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J Barrett

Publications and source records attributed to J Barrett.

At least 217 records · Page 12Linked to original sources
PubMed1992

Interaction of leukocyte integrins with ligand is necessary but not sufficient for function.

The leukocyte integrins (CD11/CD18 or beta 2-type integrins) are expressed exclusively on leukocytes and participate in many adhesion-dependent functions (Arnaout, M.A. 1990. Blood. 75:1037-1050; Springer, T. A. 1990. Nature. (Lond.) 346:425-434; Dustin, M. L., and T. S. Springer. 1991. Annu. Rev. Immunol. 9:27-66). The avidity of leukocyte integrin binding to their ligands or counter-receptors is dependent upon response to intracellular signals (Wright, S. D., and B. C. Meyer. 1986. J. Immunol. 136:1759-1764; Dustin, M. A., and T. S. Springer. 1989. Nature (Lond.). 341:619-624). We have investigated the effects of a novel mAb (mAb 24) which defines a leukocyte integrin alpha subunit epitope that is Mg(2+)-dependent and may be used as a "reporter" of the activation state of these receptors (Dransfield, I., and N. Hogg. 1989. EMBO (Eur. Mol. Biol. Organ) J. 8:3759-3765; Dransfield, I., A.-M. Buckle, and N. Hogg. 1990. Immunol. Rev. 114:29-44; Dransfield, I., C. Cabañas, A. Craig, and N. Hogg. 1992. J. Cell Biol.) Data is presented to show that this mAb inhibits monocyte-dependent, antigen-specific T cell proliferation and IL-2-activated natural killer cell assays which are both dependent on lymphocyte function-associated antigen-1 (LFA-1), and complement receptor type 3 (CR3)-mediated neutrophil chemotaxis to f-Met-Leu-Phe. This inhibitory effect is not caused by the prevention of receptor/ligand binding because LFA-1/ICAM-1, LFA-1/ICAM-2,3 and CR3/iC3b interactions are, under activating conditions, promoted rather than blocked by mAb 24. As it does not interfere with mitogen-stimulated T cell proliferation, it is unlikely that mAb 24 transduces a "negative" or antiproliferative signal to the T cells to which it is bound. Using a model system of transient activation of LFA-1, we have found that mAb 24 prevents "deadhesion" of receptor/ligand pairs, possibly locking leukocyte integrins in an "active" conformation. It is speculated that inhibition of leukocyte integrin function by this mAb reflects the necessity for dynamic leukocyte integrin/ligand interactions.

Antibodies, Monoclonal↗
PubMed1992

Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells.

Members of the Myc family of proteins share a number of protein motifs that are found in regulators of gene transcription. Conserved stretches of amino acids found in the N-terminal transcriptional activation domain of c-Myc are required for cotransforming activity. Most of the Myc proteins contain the basic helix-loop-helix zipper (bHLH-Zip) DNA-binding motif which is also required for the cotransforming activity of c-Myc. L-Myc, the product of a myc family gene that is highly amplified in many human lung carcinomas, was found to cotransform primary rat embryo cells with an activated ras gene. However, L-Myc cotransforming activity was only 1 to 10% of that of c-Myc (M. J. Birrer, S. Segal, J. S. DeGreve, F. Kaye, E. A. Sausville, and J. D. Minna, Mol. Cell. Biol. 8:2668-2673, 1988). We sought to determine whether functional differences between c-Myc and L-Myc in either the N-terminal or the C-terminal domain could account for the relatively diminished L-Myc cotransforming activity. Although the N-terminal domain of L-Myc could activate transcription when fused to the yeast GAL4 DNA-binding domain, the activity was only 5% of that of a comparable c-Myc domain. We next determined that the interaction of the C-terminal bHLH-Zip region of L-Myc or c-Myc with that of a Myc partner protein, Max, was equivalent in transfected cells. A Max expression vector was found to augment the cotransforming activity of L-Myc as well as that of c-Myc. In addition, a bacterially synthesized DNA-binding domain of L-Myc, like that o c-Myc, heterodimerizes with purified Max protein to bind the core DNA sequence CACGTG. To determine the region of L-Myc responsible for its relatively diminished cotransforming activity, we constructed chimeras containing exons 2 (constituting activation domains) and 3 (constituting DNA-binding domains) of c-Myc fused to those of L-Myc. The cotransforming potencies of these chimeras were compared with those of full-length L-Myc of c-Myc in rat embryo cells. The relative cotransforming activities suggest that the potencies of the activation domains determine the cotransforming efficiencies for c-Myc and L-Myc. This correlation supports the hypothesis that the Myc proteins function in neoplastic cotransformation as transcription factors.

