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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 271 records · Page 15Linked to original sources

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↗

Perceived health status and mortality among older men and women.

This article separately examines the relationship of perceived health status and mortality for the 1,599 men and 2,904 women self-respondents in the Longitudinal Study on Aging. Using hierarchical logistic regression, the zero-order relationships are decomposed by the serial introduction of demographic, socioeconomic, health status, and psychosocial factors. For men, only those in poor health are significantly more likely to die than those in excellent health (adjusted odds ratio = 1.754), all other things being equal. For women, those in fair or poor health are more likely to die than those in excellent health (adjusted odds ratios = 1.870 and 2.181, respectively), all other things being equal.

Aged↗

Falling, health status, and the use of health services by older adults. A prospective study.

In this study, data from the Longitudinal Study on Aging were used to prospectively assess the relationship between repetitive falling or falling only once in the year before baseline and changes in health status and the use of health services. Multiple and logistic regression were used to control for a variety of known covariates, in addition to the baseline values of the target outcomes. Repetitive falling was associated with decreased health status, measured by various activities of daily living and disability indices, at both 2- and 4-year follow-ups. One fall, however, was never associated with deteriorating health status. Similarly, repetitive falling was related to a decreased likelihood of visiting a physician (at the first follow-up, only), but to an increased likelihood of hospitalization, nursing home placement, and death (at both follow-ups). Falling just one time, however, was only associated with an increased likelihood of nursing home placement. Based on outcome trajectories, two subpopulations of repetitive fallers were identified. One subpopulation was consistent with the rapid deterioration hypothesized by the "spiral" response to falling, and includes about 35% of the repetitive fallers (i.e., those who die within 4 years of baseline). The other subpopulation was consistent with the initial decline and subsequent stabilization hypothesized by the "drop-stabilization" response.

Accidental Falls↗

Renal injury from angiotensin II-mediated hypertension.

Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.

Angiotensin II↗

Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.

Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.

Animals↗

The activated mesangial cell: a glomerular "myofibroblast"?

The glomerular mesangial cell may have several important beneficial functions in the normal glomerulus. These include the production of growth factors to allow normal cell turnover, the provision of structural support for the capillaries via the production of mesangial matrix, and the modulation of glomerular hemodynamics via their contractile properties. However, in various types of glomerular injury, the mesangial cell may acquire characteristics of a "myofibroblast", which may in fact be injurious to the glomerulus. These "activated" mesangial cells can be shown to be proliferating by one or more mechanisms that are mediated by platelets and that also involve the local production of platelet-derived growth factor. Like myofibroblasts in other tissues, the mesangial cell acquires smooth muscle cell-like properties, characterized by the de novo expression of alpha-smooth muscle actin, and by the development of fibroblast-like properties, characterized by the production of interstitial collagens in addition to normal mesangial matrix constituents. Identifying therapeutic strategies that prevent this phenotypic modulation of the mesangial cell may provide new ways to treat golmerular diseases.

Animals↗

Growth hormone increases whole-body protein turnover in growing pigs.

Ten pigs with an average initial live weight of 65 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone (pGH; .1 mg.kg-1.d-1) for a 13-d period on N retention and whole-body protein turnover. Feed intake was restricted to both the control (treated with excipient) and pGH-treated groups to ensure that animals in each group consumed equal amounts. Whole-body protein turnover was estimated from the excretion of 15N in urinary urea and ammonia after a single oral dose of [15N]glycine. Nitrogen balance and whole-body N flux were increased by 35 to 40% with pGH treatment (P less than .001). Protein synthesis and breakdown were increased by 56 and 59% (P less than .001), respectively, in pGH-treated pigs relative to controls. These higher rates of protein turnover seemed to lower slightly the efficiency of the metabolic process for protein deposition. However, the absolute increment in protein synthesis rate was greater than that for breakdown, leading to the increased net N retention. Thus, pGH treatment improved the utilization of dietary amino acids for protein deposition.

Animals↗

Markers of complement-dependent and complement-independent glomerular visceral epithelial cell injury in vivo. Expression of antiadhesive proteins and cytoskeletal changes.

