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Biomedical subjects

J M Clark

Publications and source records attributed to J M Clark.

At least 55 records · Page 3Linked to original sources
PubMed2000

Community health survey in an urban African-American neighborhood: distribution and correlates of elevated blood pressure.

While considerable improvements have been made over the last 30 years in hypertension (HTN) awareness, treatment, and control, a recent reversal of these trends has been documented with African-American adults, particularly among those continuing to suffer from uncontrolled hypertension and its adverse consequences. This paper presents data from a cross-sectional representative survey of the health status of an urban African-American community. The study was designed in partnership with community leadership to improve HTN care and control. The baseline survey was a face-to-face interview (including blood pressure [BP] measurements) of 2,196 adults residing in randomly selected blocks in the Sandtown-Winchester neighborhood in Baltimore City. These sample data were compared with national data from the NHANES III survey, and demonstrated similar awareness of hypertension. However, hypertension control rates among treated hypertensives were significantly lower in the study community (28%) than in the national survey (44%). Compared with normotensive individuals, those with HTN were significantly older, had less education, were less likely to be employed, and had lower annual incomes. Individuals with HTN were also significantly more likely to rate their health as poor/fair, to report a history of heart disease, stroke, diabetes, kidney disease, obesity, high cholesterol, and lack of exercise, as well as to be at greater risk of alcoholism or alcohol problems. Hypertensive individuals (88% with reported prior history, 12% newly detected) were significantly more likely to have a usual source of care, have seen a health professional in the last 12 months, and to be extremely satisfied with the provider; however, 20% of individuals with hypertension reported no health insurance. These data indicate the need for focused interventions to enhance hypertension maintenance of care and adherence to treatment.

Adult↗
PubMed2000

Uncontrolled central adenoid cystic carcinoma: case report.

Central adenoid cystic carcinomas are rare malignancies that are believed to arise in ectopic salivary gland tissue within the maxilla or mandible. We describe the diagnosis and treatment of a central adenoid cystic carcinoma in a 54-year-old man, which we believe was a recurrence of an earlier growth that had not been completely excised. We also present a review of the literature.

Carcinoma, Adenoid Cystic↗
PubMed1999

Characterization of the regulation of phospholipase D activity in the detergent-insoluble fraction of HL60 cells by protein kinase C and small G-proteins.

Phospholipase D (PLD) activity has been shown to be GTP-dependent both in vivo and in vitro. One protein that confers GTP sensitivity to PLD activity in vitro is the low-molecular-mass G-protein ADP-ribosylation factor (Arf). However, members of the Rho family and protein kinase C (PKC) have also been reported to activate PLD in various cell systems. We have characterized the stimulation of PLD in HL60 cell membranes by these proteins. The results demonstrate that a considerable proportion of HL60 PLD activity is located in a detergent-insoluble fraction of the cell membrane that is unlikely to be a caveolae-like domain, but is probably cytoskeletal. This PLD activity required the presence of Arf1, a Rho-family member and PKC for efficient catalysis of the lipid substrate, suggesting that the activity represents PLD1. We show that recombinant human PLD1b is regulated in a similar manner to HL60-membrane PLD, and that PKCalpha and PKCdelta are equally effective PLD activators. Therefore maximum PLD activity requires Arf, a Rho-family member and PKC, emphasizing the high degree of regulation of this enzyme.

ADP-Ribosylation Factor 1↗
PubMed1999

Disruption of the Sparc locus in mice alters the differentiation of lenticular epithelial cells and leads to cataract formation.

