Biomedical subjects
Publications and source records attributed to D M Lewis.
A new series of thiazolidine-2,4-diones was obtained by replacing the ether function of englitazone with various functional groups, i.e., a ketone, alcohol, or olefin moiety. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Appending an oxazole-based group at the terminus of the chain provided highly potent compounds.
The white-browed sparrow weaver (Plocepasser mahali) is a cooperatively breeding Ploceid finch that lives in groups of up to 11 individuals. Each group consists of a dominant breeding male and female and a varying number of nonreproductive birds that help feed young and defend the group territory. Experimental removal of the dominant male resulted in attempts by other males to take over the group. Removal of a subordinate, nonbreeding male, as a control, resulted in no change of status among group members. During takeover, there was a transitory increase in plasma levels of luteinizing hormone in the new dominant male, but no change in testosterone levels. As reported in previous investigations, dominant males tended to have higher levels of testosterone than females or subordinate males, but this was not related to the heightened aggression of the takeover. Plasma levels of luteinizing hormone, testosterone, and corticosterone did not differ between the other status groups. The possibility that luteinizing hormone, or a hitherto unidentified androgen, may regulate aggression in the white-browed sparrow weaver is discussed.
Recent investigations have demonstrated that various preparations obtained from representatives of the genus Bacteroides are poorly phagocytized by polymorphonuclear cells (PMN) and macrophages. Crude cell sonicates derived from Bacteroides have been examined for their ability to inhibit migration of PMN and monocytes using a modified migration under agarose in vitro assay. B. gingivalis and B. intermedius were found to be inhibitors of such migration while B. asaccharolyticus did not share this property (P less than 0.005). In addition, B. intermedius sonicates were found to inhibit PMN chemiluminescence to known stimulants (P less than 0.001). These data were not found to result from direct sonicate cytotoxicity and therefore lend additional support to the etiologic importance of specific Bacteroides strains in the pathogenesis of acute and chronic dentoalveolar infections.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have used intracellular recording in vivo to study fibrillation (spontaneous repetitive membrane activity) in extensor digitorum longus (fast twitch) and soleus (slow twitch) muscles of the anaesthetized rat and guinea-pig denervated for periods of about 10 to 60 days. The proportion of fibres fibrillating in the guinea-pig soleus was greater than 50% in most animals up to the longest period of denervation (65 days). Fibrillation was rarely found in rat soleus after three weeks of denervation. Its incidence in the extensor digitorum longus muscles of both species was intermediate. The mean frequency of fibrillation was higher in guinea-pig extensor digitorum longus (16 Hz) and soleus (8 Hz) than in the rat extensor digitorum longus (3 Hz) and soleus (2 Hz). The resting membrane potentials of the denervated muscles were less than normal and correlated inversely with the frequency of fibrillation but not with the incidence of fibrillation: in rat soleus, many fewer fibers were fibrillating at a given membrane potential than in the other three muscles. The incidence of fibrillation was compared with previously reported tensions of the four denervated muscles and was found to have the same rank order. We suggest that fibrillation may reduce atrophy (and hence tension loss) of denervated muscle, which may have implications for artificial stimulation. Fibrillation frequency was directly related to changes in twitch speed of the four muscles after denervation.
1. Rat soleus muscles were denervated for 6-10 months; some of these were chronically stimulated for the last 3-8 weeks before recording. The muscles were fixed at physiological lengths and embedded in epoxy resin. 2. Sections for light microscopy were stained with p-phenylenediamine. Denervation reduced the mean cross-sectional area of fibres to 3% of controls (peak at 20 microns2). The cross-sectional areas of the stimulated fibres had a peak at 70 microns 2. In light micrographs of denervated muscles, the total number of fibres appeared to be reduced; however not all fibres could be identified (see paragraph (3)). 3. In the electron microscope, many fibres showed disarrayed myofilaments. Few fibres had more or less normal cross-striations. Muscle fibres as small as 1 micron in diameter were seen. The smallest fibres did not contain myofilaments. Some unequivocally necrotic fibres were seen. 4. Most stimulated denervated fibres showed an almost normal sarcomere pattern. Scattered throughout the muscle were single fibres as small as 2 microns in diameter, but these were well organized and could be recognized in the light microscope. Few fibres were necrotic. Often fibres were serially arranged. Satellite cells were prominent. 5. It is concluded that in long-term denervated rat soleus the original fibres are lost and those seen are the result of repeated cycles of regeneration and necrosis. Stimulation maintains the sarcomeres and probably prevents secondary degeneration and necrosis.
