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Biomedical subjects

B A Jones

Publications and source records attributed to B A Jones.

At least 19 recordsLinked to original sources

Distribution of androgen receptor immunoreactivity in the brainstem of male rats.

Gonadal steroids such as testosterone and estrogen are necessary for the normal activation of male rat sexual behavior. The medial preoptic area (MPOA), an important neural substrate regulating mating, accumulates steroids and also expresses functional androgen receptors (AR). The MPOA is intimately connected with other regions implicated in copulation, such as the bed nucleus of the stria terminalis and medial amygdala. Inputs to the MPOA arise from several areas within the brainstem, synapsing preferentially onto steroid sensitive MPOA cells which are activated during sexual activity. Given that little is known about the distribution of AR protein in the brainstem of male rats, we mapped the distribution of AR expressing cells in the pons and medulla using immunocytochemistry. In agreement with previous reports, AR immunoreactivity (AR-ir) was detected in ventral spinal motoneurons and interneurons. In addition, AR-ir was detected in areas corresponding to the solitary tract, lateral paragigantocellular and alpha and ventral divisions of the gigantocellular reticular nuclei, area postrema, raphe pallidus, ambiguus nucleus, and intermediate reticular nucleus. Several regions within the pons contained AR-ir, such as the tegmental and central gray, parabrachial nucleus, locus coeruleus, Barrington's nucleus, periaqueductal gray, and dorsal raphe. In contrast with in situ hybridization studies, auditory and somatosensory areas were AR-ir negative, and, except for very light staining in the prepositus nucleus, areas carrying vestibular information did not display AR-ir. Additionally, cranial nerve motoneurons of the hypoglossal, facial, dorsal vagus, and spinal trigeminal did not display AR-ir in contrast to previous reports. The data presented here indicate that androgens may influence numerous cell groups within the brainstem. Some of these probably constitute a steroid sensitive circuit linking the MPOA to motoneurons in the spinal cord via androgen responsive cells in the caudal ventral medulla.

Animals↗

Social representations of stem cell research and preimplantation genetic diagnosis.

The study examined public thinking about stem cell research and preimplantation genetic diagnosis (PGD) using social representation theory. Social representation theory is concerned with the movement of scientific knowledge from the realm of the specialist into lay knowledge. Participants were interviewed and the data analysed qualitatively. Three social representations were found for both stem cell research and PGD. For stem cell research, one was based on irrational fears, one was based on social concerns for the technology and the final was based on the notion of the 'slippery slope'. For PGD, the first social representation was based on concern for the human impact, the second was based, again, on irrational fear, and the third was based on medical applications. Participants rated stem cell research more positively than PGD. It was concluded that while information about both topics is in the process of being transformed, knowledge of stem cell research has been transformed into lay knowledge more completely than knowledge of PGD. Directions for future research included attitude surveys and discourse analyses.

Adolescent↗

Participatory analysis of seasonal incidences of diseases of cattle, disease vectors and rainfall in southern Sudan.

During an investigation into a chronic wasting disease in southern Sudanese cattle, a participatory appraisal method called a 'seasonal calendar' was used to understand local perceptions of seasonal variations in cattle diseases, disease vectors, intermediate hosts and rainfall. Repetition of a standardized seasonal calendar with Dinka informants demonstrated good reproducibility of the method. Comparison of rainfall data produced by seasonal calendars and objective measures of rainfall demonstrated good validity of the seasonal calendar method. Subjective assessment of seasonal calendar scoring patterns by veterinarians indicated that herders' perceptions of seasonal populations of biting flies, ticks and snails were similar to modern veterinary knowledge. The uses of seasonal calendars in veterinary epidemiology are discussed.

Animal Husbandry↗

Participatory diagnosis of a chronic wasting disease in cattle in southern Sudan.

In southern Sudan, livestock keepers identified a chronic wasting disease in adult cattle as one of their most-serious animal-health problems. Participatory-appraisal (PA) methods and conventional veterinary-investigation methods were used to characterise the chronic wasting disease and identify linkages between indigenous knowledge and modern veterinary knowledge. The local characterisation of chronic wasting encompassed trypanosomosis, fasciolosis, parasitic gastroenteritis and schistosomosis (as both single and mixed infections).A standardised PA method called matrix scoring had good reproducibility when investigating local perceptions of disease-signs and disease causes. Comparison of matrix-scoring results showed much overlap with modern veterinary descriptions of cattle diseases and the results of conventional veterinary investigation. Applications of PA methods in remote areas with very limited veterinary infrastructure are discussed. The validation of data derived from PA is discussed by reference to the low sensitivity of 'field-friendly' diagnostic tests for important cattle diseases.

