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Biomedical subjects

Wiley W Souba

Publications and source records attributed to Wiley W Souba.

At least 19 recordsLinked to original sources
PubMed2006

Stimulation of expression of the intestinal glutamine transporter ATB0 in tumor-bearing rats.

BACKGROUND: Glutamine supplementation ameliorates host catabolic response in tumor bearing states. The purpose of this in vivo study was to investigate intestinal glutamine transport and expression of glutamine transporter ATB(0) in methyl-cholanthrene (MCA)-sarcoma bearing rats. METHODS: Fisher-344 rats underwent subcutaneous flank implantation of MCA-sarcoma cells (saline as control) and were pair-fed an equal quantity of chow as controls, to account for tumor-induced anorexia, until tumors reached 10 or 20% body weight. Intestinal mucosal brush border membrane [3H]-Glutamine transport was measured. Glutamine transporter ATB(0) mRNA and protein levels were measured by real-time PCR and western blot techniques, respectively. RESULTS: Glutamine transport activity across the intestinal brush border membrane (BBM) was 3.7-fold higher in tumor-bearing rats (TBR) than in controls (TBR 153 +/- 22.6 vs. Control 41.9 +/- 9.7 pmol/mg protein/10s, P < .01). Transporter ATB(0) mRNA levels were 1.4-fold higher in tumor-bearing rats (Relative value TBR .61 +/- .12 vs. Control .43 +/- .1, P < .05). A 1.4-fold increase in transporter ATB(0) protein levels was observed in the tumor-bearing rats (Relative value TBR .52 +/- .07 vs. Control .37 +/- .04, P < .05). Circulating aortic plasma glutamine levels were 1.3-fold higher in tumor bearing rats ([Glutamine] = .63 +/- .02 Control vs. [Glutamine] = .74 +/- .01 mmol/l TBR, P < .0001). Portal venous plasma glutamine levels were also higher in tumor bearing rats ([Glutamine] = .47 +/- .01 Control vs. [Glutamine] = .60 +/- .02 mmol/l TBR, P < .0001). CONCLUSION: Intestinal brush border membrane glutamine transport activity, transporter ATB(0) mRNA and protein levels are up-regulate in tumor-bearing rats.

Animals↗
PubMed2006

Glucocorticoids have a role in renal cortical expression of the SNAT3 glutamine transporter during chronic metabolic acidosis.

Glucocorticoids are involved in many aspects of regulation of acid-base homeostasis, including the stimulation of renal ammoniagenesis during chronic metabolic acidosis. Plasma glutamine is the principal substrate for ammoniagenesis under these conditions. Expression of the System N glutamine transporter SNAT3 is increased in the renal proximal tubules during acidosis. In vivo studies in rats using 1) sham and adrenalectomized rats, 2) the glucocorticoid receptor antagonist RU486, and 3) dexamethasone treatment demonstrated involvement of glucocorticoids in regulation of SNAT3 expression. Adrenalectomy attenuated the acidosis-induced increase in renal cortical SNAT3 mRNA approximately 40%, and treatment with dexamethasone (1 mg x kg(-1) x day(-1) sc) partially reversed this effect. RU486 also blunted the acidosis-induced increase in SNAT3 expression approximately 50%. Chronic dexamethasone treatment (0.1 mg x kg(-1) x day(-1) sc, 6 days) of normal rats slightly increased SNAT3 expression. In all cases, renal glutamine arteriovenous difference mirrored SNAT3 expression and activity in the proximal tubules, suggesting that SNAT3 regulates glutamine uptake during acidosis. These studies indicate that glucocorticoids regulate acid-base homeostasis during metabolic acidosis in part by regulating expression of the System N transporter SNAT3.

Acid-Base Equilibrium↗
PubMed2006

Challenges confronting female surgical leaders: overcoming the barriers.

