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1.
Front Public Health ; 8: 579773, 2020.
Article in English | MEDLINE | ID: mdl-33415096

ABSTRACT

Background: Information communication technologies (ICT) are increasingly used in health promotion, but integration is challenging and involves complex processes. Large community health promotion events are often held but the experiences and processes have rarely been evaluated and published. No reports have described and systematically evaluated an ICT-supported health promotion event using digital games. Objective: We evaluated the development and implementation of a large community family health promotion event with ICT integration to promote family happiness with collaboration between academia (The University of Hong Kong) and the social (family) service sector, and collected feedback from participants and social service workers. Methods: We (i) conducted a systematic process evaluation, (ii) administered an on-site questionnaire survey on participant satisfaction and feedback, and (iii) collected post-event qualitative feedback from social workers on using new technologies, digital game design and overall experiences. Results: Fourteen digital games were designed and run in booths at the event by 12 non-governmental social service organizations and academia. Four gaming technologies were utilized: chroma key (green screen), somatosensory (kinect and leap motion techniques), augmented reality and virtual reality. 1,365 participants joined the event, in which 1,257 from 454 families were recruited and pre-registered through 12 NGOs. About 39.3% were male and more than half (53.3%) were aged 18 years and above. About 3,487 game booth headcounts were recorded. Games using virtual reality, kinect motion and green screen technologies were most liked. The average game satisfaction score was high (4.5 out of 5). Social service workers reported positive experiences with using new technologies in health promotion, and interests in future collaborations involving more ICT. Conclusions: Our systematic evaluation showed successful integration of ICT components in the health promotion event. This event, most likely the first of its kind, served as a capacity building and knowledge transfer platform for interdisciplinary co-sharing and co-learning of new technologies. It provided a solid foundation for further academic and social service partnerships and should be a useful model for similar community events and their evaluation. Further development and integration of ICT for health promotion among social service organizations with comprehensive evaluation are warranted.


Subject(s)
Family Health , Information Technology , Adolescent , Communication , Family Relations , Female , Hong Kong , Humans , Male
2.
Curr Eye Res ; 43(4): 553-565, 2018 04.
Article in English | MEDLINE | ID: mdl-29199855

ABSTRACT

PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1ß (IL-1ß), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV) vectors expressing IL-1ß, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. RESULTS: We found that IL-1ß had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1ß resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1ß was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1ß was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1ß in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1ß alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1ß or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1ß is the most pathogenic when it is continuously expressed in the eye.


Subject(s)
Cytokines/genetics , Endophthalmitis/genetics , Gene Expression Regulation , RNA/genetics , Animals , Cytokines/biosynthesis , Disease Models, Animal , Endophthalmitis/metabolism , Endophthalmitis/pathology , Enzyme-Linked Immunosorbent Assay , Female , Inflammation/genetics , Inflammation/metabolism , Male , Mice , Mice, Inbred C57BL , Real-Time Polymerase Chain Reaction , Retinal Artery/metabolism , Retinal Artery/pathology , Tomography, Optical Coherence
3.
J Nutr Health Aging ; 20(6): 621-7, 2016.
Article in English | MEDLINE | ID: mdl-27273351

