Climate science: a sinking feeling.
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Biomedical subjects
Samir S Patel
Publications and source records attributed to Samir S Patel.
Quality of life in patients with chronic kidney disease: focus on end-stage renal disease treated with hemodialysis.
The proper measures for assessing quality of life (QOL) in patients with chronic kidney disease (CKD) remain unclear. QOL measures are subjective or objective, functional or satisfaction-based, and generic or disease-specific. Treatment of end-stage renal disease with transplantation and treatment of anemia with erythropoietin in patients with CKD have been associated with dramatic improvements of QOL. Other factors such as age, ethnic or national background, stage of CKD, modality of dialytic therapy, exercise interventions, sleep disturbances, pain, erectile dysfunction, patient satisfaction with care, depressive affect, symptom burden, and perception of intrusiveness of illness may be associated with differential perception of QOL. Recent studies showed an association between assessment of QOL and morbidity and mortality in end-stage renal disease patients, suggesting the measures do matter. Further studies are necessary in patients with early stages of CKD and in children. QOL measures should include validated psychosocial measures of depressive affect, perception of burden of illness, and social support. The challenge for the next decade will be to continue to devise interventions that meaningfully increase the QOL of patients with CKD at all stages.
Humans↗
Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded.
Nuclear transport proceeds through nuclear pore complexes (NPCs) that are embedded in the nuclear envelope of eukaryotic cells. The Saccharomyces cerevisiae NPC is comprised of 30 nucleoporins (Nups), 13 of which contain phenylalanine-glycine repeats (FG Nups) that bind karyopherins and facilitate the transport of karyopherin-cargo complexes. Here, we characterize the structural properties of S. cerevisiae FG Nups by using biophysical methods and predictive amino acid sequence analyses. We find that FG Nups, particularly the large FG repeat regions, exhibit structural characteristics typical of "natively unfolded" proteins (highly flexible proteins that lack ordered secondary structure). Furthermore, we use protease sensitivity assays to demonstrate that most FG Nups are disordered in situ within the NPCs of purified yeast nuclei. The conclusion that FG Nups constitute a family of natively unfolded proteins supports the hypothesis that the FG repeat regions of Nups form a meshwork of random coils at the NPC through which nuclear transport proceeds.
Active Transport, Cell Nucleus↗
Psychosocial issues in women with renal disease.
In this article, we review data on the epidemiology and outcomes of women in the US End-Stage Renal Disease (ESRD) Program. The complexity of the psychosocial milieu of patients is described, and levels of analysis are delineated. The relationships between age, marital status and satisfaction, and perception of quality of life and depressive affect level and diagnosis of depression, and medical outcomes have not been determined in large studies of women with renal disease. We present data from our cross-sectional and longitudinal studies of psychosocial outcomes in a population comprised primarily of black patients with ESRD and review some differences between relationships of parameters in the groups of men and women in the study. Women are more likely to be kidney donors rather than recipients in national programs. Women with ESRD treated with hemodialysis appear to be more immunologically responsive to the psychosocial milieu than men. These differences in access to and utilization of health care and relationships between perceptions and immunochemical mediators may have important ramifications for outcomes in women with chronic renal disease.
Female↗
The Saccharomyces cerevisiae nucleoporin Nup2p is a natively unfolded protein.
Little is known about the structure of the individual nucleoporins that form eukaryotic nuclear pore complexes (NPCs). We report here in vitro physical and structural characterizations of a full-length nucleoporin, the Saccharomyces cerevisiae protein Nup2p. Analyses of the Nup2p structure by far-UV circular dichroism (CD) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, protease sensitivity, gel filtration, and sedimentation velocity experiments indicate that Nup2p is a "natively unfolded protein," belonging to a class of proteins that exhibit little secondary structure, high flexibility, and low compactness. Nup2p possesses a very large Stokes radius (79 A) in gel filtration columns, sediments slowly in sucrose gradients as a 2.9 S particle, and is highly sensitive to proteolytic digestion by proteinase K; these characteristics suggest a structure of low compactness and high flexibility. Spectral analyses (CD and FTIR spectroscopy) provide additional evidence that Nup2p contains extensive regions of structural disorder with comparatively small contributions of ordered secondary structure. We address the possible significance of natively unfolded nucleoporins in the mechanics of nucleocytoplasmic trafficking across NPCs.
