-vis and fluorescence spectroscopies and circular dichroism spectropolarimetry, this study investigates the parameters involved in anti-aggregation mechanism of bovine liver catalase. Our findings clearly indicate that the modified bovine liver catalase provides better protection than the native enzyme against thermal aggregation. It seems that a decrease in hydrophobicity resulting in chemical modification plays an important role in preventing aggregation.

Animals↗

Chemometric studies of lysozyme upon interaction with sodium dodecyl sulfate and beta-cyclodextrin.

The interaction of hen egg-white lysozyme with sodium n-dodecyl sulfate (SDS) as an anionic surfactant was investigated by UV-vis spectrophotometry at different pHs at 25 degrees C using HCl/glycine and NaOH/glycine for acidic and basic pH ranges, respectively. Analysis of the spectral data using chemometric method gave the evidence for the existence of intermediate components during the cited interaction. Results also indicated a connection between turbidity of the protein solution upon interaction with SDS and distribution of our newly found intermediates. As intermediates are important in aggregation of proteins, beta-cyclodextrin was employed as an anti-aggregation agent and the results obtained for the lysozyme-SDS-beta-cyclodextrin ternary system were compared with those obtained in the absence of beta-cyclodextrin on distribution and mole fraction of intermediates with. It is also shown that as the distribution of intermediates broadens in a range of SDS concentrations, the turbidity and aggregation state of solution are reduced.

Animals↗

The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements.

Kinetics↗

Acute aortic syndrome: pathology and therapeutic strategies.

Acute aortic syndrome (AAS) describes the acute presentation of patients with characteristic "aortic pain" caused by one of several life threatening thoracic aortic pathologies. These include aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer, aneurysmal leak, and traumatic transection. AAS heralds imminent aortic rupture. Highlighting acute aortic pathology as an AAS is therefore important to encourage prompt recognition of this condition and avoid diagnostic delays. The management of AAS remains a therapeutic challenge. The traditional surgical approach to acute "type B" (descending thoracic) aortic pathology is unsatisfactory with high morbidity and mortality. Endovascular aortic stent grafts now represent an alternative minimally invasive approach in these patients who are often poor surgical candidates. Studies show endovascular repair to be technically feasible with fewer complications. This review discusses AAS pathology and in particular assesses the current role for endovascular aortic repair in its treatment.

Acute Disease↗

Evidence for non-HFE linked hemochromatosis in Asian Indians.

BACKGROUND: Hereditary hemochromatosis is commonly due to two HFE1 (Histone Family E1) gene mutations - H63D and C282Y. Mutations in the Asian Indians are less well studied. AIMS: The aim of this preliminary study was to find out the prevalence of HFE gene mutations in nonviral liver cirrhosis patients. SETTINGS AND DESIGN: Unexplained liver cirrhosis cases with transferrin saturation> 45%, attending the gastroenterology clinic in the years 2004 and 2005 were subjects of the prospective study. Asymptomatic individuals with negative family history of hemolytic anemia or liver disease served as controls. MATERIALS AND METHODS: The clinical presentation was recorded in the patients. Transferrin saturation was estimated by standard colorimetric technique. The two common mutations in HFE1 gene and Y250X mutation of TFR (transferrin receptor) gene were studied by polymerase chain reaction based methods. RESULTS: A majority of the cases were sporadic, but family history was positive in four patients. In one family with multiple affected members, there was clear evidence of autosomal dominant inheritance. Seven out of 31 (22.6%) of unexplained cirrhosis cases were positive for mutations. One was homozygous for H63D. In healthy controls, prevalence was 8.1% (6/74). None of the patients or controls was positive for C282Y mutation of HFE1 or Y250X of TFR gene. CONCLUSIONS: Thus, in a number of cases of hemochromatosis in Indians, a gene with dominant inheritance may be involved in causation of the phenotype. The prevalence of HFE mutations in Indians is comparable to that reported from neighboring countries. It is worth studying other mutations in HFE gene and other iron overload genes in cryptogenic cirrhosis cases.

Adult↗

Comparative study of the conformational lock, dissociative thermal inactivation and stability of euphorbia latex and lentil seedling amine oxidases.

The thermal stability of copper/quinone containing amine oxidases from Euphorbia characias latex (ELAO) and lentil seedlings (LSAO) was measured in 100 mM potassium phosphate buffer (pH 7.0) following changes in absorbance at 292 nm. ELAO was shown to be about 10 degrees C more stable than LSAO. The dissociative thermal inactivation of ELAO was studied using putrescine as substrate at different temperatures in the range 47-70 degrees C, and a "conformational lock" was developed using the theory pertaining to oligomeric enzyme. Moreover ELAO was shown to be more stable towards denaturants than LSAO, as confirmed by dodecyl trimethylammonium bromide denaturation curves. A comparison of the numbers of contact sites in inter-subunits of ELAO relative to LSAO led us to conclude that the higher stability of ELAO to temperature and towards denaturants was due to the presence of larger number of contact sites in the conformational lock of the enzyme. This study also gives a putative common mechanism for thermal inactivation of amine oxidases and explains the importance of C-terminal conserved amino acids residues in this class of enzymes.

