PubMed HealthSearch

Biomedical subjects

L Cameron

Publications and source records attributed to L Cameron.

At least 19 recordsLinked to original sources

Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis.

Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.

Administration, Intranasal

Expression of epsilon germ-line gene transcripts and mRNA for the epsilon heavy chain of IgE in nasal B cells and the effects of topical corticosteroid.

We have studied the expression of the gene encoding the epsilon heavy chain of IgE in nasal B cells of hayfever patients. We developed probes to detect transcripts of the epsilon germ-line gene and the rearranged gene by in situ hybridization of biopsy sections from the nasal mucosa. We compared tissue from hayfever patients out of season with that of normal controls, and also of hayfever patients treated with topical corticosteroid (fluticasone propionate) or placebo for 6 weeks and then challenged with antigen. epsilon chain mRNA was expressed in an unexpectedly high proportion of nasal B cells of both hayfever patients and normal subjects. However, although similar numbers of B cells were found in both groups, the proportion of cells that express epsilon chain mRNA was several times higher in the hayfever patients. No transcripts of the epsilon germ-line gene were detected in either group before allergen challenge. When hayfever patients were administered antigen locally, early (10-30 min) and late (1-24 h) symptoms ensued. After 24 h, coincident with an increase in the number of cells expressing mRNA for IL-4 in the tissue, epsilon germ-line gene transcripts appeared in the nasal B cells. The induction by allergen of IL-4 mRNA and epsilon germ-line gene transcripts was suppressed by fluticasone propionate treatment. Our results suggest that local IgE synthesis and cytokine regulation of heavy chain switching to IgE occur in the nasal mucosa.

Administration, Topical

Cochliobolic acid, a novel metabolite produced by Cochliobolus lunatus, inhibits binding of TGF-alpha to the EGF receptor in a SPA assay.

Cochliobolic acid (1), a novel biologically active natural product, is produced by submerged fermentation of Cochliobolus lunatus. Compound 1 was determined to be a novel polyketide possessing a substituted tetrahydrofuran ring, a conjugated polyene chain and a 1,2-diketone moiety, by interpretation of NMR, MS, and UV/vis spectroscopic data. Compound 1 inhibits the binding of TGF-alpha to the EGF receptor of the human epidermal cell line A431 in a SPA assay with an IC50 of 1.6 microM.

Chemical Phenomena

Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma.

The histopathology of bronchial asthma is associated with structural changes within the airways, including subepithelial fibrosis, as well as chronic eosinophilic inflammation. The mechanisms responsible for this tissue remodeling, and in particular the role of inflammatory cells, remain to be established. Transforming growth factor-beta (TGF-beta) is a potent profibrotic cytokine which may contribute to the thickening of the reticular lamina by the deposition of collagen fibers. To investigate the molecular mechanisms underlying these structural changes, we have investigated the expression of TGF-beta1 mRNA and immunoreactivity within the bronchial mucosa of mild to severe asthmatic individuals and normal control subjects using the techniques of in situ hybridization and immunocytochemistry. As eosinophils are prominent within the asthmatic airway and are known to synthesize pro-inflammatory cytokines, the presence of TGF-beta1 mRNA and immunoreactive protein in eosinophils was also examined. Asthmatic individuals exhibited a greater expression of TGF-beta1 mRNA and immunoreactivity in the airways submucosa than normal control subjects (P < 0.05), and these increases were directly related to the severity of the disorder. The extent of airways fibrosis, as detected histochemically, was also increased in asthmatics compared with normal control subjects (P < 0.005). In asthmatic subjects, the presence of subepithelial fibrosis was associated with the severity of the disease and correlated with the decline in forced expiratory volume in 1 s (r2 = 0.78; P < 0.05). Within the asthmatic airways, EG2-positive eosinophils represented the major source of TGF-beta1 mRNA and immunoreactivity. These results provide evidence that TGF-beta1 may play a role in the fibrotic changes occurring within asthmatic airways and that activated eosinophils are a major source of this cytokine.

Adult

Eotaxin mRNA and protein expression in chronic sinusitis and allergen-induced nasal responses in seasonal allergic rhinitis.

Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to the site of allergic inflammation. The aims of this study were to determine the expression of eotaxin in nasal biopsies from allergic and nonallergic individuals with chronic severe sinusitis, and to examine whether the expression of this chemokine is upregulated following allergen challenge in the nasal mucosa of patients with allergic rhinitis. We also undertook to phenotype of inflammatory cells within the submucosa expressing eotaxin mRNA. Nasal turbinate tissue from 16 individuals with allergic or nonallergic chronic sinusitis and 10 normal controls were examined for the presence of eotaxin mRNA and immunoreactivity by in situ hybridization and immunocytochemistry. The numbers of cells expressing eotaxin mRNA were also determined after either allergen or diluent challenge in atopic subjects with a history of allergic rhinitis. There was a constitutive expression of eotaxin-immunoreactivity and the presence of eotaxin mRNA-positive cells in nasal biopsies from normal individuals. Compared with normal controls, the numbers of cells expressing eotaxin mRNA and protein were significantly increased in both allergic and nonallergic sinusitis (P < 0.001). Eotaxin mRNA was expressed by nasal epithelial cells and primarily colocalized to CD68-positive macrophages within the subepithelium. In subjects with allergic rhinitis, allergen challenge markedly increased the numbers of cells expressing eotaxin mRNA and immunoreactivity in the epithelial and subepithelial cell layers (P < 0.05). This could be largely attributed to a local increase in eotaxin production within the nasal tissues. The results of this study demonstrate the constitutive expression of eotaxin and show that the numbers of cells expressing eotaxin mRNA are increased within the epithelial and subepithelial layers of the nasal mucosa in individuals with chronic sinusitis. Furthermore, allergen challenge of the nasal mucosa in atopic subjects results in a local upregulation of eotaxin expression. These data suggest a potential role for this chemokine in the pathogenesis of allergic and nonallergic eosinophilic inflammation characterizing chronic sinusitis and allergic rhinitis.

Adult

Sequence analysis of the bicistronic Drosophila X virus genome segment A and its encoded polypeptides.

Drosophila X virus represents the entomobirnavirus genus of the Family Birnaviridae. Segment A of this bisegmented dsRNA containing virus was cloned and sequenced. The 3360-bp-long nucleotide sequence revealed the presence of two open reading frames (ORFs). A large ORF of 3096 nucleotides, which is flanked by a 107-bp 5' and a 157-bp 3'-untranslated region, and a 711-nucleotide-long small ORF located within the carboxy half of the large ORF but in a different reading frame. The large ORF encodes a 114-kDa polyprotein which is cotranslationally processed by the virus-coded protease VP4 to generate preVP2, VP3, and VP4 (VP1 is encoded by genome segment B). N-terminal amino acid sequencing of VP3 and VP4 established the order NH2-preVP2-VP4-VP3-COOH within the polyprotein. The small ORF straddles the VP4/VP3 junction and is capable of encoding a basic, arginine-rich 27-kDa polypeptide which so far has not been detected in infected cells. The amino acid sequences specified by the two ORFs were compared to those of infectious pancreatic necrosis virus (IPNV) and infectious bursal disease virus (IBDV) that represent the two other genera (aquabirnavirus and avibirnavirus) of the Birnaviridae family. Significant sequence homology among the three viruses was found to be restricted to the amino and carboxy regions of preVP2 and to a small 21-residue-long domain near the carboxy terminal region of VP3. Significant sequence homology is exhibited by the small ORFs of the three viruses.

Amino Acid Sequence

Imaging protein kinase C activation in living sea urchin eggs after fertilization.

The fluorescent dye NBD-phorbol acetate was used to visualize the activation of protein kinase C (PKC) in living Lytechinus pictus eggs during fertilization. The dye interacts directly with PKC as determined using a competitive binding assay. Quantitative image analysis of sequential images from laser-scanning confocal microscopy showed a significant reorganization of the signal in the vicinity of the cortical granules and the plasma membrane that began immediately following fertilization and persisted up to 1 hr (P<0.0001). At the concentrations employed, the NBD-phorbol dye was not capable of inducing a significant translocation of the fluorescent signal to the membrane, nor did it appear to interfere with the cell cycle. It therefore seems likely that the present in vivo results reflect the previously reported in vitro activation of protein kinase C immediately subsequent to fertilization. Such an interpretation is parsimonious with the results of parallel subcellular fractionation experiments using an N-terminal polyclonal antibody to sea urchin PKC which showed a significant (P<0.037) translocation of the enzyme from the cytosolic fraction to the membrane fraction 40 min subsequent to fertilization. This study supports and extends previous in vitro data suggesting that PKC activation subsequent to fertilization occurs at or near the egg plasma membrane, perhaps in association with arachadonic acid-rich cortical granules.

Animals

Conservation of energy, uncertainty reduction, and swift utilization of medical care among the elderly: study II.

