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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 181 records · Page 10Linked to original sources
PubMed1992

Work-related toxic epidermal necrolysis?

A case of toxic epidermal necrolysis is described in an employee of a company that carries out plastic extrusion using various resins, including cellulose acetate, co-polyester, polyvinyl chloride, acrylonitrile-butadienestyrene, and polyethylene. Air sampling during normal operating conditions indicated only trace amounts of hydrogen chloride and the plasticizer diethylphthalate. However, pyrolysis products of resin plugs could include compounds such as formaldehyde, acrylonitrile, and chlorinated hydrocarbons that have been associated with previous case reports of either erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. The development of toxic epidermal necrolysis in this worker was directly preceded by exposure to a vapor from a machine used to dry cellulose acetate. The problems in determining work relatedness and advising about return to work are discussed.

Adult↗
PubMed1991

Convergent evolution of similar function in two structurally divergent enzymes.

An example of two related enzymes that catalyse similar reactions but possess different active sites is provided by comparing the structure of Escherichia coli thioredoxin reductase with glutathione reductase. Both are dimeric enzymes that catalyse the reduction of disulphides by pyridine nucleotides through an enzyme disulphide and a flavin. Human glutathione reductase contains four structural domains within each molecule: the flavin-adenine dinucleotide (FAD)- and nicotinamide-adenine dinucleotide phosphate (NADPH)-binding domains, the 'central' domain and the C-terminal domain that provides the dimer interface and part of the active site. Although both enzymes share the same catalytic mechanism and similar tertiary structures, their active sites do not resemble each other. We have determined the crystal structure of E. coli thioredoxin reductase at 2 A resolution, and show that thioredoxin reductase lacks the domain that provides the dimer interface in glutathione reductase, and forms a completely different dimeric structure. The catalytically active disulphides are located in different domains on opposite sides of the flavin ring system. This suggests that these enzymes diverged from an ancestral nucleotide-binding protein and acquired their disulphide reductase activities independently.

Amino Acid Sequence↗
PubMed1991

The immunosuppressive activity of the aldehydic transformation of cyclosporine on alloreactive T-cells.

Cyclosporine (CsA) is a potent immunosuppressive compound, and its metabolites have previously been shown to have pharmacologic activity. The aldehydic metabolites have been isolated and are a metabolic intermediate after the conversion of CsA to its most active hydroxylated metabolite. The in vitro sensitivity of alloreactive T-lymphocytes, which are generated from a mixed lymphocyte reaction and propagated from organ transplant biopsy specimens to the aldehydic metabolites of CsA, was tested. In secondary proliferative assays in the presence of varying concentrations of CsA and the aldehydes, the concentration required to inhibit proliferation by 50% was 50 to 150 ng/mL for CsA and 3150 to 3500 ng/mL for the aldehydes. Pretreatment of alloreactive cells with CsA or the aldehydes did not alter cell viability, as tested with dye exclusion, or cell reactivity on reculturing. These studies concluded that the structural modification formed by metabolism of CsA to the aldehydic structure eliminates its antiproliferative activity on T-lymphocytes.

Aldehydes↗
PubMed1991

A correlation between gene transcriptional activity and cerebral glucose metabolism in Alzheimer's disease-affected neocortex: cause or effect?

Our laboratory has measured mRNA pool sizes in neocortex afflicted with Alzheimer's disease (AD). We have observed a repression of gene expression in the temporal and parietal regions compared to age-matched control neocortex. These changes in messenger RNA pool size closely parallel the observed alterations in local cerebral metabolic rates for glucose (LCMR-g), as detected by positron emission tomography (PET). For example, deficits in both gene transcription and glucose metabolism appear to be the greatest in AD-affected superior temporal neocortex (Brodmann area 22) but are less apparent in the primary visual cortex (Brodmann area 17) or in the cerebellum. The unresolved question is whether changes in gene expression are the cause or effect of altered glucose metabolism. However, the non-random reductions in the pool size for certain neocortical mRNAs argue in favour of altered gene expression as the primary event.

Alzheimer Disease↗
PubMed1991

Anomalous gene expression in Alzheimer disease: cause or effect.

Altered chromatin conformation and increased amounts of aluminum have been observed in the brains of patients with Alzheimer disease. These factors have been shown to affect gene regulation. In this report, we describe how these changes may selectively alter the pool size of the human light chain neurofilament gene and play a fundamental role in the expression of this disease.

Alzheimer Disease↗
PubMed1991

Increased survival of island skin flaps by systemic heparin in rats.

