EEG Signatures of Dynamic Functional Network Connectivity States.

The human brain operates by dynamically modulating different neural populations to enable goal directed behavior. The synchrony or lack thereof between different brain regions is thought to correspond to observed functional connectivity dynamics in resting state brain imaging data. In a large sample of healthy human adult subjects and utilizing a sliding windowed correlation method on functional imaging data, earlier we demonstrated the presence of seven distinct functional connectivity states/patterns between different brain networks that reliably occur across time and subjects. Whether these connectivity states correspond to meaningful electrophysiological signatures was not clear. In this study, using a dataset with concurrent EEG and resting state functional imaging data acquired during eyes open and eyes closed states, we demonstrate the replicability of previous findings in an independent sample, and identify EEG spectral signatures associated with these functional network connectivity changes. Eyes open and eyes closed conditions show common and different connectivity patterns that are associated with distinct EEG spectral signatures. Certain connectivity states are more prevalent in the eyes open case and some occur only in eyes closed state. Both conditions exhibit a state of increased thalamocortical anticorrelation associated with reduced EEG spectral alpha power and increased delta and theta power possibly reflecting drowsiness. This state occurs more frequently in the eyes closed state. In summary, we find a link between dynamic connectivity in fMRI data and concurrently collected EEG data, including a large effect of vigilance on functional connectivity. As demonstrated with EEG and fMRI, the stationarity of connectivity cannot be assumed, even for relatively short periods.

Functional connectivity in the developing brain: a longitudinal study from 4 to 9months of age.

We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9months. However at 9months the connectivity strength decreases within local networks and increases between more distant networks. The connectivity within the default-mode network, which contains both local and more distant nodes, also increases in strength with age. The low frequency power spectrum increases with age only in the posterior cingulate cortex and posterior default mode network. These findings are consistent with a general developmental pattern of increasing longer distance functional connectivity over the first year of life and raise questions regarding the developmental importance of the posterior cingulate at this age.

Microcystic meningioma arising in a mixed germ cell tumor of the testis: a case report.

We report a case of a microcystic variant of meningioma arising in a mixed germ cell tumor of the testis composed predominantly of mature and immature teratoma with elements of seminoma and embryonal carcinoma. We believe this is the first such case of a meningioma arising in a teratoma within a gonadal or extragonadal site. The meningiomatous component showed positive immunohistochemical staining for epithelial membrane antigen and a lack of staining for cytokeratin, factor VIII, CD31, and alpha-fetoprotein. Recognition of a non-germ cell tumor arising in the setting of a teratoma in the testis may be prognostically important depending on the nature of the non-germ cell component and whether it has spread beyond the testis.

Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library.

A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence analysis, these antigenic determinants were localized to segments ranging from 17 to 105 amino acids in length. Four epitopes apparently shared by more than one antibody were identified, suggesting the presence of immuno-dominant epitopes within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to vWF, bound to the same epitope previously identified by a second monoclonal antibody which also blocks this function, suggesting that this region may be at or near the vWF/FVIII binding domain. Three antibodies recognize the same region within the vWF A2 repeat. Mutations near this region appear to be responsible for Type IIA von Willebrand's disease. The co-localization of these antibodies suggests that this domain might be exposed on the surface of vWF, consistent with its apparent increased sensitivity to plasma proteases.

Nucleotide-evoked calcium signals and anion secretion in equine cultured epithelia that express apical P2Y2 receptors and pyrimidine nucleotide receptors.

1. Experiments with a spontaneously transformed equine epithelial cell line showed that certain nucleotides increased intracellular free calcium ([Ca2+]i) in cells plated on glass coverslips. The rank order of potency was ATP UTP > 5-Br-UTP, whilst UDP and ADP were ineffective. The response thus appears to be mediated by P2Y2 receptors. 2. Nucleotides also increased short circuit current (Isc) in cells grown into epithelial monolayers and the rank order of potency was UDP> UTP > 5-Br-UTP > ATP > ADP. The increase in [Ca2+]i and the rise in ISC thus have different pharmacological properties. Cross-desensitization experiments indicated that, as well as P2Y2 receptors, the monolayer cultures express at least one additional receptor population that allowed nucleotides to increase ISC. 3. The UDP-evoked increase in ISC was essentially abolished in BAPTA-loaded epithelia suggesting that this response is dependent upon increased [Ca2+]i. Moreover, experiments in which ISC and [Ca2+]i were measured simultaneously showed that the UDP- and ADP-evoked increases in ISC were accompanied by increases in [Ca2+]i. 4. When grown under conditions which favour the development of a polarized phenotype, these epithelial cells thus appear to express [Ca2+]i-mobilizing receptors sensitive to UDP and ADP that are not present in non-polarized cells on coverslips.

Characteristics of a telecytology consultation service.

