Differential reactivity of the rat S100A4(p9Ka) gene to sodium bisulfite is associated with differential levels of the S100A4 (p9Ka) mRNA in rat mammary epithelial cells

Elevated intracellular levels of S100A4, an S100-related calcium-binding protein, induce metastatic capability in benign mammary tumor-derived epithelial cells and in transgenic mice bearing oncogene-induced benign mammary tumors. The S100A4(p9Ka) gene in rat mammary epithelial cells expressing low levels of S100A4 yields a reduced number of fragments upon digestion with the methylation-sensitive restriction enzyme, HpaII, compared with the gene from high S100A4-expressing cells. Genomic sequencing of two potential regulatory elements in the S100A4 gene, an intronic enhancer and TATA box region, revealed that in low S100A4-expressing cells, most cytosine bases exhibited high levels of resistance to conversion to thymine by sodium bisulfite. In derivative cell lines, which express high levels of S100A4, only a small number of cytosine bases were resistant to treatment with sodium bisulfite. In contrast, cytosine bases in the DNA surrounding an upstream regulatory region, which binds inhibitory GC factor in the low-expressing cell lines, are sensitive to conversion to thymine by sodium bisulfite in both low- and high-expressing cell lines. The results suggest that the rat S100A4 gene is maintained in a different state in the low-expressing cell lines and that this state might be a consequence of the pattern of methylation in this regulated gene that does not contain a CpG island.     

Intestinal tuberculosis

Since the symptoms and clinical presentation of intestinal tuberculosis is nonspecific, the diagnosis is frequently delayed and may be achieved at autopsy only. Intestinal tuberculosis is very rare in Denmark, but may now be seen more often because of increasing numbers of immigrants from countries of the third world with a high prevalence of tuberculosis. A case of intestinal tuberculosis in a 28 year old Somalian female is reported. Methods of diagnosing intestinal tuberculosis are commented, and the frequent necessity of starting medical treatment before a bacteriological diagnosis is reached is emphasized.     

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium

Estradiol-17beta (E2) acts through the estrogen receptor (ER) to regulate uterine growth and functional differentiation. To determine whether E2 elicits epithelial mitogenesis through epithelial ER versus indirectly via ER-positive stromal cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER-positive wild-type (wt) BALB/c mice were used to produce the following tissue recombinants containing ER in epithelium (E) and/or stroma (S), or lacking ER altogether: wt-S + wt-E, wt-S + ko-E, ko-S + ko-E, and ko-S + wt-E. Tissue recombinants were grown for 4 weeks as subrenal capsule grafts in intact female nude mice, then the hosts were treated with either E2 or oil a week after ovariectomy. Epithelial labeling index and ER expression were determined by [3H]thymidine autoradiography and immunohistochemistry, respectively. In tissue recombinants containing wt-S (wt-S + wt-E, wt-S + ko-E), E2 induced a similar large increase in epithelial labeling index compared with oil-treated controls in both types of tissue recombinants despite the absence of epithelial ER in wt-S + ko-E tissue recombinants. This proliferative effect was blocked by an ER antagonist, indicating it was mediated through ER. In contrast, in tissue recombinants prepared with ko-S (ko-S + ko-E and ko-S + wt-E), epithelial labeling index was low and not stimulated by E2 despite epithelial ER expression in ko-S + wt-E grafts. In conclusion, these data demonstrate that epithelial ER is neither necessary nor sufficient for E2-induced uterine epithelial proliferation. Instead, E2 induction of epithelial proliferation appears to be a paracrine event mediated by ER-positive stroma. These data in the uterus and similar studies in the prostate suggest that epithelial mitogenesis in both estrogen and androgen target organs are stromally mediated events.     

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. CONCLUSIONS: While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.     

A general phenomenological life model for insulating materialsunder combined stresses

In this paper, the general phenomenological life model proposed by the author for insulating materials with both a threshold or non-threshold behaviour, is applied to experimental data pertinent to two insulating materials for power cables. The first material, EPR, was found to be a non-threshold material for stresses close to or larger than the service stress, but extrapolation at low temperature seems to show a tendency toward a threshold. Application of the general model does appear very appropriate for this insulation and a good fit to the data has been found. The case of the second material, an old generation of XLPE, is different and the general model does not fit the data. However, an excellent fit is reached by introducing some improvements to the model, where possible and correct. Further complications seem necessary to conform this model to various practical cases, and make its application more difficult. For practical applications, such as selection of materials and/or design of apparatus, the use of properties and indices obtainable by means of long tests, such as those suggested and carried out by the author's research group, is simpler and more rapid. However, the usefulness of the model also consists in studying the various processes occurring during combined-stress aging of materials, all of which the model can take into account by simple mathematical expressions. This constitutes a significant advance in approaching the complex physical mechanisms involved in aging     

