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Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 307 records · Page 17Linked to original sources

Monoclonal antibody to a 43 000 Mr surface protein of a human leukaemia cell line (THP-1) crossreacts with the fibroblast intermediate filament protein vimentin.

Monoclonal antibodies were produced against surface antigens of live cells from a human acute monocytic leukaemia cell line (THP-1). One clone, VIC-C2, when assayed by immunofluorescence microscopy, brightly stained the surface of THP-1 cells and the cytoplasm of Langerhans cells, fibroblasts and melanocytes in sections of human skin. The immunoreactive cytoplasmic structures were filamentous and resembled intermediate filaments. By double immunofluorescence microscopy using VIC-C2 and polyclonal antibodies to vimentin, the VIC-C2 antigen was shown to be located on intermediate filaments of cultured fibroblasts and to follow these filaments during various drug-induced rearrangements. As demonstrated by immunoprecipitation, antibody gel overlay and immunoblotting of two-dimensional polyacrylamide gels, VIC-C2 recognized two different antigens in extracts of THP-1 cells: one of Mr = 43 000 and pI = 7, the other of Mr = 57 000. In extracts from various cultured fibroblast cells only the 57 000 Mr antigen was detected. This 57 000 Mr protein was identified as vimentin by immunoblotting of rat glioma C6 cytoskeletons on two-dimensional gels. When vimentin was digested with chymotrypsin, only fragments containing parts of both helical rod pieces and the connecting non-helical spacer-region were strongly antigenic, whereas the helical rods alone were only weakly crossreactive. Moreover, immunoprecipitation revealed that VIC-C2 preferentially reacted with native compared to denatured vimentin.

Antibodies, Monoclonal↗

Effect of successful thrombolytic therapy on right ventricular function in acute inferior wall myocardial infarction.

In 19 patients undergoing intracoronary fibrinolytic therapy for acute myocardial infarction, the site of coronary obstruction was in the proximal right coronary artery. Time between onset of symptoms and hospitalization was less than 4 hours. These patients were studied prospectively by radionuclide techniques immediately after admission, 48 hours and 4 weeks after AMI. Right and left ventricular (RV and LV) ejection fractions (EF) were calculated from gated blood pool scintigrams and the size of the LV perfusion defect was assessed by thallium-201 scintigraphy. Before the intervention, RV performance was significantly lower (RVEF 29 +/- 8%) than normal (53 +/- 7%). The size of the LV perfusion defect was relatively small (less than 25% of LV circumference), and as a consequence, LV pump function was only marginally impaired (LVEF 54 +/- 11%). Recanalization of the infarct artery was achieved in 12 patients (group A); in 7 patients the infarct artery remained occluded (group B). Early after the intervention (48 hours), RV performance in group A recovered significantly (RVEF: 30 +/- 9% vs 39 +/- 7%, p less than 0.01), and further improvement was noted at 4 weeks (RVEF 43 +/- 5%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Necropsy evaluation in seven patients with evolving acute myocardial infarction treated with thrombolytic therapy.

Systemic and intracoronary streptokinase application may recanalize a coronary artery occluded by a thrombus in patients with acute myocardial infarction (MI). However, thrombolysis fails in a number of patients for unknown reasons. The coronary and myocardial histologic characteristics were studied in 3 patients in whom recanalization was successful without subsequent reocclusion, and in 4 patients in whom recanalization was unsuccessful. All patients died within 4 weeks after the acute intervention. Serial sections from the angiographically localized occlusive site of the infarct vessel, and transverse slices of the heart stained with nitroblue tetrazolium for delineation of MI, were examined by light microscopy. Successfully recanalized arteries were patent at necropsy and showed obstructive fibrous atherosclerotic plaques. Among patients in whom recanalization was unsuccessful, 1 patient had occlusions from nonatherosclerotic intramural hemorrhage and 1 from persisting long, mixed old and fresh thrombus, and 2 patients had high-grade obstructions from ruptured atherosclerotic plaques with intimal hemorrhage and residual clot. Reperfused infarct tissue consisted predominantly of contraction band necroses, whereas MIs without reperfusion showed coagulation necroses of the muscle fibers. The results suggest that the success of recanalization depends, in part, on the morphologic features of the coronary occlusion, and that reperfusion after successful thrombolysis may lead to a different pattern of muscle fiber necrosis in the irreversibly injured infarct areas.

Adult↗

Estimation of left ventricular myocardial function by the ejection fraction in isolated, chronic, pure aortic regurgitation.

