Biomedical subjects

W J Johnson

Publications and source records attributed to W J Johnson.

At least 55 records · Page 3Linked to original sources

PubMed1990

Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy.

The aims of this study were to examine in a prospective, randomized trial the efficacy of plasmapheresis in preventing irreversible renal failure in patients with multiple myeloma and to study the renal biopsy tissues from such patients. Twenty-one patients with active myeloma and progressive renal failure were randomized to one of two groups: group 1, forced diuresis and chemotherapy (10 patients), and group 2, forced diuresis, chemotherapy, and plasmapheresis (11 patients). Plasmapheresis and chemotherapy lowered the serum myeloma protein value much more rapidly than chemotherapy alone. Of 5 patients who were oliguric and undergoing dialysis at presentation, only 3 who were treated by plasmapheresis recovered. Of 16 polyuric patients, 5 in group 1 and 7 in group 2 showed improvement in renal function. The main factor that determined irreversibility of renal failure was the severity of myeloma cast formation.

Aged↗

PubMed1990

Fitting the anophthalmic socket: achieving cosmesis with comfort.

In attempting to achieve acceptable cosmesis while maintaining comfort for the anophthalmic patient, communication between the ocularist and oculoplastic surgeon is of paramount importance. The ocularist must realize his limitations in correcting deformities prosthetically and must communicate these limitations to the ophthalmologist when surgical alternatives are being considered.

Blepharoptosis↗

PubMed1989

Inhibition of IFN-gamma-induced Ia antigen expression on synovial fibroblasts by IL-1.

Naturally occurring substances capable of the negative regulation of class II molecules on synovial fibroblasts may play an important role in controlling the sustained immune processes ongoing in the rheumatoid joint. We report here that rIL-1 is capable of such a negative regulatory process. The simultaneous addition of rIL-1 and rIFN-gamma to rat synovial fibroblasts resulted in decreased Ia Ag and mRNA expression when compared with synovial fibroblasts treated with IFN-gamma alone. Both rIL-1 alpha and rIL-beta inhibited to a similar degree with the level of inhibition being dependent on both the concentration of IL-1 and IFN-gamma. Other cytokines, including IFN-alpha/beta, IL-2, and TNF, had no antagonistic effect on IFN-gamma-induced Ia expression. Time course experiments showed that IL-1 inhibited when present immediately before addition of IFN-gamma or when added during the first 24 h of IFN-gamma stimulation but not at later time points. Indomethacin failed to reverse the IL-1-mediated inhibition, despite the fact that exogenously added PGE2 also inhibited IFN-gamma-induced Ia expression. IL-1 treatment of synovial cells did not alter the ability of IFN-gamma to bind to the cells. These findings provide evidence for a negative regulatory role for IL-1 on synovial fibroblasts independent of PGE2 production and thus suggest that IL-1 is capable of both pro- and antiinflammatory actions within the rheumatoid joint.

Animals↗

PubMed1989

Interleukin-1 induces interleukin-1 alpha and interleukin-1 beta gene expression in synovial fibroblasts and peripheral blood monocytes.

Cellular interactions involved in the chronic inflammatory response, characteristic of those found in the joints of rheumatoid arthritis patients, were investigated by examining the effect of interleukin-1 (IL-1), tumor necrosis factor alpha, and gamma-interferon on the regulation of IL-1 gene expression and production by synovial fibroblasts. Biologically active IL-1 was detected in lysates of IL-1-treated rat and human fibroblasts that had been isolated from synovial tissue by collagenase digestion. Northern blot analysis of RNA isolated from these cells revealed the expression of IL-1 alpha and IL-1 beta transcripts. Neither the IL-1 transcripts nor the biologic activity of IL-1 was found in untreated synovial fibroblasts. The messenger RNA induction in synovial cells was followed by a time- and dose-dependent expression of intracellular IL-1 activity. Human monocytes and human skin fibroblasts also responded to IL-1 treatment by producing IL-1-specific transcripts. These observations suggest that IL-1 plays a key role in stimulating immune and inflammatory responses and in sustaining those responses through continued production at sites of inflammation.

