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Biomedical subjects

M Saad

Publications and source records attributed to M Saad.

At least 19 recordsLinked to original sources

Use of a tissue expander and a polyglactic acid (Vicryl) mesh to reduce radiation enteritis: case report and literature review.

Management of stage IV rhabdomyosarcoma comprises systemic chemotherapy with local control by conservative surgery and radiotherapy. Abdominal radiotherapy may lead to radiation enteritis causing such serious morbidity as malabsorption, fistulae or stricture formation. The risk increases with the dose of radiation and length of bowel involved. Various methods have been utilised to displace the bowel from the radiation field. Usually these are applied in patients requiring pelvic irradiation. We report a case of metastatic alveolar rhabdomyosarcoma requiring radiotherapy to the right renal bed. Effective displacement of small bowel from the tumour site was achieved by a combined use of a tissue expander and Vicryl mesh. There were no complications from the surgery. This is the first report discussing combined use of a tissue expander and Vicryl mesh to aid radiotherapy to the renal fossa in a paediatric patient.

Biopsy↗

The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders.

Hyperlipidemia is a secondary disorder associated with many metabolic disorders including hypothyroidism. The occurrence of dyslipidemia in subclinical hypothyroidism is controversial. Hyperphosphatemia may accompany the dyslipidemia in some metabolic disorders. Both hyperlipidemia and hyperphosphatemia are considered to be risk factors for the coronary heart diseases. In the present study, we investigated the occurrence of dyslipidemia and altered serum phosphate concentrations in patients with thyroid disorders. The results indicated a significantly elevated serum cholesterol and triglyceride concentrations in the hypothyroid patients. The dyslipidemia was accompanied with significantly elevated serum phosphate level. On the other hand, no significant difference was evident in the serum lipid or phosphate concentrations of subclinical hypothyroid patients compared to euthyroid subjects. A significantly reduced serum phosphate level was shown in hyperthyroid patients with unaltered serum lipid levels. Significant correlations were evident between TSH and T(4) levels as independent parameters and the serum concentrations of triglyceride, cholesterol and phosphate. The results indicate in hypothyroidism that a secondary hyperphosphatemia may aggravate myocardial and arterial abnormalities induced by the secondary hyperlipidemia, which may need correction.

Cholesterol↗

T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface.

Recognition of virally infected cells by CD8+ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 D(b) molecule (D(b)). Recognition of both A2 and D(b) are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.

Amino Acid Sequence↗

Contribution of different sources to the pollution of wet weather flows in combined sewers.

Experiments performed on "Marais" catchment, in central Paris, aimed to follow up the quality of wet weather flows from the entry to the exit of a combined sewer network. SS, VSS, COD, BOD5, Cd, Cu, Pb, Zn concentrations were measured for an important number of rain events in roof, yard, street runoff, as well as in dry and wet weather flows at the catchment outlet. Mass entry-exit totals, at the scale of the catchment, were calculated over 31 rain events in order to evaluate the contribution of different types of runoff, of sanitary sewage and of sewer sediments to the total wet weather pollutant loads at the catchment outlet. The erosion of in-sewer pollutant stocks was found to be the main source of particles and of organic matter in wet weather flows, whereas heavy metal loads mainly originated from roof runoff, due to the corrosion of metallic roofs. Particles eroded inside the sewer during rain events were found to be quite different from the particles constituting the main part of sewer sediments: they are organic and biodegradable, with rather important settling velocities and seem to accumulate during dry weather periods. A change of the chemical form of heavy metals was noticed during the transport in the sewer and it is suspected that a fraction of the dissolved metals from the runoff is adsorbed on sewer sediments.

Cadmium↗

Automatic analysis and classification of surface electromyography.