BACKGROUND: The number of women reaching top ranks in academic surgery is remarkably low. The purpose of this study was to identify: 1) barriers to becoming a female surgical leader; 2) key attributes that enable advancement and success; and 3) current leadership challenges faced as senior leaders. METHODS: Semi-structured interviews of ten female surgical leaders queried the following dimensions: attributes for success, lessons learned, mistakes, key career steps, the role of mentoring, gender advantages/disadvantages, and challenges. RESULTS: Perseverance (60%) and drive (50%) were identified as critical success factors, as were good communication skills, a passion for scholarship, a stable home life and a positive outlook. Eighty percent identified discrimination or gender prejudice as a major obstacle in their careers. While 90% percent had mentors, 50% acknowledged that they had not been effectively mentored. Career advice included: develop broad career goals (50%); select a conducive environment (30%); find a mentor (60%); take personal responsibility (40%); organize time and achieve balance (40%); network (30%); create a niche (30%); pursue research (30%); publish (50%); speak in public (30%); and enjoy the process (30%). Being in a minority, being highly visible and being collaborative were identified as advantages. Obtaining buy-in and achieving consensus was the greatest leadership challenge reported. CONCLUSIONS: Female academic surgeons face challenges to career advancement. While these barriers are real, they can be overcome by resolve, commitment, and developing strong communication skills. These elements should be taken into consideration in designing career development programs for junior female surgical faculty.

Academic Medical Centers↗
PubMed2006

Branched-chain amino acid-enriched nutritional support in surgical and cancer patients.

Prolonged surgical stress and advanced malignant disease lead to systemic catabolism characterized by depletion of muscle protein and oxidation of skeletal muscle BCAA. BCAA oxidation provides energy for muscle and other organs and is the precursor for amino acid synthesis to replenish alanine and glutamine depleted in catabolic states. Persistent excessive catabolism leads to skeletal muscle wasting, negative nitrogen balance, and immune compromise. BCAAs, especially leucine, stimulate protein synthesis, inhibit proteolysis (in cell culture models and in animals), and promote glutamine synthesis. A number of small and diverse clinical trials studied the effects of BCAA-enriched nutritional support in moderately to severely stressed surgical and cancer patients. The findings of these clinical trials have been inconsistent; some show improved nitrogen balance, increased skeletal muscle protein synthesis, and reduced skeletal muscle catabolism whereas others show no significant improvement. The value of these trials is compromised by small sample size, heterogeneous patients, poor study design, varying degrees of metabolic stress, and inappropriate endpoints. More recent trials that evaluate clinical outcomes in hepatocellular carcinoma patients show promising results; in addition to improving metabolic parameters, BCAA-enriched oral supplementation improved morbidity and quality of life in patients undergoing major liver resection and chemo-embolization. In summary, the role of BCAAs in the nutritional support of stressed surgical and cancer patients remains to be clearly defined, despite their potential beneficial biological properties.

Amino Acids, Branched-Chain↗
PubMed2006

Leadership values in academic medicine.

PURPOSE: To gain a deeper understanding of the guiding core values that deans of academic medical centers (AMCs) considered most essential for their leadership and the major leadership challenges that confront them. METHOD: In 2003-04, semistructured interviews of 18 deans at U.S. colleges of medicine or AMCs were organized around four dimensions: background, leadership challenges, organizational effectiveness, and systems enablers/restrainers for leadership. A values Q-sort was used to determine how widely core values were shared among deans and how the complex challenges they faced did or did not align with these values. RESULTS: Fourteen of the 18 (78%) deans identified financial difficulties as their most pressing leadership challenge, followed by weak institutional alignment (61%), staffing problems (33%), and poor morale (28%). Open, candid communication was reported as the most effective means of addressing these complex problems. Enacting espoused shared values and having a positive attitude were identified as the most important enablers of systemic leadership, whereas micromanagement and difficult people were the major restraints. Q-sort results on 38 positive leadership values indicated that participants considered integrity most essential. Integrity was positively correlated with humanistic values and negatively correlated with results. Vision, another highly espoused value, correlated strongly with performance-oriented values but correlated negatively with humanistic values. CONCLUSIONS: A dynamic tension exists in AMCs between humanistic values and performance-based core values. The ability to manage that tension (i.e., when to prioritize one set of values over the other) is inherent in a dean's work.