Although numerous reports describe the application of remote video microscopy to pathologic diagnosis (telepathology), only a few address some of the special issues surrounding remote cytologic diagnosis (telecytology). These studies have generally suggested a high correlation between telecytologic diagnoses and those arising from direct examination of the glass slides, but factors affecting the clinical utility of routine cytologic diagnosis have not been examined. In this report, we describe our experience in telecytologic consultation on 99 cases seen at the Armed Forces Institute of Pathology between October 1995 and November 1999. The mean time between receipt of the telecytologic images and the contributor receipt of the faxed report was 9.9 hours (median, 5.13 hours). Using stringent criteria for agreement, we find fair to good (48%) concordance between the contributor's impression and the consultant's opinion. The concordance between the consultant's telecytologic diagnosis and the subsequent glass slide diagnosis is imperfect; in 8 (31%) of 26 cases in which the glass slide was sent after the telecytology consultation, a minor discrepancy between these diagnoses was found. No major discrepancies were found between the consultant's telecytologic and glass slide diagnoses.

Significance of the tuberculin test in the elderly.

Nine hundred thirty-three persons over 65 years of age, residing in long-term or extended-care facilities in Vancouver, Canada, had tuberculin tests. In addition to PPD-tuberculin, 5 TU and 250 TU, we used PPD-Battey, Candida albicans, mumps, and Trichophyton antigens. Twenty-five percent reacted to 5 TU of tuberculin with reactions of 10 mm or more. There was a progressive, substantial loss of reactivity with advancing age. Reactions to PPD-Battey greater than to PPD-T 5 TU were infrequent, suggesting that atypical mycobacterial infections were uncommon and that positive reactions to PPD-T, 250 TU, were predominantly caused by infections with Mycobacterium tuberculosis. Based on the results of both 5 TU and 250 TU, the prevalence of tuberculous infection exceeded 60 percent. Waning of tuberculin sensitivity appears to be an integral part of the aging process. Testing with nonmycobacterial antigens used in this study shed no further light on the problem of anergy in the elderly, as the number of reactors was smaller than that obtained with PPD-tuberculin.

Microscopic evaluation of sputum specimens submitted for Mycobacterium tuberculosis culture.

Using microscopic screening criteria employed in the study of sputum in acute bacterial pneumonia, the authors evaluated 644 sputum samples from 347 patients submitted for mycobacterial bacterial culture. After microscopic examination, these specimens were processed using standard mycobacterial laboratory technics. Salivary specimens accounted for 67.1% of the samples evaluated, and yielded 13 of the total 42 Mycobacterium tuberculosis isolates, as well as 4 of the 21 smear-positive culture-positive specimens. Although specimens from the lower respiratory tract are preferred, specimens of a salivary nature should not be discarded by the Mycobacteriology Laboratory.

Repeat biopsy strategies for men with atypical diagnoses on initial prostate needle biopsy.

OBJECTIVES: To evaluate trends in prostate sampling and the efficacy of different sampling methods to detect prostate cancer in subsequent biopsies after an initial "atypical" biopsy. METHODS: We searched Dianon Systems from March 1994 to June 1996 for cases with an initial atypical diagnosis on biopsy and that had repeat biopsies. The files of Dianon and Johns Hopkins Hospital (JHH) were also analyzed for cases with an initial atypical diagnosis on sextant biopsy and for repeat sextant biopsies showing cancer. RESULTS: Of the 1 24 Dianon cases in which we knew the site (sextant, left, right) of the initial and subsequent biopsies, 56 cases (45.2%) were cancer on repeat biopsy; in cases with repeat sextant biopsies, cancer was detected 59.3% of the time. There were 54 cases in which the initial biopsy was atypical and the repeat biopsy was cancer, where both sets of biopsies were sextants (44 Dianon, 10 JHH). Of the 46 cases with only one initial atypical site, the cancer was in the same sextant site as the previously atypical biopsy in 47.8% of cases; cancer was detected in 84.8% of the cases in either the same sextant, adjacent ipsilateral, or adjacent contralateral sites. CONCLUSIONS: Great variation exists in how urologists sample prostates both initially and after an atypical diagnosis. Of the 149 Dianon cases, only 32 were sextant to sextant biopsies, and another 32 were consistently left and right to left and right. Our study shows that in subsequent biopsies after an atypical biopsy, the chance of detecting cancer greatly increases with biopsy not only of the atypical site, but adjacent contralateral and adjacent ipsilateral areas as well. We advocate the precise labeling of the initial biopsies so that rebiopsy of atypical cases can be directed in a more concentrated fashion into the region of the initial atypical biopsy. Other sites should be biopsied as well, which urologists did not always do, because cancer may also be found away from the initial atypical site.

Glutathione (GSH) and the toxicity of oxidised low-density lipoprotein to human monocyte-macrophages.

Macrophage death, believed to be an important event in the pathogenesis of human atherosclerosis, can be induced by oxidised low-density lipoprotein (LDL) in vitro. Supplementation of the culture medium with 5 mM GSH significantly protected human monocyte-macrophages in vitro against the toxicity of copper-oxidised LDL. Oxidation products of LDL include the aldehyde 4-hydroxynonenal (HNE). We present evidence that conjugation of HNE by GSH contributes to this protection. In the absence of cells, HPLC analysis showed there were marked reductions in the levels of both pure HNE and HNE in copper-oxidised LDL in the presence of GSH. However, GSH did not reverse protein modification, as judged by agarose gel electrophoresis, nor did it influence the depletion of polyunsaturated fatty acids, which were assessed using gas chromatography. The possible implications for human atherosclerosis are discussed.