In this paper, parametric modeling of surface electromyography (EMG) algorithms that facilitates automatic SEMG feature extraction and artificial neural networks (ANN) are combined for providing an integrated system for the automatic analysis and diagnosis of myopathic disorders. Three paradigms of ANN were investigated: the multilayer backpropagation algorithm, the self-organizing feature map algorithm and a probabilistic neural network model. The performance of the three classifiers was compared with that of the old Fisher linear discriminant (FLD) classifiers. The results have shown that the three ANN models give higher performance. The percentage of correct classification reaches 90%. Poorer diagnostic performance was obtained from the FLD classifier. The system presented here indicates that surface EMG, when properly processed, can be used to provide the physician with a diagnostic assist device.

Algorithms↗

Evaluation of circulating Fasciola antigens in specific diagnosis of fascioliasis.

Ninety-eight individuals were included in this study, 60 of them were passing Fasciola eggs, 20 were infected with other parasites but not Fasciola (infected control group) and 18 individuals were free from parasite infection (normal control group). Circulating Fasciola antigens (CFAg) and anti-Fasciola IgG were estimated by ELISA technique among all groups. Highly significant increased level of CFAg was observed among Fasciola-infected cases when compared with normal control group. The percentage positivity of CFAg was 95% among Fasciola-infected cases. Solid specificity was observed by the test. Moreover, a highly significant increase in the antigen level was detected among moderately infected patients compared with lightly infected group. The level of CFAg was significantly higher in the hepatomegalic cases than those without organomegaly. Anti-Fasciola IgG antibodies were detected in only 35% of Fasciola infected cases, which indicates much lower sensitivity of the antibody detection than antigens. No correlation between the level of the circulating antibodies and either the intensity of infection or the clinical presentations was observed.

Adult↗

Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2).

We have positionally cloned and characterized a new calcium channel auxiliary subunit, alpha(2)delta-2 (CACNA2D2), which shares 56% amino acid identity with the known alpha(2)delta-1 subunit. The gene maps to the critical human tumor suppressor gene region in chromosome 3p21.3, showing very frequent allele loss and occasional homozygous deletions in lung, breast, and other cancers. The tissue distribution of alpha(2)delta-2 expression is different from alpha(2)delta-1, and alpha(2)delta-2 mRNA is most abundantly expressed in lung and testis and well expressed in brain, heart, and pancreas. In contrast, alpha(2)delta-1 is expressed predominantly in brain, heart, and skeletal muscle. When co-expressed (via cRNA injections) with alpha(1B) and beta(3) subunits in Xenopus oocytes, alpha(2)delta-2 increased peak size of the N-type Ca(2+) currents 9-fold, and when co-expressed with alpha(1C) or alpha(1G) subunits in Xenopus oocytes increased peak size of L-type channels 2-fold and T-type channels 1.8-fold, respectively. Anti-peptide antibodies detect the expression of a 129-kDa alpha(2)delta-2 polypeptide in some but not all lung tumor cells. We conclude that the alpha(2)delta-2 gene encodes a functional auxiliary subunit of voltage-gated Ca(2+) channels. Because of its chromosomal location and expression patterns, CACNA2D2 needs to be explored as a potential tumor suppressor gene linking Ca(2+) signaling and lung, breast, and other cancer pathogenesis. The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus, CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome.

Amino Acid Sequence↗

Usefulness of the response of flow velocity in the left anterior descending coronary artery to the cold pressor test for evaluating endothelium-dependent vascular relaxation in the coronary microvasculature by transesophageal echocardiography in subjects with angiographically normal coronary arteries.

Measurement of flow velocity in the left anterior descending coronary artery by transesophageal echocardiography in subjects without risk factors for coronary artery disease (group 1) and in subjects with normal coronary arteries but conditions associated with endothelial dysfunction (group 2) revealed that there was a significantly impaired coronary flow velocity response to the cold pressor test in group 2 subjects. Thus, transesophageal echocardiography provides a minimally invasive tool for the functional assessment of endothelium and can be valuable in evaluating endothelial dysfunction and recovery in a variety of disease states.

Adenosine↗

NACOB presentation to ASB Young Scientist Award: Postdoctoral. The impact of boundary conditions and mesh size on the accuracy of cancellous bone tissue modulus determination using large-scale finite-element modeling. North American Congress on Biomechanics.