Academic Medical Centers↗
PubMed2005

Regulation of amino acid arginine transport by lipopolysaccharide and nitric oxide in intestinal epithelial IEC-6 cells.

As a precursor for nitric oxide (NO) synthesis and an immune-enhancing nutrient, amino acid L-arginine plays a critical role in maintaining intestine mucosal integrity and immune functions in sepsis. However, the relationship between intestinal arginine transport and NO synthesis in sepsis remains unclear. In the present study, we investigated the effects of lipopolysaccharide (LPS) and NO on the arginine transport in cultured rat intestinal epithelial IEC-6 cell. Near-confluent IEC-6 cells were incubated with LPS (0-50 microg/ml) in serum-free Dulbecco's modified Eagles's medium, in the presence and absence of the NO donor sodium nitroprusside (SNP, 0-500 micromol/L) and the inducible nitric oxide synthase (iNOS) inhibitor N-omega-nitro-L-arginine (NNA, 0-1000 micromol/L) for various periods of time (0-48 hours). Arginine transport activity, arginine transporter CAT1 mRNA and protein levels were measured with transport assay, Northern blot analysis, and Western blot analysis, respectively. LPS increased arginine transport activity in a time- and dose-dependent fashion. Prolonged incubation of LPS (24 hours, 25 microg/ml) resulted in a 3-fold increase of arginine transport activity (control: 28 +/- 5; LPS: 92 +/- 20 pmol/mg/min, P < 0.05), with the System y(+) as the predominant arginine transport system, and a 2-fold increase of System y(+)CAT1 mRNA and transporter protein levels (P < 0.05). LPS increased the arginine transport System y(+) maximal velocity (V(max), control: 1484 +/- 180; LPS: 2800 +/- 230 pmol/mg/min, P < 0.05) without affecting the transport affinity (K(m), control: 76 +/- 8; LPS: 84 +/- 14 micromol/L, p = NS). The LPS-induced arginine transport activity was blocked by sodium nitroprusside (SNP) (control: 25 +/- 6; LPS: 97 +/- 26 *; SNP: 22 +/- 0.4(+); LPS+SNP: 33 +/- 10.3(+) pmole/mg/min, *P < 0.01 and (+)p = NS, compared with control). In contrary, the LPS-induced arginine transport activity was further augmented by NNA (control: 18 +/- 3.2; LPS: 59 +/- 2.7 *; NNA: 26.3 +/- 5.8; LPS + NNA: 127 +/- 18(+) pmol/mg/min; *P < 0.01 compared with control and (+)P < 0.01 compared with control or LPS). LPS-stimulates arginine transport activity in IEC-6 cells via a mechanism that involves increase of transport System y(+) mRNA levels and transporter protein levels. The LPS-stimulated arginine transport activity is regulated by the availability of nitric oxide.

Amino Acid Transport Systems↗
PubMed2005

Basic science faculty in surgical departments: advantages, disadvantages and opportunities.

The number of Ph.D. faculty in clinical departments now exceeds the number of Ph.D. faculty in basic science departments. Given the escalating pressures on academic surgeons to produce in the clinical arena, the recruitment and retention of high-quality Ph.D.s will become critical to the success of an academic surgical department. This success will be as dependent on the surgical faculty understanding the importance of the partnership as the success of the Ph.D. investigator. Tighter alignment among the various clinical and research programs and between surgeons and basic scientists will facilitate the generation of new knowledge that can be translated into useful products and services (thus improving care). To capitalize on what Ph.D.s bring to the table, surgery departments may need to establish a more formal research infrastructure that encourages the ongoing exchange of ideas and resources. Physically removing barriers between the research groups, encouraging the open exchange of techniques and observations and sharing core laboratories is characteristic of successful research teams. These strategies can meaningfully contribute to developing successful training program grants, program projects and bringing greater research recognition to the department of surgery.

