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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 703 records · Page 39Linked to original sources
PubMed1984

Epstein-Barr virus binding to virus-carrying cell lines is enhanced in the presence of C3 and C3d.

The relationship between the receptors for the Epstein-Barr virus (EBV) and the C3d fragment of complement was investigated at the molecular level. In the presence of cell-bound C3, virus binding was enhanced in EBV genome-carrying lines. An identical effect could be elicited by C3d at one-quarter the weight amount; C3b and methylamine-treated C3 had no effect on virus binding. The minimum concentration of C3 which produced significant enhancement was 25 micrograms/ml. Virus binding increases were observed only after 20 min of complement-cell co-incubation. The response was not noted with EBV-negative lines and was independent of virus strain assayed (B95-8 and P3HR-1). These studies suggest that the binding sites for the two moieties are distinct, although they both involve the same cell surface complex. The two receptors are believed to display cooperativity.

Cell Line↗
PubMed1984

Molecular size variation of EBNA is determined by the EB viral genome.

The size classes of the Epstein-Barr virus(EBV)-induced nuclear antigen (EB-NA) have been determined in EBV-carrying sublines of two originally EBV-negative Burkitt lymphomas, converted in vitro by two different EBV substrains, and in somatic hybrids between two EBV-carrying cell lines or between an EBV-positive and an EBV-negative line. Partially purified EBNA components were detected by Western blotting and subsequent exposure to antiserum/alkaline-phosphatase-coupled protein A complexes. Converted Ramos and BJAB sublines contained the main EBNA components characteristic for the virus donor strain. The EBNA components of the Ramos and BJAB cells converted by P3HR-1 virus were similar to each other and to the components of the P3HR-1 donor cell, whereas the EBNA of the cells converted by B95-8 virus resembled the B95-8 donor line. It was concluded that the size variation of EBNA is determined by the viral genome. The parental lines of the somatic hybrids studied (Raji, P3HR-1, Namalwa and Daudi) contained EBNA components of different molecular weight (MW) classes. The higher MW forms ranged from 70K to 80K. Several distinctive lower MW components also were present. The somatic hybrids expressed the main EBNA components of both parental lines. Hybrids between EBV-carrying and EBV-genome-negative lines contained the characteristic EBNA component of the EBV-positive parent. It was concluded that the size variation of EBNA is under strict genetic control which prevails in the hybrids in a codominant fashion.

Antigens, Viral↗
PubMed1984

Antiarrhythmic activity of esmolol (ASL-8052)--a novel ultra-short acting beta-adrenoreceptor blocking agent.

In a single-blind, placebo-controlled study, esmolol was administered intravenously to 12 patients with chronic atrial fibrillation. Esmolol produced a significant dose-dependent decrease in the ventricular rate without conversion to normal sinus rhythm in any of the patients. For most patients, a correlation was observed between the blood levels of esmolol and reductions in heart rate. There were no significant adverse effects. We conclude that esmolol is an effective and safe agent for the control of heart rate in patients with supraventricular tachycardia.

Adrenergic beta-Antagonists↗
PubMed1984

Detection of mutant-specific responses by macrophage migration inhibition reactions induced by wild-type and mutant polyoma viruses and polyoma virus-infected cells.

Macrophage migration inhibition responses of mice immunized with mutant polyoma viruses or with cells transformed and/or infected by them have been studied. The macrophage migration inhibition reaction revealed individual differences. In several cases, mice immunized with a mutant virus responded preferentially or exclusively to extracts of cells transformed or infected with the corresponding mutant. Moreover, in the macrophage migration inhibition test, mutant viruses were usually less immunogenic than were the corresponding transformed-infected cells.

Animals↗
PubMed1984

Humoral immune response in Epstein-Barr virus infections. II. IgG subclass distribution in African patients with Burkitt's lymphoma and nasopharyngeal carcinoma.

Native Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC) patients from Kenya were examined with regard to the serum concentrations and distribution of the four IgG subclasses, total IgG, and antibody activities to Epstein-Barr (EB) virus associated antigens. The results were compared with corresponding data of an African control group. As revealed by indirect immunofluorescence techniques, the patients displayed a pattern of IgG and IgA antibodies to EB virus associated antigens which is characteristic for these diseases. No significant differences could be detected between the total IgG levels of the diagnostic groups. The mean total IgG concentrations of our Kenyan patients were two to three times as high as those found in four different groups of Europeans, which is consistent with results of previous studies on Gambian, Nigerian, and Congolese Bantu populations. Quantitative determination of the four IgG subclasses by radial immunodiffusion revealed a unique pattern in the BL group which was characterized by a decreased proportion of IgG2 and significantly lower absolute IgG2 values as compared with the controls. The IgG subclass distribution pattern in the African NPC sera was essentially identical with that of European NPC and African control sera. The pathogenetic implications of these findings are discussed.

