A critical evaluation of current views regarding eye movement desensitization and reprocessing (EMDR): clarifying points of confusion.

EMDR is an active psychological treatment for PTSD that has received widely divergent reactions from the scientific and professional community. This article examines points of confusion in the published literature on EMDR, including the theoretical, empirical, and historical issues around EMDR and placebo effects, exposure procedures, the eye movement component, treatment fidelity issues, and outcome studies. It also examines historical information relevant to the scientific process and charges of "pseudoscience" regarding EMDR. We conclude that the confusion in the literature is due to (a) the lack of an empirically validated model capable of convincingly explaining the effects of the EMDR method, (b) inaccurate and selective reporting of research, (c) some poorly designed empirical studies, (d) inadequate treatment fidelity in some outcome research, and (e) multiple biased or inaccurate reviews by a relatively small group of authors. Reading the original research articles frequently helps to reduce the confusion arising from the research review literature.     

Targeted disruption of fibronectin-integrin interactions in human gingival fibroblasts by the RI protease of Porphyromonas gingivalis W50

Cell surface integrins mediate interactions between cells and their extracellular matrix and are frequently exploited by a range of bacterial pathogens to facilitate adherence and/or invasion. In this study we examined the effects of Porphyromonas gingivalis proteases on human gingival fibroblast (HGF) integrins and their fibronectin matrix. Culture supernatant from the virulent strain W50 caused considerably greater loss of the beta1 integrin subunit from HGF in vitro than did that of the beige-pigmented strain W50/BE1. Prior treatment of the W50 culture supernatant with the protease inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that this process is proteolytically mediated. Purified arginine-specific proteases from P. gingivalis W50 were able to mimic the effects of the whole-culture supernatant on loss of beta1 integrin expression. However purified RI, an alpha/beta heterodimer in which the catalytic chain is associated with an adhesin chain, was 12 times more active than RIA, the catalytic monomer, in causing loss of the alpha5beta1 integrin (fibronectin receptor) from HGF. No effect was observed on the alphaVbeta3 integrin (vitronectin receptor). The sites of action of RI and RIA were investigated in cells exposed to proteases pretreated with TLCK to inactivate the catalytic component. Use of both monoclonal antibody 1A1, which recognizes only the adhesin chain of RI, and a rabbit antibody against P. gingivalis whole cells indicated localization of RI on the fibroblasts in a clear, linear pattern typical of that seen with fibronectin and alpha5beta1 integrin. Exact colocalization of RI with fibronectin and its alpha5beta1 receptor was confirmed by double labeling and multiple-exposure photomicroscopy. In contrast, RIA bound to fibroblasts in a weak, patchy manner, showing only fine linear or granular staining. It is concluded that the adhesin component of RI targets the P. gingivalis arginine-protease to sites of fibronectin deposition on HGF, contributing to the rapid loss of both fibronectin and its main alpha5beta1 integrin receptor. Given the importance of integrin-ligand interactions in fibroblast function, their targeted disruption by RI may represent a novel mechanism of damage in periodontal disease.     

Extensive transmission of Mycobacterium tuberculosis from a child

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.     

Excitatory amino acids mediate responses elicited in vitro by stimulation of cortical afferents to reticularis thalami neurons of the rat

The effects of the excitatory amino acids on the nucleus reticularis thalami were examined by intracellular recordings from rat thalamic slices. Non-N-methyl-D-aspartate receptor agonists and glutamate induced a membrane depolarization and a reduction in input resistance, while N-methyl-D-aspartate and aspartate induced a prolonged discharge, which in some neurons took the form of a burst firing associated with an apparent increase in membrane input resistance. Both the N-methyl-D-aspartate and the aspartate effects were blocked by D-2-amino-5-phosphonovalerate, while the effects of glutamate, kainate and quisqualate were not. The excitatory postsynaptic potential evoked by corticothalamic fiber stimulation shows two components: an early, short-lasting, 2-amino-5-phosphonovalerate-insensitive portion, and a late, 2-amino-5-phosphonovalerate-sensitive decay phase. It is suggested that glutamate acts in nucleus reticularis thalami cells preferentially on the non-N-methyl-D-aspartate receptors, while aspartate shows an N-methyl-D-aspartate-like effect. The two excitatory amino acids glutamate and aspartate play a determinant role in the modulation of thalamic activity driven by corticothalamic projection.     

Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex

Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity. A transient increase in calcineurin activity is found to prevent the shift of responsiveness in the visual cortex following monocular deprivation, and this effect is reversible. These results imply that the balance between protein kinases and phosphatases is critical for visual cortex plasticity.     

Complete Nucleotide Sequence Analysis of a Western Pacific Dengue-1 Virus Strain

We have determined the complete nucleotide sequence and the deduced amino acid polypeptide sequence of the genome of a dengue-1 (DEN-1) virus strain isolated from a patient on Nauru in the Western Pacific in 1974 (West Pac 74). The complete genome is 10,735 nucleotides in length and contains a single long open reading frame of 10,176 nucleotides encoding a polyprotein of 3392 amino acids. When compared to DEN-1 Singapore S275/90, the nucleotide and amino acid sequence homology are 94% and 97.8%, respectively. This revised version was published online in July 2006 with corrections to the Cover Date.     

Characterization of the hamster FancG/Xrcc9 gene and mutations in CHO UV40 and NM3

The human FANCG/XRCC9 gene, which is defective in Fanconi anemia complementation group G (FA-G) cells, was first cloned by genetic complementation of the mitomycin C (MMC) sensitivity of CHO mutant UV40. The CHO NM3 mutant was subsequently assigned to the same complementation group. The parental AA8 CHO cells are hemizygous at the FancG locus, and we identified frameshift mutations that result in N-terminal truncations of the protein in both UV40 and NM3. Hypersensitivity to DNA cross-linking agents, such as MMC, typically characterizes FA cells. By introducing the native CHO FancG gene into mutant NM3, we demonstrate that hamster FancG fully corrects the 3-fold sensitivity to methyl methanesulfonate (MMS) as well as the 10-fold sensitivity to MMC, whereas resistance to ionizing radiation did not increase appreciably. In contrast, hamster cDNA transformants showed incomplete correction for both MMC and MMS sensitivity. The constitutively expressed FancG protein is present in the cytoplasmic, nuclear and chromatin fractions. FancG protein levels and subcellular localization do not change appreciably as a function of cell cycle position. Our results are consistent with roles of FancG in both the nuclear and cytoplasmic compartments to maintain genomic stability in response to various genotoxic agents.     

Pigeon allergens in indoor environments: a preliminary study

BACKGROUND: Few studies have measured pigeon allergens in non pigeon coop environments. This study was conducted to determine approximate pigeon dropping allergen concentrations in indoor environments. METHODS: Polyclonal antibody serum was prepared by injecting a rabbit three times with crude wild pigeon dropping extract in 50 mM Tris buffer with Freund's adjuvant. One hundred and fifteen dust samples were collected in a pigeon-infested school, pigeon coops, homes and hospitals and analyzed by a direct competitive pigeon enzyme-linked immunosorbent assay (ELISA). RESULTS: The highest level of pigeon allergen inhibitory activity were recorded in four samples from pigeon coop bedding samples with a median activity of 11.2% relative to pigeon droppings. The second highest level of pigeon allergens was in a pigeon-infested high school with a median or 7.4% activity relative to pigeon droppings. At an entrance underneath pigeon roosts, one sample had a relative inhibitory activity of 62.3%. Pigeon allergen inhibitory levels were generally low in the home and hospital samples, but nevertheless 46 out of 89 of these samples were still above detection limit. CONCLUSIONS: This study suggests that large concentrations of pigeon allergens can be found in buildings without domestic pigeons such as the pigeon-infested high school.