In patients with aortic regurgitation (AR), the left ventricular (LV) ejection fraction (EF) may not adequately reflect depressions of myocardial contractility due to decreased aortic impedance. The sensitivity of end-systolic pressure-volume relations and stress-volume relations in detecting myocardial depression in patients with AR was studied. In 12 patients with normal valvular function but with varying LV function (due to coronary heart disease in 9 patients and dilated cardiomyopathy in 3 patients) (group 1), and in 8 patients with AR (group 2), LV angiography was performed before and after sublingual application of isosorbide dinitrate. Heart rate was kept constant by right atrial pacing. In group 1, the slope k of the end-systolic pressure-volume relation was to EF at rest: k = 0.091.e0.051 EF; r = 0.88. In AR, this relation was shifted significantly to the right: k = 0.019.e0.066 EF; r = 0.92. This shift persisted when the end-systolic stress-volume relation instead of the end-systolic pressure-volume relation was calculated. Thus, in patients with AR the end-systolic pressure-volume relation is flatter than that in patients with intact valvular function at a given EF. The same is true for the end-systolic stress-volume relation. The data indicate that EF overestimates myocardial contractility in AR compared with end-systolic pressure-volume or stress-volume relations. This overestimation is probably a result of decreased aortic impedance in AR.

Adult↗

Thrombolysis in acute myocardial infarction: effect of intravenous followed by intracoronary streptokinase application on estimates of infarct size.

The effect of pretreatment with intravenous infusion of streptokinase (SK) (16,700 U/min for 90 minutes), started after diagnosis and followed by intracoronary application (2000 U/min) (protocol 1), was assessed retrospectively in 55 consecutive patients with acute transmural myocardial infarction (MI). Another 46 patients with acute MI treated previously by intracoronary thrombolysis served as control subjects (protocol 2). Reperfusion at first coronary injection was observed after pretreatment in 25 patients (45%), but in no control patient (p less than 0.001). Fifteen patients with successful pretreatment (group A), 20 patients with successful treatment according to protocol 2 (group B) and 9 patients with unsuccessful thrombolysis (group C) were restudied after 4 weeks. Data from patients with reinfarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty before restudy were excluded. Thallium-201 scintigraphy was performed before and 24 hours after treatment, serum creatine kinase activity was measured every 8 hours for 3 days and regional ejection fraction (EF) of acute MI was determined before and 4 weeks after treatment. The scintigraphic, enzymatic and hemodynamic data before treatment indicated severe and comparable ischemia among the 3 groups. The thallium-201 perfusion defect decreased in group A (from 41 to 21%, p less than 0.01) and in group B (from 38 to 26%, p less than 0.01), but did not change in group C (from 37 to 31%, difference not significant). Peak serum creatine kinase levels normalized by the perfusion area of acute MI was 20, 33 and 58 U/liter unit in groups A, B and C. The mean values of groups A and C were significantly different (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Bleomycin-induced linear hyperpigmentation].

We describe the progression of bleomycin-induced inflammatory lesions to linear hyperpigmentations in 2 patients. Striking, hitherto unreported observations were the development of streaking after a single dose of 5 mg bleomycin (patient 1) and vacuolar degeneration of melanocytes in the inflammatory stage (patient 2).

Bleomycin↗

Human large granular lymphocytes and their relationship to natural killer cell activity in various disease states.

This study investigated the numbers of large granular lymphocytes (LGL) and their relationship to natural killer (NK) function, as assessed by their capacity to lyse the human tumor target, K562. Peripheral blood mononuclear cells from 42 normal controls and from 171 patients suffering from various nonmalignant or malignant diseases were evaluated. Also studied were samples from a patient undergoing autologous bone marrow reconstitution following total body irradiation. Results suggested the existence of a close relationship between the numbers of LGL and the capacity to lyse K562 targets, further supporting the view that LGL are crucial effector cells mediating NK lysis. In certain diseases, such as malignant states, functional capacity was not simply determined by the numbers of LGL. Here preferential reduction of the capacity to lyse K562 targets was observed, indicating that additional limiting factors are involved in the determination of the cytotoxic potential. Based on the relationship between LGL and natural immune functions, as well as on the identification of leukemias affecting this cell type, we would recommend their evaluation on a large scale clinical basis.

Adolescent↗

[Function of the right ventricle in mitral valve defects before and after surgical correction].