This study examined age differences in the timing of the decision to seek medical care. The data were obtained from a longitudinal study of 366 community dwelling adults aged 45 to 93 years. Subjects were paired for age, gender, and health status, and both members of a pair were interviewed when either one initiated a medical visit for a new problem. This allowed the authors to examine delay in care-seeking for individuals with new symptoms who did not seek care as well as those who did. Survival analysis was used to test hypotheses respecting age differences for total delay (the time from first noticing symptoms until calling for care) and its two constituent phases: appraisal delay (symptom onset until deciding one was ill) and illness delay (decision one was ill until calling for care). Older persons were expected to be more avoidant of uncertainty and conserving of physical and psychic resources and thus quicker to seek care. The results and findings on reasons for delay support the uncertainly avoidance hypothesis but did not replicate signs of higher levels of avoidance behavior by middle-aged subjects than by older subjects.

Age Factors

Endothelin-1 release from the isolated perfused rat adrenal gland is elevated acutely in response to increasing flow rates and ACTH(1-24).

Data obtained from the perfused rat adrenal gland demonstrated that immunoreactive endothelin (ET) was rapidly released in response to both mechanically increased flow rates through the gland and the increase in flow rate caused by ACTH(1-24). There was a good temporal correlation between the release of immunoreactive ET and increasing flow rates through the isolated perfused adrenal gland, which was detected immediately and was continuous throughout the period during which flow rate was elevated. The effects of exogenously administered ET were found to be transient; it caused a decrease in vascular perfusion lasting < 30 min. In these respects ET fulfils the requirements for it to be a short term paracrine mediator of adrenocortical function.

Adrenal Glands

The prevalence of back pain, hand discomfort, and dermatitis in the US working population.

OBJECTIVES: The purpose of the study was to provide the health care and public health communities with national prevalence estimates of selected conditions in the US working population. METHODS: National prevalence estimates of self-reported conditions among working people were calculated from data collected for the 1988 Occupational Health Supplement to the National Health Interview Survey. RESULTS: The highest prevalence estimates were found among occupational groups. For example, the prevalence of back pain due to an injury at work among truck drivers was 6.7%; back pain due to repeated activities at work among mechanics and repairers of heavy equipment and machinery was 10.5%; hand discomfort among operators of machines that process metal, plastic, stone, and glass was 23.5%; and dermatitis due to contact with substances at work among physicians, dentists, nurses, pharmacists, and dietitians was 5.6%. CONCLUSIONS: A substantial proportion of these conditions among occupational groups with the highest prevalence estimates are occupational in origin. These prevalence estimates identify occupations in which efforts are needed to prevent these conditions.

Adult

The US prevalence of self-reported carpal tunnel syndrome: 1988 National Health Interview Survey data.

To estimate the prevalence of carpal tunnel syndrome among US adults, data from the Occupational Health Supplement of the 1988 National Health Interview Survey were analyzed. Based on a sample of 44,233 households (response rate, 91.5%), an estimated 1.55% (2.65 million) of 170 million adults self-reported carpal tunnel syndrome in 1988. Females and Whites had a higher prevalence of self-reporting carpal tunnel syndrome than males and non-Whites, respectively. Among 127 million adults who worked during the 12 months before the survey, 0.53% (0.68 million) reported that their "prolonged" hand discomfort was called carpal tunnel syndrome by a health care provider.

Activities of Daily Living

Symptom representations and affect as determinants of care seeking in a community-dwelling, adult sample population.

The cognitive and emotional determinants of health-care utilization were assessed for middle-aged and older adults matched on age, gender, and health status. Both members of a pair were interviewed when either initiated a medical visit. Interviews were based on a self-regulatory model that assumed that Ss would use symptoms to create and update representations and coping procedures. Care seekers reported more symptoms than did matched controls but did not report more symptoms than did matched controls with new symptoms. The mere presence of atypical symptoms was insufficient to trigger care seeking. Care seeking is driven by well-developed representations of a serious health threat, perceptions of inability to cope with the threat, advice to seek care, and life stress.

Adaptation, Psychological

Structure, expression, chromosomal location and product of the gene encoding Adh2 in Petunia.

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes.

Alcohol Dehydrogenase

Sprint training increases human skeletal muscle Na(+)-K(+)-ATPase concentration and improves K+ regulation.

