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Biomedical subjects

J A Nicholas

Publications and source records attributed to J A Nicholas.

At least 37 records · Page 2Linked to original sources
PubMed1990

Recombinant CD4-Pseudomonas exotoxin hybrid protein displays HIV-specific cytotoxicity without affecting MHC class II-dependent functions.

The present study describes several in vitro activities of CD4(178)-PE40, a recombinant protein containing a portion of human CD4 linked to active regions of Pseudomonas aeruginosa exotoxin A. Using assays for cell viability, we demonstrate that the hybrid toxin displays highly selective cytotoxicity for HIV-infected T lymphocytes. In a latently infected human T-cell line which is inducible for HIV expression, toxin sensitivity is observed only upon virus induction. At concentrations which readily kill HIV-infected T cells, CD4(178)-PE40 has no observable cytotoxic effects on uninfected human cell lines expressing surface major histocompatibility complex (MHC) Class II molecules, and does not interfere with cellular responses known to be dependent on functional association between CD4 and MHC Class II molecules.

ADP Ribose Transferases↗
PubMed1990

Cytolytic T-lymphocyte responses to respiratory syncytial virus: effector cell phenotype and target proteins.

Cytolytic T-lymphocyte (CTL) activity specific for respiratory syncytial (RS) virus was investigated after intranasal infection of mice with RS virus, after intraperitoneal infection of mice with a recombinant vaccinia virus expressing the F glycoprotein, and after intramuscular vaccination of mice with Formalin-inactivated RS virus or a chimeric glycoprotein, FG, expressed from a recombinant baculovirus. Spleen cell cultures from mice previously infected with live RS virus or the F-protein recombinant vaccinia virus had significant CTL activity after one cycle of in vitro restimulation with RS virus, and lytic activity was derived from a major histocompatibility complex-restricted, Lyt2.2+ (CD8+) subset. CTL activity was not restimulated in spleen cells from mice that received either the Formalin-inactivated RS virus or the purified glycoprotein, FG. The protein target structures for recognition by murine CD8+ CTL were identified by using target cells infected with recombinant vaccinia viruses that individually express seven structural proteins of RS virus. Quantitation of cytolytic activity against cells expressing each target structure suggested that 22K was the major target protein for CD8+ CTL, equivalent to recognition of cells infected with RS virus, followed by intermediate recognition of F or N, slight recognition of P, and no recognition of G, SH, or M. Repeated stimulation of murine CTL with RS virus resulted in outgrowth of CD4+ CTL which, over time, became the exclusive subset in culture. Murine CD4+ CTL were highly cytolytic for RS virus-infected cells, but they did not recognize target cells infected with any of the recombinant vaccinia viruses expressing the seven RS virus structural proteins. Finally, the CTL response in peripheral blood mononuclear cells of adult human volunteers was investigated. The detection of significant levels of RS virus-specific cytolytic activity in these cells was dependent on at least two restimulations with RS virus in vitro, and cytolytic activity was derived primarily from the CD4+ subset.

Animals↗
PubMed1990

Rehabilitation of the injured athlete.

An increase in the rate of injuries has accompanied the boom in sports participation among children and adolescents. Accurate diagnosis, prompt treatment, and comprehensive rehabilitation are keys to the safe return of the young athlete to sports. Reacquisition of flexibility, strength, and endurance forms the basis of reconditioning. A graded reacclimatization to the demands of the sport allows the athlete to attain the preinjury level of skill. Psychological ramifications of injury such as fear, anger, and depression are to be expected and must be dealt with appropriately.

Adolescent↗
PubMed1989

A 16-amino acid peptide of respiratory syncytial virus 1A protein contains two overlapping T cell-stimulating sites distinguishable by class II MHC restriction elements.

The 1A protein of respiratory syncytial (RS) virus is a small, 64-amino acid hydrophobic protein expressed in infected cells. We previously showed that the C-terminal domain of 1A contained a site for stimulation of RS virus-reactive Th lymphocytes in BALB/c and SJL/J mice. In this report we modeled a series of overlapping synthetic peptides of the 1A protein and we present evidence to suggest that the C-terminal domain of the 1A protein contains not one, but two, Th lymphocyte-stimulating sites. Although these sites are extensively overlapping they can be distinguished on the basis of presentation by distinct class II restriction elements of the murine MHC. Additionally, we present evidence to suggest that a 16-amino acid synthetic peptide which contains both of these T cell sites can stimulate T cell activity in mice of multiple different class II MHC haplotypes, perhaps representing a potential lead for designing a "universal" T cell stimulator.

Amino Acid Sequence↗
PubMed1989

Exercise-related changes in serum catecholamines and potassium: effect of sustained exercise above and below lactate threshold.

