Caenorhabditis elegans germinal center kinase (Gck-1) is a p-body component that inhibits precocious ectopic MAP kinase dependent meiotic maturation

The Caenorhabditis elegans germline is an excellent model system for studying meiosis, as the gonad contains germ cells in all stages of meiosis I prophase in a linear temporal and spatial pattern. To form healthy gametes, many events must be coordinated. Failure of any step in the process can reduce fertility. Here, we describe a C. elegans Germinal Center Kinase, GCK-1, that is essential for the accurate progression of germ cells through meiosis I prophase. In the absence of GCK-1, germ cells undergo precocious maturation due to the activation of a specific MAP kinase isoform. Furthermore, GCK-1 localizes to P-bodies, RNP particles that have been implicated in RNA degradation and translational control. Like two other components of C. elegans germline P-bodies, GCK-1 functions to limit physiological germ cell apoptosis. This is the first study to identify a role for a GCK-III kinase in metazoan germ cell development and to link P-body function with MAP kinase activation and germ cell maturation. ^

B cells in ADA deficiency

Deficiency of the enzyme adenosine deaminase (ADA) results in severe lymphopenia in humans. Mice with an inactivating mutation in the ADA gene also exhibit profound lymphopenia, as well as pulmonary insufficiency and ribcage abnormalities. In fact, the mouse model has a phenotype that is remarkably similar to that of the human disease, making the mice valuable tools for unraveling the mechanism of lymphocyte destruction in absence of this housekeeping gene. T cell deficiency in ADA deficiency has been extensively studied by others, revealing a block in early thymocyte development. In contrast, our studies revealed that early B cell development in the bone marrow is normal. ADA-deficient mice, however, exhibit profound defects in germinal center formation, preventing antigen-dependent B cell maturation in the spleen. ADA-deficient spleen B cells display significant defects in proliferation and activation signaling, and produce more IgM than their normal counterparts, suggesting that extrafollicular plasmablasts are overrepresented. B cells from ADA-deficient mouse spleens undergo apoptosis more readily than those from normal mouse spleens. Levels of ADA's substrates, adenosine and 2′-deoxyadenosine, are elevated in both bone marrow and spleen in ADA-deficient mice. S ′-adenosyihomoeysteine hydrolase (SAH hydrolase) activity is significantly inhibited in both locales, as well. dATP levels, though, are only elevated in spleen, where B cell development is impaired, and not in bone marrow, where B cell ontogeny is normal. This finding points to dATP as the causative agent of lymphocyte death in ADA deficiency. ADA deficiency results in inhibition of the enzyme ribonucleotide reductase, thereby depleting nucleoside pools needed for DNA repair. Another mouse model that lacks a functional gene encoding a protein involved in DNA repair and/or cell cycle checkpoint regulation, p53-binding protein 1, exhibits blocks in T and B cell development that are similar to those seen in ADA-deficient mice. Unraveling the mechanisms of lymphocyte destruction in ADA deficiency may further understanding of lymphocyte biology, facilitate better chemotherapeutic treatment for lymphoproliferative diseases, and improve gene and enzyme therapy regimens attempted for ADA deficiency. ^

Studies on gene expression within germinal centers

During T cell dependent immune responses, the acquisition of B cell memory from naïve cells takes place within a highly specialized microenvironment: The germinal centers (GC) of the secondary lymphoid organs. The GC reaction is a tightly regulated process in which the balance between survival and death is mediated by signals transduced through ligation of critical costimulatory molecules such as CD40 and CD154. While most cognate receptor-ligand interactions occur between T-cells and antigen (Ag)-presenting cells (APC) such as B-cells, evidence of homotypic B cell interactions has emerged. Despite the progress in our understanding of the reaction, several questions remain: (1) What determines the concomitant expression of CD40 and its ligand CD154 by GC B-cells? (2) Which molecules are responsible for inducing GC-B cell survival? and (3) how can cognate T-cell help be recruited into the organized structure of GCs? ^ Because the expression of costimulatory and survival molecules is predominant at distinct Ag-dependent maturation stages, we hypothesized the existence of stage specific gene expression responsible for the regulation of the GC reaction. Our studies reveal several novel genes whose expression may be critical for the GC reaction. The discovery of AKNA reveals the mechanism behind homotypic B cell CD40 and CD40 ligand interactions, which can explain the costimulatory signaling to GC B cells in the absence of T cells. Additionally, the identification of the pro-survival molecule PRELI may provide a novel mechanism for the survival of Ag-selected B cells. We propose that PRELI and its phylogenic homologues represent a novel family of proteins responsible for the protection of cells against caspase-independent apoptosis. Furthermore, we show that GC B cells actively participate in the recruitment of T cells through the secretion of CC and CxC chemokines, thus supporting their mutual involvement in cognate interactions. ^

The Houston Academy of Medicine--Texas Medical Center Library management information system.

