Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of alpha4beta1 and alpha5beta1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.     

Langerhans cell histiocytosis immunohistochemical expression of fascin,a dendritic cell marker

Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derivedfrom cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression offascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivityforfascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.     

Distribution of metastases at necrospy in colorectal cancer

A series of 372 necropsies on patients with colorectal cancer (CRC) was examined retrospectively. Patients were excluded if the primary tumour was not removed, if the operation was palliative or if death occurred within three months of operation. Only 43 cases remained after these exclusions and of these six died of intercurrent disease. The 37 remaining patients were all thought to have undergone a curative resection, following which they died with recurrent tumour. They represent the group of patients who might have benefited from adjuvant chemotherapy. The pattern of metastases and the cause of death was examined in these 37 patients. Local recurrence was found more commonly (25 cases, 68 per cent) than hepatic metastases (21 cases, 57 per cent) or metastases at other sites. This finding indicates that excision of the primary tumour must be as complete as possible and that adjuvant therapies must be directed both locally as well as systemically.     

Acute modulation of adrenal chromaffin cell BK channel gating and cell excitability by glucocorticoids

Although adrenal glucocorticoids cortisol and corticosterone (CORT) have numerous "genomic" effects on adrenomedullary chromaffin cells, acute modulatory actions remain largely unknown, despite rapid stress-related changes in secretion. We report that 1 microM glucocorticoids rapidly modulate gating of chromaffin cell BK channels and action potential firing. In general, CORT, or the analog dexamethasone (DEX), increased channel activity in inside-out bovine patches, an effect not blocked by the glucocorticoid receptor (GR) antagonist RU38486. By contrast, these steroids could profoundly inhibit BK activation in many rat patches, while facilitating activation in others. We show that BK inhibition arises from a negative shift in the voltage dependence of BK inactivation paralleling that for activation. We report that rat cells characteristically exhibit greater repetitive firing ability than bovine cells in the absence of glucocorticoids. In both species, steroid application typically increased firing responses to smaller current injections, attributable to BK-enhanced repolarization and Na+ channel deinactivation. However, in rat cells, where BK inactivation is generally faster and more complete, glucocorticoids tended to dampen responses to stronger stimuli. Thus, in the context of natural variation in BK gating, glucocorticoids can either promote or limit firing responses. We suggest that steroids exploit BK gating variety to tailor catecholamine output in a species- and context-specific fashion.     

Continued maturation of thymic emigrants in the periphery

Developing thymocytes are selected for recognition of molecules encoded by the major histocompatibility complex, purged of self-reactive cells and committed to either the CD4 or CD8 lineage. The 1% of thymocytes that complete these tasks emigrate and join the population of peripheral lymphocytes. Whether T cell maturation is complete at the time of thymic exit has been a subject of debate. Using mice transgenic for green fluorescent protein driven by the recombination activating gene 2 promoter to identify recent thymic emigrants, we now show that T cell differentiation continues post-thymically, with progressive maturation of both surface phenotype and immune function. In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery.     

The seroepidemiology of human T-lymphotropic viruses: types I and II in Europe: a prospective study of pregnant women

BACKGROUND: Up to 20 million persons are infected with the human retroviruses human T-lymphotropic virus (HTLV)-I and HTLV-II globally. Most data on the seroprevalence of HTLV-I and HTLV-II in Europe are from studies of low-risk blood donors or high-risk injection drug users (IDUs). Little is known about the general population. METHODS: A prospective anonymous study of HTLV-I and HTLV-II seroprevalence among 234,078 pregnant women in Belgium, France, Germany, Italy, Portugal, Spain, and the United Kingdom was conducted. Maternal antibody status was determined by standard methods using sera obtained for routine antenatal infection screens or eluted from infant heel prick dried blood spots obtained for routine neonatal metabolic screens. RESULTS: Anti-HTLV-I/II antibodies were detected and confirmed in 96 pregnant women (4.4 per 10,000, 95% confidence interval [CI]: 3.5-5.2). Of these, 73 were anti-HTLV-I, 17 were anti-HTLV-II, and 6 were specifically anti-HTLV but untyped. The seroprevalence ranged from 0.7 per 10,000 in Germany to 11.5 per 10,000 in France. CONCLUSIONS: Pregnant women better reflect the general population than blood donors or IDUs. The seroprevalence of HTLV-I and HTLV-II in Western Europe is 6-fold higher among pregnant women (4.4 per 10,000) than among blood donors (0.07 per 10,000). These data provide a robust baseline against which changes in HTLV-I and HTLV-II seroprevalence in Europe can be measured.     

