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Biomedical subjects

M Ahmad

Publications and source records attributed to M Ahmad.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of interleukin 1-induced matrix metalloproteinase 13 expression in human chondrocytes by interferon gamma.

BACKGROUND: Despite well-documented immunomodulation by interferon gamma (IFNgamma), its role and mechanism of regulation of matrix metalloproteinase 13 (MMP13) gene expression in human chondrocytes is unknown. OBJECTIVE: To investigate the ability and mechanism of IFNgamma to suppress interleukin 1 (IL1)-induced MMP13 expression in articular chondrocytes. METHODS: Human chondrocytes were treated with IFNgamma or IL1beta alone or in combination. MMP13 mRNA was analysed by semiquantitative reverse transcriptase-PCR. MMP13 protein, phospho-signal transducer and activator of transcription 1 (STAT1) and p44/42 mitogen-activated protein kinase levels were measured by western blotting. MMP13 promoter luciferase, cytomegalovirus cyclic AMP response element-binding protein (CBP)/p300 plasmids and STAT1 small interfering RNA (siRNA) were transfected by the calcium phosphate method. IFNgamma receptor was also neutralised. Activator protein (AP) 1 activity was monitored by the TransAM transcription factor kit. STAT1-CBP/p300 interaction was studied by immunoprecipitation. RESULTS: IFNgamma potently suppressed IL1-induced expression of MMP13 and promoter activity. Blockade with neutralising IFNgamma R1 antibody revealed that MMP13 inhibition by IFNgamma is mediated by the IFN receptor. IFNgamma-stimulated activation of STAT1 was directly correlated with MMP13 suppression. Knockdown of the STAT1 gene by specific siRNA or its inhibition with fludarabine partially restored the IL1beta induction of MMP13 expression and promoter activity. IFNgamma did not alter AP1 binding ability but promoted physical interaction of STAT1 and CBP/p300 coactivator. p300 overexpression reversed IFNgamma inhibition of endogenous MMP13 mRNA expression and exogenous MMP13 promoter activity. CONCLUSION: IFNgamma, through its receptor, activates STAT1, which binds with CBP/p300 coactivator, sequesters it from the cell system, and thus inhibits transcriptional induction of the MMP13 gene in chondrocytes. IFNgamma and its signalling pathways could be targeted therapeutically for diminishing IL1-induced cartilage degradation by MMP13 in patients with arthritis.

Blotting, Western↗
PubMed2006

Reverse epidemiology in peritoneal dialysis patients: the Canadian experience and review of the literature.

High Body Mass Index (BMI) has been associated with improved survival of End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD); however, studies on the relationship of BMI with survival in Peritoneal Dialysis (PD) patients have yielded conflicting results. The purpose of this study was to evaluate the impact of BMI on survival of Canadian ESRD patients on PD, correcting for their age, sex, race, diabetes mellitus, and arterial hypertension. In an intent to treat study, we reviewed data of the Canadian Organ Replacement Register (CORR), of incident patients, starting PD between 1994 and 1998 and followed up from their initial PD treatment to the end of 2003. Patients were censored at loss to follow up, transplantation, and the end of the observation period. Cox regression (multivariate) analysis was performed and adjustments were made for age, gender, race, primary renal disease and BMI. During these years, 4054 patients commenced PD, 1742 (43%) of them were females and 1471 (36.3%) were diabetics. The majority were Caucasians (n=3058, 75.4%); 120 (3%) belonged to the First Nations, 137 (3.4%) were black, and the rest (739 pts-18.2%) belonged to various other ethnicities. Based on quartiles of the BMI distribution, 1130 patients (28%) had a BMI < 18.5 kg/m(2); 1163 (28.7%), 18.5-24.9 kg/m(2); 1214 (30%), 25-29.9 kg/m(2); 547 (13.5%) > 30 kg/m(2). Intent to treat Cox regression analysis showed that being underweight was a strong risk factor for death. Specifically, a BMI less than 18.5 was associated with a death hazard ratio (HR) 1.3, (CI: 1.1-1.6). On the contrary, BMI > 30 was not associated with worse survival than those with normal BMI (HR = 1.009, CI = 0.89-1.14). High-BMI patients should not be discouraged from PD just because of their size.

Adolescent↗
PubMed2006

Functional morphology of phonation evaluated by dynamic MRI.

