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Biomedical subjects

M J Brady

Publications and source records attributed to M J Brady.

36 records · Page 2Linked to original sources
PubMed1997

Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument.

PURPOSE: This is the first published report on the validation of the Functional Assessment of Cancer Therapy-Breast (FACT-B), a 44-item self-report instrument designed to measure multidimensional quality of life (QL) in patients with breast cancer. The FACT-B consists of the FACT-General (FACT-G) plus the Breast Cancer Subscale (BCS), which complements the general scale with items specific to QL in breast cancer. The FACT-B was developed with an emphasis on patients' values and brevity and is available in nine languages. METHODS AND RESULTS: Two validation samples were used for this report. The first (n = 47) was tested twice over a 2-month period to assess sensitivity to change. Significant sensitivity to change in performance status rating (PSR) was demonstrated for the FACT-B total score, the Physical Well-Being (PWB) subscale, the Functional Well-Being (FWB) subscale, and the BCS. Sensitivity to change in QL as measured by the Functional Living Index-Cancer (FLIC) was documented in the FACT-B total score, PWB, FWB, and Emotional Well-Being (EWB). Additional validity and reliability data were obtained from a larger sample (n = 295). The alpha coefficient (internal consistency) for the FACT-B total score was high (alpha = .90), with subscale alpha coefficients ranging from .63 to .86. Evidence supported test-retest reliability, as well as convergent, divergent, and known groups validity. CONCLUSION: The FACT-B is appropriate for use in oncology clinical trials, as well as in clinical practice. It demonstrates ease of administration, brevity, reliability, validity, and sensitivity to change.

Adult↗
PubMed1996

Psychological coping with acute pain: an examination of the role of endogenous opioid mechanisms.

This study examined the relationship among endogenous opioids, Monitoring and Blunting coping styles, and acute pain responses. Fifty-eight male subjects underwent a 1-min pressure pain stimulus during two laboratory sessions. Subjects experienced this pain stimulus once under endogenous opioid blockade with naltrexone and once in a placebo condition. Blunting was found to be negatively correlated with pain ratings, but this relationship was significantly more prominent under opioid blockade. Results for coping behaviors subjects used to manage the experimental pain were generally consistent with the Blunting results, indicating that cognitive coping was related more strongly to decreased pain ratings and cardiovascular stress responsiveness under opioid blockade. Overall, the beneficial effects of Blunting and cognitive coping on pain responses did not depend upon endogenous opioids and, in fact, became stronger when opioid receptors were blocked. The relationship between endogenous opioids and coping appears to be dependent upon situational and stimulus characteristics.

Acute Disease↗
PubMed1996

The psychobiology of hostility: possible endogenous opioid mechanisms.

This study examined the role of endogenous opioids in the relation between hostility and cardiovascular stress responsiveness. Forty-six men completed the Cook-Medley Hostility Scale and experienced a laboratory pain stressor once under opioid blockade and once under placebo. Hostility scores were significantly related to the magnitude of change in cardiovascular reactivity/recovery resulting from opioid blockade. Low scorers on the Cynicism subscale displayed increases in heart rate (HR) reactivity under blockade relative to placebo, with reactivity decreases noted in high scorers. Low Hostile Affect scores were similarly associated with impaired diastolic blood pressure recovery under opioid blockade. HR recovery results were somewhat different, with high scorers on Aggressive Responding and the total Cook-Medley displaying improved HR recovery under opioid blockade, with no change noted in low scorers. These data provide preliminary support for the hypothesis that low hostile individuals rely on endogenous opioids for buffering cardiovascular stress responsiveness, but high hostiles do not.

Journal Article↗
PubMed1995

Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin.