Animals↗
PubMed1992

Single daily bottle use in the early weeks postpartum and breast-feeding outcomes.

A prospective study of breast-feeding mothers was undertaken to determine the effects of limited bottle use and infant temperament on breast-feeding outcomes. White, married, primigravida women who were committed prenatally to breast-feeding for at least 6 weeks (n = 121) were randomly assigned to one of two groups: a planned bottle group that would offer one bottle daily between the second and sixth weeks postpartum and a total breast-feeding group that would avoid bottles during the same period. Group assignment had no effect on the occurrence of breast-feeding problems, on mothers' achievement of 90% of their prenatal breast-feeding duration goals, or on weeks to weaning across the study period. At 6 months postpartum, 59% of the planned bottle group and 69% of the total breast-feeding group were still breast-feeding. No main or interactive effects of infant temperament on breast-feeding outcomes were found.

Adult↗
PubMed1992

Trauma: the leading cause of maternal death.

The records of the Cook County Medical Examiner were reviewed for the period January, 1986, to December, 1989. Ninety-five maternal deaths were identified. The causes of maternal death were categorized as direct maternal, indirect maternal, or nonmaternal. Direct maternal causes of death (18.9%) were the result of complications of pregnancy, labor, delivery, or its management. Indirect maternal causes of death (12.6%) occurred when pre-existing health problems were exacerbated by pregnancy. All other maternal deaths were the result of nonmaternal causes. Nonmaternal causes of maternal death were further classified as traumatic or nontraumatic. Traumatic maternal deaths (46.3%) were attributed to homicide in 57% and suicide in 9%. The mechanism of injury in traumatic maternal deaths included gunshot wounds (22.7%), motor vehicle crashes (20.5%), stab wounds (13.6%), strangulation (13.6%), blunt head injuries (9.1%), burns (6.8%), falls (4.5%), toxic exposure (4.5%), drowning (2.3%), and iatrogenic injury (2.3%). Trauma was therefore the leading cause of maternal death, accounting for 46.3% of deaths in this series.

Adolescent↗
PubMed1991

Cystathionine beta-synthase and gamma-cystathionase in helminths.

The activities of gamma-cystathionase and cystathionine beta-synthase were investigated in a range of gastrointestinal, free-living and entomophagous nematodes. Although nematode gamma-cystathionase used the same range of substrates as the mammalian hepatic enzyme, its activity was extremely low and there were significant interspecies variations with respect to the relative order of active substrates. Like the mammalian liver enzyme, nematode cystathionine beta-synthase showed activity in the directions of both cystathionine synthesis and the forward and reverse "L-serine sulphhydrase" reactions. However, the most important feature of the survey was the widespread ability of nematode cystathionine beta-synthase to catalyse the non-mammalian "activated L-serine sulphhydrase" reaction (L-cysteine + R-SH----cysteine thioether + H2S). Additional survey work revealed that the ability to catalyse the activated L-serine sulphhydrase reaction was almost universal amongst nematodes. Activated L-serine sulphhydrase activity was also demonstrated in the acanthocephalan Pomphorhynchus laevis but was absent from cestodes and digeneans.

Acanthocephala↗
PubMed1991

Studies on alanine aminotransferase in nematodes.

L-alanine aminotransferase was demonstrated in a range of gastrointestinal, free-living and entomophagous nematodes. As in mammals, nematode L-alanine aminotransferase was found to exist in the form of mitochondrial and cytosolic isoenzymes. Whilst the majority of nematode enzymes exhibited a greater overall capacity for L-alanine synthesis than for L-alanine catabolism in vitro, the opposite was true for rat liver L-alanine aminotransferase. In contrast with rat liver, certain gastrointestinal nematodes were apparently able to transaminate D-alanine at low rates. H. contortus cytosolic L-alanine aminotransferase differed significantly from the mammalian enzyme with respect to both thermal stability and response to potential protective reagents.

Alanine Transaminase↗
PubMed1991

Pyridoxal 5'-phosphate dependent enzymes in the nematode Nippostrongylus brasiliensis.