The complex anatomy of the larynx is a consequence of its various airway functions. The aim of the present study was to evaluate which anatomical structures of the larynx soft tissues could be defined using MRI, and to investigate the feasibility of using this technique to assess the dynamic functions of the larynx. MRI images of the larynx of six healthy volunteers during speech production were obtained in vivo. The volunteers were asked to breathe out long and deep in order to prolong in a normal voice the emission of the vowels [i] (as in key) and [a] (as in car) and the consonant [ch] (as in ship). We demonstrated the modification of the larynx position, which is high for [i] and low for [a], and the modification of the vocal folds which is adducted and abducted in [i] and kept abducted in [ch]. Dynamic MRI allows the possibility of multiplanar high-resolution imaging. It can provide information about the anatomy of the larynx and, it also has the ability to image moving laryngeal structures and to analyze vocal fold vibrations during phonation.

Adult↗
PubMed2006

alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction.

Neurotransmission at chemical synapses of the brain involves alpha-neurexins, neuron-specific cell-surface molecules that are encoded by three genes in mammals. Deletion of alpha-neurexins in mice previously demonstrated an essential function, leading to early postnatal death of many double-knockout mice and all triple mutants. Neurotransmitter release at central synapses of newborn knockouts was severely reduced, a function of alpha-neurexins that requires their extracellular sequences. Here, we investigated the role of alpha-neurexins at neuromuscular junctions, presynaptic terminals that lack a neuronal postsynaptic partner, addressing an important question because the function of neurexins was hypothesized to involve cell-adhesion complexes between neurons. Using systems physiology, morphological analyses and electrophysiological recordings, we show that quantal content, i.e. the number of acetylcholine quanta released per nerve impulse from motor nerve terminals, and frequency of spontaneous miniature endplate potentials at the slow-twitch soleus muscle are reduced in adult alpha-neurexin double-knockouts, consistent with earlier data on central synapses. However, the same parameters at diaphragm muscle neuromuscular junctions showed no difference in basal neurotransmission. To reconcile these observations, we tested the capability of control and alpha-neurexin-deficient diaphragm neuromuscular junctions to compensate for an experimental reduction of postsynaptic acetylcholine receptors by a compensatory increase of presynaptic release: Knockout neuromuscular junctions produced significantly less upregulation of quantal content than synapses from control mice. Our data suggest that alpha-neurexins are required for efficient neurotransmitter release at neuromuscular junctions, and that they may perform a role in the molecular mechanism of synaptic homeostasis at these peripheral synapses.

Animals↗
PubMed2006

Degradation of bradykinin, a cardioprotective substance, during a single passage through isolated rat-heart.

Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in different species including human. This cardioprotective effect is mainly due to the inhibition of bradykinin (BK) degradation rather than inhibition of the conversion of angiotensin I to angiotensin II. Bradykinin, a nonapeptide, has been considered to be the potential target for various enzymes including ACE, neutral endopeptidase 24.11, carboxypeptidase M, carboxypeptidase N, proline aminopeptidase, endopeptidase 24.15, and meprin. In the present study, the coronary vascular beds of Sprague Dawley rat isolated hearts were perfused (single passage) with Krebs solution alone or with different concentrations of BK i.e. 2.75x10(-10), 10(-7), 10(-6) and 10(-5) M solution. Percent degradation of BK was determined by radioimmunoassay. The degradation products of BK after passing through the isolated rat-hearts were determined using RP-HPLC and mass spectroscopy. All the four doses of BK significantly decreased the perfusion pressure during their passage through the hearts. The percentage degradation of all four doses was decreased as the concentration of drug was increased, implying saturation of a fixed number of active sites involved in BK degradation. Bradykinin during a single passage through the hearts degraded to give [1-7]-BK as the major metabolite, and [1-8]-BK as a minor metabolite, detected on HPLC. Mass spectroscopy not only confirmed the presence of these two metabolites but also detected traces of [1-5]-BK and arginine. These findings showed that primarily ACE is the major cardiac enzyme involved in the degradation of bradykinin during a single passage through the coronary vascular of bed the healthy rat heart, while carboxypeptidase M may have a minor role.

Animals↗
PubMed2006

High-pressure water jet injury to the pharynx, requiring intubation.