To ascertain whether surgical correction of mitral valve lesions can lead to postoperative improvement of right ventricular function, investigations were carried out in 17 patients with mitral valve disease, clinical severity grade III and IV, before and at an average of 18 months postoperatively. Six subjects without heart disease served as controls. Preoperatively, all patients underwent catheterization and cineangiographic evaluation of both the right and left ventricles. The right ventricular ejection fraction (RV-EF) was also determined from the radionuclide ventriculogram before and after the surgical intervention (closed mitral commissurotomy in five patients and mitral valve replacement in twelve). The patients were studied at rest and during bicycle ergometry in the supine position. As compared with control subjects, before surgery at rest, patients with mitral valve disease had significantly higher values for mean left atrial pressure (22 +/- 7 vs 8 +/- 2 mm Hg), mean pulmonary artery pressure (39 +/- 17 vs 17 +/- 5 mmHg), pulmonary arteriolar resistance (361 +/- 260, increased 5-fold, vs 69 +/- 27 dyn . s . cm-5) and right ventricular systolic pressure (55 +/- 20 vs 24 +/- 6 mmHg) while the values for right ventricular end-diastolic pressure, mean right atrial pressure, left ventricular end-diastolic pressure and left ventricular systolic pressure did not differ (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

[Thrombolysis in acute transmural heart infarction: length of ischemia as a determinant of late results after 15 months].

In 28 patients the effect of coronary artery reperfusion in acute transmural myocardial infarction was evaluated by the clinical and hemodynamic results obtained after 15 months. Patients with successful reperfusion within 4 hours after onset of symptoms were assembled in group A1 (n = 11), patients with successful reperfusion after more than 4 hours in group A2 (n = 7). Group B consists of 10 patients with unsuccessful reperfusion. Left ventricular ejection fraction (radionuclide ventriculography) and the perfusion defect (thallium-201 scintigraphy) were measured acutely and after 15 months (at rest and during exercise). The coronary anatomy and the regional ejection fraction of infarct area were determined acutely and after 4 weeks by cineangiography. Serum creatine kinase activity was measured serially during the acute phase of the infarction. Before the acute intervention, the patients of the 3 groups were comparable with regard to killip class, location of infarction, number of previous infarctions, coronary anatomy, left ventricular ejection fraction, thallium-201 perfusion defect and base-line serum creatine kinase activity. During acute infarction peak creatine kinase activity tended to be lower in group A1 (1296 U/l) than in group A2 (2100 U/l, NS) and in group B (2240 U/l, NS). After 4 weeks regional ejection fraction of infarct area was higher in group A1 (36%) than in groups A2 (24%, NS) and B (20%, p less than 0.05). After 15 months the thallium-201 perfusion defect was smaller in group A1 (7%) than in groups A2 (28%, p less than 0.05) and B (34%, p less than 0.01). At the same time left ventricular ejection fraction was higher in group A1 (52%) than in groups A2 (34%, p less than 0.05) and B (35%, p less than 0.05). Fifteen months after acute infarction patients in group A1 tended to reach a higher workload during exercise (118 watts) compared with patients of groups A2 (82 watts, NS) and B (86 watts, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Is the quotient: systolic peak pressure/end-systolic volume a useful parameter in the assessment of left ventricular function?].

The quotient: peak systolic pressure/end-systolic volume (SP/ESVI) has been proposed as a parameter of LV function and as a substitute for the slope k of the end-systolic pressure-volume relation (P-Ves), because SP/ESVI is much easier to obtain. Therefore, the relation between SP/ESVI and k and the relation between SP/ESVI and ejection fraction (EF) were investigated. In 18 patients P-Ves was obtained after vegetative blockade (1.5 mg atropine and 0.15 mg/kg propranolol) from three LV angiograms at three different afterloads (control, isosorbide dinitrate, methoxamine). - SP/ESVI and slope k showed a moderate correlation: SP/ESVI = 0.50k + 2.35; r = 0.76. SP/ESVI and EF were correlated best in an exponential way: SP/ESVI = 0.267 X e0. 045EF ; r = 0.82.- An essential disadvantage of the quotient SP/ESVI resides in the fact, that the P-Ves line has varying intercepts on the abscissa. Secondly, any quotient may belong to several P-Ves lines. The quotient SP/ESVI may be used only with caution and under specific conditions as a substitute of the slope k of the P-Ves.

Blood Pressure↗

[Improvement of the non-invasive diagnosis of coronary heart disease using a new double-isotope method for the noninvasive determination of coronary transit times].

