Columnar alteration with prominent apical snouts and secretions: a spectrum of changes frequently present in breast biopsies performed for microcalcifications

OBJECTIVE: To examine the effect of treatment with an inactivated, gp120-depleted, HIV-1 immunogen (Remune) in 30 Thai subjects infected with HIV-1 subtype E. DESIGN: Sixty-week open-label study. METHODS: Thirty HIV-positive volunteers with CD4 cell counts > or = 300 x 10(6)/l were given intramuscular injections of Remune into the triceps muscle on day 1 and then at weeks 4, 8, 12, 24, 36, 48 and 60. RESULTS: Treatment with Remune was well-tolerated and augmented HIV-1-specific immune responses. Furthermore, subjects had a significant increase in CD4 cell count (P < 0.0001), CD4 cell percentage (P < 0.0001), CD8 cell percentage (P < 0.0001), and body weight (P < 0.0001) compared with pretreatment levels. Fourteen subjects with detectable viral load at day 1 showed a decrease at week 60 (P=0.04). Retrospective Western blot analysis showed 23 subjects with increased intensity of antibody bands and 15 patients showed development of new reactivities to HIV proteins, especially towards p17 and p15. CONCLUSION: These results indicate that HIV-specific immune-based therapeutic approaches such as Remune should be further examined in countries with different clades of HIV-1 and where access to antiviral drug therapies is limited.     

Multiresidue determination of pesticides in apples and pears by gas chromatography-mass spectrometry

This paper describes a rapid, specific and sensitive multiresidue method for the routine analysis of several classes of pesticides used for the treatment of apples and pears, involving a rapid extraction procedure at pH 4.5 with a mixture of acetone-dichloromethane-hexane (50:20:30, v/v/v) and gas chromatography coupled to mass-selective detection, in order to achieve quantitative analysis down to their respective maximum residue limit. Extraction recoveries were between 55 and 98%. Limits of detection and limits of quantitation ranged respectively, from 0.01 to 0.05 mg/kg and from 0.02 to 0.1 mg/kg. Intra-assay relative standard deviation was less than 19% for all compounds. An excellent linearity was observed from these LOQs up to 500 mg/kg. Intermediate (inter-assay) precision and accuracy were satisfactory. The method has been applied to many fruit samples intended for commercialisation.     

Intra-thoracic costal sites of osteogenic exostoses in the child

INTRODUCTION: The technologic improvement of surface coils in MRI has allowed better visualization of the skin and thus permitted the clinical use of this technique in dermatology. MRI allows to assess the depth and extent of skin tumors and to detect any malignant transformation. The MR differentiation between benign and malignant skin lesions relies on morphological criteria which however do not have an absolute diagnostic value. We investigated the role of paramagnetic contrast agents in the differentiation between benign and malignant skin lesions. MATERIAL AND METHODS: Forty-one patients, 33 with benign and 8 with malignant skin tumors, were submitted to MRI. All the examinations were performed with a 1.5 T superconductive unit, with a 2.5 cm surface coil. Axial T1- and T2-weighted SE images were acquired with 2 mm slice thickness. Paramagnetic contrast material was administered to all patients. The signal intensity of the skin lesions was calculated before and after paramagnetic contrast agent administration positioning a region of interest. A percentage ratio of contrast enhancement was calculated to quantify contrast agent uptake and the relative values were compared between benign and malignant lesions. A qualitative analysis was also performed rating the contrast enhancement of each lesion as high, intermediate, or absent. RESULTS: The quantitative analysis showed a statistically significant difference (p < .5) between the contrast enhancement values of benign and malignant lesions. In particular, malignancies had values ranging 117.3 (+/- 28.7) to 125 (+/- 32.4), while benign lesions had -20.6 to 99.8 (+/- 21.1). Conversely, no difference in contrast enhancement was found at qualitative analysis. CONCLUSIONS: MRI is a promising tool for characterizing skin tumors. Our preliminary results should be confirmed on larger series of patients with the use of high temporal resolution imaging sequences.     

Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse

BACKGROUND: The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. METHODS: MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N=82) and asymptomatic (N=155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. RESULTS: Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median=68 vs. 23 weeks) and to any depressive episode > 5 times faster (median=33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR=3.65) and was stronger than history of recurrent MDEs (OR=1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. LIMITATIONS: Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. CONCLUSIONS: MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.     

Molecular mechanics parameterization of thionucleoside disulfides for modeling cross-linked duplex DNA

We describe a solution to a molecular mechanics parameterization problem involving disulfide bonds between thionucleosides. Key torsional and bending parameters developed from ab initio calculations were incorporated into the AMBER* force-field in order to accurately represent the disulfide linkage in DNA cross-linked via this bond.     