Amine Oxidase (Copper-Containing)↗

Experience with video-assisted surgery for suspected mediastinal tumours.

AIM: To assess the therapeutic feasibility of video-assisted thoracoscopic surgery (VATS) in the excision of suspected mediastinal tumours. METHODS: The case notes of 24 consecutive patients referred to a single surgeon between 1997 and 2002 for excision of suspected mediastinal tumours were reviewed. The operative, post-operative and pathological characteristics of patients treated thoracoscopically and by open procedure were analysed. RESULTS: Thirteen of 24 patients underwent thoracoscopic excision. The mean age of the two groups was similar as was the mean operating time and duration of chest drainage. However, patients in the thoracoscopic group had less chest drainage, less pain and a shorter hospital stay. CONCLUSIONS: Video-assisted thoracoscopic excision of mediastinal tumours is a safe and technically feasible procedure and may offer significant post-operative advantages over open procedures.

Adult↗

Strain gauge biomechanical evaluation of forces in orbital floor fractures.

Since the first description of orbital blow-out fractures, there has been much confusion as to their aetiology. Two principal mechanisms have been proposed to explain these fractures, the buckling and hydraulic mechanisms, caused by trauma to the orbital rim and the globe of the eye, respectively. Previous experimental and clinical studies have aimed to support one or other of these two theories. However, these studies have failed to provide quantifiable data to objectively support their conclusions. We present the results of a study of these two proposed mechanisms under identical conditions, using quantifiable intraocular pressure, variable and quantifiable force, and quantifiable bone strain distribution with strain gauge analysis in fresh intact human post-mortem cadavers. Both qualitative and quantitative findings suggest that efforts to establish one theory over the other as the primary mechanism have been misplaced. Both mechanisms produce orbital floor fractures, although these fractures differ fundamentally in their size and location. We have objectively demonstrated that it is easier to fracture the orbital floor by the hydraulic mechanism than by the buckling mechanism, and provided quantitative data for the average force required to displace the orbital floor.

Aged↗

Physician health, stress and gender at a university hospital.

OBJECTIVE: To determine personal and work related factors contributing to physician health and stress in men and women physicians in a university hospital. METHOD: Mail survey of 161 hospital-based Canadian academic physicians (51 women, 110 men). RESULTS: Women compared to men, physicians were younger (M = 43 years, S.D. = 7.4 vs. M = 48 years, S.D. = 8.64; P = .001) and fewer had spouses (76% vs. 90%; P = .01) and children (76% vs. 91%; P = .02). A five-item scale measured somatic symptoms, the dependent variable. Among physicians of both gender, the somatic symptoms scale was significantly correlated with satisfaction with amount of time spent working and scales of mental health (five items), work satisfaction (five items), workload (five items), healthy lifestyle (five items), coping abilities (three items) and support-in-stress (two items). On stepwise regression analysis, for women physicians, 70% of the variance in somatic symptoms was explained by support from colleagues when stressed, and workload. For men, 42% of the variance was explained by healthy lifestyle, mental health, support from colleagues when stressed, and workload. Regardless of gender, the majority of physicians reported an excessive workload but the sources of support when stressed varied by gender. CONCLUSION: Different strategies are needed for women and men physicians to reduce their stress levels.

Adult↗

Pregnancy after breast cancer.

The issue of pregnancy in patients previously treated for breast cancer is controversial. This paper reviews the literature using Medline and Embase databases over the last 50 years to address the issue. Overall survival in patients treated for breast cancer who subsequently become pregnant compares favourably with controls. This paper also addresses the effects of adjuvant therapy (loco-regional and systemic) on subsequent pregnancy. Introduction of a national registry of these patients may help inform such patients in the future.

Antineoplastic Agents↗

Molecular cytogenetic discrimination and reaction to wheat streak mosaic virus and the wheat curl mite in Zhong series of wheat--Thinopyrum intermedium partial amphiploids.

