Lesions in certain areas of the parietal cortex in Macaque monkeys produces deficits in visual and somatosensory perception, as well as, eye and arm activity associated with exploration of extrapersonal space. This study focused on recording from neurons in area 7b of the posterior parietal association cortex with visual or somatosensory receptive fields (RFs) that were modulated by eye or arm position. Two Macaque (Maccaca mulatta) monkeys were trained to maintain a steady gaze and arm position while a visual stimulus (illuminated circle) or a tactile stimulus (brushing of the dorsal side of the hand) was delivered. Microelectrodes were advanced into cortical area 7b of the monkeys and action potentials were recorded extracellularly from neurons while the stimuli were being delivered. When neurons with visual or tactile RFs were identified, the eye or arm position was altered, and the phasic responses to sensory stimuli and tonic activity was evaluated. Modulated phasic and tonic activity in neurons provide information on the spatial encoding of stimuli in extrapersonal space. Previous studies of area 7b have documented a sparse number of neurons with visual RFs, but in the present study, fifty percent of the neurons in the middle and posterior thirds of area 7b had visual RFs. During the eye position task, neurons with craniocentric responses, visual RFs that were dependent upon the head's position, were observed, and in more than half of the trials, neurons with tonic angle of gaze activity discharged when the eyes were directed into the contralateral hemi-field. Eighty-six percent of the neurons with tactile RFs, sensitive to passive arm positioning, increased activity when the hand moved into the contralateral hemi-field. The majority of those neurons increased activity when the arm angle approached forty-five degrees contralateral, a position that coincides with one of the most responsive visual angles in the eye position task. In contrast, fifty-six percent of the neurons with tonic angle of arm signals increased activity when the arm was moving further into ipsilateral hemi-space. All of these neuronal types describe a region of the brain that contributes to the spatial encoding of stimuli in extrapersonal space.

Home phototherapy using fiberoptic lights for the treatment of newborn hyperbilirubinemia has proven to be safe and effective. The purpose of this study was to explore whether differences in the outcomes of duration, reduction of bilirubin levels, hyperbilirubinemia resolution, or readmission could be explained by initial bilirubin levels and variations in newborn clinical characteristics at the commencement of treatment. This retrospective chart review of 187 newborns, who had received home phototherapy, revealed hyperbilirubinemia resolved in 162 of the cases (86.6 percent). Seventeen (9.1 percent) required readmission to the hospital. The strongest predictor of treatment duration using birthweight, feeding type, age at admission, and bilirubin level at commencement of treatment as independent variables was the age of the newborn at admission (R2 =.03) followed by the bilirubin level at commencement of treatment (R2 = 0.10). No variables showed predictive power in relation to the absolute drop in bilirubin. Furthermore, those newborns whose hyperbilirubinemia resolved and those who required readmission showed no significant differences in relation to their clinical characteristics of birthweight, bilirubin level at commencement of treatment, or age at admission. When variables of absolute drop in bilirubin, bilirubin level at the completion of treatment, duration of treatment, gestational age, and age at admission were analyzed based on feeding type (bottle vs. breast), the only significantly different characteristic was the bilirubin level at the completion of treatment (p =.034). Bilirubin levels at the completion of treatment were on the average lower for bottle-fed newborns when compared to breast-fed newborns. Results suggest that the older the newborn at admission, the shorter the treatment duration, and the higher the bilirubin level on admission, the longer the duration of treatment. Findings also suggest pediatricians tolerate higher bilirubin levels at the completion of treatment for breast-fed newborns than for bottle-fed. This study illustrates implications for nursing and medical management of hyperbilirubinemia by providing information regarding the home phototherapy population, treatment outcomes, and highlighting the need for proper follow-up, documentation, and continued research of this potential public health problem.

