Reversal of multidrug resistance phenotype by surfactants: relationship to membrane lipid fluidity

Previous studies have suggested that multidrug resistance (MDR) reversal by polyoxyethylene surfactants involves alterations in plasma membrane lipid physical state of resistant cells as one of the possible mechanism(s). To date, however, a detailed and critical examination of the relationship between membrane lipid fluidity and MDR reversal by these surfactants has not been performed. In the present studies, therefore, a series of experiments were conducted to critically examine the role of membrane lipid physical state in MDR reversal by employing a unique class of clinically important nontoxic lipophilic surfactants and the KB-8-5-11 drug-resistant cell line. MDR reversal was assessed by rhodamine-123 uptake. The effect of surfactants on plasma membrane lipid fluidity of these cells was assessed utilizing a fluorescence polarization technique with fluorophores DPH, TMA. DPH, 2-AS, and 12-AS. Our studies demonstrated that: (i) in vitro addition of active MDR-reversing surfactants (Solutol HS-15, Tween 40, and Cremophor EL, 10 micrograms/ml each) decreased lipid fluidity of isolated crude plasma membranes of resistant cells; (ii) the inactive surfactants (octylglucoside, hecameg) failed to influence membrane lipid fluidity; (iii) cells grown in the presence of active surfactants also exhibited a decreased plasma membrane lipid fluidity as measured with intact cells utilizing the probe TMA.DPH; and (iv) active surfactants did not influence lifetimes of the excited state of the fluorophores. These findings demonstrate that decrease of the plasma membrane lipid fluidity of KB 8-5-11 resistant cells may be one of the important mechanism(s) of MDR reversal by polyoxyethylene surfactants.     

Application of probability techniques to the objective interpretation of veterinary clinical biochemistry data

Methods for the interpretation of veterinary clinical biochemistry have not developed as rapidly as biochemical technology. However, the results of clinical biochemistry tests are only of value when they are interpreted appropriately. A retrospective study was undertaken to investigate the equine biochemistry data which had been stored in a veterinary hospital database. By applying percentile analysis and Bayesian probability methods to the clinical biochemistry and corresponding diagnosis data, a novel method for the interpretation of clinical biochemistry data has been developed. The method allows clinicians to determine whether a biochemistry value is abnormal, its degree of abnormality, and the most likely associated diagnoses. The method could be used to investigate a practice-based population and may have significant implications for the interpretation of clinical biochemistry data in veterinary medicine in the future.     

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p

The limb-girdle muscular dystrophies are a clinically and genetically heterogeneous group of disorders. We have studied two large inbred families of different ethnic origin and excluded linkage to LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceeding to a genomic linkage search, we have now identified linkage to markers D2S134 and D2S136 on chromosome 2p (maximum lod score 3.57 at zero recombination). The phenotype in the two families was similar, with onset in the pelvic girdle musculature in the late teens and usually relatively slow progression. This work identifies a second locus for autosomal recessive limb-girdle muscular dystrophy.     

Effect of mammography outreach in women veterans

The article reports some specific aspects of rehabilitation service in North America. One of the most unique and important features is interdisciplinary team approach especially effective in neurological rehabilitation. Structure of the neurological rehabilitation team is described.     

Inhibition by a capsaicin antagonist (capsazepine) of capsaicin-induced swimming capacity increase in mice

We investigated the endurance swimming capacity of mice injected with CAP antagonist (capsazepine). The increase of endurance swimming capacity by the administration of CAP was significantly suppressed by the injection of capsazepine. At the same time, serum adrenaline secretion, which was induced by CAP, was depressed by capsazepine. These findings suggested that the increase in endurance swimming capacity by CAP was mediated by the CAP receptor.     

Intestinal tuberculosis: clinicopathologic analysis and diagnosis by endoscopic biopsy

OBJECTIVES: Tuberculosis is still an important cause of granulomatous colitis in developing countries. If we can diagnose tuberculosis using endoscopic biopsy material, clinicians can avoid invasive diagnostic procedures and needless operations. For this purpose, we evaluated clinical manifestations, pathological findings, and diagnostic methods in endoscopically biopsied intestinal tuberculosis patients. METHODS: From January 1991 to December 1996, 42 patients with intestinal tuberculosis were endoscopically examined and tissue culture, immunohistochemical stain, Ziehl-Neelsen stain, and polymerase chain reaction in fresh and fixed tissue were applied. The pathological findings were analyzed and compared with the results of the other diagnostic methods. RESULTS: In tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and multiple erosions were usual colonoscopic findings. The granulomas were found in 74% of the cases. The positivity ranged from 30-45%. There were no significant differences in the positivity among those diagnostic methods (p > 0.05). The positivity of Ziehl-Neelsen stain in fixed tissue was higher in the group having granulomas and it was reversed in PCR (p < 0.05). The increasing number of biopsy particles raised the positivity of Ziehl-Neelsen stain and PCR in fixed tissue (p < 0.05). CONCLUSIONS: Transverse ulcers were the most characteristic colonoscopic finding and granulomas were frequent pathological findings in intestinal tuberculosis. Higher positivity and reliable results were found in tissue culture, Ziehl-Neelsen stain, and polymerase chain reaction. To increase the diagnostic rate, the endoscopist should take enough tissue and deep biopsy material from ulcer bases and diseased mucosae.     

Evidence from 18S ribosomal DNA that the lophophorates are protostome animals

The suspension-feeding metazoan subkingdom Lophophorata exhibits characteristics of both deuterostomes and protostomes. Because the morphology and embryology of lophophorates are phylogenetically ambiguous, their origin is a major unsolved problem of metazoan phylogenetics. The complete 18S ribosomal DNA sequences of all three lophophorate phyla were obtained and analyzed to clarify the phylogenetic relationships of this subkingdom. Sequence analyses show that lophophorates are protostomes closely related to mollusks and annelids. This conclusion deviates from the commonly held view of deuterostome affinity.     

In vivo binding of mouse IgG via polyreactive surface IgM abrogates progressive lymphocytosis in prolymphocytic leukemia

Surface IgM expressed by malignant CD5+ B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) has previously been shown to bind mouse Ig in what appears to be an example of polyreactive antigen-binding activity. This report demonstrates the in vitro and in vivo binding of mouse Ig to the surface of malignant B-cells from a patient with B-cell prolymphocytic leukemia (B-PLL). In vitro studies showed that K121, a mouse monoclonal antibody, bound to the B-PLL cells via the same low-affinity binding interaction demonstrated to occur between mouse Ig and surface IgM expressed by B-CLL cells rather than in the conventional sense against a specific antigen via its antigen-binding site. With the view to using this phenomenon to target malignant B-cells, it was important to determine whether the low-affinity interaction also occurred in vivo. Infusions of K121 totalling 286 mg were administered to a B-PLL patient over 7 days. Binding of K121 to circulating B-PLL cells was demonstrable after the administration of 36 mg of antibody and was preceded by the appearance of free antibody in the serum. Throughout the period of the infusion, the rapid rise in the peripheral blood white cell count normally observed after leukopheresis was abrogated. However, the count rose markedly after cessation of the antibody infusion in parallel with a decrease in both free and cell-bound K121. There were no observable side effects and no host immune response to either species specific or idiotypic determinants on the mouse Ig was detected. The in vivo binding of mouse Ig together with the previous in vitro data suggest the potential for a novel targeting mechanism using a region of the mouse Ig molecule to target polyreactive Ig expressed by malignant cells in B-CLL and B-PLL.