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Biomedical subjects

B Frisch

Publications and source records attributed to B Frisch.

At least 91 records · Page 5Linked to original sources
PubMed1980

Antibody-dependent, cell-mediated cytotoxicity against human red blood cells: correlation of effector cell type with enzymatic alteration of the target cell surface.

Target cell factors, which contribute to the determination of the effector cell type in an antibody-dependent, cell-mediated cytotoxicity system were studied. Human red blood cells (RBC) were treated with papain and investigated by transmission and scanning electron microscopy (TEM and SEM). Both untreated (native) and treated 0 Rh+ RBC were labeled with 51Cr, sensitized with anti-D immunoglobulin and incubated with unfractionated autologous peripheral blood mononuclear cells. With native RBC, immune lysis was proportional to the number of phagocytes: enrichment of effectors in phagocytes increased lysis, while depletion of phagocytes from effectors decreased lysis. Following papain treatment of target RBC, lysis by unfractionated mononuclear effectors was markedly augmented; since this effect was not diminished by decrease of phagocytes to less than 2%, the augmented lysis was not due to the number of phagocytic effectors. TEM and SEM of enzyme-treated RBC showed spherocytosis with varying degrees of crenation and blurring and irregularities of the cellular membranes. The results suggest that papain-induced alterations in the target RBC rendered them susceptible to lysis by interaction between anti-D antibody and peripheral blood lymphocytes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

The clinical study of micro-metastatic cancer by bone biopsy.

Bone marrow biopsies were investigated for the presence of neoplastic cells in 3150 patients with known or suspected malignancies. Marrow involvement was found in 42 per cent (359 of 838) cases of carcinomas, 15 per cent of 772 cases of Hodgkin's disease, 55 per cent of 1125 cases of malignant lymphoma, 75 per cent of 428 cases of multiple myeloma. In 139 cases of occult primaries the incidence of marrow involvement was 82 per cent. Micrometastases were found in 18 per cent of 359 positive biopsies from patients with solid tum ours. In this group no correlation was established between haematological findings in the peripheral blood and the size of the metastases. There was a striking variability in the type and components of the marginal zone at the interface between metastases and hematopoietic tissue, most probably due to differences in characteristics of the neoplastic cells. The high percentage of marrow involvement by metastatic carcinoma indicates that bone marrow biopsy could profitably be included in the initial investigation of patients with solid tumours.

Biopsy, Needle↗
PubMed1978

Cell junctions in dyserythropoiesis.

Erythroid cell junctions have previously been reported in some cases of dyserythropoietic anaemia. This study has demonstrated that they are a relatively common occurrence in dyserythropoiesis. They range from apposition of cellular membranes with preservation of the intercellular space, to membrane confluence, to interdigitation and septate-like junctions. By special staining with colloidal lanthanum, ruthenium red and tannic acid, together with studies of the effect of proteolytic enzymes, their structural composition has been identified and it was confirmed that they are not artefact. The role of cell junctions in dyserythropoiesis is discussed.

Anemia↗
PubMed1978

Localization and role of calcium in the erythrocyte coat: effects of enzymes and storage.

The effects of various treatments on erythrocyte shape, surface, cell coat and calcium binding sites have been investigated by means of high voltage electron microscopy (HVM), scanning electron microscopy (SEM) and conventional electron microscopy (TEM). Papain caused the formation of small blisters within the cellular surface as well as crenation and 'budding' of the erythrocytes. After neuraminidase treatment, long filaments were observed to radiate from the surface of the erythrocyte. The other enzymes investigated, RNA'se DNA'se, phospholipase, protease and trypsin, produced no demonstrable effect on the cellular structure, nor (with the possible exception of trypsin) on the cell coat as seen by subsequent staining with ruthenium red. Putative calcium binding sites on and in the erythrocyte membrane were demonstrated. Following incubation with radioactive calcium, activity was found in the erythrocyte membranes. Calcium binding could be reduced by prior treatment of the erythrocyte with EDTA, neuraminidase, and to a lesser extent, by papain and trypsin. Other enzymes had no demonstrable effect. Stored erythrocytes showed a progressive diminution in calcium binding over a period of up to 4 weeks.

