Biomedical subjects

Muhammad Tariq

Publications and source records attributed to Muhammad Tariq.

13 recordsLinked to original sources

PubMed2006

Epigenetic regulation of transcription in intermediate heterochromatin.

Constitutive heterochromatin is a compact, transcriptionally inert structure formed in gene-poor and repeat- and transposon-rich regions. In Arabidopsis, constitutive heterochromatin is characterized by hypermethylated DNA and histone H3 dimethylated at lysine (K) 9 (H3K9me2) together with depletion of histone H3 dimethylated at lysine 4 (H3K4me2). Here, we describe loci with intermediate properties of heterochromatin in which transcription downregulation is inherited in a manner similar to constitutive heterochromatin, although the loci are associated with opposing histone marks--H3K4me2 and H3K9me2. In the ddm1 (decrease in DNA methylation 1) mutants, their transcriptional activation is accompanied by the expected shift in the H3 modifications--depletion of H3K9me2 and enrichment in H3K4me2. In mom1 (Morpheus' molecule 1) mutants, however, a marked increase in transcription is not accompanied by detectable changes in the levels of H3K4me2 and H3K9me2. Therefore, transcriptional regulation in the intermediate heterochromatin involves two distinct epigenetic mechanisms. Interestingly, silent transgenic inserts seem to acquire properties characteristic of the intermediate heterochromatin.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2006

Autosomal recessive nonsyndromic deafness locus DFNB63 at chromosome 11q13.2-q13.3.

A genome wide linkage analysis of nonsyndromic deafness segregating in a consanguineous Pakistani family (PKDF537) was used to identify DFNB63, a new locus for congenital profound sensorineural hearing loss. A maximum two-point lod score of 6.98 at theta = 0 was obtained for marker D11S1337 (68.55 cM). Genotyping of 550 families revealed three additional families (PKDF295, PKDF702 and PKDF817) segregating hearing loss linked to chromosome 11q13.2-q13.3. Meiotic recombination events in these four families define a critical interval of 4.81 cM bounded by markers D11S4113 (68.01 cM) and D11S4162 (72.82 cM), and SHANK2, FGF-3, TPCN2 and CTTN are among the candidate genes in this interval. Positional identification of this deafness gene should reveal a protein necessary for normal development and/or function of the auditory system.

Chromosome Mapping↗

PubMed2006

Recurrent intragenic deletion mutation in desmoglein 4 gene underlies autosomal recessive hypotrichosis in two Pakistani families of Balochi and Sindhi origins.

Localized autosomal recessive hypotrichosis (LAH) is rare disorder affecting the scalp, trunk and extremities and largely sparing the facial, pubic and axillary hair. Mutations in desmoglein 4 (DSG4) gene are responsible for LAH which maps to human chromosome 18q12. In this study a recurrent intragenic deletion mutation (Ex5_8del) was identified in DSG4 gene in two Pakistani families of Balochi and Sindhi origins. Manifestation of identical intragenic deletion mutation in eight Pakistani families, six reported earlier and two here, is exceptionally evocative of the dispersion of ancestral chromosome in different ethnic groups through common ancestors.

Base Sequence↗

PubMed2006

Mass casualty management after a suicidal terrorist attack on a religious procession in Quetta, Pakistan.