The apparent properties of cancellous bone are determined by a combination of both hard tissue properties and microstructural organization. A method is desired to extract the underlying hard tissue properties from simple mechanical tests, free from the complications of microstructure. It has been suggested that microCT voxel-based large-scale finite element models could be employed to accomplish this goal (van Rietbergen et al., 1995, Journal of Biomechanics, 28, 69-81). This approach has recently been implemented and it is becoming increasingly popular as finite element models increase in size and sophistication (Fyhrie et al., 1997, Proceedings of the 43rd Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, p. 815; van Rietbergen et al., 1997, Proceedings of the 43rd Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, p. 62). However, no direct quantitative measurements of the accuracy of this method applied to porous structures such as cancellous bone have been made. This project demonstrates the feasibility of this approach by quantifying its best-case accuracy in determining the trabecular hard tissue modulus of analogues fabricated of a material with known material properties determined independently by direct testing. In addition we were able to assess the impact of mesh size and boundary conditions on accuracy. We found that the assumption of a frictionless boundary condition in the parallel plate compression loading configuration was a significant source of error that could be overcome with the use of rigid end-caps similar to those used by Keaveny et al. (1997 Journal of Orthopaedic Research, 15(1), 101-110). In conclusion, we found that this approach is an effective method for determining the average trabecular hard tissue properties of human cancellous bone with an expected practical accuracy level better than 5%.

Awards and Prizes↗

Distribution of cholinergic neurons in cell group K of the rabbit brainstem.

The cell bodies of efferent neurons supplying the masseter and digastric muscles of the rabbit are located in two brainstem nuclei: the trigeminal motor nucleus and cell group k. The latter also contains neurons innervating muscles of the middle ear and Eustachian tube, as well as neurons that project to the cerebellum and the oculomotor complex. As part of an attempt to identify the functional subpopulations within the three cell divisions (kl-k3) that make up cell group k, we have investigated the distribution of neurons containing choline acetyltransferase, because these are likely to be motoneurons. Five rabbits anaesthetized with sodium pentobarbital (90 mg/kg, i.v.) were used in this study. They were perfused with 4% paraformaldehyde and 0.1% glutaraldehyde in phosphate buffer (0.1 M, pH 7.4). Two animals were used for preliminary studies. In the other three cases, serial Vibratome coronal sections of the brainstem were cut at 50 microm and two series of alternating sections were collected. The first was stained with a monoclonal antibody (code AB8, Incstar) directed against choline acetyltransferase, using the avidin-biotin-peroxidase method. The other was stained with Cresyl Violet. Cell counts and three-dimensional reconstructions were made for both series to determine positions and ratios of cholinergic and non-cholinergic neurons within the trigeminal motor nucleus and the subdivisions of cell group k. The results showed that the numbers of choline acetyltransferase- and Nissl-stained neurons within the trigeminal motor nucleus were almost identical. In cell group k, significantly fewer choline acetyltransferase-stained cells were counted in all three animals (ratios of choline acetyltransferase/Nissl=0.53-0.71). In addition, the distribution of cholinergic neurons was not uniform throughout cell group k. Subdivisions kl and k3 contained proportionately fewer choline acetyltransferase-positive cells (ratios of choline acetyltransferase/Nissl=0.23-0.64) than did k2 (ratios choline acetyltransferase/ Nissl=0.75-0.88). Within each subdivision, there were significant differences in the spatial coordinates of Nissl- and choline acetyltransferase-positive neurons. We conclude that cell group k contains at least two populations of neurons which are unevenly distributed between and within the three subdivisions. While the majority of neurons in subgroup k2 contain choline acetyltransferase and thus are likely to be motoneurons, more than half of the neurons in subgroups k1 and k3 are not cholinergic. It remains to be determined whether these are the neurons that project to the cerebellum and to other CNS regions.

Animals↗

Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus.