Differential expression and functionally co-operative roles for the retinoblastoma family of proteins in epidermal differentiation

Terminal differentiation requires cell cycle withdrawal, suggesting the involvement of negative cell cycle controllers in the process. We have analysed the involvement of the retinoblastoma family of proteins (pRb, p107 and p130) in epidermal proliferation and differentiation. These proteins play key roles as inhibitors of cell cycle progression and are involved in muscle and neuron differentiation. We found that during in vitro differentiation of human HaCaT keratinocytes, pRb, p107 and p130 are sequentially expressed, in contrast to the co-expression observed during cell cycle progression in the same cells. Immunofluorescence studies on skin sections revealed the presence of pRb and p107 in basal and suprabasal cell layers, whilst p130 is restricted to cells already committed to differentiation in the suprabasal compartments. To explore the functional significance of the differential expression of these proteins, transfection experiments were performed in HaCaT keratinocytes. We observed that the forced over-expression of pRb, p107 or p130 individually did not induce differentiation of the transfected cells. However, the co-transfection of pRb and p107 induced the expression of early differentiation markers (keratin k10) and triple transfectants pRb+p107+p130 expressed markers representative of later stages of epidermal differentiation (involucrin). Finally, we observed that these three proteins repress keratinocyte proliferation, although to a different extent (p107>pRb> or =p130). These results indicate that the members of the pRb family play specific, yet coordinated roles during epidermal differentiation, and that the ordered progression along the different stages of this process results from the effects of different combinations of these proteins.     

IL-12 up-regulates CD40 ligand (CD154) expression on human T cells

IL-12 is a heterodimeric cytokine produced by APC that promotes the development of CD4+ Th1 cells and their IFN-gamma production after TCR/CD3 triggering. We here investigated the capacity of IL-12 to modify the expression on T cells of CD40 ligand (CD40L or CD154), a molecule transiently expressed on activated T cells and known to be of utmost importance for cognate interaction with B cells and for activation of dendritic cells and macrophages. Our data demonstrate that IL-12 up-regulates CD40L expression on anti-CD3-activated human peripheral blood T cells. For optimal induction of CD40L, IL-12 synergizes with IL-2 as well as with other costimulatory interactions, such as B7/CD28. The effect of IL-12 was observed at both the protein and the mRNA level. T cells costimulated by IL-12 provided more efficient help for IL-4-dependent B cell proliferation and for IgG production than when activated in the absence of IL-12. This helper activity was blocked by an mAb against CD40L, indicating that the effect of IL-12 on B cells is mediated indirectly through CD40L. The data thus suggest that the effects of IL-12 on cellular and humoral immune responses are partly mediated through CD40L induction.     

Information in the ICU: are we being honest with our patients? The results of a European questionnaire

BACKGROUND: We were interested in determining the current practices and views of European intensive care doctors regarding communication with patients and informed consent for interventions. METHODS: A questionnaire was sent to the 1272 western European doctor members of the European Society of Intensive Care Medicine. All questionnaires were anonymous. Five hundred four completed questionnaires from 16 western European countries were analyzed. RESULTS: Of the respondents, 25 % said they would always give complete information to a patient, although 35 % felt they should. Thirty-two percent would give complete details of an iatrogenic incident, but 70% felt they should. There were significant differences in these attitudes between doctors from different countries, with doctors from the Netherlands more likely to give complete information, and doctors from Greece, Spain and Italy less likely. Fifty percent of the respondents required written consent for surgery, but for insertion of an arterial catheter oral consent was more widely accepted. The Netherlands and Scandinavia generally accepted oral requests for procedures, while Germany and the United Kingdom preferred written requests. Doctors of all countries were generally happy with their current practice concerning informed consent. Seventy-five percent would accept the right of a patient to refuse treatment, but 19% would carry out the procedure against the patient's wishes. CONCLUSIONS: Doctors are often not completely honest with their patients regarding their diagnosis or prognosis, or in the event of an iatrogenic incident. However, most doctors will respect a patient's right to refuse treatment. Informed consent practices vary substantially and are largely determined by locally accepted policy and accepted by doctors working in those areas.     

Prediction of major depression and dysthymia from CES-D scores among ethnic minority adolescents

Two tumour cell clones, 6D1 and 4C2 cells, which are defective both in the major histocompatibility gene complex (MHC) class I expression and in the endogenous antigen presentation, are recovered with interferon (IFN)-gamma treatment. The present study describes the ultrastructure of these cells by using scanning and transmission electron microscopy in relation to the effect of IFN-gamma treatment. The general morphology of these cells was found to be similar to each other and comparable to that of a tumour cell clone, 4A1 cells, of the same origin, normal in MHC class I expression; they exhibited a fibroblast-like appearance and had many blebs on all the cell surfaces, with desmosome-like junctions between cells. On IFN-gamma treatment, surface fine blebs appeared less, and mitochondria became more densely stained. Expression of MHC class I molecules on the cell surface was much higher in the IFN-gamma treated 6D1 and 4C2 cells than in untreated cells, when estimated by immunoelectron microscopy. The addition of an epitope peptide to these cells did not enhance the class I expression, which differed from other antigen presentation-defective cells such as RMA-S cells, nor change the cell surface morphology.