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Biomedical subjects

K Wiley

Publications and source records attributed to K Wiley.

At least 19 recordsLinked to original sources
PubMed2002

Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.

Although prostate cancer is the most common non-cutaneous malignancy diagnosed in men in the United States, little is known about inherited factors that influence its genetic predisposition. Here we report that germline mutations in the gene encoding 2'-5'-oligoadenylate(2-5A)-dependent RNase L (RNASEL) segregate in prostate cancer families that show linkage to the HPC1 (hereditary prostate cancer 1) region at 1q24-25 (ref. 9). We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway and has been suggested to be a candidate tumor suppressor gene. We found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozyogous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway might provide opportunities for developing therapies for those with prostate cancer.

Adenine Nucleotides↗
PubMed2001

Evidence for a prostate cancer linkage to chromosome 20 in 159 hereditary prostate cancer families.

Prostate cancer is the most common malignancy diagnosed in men in the US. Genetic susceptibility to prostate cancer has been well documented. A region at chromosome 20q13 (HPC20) has been reported to be linked to a prostate cancer susceptibility gene. To confirm this finding, we genotyped 16 markers spanning approximately 95 cM on chromosome 20 in 159 hereditary prostate cancer (HPC) families. Positive (but not statistically significant) linkage scores were observed from 20pter to 20q11, with the highest non-parametric linkage (NPL) score for the complete dataset of 1.02 (P=0.15) being observed at D20S195 at 20q11. Evidence for linkage from parametric analyses with a dominant or a recessive model was weak. Interestingly, consistent with the original findings of linkage to 20 g higher linkage scores were observed in the subsets of families with a later age at diagnosis (> or =65 years; n=80, NPL=1.94, P=0.029 at D20S186), fewer than five affected family members (n=69, NPL=1.74, P=0.037 at D20S889), or without male-to-male disease transmission (n=60, NPL=1.01, P=0.15 at D20S117). The region with positive linkage scores spanned approximately 60 cM from 20pter to 20q11 in these subsets of families. Our results are consistent with a prostate cancer susceptibility locus on chromosome 20.

Aged↗
PubMed2001

Measurement of personal exposure to aerosols of Nephrops norvegicus (scampi) using a monoclonal-based assay.

BACKGROUND: The industrial processing of scampi (Nephrops norvegicus) generates bioaerosols which can cause occupational respiratory disease in exposed individuals. The objective of this study was to develop a monoclonal antibody-based immunoassay to measure scampi proteins collected using standard personal air sampling methods. METHODS: A monoclonal antibody was generated which predominantly bound to a single 97 Kd scampi protein, which we have shown to be a major allergen. This protein was shown by SDS PAGE immunoblotting to be present in various aqueous extracts from wastes produced during scampi processing. A quantitative immunoslotblot method was developed to quantify scampi from air sample filters. RESULTS: We demonstrated the utility of this method by showing a significant difference (P = 0.015) in the level of exposure of two groups of 12 workers processing scampi at a traditional open workstation (GM = 607 ng m(-3)) and at an enclosed workstation (GM = 451 ng m(-3)). CONCLUSION: We conclude that this assay can be used, in conjunction with health surveillance, to monitor exposure and the efficacy of measures to reduce exposure to airborne scampi allergen in an occupational environment.

Aerosols↗
PubMed2001

Development and validation of a monoclonal based immunoassay for the measurement of fungal alpha-amylase: focus on peak exposures.