Animals↗

Race, anthropometric factors, and stage at diagnosis of breast cancer.

A recent study suggested that the greater prevalence of severe obesity among African-American women explained almost one third of the observed differences between African-American and White women in stage at diagnosis of breast cancer. The objective of this investigation was to attempt to replicate these findings in a second, larger population and to expand the analyses by including a measure of body fat distribution, the waist:hip ratio. The authors used data from a population-based study in North Carolina comprising 791 breast cancer cases (302 in African-American women and 489 in White women) diagnosed between 1993 and 1996. African-American women were more likely to have later-stage (TNM stage >/=II) breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI): 1.6, 2.9). They also were much more likely to be severely obese (body mass index >/=32.3) (OR = 9.7; 95% CI: 6.5, 14.5) and to be in the highest tertile of waist:hip ratio (OR = 5.7; 95% CI: 3.8, 8.6). In multivariate logistic regression models, adjustment for waist:hip ratio reduced the odds ratio for later-stage disease in African-American women by 20%; adjustment for both waist:hip ratio and severe obesity reduced the odds ratio by 27%. These observations suggest that obesity and body fat distribution, in addition to socioeconomic and medical care factors, contribute to racial differences in stage at breast cancer diagnosis.

Black People↗

Usefulness of concurrent Papanicolaou smear at time of cervical biopsy.

The reliability and cost-effectiveness of a repeat Papanicolaou (Pap) smear performed at the time of colposcopic biopsy is uncertain. To evaluate the usefulness of this practice, Pap smear and biopsy results of 718 patients were reviewed and compared: 619 patients had Pap smears performed prior to colposcopy with a 1.1% false-negative rate, 97.5% sensitivity, and 83.6% positive predictive value. Ninety-nine patients had Pap smears performed at the time of colposcopy with a 19.1% false-negative rate, 56.8% sensitivity, and 92.6% positive predictive value. Repeat Pap smear at the time of colposcopy resulted in significant changes in the management of only 2 patients (2%) and more careful follow-up in one (1%). Pap smears performed at colposcopic biopsy are less sensitive than those done prior to biopsy (P < 0.001). The clinical benefit of this practice is marginal, considering the added costs and potential detrimental effects to the colposcopic examination, provided patients receive adequate follow-up.

Biopsy↗

Is variation in quality of mammographic services race linked?

The purpose of this investigation was to (1) determine whether there was variability in the quality of services offered in mammography facilities across Connecticut and (2) determine whether African American women were more likely than white women to receive mammograms in facilities that offered substandard services. Since most facilities do not routinely record information on race, this investigation represents a unique opportunity to address the question of race-linked variation in the quality of screening mammography. Information on equipment, personnel, and record keeping in mammography facilities was used to construct indices that represented separate domains of quality: technical attributes, educational practices, and tracking of clients. While some variation in the quality of mammography services was found, there were no significant differences between the two race categories in the mean scores for each of three quality indices. Thus, variation in quality of screening mammographic services does not appear to be race linked.

Accreditation↗

Nongynecologic cytology turnaround time: a College of American Pathologists Q-Probes study of 180 laboratories.

OBJECTIVES: To determine the turnaround time for nongynecologic cytology and to identify laboratory and specimen characteristics associated with variations in turnaround time. DESIGN AND SETTING: Prospective evaluation of nongynecologic cytology turnaround times in 180 laboratories. MAIN OUTCOME MEASURE: Nongynecologic cytology case turnaround time. RESULTS: Participants from 180 laboratories submitted turnaround times for 16 950 nongynecologic cytology cases and submitted information describing their laboratories' practice characteristics relating to the processing of nongynecologic cytology specimens. Half of the participating laboratories had mean receipt to report turnaround times of 1.6 calendar days or less and were able to complete 90% of their cases within 3.0 calendar days. Ten percent of participants had mean turnaround times greater than 3.2 days and required 6.0 or more days to report 90% of their cases. Longer turnaround times were associated with processing fluid and fine-needle aspiration specimens, issuing atypical/suspicious for malignancy and nondiagnostic diagnoses, having cytotechnologist students screen slides, having to contact the physician offices for additional information, having to retrieve prior case material for review, and having to perform cell blocks and/or special stains. CONCLUSION: There is an opportunity for laboratories to shorten nongynecologic turnaround time by altering certain laboratory practices.