1. The contractile properties of fast-twitch (extensor digitorum longus or EDL) and slow-twitch (soleus) muscles in the rat were followed for periods of between 4 and 10 months after denervation. The effects of chronic electrical stimulation during the last 3-8 weeks of denervation were investigated. 2. The fall in tetanic tension that follows axotomy ended after about 4 months' denervation. The equilibrium tension was about 0.75% of control tension in EDL and 0.2-0.3% in soleus. 3. The low tension in soleus was due partly to the small diameter of the muscle fibres (atrophy) and partly to their necrosis that resulted in an 8-fold fall in specific tension (the force per unit cross-sectional area). Similar but less extreme changes occurred in EDL. 4. It is speculated that the final level of tension reached by unstimulated denervated muscles is an equilibrium between decrease in force due to atrophy and necrosis and increase due to regeneration. Differences between the final tension levels in soleus and EDL cannot be accounted for quantitatively by known differences in atrophy alone. Therefore, the rate of necrosis in soleus and of regeneration in EDL may be higher. 5. Chronic stimulation of long-term denervated muscle increased force generation by about 7-fold in EDL and between 20 and 55 times in soleus. The final tension reached was between 4 and 5% of normal in both muscles. Specific tension of fibres was almost completely restored by stimulation and the number of fibres was normal. The failure to recover full tension was largely due to failure to reverse denervation atrophy completely. 6. Twitch contraction and relaxation times were identical in denervated-stimulated soleus and EDL. There was no evidence for dependence on duration of stimulation or tension of the muscle. The normalized maximum rate of rise of tetanic tension remained higher in EDL than soleus.
Three distinct samples collected from a barn in which an outbreak of respiratory problems occurred were examined for possible etiologic agents. No causal relationship could be established from the results of this study; however histamine concentrations as high as 0.5 ng/mg for bulk hay (in the absence of measurable creatinine levels) along with 6138.3 endotoxin units/mg of hay were present in the samples. Both endotoxin and histamine could be recovered from respirable hay dust. The authenticity of the histamine found in the hay was evaluated with high-performance liquid chromatography and radioimmunoassay. Histamine release caused by hay extracts was evaluated with the use of leukocytes from the farmer and a referent. Histamine is known to modulate the immune system, but the role of occupational or environmental exposure to histamine in respiratory disease is unknown.
Basophil activation studies commonly rely on the measurement of histamine following extraction and condensation to o-phthalaldehyde (OPT) as a quantitative measurement of degranulation. Specificity has long been recognized as a problem with this method. We have described a new high-performance liquid chromatographic method that allows for both a qualitative and a quantitative check of the purity of the OPT-histamine adduct. This method was sensitive (limit of detection = 2.55 pmol) and linear over a wide range (5 to 1000 ng/ml).
The in vitro study of mast cell degranulation utilises the measurement of histamine as a quantitative marker of this process. Histamine is most commonly assayed, following organic extraction, by condensing it with o-phthalaldehyde (OPT) and thereby obtaining a highly fluorescent adduct. A number of variables that might affect the performance of this assay, including assay conditions, stability and purity, were evaluated during the course of developing this assay for use in our laboratory. We observed the stability of OPT-histamine and found it to be very stable at 0 and 25 degrees C, following acidification. Derivatisation conditions and the purity of the leukocyte histamine extract were also assessed, and indicated that derivatisation at low temperatures slows down decay, providing a greater over-all fluorescence intensity. Extraction procedures are necessary, prior to condensation with OPT, to eliminate both positive and negative interfering substances from leukocyte preparations.
The etiologic role of Bacteroides in both periodontal and periapical infections has been well documented, with current interest focusing on the specific pathogenic mechanisms involved. The effects of cell fractions derived from Bacteroides gingivalis (BG), Bacteroides intermedius (BI), and Bacteroides asaccharolyticus (BA) have been studied in vitro through: an assessment of the direct cytotoxic effects on human gingival fibroblasts using a tetrazolium dye reduction assay, an evaluation of murine lymphocyte stimulation and interleukin-1 release, and the induction of human lymphocyte-mediated cytotoxicity. Both BG and BI stimulated interleukin-1 release (P less than 0.001), while BA, a nonoral organism, was not significantly active in this respect. Only BG sonicates were able to induce lymphocyte-mediated cytotoxicity (P less than 0.005). All three Bacteroides species demonstrated direct cytotoxic effects on cultured gingival fibroblasts, and these effects were related to the relative protein content and endotoxin activity of the sonicate preparations for each organism. These data show that BG and BI possess factors which may enhance their virulence through activities not shared with BA.
Zymogen-stimulated neutrophils release many pre- and non-preformed factors including proteolytic enzymes, oxygen free radicals and arachidonic acid metabolites. Measurement of the histamine concentration of a supernatant fluid commonly employs an organic extraction procedure followed by condensation to o-phthalaldehyde. Diamine oxidase digestion studies and high-performance liquid chromatographic analysis suggest that a factor(s) derived from zymogen-stimulated neutrophils can produce a positive interference in the fluorometric determination of histamine.
