Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.     

Development of clinical indicators for performance measurement and improvement: an HMO/purchaser collaborative effort

This article describes a collaborative effort between a major health care purchaser, three area health maintenance organizations, and a state Medicaid agency to develop clinical indicators as the basis for a comparison database. Some of the difficulties in developing a "common yardstick" of quality and value are candidly discussed.     

Application of polymerase chain reaction for the correlation of Salmonella serovars recovered from greyhound feces with their diet

The polymerase chain reaction was employed to correlate Salmonella serovars isolated from fecal material of greyhounds suffering from gastroenteritis with those isolated from the diet fed to the greyhounds prior to onset of diarrhea. Kennels around the Abilene, Kansas, area were contacted and supplied with materials needed to collect a portion of the diet each day. With the onset of diarrhea, the kennels were instructed to ship the fecal material and diet from the previous 10 days to the laboratory for testing. Forty-one fecal samples and corresponding diets were screened for Salmonella, Clostridium perfringens, Campylobacter jejuni, Staphylococcus aureus, Staphylococcus intermedius, and pathogenic (piliated) Escherichia coli by direct culture using standard procedures. The fecal material was also screened for coronavirus and parvovirus using electron microscopy. Thirty-five "normal" fecal samples were screened for all of the above mentioned microorganisms as a control. In addition, the fecal material was screened for E. coli verotoxins I and II and clostridial enterotoxins. A total of 61 Salmonella isolates were recovered from the 41 samples of feces and diet submitted for testing; 31 were recovered from the feces and 30 from the diet. Four Salmonella isolates were recovered from the normal fecal samples. Results obtained by PCR, plasmid profiles, antigenic analysis, and antibiogram profiles indicated that 16 of the 31 isolates recovered from the fecal material were the same strain as that recovered from the diet.     

Studies on antigenic relationship between grass- and cult. rye pollens by skin-test, RAST and RAST-inhibition-test in patients with pollinosis (author's transl)

Skin tests on patients suffering from pollinosis suggest frequently an antigenic relationship between various grass and cult. rye pollens. This problem was further studied using both, RAST and RAST inhibition test. The tests were performed with commercial grass pollen discs as well as with self-prepared disc labeled with cult. rye pollens and a combination of various grass antigens. Good agreement was found between self-made and commercial (single antigen) grass pollen discs (95.9%). RAST and skin test correlated also extremely well (92.3%). Mutual inhibition between grass and cult. rye pollens was measured by RAST inhibition test using self-prepared discs. High antigenic relationship between grass and cult. rye pollens was found, however, it could be demonstrated that the antibody pattern varies and contains "grass specific" antibodies.     

Application of confocal laser scanning microscopy to analysis of H2O2-induced DNA damage in human cells

Confocal laser scanning microscopy (CLSM) offers improved depth discrimination and spatial resolution to the analysis of biologic samples. We demonstrate in this paper that such technology is valuable in examining DNA single-strand breaks in human cells. The single-cell-gel (SCG) assay is a new technique for measuring DNA strand breaks in individual cells. Cells embedded in lowmelting-point agarose are treated with varying concentrations of hydrogen peroxide to induce DNA strand breaks. Following cell lysis and alkaline electrophoresis, which enables single-stranded break detection, analysis of the resulting “comets” provides an accurate method of comparing changes in DNA migration patterns, which have been shown to reflect the DNA damage levels. A statistically significant difference (p < 0.01) in single-stranded DNA damage levels was detected in cells exposed to hydrogen peroxide concentrations as low as 10 nm for 2 min. LSM analysis of the SCG technique allows rapid, sensitive and reproducible quantitation of single-stranded breaks of cellular DNA.     

中央通过《关于设立知识产权法院的方案》

6月6日，中央全面深化改革领导小组第三次会议召开，会议审议通过了“关于设立知识产权法院的方案》等方案。     

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.     

POEMS syndrome in a patient with diabetic ketoacidosis: case report and review

This article summarise the main data in the literature on the role of bacteriological contamination of the dialysate fluid in inflammatory reactions in hemodialysis. Pyrogenic substances of small molecular weight from Gram-negative bacteria grown in dialysate can pass across intact dialyzer membrane to stimulate cytokine production by peripheral blood mononuclear cells. Cellulosic hemodialysis membranes are more permeable to endotoxins than synthetic membranes. Polysulfone membranes and polyamide membranes are able to adsorb bacterial toxins on the dialysate side. The diffusive transfer of bacterial products across dialysis membrane from dialysate fluid was demonstrated. Transmembrane passage of cytokine-inducing bacterial products across reprocessed dialyzers is greater than across new dialyzers. Bacteriological contamination of the dialysate fluid is a problem which must be considered with much more care by nephrologists, especially as LAL test is unable to detect all the bacterial products which can contaminate the dialysate fluid.