Binding Sites↗
PubMed1978

Ultrastructural study of normal and leukaemic leucocyte processes.

Cellular processes of leucocytes from both normal and leukaemic subjects were studied at the ultrastructural level. By high voltage transmission electron microscopy without a metal coating, more surface features could be seen in the cells than were observed by either scanning electron microscopy or conventional transmission electron microscopy. The technique was shown to be especially useful as it allows direct visualisation of the cell surface structure at high resolution without artefact-inducing preparative processes. Demonstrating receptor sites with this technique opens up the possibility of studying lymphocyte microvilli in greater detail.

Binding Sites↗
PubMed1976

Intercellular contacts between erythroid precursors in the bone marrow in dyserythropoiesis.

The ultrastructure of the cellular interfaces between erythroid precursors has been studied in both congenital and acquired dyserythropoiesis. The types of cell-to-cell contacts found included highly convoluated interdigitating septate-like junctions as well as apparent confluence of the cellular membranes of adjacent erythroid cells. Such findings are not characteristic of the intercellular relationships found in the normal erythroblastic islands. The erythroid plasma membrane modifications are possibly related to the changes in the plasma membranes of erythroid cells known to occur in dyserythropoiesis and their presence may well contribute to the ineffective erythropoiesis with intramedullary cell destruction which characterizes many dyserythropoietic states.

Bone Marrow↗
PubMed1975

The ultrastructure of dyserythropoiesis in aplastic anaemia.

Electron microscopy of erythropoiesis in aplastic anaemia has demonstrated some unique features of dyserythropoiesis at the ultrastructural level, which contribute to understanding of the morphological features which are seen in the light microscope. The findings provide further evidence for the presence of qualitative defects in erythropoiesis in aplastic conditions. The alterations seen included bi- and multinucleated cells, intercellular bridges containing microtubules, internuclear chromatin bridges, irregular nuclear shapes, juxta-nuclear and peripheral cisternal structures, ringed sideroblasts, a diversity of intranuclear inclusions, nuclear clefts in both eu- and heterochromatin, and a variety of anomalies of the nuclear membrane. The significance of the occurrence of these anomalies in aplastic anaemia is considered and the role of the nuclear membrane and of endoplasmic reticulum in the pathogenesis of aplastic anaemia is discussed.

Adult↗
PubMed1975

A transmission electron microscope study of the effects of ion etching on cells.

The effects of ion etching on blood cells have previously been studied by scanning electron microscopy. This present study by transmission electron microscopy was undertaken to evaluate the effects of the etching process on the cells. Critical point dried preparations were made, etched and subsequently processed and embedded in Araldite. Examination of thin sections of erythrocytes revealed disintegration of the plasma membrane; the residual membrane destruction products formed the tips of cones produced by long etching times. The effect of etching varied in erythrocytes in the same preparation. Nucleated cells showed a similar disintegration of the plasma membrane, but membranes of mitochondria, granules, vesicles and vacuoles did not exhibit effects of etching comparable to those of the plasma membranes. After treatment with a number of different fixatives, erythrocytes on carbon-coated copper grids were also etched and examined directly in a high voltage electron microscope at 1 MV. The effects were comparable to those seen in thin sections. To study the etch rates of biological materials, the resonant frequencies of quartz crystals were measured after application of thin films of albumen and cholesterol and again after these had been etched. the ratio of the frequency changes indicated that the etch rate of albumen was approximately 2-5 times that of cholesterol. The results are discussed in the light of theories of the mechanisms involved in ion etching.

Cell Membrane↗
PubMed1974

T-lymphoblastic leukaemia: a distinct variant of acute leukaemia.