Blotting, Western↗
Patient satisfaction with care and behavioral compliance in end-stage renal disease patients treated with hemodialysis.
Compliance with the hemodialysis (HD) prescription is an important predictor of patient outcome. Although there is interest in the concept of patient satisfaction with medical care and caregivers, relatively few such data exist regarding HD patients. We examined whether associations exist between patient satisfaction with medical personnel and depressive affect and social support levels and behavioral compliance with prescribed HD treatment. Seventy-nine HD patients were interviewed, assessing depression, social support, and perception of satisfaction with dialysis staff. Medical and treatment data, Karnofsky functioning and severity of illness scores, and behavioral and laboratory compliance measures were determined. There was no association between patient satisfaction with care and level of depressive affect. A relationship was found between patient satisfaction with care with their nephrologist and attendance at dialysis sessions. Patients who had a poor perception of satisfaction with their nephrologist had poorer attendance at dialysis sessions. There was no relationship between behavioral compliance and patient perception of ancillary HD staff. In addition, patient perception of satisfaction with staff was related to perception of social support, protein catabolic rate, and serum albumin concentration, all of which have been linked to survival. We conclude that a nephrologist has a crucial role in patient compliance. These results suggest interventions that improve patient perception of physician support may improve patient adjustment and possibly survival.
Adult↗
Psychosocial variables, quality of life, and religious beliefs in ESRD patients treated with hemodialysis.
BACKGROUND: Religious and spiritual aspects of quality of life (QOL) have not been fully assessed in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD), but psychosocial factors are associated with patient survival. METHODS: To investigate interrelationships between religious beliefs and psychosocial and medical factors, we studied 53 HD patients. Psychosocial and medical variables included perception of importance of faith (spirituality), attendance at religious services (religious involvement), the Beck Depression Inventory, Illness Effects Questionnaire, Multidimensional Scale of Perceived Social Support, McGill QOL Questionnaire scores, Karnofsky scores, dialysis dose, and predialysis hemoglobin and albumin levels. RESULTS: Eighty-seven percent of participants were African-American. Men had higher depression scores, perceived lower social support, and had higher religious involvement scores than women. No other parameters differed between sexes. Perception of spirituality and religiosity did not correlate with age, Karnofsky score, dialysis dose, or hemoglobin or albumin level. Greater perception of spirituality and religiosity correlated with increased perception of social support and QOL and less negative perception of illness effects and depression. A one-question global QOL measure correlated with depression, life satisfaction, perception of burden of illness, social support, and satisfaction with nephrologist scores, but not with age or Karnofsky score. CONCLUSION: Religious beliefs are related to perception of depression, illness effects, social support, and QOL independently of medical aspects of illness. Religious beliefs may act as coping mechanisms for patients with ESRD. The relationship between religious beliefs and clinical outcomes should be investigated further in patients with ESRD.
Age Factors↗
New clinical practice guidelines for chronic kidney disease: a framework for K/DOQI.
Chronic kidney disease affects millions of individuals in the United States, and millions more are at risk for the development of kidney disease. The National Kidney Foundation (NKF) has recently published 15 clinical practice guidelines (CPGs) for chronic kidney disease under the Kidney/Disease Outcomes Quality Initiative (K/DOQI). This initial set of guidelines creates a framework for additional interventional CPGs currently in development. Importantly, these guidelines define and classify CKD. In addition, recommendations for the clinical assessment of kidney disease are elaborated. In reviewing the guidelines, we find that they follow the basic principles of CPG development and incorporate the essential aspects of CPGs. The validity of the CPGs is limited in some areas because of the paucity of data. Despite their limitations, the current CPGs allow for the development of clinical performance measures and continuous quality improvement in the hopes of improving public health and reducing progression to end-stage renal disease (ESRD).