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein that regulates cellular adhesion and proliferation. In this report, we show that SPARC protein is restricted to epithelial cells of the murine lens and ends abruptly at the equatorial bow region where lens fiber differentiation begins. SPARC protein was not detected in the lens capsule or in differentiated lens fibers. SPARC-null mice developed cataracts at approximately 3-4 months after birth, at which time posterior subcapsular opacities were observed by slit lamp ophthalmoscopy. Histological analyses of ocular sections from 3-month old animals revealed several microscopic abnormalities present in the SPARC-null mice but absent from the wild-type animals. Fiber cell elongation was incomplete posteriorly and resulted in displacement of the lenticular nucleus to the posterior of the lens. Nuclear debris was present in the posterior subcapsular region of the lens, an indication of the abnormal migration and elongation of either fetal or anterior epithelial cells, and the bow region was disrupted and vacuolated. In the anterior lens, the capsule appeared to be thickened and was lined by atypical, plump cuboidal epithelium. Moreover, anterior cortical fibers were swollen. Polyacrylamide gel electrophoresis of the epithelial, cortical and nuclear fractions of wild-type and SPARC-null lenses indicated no significant differences among the alpha-, beta-, and gamma-crystallins. Expression of alphaB-crystallin appeared similar in fiber cells of wild-type and SPARC-null lenses, although the distribution of alphaB-crystallin was asymmetric in SPARC-null lenses as a result of abnormal lens fiber differentiation. No evidence of atypical extracellular matrix deposition in areas other than the capsule was detected in wild-type or SPARC-null lens at 3 months of age. We conclude that the disruption of the Sparc locus in mice results in the alteration of two fundamental processes of lens development: differentiation of epithelial cells and maturation of fiber cells.

Animals↗
PubMed1999

Expression and characterization of recombinant mast cell tryptase.

Tryptase, a serine protease, is the major protein component in mast cells. In an animal model of asthma, tryptase has been established as an important mediator of inflammation and late airway responses induced by antigen challenge. Human tryptase is notable for its tetrameric structure, requirement of heparin for stability, and resistance to endogenous inhibitors. Human protryptase was expressed as a recombinant protein in Pichia pastoris. The recombinant protein consisted of two forms of protryptase, one containing the entire propeptide and the other containing only the Val-Gly dipeptide at its amino terminus. Isolation of active recombinant tryptase required a two column purification protocol and included a heparin- and dipeptidyl peptidase I-dependent activation step. Purified recombinant tryptase migrated as a tetramer on a gel filtration column and displayed kinetic parameters identical to those of a native tryptase obtained from HMC-1 cells, a human mast cell line. Recombinant and HMC-1 tryptase exhibited comparable sensitivities to an array of protein and low-molecular-weight inhibitors, including one that is highly specific for tryptase (APC-1167). Similarly, the recombinant enzyme cleaved both alpha- and beta-chains of fibrinogen to generate fibrinogen fragments indistinguishable from those generated by HMC-1-derived tryptase. Thus, recombinant tryptase expressed in P. pastoris displays physical and enzymatic properties essentially identical to the native enzyme. This system provides a cost-effective and easy to manipulate expression system that will enable the functional characterization of this unique enzyme.

Binding Sites↗
PubMed1999

Evaluating the effectiveness of a smoking cessation intervention designed for nurses.

The purpose of this study was to evaluate the effectiveness of offering an individualised approach to smoking cessation to qualified nurses and student nurses in Northern Ireland. Twenty-two qualified nurses and 32 student nurses enrolled in the intervention. A further 23 qualified nurses and 33 student nurses expressed interest in giving up smoking, but did not wish to be included in the intervention. They were assigned to the comparison group. Objective verification utilising salivary cotinine measurements of continuous abstinence at 6 months and 1 year demonstrated that 24% of student and qualified nurses in the intervention groups stopped smoking compared with 7% of those in the comparison groups. Both of these differences are statistically significant (Fisher's Exact Probability Test p = < 0.05). This suggests that the individualised approach as used in this study is an appropriate method of helping motivated nurses to quit.

Adolescent↗
PubMed1999

Systemic reactivation of otitis media with effusion in a rat model.