OBJECTIVE: To determine the effectiveness of hospital management, considering triage system, hospital staff response, medical resources availability, and surgical management depending upon the nature and pattern of injuries in a mass casualty incident. DESIGN: Descriptive. PLACE AND DURATION OF STUDY: Combined Military Hospital, Quetta, Pakistan in March 2004. PATIENTS AND METHODS: All injured by gunshot or blast in a terrorist attack and reported to the hospital were included in this study. Patients were triaged by the triage team using "triage sieve" into priority I, II, III, and IV. Priority I patients were further triaged by using "trauma index" to prioritize for surgery. Phase I included life saving, Phase II limb saving surgery and Phase III for debridement. All data was recorded and analyzed. RESULTS: Hospital received 161 casualties among whom 20 were brought in dead, and 141 patients were admitted to the hospital. Mean age was 26.63 +/- 13.97. The cases were categorized as Priority-I 22.7%, Priority-II 14.72%, Priority-III 50.31% and Priority-IV 12.27%. Maximum casualties reached within the first 2 hours. Eighty-eight patients had pre-dominantly splinter injuries and 53 patients had dominantly gunshot wound injuries. In priority I, the trauma index was 15.55 +/- 5.74. Six patients having trauma index 20 or above could not even be resuscitated. Seventy five percent of staff reported to the hospital within 15 minutes. Only 30% of reserve medical store was consumed. Total management cost to the hospital was Rs. 362,1856/- (British Pounds approx 32,052/-.) calculated by the hospital rates for treatment of non-entitled patients. Death rate in hospital survivors was 4%. CONCLUSION: Mass casualty management in a terrorist act requires prompt hospital response, appropriate triage, efficient surgical approach, and dedicated postoperative care. A good response can help to decrease mortality rate in salvageable injuries.

Blast Injuries↗

PubMed2006

Spectrum of neurological involvement in adult patients with bacterial endocarditis.

OBJECTIVE: To describe the spectrum of neurological involvement, and document in-hospital mortality in adult patients with bacterial endocarditis. DESIGN: Descriptive, non-interventional. PLACE AND DURATION OF STUDY: Department of Gastroenterology, The Aga Khan University Hospital, Karachi from November 1999 to October 2002. PATIENTS AND METHODS: Patients were enrolled from the emergency and outpatient departments, using purposive, non-probability sampling, provided they fulfilled pre-defined inclusion and exclusion criteria. Case records of patients admitted to hospital with a diagnosis of bacterial endocarditis were prospectively analyzed. Data was entered and analyzed on SPSS 11. Frequency, Mean, Mode and Percentage were calculated. RESULTS: Neurological complications were observed in 14 out of 40 patients (35%). The most frequent complication was embolic infarction (33%), followed by intra-cranial hemorrhage (22 %). Seizures, encephalopathy, abscess and meningitis were all observed in decreasing order of frequency. Out of a total of 14 patients who suffered neurological complications, 06 died (42 %). CONCLUSION: The nervous system is frequently involved in patients with bacterial endocarditis. The nature of neurological involvement can vary from a fatal embolic infarction to infective complications, such as cerebral abscess or meningitis, to mild encephalopathy. The most frequently noted complication was embolic infarction. In-hospital mortality is significantly high in patients who suffer neurological complications.

Adult↗

PubMed2004

Triage and management of mass casualties in a train accident.

OBJECTIVE: The purpose of this study was to assess the practicality and usefulness of different scoring systems of triage process in mass casualty management. DESIGN: Descriptive/observational. PLACE AND DURATION OF STUDY: An experience of management of train accident in Balochistan in the year 2003. SUBJECTS AND METHODS: One hundred and twenty-two patients injured in train accident of Quetta Express were included in the study. A trauma team reached the site of the accident. Triage was done at three levels. "Triage sieve" scoring system was used at the site of accident, "field categories of trauma patients" at Primary Health Care Centre, and "ATLS (Advanced Trauma Life Support) secondary survey" at tertiary referral centre. Helicopters and ambulances were used for evacuation of patients. RESULTS: There were 122 injured patients. " Triage sieve " system scored 14(11.47%) patients in priority I, 21(17.21%) patients in priority II, 80(65.57%) patients in priority III and 7(5.73%) dead individuals in priority IV at the site of accident. Casualties clearing time was three and half hours. By utilizing "field categories of trauma patients" at primary health care centre, 7(5.7%) patients were placed in category I who were air lifted, 19(15.57%) patients in category II, 89(72.95%) patients in category III and 7(5.73%) dead remained in category IV. Application of ATLS secondary survey in CMH, Quetta triaged 4(57.14) patients in priority I and 3(42.85) patients in priority II. There was only one death after the triage process started. CONCLUSION: Proper triage, appropriate resuscitation, and timely evacuation definitively decrease morbidity and mortality in trauma patients, and facilitates utilization of the available resources appropriately.

