Central poststroke pain and Wallenberg''s lateral medullary infarction: frequency, character, and determinants in 63 patients

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.     

Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB/c mice: role of gamma interferon and macrophage activation

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in bacterial counts in the spleens and livers of anti-IL-12-treated mice that were 10- to 100-fold higher than the ones normally observed in premortem mice; yet the animals showed only mild signs of illness. Nevertheless, they eventually died of a slow, progressive disease. Mice infected with salmonellae become hypersusceptible to endotoxin. We found that IL-12 neutralization prevented the death of infected mice following subcutaneous injection of lipopolysaccharide. Granulomatous lesions developed in the spleens and livers of control animals, as opposed to a widespread infiltration of mononuclear cells seen in the organs of anti-IL-12-treated mice. In the latter (heavily infected), salmonellae were seen within mononuclear cells, indicating an impairment of the bactericidal or bacteriostatic ability of the phagocytes in the absence of biologically active IL-12. Gamma interferon (IFN-gamma) levels were reduced in the sera and tissue homogenates from anti-IL-12-treated mice compared to those in control animals. Furthermore, fluorescence-activated cell sorter analysis on spleen cells showed that IL-12 neutralization impaired the upregulation of I-Ad/I-Ed antigens on macrophages from infected mice. Inducible nitric oxide synthase and IFN-gamma mRNA production was down-regulated in anti-IL-12-treated mice, which also showed an increased production of IL-10 mRNA and a decrease in nitric oxide synthase activity in the tissues. Administration of recombinant IFN-gamma to anti-IL-12-treated mice was able to restore host resistance, granuloma formation, and expression of major histocompatibility complex class II antigens in F4/80(+) and CD11b+ spleen cells.     

Nocistatin reverses nociceptin inhibition of glutamate release from rat brain slices

We have examined the effects of the recently described heptadecapeptide nocistatin on K+-evoked glutamate release from rat cerebrocortical slices in vitro. In vivo, nocistatin reverses the action of nociceptin. Nocistatin (100 nM, n = 7) did not inhibit K+-evoked glutamate release alone. Nociceptin (100 nM) inhibited glutamate release by 51.7 +/- 8.3% (P < 0.05, n = 6) and this was fully reversed by nocistatin (100 nM). Nocistatin also appears to be an antagonist of nociceptin action in vitro.     

Incorporation of nitric oxide-releasing crosslinked polyethyleneimine microspheres into vascular grafts

Over the years, many attempts have been made to increase the patency of small- to medium-sized prosthetic vascular grafts. However, none of them has greatly affected long-term rates. Recently, nitric oxide (NO) has been shown to inhibit thrombus formation in such grafts, suggesting that local delivery of NO may help to increase graft patency. This study describes the site-specific delivery of NO by entrapping NO-releasing microspheres in the pores of a vascular graft. NO-releasing polyethyleneimine microspheres (PEIX) were developed using a novel water-in-oil emulsion technique involving chemical crosslinking with a bis-epoxide. The PEIX microspheres were then derivatized with NO forming the [N(O)NO]- moiety of the diazeniumdiolates formerly known as NONOates. These polymeric NO-releasing particles were found to spontaneously release 194 nmol NO/mg with a half-life of over 66 h under physiologic conditions. Fluorescein isothiocyanate-labeled microspheres were then embedded into the pores of a 60-micron nonreinforced Gore-tex vascular graft using a simple evacuation technique and evaluated for microsphere placement and NO release. Scanning electron microscopic analysis showed the microspheres entrapped in the pores of the vascular graft releasing 10 nmol NO/mg with a half-life of 51 h. The microspheres remained entrapped in the graft even after immersion and NO release, as confirmed by fluorescence of the medium. These results suggest that NO-releasing particles can be incorporated into the pores of a vascular graft to deliver therapeutic amounts of NO for the prevention of thrombosis in small-diameter prosthetic grafts.     

Introduction: In-Use,In-Situ: Extending Field Research Methods—Part 2

This study used protocol analyses and user drawings of their models of the system to investigate the “getting lost” problem in hypertext navigation. The “getting lost” problem is viewed as occurring when routine expectations of naive users, concerning appropriate linear sequences, are violated. Several ways in which users persistently attempt to work within a linear model, despite its inapplicability, are examined. The transition to more hierarchical user models is described.     

Converting a Protease Assay to a Caliper® Format LabChip System

The push for higher throughput screening coupled with the desire to use smaller volumes of material has sparked the development of new technologies. Caliper Technologies, Corp. (Mountain View, CA) has designed a microfluidics chip with unique properties yet to be fully exploited. The translation from a traditional plate-based assay to a microfluidic chip format has provided insights into assay development, screening data requirements, and the technology itself. Running a screen with this new technology presented challenges in throughput, signal acquisition from slow-conversion enzymes, the provision for a negative control, the translation of a time series into a single data point per compound, reagent adhesion in the channels, and fluid property mismatches. Overcoming these obstacles has resulted in a simple, robust system with significant savings in reagent use. Measures to improve throughput and generalize the system will be discussed.     

Spontaneous output of acetylcholine from rat diaphragm preparations declines after treatment with botulinum toxin

A gas chromatographic spectrometric assay was used to measure tissue and released acetylcholine and choline in diaphragm preparations of rats previously injected with botulinum toxin type A. Botulinum intoxication was found not to alter the acetylcholine content of rat diaphragms in vivo or in fully paralyzed muscles in vitro. This result provides direct support for the hypothesis that botulinum toxin blocks transmitter release without affecting acetylcholine synthesis. However, in diaphragm preparations in vitro, this toxin was found to inhibit not only the evoked release of acetylcholine but also the spontaneous "leakage" of acetylcholine that is measured at rest. Additional experiments were performed to characterize this action of the toxin. The magnitude of the decline in resting acetylcholine output appears to be too large to be accounted for solely by the known effect of botulinum toxin to reduce the frequency of miniature endplate potentials. The mechanism of this action of botulinum toxin remains an enigma.     

Ion-pairs in proteins

A "working definition" for an ion-pair has been derived based upon analysis of the distance distributions for like- and oppositely charged groups in 38 proteins. Ion-pairs defined according to this criterion (less than or equal to 4 A between charged groups) have been analysed in respect of: (1) the frequencies of different pair types; (2) the residue separations and secondary structural locations of the residues involved; (3) the flexibility of the side-chains involved; (4) their conformation; (5) their environment (accessibility to solvent and proximity to active site or ligand binding regions); and (6) their conservation in related proteins. The results obtained indicate that on average one-third of the charged residues in a protein are involved in ion-pairs and 76% of these are concerned with stabilizing the tertiary (rather than the secondary) structure. Only 17% of ion-pairs are buried, and conservation of the interactions is generally low unless the residues involved have more specific functions to perform. In the light of the results obtained, the role of ion pairs in globular proteins is discussed.