We report a case of upper airway obstruction following high-pressure water jet injury to the pharynx incurred from a car wash jet. Injuries from high-pressure water jets are relatively rare and, to the best of our knowledge, airway obstruction as a result has not been reported. Since this unusual injury may be associated with life-threatening complications, it must be promptly recognized and treated.

Airway Obstruction↗
PubMed2005

Photofragmentation study of hexamethyldisiloxane following core ionization and direct double ionization.

X-ray photoelectron spectroscopy and Auger spectroscopy studies of gas-phase hexamethyldisiloxane (HMDSO) are presented. The photodissociation of this molecule is studied using various experimental coincidence techniques. We compare the fragmentation pathways observed after core ionization followed by Auger decay and after valence double photoionization of the molecule. A strongly selective production of the doubly charged tetramethyldisiloxane ion is observed in the low binding-energy regions. Theoretical calculations are carried out to tentatively explain the stability of the produced dication.

Journal Article↗
PubMed2005

Heme oxygenase-1 gene expression increases vascular relaxation and decreases inducible nitric oxide synthase in diabetic rats.

Hyperglycemia represents the main cause of complication of diabetes mellitus and oxidative stress, resulting from increased generation of reactive oxygen species (ROS), and plays a crucial role in their pathogenesis. Impairment of vascular responses in diabetic rats, as a result of an increase in superoxide (O2-), formation is a major complication in diabetes. Since heme oxygenase (HO) expression regulates the level of ROS by increasing antioxidant, such as glutathione and bilirubin, we investigated whether upregulation of HO-1 modulates the levels of iNOS and eNOS and altered vascular responses to phenylephrine (PE) and acetylcholine (Ach) in aorta and femoral arteries of diabetic (streptozotocin (STZ)-induced) rats. Our results showed that iNOS expression was increased, but HO activity was reduced, in diabetic compared to nondiabetic rats (p<0.05). Upregulation of HO-1 expression by cobalt protoporphyrin (CoPP), an inducer of HO-1 protein and activity, conferred an increase in eNOS and differentially decreased iNOS protein levels (p<0.05). Isolated aortic and femoral arteries obtained from diabetic rats exhibited contraction to PE and relaxation to Ach, which were markedly increased and decreased, respectively. However, HO-1 induction in diabetic rats normalized relaxation compared to controls. Therefore, overexpression of HO-1 may mediate an increase in eNOS and a decrease in iNOS, potentially contributing to restoration of vascular responses in diabetic rats.

Acetylcholine↗
PubMed2005

Influence of formation path on the CH2BrCl2+ dissociation dynamics.

To get further insight into the CH2BrCl site-selective fragmentation previously observed upon inner-shell ionization, we have performed high-resolution Br 3d and Cl 2p Auger and spin-orbit resolved Br 3d Auger spectra, and studied the dissociation properties of the CH2BrCl2+ dication formed at threshold by means of threshold electron pair-ion coincidence measurements. The key point is that the origin of site-specific bond breaking is found in the Auger decay itself, as it preferentially populates selected dication states. Whereas the predominance of the C-Br bond breaking is observed in both threshold and inner-shell studies, no signature of selective C-Cl rupture is reported for the dication formed at threshold.

Journal Article↗
PubMed2005

Fine mapping of the X-linked split-hand/split-foot malformation (SHFM2) locus to a 5.1-Mb region on Xq26.3 and analysis of candidate genes.

Split-hand/split-foot malformation (SHFM) is a genetically heterogeneous disorder, with five known loci, that causes a lack of median digital rays, syndactyly, and aplasia or hypoplasia of the phalanges, metacarpals, and metatarsals. In the only known SHFM2 family, affected males and homozygous females exhibit monodactyly or bidactyly of the hands and lobster-claw feet. This family (1) was revisited to include additional subjects and genealogical data. All 39 affected males and three females fully expressed the SHFM, while 13 carrier females examined exhibited partial expression of SHFM. We narrowed the previously linked 22-Mb genetic interval on Xq24-q26 (2), by analyzing additional family members and typing additional markers. The results define a 5.1-Mb region with a new centromeric boundary at DXS1114 and a telomeric boundary at DXS1192. We did not identify mutations in the exons and exon/intron boundaries of 19 candidate genes. These data suggest that the mutation may lie in a regulatory region of one of these candidate genes or in another gene within the SHFM2 region with unclear role in limb development.