Accidents↗

PubMed2004

Infective endocarditis: a five-year experience at a tertiary care hospital in Pakistan.

OBJECTIVES: Infective endocarditis is common and data regarding its pattern and outcome from developing countries is sparse. We therefore examined the spectrum, demographics and clinical features of infective endocarditis and sought to determine the factors affecting its clinical outcome. PATIENTS AND METHODS: Over a five-year period at our university hospital in Karachi, Pakistan, we identified 66 patients with infective endocarditis and compared their clinicoepidemiologic features and outcomes to subjects in the West. RESULTS: The male:female ratio was 2:1; overall median age was 24 years (35.5 years for men and 13.5 years for women) (p < 0.001). Median duration of symptoms before presentation was 20.5 days. Major predisposing cardiac abnormalities included congenital (50%) and rheumatic (23%) lesions, and a history of heart surgery (17%). Causative organisms and valvular sites of infection were similar to those seen in developed countries. Blood culture-negative infective endocarditis was found in 48% of cases. Renal failure was more frequent among culture-positive patients (p = 0.055). Risk factors for mortality included neurologic (p = 0.003) and embolic (p = 0.02) complications, renal (p = 0.03) and left ventricular failure (p = 0.002), and a history of cardiac surgery (p = 0.026). Overall mortality was 27%. CONCLUSIONS: Patients with infective endocarditis in Pakistan exhibit significant differences compared to their counterparts in the West, including younger age at presentation, incidence of predisposing cardiac conditions, and gender differences reflecting sociocultural bias. Neurologic and embolic complications, renal failure and heart failure predict a worse outcome.

Adult↗

PubMed2004

DNA and histone methylation in plants.

Heritable patterns of gene activity and gene silencing arise by the formation and the propagation of specific chromatin states that restrict or permit gene expression. In mammals and in plants, restrictive heterochromatin is associated with the hypermethylation of DNA at CG sites and with the specific modification of histones, such as the methylation of histone H3 at lysine 9 (H3K9(Me)). In addition to CG methylation, plant nuclear DNA packaged in restrictive chromatin is also usually methylated in cytosines outside a CG sequence context. The functional relationship between an unexpectedly complex plant DNA-methylation system and histone modifications that lead to chromatin compaction and gene silencing is under intense scrutiny. The results of recent studies indicate intriguing links between chromatin remodeling, histone methylation, DNA methylation and RNA interference.

Chromatin↗

PubMed2004

Chromatin techniques for plant cells.

A large number of recent studies have demonstrated that many important aspects of plant development are regulated by heritable changes in gene expression that do not involve changes in DNA sequence. Rather, these regulatory mechanisms involve modifications of chromatin structure that affect the accessibility of target genes to regulatory factors that can control their expression. The central component of chromatin is the nucleosome, containing the highly conserved histone proteins that are known to be subject to a wide range of post-translational modifications, which act as recognition codes for the binding of chromatin-associated factors. In addition to these histone modifications, DNA methylation can also have a dramatic influence on gene expression. To accommodate the burgeoning interest of the plant science community in the epigenetic control of plant development, a series of methods used routinely in our laboratories have been compiled that can facilitate the characterization of putative chromatin-binding factors at the biochemical, molecular and cellular levels.

Chromatin↗

PubMed2003

Erasure of CpG methylation in Arabidopsis alters patterns of histone H3 methylation in heterochromatin.