Adolescent↗
PubMed1984

T lymphocyte culture established by repeated stimulation with the autologous lymphoblastoid line. MHC class II restricted interactions with B blasts.

An OKT3+T4+T8-DR+ lymphocyte line was developed from an Epstein-Barr virus (EBV) seropositive individual by repeated stimulation in vitro with autologous EBV-infected B cells. The T cell population designated E-44 was carried for eight months in the presence of Interleukin-2 and was repeatedly tested for cytotoxicity, proliferation and lymphokine production in response to the autologous and a panel of allogenic B cells. The E-44 cells lysed the autologous lymphoblastoid cell lines (LCL) and allogenic B cell lines sharing the DR6.1 major histocompatibility complex antigen with the lymphocyte donors. The EBV genome-negative lymphoma line BJAB and its two, infected in vitro, EBV-positive sublines were lysed with similar efficiencies. Autologous Staphylococcus aureus protein A (Prot-A) induced B, but not Phytohaemagglutinin (PHA)-induced T blasts were also lysed. It is likely that E-44 recognized an antigenic component derived from the fetal calf serum in association with class II determinants expressed on the B cells. Preincubation of E-44 cells with saturating amounts of OKT3 and Leu3a monoclonal antibodies abrogated the lytic effect on the autologous LCL. Cold target competition experiments demonstrated that, within, the population, the same cells reacted with the autologous Prot-A-induced blasts, the EBV-transformed LCL, and also with Daudi (an EBV genome-positive BL line). Although Daudi was the target which was lysed with the greatest efficiency, the avidity of interaction was highest with the autologous LCL because these cells competed best. Among the cells that were sensitive for the lytic effect, only the autologous LCL and Prot-A-induced B blasts triggered release of detectable amounts of Interleukin-2 and induced proliferation of the culture. The results suggest that the affinity of interaction with the target may be decisive for the triggering of the various T cell functions.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Immunoglobulin gene organization of ultraviolet-illuminated human lymphoblastoid cell lines producing both IgM and IgG.

We have studied the immunoglobulin gene organization of ultraviolet light (u.v.)-induced variant cells derived from an Epstein-Barr virus-transformed cell line. One variant produced IgG1 and two variants produced both IgM and IgG1 whereas the parental cell line produced IgM. Southern blot analyses of DNAs of these cells revealed a newly rearranged JH fragment in all the variants. The newly rearranged JH fragment also hybridized with the C gamma 1 sequence. The mu and gamma 1 chains produced in the double isotype-producing variants share the same VH sequence. u.v. illumination also induced rearrangement of the C lambda gene in the IgG1-producing variant. The double isotype producers contained the immunoglobulin gene organization and mutation best explained by fusion of the IgG1 producer and the parental IgM producer.

Amino Acid Sequence↗
PubMed1984

[The effect of amiodarone on thyroid gland function].

Plasma concentrations of T4, FT4, T3, rT3 and TBG, as well as of TSH before and after stimulation with TRH were studied in 25 patients, who had been treated with amiodarone for up to nine years. At the beginning of therapy, all the parameters mentioned above were found to be in the normal range in all patients. After two months of therapy, T4 had increased from 100 nmol/l +/- 24 nmol/l to 155 nmol/l +/- 32 nmol/l (p less than 0.01), and FT4 from 22 pmol/l +/- 10.5 pmol/l to 32 pmol/l +/- 8 pmol/l (p less than 0.01). T3 had decreased to the lower normal range (n.s.). TBG showed no significant changes. The TRH-tests had been normal in the beginning, but they remained positive in only 20% of the cases. At the end of the study, rT3 exceeded the normal range in all 25 patients. Two patients developed definite hyperthyroidism with elevations of T3 up to 4.7 nmol/l and 7.5 nmol/l, respectively. In one of them, we decided to discontinue amiodarone. Testing of thyroid function under antithyroid drug therapy revealed a hyperfunctioning autonomous adenoma, which was successfully eliminated by radioactive iodine therapy. In the other patient, it was not possible to withdraw amiodarone, so we initiated long-term treatment with antithyroid drugs. Our data support the assumption that amiodarone causes an impairment of the peripheral conversion of T4 to T3. As a result, one finds elevated serum concentrations of T4, which, in combination with the mainly negative TRH-test, must not be interpreted as proof of a hyperthyroid metabolic state being present. Hyperthyroidism is confirmed only if serum concentrations of T3 are also elevated.

