Multisite reproducibility of colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates.

MICs of fluconazole and amphotericin B were determined independently for 100 coded yeast isolates by each of six laboratories to determine reproducibility of results by using a colorimetric oxidation-reduction-based broth microdilution test. In addition, each site tested five quality control isolates on at least four different occasions during the study. Results agreed within a three-dilution range (mode +/- 1 log2 dilution) for 96.2% of fluconazole tests and 92.7% of amphotericin B tests. Agreement among tests with the quality control isolates was 99.4% with fluconazole and 98.6% with amphotericin B. These results indicate that the colorimetric microdilution method is reproducible among laboratories.     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into ‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.     

Acridine orange--RNA histofluorescence of sarcomas and small round cell tumors of childhood.

Forty-nine pediatric malignant neoplasms were stained with acridine orange (AO) fluorochrome to qualitatively evaluate cytoplasmic RNA content. The application of AO as a supplementary stain in surgical pathologic diagnosis is based on the premise that specific neoplastic cell types characteristically and consistently contain few or many cytoplasmic ribosomes. Primitive tumors such as Ewing's sarcoma and primitive neuroectodermal tumors showed negative or low-intensity AO-RNA cytoplasmic staining. Differentiated sarcomas such as rhabdomyosarcomas and lymphomas exhibited moderate to strong AO-RNA cytoplasmic fluorescence. Acridine orange--RNA staining provides an easy, convenient, and inexpensive adjunct in the histopathologic differential diagnosis of sarcomas. It is particularly useful for distinguishing Ewing's sarcomas from other small round cell sarcomas of childhood.     

Excess thymidine induces folate sensitve fragile sites

Folate sensitive fragile sites on human chromosomes have been found to be inducible in cultured lymphocytes by high levels of thymidine but not by high levels of BrdU. The biochemical interpretation of events leading to fragile site expression has been revised since it is now clear that low levels of either thymidylate or deoxycytidine triphosphate will result in this phenomenon. A model for the DNA at a fragile site, composed of alternating repeating polypurine/polypyrimidine sequences is proposed.     

FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos.

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs.     

Sex determination and the maternal dominance hypothesis

The maternal dominance hypothesis has been derived from workwith humans which shows that women who are more dominant thanother women are more likely to conceive sons. In both animalsand humans dominance is a characteristic or personality trait,underpinned by testosterone and responsive to a range of environmentalchanges: physical, social and psychological. Studies of thesex ratio in the social sciences and animal behaviour eithersupport or are compatible with the idea that the sex-determiningrole of X- and Y-chromosome bearing spermatozoa may be precededby factors under maternal control which provide for differentialaccess of spermatozoa. Findings in reproductive physiology andphysiological psychology suggest that folh'cular testosteroneor a related hormone may play a critical role. Reproductivephysiologists have already identified maternal mechanisms whichcould provide the context for such a model.     

Analytical fan-beam and cone-beam reconstruction algorithms with uniform attenuation correction for SPECT

In this paper, we developed an analytical fan-beam reconstruction algorithm that compensates for uniform attenuation in SPECT. The new fan-beam algorithm is in the form of backprojection first, then filtering, and is mathematically exact. The algorithm is based on three components. The first one is the established generalized central-slice theorem, which relates the 1D Fourier transform of a set of arbitrary data and the 2D Fourier transform of the backprojected image. The second one is the fact that the backprojection of the fan-beam measurements is identical to the backprojection of the parallel measurements of the same object with the same attenuator. The third one is the stable analytical reconstruction algorithm for uniformly attenuated Radon data, developed by Metz and Pan. The fan-beam algorithm is then extended into a cone-beam reconstruction algorithm, where the orbit of the focal point of the cone-beam imaging geometry is a circle. This orbit geometry does not satisfy Tuy's condition and the obtained cone-beam algorithm is an approximation. In the cone-beam algorithm, the cone-beam data are first backprojected into the 3D image volume; then a slice-by-slice filtering is performed. This slice-by-slice filtering procedure is identical to that of the fan-beam algorithm. Both the fan-beam and cone-beam algorithms are efficient, and computer simulations are presented. The new cone-beam algorithm is compared with Bronnikov's cone-beam algorithm, and it is shown to have better performance with noisy projections.