The effects of systemic heparin on the survival of island skin flaps have been evaluated. Island flaps measuring 3 x 6 cm were created in the abdomen/groin of rats based on an inferior epigastric neurovascular pedicle. The venous drainage from the flap was occluded for various lengths of time ranging from 5 to 10 hours in the control rats and from 8 to 15 hours in the heparin-treated group of rats. The rats in the treated group received 1 ml of heparin solution (300-400 U/kg) through the contralateral saphenous vein immediately prior to the onset venous occlusion and an equivalent dose every 4 hours during venous occlusion. The group of control rats received 1 ml of saline solution. Flap survival was evaluated daily for 7 days. The flaps of control rats demonstrated a gradual decline of the survival rate after 6 hours of venous occlusion and no survival after 10 hours of venous occlusion. The flaps of heparin-treated rats exhibited complete survival until 12 hours of venous occlusion and no survival after 13 hours of venous occlusion. Thus, systemic heparin prolonged tissue tolerance to venous occlusion from 10 to 13 hours. The flaps of control rats demonstrated a significant accumulation of inosine plus hypoxanthine to 260% of normal after 8 hours of venous occlusion. The flaps of heparin-treated rats exhibited little alteration of inosine plus hypoxanthine, and contained a greater concentration of glucose and lactate than the flaps of control rats after 8 hours of venous occlusion. The results demonstrate that systemic heparin can increase tissue tolerance to venous occlusion and improve significantly the flap survival following subsequent reperfusion.

Animals↗
PubMed1991

The effect of rigid fixation on growth of the neurocranium.

The effects on skull growth of plating the coronal suture and frontal bone were studied in New Zealand White rabbits. Three-dimensional coordinate landmarks were digitized and analyzed to determine the differences in form between operated and unoperated animals using Euclidian distance matrix analysis. This method compares sets of interlandmark distances in three dimensions and was used to demonstrate changes induced by plating. We interpret these changes in morphology to be the result of differences in growth between the operated and unoperated groups. Periosteal elevation alone (n = 6) resulted in a minimal local growth increase. Coronal suture plating (n = 8) resulted in local growth restriction with contralateral and adjacent size increases. Frontal bone plating (n = 6) without crossing a suture line also resulted in local growth restriction and adjacent bone size increases. The timing of intervention in relation to the completion of bone growth may explain the magnitude of clinically apparent effects. Changes in bones adjacent to those directly manipulated may be an attempt to maintain a normal skull volume.

Animals↗
PubMed1990

Hepoxilin A3 blocks the release of norepinephrine from rat hippocampal slices.

Hepoxilin A3 was previously shown to display neuromodulatory actions on rat hippocampal CA1 neurons, with hyperpolarization of the membrane potential, an increase in the amplitude and duration of the post-spike train after hyperpolarization and an increase in the inhibitory post synaptic potential. The present report describes new biochemical evidence of a presynaptic action of hepoxilin A3 in rat hippocampal slices prelabeled with [3H]-norepinephrine. Hepoxilin A3 on its own had a marginal effect on the release of label, but blocked release which was induced by 4-aminopyridine (4-AP). Prostaglandin E2 also behaved in a similar way. These results demonstrate that hepoxilins modulate neurotransmission in the mammalian CNS through both pre- and postsynaptic actions.

4-Aminopyridine↗
PubMed1990

Preliminary crystallographic analysis of trypanothione reductase from Crithidia fasciculata.

Trypanothione reductase, a flavoprotein disulfide reductase specific to trypanosomatid parasites, has been crystallized by vapor diffusion of a protein solution (10 mg/ml) against 22% polyethylene glycol (average Mr 8000) containing 100 mM-ammonium sulfate. Crystals of a size suitable for structure determination by X-ray diffraction have been obtained by seeding protein solutions with smaller crystals. The space-group is P21 (a = 60.9 A, b = 161.8 A, c = 58.4 A, beta = 99.1 degrees). The molecular mass and volume of the unit cell suggest that there is a dimer of the enzyme in the asymmetric unit, and this is confirmed by self-rotation functions calculated using data to 4.5 A resolution. The crystals diffract to beyond 3 A resolution. Crystals of another P21 form (a = 91.3 A, b = 114.4 A, c = 92.0 A, beta = 141.3 degrees) are observed to grow under similar conditions.

Animals↗
PubMed1990

Occupational asthma caused by latex in a surgical glove manufacturing plant.