In conventional myocardial Thallium-201 scintigraphy, regional myocardial Thallium-201 activity is compared to the area of normal, i.e., maximal activity. In the presence of multivessel coronary artery disease, this mode of evaluation may yield false negative results. -In 87 patients suffering from coronary artery disease and in 26 controls, after simultaneous i.v. injection of Thallium-201 and Technetium-99m coronary transit times of Thallium-201 were determined as the interval between arrival of the tracer in the aortic root and the onset of its extraction in different myocardial areas. - Patients with hemodynamically significant coronary artery stenoses (greater than or equal to 75%) revealed a significant increase in coronary transit times over septum, apex, or posterolateral wall of the left ventricle. Using maximal coronary transit times, i.e., the largest of the regional values, an excellent discrimination between patients with severe coronary artery stenoses and controls was achieved. Following coronary vasodilatation with dipyridamole, even subcritical (50-75%) coronary artery stenoses could be detected with high sensitivity, since the shortening of coronary transit times in patients with subcritical stenoses was less pronounced as compared to controls. - Especially in the presence of diffuse three-vessel coronary artery disease, the quantitative assessment of regional coronary transit times yields important parametric data in addition to those obtained by conventional Thallium-201 scintigraphy combining static imaging with rapid sequence analysis of time-activity curves.

Coronary Disease↗

Distribution of anionic surface sites on human melanocytes and human melanoma cells in culture.

With cationized ferritin (CF) as an ultrastructural marker for anionic cell surface sites, cultured guinea pig melanocytes display a uniquely homogeneous labelling pattern and a striking absence of redistribution of marker material. In the present study, we applied the same technique to normal human melanocytes and melanoma cells. Unfixed primary human mixed epidermal cell cultures displayed CF labelling patterns identical to those in guinea pig epidermal cells: on keratinocytes, CF was found in distinct aggregations which, upon prolonged incubation, clustered and were shed. Melanocytes, in contrast, bound CF to the cell surface as a uniform diffuse monolayer. There were no signs of cluster formation or shedding. Melanoma cell cultures were derived from 10 primary (2 lentigo maligna, 1 lentigo maligna melanoma, 4 superficial spreading melanomas, 2 nodular portions of superficial spreading melanomas, 1 nodular melanoma) and from 7 metastatic melanomas (4 cutaneous, 3 lymph node metastases). The CF labelling patterns encountered were heterogeneous. Three out of 10 primary tumors and 5 out of 7 metastases showed alterations of the normal melanocyte labelling pattern: regions of typical CF distribution were irregularly interrupted by stretches of membrane free of marker. In some areas, CF occurred in small globular aggregates. There was considerable heterogeneity of CF labelling patterns in different clones of a given culture. Altered CF binding patterns in melanoma cells appear to be associated with high metastasizing protential of the cell clones and may thus represent an unfavourable prognostic sign.

Binding Sites↗

Intracoronary thrombolysis in acute myocardial infarction: an attempt to quantitate its effect by comparison of enzymatic estimate of myocardial necrosis with left ventricular ejection fraction.

The quantity of myocardium was estimated that can be salvaged by reperfusion of acute transmural myocardial infarction (MI). Serial analysis of serum creatine kinase (CK) activity was carried out in 41 consecutive patients with acute MI who underwent intracoronary thrombolysis. Enzymatic estimate of MI size was calculated using an average (method A) and an individually determined elimination constant (method B). Left ventricular ejection fraction 4 weeks after successful thrombolysis (cineangiogram) correlated inversely with MI size (method A: r = -0.85, method B: r = -0.76; both p less than 0.001). Patients with recanalization within 4 hours after the onset of symptoms were assembled in group A1 (n = 13, early reperfusion), and patients with successful recanalization after 4 hours in group A2 (n = 16, late reperfusion). Group B consisted of 12 patients without reperfusion. MI size in group A1 was 21 CK-g-Eq (method A) and 23 CK-g-Eq (method B), in group A2 50 CK-g-Eq (method A) and 54 CK-g-Eq (method B), and in group B 73 CK-g-Eq (method A) and 63 CK-g-Eq (method B). Mean values in group A1 were lower than in group A2 and group B (p less than 0.05). It is concluded that MI size was significantly reduced to about one third after early reperfusion as compared with no reperfusion. In contrast, MI size was not significantly reduced after late reperfusion.

Adult↗

Histiocytosis-X in gynecology.

(1) Histiocytosis-X can manifest itself in virtually every organ, but in gynecology it is an absolute curiosity. (2) Differential diagnosis must exclude specific and nonspecific ulcerations and granulations such as syphilis, tuberculosis, Boeck's disease, and also neoplastic processes like lymphomas, sarcomas, carcinomas, and malignant diseases of the hemopoietic system. (3) The diagnosis by light microscopy alone, as in our case, may be insufficient; therefore, electron microscopy should be used. As soon as the diagnosis is confirmed histologically, an extensive examination of all organs is necessary in order to establish an exact prognosis and an optimal plan of therapy. (4) Because of the unknown etiology of histiocytosis-X, a causal treatment is not yet possible. In spite of this, with a symptomatic, individualized therapy by means of excision, low-dose irradiation and cytotoxic agents a 5-year survival of 90% was obtained for the patients. (5) Because of its rarity and multidisciplinary character, histiocytosis-X is a challenge to interdisciplinary and interregional cooperation. Though not being a malignoma in the strict sense, diagnosis, therapy, and in part prognosis are not essentially different from a malignant disease.