The inhalation of flour dust has been implicated in the induction of sensitisation and elicitation of respiratory symptoms, such as asthma in bakers. In addition to the cereal allergens present in wheat flour, enzymes in flour improvers, in particular fungal alpha-amylase, are now known to be a significant cause of respiratory allergy in the baking industry.A monoclonal antibody based enzyme-linked immunoassay (ELISA) was developed using two monoclonal antibodies that recognised two distinct epitopes of the fungal alpha-amylase enzyme. The ELISA had an inter-assay variation of 12.0% at 1360 pg/ml and 12.8% at 564 pg/ml and intra-assay variation of 4.9% at 1340 pg/ml and 6.1% at 504 pg/ml. The assay had a sensitivity of 200 pg/ml. Competitive inhibition assays confirmed that the monoclonal antibodies had no cross reactivity with other enzymes used in the baking industry and could distinguish added fungal alpha-amylase from cereal amylase. We assessed the levels of exposure to dust, total protein and fungal alpha-amylase in four UK bakeries ranging in size and technical capabilities. Within the bakeries we surveyed, workers were exposed to variable levels of inhalable dust (0.8-39.8 mg/m3), total protein (0-5.7 mg/m3) and fungal alpha-amylase (0-29.8 ng/m3). Consecutive 15 min personal samples taken over a 1 h period demonstrated that the ELISA could measure fungal alpha-amylase exposure in such a 15 min period. Short term peak exposures to fungal alpha-amylase could be identified which may contribute to the sensitisation in individuals who appear to have low exposure levels if measured over a full shift period.

Antibodies, Monoclonal↗
PubMed1999

No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer.

BACKGROUND: Two genes responsible for hereditary breast cancer (BRCA1 and BRCA2) have been identified, and predisposing mutations identified. Several studies have provided evidence that germline mutations in BRCA1 and BRCA2 confer an increased risk of prostate cancer. Based on these findings, one might expect to find an increased frequency of mutations in these genes in family clusters of prostate cancer. The Ashkenazi Jewish population is unique in that it has an approximate 2% incidence of specific founder BRCA1 and BRCA2 mutations (i.e., 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2). METHODS: To address the question of whether or not mutations in either of these genes were overrepresented in prostate cancer families, we searched for these mutations in germline DNA samples collected from affected and unaffected members of 18 Ashkenazi Jewish families, each having at least 3 first-degree relatives affected with prostate cancer. RESULTS: No mutations were found in the BRCA1 gene in any of the 47 individuals tested. One individual possessed a BRCA2 mutation (6174delT). This individual was unaffected at the time of analysis, but had an affected paternal uncle, and an affected first cousin, neither of whom harbored the mutant gene. CONCLUSIONS: In this sample of Ashkenazi prostate cancer families, the frequency of founder BRCA1 and BRCA2 mutations was not elevated, suggesting that such mutations will account for only a small, perhaps minimal, fraction of familial prostate cancer.

DNA Primers↗
PubMed1999

The use of child-centered play therapy and filial therapy with Head Start families: a brief report.

Play therapy and filial therapy show promise as effective ways to provide direct services to Head Start, addressing the needs of the children, the families, and the Head Start teachers and staff. This paper examines the utility of play and filial therapies for the Head Start population, presents a systemic explanation for the benefit of filial therapy, and provides a case example for illustration.

Anxiety, Separation↗
PubMed1998

Evidence for a prostate cancer susceptibility locus on the X chromosome.

Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.

Adult↗
PubMed1998

Occupational asthma in fruit salad processing.

BACKGROUND: Three subjects employed in the preparation of fruit for fruit salads reported work-related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase. Objectives To investigate the respiratory symptoms reported by these workers and determine their causes. METHODS: The three workers were investigated by a respiratory physician, including spirometry and serial peak flow measurements. Blood was taken for the measurement of IgE and IgG antibody responses against the enzyme solution. RESULTS: Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work-related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. All three improved immensely following withdrawal from the workplace environment. CONCLUSION: Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma.

Adult↗
PubMed1997

Screening questionnaires for bakers' asthma--are they worth the effort?

