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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1993

Fertility following excision of a symptomatic craniopharyngioma during pregnancy: case report.

A 27-year-old woman in the second trimester of pregnancy presented with bitemporal hemianopsia. Total resection of a craniopharyngioma restored normal vision, and she delivered a normal infant at term. Permanent hormonal replacement therapy was not needed. Subsequent spontaneous pregnancy and delivery indicate that fertility was preserved. Literature review shows this case to be unique. Even with new developments in stereotactic radiotherapy, total excision remains a potentially achievable surgical goal.

Adult↗
PubMed1993

Differences in the subcellular localization of calreticulin and organellar Ca(2+)-ATPase in neurons.

It has become clear that calcium is an important mediator in the transduction of signals due to ligand binding to cell surface receptors. Cytosolic calcium is typically maintained at low levels in both muscle and non-muscle cells and intracellular sequestering of calcium appears to be important in this process. The identification of intracellular calcium pools has been the subject of much recent study, and it has been proposed that such pools would contain three components: a calcium-activated pump or Ca(2+)-ATPase, a calcium channel such as the inositol trisphosphate receptor or ryanodine receptor, and a high-capacity calcium-binding protein such as calsequestrin or calreticulin. We report here on the localization of two components, the organellar Ca(2+)-ATPase (SERCA) and calreticulin, in neuronal tissues. Using immunofluorescence and subcellular fractionation, we have found that for the most part, these two proteins do not co-localize in neuron cell bodies, dendrites, or axons; but may co-localize at the axon terminal.

Animals↗
PubMed1993

Magnetic resonance imaging with Gadolinium-DTPA for assessment of bladder carcinoma and its response to treatment.

Magnetic Resonance Imaging (MRI) with intravenous Gadolinium-DTPA (Gd-DTPA, Magnevist, Schering-AG) was performed in 44 patients, 32 with primary bladder carcinoma and 12 with suspected recurrence after treatment. Gd-DTPA often increased diagnostic confidence in the identification and staging of tumours confined to the bladder wall and was necessary to assess depth of bladder wall invasion when T2-weighted images were suboptimal. Enhancement after Gd-DTPA enabled distinction between necrotic and viable tumour and blood clot. There was little advantage in its use for tumours infiltrating perivesical fat or with metastases to lymph nodes or bone, in the absence of a fat suppression sequence. Gd-DTPA may therefore be useful in selected patients with tumours of Stage T3a or less in whom information about depth of bladder wall invasion is inadequately shown on pre-contrast sequences. Artefacts due to variable and inhomogeneous urine signal intensity, however, often degraded post-Gd-DTPA images of the bladder. Changes in the bladder due to radiotherapy were observed on MRI 3-4 months after treatment in patients referred for routine follow-up and in some patients with suspected recurrence. Mucosal hyperintensity, thickening and abnormal signal intensity of the muscular layers of the bladder wall, with enhancement after Gd-DTPA were demonstrated. Such changes obscured small volume or superficial recurrence of tumour after radiotherapy. Abnormal enhancement was also observed in pelvic organs and soft tissues irradiated several years earlier. Enhancement after Gd-DTPA does not therefore reliably distinguish between recurrent tumour and radiotherapy change.

Aged↗
PubMed1993

PDGF-receptor localizes to mesangial, parietal epithelial, and interstitial cells in human and primate kidneys.

There is evidence that platelet derived growth factor (PDGF) is a mediator of proliferative changes in renal arteries and mesangium in human disease, in the mesangium in experimental mesangial proliferative glomerulonephritis, and in the interstitium in a rodent model of angiotensin II mediated hypertension. We utilized a monoclonal antibody to the beta-subunit of the PDGF-receptor to localize constitutive expression of this receptor in human and nonhuman primate tissues. Tissues were fixed in cold 2 or 4% paraformaldehyde, and immunohistochemical techniques both at the light microscopic level and immunoelectron microscopy were employed. In the glomerulus, there is widespread expression of this molecule by mesangial cells, and there is frequent expression on the apical and lateral surface of parietal epithelial cells. There is also widespread expression of this molecule by cortical and medullary peritubular interstitial cells, but not by glomerular or peritubular capillary endothelium or other renal parenchymal structures. The identification of receptors capable of binding PDGF B-chain at each of these sites: (1) provides a basis for PDGF mediated mesangial proliferation in human disease; (2) provides a basis for PDGF mediated interstitial cell migration and/or proliferation and/or activation at sites of tubulointerstitial injury; and (3) suggests that glomerular parietal epithelial cells may be responsive to stimulation by PDGF.

Animals↗
PubMed1993

Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis.

