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Biomedical subjects

A Mueller

Publications and source records attributed to A Mueller.

At least 37 records · Page 2Linked to original sources

Elevated monocytic IL-12 and TNF-alpha production in Wegener's granulomatosis is normalized by cyclophosphamide and corticosteroid therapy.

Wegener's granulomatosis (WG) is characterized by a predominance of the type 1 T-helper cell (Th1) response. We have studied monocytic cytokine expression in untreated patients and in patients who did not respond to prior methotrexate or trimethoprim-sulphamethoxazole therapy, i.e. patients with active disease. Intracytoplasmic IL-12 and TNF-alpha expression was significantly increased in WG compared with healthy controls. IL-8 expression was not increased. Two and 12 weeks of daily standard oral cyclophosphamide and corticosteroid (CYC + GC) treatment induced a stable remission of the disease. Elevated IL-12 and TNF-alpha expression of monocytes was normalized. The active metabolite of CYC was shown to down-regulate IL-12 mRNA in vitro. Monocytic cytokines, especially IL-12, may have a role in the early determination and skewing of the immunoregulatory response towards a Th1 profile. It appears that CYC + GC exerts its effect by normalizing the Th1-driving cytokine pattern, and CYC may maintain this mode of action. Normalization of the skewed cytokine pattern may be a prerequisite and an indicator of inducing a remission in WG.

Adrenal Cortex Hormones↗

Pseudomembranous tracheobronchitis due to Bacillus cereus.

We present a case of a rapidly progressive pseudomembranous tracheobronchitis and pneumonia in a 52-year-old woman with severe aplastic anemia. Bacillus cereus was isolated from bronchoalveolar lavage fluids, blood cultures, and pseudomembrane biopsy specimens; despite intensive antibiotic treatment, the patient's condition deteriorated rapidly. To our knowledge, this is the first report of a B. cereus infection that has caused pseudomembranous tracheobronchitis, possibly because of the production of bacterial toxins.

Anti-Bacterial Agents↗

Photoinitiated destabilization of sterically stabilized liposomes.

A considerable effort has been devoted to the development of liposomes for the transport and buffering of drugs in the body. Several research groups have reported the increased localization of sterically stabilized liposomes (PEG-liposomes) at tumor sites. If PEG-liposomes are to be effective carriers of therapeutic agents, their drug permeability must be sufficiently low that little passive release occurs during the circulation time of the PEG-liposomes. However, once PEG-liposomes reach tumor sites, it may be desirable to accelerate the release of the encapsulated drug. The use of light to stimulate the release of encapsulated compounds from liposomes is attractive, because it is possible to control the spatial and temporal delivery of the radiation. PEG-liposomes composed in part of the photosensitive lipid, bis-SorbPC, can be prepared in a manner that effectively encapsulates water soluble compounds, yet releases them upon exposure to ultraviolet light in the presence of oxygen. The observed increase in liposome permeability is about 200-fold at high photoconversion of the monomeric bis-SorbPC. The increase in permeability is dependent on the extent of photolysis, but independent of both the charge on the PEG-lipid and the mole fraction of PEG-lipid included in the liposome. Therefore the photoinitiated destabilization of these PEG-liposomes is not a consequence of micellization of the PEG-lipid, but probably due to the formation of defects in the bilayer during crosslinking of the bis-SorbPC. The photoinduced increase in liposome permeability is great enough to make it possible to release therapeutic agents from PEG-liposomes at specific sites in a manner of tens of minutes to hours.

Drug Carriers↗

Changes in quality of life after medical intensive care.

OBJECTIVES: To determine outcome and changes in health-related quality of life (QOL) in medical intensive care patients. DESIGN AND SETTING: Prospective comparison of QOL before and 6 months after intensive care unit (ICU) admission in a 12-bed noncoronary medical ICU of a university hospital. PATIENTS: All 325 consecutively admitted adult patients who spent at least 24 h on the ICU were eligible. MEASUREMENTS AND RESULTS: QOL measurements were collected before and 6 months after ICU admission. Comorbidity classified by the Charlson index was 2.44 +/- 1.96. Mean stay in the ICU was 10.4 +/- 15.1 days, mean Acute Physiology and Chronic Health Evaluation II score was 23 +/- 10. Cumulative mortality was: ICU 24 %, hospital 34 %, 6 months 43 %. Relative to baseline, follow-up interviews of 185 survivors revealed no significant changes in the overall QOL score (p = 0.93). The subscales basic physiological activities (p = 0.07) and normal daily activities (p = 0.15) showed a nonsignificant deterioration. A significant improvement was noted for the domain emotional state (p = 0.013). CONCLUSIONS: Six months after admission to a medical ICU most survivors had regained their preadmission health-related QOL. Multivariate analysis showed that preadmission QOL, age, and severity of illness were most strongly associated with follow-up QOL. Of the survivors 86 % were living at home, and all but one of those previously in employment had returned to their former work. Most patients (94%) would undergo ICU treatment again if necessary.