Two cases of acute lymphoblastic leukaemia (A.L.L.) of T-cell type are reported. Clinically they were characterized by very high peripheral blood blast cell counts at presentation, the early development of meningeal leukaemia, and relative resistance to treatment with combination chemotherapy. Leukaemic cells from both patients lacked all the B-cell markers investigated, but 60-65% of their cells formed rosettes with sheep red cells. Cytochemical and surface structure studies helped to define additional features of these cells and confirmed their T-cell nature.It seems that this variant of A.L.L. may not be uncommon and that it can be distinguished on clinical and immunological grounds from the usual type of A.L.L. which runs a less aggressive course and lacks B- or T-cell markers.

Adolescent↗
PubMed1974

The bone marrow in aplastic anaemia: diagnostic and prognostic features.

Bone marrow preparations were examined from 80 patients with aplastic anaemia. The degree of cellularity varied greatly and in a third of the cases it was normal or even hypercellular at one site of aspiration. In the severely hypoplastic marrows lymphoid cells were predominant and this situation was associated with a worse prognosis. There was no correlation between marrow lymphoid cell content and blood lymphocyte count but there was an inverse relationship between blood lymphocyte count and marrow erythroblasts and a close direct relationship between the blood neutrophil count and marrow myeloid cell content. In all cases a proportion of the erythroblasts showed morphological abnormalities. These included especially megaloblastic changes and asynchrony of nuclear-cytoplasmic maturation. There were also binucleated cells, internuclear chromatin bridges, intercellular cytoplasmic connexions, nuclear degenerative changes, namely, blurred outlines, irregular shapes, budding and fragmentation, and atypical mitotic figures. These appearances illustrate the extent to which a qualitative defect of erythropoiesis occurs as part of the haematological pattern in aplastic anaemia, and in some cases dominates the bone marrow picture. Similar cytological features were found in all cases, including five patients with Fanconi's anaemia.

Anemia, Aplastic↗
PubMedDate not supplied

Synthesis of short polyoxyethylene-based heterobifunctional cross-linking reagents. Application to the coupling of peptides to liposomes.

We describe the synthesis of [2-[2-[2-[(2-bromoacetyl)amino]ethoxy]ethoxy]ethoxy acetic acid (7), [2-[2-(2,5-dioxo-2,5-dihydropyrrol-1-yl)ethoxy]ethoxy] acetic acid (11), and [2-[2-(pyridin-2-yldisulfanyl)-ethoxy]ethoxy] acetic acid (16), three new thiol-reactive heterobifunctional reagents, and the preparation of their corresponding dipalmitoylphosphatidylethanolamine derivatives (8, 12, and 17). Such phospholipid amide derivatives were aimed to be incorporated into the bilayers of liposomal constructs used for immunization with e.g. synthetic peptides. The spacer arms introduced by 8, 12, and 17 are hydrophilic polyoxyethylene chains of variable lengths that were expected to provide a good accessibility to their conjugates and have a lesser intrinsic immunogenicity than the spacer introduced by N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine (MPB-PE), a classical reagent used for conjugation of ligands to the surface of liposomes. Such an immunogenicity might be prejudicial (e.g. carrier-induced epitopic suppression) to the development of synthetic vaccination formulations. Moreover, the derivatives 8, 12, and 17 allowed the coupling of peptides, bearing a thiol function, to their liposomal carrier via two types of linkages, i.e. stable thio ether (8 and 12) and bioreducible disulfide (17) bonds; this might be of importance in the mechanism of antigen presentation by competent cells. Using CG-IRGERA as a model peptide, the rate of coupling to 8, 12, and 17 was assessed as a function of pH.

Acetates↗
PubMedDate not supplied

Differential reactivity of maleimide and bromoacetyl functions with thiols: application to the preparation of liposomal diepitope constructs.