Proteus mirabilis, a motile gram-negative bacterium, is a principal cause of urinary tract infections in patients with functional or anatomic abnormalities of the urinary tract or those with urinary catheters in place. Although a number of putative virulence factors have been determined, when and where these genes are expressed in vivo are not yet known. Therefore two approaches were undertaken: (1) To study the in vivo expression of urease, the gfp gene (which encodes green fluorescent protein) was used to construct reporter fusions with ureD. Wild type P. mirabilis carrying the fusion plasmid was inoculated into experimental mice with ascending UTI. After seven days infection, fluorescent bacteria were detected in the kidney and the bladder by fluorescence microscopy, indicating that the urease genes are actively expressed during infection. Principally, vegetative forms of bacteria colonizing the bladders were observed; (2) MR/P fimbriae produced by P. mirabilis undergo phase variation in vitro. By DNA sequence analysis, an invertible element was found in the intergenic region between mrpI and mrpA. A sigma70 promoter within the invertible element drives the transcription of mrpA when in the ON position. MrpI, a putative recombinase, was able to confer inversion of the mrp switch region from both ON to OFF and OFF to ON. By in vivo PCR, MR/P phase variation could also be detected in vivo. In the absence of urolithiasis, the switch was found >99% in the ON position, suggesting that expression of MR/P fimbriae is selected in P. mirabilis in vivo. In addition, signature-tagged mutagenesis was used to identify more potential virulence genes of P. mirabilis. Random mutations in the chromosome were made by transposon mutagenesis. A 96-mutant pool was experimentally inoculated into the bladders of CBA mice. After two days infection, bacteria from the bladders and the kidneys were collected. By PCR and dot blot, two mutants were reproducibly unrecoverable and found to be attenuated for virulence. The two interrupted genes were cloned and sequenced. By sequence homology search and in vitro analyses, one of them appears to be a gene encoding a protease or collagenase; The other is a gene in the rpoN operon, which also encodes the sigma54 factor of RNA polymerase, and is presumably involved in expression of nitrogen regulated genes.

The purpose of this investigation was to describe and examine the impact of executive team excellence and the work environment of acute care, general hospitals as expected to contribute to organizational creativity. Selected dimensions of the work environment included stimulants and obstacles to creativity. The principal foundation of the study was the interactionist model of organizational creativity by Woodman, Sawyer, and Griffin (1993). Team excellence was derived from the Team Excellence Model by Larson and LaFasto (1989). Amabile's (1988a) model of creativity and innovation served as the basis for the examination of impact of the work environment on organizational creativity. The randomly selected sample was 13 hospital executive teams, which represented 8% of the 170 requests mailed to potential participants, in four south Atlantic region states and the District of Columbia. Executive teams were defined as including the team leader (chief executive officer) and two team members (chief financial and nurse executives). A descriptive, correlational research design was used. Team excellence was measured using the "Team Excellence" assessments (Larson & LaFasto, 1987). Work environmental stimulants and obstacles to creativity and organizational creativity were measured using the "KEYS Assessing the Climate for Creativity" survey by Amabile (1987a, 1990, 1995a). A researcher-developed questionnaire was used to obtain information on the hospital attributes. Data analysis included correlations and descriptive statistics. Nonparametric tests were used due to sample size and departures from normality. Overall respondents rated their team performance, stimulants to creativity in the work environment and organizational creativity higher on all assessment scales than normative data. In this study sample, hospital executive teams perceived clear, elevating goal, organizational encouragement, supervisory encouragement and challenging work as important aspects for organizational creativity. Organizational impediments and workload pressure were negatively correlated with organizational creativity, but non-significant. It seems that the most important lesson for hospital executives is that team performance and the intra-organizational environment play a role in distinguishing high from low levels of creativity in organizations. Despite the limitations, outcomes suggest further expansion and delineation of this research.

The purposes of the study are to test relationships among injury appraisals, coping, social support and outcomes of coping efficacy, mood states, and post-traumatic stress; and to test the interaction effects of coping and social support on the relationship of stress and outcomes in the traumatically injured individual one week following accidental injury. The conceptual model for the study is primary derived from the stress and coping theory which includes major components of stress appraisals, coping, social support, and outcomes. A sample of 152 hospitalized trauma patients a week following accidental injury were recruited from two trauma centers. The measures included the injury appraisal of perceived stressor, perceived stressfulness, perceived controllability, and perceived injury severity; the modified Ways of Coping Scale (WCS); the brief Social Support Questionnaire (SSQ); the brief Profile of Mood State (POMS); the Impact of Event Scale (IES); and selected demographic and injury related variables.;Data were analyzed by multivariate statistics. The results indicated that perceived controllability (beta=.17, p<.01), satisfaction with social support (beta=.27, p<.01), wishful thinking (beta=-.33, p<.01), and problem-focused coping (beta=.23, p<.01), were the significant predictors for coping efficacy; perceived stressfulness (beta=.33, p<.01), problem-focused coping (beta=-.19, p<.01), and wishful thinking (beta=.47, p<.01),explained a significant amount of variance in mood states; and avoidance coping (beta=.42, p<.01), and wishful thinking (beta=.23, p<.01), were the significant predictors for post-traumatic stress. The moderating effects of emotion-focused coping at high and medium levels were identified as the underlying mechanism that affects coping efficacy by enhancing negative effect of stress on outcome. No buffering effects of social support were identified in the study. These findings can be used to identify traumatically injured patients who are at risk for mood disturbance and post-traumatic stress in the trauma center. Nursing interventions to address these factors can be developed and tested. Longitudinal studies are needed for understanding the mechanism of relationships among appraisals, coping, social support and outcomes of coping efficacy, mood states, and post-traumatic stress.

