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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 361 records · Page 20Linked to original sources
PubMed1983

Fibronectin beneath reepithelializing epidermis in vivo: sources and significance.

Fibronectin and fibrinogen occur under the migrating epidermal tongue during reepithelialization of an excisional wound, and fibronectin increases in conjunction with capillary and fibroblast ingrowth during wound healing. Although we have previously shown that fibronectin is produced by proliferating blood vessels, the source of fibronectin associated with reepithelialization and fibroblast ingrowth has not been determined. In this report we demonstrate that subepidermal fibronectin derives mostly from plasma early in reepithelialization of an excisional wound and comes from both plasma and in situ production late in reepithelialization. This finding was established by extirpating 3 mm of skin from the center of a well-healed rat xenograph on the flanks of immunosuppressed mice, harvesting the open wound sites at 2, 4, 7, and 10 days after injury, and staining the specimens with reciprocal species-specific anti-fibronectin antibodies conjugated with fluorescein. In the first 4 days after wounding, newly forming rat epidermis migrated mainly over mouse fibronectin. In contrast, by 7 days after excision, the rat epidermis transits over a matrix containing both mouse and rat fibronectin, or rat fibronectin alone, indicating that a major component of the fibronectin is produced in situ. Although the biologic significance of these observations has not been fully elucidated, fibronectin may be part of a provisional matrix that functions to support, if not actively participate in, cell recruitment to sites of inflammation or wound healing.

Animals↗
PubMed1983

Bronchocentric granulomatosis: a review and thoughts on pathogenesis.

Bronchocentric granulomatosis has no specific clinical, radiological or immunological features, the diagnosis remains that of morphology on biopsy or resected lung tissue. The morphological features of bronchocentric granulomatosis can occur in a variety of situations and we believe this pathology reflects one of the limited ways in which bronchi can respond to injury, the essential requirement for its development being a sustained and/or intense inflammatory insult within the bronchial lumen.

Adolescent↗
PubMed1983

Abscess drainage with CT and ultrasound guidance.

The technique of catheter drainage of abscesses, while appearing to be a departure from standard surgical tenets, in reality adheres to accepted principles of abscess management. In properly selected candidates, most abscesses are adequately and safely drained by catheter. Catheter drainage has the advantages of avoidance of general anesthesia, less morbidity, and lower cost when compared with that of surgical drainage. Since catheter drainage does not preclude surgical drainage, in appropriate candidates percutaneous drainage should be considered initially for definitive therapy. Ultrasonography and CT have become the preferred methods of detecting abdominal abscesses and also of guiding percutaneous catheter drainage. Real-time sonography has the advantages of being inexpensive, "portable," and able to provide simultaneous imaging during catheter placement. CT provides greater accuracy in guiding drainage of small, deep abscesses, more accurate delineation of the extent and location of the collection, and better definition of the relationship of abscesses to bowel and blood vessels.

Abdomen↗
PubMed1982

Fibronectin is produced by blood vessels in response to injury.

During the time of tissue repair that ensues subsequent to tissue injury, blood vessel wall fibronectin increases concomitantly with endothelial proliferation and angiogenesis. However, the source of this blood vessel fibronectin had not been delineated. In this report we have demonstrated that microvascular fibronectin is produced in situ by the proliferating vessels surrounding excisional wounds. This finding was established by extirpating 3 mm of skin from the center of a well-healed rat xenograph on the flanks of immunosuppressed mice, harvesting the injured skin sites at various stages during the healing process, and staining the specimens with reciprocal species-specific anti-fibronectin. The proliferating donor vessels that surrounded the wounded graft had increased fluorescence staining with FITC conjugated mouse anti-rat fibronectin and no staining with rat anti-mouse fibronectin. This finding was taken as direct evidence that the fibronectin was produced in situ by the rat vessels and not derived from circulating mouse plasma.

Animals↗
PubMed1982

Computed tomography of gastrointestinal leiomyosarcoma.

