Search PubMed⌕ Search

Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 703 records · Page 39Linked to original sources
PubMed1993

Antibodies to Toxoplasma gondii major surface protein (SAG-1, P30) inhibit infection of host cells and are produced in murine intestine after peroral infection.

Monoclonal and polyclonal, monospecific antibodies to the major surface antigen of Toxoplasma gondii (SAG-1, P30) inhibit infection of human fibroblasts and murine enterocytes. Fab prepared from polyclonal, monospecific antibody to P30 also have this inhibitory effect on invasion, which indicates that this antibody directly blocks parasite infection of host cells rather agglutinating the parasite. Antibodies to another surface protein (P22) did not alter in vitro infection. If the inhibitory effect of antibody to P30 was due to steric hindrance or complexing of surface epitopes contiguous to P30, antibodies to other surface epitopes would also be inhibitory and they are not. Urea treatment of antibody (which permits discrimination of high and low avidity antibody) did not alter the effect of anti-P30 antibody. This observation indicates that the effect of the antibody to P30 was not an artifact of differences in the avidity of the antibody to P22 and P30. Heat inactivated antisera from mice infected with either RH or PTg strain T. gondii (P30+) inhibit infection of fibroblasts when challenged with autologous wild-type parasites by 87 and 40%, respectively. In contrast, these antisera have little inhibitory effect (13 and 19%, respectively) against infection of human fibroblasts by a P30-deficient mutant (PTgB). Antisera raised to the P30-deficient mutant had no significant effect on infection of cells by wild-type strains that have surface P30. The neoglycoprotein, BSA-glucosamide, competitively blocks infection of human fibroblasts by P30+ tachyzoites with surface P30 in higher level than those without surface P30. This observation indicates that there is likely to be a glycosylated host cell receptor to which T. gondii's major surface Ag SAG-1 (P30) binds. Mice infected perorally develop intestinal IgA antibody to the major 30-kDa epitope of T. gondii. Thus, the major surface epitope of T. gondii, SAG-1 (P30), has an important, functional role in infection of host cells by T. gondii and elicits an intestinal antibody response after peroral infection.

Animals↗
PubMed1993

Mutation of the gene for the human lysosomal serine protease cathepsin G is not the cause of aberrant APP processing in familial Alzheimer disease.

Recent genetic linkage studies have implicated a gene on chromosome 14 in the pathogenesis of FAD. The identity of this gene remains unknown but it has been speculated that it may be involved in the cellular processing of the amyloid precursor protein (APP). We have analyzed the nucleotide sequence of the entire open reading frame of the cathepsin G gene located on chromosome 14q. No mutations were observed, suggesting that defects in this lysosomal protease are not responsible for aberrant accumulation of proteolytic products of APP in FAD brain tissue.

Alzheimer Disease↗
PubMed1993

Selective modulation of cholinergic properties in cultures of avian embryonic sympathetic ganglia.

We have studied the expression of catecholaminergic and cholinergic phenotypes in sympathetic ganglia removed from 7- to 10-day-old quail embryos and grown in vitro under different conditions. Quantitative data were obtained by measuring the conversion of (3H) tyrosine and (3H) choline to catecholamines (CA) and acetylcholine (ACh), respectively. In explant cultures, large amounts of both neurotransmitters were synthesized from the onset, but CA generally predominated, the molar ratios of CA:ACh being, on average, of the order of 2:1. If the ganglia were dissociated before plating, there was a selective increase in ACh synthesis (three- to fivefold) such that the CA:ACh ratio fell strikingly. The early expression of the cholinergic phenotype appears to be species-specific in that, under identical conditions, dissociated cell cultures of newborn mouse superior cervical ganglia were overwhelmingly catecholaminergic (CA:ACh ratio of approximately 40:1) and ACh synthesis was only just detectable. Addition of veratridine (1.5 microM) either to explant or to dissociated cell cultures of embryonic quail sympathetic ganglia barely altered CA-synthesizing ability; in contrast, ACh synthesis and accumulation were stimulated about threefold. This effect, which we found to correspond to a quantitatively similar increase in the activity of choline acetyltransferase (ChAT), was completely blocked by tetrodotoxin, indicating that it was due to Na(+)-dependent depolarization. A preferential stimulation of ACh production was also observed when the concentration of K+ was raised to 20 mM. Veratridine treatment of cultures of presumptive sympathoblasts, in the form of sclerotome-associated neural crest cells, had identical effects. Our results reveal the quantitative importance of ACh-related properties in avian sympathetic ganglia from the earliest stages of their development and suggest that depolarization may be one of the factors selectively enhancing expression of the cholinergic phenotype during ontogeny. In these respects, the neurochemical differentiation of sympathetic neurons unfolds according to dissimilar scenarios in birds and mammals.

