Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary schistosomiasis on Zanzibar: application of two novel assays for the detection of excreted albumin and haemoglobin in urine

Abstract As part of a urinary schistosomiasis control programme on Zanzibar, an aged cross-sectional survey of 305 children from three schools on Unguja was conducted to investigate the relationships between levels of excreted albumin and haemoglobin in urine and Schistosoma haematobium infection status. Diagnosis was determined by standard parasitological methods, dipstick reagents for microhaematuria, visual inspection for macrohaematuria as well as collection of case-history questionnaire data for self-diagnosis. Prevalence of infection as determined by parasitology was 53.9% and approximately, one quarter of the children examined were anaemic (<11 g dl−1). A statistically significant negative association of blood haemoglobin levels of boys and S. haematobium infection intensity status was observed (rs=−0.23, P=0.005). Through sensitivity analysis of urine-albumin values it was determined that a concentration of above >40 mg l−1, as measured with the HemoCue urine-albumin photometer, had sensitivity, specificity, positive and negative predictive values of 0.90, 0.83, 0.86 and 0.89 respectively against ‘gold-standard’ parasitology. There was a clear association of reported pain upon micturition for children with elevated urine-albumin levels, with an odds ratio of 20 to 1. Levels of excreted blood in urine were quantified with the HemoCue Plasma/Low Hb photometer. However, dipsticks remain the method of choice for urine-haemoglobin of 0.1 g l−1 and below. Urine parameters over a 24-h period were assessed in a small sub-sample. Reductions in both albumin and haemoglobin excretion were observed in 11 children 54 days after praziquantel treatment. It was concluded that these rapid, high-through-put, portable HemoCue assays could play a role in better describing and monitoring the occurrence, severity and evolution of urinary schistosomiasis disease. The urine-albumin assay has particular promise as a biochemical marker of S. haematobium induced kidney- and upper urinary tract-morbidity.
Trefoil factor peptide 3 is positively correlated with the viscoelastic properties of the cervical mucus plug

The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1–3); peptides believed to influence mucus viscosity.
Cells strongly expressing Igκ transgenes show clonal recruitment of hypermutation: a role for both MAR and the enhancers

The V regions of immunoglobulin κ transgenes are targets for hypermutation in germinal centre B cells. We show by use of modified transgenes that the recruitment of hypermutation is substantially impaired by deletion of the nuclear matrix attachment region (MAR) which flanks the intron‐enhancer (Ei). Decreased mutation is also obtained if Ei, the core region of the κ3′‐enhancer (E3′) or the E3′‐flank are removed individually. A broad correlation between expression and mutation is indicated not only by the fact that the deletions affecting mutation also give reduced transgene expression, but especially by the finding that, within a single mouse, transgene mutation was considerably reduced in germinal centre B cells that poorly expressed the transgene as compared with strongly expressing cells. We also observed that the diminished mutation in transgenes carrying regulatory element deletions was manifested by an increased proportion of B cells in which the transgene had not been targeted at all for mutation rather than in the extent of mutation accumulation once targeted. Since mutations appear to be incorporated stepwise, the results point to a connection between transcription initiation and the clonal recruitment of hypermutation, with hypermutation being more fastidious than transcription in requiring the presence of a full complement of regulatory elements.
Age does not predict breast cancer outcome.

OBJECTIVE To determine whether age is a prognostic factor of breast cancer and should be used to make treatment recommendations, because younger patients are considered to have a poorer prognosis compared with that of older patients and, thus, often receive more aggressive therapy. DESIGN A large group of patients with operable breast cancer, all of whom were followed up prospectively as part of two multicenter trials. SETTING Case Western Reserve University, Cleveland, Ohio, was the primary hospital and study center, with 12 participating regional institutions. PATIENTS All 1353 patients underwent uniform local-regional therapy that consisted of a modified radical mastectomy. Patients who were node negative were followed up, and patients who were node positive received systemic chemoendocrine therapy. MAIN OUTCOME MEASURES Patients were followed up at regular intervals for either recurrence or death. RESULTS Patients ranged in age from 22 to 75 years with a median age of 56 years. Younger patients had more estrogen receptor-negative tumors (P < .0001) and a greater number of positive lymph nodes (P < .0001). Of the 241 black patients in the study, a greater percentage were younger compared with white patients (P < .0001). Age was considered in a Cox's multivariate model, together with nodes, tumor diameter, estrogen receptor content, and race. Age was not a significant predictor of either disease-free (P = .33) or overall (P = .30) survival. Using mixture models with covariates, the estimated average hazards (where lambda indicates the force of mortality) of breast cancer deaths per year were similar (P, not significant) for patients 45 years old or younger (lambda = 0.061), older than 45 years but 65 years old or younger (lambda = 0.052), and older than 65 years (lambda = 0.061). CONCLUSIONS In conclusion, younger patients as a group have more aggressive and advanced breast cancer at presentation compared with older patients. Considered in a multivariate model, together with other variables, age does not provide independent prognostic information and should not be used alone for management decisions.
Proteinase‐activated receptor 2 activation modulates guinea‐pig mesenteric lymphatic vessel pacemaker potential and contractile activity

