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Biomedical subjects

A Amir

Publications and source records attributed to A Amir.

At least 55 records · Page 3Linked to original sources

Protection by extracellular glutathione against sulfur mustard induced toxicity in vitro.

1. The present study characterizes the role of extracellularly added glutathione in protection against sulfur mustard (HD) toxicity in a macrophage monocyte cell line J774. 2. Toxic effects of HD depend on dose and duration of exposure with an ED50 of 50 and 75 microM for dividing and confluent cells respectively. 3. Exposure to HD, 100-200 microM caused approximately 15% decrease in the cellular glutathione (GSH) content 2 h after exposure, pretreatment with GSH, 0.2-10 mM, elevated cellular GSH approximately x 1.5. 4. GSH pretreatment increased cell viability after HD 2-3-fold. Similar protective effects of GSH treatment were found in a human epidermoid carcinoma cell line (KB). 5. Protection by post treatment with GSH was apparent even 60 min post HD exposure. 6. No protection was afforded when the intracellular GSH concentration was elevated prior to exposure and the extracellular GSH had been washed out. However, GSH depleted cells were more sensitive to HD than normal cells, and were also protected by addition of GSH to the growth medium, although the intracellular GSH content remained low. 7. We conclude that it is essential for the GSH to be present extracellularly in order to protect cells from HD toxicity. 8. Our findings have therapeutic implications in particular for the protection of lungs after inhalation exposure to HD vapor.

Cell Line↗

Skeletal muscle ribonuclease activities in chronically ethanol-treated rats.

Alcoholic myopathy occurs in up to two thirds of alcohol misusers and is characterized by selective atrophy of type II (anaerobic, fast-twitch) fibers; type I (aerobic, slow twitch) fibers are relatively unaffected. Both clinical and animal studies have indicated that skeletal muscle RNA content is reduced in response to ethanol exposure, and contributes to impaired protein synthesis. We hypothesized that the reduction in muscle RNA may be due to raised ribonuclease (RNase) activities that enhance RNA catabolism. To test this hypothesis, we measured the total tissue and plasma RNase activities as well as the activities of general (RNase A) and specific or "restriction" RNases (T1L, T2L) in ethanol-treated rats. Chronically treated rats were fed a nutritionally complete liquid diet with 35% of calories as ethanol. Weight-matched controls were pair-fed with isocaloric glucose. Rats were killed at time-points up to 6 weeks. For comparative purposes, the effect of acute (24 hr) starvation was also analyzed in a second group of rats relative to a group of control rats allowed free access to food and water over 24 hr. Results showed that the type II fiber-predominant plantaris muscle exhibited a significant increase in total RNase, RNase A and RNase T1L activities (increases ranged from +59% to +196%; P-values between 0.025 and 0.01) concomitant with large falls in RNA and protein content. In contrast, none of the RNase activities measured in the type I fiber-predominant soleus muscles were significantly affected; compositional changes were also smaller in the soleus. This effect was independent of reduced nutrition. In conclusion, the raised total RNase, RNase A and RNase T1L activities may contribute to the type II fiber-specific reduction in total RNA in chronically ethanol-treated rats. In turn, this may contribute to the alterations in cellular protein metabolism seen under these treatments.

Alcoholism↗

Genetic algorithms for protein threading.

Despite many years of efforts, a direct prediction of protein structure from sequence is still not possible. As a result, in the last few years researchers have started to address the "inverse folding problem": Identifying and aligning a sequence to the fold with which it is most compatible, a process known as "threading". In two meetings in which protein folding predictions were objectively evaluated, it became clear that threading as a concept promises a real breakthrough, but that much improvement is still needed in the technique itself. Threading is a NP-hard problem, and thus no general polynomial solution can be expected. Still a practical approach with demonstrated ability to find optimal solutions in many cases, and acceptable solutions in other cases, is needed. We applied the technique of Genetic Algorithms in order to significantly improve the ability of threading algorithms to find the optimal alignment of a sequence to a structure, i.e. the alignment with the minimum free energy. A major progress reported here is the design of a representation of the threading alignment as a string of fixed length. With this representation validation of alignments and genetic operators are effectively implemented. Appropriate data structure and parameters have been selected. It is shown that Genetic Algorithm threading is effective and is able to find the optimal alignment in a few test cases. Furthermore, the described algorithm is shown to perform well even without pre-definition of core elements. Existing threading methods are dependent on such constraints to make their calculations feasible. But the concept of core elements is inherently arbitrary and should be avoided if possible. While a rigorous proof is hard to submit yet an, we present indications that indeed Genetic Algorithm threading is capable of finding consistently good solutions of full alignments in search spaces of size up to 10(70).

Algorithms↗

Combined thermal and crush injury to the hand and fingers.

Combined thermal and crush injury is a relatively rare type of injury, although it may be more common in industrial settings. The combined insult of heat and pressure results in an injury that apparently is more severe than the simple additive effect, as the heat is transmitted deeper through the crushed tissues. The full extent of tissue destruction cannot always be fully recognized initially. Treatment in stages is the preferred approach, rather than attempted immediate reconstruction procedures. Failure of immediate skin grafting procedures in some of the cases presented herein was the result of underestimation of the severity of trauma. Early debridement should be done soon after admission. Definitive treatment as dictated by the magnitude of injury needs to be delayed until the extent of injury is delineated. Our conclusions from the presented experience with this type of injury were successfully applied in the treatment of the last presented patient.