Acetylcholine↗
PubMed1993

Induction of macrophage nitric oxide production by interferon-gamma and tumor necrosis factor-alpha is enhanced by interleukin-10.

Interleukin-10 (IL-10) has been reported to inhibit nitric oxide (NO) synthesis and microbicidal activity of interferon-gamma (IFN-gamma)-stimulated macrophages (M phi) by preventing the secretion of tumor necrosis factor-alpha (TNF-alpha) which serves as an autocrine activating signal. We have examined the effects of recombinant IL-10 on the capacity of IFN-gamma together with exogenous TNF-alpha to induce NO synthesis by bone marrow-derived M phi. Under these conditions and in contrast to its reported deactivating potential, IL-10 strongly enhanced NO synthesis measured as nitrite (NO2-) release (half maximal stimulation at approximately 10 U/ml). IL-10 further increased NO2- production by M phi stimulated in the presence of optimal concentrations of prostaglandin E2, a positive modulator of M phi activation by IFN-gamma/TNF-alpha. Increased steady state levels of NO synthase mRNA were observed in 4-h IFN-gamma/TNF-alpha cultures and enhanced NO2(-)-release was evident 24 h but not 48 h after stimulation. These results suggest that the effects of IL-10 on M phi function are more complex than previously recognized.

Amino Acid Oxidoreductases↗
PubMed1993

Transforming growth factor beta 1 regulation of macrophage activation depends on the triggering stimulus.

We have examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the regulation of murine bone marrow-derived macrophage function. TGF-beta, added simultaneously with or up to 4 h before interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS), inhibited macrophage leishmanicidal activity, nitrite (NO2-) production, and secretion of prostaglandin E2. In contrast, no effect of TGF-beta could be demonstrated on macrophages stimulated with IFN-gamma plus tumor necrosis factor-alpha (TNF-alpha) under the same conditions. These results suggested that TGF-beta inhibited LPS-induced triggering of macrophage activation, which was confirmed by studies with IFN-gamma-primed cells. Interestingly, when macrophages were pretreated with TGF-beta for 24 h, NO2- production in response to IFN-gamma plus TNF-alpha was also inhibited. Although control and IFN-gamma/LPS-stimulated macrophages were found to secrete latent TGF-beta, only the IFN-gamma/LPS cultures produced biologically active TGF-beta. Significantly, active TGF-beta was present at concentrations shown earlier to inhibit macrophage function.

Animals↗
PubMed1993

Role of a gamete-specific sulfoglycolipid immobilizing protein on mouse sperm-egg binding.

A sulfoglycolipid immobilizing protein, termed SLIP1, is a conserved germ cell membrane protein that has been shown in vitro to bind specifically to the mammalian germ-cell-specific sulfoglycolipid, sulfogalactosylglycerolipid (SGG). SLIP1 was extracted from the mouse sperm surface by a sucrose/ATP/EDTA solution. Indirect immunofluorescence and immunoprotein A-gold labeling of live mouse sperm indicate that SLIP1 was present on the acrosomal plasma membrane. Inclusion of low concentrations of exogenous purified SLIP1 in the in vitro mouse sperm-egg binding assay culture significantly decreased the number of sperm bound per egg. Inhibition was heat labile. SLIP1 on sperm, rather than that on eggs, appeared to be important for the binding process since preexposure of sperm to anti-SLIP1 decreased sperm binding to the eggs. Eggs preincubated with anti-SLIP1 were unaffected. Immunoblotting studies confirmed that SLIP1 was not present on the zona pellucida (ZP). SLIP1 binding ligand(s) on eggs were also involved in sperm-ZP binding since preincubation of eggs with exogenous SLIP1 before gamete coincubation significantly reduced the number of sperm bound per egg. The results suggest that SLIP1 is involved in mouse sperm-ZP binding.

