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Biomedical subjects

C L Bell

Publications and source records attributed to C L Bell.

At least 19 recordsLinked to original sources
PubMed1997

Cystic fibrosis affects specific cell type in sweat gland secretory coil.

The sweat gland has three distinct cell types: a myoepithelial (ME) cell, a beta-adrenergic-insensitive (beta-I) cell, and a beta-adrenergic-sensitive (beta-S) cell. Using intracellular microelectrodes, we sought to functionally identify the specific cell type(s) affected in cystic fibrosis (CF). We found that in CF secretory coils 1) the ME calls are unaffected, as indicated by normal cell membrane potentials and spontaneous and cholinergically induced depolarizing potentials, 2) the beta-I cells showed normal physiological properties, including a relatively smaller cell membrane potential (approx -25 mV) and a Ba(2+)-inhibitable cholinergic response, and, in contrast, 3) the beta-S cell is abnormal, as shown by the lack of a beta-adrenergically activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- conductance (GCl). Lack of CFTR GCl in this cell type does not affect either the magnitude of cell membrane potential (approx -56 mV) or the relative cell membrane GCl or the cholinergic response, as compared with that of normal beta-S cells. We conclude that, of the three cell types in secretory coil, only the beta-S cell is specifically affected in the CF secretory tissue of the human sweat gland.

Barium↗
PubMed1997

Safety and efficacy of hydroxychloroquine as maintenance therapy for rheumatoid arthritis after combination therapy with methotrexate and hydroxychloroquine.

OBJECTIVE: To evaluate the ability of hydroxychloroquine sulfate (HCQ) to extend the response to combination therapy with HCQ and methotrexate (MTX) and the safety of longterm HCQ maintenance therapy in patients with active rheumatoid arthritis (RA). METHODS: Two-part study consisting of an open label segment evaluating combination HCQ/MTX therapy followed by a double blind segment evaluating maintenance therapy for a total of 60 weeks. First, all patients were treated with HCQ 400 mg/day and MTX 7.5 to 15 mg/week for 24 weeks. Then, responders were randomized into 3 groups: (1) HCQ with MTX as needed for disease flare (n = 40), (2) HCQ 400 mg/day (n = 41), or (3) placebo with MTX as needed for disease flare (n = 40), each for 36 weeks. RESULTS: Clinical disease and laboratory variables improved significantly during initial combination therapy with HCQ and MTX. After MTX withdrawal, HCQ-containing maintenance regimens delayed the onset of disease flare (p = 0.023). There were no unexpected adverse events at any time or between-group differences in the distribution of adverse events during the double blind segment. CONCLUSION: Combination of HCQ and MTX appeared to be effective and well tolerated for 24 weeks. After withdrawal of MTX, HCQ extended the response seen with combination therapy and was well tolerated for 36 weeks. Initial therapy with HCQ and MTX, followed by maintenance HCQ, may be a useful alternative for the treatment of RA.

Aged↗
PubMed1996

Water, solute and protein diffusion in physiologically responsive hydrogels of poly (methacrylic acid-g-ethylene glycol).

Grafted poly (methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)] copolymers were synthesized and their pH sensitivity was investigated. P(MAA-g-EG) membranes showed pH sensitivity due to complex formation and dissociation. Uncomplexed equilibrium swelling ratios were 40 to 90 times higher than those of the complexed states and varied according to copolymer composition and poly(ethylene glycol) (PEG) graft length. Mesh sizes in the two states were determined. Swelling under oscillatory pH conditions revealed the dynamic sensitivity of P(MAA-g-EG) membranes as well as the diffusional mechanisms causing network expansion and collapse. Network collapse (complexation) occurred more rapidly than network expansion (decomplexation). A Boltzmann superposition model was used to analyse this behaviour. Mechanical testing was used to evaluate the strength of P(MAA-g-EG) membranes and to elucidate the mesh size under various conditions. Solute diffusion coefficients were higher in uncomplexed than in complexed P(MAA-g-EG) membranes and decreased as solute size increased. Lower diffusion coefficients were observed with membranes or hydrogels containing longer PEG grafts, since in the uncomplexed state the PEG grafts dangled into the polymer mesh space. Membrane permeability was responsive to changing pH conditions, and separation of solutes was achieved.