OBJECTIVE: This study addresses the interaction of bacterial antigens, specifically peptidoglycan-polysaccharide (PG-PS) and lipopolysaccharide (LPS), in the induction and reactivation of mucoid middle ear effusions. METHODS: Twenty-seven rats underwent eustachian tube obstruction before inoculation of the middle ear bulla with PG-PS. Three weeks later, after resolution of all middle ear effusions, 6 rats were randomly selected and euthanized as the first control group (control I). The remaining 21 animals were randomly assigned to 3 groups that received intravenous injections of Krebs Ringer (control II), PG-PS, and LPS, respectively. These rats were euthanized 2 days after intravenous injection. Middle ear mucin production and histologic changes were measured in all animals. RESULTS: The mean concentrations of mucin were 0.94 +/- 0.52 mg/mL, 0.41 +/- 0.87 mg/mL, 16.33 +/- 3.67 mg/mL, and 1.15 +/- 0.41 mg/mL in the control I, control II, PG-PS, and LPS groups, respectively. Thus the mean concentration of mucin in the middle ear lavage samples was significantly greater in rats that were injected intravenously with PG-PS than in rats in other groups (P < 0.05). Histologic analyses demonstrated a greater degree of goblet cell hyperplasia in the PG-PS group than in other groups. CONCLUSIONS: This is the first animal model of recurring otitis media with effusion in which a systemic injection of PG-PS was used to reactivate a middle ear effusion in rats previously primed with a transtympanic injection of PG-PS. This study suggests that after otitis media with effusion has resolved, it may be reactivated by the presence of bacterial antigens and/or cytokines in the systemic circulation.

Animals↗
PubMed1999

Hapten design in the development of competitive enyme-linked immunosorbent assays for genotoxic metabolites of alachlor.

The acetanilide compounds 2-chloro-2',6'-diethylacetanilide (CDA) and 2-hydroxy-2',6'-diethylacetanilide (HDA) are environmental degradative products of the chloroacetanilide herbicide alachlor. CDA, HDA, and alachlor are ground and surface water contaminants. CDA and HDA are genotoxic in bacterial and mammalian test systems. This paper reports hapten design in the development of two competitive enzyme-linked immunosorbent assays (cELISA) for the detection of CDA and HDA. Chloroacetanilide herbicides and other alachlor metabolites that may be present in environmental samples do not cross-react with the detection of CDA and HDA. Solid-phase extraction of CDA and HDA residues from aqueous samples results in a 1000-fold concentration factor, resulting in an effective detection limit of 15 pg/mL for both assays. The specificity of the cELISAs required preservation of the degree of substitution of the acetanilide moiety in the hapten design. The hapten synthesis strategies are suitable for metabolites of other chloroacetanilide herbicides (i.e., acetochlor, butachlor, metolachlor, and propachlor).

Acetamides↗
PubMed1999

Lens cytoskeleton and transparency: a model.

The function of the cytoskeleton in lens was first considered when cytoplasmic microtubules were observed in elongating fibre cells of the chick lens nearly 40 years ago. Since that time, tubulin, actin, vimentin and intermediate filaments have been identified and found to function in mitosis, motility and cellular morphology during lens cell differentiation. A role for the cytoskeleton in accommodation has been proposed and modification of the cytoskeletal proteins has been observed in several cataract models. Recently, a progressive increase in protein aggregation and lens opacification was found to correspond with the loss of cytoskeletal protein in the selenite model for cataract. In the present report a model is proposed for the role of tubulin, actin, vimentin, spectrin and the lens-specific filaments, filensin and CP49, in the establishment and maintenance of transparent lens cell structure.

Animals↗
PubMed1999

The surface contour of articular cartilage in an intact, loaded joint.

The friction coefficients measured in diarthrodial joints are small. Theories of joint lubrication attribute this efficiency to entrapment or movement of synovial fluid, yet anatomical models of the surface are based on studies of isolated fragments of cartilage, not functional joints. To investigate the functional interrelationship of joint surfaces and synovial fluid, the ultrastructure of loaded joints was examined. Twenty-four New Zealand white rabbit knee joints were loaded either statically or moved ex vivo using simulated muscle forces and then plunge-frozen under load. After fixation in the frozen/loaded state by freeze-substitution fixation, the medial joint compartments were embedded in epoxy resin while still articulated. Bone was trimmed away from the articular surfaces, permitting the cartilage to be sectioned for light and electron microscopy. These joint surfaces were then compared with controls which were not loaded, not moved or had been disarticulated prior to embedding. Articular surfaces of loaded joints were smooth at magnifications from x 35 to x 7500, whereas the tibial surfaces of nonloaded joints were irregular. Small pools of joint fluid were observed at the meniscal edge and beneath the anterior horn of the meniscus. At magnifications of x 40000, the joint surfaces were separated by a uniform 100 nm space containing fluid. An amorphous, electron dense articular surface lamina was present but, when loaded, was thicker and flatter than previously reported. No surface pits or bumps were visible in embedded, loaded joints. This is the first ultrastructural study of intact loaded joints. The findings suggest that fluid film lubrication is present in diarthrodial joints, but the fluid sequestration postulated in several models is not apparent.

