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Biomedical subjects

G Csako

Publications and source records attributed to G Csako.

83 records · Page 5Linked to original sources

The concentration, physical state, and purity of bacterial endotoxin affect its detoxification by ionizing radiation.

Increasing concentrations of a highly purified bacterial lipopolysaccharide preparation, the U.S. Reference Standard Endotoxin, were exposed to increasing doses of ionizing radiation from a 60Co source. At identical radiation doses both the structural change and Limulus amebocyte lysate (LAL) reactivity were progressively smaller with increasing concentrations of the lipopolysaccharide in an aqueous medium. Under the experimental conditions used, there was a linear relationship between the endotoxin concentration and radiation dose for the structural changes. In contrast to endotoxin in aqueous medium, endotoxin irradiated in its dry state showed no decrease in LAL reactivity and rabbit pyrogenicity. Endotoxin exposed to radiation in water in the presence of albumin showed a much smaller decrease in LAL and pyrogenic activities than expected. The results show that the concentration, physical state, and purity of endotoxin influence its structural and functional alteration by ionizing radiation.

Chemical Phenomena↗

Monomeric and polymeric collagen-induced platelet aggregation in citrated and heparinized platelet-rich plasma.

The physical and chemical properties of Type I bovine collagens were studied in relation to their platelet aggregating activity in citrated and heparinized human platelet-rich plasmas (PRP). Despite close similarities in physical and chemical properties, significant differences were found in platelet aggregating potency between two monomeric atelocollagens. Skin atelocollagen was a potent and corneal atelocollagen was a very weak inducer of platelet aggregation in citrated and heparinized PRP. In a polymeric form, however, corneal atelocollagen was a stronger platelet aggregating agent than monomeric skin acid-soluble or atelocollagen. Removal of the telopeptides altered some of the characteristics of the platelet aggregation induced by monomeric skin collagen. The rate and maximum extent of aggregation were the same with skin acid-soluble (intact) and atelocollagens in either type of PRP, but the lag periods and aggregation times were longer in citrated and somewhat shorter in heparinized PRP with skin atelocollagen than with acid-soluble collagens. The possible mechanisms leading to the differences observed in platelet aggregating activity of collagens in different physical states and from different tissues, and their distinct platelet aggregation patterns in differently anticoagulated PRP, are discussed.

Adult↗

Effect of calibration material lot changes on results for the "SMAC".

The effect of two changes of calibration material (separated by five months) for the SMAC continuous-flow analyzer was followed by means of five quality-control indices: three normal and abnormal control sera, the mean of the central 50th percentile of patients' results, and the mean value for normal individuals. After the first and second changes of calibration materials, eight and six, respectively, of the 20 different tests exhibited statistically significant changes as shown by the indices. The cumulative shift for two of the 20 tests was considered medically significant. Prospective studies on split samples of patients' sera before the change in calibration material only predicted half the significant changes in test results later evidenced by the above-mentioned indices.

Autoanalysis↗

On the reactivity of corneal collagen and subcomponent C1q of the complement system with human platelets and IgG-coated latex particles.

Collagen was isolated from bovine cornea and tested for reactivity towards platelets and IgG-coated polystyrene latex particles. The corneal collagen caused a dose- and temperature-dependent platelet aggregation in all human platelet-rich plasmas studied. As little as 0 . 31 micrograms of purified corneal collagen could trigger platelet activation. Human C1q, a subcomponent of the first complement component (C1), which shares extensive chemical-structural similarities with collagen, was able to inhibit the platelet aggregation provoked by corneal collagen. This blocking effect could be, however, overcome by increasing collagen doses. In a slide method or in aggregometry both corneal collagen and C1q agglutinated IgG-coated latex particles in a dose-dependent manner. Addition of such latex particles to platelet-rich plasmas or preincubation of the particles with collagen reduced or prevented the platelet action of collagen, suggesting that due to their reactivity with collagen immune complexes may play an inhibitory role in collagen-caused platelet aggregation. The results are discussed in relation to pathological events that lead to collagenolysis and also with respect to wound healing in the injured cornea.

Amino Acids↗

Physical and biological properties of U.S. standard endotoxin EC after exposure to ionizing radiation.

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to 60Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component, lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.

Animals↗

Serum total and isoenzyme lactate dehydrogenase activity in American Burkitt's lymphoma patients.

Serum total lactate dehydrogenase (LDH) and LDH isoenzyme activities were studied in 45 American patients with a tissue diagnosis of Burkitt's lymphoma. Serum total LDH activity correlated with tumor burden as determined by clinical staging at presentation or clinical stage of the disease process ("disease status"). Tumor lysis by chemotherapy considerably increased the serum total LDH activity. For the LDH isoenzyme pattern, the largest relative increases were found with LDH3 and LDH4, whereas the highest isoenzyme activities occurred with LDH2 and LDH3. Thus, the total and isoenzyme LDH activities are helpful to evaluate the tumor burden and prognosis in patients with Burkitt's lymphoma.

Adolescent↗

Five creatine kinase isoenzymes in serum of a patient with severe heart disease.