The helix-loop-helix (HLH) protein NEUROD1 (also known as BETA2) functions as a regulatory switch for endocrine pancreatic development. In mice homozygous for a targeted disruption of Neurod, pancreatic islet morphogenesis is abnormal and overt diabetes develops due in part to inadequate expression of the insulin gene (Ins2). NEUROD1, following its heterodimerization with the ubiquitous HLH protein E47, regulates insulin gene (INS) expression by binding to a critical E-box motif on the INS promoter. Here we describe two mutations in NEUROD1, which are associated with the development of type 2 diabetes in the heterozygous state. The first, a missense mutation at Arg 111 in the DNA-binding domain, abolishes E-box binding activity of NEUROD1. The second mutation gives rise to a truncated polypeptide lacking the carboxy-terminal trans-activation domain, a region that associates with the co-activators CBP and p300 (refs 3,4). The clinical profile of patients with the truncated NEUROD1 polypeptide is more severe than that of patients with the Arg 111 mutation. Our findings suggest that deficient binding of NEUROD1 or binding of a transcriptionally inactive NEUROD1 polypeptide to target promoters in pancreatic islets leads to the development of type 2 diabetes in humans.

Adolescent↗

Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study.

CONTEXT: Exercise training is associated with improved insulin sensitivity (SI), but the potential impact of habitual, nonvigorous activity is uncertain. OBJECTIVE: To determine whether habitual, nonvigorous physical activity, as well as vigorous and overall activity, is associated with better SI. DESIGN: A multicultural epidemiologic study. SETTING: The Insulin Resistance Atherosclerosis Study, conducted in Oakland, Calif; Los Angeles, Calif; the San Luis Valley, Colo; and San Antonio, Tex. PARTICIPANTS: A total of 1467 men and women of African American, Hispanic, and non-Hispanic white ethnicity, aged 40 to 69 years, with glucose tolerance ranging from normal to mild non-insulin-dependent diabetes mellitus. MAIN OUTCOME MEASURE: Insulin sensitivity as measured by an intravenous glucose tolerance test. RESULTS: The mean SI for individuals who participated in vigorous activity 5 or more times per week was 1.59 min(-1) x microU(-1) x mL(-1) x 10(-4) (95% confidence interval [CI], 1.39-1.79) compared with 0.90 (95% CI, 0.83-0.97) for those who rarely or never participated in vigorous activity, after adjusting for potential confounders (P<.001). When habitual physical activity (estimated energy expenditure [EEE]) was assessed by 1-year recall of activities, the correlation coefficient between SI and total EEE was 0.14 (P<.001). After adjustment for confounders, vigorous and nonvigorous levels of EEE (metabolic equivalent levels > or = 6.0 and <6.0, respectively) were each positively and independently associated with SI (P< or =.01 for each). The association was attenuated after adjustment for the potential mediators, body mass index (a measure of weight in kilograms divided by the square of the height in meters), and waist-to-hip ratio. Results were similar for subgroups of sex, ethnicity, and diabetes. CONCLUSIONS: Increased participation in nonvigorous as well as overall and vigorous physical activity was associated with significantly higher SI. These findings lend further support to current public health recommendations for increased moderate-intensity physical activity on most days.

Adult↗

Anatomical organization of efferent neurons innervating various regions of the rabbit masseter muscle.

Previous studies have shown that the masseter muscle is supplied by motoneurons located in the anterodorsal region of the trigeminal motor nucleus and by an additional group of efferent neurons located in cell group k. The present experiments were performed on nine rabbits and were designed to establish the locations of neurons innervating the different regions of this muscle. Retrograde labeling with two fluorescent tracers (FluoroGold and Fast Blue) was applied to the central ends of cut branches of the masseter nerve. Serial coronal sections of the brainstem were viewed with fluorescence microscopy. The labeled cells were counted in all animals, and three-dimensional reconstructions of their distribution were made in five cases. In each successful experiment, labeled neurons were seen in the anterodorsal region of the trigeminal motor nucleus and in the two dorsal cell columns of cell group k (k1 and k3). Within-animal comparisons of the median position of populations innervating two distinct muscle regions in five rabbits showed that there were no significant differences in either the dorsoventral or rostrocaudal axes. However, in each case, there was a small but significant difference (83-173 microm) in the mediolateral axis within the motor nucleus but not within cell group k. Even in this axis, there was a 94-99% overlap of the two populations. Comparisons of the neuronal cross-sectional area showed that the deep regions were innervated by a larger proportion of small neurons from both nuclei than were the superficial and intermediate regions. Our results suggest that there is no simple topographical arrangement of motoneurons that corresponds to the peripheral pattern of nerve supply to the different regions of the masseter muscle.

