Activation of mechanical responses in leukocytes

Different kinds of leukocytes undergo cytoskeleton-dependent mechanical responses associated with their specific physiological functions. We have investigated cellular stiffening of several types of leukocytes using a method which measures the force resisting cellular indentation. We have found that lymphocytes stiffen in response to crosslinking cell surface antigens in a process associated with the much studied capping and patching processes. Further studies of myosin-deficient mutants of the ameba Dictyostelium discoideum suggest that this stiffening process results from a myosin dependent contractile process. Rat basophilic leukemia cells and pancreatic islet cells stiffen when triggered to secrete. The function of these cytoskeleton dependent processes is now unknown, but, at least in the islet cells, may be related to a regulation of the rate of secretion. Primary neutrophils stiffen in response to the chemotactic agent, fMet-Leu-Phe. This stiffening may be responsible for retention of these cells in the pulmonary microcirculation during response to inflammation. These observations pose the challenge of determining the structural basis, mechanism, and physiological function of each of these cellular responses.     

NAPHTHOQUINONE INTERMEDIATE IN THE RESPIRATION OF BACILLUS STEAROTHERMOPHILUS.

Downey, R. J. (U.S. Department of Agriculture, Washington, D.C.). Naphthoquinone intermediate in the respiration of Bacillus stearothermophilus. J. Bacteriol. 84:953-960. 1962.-A vitamin K-like naphthoquinone has been isolated from Bacillus stearothermophilus. The compound was susceptible to light (360 mmu) and can be extracted from electron-transport particles with organic solvents. The reduced diphosphopyridine nucleotide (DPNH) oxidase and DPNH-cytochrome c reductase activities in such particles were restored to original levels by the addition of the extracted intermediate, by vitamin K(1), or by menadione. Phosphorylation coupled to the oxidation of malate was restored by addition of the isolated naphthoquinone. Discrepancies in the rate of succinate oxidase and succinate-naphthoquinone reductase activities suggested the intermediate functions in a collateral pathway in the succinate oxidase system of this organism. Anaerobic and aerobic cultivation of the microorganism produced no detectible differences in the character of the intermediate. Reduction of nitrate by the thermophile was not completely dependent upon the naphthoquinone but was significantly stimulated in its presence. No evidence was obtained for the existence of a mixed quinone system in the bacillus.     

Echolocation among the blind: an argument for an ontogenetic turn

Proponents of the ontological turn typically advance a highly conceptual understanding of variation in ontology. In contrast, this article argues theoretically that cultural canalizations of embodied ontogenetic processes — especially the development of local neurologies — underwrite distinct lived worlds. This theoretical argument for a corporeal basis of world-making draws on the case of vision-impaired individuals who actively echolocate, or perceive space using sound. Neurological evidence shows that echolocators’ sensory practices over developmental time produce specialized brain adaptations to behaviour. Human echolocation thus demonstrates how enculturation effaces the distinction between biology and culture in a behavioural-developmental spiral with implications for our understanding of human being.     

Laboratory Diagnosis and Characterization of Fungal Disease in Patients with Cystic Fibrosis (CF): A Survey of Current UK Practice in a Cohort of Clinical Microbiology Laboratories

There is much uncertainty as to how fungal disease is diagnosed and characterized in patients with cystic fibrosis (CF). A 19-question anonymous electronic questionnaire was developed and distributed to ascertain current practice in clinical microbiology laboratories providing a fungal laboratory service to CF centres in the UK. Analyses of responses identified the following: (1) current UK laboratory practice, in general, follows the current guidelines, but the scope and diversity of what is currently being delivered by laboratories far exceeds what is detailed in the guidelines; (2) there is a lack of standardization of fungal tests amongst laboratories, outside of the current guidelines; (3) both the UK CF Trust Laboratory Standards for Processing Microbiological Samples from People with Cystic Fibrosis and the US Cumulative Techniques and Procedures in Clinical Microbiology (Cumitech) Guidelines 43 Cystic Fibrosis Microbiology need to be updated to reflect both new methodological innovations, as well as better knowledge of fungal disease pathophysiology in CF; (4) there is a need for clinical medicine to decide upon a stratification strategy for the provision of new fungal assays that will add value to the physician in the optimal management of CF patients; (5) there is also a need to rationale what assays should be performed at local laboratory level and those which are best served at National Mycology Reference Laboratory level; and (6) further research is required in developing laboratory assays, which will help ascertain the clinical importance of ‘old’ fungal pathogens, as well as ‘emerging’ fungal pathogens.     

HIV as a surrogate marker for drug use: A re-analysis of the San Francisco Men's Health Study

Our analysis of drug use and morbidity data from a cohort of 1034 men yields the following results: 1) HIV infection is a strong indicator of drug use — HIV-positive respondents reported an average lifetime dose of recreational drugs (excluding marijuana) 2.3 times higher than HIV-negative respondents. 2) Homosexuality is a strong indicator of drug use — homosexual respondents reported an average lifetime dose 2.0 times higher than heterosexual respondents. 3) The incidence of AIDS-defining diseases was not limited to respondents infected with HIV, but was almost completely limited (98%) to respondents who reported using drugs. We also address a previous report (Ascheret al., 1993) that was based on the same database and purported to show that HIV alone correlates with the development of AIDS. Specifically, we show that the relationship between HIV infection and CD4+ T Cell loss is weaker than reported by Ascheret al., and provides little evidence for a causative relationship. These results support the hypothesis that long-term, habitual drug use can cause the conditions known as AIDS (independent of the presence of HIV), and refute the hypothesis that HIV alone causes these conditions independent of drug use.