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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

At least 109 records · Page 6Linked to original sources

The frequency of sicca syndrome in an elderly female population.

In a population of 103 elderly Caucasian women, 39% had sicca symptoms and 24% had abnormal Schirmer's tear tests. Two (2%) satisfied criteria for Sjögren's syndrome and 12 (12%) were felt to have possible Sjögren's syndrome. Fifty percent of those with sicca were taking medications that might induce mucosal dryness. Fibrosis was noted on all 23 labial minor salivary gland biopsy specimens obtained. Mucosal drying medications and senile salivary gland atrophy seemed to contribute to the high frequency of sicca in this population with a lesser proportion of the subjects demonstrating previously undiagnosed Sjögren's and possible Sjögren's syndrome.

Aged↗

Chronic stimulation modifies the isotonic shortening velocity of denervated rat slow-twitch muscle.

Rat soleus muscles were denervated and stimulated in vivo for periods of up to 104 days. Stimuli used were trains of 1 ms pulses at 100 Hz delivered for periods of 1 s; trains were repeated every 10-100 s. In a majority of animals the tension of the muscles was maintained at about 10% of normal, equivalent to muscles denervated but unstimulated for 20 days. At the longest periods the stimulated muscles developed ten times more tension than ones that were denervated but not stimulated. In denervated and denervated-stimulated muscles twitch contraction and relaxation times were prolonged, compared with controls, for up to 3 weeks. Thereafter both sets showed a speeding of the isometric twitch that was greater in the stimulated muscles. At the longest periods the twitch was as short as that of a denervated fast muscle. Stimulation did not affect contralateral denervated muscles. Twitch: tetanus ratios remained high despite stimulation, and muscles showed little post-tetanic potentiation. Tension developed more rapidly in the tetani of the stimulated muscles, even allowing for larger final values. Maximum velocity of shortening was increased in many of the stimulated muscles, and there was a proportional flattening of the force-velocity curve, i.e. a/P0 increased. Maximum velocity and a/P0 increased reciprocally with twitch time to peak, so that those muscles that had twitches most changed by stimulation also had their isotonic properties modified to the greatest extent. Even at the longest period of stimulation, twitch time course and tetanic tension were not converted to those of normal fast muscle.

Animals↗

Mechanical properties of denervated amphibian muscle.

Denervated amphibian muscle does not show the prolongation of action potential found in mammalian denervated muscle. It was, therefore, predicted that denervated amphibian muscle would not show prolongation of the mechanical twitch. The sartorius muscles in one leg of toads--Xenopus borealis--were denervated for 140-268 days. Isometric twitch time to peak, time to half relaxation and twitch/tetanus ratio were not changed following denervation, confirming our prediction. Twitch tension decreased to 68% and tetanic tension decreased to 75% of control values. The maximum velocity of unloaded shortening (muscle length/s) was also unchanged.

Action Potentials↗

Micropuncture studies of receptor-mediated endocytosis of transferrin in the rat epididymis.

The concentration of transferrin in fluids collected by micropuncture techniques from the rete testis and zones 1A, 2, 5A, and 6B of the rat ductus epididymidis was 44, 527, 113, and 49 ng/microliter, respectively. When changes in fluid volume were taken into account, it was found that transferrin was concentrated by the efferent ducts, whereas the amount of endogenous luminal transferrin declined from the caput to the cauda epididymidis. Using transferrin-gold as an electron dense marker, we showed that the decline in the concentration of transferrin along the epididymis could be attributed to its cumulative receptor-mediated endocytosis by the lining principal cells. No significant difference in the net receptor-mediated endocytosis of transferrin-gold was found between the proximal caput and corpus epididymidis in vivo.

Animals↗

Composition of extracts of airborne grain dusts: lectins and lymphocyte mitogens.

Airborne grain dusts are heterogeneous materials that can elicit acute and chronic respiratory pathophysiology in exposed workers. Previous characterizations of the dusts include the identification of viable microbial contaminants, mycotoxins, and endotoxins. We provide information on the lectin-like activity of grain dust extracts and its possible biological relationship. Hemagglutination of erythrocytes and immunochemical modulation by antibody to specific lectins showed the presence of these substances in extracts of airborne dusts from barley, corn, and rye. Proliferation of normal rat splenic lymphocytes in vitro provided evidence for direct biological effects on the cells of the immune system. These data expand the knowledge of the composition of grain dusts (extracts), and suggest possible mechanisms that may contribute to respiratory disease in grain workers.

Animals↗

Prevalence of IgE antibodies to grain and grain dust in grain elevator workers.

IgE-mediated allergic reactions have been postulated to contribute to respiratory reactions seen in workers exposed to grain dusts. In an attempt better to define the prevalence of IgE antibodies in workers exposed to grain dusts, we performed the radioallergosorbent test (RAST) on worker sera using both commercial allergens prepared from grain and worksite allergens prepared from grain dust samples collected at the worksite. We found that the two types of reagents identified different populations with respect to the specificity of IgE antibodies present. The RAST assay performed using worksite allergens correlated well with skin test procedures. These results may allow us to gain better understanding of allergy associated with grain dust exposure, and document the utility of the RAST assay in assessment of occupational allergies.

