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R J Johnson

Publications and source records attributed to R J Johnson.

At least 289 records · Page 16Linked to original sources
PubMed1991

Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization.

We used the technique of in situ hybridization to determine if cells expressing PDGF B-chain mRNA can be detected in a model of mesangial proliferative nephritis in the rat induced with antibody directed against the Thy 1 antigen present on the mesangial cell membrane. The method involved hybridization with a digoxigenin-labeled cRNA probe for the murine PDGF B-chain followed by detection with an anti-digoxigenin-alkaline phosphatase conjugate and subsequent colorimetric reaction. In normal rats (N = 4), the majority of glomeruli (74%) were negative for PDGF B-chain mRNA, whereas 65% of glomeruli from rats with mesangial proliferative nephritis (N = 4) had segmental or diffuse staining for PDGF B-chain mRNA in a mesangial pattern. The difference, as measured using a semiquantitative scale, was significant (mean scores 0.4 +/- 0.2 vs. 1.9 +/- 0.2; scale 0 to 3+; P less than 0.001). The increase in PDGF B-chain mRNA positive cells localized to areas of hypercellularity and was associated with a significant increase in cells positive for PDGF B-chain by immunostaining with a specific monoclonal antibody (0.8 +/- 0.1 vs. 1.7 +/- 0.4, scale 0 to 3+, normal vs. diseased rats, P less than 0.005). Complement depletion, which prevents the mesangial cell proliferation, also prevented the increase in cells expressing PDGF B-chain mRNA and protein. Thus, this method of in situ hybridization can successfully detect cells expressing PDGF mRNA in active glomerulonephritis, and may be useful for detecting cells expressing genes for other growth factors and cytokines in both human and experimental models of glomerular injury.

Animals↗
PubMed1991

Increased synthesis of extracellular matrix in mesangial proliferative nephritis.

Extracellular matrix expansion is frequently noted in mesangioproliferative renal diseases. This study investigates the role of immunologic factors in glomerular matrix accumulation. The gene expression of type I and IV collagen, laminin and s-laminin was examined in the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Northern analysis was performed on glomerular RNA isolated one, three and five days after disease induction and at day 3 following prior complement depletion. Tissue was immunostained for the protein products of these genes as well as for heparan sulfate proteoglycan, entactin and PCNA (a marker of cell proliferation) at days 1, 3, 5, 14, 21 and 42. A seven- to ten-fold increase of collagen IV and laminin mRNA as well as de novo expression of collagen I mRNA occurred at days 3 and 5 corresponding to the time of maximal proliferation. S-laminin mRNA levels only increased three-fold. With the exception of s-laminin, mesangial staining for all examined matrix proteins increased to a maximum at day 5 and decreased thereafter. Focal alterations of the glomerular architecture and matrix persisted at day 42. Complement depletion prevented the histological abnormalities as well as the increased expression of matrix proteins at day 3. These findings indicate that immunologic injury in the mesangium may result in overproduction of extracellular matrix components and may ultimately contribute to the development of glomerulosclerosis.

Animals↗
PubMed1991

Elevated urinary excretion of the C5b-9 complex in membranous nephropathy.

In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar mechanism might be operative in human membranous nephropathy, we measured urinary excretion of C5b-9 and C5 in 146 proteinuric patients with biopsy-proven glomerular diseases or diabetes mellitus. Urinary excretion of C5b-9 relative to C5 excretion was higher in 40 patients with membranous nephropathy than in 106 patients with proteinuria due to non-membranous glomerulonephritis when analyzed by covariance analysis (P less than 0.0002). Urinary C5b-9 excretion was higher in membranous nephropathy than in membranoproliferative glomerulonephritis (N = 13, P less than 0.05), minimal change-focal sclerosis (N = 33, P less than 0.001), mesangial proliferative glomerulonephritis (N = 9, P less than 0.02) and IgA nephropathy (N = 7, P less than 0.025). Urinary C5b-9 excretion was also higher in patients with lupus nephritis (N = 18, P less than 0.02) compared to those with non-membranous glomerulonephritis. The lupus patients with the highest excretion had clinical or pathological features of membranous nephropathy. Nine patients with membranous nephropathy and elevated urinary C5b-9 excretion had a shorter duration of disease (P less than 0.05), lower serum creatinine levels (P less than 0.05) and more proteinuria (P less than 0.02) than the 31 membranous nephropathy patients with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Inheritance of plasma insulin-like growth factor-I and growth rate, food intake, food efficiency and abdominal fatness in chickens.