Adolescent↗
PubMed1984

[Echocardiographic study for optimizing therapy with physiologic heart pacemakers--the relevance of mitral valve motion].

The hemodynamic effects of the AV-intervals 50, 150 and 250 ms were studied in 19 patients with VDD pacemakers and compared to VVI stimulation and 12 normal individuals. LV dimensions and systolic and diastolic time intervals were measured with echo-phonoapexcardiography. The amplitude of LV-contraction, LV enddiastolic diameter, PEP, LVET and PEP/LVET significantly improved with physiological pacing when compared to VVI-stimulation. The optimal AV-interval was 50 ms in 8 patients, 150 ms in 7 and 250 ms in 4. Mitral valve closure (128 +/- 13 ms) and PEP (193 +/- 19) were grossly delayed in comparison to normal individuals. With increasing AV-intervals PEP and the onset of rise in the apexcardiogram were not changed but mitral valve closure occurred earlier, being 128 +/- 13 ms at AV = 50, 82 +/- 36 ms at AV = 150 and 20 +/- 73 ms at AV = 250. Simultaneously LV-filling time normalized for cycle length decreased from 50 +/- 5% to 45 +/- 8% and 38 +/- 10% respectively. In the presence of early mitral valve closure there was a late mitral notch, which occurred 10 +/- 20 ms after the onset of rise of the apexcardiogram. Thus the onset of the isovolumic contraction period was defined. In patients with VDD pacemakers therefore, echocardiography allows measurements of LV function, of the late onset of systole, and of mitral valve closure, which depends on the previous PR-interval. These values need to be considered in programming the optimal AV-interval and cannot be derived from normal individuals.

Adult↗
PubMed1984

TPA (12-O-tetradecanoyl-phorbol-13-acetate) activation and differentiation of human peripheral B lymphocytes.

The effect of the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate) on normal human peripheral blood and tonsil B lymphocytes was investigated. A strong DNA-synthesis response with the maximum at day 4 was detected. This response was, however, inhibited by increasing concentrations of serum in the medium. The membrane Ig expression was changed with a rapid decrease in IgD expression and a slower decrease in IgM and IgG expression. TPA-induced Ig secretion was detected in 12 out of 22 tested donors and the response was found to be independent of T cells and macrophages. The expression of four monoclonal antibody-detected B cell activation and differentiation markers, B1, B2, LB1 and BB1, was followed. The results indicate activation and differentiation of the B cells.

Antibodies, Monoclonal↗
PubMed1984

Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens.

Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.

Antigens, Neoplasm↗
PubMed1984

[Systemic lupus erythematosus in hereditary complement 4 deficiency].

A genetically determined complete absence of the fourth component of complement, C4, associated with systemic lupus erythematosus has been detected in one member of another family. Observations made in this patient, the ninth described so far in whom systemic lupus erythematosus and C4 deficiency occur have confirmed that this condition presents with a characteristic clinical picture: there is pronounced sensitivity to sunlight and to cold with Raynaud's phenomenon; skin lesions are found predominantly in locations typical for subacute cutaneous lupus erythematosus and, remarkably, on the palms and soles. As was the case in two families described earlier, the C4-deficient gene was associated with the HLA-haplotype AW30, B18, DR7; BfS1.

Adult↗
PubMed1984

Cardiac pacemaker leads--a radiographic perspective.

To comment on the adequacy of positioning of single- or dual-chambered pacemaker leads requires some knowledge of the type of electrode used. Earlier leads relied upon force transmitted along the body of the lead to the electrode-myocardial interface to maintain positioning. These relatively large stiff leads were placed almost exclusively near the apex of the right ventricle to prevent dislodgement. More recent leads incorporate mechanical fixation devices to maintain position, commonly either tined or screw-in electrodes (or variations of these) representing passive and active fixation mechanisms respectively. The tines are not radiopaque; the screw-in devices are metallic. Such newer electrodes permit the use of smaller, more flexible leads, reduce the necessity for precise positioning, and reduce the frequency of lead dislodgement.

Adult↗
PubMed1983

A 3q+ marker chromosome in EBV-carrying nasopharyngeal carcinomas.

The malignant epithelial cells of two anaplastic EBV-carrying nasopharyngeal carcinomas (NPC) were investigated cytogenetically by Giemsa banding technique. Both tumors had a similar 3q+ marker chromosome with an involvement of band q25, either a duplication of the region q25-q27, or insertion of an unidentified segment at band q25.

Animals↗