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Biomedical subjects

R Schreiber

Publications and source records attributed to R Schreiber.

At least 163 records · Page 9Linked to original sources

Reduction of morbidity and cytokine release in anti-CD3 MoAb-treated mice by corticosteroids.

In keeping with the in vitro mitogenic properties of anti-CD3 MoAbs, the first injections of anti-CD3 are invariably responsible for an in vivo cellular activation. This activation induces a massive cytokine release in the circulation (TNF, IFN gamma, IL-2, IL-6, and IL-3). Paralleling this release, a severe clinical reaction occurs in OKT3-treated patients and in 145 2C11-treated mice. Corticosteroids both in vitro and in vivo inhibit the production of several cytokines involved in the anti-CD3 reaction. A single 1 mg hydrocortisone dose was administered to 145 2C11-treated mice according to different kinetics schedules. When given 1 hr prior to the anti-CD3 MoAb, hydrocortisone exerted a beneficial effect on the mouse physical reaction. Hypothermia was totally abrogated at the 4-hr time point. Diarrhea decreased by 50%. Hypomotility improved although not significantly. This improvement correlated with a major modification in the anti-CD3 pattern of cytokine release. At the 90-min blood withdrawal time point cytokine serum levels showed a 100% decrease for IFN gamma, an 88% decrease for IL-6, and 85% decrease for IL-2, and a 75% decrease for TNF. At 4 hr IL-2 serum levels were diminished by 65%; IL-6, IL-3, and IFN gamma serum levels were comparable to controls; and, interestingly, TNF was still detected, whereas it has already disappeared when 145 2C11 was administered alone. Importantly, when given more than 1 hr prior to anti-CD3 injection, corticosteroids were ineffective. To conclude, high doses of corticosteroids must be given with a precise kinetics--i.e. 1 hr prior to anti-CD3 MoAb--to achieve their maximal beneficial effect in the prevention of the anti-CD3 reaction.

Adrenal Cortex Hormones↗

A specific Fc gamma receptor on cultured rat mesangial cells.

Mesangial cells represent specialized pericytes in the renal glomerulus that contribute to the regulation of a variety of glomerular functions. Recently we and others have shown that cultured mesangial cells bind and take up immune complexes in an Fc-dependent manner leading in turn to generation of PGE2, reactive oxygen, and platelet-activating factor. The present studies were designed to further characterize potential Fc-gamma R on mesangial cells. Binding assays with either monomeric or heat aggregated (HA) [125I] labeled rat subclass-specific IgG were performed at 4 degrees C for 2 h on subcultured rat mesangial cells. Monomeric rat IgG2a, IgG2b, IgG1 and HA IgG2a bound only nonspecifically. Saturable Fc-dependent binding occurred for HA IgG2b and HA IgG1 though maximal binding and affinity were much higher for IgG2b. The presence of an Fc-gamma R was confirmed by surface protein iodination of mesangial cells (MC) and immunoprecipitation with either a polyclonal or mAb 2.4G2 prepared against murine Fc-gamma R. Both antibodies precipitated a 45-kDa iodinated protein band from cultured rat MC that comigrated with that from murine macrophage J774 cells on SDS-PAGE. This protein band also reacted with the polyclonal anti Fc-gamma R antibody on immunoblots. In contrast rat renal papillary epithelial cells were negative. The 45-kDa protein recognized by the rat anti-Fc-gamma R antibody 2.4G2 probably represents the binding site for HA IgG2b, as the 2.4G2 antibody also blocked binding of HA IgG2b. By immunofluorescence microscopy all MC stained positively with the polyclonal anti-Fc-gamma R antibody. A cDNA probe for the Fc-gamma RII-alpha on murine macrophages hybridized to mRNA from cultured rat MC which was of the same size (though less abundant) as that from J774 macrophages. These results further characterize the Fc-gamma R on cultured rat MC, and raise the possibility that the mesangial Fc-gamma R may play a role in the handling of immune-complexes by the renal glomerulus.

Animals↗

Sideways killing: the cytolysis of Fc receptor-bearing cells through bridging to cytolytic T lymphocytes by antibodies specific for the T-cell receptor-T3 complex.

