Biomedical subjects

Barbara J Bowers

Publications and source records attributed to Barbara J Bowers.

15 recordsLinked to original sources

PubMed2006

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cgamma.

Protein kinase Cgamma (PKCgamma) null mutant mice demonstrate increased behavioral impulsivity and ethanol consumption. Pharmacological studies have shown that 5-HT(2A/C) receptors modulate impulsivity and ethanol consumption in rodents and that PKC can regulate 5-HT(2A/C) receptors. To determine whether PKCgamma plays a selective role in 5-HT(2A/C) receptor regulation, biochemical and behavioral experiments were performed in PKCgamma mutant and wild-type mice. DOI-stimulated phosphoinositol hydrolysis and [(125)I]-DOI saturation binding in the PFC, and quantitative autoradiography of [(125)I]-DOI binding sites in 15 brain regions were analyzed. DOI-induced head twitch responses (HTR) were measured in naive mice after an acute 2.5 mg/kg injection of DOI. Results indicated that DOI-induced HTR was significantly greater in mutant mice compared to wild-type mice. Results of the phosphoinositol hydrolysis, membrane binding, and autoradiography experiments indicated that in mutant mice, increased HTR was associated with increased 5-HT(2A/C) receptor function in the PFC, but not increased receptor number or affinity suggesting that PKCgamma regulates receptor function but not receptor number. These data support a role for 5-HT(2A/C) receptors in the PFC in mediating some of the behavioral differences observed between PKCgamma mutant and wild-type mice.

Alcohol Drinking↗

PubMed2006

Microarray analysis of the effects of a gamma-protein kinase C null mutation on gene expression in striatum: a role for transthyretin in mutant phenotypes.

A constitutive null mutation of the neural-specific isotype of protein kinase C (gamma-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that gamma-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of gamma-PKC gene deletion also may be due to altered gene expression. To examine alterations in gene expression, microarray analyses were performed on striatal tissue from wild types and mutants. A total of 143 genes and ESTs were identified as potential candidates related to differences between null mutants and wild types. Confirmation studies using qRT-PCR indicated that the expression of transthyretin was increased about 8-fold in striatum of naïve mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because gamma-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naïve and control-diet treated mutants, but did not affect transthyretin expression in wild types.

Animals↗

PubMed2006

Microarray analysis identifies cerebellar genes sensitive to chronic ethanol treatment in PKCgamma mice.

Neuroadaptive changes that occur in the development of ethanol tolerance may be the result of alterations in gene expression. We have shown that PKCgamma wild-type mice develop tolerance to the sedative-hypnotic effects of ethanol after chronic ethanol treatment; whereas, mutant mice do not, making these genotypes a suitable model for identifying changes in gene expression related to tolerance development. Using a two-stage process, several genes were initially identified using microarray analyses of cerebellar tissue from ethanol-treated PKCgamma mutant and wild-type mice. Subsequent confirmation of a subset of these genes using quantitative real time reverse transcriptase polymerase chain reactions (qRT-PCR) was done to verify gene expression changes. A total of 109 genes from different functional classifications were identified in these groups on the microarrays. Eight genes were selected for verification as follows: three, Twik-1, Plp, and Adk2, were chosen as genes related to tolerance; another three, Hsp70.2, Bdnf, and Th, were chosen as genes related to resistance to tolerance; and two genes, JunB and Nur77, were selected as candidate genes sensitive to chronic ethanol. The results from the verification experiments indicated that Twik-1, which codes for a potassium channel, was associated with tolerance and appeared to be dependent on the presence of PKCgamma. No genes were confirmed to be related to resistance to tolerance; however, expression of two of these, Hsp70.2 and Th, were found to be sensitive to chronic ethanol and were added to the transcription factors, JunB and Nur77, confirmed by qRT-PCR, as a subset of genes that respond to chronic ethanol.

Alcoholism↗

PubMed2006

Internet recruitment and e-mail interviews in qualitative studies.

In 2004, 111 million adults accessed the Internet looking for health and medical information. Qualitative researchers can apply long-standing principles of recruitment and interviewing to the Internet. The purpose of this article is to examine the theoretical and methodological aspects of Internet recruitment and e-mail interviewing. The authors address issues of appropriateness, adequacy, representativeness, sample bias, data fraud, flexibility and consistency in interviewing, timing, elimination of the need for transcription, oral versus written communication, reliability and validity, and ethical concerns. They include some practical suggestions on a research design for a qualitative study employing both Internet recruitment and e-mail interviewing.

Adult↗

PubMed2005

Performance of alpha7 nicotinic receptor null mutants is impaired in appetitive learning measured in a signaled nose poke task.

