Expression of activated mutants of the human interleukin-3/interleukin-5 granulocyte-macrophage colony-stimulating factor receptor common beta subunit in primary hematopoietic cells induces factor-independent proliferation and differentiation

To date, several activating mutations have been discovered in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Two of these, Fl Delta and 1374N, result in a 37 amino acid duplication and a single amino acid substitution in the extracellular domain of h beta c, respectively. A third, V449E, results in a single amino acid substitution in the transmembrane domain, Previous studies comparing the activity of these mutants in different hematopoietic cell lines imply that the transmembrane and extracellular mutations act by different mechanisms and suggest the requirement for cell type-specific molecules in signalling. To characterize the ability of these mutant hpc subunits to mediate growth and differentiation of primary cells and hence investigate their oncogenic potential, we have expressed all three mutants in primary murine hematopoietic cells using retroviral transduction. It is shown that, whereas expression of either extracellular hpc mutant confers factor-independent proliferation and differentiation on cells of the neutrophil and monocyte lineages only, expression of the transmembrane mutant does so on these lineages as well as the eosinophil, basophil, megakaryocyte, and erythroid lineages, Factor-independent myeloid precursors expressing the transmembrane mutant display extended proliferation in liquid culture and in some cases yielded immortalized cell lines. (C) 1997 by The American Society of Hematology.

Multiple Mononeuropathy Secondary to Thrombosis of the Vasa Nervorum in Primary Antiphospholipid Syndrome

Federico Foundation

Traditional risk factors for cardiovascular disease in primary antiphospholipid syndrome (APS) when compared with secondary APS: a study with 96 patients

Objective: To evaluate the prevalence of traditional risk factors in patients with primary antiphospholipid syndrome (APS) in comparison to those with systemic lupus erythematosus-secondary APS. Methods: Transversal study of 96 APS patients (Sapporo`s criteria). Demographic and clinical data, cardiovascular risk factors and drug use were investigated. Results: Thirty-nine Primary APS and 57 secondary APS were included. The groups did not differ regarding age (38.5 +/- 9.9 vs. 39.4 +/- 10.5 years, p=0.84) and female gender (84.6 vs. 96.5%, p=0.06), respectively. Arterial events were more observed in primary than secondary APS (59 vs. 36.8%, p=0.04) patients. No difference was seen concerning venous and obstetric events. In regard to traditional risk factors for cardiovascular disease, both groups were comparable related to current or previous smoking, sedentarism, family history for coronary disease, systemic hypertension, diabetes mellitus, overweight and obesity. The frequencies of altered lipid profiles were alike in the two groups, except for a higher prevalence of low HDL-c levels in primary APS group (84.6 vs. 45.5%, p=0.0001). Concerning drug use, no significant differences were observed related to chloroquine and statin use, however the secondary APS patients had a higher rate of prednisone use (10.2 vs. 57.9%, p<0.001) as well as mean dose of corticosteroid (1.5 +/- 5.7 vs. 9.2 +/- 12.5mg/ /day, p=0.0001). Conclusion: Traditional risk factors for cardiovascular disease are present and comparable between patients with primary and secondary APS, except for a high frequency of low HDL-c in primary APS patients.

Agreement between stress intraocular pressure and long-term intraocular pressure measurements in primary open angle glaucoma

The aim of this paper is to study the correlation between the intraocular pressure peaks and fluctuation detected during the water drinking test and the same parameters observed during long-term follow up. This prospective cohort study enrolled 22 eyes of 22 newly diagnosed primary open angle glaucoma patients. After an initial complete ophthalmological examination, patients were started on antiglaucoma medication and returned 4 weeks later to perform the water drinking test. Thereafter, patients were evaluated at least eight times within a period of 6-12 months. The intraocular pressure peaks and fluctuation detected during the water drinking stress test were compared with those observed during regular office visits. Spearman`s correlation coefficient and Bland-Altman Plots were used for statistical analysis. The mean age of participants was 54.3 +/- 8.2 years (+/- SD), 59% were women, and average mean deviation -10.2 +/- 4.5 dB. The mean follow-up period was 8.2 +/- 2.0 months. The average intraocular pressure peaks and fluctuation during the water drinking test were 20.0 +/- 2.9 mmHg and 40 +/- 10%, respectively, and 18.1 +/- 2.8 mmHg and 30 +/- 10% during follow up. Spearman`s correlation coefficients were significant and strong between the intraocular pressure peaks and fluctuation detected during the water drinking test and during the follow-up period (P < 0.001, rho = 0.76 and 0.82, respectively). There was good agreement between the variables. The intraocular pressure peaks and fluctuation detected during the water drinking test showed significant correlation and agreement with the pressures observed during follow-up visits. Stress tests could be used to estimate long-term intraocular pressure variation.