Adolescent↗

Contribution of lymphatic drainage system in corneal allograft rejection in mice.

PURPOSE: To modulate aqueous outflow via the uveoscleral pathway and to determine its influence on corneal graft survival in mice. METHODS: BALB/c mice received corneal transplants from C3H mice and were placed randomly in three treatment groups: saline, pilocarpine or latanoprost. Three further groups received adjuvant systemic and topical corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection. RESULTS: Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection. CONCLUSION: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

Animals↗

CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis.

BACKGROUND: Lack of CD28 expression on peripheral blood CD4+ and CD8+ T cells has been reported in patients with Wegener's granulomatosis (WG), suggesting a pathogenetic role of CD28- T cells in WG. METHODS: Ten patients with WG and six with sarcoidosis (disease control) were analysed. Fluorescence activated cell sorter (FACS) analysis was used to detect CD28 expression on T cells from peripheral venous blood and from bronchoalveolar lavage (BAL) fluid. T cells in biopsy specimens from granulomatous lesions of the upper respiratory tract were analysed for CD28 expression by double immunofluorescence staining. RESULTS: A significantly higher fraction of CD28- T cells was found in the CD4+ and CD8+ T cell compartment in BAL fluid (65.6 (5.4)% and 76.3 (4.1)%, respectively) than in blood (13.4 (6.2)% and 42.9 (6.2)%; p<0.001) in patients with WG but not in those with acute sarcoidosis (6.7 (2.2)% and 53.4 (7.3)% in BAL fluid v 4.1 (2.5)% and 52.0 (9.4)% in blood). The total number of CD4+/CD28- T cells but not of CD8+/CD28- T cells was also significantly higher in BAL fluid than in blood in patients with WG (p<0.05). Patients with WG had a significantly higher fraction of CD28- T cells in the CD4+ and CD8+ T cell compartment in BAL fluid than patients with acute sarcoidosis (65.6 (5.4)% v 6.7 (2.2)%; p<0.001; and 76.3 (4.1)% v 53.4 (7.3)%; p<0.05). The total number of CD4+/CD28- and CD8+/CD28- T cells was also significantly higher in patients with WG than in those with sarcoidosis (p<0.01). An abundance of CD28- T cells was found in granulomatous lesions by double immunofluorescence staining in patients with WG. CONCLUSIONS: Our data indicate enrichment of CD28- T cells in BAL fluid and suggest recruitment of CD28- T cells into granulomatous lesions in WG. Further analysis of the phenotype and function of T cell subsets in WG is needed to better understand leucocyte homing in WG and to find new therapeutic targets.

Aged↗

Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism.

OBJECTIVE: Recent studies have shown an influence of the calcium-sensing receptor variant A986S on the serum calcium concentration, suggesting that this genetic variant could be a candidate for various bone and mineral disorders. The intention of this study was therefore to investigate the frequency of the described calcium-sensing receptor variants A986S, R990G and Q1011E in patients with primary hyperparathyroidism to test the hypothesis as to whether these variants represent risk factors for the development of primary hyperparathyroidism. DESIGN: Fifty patients with primary hyperparathyroidism were included in the study. One hundred and two healthy blood donors served as controls. METHODS: Detection of the genetic variants A986S, R990G and Q1011E was done by direct sequencing of exon 7 of the calcium-sensing receptor in leucocyte DNA. RESULTS: The heterozygous variant A986S was found in 34% (17 of 50) of the healthy age- and sex-matched controls and 40% (20 of 50) of the patients with primary hyperparathyroidism. This difference was not statistically significant (P=0.68). However, in male patients the heterozygous variant A986S was found more frequently (67%, 6 of 9) than in male controls (20%, 2 of 10, P=0.07). The variants R990G and Q1011E were found less frequently (8-20%) in patients and controls without significant differences between the groups. Patients with the heterozygous variant Q1011E had significantly higher serum calcium and parathyroid hormone levels than patients with the wild-type variant (P<0.01). There was no correlation of serum calcium (total and corrected for albumin) with the calcium sensing receptor variant A986S in 102 healthy blood donors (P=0.45). CONCLUSIONS: The calcium-sensing receptor variants do not, therefore, seem to be major genetic determinants for the development of primary hyperparathyroidism. The variant A986S may possibly represent a risk factor for the development of parathyroid neoplasia in men. Moreover, the presence of the genotype Q1011E might influence the clinical course of the disease. The previously reported significant correlation of serum calcium levels with the genetic variant A986S in healthy subjects could not be confirmed.