Computed tomography (CT) was performed in 6 patients with gastrointestinal leiomyosarcoma. The characteristic CT findings were a large extraluminal mass, apparently mesenteric in location, with central areas of necrosis. These findings were present in 5 of the 6 patients. Enhancement of the rim of the tumor was seen in 2 of 3 patients who had scans before and after administration of intravenous contrast material. CT identified the site of origin of tumor in only 2 patients. The characteristic CT findings should suggest the diagnosis of gastrointestinal leiomyosarcoma.

Gastrointestinal Neoplasms↗
PubMed1982

Fistulas and sinus tracts: radiographic evaluation, management, and outcome.

A retrospective review of 50 sinus tracts and 87 fistulas is presented. The etiologies, methods of radiographic evaluation including computed tomography and ultrasound, means of radiographic intervention, and disposition of sinus tracts and fistulas are discussed. Despite the newer imaging modalities, a sinogram or a fistulogram is still the best means of evaluating a sinus tract or fistula when an external communication is present. Computed tomography is helpful if exact spatial delineation of the tract is necessary or an associated abscess is suspected. Ultrasound examination is generally not useful, being limited by bowel gas and surgical incisions.

Adolescent↗
PubMed1982

Nonocclusive intestinal ischemia treated with intraarterial infusion of prostaglandin E1.

An elderly woman with a history of cardiac failure treated with digitalis had both abdominal pain and dehydration. Parenteral fluid and electrolyte support failed to alleviate abdominal pain. Superior mesenteric arteriography combined with "spillover" method of estimating blood flow revealed an intestinal nonocclusive ischemic state which was treated successfully with 44-hour intraarterial infusion of prostaglandin E1. Laparotomy performed during the drug infusion revealed viable intestine.

Aged↗
PubMed1982

Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization.

Factors regulating the attachment and directional migration of a regenerating epidermis in wound healing are poorly understood. In studies of guinea pig 4-mm skin wounds, left uncovered for 1-28 days, biopsied and processed for 1-micrometer section and immunofluorescence, the epidermis migrated over an irregular thickened provisional matrix containing fibrin and fibronectin. The provisional matrix lacked two major components of normal basement membrane, laminin and type IV collagen, which can mediate tenacious epithelial attachment to plastic in vitro and may limit epidermal cell migration in vivo. Upon completion of wound reepithelialization at 7-9 days after wounding, the basement membrane zone lost its thickened appearance, fibronectin and fibrinogen disappeared, and type IV collagen and laminin reappeared. Although these findings do not prove that epidermal cell migration during reepithelialization required a fibrin and fibronectin matrix, they demonstrate that epidermal cells do move over such a substratum during in vivo wound repair.

Animals↗
PubMed1982

Blood vessel fibronectin increases in conjunction with endothelial cell proliferation and capillary ingrowth during wound healing.

The regulation of angiogenesis and alterations in the structure of blood vessels taking part in wound healing are poorly understood. In studies of guinea pig 4-mm skin wound, left uncovered for 1-28 days, biopsied and processed for 1-micrometer section and immunofluorescence, we found that fibronectin in blood vessel walls markedly increased in conjunction with endothelial cell proliferation and capillary ingrowth. Both the endothelial cell proliferation and the increased vessel wall fibronectin were restricted to a 0.5-mm area along the margin of the wound and occurred 3-7 days after injury. Fibronectin was easily demonstrated in capillaries of the peripheral granulation tissue but was difficult to demonstrate in central areas of the granulation tissue secondary to a brightly fluorescent reticular background staining probably attributable to fibroblast-related fibronectin. The fibronectin in blood vessel walls rapidly diminished as endothelial cell proliferation and capillary ingrowth ceased. These data suggest that fibronectin may provide a provisional substratum for endothelial cell mitosis and movement.

Animals↗
PubMed1982

Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro.

Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of (14)C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative mechanisms in damage to hyphae. In contrast, neutrophils from one patient with hereditary myeloperoxidase deficiency damaged R. oryzae but not A. fumigatus hyphae. Cell-free, in vitro systems were then used to help determine the relative importance of several potentially fungicidal products of neutrophils. Both A. fumigatus and R. oryzae hyphae were damaged by the myeloperoxidase-hydrogen peroxide-halide system either with reagent hydrogen peroxide or enzymatic systems for generating hydrogen peroxide (glucose oxidase with glucose, or xanthine oxidase with either hypoxanthine or acetaldehyde). Iodide with or without chloride supported the reaction, but damage was less with chloride alone as the halide cofactor. Hydrogen peroxide alone damaged hyphae only in concentrations >/=1 mM, but 0.01 mM hypochlorous acid, a potential product of the myeloperoxidase system, significantly damaged R. oryzae hyphae (a 1 mM concentration was required for significant damage to A. fumigatus hyphae). Damage to hyphae by the myeloperoxidase system was inhibited by azide, cyanide, catalase, histidine, and tryptophan, but not by superoxide dismutase, dimethyl sulfoxide, or mannitol. Photoactivation of the dye rose bengal resulted in hyphal damage which was inhibited by histidine, tryptophan, and 1,4-diazobicyclo(2,2,2)octane. Lysates of neutrophils or separated neutrophil granules did not affect A. fumigatus hyphae, but did damage R. oryzae hyphae. Similarly, three preparations of cationic proteins purified from human neutrophil granules were more active in damaging R. oryzae than A. fumigatus hyphae. This damage, as with the separated granules and whole cell lysates, was inhibited by the polyanion heparin. Damage to R. oryzae hyphae by neutrophil cationic proteins was enhanced by activity of the complete myeloperoxidase system or by hydrogen peroxide alone in subinhibitory concentrations. These data support the importance of oxidative products in general and the myeloperoxidase system in particular in damage to hyphae by neutrophils. Cationic proteins may also contribute significantly to neutrophil-mediated damage to R. oryzae hyphae.

Aspergillus fumigatus↗
PubMed1982

Dissemination of gonococcal infection is associated with delayed stimulation of complement-dependent neutrophil chemotaxis in vitro.

Gonococci isolated from patients with uncomplicated gonorrhea or disseminated infection were examined for their ability to stimulate neutrophil chemotaxis in vitro. A neutrophil chemotactic response was not observed when as many as 10(9) colony-forming units of gonococci were incubated in buffer alone. However, a striking response was observed when 4 x 10(7) colony-forming units were incubated in 10% pooled normal human serum. Activation of complement was required for chemotaxis as demonstrated by complement consumption and failure of chemotactic activity generation in serum treated with heat or EDTA. Chromatography of activated serum demonstrated a single peak of chemotactic activity with an apparent molecular weight of 15,000 and was shown to be due to C5a. Examination of the kinetics of chemotactic factor generation demonstrated that local isolates stimulated a rapid response (about 60% maximal in 5 min), whereas the response to disseminated isolates was delayed (50% maximal in 20 to 30 min). Chemotactic activity generated by both types of isolates was suppressed at early time periods in agammaglobulinemic serum, indicating that immunoglobulins contribute to the generation of activity. Both pathways of complement activation were utilized by the two types of gonococci, but there was preferential dependence on the alternative pathway for disseminated strains and on the classical pathway for local isolates. We suggest that delayed stimulation of complement-dependent neutrophil migration may account in part for the infrequency of genital symptoms and may contribute to the mechanism of dissemination in patients with systemic gonococcal infection.

Chemotaxis, Leukocyte↗
PubMed1982

Involvement of cytochrome b-245 in the respiratory burst of human neutrophils.

The cytochrome b 245 of human neutrophils was reduced when the neutrophils under anaerobic conditions were stimulated by serum-treated zymosan, immune complexes, or phorbol myristate acetate. Reintroduction of oxygen rapidly reoxidized the cytochrome; azide was without effect on any of these reactions. This indicates that cytochrome b 245 participates in the respiratory burst of neutrophils.

Adult↗