Abnormal creatine kinase (CK) isoenzyme patterns were observed in the serum of a 64-year-old woman with severe heart disease. Agarose electrophoresis revealed the presence of all the usual CK isoenzymes (MM, MB, and BB) plus an extra band between MM and MB. Total serum CK activity was within the normal range. Within 2 h after the patient suffered cardiorespiratory arrest, a fifth CK isoenzyme appeared, cathodal to MM. After cardiac valve replacement, the patient's serum showed a high activity of CK, but the isoenzyme pattern showed only MM and, transiently, an MB band. With return of the serum CK activity to normal, the CK isoenzymes pattern also became normal, virtually ruling out genetic variant(s). The abnormal CK isoenzyme patterns might have been the consequence of severe hypoxemia in the patient, thus such patients may represent an ominous prognostic sign. The association of the abnormal pattern upon admission with rapid deterioration of the condition of the patient suggests prompt attention for the prevention of complications.

Alanine Transaminase↗

Cloning of human lymphocytes reactive with autologous leukemia cells.

The primed lymphocyte typing test has been used to detect leukemia-associated antigens, but interpretation has been difficult because of significant levels of reactivity with normal cells. Elimination of unwanted reactivities could be accomplished by (a) use of the patient's own lymphocytes as responders to the leukemia cells and (b) cloning of the responding cells. Cloning of antigen-activated human lymphocytes can be accomplished through the use of T-lymphocyte growth factor, which permits the long-term growth of antigen-activated lymphocytes. In the study reported here, the remission lymphocytes of a patient with acute myelogenous leukemia were sensitized in culture to the patient's own leukemic myeloblasts and then grown from wells containing one or a few replicating units. Sufficient cells of three clones were growth for further testing of specificity: one responded only to the sensitizing myeloblast but not to normal cells tested; one responded to the sensitizing myeloblasts and one allogeneic myeloblast but not to normal cells; and one responded to none of the cells tested, although it proliferated vigorously with growth factor alone. These results demonstrate the feasibility of cloning human lymphocytes putatively responsive to leukemia-associated antigens in order to improve their discriminatory capacity in the primed lymphocyte typing test. The response pattern observed was that expected of a clone responding to a leukemia-associated antigen.

Antigens, Neoplasm↗

C1q (c1) receptor on human platelets: inhibition of collagen-induced platelet aggregation by C1q (C1) molecules.

Hemolytically active human C1q incubated with EA before the addition of complement inhibited the immune hemolysis. On the contrary, heat-inactivated preparation (30 min 56 degrees C) was ineffective. Preincubation of EA with bovine collagen also resulted in a decreased hemolysis. When aggregation was measured by a turbidimetric method in citrated human platelet-rich plasma, it was found that hemolytically active human C1q (C1) alone does not induce platelet aggregation. However, in its presence the platelets failed to aggregate or exhibited a significantly reduced aggregation response to bovine collagen. The inhibition by C1q depended on the preincubation time with platelets. Heat treatment (30 min 56 degrees C) destroyed the inhibitory action of C1q (C1). The effect of C1q proved to be highly specific because different C1q preparations at their inhibitory doses in collagen-induced platelet aggregation did not influence the response to other aggregating agents (bovine thrombin, ADP, horse anti-human thymocyte globulin, goat anti-baboon platelet antiserum). The results prove that collagen and C1q are capable of binding to the same site(s); namely, to those of EA and human platelets; furthermore, they suggest the presence of a receptor for C1q (C1) on human platelets.

Adenosine Diphosphate↗

Bronchioloalveolar carcinoma presenting with meningeal carcinomatosis. Cytologic diagnosis in cerebrospinal fluid.

The cytologic findings in a 35-year-old patient with bronchioloalveolar carcinoma who initially presented with central nervous system involvement are reported. Following the cytologic diagnosis of carcinomatous meningitis (metastatic adenocarcinoma), an open lung biopsy was performed, which confirmed the presence of a primary pulmonary neoplasm (bronchioloalveolar carcinoma). This case illustrates the importance of the cytologic diagnosis of a clinically unsuspected primary neoplasm. Further, together with three earlier reported cases, it indicates that, in young patients, tumor cells shedding into the cerebrospinal fluid can be the first indication of bronchioloalveolar carcinoma.

Adenocarcinoma↗

Effects of restricting levothyroxine dosage strength availability.

We conducted a prospective, randomized, controlled trial to assess whether hospital formulary restrictions involving limiting dosage strengths of levothyroxine affect physicians' ability to manage patients effectively and provide pharmacy cost savings in a tertiary care federal government research hospital. Thirty-three endocrinologists were randomly assigned to prescribe levothyroxine from a restrictive (dosage strengths of 25, 50, 100, 125, and 150 micrograms) or a nonrestrictive (dosage strengths of 25, 50, 75, 100, 112, 125, 150, 175, 200, and 300 micrograms) formulary through a central computer system. Their 241 respective outpatients' laboratory results and drug compliance were outcome measures. Achievement of treatment objectives was measured by thyroid function tests (free and total thyroxine, total triiodothyronine, thyrotropin), number of clinic visits, and compliance (survey method). Additional measures were drug distribution patterns, drug costs, and pharmacy inventory costs. Restriction of levothyroxine's dosage strength did not significantly alter therapeutic outcomes. However, the restricted formulary was associated with more complex dosing regimens, and resulted in no significant cost savings. It is not known whether such restriction would adversely affect the care of patients of nonspecialists. Prospective studies are required to verify presumed cost-containment measures before such measures are adopted for widespread application.

Adult↗