Plasma potassium and catecholamines exhibit rapid shifts during exercise testing, particularly when exercise intensity exceeds lactate threshold. To assess changes that may occur during sustained exercise, we studied 10 healthy men to determine the effect of 20 minutes of exercise at 25 W above lactate threshold (ALT) and 20 minutes of exercise at 25 W below lactate threshold (BLT). Both conditions showed elevation of catecholamines at end exercise compared to baseline, but catecholamine levels ALT were significantly higher than the levels BLT (2270 +/- 190 versus 900 +/- 230 pg/ml norepinephrine, p less than 0.001; 509 +/- 69 versus 150 +/- 18 pg/ml epinephrine, p less than 0.001). This difference persisted at 2 minutes of recovery (1620 +/- 130 versus 590 +/- 60 pg/ml norepinephrine, p less than 0.001; 216 +/- 31 versus 98 +/- 16 pg/ml epinephrine, p less than 0.001). Both conditions resulted in a significant elevation in potassium at end exercise compared to baseline, but the potassium levels ALT were significantly higher than the levels BLT (1.1 +/- 0.1 mEq/L versus 0.5 +/- 0.1 mEq/L, p less than 0.001. The fall in potassium in the immediate post-exercise period was significantly greater following exercise ALT (-0.8 +/- 0.1 mEq/L versus -0.2 +/- 0.1 mEq/L, p less than 0.001). Thus sustained exercise slightly ALT resulted in a significant potassium flux and very elevated catecholamine levels. Avoiding these metabolic stresses by exercising BLT may decrease chances for exercise-related arrhythmia or other cardiac dysfunction in susceptible patients.

Adult↗
PubMed1989

Monoclonal antibodies that cross-react with the E1 glycoprotein of different alphavirus serogroups: characterization including passive protection in vivo.

A panel of four monoclonal antibodies (mAb) were produced that cross-react with representatives of two different togavirus serogroups, namely sindbis (SIN) and Semliki Forest (SF) viruses, by ELISA and ADCMC assays. Three of these mAb, IgG2a and IgG2b isotypes, passively protected C3H/Hej mice against 10 and 100 LD50 of SF challenge and one, IgM, did not protect against either challenge dose, or even at 1 LD50. All these mAb were cross-reactive with the E1 glycoprotein of the viruses by immunoblotting in which three different patterns of reactivity were evident, suggesting that three epitopes were involved. The patterns depended upon whether the mAb recognized E1 extracted from purified virions or infected cells and whether SDS-PAGE and immunoblotting were done in the presence or absence of beta-mercaptoethanol. One mAb (IgM) reacted with nonreduced or reduced E1 from either virions or cells suggesting recognition of a linear epitope. The other three mAb reacted with nonreduced but not reduced E1 from virions suggesting that recognition depends upon conformational epitopes. These three mAb reacted also with nonreduced E1 extracted from SF-infected cells whereas only one reacted with nonreduced E1 extracted from SIN-infected cells.

Animals↗
PubMed1988

A historical perspective of injuries in professional football. Twenty-six years of game-related events.

A professional football franchise was studied consecutively from 1960 through 1985 for injuries incurred during regular-season games. A "significant" injury was defined as one requiring the player to miss at least two consecutive games (N = 331) and a "major" injury as one that caused the player to miss at least eight games or the equivalent time (N = 130). Significant injuries averaged 0.89 per game and major injuries 0.35 per game for the entire 26 years. Following a high injury rate prior to 1965, significant injury rates were episodic. Major injuries declined (rs = -.68; P less than .01). Since the team's first games on synthetic surfaces in 1968, there was no difference in the rates of significant injuries per game (0.57 vs 0.67) or major injuries per game (0.22 vs 0.33) between games played on grass or artificial turf, respectively. Since 1969 there has been a decline in major knee injuries (rs = -.51; P less than .05) and a decline in major injuries incurred during special-teams play (rs = -.55; P less than .05). The data indicate that this team suffered fewer injuries with the passing of time, primarily in injuries that caused a player to miss at least eight consecutive games. Observations of short duration do not lend themselves to current media perception that injury rates are higher and more serious today in professional football.

Athletic Injuries↗
PubMed1988

Mapping an antibody-binding site and a T-cell-stimulating site on the 1A protein of respiratory syncytial virus.

