Biomedical subjects

J Ahmad

Publications and source records attributed to J Ahmad.

At least 37 records · Page 2Linked to original sources

PubMed1999

Urinary thymine dimers and 8-oxo-2'-deoxyguanosine in psoriasis.

Psoralen in conjunction with UVA (PUVA) is perhaps the most effective treatment for psoriasis. It is, however, a risk factor for skin cancer in these patients and there is a need to develop non-invasive assays reflective of treatment-induced DNA damage. We report here the assessment of two important lesions, thymine dimer (T<>T) and 8-oxo-2'-deoxyguanosine (8-OHdG), in the urine of psoriasis patients. It was found that, once corrected for urine concentration, the psoriatic group had significantly higher (P<0. 0001) urinary levels of thymine dimers compared to the control group. No significant differences in urinary 8-OHdG levels were noted between the psoriatic, atopic dermatitis and control groups. Therefore biomonitoring of therapy from the very start with this simple and non-invasive assay could perhaps be an effective measure of the risk involved with the treatment allowing optimization for minimal-risk therapy.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Detection of oxidative DNA damage by a monoclonal antibody: role of lysyl residues in antigen binding.

Hydroxyl radical, a prominent entity of reactive oxygen species, is known to modify cellular DNA and has been implicated in several human diseases. A previously described monoclonal antibody (Mab) against reactive oxygen species-modified DNA (ROS-DNA), which preferentially recognizes ROS-modified epitopes on DNA, was used in this study. The epsilon-amino groups of lysine of the Mab were modified to study the role of these residues in Mab binding to ROS-DNA. The results demonstrate that modification of lysyl residues paralleled loss in Mab binding to ROS-DNA to the extent of 73%, suggesting the probable role of these positively charged amino acid residues in the complementarily determining regions of the Mab. The Mab was also used as an immunochemical probe to detect oxidative DNA damage in vivo in SLE. The Mab distinctly recognized five DNA samples out of eight from SLE patients and gave maximum inhibitions of 57, 58, 63, 64 and 70% in inhibition assay, while not reacting with DNA from normal, healthy population which served as negative control. High recognition of DNA isolates from SLE patients by the Mab having preferential binding to ROS-modified epitopes indicates increased oxidative stress in these patients leading to DNA damage which may contribute to the induction of antibodies cross-reacting with native DNA (nDNA).

Animals↗

PubMed1998

Miyoshi myopathy in Saudi Arabia: clinical, electrophysiological, histopathological and radiological features.

Miyoshi myopathy (MM) is a rare autosomal recessive distal myopathy linked to chromosome 2p12-14 that has not been described in Saudi Arabia. A Saudi family with five siblings aged 3-25 years, an unrelated 18-year-old woman and a 40-year-old man with MM were identified. All patients underwent a neurological examination, serum chemistry, electromyography and MRI of the legs. Four patients underwent a muscle biopsy that was processed for routine enzyme histochemistry and immunocytochemical analyses for dystrophin and adhalin (alpha-sarcoglycan). The two sporadic and two familial cases showed classic findings of MM, including early adult onset, preferential involvement of gastrocnemius muscles, markedly elevated serum creatine kinase levels and dystrophic-appearing muscle without vacuoles. Magnetic resonance imaging revealed selective involvement of the posterior compartment muscles and myoedema by STIR sequences. The remaining three familial cases had elevated serum creatine kinase levels and two also had early myopathic findings by EMG suggestive of MM.

Adolescent↗

PubMed1998

Immunochemical detection of oxidative DNA damage in cancer and aging using anti-reactive oxygen species modified DNA monoclonal antibody.