1. The inheritance of, and genetic and phenotypic correlations between, plasma insulin-like growth factor-I (IGF-I) and 28-(28dW) and 56-d (56dW) body weight, 28- to 56-d body weight gain (BWG), food intake (FI), food conversion ratio (FCR) and abdominal fatness (AF) at 56 d were determined by sib analyses in a population of 327 pedigreed progeny produced by matings between 18 cockerels and 72 pullets from a broiler strain of chickens bred at random for 8 generations. 2. Plasma IGF-I was measured in fed (IGF-If) and fasted (IGF-I) birds at 42 d. 3. Heritability estimates (sire + dam) were: 28dW 0.35 +/- 0.11, 56dW 0.49 +/- 0.13, BWG 0.51 +/- 0.13, FI 0.55 +/- 0.13, FCR 0.73 +/- 0.14, AF 0.49 +/- 0.13, IGF-If 0.10 +/- 0.08, IGF-Is 0.08 +/- 0.08. 4. The low heritability estimates with their high standard errors for the IGF-I measures precluded the calculation of meaningful genetic correlations between these and the performance traits. There were moderate to strong positive genetic correlations between 28dW, 56dW, FI and AF.

Abdomen↗
PubMed1991

Muscle protein turnover in chickens selected for increased growth rate, food consumption or efficiency of food utilisation: effects of genotype and relationship to plasma IGF-I and growth hormone.

1. Rates of muscle protein turnover, growth, and food consumption were determined in 4 lines of chickens selected for either weight gain (line W), food consumption (line F), efficiency of food conversion (line E), or at random (line C) and in two Australian commercial broiler strains (S and H). These measures were related to body composition and the circulating concentrations of plasma growth hormone (GH) and IGF-I. 2. N tau-methylhistidine excretion was 10-14% higher in line F and 7-13% lower in line E compared to line C, showing divergence in the rate of muscle protein breakdown with selection. 3. There were no differences between the 4 experimental lines (W, F, E and C) in muscle protein fractional synthesis rates, whether calculated from N tau-methylhistidine excretion or measured directly by 3H-phenylalanine incorporation. 4. No consistent differences were found between lines in circulating concentrations of either GH or IGF-I but plasma IGF-I concentrations were positively correlated over all lines with protein accretion rates. There was a strong inverse correlation over all lines between the rates of protein degradation and FCR. 5. The correlated responses in protein degradation rates are consistent with the notion of a positive genetic association between the overall efficiency of food utilisation for growth and the efficiency of protein metabolism.

Animals↗
PubMed1991

The use of health services by older adults.

Using baseline data on the 5,151 respondents surveyed as part of the panel design of the Longitudinal Study on Aging (LSOA), this article estimates, cross-sectionally, the relationships hypothesized in the behavioral model of health services utilization. In addition to the traditional indicators of the predisposing, enabling, and need characteristics, the richness of the LSOA permits the inclusion of measures of multigenerational living arrangements, kin and nonkin social supports, health worries and the sense of health control, health insurance coverage, residential stability, and several multiple-item scales of functional limitations. Despite these innovations, the ability of the behavioral model to accurately predict the use of health services by older adults remains relatively unchanged. Important conceptual clarifications involving the hypothesized relationships, however, are identified and discussed.

Activities of Daily Living↗
PubMed1991

An analysis of prognostic factors in stage III and IV Hodgkin's disease treated at a single centre with MVPP.

Two hundred and twenty seven patients with stage IIIA-IVB Hodgkin's disease have been treated at a single centre with MVPP chemotherapy followed by radiotherapy to sites of previously bulk disease. The median follow up is 58 months. 119 patients (52%) had stage IV disease. Overall complete remission (CR) rate was 72%. Discriminant analysis of factors predictive for complete remission showed that low albumin was the only independent factor that predicted a significantly lower chance of CR. Overall five year survival was 73%. A Cox multivariate analysis demonstrated that age greater than 40 years, stage IV disease, presence of bulk disease, low serum IgG and male sex to be variables which independently predicted poorer prognosis in terms of overall survival. Stage IV and lymphocyte depleted or unclassified histologies were independently predictive for poorer progression-free survival. Patient weight greater than 70 kg and stage IV disease were adverse prognostic factors for relapse free survival. Results are compared to other published multivariate analyses of prognostic factors in advanced Hodgkin's disease.

