Analysis of peripheral blood lymphocyte Giemsa-banded karyotypes was performed on 163 family members from 13 melanoma-prone families. Patients were classified regarding the presence of cutaneous ...melanoma and dysplastic nevi (a well characterized melanoma precursor), and each karyotype was scored for the number of cells containing the following: major structural, minor structural, and numerical abnormalities. No clonal cytogenetic abnormalities were observed. Cutaneous malignant melanoma and dysplastic nevi syndrome patients each had increased abnormalities of all types combined, compared with pooled controls (i.e., normal family members, and spouses; respectively, chi 2 = 6.02, p = 0.01; chi 2 = 5.29, p = 0.02). There was a statistically significant p-value for major structural abnormalities for melanoma patients and numerical abnormalities for the dysplastic nevi patients. Minor structural abnormalities did not differ in any of the groups. In addition, studies of ultraviolet induced sister chromatid exchange, in vitro tetraploidy, and extended prophase banding were performed on a limited number of patients. No significant differences between cases and controls were observed in these tests. Our data suggest that a chromosome instability abnormality may contribute to the pathogenesis of hereditary melanoma.
This was an exploratory study to test two hypotheses related to potential epithelial precursors to ovarian cancer: (a) histologically normal ovarian surface epithelium exhibited changes in the ...nuclear chromatin pattern, which indicate an ovarian abnormality, and (b) such changes were detectable in the ovarian surface epithelium of cancer-free subjects who were at high risk for ovarian cancer.
Ovaries were carefully collected to avoid damage to the surface epithelium. Five-micron-thick histologic sections were cut and stained with H&E. High-resolution images were recorded from the ovarian surface epithelium and from the underlying stroma of ovaries from normal women (10 cases), women at high risk of developing ovarian cancer (7 cases), and histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric features and measurements of nuclear abnormality were computed for 3,390 epithelial nuclei. Discriminant function analyses and unsupervised learning algorithms were employed to define deviations from normal and to identify the subpopulations of nuclei exhibiting these changes.
Epithelium from ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern consistent with a second phenotype, which were not visually detected with histopathologic surveillance. This phenotype was also present in the ovaries obtained from women at increased risk of ovarian cancer, suggesting that it may represent a premalignant abnormality. These changes were statistically significant.
The observed changes in karyometric features were sufficiently distinct to warrant further study as both diagnostic and prognostic biomarkers for early detection and prevention of ovarian cancer.
Batten disease or JNCL, is the juvenile form of Neuronal Ceroid Lipofuscinosis (NCL) an autosomal recessive neurodegenerative disorder. Since retinal degeneration is an early consequence of Batten ...disease, we examined the eyes of Cln3 knockout mice (1–20 months of age), along with heterozygotes and appropriate controls, to determine whether or not the Cln3 defect would lead to characteristic retinal degeneration and visual loss. Accumulation of autofluorescent material and intracellular inclusions were markedly increased in Cln3 knockout retinal ganglion cells, as well as most other nuclear layers. Nerve fiber density was also significantly decreased in Cln3 knockout retinae. Apoptosis was observed in the photoreceptor layer of Cln3 knockout. However, the degree of retinal degeneration up to age 20 months was not extensive. Fundus examinations of Cln3 knockout mice showed no significant abnormalities, while electroretinograms remained robust through 11 months of age. In summary, it appears that accumulation of autofluorescent material, carbohydrate storage material, as well as apoptotic cell death are retinal manifestations of the Cln3 defect that do not appear to extinguish retinal function in this mouse model of Batten disease.
Emerging evidence suggests that atrial fibrillation is not a benign arrhythmia. It is associated with increased risk of death. The magnitude of association is controversial and potential causes ...remain unknown. Patients in the registry of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial form the basis for this report. Baseline variables, in particular the presence or absence of a history of atrial fibrillation/flutter, were examined in relation to survival. Multivariate Cox regression was used to adjust for differences in important baseline co-variables using 27 pre-selected variables. There were 3762 subjects who were followed for an average of 773+/-420 days; 1459 (39 %) qualified with ventricular fibrillation and 2303 (61 %) with ventricular tachycardia. A history of atrial fibrillation/flutter was present in 24.4 percent. There were many differences in baseline variables between those with and those without a history of atrial fibrillation/flutter. After adjustment for baseline differences, a history of atrial fibrillation/flutter remained a significant independent predictor of mortality, (relative risk=1.20; 95 % confidence intervals=1.03-1.40; p=0.020). Antiarrhythmic drug use, other than amiodarone or sotalol, was also a significant independent predictor of mortality (relative risk 1.34; 95 % confidence intervals 1.07-1.69, p=0.011. Atrial fibrillation/flutter is a significant independent risk factor for increased mortality in patients presenting with ventricular tachyarrhythmias. This risk may have been overestimated in previous studies that could not adjust for the proarrhythmic effects of antiarrhythmic drugs other than amiodarone or sotalol.