ABSTRACT

BACKGROUND: Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re-assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions. However, the literature contains little guidance on a systematic interdisciplinary team approach to the oral feeding reassessment of patients with TF, who are admitted to NHs. METHODS: This project had two parts that were conducted in one 170-bed intermediate/skilled, Medicare-certified NH in Honolulu, Hawai'i. Part 1 consisted of a retrospective observational study of characteristics of TF patients versus non-tube fed patients at NH admission (2003-2006) and longitudinal follow-up (through death or 6/30/2011) with usual care of the TF patients for outcomes of: feeding and swallowing reassessment, goals of care reassessment, feeding status (TF and/or per oral (PO) feedings), and hospice status. Part 2 involved the development of an interdisciplinary TF reassessment protocol through working group discussions and a pilot test of the protocol on a new set of patients admitted with TF from 2011-2014. RESULTS: Part 1: Of 238 admitted patients, 13.4% (32/238) had TF. Prior stroke and lack of DNR status was associated with increased likelihood of TF. Of the 32 patients with TF at NH admission, 15 could communicate and interact (mild, moderate or no cognitive impairment with prior stroke or pneumonia); while 17 were nonverbal and/or bedbound patients (advanced cognitive impairment or terminal disease). In the more cognitively intact group, 9/15 (60%) were never reassessed for tolerance of oral diets and 10/15 (66.7%) remained with TF without any oral feeding until death. Of the end-stage group, 13/17 (76.5%) did not have goals of care reassessed and remained with TF without oral feeding until death. Part 2: The protocol pilot project included all TF patients admitted to the facility in 2011-2014 (N=33). Of those who were more cognitively intact (n=22), 21/22 (95.5%) had swallowing reassessed, 11/22 (50%) resumed oral feedings but 11 (50%) failed reassessment and continued exclusive TF. Of those with end-stage disease (n=11), 100% had goals of care reassessed and 9 (81.8%) families elected individualized oral feeding (with or without TF). CONCLUSION: Using findings from our retrospective study of usual care, our NH's interdisciplinary team developed and pilot-tested a protocol that successfully reintroduced oral feedings to tube-fed NH patients who previously would not have resumed oral feeding.


Subject(s)
Enteral Nutrition/methods , Aged , Female , Humans , Male , Nursing Homes , Pilot Projects , Retrospective Studies , Terminal Care
5.
Opt Express ; 17(12): 9834-9, 2009 Jun 08.
Article in English | MEDLINE | ID: mdl-19506633

ABSTRACT

The performance of an external cavity diode laser based noise immune cavity enhanced optical heterodyne molecular spectrometer is presented. To reduce the noise on the signal a ring cavity and a circuit to remove residual amplitude modulation on the pre-cavity laser radiation was implemented. We demonstrate a sensitivity of 4 x 10(-11) cm(-1) Hz(-1/2) using a cavity with a finesse of 2600 on a Doppler-broadened transition of CH(4) at 6610.063 cm(-1).


Subject(s)
Lasers, Semiconductor , Transducers , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity
6.
Palliat Med ; 23(6): 482-90, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19494055

ABSTRACT

Congruence between preferred and actual place of death is an important palliative care outcome reported in the literature. We examined methods of measuring and reporting congruence to highlight variations impairing cross-study comparisons. Medline, PsychInfo, CINAHL, and Web of Science were systematically searched for clinical research studies examining patient preference and congruence as an outcome. Data were extracted into a matrix, including purpose, reported congruence, and method for eliciting preference. Studies were graded for quality. Using tables of preferred versus actual places of death, an overall congruence (total met preferences out of total preferences) and a kappa statistic of agreement were determined for each study. Twelve studies were identified. Percentage of congruence was reported using four different definitions. Ten studies provided a table or partial table of preferred versus actual deaths for each place. Three studies provided kappa statistics. No study achieved better than moderate agreement when analysed using kappa statistics. A study which elicited ideal preference reported the lowest agreement, while longitudinal studies reporting final preferred place of death yielded the highest agreement (moderate agreement). Two other studies of select populations also yielded moderate agreement. There is marked variation in methods of eliciting and reporting congruence, even among studies focused on congruence as an outcome. Cross-study comparison would be enhanced by the use of similar questions to elicit preference, tables of preferred versus actual places of death, and kappa statistics of agreement.