The formation of reactive oxygen species (ROS), although a normal cellular activity, is considerably enhanced under chronic inflammatory conditions and ischemia. These species have been implicated in various disorders, mutagenesis, carcinogenesis and aging. Of many macromolecules, DNA is the most susceptible to hydroxyl radical, the most reactive of the ROS. The present study is designed to detect oxidative DNA damage in cancer patients and healthy aged humans using an anti-ROS-DNA monoclonal antibody (mAb). Purified calf thymus DNA fragments (approximate size 400 bp) were modified with OH, generated by UV-irradiation (254 nm) of hydrogen peroxide. ROS-modified DNA was characterized by UV-spectroscopy, melting temperature, alkaline sucrose density gradient ultracentrifugation and ion-exchange chromatography. ROS-DNA showed single strand breaks, decrease in Tm, modification of thymine (58.3%) and guanine (20%). The mAb generated against ROS-DNA was characterized for antigen binding specificity by competition ELISA. Monoclonal antibody showed strong binding to ROS-modified DNA, its modified fragments, polynucleotides and bases. With the exception of native DNA, binding of unmodified polynucleotides and bases was much lower. The mAb distinctly recognized DNA samples from lymphocytes of healthy aged humans and gave maximum inhibitions of 49, 53, 64 and 70%, while not reacting with DNA from young population. Similarly, oxidative lesions in DNA from cancer patients were also efficiently recognized by the mAb. DNA from healthy controls served as negative control. The studies demonstrate that the mAb, although cross-reactive, preferentially binds ROS-modified epitopes on DNA. High reactivity of mAb to DNA samples from cancer patients and healthy aged humans indicates increased oxidative stress leading to DNA damage.

Aging↗

PubMed1997

Reactive oxygen species modified thymine and poly(dT) present unique epitope for human anti-DNA autoantibodies.

Hydroxyl radical, one of the most potent of all reactive oxygen species has been implicated in many human degenerative diseases and is known to modify adenine and thymine in cellular DNA. In the present studies, adenine, thymine and their synthetic homopolymers poly(dA), poly(dT) were ROS-modified and subsequently used as inhibitors of native DNA binding to human anti-DNA autoantibodies. Besides nDNA, modified thymine and poly(dT) were effective inhibitors of DNA-anti-DNA antibody interaction. The relative affinity of ROS-modified poly(dT) was better than that of native DNA. Visual detection of modified thymine and poly(dT) binding to affinity purified anti-DNA IgG by an indirect band shift assay support competition inhibition data. The enhanced recognition of ROS-DNA by anti-DNA autoantibodies, as reported earlier, could be due to the ROS-induced modification of thymine.

Adenine↗

PubMed1997

Anti-ROS-DNA monoclonal antibody as molecular probe for oxidative DNA damage.

Modification of 400 bp (approximate size) calf thymus DNA with OH radical resulted in lowered Tm, modification of thymine (58.3%), guanine (20%) and single strand breaks. Monoclonal antibodies (mAb) generated against ROS-DNA were of IgG1 subclass. The mAb showed strong binding to ROS-DNA and ROS-modified bases and polymers, in particular, of thymine. The mAb, therefore, preferentially recognizes ROS-modified epitopes on nucleic acids. Distinct binding to DNA isolated from aged, but not from normal humans by the monoclonal antibody was observed. The antibody effectively recognized oxidative lesions in DNA from cancer patients. These studies demonstrate the potential application of the mAb as an immunochemical probe to detect oxidative DNA lesions.

Aging↗

PubMed1997

Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria.

OBJECTIVE: This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 micrograms/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA1 were measured very 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months. RESULTS: In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 micrograms/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 micrograms/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI -18.3 to -15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups. CONCLUSIONS: After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.

Adult↗

PubMed1996

Protective efficacy of a recombinant herpesvirus of turkeys as an in ovo vaccine against Newcastle and Marek's diseases in specific-pathogen-free chickens.

We investigated the potential of a herpesvirus of turkey (HVT)-based recombinant virus (rHVT) as an in ovo vaccine to protect specific-pathogen-free chickens against Newcastle disease (ND) and Marek's disease (MD). The rHVT, designed to express fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of the lentogenic Hitchner B1 strain of ND virus (NDV), as well as glycoproteins A and B of the GA strain of serotype 1 MD virus (MDV) was efficacious in protecting chickens against ND and MD. No adverse effects on hatchability or the survival of chickens were observed following in ovo vaccination with rHVT. A single administration at embryonation day 18 (ED18) or at hatch protected chickens against challenge-exposures with virulent MDV strain RB-1B and velogenic NDV strain GB-Texas (NDV-GB-TX). Vaccinated chickens developed antibodies against both viruses as detected by serological tests, namely, hemagglutination inhibition, virus neutralization and western immunoblotting for NDV, and immunofluorescence and radioimmunoprecipitation assays for MDV. PCR analysis showed that in ovo vaccination with rHVT resulted in a persistent infection leading to systemic immunity against ND for up to 8 weeks of age, the longest period of time tested in this study. However, virus isolation tests indicated that rHVT-vaccinated chickens were only partially protected from the replication of NDV-GB-TX in the trachea. The results of the study indicate that rHVT is safe for both ED18 and posthatch vaccination for ND and MD, and because the vaccine persists, it may induce longer lasting immunity than conventional live NDV vaccines.

