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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 19 recordsLinked to original sources

HIV infection in athletes. What are the risks? Who can compete?

The activities of athletes and personnel who provide their medical care may place them at slightly greater risk for infection with human immunodeficiency virus (HIV) than their nonathletic peers. At this point, there is no reason to disallow participation of athletes who are HIV-infected. Thus, sports physicians need to assume that they are at risk for accidental exposure to HIV and use appropriate precautions. Most important, physicians can educate athletes, coaches, and trainers to practice "safe" athletics and medical care to minimize the risks of exposure to and transmission of HIV. Testing for HIV can be encouraged for athletes who may be at risk and should be done for any athlete who specifically requests it. Physicians should encourage further study to clarify the specific issues and risks of HIV infection created by athletic competition and prepare to deal with the changing knowledge about HIV and AIDS.

AIDS Serodiagnosis

Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor.

Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells in culture, is expressed in vivo in a variety of inflammatory conditions associated with cell proliferation, including atherosclerosis, wound repair, pulmonary fibrosis, and glomerulonephritis. However, it is not known if PDGF mediates the fibroproliferative responses that characterize these inflammatory disorders. We administered neutralizing anti-PDGF IgG or control IgG to rats with mesangial proliferative nephritis. Inhibition of PDGF resulted in a significant reduction in mesangial cell proliferation, and largely prevented the increased deposition of extracellular matrix associated with the disease. This suggests that PDGF may have a central role in proliferative glomerular disease.

Animals

Wheat germ agglutinin inhibits the C5a receptor interaction: implications for receptor microheterogeneity and ligand binding site.

Wheat germ agglutinin (WGA) has been shown to inhibit the interaction of C5a with the C5a receptor on both polymorphonuclear neutrophils (PMNs) and the histiocytic cell line U937. The level of inhibition with isolated receptor preparations is 100%, and on intact cells 10 to 20% of the receptor population appear to retain their ability to bind C5a in the presence of WGA. In contrast, this lectin completely inhibits the C5a-mediated degranulation of PMN primary and secondary granules, suggesting that the population of C5a receptors responsible for mediating degranulation is also recognized by WGA. More than 50% of the receptors appear to be blocked before an effect on degranulation occurs. This inhibition by WGA does not appear to be due to down-regulation of C5a receptors from the cell surface, excessive aggregation of receptor sites, or interaction of WGA with the carbohydrate portion of the C5a molecule. The inhibition is reversed by N-acetylglucosamine but not by sialic acid. This effect appears to be specific for WGA because various other lectins do not inhibit the C5a receptor interaction. That the inhibition by WGA is due to direct binding of the lectin to N-acetylglucosamine residues on the C5a receptor is strongly supported by the ability of the cross-linked C5a-receptor complex to bind to and be specifically eluted from a WGA-Affigel affinity matrix. These observations are consistent with hypothesis that the population of C5a receptors on leukocytes exhibits microheterogeneity with respect to structure (carbohydrate content) and/or function.

Binding Sites

Mesangial cells in the pathogenesis of progressive glomerular disease in animal models.

Increasing evidence supports a role for glomerular mesangial cell proliferation and over-production of extracellular matrix by mesangial cells in the development of focal or diffuse glomerulosclerosis. Experimental data obtained mainly in the chronic progressive remnant kidney model and in the acute mesangioproliferative anti-Thy 1.1 glomerulonephritis in rats have shed some insights into the factors governing mesangial cell proliferation and matrix synthesis in vivo. In these experimental models, mesangial cell activation can be demonstrated early in the course of disease as exemplified by the de novo expression by the mesangial cell of a smooth muscle "specific" actin isotype (i.e., alpha-smooth muscle actin). Following mesangial cell activation, cellular proliferation ensues both in the acute anti-Thy 1.1 model and, to a lesser degree, in the chronic remnant kidney model. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. Three growth factors which may have important roles in the in vivo mesangioproliferative response are platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokine growth factors are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to mediate cell proliferation by either paracrine and/or autocrine pathways. In vivo studies show that PDGF, bFGF, and TGF-beta participate in the mesangial cell proliferation and/or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The measurement of anterior cruciate ligament strain in vivo.