A 33-year-old latex glove inspector was diagnosed as having occupational asthma on the basis of peak flow and methacholine-responsiveness changes related to workplace exposure. She had latex sensitivity by skin prick testing. This finding led to a survey of her workplace. Of the 81 workers, 84% completed a questionnaire to assess work-related respiratory symptoms, 79% underwent skin prick testing to latex and six other workplace chemicals, and 62% performed workshift spirometry. Seven workers had spirometric changes consistent with asthma, of whom five had greater than or equal to 15% fall in FEV1 during the workshift. Six of these workers underwent methacholine-challenge testing, and three were found to have a significant improvement in responsiveness to methacholine away from work, suggestive of occupational asthma. Two of these workers had positive skin test responses to latex. Including the index case, 6% of workers who had pulmonary function testing had findings of latex-related occupational asthma. Skin test responses to latex occurred in 11% of workers tested. Our findings suggest that latex should be considered among the causes of occupational asthma.

Adult↗
PubMed1990

Health effects associated with exposure to anaesthetic gases in Ontario hospital personnel.

In a retrospective study (by questionnaire) of 8032 personnel exposed to anaesthetic gases in operating and recovery rooms in Ontario hospitals, and 2525 non-exposed hospital staff, the response was 78.8% for the exposed and 87.2% for the unexposed personnel during the period 1981-5. Logistic regression analysis, with age and smoking standardised, showed that women in the exposed group had significantly increased frequencies of spontaneous abortion and their children had significantly more congenital abnormalities (p less than 0.05). No chronic disease was significantly associated with the exposed group. These findings, together with similar ones from other studies, suggest that it is prudent to minimise exposure to waste anaesthetic gases.

Abortion, Habitual↗
PubMed1990

Cytoskeletal messenger RNA stability in human neocortex: studies in normal aging and in Alzheimer's disease.

Total RNA was extracted from human brain temporal and parietotemporal neocortical grey matter with postmortem intervals (PMI) of up to 13.5 hours. The integrity and rank abundance of heterogeneous nuclear RNA (HnRNA) and messenger RNA (mRNA) were analyzed by Northern gel dot blot hybridization with specific cloned probes of neurobiological interest: the RNA messages for four cytoskeletal components including glial fibrillary acidic protein (GFAP), alpha-tubulin, beta-actin and the human neurofilament light chain (HNF-L) genomic sequence, the Alu repetitive element, the scrapie prion PrP DNA probe and the chromatin condensing agent linker histone H1(0) genomic probe. Our observations indicate that for the cytoskeletal RNA messages studied here: (1) short postmortem intervals (of up to 4.5 hours) had only small effects upon RNA quality in these neocortices, (2) GFAP and HNF-L transcripts were represented at relatively high levels in the cerebral neocortex and (3) each RNA species in normal human brain had both unique and characteristic intracellular levels of abundance and decay kinetics. In the pathological condition, Alzheimer's disease (AD), cells of the temporal and parietotemporal neocortices of afflicted brains showed selective reductions in cytoskeletal RNA pool size which are not attributable to RNA transcript stability.

Adult↗
PubMed1989

Crystallization and preliminary x-ray characterization of thioredoxin reductase from Escherichia coli.

Single crystals of thioredoxin reductase, suitable for x-ray diffraction studies, have been obtained at room temperature by vapor diffusion of 10-20 mg/ml protein solution against 35% polyethylene glycol containing 200 mM ammonium sulfate. Good quality crystals appear spontaneously only from a protein solution that had been stored for more than a year at 4 degrees C, although large single crystals are reproducibly obtained from fresh protein solutions by micro-seeding. The space group is P6(3)22 (a = b = 123.8 A, c = 81.6 A), with one monomer of the enzyme (34.5 kDa) in the crystallographic asymmetric unit. The crystals are well ordered and diffract to beyond 2 A resolution.

Crystallization↗
PubMed1989

Efficient electroblotting of human very-low-density lipoproteins and low-density lipoproteins from composite gradient gels to nylon membranes.

Rinsing of gradient composite acrylamide/agarose gels with 1% Triton X-100 permits the efficient electrotransfer of very-low-density and low-density lipoproteins from the gels and does not appear to interfere with subsequent capture of the lipoproteins by charged nylon membranes. Overall efficiency of the transfer/capture process can approach 95% and does not appear to be significantly affected by total lipoprotein concentrations up to 5000 mg/dl. Direct immunoquantification of transferred apolipoproteins on the membrane is feasible as well. The nylon membranes used, however, must be pretested to ensure capture efficiency.

Detergents↗