Disease Progression↗
Deciphering networks of protein interactions at the nuclear pore complex.
The nuclear pore complex (NPC) gates the only known conduit for molecular exchange between the nucleus and cytoplasm of eukaryotic cells. Macromolecular transport across the NPC is mediated by nucleocytoplasmic shuttling receptors termed karyopherins (Kaps). Kaps interact with NPC proteins (nucleoporins) that contain FG peptide repeats (FG Nups) and altogether carry hundreds of different cargoes across the NPC. Previously we described a biochemical strategy to identify proteins that interact with individual components of the nucleocytoplasmic transport machinery. We used bacterially expressed fusions of glutathione S-transferase with nucleoporins or karyopherins as bait to capture interacting proteins from yeast extracts. Forty-five distinct proteins were identified as binding to one or several FG Nups and Kaps. Most of the detected interactions were expected, such as Kap-Nup interactions, but others were unexpected, such as the interactions of the multisubunit Nup84p complex with several of the FG Nups. Also unexpected were the interactions of various FG Nups with the nucleoporins Nup2p and Nup133p, the Gsp1p-GTPase-activating protein Rna1p, and the mRNA-binding protein Pab1p. Here we resolve how these interactions occur. We show that Pab1p associates nonspecifically with immobilized baits via RNA. More interestingly, we demonstrate that the Nup84p complex contains Nup133p as a subunit and binds to the FG repeat regions of Nups directly via the Nup85p subunit. Binding of Nup85p to the GLFG region of Nup116p was quantified in vitro (K(D) = 1.5 micro M) and was confirmed in vivo using the yeast two-hybrid assay. We also demonstrate that Nup2p and Rna1p can be tethered directly to FG Nups via the importin Kap95p-Kap60p and the exportin Crm1p, respectively. We discuss possible roles of these novel interactions in the mechanisms of nucleocytoplasmic transport.
Active Transport, Cell Nucleus↗
The impact of social support on end-stage renal disease.
Social support is a concept recognizing patients exist to varying degrees in networks through which they can receive and give aid, and in which they engage in interactions. Social support can be obtained from family, friends, coworkers, spiritual advisors, health care personnel, or members of one's community or neighborhood. Several studies have demonstrated that social support is associated with improved outcomes and improved survival in several chronic illnesses, including cancer and end-stage renal disease (ESRD). The mechanism by which social support exerts its salutary effects are unknown, but practical aid in achieving compliance, better access to health care, improved psychosocial and nutritional status and immune function, and decreased levels of stress may all play key roles. Few data exist regarding social support in patients with ESRD and chronic renal insufficiency, but links between social support and depressive affect and quality of life have been established. Interventions that enhance social support in ESRD patients should be evaluated.
Depression↗
Sleepiness, sleeplessness, and pain in end-stage renal disease: distressing symptoms for patients.
Symptoms are increasingly recognized as problematic for patients with end-stage renal disease (ESRD) treated with dialysis. Sleep disorders are common in ESRD patients treated with dialysis and are associated with patients' perceptions of quality of life, assessed by diverse measures, as well as depressive affect. Sleep disorders appear to be equally prevalent in peritoneal dialysis (PD) and hemodialysis (HD) patients. Treatment for sleep disorders in dialysis patients depends on establishing the diagnosis, often in a sleep laboratory, using polysomnography. Reversing coexistent medical and psychological disorders is important. The sleep apnea syndrome (SAS) can be treated with continuous positive airway pressure in dialysis patients, but conventional hemodialytic techniques have little effect on its severity. In contrast, nocturnal HD and transplantation appear to have important beneficial effects on sleep disordered breathing in ESRD patients. Although pain has been appreciated as a problem for ESRD patients for more than 20 years, few studies exist on this subject. Pain appears to be an underappreciated problem for ESRD patients. More research must be performed on the problem of pain in patients with chronic kidney disease (CKD).
Blood Pressure↗