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Biomedical subjects

C D Allred

Publications and source records attributed to C D Allred.

10 recordsLinked to original sources

Arthritis severity and spirochete burden are determined by serotype in the Borrelia turicatae-mouse model of Lyme disease.

Immunodeficient mice infected with Borrelia turicatae, a relapsing fever agent, have a disorder that resembles disseminated Lyme disease. Two serotypes, A and B, differed in their arthritogenicity in both CB-17 SCID and C3H SCID mice. In CB-17 SCID mice infected with serotype A or B, arthritis was assessed by measurement of tibiotarsal diameter, functional ability on a beam walk test, and microscopic assessment of joint inflammation. Serotype B-infected mice had greater joint swelling, functional disability, and leukocytic infiltration in the joints than serotype A-infected mice. Joint swelling and disability peaked at 2 weeks of infection and then decreased, while leukocyte infiltration in the joints persisted. To investigate the basis for the differences in arthritogenicity of serotypes A and B, spirochete burdens in infected mice were measured by quantitative PCR of spirochete DNA in joints, direct immunofluorescence of spirochetes in joints, and counts of spirochetes in the blood. At 2 weeks of infection there were seven times more spirochetes in the joints of serotype B-infected mice than in those of serotype A-infected mice, measured by both quantitative PCR and direct enumeration. Although serotypes A and B had the same infectivity and growth rate in vivo, serotype B spirochetes were eightfold more abundant in the blood than serotype A spirochetes and produced greater fatality in newborn mice. These findings indicate that differences in disease severity in mice infected with serotype A or B are attributable to differences in the spirochete burden in the joints and blood.

Animals

Ultrastructure of synovial chondromatosis.

Electron microscopic examination in a case of synovial chondromatosis associated with moderate cytological atypia showed chondrocytes with abundant rough endoplasmic reticulum, prominent Golgi complexes, and peripheral aggregates of glycogen. These findings emphasize the similarity in ultrastructural appearance of chondromatosis, mature hyaline cartilage, and benign cartilaginous tumors and thus support the generally benign nature of synovial chondromatosis.

Ankle Joint

Primary fenal angiosarcoma: a case report.

A 67 year old white male presented with a two week history of mild hematuria and flank pain. Various radiologic studies demonstrated a vascular mass in the right kidney. At nephrectomy a large renal angiosarcoma with fixation to the liver and multiple pulmonary metastases was found.

Aged

Luminol-induced neutrophil chemiluminescence.

Out studies suggest that luminol directly enhances the chemiluminescence of human neutrophils. We show that a significant peak in chemiluminescence production in a particle-free system occurs between 5 and 15 min following exposure of cells to micromolar concentrations of luminol. The response is directly related to dose over a wide rane of luminol concentrations and can be inhibited by superoxide dismutase (90%), catalase (100%) and sodium azide (40%). Evidence is presented which suggests that the effect of luminol eliciting a peak in neutrophil chemiluminescence is mediated within intact cells rather than at the cell membrane. Luminol may produce a peak in chemiluminescence by stimulating very low levels of hexose monophosphate shunt activity and superoxide generation or it may simply amplify light production generated by the production of excited oxygen radicals resulting from surface interactions.

Azides

Chemiluminescence by polymorphonuclear leukocytes from patients with active bacterial infection.

Polymorphonuclear leukocytes of 18 patients during 19 episodes of active bacterial infection produced increased chemiluminescence (mean +/- standard error [SE], 56.3 +/- 4.4 X 10(3) cpm) when the production was compared to that of 29 uninfected controls (35.3 +/- 2.4 X 10(3) cpm; P less than 0.01). Chemiluminescence production remained increased with persistent infection but fell to the levels of controls with appropriate therapy. Phagocytic uptake as determined with radiolabeled bacteria was increased, and chemotactic responsiveness was markedly enhanced in the patients (mean index +/- SE, 260 +/- 51) when these responses were compared with those of controls (77 +/- 18). Chemiluminescence and chemotactic activity correlated in the patients with bacterial infection (r = 0.76), but one function did not appear to depend upon the intactness of the other. The ratio of cyclic guanosine 3',5'-phosphate to cyclic adenosine 3',5'-hosphate in the polymorphonuclear leukocytes of patients with infections (mean +/- SE, 0.102 +/- 0.0008) was also significantly higher than in controls (0.067 +/- 0.007). These data indicate that the polymorphonuclear leukocytes of the majority of patients with active bacterial infection are in an activated state both functionally and metabolically.

