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Biomedical subjects

A Morell

Publications and source records attributed to A Morell.

At least 19 recordsLinked to original sources

[Sequential immunologic, cytochemical and autoradiographic studies on lymphoid cells in the blood of healthy adults].

Simultaneous characterization on a single slide of computer-mapped lymphoid blood cells by sequential analysis of 3 parameters (surface immunoglobulins, AET-SRBC-rosetting, unspecific acid alpha-naphthyl-acetate-esterase) served to distinguish 8 subpopulations. By previous in vitro incubation with 3HdT, the proliferative activity of the latter could also be assessed.

Autoradiography

[Angioimmunoblastic lymphadenopathy. 3 cases with polyclonal gammopathy].

Three patients with an atypical lymphoproliferative disorder disorder and polyclonal gammopathy have been reviewed retrospectively. The clinical and histological findings are compatible with the recently described entity of angioimmunoblastic lymphadenopathy. Two patients died within 6 months after the first symptoms of the disease. Circulating immuncomplexes were demonstrated in the serum of 2 patients. In one patient with a nearly fourfold increase of IgG, persistent hyponatremia was found.

Aged

[BCG sepsis as a fatal complication of BCG vaccination].

Fatal septicemia with Bacillus Calmette-Guérin (BCG) following BCG vaccination is always caused by an underlying defect of immunologic mechanisms. At the Children's Hospital, University of Berne, two cases of BCG septicemia were recently observed. The clinical picture, course, and pathogenesis of the illness are discussed. The harmless complications of BCG vaccination are summarized, and a review of the literature on fatal disseminated BCG infection stresses the different type of immunologic mechanism defect and clinical course. Therapy with antituberculous drugs is ineffective. Other therapeutic measures are mentioned. Immunologic tests must be performed rapidly when fatal disseminated BCG infection is suspected, in order to organize genetic counselling as soon as possible. The question whether newborns should still be vaccinated in spite of the numerous complications is discussed and answered in the affirmative.

Antigen-Antibody Reactions

[Acute "high risk" and "low risk" juvenile lymphatic leukemia (proceedings)].

After an initial blood and thorax examination, 97 children with ALL were divided into "high risk" and "low risk" groups. From the 20 new "high risk" patients seen between 1972 and 1975 about one quarter were still alive 3 years later, the corresponding proportion from 37 "low risk" patients being about two thirds. Despite increased therapy, the number of early relapses does not appear to have decreased in the new "high risk" cases seen between 1976/77. An investigation of cell surface markers established that T-ALL always occurred in the "high risk" group, whereas B-negative/T-negative ALL was found not only in the "low risk" group but also occasionally in the "high risk" group.

B-Lymphocytes

Fluorometric determinations of the relative immunoglobulin content of plasma cells of patients with monoclonal gammopathy.

The relative cytoplasmic immunoglobulin content of fixed plasma cells taken from the bone marrow of five patients with myeloma and five patients with benign monoclonal gammopathy was determined with a microscope fluorometer. In eight of the ten piasma cell populations studied, the distribution of the fluorescence intensities was close to normal. In three of these eight populations a significant difference in the variances of the heavy and light chain fluorescence intensities was found. Variances of heavy and light chain fluorescence intensities were smaller in patients with an immunoglobulin A-type gammopathy than in those with an immunoglobulin G-type gammopathy. No difference was found if normalized relative frequency distribution patterns of heavy or light chain fluorescence intensities of patients with myeloma were compared with those of patients with benign monoclonal gammopathies.

Bence Jones Protein

Differentiation between benign and malignant monoclonal gammopathies by discriminant analysis on serum and bone marrow parameters.

Bone marrow samples of 28 individuals with clinically benign and of 41 patients with malignant monoclonal gammopathy were analyzed for the total number of lymphoplasmocellular elements containing cytoplasmic immunoglobulins and for the monoclonal fraction of these cells. Monoclonal immunoglobulin components were determined in sera. A discriminant analysis was performed on the data: the variables were transformed and in a stepwise procedure used for the construction of a discriminant function which by adividing point allowed a good distinction between the two groups of patients. By use of this discriminant function, 91% of the patients in the sample were correctly classified.

