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Biomedical subjects

A Kassam

Publications and source records attributed to A Kassam.

29 records · Page 2Linked to original sources
PubMed1998

Subtype- and response element-dependent differences in transactivation by peroxisome proliferator-activated receptors alpha and gamma.

Peroxisome proliferator-activated receptors (PPAR) modulate transcription by binding to specific peroxisome proliferator-response elements (PPRE) through heterodimerization with the 9-cis retinoic acid receptor (RXR). To investigate potential subtype- and response element-dependent differences in transcriptional activation by PPARs, we expressed PPARalpha or PPARgamma2, along with RXRalpha, in the yeast Saccharoromyces cerevisiae and compared their ability to activate transcription of reporter genes containing a PPRE from either the rat acyl-CoA oxidase (AOx) or hydratase-dehydrogenase (HD) gene. PPARgamma2 and RXRalpha, when coexpressed from low copy vectors, potently and synergistically activated transcription of the AOx-PPRE reporter gene, but only weakly stimulated transcription of the HD-PPRE reporter gene. This response element preference, which was also observed in mammalian cells, could not be attributed to differences in binding affinity of PPARgamma2/RXRalpha heterodimers to these elements in vitro. Interestingly, PPARgamma2 expressed from a high copy vector was able to strongly activate transcription of the HD-PPRE reporter gene, even in the absence of coexpressed RXRalpha. In comparison to the findings with PPARgamma2, the HD-PPRE served as a significantly more robust response element for PPARalpha as compared to the AOx-PPRE. PPRE-dependent transcriptional activation by PPARalpha correlated with binding efficiencies of PPARalpha/RXRalpha to the response element. Our findings demonstrate that the transactivation potential of PPAR subtypes can be differentially modulated by distinct PPREs.

Acyl-CoA Oxidase↗
PubMed1996

Crosstalk between the thyroid hormone and peroxisome proliferator-activated receptors in regulating peroxisome proliferator-responsive genes.

Peroxisome proliferators and thyroid hormones have overlapping metabolic effects and regulate a similar subset of genes involved in maintaining lipid homeostasis. Transcriptional activation by peroxisome proliferators is mediated by peroxisome proliferator-activated receptors (PPARs) that bind to specific peroxisome proliferator-response elements (PPREs) through heterodimerization with retinoid X receptors (RXRs). We examined the effect of thyroid hormone receptor alpha (TR alpha) on DNA binding in vitro and transcriptional activation in vivo by rat PPAR. Gel mobility shift assays using in vitro translated receptors demonstrated that TR alpha was capable of binding on its own and cooperatively with RXR alpha to the rat acyl-CoA oxidase PPRE and of inhibiting the binding of rat PPAR/RXR alpha heterodimers to this element. This inhibition was the result of competition between TR alpha and PPAR for limiting amounts of the heterodimerization partner RXR alpha and for binding to the PPRE. Interestingly, cotransfection of a TR alpha expression plasmid into mammalian cells resulted in potentiation of the peroxisome proliferator- and PPAR/RXR alpha-dependent transcriptional induction of a reporter gene containing the acyl-CoA oxidase PPRE. TR alpha therefore appears to cooperate with RXR and PPAR to positively modulate peroxisome proliferator-dependent transactivation in vivo. Our findings suggest that there is crosstalk between the thyroid hormone and peroxisome proliferator signaling pathways in the regulation of peroxisome proliferator-responsive genes.

Acyl-CoA Oxidase↗
PubMed1996

Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm.

The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.

Adult↗
PubMed1994

Physiological properties of single thenar motor units in the F-response of younger and older adults.