Characterization of Non-Hodgkin''s Lymphomas Using Multiple Cell Markers: Immunologic, Morphologic, and Cytochemical Studies of 72 Cases

Tissues from 72 cases (87 specimens) of various non-Hodgkin's lymphomas were analyzed for cell markers using multiple techniques. Cell suspensions were evaluated for E, EAC, and IgGEA rosette forming cells; Fc receptor cells; and surface immunoglobulin bearing cells. Cryostat section studies topographically defined EAC binding cells. Cytochemical determinations and immunoperoxidase methods for detection of intracellular immunoglobulin and lysozyme complemented other techniques in evaluating infiltrates containing large neoplastic cells. B-cell malignancies comprised 58 cases (80%) of this series and included well and moderately well differentiated lymphocytic lymphomas (10/10); nodular (23/23) and diffuse (10/18) poorly differentiated lymphocytic lymphomas; and lymphomas of mixed lymphocytic-“histiocytic” (3/3), “undifferentiated” (3/3), and “histiocytic” (9/13) types. Nodular lymphomas were characterized as B-cell neoplasms but also revealed a prominent population of T lymphocytes (39 ± 12%). Alkaline phosphatase activity, a cytochemical marker for lymphoid cells of follicular cuffs, was most consistently observed in B-cell lymphomas of moderately well differentiated lymphocytic type (4/6 cases). In some diffuse lymphomas, cryostat section studies (EAC rosettes) suggested a pre-existing nodular proliferation. One unusual B-cell lymphoma of large cell type exhibited IgGEA rosette formation and a strong receptor for the Fc portion of IgG. Ten lymphomas (14%) were of T-cell type and were represented by cases of diffuse poorly differentiated lymphocytic lymphoma (5/18, including 3 lymphoblastic lymphomas), Sézary syndrome (1), mycosis fungoides (1), and a cytologically distinctive large cell (“histiocytic”) lymphoma (3/13). Acid phosphatase activity was a consistent marker for the T-cell malignancies, some of which also revealed α-naphthyl butyrate esterase activity. No true histiocytic lymphomas were detected. Three cases of diffuse poorly differentiated lymphocytic lymphoma and one “histiocytic” lymphoma were null.     

Optimal leaf sequencing with elimination of tongue-and-groove underdosage

The individual leaves of a multileaf collimator (MLC) have a tongue-and-groove or stepped-edge design to minimize leakage radiation between adjacent leaves. This design element has a drawback in that it creates areas of underdosages in intensity-modulated photon beams unless a leaf trajectory is specifically designed such that for any two adjacent leaf pairs, the direct exposure under the tongue-and-groove is equal to the lower of the direct exposures of the leaf pairs. In this work, we present a systematic study of the optimization of a leaf sequencing algorithm for segmental multileaf collimator beam delivery that completely eliminates areas of underdosages due to tongue-and-groove or stepped-edge design of the MLC. Simultaneous elimination of tongue-and-groove effect and leaf interdigitation is also studied. This is an extension of our previous work (Kamath et al 2003a Phys. Med. Biol. 48 307) in which we described a leaf sequencing algorithm that is optimal for monitor unit (MU) efficiency under most common leaf movement constraints that include minimum leaf separation. Compared to our previously published algorithm (without constraints), the new algorithms increase the number of sub-fields by approximately 21% and 25%, respectively, but are optimal in MU efficiency for unidirectional schedules.