Early side effects of intrathoracic BCG therapy in patients with stage I squamous cell carcinoma,adenocarcinoma, or large cell lung cancer

Summary Data are presented on 179 stage I lung cancer patients subjected to resection operations and then given adjuvant intrapleural BCG and subsequent isoniazid (INH) therapy and on 167 control patients given intrapleural saline and placebo pills in a two-arm randomized double-blind study. The predominant immediate response to BCG/INH therapy was hyperpyrexia, which was found to be more pronounced in patients with larger induration in pretreatment PPD skin tests. Subsequently, chemical hepatitis (6 cases after BCG/INH versus 1 case after saline/placebo), peripheral neuropathy (3 versus 1), dermatitis/hives (5 versus 2), pleural thickening (4 versus 0), and persistent fever (10 versus 0) were noted. Analysis of laboratory changes measured at 18 weeks following randomization revealed that patients with BCG/INH lost 1.1 kg in weight and 0.30 g/dl in hemoglobin concentration on average, whereas control patients gained 1.2 kg and 0.33 g/dl, respectively. Modest rises in SGOT and alkaline phosphatase were apparent at 6 weeks after instillation of BCG compared with controls, but these differences were no longer statistically signifikant after 18 weeks. These side effects notwhithstanding, the BCG/INH therapy was well tolerated.Members of the Lung Cancer Study Group include R. T. Eagan*, R. E. Lee, W. S. Payne, R. E. Ritts, and L. Weiland from the Mayo Clinic, Rochester; C. F. Mountain*, H. T. Barkley, O. H. Frazier, K. Hermes, E. Hersh, and M. Valdivieso from M.D. Anderson Hospital, Houston; L. D. Hill*, M. D. Hafermann, and E. Morgan from The Mason Clinic, Seattle; P. W. Wright* and K.-E. Hellstrom from the Hutchinson Cancer Center, Seattle; C. Bagley, L. P. Johnson, H. Kellogg, and R. D. Pinkham from the Swedish Medical Center, Seattle; T. D. Ivey from University Hospital, Seattle; S. Hammar from Virginia Mason Hospital, Seattle; W. Nelems from St. Paul's Hospital, Vancouver; R. Feld*, D. Bergsagel, T. C. Brown, J. Curtis, C. Keen, J. F. Pringle, I. Quirt, and L. Yeoh from The Princess Margaret Hospital, Toronto; M. Blackstein and M. Goldberg from Mount Sinai Hospital, Toronto; F. G. Pearson*, D. W. Chamberlain, J. Cooper, W. Evans, and T. Todd from Toronto General Hospital, Toronto; M. Baker and R. Ginsberg from Toronto Western Hospital, Toronto; R. I. Mitchell from Wellesley Hospital, Toronto; E. C. Holmes*, W. F. Coulson, K. P. Ramming, and T. H. Weisenburger from the University of California, Los Angeles; Z. Petrovich from Wadsworth Veterans Hospital, Los Angeles; R. K. Oldham*, J. T. Forbes, F. A. Greco, D. L. Page, R. Prager, R. L. Richardson, and S. L. Stroup from Vanderbilt University, Nashville; J. M. Lukeman* and S. M. Sajjad from the Pathology Reference Center of M.D. Anderson Hospital, Houston; P. Grifone, A. Lebeck, and T. Voss from the Operations Office, Silver Spring, Maryland; M. Gail, W. McGuire, J. Allegra, and L. Rubinstein from the National Cancer Institute, Bethesda, Maryland; and L. Eirich, W. Heineman, and J. Beach from Information Management Services, Bethesda, Maryland. Asterisks designate principal investigators.     

紫色土Zn,Cd复合污染生态效应研究

通过盆栽生物试验结合野外典型污染调查 ,研究紫色土Zn、Cd复合污染对莴笋、蕃茄、甘兰、小麦等的作物效应 .结果表明 ,Zn、Cd复合污染对Zn表现为加和作用 ,低浓度Cd促进Zn吸收 ,加重Zn对养分吸收的抑制 ,加剧Zn的毒害作用 ;复合效应对Cd表现为竞争作用 ,高浓度Zn抑制Cd吸收 ,减轻Cd对养分吸收的抑制 ,缓解Cd毒性 ,向土壤添加Zn 50 0mg·kg- 1 为供试盆栽条件下拮抗效应的临界值 .     

