The nucleotide: DNA sequencing and its clinical application.

Information determining cellular structure and function is contained in chromosomal DNA. Genes, regions of DNA encoding this information, are composed of specific sequences of nucleotides. DNA sequencing methods have been developed to identify these sequences. Even subtle alteration (or mutation) of these sequences can lead to many human syndromes and diseases. This article reviews 1) the structure of the nucleotide, 2) the methods of DNA sequencing, and 3) its recent clinical application in analysis of the nevoid basal cell carcinoma syndrome.     

Morphometric analysis, ploidy and response to chemotherapy in squamous carcinomas of the head and neck

The histopathology of 54 squamous carcinomas of the head and neck was evaluated by qualitative grading and morphometry in order to identify those features which predicted a good response to cisplatinum chemotherapy. The histopathology of 66 cases was correlated with tumour ploidy, determined by flow cytometry of paraffin-embedded material, since a separate study has shown that aneuploid carcinomas respond better to chemotherapy. The degree of differentiation was a poor predictor of ploidy, although diploid carcinomas did show more keratin and less nuclear pleomorphism than aneuploid carcinomas. The prominence of nucleoli in tumour cells and the surface area to volume (s/v) ratio of the tumour islands were the variables most strongly correlated with ploidy, with diploid carcinomas having prominent nucleoli and a low s/v ratio. A good response to chemotherapy was related partly to the architecture of the carcinoma (pushing border and low s/v ratio), and partly to the tumour cells (well differentiated) and the percentage of necrotic tumour. A lack of inflammatory reaction or desmoplasia was associated with a poor response. The results indicate that both subjective and objective histopathological criteria may be used to predict ploidy and the response to cisplatinum chemotherapy of squamous carcinoma of the head and neck. A combination of s/v ratio and the percentage of necrotic tumour can be used to identify a group of patients with a relatively good survival.     

Reactive arthritis of the temporomandibular joints and cervical spine in a child

Background  

Temporomandibular joint (TMJ) arthritis is frequently seen in children with chronic arthritis. It has rarely been described in a non-infectious acute setting. We report a case of reactive arthritis isolated to the TMJs and cervical spine.     

Renal vein renin analysis: Limitations of its use in predicting benefit from percutaneous angioplasty

Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated with clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p>0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA.     

Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice

To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a model of Down Syndrome (DS, trisomy 21), we assessed spatial working and reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater number of reference memory errors across trials compared to control mice. Both genotypes showed improvement across trials, although improvement was slower in Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on the RAM, and in contrast to control mice, did not improve across trials, always performing at near-chance levels. These results provide evidence for both spatial working and reference memory deficits in Ts65Dn mice, characteristics of cognitive dysfunction.     

The effects of photoperiod on olfactory c-fos expression in prairie voles,Microtus ochrogaster

Reproduction stops among the majority of prairie voles (Microtus ochrogaster) during the winter. Short day lengths suppress male reproductive function dramatically in the laboratory, but photoperiod exerts only subtle effects on female reproductive function. Thus, the regulation of seasonal breeding in this species remains partially unspecified. In contrast to commonly studied rodents, female prairie voles do not undergo spontaneous estrous cycles; rather, they are induced into estrus by exposure to chemosignals expressed in conspecific male urine. In the present study, the hypothesis was tested that seasonal breeding among female prairie voles in the field reflects photoperiod-mediated changes in the responsiveness of the chemosensory system to male urine. Responsiveness was assessed by localizing the product of the c-fos immediate early gene with an immunocytochemical procedure. Female prairie voles were maintained in either long (LD 16:8) or short (LD 8:16) photoperiods from birth until adulthood, and exposed to either male urine or skim milk. Immunocytochemistry forfos protein revealed an increased number of immunoreactive cells within the accessory olfactory system of female prairie voles, including the accessory olfactory bulbs, granule cell layer, as well as the medial and cortical divisions of the amygdala 1 h after exposure to a single drop of urine as compared to individuals exposed to skim milk. The number of immunoreactivefos cells induced in females by conspecific male urine was also affected by photoperiod; short day females displayed fewer immunoreactivefos neurons in the accessory olfactory system as compared to long-day animal. Taken together, these results indicate that similar mechanisms underlie the responses of different rodent species to the chemosignals of conspecifics and that the pattern offos expression observed in the present study has functional significance for the regulation of reproduction in prairie voles.     

Cancer mortality in a cohort of United Kingdom steel foundry workers: 1946-85

The mortality experienced by a cohort of 10,491 United Kingdom steel foundry workers during the period 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 10 participating foundries in 1946-65; all had worked in the industry for a minimum period of one year. Compared with the general population of England and Wales, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 77.4, O = 106, SMR = 137) and cancer of the lung (E = 229.2, O = 441, SMR = 147). A statistically significant deficit was found for cancer of the brain (E = 19.4, O = 10, SMR = 51). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, in "dust exposed" jobs, in "fume exposed" jobs, in foundry area jobs, in fettling shop jobs, and in foundry area or fettling shop jobs, of those dying from cancers of the stomach and lung with those of all matching survivors. The RMLT analyses provided evidence of an occupational involvement in the risk of death from lung cancer from work in the foundry area or fettling shop, and weaker evidence of an occupational involvement in the risk of death from stomach cancer from work in the foundry area.