Proliferation and extracellular matrix (ECM) overproduction by glomerular mesangial cells characterizes many types of glomerulonephritis and often precedes the development of glomerulosclerosis. Heparin is a potent inhibitor of mesangial cell growth in vitro. We examined whether standard heparin can inhibit mesangial cell proliferation in vivo in the mesangioproliferative anti-Thy 1.1 nephritis. Untreated control rats were compared to rats infused with heparin either early (day -2 to 1) or late (day 2 to 5) after induction of anti-Thy 1.1 nephritis. The results show that heparin treatment significantly reduced mesangial cell proliferation regardless of when it was initiated. Heparin (either early or late treatment) also reduced mesangial basic fibroblast growth factor (bFGF) expression and platelet-derived growth factor (PDGF) receptor up-regulation as reflected by immunostaining, whereas PDGF B-chain expression was reduced only by late heparin treatment. Furthermore, heparin treatment markedly inhibited the mesangial matrix expansion for a variety of ECM proteins, including laminin, type I and IV collagen, fibronectin and entactin. Heparin did not affect the initial mesangiolysis, glomerular macrophage influx, deposition of anti-Thy 1.1 IgG or fibrinogen, or the glomerular platelet influx. These results suggest that heparin, via its antiproliferative rather than anticoagulant effect, can inhibit mesangial cell proliferation, overexpression of polypeptide growth factors, and ECM protein overproduction in vivo. The beneficial effect of heparin can be demonstrated even if treatment is initiated after the development of nephritis. By virtue of these properties, heparin may be an effective agent in the treatment of human mesangioproliferative disease and in the prevention of glomerulosclerosis.

Animals↗
PubMed1993

Cytokines in renal inflammation.

Cytokines play pivotal roles in most physiologic and pathologic processes. This paper reviews recent data on the role of cytokines in mediating renal inflammatory diseases. These data show that cytokines are involved in every phase of inflammatory injury. Cytokines induce expression of major histocompatibility complex class II and adhesion molecules on renal cells and are thereby involved in antigen presentation and leukocyte localization. Cytokines also induce the synthesis of leukocyte chemoattractants, eg, interleukin-8 and monocyte chemotactic peptide-1, in renal cells. Finally, cytokines, and in particular, platelet-derived growth factor and transforming growth factor-beta, appear to play a role in the long-term consequences of renal inflammation such as the induction of cell proliferation and the accumulation of extracellular matrix, both of which characterize glomerular and tubulointerstitial fibrosis. Better understanding of the disturbances of the cytokine network in renal inflammation may ultimately lead to novel therapeutic approaches to renal disease.

Animals↗
PubMed1993

Amyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized.

We have investigated the synthesis, axonal transport, and processing of the beta-amyloid precursor protein (APP) in in vivo rabbit retinal ganglion cells. These CNS neurons connect the retina to the brain via axons that comprise the optic nerve. APP is synthesized in retinal ganglion cells and is rapidly transported into the optic nerve in small transport vesicles. It is then transferred to the axonal plasma membrane, as well as to the nerve terminals and metabolized with a t1/2 of less than 5 h. A significant accumulation of C-terminal amyloidogenic or nonamyloidogenic fragments is seen in the optic nerve 5 h after [35S]-methionine, [35S]cysteine injection, which disappears by 24 h. The major molecular mass species of APP in the optic nerve is approximately 110 kDa, and is an APP isoform that does not contain a Kunitz protease inhibitor domain. Higher molecular mass species containing this sequence are seen mostly in the retina. A protease(s) that can potentially cleave APP to generate an amyloidogenic fragment is present in the same optic nerve membrane compartment as APP.

Amino Acid Sequence↗
PubMed1993

Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats.

Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.

Animals↗
PubMed1993

Role of platelet-derived growth factor in glomerular disease.

An approach for establishing a role for a growth factor in glomerular disease is presented. Using platelet-derived growth factor (PDGF) as an example, there is strong evidence to support the hypothesis that PDGF is a mediator of mesangial cell proliferation in glomerulonephritis. This includes evidence that (1) PDGF is a mitogen for mesangial cells in culture; (2) PDGF is expressed in both experimental and human glomerulonephritis in which mesangial cell proliferation occurs; (3) infusion of PDGF into rats induces mesangial cell proliferation and a hypercellular lesion; and (4) inhibition of PDGF in a model of experimental nephritis significantly reduces the mesangial cell proliferation. However, these data do not answer the question of whether or not the inhibition of PDGF in human diseases would be beneficial in the long term, because some cell proliferation is likely required for normal healing and repair. Further studies will be necessary to resolve this issue.