Faculty, Medical↗
PubMed2005

Reinventing the academic health center.

Academic health centers have faced well-documented internal and external challenges over the last decade, putting pressure on organizational leaders to develop new strategies to improve performance while simultaneously addressing employee morale, patient satisfaction, educational outcomes, and research growth. In the aftermath of a failed merger, new leaders of The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center encountered a climate of readiness for a transformational change. In a case study of this process, nine critical success factors are described that contributed to significant performance improvement: performing a campus-wide cultural assessment and acting decisively on the results; making values explicit and active in everyday decisions; aligning corporate structure and governance to unify the academic enterprise and health system; aligning the next tier of administrative structure and function; fostering collaboration and accountability-the creation of unified campus teams; articulating a succinct, highly focused, and compelling vision and strategic plan; using the tools of mission-based management to realign resources; focusing leadership recruitment on organizational fit; and "growing your own" through broad-based leadership development. Outcomes assessment data for academic, research, and clinical performance showed significant gains between 2000 and 2004. Organizational transformation as a result of the nine factors is possible in other institutional settings and can facilitate a focus on crucial quality initiatives.

Academic Medical Centers↗
PubMed2004

Building our future: a plea for leadership.

In recent years the spastic nature of the health care marketplace has continued to increase, which has greatly escalated the demands of leadership in academic medical centers. The expectations of leaders, including surgery chairs, have increased considerably, whereas their capacity for independent action has undeniably diminished. In such a predicament, it is useful to revisit fundamentals, using them as a guide to build a sound future. Five leadership principles are critical to building a better future: (1) recognizing that the work of leadership involves an inward journey of self-discovery and self-development; (2) establishing clarity around a set of core values that guide the organization as it pursues its goals; (3) communicating a clear sense of purpose and vision that inspires widespread commitment to a shared sense of destiny; (4) building a culture of excellence and accountability throughout the entire organization; and (5) creating a culture that emphasizes the development of leaders and leadership as an organizational capacity. Leadership and learning are inextricably linked. We must change the perception that learning in academic surgery is about correcting a deficit rather than a natural part of human growth and development. Our ability to learn, grow, and contribute to an organization is what provides each of us with meaning and identity. This feeling of being part of something special that is larger than ourselves is a powerful force and an important dividend of great leadership.

Academic Medical Centers↗
PubMed2004

New ways of understanding and accomplishing leadership in academic medicine.

Understanding leadership as being about a person in charge is not wrong, but it is no longer adequate. The challenges and problems confronting medicine today are so complex and unpredictable that it is practically impossible for one person to accomplish the work of leadership alone. More leadership requires more shared work, but as hospitals and medical centers begin to break down departmental barriers, people have to learn to work with individuals and groups who may have different work ethics, dissimilar styles of solving problems, or even contrasting values. Successful academic medical centers will make use of a broader repertoire of leadership strategies--besides developing leaders, they will develop leadership as a property of the system, as an organizational capacity. While leader development involves enhancing human (individual) capital, the emphasis in leadership development is on social capital and building more productive relationships that enhance networking, collaboration, and resource exchange. Leadership is created in and emerges from the relational space that connects people--accordingly, leadership development involves building high-quality connections between people. To make leadership happen more effectively, academic medical centers will have to identify and study the ingredients that catalyze and enhance human connectivity, augment social capital and activate leadership. Leadership is a uniquely human activity--studying it and how it works is core to the learning organization.

Conflict, Psychological↗
PubMed2004

Stimulation of intestinal glutamine absorption in chronic metabolic acidosis.

