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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 361 records · Page 20Linked to original sources
PubMed1988

Oral absorption of cephalosporin antibiotics. 1. Synthesis, biological properties, and oral bioavailability of 7-(arylacetamido)-3-chloro cephalosporins in animals.

A number of 7-(arylacetamido)-3-substituted cephalosporins were prepared and tested in animals for oral absorbability. Bioavailability in mice, rats, dogs, and monkeys was determined after oral or parenteral administration. Oral bioavailability of five compounds selected for more intensive study was generally higher than that of penicillin V in all species tested. The results of ED50 testing against experimental infections in mice generally supported the bioavailability studies. Antibiotic activities were evaluated against Gram-positive and Gram-negative organisms with some derivatives expressing in vitro activity similar to cefaclor. The plasma half-life in rats was relatively short and the plasma curves were strongly influenced by probenecid, indicating rapid renal secretion. Some 7-(arylacetamido)-3-chloro cephalosporins are orally absorbed in animals to a greater extent than penicillin V, and antibacterial agent of proven clinical utility.

Administration, Oral↗
PubMed1988

The prediction of body composition in poultry by estimation in vivo of total body water with tritiated water and deuterium oxide.

1. Birds (n 169) which varied in age, live weight, nutritional history, physiological state and genotype were slaughtered and analysed for total body water. Before slaughter, birds were injected with the water isotopes tritiated water (TOH) or deuterium oxide (D2O), or both, to determine TOH space or D2O space, or both, as estimates of total body water in vivo. 2. At the mean total body water of all birds determined by desiccation, of 1096.4 (SD 424.1) g, TOH space and D2O space overestimated total body water by 10.4 and 8.5% respectively. The difference between the isotopes was significant (P less than 0.05). 3. Based on recovery of isotope it was postulated that the main reason for the observed overestimation of total body water in vivo was incomplete recovery of isotope due to the vacuum sublimation technique. The mean recovery (%) of added isotope to whole blood after vacuum sublimation was 93.0 (SD 2.6) and 92.4 (SD 5.5) of the theoretical concentrations of TOH and D2O respectively. 4. Nevertheless, accurate prediction of total body water was obtained from regression equations which included live weight and isotope-dilution space. Values required logarithmic (base 10) transformation before derivation of linear and multiple linear regression equations, and the precision of prediction was determined by the residual standard deviation (RSD). 5. Total body water could be predicted with nearly equal accuracy from live weight or isotope-dilution space (RSD 0.025 and 0.020 respectively). Prediction of carcass protein was more accurate from live weight (RSD 0.033) than from TOH space (RSD 0.036), and inclusion of both variables resulted in only a marginal decrease in RSD to 0.031. 6. The prediction of carcass fat and energy was markedly improved by the inclusion of isotope-dilution space in conjunction with live weight compared with live weight alone. 7. The relations show the developmental nature of body composition of domestic fowl given diets adequate in nutrients. The prediction equations demonstrate the precision possible for studies in which estimates of body composition in poultry are required without slaughter.

Animals↗
PubMed1988

Explaining adolescent drug use: an elaboration strategy for structural equations modeling.

We report a series of analyses designed to estimate increasingly elaborated theoretical models that explain adolescent drug use. Each of the successive elaborations adds a theoretical construct to the explanatory model in order to increase our understanding of drug use by specifying in greater detail the nature of the structural relationships among the latent variables. The more detailed specification is accomplished by 1) specifying new direct effects that increase explained variance in drug use, 2) decomposing direct effects through the interpolation of hypothesized intervening variables, 3) specifying antecedents of variables that modify their direct effects, and 4) exposing suppressor effects. Where indicated, we evaluate alternative explanations of the observed relationships. We do this by controlling for common antecedent effects to reduce spuriousness or by examining different specifications of causal linkages among the explanatory constructs.

Adolescent↗
PubMed1988

Platelets mediate neutrophil-dependent immune complex nephritis in the rat.

Neutrophils and platelets are frequently present in glomeruli in immune glomerulonephritis (GN). No role for the platelet in acute neutrophil-mediated renal injury has been defined. We investigated a neutrophil-mediated model of subendothelial immune complex GN in the rat. Rats were platelet-depleted (mean platelet less than 10,000/microliter) with goat anti-platelet IgG before induction of GN by the renal artery perfusion of concanavalin A followed by anti-concanavalin A IgG. Platelet-depletion resulted in a significant reduction in albuminuria (7 +/- 2 vs. 55 +/- 10 mg/24 h) and fractional albumin excretion (0.045 +/- 0.01 vs. 0.410 +/- 0.09) compared with controls. The decrease in albuminuria was not due to differences in blood or glomerular neutrophil counts, complement, renal function, or glomerular antibody binding. Platelet-depleted rats had equivalent subendothelial deposits and glomerular endothelial cell injury but had minimal platelet infiltrates and fibrin deposition compared with controls. These studies demonstrate a role for platelets in mediating acute neutrophil-induced glomerular injury and proteinuria in this model of GN.