Animals↗
PubMed1993

Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis.

In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation.

Animals↗
PubMed1993

Glomerulosclerosis in the rat induced by repeated immune-mediated mesangial cell injury.

Glomerulosclerosis is a common feature of progressive glomerular injury. We investigated whether experimental glomerulosclerosis could be induced by repeated immunologic injury to mesangial cells. Chronic mesangial proliferative glomerulonephritis (GN) was induced by repeated injections of polyclonal antibody directed against the Thy 1 antigen present on the mesangial cell membrane. An intravenous injection of anti-Thy 1 serum (ATS) was given weekly to 18 male Wistar rats, which were sacrificed at weeks 2, 4 and 6 after induction of GN. Blood urea nitrogen and serum creatinine were significantly elevated in rats with anti-Thy 1 nephritis at weeks 4 and 6 compared to normal rats. Progressive expansion of the mesangial matrix with diffuse sclerosis was observed at weeks 4 and 6 by silver methenamine staining. Ultrastructurally there was a prominent rough endoplasmic reticulum in the mesangial cells and collagenous fibrils in an expanded mesangial matrix. Immunohistochemical staining revealed a marked increase in type IV collagen and laminin in the mesangium at weeks 4 and 6. Thus, repeated immunologic injury restricted to the mesangium may result in the accumulation of extracellular matrix and the development of glomerulosclerosis. These studies emphasize the importance of the mesangial cell in progressive glomerular injury.

Animals↗
PubMed1993

Nerve growth factor receptor expression in fetal, mature, and diseased human kidneys.

BACKGROUND: Nerve growth factor (NGF) has been proposed to be critical to normal renal development in rodents. However, little is known about expression of NGF or its receptors in human kidneys, or their potential function in development or disease. EXPERIMENTAL DESIGN: A previously characterized monoclonal antibody (NGFR 5) was utilized for immunohistochemical localization of the p75 NGF receptor (NGFR) in alcohol-fixed tissue sections of human fetal kidney (N = 27, 54 to 105 days gestation), normal mature kidney obtained from nephrectomies for neoplasia (N = 7), and renal biopsies (N = 54) with various glomerulopathies previously characterized for degree of mesangial alpha smooth muscle actin (alpha SM) expression. A second monoclonal antibody (NGFR2) was also utilized on fetal and normal kidney. Immunohistochemical localization of alpha SM and proliferating cell nuclear antigen expression was also performed. RESULTS: Glomerular expression of NGFR in the fetus is limited to the mesangium in later stages of glomerulogenesis; at these stages this expression is similar to that which has been previously reported for platelet-derived growth factor receptor-beta and alpha SM. There is focal, weak persistence of NGFR in normal adult glomeruli, similar to alpha SM. In renal biopsies, glomerular NGFR expression was upregulated in a variety of disease states, which frequently but not invariably correlated with alpha SM expression. Fetal and adult expression of NGFR is also prominent in periarterial connective tissue cells and nerve. Apparent de novo expression by many interstitial cells in normal and diseased adult kidneys is also present. CONCLUSIONS: These studies indicate: (a) NGF or other neurotrophins that bind NGFR may be important in human kidney development and glomerular response to injury; (b) NGFR is a marker of developing mesangial cells similar to alpha SM and platelet-derived growth factor receptor-beta; (c) enhanced expression of NGFR, like alpha SM, is a marker of mesangial cell injury or activation, and that their coordinate upregulation in some glomerular disease states appears to recapitulate a normal developmental state; (d) a population of NGFR and platelet-derived growth factor-beta expressing interstitial cells can be identified in normal kidneys, which suggests potential signaling mechanisms to recruit or activate these cells at sites of tubulointerstitial injury.

Antibodies, Monoclonal↗
PubMed1993

The structure of health status among older adults: disease, disability, functional limitation, and perceived health.

This article builds on earlier conceptualizations of the structure of health status to propose a more complex, multiequation model that examines the interrelationships among its various dimensions. As such, the focus is not merely on the identification of the direct effects of a variety of factors on perceived health status, but on how the constructs of disease, functional limitation, and self-rated health interrelate. In so doing, we expose the inherent problems of several complex and contaminated items routinely included in applications of established functional health status measures. The source of these problems lies in the lack of specificity or conceptual clarity for the individual items in these established measures. Potential biases are discussed, and several methods and strategies for addressing these problems are explored. Alternative scales are constructed and their psychometric properties are presented. Researchers who rely on public use data bases containing these scales should be aware of the potential biases and either modify the scales or use other appropriate methodologies to control for the measurement contamination.

Activities of Daily Living↗