Adult↗
PubMed1991

Isolation and characterization of rapid transport vesicle subtypes from rabbit optic nerve.

Subcellular fractionation of rabbit optic nerve resolves three populations of membranes that are rapidly labelled in the axon. The lightest membranes are greater than 200 nm and are relatively immobile. The intermediate density membranes consist of 84 nm vesicles which disappear from the nerve with kinetics identical to those of the rapid component. A third population of membranes, displaying a distinct protein profile, is present in the most dense region of the gradient. Immunological characterization of these membranes suggests the following. (1) The lightest peak contains rapidly transported glucose transporter and most of the total glucose transporters present in the nerve; this peak is therefore enriched in axolemma. (2) The intermediate peak contains rapidly transported glucose transporters and synaptophysin, an integral synaptic vesicle protein, and about half of the total synaptophysin; this peak therefore contains transport vesicles bound for both the axolemma and the nerve terminal, and these subpopulations can be separated by immunoadsorption with specific antibodies against the aforementioned proteins. (3) The heaviest peak contains rapidly transported synaptophysin and tachykinin neuromodulators and about half of the total synaptophysin, and 80% of the total tachykinins present in the nerve; this peak appears to represent a class of synaptic vesicle precursor bound for the nerve terminal exclusively. (4) Synaptophysin is present in the membranes of vesicles carrying tachykinins. (5) Both the intermediate and the heaviest peaks are enriched in kinesin heavy chain, suggesting that both vesicle classes may be transported by the same mechanism.

Adenosine Triphosphatases↗
PubMed1991

Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation.

Mesangial cell proliferation is common in glomerulonephritis but it is unclear if proliferation is associated with any in vivo alteration in phenotype. We investigated whether mesangial of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells. At day 3 glomeruli displayed de novo immunostaining for alpha-smooth muscle actin in a mesangial pattern, correlating with the onset of proliferation, and persisting until day 14. An increase in desmin and vimentin in mesangial regions was also noted. Immunoelectron microscopy confirmed that the actin-positive cells were mesangial cells, and double immunolabeling demonstrated that the smooth muscle actin-positive cells were actively proliferating. Northern analysis of isolated glomerular RNA confirmed an increase in alpha and beta/gamma actin mRNA at days 3 and 5. Complement depletion or platelet depletion prevented or reduced proliferation, respectively; these maneuvers also prevented smooth muscle actin and actin gene expression. Studies of five other experimental models of nephritis confirmed that smooth muscle actin expression is a marker for mesangial cell injury. Thus, mesangial cell proliferation in glomerulonephritis in the rat is associated with a distinct phenotypic change in which mesangial cell assume smooth muscle cell characteristics.

Actins↗
PubMed1991

Developmental changes in growth hormone, insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in plasma of young growing pigs.

The relationship between plasma concentrations of normally secreted GH and insulin-like growth factor-I (IGF-I) was investigated in pigs after weaning. Frequent blood sampling for between 12 and 24 h showed that plasma GH was pulsatile in pigs of 10, 20 and 35 kg liveweight. Pulses were brief in duration, low in amplitude and variable in frequency. Basal and average daily plasma concentrations of GH changed significantly with development, increasing by about 50% between 10 and 20 kg liveweight. Concentrations of IGF-I in plasma showed little or no evidence of diurnal periodicity and were not increased by GH pulses. Average daily concentrations of both IGF-I and IGF-II in plasma progressively increased between 10 and 35 kg liveweight, as did the total desaturated IGF-binding protein (IGFBP) activity of plasma. A strong positive correlation was observed between the total concentration of IGFs (IGF-I plus IGF-II) in the circulation and plasma IGFBP activity. The developmental rise in IGFBP activity of plasma was associated with increased labelling with 125I-labelled human IGF-II in ligand blots of binding proteins of apparent molecular masses greater than 200, 50, 43 and 29 kDa. One class of binding proteins of 34.5 kDa decreased with development. This study of young growing pigs shows that normally secreted endogenous GH exerts no significant immediate control over plasma IGF-I concentrations, and that plasma levels of IGF-I and IGF-II increase with maturation in this species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

C6 depletion reduces proteinuria in experimental nephropathy induced by a nonglomerular antigen.