Aged↗

Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms.

Mouse 6Ckine/SLC (secondary lymphoid tissue chemokine) is a chemotactic factor for dendritic cells, T cells, and NK cells in vitro. In addition, mouse 6Ckine/SLC interacts with the chemokine receptor CXCR3, as do several chemokines with antiangiogenic properties. These dual properties of mouse 6Ckine/SLC were tested for the induction of an antitumor response by transducing the C26 colon carcinoma tumor cell line with a cDNA encoding mouse 6Ckine/SLC. The C26-6CK-transduced cells showed reduced tumorigenicity in immunocompetent or in nude mice. Part of this effect was likely due to angiostatic mechanisms as shown by immunohistochemistry and Matrigel assay. C26-6CK tumors were also heavily infiltrated with leukocytes, including granulocytes, dendritic cells, and CD8+ T cells. In vivo, anti-CD8 treatment increased the tumorigenicity of the C26-6CK tumor cells, and tumor-infiltrating CD8+ T cells had the phenotype of memory effector cells, suggesting the induction of cytotoxic tumor-specific T lymphocytes. On the other hand, anti-asialo-GM1 depletion also increased the tumorigenicity of C26-6CK cells, supporting the participation of NK cells. Finally, tumor-infiltrating dendritic cells had the phenotype and functional features of immature dendritic cells. Overall, these results suggest that mouse 6Ckine/SLC has strong antitumor effects by inducing both angiostatic, CD8+ T cell-mediated, and possibly NK-mediated tumor resistance mechanisms.

Angiogenesis Inhibitors↗

Impact of the Banff '97 classification for histological diagnosis of rejection on clinical outcome and renal function parameters after kidney transplantation.

BACKGROUND: Data on a systematic correlation of specific pathomorphologic lesions in renal allograft biopsy specimens with clinical outcome parameters are crucial to determine the relevance of kidney biopsy findings after transplantation for graft prognosis. Specific histologic lesions of the revised Banff '97 classification were correlated with clinical follow-up data. METHODS: The analysis was done on a series of 48 consecutive renal allograft biopsy specimens. Logistic regression was used to compare for response to rejection treatment dependent on histologic grading. Cox regression was applied to analyze the impact of the histologic findings on graft failure during ongoing follow-up. RESULTS: Severity of acute rejection was statistically associated with unresponsiveness to antirejection treatment (odds ratio 2.39, 95% confidence interval 1.13-5.03) and predicted an increased risk of graft failure (hazard ratio 2.16, 95% confidence interval 1.48-3.14). Intimal arteritis (hazard ratio 1.85, 95% confidence interval 1.40-2.45) was the only determinate of a poor survival prognosis. Mean serum creatinine level and the need for antihypertensive drugs were significantly higher in the Banff I-III graded groups after 1 and 2 years of follow-up, whereas patients with borderline rejection were not significantly different from the control group. CONCLUSION: We confirmed a significant association between the revised Banff '97 classification and graft outcome. Intimal arteritis was the only significant predictor of a poor survival probability. The distinction of borderline rejection and Banff grade I rejection seems to be important from a prognostic point of view.

Acute Disease↗

The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Animals↗

Gammadelta T cell response induced by vaginal Herpes simplex 2 infection.