This article describes the use of the Hall Effect strain transducer (HEST) in a new arthroscopic technique to study the normal anterior cruciate ligament (ACL) in-vivo. Study participants were patient volunteers with normal ACLs undergoing diagnostic arthroscopic or meniscal surgery under local anaesthesia. The HEST was implanted into the Anterior Medial Band (AMB) of the ACL. Anterior shear loading of the tibia in relation to the fixed femur at 30 degrees of knee flexion (Lachman test), produced significantly greater strain values in comparison to anterior shear loading at 90 degrees (Anterior Drawer test). During isometric quadriceps contraction a significant increase in AMB strain was measured with the knee flexed to 30 degrees, while no significant change was measured at 90 degrees. For quadriceps contraction there were significantly higher values of AMB strain measured at 30 degrees of knee flexion in comparison to that observed at 90 degrees. For active range of motion (AROM) the AMB was strained between 10 degrees and 48 degrees, and unstrained between 48 degrees and 110 degrees. During passive range of motion (PROM) the AMB remained unstrained until the joint was brought into extension. There were significant differences in strain values found between AROM and PROM at the flexion angles 10 degrees, 20 degrees, 30 degrees and 40 degrees, while between 50 degrees and 110 degrees there were no significant differences. These results confirm previous studies that the Lachman test is a superior technique in comparison to the classic anterior drawer test for evaluating the AMB. They suggest that isometric quadriceps activity at 90 degrees of knee flexion can be prescribed for rehabilitation immediately after ACL reconstruction. These data indicate that AROM (between the limits of 50 degrees and 110 degrees) and PROM may also be performed with minimal risk of strain to a reconstructive replacement. The PROM data may also serve as an important standard for the reconstruction of the ACL.

Adult

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult

Isolation of a calreticulin-like calcium binding protein from bovine brain.

Intracellular calcium levels are stringently regulated in all cells. The nature of this regulation is incompletely understood, but recent evidence indicates that the endoplasmic reticulum plays an important role in sequestering intracellular calcium. Using methods for isolating both calsequestrin and calreticulin, we have isolated a 58 kDa, high capacity calcium binding protein that exists in microsomes that shift their density in an oxalate-mediated density shift assay. This protein which we call CBP-58 bears similarities to the endoplasmic reticulum protein, calreticulin, in that it has a pI of 4.7 containing approximately 30% glutamate and aspartate, has a high capacity for calcium, and stains blue with the carbocyanine dye, 'Stains-all'. Peptide, amino acid, nucleotide and immunochemical analyses reveal further similarities between CBP-58 and calreticulin, but also some marked differences. Its tissue distribution suggests it is highly enriched in brain versus other tissues. We believe that CBP-58 is a calreticulin-like protein and that differences in the amino acid composition and sequences may reflect species diversity in calreticulin.

Amino Acid Sequence

Case report: inverted contrast medium--urine level in the bladder on computed tomography.

Fluid-fluid levels within structures are caused by differences between the specific gravity of the fluids. This results in a characteristic appearance on computed tomography (CT), with urine which contains contrast medium and has a high specific gravity layering posteriorly in the dependent portion of the bladder, while lower specific gravity, non-opacified urine is found uppermost. We report a patient in whom the contrast medium-urine level was inverted because of sediment in the dependent part of the bladder.

Adult

Enhanced expression of "muscle-specific" actin in glomerulonephritis.

Increased expression of "muscle-specific" actin can be correlated with mesangial cell injury and proliferation in the rat. We performed similar immunohistochemical studies using two monoclonal antibodies (MoAb) to "muscle-specific" actins (HHF-35, a MoAb to pan muscle actin and alpha-SM-1, a MoAb to alpha-smooth muscle actin) on methyl Carnoy's fixed human renal biopsies which demonstrated a wide variety of inflammatory, proliferative, and non-proliferative glomerular diseases. Most glomerular diseases were associated with increased "smooth-muscle" actin expression. Exceptions almost invariably were disease settings without prominent cellular proliferation. As in the rat, there was a correlation of induced actin expression with increased glomerular cell proliferation, as detected by staining with a MoAb to proliferating cell nuclear antigen (PCNA). Double immunolabeling studies with an antibody to the leukocyte common antigen showed the great majority of PCNA+ proliferating cells to be intrinsic glomerular cells rather than infiltrating leukocytes. These studies demonstrate that phenotypic changes of mesangial cells occur in both human and experimental glomerulonephritis, and are identifiable in fixed tissue sections. These studies also suggest that markers of mesangial cell injury or activation and proliferation, such as immunostaining of renal biopsies for "muscle-specific" actins, might be useful diagnostic and/or prognostic indicators in proliferative or sclerosing glomerular diseases.

