Nucleolar organizer regions in transitional cell tumors of the bladder

The traditional silver staining technique that identifies nucleolar organizer region-associated proteins has recently been adapted and applied to paraffin sections, and used to examine changes in nucleolar organizer region numbers in a variety of benign and malignant conditions. We describe herein the enumeration of nucleolar organizer regions in a variety of benign and malignant conditions of the transitional epithelium of the urinary bladder. While there is a statistical separation between normal and neoplastic groups, there is a degree of overlap between normal, inflammatory, dysplastic, and neoplastic urothelium.     

No evidence for chromosomal mosaicism in multiple tissues of 10 patients with 45 XO Turner syndrome

Why the frequency of spontaneous abortions among monosomy X conceptuses is 98 % while the postnatal course of Turner syndrome is relatively benign has not been understood. One explanation could be that mosaicism for a euploid cell line confers viability and that those 2 % of 45, XO zygotes surviving in utero have some degree of mosaicism. We thus reasoned that if the non-mosaic 45, XO karyotype is lethal, a thorough study of living Turner syndrome patients might reveal a much higher frequency of mosaicism than the 30–40 % reported. Ten adult women with a 45 , XO leukocyte karyotype were investigated, looking at five tissue types from all three germ layers: buccal mucosa and hair from ectoderm, urinary epithelium from endoderm and ectoderm, and lymphocytes and skin fibroblasts from mesoderm. We were unable to confirm mosaicism in these patients, although in 2 out of 10 there was the suggestion of a small percentage of euploid cells in skin and blood karyotypes.     

Does hope predict adjustment to end‐stage renal failure and consequent dialysis?

Objectives Hope is important in determining positive outcomes in a range of chronic illnesses. This study examined the role of hope in adjustment to end‐stage renal failure (ESRF) and consequent dialysis. Design A cross‐sectional design examined the ability of hope to predict adjustment to ESRF over and above other relevant variables. Methods Individuals receiving dialysis at 4 units in the North‐West UK were invited to take part in the study. 103 questionnaire packs were included in the analysis. Multiple regression equations determined whether hope was able to predict significant variance in adjustment over and above that accounted for by other factors (demographic and illness‐related factors, perceived control, and social support). Measures of anxiety, depression, and quality of life constituted a multidimensional measure of adjustment to ESRF. Results Each of the regression models was significant. Hope emerged as an independent significant predictor in five of the multiple regressions: anxiety; depression; effects and symptoms of kidney disease; and mental health quality of life. Age also emerged as an important predictor of outcome. Conclusions It appears that hope is a significant predictor of adjustment to ESRF. Clinical implications of this research are discussed, along with suggestions for future research.     

Exercise improves biomarkers of health and stress in animals fed ad libitum

Voluntary and forced exercise decrease morbidity and mortality in laboratory animals. Caloric restriction has similar effects on health and unique benefits on life span. Nonetheless, in most experiments, animals do not have access to physical activity and are fed ad libitum (AL). We hypothesized that with regular access to either unlimited running wheel exercise (EX) or limited physical activity (PA), key biomarkers of health would be enhanced enough to counter some consequences of a sedentary AL lifestyle. This 16-month study compared body weight, tumor number and size, tissue lesions, oxidative stress, and reactive stress in (1) sedentary animals with no access to physical activity (SED); (2) animals with access to hour-long, twice weekly activity in a large box (PA); and (3) animals with access every other day to a running wheel (EX). At the end of the study, EX body weight was 8-9% lower than PA and SED. In addition, EX had no kidney lesions versus 50% in PA and SED, and had smaller tumor size (10+/-2 vs. 14+/-4 and 30+/-4 mm). Exhaustive exercise lowered glutathione/oxidized glutathione ratio in EX and PA, but in SED, the ratio was depressed even in resting animals. In all treatments, prolactin (PRL) levels were lower in resting animals than in acutely exercised animals. In conclusion, EX had the most favorable health biomarkers while SED had the least. PA did not confer gross health benefits different than the SED group, but was biochemically more similar to EX animals.     

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.     

Tissue fixation effects on immunohistochemical staining of caspase-3 in brain tissue.