This study investigated the effects of sprint training on muscle Na(+)-K(+)-adenosinetriphosphatase (ATPase) concentration, plasma [K+] regulation, muscle performance, and fatigue during severe intermittent exercise. Six untrained male subjects underwent intensive cycle-sprint training for 7 wk. Muscle biopsies were taken at rest from the vastus lateralis muscle before and after 7 wk of training and were assayed for Na(+)-K(+)-ATPase concentration using vanadate-facilitated [3H]ouabain binding to intact samples. Before and after the training period, subjects performed four maximal 30-s exercise bouts (EB) on a cycle ergometer, each separated by a 4-min recovery. Arterialized venous blood samples were drawn immediately before and after each sprint bout and were analyzed for plasma [K+]. The work output was significantly elevated (11%) across all four EBs after training. The muscle [3H]ouabain binding site concentration was significantly increased (16%) from 333 +/- 19 to 387 +/- 15 (SE) pmol/g wet wt after training but was unchanged in muscle obtained from three control subjects. Plasma [K+] rose by 1-2 mmol/l with each EB and declined rapidly by the end of each recovery period. The increases in plasma [K+] resulting from each EB were significantly lower (19%) after training. The ratios of rise in plasma [K+] relative to work output during each EB were also significantly lower (27%) after training. The increased muscle [3H]ouabain binding site concentration and the reduced ratio of rise in [K+] relative to work output with exercise are both consistent with improved plasma and skeletal muscle K+ regulation after sprint training.

Adolescent

Characterization of a scintillation proximity assay to detect modulators of transforming growth factor alpha (TGF alpha) binding.

A scintillation proximity assay (SPA) for transforming growth factor alpha (TGF alpha) using SPA beads coated with A431 membranes has been studied. Binding of TGF alpha to the beads was characteristic of a receptor interaction. A class of high-affinity receptors for [125I]-TGF alpha (Kd = 0.10-0.26 nM) was detected by competition studies between [125I]TGF alpha and cold TGF alpha and by analysis of association and dissociation rate constants. An antibody to the epidermal growth factor receptor (clone 528) inhibited binding of [125I]TGF alpha (IC50 = 0.20 micrograms/ml), but an anti-TGF alpha antibody (clone 134A-2B3) (less than 25 micrograms/ml) did not block binding. Suramin inhibited [125I]-TGF alpha binding (IC50 = 0.20 mM). The ether lipids 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphocholine, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine, and rac-lyso-platelet activating factor inhibited TGF alpha binding (IC50 values of 49, 69, and 57 microM, respectively). SPA is a convenient method for identifying agents that may act by interfering with TGF alpha binding.

Antibodies, Monoclonal

Effects of tamoxifen on cardiovascular risk factors in postmenopausal women.

OBJECTIVE: To determine the effects of tamoxifen on risk factors for cardiovascular disease in disease-free postmenopausal women. DESIGN: Double-blind, placebo-controlled, randomized 2-year clinical trial. SETTING: University health sciences center. PATIENTS: Clinically postmenopausal women (140) with a diagnosis of axillary node-negative breast cancer, who were disease-free by laboratory and clinical evaluations. MEASUREMENTS: Levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, glucose, weight, blood pressure, and reported exercise and work activity were measured. MAIN RESULTS: Postmenopausal women receiving tamoxifen were evaluated at 3- or 6-month intervals during a 2-year assessment period and showed a mean decrease of 12% in total cholesterol levels (at 24 months -0.672 mmol/L; 95% CI, -0.839 to -0.505 mmol/L) and a mean decrease of 20% in calculated low-density lipoprotein (LDL) cholesterol levels (at 24 months, -0.725 mmol/L; 95% CI, -0.868 to -0.583 mmol/L) (P less than 0.001). Women with greater baseline cholesterol levels had greater decreases with tamoxifen treatment. Levels of HDL cholesterol decreased in patients treated with tamoxifen, but this decrease was only statistically significant at one of five measurement times. Apolipoprotein A-I levels increased significantly at the two time points at which it was measured (P = 0.02), and apolipoprotein B levels decreased significantly at these times (P less than 0.01) in patients treated with tamoxifen. Plasma glucose levels, reported exercise and work activity, reported smoking, weight, and systolic and diastolic blood pressures did not change with treatment. CONCLUSION: During 2 years of treatment, tamoxifen showed generally favorable effects on the lipid and lipoprotein profile of treated postmenopausal women. These effects may partially explain the decrease in adverse events and in mortality related to coronary heart disease seen in patients receiving adjuvant tamoxifen treatment.

Apolipoprotein A-I