The use of a respiratory screening questionnaire is recommended annually to screen bakery workers in the UK. We compared questionnaire screening with other methods of detecting workers with asthmatic symptoms and then assessed the significance of these symptoms with careful investigation and follow-up. Reasons for questionnaire failures were then explored. A questionnaire was issued to 362 flour-exposed workers in a large bakery. All positive respondents to respiratory symptom questions were interviewed by an occupational nurse. Workers with occupationally related symptoms at this interview were referred to the chest clinic. In addition, workers with negative questionnaires were screened using attendance records, sick notes and direct workplace observations. Workers with frequent absence from work or sick notes with respiratory diagnoses were interviewed in the same manner as those answering the questionnaire positively and then referred to clinic. At clinic, a diagnosis was made for each worker on the basis of clinical assessment, spirometry, serial peak expiratory flow rate (PEFR) analysis and radioallergosorbent testing (RAST) testing for specific IgE. Using the clinic diagnoses, the referral routes were audited to assess the rates of case detection of asthma and occupational asthma. The respiratory screening questionnaire identified 68 workers with respiratory symptoms. Of these, 21 proceeded to full assessment. A diagnosis of asthma was made in five cases, one of which was bakers' asthma. In addition, 11 workers not reporting any symptoms by questionnaire were referred to clinic and five were diagnosed as having asthma. Screening questionnaires may lead to an underestimate of the prevalence of asthmatic symptoms and as such should not be used alone in workplace screening.

Adult↗
PubMed1997

Measurement of airborne flour exposure with a monoclonal antibody-based immunoassay.

BACKGROUND: The development of simple and standardised methods to measure airborne levels of workplace biological allergens is an important step in reducing the incidence of occupational asthma. Such a method would be useful for measuring wheat flour allergens which cause asthma in bakers. Measurement of allergen per se rather than total dust enables exposure to be better defined. METHODS: Monoclonal antibodies were produced, their specificity analysed by immunoblotting and then used to affinity-purify a putative flour allergen. The importance of this protein as an allergen was tested by RAST using sera from allergic bakers and it was identified by N-terminal sequencing. Suitable monoclonal antibodies were chosen to develop an enzyme-linked immunosorbent assay. Commercial baking flours and personal airborne dust samples were analysed using the immunoassay. RESULTS: A sensitive and specific monoclonal antibody-based enzyme-linked immunosorbent assay was developed to measure a wheat alpha-amylase inhibitor. The wheat alpha-amylase inhibitor content of bulk wheat flours was 0.124% (95% confidence limits 0.083-0.164%) and airborne levels in bakeries had a geometric mean of 744 ng/m3 (95% confidence limits 371-1,496 ng/m3). CONCLUSION: This assay is suitable for widespread use as the monoclonal antibodies and standards are well defined and potentially infinitely available. The assay therefore offers distinct advantages over those exposure assessment methods currently in use. Comparable results would be obtained by different investigators over a prolonged time period. The assessment of flour allergen exposure and the relationship with clinical response could then be investigated using a multi-centered approach.

Air Pollutants, Occupational↗
PubMed1997

Glass bottle workers exposed to low-dose irritant fumes cough but do not wheeze.

Workers exposed to irritant fumes experience symptoms both during the acute episode and afterwards. High-dose irritant exposure can result in permanent asthma, but the effects of chronic low-dose irritant exposure are not known. Glass bottle workers are exposed to irritant fumes, and have previously been reported to have an excess of symptoms. We designed a study to compare irritant-exposed glass bottle workers with hospital workers matched for socioeconomic group, area of residence, age, sex, smoking habit, and allergic history. Symptoms reported, spirometry, flow cytometric indices of lymphocyte activation, and past medical and employment histories were compared. We also investigated the prevalence of bronchial hyperresponsiveness to inhaled methacholine and the cough response after inhalation of citric acid and capsaicin. Glass bottle workers showed an excess of upper respiratory tract symptoms, cough, and shortness of breath compared with matched hospital control workers. There was a significant excess of cough induced by citric acid and capsaicin in the bottle workers. However, wheeze, baseline spirometry, flow cytometry, and methacholine challenge were not significantly different between the two groups. These findings suggest that chronic irritant exposure produces an excess of symptoms and increased cough sensitivity but not asthma.

Adult↗
PubMed1996

Clinical and immunologic evaluation of workers exposed to glutaraldehyde.