The purpose of this study was to characterize the properties of single thenar motor units in the F-response of healthy younger (n = 15; age 33 +/- 11 years) and older subjects (n = 15; age 68 +/- 3 years). Trains of 300 stimuli at intensities evoking M-potentials 10%, 20%, and 30% of the peak-to-peak amplitude of the maximum M-potential, were delivered to the median nerve. In the young, observed firing probabilities of surface-detected motor unit action potentials (S-MUAPs) extracted from the F-response ranged from less than 1-10%, the S-MUAPs varied in size from 0.015% to 5.3% of the maximum M-potential negative peak area, and they were similar in size to the population of S-MUAPs collected by multiple point stimulation of the median nerve. The percentage difference between the slowest and fastest conducting fibers for individual subjects ranged from 8% to 20%, which translated to conduction velocities (CVs) of 48-68 m.s-1 (mean 59 +/- 4). The preceding were all independent of stimulus intensity. The S-MUAP sizes were significantly larger in older subjects (39%), and the range and distribution of motor unit CVs (38-61 m.s-1; mean 52 +/- 3) were markedly shifted to reflect a slower population of motor fibers. These findings suggest that age-related axonal slowing may uniformly affect all median motor fibers.

Action Potentials↗
PubMed1994

Motor unit number estimates based on the automated analysis of F-responses.

An automated technique for estimating the number of motor units based on single motor unit action potentials in the F-response is described. The average surface detected motor unit action potential (S-MUAP) was calculated from the datapoint-by-datapoint average of a sample of S-MUAPs automatically selected from a population of F-responses. The technique was applied to the thenar muscles of young (n = 18, aged 31 +/- 11 years) and older (n = 15, aged 68 +/- 3) subjects. Motor unit number estimates based on the automated selection of S-MUAPs from the F-responses compared well with those derived using a computer-assisted manual method for selecting S-MUAPs from the F-response (automated 245 +/- 105 vs. manual 241 +/- 100, r = 0.93) and were similar to estimates obtained using multiple point stimulation (219 +/- 77). The advantages of the automated technique for collecting S-MUAPs from the F-response include the ready tolerance of the technique by subjects, the minimal amount of operator interaction required, and the additional information relating to the conduction velocities and latencies of single motor axons.

Action Potentials↗
PubMed1994

Assessment of respiratory limitation in activities of daily life among retired workers.

Epidemiologic studies of occupational lung diseases generally compare symptoms and pulmonary function between groups with differing exposure risks. However, the functional consequences (e.g., on activities of daily life) of statistically significant group differences in either symptoms or pulmonary function are rarely addressed. An understanding of this is important for both the scientific investigators and users of these public health investigations. To address this issue, we developed a 15-item questionnaire to assess breathing-related limitations in activities of daily life, and applied this in a study of 112 retired workers. For each subject, we calculated a limitation score as the number of items associated with breathing difficulty divided by the total number of applicable items. Results from this questionnaire were compared to respiratory symptoms, the Sickness Impact Profile (SIP), lung function test results, 6-min walking distance, and participants' assessment of breathing effort after the walk. The limitation score was significantly higher in subjects reporting dyspnea (22% versus 4%, p < 0.01) or occasional wheeze (27% versus 6%, p < 0.01), and correlated negatively with FEV1, MMEF, and FEV1/FVC (R2 = -0.47, -0.36, and -0.45, respectively, p < 0.0001) and breathing effort after the 6-min walk (R2 = 0.31, p < 0.01). Breathing related limitation in daily activities was also associated with a general health related limitation in household maintenance and ambulation in the SIP (p < 0.01). For each questionnaire item, we compared the responses among subjects with a normal FEV1 to those of subjects with an abnormal FEV1 (below the lower 95% confidence limit).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1994

Respiratory health among retired grain elevator workers.

Previous studies of grain elevator workers have shown exposure-related increased rates for respiratory symptoms and reduced levels of lung function compared with those of other employed populations. However, some reports have suggested that this effect may be reversible after cessation of exposure. To investigate this, we conducted a respiratory health survey among 75 retired grain elevator workers and 37 retired civic workers. Methods included a standard respiratory questionnaire, routine spirometry, chest radiography, a 6-min walk test, and a specialized questionnaire to assess the impact of breathing trouble on the activities of daily life. Grain retirees were slightly older than civic retirees (69 versus 67 yr, p < 0.05) and less likely to be atopic (7 versus 35%, p < 0.01). Grain elevator retirees reported more dyspnea (44 versus 11%, p < 0.01) and had significantly lower levels for both FEV1 (78.6 versus 88.2% pred) and FVC (90.0 versus 97.7% pred) (both p < 0.05). Compared with civic retirees, grain retirees reported the same average level of breathlessness after the 6-min walk test, but they walked a significantly shorter distance (p < 0.01); they also scored higher on the impairment of activities scale and had a greater proportion of persons reporting impairment of daily activities caused by breathing trouble (p < 0.05). Comparison of the changes in lung function from 1975 to the present study (i.e., from active employment to retirement) showed that grain workers had consistently lower levels of lung function than did civic workers while still employed, with no reversibility after retirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1991

Lung function and chest radiograph abnormalities among construction insulators.