Insulin stimulates the activity of mitogen-activated protein kinase (MAPK) via its upstream activator, MAPK kinase (MEK), a dual specificity kinase that phosphorylates MAPK on threonine and tyrosine. The potential role of MAPK activation in insulin action was investigated with the specific MEK inhibitor PD98059. Insulin stimulation of MAPK activity in 3T3-L1 adipocytes (2.7-fold) and L6 myotubes (1.4-fold) was completely abolished by pretreatment of cells with the MEK inhibitor, as was the phosphorylation of MAPK and pp90Rsk, and the transcriptional activation of c-fos. Insulin receptor autophosphorylation on tyrosine residues and activation of phosphatidylinositol 3'-kinase were unaffected. Pretreatment of cells with PD98059 had no effect on basal and insulin-stimulated glucose uptake, lipogenesis, and glycogen synthesis. Glycogen synthase activity in extracts from 3T3-L1 adipocytes and L6 myotubes was increased 3-fold and 1.7-fold, respectively, by insulin. Pretreatment with 10 microM PD98059 was without effect. Similarly, the 2-fold activation of protein phosphatase 1 by insulin was insensitive to PD98059. These results indicate that stimulation of the MAPK pathway by insulin is not required for many of the metabolic activities of the hormone in cultured fat and muscle cells.

3T3 Cells↗
PubMed1995

Insulin stimulates the tyrosine phosphorylation of caveolin.

The specialized plasma membrane structures termed caveolae and the caveolar-coat protein caveolin are highly expressed in insulin-sensitive cells such as adipocytes and muscle. Stimulation of 3T3-L1 adipocytes with insulin significantly increased the tyrosine phosphorylation of caveolin and a 29-kD caveolin-associated protein in caveolin-enriched Triton-insoluble complexes. Maximal phosphorylation occurred within 5 min, and the levels of phosphorylation remained elevated for at least 30 min. The insulin-dose responses for the tyrosine phosphorylation of caveolin and the 29-kD caveolin-associated protein paralleled those for the phosphorylation of the insulin receptor. The stimulation of caveolin tyrosine phosphorylation was specific for insulin and was not observed with PDGF or EGF, although PDGF stimulated the tyrosine phosphorylation of the 29-kD caveolin-associated protein. Increased tyrosine phosphorylation of caveolin, its associated 29-kD protein, and a 60-kD protein was observed in an in vitro kinase assay after incubation of the caveolin-enriched Triton-insoluble complexes with Mg-ATP, suggesting the presence of an intrinsic tyrosine kinase in these complexes. These fractions contain only trace amounts of the activated insulin receptor. In addition, these complexes contain a 60-kD kinase detected in an in situ gel kinase assay and an approximately 60 kD protein that cross-reacts with an antibody against the Src-family kinase p59Fyn. Thus, the insulin-dependent tyrosine phosphorylation of caveolin represents a novel, insulin-specific signal transduction pathway that may involve activation of a tyrosine kinase downstream of the insulin receptor.

3T3 Cells↗
PubMed1995

Physical and psychosocial status of adults one-year after bone marrow transplantation: a prospective study.

Assessment of the impact of bone marrow transplantation (BMT) on long-term physical and psychosocial functioning has been hampered by a paucity of prospective research. While evidence suggests that many adult BMT recipients experience deficits in physical and psychosocial functioning > or = 1 year following BMT, whether these deficits existed prior to BMT is not known. Observed post-BMT deficits could be attributable to conventional treatments received prior to BMT and thus could have antedated BMT. The physical and psychosocial status of 28 adult BMT recipients was assessed prior to BMT and 12-16 months after BMT. Analysis of group means indicated few significant differences between pre- and post-BMT assessments. However, inspection of residual change scores suggested that physical and psychosocial status improved following BMT for some individuals, while that of others declined. Analysis of residual change scores indicated that males and older patients at time of BMT reported the largest declines in physical and psychosocial status. Longer follow-up is necessary to determine whether decrements observed 12-16 months after BMT reflect a slower process of post-BMT recovery or whether they constitute fairly permanent deficits.

Adult↗
PubMed1995

'Returning to normal' following bone marrow transplantation: outcomes, expectations and informed consent.

The psychosocial impact of bone marrow transplantation (BMT) was investigated in 172 disease-free adult BMT survivors drawn from five different BMT treatment centers. Respondents were a mean of 43.5 months after BMT. Both questionnaire and interview assessments were utilized. Survivors' perceptions of whether they had 'returned to normal' following BMT, recollections of pre-BMT expectations for returning to normal and current psychological distress were assessed. The results indicated that only a minority of respondents considered themselves to have 'returned to normal' following BMT. Reports of less than normal physical, cognitive, occupational, sexual and/or interpersonal functioning were common. In contrast, few patients reported pre-BMT expectations for such. Discordance between pre-BMT expectations for returning to normal and current functional status was associated with greater current psychological distress. Finally, despite the presence of any functional deficits and despite any discordance between pre-BMT expectations and current functional status, survivors' evaluations of their decision to pursue BMT were generally quite positive. Results are discussed in terms of their implications for: (1) the process of obtaining informed consent for BMT, and (2) clinical strategies for enhancing post-BMT psychological adjustment.