In mammals and plants, formation of heterochromatin is associated with hypermethylation of DNA at CpG sites and histone H3 methylation at lysine 9. Previous studies have revealed that maintenance of DNA methylation in Neurospora and Arabidopsis requires histone H3 methylation. A feedback loop from DNA methylation to histone methylation, however, is less understood. Its recent examination in Arabidopsis with a partial loss of function in DNA methyltransferase 1 (responsible for maintenance of CpG methylation) yielded conflicting results. Here we report that complete removal of CpG methylation in an Arabidopsis mutant null for DNA maintenance methyltransferase results in a clear loss of histone H3 methylation at lysine 9 in heterochromatin and also at heterochromatic loci that remain transcriptionally silent. Surprisingly, these dramatic alterations are not reflected in heterochromatin relaxation.

Arabidopsis↗

PubMed2003

Validaty of Siriraj Stroke Scoring.

OBJECTIVE: To study the sensitivity and specificity of Siriraj Stroke Scoring (SSS) and to validate the accuracy of SSS in acute supratentorial stroke syndromes. DESIGN: Noninterventional descriptive study. PLACE AND DURATION OF STUDY: Department of Neurology, Pakistan Institute Of Medical Sciences, Islamabad, and Department of Medicine, Federal Government Services Hospital, Islamabad, from July to December 2000 and February to July 2002, respectively. SUBJECTS AND METHODS: One hundred (100) consecutive cases of acute supratentorial strokes were studied in accordance with SSS and sensitivity and specificity of SSS for supratentorial infarction and haemorrhage was tested against the computerised brain scanning (CT) as a gold standard. Siriraj Stroke Scoring was applied. Patients with subarachnoid haemorrhage and transient ischemic attacks were excluded from the study. The findings were recorded, compared and statistically analyzed. RESULTS: Out of 100 patients 45 were male and 55 female with mean age of 59 years. Sixty-two patients had hypertension, 36 patients had one or more atheroma markers (diabetes, coronary artery disease and claudication). Mean diastolic blood pressure was 98 mmHg with range of 60-140 mmHg and mean systolic blood pressure of 163 mmHg with the range of 90-240 mmHg. Forty-eight patients had cerebral infarction, 36 had cerebral hemorrhage while 16 were borderline cases on the basis of Siriraj stroke scoring. CT brain showed 56 and 39 patients had cerebral infarction and haemorrhage respectively while 5 of CT scans were normal. The sensitivity and specificity of SSS for cerebral infarction was 71 and 85 respectively and for intracerebral haemorrhage, it was 73 and 90 respectively. The positive predictive values of SSS for cerebral infarction and haemorrhage were 87% and 83 respectively. CONCLUSION: The siriraj stroke scoring system is a valid and specific scoring system for the diagnosis of acute supratentorial stroke and intracerebral haemorrhage.

Adult↗

PubMed2003

Pulmonic valve endocarditis.

Pulmonic valve endocarditis is an extremely rare infection that shares epidemiologic, clinical, radiologic, microbiologic, and prognostic features with tricuspid valve endocarditis. We report a case of pulmonic valve infection on a structurally normal heart and review the English-language literature on this subject.

Echocardiography, Transesophageal↗

PubMed2002

Depletion of MOM1 in non-dividing cells of Arabidopsis plants releases transcriptional gene silencing.

Mitotic and meiotic inheritance of epigenetic information is coupled to the reproduction of chromatin conformation and DNA methylation patterns. This implies that the S phase of the cell cycle provides a window of opportunity for changes in epigenetic determination. Recent studies, however, have suggested that chromatin structure is also rather dynamic in quiescent cells of multicellular eukaryotes and that silent heterochromatic regions can become accessible to transcription. Such epigenetic flexibility in differentiated tissues could be of physiological importance. The mechanisms and molecular components involved are of great interest but as yet unknown. We examined MOM1 (Morpheus' Molecule 1), a regulator of transcriptional gene silencing (TGS) that acts independently of DNA methylation, for its role in the maintenance of TGS in non-dividing, differentiated cells. The results provide evidence that TGS maintenance mediated by MOM1 is a dynamic process that can be modified in non-dividing cells of mature plant organs by depletion of MOM1.

ATPases Associated with Diverse Cellular Activitie↗