A collagen‐like protein was identified from the otoliths of the chum salmon, Oncorhynchus keta. The otolith, composed mainly of calcium carbonate with small amount of organic matrices, is formed in ...the inner ear and serves as a part of the hearing and balance systems. Although the organic matrices may play important roles in the growth of otolith, little is known about their chemical nature and physiological function. In this study, a major organic component of the otolith, designated otolin‐1, which may serve as a template for calcification, was purified. The sequences of two tryptic peptides from otolin‐1 revealed high homology with parts of a saccular collagen which had been described previously Davis, J.G., Oberholtzer, J.C., Burns, F.R. & Greene, M.I. (1995) Science267, 1031–1034. Cloning of a cDNA coding for otolin‐1 revealed that the deduced amino‐acid sequence contained a collagenous domain in the central part of the protein. Although collagen is the most abundant structural protein in the animal body, otolin‐1 mRNA was expressed specifically in the sacculus. Immunohistochemical studies showed that otolin‐1 is synthesized in the transitional epithelium and transferred to the otolith and otolithic membrane. This is the first report concerning characterization of a structural protein containing many tandem repeats of the sequence, Gly‐Xaa‐Yaa, typical for collagen from the biomineral composed of calcium carbonate.
In June 1982, sexual and other behavioral patterns were examined in 245 homosexual men in relationship to T-lymphocyte phenotypes that are characteristic of the acquired immunodeficiency syndrome ...(AIDS). Mean helper T-cell counts in New York City (579 +/- 32 cells/mm3) and Washington, DC, homosexual men with sexual contacts in areas at high risk (endemic) for AIDS (567 +/- 24 cells/mm3) were significantly lower than in Washington, DC, residents without such contacts (672 +/- 36 cells/mm3, p = 0.04 by analysis of variance). Helper T-cell counts in the Washington men were inversely correlated with a greater number of endemic-area homosexual contacts (p = 0.005), even after adjustment for multiple confounding variables (p = 0.02). The 31 Washington men with more than 15 endemic-area partners had a mean helper T-cell count of 517 +/- 44 cells/mm3, and 12 of those 31 men had helper T-cell counts less than 400 cells/mm3. AIDS patients are known to have a marked reduction in the number and function of helper T-lymphocytes. The data suggest that deficits of helper T lymphocytes can be acquired by homosexual contact with men in cities where AIDS is common. This supports the hypotheses that low helper T-cell counts may be caused by a sexually transmissible agent and that frequent homosexual exposure to residents of high-risk areas for AIDS may be an important means of spread of this agent.
Situated in an océeanographic transition zone, the Gulf of Maine/Western Scotian Shelf (GOM/WSS) region of the Northwest Atlantic is especially susceptible to changes in the climate system. Recent ...studies have shown that a coupled slope water system (CSWS) operates in the Northwest Atlantic and responds in a similar manner to climatic forcing over a broad range of time scales. These studies further suggest that it may be possible to associate different modes of the CSWS with different phases of the North Atlantic Oscillation (NAO). Results from recent GLOBEC field studies in the Northwest Atlantic provide strong evidence linking physical responses of the CSWS to basin-scale forcing associated with the NAO. By placing these results in the context of time-series data collected from the GOM/WSS region over the past half century, we show that: (i) the region's shelf ecosystems respond both physically and biologically to modal shifts in the CSWS; (ii) the CSWS mediates the effects on these ecosystems of basin-scale climatic forcing associated with the NAO; and (iii) certain planktonic species can be good indicators of the CSWS's modal state on interannual to interdecadal time scales.
Studies of NF-kappa B suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T ...cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-kappa B, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd polypeptide and its regulatory subunits I kappa B and p65. All four members of this kappa B-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR. These findings suggest a Rel-related family of kappa B enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is linked to its inhibitory action on cellular genes under NF-kappa B control.
A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels. The results are obtained ...from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is m_{H}=125.09±0.21 (stat)±0.11 (syst) GeV.
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