Animals↗

PubMed1989

Elastic constants of composites formed from PMMA bone cement and anisotropic bovine tibial cancellous bone.

An ultrasonic pulse-transit time technique is used to determine the nine orthotropic engineering constants of 32 cement-cancellous bone composites as a function of volume fractions of bone ranging from 0.0 to 0.4. The composites are manufactured using well-aligned bovine cancellous bone from the proximal end of the tibia and low viscosity bone cement. Selected composites are also subjected to mechanical compression tests to compare with the ultrasonic results. There is excellent correlation between the dynamic or ultrasonically determined moduli and the static or mechanically determined moduli; the dynamic moduli are approximately twice the static moduli and this difference is thought to be due to the effect of strain rate. An orthotropic model is assumed requiring nine independent elastic constants to be determined. The dynamic Young's modulus in the direction of major trabecular alignment, E1, increases linearly from 4.9 to 10.4 GPa as bone volume fraction increases from 0 to 0.4; dynamic E2 and E3 values increase from 4.9 to 7 GPa as bone volume fractions increase from 0 to 0.4, with E2 being slightly higher than E3. The dynamic shear modulus, G12, increases from 1.8 to 3.0 GPa, and G31 and G23 increase slightly from 1.8 to 2.2 GPa as bone volume fractions increase from 0 to 0.4. The Poisson's ratios are more sensitive than the Young's moduli and shear moduli to experimental error in the velocity measurements. The mechanically tested modulus (static modulus) in the direction of major trabecular alignment, E1, increases with volume fraction of bone from 2.4 to 4.4 GPa as the bone volume fraction increases from 0 to 0.25; static E2 and E3 values are either equal to or lower than that of pure PMMA.

Animals↗

PubMed1989

Transfusional iron overload in patients undergoing dialysis: treatment with erythropoietin and phlebotomy.

Five patients undergoing long-term hemodialysis with transfusional iron overload received treatment for 18 weeks with a regimen of recombinant human erythropoietin (150 U/kg) and regular phlebotomy to maintain the hematocrit value at 25% and reduce the total body iron burden. In the 149 phlebotomy sessions performed in these patients, a mean of 228 +/- 8 ml (mean +/- SEM) of whole blood was removed; it had a hematocrit value of 27.7% +/- 0.2%. The iron content of the erythrocytes removed (erythrocyte iron concentration, 787 +/- 11 micrograms/ml in 133 samples) accounted for more than 99% of the total iron removal by phlebotomy. Serum iron (serum iron concentration, 1.57 +/- 0.09 micrograms/ml in 65 samples) accounted for an insignificant fraction of the total iron removed. The iron removed at each phlebotomy session averaged 49.1 +/- 2.0 mg, similar to the amount of iron removed with deferoxamine administration in patients undergoing dialysis who had iron overload, but without the potential for adverse side effects reported with long-term deferoxamine therapy. Total iron removal during the 18 weeks of this study ranged from 732 to 2797 mg. Mean serum ferritin level decreased from 3189 +/- 1076 micrograms/L to 1676 +/- 342 micrograms/L (p less than 0.02, Wilcoxon signed rank test). When compared with a group of five patients without transfusional iron overload who received recombinant human erythropoietin and did not undergo therapeutic phlebotomy, the patients with iron overload had much greater iron losses and a larger decrease in serum ferritin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

The influence of cellular and lipoprotein cholesterol contents on the flux of cholesterol between fibroblasts and high density lipoprotein.

