Despite Equivalent Outcomes,Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer

Annals of Surgical Oncology -     

Analysis of supercoiled circular plasmids in infectious and non-infectious Borrelia burgdorferi

Linear plasmids are widely distributed in isolates of Borrelia burgdorferi, but the prevalence of supercoiled circular (SC) plasmids has not been clearly established. Enriching for SC plasmids on ethidium bromide density-gradients revealed that a low passage of strain Sh-2-82 of B. burgdorferi has at least six SC plasmids (8.4, 8.8, 20, 26, 29 and 51 kb). In addition, several of the SC plasmids were observed by electron microscopy to form concatenated structures. Because of the high incidence of coupled SC plasmids and the effect of such structures on plasmid mobility, we suggest that they could be mistaken for a single DNA species having a high molecular weight when total DNA from B. burgdorferi is examined by agarose-gel electrophoresis. Of the six SC plasmids in strain Sh-2-82, four could still be detected after two years of continuous in vitro passaging in BSK II medium. The two SC plasmids lost after a maximum of 20 passages, pBBC1 (8.4 kb) and pBBC2 (8.8 kb), shared a high degree of DNA sequence similarity, suggesting that their apparent instability may be a unique feature of these closely related plasmids. Two higher passaged variants of strain Sh-2-82, P20 and P202, were shown by hybridization to lack pBBC1 and pBBC2 sequences and were unable to infect the white-footed mouse, Peromyscus leucopus. However, six of 14 unrelated isolates that infected this rodent and Syrian hamsters also lacked pBBC1 and pBBC2 sequences. None of five unrelated but highly passaged non-infectious isolates carried either pBBC1 or pBBC2 sequences. These data indicate that pBBC1 and pBBC2 do not encode constitutively expressed proteins required for infectivity in our experimental system. Nevertheless, eight of the 13 infectious strains examined did carry pBBC1 and/or pBBC2, indicating that these two closely related plasmids can be detected in a wide range of unrelated isolates of B. burgdorferi.     

Tryptase inhibitors: a novel class of anti-inflammatory drugs

Tryptase, a serine protease released from mast cell secretory granules, is found at elevated levels in pathophysiologic conditions associated with allergic inflammation. The in vitro and in vivo biological activities of tryptase strongly suggest that tryptase influences lung function, inflammation, matrix degradation, and tissue remodelling. The pathophysiologic role for tryptase in diseases of airway inflammation such as asthma has been confirmed from studies using the selective tryptase inhibitor APC 366 in the allergic sheep model. APC 366 inhibited the allergen-induced early and late airway responses, blocked postchallenge airway hyperresponsiveness, and reduced airway inflammation. A pilot clinical trial with mild to moderate asthmatics also showed that APC 366 protected against allergen-induced early and late responses and reduced airway hyperresponsiveness. Current data provide compelling evidence that tryptase plays a fundamental role in allergic inflammation, and selective tryptase inhibitors may represent a novel class of anti-inflammatory therapeutics for treating asthma and other mast cell-mediated diseases.     

Malignant lymphoma of the bladder and female urethra

Primary malignant non-Hodgkin's lymphomas account for 0.4% of malignant neoplasms arising in the bladder and female urethra, but do not comprise a uniform group, and three subgroups can be identified which account for a majority of cases. The most common is a low-grade B-cell lymphoma similar to neoplasms arising in the mucosa-associated lymphoid tissue at other sites — so-called MALTomas. These generally display indolent behavior. A second group accounting for approximately one-fifth of cases is composed almost entirely of large lymphoid cells, and these tumors have a poor prognosis. A third possible group comprises only a few patients who present with diffuse thickening of the bladder wall, and have a poor prognosis. The authors present a new case which suggests that this latter group may be of T-cell origin. In addition to these three subtypes, others no doubt await recognition. The different forms of primary lymphoma appear to require different treatments, and some guidelines are proposed.     

Characterization of synaptic vesicles and related neuronal features in nerve growth factor and ras oncogene differentiated PC12 cells

PC12 cells can differentiate into neuron-like cells after treatment with either nerve growth factor (NGF) or transduction with a retrovirus which expresses the K-ras oncogene. The concomitant treatment of NGF plus ras differentiates PC12 cells further than either agent alone with respect to neurite outgrowth, acetylcholinesterase levels, and most strikingly, the number of synaptic vesicle (SV) clusters. These SV clusters in PC12 cell neurites closely resemble those in the presynaptic terminals of neurons. Such SV clusters have not been described in cell lines previously. The SV clusters from all three differentiated groups (NGF, ras, and NGF plus ras) were similar in size, shape, and configuration, except that the ones in the doubly treated group occur in higher frequency and have more vesicles. The synaptic nature of these vesicle clusters was demonstrated by their regulated depletion after potassium stimulation. Furthermore, these vesicle clusters stained positively for two SV-associated proteins, synapsin I and synaptophysin, by EM immunocytochemistry (ICC). Such SV clusters in a cell line are very useful for characterizing the regulated release of SVs and the distribution of SV-related antigens in intact cells. Analysis by SDS-gel electrophoresis and immunoblotting indicated that synapsin I levels are higher in all three differentiated groups compared to untreated cells; whereas synaptophysin levels are lower in cells exposed to NGF alone or with NGF and ras double treatment. Possible convergence and/or divergence on the mechanisms of NGF and ras differentiation in PC12 cells are discussed. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Parental satisfaction and outcome: a 4-year study in a child and adolescent mental health service

OBJECTIVE: The aim of this paper is to examine the facets of parental satisfaction and its relationship with clinician-rated outcome in a child and adolescent mental health service. METHOD: Patients (n = 1278) consecutively assessed between 1992 and 1996 were included in the study. When treatment ended, clinicians rated the outcome of the intervention and parents were asked to complete a satisfaction questionnaire. RESULTS: Sixty-nine per cent of cases were rated by clinicians as having a positive outcome. Outpatients were more likely to be given a positive rating than inpatients. Satisfaction questionnaires were returned by 40% of parents; 76% of these were mostly or very satisfied. Satisfaction scores increased with the number of outpatient sessions attended but did not differ between inpatients and outpatients. There was a significant but small agreement (27% better than chance) between clinicians' rating of outcome and parental satisfaction. Level of agreement varied according to service provided and the number of sessions attended. While rates of positive outcome increased over the study period, ratings of satisfaction were stable. CONCLUSIONS: Overall, ratings of satisfaction were comparable with those reported in other studies. Variations in concordance between parents and clinicians show that outcome and satisfaction, although related, are different constructs influenced by different factors depending on the services provided. Focusing on specific aspects of satisfaction, as opposed to global measures, may be more useful for services, although such undertakings must be supported with efforts to improve clinical outcomes.