Ileal atresia with total colonic aganglionosis

This is the 17th report of the case of an infant who had ileal atresia associated with Hirschsprung's disease, and the second with ganglion cells distal to the atresia. Experience suggests that Hirschsprung's disease should be suspected in all forms of bowel atresia.     

Co-witness information can have immediate effects on eyewitness memory reports

When questioning a reluctant witness, investigators sometimes encourage the witness by providing information about what other witnesses have said. Three experiments were conducted to test the combined effects of such co-witness information and suggestive questioning on the accuracy of eyewitness memory reports. Experiment 1 was analogous to the experience of a witness who receives information from an interviewer or questioner about what other witnesses have already said, whereas Experiments 2 and 3 simulated the situation in which a witness receives information directly from a co-witness. In all three experiments, when participants received incorrect information about a co-witness's response, they were significantly more likely to give that incorrect response than if they received no co-witness information. This effect persevered in a delayed memory test 48 h after the initial questioning session in Experiment 3. Accuracy rates were lowest of all when incorrect co-witness information was paired with questioning that suggested an incorrect response. These results have implications not only for the immediate effects on the accuracy of witnesses' memory reports, but also for the impact that even one such inaccurate report can have on the manner in which a case is investigated by the police or other authorities.     

Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies

Fluoromisonidazole (FMISO), labeled with the positron emitter 18F, is a useful hypoxia imaging agent for PET studies, with potential applications in patients with tumors, cardiovascular disease and stroke. METHODS: Radiation doses were calculated in patients undergoing imaging studies to help define the radiation risk of FMISO-PET imaging. Time-dependent concentrations of radioactivity were determined in blood samples and PET images of patients following intravenous injection of [18F]FMISO. Radiation absorbed doses were calculated using the procedures of the Medical Internal Radiation Dose (MIRD) committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. As part of this study we also calculated an S value for brain to eye. Effective dose equivalent was calculated using ICRP 60 weights. RESULTS: Effective dose equivalent was 0.013 mSv/MBq in men and 0.014 mSv/MBq in women. Individual organ doses for women were not different from men. Assuming bladder voiding at 2- or 4-hr intervals, the critical organ that received the highest dose was the urinary bladder wall (0.021 mGy/MBq with 2-hr voiding intervals or 0.029 mGy/MBq with 4-hr voiding intervals). CONCLUSION: The organ doses for [18F]FMISO are comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this study are within generally accepted limits.     

Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection

The contribution of endogenous NK cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. In immunocompetent C57BL/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. The inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression. The largest number of necrotic foci was found 2 days after infection. Overall hepatic damage, assessed as increased expression of liver enzymes in serum, accompanied the development of inflammatory and necrotic foci. Experiments with neutralizing antibodies demonstrated that although virus-induced tumor necrosis factor (TNF) can have antiviral effects, it also mediated significant liver pathology. TNF was required for development of hepatic necrotic foci and increased levels of liver enzymes in serum but not for increased numbers of inflammatory foci. The necrotic foci and liver enzyme indications of pathology occurred independently of NK and T cells, because mice rendered NK-cell deficient by treatment with antibodies, T- and B-cell-deficient Rag-/- mice, and NK- and T-cell-deficient E26 mice all manifested both parameters of disease. Development of necrotic foci and maximally increased levels of liver enzymes in serum also were TNF dependent in NK-cell-deficient mice. Moreover, in the immunodeficient E26 mice, virus-induced liver disease was progressive, with eventual death of the host, and neutralization of TNF significantly increased longevity. These results establish conditions separating hepatitis from significant liver damage and demonstrate a cytokine-mediated component to viral pathogenesis.     

De-novo reversible stenoses in tortuous arteries during coronary angioplasty due to the accordion effect. A clinical case and review of the literature

During the performance of PTCA, the operator must be able to differentiate true complications from pseudocomplications. Mechanical coronary shortening and vessel wall invagination due to accordion effect, "pseudo-transection", dissection, coronary spasm, and localized thrombosis are sources of iatrogenic obstruction during angioplasty. We report a case in which straightening of a right tortuous coronary artery during angioplasty produced an iatrogenic lesion that has a typical invaginate appearance. Conservative management is indicated in the absence of definitive angiographic aspect of vessel trauma, because they disappear after withdrawal of angioplasty equipment or adequate management of the guidewire.     