We carried out a prevalence survey of pulmonary health parameters among current and retired construction insulators (50 years old and older) from all areas of British Columbia, Canada. The study population included 59 active workers (81 percent participation in this group) and 29 workers who were retired or inactive due to illness (69% participation). Radiograph results were compared to those from actively working bus mechanics from the same age group, and retired grain and civic workers, who were all tested in the same manner. Chest radiographs were read independently by two readers and were graded according to the ILO classification system. Pleural abnormalities alone were found in 34% (20) of active workers (5% in comparison group) and 45% (13) of non-active workers (14% in comparison group). Rates for parenchymal abnormalities for these same groups (ILO grade 1/0 or higher) were 17% (5%) and 20% (5%), respectively. Airflow obstruction was present in 35% (31) of the insulators and was associated with age and the presence of diffuse pleural thickening, and 5 or more years of employment in pulp mills. Restrictive lung function was present in 22% (19) of the insulator population and was associated with age and radiographic evidence of parenchymal fibrosis. The results indicate that construction insulators, a group at high risk for asbestos-related lung disease, also have a high prevalence of airflow obstruction. This was associated not only with smoking, but also with diffuse pleural thickening and a history of pulp-mill employment, suggesting that airflow obstruction in this population is also partly work related.

Aged↗
PubMed1987

Clinical and endocrine responses to embryonic and fetal death induced by manual rupture of the amniotic vesicle during early pregnancy in cows.

Pregnancy was terminated in 4 cows by manual rupture of the amniotic vesicle on day 41 (n = 1) and day 46 (n = 3) after insemination. Each cow was necropsied 36 days after vesicle rupture, by which time only one cow had come into estrus. Luteal activity, monitored daily by plasma progesterone assay, was still evident in 2 cows 35 days after fetal death; in the remaining 2 cows, regression of the corpus luteum (CL) was achieved at 28 and 32 days, respectively. Uterine release of prostaglandin F2 alpha (PGF2 alpha), measured as the 15-keto metabolite (PGFM) PGF2 alpha, was monitored by a plasma sampling schedule; specimens were obtained every 4 hours. There were no appreciable releases of PGF2 alpha associated with fetal death. The first appreciable PGF2 alpha release in episodic form was seen only in conjunction with CL regression. In all cows, a palpable membrane slip was evident for 18 days after rupture of the amniotic vesicle, although at that time, uterine resilience was diminished in the 2 cows in which the CL subsequently regressed. After 18 days, the uterus was noticeably edematous and fluid-filled in all cows; in 1 of the cows with a regressed CL, the uterus had returned to prepregnancy size and tone by day 33.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Fourier registration of three-dimensional brain MR images: exploiting the axis of rotation.

We have developed a novel algorithm to register three-dimensional MR images that have undergone rigid body motion. The most interesting feature of the algorithm is that it reduces a general three-dimensional rotation to a simple planar rotation by finding the axis of rotation. The algorithm, which is a nontrivial three-dimensional extension of existing Fourier registration algorithms, has been tested on 30 artificially misaligned MR images of a phantom, four artificially misaligned MR images of a brain, and one case of actual patient motion. The algorithm successfully registered every image. The registration error for a voxel 10 cm from the origin for the artificially misaligned phantom images was 2.8 mm at most and had a mean of 1.2 mm and standard deviation of .7 mm. The registration parameters for the images contaminated by actual patient motion were similar to that from an established image registration algorithm. The results indicate that the algorithm is accurate, reliable, and fast. The rigid body model requires the brain to be segmented from MR images of the head before registration.

Algorithms↗