Biopsy, Needle↗

Follow-up of abnormal gynecologic cytology: a college of American pathologists Q-probes study of 16132 cases from 306 laboratories.

OBJECTIVES: To measure the percentage of women with abnormal gynecologic cytology who have follow-up within 1 year and to identify patient and laboratory characteristics associated with higher percentages of follow-up. DESIGN AND SETTING: Retrospective identification of patients with abnormal cervicovaginal cytology and identification of the initial clinical follow-up activity during the 12 months following the cytologic diagnosis. MAIN OUTCOME MEASURE: Percentage of women receiving follow-up. RESULTS: Three hundred six laboratories reported follow-up information on 16 132 patients with gynecologic cytology diagnoses of carcinoma, high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, or glandular intraepithelial lesion. The following percentages of women received follow-up within 1 year: 85.6% of patients with cytologic diagnoses of carcinoma, 87.2% with diagnoses of high-grade squamous intraepithelial lesion, 82.7% with diagnoses of low-grade squamous intraepithelial lesion, and 84.9% with diagnoses of glandular intraepithelial lesion. Within 6 months, 82.2% of patients with cytologic diagnoses of carcinoma, 82.4% with diagnoses of high-grade squamous intraepithelial lesion, 71.9% with diagnoses of low-grade squamous intraepithelial lesion, and 74.7% with diagnoses of glandular intra-epithelial lesion received follow-up. Overall, 90. 8% of patients who received follow-up within the 1-year time frame of this study had their follow-up completed within 6 months. Specific follow-up activities and their frequencies are listed for each diagnostic category. Patients 30 years old or younger and pregnant patients had lower follow-up percentages. CONCLUSIONS: With less than 83% of patients with high-grade squamous intraepithelial lesion or carcinoma cytology findings having available documentation of follow-up within 6 months, and less than 88% within 1 year, there is room for improvement in this area of health care. Monitoring and critical analysis of the follow-up process is a starting point for improvement.

Adult↗

Quality management in gynecologic cytology using interlaboratory comparison.

OBJECTIVE: To describe a comprehensive integrated laboratory quality management plan for gynecologic cytology. DESIGN AND SETTING: Cytopathology laboratory performance monitors with interlaboratory comparison. RESULTS: Utilizing College of American Pathologists Q-Probes studies, the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, and other published data, a quality management program for gynecologic cytology involving diagnostic statistics, screening limits and competency assessment, retrospective rescreening, real-time rescreening, cytology-biopsy correlation, follow-up of patients with abnormal cytology results, turnaround time, examination of unknown slides (survey programs), and new technology is described. CONCLUSION: Regular coordinated monitoring of performance, with longitudinal and interlaboratory comparison utilizing the methods described, provides an opportunity to optimize gynecologic cytology service.

Clinical Competence↗

Use of selective hypothermia to protect the spinal cord during resection of thoracoabdominal aneurysms.

Neurologic complications remain a threat to patients after repair of thoracoabdominal thoracic aneurysms. We have recently used a simple technique of selective hypothermia during such repairs in 7 high-risk patients. None of the patients had neurologic complications. In the 1st patient, we used cardiopulmonary bypass, but we have subsequently found that the procedure can be performed safely without an oxygenator in the circuit by using only a centrifugal pump, heat exchanger, thermistor, and pressure gauge. We believe that this technique deserves additional consideration for avoiding neurologic complications after repair of such lesions.

Aged↗

Modulation of endogenous GABA release by an antagonistic adenosine A1/dopamineD1 receptor interaction in rat brain limbic regions but not basal ganglia.