The comparative reactivity of maleimide and bromoacetyl groups with thiols (2-mercaptoethanol, free cysteine, and cysteine residues present at the N-terminus of peptides) was investigated in aqueous media. These studies were performed (i) with water-soluble functionalized model molecules, i.e., polyoxyethylene-based spacer arms that could also be coupled to lipophilic anchors destined to be incorporated into liposomes, and (ii) with small unilamellar liposomes carrying at their surface these thiol-reactive functions. Our results indicate that an important kinetic discrimination (2-3 orders of magnitude in terms of rate constants) can be achieved between the maleimide and bromoacetyl functions when the reactions with thiols are performed at pH 6.5. The bromoacetyl function which reacts at higher pH values (e.g., pH 9.0) retained a high chemoselectivity; i.e., under conditions where it reacted appreciably with the thiols of, e.g., HS-peptides, it did react with other nucleophilic functions such as alpha- and epsilon-amino groups or imidazole, which could also be present in peptides. This differential reactivity was applied to design chemically defined and highly immunogenic liposomal diepitope constructs as synthetic vaccines, i.e., vesicles carrying at their surface two different peptides conjugated each to a specific amphiphilic anchor. This was realized by coupling sequentially at pH 6.5 and 9.0 two HS-peptides to preformed vesicles containing lipophilic anchors functionalized with maleimide and bromoacetyl groups [Boeckler, C., et al. (1999) Eur. J. Immunol. 29, 2297-2308].

Acetates↗
PubMedDate not supplied

[The clinical significance of pseudouridine determination of the urine in children and adolescents].

A HPLC-method is described to determine the Pseudouridine/creatinine ratio in spontaneous urine samples in infancy and childhood. The urines of 74 healthy children between 1 and 18 years of age and of 231 children with different diseases were examined for this ratio, making 1097 measurements. 157 children suffered from a malignant disease, 66 of them having an acute leukemia. Those patients, who remain in remission of the leukemia showed normal values, whereas the others had elevated ratios, reflecting the activity of the leukemia, when they were followed up by multiple determinations. Perhaps it is also possible to detect preclinical stages of leukemia by measuring the pseudouridine/creatinine ratio routinously over a long period of time. Today no strict correlation between the prognosis of leukemia and the level of this ratio can be drawn. Similar behaviour of the pseudouridine/creatinine ratio is seen in other malignant diseases with exception of brain tumors. The difference to leukemias is, that all other malignant tumors show more often normal values in patients with a remaining tumor. A pathological value of pseudouridine may also be seen in others than malignant diseases.

Adolescent↗
PubMedDate not supplied

[Osteopenia, marrow atrophy and capillary circulation. Comparative studies of the human iliac crest and 1st lumbar vertebra].

Histological and histomorphometrical measurements were made on normal and on osteoporotic bone from the first lumbar vertebra and the iliac crest of 15 cases. A decrease in cancellous bone was found in both. This was accompanied by a reduction in haematopoietic marrow and a corresponding increase in fat cells. In addition, the numbers of arterial capillaries and sinuses per unit area were also reduced. There is a greater overall vascularization in the first lumbar vertebra than in the iliac crest, even though the amount of cancellous bone is normally less in the former. However, the arborization of the terminal vessels in the iliac crest is more extensive than that in the first lumbar vertebra. These observations provide support for the participation of a vascular component in the pathogenesis of osteoporosis.

Adipose Tissue↗
PubMedDate not supplied

Bone scan and bone biopsy in the detection of skeletal metastases.

This study provides the first quantitative indication of the limits of sensitivity of a bone scan with technetium (99Tc-MDP) in detecting skeletal metastases and thereby also helps to explain the fact that bone scans may be negative when metastases are present in the bone marrow. Since 99Tc-MDP remains the least noxious and most widely used isotope for bone scanning, these results have direct clinical relevance in the evaluation of patients with solid tumors and possible metastatic spread.

Adult↗