Activities of Daily Living↗
PubMed1994

Health locus of control and psychological distress in cancer patients: interactive effects of context.

Delineation of the relationship between health locus of control (HLOC) and psychological adjustment in chronic disease has been hampered by the failure to consider the moderating effect of contextual factors. The extent to which HLOC beliefs match the control realities in a situation (Reality Matching hypothesis) as well as the degree of threat (Threat hypothesis) posed by the situation were hypothesized to moderate the HLOC-distress relationship. Distress, disease severity (i.e., threat), and HLOC were assessed in 69 individuals with malignant disease undergoing evaluation for bone marrow transplantation. Hierarchical regression analyses indicated that the HLOC-distress relationship was moderated by disease severity and treatment history (i.e., whether an individual had failed prior cancer therapy). However, in some instances, the specific interaction relationships obtained differed from those evident in previous research with ESRD patients. It was concluded that there is no simple main effect relationship between HLOC beliefs and psychological adjustment. Rather, this relationship is best described by joint consideration of factors descriptive of the context in which the individual is embedded.

Acute Disease↗
PubMed1993

Rapid and sustained phosphorylation of a calmodulin-binding protein (CaM-BP100) in NGF-treated PC12 cells.

Nerve growth factor (NGF) treatment of PC12 cells led to the rapid phosphorylation of a calmodulin-binding protein of 100 kDa (CaM-BP100) identified on blot overlays with 125I-labeled CaM. The effect was detected as a retardation in the mobility of the protein by an apparent 10 kDa on SDS gels. The mobility shift was complete within 5 min and was maintained for 24 h in the continued presence of NGF. The protein was present in both the soluble and crude particulate fractions, and the gel mobility shift occurred in both fractions. Epidermal growth factor elicited a similar response, but the mobility shift was reversed within 12 h. The gel retardation was due to phosphorylation of CaM-BP100, as it could be reversed if cytoplasmic extracts were held under dephosphorylating conditions at 37 degrees C for 10 min prior to electrophoresis; dephosphorylation was inhibited by okadaic acid but not vanadate, suggesting the participation of a Ser/Thr phosphatase. Treatment with either acid or alkaline phosphatase also reversed the mobility shift. CaM-BP100 phosphorylation was stimulated by 12-O-tetradecanoylphorbol-13-acetate in intact cells, but the effect of NGF did not involve a protein kinase C-dependent process, because it occurred in PC12 cells depleted of protein kinase C. The phosphorylation event appeared to be due to an NGF-stimulated protein kinase, as mixing extracts from NGF-treated cells with extracts from control cells in the presence of ATP and Mg2+ reconstituted the mobility shift in vitro. CaM-BP100 appears to be a minor cellular phosphoprotein, as 32P labeling of the protein could not be detected in crude cell extracts. These results suggest that receptor tyrosine kinases communicate with at least one component of the Ca2+/calmodulin-signaling pathway early in signal transduction.

Animals↗
PubMed1992

Neuropsychologic impairment in adult bone marrow transplant candidates.

BACKGROUND: Long-term cognitive impairment has been reported in adult bone marrow transplant (BMT) recipients. However, the degree to which such impairment is attributable to the procedure or is a condition existing before BMT is not known. METHODS: The presence, nature, and correlates of neuropsychologic impairment were investigated in 55 adult BMT candidates, all of whom had a malignant condition. Impairment was assessed using a screening battery of standardized neuropsychologic tests. RESULTS: Results indicated that: (1) neuropsychologic performance was associated with specific disease and treatment risk factors, in particular a history of cranial radiation or central nervous system disease treated with intrathecal chemotherapy; (2) performance on tests reflecting memory or higher cognitive processing was more likely to be impaired; and (3) the risk of impairment increased as the number of disease and treatment risk factors for cognitive impairment in the patient increased. CONCLUSIONS: It was concluded that neuropsychologic impairment occurs in a significant minority of adult patients before BMT. Research is necessary to determine the extent to which such impairment significantly compromises patients' abilities to: (1) make decisions regarding undergoing BMT or participating in research protocols and (2) understand and execute self-care behaviors after BMT. More broadly, greater attention should be devoted to investigating the presence of long-term neuropsychologic impairment in adult patients with cancer.