Animals↗

PubMed1996

Genomic distribution of 5' TTCCA 3' repeat motif and its diagnostic potential in human Y-chromosome-related anomalies.

We have studied genomic distribution of a simple repeat motif 5' TTCCA 3' derived from the DYZ1 fraction of the human Y chromosome employing restriction fragment length polymorphism and in situ hybridization techniques. This has led us to develop a synthetic DNA based genetic marker specific to human genome. Randomly selected human genomic DNA from both sexes, digested with a total of 16 restriction enzymes, OAT20Y probe comprising four repeat units of 5'TTCCA 3' motif failed to reveal fragment length polymorphisms. In contrast, with most of the enzymes, several multilocus monomorphic bands and with a few enzymes, smeary signals were detected. In situ hybridization of the OAT20Y probe with human chromosomes revealed grains on the long arm of the Y chromosome, whereas the X-chromosome and autosomes showed random distribution of the grains without any preferential labeling in the centromeric or telomeric regions. The OAT20Y probe uncovers a 3.4 kb isomorphic band exclusively in the human male DNA digested with Hae III enzyme. Using the OAT20Y probe, we have detected the presence of Y chromosome in mosaic cell populations of Turner's patients with dysgenetic gonads and high levels of LS/FSH. The presence of Y chromosome in these patients has been associated with an increased risk of gonadoblastoma. The OAT20Y probe offers sensitivity and accuracy for the detection of Y-chromosome-bearing cells in a mosaic cell population and, consequently, help in better management of the patients.

Blotting, Southern↗

PubMed1995

Rheumatic heart disease in India.

A cross-sectional study was carried out in rural areas of Jawan Block, District Aligarh, Uttar Pradesh, India, covering a total population of 3760 drawn from 11 villages. The total number of confirmed cases of rheumatic heart disease was 24 with a prevalence rate of 6.4 per 1000 of the general rural population. The prevalence of rheumatic heart disease increased with age until the age of 25 years. Females were more prone to rheumatic heart disease compared to males. Socio-economic class had a direct impact on the occurrence of rheumatic heart disease.

Adolescent↗

PubMed1994

A clinical-epidemiological study of hypertension in rural population of Jawan Block, Distt, Aligarh (UP) India.

A cross-sectional study was carried out in rural areas of Jawan Block District Aligarh, Uttar Pradesh, India covering a total population of 3760 drawn from 11 villages. The total number of confirmed hypertensives was 59 with a prevalence rate of 15.7 per 1000 of the general rural population. The prevalence of hypertension gradually increased with increase in age. Males were more prone to develop hypertension as compared to females. Obesity, social class and occupation had a direct impact on hypertension.

Adolescent↗

PubMed1992

Discriminant analysis of the standard 12-lead ECG for diagnosing non-Q wave myocardial infarction.