We describe immunologic responses in subjects exposed to glutaraldehyde (GA) who were diagnosed as having occupational asthma, or who described work-related respiratory symptoms. A series of GA-modified proteins was characterized, and used to analyse sera from 20 GA-exposed workers and 21 unexposed workers for IgE antibodies. Inhibition studies were used to determine the specificity of binding. The reaction of GA with albumin in different molar ratios produced a range of modified proteins, which were used to measure specific IgE antibodies. A significant difference between exposed and unexposed subjects with serum IgE less than 150 kU/l could be detected for GA-specific IgE antibodies (P - 0.026), and 31% of exposed workers with occupational asthma had antibody levels greater than the unexposed population (mean +2.5 SD). False-positive results were obtained with serum from unexposed workers who had total IgE levels greater than 150 kU/l, but this binding was not inhibited by GA-modified proteins. We report the first evidence of immunologic sensitization in some workers exposed to GA. However, GA may behave like many other low-molecular-weight chemicals in that specific antibodies can be detected in only a small percentage of exposed workers who report work-related respiratory symptoms.

Adult↗
PubMed1992

AIDS course: a university elective.

Developing and teaching a nonnursing elective on AIDS is both challenging and rewarding. We encourage nursing faculty elsewhere to teach an AIDS course for university students on their campus.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Selecting empiric drug therapy for pneumonia in geriatric patients.

Rather than produce extensive lists of pathogens and antibiotics to cover every situation, we have tried to provide some insight into how we make decisions regarding the drug therapy of our geriatric patients when they develop pneumonia, and give some practical examples of how we would use those agents.

Aged↗
PubMed1991

Prevalence of illicit drug use among prenatal patients and predictive validity of nurses' judgments.

The purposes of this investigation were to: (1) estimate the prevalence of illicit drug use within the prenatal population of a midwestern suburban ambulatory care center; (2) explore the relationship between nurses' judgments of patient illicit drug use and urine toxicology results; and (3) determine if a difference exists between nurses' judgments of illicit drug use by private physicians' patients (PPP) and nurses' judgments of illicit drug use by resident physicians' patients (RPP). For a 16-week period, all new prenatal patients (N = 189) were included in this study; 78 (41%) were in the RPP group and 111 (59%) were in the PPP group. Urine remaining from routine urinalysis was assayed for seven drugs or drug classes. Fourteen (7.5%) subjects tested positive for illicit drugs, 8 (10.3%) in the RPP group, and 6 (5.4%) in the PPP group (chi 2, P greater than .33). Using a Likert-type scale, nurses rated the likelihood of a positive result of each patient's urine test. Nurses' judgments of patient illicit drug use and positive results were related, r = .28. Nurses were more likely (P less than .0001) to suspect residents' patients of illicit drug use than private physicians' patients.

Adult↗
PubMed1990

Comparison of constant time delay and the system of least prompts in teaching preschoolers with developmental delays.

This investigation compared the effectiveness and efficiency (sessions, errors, percent of errors, and minutes of instructional time through criterion) of constant time delay and the system of least prompts in teaching sight words to developmentally delayed preschoolers. Maintenance of sight words and generalization across instructors and materials were assessed. Also, students' acquisition of relationships between the target behavior and previously learned information were assessed. Two sessions were conducted each day in their classroom, one with each procedure. Two of the children were taught 16 words and one child learned 12 words. The parallel treatments design was used to assess the effectiveness of the two instructional strategies. The results indicated that (a) both strategies produced criterion level responding in the instructional setting, (b) constant time delay resulted in fewer total trials, errors, percent of errors, and minutes of direct instructional time through criterion than the system of least prompts, (c) both strategies produced criterion-level responding that maintained in 1-, 3- and 5-week follow-up probes, (d) both strategies resulted in generalization across instructors and materials, and (e) both strategies resulted in cross-modal generalization from expressive to receptive, receptive and expressive identification of the words' function or action, and matching the written word to a photograph of its referent.

Attention↗