Lymphatic vessels rhythmically constrict to avoid fluid and protein accumulation in the interstitial space. This activity is critical during inflammation to prevent excessive oedema. Lymphatic pumping is intrinsic to the smooth muscle in the vessel wall and is due to the spontaneous occurrence of action potentials, the pacemaker of which is proposed to be spontaneous transient depolarizations (STDs). This function is highly susceptible to the fluid load and modulated by chemical agents, amongst which inflammatory mediators are important players. Activation of proteinase‐activated receptors (PARs) has been involved in inflammation and affects vascular smooth muscle tone. The present study aims to investigate the role of PAR2, a member of the PAR family, in lymphatic vessel pumping. RT‐PCR experiments revealed that PAR2 message is present in lymphatic vessels of the guinea‐pig mesentery. Agonists of PAR2 such as trypsin and the activating peptide, SLIGRL‐NH2, caused a decrease in the contractile activity of intraluminally perfused lymphatic vessels. Moreover, intracellular microelectrode recordings from isolated vessels revealed that PAR2 activation hyperpolarized the lymphatic smooth muscle membrane potential and altered STD amplitude and frequency. The decreases in constriction frequency and STD activity as well as the hyperpolarization were dependent on a functional endothelium, not affected by NO synthase or guanylyl‐cyclase inhibition, but mimicked by PGE2 and iloprost and blocked by indomethacin (10 μm) and glibenclamide (1 μm). These results show that PAR2 activation alters guinea‐pig lymphatic vessel contractile and electrical activity via the production of endothelium‐derived cyclo‐oxygenase metabolites.
Predictors of Human Immunodeficiency Virus Counseling and Testing Among Sexually Transmitted Disease Clinic Patients

Objectives: To determine the predictors of prior or current, and repeat human immunodeficiency virus (HIV) testing. Study Design: Cross‐sectional survey. Methods: Sexually transmitted disease (STD) clinic patients who participated in a blinded HIV seroprevalence survey completed a voluntary questionnaire regarding their reasons for accepting or declining HIV testing. Results: Eighty‐seven percent of participants reported a previous HIV test or were HIV testing the day they completed the questionnaire. African Americans were less likely to have been HIV tested (adjusted odds ratio 0.3, 95% confidence limits 0.1, 0.8). The most common reasons for testing were to be reassured and to receive medical care if infected. The most common reason for not testing was that nontesters did not think that they were infected. Repeat testing was reported by 51% of the participants and was more frequent among patients who were older or members of high‐risk groups (P < 0.05). Patients tested repeatedly to confirm a prior HIV test result or because of continued risky behavior. Conclusions: Testing for HIV is frequent among STD clinic patients but less so among African Americans. Receipt of medical care appears to be an important motivation for HIV testing, whereas lack of perceived risk may discourage testing. Continued high‐risk behavior contributes to repeat HIV testing.
Changes in periodontal and microbial parameters after the space maintainers application