Animals↗
PubMed1988

The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin's disease.

The chest radiographs (CXRs) of 110 patients with mediastinal Hodgkin's disease (HD) were reviewed to determine the incidence, degree, and significance of mediastinal abnormalities following treatment. Residual mediastinal abnormalities were defined as either minimal or measurable, and occurred in 64% of all patients at the completion of treatment, but were more common in those with bulky mediastinal disease at presentation (40 of 48, 83%). Fifty-one patients with a mediastinal abnormality at the end of treatment had follow-up films available. Partial or complete regression of the abnormality occurred by 1 year in 30 of these patients (59%). Over a median follow-up of 80.5 months, there were more relapses (13 of 70, 19%) in patients with residual abnormalities following treatment than in those where the mediastinum was considered normal (four of 40, 10%). Measurable abnormality was associated with a higher relapse rate (six of 25, 24%) than minimal abnormality (seven of 45, 16%), but none of these differences were statistically significant. the subsequent relapse rate for patients with persisting abnormality at 1 year was 14%, compared with 17% for patients in whom regression had occurred and 14% in whom the mediastinum had always been considered normal. Considering the whole group, the presence of a mediastinal abnormality following treatment did not predict for relapse, but for the 34 patients treated by chemotherapy (CTR) alone, a residual abnormality was associated with a significantly higher relapse rate (P = .029). We conclude that following mediastinal radiotherapy (XRT) administered either alone or combined with CTR, residual mediastinal abnormalities do not indicate the need for further treatment. However, following CTR alone, such abnormalities may signify persisting disease and we recommend that XRT be considered for these patients.

Adolescent↗
PubMed1988

Diminution of pulsatile growth hormone secretion in the domestic fowl (Gallus domesticus): evidence of sexual dimorphism.

Temporal plasma GH secretory patterns were measured in cannulated male and female meat-type chickens of two commercial strains at 17, 38 and 60 days of age. Pulse height, amplitude and baseline values were similar in both male and female chickens at 17 days of age, with high amplitude and low baseline values. However, by 38 days of age pulsatile GH secretion was not detectable in females, whereas males exhibited a continued pulsatile secretory pattern similar to that at 17 days of age. Pulsatile GH secretion was not evident in either males or females at 60 days of age. These results clearly demonstrate a sexually dimorphic ontogeny of GH secretion in meat-type chickens.

Aging↗
PubMed1988

Morphologic correlates of glomerular oxidant injury induced by the myeloperoxidase-hydrogen peroxide-halide system of the neutrophil.

Neutrophilic polymorphonuclear leukocytes can mediate glomerulonephritis by releasing reactive oxygen species such as H2O2. We have previously demonstrated that H2O2-mediated glomerular injury can be potentiated by reaction with polymorphonuclear leukocyte myeloperoxidase (MPO). When MPO was perfused into renal arteries of rats, it bound to the glomerular capillary wall due to its cationic charge. Subsequent perfusion with nontoxic concentrations of H2O2 and halides resulted in acute glomerular injury, halogenation of the glomerular basement membrane, and proteinuria. The studies reported here document the morphologic changes that accompany MPO-mediated glomerular injury. Acutely, there is severe injury to the endothelium with cell swelling and lysis. Within 10 minutes, a marked platelet influx occurs. Platelets frequently occlude capillary lumens and bind to areas of denuded glomerular basement membrane where platelet degranulation results. By 4 days, the platelet infiltration has ceased, and a reparative phase develops characterized by marked proliferation of resident endothelial cells and possibly mesangial cells. By 21 days postperfusion, the glomerular lesion had largely resolved. In contrast, control rats perfused with MPO alone, H2O2 alone, or buffered saline alone demonstrate minimal glomerular injury at all times studied. MPO-mediated glomerular disease results in endothelial and mesangial cell injury, activation of platelets, and a subsequent proliferative response. These morphologic changes resemble those seen in several forms of inflammatory and proliferative glomerulonephritis in man.

Animals↗
PubMed1987

Synthesis of a new photoreactive C5a analog that permits identification of the ligand binding component of the granulocyte C5a receptor.