Actins

Developmental patterns of PDGF B-chain, PDGF-receptor, and alpha-actin expression in human glomerulogenesis.

Expression of PDGF B-chain and the PDGF receptor beta-subunit (PDGFR beta) is detected immunocytochemically during the development of glomeruli in human kidneys of 54 to 105 days gestational age. During the early stages (vesicular, comma-shape and S-shape) of glomerulogenesis, PDGF B-chain is localized to differentiating epithelium of the glomerular vesicle, while PDGFR beta is expressed in the undifferentiated metanephric blastema, vascular structures, and interstitial cells. During this stage PDGF may be acting as a paracrine growth factor and as a chemoattractant acting to recruit mesangial progenitor cells into the developing glomerulus. As the glomerular tuft forms, both PDGF B-chain and PDGFR beta can be detected in an arboreal pattern radiating from the hilus of the glomerular tuft. Immunocytochemical studies using markers specific to endothelium (Ulex europaeus I lectin, Factor VIII related antigen), and smooth muscle (alpha-smooth muscle actin), indicate that the PDGF B-chain and PDGFR beta are both expressed primarily by mesangial cells. During this stage, PDGF may be acting primarily to provide an autocrine factor to mediate further mesangial cell proliferation. Glomerular expression of alpha-smooth muscle actin is limited to later stages of glomerulogenesis; at these stages the pattern of expression is similar to that of PDGF-B chain and PDGFR beta. The upregulation of mesangial PDGF, PDGFR beta, and alpha-smooth muscle actin expression that has been identified in some disease states in both humans and experimental animals appears to represent a recapitulation of this normal developmental process.

Actins

Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy.

Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.

Animals

Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model.

Increasing evidence supports a role of glomerular cell proliferation in the development of focal or diffuse glomerulosclerosis. This study investigates the chronology and sequence of cellular events that precede glomerulosclerosis in 5/6 nephrectomized rats. Within three days of renal ablation, a phenotypic switch occurred in which some mesangial cells expressed alpha-smooth muscle actin. This was followed by proliferation of mesangial cells, and to a lesser degree endothelial cells from day 5 to week 4 as detected by immunostaining for the proliferating cell nuclear antigen (PCNA). Glomerular cell proliferation was accompanied by increased immunohistochemical expression of PDGF B-chain. In situ hybridization showed no glomerular PDGF B-chain mRNA expression at the induction of proliferation (day 5), and a marked increase between week 1 and 4 in operated rats. In parallel, increased expression of PDGF receptor beta-subunit protein and mRNA was demonstrated by immunohistochemistry and Northern analysis of total glomerular RNA. The onset of glomerular cell proliferation was also associated with mild glomerular platelet accumulation (as defined by 111In-labelled platelet studies) as well as with fibrinogen deposition. Proteinuria, glomerular sclerotic changes, and leukocyte infiltration all followed cell proliferation. The glomerular leukocyte infiltrate consisted of monocytes/macrophages and increased markedly at week 10 in rats with renal ablation. Thus, our results suggest that in the remnant kidney model: 1) proliferation of intrinsic glomerular cells precedes glomerulosclerosis; 2) proliferation may be initiated by degranulating platelets and sustained by PDGF released from intrinsic glomerular cells; and 3) glomerular monocyte/macrophage infiltration occurs after the proliferation, and may possibly contribute to the development of glomerular sclerotic changes.

Actins

Short-term reduction in egg production in laying hens treated with an agonist of GnRH.