Report from the Maryland Epidemiology Schizophrenia Linkage Study: no evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model

Our collaborative group has undertaken a linkage study of schizophrenia, using a systematic sample of patients admitted to Maryland hospitals. An initial sample of 39 families, each having two or more affecteds, was available for genotyping candidate genes, candidate regions, and highly polymorphic markers randomly distributed throughout the genome. We used a single complex dominant model (with a disease gene frequency of 0.005 and age-dependent penetrance for affected phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85). We report here 130 markers, which met the exclusion criteria of LOD score < -2.00 at theta > 0.01 in at least 10 informative families, and no evidence for heterogeneity. We also report here markers that were tested as candidates for linkage to the schizophrenic phenotype. They were selected based on the following criteria: a) proximity to reported chromosomal rearrangements (both 5q and 11q), b) suggestions of linkage from other families (5q), or c) presence of a candidate gene (5q, 11q, 3q: Dopamine receptors 1, 2, and 3, respectively). We also tested for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene and were unable to detect the C to T substitution in our schizophrenic group.     

Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap

Ethylene glycol poisoning classically presents as a metabolic acidosis with an increased anion gap. Metabolism of ethylene glycol to organic acids, and increased production of lactate, are responsible for the increased gap. We report the case of an alcohol user who consumed ethanol and ethylene glycol concurrently, and presented without acidosis, with a normal anion gap. Several hours later, when his serum ethanol level had declined, he developed severe acidosis with an elevated anion gap. An increased osmolal gap, not accounted for by the serum ethanol level, proved to be an important clue to the diagnosis. In this patient, ingestion of ethanol inhibited the hepatic metabolism of ethylene glycol to organic acids, obscuring the diagnosis. In intoxicated alcohol users, even in the absence of metabolic acidosis, serum osmolality measurements and calculation of the osmolal gap may facilitate the rapid diagnosis of ethylene glycol poisoning.     

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

Corneas of diabetic patients have abnormal healing and epithelial adhesion, which may be due to alterations of the corneal extracellular matrix (ECM) and basement membrane (BM). To identify such alterations, various ECM and BM components and integrin receptors were studied by immunofluorescence on sections of normal and diabetic human corneas. Age-matched corneas from 15 normal subjects, 10 diabetics without diabetic retinopathy (DR), and 12 diabetics with DR were used. In DR corneas, the composition of the central epithelial BM was markedly altered, compared to normal or non-DR diabetic corneas. In most cases the staining for entactin/nidogen and for chains of laminin-1 (alpha1beta1gamma1) and laminin-10 (alpha5beta1gamma1 was very weak, discontinuous, or absent over large areas. Other BM components displayed less frequent changes. The staining for alpha3beta1 (VLA-3) laminin binding integrin was also weak and discontinuous in DR corneal epithelium. Components of stromal ECM remained unchanged even in DR corneas. Therefore, distinct changes were identified in the composition of the epithelial BM in DR corneas. They may be due to increased degradation or decreased synthesis of BM components and related integrins. These alterations may directly contribute to the epithelial adhesion and wound healing abnormalities found in diabetic corneas.     

Development of attitude strength over the life cycle: surge and decline

This article explores the relation of age to manifestations and antecedents of attitude strength. Three studies demonstrate that susceptibility to attitude change is greater during early and late adulthood than during middle adulthood. Three additional studies demonstrate that attitude importance, certainty, and perceived quantity of attitude-relevant knowledge are greater in middle adulthood than during early or late adulthood. These antecedents may therefore explain life cycle shifts in susceptibility to change. Susceptibility to change, importance, certainty, and perceived knowledge differ from one another in terms of their correlations with education, gender, and race, challenging the notion that attitude strength is a unitary construct. Evidence that people incorrectly believe that susceptibility to change declines steadily over the life course reinforces the distinction between operative and meta-attitudinal measures of attitude strength.     

Ethical and pragmatic issues in the use of psychotropic agents in young children

OBJECTIVE: To provide an overview of the knowledge base concerning the prescribing of psychotropic agents in young children with mental disorder and related mental health problems. METHOD: Relevant information is reviewed concerning the knowledge base available to inform pediatric psychopharmacology prescribing practices. RESULTS: Very few psychoactive medications have been adequately tested for safety and efficacy in young children, despite relatively high rates of prescribing. CONCLUSION: Behavioral and psychotherapeutic strategies are often the wisest first therapeutic intervention for this age group. Psychotropic medications may be required, but should be used cautiously in young children, while additional studies are being conducted.