Adult↗

Expression of Thy-1 antigen by murine epidermal cells.

We report on the occurrence of a cell population within the murine epidermis which, by both morphologic and surface property criteria, is distinct from all other epidermal cell types known so far. These previously unrecognized cells are evenly distributed within the epidermis, display a primarily dendritic shape, exhibit a lobulated nucleus, contain large amounts of vimentin type intermediate-sized filaments, but lack desmosomes, melanosomes, Merkel cell granules, and Birbeck granules. As opposed to melanocytes, these cells fail to display tyrosinase activity. Surface marker analysis reveals these cells to uniformly express the Thy-1 antigen and to lack I-A and I-E/C antigen specificities. A major portion of these Thy-1-bearing cells are reactive with a monoclonal antibody to the Ly-5 determinant whereas attempts to demonstrate Lyt-1,2,3 antigens consistently yield negative results. These findings strongly suggest that Thy-1+ epidermal cells originate from the bone marrow; however, their precise relationship to distinct members of the hemopoietic differentiation pathway remains to be established.

Animals↗

Subsets of epidermal Langerhans cells as defined by lectin binding profiles.

In this study we characterize the cell surface glycoconjugate moieties of strain 2 guinea pig epidermal Langerhans cells (LC) in single cell suspension by using a battery of 17 fluorescent lectins. All LC displayed binding sites for concanavalin A, succinylated concanavalin A, Lens culinaris agglutinin, Pisum sativum agglutinin, wheat germ agglutinin, succinylated wheat germ agglutinin, Griffonia simplicifolia agglutinin I, Ricinus communis agglutinin I, Phaseolus vulgaris E agglutinin, and Phaseolus vulgaris L agglutinin, but failed to bind Sophora japonica agglutinin (SJA), Dolichos biflorus agglutinin (DBA), and Ulex europaeus agglutinin I (UEA I). Neuraminidase pretreatment rendered LC reactive for SJA, but not for DBA and UEA I. The binding profiles of certain lectins point to the existence of LC subpopulations in that Griffonia simplicifolia I-B4 isolectin, peanut agglutinin (PNA), Helix pomatia agglutinin, and soybean agglutinin bound to only 80% (range 70-90%) of Ia-positive epidermal cells; binding sites for these lectins on primarily unreactive Ia-positive cells were unmasked when epidermal cells were treated with neuraminidase prior to lectin labeling. Ultrastructural PNA labeling studies revealed that the vast majority of Birbeck granule-containing LC displayed PNA binding sites, whereas indeterminate cells were consistently PNA-negative. Identification of carbohydrate configurations expressed on LC surfaces by lectin binding may provide a clue for the elucidation of the mechanisms of established LC functions and possibly the discovery of as yet unknown properties of this cell type.

Animals↗

Identical lectin binding patterns of human melanocytes and melanoma cells in vitro.

Cell surface glycoconjugate patterns of human epidermal cells and of melanoma cells (MC) in primary culture derived from 11 primary and metastatic melanomas were investigated using fluorescent and horseradish peroxidase conjugated lectins for visualization at the light and electron microscopic level. The lectin labeling profiles of human melanocytes (M) and MC were found to be identical. According to their binding patterns, the lectins tested were grouped into three categories: (1) lectins binding to both keratinocytes (K) and M/MC, irrespective of neuraminidase pretreatment (concanavalin-A, wheatgerm agglutinin, succinylated wheatgerm agglutinin); (2) lectins binding to K but not to M/MC, irrespective of neuraminidase pretreatment (Ulex europaeus agglutinin I); (3) lectins binding to K, but to M/MC only after neuraminidase pretreatment (soybean, Helix pomatia, and peanut agglutinins). Untreated M were reactive for soybean and peanut agglutinins only at contact sites with K. Since the lectins from soybean, Helix, and peanut bind specifically to D-galactose and N-acetyl-D-galactosamine residues, we conclude that these particular glycoconjugates are normally masked by sialic acid on M/MC surfaces and can be unmasked by neuraminidase. These features, which have been previously observed in guinea pig M, appear to be interspecies surface markers of melanocytic cells which remain unaltered in the course of malignant transformation.

Animals↗