Chemical Phenomena↗
PubMed1996

Stress fractures of the sacrum and lower extremity.

Stress fractures of the lower extremity and sacrum occur in a variety of patients, ranging from young, healthy athletes to elderly persons with underlying illnesses. Knowledge of the activities and risk factors associated with these fractures may heighten clinical suspicion and help direct an appropriate evaluation. Diagnosis is usually based on characteristic features of the history and physical examination accompanied by radiologic findings. Bone scintigraphy remains the standard, but the specificity of computed tomography scanning or magnetic resonance imaging may be required to differentiate stress fractures from other processes such as malignant bone lesions. Management of stress fractures is usually conservative, with variation depending on fracture location and patient characteristics.

Adult↗
PubMed1996

Distinct cellular mechanisms of cholinergic and beta-adrenergic sweat secretion.

The cholinergic and beta-adrenergic sweat secretions from human sweat glands differ with respect to secretory rates and their susceptibility to cystic fibrosis (CF). Using the cultured beta-adrenergic-sensitive sweat secretory cell, we sought to determine the intracellular electrophysiological mechanisms underlying these functional differences. We found that the cholinergic agonist methacholine (10(-6) M) induced a Ca(2+)-dependent biphasic membrane potential (Vm) response: an initial hyperpolarization and a secondary depolarization. The initial hyperpolarization was independent of bath Cl- and dependent on transmembrane K+ gradient. However, the secondary depolarization of Vm was dependent on bath Cl-. In contrast, the beta-adrenergic agonist isoproterenol (10(-5) M) induced a monophasic depolarization of Vm. This depolarization was 1) dependent on bath Cl-, 2) independent of K+ conductance (GK) blocker Ba2+ (5mM), 3) unaffected by the methacholine-induced secondary depolarization of Vm, and 4) absent in cells derived from CF subjects. These results indicated that the cholinergic agonist-induced secretion mainly involves the activation of Ca(2+)-dependent GK and Cl- conductance (GCl), whereas the beta-adrenergic secretion seems to mainly depend on the activation of cystic fibrosis transmembrane conductance regulator-GCl.

Adrenergic beta-Agonists↗
PubMed1996

Swelling/syneresis phenomena in gel-forming interpolymer complexes.

Grafted poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) copolymers were synthesized and their pH sensitivity investigated as a function of copolymer composition and PEG graft molecular weight. Interpolymer complexation occurred by hydrogen bonding between carboxylic groups on poly(methacrylic acid) (PMAA) and ether groups on poly(ethylene glycol) (PEG). This complexation was sensitive to the surrounding environment as complexes formed at pH levels low enough to insure substantial protonation of PMAA acid groups. At high pH, the acid groups became neutralized and did not form complexes. P(MAA-g-EG) membranes showed pH-sensitivity due to complex formation and dissociation. Uncomplexed equilibrium swelling ratios were much higher than those of the complexed states and varied according to copolymer composition and PEG graft length. Mesh sizes in the two states were determined. Swelling under oscillatory pH conditions and constant ionic strength revealed the dynamic sensitivity of P(MAA-g-EG) membranes. Under changing pH conditions, network syneresis (complexation) occurred more rapidly than network expansion (decomplexation) because of the rates of diffusion of specific ions causing the responses. No distinct water fronts were observed. Instead, water transport was continuous through the gel. These gels show great promise for a number of biomedical applications where fast biomaterial response is necessary.

Biocompatible Materials↗
PubMed1995

An immortal cell line to study the role of endogenous CFTR in electrolyte absorption.