Human C5a is a complement derived inflammatory mediator that binds to specific receptors that are found in the granulocyte plasma membrane. A new photoreactive C5a analog, that can be radiolabeled in the aryl azide moiety, has been synthesized by coupling p-azidosalicyl-2-mercapto-N-ethylamide-2'-thiopyridine disulfide to a partially reduced form of C5a. This unique analog (ASAMEA-SC5a) specifically bound to the granulocyte C5a receptor with an apparent Kd of 1.8 nM, a value that is comparable to that of the native ligand. Photoactivation resulted in crosslinking of this probe to the granulocyte C5a receptor. Subsequent reductions of the complex produced a radiolabeled C5a receptor, or a subunit of this receptor that had an apparent molecular weight of 47,000 Daltons on SDS-PAGE.

Affinity Labels↗
PubMed1987

Identification of an antigenic epitope and receptor binding domain of human C5a.

Nine different murine anti-human C5a monoclonal antibodies have been produced and characterized. They exhibit Kas for the 125I-labeled ligand that range from 0.4 to 48 X 10(8) M-1, and they display limited cross-reactivity with C5a from other species. Each of these antibodies has been found to compete with the granulocyte C5a receptor for binding site(s) on the C5a polypeptide. Exploration of the antigenic topography of C5a revealed that the immunodominant portion of this glycopolypeptide resides between residues Lys20 and Arg37, with the area surrounding Cys27 being particularly important. In addition, a specific C5a derived tryptic peptide containing these amino acid residues competes with 125I-C5a for binding to the receptor. These observations are consistent with previously published data and suggest that this area of the C5a molecule is an important part of the receptor "recognition domain", and thus plays a critical role in the C5a receptor interaction.

Antibodies, Monoclonal↗
PubMed1987

Prognostic significance of nodal involvement in locally advanced (stage C) carcinoma of prostate--RTOG experience.

A total of 500 patients with extracapsular extension (clinical Stage C) carcinoma of the prostate received definitive radiotherapy directed to the prostate and the regional lymphatics. Pretreatment evaluation of the regional lymphatics was optional and was done in 245 patients who underwent either staging laparotomy or lymphangiography. The remaining 255 patients had no nodal evaluation. In 72 of the node-evaluated patients there was evidence of spread to the pelvic lymphatics and in 173 patients lymph nodes were negative. The three populations (lymph nodes-not evaluated, lymph nodes-involved, and lymph nodes-not involved) were analyzed as to the distribution of the recognized prognostic variables and compared as to the study end points (locoregional failure, incidence of distant metastases, disease-free survival, and survival).

Carcinoma↗
PubMed1987

Prognostic factors in carcinoma of the prostate--analysis of RTOG study 75-06.

A total of 566 evaluable patients were accessioned to a phase III RTOG study of extended field irradiation in carcinoma of the prostate from 1976 to 1983. Eligible patients were those with locally advanced disease, either clinical Stage C or clinical Stage A2 or B with pelvic lymph node involvement. The treatment consisted of irradiation of the regional lymphatics followed by a boost to the prostate. The data have been analyzed extensively to identify variables of potential prognostic significance. The assessed factors include tumor size, clinical stage, the degree of histological differentiation, nodal status, serum acid phosphatase status, hormonal management status, age, and race. These factors have been assessed as to their interdependence and correlation with the clinical course (study endpoints) using univariate analyses and Cox's Regression model. Significant interdependence of tumor size and Gleason score and tumor size and acid phosphatase was identified. The population receiving hormonal management either prior to or during radiotherapy had a significantly higher proportion of high grade tumors. Correlation of the assessed variables and the study endpoints (local control, incidence of distant metastases, NED survival, survival) singled out the degree of histological differentiation as the most powerful prognostic factor for all the endpoints. Age proved a useful predictor of local control (younger patients failed at a significantly higher rate), as did tumor size. Elevation of serum acid phosphatase correlated well with the incidence of metastatic disease but was not a useful predictor of survival. Tumor size and hormonal management status correlated well with the incidence of metastatic disease but only when analyzed separately from other factors. Their prognostic value was absent when Cox regression analysis was applied. Nodal status did not correlate well with any of the study endpoints, indicating then that in patients with clinical Stage C disease, treated with definitive radiotherapy to the prostate and regional lymphatics, this parameter may have limited prognostic usefulness. Although patients who received concomitant hormonal management had a significantly higher proportion of high grade lesions, their clinical course fared favorably in comparison with the population not receiving concomitant hormonal management. This may indicate a beneficial effect of adjuvant hormonal treatment which needs to be tested in a prospective study.

Acid Phosphatase↗
PubMed1987

Correlation of radiotherapeutic parameters and treatment related morbidity in carcinoma of the prostate--analysis of RTOG study 75-06.