The role of the complement membrane attack complex, C5b-9, in mediating glomerular injury has been well defined in models of membranous nephropathy induced by antibody to endogenous glomerular epithelial cell membrane antigens. The effect of selective C6 depletion (to prevent C5b-9 formation) on morphologic characteristics and proteinuria in a model of in situ subepithelial immune complex nephritis induced by an exogenous cationized antigen (human immunoglobulin G (IgG)) followed by rabbit antibody to human IgG was studied. Selective C6 depletion was achieved by repeated administration of a goat antibody to rat C6. Other groups were treated with cobra venom factor to induce generalized complement depletion and with sublethal irradiation to deplete circulating leukocytes. In C6-depleted rats, C6 levels were reduced to less than 3% of baseline throughout the 2 days of the study compared with over 100% in controls. At 4 h after disease induction, glomerular deposition of antigen and antibody were similar in C6D and control groups by immunofluorescence and by direct measurement of glomerular deposition of radiolabeled antigen and antibody (cationized 131I human IgG, 9.1 +/- 0.1 micrograms/38,000 glomeruli in C6D versus 9.8 +/- 0.9 in controls; P = was not significant; rabbit 125I-labeled anti-human IgG, 104 +/- 10 ng in C6D versus 80 +/- 9 ng in controls; P = was not significant). Circulating C3 levels and glomerular C3 deposition were also similar in C6D and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Injuries to the posterior cruciate ligament of the knee.

The posterior cruciate ligament (PCL) is the strongest ligament about the knee and is approximately twice as strong as the anterior cruciate ligament. Its main function is to prevent the posterior dislocation of the tibia in relation to the femur, providing 95% of the strength to resist the tibial posterior displacement. Along with the anterior cruciate ligament (ACL) the PCL controls the passive 'screw home' mechanism of the knee in terminal knee extension. It also provides mechanical support for the collateral ligaments during valgus or varus stress of the knee. PCL ruptures are uncommon apparently due to its strong fibre structure. The most frequent injury mechanism in isolated PCL tears is a direct blow on the anterior tibia with the knee flexed thus driving the tibia posteriorly. Automobile accidents (in which the knee hits the dashboard) and soccer injuries (in which an athlete receives a blow to the anterior surface of the tibia during knee flexion) characteristically produce this type of injury. In other PCL injury mechanisms (hyperextension, hyperflexion or rotational injuries with associated valgum/varum stress), other knee structures are also often damaged. The most characteristic diagnostic finding in a knee with a PCL rupture is the 'posterior sag sign' meaning the apparent disappearance of the tibial tubercle in lateral inspection when the knee is flexed 90 degrees. This is due to gravity-assisted posterior displacement of the tibia in relation to the femur. A positive posterior drawer test performed at 90 degrees of flexion and a knee hyperextension sign are sensitive but nonspecific tests. False negative findings are frequent, especially in acute cases. If necessary, the clinical diagnosis of the PCL tear can be verified by magnetic resonance imaging, examination under anaesthesia, arthroscopy, or a combination of these modalities. If a PCL avulsion fragment has been dislocated, surgical treatment is recommended. In isolated, complete midsubstance tears of the PCL the majority of the recent studies recommend conservative treatment, since abnormal residual posterior laxity1 in most of these knees is consistent with functional stability and minimal symptoms. This has been the case even in athletes. In isolated PCL tears, the outcome seems to depend more on the muscular (quadriceps) status of the knee than on the amount of residual posterior laxity. Therefore, the conservative treatment protocol emphasises intensive quadriceps exercises, and only a short (under 2 weeks) immobilisation period followed by early controlled activities and early weightbearing.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Interrelationships between exogenous porcine somatotropin (PST) administration and dietary protein and energy intake on protein deposition capacity and energy metabolism of pigs.