A management information system (MIS) provides a means for collecting, reporting, and analyzing data from all segments of an organization. Such systems are common in business but rare in libraries. The Houston Academy of Medicine-Texas Medical Center Library developed an MIS that operates on a system of networked IBM PCs and Paradox, a commercial database software package. The data collected in the system include monthly reports, client profile information, and data collected at the time of service requests. The MIS assists with enforcement of library policies, ensures that correct information is recorded, and provides reports for library managers. It also can be used to help answer a variety of ad hoc questions. Future plans call for the development of an MIS that could be adapted to other libraries' needs, and a decision-support interface that would facilitate access to the data contained in the MIS databases.

Interruptions in Workflow for RNs in a Level One Trauma Center

An understanding of interruptions in healthcare is important for the design, implementation, and evaluation of health information systems and for the management of clinical workflow and medical errors. The purpose of this study is to identify and classify the types of interruptions experienced by Emergency Department(ED) nurses working in a Level One Trauma Center. This was an observational field study of Registered Nurses (RNs) employed in a Level One Trauma Center using the shadowing method. Results of the study indicate that nurses were both recipients and initiators of interruptions. Telephones, pagers, and face-to-face conversations were the most common sources of interruptions. Unlike other industries, the healthcare community has not systematically studied interruptions in clinical settings to determine and weigh the necessity of the interruption against their sometimes negative results such as medical errors, decreased efficiency, and increased costs. Our study presented here is an initial step to understand the nature, causes, and effects of interruptions, thereby improving both the quality of healthcare and patient safety. We developed an ethnographic data collection technique and a data coding method for the capturing and analysis of interruptions. The interruption data we collected are systematic, comprehensive, and close to exhaustive. They confirmed the findings from earlier studies by other researchers that interruptions are frequent events in critical care and other healthcare settings. We are currently using these data to analyze the workflow dynamics of ED clinicians, to identify the bottlenecks of information flow, and to develop interventions to improve the efficiency of emergency care through the management of interruptions.

Interruptions in workflow for RNs in a Level One Trauma Center.

An understanding of interruptions in healthcare is important for the design, implementation, and evaluation of health information systems and for the management of clinical workflow and medical errors. The purpose of this study is to identify and classify the types of interruptions experienced by ED nurses working in a Level One Trauma Center. This was an observational field study of Registered Nurses employed in a Level One Trauma Center using the shadowing method. Results of the study indicate that nurses were both recipients and initiators of interruptions. Telephone, pagers, and face-to-face conversations were the most common sources of interruptions. Unlike other industries, the outcomes caused by interruptions resulting in medical errors, decreased efficiency and increased cost have not been systematically studied in healthcare. Our study presented here is an initial step to understand the nature, causes, and effects of interruptions, and to develop interventions to manage interruptions to improve healthcare quality and patient safety. We developed an ethnographic data collection technique and a data coding method for the capturing and analysis of interruptions. The interruption data we collected are systematic, comprehensive, and close to exhaustive. They confirmed the findings from early studies by other researchers that interruptions are frequent events in critical care and other healthcare settings. We are currently using these data to analyze the workflow dynamics of ED clinicians, identify the bottlenecks of information flow, and develop interventions to improve the efficiency of emergency care through the management of interruptions.

New library buildings: the Houston Academy of Medicine--Texas Medical Center Library.

A historical account is given of the Houston Academy of Medicine--Texas Medical Center Library within its Texas Medical Center setting in Houston, Texas. Outlined are planning, financing, and construction of the new library, which consists in part of new building and in part of renovated interiors of an old building originally completed in 1954. A concise picture is given of the new library's interiors, showing its functional success for users and employees alike. An architectural summary is appended showing gross and net footages, source of funds, costs and capacities.

Phase I clinical trials in 56 patients with thyroid cancer: the M. D. Anderson Cancer Center experience.

INTRODUCTION: Thyroid cancer is the most common endocrine malignancy. The outcomes of patients with relapsed thyroid cancer treated on early-phase clinical trials have not been systematically analyzed. PATIENTS AND METHODS: We reviewed the records of consecutive patients with metastatic thyroid cancer referred to the Phase I Clinical Trials Program from March 2006 to April 2008. Best response was assessed by Response Evaluation Criteria in Solid Tumors. RESULTS: Fifty-six patients were identified. The median age was 55 yr (range 35-79 yr). Of 49 patients evaluable for response, nine (18.4%) had a partial response, and 16 (32.7%) had stable disease for 6 months or longer. The median progression-free survival was 1.12 yr. With a median follow-up of 15.6 months, the 1-yr survival rate was 81%. In univariate analysis, factors predicting shorter survival were anaplastic histology (P = 0.0002) and albumin levels less than 3.5 g/dl (P = 0.05). Among 26 patients with tumor decreases, none died (median follow-up 1.3 yr), whereas 52% of patients with any tumor increase died by 1 yr (P = 0.0001). The median time to failure in our phase I clinical trials was 11.5 months vs. 4.1 months for the previous treatment (P = 0.04). CONCLUSION: Patients with advanced thyroid cancer treated on phase I clinical trials had high rates of partial response and prolonged stable disease. Time to failure was significantly longer on the first phase I trial compared with the prior conventional treatment. Patients with any tumor decrease had significantly longer survival than those with any tumor increase.