Behavioral and biochemical studies suggest that a negative interaction exists between adenosine A(1) and dopamine D(1) receptors in the brain and that this may contribute to the psychomotor effects of adenosine receptor agonists and antagonists. We examined the functional significance of A(1) and D(1) receptor subtypes in modulating electrically evoked endogenous GABA release from slices/punches of rat basal ganglia (striatum, globus pallidus, striatum containing globus pallidus, and substantia nigra reticulata) and limbic regions (ventral pallidum and nucleus accumbens). In basal ganglia, stimulation of A(1) receptors with the selective agonist R-PIA (1-100 nM) resulted in a concentration-dependent decrease in GABA release. The selective A(1) antagonist DPCPX (10-100 nM) increased GABA release, suggesting that endogenous adenosine tonically inhibits GABA release. However, in basal ganglia, consistent dopamine D(1) receptor modulation of GABA, release was not observed in response to either D(1) agonists or antagonists. Furthermore, the A(1) receptor-mediated inhibition of GABA release was not changed by concurrent activation of D(1) receptors, thus confirming the lack of D(1) receptor modulation under these conditions. In contrast, in ventral pallidum and nucleus accumbens, stimulation of D(1) receptors with SKF-82958 (1 microM) increased GABA release significantly. The D(1) receptor-mediated increase in GABA release was attenuated by concurrent activation of adenosine A(1) receptors. These results are consistent with the hypothesis that an antagonistic A(1)/D(1) receptor interaction may be important in modulating GABA release in limbic regions.

Adenosine↗

Gynecologic cytology turnaround time. A College of American Pathologists Q-Probes Study of 371 laboratories.

OBJECTIVES: To determine the turnaround time for gynecologic cytology in a large sample of laboratories and to identify laboratory and specimen characteristics associated with better and worse performance. DESIGN AND SETTING: Prospective evaluation of gynecologic cytology turnaround times in 371 laboratories. MAIN OUTCOME MEASURE: Gynecologic cytology case turnaround time. RESULTS: Three hundred seventy-one laboratories submitted information regarding laboratory characteristics and processes, and turnaround times of 66 042 gynecologic cytology cases. Half of the participating laboratories had mean turnaround times of 6 calendar days or less and were able to complete 90% of their cases within 8 calendar days. Ten percent of participants had mean turnaround times greater than 13 days and required 19 or more days to report 90% of their cases. Longer turnaround times were associated with the use of reference laboratories for all or part of the evaluation; contacting the physician's office for additional information; using cytotechnology students, residents, or fellows in the evaluation; and providing service on the weekend. CONCLUSION: Practice patterns contribute to the long turnaround times for gynecologic cytology found in some laboratories and may be improved by local site-specific process analysis.

Cytodiagnosis↗

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.

3',5'-Cyclic-GMP Phosphodiesterases↗

Remission of infantile systemic lupus erythematosus with intravenous cyclophosphamide.

We report an 8-month-old boy with systemic lupus erythematosus and World Health Organization class IV lupus nephritis who has gone into complete clinical and serological remission with pulse i.v. cyclophosphamide therapy. To our knowledge this is the first case of pulse i.v. cyclophosphamide therapy in infantile systemic lupus erythematosus resulting in long-term remission.

Anti-Inflammatory Agents↗

Cholestasis confers resistance to the rat liver mitochondrial permeability transition.

BACKGROUND & AIMS: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. METHODS: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). RESULTS: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl-xL was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. CONCLUSIONS: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.

Animals↗

Hepatobiliary malignancy.

Chronic cholestatic liver disease may be complicated by hepatobiliary malignancy. The early detection of hepatocellular carcinoma and cholangiocarcinoma is of paramount importance in the evaluation of candidates for liver transplantation, which remains the only effective treatment modality for advanced primary biliary cirrhosis and primary sclerosing cholangitis. This article reviews the identification of patients at high risk, current techniques for diagnosis, and makes recommendations for screening high-risk patients. This article also reviews preliminary data from the Mayo Clinic regarding liver transplantation for cholangiocarcinoma following radiation therapy.

Bile Duct Neoplasms↗

Dysregulation of apoptosis as a mechanism of liver disease: an overview.

Apoptosis is a morphologically distinct form of cell death which occurs in a wide variety of liver diseases. In this overview chapter, we review: (1) the current definitions of apoptosis; (2) the biochemical pathways effecting apoptosis; and (3) the intracellular pathways regulating apoptosis. We also describe how apoptosis is identified in the liver and review the ligand/receptor interactions which trigger hepatobiliary apoptosis. Finally, we speculate on potential therapeutic applications for modulating apoptosis in human liver diseases. This information is meant to provide a foundation for the following chapters each focused on a specific role of apoptosis in liver diseases.

Apoptosis↗