Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

Pain after use of the central third of the patellar tendon for cruciate ligament reconstruction: 33 patients followed 2-3 years

We performed reconstruction of the anterior cruciate ligament in 33 patients using the central third of the patellar tendon. In 20 patients we did an arthroscopies! ly-assisted procedure, while 13 patients had an additional mini-arthrotomy through the gap in the patellar tendon. After 2-3 years the subjective knee function, according to the Lysholm score, was excellent or good in 18 knees and fair or poor in 15 knees, mainly due to anterior knee pain. Although 18 patients complained about anterior knee pain, only 1 patient required further surgery. After the operatio the patella had a lower position. A flexion contractur was found in 7 patients, and 13 had heterotopic bon formation at the apex of the patella. Although stabilit was restored in 31 of the 33 reconstructed knees anterior knee pain was a frequent complicatior There were no correlations between the anterior kne pain and patellar height, flexion contracture or hetei otopic bone formation.     

Function and structure of pressurized and perfused porcine carotid arteries: effects of in vitro balloon angioplasty

In this report we describe the application of an in vitro pressure-perfusion system for study of functional/structural changes after in vitro balloon dilation injury. Pig carotid arteries were perfused at P = 100 mm Hg and Q = 100 ml/min, balloon angioplastied (BA), and cultured under these hemodynamic conditions for 4 or 8 days (n = 5 BA and 6 controls for each time point). To assess endothelial function, outer diameter changes in response to bradykinin (BK) were measured daily. Remodeling was determined from the shift in pressure-passive diameter relation, as obtained after papaverine addition. Arterial samples were processed for histology. Control arteries showed spontaneous tone, BK-induced relaxation, and inward remodeling that was more pronounced at day 8 (ratio end-to-start passive diameter at P = 100 mm Hg, 0.69 +/- 0.04; P < 0.001) than at day 4 (0.85 +/- 0.03, P = 0.03). Intimal hyperplasia was detectable in these control vessels at day 8 with accumulation of alpha-smooth muscle actin-positive cells around the lumen. Angioplasty caused ruptures and dissections and abolished tone that returned after 5 days of perfusion along with BK-dependent relaxation. No significant inward remodeling or intimal hyperplasia was observed at day 8 after angioplasty. Thus, BA inhibits remodeling, which occurs after in vitro perfusion of conductance arteries.     

Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.     

Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere.     

In vivo and in vitro IgE isotype switching in human B lymphocytes: Evidence for a predominantly direct IgM to IgE class switch program

Molecular analysis of circular excision products and composite genomic switch regions has demonstrated that in mice, immunoglobulin (Ig) isotype switching from IgM to IgE often proceeds sequentially via IgG1. Based on analysis of Ig production in cell cultures, it has been suggested that human B cells may switch to IgE via IgG4, whereas limited molecular data from in vitro switched B cells suggest a direct IgM to IgE switch program. To obtain a quantitative assessment of direct versus sequential IgE switching in humans, we have analyzed the nucleotide sequences of 29 composite Sμ/S? switch regions from freshly isolated human B lymphocytes from patients with atopic dermatitis and from B lymphocytes induced to switch to IgE synthesis in vitro. The data show that in these B cells IgE isotype switching progressed directly from IgM to IgE. We conclude that, in contrast to the murine IgM/IgE switch program, the IgM to IgE switch in B lymphocytes from patients with atopic dermatitis as well as in vitro stimulated B cells from healthy donors preferentially proceeds via direct Sμ to S? switch recombination.     

Expression of Tn and sialyl-Tn antigens in tumor tissues of the ovary.

The expression of sialyl-Tn and Tn antigens in various benign, borderline, and malignant ovarian tumors was examined immunohistochemically using newly developed antibodies specific for sialyl-Tn and Tn antigens. Sialyl-Tn antigen was detected in only one benign tumor, a mucinous adenoma that showed faint cytoplasmic staining in a few cells. However, sialyl-Tn was present in 5 of 12 serous borderline tumors, 10 of 19 mucinous borderline tumors, 10 of 13 serous adenocarcinomas, 15 of 16 mucinous adenocarcinomas, 14 of 15 endometrioid adenocarcinomas, and 7 of 7 clear cell carcinomas of the ovary. The antigen expression was observed throughout the cytoplasm of cancer cells and in the apical cytoplasm and luminal contents of some glands. The incidence and intensity of staining for sialyl-Tn antigen were higher in malignant tumors than in borderline tumors, but these results did not correlate with the histologic classification or differentiation. Coexpression of sialyl-Tn antigen and Tn antigen was observed in two serous adenocarcinomas, six mucinous borderline tumors, five mucinous adenocarcinomas, eight endometrioid, and seven clear cell carcinomas. In no case was Tn antigen expressed without concomitant sialyl-Tn antigen expression. Accumulation of sialyl-Tn antigen seems to be an early event of carcinogenesis of the ovary.     

Neuropsychological evaluation in transient ischaemic attack and minor stroke

Summary Two groups of patients with transient ischaemic attack and minor stroke without detectable haemodynamic stenotic lesions were evaluated by neuropsychological tests and compared with a control group. The mean values of the scores adjusted for age and educational background demonstrated that (a) the patients with transient ischaemic attack did not have a worse performance than normal subjects in any of the tests, (b) the patients with minor stroke had a worse performance than normals, particularly in Rey's figure-copying test (P<0.025), and (c) the latter test was not affected by educational background or age of the subjects. The results are discussed with reference to other case series, and the importance of age and cerebral damage in causing intellectual impairment evaluated by neurophysiological tests is stressed.