Search PubMed⌕ Search

Biomedical subjects

D E Hammerschmidt

Publications and source records attributed to D E Hammerschmidt.

At least 109 records · Page 6Linked to original sources
PubMed1981

Sudden blindness in acute pancreatitis. Possible role of complement-induced retinal leukoembolization.

During an episode of acute alcoholic pancreatitis, severe visual loss and the funduscopic appearance of Purtscher's retinopathy-a syndrome thought to be caused by posterior retinal microembolization-developed in a patient. We propose that emboli in this case may have consisted of aggregated granulocytes since plasma samples from eight to 12 patients with subsequently studied acute pancreatitis caused granulocyte aggregation in vitro. The aggregant was demonstrated to be an activated fragment of the complement system, derived from C5. Since we could generate identical granulocyte aggregating activity by treating serum or purified C5 with trypsin, we suggest that proteases released from an inflamed pancreas might have produced a C5-derived aggregant in this case, as well as in three other previously reported cases of acute pancreatitis and Purtscher's retinopathy. We conclude that complement-induced leukoembolization may be a previously unsuspected cause of vital-tissue damage.

Acute Disease↗
PubMed1981

Complement-induced granulocyte aggregation in vivo.

Previous studies from our laboratories have demonstrated that granulocytes (PMNs), when exposed to activated complement (C) (specifically C5a), will aggregate and be provoked to damage cultured endothelial cells in vitro; it was postulated that these phenomena might also occur in vivo, constituting a previously unsuspected mechanism of immune tissue damage. The studies here presented confirm by intravital microscopy that PMN aggregation and leukoembolization in fact occur in live animals when C is activated or C5a is infused, and that these are accompanied by extravasation of plasma proteins in a pattern suggesting endothelial damage. It is concluded that altered microvascular behavior of PMNs is a possible pathogenetic mechanism in disease states associated with C activation.

Animals↗
PubMed1980

A new form of Ehlers-Danlos syndrome. Fibronectin corrects defective platelet function.

In a kindred with a mild, recessively inherited variant of the Ehlers-Danlos syndrome (EDS), a platelet aggregation defect segregated concordantly with skin and joint abnormalities. This defect was partially corrected in vitro by addition of normal plasma or cryoprecipitate. The plasma of the patients with EDS failed to support the aggregation of normal gel-filtered platelets in response to collagen; this defect was completely corrected by the addition of normal human fibronectin. Since fibronectin is an important adhesive glycoprotein in connective tissue and is required for normal platelet interactions with collagen, we propose that both platelet malfunction and joint hypermobility in this kindred are likely explained by a defective fibronectin.

Adolescent↗
PubMed1980

Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome. Pathophysiological relevance and possible prognostic value.

Clinical and experimental observations suggest that aggregation of polymorphonuclear granulocytes (PMN) in response to activated complement (C) might contribute to the genesis of the adult respiratory distress syndrome (ARDS), aggregating PMN causing pulmonary dysfunction by becoming lodged in the lung as leucoemboli. PMN-aggregating activity can be detected in C-activated plasma and reflects C5a levels. In 61 patients at risk for ARDS a strong and highly significant correlation was found between the presence of PMN-aggregating activity in the plasma and the development of ARDS; this correlation was also significant when patients with sepsis were excluded from analysis. In patients followed prospectively detection of elevated C5a seemed to be a useful predictor of ARDS. Since corticosteroids have been shown to inhibit PMN aggregation both in vitro and in vivo, the evidence for a role for PMN aggregation in the genesis of ARDS supports the use of corticosteroids in this disorder.

Cell Aggregation↗
PubMed1980

Digital integration of granulocyte aggregation responses. A simple and reproducible method for the quantitation of granulocyte adhesiveness.

The pulmonary leukostasis and lung dysfunction associated with intravascular complement activation results from C5a-mediated granulocyte (GR) aggregation, a phenomenon which can be reproduced in vitro using standard nephelometric techniques. To produce a more subjective measure of the extent and rate of GR aggregation responses we added a digital integrator to the system. The validity of this approach was substantiated by the close correlation between the aggregating and chemotactic activities of C5a and N-formyl-methionine-leucine-phenylalanine. Use of this technique enabled us to define the dose-response relationship of the aggregation produced by the cationophore A23187 and the inhibitory effect of tetracaine on divalent cation-dependent aggregation responses. The aggregation produced by these three stimuli does not result primarily from simple cross-linking of surface changes because, unlike the passive cell-cell association produced by the cation poly-L-lysine, it is not inhibited by anionic poly-L-glutamic acid. The importance of microtubules as regulators of GR adhesiveness was substantiated by the inhibitory effects of colchicine (but not lumicolchicine) on aggregation in this system. These data suggest that this integration of light transmission increments is a useful adjunct to this basic technique, whether used as a bioassay for chemotactic stimuli or as a model to study the many factors which regulate GR adhesiveness.

Calcimycin↗
PubMed1980

Artifactual complement activation by blood-drawing apparatus. A clinical and investigational caveat.

An increase in the occurrence of false-positive assays for C5a and C3 conversion, combined with hemolytic C assays discrepant between two laboratories, led to the suspicion that serum tubes with silicone separators might activate complement. Plasma incubated with some lots of such tubes showed evidence of complement activation via the alternative pathway, to an extent capable of influencing interpretation of results. The authors recommmend that such tubes not be used for C split-product assays, and be used only with caution for routine hemolytic C assays.

Blood Specimen Collection↗
PubMed1980

Granulocyte aggregometry: a sensitive technique for the detection of C5a and complement activation.

