Consequences of a short pulse of pesticide exposure for survival and reproduction of Gammarus pulex

The aim of the present study was to examine the effects of a short and environmentally realistic pulse exposure of different life stages of the freshwater amphipod, Gammarus pulex, to the pyrethroid insecticide, esfenvalerate. We were particularly interested in determining the extent to which detectable effects on key life-history traits persisted following cessation of a brief exposure to this pesticide. Our results indicate that environmentally realistic exposure concentrations of this widely used insecticide can have a significant effect on the survival and reproduction of Gammarus pulex. Comparison of LC(50) values indicates that G. pulex has a similar sensitivity to esfenvalerate as the standard test invertebrate, Daphnia magna and is more sensitive than other common stream invertebrates. Despite 100% survival during pulses of up to 2 microg l(-1), mortality increased, in some cases markedly, following transfer to clean conditions. Pulse exposure to esfenvalerate at concentrations in the range 0.1-0.6 microg l(-1) for as little as 1h can have effects on G. pulex survival, pairing behaviour, and reproductive output that can still be detected at least 2 weeks following the pulse. Reproductive traits were very sensitive to esfenvalerate, and exposure to 0.05 microg l(-1) for 1h led to immediate disruption of reproducing pairs, release of eggs or offspring from the brood pouch, and substantial delays in pair formation and subsequent reproduction following transfer to clean water. The kinds of effects on reproductive behaviour observed in this study could potentially impact the population dynamics of G. pulex in the field. Whether such effects occur will depend on the frequency, duration, timing, and spatial extent of pesticide exposure in freshwater stream ecosystems, about which relatively little is known. Such information is essential if effects on non-target aquatic species are to be more accurately assessed.     

Modified radical vaginal hysterectomy with or without laparoscopic nerve-sparing dissection: a comparative study

OBJECTIVE: Nerve-sparing dissection of the lateral portion of the cardinal ligament (paracervical lymphadenectomy) has been recently developed with the goal of reducing the late urinary adverse effects of radical hysterectomy without impairing the outcome. This work has been carried out in order to investigate the influence of additional paracervical lymph node dissection at the time of laparoscopically assisted modified radical hysterectomy on outcome and urinary sequelae. METHODS: A total of 95 patients underwent a modified radical hysterectomy using a combined laparoscopic and vaginal approach since 1991. In 47 of these patients treated since 1996 an additional laparoscopic paracervical lymphadenectomy was performed. The operative, postoperative, and survival outcomes were assessed. In 60 patients, 32 and 28 in the groups of patients with or without paracervical dissection, respectively, a careful interview on urinary symptoms was conducted by an independent investigator. RESULTS: Paracervical dissection involves no operative complication and lenghthens the postoperative urinary retention, but has no adverse influence on long-term urinary discomfort. The yield of paracervical dissection is negligible for small tumors: no positive node was found in 38 patients with tumors less than 2 cm in diameter. The outcome of patients after minimal access surgery for tumors less than 2 cm is excellent whether or not a paracervical dissection has been performed. CONCLUSION: Paracervical dissection does not worsen the late urinary symptoms after vaginal radical hysterectomy. It has a limited value in the surgical management of small-size (less than 2 cm) cervical cancers, although it may prevent long-term lateropelvic recurrences.     

Retroperitoneal leiomyosarcoma and enlarged epididymis associated with a positive pregnancy test

A 57-year-old man presented with a 1-month history of progressive abdominal pain and weight loss. A palpable, nonpulsatile, firm abdominal mass was felt below the xiphisternum down to the pelvis. A pregnancy test performed on a urine sample was positive. Testicular examination and testicular ultrasound were normal. Computerized tomography of the abdomen revealed a retroperitoneal mass measuring 30 x 21 x 13 cm. Serum beta-human chorionic gonadotropin (beta-HCG) was serially increased (19.71-22.71 mIU/mL). Results of histopathology tests confirmed the diagnosis of leiomyosarcoma. The level of serum beta-HCG decreased to < 0.2 mlU/mL after chemotherapy. Beta-HCG is usually increased in germ-cell tumors but few reports in the literature describe beta-HCG-secreting leiomyosarcomas. The incidence of increased levels of beta-HCG in sarcomas in general, and its potential role as a tumor marker, is not known. A simple urine pregnancy test may be done in the work-up of abdominal masses.     

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.     

SV40 in human brain cancers and non-Hodgkin's lymphoma

Simian virus 40 (SV40) is a potent DNA tumor virus that is known to induce primary brain cancers and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor-suppressor proteins p53 and pRb family members. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain cancers, and a systematic assessment of the data indicates that the virus is significantly associated with this group of human tumors. In addition, recent large independent studies showed that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). Although the prevalence of SV40 infections in humans is not known, numerous observations suggest that SV40 is a pathogen in the human population today. This review examines the molecular biology, pathology, and clinical data implicating SV40 in the pathogenesis of primary human brain cancers and NHL and discusses future research directions needed to define a possible etiologic role for SV40 in these malignancies.     

