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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 19 recordsLinked to original sources
PubMed1992

Social support and depressive symptoms in the elderly.

The purpose of this study was to examine the effect of characteristics of social networks and support on depressive symptoms in the elderly. The subjects were 1,962 noninstitutionalized persons 65 years and older from the New Haven Establishment of Populations for Epidemiologic Study of the Elderly in 1982, who were available to give a complete follow-up interview in 1985. Baseline depression, functional disability in 1982, and any change in disability by 1985 were considered as additional influences on 1985 depression, requiring adjustment along with sociodemographic variables. Multiple regression procedures were used to simultaneously examine the variables. Baseline depression, functional disability, and change in functional disability made the largest contribution to explaining the variance in depression. Among the social support and network characteristics, loss of a spouse, adequacy of emotional support, and its change during 1982-1985 made the largest contributions. Other significant characteristics in relative order of magnitude of effect, based on contrast tests, included tangible support adequacy and its change, loss of a confidant between 1982 and 1985, number of children making weekly visits and change in this number by 1985, and the absence of a confidant in both 1982 and 1985. For mental health outcomes, these findings emphasize the need to consider specific dimensions of social support and networks rather than global measures.

Aged↗
PubMed1992

Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.

Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1992

Biochemical characterisation of the enzyme responsible for "activated L-serine sulphydrase" activity in nematodes.

The biochemical properties of the enzyme responsible for nematode "activated L-serine sulphydrase" activity (L-cysteine + R-SH----cysteine thioether + H2S) have been investigated using primarily the gastro-intestinal nematodes Nippostrongylus brasiliensis and Haemonchus contortus. The activated L-serine sulphydrase enzyme was found to be cytosolic in origin and exhibited maximal activity at pH 9.0. Enzyme activity was widely distributed amongst the major tissues of adult female Ascaris suum but was particularly abundant in longitudinal muscle. The enzyme appeared to have a rigid specificity for L-cysteine as the primary thiol substrate, but was capable of utilising a number of sulphur amino acids (and derivatives) and nonphysiological thiols as second substrates. The best second thiol substrates were nonphysiological, hydroxyl-containing thiols that showed some structural similarity to the standard second substrate, 2-mercaptoethanol. Kinetic analyses revealed that the enzyme operates by a sequential catalytic mechanism, and the absolute Michaelis constants were: KL-cysteine = 0.21 +/- 0.02 mM and K2-mercaptoethanol = 5.58 +/- 0.59 mM. The enzyme was relatively insensitive to inhibition by a variety of substrate analogues and known inhibitors of pyridoxal 5'-phosphate dependent enzymes, whilst plant phenols caused significant levels of inhibition. The most potent inhibitors discovered were the anthelmintics bithionol, dichlorophene and hexachlorophene. Further characterisation revealed that hexachlorophene was a parabolic competitive inhibitor of the activated L-serine sulphydrase enzyme.

Animals↗
PubMed1992

The identification of a variant form of cystathionine beta-synthase in nematodes.

Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes.

Animals↗
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗
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↗