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Biomedical subjects

A Witt

Publications and source records attributed to A Witt.

At least 19 recordsLinked to original sources

Absorption of D(+)-xylose, cobalamin, and folic acid after autologic-allotopic ileum mucosa transplantation in beagles.

BACKGROUND/PURPOSE: Ileum mucosa transplantation in a demucosed colon coat was developed as a new method for small bowel elongation. In an animal model, the authors investigated the absorptive capacity of the transplanted mucosa for D(+)-xylose, cobalamin (vitamin B12), and folic acid. METHODS: Ileum mucosa was transplanted in a vascularized demucosed segment of transverse colon in 18 beagle dogs. The colon coat-ileum mucosa complex then was integrated in the ileal continuity. Absorptive capacity for D(+)-xylose, cobalamin, and folic acid was measured before and 4 weeks after transplantation. The results were compared and analyzed with the Students' t test for matched pairs. All determined blood values with P values less than.05 were considered to show a significant reduction in the absorptive capacity of the transplanted ileum mucosa. RESULTS: Fifteen minutes after application there was no significant difference in the absorption of D(+)-Xylose and cobalamin between normal and transplanted ileum mucosa (P >.1). Absorption of folic acid in the transplanted segment was lower but not significant (P <.1). After 30 minutes D(+)-xylose and cobalamin again showed no difference between the absorptive capacity of normal and transplanted ileum mucosa (P >.1), whereas folic acid continued with the tendency toward an impaired absorption (P <.1). However, after 60 minutes, the difference of the absorptive capacity of the transplanted ileum mucosa was significant (P <.05) for folic acid. D(+)-xylose showed a tendency for an impaired uptake (P <.1), whereas absorption of cobalamin did not differ significantly after transplantation (P >.1). CONCLUSIONS: Experimental autologic-allotopic ileum mucosa transplantation is a feasible new method for small bowel elongation in an animal model. Examination of the absorptive capacity of the transplanted ileum mucosa showed a normal uptake for cobalamin, while there was an impaired absorption of D(+)-xylose and folic acid.

Animals↗

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

PURPOSE: After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. METHODS: In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. RESULTS: In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). CONCLUSIONS: Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

Animals↗

Dynamo effect in a driven helical flow.

The Roberts flow, a helical flow in the form of convectionlike rolls, is known to be capable of both kinematic and nonlinear dynamo action. We study the Roberts dynamo with particular attention being paid to the spatial structure of the generated magnetic field and its back-reaction on the flow. The dynamo bifurcation is decisively determined by the symmetry group of the problem, which is given by a subgroup of discrete transformations and a continuous translational invariance of the flow. In the bifurcation the continuous symmetry is broken while the discrete subgroup symmetry completely survives. Its actions help in understanding the spatial structures of the magnetic field and of the modified flow. In accordance with experimental observations, the magnetic field component perpendicular to the originally invariant direction is much stronger than the component in this direction. Furthermore, the magnetic field is largely concentrated in layers separating the convectionlike rolls of the flow and containing, in particular, its stagnation points, which are isolated for the modified flow while they are line filling for the original Roberts flow. The magnetic field is strongest near beta-type stagnation points, with a two-dimensional unstable and a one-dimensional stable manifold, and is weak near alpha-type stagnation points, with a two-dimensional stable and a one-dimensional unstable manifold. This contrasts with the usual picture that dynamo action is promoted at the alpha points and impeded at the beta points. Both the creation of isolated stagnation points and the concentration of strong fields at the beta points may be understood as a result of the way in which the Roberts dynamo saturates. It is also found that, while the original Roberts flow is regular, the modified flow is chaotic in the layers between the convectionlike rolls where the magnetic field is concentrated. This chaoticity, which results from the back-reaction of the magnetic field on the flow, appears to merely enhance magnetic diffusion rather than to strengthen the dynamo effect.

Journal Article↗

The detection of HPV DNA improves the recognition of cervical intraepithelial lesions.