The purpose of the present studies was to determine whether acute vaginal infection with Herpes virus 2 altered the vaginal population of gammadelta T cells, and whether gammadelta T cells influenced the vaginal clearance of HSV-2. BALB/c mice were infected intravaginally with the progressively lethal wild type 333 strain, or the non-lethal thymidine kinase deficient (deltaTK- -HSV-2) mutant strain of HSV-2 virus. Changes in vaginal T cell composition were examined by FACS analysis 4 days after infection. Clearance of vaginal deltaTK- -HSV-2 infection was compared between mice with normal gammadelta T cell populations (BALB/c) and transgenic mice in which all the gammadelta T cells express a receptor that is specific for the b allotype of MHC class Ib T10 antigen (G8/BALB/c). In HSV-2 infected BALB/c mice, but not G8/BALB/c, a subset of gammadelta T cells that express a Vgamma2 TCR accumulated in the vaginal mucosa by the fourth day after infection. Unexpectedly, we found that gammadelta TCR transgenic mice exhibited a more rapid clearance of the virus than control mice (P < 0.05). These findings argue against the hypothesis that the normal populations of vaginal intraepithelial gammadelta T cells play a direct role in the elimination of virally infected epithelial cells.

Animals↗

Transcriptional pause, arrest and termination sites for RNA polymerase II in mammalian N- and c-myc genes.

Using either highly purified RNA polymerase II (pol II) elongation complexes assembled on oligo(dC)-tailed templates or promoter-initiated (extract-generated) pol II elongation complexes, the precise 3" ends of transcripts produced during transcription in vitro at several human c- and N- myc pause, arrest and termination sites were determined. Despite a low overall similarity between the entire c- and N- myc first exon sequences, many positions of pol II pausing, arrest or termination occurred within short regions of related sequence shared between the c- and N- myc templates. The c- and N- myc genes showed three general classes of sequence conservation near intrinsic pause, arrest or termination sites: (i) sites where arrest or termination occurred after the synthesis of runs of uridines (Us) preceding the transcript 3" end, (ii) sites downstream of potential RNA hairpins and (iii) sites after nucleotide addition following either a U or a C or following a combination of several pyrimidines near the transcript 3" end. The finding that regions of similarity occur near the sites of pol II pausing, arrest or termination suggests that the mechanism of c- and N- myc regulation at the level of transcript elongation may be similar and not divergent as previously proposed.

Base Sequence↗

Cyclin D1 overexpression combined with N-nitrosomethylbenzylamine increases dysplasia and cellular proliferation in murine esophageal squamous epithelium.

We previously described the oral-esophageal tissue-specific expression of cyclin D1 with the Epstein-Barr virus ED-L2 promoter in transgenic mice, and resulting dysplasia. Given the evidence for an interplay between environmental and genetic factors in esophageal squamous carcinogenesis, the aim of this study was to determine the potential cooperation of the nitrosamine compound N-nitrosomethylbenzylamine (NMBA), an esophageal specific carcinogen, in the cyclin D1 transgenic mice. NMBA was first demonstrated to induce dysplasia in two strains of inbred mice, C57BL/6 and FVB/N. Subcutaneous NMBA was then administrated to wild type and transgenic mice beginning at 4 weeks of age. Mice were monitored for the duration of the study for general appearance, activity and weight, and were euthanized at 12 and 15 months. Histopathologic analysis revealed increased severity of dysplasia in cyclin D1 mice treated with NMBA compared with treated age-matched wild-type mice and untreated mice. There was also increased proliferating cell nuclear antigen (PCNA) expression in the esophagi of NMBA treated cyclin D1 mice. Taken together, these findings suggest that a genetic alteration, specifically cyclin D1 overexpression and a chemical carinogen, NMBA, may cooperate to increase the severity of esophageal squamous dysplasia, a prominent precursor to carcinoma.

Animals↗

Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation.

S100 proteins, a subgroup of the EF-hand Ca2+-binding protein family, regulate a variety of cellular processes via interaction with different target proteins. Several pathological disorders, including cancer, are linked to altered Ca2+ homeostasis and might involve the multifunctional S100 proteins, which are expressed in a cell- and tissue-specific manner. The present work demonstrates a distinct intracellular localization of S100A6, S100A4, and S100A2 in two tumor cell lines derived from metastatic epithelial breast adenocarcinoma (MDA-MB231) and cervical carcinoma (HeLa). Treatment of the cells by thapsigargin, the ionophore A23187, or cyclic ADP-ribose, to increase [Ca2+]i via different pathways, led to relocation of S100A6 and S100A4 but only partially of the nuclear S100A2, as demonstrated by confocal laser scanning microscopy. These findings support the hypothesis that S100 proteins could play a crucial role in the regulation of Ca2+ homeostasis in cancer cells.