A synthetic peptide modeled on residues 45 to 60 of the 1A protein of respiratory syncytial (RS) virus [1A(45-60)] was constructed and used for immunization of mice and rabbits. The immunoglobulin G fraction of the resulting rabbit antibody, purified on protein A-Sepharose, immunoprecipitated from RS-infected HEp-2 cells a protein with a molecular size of approximately 9.5 kilodaltons, which corresponds to the previously published molecular size of the 1A protein (Y. T. Huang, P. L. Collins, and G. W. Wertz, Virus Res. 2:157-173, 1985). To investigate the T-cell-inducing properties of 1A(45-60), six strains of mice were immunized and their popliteal lymph node cells were tested for proliferation upon restimulation with peptide in vitro. The lymph node cells of all six strains of mice were responsive to restimulation with 1A(45-60) and showed high- and low-responder strain variation. These peptide-primed lymph node cells also proliferated upon in vitro restimulation with RS virus-infected cells. Correlation of proliferation with interleukin 2 production suggested that the responding lymphocytes were T-helper cells. The antibody-binding and T-cell-stimulating sites of 1A were mapped by constructing a series of overlapping synthetic peptides and testing each for ability to react with antiserum prepared by immunization of BALB/C mice with free peptide 1A(45-60) or for ability to restimulate proliferation in 1A(45-60)-primed lymph node cells of BALB/C mice. Human antibody, obtained during confirmed RS virus infection, was similarly tested with the truncated peptides. Antibody-binding activity was reduced after truncation from the carboxy terminus, and a binding site was mapped to residues 51 through 60, the smallest peptide tested. T-cell-stimulating activity in mice was relatively resistant to truncation from the carboxy terminus and sensitive to truncation from the amino terminus. The smallest region which retained significant T-cell-stimulating activity mapped to residues 46 through 56. However, addition of the naturally occurring Cys at residue 45 and extension of the C terminus to residue 62 resulted in maximum T-cell-stimulating activity of the peptide. These data define both a T-cell epitope and a B-cell epitope of the 1A protein of RS virus and suggest that the carboxy terminus of 1A contains a B-cell epitope, involving residues 51 through 60, which is recognized during natural human infection.

Amino Acid Sequence↗
PubMed1988

Injuries in youth football.

The injury experience of 5,128 boys (8 to 15 years of age, weight 22.5 to 67.5 kg [50 to 150 lb]) participating in youth football revealed an overall rate of significant injury of 5%, with 61% classified as moderate and 38.9% as major injuries. No catastrophic injuries occurred, and it was rare for a permanent disability to result from any injury. The upper extremity was most likely to be injured, and fractures were the most common injury to occur. The rate, site, and type of injuries experienced by the pre- and early adolescent players differed from the pattern for older players at higher levels of competition. Variables related to an increased risk of injury included participation in the older and heavier divisions, heavier weight, and involvement in contact activities. Factors associated with the occurrence of an injury were evaluated and provided areas for future study for the prevention of injuries. The medical care received by youth football participants was appropriate, although improved sideline surveillance for injured players is required.

Adolescent↗
PubMed1987

Comparison of arm and treadmill exercise at 85% predicted maximum heart rate.

Both treadmill exercise and arm exercise are used for evaluating coronary artery disease, but arm exercise has lower diagnostic sensitivity. We compared the two exercise modalities with respect to the rate-pressure product at 85% predicted maximal heart rate, a parameter frequently used to denote performance of sufficient exercise to derive clinical conclusions. At this heart rate, treadmill exercise resulted in a significantly greater systemic oxygen consumption (2.7 +/- .8 vs. 2.1 +/- .6 l/min) and rate-pressure product (30.6 +/- 4.4 X 10(3) vs. 28 +/- 3.3 X 10(3)) than arm ergometry. An inability to generate sufficient imbalance of myocardial oxygen supply and demand may account for the relatively higher incidence of false negative exercise tests seen with arm ergometry, especially if the exercise test is stopped when the patient attains 85% predicted maximal heart rate.

Adult↗
PubMed1987

During recovery from cytomegalovirus infection T-lymphocyte subsets become selectively responsive to activation and have depressed interleukin 2 (IL2) secretion and IL2 receptor expression.