Allergens↗

Toxicity of mycotoxins for the rat pulmonary macrophage in vitro.

The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages in vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers.

Animals↗

In vitro and in vivo changes in human complement caused by silage.

Aqueous extracts of silage samples from four farms in up-state New York were reacted in vitro with normal human serum. Hemolytic levels of complement component C3 were consumed in a dose-dependent fashion, and the four extracts differed in their relative activity rankings. Studies with chelated serum indicate that the alternative complement pathway is involved in the activation, and the active fragment C3b was demonstrated. Serum levels of hemolytic C3 and C4 in vivo were quantified before and after farmers performed their normal silo unloading operations. Although the study groups were small, suggestive evidence of in vivo complement consumption was found. IgE-related allergy did not appear to be of significance to the study groups. Complement activation may be an initiator of or contributor to adverse reactions in farmers who are exposed to airborne silage dusts.

Animal Feed↗

Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. I. Systemic toxicity.

The effects of subchronic inhalation exposure to isobutyl nitrite (IBN) on body weight, selected organ weights, hematology, and gross pathology and histopathology of BALB/c mice were evaluated. Mice of both sexes were exposed at 0, 20, 50, or 300 ppm IBN for 6.5 h/d, 5 d/wk for up to 18 wk. Most changes in measured indices occurred in mice exposed at 300 ppm IBN and included decreased thymus weight (females); decreased liver weight (males); decreased white blood cell counts (males); mild focal hyperplasia and vacuolization of the epithelium lining bronchi and bronchioles of the lungs (males and females). Organ weight and hematologic changes, however, were not accompanied by any observed histologic changes. In addition, elevated methemoglobin concentrations were detected in mice of both sexes exposed at 50 and 300 ppm IBN. Body weights were not adversely affected by exposure. These data suggest that mild tissue injury, restricted to the lung, and methemoglobinemia are the major toxic effects observed following exposures of mice to IBN at concentrations up to 300 ppm for 18 wk. No treatment-related effects were noted in mice exposed at 20 or 50 ppm IBN, except for slight elevations in methemoglobin concentrations in mice exposed at 50 ppm.

Animals↗

Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. II. Immunotoxicity studies.

Initial epidemiologic studies of acquired immunodeficiency syndrome (AIDS) occurring in homosexual men identified the use of the inhalants amyl, butyl, and isobutyl nitrite as possible risk factors contributing to the disease. Because of the lack of immunotoxicological data on these chemicals, we studied the effects of subchronic exposure to isobutyl nitrite (IBN) on the immune system. BALB/c mice were exposed to either 50 or 300 ppm IBN for 6.5 h/d, 5 d/wk for up to 18 wk. After 7, 13, or 18 wk of exposure, mice were killed and the following assays were performed. Antibody producing cells were enumerated by a slide plaque assay on animals immunized with sheep red blood cells while still in exposure chambers. The lymphocyte proliferative response to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen, and lipopolysaccharide) was tested using several concentrations of each mitogen. Additional mice were immunized with Freund's complete adjuvant 21 d prior to death and were tested for delayed hypersensitivity response to purified protein derivative by a radiometric skin test. Finally, the relative numbers of T cells and T-cell subsets among splenic lymphocytes from exposed and control animals were determined. At the time periods tested there were no discernable immunotoxic effects observed in the exposed animals in any of the assays performed. These results indicate that IBN, at the dosages tested, had no discernable detrimental effect on the immune system of mice.

Animals↗

Cryptic plasmid and rifampin resistance in Rhizobium meliloti influencing nodulation competitiveness.

An assessment was made of the relative contributions of a spontaneous mutation to rifampin resistance and a cryptic plasmid, pTA2, to competitive nodulation of Medicago sativa by a strain of Rhizobium meliloti. This was facilitated by use of rifampin-resistant derivatives of this strain in which pTA2 was originally present, cured, or reintroduced. Both curing of pTA2 and spontaneous mutation to rifampin resistance significantly influenced nodulating competitiveness, but the effect of rifampin resistance was greater and such that the contribution of pTA2 was evident only in cases in which paired competitors had the common rifampin resistance background. The data suggest that rifampin-resistant derivatives contain an altered RNA polymerase insensitive to the action of rifampin. All R. meliloti derivatives had symbiotic characteristics and phage susceptibility patterns similar to those of the wild type. Plasmid pTA2 transfer or other genetic interchange was not detected in nodules of M. sativa inoculated with paired competitors.

DNA Transposable Elements↗

The effects of T-2 toxin on alveolar macrophage function in vitro.

