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Biomedical subjects

Z Syed

Publications and source records attributed to Z Syed.

8 recordsLinked to original sources

Atrial cell action potential parameter fitting using genetic algorithms.

Understanding of the considerable variation in action potential (AP) shape throughout the heart is necessary to explain normal and pathological cardiac function. Existing mathematical models reproduce typical APs, but not all measured APs, as fitting the sets of non-linear equations is a tedious process. The study describes the integration of a pre-existing mathematical model of an atrial cell AP with a genetic algorithm to provide an automated tool to generate APs for arbitrary cells by fitting ionic channel conductances. Using the Nygren model as the base, the technique was first verified by starting with random values and fitting the Nygren model to itself with an error of only 0.03%. The Courtemanche model, which has a different morphology from that of the Nygren model, was successfully fitted. The AP duration restitution curve generated by the fit matched that of the target model very well. Finally, experimentally recorded APs were reproduced. To match AP duration restitution behaviour properly, it was necessary simultaneously to fit over several stimulation frequencies. Also, fitting of the upstroke was better if the stimulating current pulse replicated that found in situ as opposed to a rectangular pulse. In conclusion, the modelled parameters were successfully able to reproduce any given atrial AP. This tool can be useful for determining parameters in new AP models, reproducing specific APs, as well as determining the locus of drug action by examining changes in conductance values.

Action Potentials↗

Tsetse flies are attracted to the invasive plant Lantana camara.

In tsetse both sexes feed exclusively on the blood of vertebrates for a few minutes every 2-3 days. Tsetse flies seek cover from high temperatures to conserve energy and plants provide shelter for tsetse in all the biotopes they occupy. Recently, tsetse have taken cover in plantations and under the invasive bush Lantana camara that has invaded large areas of the tsetse fly belt of Africa. Flies from such refugia are implicated in sleeping sickness epidemics. In a wind tunnel we show that both foliage and an extract of volatiles from foliage of L. camara attract three tsetse spp. from different habitats: Glossina fuscipes fuscipes (riverine), G. brevipalpis (sylvatic) and G. pallidipes (savannah). Gas chromatography analysis of volatiles extracted from leaves and flowers of L. camara coupled to electroantennograme recordings show that 1-octen-3-ol and beta-caryophyllene are the major chemostimuli for the antennal receptor cells of the three tsetse spp. studied. A binary mixture of these products attracted these flies in the wind tunnel. The gas chromatography linked electroantennograme analysis of the L. camara extracts also show that the antennal receptor cells of the three tsetse spp. respond similarly to groups of volatiles derived from the major biosynthetic and catabolic pathways of plants, i.e. to mono- and sesquiterpenes, to lipoxidation products and to aromatics. Mixtures of these plant volatiles also attracted tsetse in the wind tunnel. These findings show that tsetse flies have conserved a strong sensitivity to volatile secondary products of plants, underlining the fundamental role of vegetation in tsetse survival.

Animals↗

Antennal responses of the two host races of the larch bud moth, Zeiraphera diniana, to larch and cembran pine volatiles.

The larch bud moth (LBM) Zeiraphera diniana Guenée causes defoliation on larch in the Alps at 8- to 10-year intervals, after which populations crash. There are two LBM host races, one on larch and the other on cembran pine. These host races are morphologically indistinguishable as adults but they differ genetically in larval color types. Furthermore, females of each host race produce distinct pheromone blends and show oviposition preferences for their respective hosts. It is not clear to what extent host choice contributes to assortative mating in the LBM. Here, we compare the olfactory sensitivities of the two host races to the odors of fresh foliage of the host plants using the electroantennogram (EAG) technique, and the responses of the two host races to volatiles collected from the two host plants as analyzed by gas-chromatography-linked antennographic detection (GC-EAD). Both sexes of the larch and cembran host races show the same EAG responses to vapors of fresh larch and cembran pine foliage. Fifteen plant volatiles identified as chemostimuli by GC-EAD from larch and cembran pine odors elicited the same antennogram responses from the two host races. However, the GC-EAD analyses indicate that the number and quantity of chemostimuli emanating from each host plant is different. It is, therefore, most probably the array of olfactory receptors responding to the bouquet of volatiles unique to each host plant that underlies the host preferences of the two races. What remains open is the extent to which the similarity of the olfactory systems may contribute to cross-attraction. The fact that LBM individuals with intermediate characteristics between the two host races exist, suggests that olfactory perception does not hinder gene flow and contributes to sustained genetic diversity within the species Z. diniana.