Fixation methods for tissue often vary amongst clinical and research laboratories. To evaluate the effects of fixation method on studies of brain tissue, we examined immunohistochemical outcomes amongst 2 fixatives, 4 caspase-3 antibodies, and 2 species (human infants and piglets). Fixatives were 10% neutral buffered formalin (NBF) or 10% NBF and glacial acetic acid (FAA). Antibodies for caspase-3 were commercially obtained and included 2 for active caspase-3, and 2 for procaspase-3 (CASP3 and CPP32). Immunohistochemical staining of caspase-3 varied with fixation method, with the greatest effect of fixation method observed for the active caspase-3 antibodies and this effect was present in both species. In NBF-fixed tissue, active caspase-3 immunoreactivity was only visible microscopically, and was specific to neuronal cell bodies. In FAA-fixed tissue, active caspase-3 immunoreactivity was visible macroscopically, and predominantly present in fiber tracts and fasciculi compared with neuronal bodies. Fixation and species differences were also identified for the procaspase-3 antibodies, CASP3 and CPP32, where FAA-fixed pig tissue showed abundant staining of blood vessels that were not observed in the NBF-fixed pig tissue or in the human tissue. This study characterizes differences in immunohistochemical outcomes using commercially available antibodies for caspase-3, according to tissue fixation method and species.     

Confidentiality and medical records

Protecting confidential information disclosed to doctors has been one of the most important ethical traditions of the medical profession. However, the patient's right to such confidentiality is threatened because it is legally unclear how far ownership by Government of the paper on which NHS records are kept or of the computer system in which they are stored confers right of access.

We hope the medical profession will examine this problem urgently and offer some suggestions as to how patients' confidences can continue to be protected in the future.

     

Detection of somatic mutations in man: evaluation of the microtitre cloning assay for T-lymphocytes

A method of detecting 6-thioguanine-resistant lymphocytes bythe cloning of T-lymphocytes in microtitre wells is evaluatedfor its usefulness in population monitoring. Factors shown toaffect the cloning efficiency of lymphocytes include the strainand irradiation level of the lymphoblastoid feeder cells andthe use of a pre-incubation period in bulk culture without mitogenicstimulus before plating at limiting dilutions. Cord blood sampleshave markedly lower mutant frequencies than adult blood samples.The adult range was 8.0 x 10^–7 to 1.8 x 10^–5. Sevenmales and seven females aged between 23 and 47 years were sampled.No effect of sex or age was found. Individual samples whichwere divided at collection and treated separately did not varyfrom each other, but repeat samples taken at different timesshowd up to a 2-fold variation. The application of this methodin population monitoring is discussed.     

Pathologic study and clinical significance of Hürthle cell papillary thyroid carcinoma.

Hürthle cell papillary thyroid carcinoma is a variant of papillary thyroid carcinoma (PTC). Its pathologic and clinical significance has not been well documented. The authors studied the relative incidence of Hürthle cell PTC and the relationship of Hürthle cell PTC to other variants of thyroid carcinoma. Three hundred eighty consecutive cases of thyroid carcinoma were reviewed to identify cases with focal or extensive areas of Hürthle cell PTC, classic PTC, Hürthle cell carcinoma (ie, non-Hürthle cell PTC), and follicular carcinoma. In addition, the status of lymphoid infiltrate in the tumor, stromal invasion with desmoplastic reaction, vascular invasion, and distant and lymph node metastasis were noted by microscopic examination, review of clinical charts, or both. A total of 24 (HCs) and 42 PTCs with Hürthle cells were identified. The latter category was divided into pure Hürthle cell PTC or extensive Hürthle cell (HPTC) (28 cases) and PTC or Hürthle cell carcinoma with focal areas of Hürthle cell PTC (14 cases). The Hürthle cell PTC/Hürthle cell carcinoma ratio was lower than that of PTC/follicular carcinoma (39:289) (P = 0.001). Follicular or solid structures were present in all HPTCs. HPTCs were associated with frequent stromal intrathyroid and extrathyroid invasion, but they tended to have a lower rate of lymph node metastasis (8/28) compared with classic PTC with stromal invasion (108:200) (P = 0.12) and a lower rate of distant metastasis (2:28) compared with Hürthle cell carcinoma (15:24) (P = 0.02) or follicular carcinoma (13:39) (P = 0.04). Warthin-like Hürthle cell PTC (10 cases) was associated with extrathyroid invasion in five cases. In Hürthle cell PTC associated with tall cell variant (10 cases), areas of gradual transition between Hürthle cell PTC and tall cell variant were identified. The latter variant showed the highest rate of extrathyroid stromal and vascular invasion with distant metastasis and patient death compared with all Hürthle cell PTCs and classic PTCs. In conclusion, Hürthle cell PTC is frequently associated with tall cell variant. It has a higher potential for extrathyroid invasion than classic PTC and has vascular invasion and distant metastasis characteristics intermediate between those of classic PTC and Hürthle cell carcinoma with or follicular carcinoma. Hürthle cell PTC tends to show a greater likelihood of extrathyroid invasion when associated with Warthin-like features and tall cell variant PTC, and higher vascular invasion and distant metastasis when associated with tall cell variant.