Intermediate filament (IF) proteins are found in the cytoplasm as long 10 nm filaments and in the nucleus as a meshwork underlying the nuclear envelope. IF proteins contain a central conserved rod domain flanked by variable N- and C-terminal domains. At mitosis IFs disassemble, intermixing freely, but after mitosis the proteins resegregate to their respective compartments. In this work, three motifs, the nuclear localization signal (NLS), the CAAX motif, and the 42 AA insert, specific to lamin proteins, were studied as to their role in targeting and assembly. The NLS is believed to target lamins to the nucleus while the CAAX motif acts to confer association of lamins with the nuclear envelope. The 42 AA insert is thought to inhibit association of lamins with their cytoplasmic counterparts. To examine these theories HeLa cells were transiently transfected with IF molecules containing or lacking the three motifs and their cellular localization was studied. Chimeric molecules were also created from the cytoplasmic IF, NF-L, and lamin to further test the role of other IF domains in assembly and sorting. Lamin B mutants deleted of any one of the three motifs showed delayed but appropriate targeting to the nucleus. In contrast, mutants deleted of more than one motif were defective in targeting indicating that the three motifs act in concert with one another to ensure timely and correct lamina assembly. Stable cell lines expressing lamin B either with or without a CAAX motif were created. Biochemical analysis of the cell lines indicated that a large portion of lamin B does not co-fractionate with its putative receptor (p58), suggesting that the two proteins do not bind directly with one another. Overexpression of lamin mutants lacking a CAAX motif resulted in accumulation into multiple aggregates within the nucleus that did not colocalize with coiled bodies. Assembly phenotypes of IF mutants were dependent on the head domain sequences. Long filaments were formed with cytoplasmic head domains were present on lamin rods, but the converse phenotype of reticular filaments formed whenever the lamin head domain was present.

Human hepatocyte growth factor (hHGF) is a potent mitogen, motogen and/or morphogen in various organ systems including the liver, mammary gland, bone marrow, lungs, and gastrointestinal tract. c-met, a proto-oncogene is the cellular receptor for hHGF. In this study, I report the development and characterization of two transgenic animal models: human hepatocyte growth factor/severe combined immunodefeciency (hHGF/SCID) and human hepatocyte growth factor/recombinase activating gene I mice (hHGF/RAG1). SCID and RAG1 mice were serially backcrossed with TG.AH2 (a transgenic mouse overexpressing human HGF), in order to select for both the immunodeficiency trait and for expression of serum human HGF production. Both models demonstrated characteristic liver enzyme profiles pre and post partial hepatectomy, specific responses to whole body irradiation, serum hHGF concentrations of up to 250 ng/ml, and an increased Bromodexoyuridine labeling index (up to 4 x control) in the liver. There were histopathologic changes in the liver: severe, diffuse hepatocellular hypertrophy with pleiotrophic nuclei, numerous bi- and tri-nucleated hepatocytes, and cribriform-shaped nuclei. Up to 15% of the hHGF/SCID animals demonstrated tumors of epithelial and mesencyinal origin. Mammary adenocarcinoma, well-differentiated papillary adenocarcinoma, multi-organ lymphoma with metastasis, and hemorrhagic ovarian cyst with dysplastic epithelium also were seen and characterized. Non-neoplastic changes included diffuse lymphoplasmacytic interstitial pneumonia, interstitial nephritis and hypoplastic bronchi-associated lymphoid tissue. We transplanted a human liver epithelial cell line intrasplenically and subcutaneously in the presence of gelfoam. Histological and immunohistochemical techniques identified hepatocytes in the spleen, liver and gelfoam sponge after 2, 7 and 14 days post-transplantation, and the cells were detectable in the gelfoam sponge up to 60 days post-transplantation. I have developed and characterized an immunodeficient transgenic mouse model expressing high level of serum hHGF. Transformed human hepatocytes were transplanted into the model, and they were sustained for at least 60 days post-transplantation. The model should be useful for cellular and molecular biology studies of human hepatocytes, human gene therapy and infectious diseases of human hepatocytes.