UNLABELLED: Reasons that influence the efficacy of cervical cancer screening are failure to screen all women at risk, as well as inherent technical limitations of the conventional cervical smear. HPV DNA testing is a supplementary, objective test less independent on sampling failure. The aim of this study was to compare results of HPV DNA screening to cytological smears (CS) and histological diagnosis. From January 1995 to January 1999, cytological smears, cells for HPV DNA analysis and cervical biopsies were obtained from 280 women included in this study. STATISTICAL METHODS: Fisher's exact test (2x2 contingency tables, P<0.01), Pearson Chi-square, P< 0.05, Spearman's rank correlation R. Sixty patients (21.4%) tested positive for low-risk (LR-HPV), 227 (81.1%) positive for high-risk HPV (HR-HPV). The CS proved to be a strong predictor for the histological diagnosis, reaching a sensitivity of 93.4%, a specificity of 65.8% and a positive predictive value (PPV) of 77.4%. By combining cytology and HPV DNA testing, the sensitivity could be considerably enhanced (99.0%), though at a price of loss in specificity (30.1%). HPV DNA testing, available as a commercially standardized product, leads to a significant rise in sensitivity when used as an additional diagnostic tool to cytological screening methods and thus contributes to reduce the incidence of cervical carcinomas.

Adolescent↗

Total syntheses of the benzodiazepine alkaloids circumdatin F and circumdatin C.

Total syntheses of circumdatin F and circumdatin C, which both possess a 3H-quinazolin-4-one as well as a 1,4-benzodiazepin-5-one moiety, are described. A tripeptide derivative was synthesized as a key intermediate and dehydrated to a benzoxazine by reaction with triphenylphosphine, iodine, and a tertiary amine. The natural products were attained via rearrangements to an amidine intermediate, deprotection with 45% HBr in acetic acid, and cyclization on silica gel.

Alkaloids↗

Circulating breast cancer cells are frequently apoptotic.

Automatic search for cytokeratin/mucin-1 double immunofluorescence was performed to detect and characterize circulating epithelial tumor cells in patients with advanced breast cancer. The peripheral blood samples in 8 of 19 patients (42.1%) presented with cytokeratin-positive and epithelial-type mucin-positive (CK(+)/MUC1(+)) tumor cells. Detailed microscopic analysis, however, suggested that the majority of the double immunopositive cells was apoptotic according to an "inclusion type" cytokeratin staining pattern and nuclear condensation. Furthermore, apoptosis-related DNA strand breaks could be demonstrated by applying the TdT-uridine nick end labeling assay in these cells. In 3 of 8 positive samples all of the CK(+)/MUC1(+) cells displayed apoptotic features. We conclude that apoptotic cells significantly contribute to the circulating tumor cell fraction in breast cancer patients. As the predictive value of such cells for the outcome of the disease is unclear, they should be considered separately when analyzing tumor cell dissemination.

Apoptosis↗

Oriented Schwann cell growth on micropatterned biodegradable polymer substrates.

This paper investigates the influence of substrate-mediated chemical and physical guidance on the growth and alignment of Schwann cells in vitro. Novel techniques were developed to fabricate microgrooves with adsorbed proteins on biodegradable polymer substrates made of poly(D,L-lactic acid). Compression molding and solvent-casting were used to transfer micropatterns from quartz and silicon substrates onto biodegradable polymer films. Laminin was selectively adsorbed onto the grooves and rat sciatic Schwann cells were seeded on the substrates. Laminin was found to improve adhesion of Schwann cells on the substrates. The microgrooves were found to cause the Schwann cells to align along the direction of the grooves. The groove width influenced Schwann cell alignment the most, while groove depth did not seem to play a significant role. The degradation of the grooves in the solvent cast films was much slower than those in the compression-molded films, making them the preferred substrates for Schwann cell culture.

Biocompatible Materials↗

Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs.

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

Adult↗

Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: tissue distribution in male rats.

BAY 12-8039 (moxifloxacin-HCl) and 14C-labelled BAY 12-8039 were administered to male rats as single i.v. and oral doses of 4.6 and 5.0 mg/kg bodyweight respectively. The distribution of substance-associated radioactivity in the body was investigated by whole-body autoradiography. The concentrations of the unchanged compound in plasma, skin suction blister fluid and lung tissue were determined by HPLC. Whole-body autoradiography revealed distinctly higher concentrations of radioactivity in the gastrointestinal tract, urinary bladder and in most organs and tissues (e.g. kidneys, liver, spleen, lungs, various glands, cartilaginous tissues and in melanin-containing structures located in the eye, meninges and hair follicles of pigmented skin) than in blood. Radioactivity crossed the blood-brain barrier only to a small extent. The results show a high tissue affinity and a rapid and homogeneous distribution of radioactivity from blood to organs or tissues. No relevant difference in the distribution of radioactivity was found following i.v. and oral administration. After i.v. and oral dosing similar concentrations of the unchanged compound were determined in skin suction blister fluid and plasma. The concentrations of the unchanged compound in lung tissue were about three times higher than those in plasma following both i.v. and oral administration. The concentration-time courses for moxifloxacin in plasma and lung tissue were parallel.

