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Biomedical subjects

M Schaefer

Publications and source records attributed to M Schaefer.

At least 19 recordsLinked to original sources

Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype.

To seek information on the potential lifespan of normal B and T lymphocytes, lymph node (LN) cells from unprimed mice were transferred to H-2-identical severe combined immunodeficiency (SCID) hosts. At a population level, the donor B and T cells survived for at least 10 mo post-transfer with no reduction in their numbers. In terms of antibody production, LN-injected SCID mice remained responsive to several different antigens and contained unprimed precursors of memory cells for greater than or equal to 6 mo post-transfer. Most of the B and T cells recovered from LN-injected SCID mice expressed the typical virgin phenotype of mature lymphocytes from young mice. These findings suggest that many of the transferred lymphocytes might have remained in interphase as virgin cells from the time of injection. This did not apply to all of the transferred cells, however, because 20-40% of CD4+ cells from long-term SCID hosts displayed a memory phenotype, 7% incorporated 2-bromodeoxyuridine over 5 d, and total numbers of B and T cells increased gradually (twofold) over a 10-mo period. Collectively, the data favor the view that the pool of mature B and T cells in adult mice is largely self sufficient: some of the cells proliferate, presumably in response to environmental antigens, but many mature cells can remain quiescent for prolonged periods. Input of new cells from the primary lymphoid organs continues, but at a much reduced rate relative to young life.

Animals

[Defined cyclic doses (DCD)--a proposal for the application of the DDD method to the antineoplastic group].

The establishment and implementation of defined daily doses (DDD) has provided a useful tool to compare drug consumption studies on regional as well as international level. One of the limitations of the concept so far is the fact that according to the definition of the DDD there are no DDDs for certain groups of drugs like antineoplastic drugs. In order to close that methodological gap we suggest a special technical unit of measurement with regard to the therapeutical routine of application of antineoplastic drugs: the defined cycle dosis (DCD). That the DCD can be applied to comparing the consumption of antineoplastic drugs in principle is shown by means of statistical data covering the years from 1983 to 1988 in East Germany.

Antineoplastic Agents

A precise analytical method for calculating the electrostatic energy of macromolecules in aqueous solution.

A new method for calculating the total electrostatic free energy of a macromolecule in solution is presented. It is applicable to molecules of arbitrary shape and size, including membranes or macromolecular assemblies with substrate molecules and ions. The method is derived from integrating the energy density of the electrostatic field and is termed the field energy method. It is based on the dielectric model, in which the solute and the surrounding water are regarded as different continuous dielectrics. The field energy method yields both the interaction energy between all charge pairs and the self energy of single charges, effectively accounting for the interaction with water. First, the dielectric boundary and mirror charges are determined for all charges of the solute. The energy is then given as a simple function of the interatomic distances, and the standard atomic partial charges and volumes. The interaction and self energy are shown to result from three-body and pairwise interactions. Both energy terms explicitly involve apolar atoms, revealing that apolar groups are also subject to electrostatic forces. We applied the field energy method to a spherical model protein. Comparison with the Kirkwood solution shows that errors are within a small percentage. As a further test, the field energy method was used to calculate the electrostatic potential of the protein superoxide dismutase. We obtained good agreement with the result from a program that implements the numerical finite difference algorithm. The field energy method provides a basis for energy minimization and dynamics programs that account for the solvent and screening effect of water at little computational expense.

Electricity

Role of T cell subsets in lethal graft-versus-host disease (GVHD) directed to class I versus class II H-2 differences. II. Protective effects of L3T4+ cells in anti-class II GVHD.

