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Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 325 records · Page 18Linked to original sources

In vitro complement binding in human skin cells with altered differentiation.

Exposure of cytoskeletal intermediate-sized filaments (ISF) of various cell populations in normal human skin to normal human serum (NHS) results in the deposition of C3 upon these structures; this phenomenon most likely occurs antibody-independently, is initiated by Clq binding to ISF, and is followed by the activation of the classical complement pathway. In the present study we investigated the cytoplasmic C3-binding properties of skin cells undergoing altered differentiation. Incubation of cryostat skin sections of dermal melanocytic nevi with NHS and, subsequently, with fluorescein isothiocyanate-conjugated rabbit antihuman C3 resulted in a bright cytoplasmic staining of the vast majority of nevus cells. Immunoelectron microscopic studies demonstrated that ISF within nevus cells represented the only cytoplasmic C3-binding structures. In contrast, ISF within melanoma cells, basal cell carcinoma cells, and keratinocytes constituting psoriatic lesions lacked C3-binding properties. We propose that changes in structure and subunit protein composition of ISF in certain cells undergoing altered differentiation results in a decrease or loss of their C3-binding capacity.

Basal Cell Carcinoma↗

Histiocytosis X cells in eosinophilic granuloma express Ia and T6 antigens.

Morphologic similarities between histiocytosis X (HX) cells and epidermal Langerhans cells (LC) have led to the hypothesis that HX represents a proliferative disorder of LC. In order to prove the validity of this assumption, we tested single cell suspensions isolated from an eosinophilic granuloma type HX lesion for the presence of various antigenic determinants defined by monoclonal antibodies using an immunoelectron microscopic technique. An anti-Ia reagent reacted with essentially all histiocytic cells and a small portion of lymphocytes whereas plasma cells and eosinophils were negative. T6 antigen, in contrast, was disclosed exclusively on HX cells either with or without Birbeck granules. Pan-T cell-reagent OKT3 reacted only with small lymphocytes. The finding that HX cells from eosinophilic granuloma lesions are the only cells that have the identical surface marker equipment as epidermal LC (Ia antigens, T6 antigen, Fc-IgG, and C3 receptors) strongly supports the concept that these cells are derived from the LC lineage.

Adult↗

Junctional blisters in acquired bullous disorders of the dermal-epidermal junction zone: role of the lamina lucida as the mechanical locus minoris resistentiae.

The level of cleavage was determined in a variety of acquired bullous diseases of the dermal-epidermal junction zone (bullous pemphigoid, dermatitis herpetiformis, porphyria cutanea tarda and epidermolysis bullosa acquisita). We used an indirect immunofluorescence technique to examine the basal membrane zone with anti-type IV collagen and anti-laminin antisera and bullous pemphigoid sera. The majority of blisters examined proved to be junctional, including those from disorders hitherto considered to be dermolytic. Dermolytic cleavage was encountered only sporadically in microvesicles of dermatitis herpetiformis, in one small vesicle and in one out of five large blisters of porphyria cutanea tarda and in a large lesion of epidermolysis bullosa acquisita. We conclude that in acquired bullous disorders of the dermal-epidermal junction zone the preferential site of split formation is the lamina lucida which appears to act as a locus minoris resistentiae; dermolytic split formation of substantial extent occurs only when the sublaminal fibrillar apparatus is mechanically compromised.

Blister↗

Coated Langerhans cell granules in histiocytosis X cells.

Histiocytosis X cells (HXC) and epidermal Langerhans cells (LC) are thought to be closely related because they share morphologic features and immunologic markers. One of these common markers, the LC granule, is an acknowledged morphologic criterion for the identification of these cell types, but its function and, thus, significance are as yet unknown. In this study, we report the presence of a fuzzy coat radiating from the cytoplasmic face of the LC granule membrane in HXC. This bristly coat is indistinguishable from that of coated vesicles and pits and, thus, represents a strong morphologic clue to the function of LC granules because coated structures have been shown to be involved in the selective transport of molecules in eukaryotic cells.