Previous studies indicate that free cholesterol moves passively between high density lipoprotein (HDL) and cell plasma membranes by uncatalyzed diffusion of cholesterol molecules in the extracellular aqueous phase. By this mechanism, the rate constants for free cholesterol influx (Cli) and efflux (ke) should not be very sensitive to the free cholesterol content of cells or HDL. Thus, at a given HDL concentration, the unidirectional influx and efflux of cholesterol mass (Fi, Fe) should be proportional to the cholesterol content of HDL and cells, respectively, and net efflux of cholesterol mass (Fe-Fi greater than 0) should occur when either cells are enriched with cholesterol or HDL is depleted of cholesterol. We have examined the influence of cell and HDL free cholesterol contents on the bidirectional flux of free cholesterol between HDL and human fibroblasts and also attempted to detect some dependence of flux on the binding of HDL to the cells. In the range of HDL concentrations from 1 to 1000 micrograms of protein/ml, ke for cell free cholesterol approximately doubled for every 10-fold increase in HDL concentration, reaching 0.04 h-1 at 1000 micrograms of HDL/ml. ke and Cli were not influenced by the doubling of fibroblast free cholesterol content (from 31 +/- 5 to 62 +/- 13 micrograms of cholesterol/mg of protein). There was an approximate exchange of cholesterol between HDL and the unenriched fibroblasts (e.g. at [HDL] = 100 micrograms/ml, Fe and Fi = 3.2 and 3.0 micrograms of cholesterol/[4 h.mg of cell protein], respectively). In contrast, there was substantial net efflux from the enriched cells (at [HDL] = 100 micrograms/ml, Fe and Fi = 5.5 and 3.1 micrograms of cholesterol/[4 h.mg of cell protein], respectively). The rate constants for cholesterol flux were not influenced by changing the free cholesterol content of HDL, so that there was net efflux of cell cholesterol in the presence of cholesterol-depleted HDL and net influx from cholesterol-rich HDL. The Kd of HDL binding to fibroblasts was reduced from 1.7 to 0.9 micrograms/ml by the enrichment of the cells with free cholesterol; this increase in affinity for HDL was not reflected in enhanced rate constants for cholesterol flux. The inhibition of specific HDL binding by treatment of the lipoprotein with dimethyl suberimidate did not affect cholesterol flux using either control or cholesterol-rich cells at any HDL concentration in the range 1-1000 micrograms/ml. The above results are consistent with the concept that net movement of free cholesterol between cells and HDL occurs by passive, mass-action effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport↗

PubMed1988

Interleukin-1 stimulation of phospholipase activity in rat synovial fibroblasts. Possible regulation by cyclooxygenase products.

Tritiated arachidonic acid (3H-AA)-labeled rat synovial fibroblasts stimulated with human recombinant interleukin-1 beta (rIL-1 beta) released incorporated radiolabel in a time-dependent and dose-dependent manner, with labeled prostaglandins representing 29% of the released radiolabel. Treatment of the cells with dibutyryl cAMP or prostaglandin E2 enhanced both spontaneous and rIL-1 beta-induced 3H-AA release; treatment with indomethacin or naproxen inhibited the response. The effects of these cyclooxygenase inhibitors on 3H-AA release were not reversed by the addition of prostaglandin E2. The activities of phospholipase A, phospholipase C, and diglyceride lipase were detected in the homogenates of rat synovial fibroblasts. Pretreatment of synovial cells with rIL-1 beta resulted in a threefold stimulation of phospholipase A activity and a slight increase in phospholipase C activity in cell homogenates. These data show that rIL-1 beta stimulates phospholipase activities in rat synovial fibroblasts and that at least one of these activities may be regulated by either prostaglandins or cAMP.

Animals↗

PubMed1988

Human non-interferon macrophage activating factor: biological and biochemical characterization.

A HTLV-1 transformed T cell line has been demonstrated to constitutively produce and secrete a lymphokine with macrophage activating properties. This lymphokine was biologically and biochemically distinct from interferon gamma, the interleukins, the colony stimulating factors and lymphotoxin. In vitro treatment of human monocytes with the partially purified lymphokine resulted in the acquisition of microbicidal and tumoricidal activities. The activity was associated with a protein with an apparent molecular weight of 55,000 daltons and an isoelectric point of 5.5. The potential for the efficacy of such a lymphokine in activating macrophages in vivo provides aspirations for its use in the therapy/prevention of opportunistic infections in immunocompromised hosts.