T-2 toxin, a metabolite of several Fusarium species, is a mycotoxin of the trichothecene family which occurs in a variety of grains. Previous work in our laboratory showed that T-2 toxin is highly toxic to rat alveolar macrophages in vitro at submicromolar concentrations. The present investigation was undertaken to study the basis of the cytotoxic effects observed. The following parameters of macrophage function were measured: macromolecular synthesis, release of 51Cr, cellular ATP, phagocytosis, and alveolar macrophage "activation." The incorporation of radiolabeled leucine into acid-precipitable molecules was significantly inhibited within 1 hr of treatment at sublethal concentrations, although amino acid uptake was unaffected. Cell volume and release of 51Cr was unaffected by 0.1 microM T-2 toxin after 6 hr but evidence of significant leakage was seen after 18 hr treatment. The capacity of alveolar macrophages to phagocytize Saccharomyces cerevisiae and 3H-Staphylococcus aureus was significantly reduced whereas binding of 3H-S. aureus to the macrophage was not. Macrophage activation with endotoxin (Escherichia coli lipopolysaccharide) and mitogen-generated lymphokines, as monitored by incorporation of [14C]glucosamine, was significantly altered at 0.01 microM T-2 toxin. Thus, the data clearly demonstrate that T-2 is toxic to alveolar macrophage function in vitro and suggest that the primary mechanism of this toxicity is related to the inhibition of protein synthesis.

Adenosine Triphosphate↗

Effects of coal dust and diesel exhaust on immune competence in rats.

The effects on the immune system of rats that had been exposed to a 2-mg/m3 dose of either respirable coal dust, diesel exhaust fumes and particulates, or the combination of these were studied. Animals that were housed similarly but exposed only to filtered air served as controls. After 12 and 24 mo of exposure, the rats were tested for immunocompetency by enumerating antibody-producing cells in the spleen 4 d after immunization with sheep erythrocytes and by monitoring the proliferative response of splenic T-lymphocytes to the mitogens concanavalin A and phytohemagglutinin. The results of this study indicate that no major alterations occurred in the immunologic functions measured as a result of exposure to either coal dust, diesel exhaust fumes and particulates, or their combination.

Animals↗

Immunoglobulin G receptors of intestinal brush borders from neonatal rats.

Intestinal absorptive cells of the neonatal rat display on their brush border membranes receptors for immunoglobulin G (IgG) which function in selective transfer of maternal IgG. Our Scatchard analysis of [125I]IgG binding to isolated brush borders has corroborated the presence of two classes of specific binding sites (KA1 = 2.4 X 10(7) M-1 and KA2 = 3.7 X 10(5) M-1) and the increase in overall binding with decreased buffer concentration, as shown by Wallace & Rees 1980. However, our Scatchard analysis of binding at different buffer concentrations indicates that the only significant effect of lowered buffer concentration is to increase the number of low-affinity sites. Neither the number nor the affinity of the high-affinity sites is affected. Furthermore, brush borders from rats at 21 days have only the low-affinity sites and at this age the selective transfer of IgG has ceased. Morphological experiments with tracers for both light and electron microscopy suggest that the high-affinity sites correspond to the specific IgG receptors on the apical membrane. The majority of the low-affinity sites are found within the terminal web and are likely not to be involved in selective transport of IgG.

Animals↗

Sulpiride trial in chronic schizophrenia with comparison of two dosage regimens.

In a study with both open and double-blind phases, a therapeutic response to sulpiride was first established in 18 chronic schizophrenic inpatients. Following this, two dosage regiments, a morning only dose, and the same daily total dose in two equal fractions at 8 a.m. and 4 p.m., were compared using a balanced design, crossover, placebo controlled study. Clinical effects were evaluated by means of the Brief Psychiatric Rating Scale (BPRS). There was a significant reduction in the mean BPRS score in all phases of the study. There was no significant difference between the mean BPRS scores resulting from the two dosage regimens. The study indicated that the two dosage regimens were equally efficacious.

Adult↗

Changes in humoral immunologic parameters after exposure to volcanic ash.

Occupational exposure to volcanic ash from Mount St. Helens continues during the salvaging of trees in the high dust blow-down area of Washington. We studied the effects of volcanic ash exposure on the level of humoral immune factors IgG, IgA, IgM, C3, C4, and ANA (antinuclear antibody) in a group of volcanic ash-exposed loggers shortly after the major eruption and one year later. Comparisons with similar levels in nonexposed, similarly employed, matched loggers were made. C3 and C4 levels were significantly lower at both time periods in the exposed loggers when compared to the reference group. No differences between groups were observed at either time period for the immunoglobulin levels or ANA. The exposed loggers did show a marked decrease (not seen in the reference group) in serum IgG levels after 1 yr of exposure to the volcanic ash. They likewise showed a significant mean increase in IgA, while the reference group had a mean increase in IgM after 1 yr. These data suggest that exposure to volcanic ash may affect humoral immunologic parameters.

Adult↗