Disorders of apoptosis: Mechanisms for autoimmunity in primary immunodeficiency diseases

A number of primary immunodeficiency diseases represent a paradox of immunodeficiency and autoimmunity. In this minireview, we present basic concepts of apoptosis and disorder of apoptosis as one of the mechanisms to explain such a paradox between immunodeficiency and autoimmunity, which is exemplified by autoimmune lympho-proliferative syndrome (ALPS).

Validity and applicability of the Mini International Neuropsychiatric Interview administered by family medicine residents in primary health care in Brazil

Objective: To evaluate the validity and applicability of the Mini International Neuropsychiatric Interview (MINI) used by family medicine residents in primary health care (PHC) in Brazil. Methods: Training for administrating the MINI was given as part of a broad psychiatry education program. Interviews were held with 120 PHC patients who were at least 15 years old. MINI was administered by 25 resident physicians, while the Structured Clinical Interview for Diagnosis (SCID) was administered by a psychiatrist blind to patients` results on the MINI, and the diagnoses on both interviews were compared. The resident physicians answered questions on the applicability of the MINI. Results: Concordance levels for any mental disorder, the broader current diagnostic categories and the most common specific diagnoses were analyzed. Kappa coefficients ranged between 0.65 and 0.85; sensitivity, between 0.75 and 0.92; specificity, between 0.90 and 0.99; positive predictive values (PPV), between 0.60 and 0.86; negative predictive values (NPV), between 0.92 and 0.99; and accuracy, between 0.88 and 0.98. The resident physicians considered MINI comprehensibility and clinical relevance satisfactory. Conclusions: These good psychometric results in a real-world setting may be related to a special training program, which is more frequent, intensive and diversified. In these conditions, the MINI is a useful tool for general practitioners. (c) 2008 Elsevier Inc. All rights reserved.

Accuracy of intraoperative cultures in primary total hip arthroplasty

The aim of this investigation was to assess the diagnostic accuracy of intraoperative cultures for the early identification of patients who are at risk of infection after primary total hip arthroplasty. Four or six swabs were obtained immediately before the wound closure in 263 primary total hip replacements. Patients with a maximum of one positive culture were denoted as patients with a normal profile and did not receive any treatment. Patients with two or more positive cultures, with the same organism identified, were denoted as patients with a risk profile and received treatment with a specific antibiotic as determined by the antibiogram for six weeks. The follow-up ranged from a minimum of one year to five years and eleven months, concentrating on the presence or absence of infection, which was defined as discharge of pus through the surgical wound or as a fistula at any time after surgery. The accuracy of this procedure ( number of cases correctly identified in relation to the total number of cases) in the group of 152 arthroplasties in which 4 swabs per patient were collected was 96%. In the group of 111 arthroplasties in which 6 swabs per patient were collected the accuracy was 95.5%. We conclude that the collection of swabs under the conditions described is a method of high accuracy ( above 95%) for the evaluation of risk of infection after primary total hip arthroplasty.