Eight classes of pyridoxal 5'-phosphate dependent enzymes have been investigated in Nippostrongylus brasiliensis in parallel with rat tissues. The range of decarboxylases detected in N. brasiliensis was limited in comparison with rat tissues. N. brasiliensis possessed a highly active L-serine hydroxymethyltransferase, but in contrast with rat liver, 5-aminolevulinic acid synthetase was absent. Similar levels of L-serine and L-threonine dehydratase activities were detected in N. brasiliensis and rat liver, and both organisms lacked L-alanine racemase, L-tryptophan synthetase and L-methionine gamma-lyase. The demonstration of cystathionine beta-synthase and gamma-cystathionase in N. brasiliensis suggests the presence of a functional trans-sulphuration sequence. The substrate specificities of the nematode cystathionine beta-synthase and gamma-cystathionase varied significantly from those of the corresponding mammalian enzymes. Particularly striking was the ability of N. brasiliensis cystathionine beta-synthase to catalyse the non-mammalian 'activated L-serine sulphydrase' reaction (L-cysteine + R-SH----cysteine thioether + H2S). N. brasiliensis and rat liver exhibited comparable abilities to transaminate amino acids via the 2-oxoglutarate: glutamate system.

Animals↗
PubMed1991

Toxicity of aldehyde products of lipid peroxidation to adult Schistosoma intercalatum in vitro.

The host's immune response results in oxidative damage to parasite membranes. Known aldehyde breakdown products from lipid peroxidation have been investigated for their in vitro toxicity to Schistosoma intercalatum. Saturated and monounsaturated aldehydes were found to be relatively non-toxic, whilst dienal and hydroxyenal aldehydes had LD50 values in the range of 10-20 microM. Conversion of the toxic aldehydes to their corresponding alcohols or glutathione conjugates reduced toxicity to S. intercalatum by one or two orders of magnitude. This suggests that parasite detoxification enzymes might be useful targets for chemotherapy and raises the possibility of combining chemo- and immunotherapy.

Aldehydes↗
PubMed1991

Soft-tissue infections after trauma.

Soft-tissue infections are best prevented by proper initial management of the wound. When they do occur, they produce certain characteristic physical signs, the appearance of which mandates prompt operative intervention. The extent of debridement is determined by the intraoperative findings. Diagnostic categorization of the infection is performed postoperatively on the basis of the level of soft-tissue involvement and the results of bacterial cultures.

Anti-Bacterial Agents↗
PubMed1991

Amino acid metabolism in helminths.

Amino acids are major constituents of biological material. Chemically they are extremely stable and combine a relatively simple molecular structure with a wide range of properties and functions. In general, amino acid metabolism in helminths has been relatively neglected and the information available is often uneven and of uncertain quality. However, the search for new target sites for anthelmintic development has led to a renewed interest in this area. The amino acid composition of helminths is similar to that of other invertebrates and no unique amino acids have been reported. With the possible addition of tyrosine, helminths seem to require the same 10 essential amino acids as mammals and, where studied in detail, the pathways of amino acid synthesis in helminths are similar to those of mammals. Although amino acids are not a significant energy source in parasites, helminths are able to catabolize amino acids by pathways which, again, appear identical to those found in mammals. Helminths have also been shown to carry out a number of oxidative reactions associated with amino acid metabolism, including cysteine dioxygenase, proline hydroxylase and tryptophan hydroxylase. There are, however, differences in detail between the pathways of amino acid metabolism in helminths and mammals, particularly in the metabolism of the sulphur amino acids and arginine and proline. These differences may be exploitable in anthelmintic design and proline analogues and proline biosynthesis inhibitors show some potential as fasciolicides (Sheers et al., 1982). Differences in metabolism between parasites and their hosts may be the result of parasitic adaptation or they may merely reflect general features of the invertebrate phyla as a whole. Thus a comparison of amino acid metabolism in parasitic helminths with that of their free-living relatives may give some insight into the biochemical basis of parasitism.

Amino Acids↗
PubMed1991

Outcome of CPR in a large metropolitan area--where are the survivors?

STUDY OBJECTIVES: Survival from out-of-hospital cardiac arrest in cities with populations of more than 1 million has not been studied adequately. This study was undertaken to determine the overall survival rate for Chicago and the effect of previously reported variables on survival, and to compare the observed survival rates with those previously reported. DESIGN: Consecutive prehospital arrest patients were studied prospectively during 1987. SETTING: The study area was the city of Chicago, which has more than 3 million inhabitants in 228 square miles. The emergency medical services system, with 55 around-the-clock ambulances and 550 paramedics, is single-tiered and responds to more than 200,000 emergencies per year. TYPE OF PARTICIPANTS: We studied 3,221 victims of out-of-hospital cardiac arrest on whom paramedics attempted resuscitation. MEASUREMENTS AND MAIN RESULTS: Ninety-one percent of patients were pronounced dead in emergency departments, 7% died in hospitals, and 2% survived to hospital discharge. Survival was significantly greater with bystander-witnessed arrest, bystander-initiated CPR, paramedic-witnessed arrest, initial rhythm of ventricular fibrillation, and shorter treatment intervals. CONCLUSIONS: The overall survival rates were significantly lower than those reported in most previous studies, all based on smaller communities; they were consistent with the rates reported in the one comparable study of a large city. The single factor that most likely contributed to the poor overall survival was the relatively long interval between collapse and defibrillation. Logistical, demographic, and other special characteristics of large cities may have affected the rates. To improve treatment of cardiac arrest in large cities and maximize the use of community resources, we recommend further study of comparable metropolitan areas using standardized terms and methodology. Detailed analysis of each component of the emergency medical services systems will aid in making improvements to maximize survival of out-of-hospital cardiac arrest.

