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Biomedical subjects

C C Clawson

Publications and source records attributed to C C Clawson.

At least 37 records · Page 2Linked to original sources
PubMed1980

Bactericidal function of neutrophils from patients with acute bacterial infections and from diabetics.

Killing of Staphylococus aureus by neutrophils from untreated patients with acute bacterial infection was increased compared with neutrophils from uninfected controls or the same patients after antibiotic treatment. In contrast, neutrophils from diabetics failed to increase their bactericidal activity in response to infection to the same degree as neutrophils from nondiabetic subjects. The latter abnormality was pronounced in poorly controlled (plasma glucose level, greater than 130 mg/100 ml), but was also present in well-controlled (plasma glucose levels, less than 130 mg/100 ml), diabetics. In parallel studies neutrophils from poorly controlled, uninfected diabetics did not kill S. aureus to the same degree as neutrophils from normal subjects or controlled diabetics. Finally, neutrophils from two diabetics who underwent controlled insulin withdrawal developed a bactericidal defect that was corrected by treating the patients with insulin or by preincubating their neutrophils with insulin in vitro. These results support the possibility that defective neutrophil bactericidal activity may contribute to the proposed increased susceptibility to bacterial infection of diabetics.

Acute Disease↗
PubMed1980

Effect of variations in sequencing of clinical tutorials.

The sequence in which different specialties are presented to medical students may influence their impact. However, the subjects has been rarely examined. In the present study a variety of educational outcomes were evaluated for a second-year medical school class. They followed a series of eight clinical tutorials but did so in four different sequences. The outcomes assessed were: (1) student achievement during their tutorial year and in several major clinical courses taken in the third medical school year; (2) student perceptions of the tutorial experiences and the impact of the tutorials on subsequent clinical training; and (3) student choices of clinical courses and programmes in their third and fourth years. The results indicated that the sequence of the eight tutorials had no adverse effect upon the educational outcomes examined.

Achievement↗
PubMed1980

The Chédiak-Higashi syndrome; the nature of the giant neutrophil granules and their interactions with cytoplasm and foreign particulates. I. Progressive enlargement of the massive inclusions in mature neutrophils. II. Manifestations of cytoplasmic injury and sequestration. III. Interactions between giant organelles and foreign particulates.

Defective bactericidal functioning of polymorphonuclear leukocytes (PMNs) from patients with the Chédiak-Higashi syndrome (CHS) has been related in previous reports to a failure of the giant granules characteristics of the disorder to participate in degranulation after uptake of foreign particulates by neutrophils. However, the reason massive CHS inclusions do not fuse with and discharge their contents into phagocytic vacuoles has not been defined. The problem is particularly puzzling because it has been postulated that the hugh organelles in CHS neutophils originate by fusion of small azurophilic granules in promyelocytes and myelocytes. The present series of investigations into the cytopathology of the CHS has employed electron microscopy and ultrastructural cytochemistry to characterize the progressive enlargement of the hugh bodies in mature PMNs, their interaction with cytoplasmic constituents resulting in various manifestations of cell injury, and their response to foreign particulates. Each study clarifies abnormal features of the giant organelles essential to the understanding of their role in the defective bactericidal function of CHS neutrophils. The first report demonstrates that most of the hugh inclusions in PMNs are not primary lysosomes. The interaction and fusion of giant azurophilic granules with each other, with normal-sized primary and secondary granules, and with cytoplasmic components converts the massive primary granules into huge secondary lysosomes. Transformation to secondary hysosomes represents a critical alteration in the state of the giant granules that underlies their damaging influence on the cytoplasm and loss of reactivity wtih phagocytic vacuoles.

Adolescent↗
PubMed1980

Platelet interaction with bacteria. V. Ultrastructure of congenital afibrinogenemic platelets.