Cell Line, Transformed↗

PubMed1988

Results of subtotal parathyroidectomy in hemodialysis patients.

In 61 hemodialysis patients undergoing subtotal parathyroidectomy, there was a good correlation between the preoperative serum immunoreactive parathyroid hormone value (iPTH) and the weight of parathyroid tissue removed surgically (p less than or equal to 0.001). Postoperatively, iPTH decreased rapidly from an initial mean (+/- SD) of 2,928 +/- 1,600 muleq/ml and remained at 365 +/- 296 muleq/ml at last follow-up of patients still undergoing hemodialysis (normal, less than 50 muleq/ml). Of six patients who had recurrent hyperparathyroidism (10 percent of total), three required a second subtotal parathyroidectomy. Aluminum-related osteomalacia eventually developed in six patients with bone biopsy-proven hyperparathyroidism before parathyroidectomy. Nine patients with severe fracturing bone disease and hypercalcemia preoperatively but without clear evidence of hyperparathyroidism did not show a favorable response to subtotal parathyroidectomy (high mortality within 28 months, persistence of hypercalcemia, and symptomatic bone disease). Thus, subtotal parathyroidectomy can benefit patients with clearly established severe progressive hyperparathyroidism not responsive to medical therapy but is contraindicated in patients with low iPTH values and no bone biopsy evidence of severe hyperparathyroidism.

Aluminum↗

PubMed1988

Interleukin-1 and tumor necrosis factor are not synergistic for human synovial fibroblast PLA2 activation and PGE2 production.

Patterns of arachidonic acid release and metabolism were altered in human synovial fibroblasts following exposure to cytokines. Recombinant interleukin-1 induced an approximate 3-fold increase in [3H]-AA release, a 7-fold increase in PGE2 production and a 2-fold increase in PLA2 activity in human synovial fibroblasts. Recombinant tumor necrosis factor induced similar responses, however, the magnitude was less than that mediated by interleukin-1. A combination of the two cytokines had an additive effect on [3H]-AA release and PLA2 activity while PGE2 production was similar to that detected using interleukin-1 alone. [3H]-AA, was released in substantial amounts when sodium fluoride was used as a stimulus but PGE2 was not. These data show that tumor necrosis factor and interleukin-1 can both activate synovial cell PLA2 and induce generation of PGE2, but act in an additive rather than a synergistic fashion. Furthermore, the data show that PGE2 production is not always concordant with [3H]-AA release, suggesting that appropriate enzyme(s) must be activated.

Arachidonic Acid↗

PubMed1988

The selective uptake of cholesterol by the rat tapeworm Hymenolepis diminuta (Cestoda).

1. The sterols of Hymenolepis diminuta are almost exclusively cholesterol or similar C-27 sterols; the free sterols of its environment (the lumen of the rat intestine) are cholesterol and various phytosterols. 2. During incubation of tapeworms with mixed micelles of taurocholate, glyceryl monooleate, and equimolar [3H]cholesterol and [14C]beta-sitosterol, the uptake of cholesterol is 40 times more rapid than the uptake of sitosterol. 3. Following uptake, the desorption of labeled sitosterol is six times more rapid than that of cholesterol. 4. We did not detect the esterification of absorbed sterols or the conversion of absorbed sitosterol of cholesterol. 5. The highly selective uptake of cholesterol and the moderately selective desorption of phytosterols can account for the selective accumulation of C-27 sterol by the tapeworm.

Animals↗

PubMed1988

Studies on the mechanism of cholesterol uptake by the rat tapeworm Hymenolepis diminuta (Cestoda).