Subject(s)
Attitude to Death , Choice Behavior , Palliative Care/psychology , Patient Preference , Research Design/standards , Terminally Ill/psychology , Humans , Randomized Controlled Trials as Topic , Residence Characteristics
7.
Gene Ther ; 16(3): 441-7, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19129859

ABSTRACT

In vivo bioluminescence imaging of reporter enzymes has proven to be a uniquely powerful tool that allows the study of the biology of viral and nonviral gene transfer agents. Cost-effective, noninvasive, longitudinal gene transfer studies in individual animals yield important information, which can influence the design of subsequent preclinical studies. The broad and expanding use of luciferase transgenes, specifically firefly luciferase, has prompted the study of luciferase-specific T-cell activation following in vivo gene transfer. Herein, we report the mapping of the dominant T cell epitope in C57BL/6 mice (LMYRFEEEL) and the mapping of the dominant and minor T-cell epitopes in BALB/c mice (GFQSMYTFV and VPFHHGFGM, VALPHRTAC, respectively). These CD8 T-cell epitopes can be used to monitor cellular responses in vivo as well as be important tools in studies designed to suppress transgene-specific T cells.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Epitopes, T-Lymphocyte/analysis , Luciferases, Firefly/immunology , Animals , Epitope Mapping/methods , Gene Transfer Techniques , Luciferases, Firefly/genetics , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
8.
Neurology ; 71(8): 578-82, 2008 Aug 19.
Article in English | MEDLINE | ID: mdl-18711111

ABSTRACT

BACKGROUND: People with epilepsy are known to be at increased risk of death by drowning but there are few data available regarding the size of the risk. We aimed to quantify the risk using meta-analysis. METHODS: A literature search identified 51 cohorts of people with epilepsy in whom the number of deaths by drowning in people with epilepsy and the number of person-years at risk could be estimated. Population data were taken from the WHO Statistical Information Service or from the UK Office for National Statistics where available. Standardized mortality ratios (SMRs) with 95% CIs were calculated for each cohort, for groups of cohorts, and for the total population. Additionally, an SMR for drowning in people with epilepsy in England and Wales (1999-2000) was calculated using National Registries. RESULTS: Eighty-eight drowning deaths were observed compared with 4.70 expected, giving an SMR of 18.7 (95% CI 15.0 to 23.1). Compared with community-based incident studies (SMR 5.4), the SMR was significantly raised in prevalent epilepsy (SMR 18.0), in people with epilepsy and learning disability (SMR 25.7), in those in institutional care (SMR 96.9), and in those who had a temporal lobe excision (SMR 41.1). The SMR for people with epilepsy in England and Wales was 15.3. CONCLUSION: The risk of drowning in people with epilepsy is raised 15- to 19-fold compared with people in the general population. It is important that people with epilepsy and their carers be informed of these risks so that deaths can be prevented.


Subject(s)
Drowning/mortality , Epilepsy/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Comorbidity , Female , Global Health , Humans , Incidence , Male , Middle Aged , Prevalence , Registries/statistics & numerical data , Risk Assessment , United Kingdom/epidemiology
9.
J Rheumatol ; 24(10): 1896-902, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9330929

ABSTRACT

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.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Hydroxychloroquine/administration & dosage , Methotrexate/administration & dosage , Aged , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
10.
Am J Physiol ; 273(2 Pt 1): C426-33, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9277340

ABSTRACT

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.


Subject(s)
Cystic Fibrosis/metabolism , Cystic Fibrosis/pathology , Sweat Glands/metabolism , Sweat Glands/pathology , Barium/pharmacology , Cells, Cultured , Cholinergic Agents/pharmacology , Cystic Fibrosis/physiopathology , Electrophysiology , Epithelium/drug effects , Epithelium/pathology , Epithelium/physiopathology , Humans , Muscle, Smooth/drug effects , Muscle, Smooth/pathology , Muscle, Smooth/physiopathology , Sweat Glands/physiopathology
11.
Am J Physiol ; 271(2 Pt 1): C486-94, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8769987

ABSTRACT

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.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Cholinergic Agents/pharmacology , Isoproterenol/pharmacology , Methacholine Chloride/pharmacology , Skin/metabolism , Sweat/metabolism , Cells, Cultured , Chlorides/physiology , Electric Conductivity , Humans , Potassium/physiology , Skin/cytology , Skin Physiological Phenomena
12.
Biomaterials ; 17(12): 1203-18, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8799505

ABSTRACT

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.