Animals↗

Study of neuromyopathy in amyloid kidney transplant patients.

Neuromuscular status of amyloid and control groups of kidney transplant recipients was assessed through complete neurological examination, assay for serum levels of muscle enzymes (CPK and LDH), electromyography and nerve conduction velocity studies. Neuromyopathic findings were detected in both groups but without severe disabling clinical manifestations. These findings were more prominent in the amyloid group, evidenced by a more significant increase in polyphasicity detected by electromyography and longer prolongation of terminal latency measured in the median nerve. From this study, we concluded that amyloid kidney transplant recipients are more prone to neuromyopathy than the general kidney transplant population, which is mostly due to the amyloidosis itself and/or the colchicine therapy.

Amyloidosis↗

Effect of age, comorbidity and type of surgery on perioperative complications and mortality of prostatectomy.

OBJECTIVE: To study the effect of age, type of surgery and comorbidities (cardiovascular diseases, chronic lung diseases, diabetes mellitus and renal impairment) on the peri-operative complications and mortality of prostatectomy. PATIENTS AND METHODS: A series of 236 consecutive patients who underwent prostatectomy (171 by transurethral resection, TUR, and 65 by open procedure) were reviewed. Ninety patients at risk with one or more of the comorbidities were grouped together and compared with the remaining 146 fit patients. Also, 148 patients aged < or = 70 years were compared with 88 patients aged > 70 years. The peri-operative morbidity variables compared were haemorrhage, > or = 3 units of blood transfusion, bacteriuria, orchitis, pyrexia, uraemia and bed-stay. RESULTS: Mean post-operative bed-stay for patients at risk was significantly longer than that for fit patients (12 +/- 7 and 9.7 +/- 6 days, respectively). Mortality and the other morbidity variables, apart from post-operative bacteriuria which was more frequent in diabetics, were not significantly different between the groups. Similarly, comparing age groups revealed no significant differences. However, open surgery was associated with more haemorrhage, blood transfusion, post-operative pyrexia and a longer bed-stay. CONCLUSION: The comorbidities studied and age did not significantly influence the complications and mortality of prostatectomy. However, comorbidities prolonged post-operative bed-stay. Open surgery was associated with more bleeding and pyrexia and a longer bed-stay than TUR.

Adult↗

Associations of esterase 6 allozyme and activity variation with reproductive fitness in Drosophila melanogaster.

Previous studies have shown that the esterase 6 (EST6) enzyme of D. melanogaster is mainly produced in the sperm ejaculatory duct of the adult male and comparisons of wild-type males with laboratory null mutants have suggested that the enzyme plays a role in reproductive fitness. In this study we have compared 18 field-derived lines each isoallelic for Est6 for differences in five components of male reproductive fitness. No consistent fitness differences were found among lines differing in respect of the two major allozyme classes EST6-F and EST6-S, despite other evidence that these two classes are not selectively equivalent in the field. However, differences in reproductive fitness were found among lines differing in the minor mobility variants that segregate within EST6-F and EST6-S. A failure to distinguish among these minor forms may explain the discrepancies in previous studies on the effects of the major EST6 allozymes on reproductive fitness. The most significant associations we have found between EST6 and reproductive fitness were due to variation in EST6 activity levels. Male EST6 activity levels were found to be positively correlated with their time to first mating, negatively correlated with the numbers of eggs laid and progeny produced by their mates, and negatively correlated with the frequency with which their mates remate. We conclude that some EST6 variants differ in components of male reproductive fitness operative in laboratory cultures. However, the evidence for fitness differences is stronger for variants affecting the amount, rather than the structure of the enzyme, and the direction of the differences varies between some of the fitness components tested.

Alleles↗