Adult

Cytoplasmic immunoglobulins in bone marrow cells of polyclonal and of monoclonal origin.

Cytoplasmic immunoglobulins in human bone marrow plasma cells and lymphoid cells were characterized by direct immunofluorescence with fluorochrome-labelled reagents specific for immunoglobulin heavy and light chains. The percentage distribution of cells containing IgA, IgG or IgM and kappa- or lambda-immunoglobulins was determined in bone marrow samples from 168 immunologically normal individuals, in 11 patients with polyclonal increase of bone marrow plasma cells and in 80 patients with benign or malignant monoclonal gammopathies. A clear differentiation between monoclonal and polyclonal cell populations could be obtained in all cases.

Adult

Differentiation of plasma and myeloma cells of man. Combined planimetric and cytophotometric studies.

Plasmacytoid cells in the bone marrow of 3 patients with myeloma and plasma cells in the bone marrow of a 6-year-old boy with an infectious disease were assessed cytophotometrically, first after Giemsaand second after Feulgen staining. The cell and nuclear surface and the nuclear/cytoplasmic ratio were determined from the number of measuring points. The nuclear DNA content of individual cells was registered and the distribution of DNA within the nucleus was assessed by the distributional error. Both the mean nuclear/cytoplasmic ratio and the distributional error of myeloma cells varied from patient to patient but could not be used to differentiate between normal plasma cells and myeloma cells. It was not possible either to differentiate these cell types by multiplying the mean nuclear/cytoplasmic ratio with the mean distributional error of the nuclear DNA. A strong correlation between cell and cytoplasmic surface area was observed both in normal plasma cells and in myeloma cells.

Bone Marrow

[Prophylaxis and therapy with gamma globulin. General characterization and clinical use of gamma globulin preparations].

For accurate evaluation of the usefulness of gamma-globulin treatment, the clinical indications for passive immune prophylaxis and immunotherapy and the specific characteristics of commercially available gamma-globulin preparations have to be considered. Detailed investigations of currently used gamma-globulin preparations have shown that as yet no ideal product is available. Classical standard gamma-globulin and, in particular, enzymatically treated (Gamma-Venin, Veinoglobuline) or chemically modified preparations (Gamma-Globulin i.v. SRK, Intraglobin) for intravenous use have some deficiencies and involve potential risks for the patient. Nor is the infusion of "fresh frozen plasma" a safe and generally applicable alternative to the use of gamma-globulin concentrates. Thus from the outset the preconditions for effective treatment with gamma-globulin are not optimal. Standard and hyperimmune preparations, given once intramuscularly, are suitable for the prophylaxis of viral and bacteriotoxic diseases. In patients apt to react abnormally it is important to distinguish clearly between the few accepted indications and those that are more doubtful. Anti-D immunoglobulin is essential for the prevention of Rhesus sensitization after the delivery of a Rhesus-positive child. In general, gamma-globulin is recommended for substitution therapy and for the prophylaxis of recurrent acute bacterial infections in patients suffering from transient, congenital and acquired antibody-deficiency states. In such cases, high doses of an intravenously administrable preparation with a relatively long biologic half-life are recommended. The evidence for the effectiveness of gamma-globulin treatment of bacterial infections in patients without manifest disturbance of humoral immunity is equivocal. This is true, for example, of the oft-recommended combined use of antibiotics and high doses of intravenous gamma-globulin which is said to provide optimum antibacterial and antitoxic protection. There is even less chance of obtaining beneficial effects if gamma-globulin is given as an "ultimo ratio" in severe generalized bacterial infections resistant to antibiotic treatment. Localized and predominantly chronic infections are barely influenced by gamma-globulin. It is still too early to make a final assessment regarding the place and value of immunoglobulin concentrates for prophylactic and therapeutic purposes. This will only be possible if a preparation becomes available which contains all immunoglobulins in a biologically optimum state and concentration, is well tolerated and can be given in adequate doses both intramuscularly and intravenously.

Complement System Proteins

Restriction of immunoglobulin heterogeneity, autoimmunity and serum protein levels in aged people.