Wild-type and mutant mice lacking expression of alpha5, alpha7, beta2, beta3, or beta4 neuronal nicotinic cholinergic receptors (nAChRs) were compared on a signaled nose poke task, a multi-phased task used to measure appetitive learning and impulsivity. In the early phases of training, mutants of all nicotinic lines did not differ compared to wild types in the days to reach criterion when mice were required to nose poke for a sucrose reward on FR1 or FR3 schedules, or in their ability to respond to an auditory clicker to receive a sucrose reward. However, mutants lacking alpha7 nAChRs, but not lines lacking other nAChRs, showed impairments when task difficulty was increased such that an auditory stimulus was presented on a variable schedule and mice were required to withhold their responses until the presentation of the auditory cue to obtain a reward. alpha7 mutants were impaired compared to wild types in appetitive learning as measured by the percentage of conditioned responses but overcame their deficits with extensive training for 10 days. However, when efficiency ratios were used to measure impulsivity, alpha7 mutants exhibited lower efficiency ratios even after 10 days of training. These results support a role of the alpha7 nicotinic receptor in mediating appetitive learning and suggest a potential role for the alpha7 nAChRs in the regulation of behavioral disinhibition.

Analysis of Variance↗

PubMed2005

Deletion of the alpha7 nicotinic receptor subunit gene results in increased sensitivity to several behavioral effects produced by alcohol.

BACKGROUND: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric alpha7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used alpha7 gene knockout (null mutant) mice to evaluate the potential role of alpha7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. METHODS: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (alpha7(-/-)) and wild-type (alpha7(-/-)) mice. RESULTS: Relative to alpha7(+/+) mice, alpha7(-/-) mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the alpha7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. CONCLUSIONS: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the alpha7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.

Acoustic Stimulation↗

PubMed2005

Disclosing genetic test results to family members.

PURPOSE: To describe the experiences of disclosing genetic test results to biological family members among people tested for Huntington's disease (HD) or hereditary breast and ovarian cancer (HBOC). DESIGN: Grounded theory methodology. METHODS: Open-ended, tape-recorded interviews were conducted with 29 participants-24 who had received genetic test results and 5 who had decided not to be tested. The participants were from three countries, including 15 U.S. states. Interviews occurred from 2 months to 4 years after receiving test results. Tapes were transcribed and analyzed for conceptual categories to describe the experience of disclosing genetic test results. FINDINGS: Participants described the effects and meaning of disclosing test results to their various family members, and they selectively disclosed results to family members. The timing of disclosure was influenced by the particular disease and the person's perceived need to prepare. Disclosure of genetic test results brought the risk of HD and HBOC to the foreground, not only for the person tested but for family members as well. CONCLUSIONS: This study elucidated the perspective of the "discloser" and the consequences they anticipated and experienced.

Adaptation, Psychological↗

PubMed2005

Disability in everyday life.

The authors explored how persons with disabilities perceived the experience of disability in their everyday lives. The findings suggest that the current models in the literature do not address disability adequately. Instead, disability was described as a multifaceted, complex experience that is integrated into the lives of persons with disabilities. The degree to which integration was possible was influenced by three disability-related factors: (a) the fundamental effects of the disabling condition, (b) others' perceptions of disability, and (c) the need for and use of resources. Important contextual conditions included the environment, time, and experience. Ultimately, it was the match between how these persons perceived themselves and what was important in their lives, and the influence of the three factors that determined how well they were able to integrate disability into their lives. The findings suggest the need for a conceptual model that reflects the personal experience of disability.

Activities of Daily Living↗

PubMed2003

Ethanol differentially enhances hippocampal GABA A receptor-mediated responses in protein kinase C gamma (PKC gamma) and PKC epsilon null mice.

Ethanol intoxication results partly from actions of ethanol at specific ligand-gated ion channels. One such channel is the GABA(A) receptor complex, although ethanol's effects on GABA(A) receptors are variable. For example, we found that hippocampal neurons from selectively bred mice and rats with high hypnotic sensitivity to ethanol have increased GABA(A) receptor-mediated synaptic responses during acute ethanol treatment compared with mice and rats that display low behavioral sensitivity to ethanol. Here we investigate whether specific protein kinase C (PKC) isozymes modulate hypnotic and GABA(A) receptor sensitivity to ethanol. We examined acute effects of ethanol on GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in mice lacking either PKCgamma (PKCgamma(-/-)) or PKCepsilon (PKCepsilon(-/-)) isozymes and compared the results to those from corresponding wild-type littermates (PKCgamma(+/+) and PKCepsilon(+/+)). GABA(A) receptor-mediated IPSCs were evoked in CA1 pyramidal neurons by electrical stimulation in stratum pyramidale, and the responses were recorded in voltage-clamp mode using whole-cell patch recording techniques. Ethanol (80 mM) enhanced the IPSC response amplitude and area in PKCgamma(+/+) mice, but not in the PKCgamma(-/-) mice. In contrast, ethanol markedly potentiated IPSCs in the PKCepsilon(-/-) mice, but not in PKCepsilon(+/+) littermates. There was a positive correlation between ethanol potentiation of IPSCs and the ethanol-induced loss of righting reflex such that mice with larger ethanol-induced increases in GABA(A) receptor-mediated IPSCs also had higher hypnotic sensitivity to ethanol. These results suggest that PKCgamma and PKCepsilon signaling pathways reciprocally modulate both ethanol enhancement of GABA(A) receptor function and hypnotic sensitivity to ethanol.

