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Biomedical subjects

F Ali

Publications and source records attributed to F Ali.

At least 19 recordsLinked to original sources

Problems in the interpretation of hemorrhage into neck musculature in cases of drowning.

To investigate the possible causes of unexplained hemorrhage into the neck musculature in deaths due to drowning, all cases of drowning between the years 1985 and 1995 examined by members of the Department of Forensic Pathology, University of Sheffield were reviewed. Cases were selected in which hemorrhage was found within the neck musculature but in which no apparent explanation for the hemorrhage, such as compression of the neck or trauma, was present. Eight cases were identified from a total of 99 deaths from drowning. Postmortem hypostasis was distributed in the back or diffusely in 6 cases and in the face in 3 cases. The degree of decomposition varied but was severe in only 1 case. A raised blood alcohol level was detected in 3 cases. Anterior neck compartment hemorrhage is probably due to hypostasis in a high proportion of cases. The Prinsloo and Gordon artifact may be an operative factor in at least some cases. Hemorrhage may result from violent neck movements during the process of drowning. Apparent "bruising" of the neck musculature does not always indicate compression of or trauma to the neck.

Adult

Cloning and characterization of a novel integrin beta3 subunit.

We have identified a novel integrin beta3 subunit, termed beta3C, from a human osteoclast cDNA library. The COOH-terminal sequence and 3'-untranslated region of the beta3C subunit differs from the previously reported beta3A (platelet) and beta3B (placenta) sequences, while the regions coding for the transmembrane and extracellular domains are identical. The beta3C cytoplasmic domain contains 37 amino acids, the last 17 of which are encoded by a novel exon located about 6 kilobase pairs downstream of exon 14 of the beta3A gene. HEK 293 cells were stably co-transfected with alphaV and either beta3C (HEKbeta3C) or beta3A (HEKbeta3A). The viability of HEKbeta3C cells was lower than that of HEKbeta3A cells, and HEKbeta3C cells in culture grew as clusters rather than as a monolayer. The novel cytoplasmic domain did not affect receptor binding affinity; both alphaVbeta3A and alphaVbeta3C isoforms exhibited high affinity binding to 125I-echistatin and cyclic and linear RGD peptides. However, in contrast to HEKbeta3A, HEKbeta3C cells failed to adhere to osteopontin, an alphaVbeta3 matrix protein. The data provide further support for the key role of the cytoplasmic domain of the beta3 integrin in cell adhesion and suggest a potential role for the beta3C integrin subunit in modulating cell-matrix interactions.

Amino Acid Sequence

Differentiation and resolution of erythrocyte and muscle adenylate kinase activities in serum by electrophoresis.

Adenylate kinase activity originating from erythrocytes has been shown to be distinct from muscle adenylate kinase or myokinase activity, until now considered to be identical enzyme activities. The two activities can be differentiated by electrophoretic fractionation, thus making it possible to quantify the erythrocyte adenylate kinase activity present in serum.

Adenylate Kinase

Examination of the mixed-alkali effect in (Li,Na) disilicate glasses by nuclear magnetic resonance and conductivity measurements.

Results from 29Si, 23Na and 7Li magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy, 7Li NMR relaxation and electrical conductivity in a series of [Li(1-x).Nax]2O.2SiO2 (disilicate) glasses are used to investigate the mixed-alkali effect. From the 29Si NMR spectra there is relatively little change of the network with alkali composition. 23Na and 7Li NMR linewidths and shifts change continuously as a function of composition, indicating that the alkali ions are intimately and uniformly mixed rather than separated into lithium and sodium-rich domains. The activation energy from electrical conductivity shows a distinct maximum at the central composition (x = 0.5), whereas the local activation energy for lithium motion determined from NMR shows only a smaller but monotonic increase as the lithium-content decreases.

Electric Conductivity

A 7Li and 19F NMR relaxation study of LiCF3SO3 in plasticised solid polyether electrolytes.