Accidents, Occupational↗

A simple, rapid, reproducible tie-over dressing.

A simple and quickly performed technique for the construction of tie-over dressings is described. After adjustment of the graft to the skin defect, skin staples are used to tack simultaneously the graft and looped silk threads circumferentially. Securing the threads is achieved by using a shortened disposable syringe cylinder through which the threads are passed and held in place by the adjusted piston. A stable fixation is easily achieved in all cases using one or more of these devices depending on the size of the defect. This technique enables the subsequent application of the dressing if needed.

Bandages↗

Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Algorithms↗

Serum carnosinase activities in central nervous system disorders.

Serum carnosinase activity was assayed in five groups of patients with neurological disorders. Enzyme activities in patients with idiopathic epilepsy (mean +/- S.E.M., 148 +/- 11 nmol/ml per min) and motor neurone disease (155 +/- 15 nmol/ml per min) were similar to the control group (161 +/- 7 nmol/ml per min). Reduced serum carnosinase activity was observed in patients with Parkinson's disease (109 +/- 11 nmol/ml per min, P < 0.005), multiple sclerosis (82.5 +/- 10.0 nmol/ml per min, P < 0.005) and patients following a cerebrovascular accident (74.6 +/- 5.4 nmol/ml per min, P < 0.001) compared with the control group. Carnosinase activity, 5-10% of that found in serum, was detected in CSF samples. The cause of reduced serum carnosinase activities in central nervous system disorders is unclear, although anoxic damage to carnosinase-producing cells or disruption of the blood-brain barrier may be responsible.

Adult↗

Uniqueness of the generators of brain evoked potential maps.

This study considers the uniqueness of neuronal generators of human brain evoked potentials measured on the scalp using the physical and mathematical properties of the volume conductor model. The results are applicable to a realistic, nonhomogeneous head shape where the potential map is known on a continuous set of points on the scalp. It is shown that sources which occupy "zero volume" in space such as point dipoles or sources distributed on an open surface or a line are uniquely defined by the potential maps. Finite volume nonoverlapping sources are also uniquely defined by their potential map. However, there are infinitely many different but overlapping sources which can create the same map. Several examples of such sources are provided. It is shown that there is a unique, minimum volume source which can be defined in this case. Results suggest that if a reconstruction of the sources starts from a continuous scalp map (obtained by interpolation of the data between electrode sites), one can obtain unique results concerning the source parameters that are not available in a search for a source whose potential map fits only at a discrete set of points.

Brain↗

Artifactually high coherences result from using spherical spline computation of scalp current density.

Coherence computed from common reference montages inextricably confounds true coherence with power and phase at the recording and reference electrodes. Direct measurement of coherence requires reference-free EEG data, such as data from EEG scalp current densities (SCDs), which estimate the potential gradient perpendicular to the scalp. Perrin et al. (1989) presented a method for computing SCDs by taking the Laplacian of the scalp potential surface generated by spherical spline interpolation. When this method of computing SCDs was applied to EEG data gathered from young adults, very high values were observed for inter-electrode coherences computed from the spherical spline derived SCD data but not from coherences computed from the common reference data. These high coherences prompted further examination of the properties of the spherical spline function and of spherical spline derived SCDs. Simulated data were constructed, and coherence was computed on the simulated data and on the SCDs derived from the spherical spline procedure and from the Hjorth (1980) procedure. The results of those simulations are presented, which demonstrate that a major artifact is introduced by using the spherical spline procedure. This artifact results from the spline weighting matrix used to derive the SCDs and strongly inflates the inter-electrode coherences of the SCD transformed data.

Artifacts↗

Cholinotoxicity of the ethylcholine aziridinium ion in primary cultures from rat central nervous system.

The cytotoxic effects of ethylcholine aziridinium ion (AF64A) were studied in primary cultures prepared from either whole brain, septum, or midbrain of fetal rats. AF64A, at concentrations up to 22.5 microM, significantly reduced the number of acetylcholinesterase-stained cells without affecting the number of dopaminergic neurons or their ability to take up and release [3H]dopamine. Many of the survived acetylcholinesterase-stained cells appeared with intact somata but damaged processes, indicating a retrograde degeneration starting at the nerve terminal. Higher concentrations of AF64A (greater than 22.5 microM), caused general toxicity which was expressed by degeneration of various neuronal and glial cells. Choline (500 microM), significantly protected the cells from AF64A induced cytotoxicity. The results are consistent with a previously described kinetic model, that predicted a dual action of AF64A: selective cholinotoxicity at low concentrations and non-selective cytotoxicity at higher concentrations.

Acetylcholinesterase↗

Theiler's virus replication in isolated Schwann cell cultures.

Theiler's murine encephalomyelitis viruses causing both fatal encephalitis (GDVII virus) and chronic demyelinating disease (WW virus) are capable of replicating in isolated Schwann cell cultures. Light microscopy combined with immunohistochemical staining of viral antigens revealed that large numbers of Schwann cells infected with the two viruses show cytopathic effect (rounding) and contain viral antigens. Electron microscopy of virus-infected Schwann cells shows that the morphological alterations that the cells undergo following infection by the two virus isolates are different. In the early stages of GDVII and WW virus infection, different inclusion bodies are formed in the cells cytoplasm. At late stages of the infection GDVII virions are found in all infected cells and are arranged in crystalline arrays around inclusion bodies. In contrast, in WW virus-infected Schwann cells only in few cells virions were observed and they appeared aligned between two membrane units.

Animals↗