Coronary heart disease (CHD) is the leading cause of death for women in the United States. The relationship between anger and cardiovascular reactivity, studied extensively in men, indicates that anger may be a contributing factor in the development of CHD. Only recently has research suggested that anger also may increase the risk of CHD in women. The purpose of this study was to examine the combined effects of anger and denial on cardiovascular responses to mental stressor tasks and CHD risk factors in postmenopausal women. Eighty postmenopausal women (58 +/- 5 years old, mean + SD) participated in the study. A median split on trait anger and denial was used to classify subjects into three groups: (1) low anger/low denial; (2) low anger/high denial; and (3) high anger/low or high denial. Mental stressors given to the women were speech and anger recall tasks. CHD risk factors included cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) body mass index (BMI), and waist-hip ratio (WHR) At baseline WHR (0.80 +/- 0.10), CHOL (201 +/- 33), TG (125 +/- 56), HDL-C (56 +/- 16), and LDL-C (119 +/- 31) were with in normal limits. BMI (29 +/- 8) indicated obesity. Repeated measures analysis of variance revealed statistically significant (P < .05) changes in heart rate and systolic and diastolic blood pressure from baseline to each stress task, however there were no significant differences between the groups. The speech task precipitated a greater heart rate change than the anger recall task. A significant change in both negative and positive affect accompanied the cardiovascular changes, but the groups did not differ on CHD risk factors. Anger and denial may be part of a complex pattern of psychological vulnerability to CHD risk and disease end-points. If cardiovascular reactivity is the mediating mechanism, then women may be at increased risk. Continued efforts toward refining the relationship of anger and denial and its biological impact will contribute to a better understanding of women's coronary-prone behavior association with CHD.

Spacers are commonly prescribed for use with pressurized metered dose inhalers (MDIs), in the hope of increasing the total drug dose inhaled by a patient. The effect of spacer geometry, size, design and mode of use on the quality of aerosol output was critically examined to assess the validity of typical in-vitro test protocols used by spacer manufacturers to document spacer performance. (1) A pilot clinical study showed that patients induced delays between actuation and the onset of inhalation, even after extensive training on AeroChamber, ACE and OptiHaler spacers. Total drug output (TDO) from these spacers was reduced substantially when such delays were simulated in-vitro. (2) AeroChamber and OptiChamber (differently sized spacers with mouthpiece valves) were tested with Ventolin, Beclovent and Intal to determine TDO and fine particle dose (FPD). OptiChamber yielded a higher TDO and FPD, which was less sensitive to actuation-inhalation delays than AeroChamber. Spacer size and valve design were found to affect performance. (3) Spacers 2 to 8 inches long, with internal diameters of 1 to 2.5 inches were tested with Ventolin and Intal. For Ventolin, the 2.5 inch spacer gave the highest TDO and FPD of all the lengths tested. Length had a minimal effect. Drug output from Intal was affected by both spacer length and width. (4) Sites of maximum drug loss within these spacers were determined by building equivalently sized spacers from interlocking rings. Ventolin deposition was concentrated 1 to 2 inches from the actuator spray nozzle, while almost uniform Intal distribution was observed along the spacer length. (2) and (3) suggest that all spacer-MDI combinations may not function equivalently. Determining spacer performance under ideal in-vitro conditions, and ignoring patient use scenarios can potentially over estimate spacer efficiency. All valved spacers do not perform identically and larger spacers do not always enhance dose delivery. There are significant differences in meaningful performance parameters of marketed spacers deemed equivalent by the United States Food and Drug Administration. Spacer performance with one inhaler may not be indicative of all inhaled medications.