Resource Guide about the Texas Medical Center for International Visitors. 2011-2012

Information and contacts for the multiple institutions in the Texas Medical Center. Created by the International Affairs Advisory Council (IAAC).

Risk, outcomes, and cost of emergency center visits in cancer patients

Cancer is a chronic disease that often necessitates recurrent hospitalizations, a costly pattern of medical care utilization. In chronically ill patients, most readmissions are for treatment of the same condition that caused the preceding hospitalization. There is concern that rather than reducing costs, earlier discharge may shift costs from the initial hospitalization to emergency center visits. ^ This is the first descriptive study to measure the incidence of emergency center visits (ECVs) after hospitalization at The University of M. D. Anderson Cancer Center (UTMDACC), to identify the risk factors for and outcomes of these ECVs, and to compare 30-day all-cause mortality and costs for episodes of care with and without ECVs. ^ We identified all hospitalizations at UTMDACC with admission dates from September 1, 1993 through August 31, 1997 which met inclusion criteria. Data were electronically obtained primarily from UTMDACC's institutional database. Demographic factors, clinical factors, duration of the index hospitalization, method of payment for care, and year of hospitalization study were variables determined for each hospitalization. ^ The overall incidence of ECVs was 18%. Forty-five percent of ECVs resulted in hospital readmission (8% of all hospitalizations). In 1% of ECVs the patient died in the emergency center, and for the remaining 54% of ECVs the patient was discharged home. Risk factors for ECVs were marital status, type of index hospitalization, cancer type, and duration of the index hospitalization. The overall 30-day all-cause mortality rate was 8.6% for hospitalizations with an ECV and 5.3% for those without an ECV. In all subgroups, the 30-day all-cause mortality rate was higher for groups with ECVs than for those without ECVs. The most important factor increasing cost was having an ECV. In all patient subgroups, the cost per episode of care with an ECV was at least 1.9 times the cost per episode without an ECV. ^ The higher costs and poorer outcomes of episodes of care with ECVs and hospital readmissions suggest that interventions to avoid these ECVs or mitigate their costs are needed. Further research is needed to improve understanding of the methodological issues involved in relation to health care issues for cancer patients. ^

PREMATURE CONDENSATION OF SPERMATOGENIC CELL CHROMOSOMES

The technique of premature chromosome condensation (PCC) has been used primarily to study interphase chromosomes of somatic cells. In this study, mitotic cells were fused to cells from the mouse testes to examine the chromosomes of germ cells. The testes contain various types of cells, both germinal and nongerminal. In these initial studies, four types of PCC morphologies were observed. Chromosome morphology of the PCC and labeling experiments demonstrated the mouse cell origin of various PCC. Attempts were next made to determine the cell types producing the PCC. Spermatogonia, diplotene spermatocytes, secondary spermatocytes and round spermatids are proposed to be the origin of the PCC morphologies. Some PCC could be banded by G and C banding techniques and the mouse chromosomes identified.^ Studies were subsequently undertaken to evaluate this technique as a method of evaluating damage to germ cells. Testicular cells from irradiated mice were fused to mitotic cells and the PCC examined. Both round spermatids and secondary spermatocytes exhibited chromosome damage in the form of chromatid breaks. A linear correlation was found between the dose of irradiation and the number of breaks per cell. This technique may develop into a useful method for evaluating the clastogenic effect of agents on the germ cells. ^

AN OCCUPATIONAL INJURY MANAGEMENT INFORMATION SYSTEM FOR THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON

The purpose of this research and development project was to develop a method, a design, and a prototype for gathering, managing, and presenting data about occupational injuries.^ State-of-the-art systems analysis and design methodologies were applied to the long standing problem in the field of occupational safety and health of processing workplace injuries data into information for safety and health program management as well as preliminary research about accident etiologies. The top-down planning and bottom-up implementation approach was utilized to design an occupational injury management information system. A description of a managerial control system and a comprehensive system to integrate safety and health program management was provided.^ The project showed that current management information systems (MIS) theory and methods could be applied successfully to the problems of employee injury surveillance and control program performance evaluation. The model developed in the first section was applied at The University of Texas Health Science Center at Houston (UTHSCH).^ The system in current use at the UTHSCH was described and evaluated, and a prototype was developed for the UTHSCH. The prototype incorporated procedures for collecting, storing, and retrieving records of injuries and the procedures necessary to prepare reports, analyses, and graphics for management in the Health Science Center. Examples of reports, analyses, and graphics presenting UTHSCH and computer generated data were included.^ It was concluded that a pilot test of this MIS should be implemented and evaluated at the UTHSCH and other settings. Further research and development efforts for the total safety and health management information systems, control systems, component systems, and variable selection should be pursued. Finally, integration of the safety and health program MIS into the comprehensive or executive MIS was recommended. ^