Acrosome↗
PubMed1993

Case report 772. Stress fracture of the hip secondary to renal osteodystrophy and erosion of ischium due to amyloid deposition.

We have reported the case history of a 72-year-old woman who was on hemodialysis for 15 years. Her course was marked by many of the musculoskeletal complications of ESRD including CTS, stromal amyloid deposition of synovium, amyloid cystic degeneration of bone, and inflammation of the synovium due to the deposition of calcium oxalate and calcium pyrophosphate microcrystals. She also had evidence of metabolic bone disease: moderate osteoporosis related to secondary hyperparathyroidism and osteomalacia related to aluminum deposition at the mineralization front. The pathological and radiological findings associated with her bone disease are described.

Aged↗
PubMed1993

The effects of intensity of exercise on excess postexercise oxygen consumption and energy expenditure in moderately trained men and women.

This experiment investigated the effects of intensity of exercise on excess postexercise oxygen consumption (EPOC) in eight trained men and eight women. Three exercise intensities were employed 40%, 50%, and 70% of the predetermined maximal oxygen consumption (VO2max). All ventilation measured was undertaken with a standard, calibrated, open circuit spirometry system. No differences in the 40%, 50% and 70% VO2max trials were observed among resting levels of oxygen consumption (VO2) for either the men or the women. The men had significantly higher resting VO2 values being 0.31 (SEM 0.01) l.min-1 than did the women, 0.26 (SEM 0.01) l.min-1 (P < 0.05). The results indicated that there were highly significant EPOC for both the men and the women during the 3-h postexercise period when compared with resting levels and that these were dependent upon the exercise intensity employed. The duration of EPOC differed between the men and the women but increased with exercise intensity: for the men 40%--31.2 min; 50%--42.1 min; and 70%--47.6 min and for the women, 40%--26.9 min; 50%--35.6 min; and 70%--39.1 min. The highest EPOC, in terms of both time and energy utilised was at 70% VO2max. The regression equation for the men, where y = O2 in litres, and x = exercise intensity as a percentage of maximum was y = 0.380x + 1.9 (r2 = 0.968) and for the women is y = 0.374x - 0.857 (r2 = 0.825).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The needs of high and low expressed emotion families: a normative approach.

Comparison of the needs and characteristics of relatives classified as high and low expressed emotion (EE) across a range of measures including social functioning and indices of stress and family burden revealed that high EE relatives reported higher levels of disturbed behaviour, subjective burden, and perceived themselves as coping less effectively. Individuals from high-EE households were more impaired in terms of social functioning, particularly in terms of independence and interpersonal functioning. No difference in overall knowledge about schizophrenia was observed between high and low EE relatives, although high EE relatives possessed more information about hospital procedures. Analysis of needs assessment data, based on a normative approach to need, revealed that two-thirds of high EE relatives, as against one-third of low EE relatives had high needs in at least one or more of the following five areas: knowledge about schizophrenia, subjective burden, personal stress, behavioural disturbance and perceived coping. No low EE relative had high needs on all five criteria. The implications of the results for the meaning and genesis of EE and for service provision are considered.

Adaptation, Psychological↗
PubMed1993

Cardiopulmonary resuscitation skills in non consultant hospital doctors--the Irish experience.

We assessed the Cardiopulmonary Resuscitation (CPR) skills in 30 Non Consultant Hospital Doctors (N.C.H.D.'s) chosen randomly from a total of 110 on the staff of a university associated teaching hospital. The candidates filled out a questionnaire and were asked to perform initial assessment and CPR on a mannikin for two minutes. None of the candidates followed the recognised airway, breathing and circulation ABC sequence and only one provided effective CPR. We suggest there is a need for encouragement for doctors to undergo CPR training with subsequent certification and ongoing refresher courses during their career.

