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Biomedical subjects

C A Clark

Publications and source records attributed to C A Clark.

At least 73 records · Page 4Linked to original sources
PubMed1989

The release of neutrophil chemoattractant activity by bronchoalveolar macrophages from adult and senescent mice.

To assess the effects of advanced age on the release of neutrophil chemoattractant activity by resident bronchoalveolar macrophages (BAM), cells from three strains of pathogen- and disease-free mice were secured by lung lavage and stimulated in vitro with unopsonized zymosan or the calcium ionophore, A23187. Chemoattractant release by BAM from adult (5-8 mos) and senescent (19-26 mos) C57BL/6 and DBA/2 mice in response to both stimulants was comparable; however, the generation of chemoattractant activity by BAM from senescent (18-20 mos) BALB/c mice was greater than that observed with cells from younger (4-6 mos) animals with both zymosan and A23187. In the presence of 50 microM piriprost potassium, a 5-lipoxygenase inhibitor, the release of chemoattractant activity and leukotriene B4 (LTB4) in response to zymosan and A23187 by BAM from both groups of C57BL/6 mice was significantly impaired. With BAM from BALB/c mice, 100 microM piriprost potassium was required to produce changes in A23187-stimulated chemoattractant and LTB4 release; of note, the generation of LTB4 in response to A23187 by BAM from aged BALB/c mice was significantly greater than that observed with cells from the younger animals under all conditions studied. Finally, with BAM from DBA/2 mice, 50 microM piriprost potassium significantly reduced chemoattractant activity in both groups of animals, but the lipoxygenase inhibitor had no effect on LTB4 production. Thus, although these studies revealed substantial age and strain-related differences in the release of neutrophil chemoattractant activity by murine BAM, they did not demonstrate deficiencies that might enhance the susceptibility of the senescent host to infection of the lower respiratory tract.

Aging↗
PubMed1989

The cardiac glycoside digoxin disrupts host defense in experimental pneumococcal pneumonia by impairing neutrophil mobilization.

Normal CD-1 mice were administered digoxin (4 micrograms/kg/24 h) and infected with type 3 Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on the chemotactic responsiveness of peripheral blood neutrophils and the mobilization of granulocytes from storage pools. The chemotactic responses to autologous zymosan-activated serum (C5a) by neutrophils obtained from uninfected digoxin-treated and control animals were similar; comparable observations were made with circulating granulocytes isolated from animals at 24 or 48 h after intratracheal challenge with 5 x 10(5) colony-forming units (cfu) of bacteria. However, at 4 and 6 h after intratracheal pneumococcal challenge, the number of immature neutrophils in the peripheral blood was significantly lower in the glycoside-treated animals versus controls; at 24 and 48 h, these differences were not apparent. Following the intravenous inoculation of pneumococci, the number of circulating immature neutrophils was also found to be significantly lower at 4 and 24 h in animals given the cardiac glycoside versus controls. We conclude that digoxin disrupts host defense in experimental pneumococcal pneumonia and bacteremia by impairing the mobilization of neutrophils.

Animals↗
PubMed1988

An assessment of the respiratory burst and bactericidal activity of alveolar macrophages from adult and senescent mice.

To assess the effects of advanced age on the nonspecific antimicrobial activity of resident alveolar macrophages (AM), superoxide anion (O2-) release and the phagocytic and bactericidal capacity of cells from three genetically distinct murine strains were evaluated. In initial experiments, resident AM, obtained by bronchoalveolar lavage of pathogen-free adult female CD-1 mice and studied in suspension, were found to produce O2- spontaneously and in response to phorbol myristate acetate (PMA) snd unopsonized zymosan. Maximum quantities of O2- were released following stimulation with 1 microgram/ml PMA and by a particle-to-cell ratio of 100:1 with zymosan; responses to the agonists peaked between 60 and 90 min. Resident AM obtained from pathogen and disease-free senescent (18-26-month-old) female C57BL/6, BALB/c, and DBA/2 mice released significantly more O2- in response to both PMA and zymosan than did cells secured from adult (4-8-month-old) animals. In vivo, the capacity of AM from adult and senescent animals to phagocytose Streptococcus pneumoniae (unencapsulated strain) and Staphylococcus aureus was comparable, and although the cells from the senescent mice tended to be more efficient in their ability to kill internalized bacteria, statistically significant differences between the two groups were not observed. The results of these studies indicate that the enhanced susceptibility of the senescent host to infection of the lower respiratory tract cannot be attributed to age-related changes in the nonspecific antimicrobial activity of resident AM.