Adult↗

Enrichment of epidermal Langerhans cells by immunoadsorption to Staphylococcus aureus cells.

In addition to keratinocytes and melanocytes, the mammalian epidermis harbors the so-called Langerhans cells (LC)2 as a third cell population, which is thought to participate in immune reactions involving the epidermis (1, 2). LC are dendritic cells located above the basal cell layer, have a characteristic ultrastructural appearance (3), and originate from a bone marrow precursor (4, 5). They lack membrane-incorporated surface immunoglobulin and sheep red blood cell receptors, but are the only epidermal cells (EC) that bear receptors for the Fc portion of IgG (Fc-IgG) and for C3 and express Ia antigens (1, 2). Because LC constitute only 3 to 5% of all EC, enrichment procedures are important for functional studies. Moderate enrichment of LC to 18 to 35% by separation of Fc-IgG rosetting EC on density gradients was sufficient to show the critical role of LC in EC-induced T cell proliferation (6). More powerful isolation procedures are needed, however, for more exacting analysis of LC functions, such as their role in immune induction, their secretory capacities including production of EC-derived thymocyte-activating factor (7, 8) and prostaglandins, immune endocytosis, the role of LC granules, etc. Methods hitherto available for enriching LC beyond 60% (9, 10) are time consuming and of low yield and viability, and thus are of limited practical value. In this report we describe a simple and efficient procedure to obtain viable LC suspensions of high purity based on the use of monolayers of protein A-bearing Staphylococcus aureus cells as a solid-phase immunoadsorbent (11).

Animals↗

[Prognostic value of preoperatively determined end-systolic left ventricular diameter in patients with chronic aortic insufficiency--an echocardiographic study].

Serial echocardiographic studies of Henry et al. (Circulation 61, 471 [1980]) in patients with chronic aortic regurgigation (AR) indicate that preoperative left ventricular end-systolic dimension (ESD) greater than 55 mm and fractional shortening (FS) less than 25% may identify patients with reduced postoperative survival. We retrospectively analyzed the onedimensional echocardiograms of 33 patients with AR without coronary artery disease who underwent operation from 1977 to 1981. Twenty-three patients with ESD less than or equal to 55 mm (group A, mean age 48 +/- 10 years) were followed 36 +/- 14 months postoperatively, ten patients with ESD greater than 55 mm (group B, eight patients with FS less than 25%; mean age 48 +/- 12 years) 40 +/- 10 months. In both groups there were no perioperative or late deaths. In group A the average preoperative NYHA functional class decreased from 2.6 to 1.4 postoperatively, in group B from 3.0 to 1.5 (A vs. B: NS). Preoperative FS was 35 +/- 8% in group A and 22 +/- 3% in group B, preoperative ESD 44 +/- 5 mm in group A and 62 +/- 7 in group B. Three years after operation, end-diastolic dimension was 54 +/- 8 mm compared with 68 +/- 5 mm preoperatively in group A (p less than 0.001) and 61 +/- 11 mm compared to 79 +/- 8 mm preoperatively in group B (p less than 0.001). According to these data, a significant postoperative decrease of end-diastolic dimension can be expected in most patients with AR and ESD greater than 55 mm. The long-term prognosis of this subgroup is not so impaired as to recommend aortic valve replacement to asymptomatic patients a priori.

Aortic Valve Insufficiency↗

Primary leptomeningeal melanoma. Diagnosis by ultrastructural cytology of cerebrospinal fluid and cranial computed tomography.

A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue ("leptomeningeal melanomatosis"), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

Brain↗

Noninvasive assessment of myocardial contractility in asymptomatic patients with sever aortic regurgitation and normal left ventricular ejection fraction at rest.