1. With increasing cholesterol content in mixed micelles, the rate of cholesterol uptake by the tapeworm approaches a limiting, maximal value. 2. This uptake is inhibited only 32-40% by other sterols, but is not markedly dependent on medium pH or tapeworm energy metabolism. 3. The competitive exchange diffusion of absorbed [14C]cholesterol could not be demonstrated. 4. The above results partially support the hypothesis that the tapeworm absorbs cholesterol by a specific carrier-mediated process. 5. Cholesterol uptake is reduced when the capacity of the micellar phase of the medium is increased, suggesting that uptake involves the intermediate partitioning of sterol from micelles into the aqueous phase of the medium.

Absorption↗

PubMed1988

Erosive spondyloarthropathy in long-term dialysis patients: relationship to severe hyperparathyroidism.

We describe the development of a destructive, erosive spondyloarthropathy in three long-term dialysis patients (mean duration of dialysis, 96 months). In all three patients, the lesions caused symptomatic vertebral pain and developed during a period of only a few months. All patients had extremely elevated levels of immunoreactive parathyroid hormone, and two patients had evidence of severe hyperparathyroidism on bone biopsy specimens. Two patients who underwent subtotal parathyroidectomy had rapid relief of symptoms and no further radiographic evidence of progression of the spondyloarthropathy. The third patient refused subtotal parathyroidectomy and had pronounced progression of the destructive spondyloarthropathy in the cervical spine. The limited experience of others, along with our currently reported findings, strongly suggests that hyperparathyroidism plays a major role in the development of this disorder. Erosive spondyloarthropathy is increasingly recognized in long-term dialysis patients and may be a unique clinical and radiographic manifestation of severe hyperparathyroidism in this population.

Aged↗

PubMed1988

Deferoxamine and coated charcoal hemoperfusion to remove aluminum in dialysis patients.

We studied the in vitro and in vivo characteristics of aluminum (Al) removal by coated charcoal hemoperfusion (HP) in combination with intravenous deferoxamine (DFO). DFO enhanced the clearance of Al by HP in vitro after 180 minutes of perfusion with a solution containing 403.3 +/- 14.0 ng/ml of Al at 150 ml/min. The Al clearance was 139 +/- 1.0 ml/min with DFO and 49 +/- 10.0 ml/min (P less than 0.001) without DFO. Addition of DFO enhanced in vitro Al removal from 5.5 +/- 0.9 mg to 10.0 +/- 1.2 mg (P less than 0.05). During our in vivo studies, an HP device was in series in the dialysis circuit after a Cuprophan hemodialyzer. Eight patients with Al toxicity were studied on twelve occasions. Patients received DFO (40 mg/kg) 40 hours before the study. The total Al clearance with the combined hemodialysis (HD) and HP devices was higher than that obtained by the dialyzer alone at 30 minutes (62 +/- 4.9 ml/min vs. 25 +/- 2.5 ml/min, P less than 0.02) and after 180 to 210 minutes (32 +/- 3.0 ml/min vs. 19 +/- 2.9 ml/min, P less than 0.02). After 120 minutes the Al clearance by the HP device alone was significantly lower than the initial Al clearance by HP. Combined HD plus HP removed 2.9 +/- 0.4 mg of Al, whereas the total removal of Al by HD alone was 1.5 +/- 0.3 mg (P less than 0.01).

Aluminum↗

PubMed1988

Methotrexate inhibits macrophage activation as well as vascular and cellular inflammatory events in rat adjuvant induced arthritis.

We demonstrated previously that variables of macrophage activation are associated with the development and progression of the arthritic lesion in the model of adjuvant induced arthritis. This association was investigated further by assessing the ability of antiarthritic agents to modulate variables of macrophage activation in direct comparison to effects on the arthritic lesion. Whereas indomethacin effectively reduced hindpaw edema, it had no significant effect on Ia expression or on any measurement of activation. Prednisolone inhibited hindpaw edema and the production of interleukin-1 (IL-1) by splenic macrophages. Only methotrexate inhibited hindpaw edema and all variables of macrophage activation (PGE2 and IL-1 production, cyanine dye accumulation) as well as the influx of Ia positive macrophages into synovial tissue.