Adult↗
PubMed1990

Nerve growth factor-induced down-regulation of calmodulin-dependent protein kinase III in PC12 cells involves cyclic AMP-dependent protein kinase.

Treatment of PC12 cells with nerve growth factor (NGF), epidermal growth factor (EGF), or agents that raise intracellular cyclic AMP (cAMP) levels (e.g., forskolin) reduces the activity of calmodulin-dependent protein kinase III (CaM-PK III) over a period of 8 h. The mechanism of this effect of NGF has now been examined in more detail, making use of a mutant PC12 cell line (A126-1B2) that is deficient in cAMP-dependent protein kinase activity. Control experiments showed that A126-1B2 cells retain other NGF-mediated responses (e.g., the induction of ornithine decarboxylase, a cAMP-independent event) and contain a complement of CaM-PK III and its substrate, elongation factor-2, comparable to that of wild-type cells. The ability of NGF or forskolin, but not of EGF, to down-regulate CaM-PK III was markedly attenuated in A126-1B2 compared to wild-type cells. Treatment of wild-type cells with the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, enhanced the effects of NGF, but not of EGF. The possibility that NGF led to a stimulation of cAMP-dependent protein kinase activity in wild-type cells was assessed by measurement of the "activation ratio" (-cAMP/+cAMP) of this enzyme before and at various times after NGF addition. A small, but significant, increase in the activation ratio from 0.3 to 0.48 was observed, reaching a peak 5 min after NGF treatment. EGF had no effect on the activation ratio in wild-type cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1989

Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing.

Meconium specimens (first 3 days' stool) obtained from 20 infants of drug-dependent mothers and five control infants were analyzed by radioimmunoassay for the metabolites of three commonly abused drugs, heroin, cocaine, and cannabinoids. Control stools contained no drug. Meconium from the infants of drug-dependent mothers showed the presence of at least one drug metabolite: 80% of the infants of drug-dependent mothers showed cocaine (range 0.14 to 19.91 micrograms/gm stool), 55% showed morphine (range 0.41 to 14.97 micrograms/gm stool), and 60% showed cannabinoid (range 0.05 to 0.67 micrograms/gm stool). The concentrations of metabolites were highest during the first 2 days; some stools tested positive up to the third day. In contrast, only 37% of the infants had positive results on a urine screen (fluorescent polarization immunoassay method). Paired urine and meconium specimens, both analyzed by radioimmunoassay, showed a higher concentration of drug metabolites in the latter; eight urine samples had no detectable drugs despite a corresponding positive stool test result. We conclude that meconium is useful for drug screening in the neonate.

Animals↗
PubMed1987

Nerve growth factor treatment or cAMP elevation reduces Ca2+/calmodulin-dependent protein kinase III activity in PC12 cells.

Ca2+/calmodulin-dependent protein kinase III (Ca2+/CaM kinase III) phosphorylates a protein of Mr = 100,000 (the 100-kDa protein), a major substrate for Ca2+/CaM-dependent protein phosphorylation found in many mammalian tissues and cell lines (Nairn, A.C., Baghat, B., and Palfrey, H.C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7939-7943). Treatment of PC12 cells with nerve growth factor (NGF) or forskolin resulted in a decrease in the depolarization-dependent phosphorylation of the 100-kDa protein in intact cells and in a decrease in the Ca2+/CaM-dependent phosphorylation of the 100-kDa protein in cytosolic extracts. In experiments using cytosolic extracts, the initial effect of NGF on the phosphorylation of the 100-kDa protein was observed in less than 1 h, was maximal (70% decrease) after 12 h, and began to recover after 24 h. The effect of forskolin was more rapid and the maximal effect was greater (90-95% decrease). Decreased Ca2+/CaM kinase III activity was also found in PC12 cells treated with epidermal growth factor, 2-chloroadenosine plus isobutylmethylxanthine, or dibutyryl cAMP. The effect of forskolin did not reverse unless it was removed. Cycloheximide blocked the recovery of Ca2+/CaM kinase III activity observed following the removal of forskolin but did not affect the ability of forskolin to reduce kinase activity. Short-term treatment with phorbol ester had little effect on Ca2+/CaM kinase III activity; long-term treatment with phorbol ester, which results in the disappearance of enzymatically detectable protein kinase C, had no effect on the ability of NGF or 2-chloroadenosine to reduce Ca2+/CaM kinase III activity. The level of the 100-kDa protein as determined by immunological techniques was not changed by any treatment. These results suggested that the effect of treatment of PC12 cells with NGF or forskolin was to reduce the level of Ca2+/CaM kinase III per se.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Telephone counseling of breast cancer patients after treatment: a description of a randomized clinical trial.