Fourteen samples of settled dust from two factories processing rice and wheat straw near Shanghai, China, were examined by dilution plating for total bacteria, gram-negative bacteria, thermophilic actinomycetes, and fungi. They were also examined for aflatoxin, endotoxin, and potential to stimulate production of human interleukin 1 beta (IL-1 beta) and to consume complement. The concentrations of total microorganisms were consistently greater than 10(7) CFU/g and ranged from 10(7) to 10(9) CFU/g. In general, the level of microbial contamination was greater in the hay dust samples than in the rice dust samples, with bacteria being the most numerous microorganisms observed followed by molds, thermophilic actinomycetes, and yeasts. The predominant fungi were species of Aspergillus, Cladosporium, Penicillium, Trichosporon, and Cryptococcus. No significant levels of aflatoxin were observed and the isolates of A. flavus examined lack significant aflatoxigenic potential. The levels of microorganisms in these samples, the types of organisms found, and the inflammatory mediators such as endotoxin suggest that workers exposed to these dusts may be at risk for respiratory illness.
Bone scans were evaluated in 57 patients referred from the nuclear medicine clinic. Areas of normal and abnormal radiopharmaceutical accumulation in the maxilla and mandible were correlated with a clinical and radiographic dental examination. There was an 80% agreement between the areas of normal and abnormal uptake with the clinical and radiographic findings. This was statistically significant (p less than 0.001). Twenty-one patients had clinical and radiographic dental examinations that were within normal limits and yet had abnormal bone scans. Five of these 21 patients were subsequently seen on an emergency basis for treatment of dental abnormalities. These positive areas on the bone scans may be indicating areas of pathosis not detectable by conventional clinical and radiographic diagnostic techniques.
1. Physiological properties of motor units in the soleus muscle were studied in anaesthetized rats using ventral root splitting to isolate single units. 2. Motor unit types were classified by the same criteria used to classify cat hindlimb motor units into types FR (fast-twitch, fatigue-resistant) and type S (slow-twitch, fatigue-resistant). Type FR units were estimated to generate 10% of whole-muscle tension and type S 90%. All FR units showed sag in the unfused tetanus at frequencies with interpulse intervals greater than 175% of twitch time to peak, but not at 125% (Burke, Levine, Tsairis & Zajac, 1973). 3. The muscle fibres belonging to twelve single motor units were depleted of glycogen by prolonged stimulation, permitting analysis of their histochemical profiles. Type FR units were found to consist of type IIA muscle fibres and type S units of type I muscle fibres. 4. Direct determinations were made of fibre area, innervation ratio (number of muscle fibres supplied by one motoneurone) and hence specific tension (tetanic tension generated per unit cross-sectional area) of individually identified motor units. Motoneurons were found to innervate between 84 and 178 muscle fibres (mean 110) in type S units and between 126 and 161 fibres in type FR units (mean 142). Fibre areas were larger for type FR units and there was a significant difference in specific tension of the two unit types (type S lower). 5. Indirect estimates of innervation ratio and specific tension were obtained from counts of muscle fibre types, and relative frequencies of motor unit types in the soleus unit pool. Observations agreed well with results of direct measurements. 6. The evidence provided suggests that differences in tension generated by type FR and S units in rat soleus muscle are primarily due to differences in innervation ratio and fibre area, with a small contribution from differences in specific tension.
1. A fast (extensor digitorum longus) and slow (soleus) twitch muscle were denervated in rats and guinea-pigs and isometric and isotonic contractions were followed for periods of up to 6 months after. 2. The decay of tetanic tension with time could be described as exponential. The rate of decay of tension was greatest in rat soleus and least in guinea-pig soleus by a factor of more than three. The fast muscles atrophied at intermediate rates. 3. The contraction and relaxation times of soleus and extensor digitorum longus of rat, initially prolonged by denervation, became shorter after 3 weeks. There was no such reversal in either guinea-pig muscle, indeed extensor digitorum longus twitch became even more prolonged. Guinea-pig muscles often showed signs of repetitive response to a single stimulus, resulting in distortion of relaxation of the twitch. 4. There was a slowing of isotonic shortening velocity in the late stage of denervation of guinea-pig extensor digitorum longus, accompanied by a fall in the rate of development of isometric tetanic tension. There was a just-significant (P less than 0.1) increase in the shortening velocity of rat soleus. None of the other muscles showed any change in either rate characteristic. 5. In guinea-pig extensor digitorum longus the type I fibres atrophied less than type II fibres; in all other muscles the atrophy was more uniform, possibly faster in type II. Guinea-pig soleus remained pure type I contrasting with an increase in the numbers of type II fibres in rat soleus. There was a possible increase in the number of type I fibres in guinea-pig fast muscle and no change in the rat.