Aging↗
PubMed1988

Protease inhibitor eglin-c affects superoxide anion release but not bacterial killing by human polymorphonuclear leukocytes.

In order to assess the influence of the protease inhibitor eglin-c on superoxide anion (O-2) release by human polymorphonuclear leukocytes (PMN), cells were secured from normal donors and stimulated with phorbol myristate acetate (PMA), opsonized zymosan, or n-formyl-methionyl-leucyl-phenylalanine (FMLP). In the presence of 100 micrograms/ml eglin-c, the activation time was prolonged and the maximum linear rate of O-2 formation was depressed following stimulation with PMA; a concentration of 1000 micrograms/ml eglin-c was required to produce a similar effect with opsonized zymosan. Eglin-c did not influence the activation time following stimulation with FMLP, but at 2000 micrograms/ml, the protease inhibitor attenuated the rate of O-2 production in response to the chemotactic peptide. In the presence of cytochalasin B, the inhibitory effect of eglin-c on O-2 release following stimulation with FMLP became more pronounced. In spite of these alterations in O-2 formation, the protease inhibitor did not impair the bactericidal activity of PMN against Staphylococcus aureus. Therefore, we conclude that although eglin-c can disrupt the activation and the activity of the superoxide-generating system of human PMN, the effect is stimulus dependent and is not associated with an alteration in the microbicidal capacity of neutrophils against S. aureus.

Anions↗
PubMed1985

Evaluation of thermal and vibration sensation in diabetic neuropathy.

Sensory evaluation of diabetic neuropathy was undertaken by a new technique for assessment of thermal sensitivity. The method is simple and reproducible, and the mean normal value of the lateral border of the foot was 6.0 degrees C (3.6-9.8 degrees C, 95% confidence limits). Four groups of patients with diabetic neuropathy were examined: 22 with neuropathic ulcers and/or Charcot joints (groups 1 and 2); all showed severe abnormalities (range 10.8- greater than 30 degrees C), frequently more than three times the upper limit of normal. In contrast thermal sensitivity in 15 patients with painful neuropathy (group 4) varied from normal to grossly abnormal (range 3.9- greater than 30 degrees C) confirming this form of neuropathy as a distinct entity. The majority of those 10 patients with autonomic neuropathy alone (group 3) had abnormal thermal sensitivity (range 6.4- greater than 30 degrees C). Comparison of thermal sensitivity (a small fibre modality) with vibration perception threshold (a large fibre modality) showed that thermal sensitivity is sometimes selectively affected, especially in those with painful neuropathy, suggesting that the small fibres are more vulnerable in diabetes. Frequent involvement of the hands confirms the "stocking and glove" distribution of diabetic neuropathy. We conclude that impairment of thermal sensitivity is the rule in symptomatic diabetic neuropathy and its assessment provides a simple quantitative measurement suitable for long-term studies of its natural history.

Adult↗
PubMed1984

Detection of double-stranded RNA by serologically specific electron microscopy.

Details of a procedure for detecting double-stranded RNA (dsRNA) in virus and viroid infected tissue extracts using serologically specific electron microscopy are given. A method for staining dsRNA, based on in situ formation of uranyl phosphate, that consistently permits the examination of dsRNA by electron microscopy without shadowing with heavy metals, is described. The method provides for routine assays for dsRNA in crude extracts without the variable results associated with shadowing procedures. DsRNA was found to accumulate in older leaves of sorghum systemically infected with sugarcane mosaic virus. In contrast, dsRNA was not detected in older cowpea leaves systemically infected with cowpea mosaic virus but was readily found in inoculated leaves 4 days post inoculation and young systemically infected leaves.

Microscopy, Electron↗
PubMed1984

Reactivation blastomycosis presenting as a tuboovarian abscess.

A 32-year-old Korean woman presented with a rapidly enlarging abdominal mass six months after an undiagnosed illness of fever and a large pleural effusion. Exfoliative cytology of a cervical discharge revealed Blastomyces dermatiditis. At laparotomy, a large peritoneal inclusion cyst was found surrounding a tuboovarian abscess with involvement from the cervix to the peritoneum. B dermatiditis was cultured from the excised uterus and fallopian tube. Female genital blastomycosis has rarely been described. The importance of cytology in making the diagnosis in the present case is emphasized.