7Li and 19F NMR relaxation time (T1, T2, T1 rho) measurements have been used to probe the dynamics of LiCF3SO3 dissolved in an amorphous co-polymer poly(ethylene oxide-co-propylene oxide), and in particular the influence of the plasticising agents propylene carbonate and dimethyl formamide. The changes in relaxation behaviour of 19F and 7Li with increasing plasticiser concentration are very different, as is the effect of each plasticiser. These differences can be explained qualitatively in terms of the interaction between the plasticiser and the ions. Preliminary 7Li T1 rho measurements reveal two components at low temperatures.

Dimethylformamide

Late "rim sign"--a variant of an old sign.

Classically, the "rim sign" has been described throughout the hepatobiliary scan. The authors present a case of a late rim sign visualized at 25 minutes postinjection that proved to be acute upon chronic acalculous cholecystitis without gangrene.

Acute Disease

Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro.

The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575 -Arg-Gly-Asp-Ser- and Fg-gamma 400-411 -HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1 microM [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, Ki 2.9 +/- 1.9 microM (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, Ki 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (Ki 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4 microM dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.

Amino Acid Sequence

Short-term effect of tidal pleural pressure swings on pulmonary blood flow during rest and exercise.

Because pleural pressure (Ppl) has important effects on venous return and left ventricular function, it is possible that the magnitude of respiratory fluctuations in Ppl importantly influences cardiac output (pulmonary blood flow, QL) during exercise. To examine this question, we increased (+15 cmH2O) and decreased (-11 cmH2O) the amplitude of fluctuations in Ppl by elastic loading and unloading, respectively, during steady-state exercise (50 W) and estimated the corresponding changes in QL from measurement of breath-by-breath alveolar O2 consumption [(Vo2)A] by a modification of the technique of Beaver et al. (J. Appl. Physiol. 51: 1662-1675, 1981). Load changes were applied for three breaths. Using oscilloscopic volume feedback, subjects maintained constant breathing pattern and end-expiratory volume during control and experimental breaths. This procedure minimized errors in computing (Vo2)A. Furthermore, because over the brief period of load change (especially the first 1 or 2 breaths) mixed venous and arterial O2 contents were not likely to have changed, changes in (Vo2)A reflected changes in QL according to the Fick principle. In six normal subjects, neither loading nor unloading had any effect on (Vo2)A in the first, second, or third breath (P greater than 0.5). Additional studies at rest produced equally negative results. We conclude that the magnitude of respiratory fluctuations in Ppl has no short-term effect on pulmonary blood flow at rest or during mild exercise.

Adult

Measurement of brain tissue density using pycnometry.

A novel method to measure specific gravity (SG) of tissues, pycnometry (PYC), is described. This method utilizes a 2ml glass pycnometer filled with distilled H2O to determine the displacement volume of a tissue sample and an equation to compute SG from the sample's weight and the pycnometer's weight before and after adding the sample. The PYC method was validated using glass SG standards over the range 1.02-1.26, and against the column density gradient (DG) method using brain tissue from 250-300 g male rats. Factors which affect PYC accuracy, i.e. sample size, were also evaluated. Our results indicate that PYC SG values are highly correlated with the glass SG standards (slope = 1.0107, r = 0.9955, p less than 0.001), and highly correlated with DG when approximately 0.120 ml tissue samples are used in the pycnometer. The DG method was preferable to the PYC method, however, when small tissue samples, i.e. 0.60 ml or less, were used.

Animals

The effect of the aminosteroid U-78517G on peritumoural brain oedema.