Thinopyrum intermedium (2n = 6x = 42, JJJsJsSS) is potentially a useful source of resistance to wheat streak mosaic virus (WSMV) and its vector, the wheat curl mite (WCM). Five partial amphiploids, namely Zhong 1, Zhong 2, Zhong 3, Zhong 4, and Zhong 5, derived from Triticum aestivum x Thinopyrum intermedium crosses produced in China, were screened for WSMV and WCM resistance. Zhong 1 and Zhong 2 had high levels of resistance to WSMV and WCM. The other three partial amphiploids, Zhong 3, 4, and 5, were resistant to WSMV, but were susceptible to WCM. Genomic in situ hybridization (GISH) using a genomic DNA probe from Pseudoroegneria strigosa (SS, 2n = 14) demonstrated that two partial amphiploids, Zhong 1 and Zhong 2, have almost the identical 10 Th. intermedium chromosomes, including four Js, four J, and two S genome chromosomes. Both of them carry two pairs of J and a pair of Js genome chromosomes and two different translocations that were not observed in the other three Zhong lines. The partial amphiploids Zhong 3, 4, and 5 have another type of basic genomic composition, which is similar to a reconstituted alien genome consisting of four S and four Js genome chromosomes of Th. intermedium (Zhong 5 has two Js chromosomes plus two Js-W translocations) with six translocated chromosomes between S and Js or J genomes. All three lines carry a specific S-S-Js translocated chromosome, which might confer resistance to barley yellow dwarf virus (BYDV-PAV). The present study identified a specific Js2 chromosome present in all five of the Zhong lines, confirming that a Js chromosome carries WSMV resistance. Resistance to WCM may be linked with J or Js chromosomes. The discovery of high levels of resistance to both WSMV and WCM in Zhong 1 and Zhong 2 offers a useful source of resistance to both the virus and its vector for wheat breeding programs.

Agropyron↗

Effect of pure and oxidized cholesterol-rich diets on some biochemical parameters in rats.

The present study was undertaken to evaluate the peroxidative damage and hypercholesterolemia induced in male Wistar albino rats by diets enriched either with 1% oxidized cholesterol (OC) (containing 49.8% of cholesterol oxidation products) or pure cholesterol (PC). The damage caused by the OC diet was revealed by a significant rise in red blood cell hemolysis, increased tissue lipid peroxidation and elevated aspartate amino transferase activity as compared with control and PC diets. Liver glutathione-S-transferase activity was decreased by both OC (P < 0.01) and PC (P < 0.05) diets, but glutathione was observed to be decreased only by the OC diet. Plasma triacylglycerol and cholesterol were increased significantly with both the OC and PC diets. Liver cholesterol and triacylglycerol were increased significantly with the OC diet only. These results indicate that the oxidative damage caused by the OC diet is much more pronounced than that caused by the PC diet.

Animals↗

Identification of a gene responsible for familial Wolff-Parkinson-White syndrome.

BACKGROUND: The Wolff-Parkinson-White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families in which the Wolff-Parkinson-White syndrome segregated as an autosomal dominant disorder. METHODS: We studied 70 members of the two families (57 in Family 1 and 13 in Family 2). The subjects underwent 12-lead electrocardiography and two-dimensional echocardiography. Genotyping mapped the gene responsible to 7q34-q36, a locus previously identified to be responsible for an inherited form of Wolff-Parkinson-White syndrome. Candidate genes were identified, sequenced, and analyzed in normal and affected family members to identify the disease-causing gene. RESULTS: A total of 31 members (23 from Family 1 and 8 from Family 2) had the Wolff-Parkinson-White syndrome. Affected members of both families had ventricular preexcitation with conduction abnormalities and cardiac hypertrophy. The maximal combined two-point lod score was 9.82 at a distance of 5 cM from marker D7S636, which confirmed the linkage of the gene in both families to 7q34-q36. Haplotype analysis indicated that there were no alleles in common in the two families at this locus, suggesting that the two families do not have a common founder. We identified a missense mutation in the gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase (PRKAG2). The mutation results in the substitution of glutamine for arginine at residue 302 in the protein. CONCLUSIONS: The identification of this genetic defect has important implications for elucidating the pathogenesis of ventricular preexcitation. Further understanding of how this molecular defect leads to supraventricular arrhythmias could influence the development of specific therapies for other forms of supraventricular arrhythmia.

AMP-Activated Protein Kinases↗

Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes.

We have identified a new cyclic-nucleotide phosphodiesterase isoform, PDE3A, and cloned its cDNA from cultured aortic myocytes. The nucleotide sequence of its coding region is similar to that of the previously cloned myocardial isoform except for the absence of the initial 300-400 nt that are present in the latter, as confirmed by reverse-transcriptase-mediated PCR, 5' rapid amplification of cDNA ends and a ribonuclease protection assay. Expression in Spodoptera frugiperda (Sf9) cells yields a protein with catalytic activity and inhibitor sensitivity typical of the PDE3 family. The recombinant protein's molecular mass of approx. 131 kDa is compatible with translation from an ATG sequence corresponding to nt 436-438 of the myocardial PDE3A coding region. Antibodies against residues 424-460 (nt 1270-1380) and 1125-1141 (nt 3373-3423) of the myocardial isoform react with an approx. 118 kDa band in Western blots of homogenates of human aortic myocytes, whereas antibodies against residues 29-42 (nt 85-126) do not react with any bands in these homogenates. Our results suggest that a vascular smooth-muscle isoform ('PDE3A2') is a product of the same gene as the longer myocardial ('PDE3A1') and the shorter placental ('PDE3A3') isoforms and is generated pre-translationally in a manner that results in the absence of the 145 N-terminal amino acids of PDE3A1.

3',5'-Cyclic-AMP Phosphodiesterases↗

Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.

The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization. RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice, dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.

Adolescent↗