Evidence of an age-related threshold effect of polychlorinated biphenyls (PCBs) on neuropsychological functioning in a Native American population

Polychlorinated biphenyls (PCBs) have been suspected for some time of having adverse effects on neuropsychological functioning in humans. While there is evidence of slowing of cognitive function in children associated with exposure to PCBs, the evidence of comparable effects on adults is far less well understood. We report here on the neuropsychological evaluation of 277 Native American adults, ranging in age from 18 to 79, who were exposed to PCBs by way of environmental contamination in the St. Lawrence region of upstate New York. PCB body burden was estimated by 101 PCB congeners and neuropsychological functioning was assessed by a battery of 18 tests. Spline regression models were fitted to the latent variables of memory, motor function, and higher-order executive functioning. After adjusting for age, gender, and education the analyses revealed a threshold effect of PCBs at approximately 2 ppb. An age-by-PCB interaction effect was also observed for several variables which suggests that the threshold effect was largely confined to the age range of 40-79 and was not observable in the 18-40-year-old group. Implications of these results are discussed in comparison to previously published similar work with adults and in terms of its potential clinical meaningfulness.     

EXPERIMENTAL MENINGOCOCCUS INFECTION OF THE CHICK EMBRYO

1. A strain of meningococci obtained directly from the spinal fluid of a patient has been propagated in serial passage in 10 to 12 day old chick embryos without change in its essential characteristics. 2. The chick embryo is susceptible to infection with the meningococcus, and, depending on its stage of development, reacts to the infection with more or less specific lesions. 3. In chick embryos of 15 days incubation, following the utilization of definite portals of entry, such as the nasopharynx, or by inoculation of the amniotic fluid or by inoculation of the body wall, the meningococcus is localized in specific areas, namely in the cranial sinuses, the lungs or meninges, or in all of these areas. 4. The lesions of the meningococcus infection in man, a septicemia, sinusitis, pneumonia and meningitis can be reproduced in the chick embryo by choosing embryos at the proper state of development and utilizing the various portals of entry experimentally available.     

Biological effects of native and oxidized low-density lipoproteins in cultured human retinal pigment epithelial cells

Age-related macular degeneration (AMD) and artherosclerosis share common characteristics in their pathogenesis. In this study, we investigated the effects of lipoproteins like native (n)-LDL, oxidized (ox)-LDL and high-density lipoprotein (HDL) on advanced senescence, extracellular matrix accumulation, cell loss, and transforming growth factor-beta2 (TGF-β2) expression in cultured human retinal pigment epithelial (RPE) cells. Primary human RPE cells were incubated with 10-100 μg/ml n-LDL, ox-LDL, and HDL for 24 h. For determination of advanced senescence, beta-galactosidase staining was used. The induction of fibronectin (Fn), laminin alpha 1 (Laa1), and collagen type IV alpha 2 (Col4a2) mRNA was quantified by real-time PCR. Cell loss was investigated by live dead assay. Expression of TGF-β2 was analyzed by real-time PCR and ELISA assays. Ox-LDL accelerated dose-dependently the onset of RPE senescence, whereas LDL and HDL had no effect. LDL and ox-LDL led to induced expression of Fn, Laa1 and Col4a2, whereas HDL had no influence. Incubation of RPE cells with 100 μg/ml ox-LDL induced marked cell death compared to untreated control cells. Expression of TGF-β2 was dose-dependently increased by LDL and ox-LDL.LDL and ox-LDL induced cellular changes in RPE cells in vitro, which may resemble pathogenic events of AMD. These results may provide further information about the effects of LDL and ox-LDL in the human RPE and their potential role in the pathogenesis of AMD.     

Orthographic familiarity,phonological legality and number of orthographic neighbours affect the onset of ERP lexical effects

Background  

It has been suggested that the variability among studies in the onset of lexical effects may be due to a series of methodological differences. In this study we investigated the role of orthographic familiarity, phonological legality and number of orthographic neighbours of words in determining the onset of word/non-word discriminative responses.     

Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast cancer: a Brazilian experience

Gemcitabine and cisplatin combination (Gem–Cis) is a commonly used regimen in metastatic breast cancer (MBC), with proven activity in phase II trials. It is mostly used as a salvage regimen for progressive disease refractory to anthracyclines and taxanes, and when liver dysfunction secondary to liver metastasis precludes these drugs. Retrospective review of medical charts was conducted for patients treated with Gem–Cis for MBC in a single institution in Brazil between January 2004 and July 2007. The purpose of this study was to evaluate the outcomes and toxicity of Gem–Cis in a broad indication, including patients with deteriorated performance status (PS) and liver dysfunction, which were excluded from clinical trials. Fifty-six patients were included. Median age was 52 years, 46.4% were hormone–receptor negative, 57.2% received 3 or more prior chemotherapy lines, and 34 had liver metastasis. The median overall survival (OS) was 7.6 months, the median progression-free survival was 3.3 months, and the response rate was 21.2%. In variable analysis, PS was significantly associated with OS, even after adjusting to other factors. Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and thrombocytopenia in 12.3%. Gem–Cis was a relatively active combination in this population that typically carries a poor prognosis. The subgroup of patients with favorable PS experienced longer survival, even when liver metastasis and hepatic dysfunction were a concern. Toxicity was manageable and it was not correlated with PS or liver dysfunction.

     

CHANGES IN THE CONTENT OF DOPAMINE AND ITS METABOLITES IN THE BASAL GANGLIA FOLLOWING RIGHT MIDDLE CEREBRAL ARTERY OCCLUSION AND REFLOW IN MONKEYS

Focal ischaemia was produced experimentally in Macaca radiata monkeys by occlusion of middle cerebral artery (MCA). There was a lowering of the dopamine (DA) content of basal ganglia after 4 and 12 h of occlusion. DA content was restored to normal in basal ganglia after restoration of blood flow. With the progress of time the DA content was increased above that of sham controls. Changes were also observed in the non-occluded left basal ganglia. The homovanillic acid (HVA) content was decreased significantly at 12 h after occlusion. After the onset of reflow, the HVA content of the right basal ganglia was higher than that of sham controls. The 3,4 dihydroxyphenylacetic acid (DOPAC) content of right basal ganglia was significantly decreased after 12 h occlusion. Reflow restored the level of DOPAC to normal within 1 h after removal of clip. Discrete changes were also observed in the left basal ganglia at some of the time intervals.     

Antitumor Effector Mechanism of Interleukin-lβ at a Distant Site in the Double Grafted Tumor System

Recombinant human interleukin-lβ (IL-lβ) Inhibited the growth of not only the right, but also the left non-treated tumor in a double grafted tumor system. Since the antitumor activity of IL-lβ against the right and left tumors was not seen in nude mice, lymphocytes have a key role in the antitumor effect of intratumoral administration of IL-lβ. TIL (tumor-infiltrating leukocytes) obtained from left and right side tumors treated with IL-1β were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from the right side clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. Spleen cells and right and left regional lymph node cells prepared from IL-1-treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1-positive lymphocytes increased in the spleen and in the right regional lymph nodes after intratumoral administration of IL-1. Isolated tumor cells obtained from the right tumor treated with IL-lβ and the left side tumor on day 6 were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor and macrophage chemotactic factor activities were detected in the culture media from IL-1-treated tumor tissues cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated tumor tissues. These results suggest that intratumoral administration of IL-1 first induces neutrophils and macrophages in the right tumor, then Lyt-1-positive cells in the right regional lymph nodes and in the spleen, and subsequently induces macrophages in the left, non-treated tumor.