We have previously shown that complement (C) activated plasma causes granulocyte (PMN) aggregation in vitro and that C5a is responsible. The C-induced aggregation of PMNs treated with cytochalasin-B (CB) is markedly enhanced and irreversible, and the magnitude of the response is proportional to the log (concentration of activated plasma), allowing use of this technique to detect C5a and hence C-activation. To compare the sensitivity of granulocyte aggregometry to that of more standard methods of detecting C-activation, we produced graded C-activation in vitro by treating fresh serum with varying amounts of zymosan. Aggregometry was the most sensitive index of C-activation, detecting C-activation, produced by 0.02 mg zymosan/ml of serum--1/10 that required to produce C-activation detectable by C3 immunoelectrophoresis (the next most sensitive technique). Granulocyte aggregometry may also be used to detect in vivo C-activation. We have found aggregating activity in plasmas from patients with systemic lupus erythematosus, immune vasculitis, transfusion reactions, and other conditions associated with in vivo C-activation, but not in the plasmas of normal subjects.

Cell Aggregation↗
PubMed1979

Chemotaxigenesis by cell surface components of Staphylococcus aureus.

In an attempt to delineate the staphylococcal cell surface components of importance in chemotaxigenesis, we incubated intact Staphylococcus aureus H, crude cell walls, purified cell walls, peptidoglycan, teichoic acid, and cell membranes with human sera. The results reported indicate that both crude cell walls and purified cell walls, as well as peptidoglycan, were potent chemotaxigens. These particles led to the generation in normal human serum of a factor that was chemotactic for human polymorphonuclear leukocytes. Cell wall peptidoglycan and teichoic acid both appeared to play a role in chemotaxigenesis. Kinetic studies employing C2-deficient serum and immunoglobulin-deficient serum revealed that optimal chemotaxigenesis required the presence of an intact classical complement pathway, as well as antibody. Granulocyte aggregometry studies showed that significant levels of C5a were generated in normal serum and that this activated complement component appears to be a major chemotactic factor produced in serum upon interaction with staphylococcal cell wall components.

Cell Membrane↗
PubMed1979

Corticosteroids inhibit complement-induced granulocyte aggregation. A possible mechanism for their efficacy in shock states.

Granulocyte (PMN) aggregation and embolization may underlie complement (C)-mediated organ dysfunction in such syndromes as hemodialysis neutropenia and Purtscher's ischem;c retinopathy. Because of clinical and pathologic parallels, we have further suggested a role for this phenomenon in the genesis of the adult respiratory distress syndrome (ARDS). Because corticosteroids are commonly used in immune diseases, and have particularly been claimed efficacious in shock and ARDS, we tested the capability of methylprednisolone (MP), hydrocortisone (HC), and dexamethasone (DEX) to inhibit PMN aggregation. Aggregation engendered in vitro by zymosan-activated plasma (ZAP) was inhibited by MP and HC at concentrations approximating plasma levels achieved with the large bolus (30 mg/kg i.v) therapy advocated in shock states; DEX was almost without effect. Using intravital fluorescence microscopy, we observed PMN aggregation and embolization in the mesenteric vessels of rats given intra-arterial infusions of ZAP; this was also prevented by pretreatment with 30 mg/kg MP. Steroid inhibition of aggregation seemed not to involve disruption of receptor function, because aggregation induced by alternative agents, n-formyl-Met-Leu-Phe and the ionophore A23187, was also inhibited by MP. Moreover, corticosteroid inhibition of PMN prostaglandin synthesis is also an unlikely explanation for our results, since aspirin and ibuprofen failed to block aggregation and arachidonic acid neither effected aggregation itself nor ameliorated the steroid effect. Our studies provide a plausible rationale for the empiric observation that high-dose corticosteroids may benefit patients with syndromes associated with microvascular leukostasis.

Cell Aggregation↗
PubMed1979

Granulocyte aggregation as a manifestation of membrane interactions with complement: possible role in leukocyte margination, microvascular occlusion, and endothelial damage.

Activation products of the terminal complement cascade potently affect granulocyte function, inducing, for example, their migration toward (chemotaxis), and adherence to (opsonization), microbes, and stimulating their production of microbicidal oxygen radicals such as superoxide anion, and the like. We present studies that demonstrate that a C5-derived peptide, probably C5a, is a potent promoter of granulocyte and monocyte adhesion to endothelium (margination) and, in addition, causes granulocyte autoaggregation in vitro and in vivo. Although possibly beneficial by producing phagocyte clumps to mechanically entrap unwanted microbes, such aggregates may be deleterious, particularly if sustained, especially in the lung.

Animals↗
PubMed1978

Impaired fibrin polymerization in viral hepatitis. Report of a case: probable identity of the inhibitor with beta2-microglobulin.

A case is described in which a patient developed TT prolongation and bleeding during CMV hepatitis following successful renal transplantation. Bence-Jones proteinuria was noted, but there was no other evidence of myeloma. Bence-Jones proteinuria, TT prolongation, and bleeding abated as hepatitis resolved. In vitro, a protein isolated from the patient's urine was capable of prolonging the TT markedly, but it did not impair thrombin esterase activity. The effect of the protein seemed to be inhibition of fibrin polymerization. Sephadex gel filtration revealed a single TT-prolonging peak at 11,000 daltons, containing kappa, lambda, and delta antigens. By radioimmunoassay, virtually all the protein present reacted as beta2-microglobulin. Incubation with anti-beta2-microglobulin antiserum markedly attenuated anticoagulant activity. The paraprotein observed transiently in this patient's urine during hepatitis had potent anticoagulant activity and may well have accounted for his abnormal TT and bleeding diathesis; this paraprotein was not distinguishable from beta2-microglobulin.

Adult↗