Cytolytic T lymphocytes (CTL) cause cytolysis of foreign or virus-infected syngeneic cells when recognition of the target plus major histocompatibility complex (MHC) occurs via the T-cell receptor (TCR). The recognition event leads to intimate contact between the two cells and activation of the cytolytic effector. Activation and target cell lysis can also occur in the presence of antibodies to the TCR. This is accomplished by bridging the effector cell TCR to the target cell FcR by an anti-TCR monoclonal antibody (MoAb). Recent findings have placed the role of the FcR in this event in a questionable light. We confirm the importance of Fc gamma R by demonstrating that: (a) melanoma cells are killed by CTL clones in the presence of anti-TCR-CD3 antibodies only when the melanoma cells express the Fc gamma R on their surface; (b) native Ig, heat-aggregated Ig, or an Fc fragment from an antibody expressing the same isotype as the anti-TCR antibody can block the killing of high avidity Fc gamma RI-bearing cells mediated by anti-TCR antibody (F23.1); and (c) anti-Fc gamma R MoAb (2.4G2) and a truncated soluble Fc gamma RII molecule inhibit the killing of low-avidity Fc gamma RII-bearing cells mediated by anti-CD3 MoAb (145-2C11). Thus, we show that both high-avidity Fc gamma RI and low-avidity Fc gamma RII can mediate sideways killing depending upon the isotype of the anti-TCR antibody and the type of FcR present on the target cell surface.

Animals↗

[Changeable bridge-work prosthesis. Proposal for solution].

A newly developed solution is introduced, which makes it possible to design artificial bridges conditionally variable. Thus the frame is fixed on tangential bridges--departing from common techniques--by means of lateral assembled barriers.

Denture Design↗

Concept of the month: implementing King's Conceptual Framework at the bedside.

Acknowledging the use of conceptual frameworks as the future of nursing, administrators are searching for methods to incorporate theory into practice. The challenge is to do this in a way that is meaningful and useful to the nurse at the beside. The authors describe how one directorate, in a 650-bed community hospital, developed a program that enabled nurses to understand and apply Imogene King's systems and concepts to their practice.

Humans↗

Evaluation of renal angiomyolipoma by traditional and modern imaging in a case of tuberous sclerosis.

Renal angiomyolipoma is known to affect mainly patients with tuberous sclerosis, although it can be found in a significant number of otherwise normal individuals. Few cases have been published in which angiomyolipoma and renal cell carcinoma occurred in the same kidney. In such cases the radiologist may be asked if it is possible to distinguish between the two tumors in the same kidney. The present case report describes systemic traditional and modern imaging of huge bilateral angiomyolipoma in tuberous sclerosis. The analysis of the data implies that, although the diagnosis of angiomyolipoma can be established with noninvasive techniques only, it is impossible to distinguish between the two mentioned tumors if they coexist in the same kidney, even if all available imaging techniques are used.

Adult↗

Magnetic resonance imaging (MRI) in patients with complex partial seizures and normal computerized tomography (CT) scan.

Magnetic resonance imaging (MRI) examination was performed in 18 patients with complex partial seizures (CPS) of long duration, who had normal computerized tomographic (CT) scans of the brain. Small MRI abnormalities correlating with the location of the epileptogenic focus in the EEG were demonstrated in 4 cases. The findings with strong signals were better demonstrated in the coronal view with longer time to echo (TE). In one patient, a lower signal lesion was documented, which was better visualized in the axial view with shorter TE. Patients with CPS should be subjected to MRI examinations with coronal and sagittal planes, using short and long TE in each slice. This method minimizes the chance for missing pathology.

Adult↗

Expression of histocompatibility antigen HLA-DR by salivary gland epithelial cells in Sjögren's syndrome.

Recent studies have suggested that the induction of HLA-DR antigens on epithelial cells plays an important role in the pathogenesis of autoimmune endocrine-exocrine disorders. We found that salivary gland epithelial cells (i.e., acinar and ductal cells) in salivary gland biopsy specimens from patients with primary Sjögren's syndrome (keratoconjunctivitis sicca) expressed high levels of HLA-DR antigen, which were detected by staining frozen tissue sections with monoclonal antibodies and immunoperoxidase technique. In contrast, salivary gland epithelial cells from normal subjects did not express this antigen. Lymphocytes eluted from the salivary gland biopsy specimens of patients who had Sjögren's syndrome produced a soluble factor that stimulated HLA-DR synthesis by a salivary gland-derived cell line (Sal-1). These tissue culture supernatants contained gamma-interferon, and their ability to induce HLA-DR synthesis was blocked by monoclonal anti-gamma-interferon antibody. These results demonstrate the presence of HLA-DR antigen on salivary gland epithelial cells and suggest that local production of gamma-interferon plays a role in this induction.