Animals↗

1-octen-3-ol isolated from bont ticks attracts Amblyomma variegatum.

Volatiles from various life-stages of the bont ticks Amblyomma variegatum and A. hebraeum were collected by using solid-phase microfibers and charcoal traps. An octenol isomer was found to be a major constituent of most of the tick material sampled and was identified as 1-octen-3-ol by gas chromatography-mass spectrometry and by using antenna of the tsetse fly Glossina brevipalpis in gas chromatography-linked antennogram detection. Release of this compound increased during molt to adulthood and following mechanical disturbance of adult ticks. (R)-(-)-1-Octen-3-ol and racemate 1-octen-3-ol both induce an increase in upwind walk to the odor source from A. variegatum in an airstream on a servosphere. Volatiles from tick exuviae plus feces and from dead ticks also attracted A. variegatum, suggesting that 1-octen-3-ol may contribute to the aggregation response of Amblyomma spp. on such substrates. 2,6-Dichloroanisol and 2,5-dimethylpyrazine also were detected in volatiles from the ticks but induced no behavioral responses on the servosphere. The suspected tick pheromone component, 2,6-dichlorophenol, was detected from A. variegatum adults cut into pieces but had no effect on the behavior of A. variegatum on the servosphere at a range of doses.

Animals↗

The occurrence of sleep-disordered breathing among patients with head and neck cancer.

OBJECTIVE: To identify the incidence of obstructive sleep apnea (OSA) in patients treated for head and neck cancer. Obstructive sleep apnea is a relatively common and highly morbid condition that affects 9.1% of male and 4% of female middle-aged adults.1 Patients who have been successfully treated for head and neck cancer may often have a partially obstructed upper airway which is functional during the day, but collapses during sleep. STUDY DESIGN/METHODS: Twenty-four patients successfully treated for tumors of the tongue-base, pharynx, or supraglottic larynx were enrolled. Through OSA-related questionnaires, physical examination, and polysomnography, the incidence of OSA in this patient population was determined and compared with that of the general population. RESULTS: The incidence of OSA (91.7%) in this head and neck cancer patient population was found to be significantly (P =.001) higher than that of the general population. (In a random sampling of middle-aged adult males between the ages of 30 and 60 years old with a respiratory disturbance index (RDI) >15, the prevalence was previously reported to be 9.1%.1) Sixteen of 24 patients (72.7%) had clinically defined symptoms of sleep apnea. Ten of 24 patients (41.7%) received radiation therapy; all had an RDI >15. Eleven of the 14 patients (78.5%) who did not receive radiation therapy also had an RDI >15. Eight patients (33.3%) continue to regularly use continuous positive airway pressure with significant improvement in symptoms. CONCLUSIONS: Identification and treatment of OSA may be an important factor in improving quality of life for patients with head and neck cancer.

Body Mass Index↗

ICD waveform optimization: a randomized, prospective, pair-sampled multicenter study.