Abnormalities, Multiple↗
PubMed2005

Epstein-barr virus detection in tumors of upper gastrointestinal tract. An in situ hybridization study in Pakistan.

To examine the potential role of Epstein-Barr virus (EBV) in the carcinogenesis of upper gastrointestinal tract, we conducted an in situ hybridization assay for EBV-encoded small RNA (EBER) expression in the tumors of 56 oral and 50 esophageal squamous cell carcinoma (SCC) cases, and 52 stomach adenocarcinoma cases diagnosed in the King Edward Medical College and Allama Iqbal Medical College Lahore, Pakistan between 1996-2002. There were no malignancies with positive EBER expression in oral and esophageal SCC. Only one out of the 52 gastric adenocarcinoma cases (1.9%) was positive for EBER expression, and this frequency was relatively low as compared to cases reported worldwide. The case was a 42 year-old male patient and histologically classified as moderately differentiated tubular adenocarcinoma. In conclusion, the frequency of EBV-associated gastric carcinoma was relatively low in Pakistan. The present study could not confirm the involvement of EBV in the carcinogenesis of oral and esophageal SCC.

Adenocarcinoma↗
PubMed2004

Adrenal insufficiency due to primary bilateral adrenal non-Hodgkin's lymphoma.

A case of primary adrenal insufficiency, secondary to primary bilateral adrenal lymphoma is reported. A 50-year-old woman presented with features of primary adrenal insufficiency (darkening of skin, asthenia, anorexia, constipation) for at least 8 months. Clinical examination was unremarkable except for low body mass index and generalized skin and buccal mucosal pigmentation. Routine investigations including complete hemogram, serum chemistry, urine analysis, chest radiograph and electrocardiogram were normal; serum lactate dehydrogenase was moderately elevated. Primary adrenal insufficiency was confirmed on cortisol dynamics (very low basal and peak cortisol) after insulin-induced hypoglycemia. Routinely detected adrenal masses on ultrasonography were confirmed by contrast enhanced CT abdomen. A diagnosis of primary adrenal non- Hodgkin's lymphoma (B-cell) was made after exploratory laprotomy and further staging. The patient was put on combination chemotherapy (CHOP) protocol, but was lost to follow-up after receiving two cycles of treatment. Primary adrenal lymphoma, although a rare entity, needs to be suspected in patients with features of primary adrenal insufficiency who have evidence of bilateral adrenal masses on imaging.

Adrenal Gland Neoplasms↗
PubMed2004

Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis).

Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.

Base Sequence↗
PubMed2004

Efficacy of bronchial wash cytology and its correlation with biopsy in lung tumours.

OBJECTIVE: To evaluate bronchial wash cytology with histology in our set up. METHODS: Seventy three specimens were obtained by flexible fiberoptic bronchoscope at pulmonology department of Military Hospital Rawalpindi. All the preserved samples were processed under standard conditions. The slides were stained with Papanicolaou and Haematoxylin and Eosin stains. RESULTS: A total of 73 patients were studied. The age range was 21 to 80 years. Male to female ratio was 8:1. Complete cytological and biopsy consensus was found in 55 (77.4%) cases. Cytology revealed 24 cases as malignant and nine as atypical/suspicious. Benign and inadequate were 29 and 2 respectively. Histopathology of these cases confirmed 24 (32.9%) as malignant and 29 (39.8%) as benign. True positive alongwith suspicious/atypical were 33 and true negative cases were 29. False positive was one case only whereas false negative cases were eight. The bronchial wash cytology showed sensitivity (80.5%), specificity (96.6%) and accuracy (87.3%). Positive predictive value and negative predictive value were 97% and 78.4% respectively. The commonest types of tumours were squamous cell carcinoma and small cell carcinoma. CONCLUSION: It is concluded that bronchial wash cytology is a valuable tool and yields almost same information as biopsy. It is useful in patients with evidence of obstruction or risk of haemorrhage.

Adult↗
PubMed2004

Comparison of optimal malarial test with light microscopy for the diagnosis of malaria.