The intact human reabsorptive sweat duct (RD) has been a reliable model for investigations of the functional role of "endogenous" CFTR (cystic fibrosis transmembrane conductance regulator) in normal and abnormal electrolyte absorptive function. But to overcome the limitations imposed by the use of fresh, intact tissue, we transformed cultured RD cells using the chimeric virus Ad5/SV40 1613 ori-. The resultant cell line, RD2(NL), has remained differentiated forming a polarized epithelium that expressed two fundamental components of absorption, a cAMP activated Cl- conductance (GCl) and an amiloride-sensitive Na+ conductance (GNa). In the unstimulated state, there was a low level of transport activity; however, addition of forskolin (10(-5) M) significantly increased the Cl- diffusion potential (Vt) generated by a luminally directed Cl- gradient from -15.3 +/- 0.7 mV to -23.9 +/- 1.1 mV, n = 39; and decreased the transepithelial resistance (Rt) from 814.8 +/- 56.3 omega.cm2 to 750.5 +/- 47.5 omega.cm2, n = 39, (n = number of cultures). cAMP activation, anion selectivity (Cl- > I- > gluconate), and a dependence upon metabolic energy (metabolic poisoning inhibited GCl), all indicate that the GCl expressed in RD2(NL) is in fact CFTR-GCl. The presence of an apical amiloride-sensitive GNa was shown by the amiloride (10(-5) M) inhibition of GNa as indicated by a reduction of Vt and equivalent short circuit current by 78.0 +/- 3.1% and 77.9 +/- 2.6%, respectively, and an increase in Rt by 7.2 +/- 0.8%, n = 36. In conclusion, the RD2(NL) cell line presents the first model system in which CFTR-GCl is expressed in a purely absorptive tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Rheumatoid arthritis. Complications beyond the joints.

In addition to affecting the joints, rheumatoid arthritis may wreak havoc on a number of organs in the body, including the heart, lungs, and eyes. Results of long-term studies suggest that morbidity and mortality increase in patients with rheumatoid arthritis. It is hoped that the new approach to pharmacologic treatment that uses aggressive medications shortly after onset of symptoms will alter the disease course, diminish morbidity, and eliminate the excess mortality seen in patients with long-standing rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1993

Regulation of CFTR Cl- conductance in secretion by cellular energy levels.

Recent studies suggested dual regulation of the Cl- conductance (GCl) affected in cystic fibrosis, one by protein kinase A-dependent phosphorylation and a second by low-affinity ATP binding. We proposed that ATP binding may couple the transport demands to the energy level of the cell. In the present study we examined this hypothesis further in a purely secretory function using the epithelial cell line T84. We used a depletion-permeabilization protocol on cells grown on permeable supports to deplete the cells of endogenous ATP and to provide access to the intracellular compartment for the impermeable nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and ATP. In contrast to non-depleted permeabilized cells, which responded to 0.1 mM cAMP with an increase in transepithelial potential (delta Vt = 29.8 +/- 3.0 mV, n = 4) and conductance (delta Gt = 1.23 +/- 0.54 mS/cm2, n = 4), addition of cAMP to ATP-depleted cells resulted in insignificant changes in Vt (delta Vt = 0.7 +/- 0.2 mV, n = 26; P < 0.05) and Gt (delta Gt = 0.020 +/- 0.003 mS/cm2, n = 26; P < 0.05). However, the cAMP response was restored by addition of 5 mM ATP (delta Vt = 21.7 +/- 1.5 mV, n = 26; delta Gt = 0.59 +/- 0.06 mS/cm2, n = 26). ATP dose-response experiments, taken together with the effect of cAMP with and without ATP, suggest that phosphorylation is necessary, but not sufficient, for activation. The data provide evidence for a second level of regulation of GCl, which requires high concentrations of ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Reversed anion selectivity in cultured cystic fibrosis sweat duct cells.

