A comparative study on potential cytogenetic fingerprints for radiation LET in human lymphocytes

PURPOSE: To carry out a comparative study on potential cytogenetic fingerprints for radiation LET in human metaphase lymphocytes. MATERIALS AND METHOD: Human lymphocytes were irradiated in vitro with 3.0 Gy 60Co gamma-rays, 0.9 Gy 3H beta-rays or 0.2 Gy 2.7 Mev neutrons. Detailed chromosome aberrations were analysed by combined FISH with pan-telomere staining and specific whole-chromosome painting (1, 2 and 4). Total chromosome translocations and insertions were also analysed by multicolour whole-chromosome painting (chromosomes 1, 2 and 4 orange, chromosomes 3, 5 and 6 green). RESULTS: Among the six proposed radiation cytogenetic fingerprints, the ratio of total simple translocations to insertions (I-ratio), showed the largest difference between low-LET 60Co gamma-ray and high-LET neutron radiation. The ratios of complete exchanges to incomplete rejoinings [S(I)-ratio] and dicentrics to interstitial deletions (H-ratio), showed a similar significant difference between low- and high-LET radiation. The ratios of centric rings to interstitial deletion (G-ratio) showed a trend of LET-related difference, but the difference was not significant in this data set. The ratios of dicentrics to centric rings (F-ratio) and apparent complete exchanges to hidden complete exchanges [S(II)-ratio], showed no difference between low- and high-LET radiation. In the 1426 radiation-induced chromosome aberrations observed after 52 h culture, evidence for sister-chromatid fusion but not telomere addition was found. CONCLUSION: Pan-telomere staining plus specific whole chromosome painting allows simultaneous and objective detection of complete or incomplete chromosome exchanges and interstitial or terminal deletions in human peripheral lymphocytes. Of the six proposed cytogenetic ratios, the I-ratio is the most effective cytogenetic fingerprint for distinguishing low-LET from high-LET radiation in human metaphase human lymphocytes.     

A new look at reaction time in schizophrenia

Schizophrenia patients demonstrate impaired manual reaction time (RT), but not saccadic RT, when given traditional tasks. To determine whether the manual RT time impairment could be eliminated by providing imperative stimuli to the finger (thus providing stimulus-response compatibility), we tested 28 chronic schizophrenic patients on finger-lift RT to visual (VIS), tactile plus visual (TAC+VIS), and auditory plus tactile plus visual (AUD+TAC+VIS) stimuli. The patients (a) were significantly slower than controls (n=28) in all three tasks, (b) showed bimodality, with 43% of patients having means and variances nearly identical to control values, and (c) had RTs significantly closer to control values in the TAC+VIS and AUD+TAC+VIS tasks than in the VIS task. The inability to normalize finger-lift RT in schizophrenia represents a genuine slowing of this response system regardless of stimulus-response compatibility. We consider other possible explanations for the differences between manual and saccadic RT, including the notion that excess processing capacity for saccadic RT may be masking possible deficits in that system.     

Cortical Atrophy Predicts Visual Performance in Long-Term Central Retinal Disease; GCL,pRNFL and Cortical Thickness Are Key Biomarkers

PurposeThe aim of this study was to assess both retinal and cortical structure in a cohort of patients with long-term acquired central retinal disease in order to identify potential disease biomarkers and to explore the relationship between the anterior and posterior visual pathways.MethodsFourteen participants diagnosed with long-term central retinal disease underwent structural assessments of the retina using spectral-domain optical coherence tomography, including macular ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Structural magnetic resonance imaging was used to measure visual cortex, including cortical volume of the entire occipital lobe and cortical thickness of the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively.ResultsMean thickness was significantly reduced in both the macular GCL and the inferior temporal pRNFL across patients. Cortical thickness was significantly reduced in both the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Disease duration significantly correlated with GCL thickness with a large effect size, whereas a medium effect size suggests the possibility that cortical thickness in the occipital pole may correlate with visual acuity.ConclusionsLong-term central retinal disease is associated with significant structural changes to both the retina and the brain. Exploratory analysis suggests that monitoring GCL thickness may be a sensitive biomarker of disease progression and reductions in visual cortical thickness may be associated with reduced visual acuity. Although this study is limited by its heterogeneous population, larger cohort studies would be needed to better establish some of the relationships detected between disease dependent structural properties of the anterior and posterior visual pathway given the effect sizes reported in our exploratory analysis.     

Paget''s disease of the vulva and urogenital malignancies: A case report and review of the literature

The vulva is one of the extramammary sites which has a potential for developing Paget's Disease with which an underlying sweat gland carcinoma or breast carcinoma is frequently associated. Urogenital malignancy may be a third contender. Such a case managed by the authors herein reported and a review of the literature about such lesions support this assumption.     

Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.     

Cell Surface Antigens Detected on Mature and Leukemic Granulocytic Populations by Cytotoxicity Testing

Using a microcytotoxicity assay, the serological reactivity of human granulocytes, namely neutrophils and eosinophils, and chronic myeloid leukemia (CML) cells and cultured CML cell lines (K562, NALM-1) were examined. Mature granulocyte forms and cord granulocytes are readily lysed by specific granulocyte cytotoxins that do not react with random T and B lymphocytes, monocytes, red blood cells, or platelets. Furthermore, certain antisera were preferentially cytotoxic for eosinophil-enriched populations. Granulocytotoxin detected antigens on one of three CML blast cell populations tested and K562, but failed to react with NALM-1. By cytotoxicity, mature granulocytes were poor targets for B2-microglobulin and the appropriate HLA antisera although both sera types are absorbed with granulocytes. Furthermore, granulocytes did not possess B-lymphocytes (Ia-like) or blood group A, B, and Rh (D) antigens. Except for K562, both HLA and heterologous B-lymphocyte antisera were cytotoxic for the CML blast cell populations tested.     

Intranigral muscimol attenuates electrographic signs of seizure activity induced by intravenous bicuculline in rats

Rats were implanted with infusion cannulas in the substantia nigra (SN), and intracranial electrodes for recording the electroencephalogram (EEG). These rats received intravenous injections of bicuculline, producing repetitive high voltage spike-and-wave complexes. Pretreatment with bilateral intranigral infusions of the GABA agonist muscimol reduced the duration of EEG epileptic activity by over 80%, as compared to the effect of pretreatment with intranigral saline in the same rats. This antiepileptic effect of intranigral muscimol may reflect a primary influence of SN outputs on brain excitability.     

Anticonvulsant action of 2-amino-7-phosphonoheptanoic acid and muscimol in the deep prepiriform cortex

Microinjection of 2-amino-phosphonoheptanoic acid (2APH, 1 nmol), and antagonist for n-methyl-d-aspartate-sensitive receptors, into the deep prepiriform cortex (DPC) of the rat, prevented seizures induced by the intravenous administration of bicuculline. The GABA agonist, muscimol (39 pmol), injected into DPC produced a similar anticonvulsant effect. The DPC may therefore represent an important site of action for the anticonvulsant effects of GABA agonists and excitatory amino acid antagonists. Moreover, our data support the hypothesis that seizures induced by a deficiency in GABA transmission result, at least in part, from a relative overactivity of excitatory amino acid transmission in the DPC.