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Biomedical subjects

M Madden

Publications and source records attributed to M Madden.

At least 37 records · Page 2Linked to original sources
PubMed1993

Interaction of IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in human T cells activated by murine antigens.

We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up-regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1 beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1 beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up-regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1 beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-1R antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarly, addition of IL-6 or TNF-alpha induces up-regulation of IL-1 beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1 beta. These findings suggest that IL-6 and TNF-alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1 beta production.

Animals↗
PubMed1993

An improved technique for needle localized biopsies of the breast.

A technique using basic geometric principles is described that allows accurate determination of the location of the nonpalpable lesion in relation to the localizing wire tip and the skin. This method allows the surgeon to make the skin incision directly over the lesion, thus avoiding the creation of tissue flaps and minimizing the amount of tissue removed. While this technique is most helpful for lesions that are remote from the wire tip or buried deep within the breast, these principles are important in all biopsies of the breast. As the number of mammograms performed continues to increase, so will the number of needle localized biopsies, and surgeons must be familiar with techniques to simplify and improve these procedures. Breast conserving treatment for early stage carcinoma of the breast is an accepted form of treatment, and meticulous attention to the technical details of the biopsy will allow it to serve as the definitive surgical procedure. Avoidance of a second operation on the breast is preferable for the patient and will help to reduce health care costs.

Biopsy, Needle↗
PubMed1992

Functional reconstruction for severe postburn microstomia.

A man with severe burn microstomia refractory to traditional management (Z release, skin grafting, splinting, bilateral commissuroplasty, and extensive physical therapy) is presented. Successful functional microstomia reconstruction was achieved with a three-stage approach consisting of the following: (1) lip, commissure, and cheek reconstruction with bilateral temporalis muscle transfers; (2) free flap neck and lower lip contracture release; and (3) vestibuloplasty with a stented full-thickness skin graft.

Adult↗
PubMed1990

Citrate substitutes for homocitrate in nitrogenase of a nifV mutant of Klebsiella pneumoniae.

An organic acid extracted from purified dinitrogenase isolated from a nifV mutant of Klebsiella pneumoniae has been identified as citric acid. H2 evolution by the citrate-containing dinitrogenase is partially inhibited by CO, and by some substrates for nitrogenase. The response of maximum velocities to changes in pH for both the wild-type and the NifV- dinitrogenase was compared. No substantial differences between the enzymes were observed, but there are minor differences. Both enzymes are stable in the pH range 4.8-10, but the enzyme activities dropped dramatically below pH 6.2.

Citrates↗
PubMed1990

Truncation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum affects the holoenzyme assembly and activity.

Truncations of the subunit of ribulose bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum were generated by site-directed mutagenesis to examine the role of the C-terminal tail section. Removal of the last and the penultimate alpha-helices in the tail section changes the quaternary structure of the protein. Electrophoretic and electron microscope analysis revealed that the truncated subunits assemble into an octamer, whereas the wild-type enzyme has a dimeric structure. The octomerization of the mutant protein is due to a hydrophobic patch exposed to the solvent by truncation of the subunit. The mutant protein thus consists of four dimers, bound end-to-end by hydrophobic interactions. Insertion of a polar amino acid in the hydrophobic patch by a L424 to N424 substitution restores the familiar dimeric structure. Truncation of the subunit is associated with a considerable decrease in catalytic activity. The mutants undergo carbamylation but bind the reaction intermediate analog, 2-carboxy arabinitol-1,5-bisphosphate, poorly. This indicates that loss of activity in the mutant is due to weakened substrate binding. These findings suggest that the mutations in the tail section of the subunit are transmitted to the active site, although the C-terminal region is far from the active site. On the basis of the crystal structure of Rubisco, we propose a model for how the truncations of the enzyme subunit induce conformational changes in one of the two phosphate binding sites.

Amino Acid Sequence↗
PubMed1990

Full-length DQ beta cDNA sequences of HLA-DR2/DQw1 subtypes: genetic interactions between two DQ beta loci generate human class II HLA diversity.

Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one alpha beta heterodimer of DQ molecule is expressed by each subtype and the DQ beta chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQ beta cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQ beta chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10-17 amino acids in the first domain and by 3-7 residues in the C-terminal sequence. Comparison among the available DQ beta sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2,Dw2,DQw1 and DR3,DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 beta alleles and (2) an evolutionary scheme may be proposed to relate the various beta alleles of the four major DQ specificities.