The human genetic disease cystic fibrosis (CF) is characterized by defective epithelial Cl- conductance (GCl). To distinguish the CF-affected GCl from other Cl- channels, we have studied the properties of GCl in normal and CF cells grown from explanted reabsorptive sweat ducts (RD). The cultured cells from normal subjects retained some of the typical duct cell properties. The Na+ conductance inhibitor amiloride hyperpolarized intracellular potentials (Vm) by 10.4 +/- 1.6 mV (n = 12). Substitution of gluconate for Cl- depolarized Vm by 15.5 +/- 1.1 mV (n = 33). The apparent GCl (G'Cl) of normal cells was sensitive to adenosine 3',5'-cyclic monophosphate (forskolin, 10(-6) M), as evidenced by a significant increase (63%, n = 9) in the Cl- gradient induced depolarization, and more selective for Cl- than I- (substitution of Cl- by I- depolarized Vm by 6.3 +/- 0.3 mV, n = 49). Although the cells from CF subjects were statistically indistinguishable from normal cells based on Vm (-18.5 +/- 1.2 mV, n = 49 vs. -20.1 +/- 1.8 mV, n = 28), CF cells expressed differences in G'Cl, responses to forskolin, and anion selectivity. CF cells had a significantly reduced G'Cl as indicated by blunted responses to imposed Cl- gradients (26% of normal, n = 28). In contrast to our observations in normal cells, the G'Cl of CF cells was insensitive to forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anions↗
PubMed1992

T84 cells: anion selectivity demonstrates expression of Cl- conductance affected in cystic fibrosis.

The T84 cell line possesses an adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- conductance and expresses high levels of the cystic fibrosis (CF) gene product, implicating it as a good model for CF research. To evaluate whether T84 Cl- conductance properties are consistent with those described in CF target epithelial, we used transepithelial measurements (verified by selective permeabilization of the basal membrane) to determine the apparent anion selectivity properties of the apical and basolateral membranes of stimulated and unstimulated T84 cells. Unstimulated epithelial cells were almost electrically inert, having a low transepithelial voltage (Vt; -6 mV, apical surface negative), a small equivalent short-circuit current (Isc,(eq.) 2.2 microA/cm2), a very high transepithelial resistance (Rt; 2,500 omega.cm2), and poor anion permselectivity properties at both membrane surfaces (0.8 less than PX/PCl- less than 1.1), where X is NO3-, Br-, I-, or gluconate. When stimulated with forskolin (10(-6) M), Vt increased 8-fold, Isc(eq) increased 30-fold, Rt fell to one-third of unstimulated values, and the apical surface became highly anion selective, i.e., NO3- (1.4) greater than Br- (1.2) greater than Cl- (1.0) greater than I- (0.7) greater than gluconate (0.0), where numbers in parentheses are PX/PCl-. I- was less permeable than Cl- and probably directly inhibits the anion conductance, since Rt was substantially greater after I- substitution than after substitution with the impermeable anion gluconate. Bumetanide (10(-4) M) significantly attenuated the response of Vt to anion substitutions at the basal membrane surface, indicating that the effects of substitution were predominantly on the Na(+)-K(+)-2Cl- cotransporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1992

Evidence of two distinct epithelial cell types in primary cultures from human sweat gland secretory coil.

The human sweat gland secretory coil (SC) is comprised of myoepithelial (ME) and two types of secretory epithelial cells. The secretory cells include beta-adrenergic-sensitive (beta-S) cells [responsive to the beta-adrenergic agonist isoproterenol (IPR)] and beta-adrenergic insensitive (beta-I) cells. We have grown segments of SC in primary culture and found that under the conditions described here, only epithelial cells form outgrowths as indicated by morphological and physiological properties. As in the native SC epithelium, the secretory cells in primary culture were comprised of polygonal epithelial cells with a characteristic hyperpolarization of cell potentials (Vm) to cholinergic stimulation by mecholyl (magnitude of change of Vm = delta Vm = 21.5 +/- 1.3 mV, mean +/- SE, n = number of cells = 44). We have found both beta-S and beta-I cells as determined by unstimulated membrane potentials, sensitivity to IPR, and K+ conductance (GK+). The frequency distribution of unstimulated cells indicated two distinct populations of cells, one with high membrane potentials (Vm = -63 +/- 2.6 mV), which correlated with beta-S cells, and a second with low membrane potentials (Vm = -22 +/- 1.5 mV), which correlated with the beta-I cells. IPR depolarized the Vm of beta-S cells (delta Vm = 11.0 +/- 0.8 mV, n = 25) without affecting the Vm of beta-I cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1991

Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers.