Subject(s)
Proteins/chemistry , Water/chemistry , Chemical Phenomena , Chemistry, Physical , Diffusion , Gels , Hydrogen-Ion Concentration , Membranes, Artificial , Permeability , Polyethylene Glycols , Polymethacrylic Acids , Solutions , Tensile Strength
13.
Curr Opin Rheumatol ; 8(2): 158-62, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8732801

ABSTRACT

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.


Subject(s)
Fractures, Stress/etiology , Leg Injuries/etiology , Sacrum/injuries , Spinal Fractures/etiology , Adult , Aged , Female , Fractures, Stress/diagnosis , Fractures, Stress/therapy , Humans , Leg Injuries/diagnosis , Leg Injuries/therapy , Male , Middle Aged , Spinal Fractures/diagnosis , Spinal Fractures/therapy
14.
J Biomater Sci Polym Ed ; 7(8): 671-83, 1996.
Article in English | MEDLINE | ID: mdl-8639476

ABSTRACT

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.


Subject(s)
Biocompatible Materials , Polyethylene Glycols/chemistry , Polymethacrylic Acids/chemistry , Gels , Hydrogen-Ion Concentration , Indicators and Reagents , Kinetics , Prostheses and Implants , Structure-Activity Relationship , Time Factors
16.
In Vitro Cell Dev Biol Anim ; 31(1): 30-6, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7535636

ABSTRACT

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)


Subject(s)
Cell Line, Transformed , Chlorides/metabolism , Eccrine Glands/cytology , Membrane Proteins/physiology , Sodium/metabolism , Absorption , Adult , Amiloride/pharmacology , Anions , Cell Line, Transformed/metabolism , Colforsin/pharmacology , Cyclic AMP/pharmacology , Cystic Fibrosis Transmembrane Conductance Regulator , Eccrine Glands/metabolism , Electric Conductivity , Epithelial Cells , Epithelium/metabolism , Female , Humans
17.
Postgrad Med ; 95(4): 127-9, 133-4, 139-40, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8121849

ABSTRACT

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.


Subject(s)
Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/mortality , Cardiovascular Diseases/etiology , Eye Diseases/etiology , Female , Hematologic Diseases/etiology , Humans , Longevity , Lung Diseases/etiology , Male , Rheumatoid Nodule/etiology
18.
Am J Physiol ; 264(4 Pt 1): C925-31, 1993 Apr.
Article in English | MEDLINE | ID: mdl-7682778

ABSTRACT

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)


Subject(s)
Chlorides/metabolism , Cystic Fibrosis/metabolism , Energy Metabolism , Membrane Proteins/metabolism , Adenosine/pharmacology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Adenylyl Imidodiphosphate/pharmacology , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Cell Line , Cell Membrane Permeability , Cyclic AMP/analogs & derivatives , Cyclic AMP/metabolism , Cyclic AMP/pharmacology , Cystic Fibrosis Transmembrane Conductance Regulator , Deoxyglucose/pharmacology , Electric Conductivity/drug effects , Epithelium/drug effects , Epithelium/physiology , Humans , Kinetics , Membrane Potentials/drug effects , Thionucleotides/pharmacology , Time Factors
19.
Am J Physiol ; 262(4 Pt 1): C891-8, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1314491

ABSTRACT

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)


Subject(s)
Sweat Glands/cytology , Cells, Cultured , Chlorides/physiology , Cyclic AMP/pharmacology , Electric Conductivity , Epithelial Cells , Epithelium/physiology , Humans , Isoproterenol/pharmacology , Methacholine Chloride/pharmacology , Potassium/physiology , Sodium/physiology , Sweat Glands/physiology
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