1. In two experiments laying hens were treated with an agonist of gonadotrophin releasing hormone (GnRH) to induce a reduction in the secretion of luteinising hormone (LH) and a pause in egg production. 2. In experiment 1, 70-week-old laying hens were either given daily subcutaneous injections of saline for 7 d, offered whole oats for 7 d (nutrient restriction), given daily injections of the GnRH agonist [D-Trp6-Pro9 N-ethyl amide]GnRH for 7 d at 50 micrograms/kg or 100 micrograms/kg or administered 4 biocompatible implants each containing 120 micrograms of the GnRH agonist. 3. Weekly egg production was monitored for 7 weeks and blood samples were taken at weekly intervals and assayed for plasma LH and oestradiol. Egg production was reduced in the birds treated with the agonist (28 to 46% reduction) but not to the same extent as in the birds offered whole oats (92.3% reduction). 4. The treatments also reduced plasma LH and oestradiol in treated hens but again to a greater extent in the birds offered whole oats than the birds treated with the agonist. Egg production and plasma LH and oestradiol increased following the termination of the treatments. 5. The birds fed whole oats suffered a reduction in weight of 16.7% over the treatment period whereas there were increases in the weights of the birds treated with saline, 50 micrograms of GnRH agonist and the implants of GnRH agonist, but no change in birds treated with 100 micrograms of GnRH agonist. 6. The birds fed oats lost feathers over the treatment period but the birds in the other treatment groups suffered no loss. 7. In experiment 2 laying hens were either injected daily with saline or 200 micrograms GnRH agonist and weekly egg production and plasma LH and oestradiol were measured. As egg production was reduced by almost 60% in the birds treated with the agonist but did not completely cease. Reductions in plasma LH and oestradiol were also observed. All variables increased to pretreatment levels once treatment ceased. 8. These data confirm the effects of severely depriving hens of nutrients on egg production and the secretion of LH and oestradiol.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed

Sudden death during exercise. A cruel turn of events.

The causes of sudden death in exercisers age 35 and younger are generally not preventable because they are typically structural and difficult to detect. The best a physician can do is be alert to important information in the family and patient history and to the occasional sign or symptom that may warrant further evaluation. For the over-35 exerciser, screening tests may be appropriate, especially if the person is just beginning an exercise program, although this remains an area of controversy. The screening tests available are far from perfect. If exercise testing is performed, the asymptomatic patient must be apprised of the possibility of a false-positive result and the consequences and attendant risks of overdiagnosis or additional testing (coronary angiography). Physicians should be alert to suspicious symptoms in physically active patients, but they should avoid the tendency to have these patients stop their exercise program. Instead, after appropriate diagnostic testing, they should advise a modified exercise program that is safely within the limits of the disease process involved. It is important to realize that physical activity can be a preventer of cardiac disease but also a provoker of sudden death. Even so, the benefits of regular exercise clearly outweigh the risk.

Adult

Widowhood, health status, and the use of health services by older adults: a cross-sectional and prospective approach.

Using data from the LSOA, we examined the relationship between widowhood, health status, and the use of health services. Controlling for the characteristics specified in the behavioral model, a cross-sectional assessment of the 2,354 respondents widowed at baseline showed that regardless of how the recency of widowhood is modeled, it is not related to any measure of health status, and it is only marginally associated with two measures of health services utilization: nursing home placement and death. A prospective assessment of the 4,113 respondents reinterviewed at follow-up produced similar results. Becoming widowed did not alter previous reports of health status, nor prior patterns of physician or hospital utilization. Being widowed did, however, significantly increase the likelihood of being placed in a nursing home. For the 14 respondents who were both widowed and placed in a nursing home after baseline, the sequence is always widowhood first, and then nursing home placement.

Aged

The risk of nursing home placement and subsequent death among older adults.

This article examines the effects of the characteristics specified in the behavioral model of health services utilization and measured at baseline on the subsequent risk of nursing home placement and death within four years. Analyses of the 5,151 respondents in the Longitudinal Study on Aging indicate that the risk for nursing home placement is greater for older adults, Whites, those who lived alone, persons with telephones, those with fewer nonkin social supports, those who did not feel that they had much control over their future health, those with more household ADL or lower body limitations, and those who had been in the hospital during the year prior to baseline, or in a nursing home at any time before baseline. Among the 549 respondents placed in nursing homes, the risk of dying there was greater for older adults, men, those who had not lived in multigenerational households, persons who did not worry about their health, individuals with more upper body limitations, and respondents having a history of valvular heart disease or cancer. The odds of dying were 2.74 times greater among the 549 respondents placed in nursing homes than among the 4,602 respondents who remained in the community.

Aged