The Telephone Counseling Trial for Breast Cancer Survivors is a randomized, controlled study designed to test the impact of a telephone-based counseling intervention on quality of life of early-stage breast cancer patients who have completed adjuvant treatment. A psychoeducational counseling model is utilized to promote adaptive coping to re-entry stressors and survivorship issues. Adaptation is fostered through the exploration of thematic materials, application of active coping strategies, encouragement of a personal expression of the breast cancer experience and the provision of psychological support. Patients are being recruited in collaboration with two NCI-designated clinical cooperative oncology groups: the Eastern Cooperative Oncology Group (ECOG) and the Southwest Cooperative Oncology Group (SWOG). The recruitment goal is 400 breast cancer survivors with Stage 1, Stage 2 and Stage 3 disease (with no greater than 10 positive lymph nodes involved). Patients are being enrolled by data managers on-site during their last treatment visit. The intervention is being delivered by the Cancer Information and Counseling Line (CICL) of the AMC Cancer Research Center. It includes 16 telephone outcalls which are delivered over a 12-month period. Primary outcome measures are quality of life, mood, social support, self-efficacy, and sexual functioning, assessed at baseline, 3, 6, 12 and 18 months follow-up. This article provides a description of the intervention protocol and study design. It is argued that this study could provide a model for developing and testing other psychosocial interventions within clinical cooperative groups nationwide.

Adaptation, Psychological↗
PubMedDate not supplied

A case for including spirituality in quality of life measurement in oncology.

Most of the commonly used quality of life (QOL) instruments in oncology do not include spirituality as a core domain. However, previous research suggests that spirituality might be an important aspect of QOL for cancer patients and that it may, in fact, be especially salient in the context of life-threatening illness. This study used a large (n=1610) and ethnically diverse sample to address three questions relevant to including spirituality in QOL measurement: (1) Does spirituality demonstrate a positive association with QOL?; (2) Is this association unique?; and (3) Is there clinical utility in including spirituality in QOL measurement? Spirituality, as measured by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), was found to be associated with QOL to the same degree as physical well-being, a domain unquestioned in its importance to QOL. The significant association between spirituality and QOL was unique, remaining after controlling for core QOL domains as well as other possible confounding variables. Furthermore, spiritual well-being was found to be related to the ability to enjoy life even in the midst of symptoms, making this domain a potentially important clinical target. It is concluded that these results support the move to the biopsychosocialspiritual model for QOL measurement in oncology.

Adaptation, Psychological↗
PubMedDate not supplied

Psychosocial factors predictive of survival after allogeneic bone marrow transplantation for leukemia.

Previous research suggesting a link between psychosocial variables and survival after bone marrow transplant (BMT) has been limited by: a) retrospective assessment of psychosocial variables; and b) failure to concurrently examine a comprehensive set of disease, treatment, and demographic variables potentially related to post-BMT survival. The present study prospectively assessed psychosocial variables (depressed mood, functional quality of life, and mental adjustment to cancer) that have been linked to survival after BMT and/or malignant disease. Study participants (N = 42) received allogeneic BMT for either acute or chronic leukemia. Analyses using Cox proportional hazards regression indicated that quality of bone marrow graft match was the only disease, treatment, or demographic variable significantly associated with post-BMT survival (p = .05). Addition of psychosocial variables to a multivariate Cox regression model including quality of graft match suggested that an attitude toward cancer characterized by "anxious preoccupation" (p = .008), as well as poorer functional quality of life (p = .052), were each independently associated with poorer post-BMT survival. Further research is necessary to identify the mechanisms by which psychosocial variables could contribute to post-BMT survival.

Adaptation, Psychological↗