Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome

Clinical observations and experimental evidence link bone marrow failure in myelodysplastic syndrome (MDS) with a T cell-dominated autoimmune process. Immunosuppressive therapy is effective in improving cytopenias in selected patients. Trisomy 8 is a frequent cytogenetic abnormality in bone marrow cells in patients with MDS, and its presence has been associated anecdotally with good response to immunotherapy. We studied 34 patients with trisomy 8 in bone marrow cells, some of whom were undergoing treatment with antithymocyte globulin (ATG). All had significant CD8+ T-cell expansions of one or more T-cell receptor (TCR) Vbeta subfamilies, as measured by flow cytometry; expanded subfamilies showed CDR3 skewing by spectratyping. Sorted T cells of the expanded Vbeta subfamilies, but not of the remaining subfamilies, inhibited trisomy 8 cell growth in short-term hematopoietic culture. The negative effects of Vbeta-expanded T cells were inhibited by major histocompatibility complex (MHC) class 1 monoclonal antibody (mAb) and Fas antagonist and required direct cell-to-cell contact. Sixty-seven percent of patients who had de novo MDS with trisomy 8 as the sole karyotypic abnormality responded to ATG with durable reversal of cytopenias and restoration of transfusion independence, with stable increase in the proportion of trisomy 8 bone marrow cells and normalization of the T-cell repertoire. An increased number of T cells with apparent specificity for trisomy 8 cells is consistent with an autoimmune pathophysiology in trisomy 8 MDS.     

Antibiotic prescribing and penicillin-resistant pneumococci in a Merseyside Health District

OBJECTIVES: To measure the effects of antibiotic prescribing changes in the community on the prevalence of penicillin-resistant pneumococci. METHODS: Penicillin-resistant pneumococci were isolated from clinical samples taken from 549 patients between January 1987 and December 2000. Changes in the percentage of penicillin-resistant pneumococci isolated over the 14-year period and changes in prescribing practices were determined. RESULTS: Between January 1987 and December 2000, the prevalence of penicillin resistant pneumococci increased from 1.4% to a peak of 12.9% in 1997, subsequently falling to 8.9% after changes in antibiotic prescribing practices in the community.Over 65% of isolates were community acquired with 53% of patients having received antibiotics in the 3 months prior to their first isolate. Thirteen patients had a history of recent travel abroad. CONCLUSION: Reduction in antibiotic prescribing in general practice was followed by a reduction in the prevalence of penicillin-resistant pneumococci.     

Neuroinflammation in neurological disorders: pharmacotherapeutic targets from bench to bedside

Metabolic Brain Disease - Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover,...     

G-coupled protein receptors and breast cancer progression: potential drug targets

Breast cancer remains a leading cause of death despite early screening and advances in medicine. Bone marrow metastasis often complicates the clinical picture by requiring more aggressive treatment and worsening long-term prognoses. Recent therapeutic targeting of hormonal receptors such as human epidermal growth factor receptor 2 and estrogen receptor has shown limited success in treating localized disease for those patients whose cancer cells are responsive. Although traditional approaches such as chemotherapy have demonstrated many successes, these agents fail to target quiescent cancer stem cells, which might have entered the bone marrow where they might be responsible for the quiescence population. Following years of clinical remission, these dormant cells could lead to secondary cancer resurgence. To date, little progress has been made in the development of targeted treatments for receptor negative and metastatic disease. In this review, we discuss the role of G-protein coupled receptors, including neurokinin-1, neurokinin-2 and chemokine receptor 4, as novel targets in the treatment of breast cancer.     

Effect of Dendrophthoe falcata (L.f.) Ettingsh on female reproductive system in Wistar rats: a focus on antifertility efficacy

Background

This study was designed to assess the effect of one traditionally used antifertility plant, Dendrophthoe falcata (L.f.) Ettingsh (Loranthaceae), on female reproductive system, fertility and safety, by oral administration to adult female Wistar rats.

Study Design

After the oral acute toxicity study, the hydroalcoholic extract of the aerial parts was administered at three doses. Treatment started at weaning and continued until Day 0 postpartum.

Results

The LD₅₀ value was found to be 4.55 g/kg body weight. Vaginal opening occurred earlier in treated females when compared with controls. Analysis of vaginal smears revealed that all animals were cycling, although the length of the diestrus was longer in treated groups. In postcoital testing, the extract was found to be more effective in causing significant anti-implantation activity and reduction in the number of litters born. The extract also exhibited weak estrogenic activity when given alone, and when given along with ethinyl estradiol, it exhibited slight antiestrogenic activity in immature ovariectomized rats.

Conclusion

All observations suggest that the extract has antifertility effect and is safe at effective doses employed in the study.     

A Cross-sectional study evaluating chemiluminescence and autofluorescence in the detection of clinically innocuous precancerous and cancerous oral lesions

BackgroundViziLite Plus with TBlue system (Zila Pharmaceuticals; now Zila, a division of Tolmar, Fort Collins, Colo.) and VELscope (LED Dental, White Rock, British Columbia, Canada) are oral cancer screening aids that have been developed to assist dentists in identifying precancerous and cancerous oral lesions.MethodsThe authors screened patients with an overhead examination light and then with VELscope or ViziLite. Patients with a clinically innocuous lesion underwent a biopsy, and the authors compared the results of tissue pathological analysis with findings from the screening aid tests to determine the sensitivity and specificity of each device. The authors tested these devices to determine their ability to aid in the decision-making process regarding whether further evaluation of a clinically innocuous lesion was required.ResultsThe authors biopsied 102 lesions and examined them with the ViziLite. They found three dysplasias and one malignancy, none of which were detected with the ViziLite (sensitivity = 0 percent, confidence interval [CI] = 0–60.2 percent; specificity = 75.5 percent, CI = 66.7–82.8 percent). The authors biopsied another 156 lesions and examined them with VELscope. They found 11 dysplasias and one malignancy, six of which were detected with VELscope (sensitivity = 50 percent, CI = 21.1–78.9 percent; specificity = 38.9 percent, CI = 30.8–46.9 percent).ConclusionsThe study results indicate that use of ViziLite or VELscope along with a conventional screening examination for lesions deemed clinically innocuous was not beneficial in identifying dysplasia or cancer. Additional clinical studies are needed before these devices can be recommended.Clinical ImplicationsClinicians and patients could have a false sense of security after obtaining a negative ViziLite or VELscope examination result because potentially large numbers of precancerous and cancerous lesions will be missed by both devices.