Animals↗

Surrogates for finding unstable periodic orbits in noisy data sets.

Recently, searches for unstable periodic orbits in biological and medical applications have become of interest. The motivations for this research range, in order of ascending complexity, from efforts to understand the dynamics of simple sensory neurons, through speculations regarding neural coding, to the hopeful development of new diagnostic and/or control techniques for cardiac and epileptic pathologies. Biological and medical data are, however, noisy and nonstationary. Findings of unstable periodic orbits in such data thus require convincing assessments of their statistical significance. Such tests are accomplished by comparison with surrogate data files designed to test an appropriate null hypothesis. In this paper we test surrogates generated by three different algorithms against correlated noise as well as stable periodic orbits. One of the surrogates is new, and has been specifically designed to preserve the shape of the attractor. We discuss the suitability of these surrogates and argue that the simple shuffled one correctly tests the appropriate null hypothesis.

Journal Article↗

A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score </= -2) for lambdas >/= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

Aged↗

The legal and scientific basis for FDA's assertion of jurisdiction over cigarettes and smokeless tobacco.

On August 28, 1996, the US Food and Drug Administration (FDA) asserted jurisdiction over cigarettes and smokeless tobacco under the Federal Food, Drug, and Cosmetic Act. Under this Act, a product is a "drug" or "device" subject to FDA jurisdiction if it is "intended to affect the structure or any function of the body." The FDA determined that nicotine in cigarettes and smokeless tobacco does "affect the structure or any function of the body" because nicotine causes addiction and other pharmacological effects. The FDA then determined that these pharmacological effects are "intended" because (1) a scientific consensus has emerged that nicotine is addictive; (2) recent studies have shown that most consumers use cigarettes and smokeless tobacco for pharmacological purposes, including satisfying their addiction to nicotine; and (3) newly disclosed evidence from the tobacco manufacturers has revealed that the manufacturers know that nicotine causes pharmacological effects, including addiction, and design their products to provide pharmacologically active doses of nicotine. The FDA thus concluded that cigarettes and smokeless tobacco are subject to FDA jurisdiction because they contain a "drug," nicotine, and a "device" for delivering this drug to the body.

Ganglionic Stimulants↗

High-resolution CT of the temporal bone in dysplasia of the auricle and external auditory canal.

PURPOSE: To determine CT findings in the external, middle, and inner ear of patients with microtia and external auditory canal dysplasia. METHODS: We used high-resolution CT, with multiplanar or axial 1-mm continuous sections, coronal or sagittal reformations, or low-dose spiral acquisitions, to examine 184 temporal bones of children with microtia. RESULTS: In cases of minor microtia, auditory canal stenosis was the most common associated abnormality; in those with major microtia, atresia was predominant. Middle ear malformations depended on the severity of the auricular anomalies. Inner ear changes could also be noted. Ossicle dysplasias occurred in 98% of patients (stapes, 72%), absence of the oval window in 36%, labyrinthine malformations in 13%, closed round window in 6%, facial canal displacement in up to 75%, and aberrations of the vascular canal in 38% of patients with third-grade auricular deformity. CONCLUSION: A variety of external, middle, and, less frequently, inner ear changes were detected in connection with microtia.

Abnormalities, Multiple↗

HIV colonizing peripheral blood monocytes follows lymphocytic isolates in shifting from NSI to SI genotype.

Non-syncytium inducing (NSI) and syncytium inducing (SI) variants of human immunodeficiency virus (HIV) isolated from peripheral blood mononuclear cells (PBMC) could be definitely typed by sequence analysis of the env-gene V3 region. It was thus possible to compare the genotypes of viral variants isolated from PBMC and accompanying monocyte cultures and those derived directly from the patients' blood cells prior to cultivation. Within the investigated group of patients it was shown that HIV variants colonizing monocytes displayed a similar shift from NSI to SI as observed previously for PBMC, i.e. lymphocyte derived isolates. Lymphocytic SI variants could be isolated from the blood of patients, while simultaneously the predominant provirus in both blood and monocytic isolate was NSI. Consequently, we observed a delayed switch in the predominant provirus genotype found in blood which was associated with a synchronous change in the genotype of the corresponding monocytic isolate. The results show that monocytes/macrophages can be colonized by heterogeneous HIV variants in vivo and can therefore also function as carriers for the spread of highly virulent SI variants into the tissues.

Amino Acid Sequence↗