Aged↗
PubMed1991

Breeding behaviour of pilot whales revealed by DNA fingerprinting.

Most species of whale spend the majority of their lives well away from land, are capable of migrating over large distances and are difficult to identify individually. However, conservation measures require a detailed understanding of their social structure, breeding behaviour and migration patterns. The advent of DNA fingerprinting permits a systematic investigation of such parameters. In the Faeroe Islands there exists a traditional harvest of long-finned pilot whales (Globicephala melas), in which intact social groups (pods) are captured. This affords a unique opportunity to study genetic relationships within and between pods. We report here on a paternity analysis, using DNA fingerprinting, of mother-fetus pairs and males sampled from complete pods. In addition, a single, highly polymorphic minisatellite locus was used to infer degrees of relatedness between groups of fetuses and females. Taken together, our results suggest that pods consist of closely related adult females and their offspring. Sexually mature males either move frequently between pods or remain in their natal pod but refrain from mating with female relatives. Whichever hypothesis is correct, the data suggest that each male spends only a few months with the female post-mating and individual males often father several fetuses within a pod.

Animals↗
PubMed1991

Intracellular leucine zipper interactions suggest c-Myc hetero-oligomerization.

The physiological significance of in vitro leucine zipper interactions was studied by the use of two strategies which detect specific protein-protein interactions in mammalian cells. Fusion genes were constructed which produce chimeric proteins containing leucine zipper domains from several proteins fused either to the DNA-binding domain of the Saccharomyces cerevisiae GAL4 protein or to the transcriptional activation domain of the herpes simplex virus VP16 protein. Previous studies in mammalian cells have demonstrated that a single chimeric polypeptide containing these two domains will activate transcription of a reporter gene present downstream of the GAL4 DNA-binding site. Similarly, if the GAL4 DNA-binding domain of a chimeric protein could be complexed through leucine zipper interactions with the VP16 activation domain of another chimeric protein, then transcriptional activation of the reporter gene would be detected. Using this strategy for detecting leucine zipper interactions, we observed homo-oligomerization between leucine zipper domains of the yeast protein GCN4 and hetero-oligomerization between leucine zipper regions from the mammalian transcriptional regulating proteins c-Jun and c-Fos. In contrast, homo-oligomerization of the leucine zipper domain from c-Myc was not detectable in cells. The inability of the c-Myc leucine zipper to homo-oligomerize strongly in cells was confirmed independently. The second strategy to detect leucine zipper interactions takes advantage of the observation that the addition of nuclear localization sequences to a cytoplasmic protein will allow the cytoplasmic protein to be transported to and retained in the nucleus. Chimeric genes encoding proteins with sequences from a cytoplasmic protein fused either to the GCN4 or c-Myc leucine zipper domains were constructed. Experiments with the c-Myc chimeric protein failed to demonstrate transport of the cytoplasmic marker protein to the nucleus in cells expressing the wild-type c-Myc protein. In contrast, the cytoplasmic marker was translocated into the nucleus when the GCN4 leucine zippers were present on both the cytoplasmic marker and a nuclear protein, presumably as a result of leucine zipper interaction. These results suggest that c-Myc function requires hetero-oligomerization to an as yet undefined factor.

Amino Acid Sequence↗
PubMed1991

(6R,8S)-(2-benzimidazolyl)hydroxymethylpenicillanic acids as potent antibacterial agents and beta-lactamase inhibitors.

(6R,8S)-(2-Benzimidazolyl)hydroxymethylpenicillanic acids (1a-1x) are potent antibacterial agents and beta-lactamase inhibitors against Gram-positive bacteria and Haemophilus influenzae. The corresponding (6R,8R)-isomers (2a-2x), the 6,6-spiro benzimidazole-penam alcohol (3), (7R,9S)-(2-benzimidazolyl)hydroxymethylcephalosporanic acid (4), and 6 beta-(2-benzimidazolyl)aminopenicillanic acid (5) are much less active as antibacterials or beta-lactamase inhibitors. The syntheses and structure-activity relationships of these compounds are discussed. Antibacterial activity and beta-lactamase inhibition data are presented.

Anti-Bacterial Agents↗