Interleukin-1beta increases expression and activity of matrix metalloproteinase-2 in cardiac microvascular endothelial cells: role of PKCalpha/beta1 and MAPKs

Matrix metalloproteinases (MMPs), a family of extracellular endopeptidases, are implicated in angiogenesis because of their ability to selectively degrade components of the extracellular matrix. Interleukin-1 (IL-1), increased in the heart post-myocardial infarction (post-MI), plays a protective role in the pathophysiology of left ventricular (LV) remodeling following MI. Here we studied expression of various angiogenic genes affected by IL-1 in cardiac microvascular endothelial cells (CMECs) and investigated the signaling pathways involved in the regulation of MMP-2. cDNA array analysis of 96 angiogenesis-related genes indicated that IL-1 modulates the expression of numerous genes, notably increasing the expression of MMP-2, not MMP-9. RT-PCR and Western blot analyses confirmed increased expression of MMP-2 in response to IL-1. Gelatin in-gel zymography and Biotrak activity assay demonstrated that IL-1 increases MMP-2 activity in the conditioned media. IL-1 activated ERK1/2, JNKs, and protein kinase C (PKC), specifically PKC/₁, and inhibition of these cascades partially inhibited IL-1-stimulated increases in MMP-2. Inhibition of PKC/₁ failed to inhibit ERK1/2. However, concurrent inhibition of PKC/₁ and ERK1/2 almost completely inhibited IL-1-mediated increases in MMP-2 expression. Inhibition of p38 kinase and nuclear factor-B (NF-B) had no effect. Pretreatment with superoxide dismutase (SOD) mimetic, MnTMPyP, increased MMP-2 protein levels, whereas pretreatment with SOD and catalase mimetic, EUK134, partially inhibited IL-1-stimulated increases in MMP-2 protein levels. Exogenous H₂O₂ significantly increased MMP-2 protein levels, whereas superoxide generation by xanthine/xanthine oxidase had no effect. This in vitro study suggests that IL-1 modulates expression and activity of MMP-2 in CMECs. MMP-2; protein kinase C; ERK1/2; JNK     

Climate and ecosystem linkages explain widespread declines in North American Atlantic salmon populations

North American Atlantic salmon (Salmo salar) populations experienced substantial declines in the early 1990s, and many populations have persisted at low abundances in recent years. Abundance and productivity declined in a coherent manner across major regions of North America, and this coherence points toward a potential shift in marine survivorship, rather than local, river‐specific factors. The major declines in Atlantic salmon populations occurred against a backdrop of physical and biological shifts in Northwest Atlantic ecosystems. Analyses of changes in climate, physical, and lower trophic level biological factors provide substantial evidence that climate conditions directly and indirectly influence the abundance and productivity of North American Atlantic salmon populations. A major decline in salmon abundance after 1990 was preceded by a series of changes across multiple levels of the ecosystem, and a subsequent population change in 1997, primarily related to salmon productivity, followed an unusually low NAO event. Pairwise correlations further demonstrate that climate and physical conditions are associated with changes in plankton communities and prey availability, which are ultimately linked to Atlantic salmon populations. Results suggest that poor trophic conditions, likely due to climate‐driven environmental factors, and warmer ocean temperatures throughout their marine habitat area are constraining the productivity and recovery of North American Atlantic salmon populations.     

VL:VH domain rotations in engineered antibodies: Crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs

The crystal structures of two pairs of Fab fragments have been determined. The pairs comprise both a murine and an engineered human form, each derived from the antitumor antibodies A5B7 and CTM01. Although antigen specificity is maintained within the pairs, antigen affinity varies. A comparison of the hypervariable loops for each pair of antibodies shows their structure has been well maintained in grafting, supporting the canonical loop model. Detailed structural analysis of the binding sites and domain arrangements for these antibodies suggests the differences in antigen affinity observed are likely to be due to inherent flexibility of the hypervariable loops and movements at the V_L:V_H domain interface. The four structures provide the first opportunity to study in detail the effects of protein engineering on specific antibodies. Proteins 29:161–171, 1997. © 1997 Wiley-Liss, Inc.     

Molecular evolution and modern human origins

While molecular evolutionists may be fascinated by the features and history of a particular gene or DNA segment, evolutionary anthropologists are often more interested in the activities and history of groups of people. We may want to know, for instance, when and where humans have migrated, how much exchange between groups has taken place, and how population sizes have changed. Population genetic theory provides the hope that through analyses of genetic data we will gain insight into the history of populations. Genetic data from extant human populations are now accruing at a remarkable rate. We might, therefore, expect to have answers in hand. There remains, however, a wide gap between the available theory and data; too often we fail to draw firm conclusions because our interpretation of analytic results requires that we make myriad assumptions about our data. In any one instance, these assumptions might include estimates of mutation rate, mutational mechanism, population sizes, the role that natural selection has played, and the rate of migration among groups. Often these assumptions are implicit, invisible to most. How, then, are we to make any progress? © 1998 Wiley-Liss, Inc.     

Cryptic distant relatives are common in both isolated and cosmopolitan genetic samples

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2^nd to 9^th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100–300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount of DNA shared IBD in most ethnolinguistically-defined populations, for example Native American groups, Finns and Ashkenazi Jews, differs from continentally-defined populations by several orders of magnitude. Via extensive pedigree-based simulations, we determined bounds for predicted degrees of relationship given the amount of genomic IBD sharing in both endogamous and ‘unrelated’ population samples. Using these bounds as a guide, we detected tens of thousands of 2^nd to 9^th degree cousin pairs within a heterogenous set of 5,000 Europeans. The ubiquity of distant relatives, detected via IBD segments, in both ethnolinguistic populations and in large ‘unrelated’ populations samples has important implications for genetic genealogy, forensics and genotype/phenotype mapping studies.