Cells, Cultured↗

Interrupted aortic arch: natural history and operative results.

The chances of survival for patients with interruption of the aortic arch depend mainly on early recognition and medical treatment before symptoms of cardiogenic shock appear, and specifically on early operative repair after the exact diagnosis has been established. Accurate angiography with visualization of the interrupted aortic arch and delineation of associated cardiac malformations is of prime importance for the surgical management and prognosis. Among our 36 patients with interrupted aortic arch, 27 were operated on. The operative mortality in 22 patients with associated ventricular septal defect (VSD) and persistent ductus arteriosus (PDA) was reduced from 43% (in seven patients seen up until 1979) to 7% (in 15 patients seen since 1980). One patient with interrupted aortic arch type C and another infant with associated truncus arteriosus were successfully corrected on day 9 and day 17 of life, respectively. In the patients with associated VSD and PDA as well as in the one patient with associated truncus arteriosus, the primary correction--direct anastomosis of the interrupted segments without prosthesis and VSD closure and in the case with truncus, the additional positioning of a valve-bearing allograft conduit from the right ventricle to the pulmonary artery--has been more successful than a two-step approach with initial pulmonary artery banding.

Aorta, Thoracic↗

Gaucher disease: assessment with MR imaging.

The skeletal system, spleen, and liver of five patients with proved Gaucher disease were studied with magnetic resonance (MR) imaging. Homogeneous, low intensity signals resulting from relaxation times different than normal (longer T1 and shorter T2 values) were found in the marrow of long bones, vertebrae, and hips in all patients. In three patients, normal signals were noted in the patella, epiphysis of the knee, and capital femoral epiphysis. In two patients with acute bone pain in the tibial region, a higher signal was received from the tibial marrow. This signal was related to increased accumulation of fluid following an avascular episode. Soft tissues in the same area were also involved. Liver and spleen enlargement was readily visible, especially on coronal images. T1 values of spleen were significantly shorter than normal. MR imaging provides an excellent assessment of the extent of involvement of the liver, spleen, and bone marrow in Gaucher disease.

Adolescent↗

Magnetic resonance imaging of the temporo-mandibular joint and meniscus dislocation.

A preliminary study of the temporo-mandibular joint (TMJ) by magnetic resonance imaging (MRI) was performed. Ten asymptomatic volunteers with no clinical history of TMJ disorder and five patients with a recent history of trauma to the TMJ were examined using a special surface coil. The meniscus, which is only slightly brighter than the surrounding tissue, gave a high signal and was demonstrated very clearly in its normal position in the controls and shown to be dislocated in the post-trauma cases. Four criteria for identification of the temporo-mandibular meniscus were established in the normal cases and compared with the findings in the pathological cases.

Adolescent↗

Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase.

Fatty-acid synthase has been purified to homogeneity from human liver by a 3-step procedure including protamine sulfate/ammonium sulfate fractionation, affinity chromatography on 2',5'-ADP-Sepharose 4B and gel filtration on Sephacryl S-300. Both the human and rat fatty-acid synthase had similar characteristics regarding molecular mass, subunit structure, amino-acid composition, and substrate affinities. In order to measure the fatty-acid synthase activities in small tissue samples it was necessary to improve the sensitivity of an isotopic assay using [14C]malonyl-CoA as tracer. Special attention was paid to the dual role of free CoASH as an activator and inhibitor of the enzyme. Considerable differences existed between the specific activities of the fatty-acid synthase complex measured in human and rat lipogenic organs. Only negligible values of about 1 mU/mg protein were found in human liver and adipose tissue, while the corresponding activities were 10- to 50-fold higher in young lean rats. Less pronounced but still remarkable differences were determined for the activity of the acetyltransferase which catalyses the initial primer reaction of the fatty-acid synthase complex. In some selected cases under long-term fat-free diet (alcoholism, parenteral nutrition) elevated values of fatty-acid synthase activities were detected in human tissues. Under usual diet, with a relatively high fat content of up to 40 percent, and even after a carbohydrate-rich diet for three days, fatty-acid synthase activity remained low. It is concluded that under the dietary conditions, common for the industrialized world, de novo lipogenesis in man is negligible.

Adipose Tissue↗