BACKGROUND: Visceral glomerular epithelial cells (GEC) are an important component of the glomerular filtration barrier to proteins. While ultrastructural GEC changes have frequently been observed in proteinuric states, no suitable light microscopic markers of GEC injury have yet been identified. EXPERIMENTAL DESIGN: We have analyzed in vivo the GEC expression of proteins known to be involved in cell shape changes. SPARC (osteonectin, BM-40) and tenascin (cytotactin, J1, hexabrachion) belong to a group of anti-adhesive glycoproteins, that modulate cell-matrix interactions. We also studied cytoskeletal intermediate filament proteins, including desmin and vimentin. The GEC expression of SPARC, tenascin, desmin, and vimentin was analyzed in various types of GEC injury in the rat, including complement-mediated injury (passive Heymann nephritis, autologous immune complex nephritis, conA anti-conA nephritis), complement-independent injury (nephrotoxic nephritis), toxic injury (aminonucleoside nephrosis) and hypertensive injury (5/6 nephrectomy, angiotensin-II infusion). A complement-mediated model of mesangial cell injury (anti-Thy 1.1 mesangial proliferative nephritis) served as a control. RESULTS: SPARC mRNA and protein were constitutively expressed in normal rat glomeruli. Immunostaining and immunoelectron microscopy primarily localized SPARC to the cytoplasm of GEC. Markedly increased glomerular SPARC synthesis and GEC immunostaining was observed in all instances of complement-mediated GEC injury but in none of the other conditions. In contrast, glomerular immunostaining for tenascin, that also stained in a GEC pattern, either remained unchanged or increased to a minor degree (complement-mediated models). GEC immunostaining for desmin in normal rats was low and variable, and increased significantly in any form of GEC injury but not in anti-Thy 1.1 nephritis. No concomitant increase of GEC immunostaining for vimentin was detectable, which could have been due to the constitutively high expression of vimentin in GEC. CONCLUSIONS: SPARC and desmin, but not tenascin or vimentin, are suitable light microscopic markers of GEC injury. The combined staining for these proteins may be useful in differentiating the mechanisms of GEC injury.

Animals↗

Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis.

Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury.

Amino Acid Sequence↗

The effect of functional knee-braces on strain on the anterior cruciate ligament in vivo.

Functional knee-braces are widely used to protect injured or reconstructed anterior cruciate ligaments, despite the fact that few scientific data support their efficacy. We studied seven functional braces, representative of both the typical custom-fit and off-the-shelf designs. The braces were tested on subjects who had a normal anterior cruciate ligament and were scheduled for arthroscopic meniscectomy or exploration of the knee under local anesthesia. After the operative procedure, a Hall-effect strain-transducer was applied to the anterior cruciate ligament. Under low anterior shear loads, two braces provided some protective strain-shielding effect compared with no brace, but this strain-shielding effect did not occur at the higher anterior shear loads expected during the high-stress activities common to athletic events. The DonJoy, Townsend, C.Ti., and Lenox Hill braces demonstrated a strain-shielding effect on the anterior cruciate ligament with an internal torque of five newton-meters applied to the tibia. None of the braces had any effect on strain on the anterior cruciate ligament during active range of motion of the knee from 10 to 120 degrees or during isometric contraction of the quadriceps. Wearing of a brace did not produce an increase in the value for strain on the anterior cruciate ligament. For the activities that were evaluated in this study, none of the braces produced adverse effects on the anterior cruciate ligament, and there were no significant differences in the strain on the anterior cruciate ligament between the use of a custom-fit or an off-the-shelf brace design. There were no apparent advantages of the more expensive custom-made braces compared with the off-the-shelf designs.

Adult↗

Clinical versus instrumented knee testing on autopsy specimens.

The accuracy, reliability, and reproducibility of the Genucom Knee Analysis System and Knee Signature System (KSS) for anteroposterior knee laxity evaluations were compared. The devices detected the same relative change in laxity between normal and anterior cruciate ligament-deficient specimens during Lachman and drawer testing; however, the absolute values differed. In a clinical study, two examiners performed three independent Lachman and drawer tests using the Genucom, KSS, and a subjective clinical examination on ten patients. The Genucom demonstrated interexaminer differences during the Lachman test. The clinical examination proved to be more reliable than either instrumented device for both Lachman and drawer testing. The intraexaminer variability of the Genucom and KSS was large, with the average 95% confidence limits about the mean for the Genucom and KSS equal to +/- 4.2 and +/- 2.8 mm, respectively. These findings question the accuracy, reliability, and reproducibility of the instrumented methods.

Adolescent↗

Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model.

Expansion of the mesangial extracellular matrix (ECM) with subsequent glomerular sclerosis is a prominent finding in most progressive renal diseases. To investigate the chronology of accumulation of ECM components as it relates to previously described cellular events, biopsies were obtained from rats at various times following 5/6-nephrectomy as well as from sham-operated controls. The biopsies were stained with PAS as well as immunostained for PCNA (a cell proliferation marker), monocytes/macrophages, types I and IV collagen, laminin, s-laminin, fibronectin, heparan sulfate proteoglycan and entactin/nidogen. Immunostaining of biopsies obtained from 5/6 nephrectomized rats demonstrated an early glomerular cell proliferation, peaking at week 2. Expansion of the glomerular tuft area with rare glomeruli demonstrating focal sclerosis were also seen at week 2. Glomerular macrophage influx correlated with later ECM expansion and glomerulosclerosis. A progressive accumulation of all ECM proteins investigated was noted in the pathological mesangial matrix at week 2 and later time points. Northern analysis of total glomerular RNA at weeks 2 and 6 after 5/6 nephrectomy showed de novo expression type I collagen mRNA as well as small increases of glomerular mRNA levels for type IV collagen (1.2- and 1.4-fold over control RNA) and laminin (1.3- and 1.5-fold) but not s-laminin (1.1- and 0.9-fold). We conclude that cellular events including glomerular cell proliferation and macrophage influx are associated with increased gene and protein expression by ECM proteins in the remnant kidney model and may contribute to the development of sclerosis.

Animals↗