Clinical, magnetic resonance imaging (MRI), and serologic studies were performed on 11 patients with diffuse central nervous system (CNS) systemic lupus erythematosus and 8 patients with focal CNS lupus. MRI of patients with diffuse clinical disease showed symmetrically distributed areas of increased signal intensity in the subcortical white matter; these resolved after treatment with high-dose methylprednisolone. These patients' sera contained elevated levels of antineurofilament antibodies. Patients with focal CNS lupus had areas of increased signal intensity and atrophic changes in regions corresponding to the major cerebral vessels. These MRI abnormalities did not improve after treatment with high-dose steroids. The sera of patients with focal CNS lupus had elevated levels of cardiolipin and lupus anticoagulant but normal levels of antineurofilament antibody. Our findings suggest that results of a combined clinical, MRI, and serologic evaluation of patients with CNS lupus may predict the response of patients to high-dose steroid therapy.

Adult↗
PubMed1991

Effects of media buffer systems on growth and electrophysiologic characteristics of cultured sweat duct cells.

Primary cultures of human reabsorptive sweat duct cells were grown in MCDB 170 medium buffered with either HEPES, bicarbonate, or a mixture of HEPES and bicarbonate buffers. Cultures grown in MCDB media containing bicarbonate seemed to differentiate into a multilayered, keratinized epithelium and began senescing after 1 wk in culture. In contrast, cultures grown in media containing HEPES as the only buffer seemed to undergo a selection process, resulting in the outgrowth of cells that did not multilayer or keratinize extensively for up to 3 or 4 wk in culture. Despite marked differences in growth, cells grown in both bicarbonate and HEPES-buffered media retained electrophysiologic characteristics appropriate to the progenitor. Mean resting potentials were -21.8 +/- 0.8 mV (n = 82), -23.3 +/- 1.3 mV (n = 70) and -18.2 +/- 0.8 mV (n = 82) for duct cells grown in HEPES, bicarbonate, and HEPES-bicarbonate media, respectively. Substitution of Cl- with the impermeant anion gluconate in the bathing medium caused membrane potential depolarization in all media, revealing the presence of a Cl- conductance. Administration of the Na+ conductance inhibitor amiloride hyperpolarized the mean resting potential of cells grown in HEPES medium (-6.8 +/- 0.6 mV, n = 68), bicarbonate medium (-6.9 +/- 0.5 mV, n = 60), and HEPES-bicarbonate medium (-5.9 +/- 0.6 mV, n = 69), demonstrating expression of a Na+ conductance. We observed some but minimal variation with age in any of these conditions.

Adult↗
PubMed1990

Preparation and use of double-labelled enterobactin.

Double-labelled 3H/14C-enterobactin was isolated from bacterial cultures, and evaluated as a potential tool for studying the mammalian metabolism of this iron chelator. Microbial yields were low, but adequate, with a final 3H/14C ratio of 2.95 to 1. Studies conducted with mice indicated that considerable metabolism and rapid elimination of an intraperitoneally injected sample had occurred in 24 hours.

Animals↗
PubMed1989

Patch-clamp study of cultured human sweat duct cells: amiloride-blockable Na+ channel.

The reabsorptive duct of the eccrine sweat gland has a large transepithelial conductance consisting mainly of a high conductance to Cl- and a smaller, amiloride-blockable Na+ conductance (Bijman and Frömter 1986; Quinton 1986). Cells have been cultured from sweat ducts and their properties previously studied in Ussing chambers (Pedersen 1988) and with microelectrodes (Jones et al. 1988). We have now studied the ion channels present in excised, inside-out patches of human cultured sweat duct cells, and find a marked predominance of linear, 15 pS, amiloride-blockable, low selectivity, Na+ channels. Such channels were seen in 54/92 (59%) of the patches, with up to 7 channels recorded in a single patch. Other channel types were seen at much lower densities. The prevalence of an amiloride-blockable Na+ channel in cultured duct cells clearly distinguishes these cells from cultured sweat gland secretory cells, which lack such a channel.

Amiloride↗