The theoretical tissue model-based estimates of phase 1 and phase 2 duration of biphasic waveforms are considerably shorter than the pulse widths currently used in ICDs with standard tilt. This study used a tissue resistance/capacitance (RC) model to identify optimal biphasic pulse widths. By paired step-down defibrillation threshold (DFT) testing, the efficacy of standard versus "tuned" biphasic waveforms was evaluated in 91 patients. Standard waveforms consisted of a phase 1 set to 65% tilt and phase 2 = phase 1. The tuned waveform was based on an RC model of membrane characteristics with a time constant of 3.5 ms. The optimal phase 1 truncation point is at the peak of membrane response. The optimal phase 2 duration ends with a membrane response near or just below 0. In paired analysis, no significant differences were found in DFT or impedance between standard and tuned waveforms. In patients with DFTs > 400 V, the tuned waveform lowered the DFT by an average of 38 V (P < 0.05). Multivariate analyses showed a significant inverse relationship between DFT and impedance (P < 0.001). As impedance increased, the tuned waveform was associated with DFTs comparable to the standard waveform with shorter pulse duration and lower delivered energy. No single tilt value allowing an easy calculation of delivered energy was related to ICD waveform efficacy. The use of ICDs with tuned optimal pulse durations offer a greater flexibility of choice for patients with high DFTs.

Aged↗

Kinesin and tau bind to distinct sites on microtubules.

We have used a fluorescent derivative of kinesin, AF-kinesin (kinesin conjugated with 5-(iodoacetamido)fluorescein), to investigate the binding site of kinesin on microtubules and to compare this site with that to which tau binds. Microtubules saturated with tau will bind AF-kinesin in the presence of the ATP analogue, 5'-[beta,gamma-imino]triphosphate (AdoPP[NH]P). This shows that there are distinct binding sites for the two proteins. Further evidence comes from digestion studies where taxol-stabilised microtubules were treated with subtilisin, resulting in the cleavage of C-terminal residues from both the alpha- and beta-tubulin subunits. These treated microtubules can no longer bind tau, but are able to bind AF-kinesin in the presence of AdoPP[NH]P. Finally, AF-kinesin will support the gliding of subtilisin-digested microtubules in the presence of ATP at rates comparable to those obtained with non-digested microtubules. These results show directly that the binding site for kinesin is outside the C-terminal region of tubulin that is removed by subtilisin and is distinct from the binding site of tau.

Adenylyl Imidodiphosphate↗

Skeletal effects of primary hyperparathyroidism.

OBJECTIVE: To review the effect of primary hyperparathyroidism on bone mass and occurrence of fractures as well as the advances in medical management of this relatively common condition. METHODS: We conducted a MEDLINE search of peer-reviewed publications for the period from 1960 to 1999. Studies reviewed were those that evaluated bone mass and fracture risk in primary hyperparathyroidism in both male and female populations. Studies that assessed intervention with hormone replacement therapy, bisphosphonates, calcimimetic agents, and surgical treatment and their effect on bone mass and fracture were also reviewed. Preference was given to prospective studies, but retrospective, cross-sectional, and case-control studies were also evaluated. RESULTS: Most densitometry studies completed to date have been limited by their design. Some cross-sectional studies that used both single-photon absorptiometry and dual-energy x-ray absorptiometry have demonstrated preferential bone loss at cortical skeletal sites. Bone density seems to be relatively well preserved at cancellous bone sites. The absence of large prospective controlled trials makes it difficult to evaluate fracture incidence associated with hyperparathyroidism. Retrospective and case-control studies have found conflicting results relative to fracture incidence in patients with primary hyperparathyroidism. Parathyroidectomy has been shown to be of value in improving bone mineral density at both the lumbar spine and the femoral neck. Hormone replacement therapy in postmenopausal women with primary hyperparathyroidism has also been effective in improving bone mineral density and decreasing bone turnover. Bisphosphonates are currently being evaluated for effectiveness in improving bone mineral density and reducing the risk of fracture. Early results with alendronate treatment have demonstrated improvements in bone mass. Calcimimetic agents are a new treatment option that may become useful in the medical management of primary hyperparathyroidism. CONCLUSION: Although conflicting findings have been reported, bone loss has been noted in patients with primary hyperparathyroidism, especially at cortical skeletal sites. Medical management does not seem to be associated with increased morbidity or mortality in patients with asymptomatic primary hyperparathyroidism. Bone densitometry is advised, particularly for monitoring of bone mass at the midradius or femoral neck, in patients with primary hyperparathyroidism.

Bone Density↗