OBJECTIVE: To evaluate the efficacy of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (optimal) against conventional light microscopy in the diagnosis of malaria at Military Hospital, Rawalpindi and Department of Pathology Army Medical College Rawalpindi from August to October 2002 in patients reporting sick with history suggestive of malaria. METHODS: The blood samples were collected from 215 patients reporting with symptoms suggestive of malaria. Thick and thin blood films were prepared, stained with Leishman's stain and examined by light microscopy for the presence of malarial parasites. Parasitaemia was estimated on all positive slides. All samples were tested for presence of malarial parasite by optimal dipstick method according to the manufacturer's instructions. RESULTS: A total of 215 cases were studied. Malarial parasites were visualized in 98 (45.5%) cases with light microscopy. Optimal test revealed 93 (43.2%) of these samples as positive. Microscopy showed 61 out of 98 positive cases to be P. vivax and 37 P. falciparum. The Optimal dipstick method revealed that 58 out of 93 were positive for P. vivax and 35 positive for P. falciparum. These results demonstrated that Optimal had sensitivities of 95% and 94.5% for P. vivax and P. falciparum respectively. It has 100% specificity for both malarial species, when compared to conventional microscopy. CONCLUSION: Optimal test showed excellent correlation with microscopy in the diagnosis of P. vivax and P. falciparum. It is expensive but it has an advantage of being simple, rapid and effective test in the diagnosis of malaria especially where well trained microscopists are not available or work load is too high.

Animals↗
PubMed2004

Morphological study of liver biopsy in Thalassaemia major.

OBJECTIVE: To see the morphological changes in liver in transfusion dependent Thalassaemia major children undergoing bone marrow transplantation. METHODS: This retrospective cross-sectional survey was conducted at Pathology department of Army Medical College and Paediatric department of Military Hospital, Rawalpindi from Jul 2000 to Aug 2003. Liver biopsies were done in 40 thalassaemic major children and histological changes including Knodell Histological activity index (HAI); grade, stage and score along with degree of haemosiderosis were noted. Serum ALT levels, ferritin assays and screening for HBsAg and Anti- HCV antibody were also carried out in these cases. RESULTS: Forty children 1.5-10.5 years of age (mean 6.1 years) with a male to female ratio of 1.2:1 were included in the study. According to Knodell HAI scoring, 24 (60%) cases had Knodell HAI score between 13/22 to 18/22 and 18 patients (45%) in grade 9-12/18. Six children had fully developed cirrhotic changes whereas 22 and 12 patients showed stage 3 and 1 respectively. Twenty eight (70%) patients had grade 3-4 haemosiderosis. HBsAg was positive in 6 and anti- HCV antibody in 14 patients. Serum ferritin and ALT levels were markedly raised in most of the patients. CONCLUSION: Seventy percent patients had moderate to severe haemosiderosis and high Knodell HAI score was found in children with severe haemosiderosis, raised ALT and Ferritin levels and with positive serology for HBsAg and anti- HCV antibody. Liver biopsy is useful in thalassaemic children to assess the stage of liver disease and selection of suitable cases for bone marrow transplantation (BMT).

Biopsy↗
PubMed2004

Treatment of acute fractures of the femoral shaft with reamed intramedullary interlocking AO nails.

OBJECTIVE: To review and audit our experience with closed intramedullary interlocking nailing for acute femoral shaft fractures. METHODS: All patients admitted to The Aga Khan University Hospital, over the last six years and with a minimum follow-up of twelve months, with acute fractures of the femoral shaft were included in the study. All patients treated for established non-unions and infections or with pathological fractures were excluded from the study. RESULTS: There were 89 fractures, 74% of whom were closed and 50% were associated with other orthopedic injuries. Most of these were younger patients involved in high velocity road traffic accidents. The union rate was 88% with 4.4% of fractures going into non-union. The remaining 8% of the fractures went into a phase of delayed union, but ultimately united, making the overall success rate to be 95.6%. The mean time for union was 11.5 weeks. At the final clinical follow-up, 4% of the patients had minor pain, 7% had limp, 4% had leg length discrepancy of more than 2 cm and 4% had decreased range of motion at the hip or knee joints. We had a 4% rate of superficial infection. There were 3 cases of pudendal nerve neuropraxia and 2 cases of deep vein thrombosis. CONCLUSION: Intramedullary Interlocking nailing is a safe and effective treatment modality for acute fractures of the femoral shaft. Proper surgical decision making regarding static versus dynamic mode of locking can avoid problems of delayed union.

Acute Disease↗