Animals↗

PubMed2003

Deciding whether to continue, share, or relinquish caregiving: caregiver views.

Using grounded theory, the authors explore informal caregiving and develop the beginnings of a substantive caregiving theory explaining some of the decision making involved in providing care to an older family member. Sixteen caregivers (CGs) participated in the study. Line-by-line and dimensional analyses reveal various purposes of caregiving for an older family member. These purposes influence whether and how CGs continue to provide the care or decide to share or relinquish caregiving to health care providers. This study suggests that a broader conceptualization of caregiving is needed to illuminate fully the complexity involved in providing care to older adults.

Adaptation, Psychological↗

PubMed2003

Turnover reinterpreted CNAs talk about why they leave.

This study's purpose was to contribute to the development of a theory of turnover by understanding how CNAs employed in long-term care facilities conceptualize the factors that cause them to leave their jobs. Using grounded dimensional analysis, the authors conducted in-depth interviews with CNAs currently and formerly employed by three nursing homes. The CNAs' perception that they are unappreciated and undervalued by the organizations for which they work contributes significantly to turnover. The origins of this perception lie in policies and practices that lead, CNAs to feel personally and professionally dismissed. The authors suggest how long-term care facilities might change their staffing and personnel policies to better demonstrate respect and appreciation, thus reducing turnover and enhancing the quality of work and care.

Aged↗

PubMed2002

Patient-centered interventions.

Patient-centered care is valued in nursing. However, until recently, nurse-researchers have focused on testing the effects of standardized rather than patient-centered interventions (PCIs). The latter are those interventions that are altered to address selected patient characteristics (e.g., beliefs, habits, or goals). PCIs have been well received, and in some studies they have been associated with improved health outcomes. In this article we describe briefly the concept patient centered, summarize the development of research on PCIs, discuss kinds of PCIs, provide examples of PCIs and how they have been derived and implemented, and raise issues for theory and future research.

Forecasting↗

PubMedDate not supplied

Understanding how disability is defined and conceptualized in the literature.

A goal of rehabilitation nursing is to advance the care of persons with chronic disabling conditions by minimizing disability. There are two distinct perpectives in the literature about how to conceptualize disability. Definitions and models of disability that inform rehabilitation nursing practice are based on a functionalist perspective of illness and locate disability as a problem of individual functioning. Alternatively, there are definitions and models that have evolved from the civil rights and social justice perspectives, and that locate the problem of disability within a disabling society. Recent attempts to integrate these two perspectives are based on earlier rehabilitation models and the functionalist assumptions remain. Rehabilitation nursing research and practice based on either of these two perspectives is fragmented and incomplete. To know how to define and approach disability-related issues, it is important to understand how people living with disability perceive its influences on their lives.

Attitude to Health↗

PubMedDate not supplied

The recognition of depression: the primary care clinician's perspective.

PURPOSE: The purpose of this study was to explore the responses of primary care clinicians to patients who complain of symptoms that might indicate depression, to examine the clinical strategies used by clinicians to recognize depression, and to identify the conditions that influence their ability to do so. METHODS: The grounded theory method was used for data collection and analysis. In-depth, in-person interviews were conducted with a purposeful sample of 8 clinicians. All interviews were audiotaped and transcribed. RESULTS: This study identified 3 processes clinicians engage in to recognize depression-ruling out, opening the door, and recognizing the person-and 3 conditions-familiarity with the patient, general clinical experience, and time availability-that influence how each of the processes is used. CONCLUSIONS: The likelihood of accurately diagnosing depression and the timeliness of the diagnosis are highly influenced by the conditions within which clinicians practice. Productivity expectations in primary care will continue to undermine the identification and treatment of depression if they fail to take into consideration the factors that influence such care.

Decision Trees↗

PubMedDate not supplied

Patient preferences in choosing chemotherapy regimens for advanced non-small cell lung cancer.

The major difference between cisplatin-based chemotherapy doublets for advanced non-small cell lung cancer (NSCLC) is not in the outcomes of their use--rather, it is in the side effects and toxicities that they cause. The degree to which oncologists involve lung cancer patients in discussions regarding the selection of chemotherapy is unknown. A questionnaire regarding patient concerns about chemotherapy and physician discussions was sent to patients registered in the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE) database from 2000--2002. About three-quarters of the respondents reported that if they were given the option, they would consider side effects important in choosing a particular regimen--and nausea was the most important side effect that would influence that decision. Female patients were more likely to worry about infection and hair loss resulting from therapy than were men. Further, about two-thirds of patients reported that they had discussed differences in chemotherapy side effects with their physicians, particularly if the physicians were female, although less than half of those patients recalled discussing the selection of a particular regimen based upon its side-effect profile. Different chemotherapy regimens with varied side-effect profiles have been developed, but medical oncologists do not present options for chemotherapy uniformly to their patients based on possible or probable adverse reactions. Better communication between physician and patient about the likelihood of side effects may reduce chemotherapy-related stress for patients.

Carcinoma, Non-Small-Cell Lung↗