Platelets from a patient with congenital afibrinogenemia (CA) were tested in their native plasma for reactivity in vitro to Staphylococcus aureus 502A. Previous studies of the interactions between normal human platelets and this organism have shown rapid irreversible aggregation responses in which the bacteria were regularly trapped between aggregating platelets. Engulfment of microbes by single normal platelets in a process akin to phagocytosis was a very rare occurrence. In contrast, CA platelets showed a delayed aggregation response to contact with this microorganism. The CA platelets were also much more sensitive to the concentration of bacteria than were normal platelets. Electron microscopy showed that individual CA platelets often engulfed the stimulatory organism rather than participating in aggregation. Postfixation staining with a colloidal tracer, lanthanum nitrate, indicated that the bacteria were sequestered in the open canalicular system of the CA platelets in a manner analogous to that previously observed with latex particles. Restoration of normal levels of human fibrinogen to the CA platelet-rich plasma corrected the delay in aggregation but did not eliminate the frequent engulfment of bacteria by the CA platelets. These findings indicate that fibrinogen is an important, although not essential, cofactor in the response of human platelets to contact with this common bacterial pathogen.

Afibrinogenemia↗
PubMed1980

Interactions of blood with solid and porous endocardial electrodes for cardiac pacemakers.

Two forms of implantable endocarial electrodes, solid and porous, used in conjunction with cardiac pacemakers have been compared in their interactions with human blood components. The platinum-iridium electrode tips were suspended in stirred, anticoagulated whole blood or blood products at 37 degrees C for period of 1 to 20 minutes, and then were examined by scanning electron microscopy. The various media employed were heparinized or citrated fresh whole blood, platelet-rich plasma, platelet-poor plasma, and washed platelets in a protein-free balanced salt solution. There were no significant qualitative differences between the reactions of the two forms of electrode. Plasma products, platelets, and erythrocytes adhered freely to the surfaces of both forms of electrode. Leukocytes were much less frequently encountered. Platelets were seen in two forms, those adherent directly to the metal surface with extensive spreading and formation of a monolayer, and platelets attached to the monolayer without spreading but with early shape-change. Quantitative differences between the two electrode forms were prominent. Solid electrodes had broad areas free of cellular accumulations or with only sparsely scattered platelets and erythrocytes. The wires of the porous electrodes were extensively coated on their outer surfaces with platelets and erythrocytes. It is postulated that the porous electrodes will carry appreciably more blood cells, particularly platelets, to the site of endocardial implantation, and these cells or their products may play a role in the tissue responses that result in implantation of the electrode.

Blood Coagulation↗
PubMed1980

Lysophosphatidic acids: III. Enhancement of neutrophil chemotaxis.

1-Palmitoyl-lysophosphatidic acid (LPA) was studied for its influence on the chemotaxis and ultrastructure of human neutrophils. By itself, LPA had no effect on the indices of chemotaxis or random migration of neutrophils. However, LPA on either the cellular or attractant side of Boyden chambers significantly enhanced the chemotactic responses of neutrophils to suboptimal concentrations of formyl-methionyl-phenylalanine. The enhancement of chemotaxis was achieved with concentrations of LPA (120-240 microM) that had no effect alone on neutrophil ultrastructure. The results, taken together with recent advances in knowledge of the role of the phosphatidylinositol turnover response in mediating effects of stimulating agents on cells, may provide a novel concept for understanding neutrophil chemotaxis.

Chemotactic Factors↗
PubMed1980

The surface-connected canalicular system of blood platelets--a fenestrated membrane system.

Recent reports have suggested that channels of the surface-connected or open canalicular system (OCS) in discoid blood platelets represent a reservoir of membrane that can be evaginated following activation and shape change and contribute to an increased ratio of surface area to volume. The present study has used electron cytochemistry and freeze-fracture to examine the organization of the OCS in unaltered platelets. Results of the investigation indicate that channels of the OCS are seldom if ever single tubular invaginations of the surface membrane. Each channel joins with other canaliculi of the OCS to form an anastomosing network of fenestrated conduits spreading throughout the cytoplasm from one side of the platelet to the other. The multiple connections of the interlocked channels to different sites on the platelet surface, their association in a continuous labyrinth, and participation with elements of the dense tubular system to form membrane complexes suggest that the OCS would have to be torn apart or undergo radical rearrangement before it could be evaginated and contribute to an increased surface area on activated cells.

Blood Platelets↗
PubMed1980

Development of giant granules in platelets during prolonged storage.