U-78517G belongs to a novel group of compounds-aminosteroids (AS) which are potent inhibitors of central nervous system tissue lipid peroxidation and are devoid of classical glucocorticoid and mineralocorticoid activities. The AS have been found to possess cerebral protective properties against ischaemia, ischaemic oedema, trauma to the cerebrum and spinal cord and in sub-arachnoid hemorrhage. The possible efficacy of U-78517G in attenuating peritumoural oedema was examined in rats harbouring cerebral 9L gliosarcomas. 19 Sprague-Dawley rats were implanted intracranially with 9L gliosarcoma cells. On day 14 post implantation rats were randomized to control (no treatment n = 10) and AS treated animals (n = 9). On day 20 animals were sacrificed and six brain samples per rat were examined for the percentage of water content. Oedema was assessed with the wet/dry weight technique. The AS treated animals were found to have a significant increase in peritumoural oedema (+1.38%, P less than 0.001) possibly related to an increase in cerebral blood flow associated with AS treatment. Further studies are, however, underway to precisely clarify this unexpected observation.

Animals

Demonstration of Ac-Arg-Gly-Asp-Ser-NH2 as an antiaggregatory agent in the dog by intracoronary administration.

This study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100-400 mM, acute platelet-dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet-dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NH2 on collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.

Animals

Catecholamines in heat stroke.

In order to find out whether the sympatho-adrenal system is activated in relation to heat stroke, plasma levels of norepinephrine (NE) and epinephrine (E) were measured using high pressure liquid chromatography in seven patients with heat stroke. The mean NE +/- SD levels on admission and six hours afterwards were 1397 +/- 317 and 717 +/- 239 pg/ml, respectively. The corresponding values for E were 257 +/- 55 and 32 +/- 15 pg/ml. The levels of both NE and E on admission were considerably higher than those of the controls: 328 +/- 62 and 88 +/- 16 pg/ml (12 normal subjects). This increase in both NE and E indicates activation of the sympatho-adrenal system in patients with heat stroke. The alpha-mediated effect of catecholamines may be important in impairing heat dissipation and thus may contribute to the pathogenesis of heat stroke.

Aged

Mechanisms of fetal alcohol effects: role of acetaldehyde.

Pregnant rats were treated from day 9 through 12 of gestation with 12.5% ethanol, 25% ethanol, 1% acetaldehyde, cyanamide (an inhibitor of the enzyme aldehyde dehydrogenase), or a combination of cyanamide and ethanol. Embryos were recovered on gestational day 12 and were quantitatively assessed on the basis of 16 recognizable developmental endpoints (morphological scores). The head and the crown-rump lengths of the embryos were also measured. Total resorption occurred in two animals treated with cyanamide and two treated with cyanamide and ethanol. Acetaldehyde and ethanol (at both concentrations) were found to reduce the head length of the embryos but had no significant effects on morphological scores and crown-rump length. The combination of ethanol with cyanamide caused a greater reduction in head length and also significantly reduced crown-rump length, as well as the morphological scores. The results suggest that the deleterious effects of ethanol could be attributed to acetaldehyde, its primary metabolite, although other underlying factors cannot be ruled out.

Acetaldehyde

Plasma and brain catecholamines in experimental uremia: acute and chronic studies.

To evaluate the role of catecholamines (CA) in uremia, we used "high performance" liquid chromatographic technique with electrodetection to determine plasma and brain concentration of dopamine (DA), norepinephrine (NE) and epinephrine (E) in rats with acute and chronic uremia. The results revealed a steady elevation in plasma CA (p less than 0.05) in both acutely and chronically uremic rats when compared to the level of these neurotransmitters in controls. The highest changes were observed in DA and the least in NE (16.8 +/- 3.2 vs. 0.5 +/- 0.2 ng/ml and 93.2 +/- 11.1 vs. 68.1 +/- 16.3 ng/ml). There was a positive correlation between plasma CA and the duration of uremia (r = 0.97; p less than 0.05). The elevations were more pronounced in acutely uremic rats than in chronically uremic rats. This was followed by a concomitant depletion in the concentration of DA, NE and E in the brain. The defects in catecholaminergic neurotransmission as evidence of dysfunction in the autonomic nervous system may contribute to the development of neuropathy.

Acute Kidney Injury