Attitude of Health Personnel↗
PubMed1993

Quantification of diarrhetic shellfish toxins and identification of novel protein phosphatase inhibitors in marine phytoplankton and mussels.

Liquid chromatography (LC)-linked protein phosphatase 1/2A (PP-1/PP2A) bioassay was used to quantitatively identify diarrhetic shellfish toxins in marine phytoplankton (cultured and natural assemblages) and commercially available mussels. Using this approach, multiple protein phosphatase inhibitor profiles of varying composition were found in diarrhetic mussels from Holland and Canada. Based on LC elution positions and relative activity versus PP-1 and PP-2A, at least six inhibitors distinct from known diarrhetic shellfish toxins were identified and termed mussel phosphatase inhibitor (MPI) 19,22,23,25,33 and 42. The levels of these inhibitors, in okadaic acid equivalent units, varied from 100 pg to 3350 ng per g shellfish tissue. The combined levels of PP-1/2A inhibitors in all instances superseded that of okadaic acid/dinophysistoxin-1 and may contribute to the diarrhetic shellfish toxin profile of the contaminated mussels. The efficacy of LC-protein phosphatase bioassay was established for cultured phytoplankton where picogram levels of okadaic acid could be detected from microgram extracts of Prorocentrum lima. Analyses of plankton net tows from estuarine mussel culture sites in Eastern Canada revealed a heterogeneous population of protein phosphatase inhibitors, with dinophysistoxin-1 being most prevalent. This toxin was predominant for at least 2 months in mussel populations in the immediate vicinity of plankton sampling sites. The results are consistent with a hypothetical model in which marine bacteria, cyanobacteria and dinoflagellates combine to produce a variety of protein phosphatase inhibitors effective against signal transduction pathways in higher eukaryotes.

Animals↗
PubMed1993

Does hypoxemia prevent brain damage in birth asphyxia?

The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in association with birth asphyxia, is thought to represent a reperfusion injury consequent upon the generation of cytotoxic oxygen derived free radicals. It has recently been suggested that resuscitation of asphyxiated infants with unrestricted oxygen may aggravate the brain damage by causing hyperoxia and increased free radical production. To determine whether sustained hypoxemia may be protective in birth asphyxiated infants, we investigated the relationship between HIE and persistent pulmonary hypertension of the neonate (PPHN). The latter condition is also related to intrauterine and intrapartum birth asphyxia but is associated with persistent hypoxemia in the infant. In a retrospective analysis of 39 asphyxiated neonates admitted to the neonatal intensive care unit, we found that 28 had HIE, 10 had PPHN and only 1 had both HIE and PPHN. We therefore suggest that the hypoxemia due to PPHN may limit the production of oxygen derived free radicals in asphyxiated neonates and hence protect against the development of HIE. These findings lend support to current research into air vs. oxygen resuscitation for infants with birth asphyxia.

Asphyxia Neonatorum↗
PubMed1993

The effect of endocrine therapy on fibroblast growth factor-like activity in nitrosomethylurea-induced rat mammary tumours.

Tumour regression following ovariectomy of rats bearing nitrosomethylurea-induced mammary tumours has been well characterised as a model for oestrogen receptor (ER)-positive breast cancer. We have shown that a similar regression response can be induced in these rats by the cytotoxic drug doxorubicin. Conditioned medium (CM) from serum-free explant cultures of the mammary tumours of ovariectomised rats showed a striking increase in its ability to transform NR6 cells compared to that of control or doxorubicin-treated rats (P = 0.001, t-test). Activity was also present in CM derived from rat uteri but not in ER-negative tissues such as skin and liver. Activity was further defined as fibroblast growth factor (FGF)-like by its strong affinity to heparin, partial neutralisation by antibodies to acidic FGF (aFGF) and partial co-elution with aFGF on salt elution from heparin. Both aFGF protein and mRNA were detected in tissue preparations of rat tumours and uterus.

Animals↗