Abscess↗
PubMed1982

An unlabeled antibody method using glucose oxidase-antiglucose oxidase complexes (GAG): a sensitive alternative to immunoperoxidase for the detection of tissue antigens.

Immunoenzyme staining for tissue antigens using glucose oxidase as marker enzyme was compared with immunoperoxidase techniques. Both the indirect, conjugated antibody method and the unlabeled antibody procedure employing preformed complexes of glucose oxidase-antiglucose oxidase (GAG) and peroxidase-antiperoxidase (PAP) were used to stain carcinoembryonic antigen (CEA) in paraffin tissue sections. The localization of CEA within a tissue specimen was the same in all cases, and background staining was minimal. The percentage of positive specimens detected with GAG and PAP was similar but was slightly greater with glucose oxidase compared to peroxidase conjugates. The glucose oxidase conjugates and GAG were similar to the comparable immunoperoxidase reagents in enzyme-antibody molar ratio, retention of antibody and enzyme activity, immunohistochemical staining dilutions, and stability. Immunoglucose oxidase and immunoperoxidase were combined to localize CEA and colon-specific antigen-p simultaneously. Excellent contrast and staining separation were shown between the enzymatic reaction products of the two systems. Since immunoglucose oxidase methods are as sensitive as the comparable immunoperoxidase techniques, they should be considered as a reliable alternative to the latter, especially when endogenous peroxidase activity may be a problem. Furthermore, the two methods can be conveniently combined for the simultaneous detection of two antigens.

Carcinoembryonic Antigen↗
PubMed1981

Morphology of spore-bearing structures in Streptomyces ipomoea.

Sporulating colonies of Streptomyces ipomoea were observed using light and scanning electron microscopy. In addition to the open loops and spiral chains of spores characteristic of S. ipomoea, globose structures resembling sporangia of the genus Streptosporangium were found. The "sporangia" had a smooth surface, were 5-6 micrometers in diameter, and consisted of an unbranched coiled hypha within an enveloping sheath. As the sporangia matured, septa formed in the internal sporogenous hypha forming coiled chains of spores morphologically similar to those formed on the typical spore chains. The sporangia germinated on agar, without releasing the nonmotile spores, by formation of several germ tubes at several locations on the sporangia.

Microscopy, Electron, Scanning↗
PubMed1981

Immunoperoxidase localization of carcinoembryonic antigen in normal human intestinal mucosa.

The indirect, labeled antibody and peroxidase-antiperoxidase complex (PAP) methods were studied to determine their sensitivity in detecting carcinoembryonic antigen (CEA) in conventionally processed specimens of morphologically normal human colon mucosa. CEA-positive staining was demonstrated in 13 of 19 specimens reacted with the PAP method, whereas only 4 of these specimens stained positive with the labeled antibody procedure. Detection of CEA with either technique was unrelated to normal mucosa content of antigen as determined by radioimmunoassay. Tissue fixation in 95% ethanol 1% acetic acid (EA) resulted in an enhanced and defined cytoplasmic staining of the normal colon cell lining the mucosal surface and upper levels of the glandular crypts. Cytoplasmic localization in Formalin-fixed specimens was absent or markedly reduced. Colon goblet cells and the small intestinal epithelium were CEA-negative in both Formalin- and EA-fixed specimens. These results show that the PAP immunoperoxidase method is more sensitive than the indirect, labeled antibody procedure in detecting CEA in morphologically normal colon mucosa. Furthermore, staining of tissues fixed in EA demonstrated that CEA is a product of the columnar epithelial cell and is not associated with goblet cells.

Carcinoembryonic Antigen↗
PubMed1980

Health centres: does small mean success?

On May 16 this year the Journal published a special issue entitled 'Sixty years after the Dawson Report' in which Dr J. Gerald Beale wrote that a study of health centres proved that in many respects they had done more harm than good. Here Dr J. Ivory, GP; Mr F. H. Kirton, area works officer; and Mr. C. A. Clark, planning administrator, Northumberland AHA put an alternative view.

Community Health Centers↗