Breast cancer revisited using DNA array-based gene expression profiling

Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The resulting clinical heterogeneity makes current diagnostic and therapeutic strategies less than perfectly adapted to each patient. Pathological and clinical factors are insufficient to capture the complex cascade of events that drive the clinical behavior of tumors. High-throughput molecular technologies provide novel tools to tackle this complexity. In particular, DNA arrays allow the simultaneous and quantitative analysis of the mRNA expression levels of thousands of genes in a single assay. Potential applications are multiple in the cancer field and the first research results are promising; comprehensive gene expression profiles of breast tumors are providing insights into mammary oncogenesis and are revealing new tumor subgroups previously indistinguishable. Significant advances will be the identification of new diagnostic, prognostic and predictive biomarkers as well as the discovery of new potential therapeutic targets. This review presents recent applications of DNA arrays in breast cancer research and discusses some issues to address in the near future to allow the technology to reach its full potential.     

Direct Evidence That Polysorbate-80-Coated Poly(Butylcyanoacrylate) Nanoparticles Deliver Drugs to the CNS via Specific Mechanisms Requiring Prior Binding of Drug to the Nanoparticles

Purpose. It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain. Methods. Both in vivo and in vitro methods have been applied to examine the possible toxic effects of PBCA nanoparticles and polysorbate-80 on cerebral endothelial cells. Human, bovine, and rat models have been used in this study. Results. In bovine primary cerebral endothelial cells, nontoxic levels of PBCA particles and polysorbate-80 did not increase paracellular transport of sucrose and inulin in the monolayers. Electron microscopic studies confirm cell viability. In vivo studies using the antinociceptive opioid peptide dalargin showed that both empty PBCA nanoparticles and polysorbate-80 did not allow dalargin to enter the brain in quantities sufficient to cause antinociception. Only dalargin preadsorbed to PBCA nanoparticles was able to induce an antinociceptive effect in the animals. Conclusion. At concentrations of PBCA nanoparticles and polysorbate-80 that achieve significant drug delivery to the brain, there is little in vivo or in vitro evidence to suggest that a generalized toxic effect on the BBB is the primary mechanism for drug delivery to the brain. The fact that dalargin has to be preadsorbed onto nanoparticles before it is effective in inducing antinociception suggests specific mechanisms of delivery to the CNS rather than a simple disruption of the BBB allowing a diffusional drug entry.     

Association between SV40 and non-Hodgkin's lymphoma

Millions of people worldwide were inadvertently exposed to live simian virus 40 (SV40) between 1955 and 1963 through immunization with SV40-contaminated polio vaccines. Although the prevalence of SV40 infections in humans is not known, numerous studies suggest that SV40 is a pathogen resident in the human population today. SV40 is a potent DNA tumor virus that is known to induce primary brain cancers, bone cancers, mesotheliomas, and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor suppressor proteins p53 and pRb. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain and bone cancers and malignant mesotheliomas. Evidence suggests that there may be geographic differences in the frequency of these virus-positive tumors. Recent large independent controlled studies have shown that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). In our study, we analyzed systemic NHL from 76 HIV-1-positive and 78 HIV-1-negative patients, and nonmalignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumors; 54 colon and breast carcinoma samples served as cancer controls. We used polymerase chain reaction (PCR) followed by Southern blot hybridization and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. SV40-specific DNA sequences were detected in 64 (42%) of 154 NHL, none of 186 nonmalignant lymphoid samples, and none of 54 control cancers. For NHL from HIV-1-positive patients, 33% contained SV40 DNA and 39% Epstein Barr virus (EBV) DNA, whereas NHLs from HIV-1-negative patients were 50% positive for SV40 and 15% positive for EBV. Few tumors were positive for both SV40 and EBV. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B cell and follicular-type lymphomas. We conclude that SV40 is significantly associated with some types of NHL and that lymphomas should be added to the types of human cancers associated with SV40.     

Phage probes for malignant glial cells

Early diagnosis and effective treatment of malignant gliomas, which are heterogeneous brain tumors with variable expression of cell surface markers, are inhibited by the lack of means to characterize and target tumor-selective molecules. To create molecular profiles for RG2 rat glioma cells, we used phage display technology, an approach capable of producing valuable ligands to unknown cell surface targets. The ligands were selected from libraries of peptides displayed as fusion molecules on phage particles. Modifications of the selection conditions resulted in identification of three distinctive families of peptide ligands for malignant glioma cells. The first family with V (D)/(G) L P (E)/(T) H(3) binding motif appeared to target a marker that is common for glioma cells, normal brain cells, and cells of non-brain origin. The second group of peptide-presented phage displayed D (T)/S/(L) T K consensus sequence and contained peptides with pronounced glioma-selective properties. Phage clones expressing peptides with E (L)/V/(S) R G D S motif were found in cell lysates and represented the third family of glioma-specific ligands. All peptides within this family contain the RGD amino acid sequence, which is known to bind to a number of integrins. Phage clones that belong to this family were internalized by RG2 glioma cells about 63-fold more efficiently than by astrocytes. The approach described could be applicable for accurate detection of glioma expression patterns in individual tumors. Such patterns could be beneficial in the design of effective combinations of drugs for anti-glioma treatments.