Aim: This study aims to evaluate the clinical and microbiological changes accompanying the inflammatory process of periodontal tissues during treatment with space maintainers (SMs). Materials and Methods: The children were separated into fixed (Group 1, n = 20) and removable (Group 2, n = 20) appliance groups. A full periodontal examination, including probing pocket depth (PPD), bleeding on probing (BOP), and plaque index (PI), was performed. Anaerobic microorganisms in the crevicular fluid were detected with the culture method. Clinical and microbial evaluations were performed before (T0) applications. as well as at three (T1), and 9 months intervals (T2) after the application of the fixed or removable appliances. Results: The PI, PPD, and BOP scores at the testing sites of both groups increased significantly from before treatment (T0) to the 9 months' time frame (T2) (P < 0.05), The presence of anaerobic bacteria in the subgingival dental plaque increased from T0 (n = 13, 65%) to T1 (n = 16, 80%) in the fixed SM group, but not statistically significant. The same values were obtained in T1 and T2 (n = 16, 80%). Conclusion: Although, the results of this study demonstrate that the application of fixed or removable SM appliances in children induced an increase of clinical periodontal parameters, anaerobic microbiota consisting of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forshia were not observed in any of the samples in short-term. Further long-term and comprehensive investigations are necessary.
Characterization of the adherence of human monocytes to cytokine-stimulated human macrovascular endothelial cells.

At sites of inflammation, interactions between monocytes and vascular endothelium play an important role in the margination and extravasation of monocytes. The aim of this study was to investigate the relative contributions of the CD11/CD18 family of leucocyte adhesion molecules on monocytes and ICAM-1 and ELAM-1 molecules on endothelial cells (EC) to the binding of monocytes to EC stimulated with recombinant interleukin-1 alpha (rIL-1 alpha), rIL-6, recombinant tumour necrosis factor-alpha (rTFN-alpha) or recombinant interferon-gamma (rIFN-gamma). The adhesiveness of EC for monocytes increased 1.8-2.3-fold after incubation of monolayers of venous or arterial EC with rIL-1 alpha or rTNF-alpha for 4 hr, and 1.6-2.0-fold after stimulation of both types of EC with rIL-1 alpha, rTNF-alpha or rIFN-gamma for 24 hr. Incubation with rIL-6 was without effect. The monoclonal antibodies (mAb) against CD11a, b, c and CD18 on monocytes did not inhibit the increase in the number of monocytes bound to rIL-1 alpha-, rTNF-alpha-, or rIFN-gamma-stimulated EC. However, mAb against ELAM-1 expressed on the surface of 4 hr rIL-1 alpha-stimulated EC slightly inhibited (15-21%) the enhanced monocyte binding. ICAM-1, which exhibited marked expression on 24 hr rIL-1 alpha-, rTNF-alpha- or rIFN-gamma-stimulated EC, did not contribute to the enhanced monocyte binding. The percentage of EC-bound monocytes which had stretched out over the surface of cytokine-stimulated venous or arterial EC was significantly increased compared to the percentage found for non-stimulated EC. It was observed that mild fixation of EC as well as treatment of EC with cytochalasin B or mAb against ICAM-1 did not affect the number of monocytes that were bound to EC, but considerably reduced the percentage of EC-bound monocytes with a stretched morphology. It is concluded that the binding of monocytes to cytokine-stimulated EC is dependent on the type of cytokine and the duration of cytokine stimulation. The increase in the binding of monocytes to cytokine-stimulated EC occurred as a result of CD11/CD18- and ICAM-1-independent factors. The subsequent morphological changes, i.e. stretching of monocytes over the surface of EC, required viable EC and ICAM-1.
Vascular resistance and endothelial function in cyclosporine‐treated lung transplant recipients

The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide‐mediated endothelial‐dependent and independent vasoreactivity between cyclosporine‐treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)‐monomethyl‐l‐arginine acetate (l‐NMMA) infusion in 11 lung transplant recipients 3–5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin‐1 (ET‐1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial‐dependent and independent vasodilation did not differ. Plasma levels of ET‐1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET‐1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = −0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET‐1 do not cause increased FVR in lung transplant recipients.
Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34+ and CD3+ cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34+ cell dose more than 4.5×106/kg (HR: 0.56; P=0.002) and CD3+ cell dose more than 3×108/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an “adapted Disease Risk Index” by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).
Differentially Regulated Expression and Function of CD22 in Activated B-1 and B-2 Lymphocytes1

