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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

At least 73 records · Page 4Linked to original sources

A faster twitch contraction of soleus in the spontaneously hypertensive rat is partly due to changed fibre type composition.

Contractile properties and fibre type composition of slow-twitch soleus muscles from spontaneously hypertensive rats (SHR) were compared with those from a control normotensive strain (Wistar-Kyoto, WKY). Male rats aged around 100 days were used, and muscle tension was recorded isometrically in vitro. Tetanic tension was reduced by about 15% in SHR; this decrease was highly significant when tension was expressed relative to muscle cross-sectional area. Twitch contraction and relaxation were 12-15% faster in SHR. There were no differences in the rate of rise of tension of either tetani or twitches, but the relaxation of tetanic tension was 17% faster in SHR. Twitch:tetanus ratios were 20% smaller in SHR. Histochemistry showed that SHR muscles had a threefold higher proportion of fast type II fibres compared to WKY. There were no significant changes in the contractile properties of the fast-twitch extensor digitorum longus (EDL) muscles of SHR compared with WKY. Whilst the higher proportion of type II fibres could account for some of the contractile changes in SHR soleus muscles, the lack of any difference in the rate of rise of twitch and tetanic tension is not consistent. The faster rate of relaxation of both twitch and tetanus in SHR suggests that a higher rate of removal of calcium, either from the myofilaments or from the cytoplasm, may be an important factor in causing the changes in SHR soleus. The faster relaxation may be compared with a similar change reported in SHR cardiac myocytes.

Animals↗

The role of social support in compliance and other health behaviors for African Americans with chronic illnesses.

Social support plays a positive role in compliance and other health behaviors. The purpose of this study was to investigate the role of social support in compliance and other health behaviors for patients with sickle cell disease and diabetes. Subjects consisted of 49 patients with sickle cell disease and 78 patients with diabetes attending outpatient clinics at an urban hospital. Subjects were given questionnaires which assessed their appointment-keeping behavior, adherence to health activities, and social support. The results indicated that social support was significantly associated with appointment-keeping behavior and adherence to health activities in both the sickle cell and the diabetic sample. Implications of the study findings for improving compliance by increasing social support are discussed.

Adolescent↗

Investigation of an outbreak of "humidifier fever" in a print shop.

An outbreak of "humidifier fever" affected 16 (57%) of 28 workers in a print shop. The most common symptoms were myalgia, chills or subjective fever, and cough. Illness began 5-13 hours after entering the workplace, and lasted 2-24 hours. A humidifier in use the day of the outbreak was found to be contaminated with fungi, amebae, and Gram-negative bacteria. The risk of illness was highest for those who had been on the job 3 months before the outbreak, a time when the humidifier was in constant use. Serologic studies of print shop workers showed positive reactions to extracts of organisms isolated from the humidifier, but could neither distinguish ill from well workers, nor identify causative organisms. The presence of endotoxin-producing bacteria and the clinical syndrome are consistent with an organic dust toxic syndrome. Previous exposure appeared to be the major risk factor for illness.

Acute Disease↗

Differences between contractions in vitro of slow and fast rat skeletal muscle persist after random reinnervation.

1. The medial popliteal nerve was sectioned in adult rats, and reinnervation was permitted after nerve reunion. Reinnervation was observed in soleus (slow twitch) and plantaris (fast twitch) muscles for periods of 4-21 months after the initial operation. 2. In the reinnervated muscles, isometric twitch time to peak (contraction time) and time to half-relaxation were longer in soleus than plantaris in every muscle examined. 3. Some of the muscles were stained for actomyosin ATPase activity. The proportion of type I fibres (presumed slow) was at least twice as high in soleus compared with plantaris muscles. The proportion in the latter was similar to that predicted from random reinnervation. 4. The effects of differing proportions of fast and slow fibres on the twitch contraction and half-relaxation times were modelled, and the experimental twitch data were found to be compatible with the proportions of fibre types in individual muscles. 5. It is speculated that the mechanism accounting for the higher proportion of slow fibres in soleus muscle probably does not involve selective reinnervation. It is suggested that fast motoneurones may be transformed to slow by a trophic chemical released by slow muscle fibres; such a process would be more extensive in predominantly slow twitch soleus than a fast muscle, and the resulting decrease in the proportion of fast motoneurones would account for the less extensive conversion in soleus.

Adenosine Triphosphatases↗

Complex iliac arterial trauma: autologous or prosthetic vascular repair?

The methods for vascular reconstruction of iliac arterial trauma can be a challenging problem. Primary arterial repair is usually possible, but an extensive injury may require interposition grafting or extra-anatomic bypass. Some investigators have advocated prosthetic grafting as a reasonable method of repair for complex iliac arterial injuries. We challenge this concept and describe our experience with the exclusive use of autogenous vascular repair during involvement with 87 consecutive patients surviving iliac arterial trauma.

Adult↗

Novel thiazolidine-2,4-diones as potent euglycemic agents.

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.

Alcohols↗

Hormonal responses to removal of a breeding male in the cooperatively breeding white-browed sparrow weaver, Plocepasser mahali.

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.

Aggression↗

Migration and chemiluminescence of polymorphonuclear cells and monocytes to Bacteroides sonicates.

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.

Bacteroides↗

A comparison of fibrillation in denervated skeletal muscle of the anaesthetized rat and guinea-pig.

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.

Animals↗

Morphology of long-term denervated rat soleus muscle and the effect of chronic electrical stimulation.

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.

Actin Cytoskeleton↗

Effects of chronic electrical stimulation on contractile properties of long-term denervated rat skeletal muscle.

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.

Animals↗

Histamine and endotoxin contamination of hay and respirable hay dust.

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.

Agricultural Workers' Diseases↗

High-performance liquid chromatographic method for the evaluation of possible interferences in basophil-histamine release measurements.

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).

Basophil Degranulation Test↗

Observations of the use of o-phthalaldehyde condensation for the measurement of histamine.

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.

Histamine↗

Cytotoxic and immunostimulatory effects of Bacteroides cell products.

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.

Analysis of Variance↗