Detailed information was sought on the capacity of purified B6 L3T4+ cells to elicit lethal graft-versus-host disease (GVHD) in irradiated class II-different class I-identical (C57BL/6 (B6) x bm 12)F1 hosts. When B6 L3T4+ cells were transferred in small doses (10(5) to 10(6) together with donor bone marrow (BM) cells, the recipients all developed acute lethal GVHD and most of the mice died within 2 wk, probably from gut damage; this syndrome was conspicuous only in mice treated with very heavy irradiation, i.e., 1000 rad. In marked contrast to L3T4+ cells given in small doses, transfer of large doses of B6 L3T4+ cells to heavily irradiated (B6 x bm 12)F1 hosts paradoxically resulted in only limited mortality: most of the recipients survived for greater than 6 mo and manifested little or no evidence of ill health. It is suggested that the capacity of large doses of L3T4+ cells to protect mice against lethal GVHD is a reflection of T helper function: the cellular immunity provided by the donor L3T4+ cells enables the host to repel pathogens entering through damaged mucosal surfaces, with the result that GVHD becomes sublethal. The protective function of L3T4+ cells in the B6----bm 12 combination was only seen in hosts given donor BM. With transfer of donor L3T4+ cells plus host BM, even lightly irradiated recipients died rapidly from hemopoietic failure. Because this syndrome failed to occur in mice given a mixture of donor and host BM, it would appear that L3T4+ cells destroyed host lymphohemopoietic cells by direct cytotoxicity rather than via a bystander effect.

Animals

Complications and pseudocomplications after Lich-Grégoir antireflux plasty.

With exact diagnosis and correct surgical technique, the Lich-Grégoir anti-reflux plasty is safe and complications are few--reflux recurrences are rare. The only serious complication is neurogenic bladder voiding disturbance, which has been observed in some cases after one-stage bilateral procedure and excessive mobilization of the bladder neck. Postoperative ureteral obstructions of the urine flow, generally due to oedemas, are thus temporary. They can be regarded as pseudocomplications.

Humans

Antigen-presenting cells for CD8+ T cells.

Evidence is presented that a wide variety of cell types are capable of presenting class I alloantigens to purified unprimed CD8+ cells in the absence of added help. These cells include dendritic cells, a population of Ia- Thy 1- cells in spleen, peritoneal exudate cells and one of three T-tumor lines. Some cell types, e.g. T-blast cells and overnight-adherent peritoneal exudate cells (OA-PEC) only expressed antigen-presenting cell (APC) function in the presence of added lymphokines. Stimulation of OA-PEC with small concentrations of lipopolysaccharide or treatment of T-blast cells with neuraminidase (N'dase) strongly enhanced the APC function of these cells and led to helper-independent responses. N'dase treatment of small resting T stimulators caused partial restoration of APC function: strong responses were observed but only in the presence of exogenous lymphokines. Studies with T-tumor lines preincubated with IFN-gamma suggested that APC function correlates closely with antigen (class I) expression. Collectively, the data support the view that APC function depends upon a multiplicity of factors including antigen density, the level of accessory (adhesion) molecules and net surface charge. It is suggested that the potency of APC function is largely a reflection of the overall avidity of T-APC interaction: high-avidity binding leads to helper-independent responses whereas weaker binding results in helper-dependent responses.

Animals

[Low pressure trocar resection versus Iglesias suction resection].

Trocar resection is superior to Iglesias' backwash resection. The main criteria on which this assessment is based are the larger operative specimen obtained, the shorter duration of the operation, and the much smaller intraoperative infiltration volume. This last was determined using a glycine irrigation solution, by measuring the increase in glycine in the serum by means of column chromatography. This showed that the intravesical irrigation pressure determines the absorption volume after opening of the venous sinus, while the duration of the resection and the volume of irrigation solution employed perioperatively are of less importance. In the case of alcohol-based irrigation solutions these results can be confirmed by measuring the "standby" alcohol in the respiratory air.

Glycine

[Analysis of structural relationship between drug consumption and its influencing factors using multivariate statistical methods].

Based upon various multivariate statistical methods consumption data of antihypertensive drugs and their causal or functional relationship with different influencing factors were investigated, exploratively and exemplarily. Several analytical examinations (principal components analysis, factor analysis, cluster analysis) were performed aiming at the reflection of these factors in a classified and quantified form.

Antihypertensive Agents

[Self-medication and social-political conditions--the situation in the GDR].

Self-medication is determined by social policy decisions and controlled by the drug law in order to ensure a justifiable proportion of risk and benefit for the application of drugs licensed for self-medication. Special emphasis is put on the situation and the self-medication market in the GDR.

Germany, East