Alleles↗
PubMed1990

Interregional migration in an extended input-output model.

"This article develops a two-region version of an extended input-output model that disaggregates consumption among employed, unemployed, and inmigrant households, and which explicitly models the influx into a region of migrants to take up a proportion of any jobs created in the regional economy. The model is empirically tested using real data for the Scotland (UK) regions of Strathclyde and Rest-of-Scotland. Sets of interregional economic, demographic, demo-economic, and econo-demographic multipliers are developed and discussed, and the effects of a range of economic and demographic impacts are modeled. The circumstances under which Hawkins-Simon conditions for non-negativity are breached are identified, and the limits of the model discussed."

Demography↗
PubMed1989

Drug-induced toxic epidermal necrolysis in children.

Nine pediatric patients with drug-induced toxic epidermal necrolysis were treated with a regimen of basic burn care and without the use of steroids or topical or systemic antimicrobial agents. Although septic complications continue to occur frequently, infections are better tolerated when potential iatrogenic sources of decreased host resistance, such as steroids, are eliminated. Neutropenia, gram-negative sepsis, and mortality were all greatly reduced with this regimen, while healing was neither impaired nor prolonged. Thus, steroids and sulfa-containing topical agents should be avoided in the treatment of this disorder.

Adolescent↗
PubMed1989

Tracheostomies in burn patients.

The use of tracheostomies in burned patients with inhalation injuries is now reserved for specific indications rather than as prophylactic airway management. A 5-year burn center experience with tracheostomies used in this fashion is presented. Ninety-nine tracheostomies were performed in 3246 patients who had indications of prolonged respiratory failure or acute loss of airway. Although colonization of the sputum was universal, neither rates of pulmonary sepsis nor mortality were significantly increased in patients who underwent tracheostomies. Twenty-eight patients developed late upper airway sequelae, including tracheal stenosis (TS), tracheoesophageal fistula (TEF), and tracheoarterial fistula (TAF). Duration of intubation correlated only with development of TAF, whereas patients in whom TEF developed were significantly older and more likely to have evidence of tracheal necrosis at the time of tracheostomy. The pathogenesis of upper airway sequelae in these patients as divergent responses to the combined insults of inhalation injury, infection, and intubation is considered.

Burns↗
PubMed1987

cDNA cloning and sequencing reveals that the electrophoretically constant DR beta 2 molecules, as well as the variable DR beta 1 molecules, from HLA-DR2 subtypes have different amino acid sequences including a hypervariable region for a functionally important epitope.

Two-dimensional gel electrophoresis (2D-PAGE) of DR molecules from three different Dw subtypes (Dw2, Dw12, and FJO) of the HLA-DR2 haplotype reveals that at least two DR beta genes are expressed. Protein mixing experiments demonstrate that one of the two expressed DR beta molecules is electrophoretically variable (referred to as DR beta 1), and the other (DR beta 2) migrates constantly among DR2 subtypes. We have constructed cDNA libraries from Dw12 and FJO homozygous typing cells (HTC DHO for Dw12 and HTC FJO for FJO) and isolated DR beta cDNA clones. Four of these clones (FJO-13, DHO-8, FJO-6, and DHO-7) were sequenced, and the deduced amino acid sequences were compared with each other and with two published amino acid sequences for the DR beta molecules derived from a DR2-Dw2HTC. Prediction of the migration patterns on 2D-PAGE from the amino acid sequences of these and other DR beta molecules allows the tentative designation of the two full-length cDNA (DHO-8 and FJO-13) as coding for DR beta 2 molecules and the other two cDNA (DHO-7 and FJO-6) for DR beta 1 molecules. Amino acid sequence comparisons also show that the constantly migrating DR beta 2 molecules, as well as the electrophoretically variable DR beta 1 molecules, from Dw2, Dw12, and FJO have different primary amino acid sequences, including a clustered difference in the third hypervariable region of the polymorphic first domain.

Amino Acid Sequence↗
PubMed1987

An epidemiological study of high school ice hockey injuries.