Animals↗
PubMed1999

Potential for aging female Aedes aegypti (Diptera: Culicidae) by gas chromatographic analysis of cuticular hydrocarbons, including a field evaluation.

Gas chromatography with flame-ionization detection was used to measure the time-associated, quantitative changes in the cuticular hydrocarbons of female Aedes aegypti (L.). Cohorts of unstressed Ae. aegypti, Rockefeller strain, were reared and held at 3 constant temperatures (24, 28, and 30 degrees C). Five females from each cohort were taken at 33 degree-day (DD) intervals from 0 to 231 DD (using 17 degrees C as the threshold temperature). Quantitative changes over time of cuticular hydrocarbons associated with gas chromatographic peaks 1 and 5 were identified as having promise for age grading. The relative abundance of peak 1 (pentacosane) decreased linearly from 0 to 132 DD, whereas peak 5 (nonacosane) increased linearly over the same period. Suboptimal larval conditions (crowded and starved), which resulted in physiological stress (decreased size), had negligible effect on the relative abundance of pentacosane and nonacosane. Additionally, the rate of change in the relative abundance of pentacosane and nonacosane were the same for both a recently colonized Chachoengsao (Thailand) strain of Ae. aegypti compared with the long-colonized Rockefeller (Caribbean) strain over a 0-99 DD interval. Two linear regression models, one based on the relative abundance of pentacosane and the other on the logit transformation of these values, were developed for aging female Ae. aegypti. A blind study using laboratory-reared mosquitoes and a mark-release-recapture experiment using field mosquitoes validated these age-grading models and produced promising results for aging females up to 132 DD (19, 12, and 10 calendar days at 24, 28 and 30 degrees C, respectively). Therefore the regression models, based on the relative abundance of these 2 cuticular hydrocarbons, appeared to be a useful approach for age-grading Ae. aegypti up to at least 12 d of age regardless of environmental conditions (temperature and stress) and population history (origin and colonization time).

Aedes↗
PubMed1999

Aedes aegypti (Diptera: Culicidae) age determination by cuticular hydrocarbon analysis of female legs.

We previously described methods for age-grading female Aedes aegypti (L.) by gas chromatographic (GC) analysis of whole-body cuticular hydrocarbon patterns. Two regression models were developed that were based on the age-dependent, relative abundance of 2 cuticular hydrocarbons, pentacosane (GC peak 1) and nonacosane (GC peak 5). We have refined this method so that only the legs are required to age individual females. Two new regression models were developed that also use the relative abundance of a 3rd cuticular hydrocarbon, octacosane (GC peak 4). These models improve the overall accuracy of the cuticular hydrocarbon method for aging female mosquitoes, especially for older females from 132 to 165 degree-days (DD) of age (12-15 calendar days at 28 degrees C). The correlation coefficients (R2) for the best-fitted linear regression models for aging females from 0 to 132 and 0-165 DD were 0.80 and 0.81, respectively (P < 0.001 in all cases). The use of leg cuticular hydrocarbons for estimating the age of female Ae. aegypti has a significant advantage over whole-body extracts as indicated by the decreased variability associated with the relative abundance of pentacosane and the expanded range over which the models were able to predict age accurately by the addition of the relative abundance of octacosane.

Aedes↗
PubMed1999

Polyisoprenyl phosphate (PIPP) signaling regulates phospholipase D activity: a 'stop' signaling switch for aspirin-triggered lipoxin A4.