Giant granules are uncommon in normal human platelets but are frequently observed in platelets from patients with the Chédiak-Higashi syndrome, some case of May-Hegglin anomaly, and individuals with chronic refractory anemia (preleukemia) or myelomonocytic leukema. However, the numbers of platelets containing the giant granule anomaly are so low that it has been impossible to isolate them in sufficient quantity to identify the mechanisms involved in their formation. Recently conditions were found that foster the long-term preservation of functional platelets in vitro. Ultrastructural examination of samples of C-PRP stored for 15--21 days revealed the presence of giant granules in 10--20% of the cells. Although factors involved in large organelle development were not determined in the present study, the new in vitro system for platelet storage may provide a useful approach for investigation of giant granule formation in normal and abnormal platelets.

Blood Platelets↗
PubMed1979

The Chediak-Higashi syndrome: microtubules in monocytes and lymphocytes.

Recent investigations of Chediak-Higashi syndrome (CHS) leukocytes have suggested that defective cell function and formation of giant granules may be due to an inability of the cells to assemble microtubules because of an abnormality in synthesis of cyclic 3',5'-guanosine monophosphate (cGMP). In the present study we have examined normal and CHS lymphocytes and monocytes for the presence and frequency of centriole-associated microtubules. No statistically significant differences between the mean numbers of centriole associated microtubules in normal and CHS mononuclear cells could be detected. Results of the study fail to support the hypothesis that microtubule assembly is a fundamental defect in all CHS leukocytes.

Chediak-Higashi Syndrome↗
PubMed1979

Bactericidal effect of oleic acid on group A streptococci: mechanism of action.

In contrast to Staphylococcus aureus and coagulase-negative staphylococci, group A streptococci are infrequently present on normal human skin, except in certain populations with endemic impetigo. This has been attributed to differences in susceptibility to the bactericidal effect of skin surface lipids, particularly unsaturated fatty acids. When an M type 6 strain group A streptococcus was exposed to 500 mug of oleic acid per ml, viable counts decreased by 4 logs in 5 min. The rank order of killing was 35 > 20 > 4 degrees C. Oleic acid did not kill a strain of S. aureus, a strain of coagulase-negative staphylococcus, or a strain of Escherichia coli, but bound rapidly to these bacteria as well as to the group A streptococcus. The loss of [(3)H]uridine from labeled oleic acid-treated group A streptococcal cells was greater than 100 times that of controls. There was no loss of [(3)H]-thymidine from group A streptococci or of [(3)H]uridine or [(3)H]thymidine from identically exposed coagulase-negative staphylococci. When [(3)H]uridine was added to group A streptococci during mid-log-phase growth, cessation of uptake occurred within 5 min of addition of 50 mug of oleic acid per ml. Electron microscopic changes seen within 5 min included condensation of the nucleoid and distortion of the streptococcal surface by numerous clumps and blebs. Coagulase-negative staphylococci, S. aureus, and E. coli similarly exposed showed no comparable electron microscopic changes. We propose that oleic acid kills group A streptococci by altering the integrity of the cell membrane with resulting loss of ribonucleic acid but not deoxyribonucleic acid.

Escherichia coli↗
PubMed1979

The Chediak-Higashi syndrome: quantitation of a deficiency in maximal bactericidal capacity.

The maximum bactericidal capacity of neutrophils from a patient with the Chediak-Higashi syndrome (CHS) was measured by a quantitative assay in which the neutrophils were challenged with increasing multiples of Staphylococcus aureus, 502A. At various bacterial challenges from 0.5 to 65 bacteria per neutrophil, the CHS cells killed normal numbers of bacteria in 60 minutes. However, at higher ratios with a mean of 118 bacteria per neutrophil, the percentage of bacteria killed in 60 minutes by CHS neutrophils (8.1 +/- 2.3%) was significantly less (P < 0.001) than that killed by normal neutrophils (44 +/- 2.3%). The CHS neutrophils lagged in their ability to kill low challenges of bacteria (0.5 or 1.2 bacteria per neutrophil) only at 20 minutes. A hydrogen-peroxide-producing strain of Streptococcus faecalis was killed normally by the CHS neutrophils at 60 minutes, with all ratios of challenge up to 114 to 1. Electron microscopic examination of 60-minute specimens from high ratios of challenge that were stained for myeloperoxidase activity revealed a failure of many bacteria-laden phagosomes to display this marker of degranulation. The results of this study indicate that the maximal bactericidal capacity of CHS neutrophils is saturated by a significantly lower challenge of bacteria than is required to saturate normal cells. This appears to be the result of sequestration of a significant portion of these cells' bactericidal resources in the giant granules that do not participate appreciably in degranulation.