Predictors of weight stability in women and men: The aerobic center longitudinal study, 1987--1995

It is estimated that more than half the U.S. adult population is overweight or obese as classified by a body mass index of 25.0–29.9 or ≥30 kg/m 2, respectively. Since the current treatment approaches for long-term maintenance of weight loss are lacking, the National Institutes of Health state that an effective approach may be to focus on weight gain prevention. There is a limited body of literature describing how adults maintain a stable weight as they age. It is hypothesized that weight stability is the result of a balance between energy consumption and energy expenditure as influenced by diet, lifestyle, behavior, genetics and environment. The purpose of this research was to examine the dietary intake and behaviors, lifestyle habits, and risk factors for weight change that predict weight stability in a cohort of 2101 men and 389 women aged 20 to 8 7 years in the Aerobic Center Longitudinal Study regardless of body weight at baseline. At baseline, participants completed a maximal exercise treadmill test to determine cardiorespiratory fitness, a medical history questionnaire, which included self-reported measures of weight, dietary behaviors, lifestyle habits, and risk factors for weight change, a three-day diet record, and a mail-back version of the medical history questionnaire in 1990 or 1995. All analyses were performed separately for men and women. Results from multivariate regression analyses indicated that the strongest predictor of follow-up weight for men and women was previous weight, accounting for 87.0% and 81.9% of the variance, respectively. Age, length of follow-up and eating habits were also significant predictors of follow-up weight in men, though these variables only explained 3% of the variance. For women, length of follow-up and currently being on a diet were significantly associated with follow-up weight but these variables explained only an additional 2% of the variance. Understanding the factors that influence weight change has tremendous public health importance for developing effective methods to prevent weight gain. Since current weight was the strongest predictor of previous weight, preventing initial weight gain by maintaining a stable weight may be the most effective method to combat the increasing prevalence of overweight and obesity. ^

Risk factors for Clostridium difficile nosocomial diarrhea in patients at the Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas

Background. Clostridium difficile is the leading cause of hospital associated infectious diarrhea and colitis. About 3 million cases of Clostridium difficile diarrhea occur each year with an annual cost of $1 billion. ^ About 20% of patients acquire C. difficile during hospitalization. Infection with Clostridium difficile can result in serious complications, posing a threat to the patient's life. ^ Purpose. The aim of this research was to demonstrate the uniqueness in the characteristics of C. difficile positive nosocomial diarrhea cases compared with C. difficile negative nosocomial diarrhea controls admitted to a local hospital. ^ Methods. One hundred and ninety patients with a positive test and one hundred and ninety with a negative test for Clostridium difficile nosocomial diarrhea, selected from patients tested between January 1, 2002 and December 31, 2003, comprised the study population. Demographic and clinical data were collected from medical records. Logistic regression analyses were conducted to determine the associated odds between selected variables and the outcome of Clostridium difficile nosocomial diarrhea. ^ Results. For the antibiotic classes, cephalosporins (OR, 1.87; CI 95, 1.23 to 2.85), penicillins (OR, 1.57; CI 95, 1.04 to 2.37), fluoroquinolones (OR, 1.65; CI 95, 1.09 to 2.48) and antifungals (OR, 2.17; CI 95, 1.20 to 3.94), were significantly associated with Clostridium difficile nosocomial diarrhea Ceftazidime (OR, 1.95; CI 95, 1.25 to 3.03, p=0.003), gatifloxacin (OR, 1.97; CI 95, 1.31 to 2.97, p=0.001), clindamycin (OR, 3.13; CI 95, 1.99 to 4.93, p<0.001) and vancomycin (OR, 1.77; CI 95, 1.18 to 2.66, p=0.006, were also significantly associated with the disease. Vancomycin was not statistically significant when analyzed in a multivariable model. Other significantly associated drugs were, antacids, laxatives, narcotics and ranitidine. Prolong use of antibiotics and an increased number of comorbid conditions were also associated with C. difficile nosocomial diarrhea. ^ Conclusion. The etiology for C. difficile diarrhea is multifactorial. Exposure to antibiotics and other drugs, prolonged antibiotic usage, the presence and severity of comorbid conditions and prolonged hospital stay were shown to contribute to the development of the disease. It is imperative that any attempt to prevent the disease, or contain its spread, be done on several fronts. ^