CD22 is a B cell-restricted transmembrane protein that apparently controls signal transduction thresholds initiated through the B cell Ag receptor (BCR) in response to Ag. However, it is still poorly understood how the expression of CD22 is regulated in B cells after their activation. Here we show that the expression levels of CD22 in conventional B-2 cells are markedly down-regulated after cross-linking of BCR with anti-IgM mAb but are up-regulated after stimulation with LPS, anti-CD40 mAb, or IL-4. In contrast, treatment with anti-IgM mAb barely modulated the expression levels of CD22 in CD5+ B-1 cells, consistent with a weak Ca2+ response in anti-IgM-treated CD5+ B-1 cells. Moreover, in CD22-deficient mice, anti-IgM treatment did not trigger enhanced Ca2+ influx in CD5+ B-1 cells, unlike CD22-deficient splenic B-2 cells, suggesting a relatively limited role of CD22 in BCR signaling in B-1 cells. In contrast, CD22 levels were markedly down-regulated on wild-type B-1 cells in response to LPS or unmethylated CpG-containing oligodeoxynucleotides. These data indicate that the expression and function of CD22 are differentially regulated in B-1 and conventional B-2 cells, which are apparently implicated in innate and adaptive immunity, respectively.
Renal graft rejection or cyclosporin toxicity? Early diagnosis by a combination of Papanicolaou and immunocytochemical staining of urinary cytology specimens

Abstract. A method is described for distinguishing between graft rejection and cyclosporin nephrotoxicity in renal allograft recipients by analyzing fresh morning urine samples. The technique combines classic Papanicolaou with immunocytochemical staining and was performed in urine specimens from a series of 42 patients. Early‐stage cyclosporin toxicity was usually associated with increased numbers of proximal tubular cells only, whereas in rejection and late‐stage toxicity there were increases in both tubular cells and in lymphocytes and monocytes (> 2000 cells/ml urine). Differentiation between these two clinical conditions was achieved by immunostaining, which revealed that increased numbers of CD25+ and CD8+ cells, as well as an increase in the HLA‐DR/Lu5 ratio, were typical of rejection. CD25 positivity proved to be the best indicator of rejection, with a sensitivity and specificity of more than 90%. A cytodiagnostic algorithm is presented that is based on cell numbers and types, including immunophenotypes. The proposed method has the advantage of being noninvasive and appears to represent a reliable and rapid adjunct for the monitoring of graft function, especially in high‐risk patients on cyclosporin immunosuppression.
VASCULAR ENDOTHELIAL GROWTH FACTOR GENE‐TRANSFERRED BONE MARROW STROMAL CELLS ENGINEERED WITH A HERPES SIMPLEX VIRUS TYPE 1 VECTOR CAN IMPROVE NEUROLOGICAL DEFICITS AND REDUCE INFARCTION VOLUME IN RAT BRAIN ISCHEMIA

OBJECTIVESeveral reports recently suggested that vascular endothelial growth factor (VEGF) may have a therapeutic benefit against experimental cerebral infarction animal models. In addition, bone marrow stromal cells (BMSCs) are known to have therapeutic potency in improving neurological deficits after occlusive cerebrovascular diseases. In the present study, we evaluated the hypothesis that intracerebral transplantation of VEGF gene-transferred BMSCs could provide a greater therapeutic effect than intracerebral transplantation of native (non-gene-transformed) BMSCs by using a transient middle cerebral artery occlusion (MCAO) rat model. METHODSAdult Wistar rats (Japan SLC, Inc., Hamamatsu, Japan) were anesthetized. VEGF gene-transferred BMSCs engineered with a replication-deficient herpes simplex virus type 1 1764/4-/pR19-hVEGF165 vector, native BMSCs, or phosphate-buffered saline were administered intracerebrally 24 hours after transient MCAO. All animals underwent behavioral testing for 28 days, and the infarction volume was determined 14 days after MCAO. The brain water contents in the ipsilateral and contralateral hemispheres of the MCAO were measured 2 and 7 days after the MCAO. Fourteen days after MCAO, immunohistochemical staining for VEGF was performed. RESULTSThe group receiving VEGF-modified BMSCs demonstrated significant functional recovery compared with those receiving native BMSCs. Fourteen days after the MCAO, there was a significantly lower infarct volume without aggravating cerebral edema in the group treated with VEGF gene-modified BMSCs compared with the control groups. The transplanted VEGF gene-modified BMSCs strongly expressed VEGF protein for at least 14 days. CONCLUSIONOur data suggest that the intracerebral transplantation of VEGF gene-transferred BMSCs may provide a more potent autologous cell transplantation therapy for stroke than the transplantation of native BMSCs alone.