Discriminant analysis was performed on 12 standard lead data from 159 normal subjects (N) and 304 patients with first myocardial infarction (MI): the latter group consisted of 543 patients with acute non-Q wave MI (NQMI-group A), 68 patients with acute Q wave MI (QMI-group B) and 183 patients (group C) with recent (29) or old (154) QMI. A discriminant function was computed to separate optimally the larger group of QMI patients (group C) from N. A total of 7 features accounted for a specificity of 92% and a sensitivity of 89%. The classification model was then tested on patients with acute MI, regardless of the presence of Q waves (groups A and B); rates of correct classification were 72% for acute NQMI and 85% for acute QMI. The best measurements were voltages in the late portion of the T wave in aVR, V1 and V5, in early and late QRS in V2, at mid-QRS in lead II and in the second half of the P wave in V1. A weighted combination of these features with the coefficients of the discriminant function produced individual discriminant scores for each subject. Group-mean scores were 1.82 for N, -1.27 for acute QMI, -1.14 for old QMI and -.44 for acute NQMI, indicating that acute NQMI was "closer" to N than both acute and old QMI. QRS measurements from the 12-lead ECG were also used to derive the 45 criteria/33 point Selvester score in 53 patients with NQMI: 32% of NQMI were classified as MI with a score of 3 points or more (corresponding to a posterior probability greater than .50). These results were compared with those achieved by multivariate analysis using only QRS measurements: 56% of NQMI were classified as MI with a posterior probability threshold greater than .50. Associating a point score greater than or equal to 1 with criteria for ST-T abnormalities yielded a sensitivity of 72% at a specificity level of 95%. The results emphasize the presence of diagnostic information outside the initial part of QRS, the power of multivariate statistical procedures applied on continuous measurements and the potential benefit of discriminant scores for quantitative assessment of myocardial infarction.

Discriminant Analysis↗

PubMed1992

Evaluation of a modified-live virus vaccine administered in ovo to protect chickens against Newcastle disease.

The B1 strain of Newcastle disease virus (NDV-B1), which is nonpathogenic for newly hatched chickens, killed embryos when it was used to inoculate chicken eggs at embryonation day 18. Treatment of NDV-B1 with an alkylating agent, ethylmethane sulfonate (EMS) markedly reduced the pathogenicity of the virus for 18-day-old chicken embryos. Eggs inoculated with the modified virus (NDV-B1-EMS) hatched, and the virus was isolated from lungs and spleen of 1-day-old chickens. The hatched chickens developed antibody to NDV and were protected against challenge exposure (at 4 weeks of age) with a highly virulent GB-Texas strain of NDV. Presence of maternal antibody to NDV in embryonating eggs did not influence the protective ability of NDV-B1-EMS, which also induced protective immunity when administered to 4-week-old chickens. The 50% protective dose of NDV-B1-EMS in maternal antibody-negative and -positive embryos was calculated to be 10.77 and 17.70 embryo 50% lethal doses, respectively. Results of the study indicated that NDV-B1-EMS may be used as an embryo vaccine to protect chickens against Newcastle disease.

Animals↗

PubMed1992

16-lead ECG changes with coronary angioplasty. Location of ST-T changes with balloon occlusion of five arterial perfusion beds.

Percutaneous transluminal coronary angioplasty (PTCA) occlusion in five individual coronary artery distributions produced significant ST elevation ("current of injury") in 48/50 PTCAs in 46 patients. Four patients had PTCA of two separate coronary arteries. Two patients had no significant ischemic ST changes in the 16 simultaneous lead ECG and no chest pain with PTCA. The six limb leads were recorded from Mason-Likar locations modified by moving them centrally on the anterior torso; the V leads were recorded in standard locations, except V1 was moved to V3R. Four extra leads were placed as follows: (1) left axilla, (2) left subcostal margin, (3) V8, and (4) midback at the level of V4-V8. The left axillary and back leads discriminated diagonal and left circumflex (LCX) PTCAs from the others and from each other. V6 showed ST elevation in all LCX PTCAs and in only 10% of left anterior descending occlusions. V3R showed ST elevation in 82% of right coronary PTCAs. In 48/50 (96%) of PTCA occlusions the ST elevation was localized to the torso locations defined in Forward Model Simulations as specific for the arterial perfusion bed involved. These data strongly support the hypothesis that additional resolution and sensitivity to ischemic change is to be expected with a broader array of ECG leads.

Angioplasty, Balloon, Coronary↗

PubMed1989

The contribution of the three columns of the spine to spinal stability: a biomechanical model.