Ninety-one sera of persons above 80 years of age were screened for autoantibody activity against lipoproteins (anti-LDL 7, anti-HDL 6 positive), for rheumatoid factor activity (Latex 14, Waaler-Rose 7 positive) and for antinuclear factors (11 positive). Among the sera with autoantibody activity 29 percent showed deviations of the normal kappa/lambda ratio of immunoglobulins, as opposed to 22 percent of the sera without detected autoantibody activity. In 3 percent of the sera an M component was detected. Determination of the alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, haemopexin, complement component C3c and C4, IgG, IgA and IgM levels showed significant increases in alpha-, and beta-globulins as well as in IgG and IgA in sera of the aged persons as compared to a normal population between 20 and 60 years old. No significant difference was noted between the gamma-globulin concentration in sera of aged persons with or without autoantibody activity. The evaluation of the relationship between serum protein levels and alterations of the kappa/lambda ratio indicated that the alpha- and the beta-globulins were significantly raised in sera with altered kappa/lambda ratios, whereas, with the exception of M component containing sera the gamma-globulin levels seemed not significantly affected by changes in this ratio.

Aged

Deficiency of kappa- or lambda-type immunoglobulins.

A marked imbalance of the two light chain types of immunoglobulins was observed in two young male adults suffering from primary hypogammaglobulinemia and intrinsic factor-deficient pernicious anemia. In one patient, the kappa/lambda light chain ratio of serum immunoglobulins was 0.01; in the other, it was approximately 6 (normal value, 1.8 +/- 0.3). This light chain imbalance was found within each of the three main immunoglobulin classes. The number of mature immunoglobulin-producing cells in the bone marrow and in the mucosa of the gastrointestinal tract was reduced. The relative frequency of kappa- and lambda-producing cells in these tissues corresponded to the kappa/lambda ratio of serum immunoglobulins. However, the number of peripheral lymphocytes with membrane-associated immunoglobulins as well as the percentage distribution of blood lymphocytes with kappa- or lambda-type immunoglobulins on the membrane were within normal limits in both cases. The results suggested a hitherto unknown defect in the maturation of B-cells leading to an abnormal ratio of kappa- and lambda-type immunoglobulin-secreting cells.

Adult

[Thrombocytopenia in Waldenstrom's disease with specific antithrombocytic properties of the IgM paraprotein].

The serum of a patient suffering from thrombocytopenia associated with Waldenström's macroglobulinemia was found to contain an IgM paraprotein with unusual characteristics. Following isolation of this IgM paraprotein, dilutions up to 0.01 mg/ml caused immunofluorescence of thrombocytes from man, sheep, rabbit, and horse. In control studies with isolated IgM paraprotein from another non-thrombocytopenic patient with Waldenström's disease, positive immunofluorescence could be elicited only when a 1000-fold greater concentration of the paraprotein was used. The IgM paraprotein from our thrombocytopenic patient and that from the control patient showed comparable differences in immunofluorescence of thrombocytes and megacaryocytes when bone marrow smears were used for incubation. Further studies following papain cleavage of the IgM paraprotein with antithrombocytic activity showed that the combining activity was located in the Fab fragment. This observation characterizes the IgM paraprotein from our patient as an antibody directed to a substance in human and animal thrombocytes. Paraproteins with antibody-like activity for thrombocytes have not been identified previously; the present observation suggests that this mechanism should be considered a possible cause of thrombocytopenia associated with macroglobulinemia.

Blood Platelets

Clinical tolerance and catabolism of plasmin-treated gamma-globulin for intravenous application.

Plasmin-treated gamma-globulin of placental origin was tested in clinical and laboratory studies and found to be suitable for intravenous use both for prophylactic and therapeutic purposes. Plasmin treatment of gamma-globulin (IgG) results in proteolytic cleavage of 60-70% of the molecules into Fab and Fc fragments whereas 30-40% of the molecules are plasmin resistant. The antibody spectrum of plasmin-treated gamma-globulin is similar to that of standard gamma-globulin. Catabolic properties of the plasmin-resistant portion of this preparation and of standard gamma-globulin are identical. Plasmin-treated gamma-globulin has no anticomplementary activity and its intravenous administration is well tolerated even by highly sensitive immunodeficient patients.

Adolescent