Between 1976 and 1983, 42 spinal cord injuries among ice hockey participants were documented in Canada; within a recent 3-week period, three cases involving fractured necks were reported in a metropolitan area of Minnesota. The purpose of this comprehensive epidemiological study was to document rates, types, and severities of injuries incurred among high school varsity hockey players in Minnesota, as a result of participation in the 1982-1983 season, and to determine the variables associated with these injuries. Within a 30-mile radius of the state's major metropolitan area, 12 high school varsity hockey teams were selected for participation. Specific techniques were used to ensure confidentiality, high response rates, and validation of information. Among the players an injury rate of 75 injuries per 100 players was documented. Head and neck injuries accounted for 22% of the total injuries. Increased risks of injury were associated with multiple health-care provision variables and equipment utilized. Potential strategies are identified as a result of these findings.

Adolescent↗
PubMed1987

Comparison of DR beta 1 alleles from diabetic and normal individuals.

Insulin-dependent diabetes (IDD) is positively associated with HLA-D proteins. A critical question is whether or not sequence differences within the HLA-D coding region are the same or different in diabetics and normal individuals of the same haplotype. We have isolated both DR beta 1 alleles from a Dw4/LD MN2 cDNA library and compared them to DR beta 1 genes isolated from normal individuals of the same Dw phenotype. We found no nucleotide differences in the coding region between the normal and diabetic alleles of DR beta 1 suggesting to us that DNA differences other than the DR beta 1 coding region may account for the observed association of HLA-D and diabetes.

Alleles↗
PubMed1987

T lymphocyte depletion of human peripheral blood and bone marrow using monoclonal antibodies and magnetic microspheres.

It has previously been demonstrated that graft-versus-host disease can be overcome in patients receiving HLA-mismatched bone marrow transplants by prior in vitro depletion of T lymphocytes from the marrow. In this report we describe the use of monoclonal antibodies and magnetic microspheres for the depletion of T cells from peripheral blood and bone marrow. The target cells are sensitized with antibodies directed against the CD2, CD3, CD4 and/or CD8 cell surface antigens, captured by magnetic beads coated with sheep anti-mouse IgG antibody and collected by placing the cell suspension in a magnetic field. This simple, rapid procedure results in the efficient removal of T cells from peripheral blood and from bone marrow without affecting the colony-forming potential of normal hematopoietic stem cells. The procedure is capable of being scaled up for the treatment of larger volumes of marrow that are required for clinical transplantation.

Antibodies, Monoclonal↗
PubMed1986

Carnitine status, plasma lipid profiles, and exercise capacity of dialysis patients: effects of a submaximal exercise program.

Carnitine status, blood lipid profiles, and exercise capacity were evaluated in a combined group of hemodialysis (N = 4) and continuous ambulatory peritoneal dialysis (N = 6) patients before and after an 8-week submaximal exercise program. Maximal aerobic capacity (VO2max) was only 18.5 +/- 5.9 (mean +/- SD) mL O2/kg/min, well below the expected 30 to 35 mL O2/kg/min for age-matched sedentary controls. Plasma short-chain acylated carnitine levels, which were two to three times normal values, were reduced after the exercise program, but the long-chain acylcarnitines were significantly reduced during acute exercise. Muscle biopsies of the vastus lateralis were performed at rest in five patients prior to and after the 8-week exercise program. Total carnitine in skeletal muscle was 3.09 (.076 SD) mumol/g ww, with only 11.3% acylated prior to the exercise program, which was much lower than the 4.25 +/- 1.27 mumol/g ww, with 28.5% acylated in a group of healthy athletic subjects (N = 28). Muscle free carnitine concentrations decreased significantly following the 8-week training period, with only a slight reduction in total carnitine. The percent of acylated carnitine was therefore significantly increased (P less than 0.05) from 11.3% to 25.2% after the experimental period. Pretraining carnitine palmitoyl transferase activity at rest was 0.57 +/- 0.28 nmol palmitoyl carnitine formed/5 min/mg mitochondrial protein, which was not changed by exercise training v 1.80 +/- 0.51 nmol/5 min/mg protein in 28 healthy normals (P less than 0.001). Free fatty acid concentrations were reduced significantly during acute exercise as a result of the exercise training program whereas other plasma lipids were not altered. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