The ability to induce lymphocyte activation with Concanavalin A (Con A) was suppressed in spleen cell cultures derived from BALB/c mice acutely infected with murine cytomegalovirus (MCMV) when compared to cultures derived from control, uninfected mice. This immunosuppression was observed as a reduced incorporation of 3H-thymidine in the lymphocyte proliferative response to Con A, was highly correlated with reduced secretion of interleukin 2 (IL2), and could not be augmented by addition of exogenous IL2. The degree of suppression of both the proliferative response and IL2 secretion was directly dependent on the infecting virus dose and on the time post-infection. At weekly intervals during infection, fluorescein-labeled monoclonal antibodies to various T-lymphocyte surface markers were used to stain spleen cells from control or MCMV-infected mice before or after Con A activation. Analysis of stained spleen cells by flow cytometry revealed several unusual responses to activation signals in lymphocytes derived from mice with acute MCMV-induced immunosuppression. At 4 days post-infection T-lymphocytes of each subset [Thy 1.2 (pan T), L3T4 (T-helper/inducer), Lyt 2 (T-cytotoxic/suppressor) and Lyt 1 (subset of Thy 1.2)] were each present in the spleen but each was in reduced percentage of the total spleen T cell population compared to control (52% to 75% of controls). At this time post-infection these cells were non-responsive to Con A activation as shown by inability to induce 3H-thymidine uptake, IL2 secretion or IL2 responsiveness and an inability to demonstrate an IL2 receptor-positive (IL2R+) population. By 11 days post-infection all tested subsets of T-lymphocytes (Thy 1.2+, L3T4+, Lyt 2+ and Lyt 1+) were in normal control range in fresh spleen. However, only Thy 1.2+L3T4+ (T-helper/inducer) cells were responsive to Con A activation. 3H-thymidine uptake and IL2 secretion were at levels of about 60% of the control but, surprisingly, cells were unresponsive to addition of exogenous IL2 and few, if any, of these cells were found to express IL2 receptors. By 18 days post-infection, when 3H-thymidine uptake could be induced at control level, Thy 1.2+, L3T4+, and Lyt 2+ (T-cytotoxic/suppressor) cells were each responsive to Con A activation at levels comparable to control but Lyt 1+ and IL2 R+ cells were still substantially suppressed (ca. 35% to 40% of control value). Detection of Lyt 1+ subset and IL2 R+ cells after Con A activation did not near control levels until very late in the recovery process (day 25).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

The relationship of injuries of the leg, foot, and ankle to proximal thigh strength in athletes.

Rehabilitation programs designed to restore leg, ankle, and foot function following injury frequently ignore the proximal muscles. During athletics, these knee, hip, and trunk muscles derive much of their functional power from the foot and ankle. They also serve to integrate distal segment motions into a total movement pattern such as jumping, running, or kicking. The linkage system, which is a theoretical concept, describes the normal biomechanical and physiological interactions between proximal and distal musculoskeletal structures. Immobilization or injury of distal segments interrupts the normal generation, summation, and transmission of muscular forces across joints. Adequate measures must be taken to properly assess proximal structures for weakness and tightness and to prescribe specific exercises to prevent the migration of the effects of injury away from the involved segment.

Ankle Injuries↗
PubMed1987

Pyrimidinone (bropirimine) mediated alteration of T lymphocyte subsets during murine cytomegalovirus infection.

Murine cytomegalovirus (MCMV) infection of mice resulted in suppression of mitogen induced proliferation and interleukin 2 (IL-2) responses of splenic cells. This suppression was also evident as a reduction in the number of cells expressing Thy-1 or L3T4 and a reduction in the ratio of T helper/T suppressor cells. The pyrimidinone compound, bropirimine, when administered to MCMV infected mice was able to restore mitogen-induced proliferative and IL-2 responses of splenic cells, to increase the number of cells expressing Thy-1 or L3T4, to restore the ratio of T helper/T suppressor cells and to increase the number of cells inducible for expression of IL-2 receptors.

Animals↗
PubMed1987

Effect of mouse hepatitis virus infection on combination therapy of P388 leukemia with cyclophosphamide and pyrimidinones.

At least three marked differences were noted in the results compared from two parallel experiments using identical protocols with virus-free mice and mouse hepatitis virus (MHV) infected mice inoculated with P388 leukemia. First, the therapeutic effect of cyclophosphamide (CY), a cytotoxic antitumor drug, was apparently augmented in MHV-infected mice. A 162% increase of life span (ILS) was obtained in MHV-infected mice compared to a 100% ILS in uninfected mice. Second, the experimental error in terms of the range of animal survival time was much larger with MHV-infected mice than with uninfected mice. In MHV-infected mice, the therapeutic effect of the combination treatment with CY and pyrimidinone was not statistically different from that of the treatment with CY alone. In uninfected mice, the effects of the combination therapy at all doses of pyrimidinone were statistically more effective than that of CY treatment alone.

Animals↗
PubMed1987

The chronically inflamed bursa.

Bursitis continues to be a frequent source of disability in the athlete. However, significantly less interest has been focused upon this type of injury than other types of sports injuries. This article presents a review of the problem, starting with anatomy and working through diagnosis to treatment.

Athletic Injuries↗
PubMed1987

The arthroscopic treatment of subacromial impingement.

In order to effectively employ arthroscopic techniques for a subacromial decompression, a thorough understanding of the impingement syndrome and its clinical manifestations is necessary. The authors' preliminary experience with the arthroscopic subacromial decompression suggests excellent results with early return to competitive athletics.

Arthroscopy↗