Adenosine Diphosphate Ribose↗

Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation.

BACKGROUND: Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation. METHODS: The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years). RESULTS: Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6. 52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up. CONCLUSIONS: Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.

Acute Disease↗

Nifedipine and Bay K 8644 Induce an increase of

BACKGROUND: The dihydropyridine-induced vasorelaxation is partly dependent on the endothelium, which does not express L-type calcium channels. Because nitric oxide (NO) is one of the most important endothelium-derived vasorelaxing factors, we investigated how the calcium antagonist nifedipine and the calcium agonist Bay K 8644 modulate intracellular calcium and NO formation in porcine endothelial cells. METHODS AND RESULTS: NO formation of porcine aortic endothelial cell cultures and of native endothelium of intact porcine coronary arteries was measured with an electrochemical electrode, and the intracellular concentration of Ca(2+) [Ca(2+)](i) was evaluated using the Fura-2 technique. Nifedipine induced a concentration-dependent [0,01-1 µmol/L] increase in [Ca(2+)](i) and NO formation in cultured porcine aortic endothelial cells, and moreover a dose-dependent NO formation in native endothelial cells from intact porcine coronary arteires, which was higher than in cultured cells. This effect was inhibited by N-nitro-l-arginine, a specific NO synthase inhibitor. Bay K 8644 caused a [Ca(2+)](i) increase and NO release in cultured cells, too, although to a lesser extent. Nifedipine-induced and Bay K 8644-induced [Ca(2+)](i) rise could be blocked by removal of extracellular calcium, indicating that a calcium influx may be involved. CONCLUSIONS: The calcium antagonist nifedipine as well as the calcium agonist Bay K 8644 cause an increase of [Ca(2+)](i) and NO in porcine endothelium. Therefore, these effects seem to be related to the dihydropyridines as a substance class, which may explain the endothelial component in dihydropyridine-induced vasorelaxation.

Journal Article↗

An analysis of nurses' communications in a shelter setting.

The purpose of this study was to analyze written communications among nurses providing care to battered women and their children in a community shelter setting over a 1-year period of time. Interviews were conducted with the nurses to study the perceived effectiveness of the manual used to update daily shelter health operations, clients of concern, follow-up recommendations, or other ongoing issues. The unit of analysis was each entry recorded in the manual. The Communications Process Model guided the study (Budd, Thorp, & Donohew, 1967). Communications were transcribed and analyzed for categories of meaning from the data utilizing the Ethnograph software (Seidel & Clark, 1983). When content analysis was applied, 10 distinct categories emerged: (a) injury assessment, (b) acute condition assessment, (c) chronic condition assessment, (d) pregnancy assessment, (e) emergency assessment, (f) nursing care and procedures, (g) teaching and counseling, (h) community referrals and resources, (i) housekeeping, and (j) health program issues. From the categories, 3 primary themes were identified: nursing assessments, nursing interventions, and health program operations. The nurses were positive about using the manual for various communications. Nurses who consider working in shelter settings may find descriptions of the realities of practice and application of a working tool for communications useful. Shelter administrators and board members need to recognize the importance of having nurses on staff to address inevitable injuries and health concerns of battered women and their children. Researchers are encouraged to develop models that relate to care of clients and caregivers in this challenging practice setting.

Battered Women↗

Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection.

BACKGROUND & AIMS: Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis that may progress to atrophic gastritis, a premalignant process. A mouse model of Helicobacter felis infection was used to study possible genetic determinants of the response to infection. METHODS: Three inbred mouse strains with known secretory phospholipase A2 (sPLA2) genotypes [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (-/-)] were orally infected with H. felis and examined longitudinally using routine histology, immunocytochemistry, electron microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies. RESULTS: Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide. In contrast, no significant change in these cell types was observed in BALB/c and C3H/HeJ strains. Increased expression of sPLA2 was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA2 expression was absent in C57BL/6 mice. CONCLUSIONS: H. felis infection leads to increased apoptosis and altered cellular differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA2 expression. Because sPLA2 has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp formation in the colon, these studies suggest that sPLA2 may also influence the gastric epithelial response to Helicobacter infection.

Animals↗