In 14 asymptomatic patients with isolated aortic insufficiency the slope k of the end-systolic pressure-volume relation was determined noninvasively with equilibrium radionuclide angiography. The results were compared with changes in left ventricular ejection fraction during maximal physical stress. Nine normal volunteers served as a control group. Patients with aortic insufficiency did not differ significantly from the control group with respect to left ventricular ejection fraction at rest (aortic insufficiency 62 + 8 percent, control 65 +/- 6; probability [p] = not significant [NS]), physical work capacity (aortic insufficiency 113 +/- 32 watts, control 117 +/- 25; p = NS) or age (aortic insufficiency 40 +/- 10 years, control 47 +/- 7; p = NS). The slope (k) of the end-systolic pressure-volume relation was found to be significantly lower in the group with aortic insufficiency (3.1 +/- 1.1) than in the control group (4.1 +/- 0.5; p less than 0.05). Patients with aortic insufficiency could be classified into two subgroups with respect to the slope k. In subgroup A (n = 7) the slope fell within the normal range (4.0 +/- 0.6) as defined by the control group, and the left ventricular exercise reserve was normal (6 percent +/- 1). In subgroup B (n = 7) the slope was significantly lower (2.2 +/- 0.6, p less than 0.01), indicating depressed myocardial contractility, and all patients experienced left ventricular dysfunction during exercise (left ventricular exercise reserve -5 +/- 5 percent). Thus, noninvasive determination of the end-systolic pressure-volume relation identified two subsets of asymptomatic patients with aortic insufficiency, one with impaired myocardial contractility and normal left ventricular exercise reserve and a second group with depressed myocardial contractility and left ventricular dysfunction during exercise. Therefore, an abnormal baseline contractile state in asymptomatic patients with aortic insufficiency may be uncovered by noninvasive determination of the end-systolic pressure-volume relation or by assessing the left ventricular exercise reserve. Serial studies in a larger group of patients undergoing surgical correction of the valve lesion are indicated to determine whether this information will be helpful in evaluating when to operate on asymptomatic patients with aortic insufficiency.

Adult↗

Intracoronary thrombolysis in acute myocardial infarction: duration of ischemia as a major determinant of late results after recanalization.

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15), and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction, and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured. Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area, and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59%) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p less than 0.05; regional ejection fraction: 26%, p less than 0.05) and group B (ejection fraction: 44%, p less than 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p less than 0.05) and group B (2,106 U/liter, p less than 0.05). Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.

Aged↗

The syndrome of milker's nodules in burn injury: evidence for indirect viral transmission.

Four patients with first- to second-degree burns developed multiple unusual nodular lesions confined to the burned areas 2 to 3 weeks after the accident. Electron microscopy disclosed viral particles within epidermal cells. These were identified as subgroup II poxvirus. Viral culture established the diagnosis of paravaccinia (milker's nodule) infection. Since none of the patients had had direct contact with infected animals, but had been in contact with contaminated objects, an indirect viral transmission, previously not reported for milker's nodules, appears the most likely mode of infection.

Adult↗

In vitro complement binding on cytoplasmic structures in normal human skin: immunoelectronmicroscopic studies.

We have previously provided evidence that suggests that exposure of cryostat skin sections to normal human serum (NHS) results in the antibody-independent Clq binding to cytoplasmic structures of various cell types, leading to classical complement pathway activation as evidenced by cytoplasmic C3 deposition. In the present study, we have employed immunoelectronmicroscopic methods to clarify the exact nature of cytoplasmic C3 binding structures. Incubation of cryostat skin sections with NHS followed by peroxidase-labeled rabbit anti-human C3 serum (HRP-R/Hu C3) revealed that intracytoplasmic binding of C3 occurred in suprabasal keratinocytes, melanocytes, fibroblasts, smooth muscle cells, endothelial cells, pericytes, Schwann cells, and nerve axons, but not in basal keratinocytes, Langerhans cells, and other cellular constituents of the skin. C3 binding, as revealed by the deposition of HRP reaction product, was exclusively confined to intermediate-sized filaments (ISF), which can therefore be considered to represent the subcellular site for classical complement pathway activation. Under experimental conditions that do not allow classical complement pathway activation, ISF were not decorated. Our observation that ISF of ontogenetically different cell types share the capacity of complement fixation is in accordance with the recent finding that different ISF types, despite their biochemical and antigenic heterogeneity, have common alpha-helical domains and may provide a clue to the mechanism and site of interaction between complement components and ISF.