Adolescent↗
PubMed1979

The Chédiak-Higashi syndrome: ring-shaped lysomomes in circulating monocytes.

The giant inclusion anomaly of leukocytes from three patients with the Chédiak-Higashi syndrome (CHS) has been reexamined by the ultrastructural and cytochemical techniques placing emphasis on the monocyte. Contrary to previous assumptions that all CHS leukocytes shared a common form of giant granule with similar mechanisms of formation, it is shown that CHS monocytes contain ring-shaped organelles as their principle manifestation of the disease. These granules consist of a double membrane surrounding a segment of cytoplasm, which may or may not be sequestered from the remaining cytoplasm and which usually contains one or more normal-sized azurophilic granules. The material lying between the double membranes contains the specific reaction products for peroxidase and acid phosphatase. Therefore, the ring-shaped organelles share identity with the azurophilic granules and probably share a common origin with the primary lysosomes. The double-ring form of giant CHS organelle has also been found infrequently in neutrophils, eosinophils, and lymphocytes.

Acid Phosphatase↗
PubMed1978

Defective neutrophil locomotion in human blastomycosis: evidence for a serum inhibitor.

Unstimulated or stimulated locomotion, bactericidal, and metabolic activities of polymorphonuclear leukocytes (PMN) from 12 nonimmunosuppressed patients with invasive fungal infections proved by culture, were evaluated before and after treatment of the patients with antimicrobial drugs. The major observation was that PMN from patients with blastomycosis had a defect in stimulated locomotion. The specificity of the defect for blastomycosis was substantiated by the normal stimulated locomotion of PMN from uninfected control subjects or untreated patients with histoplasmosis, cryptococcosis, coccidioidomycosis, or sporotrichosis. The defect was due to a heat-stable, cell-directed, reversible serum inhibitor. In unheated or heated serum from untreated patients with blastomycosis, control PMN had decreased stimulated locomotion. Multiple washing followed by addition of control serum corrected locomotion of PMN from untreated patients with blastomycosis. The abnormality was not present in PMN from patients who had been treated with amphotericin B or had spontaneous resolution of their infections. Inhibition was not due to absence of chemoattractant activity because zymosan-activated patient serum or mixtures of patient and control serum stimulated PMN locomotion normally. The defect did not correlate with age, sex, neutrophil count, nitroblue tetrazolium reduction, serologic reactivity, or duration or severity of infection. No defect was found in bactericidal or metabolic activities of various combinations of PMN and serum from untreated or treated patients with blastomycosis or the 4 other fungal infections tested, indicating that the inhibitor was specific for stimulated locomotion.

Adolescent↗
PubMed1978

Reversible impairment of the adherence of alveolar macrophages from cigarette smokers.

The nylon fiber adherence in vitro of alveolar macrophages (AM) from cigarette smokers was uniformly decreased. The mean adherence of AM from 16 cigarette smokers was 53 +/- 3.0 per cent, compared to a mean adherence of 77.2 +/- 1.7 per cent for AM from control nonsmokers. The defect was not present after the subjects quit smoking, was not a result of factors in lavage fluids from smokers, and was not apparent in polymorphonuclear leukocytes. The morphologic features of the surface of AM were examined with scanning electron microscopy to determine whether morphologic changes paralleled the decreased adherence of AM from smokers. Marked alterations in the surface of AM from cigarette smokers, which could affect the ability of AM to adhere optimally, were demonstrated before attachment to the fiber. In summary, there exists a reversible, intrinsic defect in the structure and adherence of AM from cigarette smokers that may influence their function and may accout, in part, for the increased yield of AM from the lavage fluid of cigarette smokers.

Cell Adhesion↗