Adolescent

Influence of phenylbutazone on leukocyte chemiluminescence and function.

The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular killing of bacteria has been examined. A marked reduction of chemiluminescence and intracellular killing of bacteria was observed. The effect on phagocytosis was less pronounced. High drug concentrations nearly abolished light emission, and concentrations equivalent to those obtained in plasma during therapy caused a 25--30% reduction. The effect occurred within less than 10 minutes. No permanent effect upon resting cells was observed. Phenylbutazone reduced the effect of sodium azide on leukocyte chemiluminescnece, indicating that the drug might also inhibit myeloperoxidase dependent chemiluminescnece. Whether these impairments of leukocyte function also take place in vivo resulting in enhanced susceptibility to infection remains unknown.

Azides

Effect of chemoattractants on chemiluminescence.

Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments reported here, the influence of three chemoattractants and three chemotactic modulators upon the chemiluminescence induced by opsonized zymosan was studied. The chemoattractants investigated (including bacterial factor derived from Escherichia coli, the simple peptide formylmethionylalanine, and activated human complement), which initiate directed movement when presented to cells in a concentration gradient, significantly enhanced zymosan-induced chemiluminescence. In the absence of opsonized zymosan, however, they had no effect on the chemiluminescence response. In contrast, the chemotactic modulators studied (including carbamylcholine, phenylephrine, and cyclic guanosine 5'-monophosphate, which are not chemotactic by themselves but can enhance or depress the movement of polymorphonuclear leukocytes initiated by chemoattractants) produced no enhancement of chemiluminescence. Other experiments were carried out in which neutrophils were pretreated with cytochalasin D, a compound that inhibits phagocytosis by interacting with microfilaments. Under these conditions, the chemiluminescence induced by opsonized zymosan was markedly reduced, but the response resulting from the addition of a chemoattractant to the leukocyte/zymosan mixture was not. This indicates that the chemiluminescence in response to chemoattractants is not dependent on phagocytosis per se. Neutrophils were also pretreated with dinitrofluorobenzene, a compound that binds amino groups and can be expected to react with proteins on the cell membrane. In these experiments, the chemiluminescence induced by opsonized zymosan and the pronounced spike of activity produced by the addition of a chemoattractant were completely abolished. These results suggest that the polymorphonuclear leukocyte chemiluminescence response to chemoattractants is mediated by cell surface proteins. Thus, chemoattractants may have a dual role in the acute inflammatory response: (i) the initiation and maintenance of directed cell movement, and (ii) enhancement of metabolic steps mediated at the cell membrane, resulting in microbicidal activity.

Bacterial Physiological Phenomena

Role of antibody and complement in opsonization of group B streptococci.

A requirement for the classic complement pathway in opsonization of group B streptococci was observed by using both a chemiluminescence and a radiolabeled bacterial uptake technique. The classic pathway increased levels of opsonization for types Ia and II stock and wild strains and for some type III wild strains. In contrast, other type III wild strains and the type III stock strain had accelerated kinetics of uptake in the presence of an intact classic pathway, but the level of opsonization was unchanged from that with antibody alone. We could not demonstrate a significant role for the alternative pathway in opsonizing stock or wild strains of group B streptococci. Futhermore, electrophoretic and complement consumption analysis by hemolytic titration failed to reveal alternative pathway activation by the majority of strains of this group. Therapy aimed at supplying opsonins for these organisms will require the presence of type-specific antibody.

Antibodies, Bacterial