Animals↗

PubMed1988

Cross-linking of apoproteins in high density lipoprotein by dimethylsuberimidate inhibits specific lipoprotein binding to membranes.

Apoprotein E-free high density lipoproteins (HDL) bind to various cells and cell membrane preparations with properties typical of ligand-receptor interactions. This specific binding can be inhibited by treatment of HDL with tetranitromethane (TNM). During treatment of HDL with TNM, in addition to the expected nitration of tyrosine residues, cross-linking of lipids to apoproteins and of apoproteins to each other occurs. We have recently shown that cross-linking of phospholipids to apoproteins is not responsible for the inhibition of binding (1987. Chacko, G. K., et al. J. Lipid Res. 28: 332-337). To determine the role of cross-linking of apoproteins to each other in the inhibition, we used the bifunctional reagent dimethylsuberimidate (DMS) to cross-link the apoproteins in HDL3. Over 80% of apoproteins in DMS-HDL3 were cross-linked, as analyzed by SDS-polyacrylamide gel electrophoresis. DMS-HDL3 was similar to control HDL3 in its lipid composition. Gel filtration chromatography did not reveal any significant difference in size between DMS-HDL3 and control HDL3. As determined by competitive binding with 125I-labeled HDL3, DMS-HDL3 was almost completely unable to bind specifically to rat liver plasma membranes and human skin fibroblasts. It is concluded from these results that TNM inhibits the specific binding of HDL3 to membranes by a mechanism that involves cross-linking of apoproteins to each other in HDL3 particles. This observation implies that the specific binding of HDL3 to cells may depend on the native quaternary structure of apoproteins in the HDL particle. Because of its reduced ability to bind to the specific binding sites, DMS-HDL3 may be useful for studies related to the functional aspects of HDL binding sites.

Animals↗

PubMed1987

Cholesterol flux between cells and high density lipoprotein. Lack of relationship to specific binding of the lipoprotein to the cell surface.

The bidirectional flux of unesterified cholesterol between cells and high density lipoprotein (HDL) was studied in relationship to the binding of HDL to cells. At 100 micrograms at HDL protein/ml, the rate constant for cholesterol efflux from rat Fu5AH hepatoma cells is 3 X 10(-3)/min (t1/2 for efflux of 3.9 h), whereas efflux from GM3468 human fibroblasts is 0.075/4 h (equivalent to a t1/2 for efflux of 37 h). The relatively slow efflux of cholesterol from fibroblasts in comparison to rat hepatoma cells was observed previously with micellar and vesicular phospholipid-containing acceptors, which promote efflux by a mechanism involving the diffusion of cholesterol in the aqueous phase between the plasma membrane and the acceptor particles. When plotted against the logarithm of HDL concentration, the isotherms for efflux are centered at 300 and 100 micrograms of HDL protein/ml with the hepatoma cells and fibroblasts, respectively. These concentrations are 8-150 times greater than the corresponding values for Kd of specific HDL binding (2 and 12 micrograms of protein/ml, for hepatoma cells and fibroblasts, respectively). The treatment of HDL with tetranitromethane reduces the lipoprotein's affinity for specific cell-surface binding sites by 80-90%. However, at HDL concentrations of 5-60 micrograms of protein/ml, this treatment does not significantly inhibit cholesterol efflux from hepatoma cells, and inhibits efflux from fibroblasts an average of about 15%. Over the same range of concentrations, nitration alters influx by amounts less than 30% in the two cell types. These effects on flux do not parallel the reduced affinity of nitrated HDL for specific cell-surface binding sites. In summary, the present results do not support the concept that cholesterol transfer is facilitated by the specific cell-surface binding of HDL, but are consistent with the aqueous diffusion model of cholesterol transfer between cells and lipoproteins.

Animals↗