Microalbuminuria and its relation to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals

Microalbuminuria has been proposed as a potential atherosclerotic risk factor in hypertensive individuals. The aim of this cross-sectional population study was to analyse whether microalbuminuria is related to a higher prevalence of cardiovascular disease, and a more atherogenic risk profile, and reversely related to the use of antihypertensive drugs. In a major health screening at the State University Hospital in Copenhagen, including urinary albumin excretion, glomerular filtration rate, blood pressure (BP), electrocardiogram, body mass index, plasma lipoproteins, fibrinogen, and albumin, and information regarding a history of acute myocardial infarction, smoking, and antihypertensive drugs, 1254 participants without diabetes mellitus or renal/urinary tract disease had arterial hypertension. Age range was 30-70 years. Microalbuminuria (nocturnal urinary albumin excretion >15 microg/min) occurred in 5%, and cardiovascular disease (previous acute myocardial infarction or electrocardiographic Q-waves) also in 5% of the study population. Microalbuminuric hypertensive subjects were characterized by higher age and systolic BP, and a male predominance, as compared to normoalbuminuric hypertensive subjects. The frequency of cardiovascular disease was similar in the two groups. In contrast, when analysed as a continuous variable, a one unit increase in the logarithmically transformed urinary albumin excretion significantly increased the likelihood of cardiovascular disease (odds ratio [95% confidence interval] 1.32 (1.02-1.70); P < 0.05), and this relation was independent of age, sex, and conventional atherosclerotic risk factors. Participants who were effectively treated with antihypertensive drugs did not have a lower urinary albumin excretion than insufficiently treated or untreated participants. It is concluded that slightly elevated albumin excretion in the urine is not only a pressure-dependent functional phenomenon in the glomerular vessel walls, but associated with permanent atherosclerotic abnormalities in the entire vascular system.     

The role of an amygdalo-nigrostriatal pathway in associative learning

The present study examined the role of an amygdalo-nigrostriatal pathway in associative learning. An asymmetrical lesion model was used to test whether a circuit from the amygdala central nucleus to the dorsolateral striatum, via the substantia nigra, is critical for mediating conditioned orienting responses. Rats with an asymmetrical lesion, consisting of neurotoxic removal of central nucleus neurons in one hemisphere and depletion of the dopamine innervation of the dorsolateral striatum in the contralateral hemisphere, failed to acquire conditioned orienting responses. In contrast, the asymmetrical lesion had no effect on spontaneous orienting or learning another response directed to the source of the food unconditioned stimulus in the same task. A second experiment tested the effect of reversible inactivation of the dorsolateral striatum contralateral to a neurotoxic central nucleus lesion on acquisition of the conditioned orienting response. Although inactivation did not affect spontaneous orienting, rats failed to acquire the conditioned orienting response during sessions in which inactivation occurred. Immediately after the inactivation procedure was terminated, however, a significant increase in orienting to the conditioned stimulus was evident. These data support the interpretation that the dorsolateral striatum provides a route for the expression of the conditioned orienting response but is not essential for acquisition of this learned behavior.     

Skin colonization of Staphylococcus aureus in atopic dermatitis patients seen at the National Skin Centre, Singapore