It is of wide interest to understand how opposing extracellular signals (positive or negative) are translated into intracellular signaling events. Receptor-ligand interactions initiate the generation of bioactive lipids by human neutrophils (PMN), which serve as signals to orchestrate cellular responses important in host defense and inflammation. We recently identified a novel polyisoprenyl phosphate (PIPP) signaling pathway and found that one of its components, presqualene diphosphate (PSDP), is a potent negative intracellular signal in PMN that regulates superoxide anion generation by several stimuli, including phosphatidic acid. We determined intracellular PIPP signaling by autocoids with opposing actions on PMN: leukotriene B4 (LTB4), a potent chemoattractant, and lipoxin A4 (LXA4), a 'stop signal' for recruitment. LTB4 receptor activation initiated a rapid decrease in PSDP levels concurrent with activation of PLD and cellular responses. In sharp contrast, activation of the LXA4 receptor reversed LTB4-initiated PSDP remodeling, leading to an accumulation of PSDP and potent inhibition of both PLD and superoxide anion generation. Thus, an inverse relationship was established for PSDP levels and PLD activity with two PMN ligands that evoke opposing responses. In addition, PSDP directly inhibited both isolated human recombinant (Ki = 6 nM) and plant (Ki = 20 nM) PLD. Together, these findings link PIPP remodeling to intracellular regulation of PMN function and suggest a role for PIPPs as lipid repressors in signal transduction, a novel mechanism that may also explain aspirin's suppressive actions in vivo in cell signaling.

Aspirin↗
PubMed1999

Effects of prolonged oxygen exposure at 1.5, 2.0, or 2.5 ATA on pulmonary function in men (predictive studies V).

As part of a study of human organ O2 tolerance, lung flow-volume and spirometric measurements were performed repeatedly before, during, and after continuous O2 exposures at 1.5, 2.0, and 2.5 ATA for average durations of 17.7, 9.0, and 5.7 h, respectively (effects of O2 breathing at 3.0 ATA for 3.5 h were reported previously; J. M. Clark, R. M. Jackson, C. J. Lambertsen, R. Gelfand, W. D. B. Hiller, and M. Unger. J. Appl. Physiol. 71: 878-885, 1991). Additional measurements of pulmonary mechanical function, gas exchange, and alveolar inflammatory cells were obtained before and after O2 exposure. Rates of pulmonary symptom development and lung volume reduction increased progressively with elevation of O2 pressure. Average rates of vital capacity reduction over a useful range of O2 pressures provided a valuable general description of pulmonary O2 tolerance in humans. However, the existence of multiple pulmonary effects of O2 toxicity and the complexity of their interactions require awareness that deviations from the average relationships may occur in different individuals or under varying conditions of O2 exposure and subsequent recovery. The associated pulmonary function deficits may represent responses to a composite of direct and indirect effects of O2 poisoning, along with related consequences and subsequent reactions to those effects.

Acid-Base Equilibrium↗
PubMed1999

Generating fixed-length sequences satisfying any given nth-order transition probability matrix.

An experimental design involving sequences of m distinct events can be conceptualized as an nth-order transition probability matrix specifying the probabilities with which each of the m distinct events is to follow certain n-grams. This paper describes a general method for constructing sequences of shortest possible length that satisfy any such matrix and presents a computer program that randomly generates such sequences.

Algorithms↗
PubMed1998

Involvement of p16CDKN2A in cell cycle delays after low dose UV irradiation.

Ultraviolet (UV) radiation contributes to the aetiology of melanoma, but the precise mechanistic details are still unclear. The CDKN2A gene which is associated with familial and sporadic melanoma, encodes a tumour suppressor, p16. We have previously shown that in response to low doses of UV radiation the level of p16 increases, and that this correlates with a G2 delay. Here we report that in melanoma cell lines which do not express p16, or express a mutant p16, no G2 delay is observed in response to UV. The loss of functional p16 also correlates with an increase in DNA damage as judged by increased numbers of bi- and multinuclear cells and cells containing 1-2 micronuclei following UV irradiation. This work provides a further link between UV radiation, CDKN2A and melanoma, suggesting that the functional inactivation of CDKN2A disrupts a p16-dependent G2 cell cycle checkpoint, thus contributing to the development of this neoplasm.

Cell Cycle↗