Exogenous porcine somatotropin (PST) administration stimulates protein deposition and inhibits lipogenesis, resulting in dose-related improvements in growth performance and reduction of carcass fat content. However, the associated impacts of this technology on dietary nutrient requirements and energy partitioning between maintenance, protein, and fat remain unclear. Studies with pigs between 25 and 60 kg body weight indicate that, because of unknown improvements in amino acid utilization and(or) in the energy available for protein synthesis, only marginal increases in dietary protein percentage are required to support 20 to 25% improvements in protein deposition induced by PST administration. In contrast, an increased dietary protein concentration is required to support maximal protein deposition in pigs 60 to 100 kg. Exogenous PST administration increased the maintenance energy requirement and altered the relationship between energy intake and protein deposition, although the magnitude of these changes and the consequent effects on expression of dietary protein (amino acid) requirements was influenced by gender. Albeit limited, information suggests that PST alters nutrient demand at the tissue level. Information of this type will form the basis for rational decisions concerning the method for expression of dietary nutrient requirements (% vs g/d) for PST-treated pigs. Further quantitative information is required on the effects of PST dosage on the relationship of protein deposition to energy intake and on any underlying changes in amino acid utilization and metabolism.

Animals↗
PubMed1991

Platelet-complement interactions in mesangial proliferative nephritis in the rat.

Complement has been reported to mediate mesangiolysis and glomerular hypercellularity in the rat in a model of glomerulonephritis (GN) induced with anti-Thy 1 antibody. To investigate the mechanism for the complement-mediated hypercellularity, the authors first determined if the effect of complement depletion was to inhibit cell proliferation or whether the effect was primarily to inhibit leukocyte infiltration. Rats depleted of complement with cobra venom factor (CVF) had 1) significantly less mesangiolysis than controls at day 5 (0.6 +/- 0.1 versus 3.4 +/- 0.4, scale 0-4+, P less than 0.001); 2) less cell proliferation, as assessed by immunostaining for the proliferating cell nuclear antigen (PCNA)/cyclin, a cell-cycle-dependent antigen (0.5 +/- 0.1 versus 2.4 +/- 0.7 cells/glomerular cross-section, P less than 0.01); and 3) less leukocyte infiltration as assessed by immunohistochemical labeling (0.6 +/- 0.1 versus 1.9 +/- 0.3 cells/glomerular cross-section, P less than 0.01). Because it was reported recently that platelets also mediate glomerular cell proliferation in this model, this study examined whether the mechanism for complement-mediated cell proliferation involved an effect on glomerular platelet localization. The glomerular uptake of 111In-labeled platelets was quantitated in normal and CVF-treated rats at 1, 4, 12, and 24 hours after induction of GN. Rats with anti-Thy 1 GN had substantial glomerular accumulation of platelets at all times studied, peaking at 4 hours (608 +/- 171 platelets per glomerulus). Complement depletion profoundly reduced glomerular platelet localization in anti-Thy 1 GN (mean less than 35 platelets per glomerulus at all times studied, P less than 0.05). Thus these studies demonstrate an important role for complement in mediating platelet localization in anti-Thy 1 GN, an effect that may account for the complement-dependent, neutrophil-independent glomerular hypercellularity in this model.

Animals↗
PubMed1991

ACL reconstruction: in vivo measurement of patellar tendon graft elongation.

The implantation of a free autogenous patellar tendon graft is the surgical technique that currently offers the best results in anterior cruciate ligament reconstruction. However, numerous aspects regarding both technique and postoperative rehabilitation can still be improved. The aim of this study was to measure the elongation of the patellar tendon in vivo in the operating room after reconstructive surgery, subjecting the knee to normal strain such as passive mobilization or anterior displacement of the tibia. Three volunteers were studied. Our results were different from those reported in a previous study conducted in vivo on a normal anterior cruciate ligament (ACL). In spite of the isometric position of the tendon, passive mobilization provoked a progressive increase in the elongation of the graft within each cycle of flexion-extension and between one cycle and the next. This also occurred during the Lachman test. These findings suggest that the graft undergoes a process of tensile adjustment when it is first put under strain. Continued elongation once this process appears stabilized raises doubts as to the reliability of isometric measuring devices.

Adult↗