Treatment related morbidity, recorded in patients entered onto a RTOG phase III study (testing the value of periaortic irradiation in locally advanced carcinoma of the prostate), has been correlated with radiotherapeutic parameters to identify and quantify the relationship with treatment volumes, doses, and techniques. Between 1976 and 1983 a total of 526 analyzable cases were entered onto the study. The study design entailed randomization to either pelvic irradiation followed by a prostate boost or pelvic and periaortic irradiation followed by a prostate boost. Periaortic irradiation was not associated with a significantly increased incidence of bowel injuries manifested by diarrhea. No correlation between the total dose to the regional lymphatics (ranging from 4400 to 5100 cGy) and the incidence of bowel and bladder injuries could be established. Doses to the prostate in excess of 7000 cGy have not resulted in a significantly increased incidence of bladder injuries, but have been associated with a significant increase in the incidence of bowel injuries manifested by diarrhea. The techniques of pelvic irradiation did not seem to significantly influence the incidence of bowel or bladder complications. The technique of delivery of the prostatic boost did seem to influence the incidence of bowel injuries. This refers to the lateral boost technique and the perineal boost technique which have been associated with a higher incidence of diarrhea. All of the conclusions based on this analysis are applicable only to treatment volumes and dose ranges used in this study and to conventional fractionation of 180 to 200 cGy per day.

Cystitis↗
PubMed1987

Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis.

Neutrophils (PMNs) mediate injury in experimental glomerulonephritis (GN) in part via the release of reactive oxygen species, particularly hydrogen peroxide (H2O2). Recent kidney perfusion studies demonstrate that H2O2 can cause glomerular injury by reaction with halides in the presence of the PMN cationic enzyme myeloperoxidase (MPO) to form oxidants which can oxidize and halogenate tissue. We sought evidence for participation of the MPO system in a model of PMN-mediated immune complex (IC) GN. A PMN-dependent model of GN was developed in rats by perfusing the renal artery with concanavalin A followed by anticoncanavalin A antibody. PMN depletion abolished glomerular PMN infiltration and significantly reduced proteinuria (35 +/- 7 mg/day vs. 113 +/- 10, P less than 0.001). Rats that received Na125I (5.0 microCi) three and six hours following disease induction had more 125I incorporation in glomeruli and GBM at 48 hours than similarly treated rats that were PMN depleted (1200 cpm vs. 88 cpm, P less than 0.01). Glomerular iodination could not be demonstrated in a PMN-independent model of nephrotoxic nephritis induced with noncomplement fixing anti-GBM antibody. These data indicate that this model of PMN-mediated IC GN is associated with activation of the MPO-H2O2-halide system, which may participate in mediating glomerular injury.

Animals↗
PubMed1987

Temporal secretory patterns of growth hormone in young meat-type poultry.

Temporal secretory patterns of plasma growth hormone were measured in young, male meat-type poultry at three stages (22, 30 and 44 d of age) during normal growth. Birds were cannulated in the jugular vein and, after a 2-d period of recovery were serially bled every 10 min for 3.5, 5.5 and 10 h for birds 22, 30 and 44 d of age respectively. GH secretion was found to be pulsatile and episodic, with a mean (+/- SE) peak frequency (number/h) of 0.85 (+/- 0.03) over all ages (n = 15). Birds at 22 d of age had significantly greater peak magnitudes, baseline concentrations and overall mean concentrations than those at 30 and 44 d of age.

Aging↗
PubMed1987

Red cell Th activation: biochemical studies.

The peanut agglutinin from Arachis hypogea is a lectin that reacts with red blood cells expressing the Th antigen. The Th antigen has been said to be qualitatively similar to the T antigen, a well-defined antigen due to desialylation of glycophorin A and B that also reacts with the peanut agglutinin. We examined Th activated red blood cells from two patients with Fanconi's anaemia using 125I radiolabelled peanut agglutinin as a probe in Western blotting of red blood cell membrane proteins. We also probed the surface of intact Th activated red blood cells for structures related to the T antigen using [3H]sialic acid and a purified sialyltransferase. Neither of these techniques found antigens on the Th activated red blood cells that were similar to the antigen found on T activated red blood cells. These results show that the Th antigen in Fanconi's anaemia is qualitatively different to the antigen found in T activation.

Anemia, Aplastic↗
PubMed1987

Horner syndrome occurring as a complication of chest tube placement.

A case of Horner syndrome occurring secondary to the high insertion of a chest tube is reported. Horner syndrome from this cause can easily be avoided. The tip of the chest tube should be kept at or below the third posterior rib unless the clinical situation dictates otherwise.

Adult↗