Axons↗

Dose-dependent haemodynamic response to prenalterol in patients with congestive heart failure.

The effect of three doses of prenalterol, 12.5, 25 and 50 micrograms, on cardiac index (CI), pulmonary artery pressure (PAP), heart rate (HR), and stroke volume index (SVI) was investigated in 18 patients with congestive heart failure (CHF). Twelve patients received only prenalterol, while 6 patients received prenalterol 1 hour after an oral dose of hydralazine and isosorbid dinitrate. In 7 out of 12 patients a dose-dependent increase in HR was observed. The response of HR was inversely correlated to resting catecholamine levels; patients with high resting catecholamines--these are patients with severe CHF--did not show any increase in HR. CI increased in 8 out of 12 patients (average 1 . 1/min m) and SVI in 5 out of 12 patients. This inconsistent response was not dependent on left ventricular ejection fraction or plasma catecholamines at rest. Pretreatment with vasodilators did not improve the haemodynamic response to prenalterol. Four out of 17 patients demonstrated an increase in severity of arrhythmias suggestive of arrhythmogenic properties of prenalterol.

Administration, Oral↗

Selective accumulation of lipid within melanocytes during photochemotherapy (PUVA) of psoriasis.

In patients undergoing photochemotherapy (PUVA) a selective accumulation of lipid droplets was observed within the cytoplasm of melanocytes. Keratinocytes did not develop lipid droplets. Within 2 months after clearing of psoriasis the droplets gradually vanished and did not reappear even during maintenance PUVA therapy. Increased intracellular lipid deposits are usually taken to herald cell degeneration. Since the maximum lipid accumulation coincided with the end of the clearing phase when melanin production was at its height, the intramelanocytic lipid may have been a morphological sign of over-stimulation of melanocytes, which could eventually result in melanocyte destruction. Since excess melanin may be cytotoxic for melanocytes this may explain the irreversible hypopigmentation which develops in some patients treated with PUVA.

Adolescent↗

Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy.

Twenty-one patients with acute myocardial infarction, admitted to the hospital within 4 hours after the onset of symptoms, were studied by seven-pinhole thallium-201 scintigraphy before and 1 hour and 24 hours after intracoronary fibrinolysis using streptokinase. The size of the thallium-201 perfusion defect was assessed from myocardial cross sections reconstructed from the original seven-pinhole data and expressed as a fraction of left ventricular circumference. Recanalization was achieved in 16 patients within 3.9 +/- 1.6 hours after onset of symptoms (group A). In these patients, the size of the perfusion defect had decreased from 36 +/- 17% to 19% +/- 15% (p less than 0.001) at 24 hours. No significant change was detected by redistribution at 1 hour after the intervention. In five patients, intracoronary fibrinolysis was unsuccessful, and the vessel remained occluded (group B). The thallium-201 perfusion defect affected 40 +/- 15% of the left ventricular circumference before the intervention; it remained virtually unchanged at 1 hour (37 +/- 16%) and at 24 hours (41 +/- 15%) after fibrinolysis. The perfusion defect was most reduced in patients with extensive collaterals supplying the ischemic area or with subtotal occlusion of the affected coronary artery. We conclude that successful intracoronary fibrinolysis may reduce the size of the thallium-201 perfusion defect in many patients with acute myocardial infarction. One important factor in the final result may be the presence of residual coronary flow supplied by extensive collaterals or by subtotal occlusion of the affected coronary artery when reperfusion is achieved around 4 hours after the onset of symptoms.

Adult↗