BACKGROUND: Amino acid glutamine plays a central role in inter-organ nitrogen transfer in acidosis, a compensatory mechanism that is essential in maintaining acidbase balance. Intestinal glutamine absorption is a key exogenous glutamine source in maintaining glutamine homeostasis. The purpose of this in vivo study was to investigate the regulation of intestinal glutamine absorption during chronic metabolic acidosis. METHODS: Metabolic acidosis in adult male Sprague-Dawley rats was induced by adding 1.5% NH4Cl to drinking water. [3H]-L-glutamine transport activity across brush border membrane vesicles and glutamine transporter ATB0 messenger RNA levels by relative reverse transcriptase-polymerase chain reaction were measured in rat jejunum. Data were analyzed by t test (P < .05). RESULTS: Acidosis occurred as early as 1 day and was partially compensated by 7 days. Glutamine transport in brush border membrane vesicles was increased after 2 days of acidosis. Chronic acidosis (7 days) resulted in an 8-fold increase of glutamine transport activity. The glutamine transport maximal capacity (Vmax) was stimulated 5-fold, while the transport affinity (Km) was not affected by acidosis. Relative reverse transcriptase-polymerase chain reaction showed a 2.5-fold increase of glutamine transporter ATB0 messenger RNA levels. CONCLUSIONS: Chronic metabolic acidosis stimulates intestinal glutamine absorption via a mechanism that involves an increase of functional membrane glutamine transporter units.

Acidosis↗
PubMed2004

The future-oriented department chair.

The authors describe the current dilemma facing academic health centers (AHCs) as they recruit department chairs. In the past, leaders at AHCs predominantly were concerned with fulfilling the esteemed tripartite missions of patient care, research, and education. Today, their time and energy are occupied by a different set of tasks that have a distinct business orientation, including winning contracts, enhancing revenue, reducing costs, recruiting and managing a diverse workforce, and dealing with consumer satisfaction and marketing. New visions and strategies must be developed--requiring different dimensions of leadership. The authors offer concrete recommendations for recruiting, retaining, and sustaining department chairs, and argue that a deliberative, thoughtful process of engaging chair candidates should begin by focusing on the candidates' values as a first priority. Candidates who most clearly share organizational values should then be engaged in an iterative process of developing a shared vision, resulting in a letter of agreement that explicitly states the mutual expectations and commitments of both the organization and the candidate. Once department chairs are in place, ongoing development through leadership training, mentoring, and other investments help to retain and sustain them.

Academic Medical Centers↗
PubMed2003

Metabolic acidosis stimulates intestinal glutamine absorption.

Glutamine is an essential nutrient for cell integrity during acidotic states such as shock, but the effect of extracellular pH on intestinal mucosal cell glutamine uptake is poorly understood. The purpose of this in vitro study was to investigate the intracellular signaling pathways involved in controlling intestinal glutamine transport during acidosis. Lowering the pH in the cell culture medium resulted in an increase in glutamine transport activity in a time- and pH-dependent fashion. Chronic acidosis (pH 6.6 for 48 hours) resulted in a twofold increase in glutamine transport activity (1.63+/-0.25 nmole/mg protein/minute in acidosis vs. 0.78+/-0.11 nmole/mg protein/minute in control) and a threefold increase in glutamine transport gene ATB(0) messenger RNA levels. This acidosis-induced increase in glutamine transport activity was due to a stimulation of transporter maximal transport capacity (V(max) 13.6+/-0.73 nmole/mg protein/minute in acidosis vs. 6.3+/-0.46 nmole/mg protein/minute in control) rather than a change in transporter affinity (K(m)=0.23+/-0.02 mmol/L glutamine in acidosis vs. 0.19+/-0.02 mmol/L glutamine in control). This acidosis-stimulated glutamine transport activity was blocked by actinomycin-D or cycloheximide. Cellular mitogen-activated protein kinase (MAPK) MEK1/2 and p42/44 levels were elevated in acidotic cells, and the acidosis-induced glutamine transport activity was blocked by the MAPK MEK 1 inhibitor PD 98059. Acidosis stimulates glutamine transport in Caco-2 cells via signaling pathways that lead to transcription of the glutamine transporter gene and translation of functional transporters. Mitogen-activated protein kinases are key intracellular regulators involved in this signal transduction cascade. An increased availability of glutamine to cells subjected to redox stress may help in maintaining cellular integrity.

Acidosis↗