UNLABELLED: The load carrying capacity (LCC) of the human spine was evaluated in 10 human cadaver spines. The specimens consisted of segments from T11 to S1 with markers placed on the specimens at each vertebral level in both Ap and lateral planes. The specimens were loaded to 1250 N and spinal deflections were recorded and photographed at 125 N intervals during the loading cycle. In 5 specimens, axial and flexion loads were applied to the intact spine. The anterior and middle columns were destroyed in sequence at L2 and the loading process repeated. In the remaining 5 specimens, axial and extension loads were applied with the spine intact and after the posterior and middle columns were destroyed in sequence at L2. Load deflection curves were generated for each test and comparisons were made between intact spines and spines with single and double column destruction. RESULTS: When the axis of loading was anterior to the posterior longitudinal ligament (PLL), destruction of the anterior and middle columns reduced the LCC by 46% and 68% respectively and destruction of the posterior and middle columns reduced the LCC by 30% and 63% respectively. There was minimal change in the LCC when the axis of loading was posterior to the PLL and the anterior and middle columns were destroyed. Two column destruction of the spine reduced its load carrying capacity for flexion loads by 70%. In thoracolumbar spinal fractures where flexion loads are predominant and anticipated, the authors conclude that surgical stabilisation is indicated with double column failure.

Humans↗

PubMed1989

The contribution of the three columns of the spine to rotational stability. A biomechanical model.

A function of the spine as a structural column is its ability to resist torsion. The goal of this study was to evaluate the contribution of the columns of the spine to torsional rigidity. Ten human cadaver spines were harvested and frozen. The specimens, consisting of segments from T11 to S1, were subjected to torsional loads of up to 20 N-m. Rotation was recorded throughout the loading cycle. The columns of the spine were destroyed at the L2-3 interspace in a predetermined fashion and loading was repeated. The data were plotted as torsion versus rotation in degrees. The curves of each loading cycle were compared and the ratios of the intact and compromised specimens were calculated. The contribution of each column of the spine to torsional rigidity was determined. In an intact lumbar spine, the anulus was the most effective structure in resisting torsion. Experience gained in this study supports the following conclusion: Flexion-distraction injuries of the thoracolumbar and lumbar spine involving soft tissue destruction of the anterior column and anulus result in rotational instability.

Aged↗

PubMed1989

Failure of long-term cyproheptadine therapy in lowering growth hormone levels in acromegaly.

Basal and post-glucose growth hormone (GH) responses were evaluated in 10 acromegalics receiving cyproheptadine (cypro) 4 mg 6 hourly at 2 and 21 days after initiating therapy. Of the 10 patients, six had macroadenomas with varying degree of suprasellar extensions, one a microadenoma and three had persistent hypersomatotropism despite pituitary adenomectomy due to residual tumour. The basal and post-glucose GH showed no significant change in all, except one with a pituitary microadenoma. His GH was reduced from 680 to 108 mU/L on the second and 82 mU/l on the 21st day of cypro therapy. These data do not suggest any therapeutic role of cypro in the management of acromegaly.

Acromegaly↗

PubMed1985

Estimation of plasma and urinary catecholamines in Guillain-Barré syndrome.

Serial estimation of plasma nor-epinephrine (PNE), 24 hours urinary vanilmandelic acid (VMA) and plasma cortisol was made in 25 adult patients of Guillain-Barré syndrome. Healthy adult age and sex matched volunteers served as controls. The mean level of PNE, VMA and plasma cortisol in controls was 1.07 +/- 0.50 ng/ml, 2.81 +/- 1.18 mg/24 hours and 12.9 +/- 3.10 micrograms/100 ml, respectively. In cases of Guillain-Barré syndrome with autonomic dysfunction the mean level of PNE, VMA and plasma cortisol was 3.34 +/- 2.47 ng/ml, 7.98 +/- 5.71 mg/24 hours and 27.25 +/- 4.94 micrograms/100 ml on the day of admission while in cases of Guillain-Barré syndrome without autonomic dysfunction it was 1.09 +/- 0.32 ng/ml, 3.04 +/- 2.22 mg/24 hours and 11.8 +/- 4.2 micrograms/100 ml, respectively. An increase in circulating PNE, VMA and plasma cortisol was demonstrated in patients of Guillain-Barré syndrome with autonomic dysfunction presenting as hypertension and tachycardia. The maximum rise of 284% (PNE) and 253% (VMA) occurred at the height of paralysis. The elevated levels fell to near control values at the time of significant recovery, and glucose tolerance tests improved. It is suggested that increased levels of catecholamines and cortisol contributed to the development of dysautonomia as these levels were within normal limits in patients of Guillain-Barré syndrome without autonomic dysfunction.

Adolescent↗