BACKGROUND: Combinatorial chemistry has become an important method for identifying effective ligand-receptor binding, new catalysts and enzyme inhibitors. In order to distinguish the most active component of a library or to obtain structure-activity relationships of compounds in a library, an efficient quantitative assay is crucial. Electrospray mass spectrometry has become an indispensable tool for qualitatively screening combinatorial libraries and its use for quantitative analysis has recently been demonstrated. RESULTS: This paper describes the use of quantitative electrospray mass spectrometry for screening libraries of inhibitors of enzymatic reactions, specifically the enzymatic glycosylation by beta-1,4-galactosyltransferase, which catalyzes the transfer of galactose from uridine-5'-diphosphogalactose to the 4-position of N-acetylglucosamine beta OBn (Bn: benzene) to form N-acetyllactosamine beta OBn. Our mass spectrometric screening approach showed that both nucleoside diphosphates and triphosphates inhibited galactosyltransferase while none of the nucleoside monophosphates, including uridine-5'-monophosphate, showed any inhibition. Additional libraries were generated in which the concentrations of the inhibitors were varied and, using mass spectrometry, uridine-5'-diphosphate-2-deoxy-2-fluorogalactose was identified as the best inhibitor. CONCLUSIONS: This report introduces quantitative electrospray mass spectrometry as a rapid, sensitive and accurate quantitative assaying tool for inhibitor libraries that does not require a chromophore or radiolabeling. A viable alternative to existing analytical techniques is thus provided. The new technique will greatly facilitate the discovery of novel inhibitors against galactosyltransferase, an enzyme for which there are few potent inhibitors.     

Correlation of interleukin-1 beta, interleukin-6, and periodontitis

In order to understand the role of IL-1 beta and IL-6 in the periodontal tissue destruction coincident to periodontitis, we assessed the levels of these two mediators in both the gingival tissue and the serum of patients with periodontal disease and of periodontally healthy subjects. In addition, production of IL-6 by six healthy human gingival fibroblast (HGF) strains in response to IL-1 beta was also investigated. The levels of IL-1 beta and IL-6 in gingival tissues and in serum were examined by ELISA. Both mediators were observed to increase in diseased tissues of patients with adult periodontitis, and there was a positively significant relationship between both mediators and clinical assessments of periodontal destruction. Moreover, a significant correlation was also noted between levels of IL-1 beta and IL-6 in gingival tissues of periodontitis patients (r = 0.4334, p < 0.01). However, there was no significant difference in the serum levels of IL-1 beta and IL-6 between periodontitis patients and periodontally healthy controls. In fibroblast cultures, confluent monolayers of HGF were incubated with recombinant human IL-1 beta for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and assayed for IL-6 activity by inducing proliferation in the IL-6-dependent hybridoma cell line 7TD1. A dose-dependent stimulatory effect of IL-1 beta on IL-6 production by HGF was noted, wherein 3 strains exhibited higher IL-6 activity than the other 3. These data indicate that the levels of IL-1 beta and IL-6 in gingival tissues are closely related to the severity of periodontal disease and that the IL-1 beta and IL-6 produced in gingival tissues may not reflect these two mediators levels in serum. Moreover, IL-1 beta responsiveness of HGF in IL-6 production depends on both the concentration of IL-1 beta and cells of individual subjects. Since HGF are present in periodontal lesion, it is possible that IL-6 secretion stimulated by exposure to inflammatory cell products such as IL-1 beta may participate in the destruction of periodontal tissue in periodontitis.     

Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. I. Invariants and validation of electron microscopy models

Solutions of selectively deuterated 70 S Escherichia coli ribosomes and of free 30 S and 50 S subunits were studied by neutron scattering using contrast variation. The integrity of the partially deuterated particles was controlled by parallel X-ray measurements. Integral parameters of the entire ribosome, of its subunits and of the protein and rRNA moieties were evaluated. The data allow an experimental validation of the two most recent electron microscopy reconstructions of the 70 S ribosome presented by the groups of J. Frank (Albany) and of M. van Heel & R. Brimacombe (Berlin). For each reconstruction, integral parameters and theoretical scattering curves from the 70 S and its subunits were calculated and compared with the experimental data. Although neither of the two models yields a comprehensive agreement with the experimental data, Frank's model provides a better fit. For the 50 S subunit of van Heel & Brimacombe's model the fit with the experimental data improves significantly when the internal channels and tunnels are filled up. The poorer fit of the latter model is thus caused by its "sponge"-like structure which may partly be due to an enhancement of high frequency contributions in some of the steps of the three-dimensional image reconstruction. It seems therefore unlikely that the ribosome has a "sponge"-like structure with a pronounced network of channels.