Accuracy of direct digital radiography for detecting occlusal caries in primary teeth compared with conventional radiography and visual inspection: an in vitro study

Objectives: The diagnosis of caries lesions is still a matter of concern in dentistry. The diagnosis of dental caries by digital radiography has a number of advantages over conventional radiography; however, this method has not been explored fully in the field of paediatric dentistry. This in vitro research evaluated the accuracy of direct digital radiography compared with visual inspection and conventional radiography in the diagnosis of occlusal caries lesions in primary molars. Methods: 50 molars were selected and evaluated under standardized conditions by 2 previously calibrated examiners according to 3 diagnostic methods (visual inspection, conventional radiography and direct digital radiography). Direct digital radiographs were obtained with the Dixi3 system (Planmeca, Helsinki, Finland) and the conventional radiographs with InSight film (Kodak Eastman Co., Rochester, NY). The images were scored and a reference standard was obtained histologically. The interexaminer reliability was calculated using Cohen`s kappa test and the specificity, sensitivity and accuracy of the methods were calculated. Results: Examiner reliability was good. For lesions limited to the enamel, visual inspection showed significantly higher sensitivity and accuracy than both radiographic methods, but no significant difference was found in specificity. For teeth with dentinal caries, no significant differences were found for any parameter when comparing visual and radiographic evaluation. Conclusions: Although less accurate than the visual method for detecting caries lesions confined to the enamel, the direct digital radiographic method is as effective as conventional radiographic examination and visual inspection of primary teeth with occlusal caries when the dentine is involved. Dentomaxillofacial Radiology (2010) 39, 362-367. doi: 10.1259/dmfr/22865872

Differential bonds degradation of two resin-modified glass-ionomer cements in primary and permanent teeth

Objectives: To evaluate the effect of chemical degradation on bond strength of resin-modified glass-ionomer cements bonded to primary and permanent dentin. Methods: Class I cavities of permanent and primary extracted human molars were restored with two resin-modified glass-ionomer cements: Fuji 11 LC and Vitremer, and stored in water for 24 h. Half samples were immersed in 10% NaOCl aqueous solution for 5 h. Teeth were sectioned into beams and tested for microtensile bond strengths. Results were analyzed with multiple ANOVA and Tukey`s tests (p < 0.05). Analysis of debonded surfaces was performed by SEM. Results: 24 h bond strengths for Vitremer and Fuji 11 LC were similar. For Fuji 11, bond strength values were higher for primary than for permanent dentin. Vitremer bond strength was similar for both. Chemical degradation did not affect Fuji I] LC bond strength to dentin. However, decreases in bond strength were found for Vitremer groups after NaOCl immersion. Signs of glass ionomer-dentin interaction were evident by SEM analysis for Fuji 11 LC specimens. Conclusions: Vitremer and Fuji II presented similar bond strength at 24. Vitremer dentin bonds were prone to chemical degradation. Fuji II LC-dentin bonds showed typical features of glass-ionomer dentin interaction at the bonded interfaces, and were resistant to in vitro degradation. (C) 2009 Elsevier Ltd. All rights reserved.

The effectiveness of mineral trioxide aggregate, calcium hydroxide and formocresol for pulpotomies in primary teeth

Aim To compare the effectiveness of mineral trioxide aggregate (MTA), calcium hydroxide (CH) and formocresol (FC) as pulp dressing agents in carious primary teeth. Methodology Forty-five primary mandibular molars with dental caries in 23 children [AUTHOR QUERY: How many children?] between 5 and 9 years old were treated by a conventional pulpotomy technique. The teeth were randomly assigned to the experimental ( CH or MTA) or control ( FC) groups. After coronal pulp removal and haemostasis, remaining pulp tissue was covered with MTA paste or CH powder in the experimental groups. In the control group, diluted FC was placed with a cotton pellet over the pulp tissue for 5 min and removed; the pulp tissue was then covered with zinc oxide-eugenol (ZOE) paste. All teeth were restored with reinforced ZOE base and resin modified glass-ionomer cement. Clinical and radiographic successes and failures were recorded at 3, 6, 12, 18 and 24 month follow-up. Results Forty-three teeth were available for follow-up. In the FC and MTA groups, 100% of the available teeth were clinically and radiographically successful at all follow-up appointments; dentine bridge formation could be detected in 29% of the teeth treated with MTA. In the CH group, 64% of the teeth presented clinical and radiographic failures detected throughout the follow-up period, and internal resorption was a frequent radiographic finding. Conclusions Mineral trioxide aggregate was superior to CH and equally as effective as FC as a pulpotomy dressing in primary mandibular molars. Internal resorption was the most common radiographic finding up to 24 month after pulpotomies performed with CH.

Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory cortex of the cat

Spontaneous and tone-evoked changes in light reflectance were recorded from primary auditory cortex (A1) of anesthetized cats (barbiturate induction, ketamine maintenance). Spontaneous 0.1-Hz oscillations of reflectance of 540- and 690-nm light were recorded in quiet. Stimulation with tone pips evoked localized reflectance decreases at 540 nm in 3/10 cats. The distribution of patches activated by tones of different frequencies reflected the known tonotopic organization of auditory cortex. Stimulus-evoked reflectance changes at 690 nm were observed in 9/10 cats but lacked stimulus-dependent topography. In two experiments, stimulus-evoked optical signals at 540 nm were compared with multiunit responses to the same stimuli recorded at multiple sites. A significant correlation (P < 0.05) between magnitude of reflectance decrease and multiunit response strength was evident in only one of five stimulus conditions in each experiment. There was no significant correlation when data were pooled across all stimulus conditions in either experiment. In one experiment, the spatial distribution of activated patches, evident in records of spontaneous activity at 540 nm, was similar to that of patches activated by tonal stimuli. These results suggest that local cerebral blood volume changes reflect the gross tonotopic organization of A1 but are not restricted to the sites of spiking neurons.

Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes

The toxicities and uptake mechanisms of two hepatotoxins, namely cylindrospermopsin and lophyrotomin, were investigated on primary rat hepatocytes by using microcystin-LIZ (a well-known hepatotoxin produced by cyanobacteria) as a comparison. Isolated rat hepatocytes were incubated with different concentrations of hepatotoxins for 0, 24, 48 and 72 h. The cell viability was assayed by the tetrazolium-based (MTT) assay. Microcystin-LR, cylindrospermopsin and lophyrotomin all exhibited toxic effects on the primary rat hepatocytes with 72-h LC50 of 8, 40 and 560 ng/ml, respectively. The involvement of the bile acid transport system in the hepatotoxin-induced toxicities was tested in the presence of two bile acids, cholate and taurocholate. Results showed that the bile acid transport system was responsible for the uptake, and facilitated the subsequent toxicities of lophyrotomin on hepatocytes. This occurred to a much lesser extent with cylindrospermopsin. With its smaller molecular weight, passive diffusion might be one of the possible mechanisms for cylindrospermopsin uptake into hepatocytes. This was supported by incubating a permanent cell line, KB (devoid of bile acid transport system), with cylindrospermopsin which showed cytotoxic effects. No inhibition of protein phosphatase 2A by cylindrospermopsin or lophyrotomin was found. This indicated that other toxic mechanisms besides protein phosphatase inhibition were producing the toxicities of cylindrospermopsin and lophyrotomin, and that they were unlikely to be potential tumor promoters. (C) 2001 Elsevier Science Ltd. All rights reserved.

Microevolution in island forms: the roles of drift and directional selection in morphological divergence of a passerine bird

Theory predicts that in small isolated populations random genetic drift can lead to phenotypic divergence; however this prediction has rarely been tested quantitatively in natural populations. Here we utilize natural repeated island colonization events by members of the avian species complex, Zosterops lateralis, to assess whether or not genetic drift alone is an adequate explanation for the observed patterns of microevolutionary divergence in morphology. Morphological and molecular genetic characteristics of island and mainland populations are compared to test three predictions of drift theory: (1) that the pattern of morphological change is idiosyncratic to each island; (2) that there is concordance between morphological and neutral genetic shifts across island populations; and (3) for populations whose time of colonization is known, that the rate of morphological change is sufficiently slow to be accounted for solely by genetic drift. Our results are not consistent with these predictions. First, the direction of size shifts was consistently towards larger size, suggesting the action of a nonrandom process. Second, patterns of morphological divergence among recently colonized populations showed little concordance with divergence in neutral genetic characters. Third, rate tests of morphological change showed that effective population sizes were not small enough for random processes alone to account for the magnitude of microevolutionary change. Altogether, these three lines of evidence suggest that drift alone is not an adequate explanation of morphological differentiation in recently colonized island Zosterops and therefore we suggest that the observed microevolutionary changes are largely a result of directional natural selection.