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Biomedical subjects

M Schaefer

Publications and source records attributed to M Schaefer.

At least 91 records · Page 5Linked to original sources

Excessive hypokalemia and hyperkalemia following head injury.

A sudden decrease of serum potassium below 2.5 mmol/l carries the risk of dangerous arrhythmias and requires immediate replacement therapy [6]. We refer to a patient with a brain stem compression after head injury, who developed a profound hypokalemia (K+ = 1.2 mmol/l) with life-threatening arrhythmias, probably due to a catecholamine induced intracellular potassium shift (beta-2-stimulation). Only by aggressive potassium replacement up to 80 mmol/h (610 mmol/16 h) could potassium levels be increased and cardiac arrhythmias terminated. Although replacement therapy was stopped when the serum K(+)-level increased to 2.4 mmol/l, 3.5 h later the patient became hyperkalemic (8.1 mmol/l). This was probably due to a secondary shift of potassium from intra- to extracellular space. In patients with severe head trauma and the potential risk of excessive catecholamine release special attention must be paid to changes in potassium balance.

Craniocerebral Trauma↗

Effect of neurotropic virus infection on neuronal and inducible nitric oxide synthase activity in rat brain.

To elucidate the potential role of inducible nitric oxide synthase (iNOS) and neuronal constitutive nitric oxide synthase (cNOS) in the pathogenesis of virus-induced encephalopathy, the activities of both NOS isoforms were determined in the brains of rats infected with Borna disease virus (BDV) or rabies virus. iNOS activity strongly increased, whereas neuronal cNOS activity significantly decreased in a time-dependent manner after either BDV or rabies virus infection. Choline acetyltransferase activity in the brain remained unchanged during both virus infections, suggesting that the decrease in cNOS activity does not reflect a generalized neuronal loss. Immunohistochemistry and Northern blot analyses indicate that the decrease in neuronal cNOS activity is due to a decrease in cNOS protein and mRNA synthesis. These results suggest that both an excessive generation of NO by activated macrophages or microglia, as well as a decrease of NO production in neurons may contribute to the neuropathogenesis of neurotropic virus infections.

Animals↗

Concepts and diagnosis of brain death.

The different concepts of brain death are subject to controversial debate. It is outlined that only the whole-brain concept, that is the irreversible loss of all functions of the entire brain, is consistent with the death of man. Cortical death or brain-stem death should not be considered in this respect. The operational procedure for determining brain death is outlined with special regard to those cases in which a definite diagnosis cannot be made clinically. It is shown that apnea testing must be accompanied by blood-gas analysis, as it may take 15 min for the PaCO2 to achieve the desired level of 8 kPa. The problem with CNS-depressing drugs and their metabolites interfering with the clinical diagnosis--e.g. sedatives, barbiturates, opioids--is described, and it is stressed that, in these cases, the cerebral panangiography (digital subtraction angiography with catheter tip in the aortic arch) is the gold standard for the final and definite proof of brain death.

Brain Death↗

Children and toxic substances: confronting a major public health challenge.

Despite early warnings of lead toxicity, until recently this metal was added to a variety of consumer and industrial products. Today, thousands of children in the United States, and probably tens of thousands more worldwide, are suffering the consequences of exposure to lead. The lead story looms as major public policy failure that will eventually cost billions of dollars to remedy. Little is known about the toxicological properties of the more than 70,000 chemicals in commerce. Consequently, it seems likely that other "leads" are finding their way into our food, water, and air. Inadequate testing of chemicals to which the public is exposed presents a serious public health risk, particularly to children whose nervous systems are still developing. The Federal government should expand toxicological testing programs for existing and new chemicals, requiring increased developmental toxicological, particularly neurotoxicological, testing of chemicals to which the public is significantly exposed. In keeping with the concept of full-cost pricing, the costs of these tests should be incurred by the manufacturer, not the government, and should be considered a routine cost of product development.

Child↗

Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

Adenosine Diphosphate↗

Effects of nitric oxide-containing compounds on increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to determine the modulatory effects of nitric oxide (NO)-releasing compounds on increases in cytosolic ionized calcium ([Ca2+]i) and on aggregation of gel-filtered human platelets induced via diverse agonists. We used various sydnonimines and organic nitrates as donors of NO. Gel-filtered and fura-2-loaded platelets were stimulated with ADP (4-8 microM), collagen (2-10 micrograms/ml) or thrombin (0.02-0.05 IU/ml), respectively. Half-maximal inhibiting effects of sydnonimines on agonist-evoked increases in [Ca2+]i were observed between 30 and 1000 nM, while half-maximal inhibiting effects of the compounds on aggregation were between 3 and 500 nM. The compound C 87-3754, which is the bioactive metabolite of pirsidomine, was a much stronger inhibitor of increases in [Ca2+]i than of platelet aggregation. This was due to an enhanced NO release from this compound exposed to ultraviolet light during Ca2+ measurement. The organic nitrates isosorbide 5-mono-nitrate and nicorandil inhibited both aggregation and increase of cytosolic ionized calcium in stimulated platelets at half-maximal concentrations of approximately 200 microM. The present results suggest that some of the effects of NO on platelets are independent of cytosolic ionized calcium. The results also suggest that some of the inhibitory effects of NO-releasing compounds correspond rather to the presence of the A forms (NO-containing intermediates) than to the presence of free NO.

Calcium↗

Role of the U.S. Congress in setting goals and priorities for research on nutrition and aging.

The U.S. Congress plays an important role in setting the broad research agenda for research agencies. It often does so by articulating major goals for federally-supported activities. Goals, longer-term objectives that agencies should work towards, should not be confused with priorities, near-term resource allocations designed to support efforts to achieve goals. Typically, federal research priorities are established by individual departments, agencies, and other organizations within the executive branch; however, when the funding levels are particularly large or public concern about an issue is particularly intense, Congress may become involved in the process of setting specific priorities. Congress influences the directions of research on aging primarily through the activities of authorization, appropriations, and special or select committees. The Special Committee on Aging in the Senate, and the Select Committee on Aging in the House of Representatives focus their attention exclusively on elderly Americans. Periodically, the activities of these committees are directed to research issues. Congress indirectly influences the directions of research on aging and nutrition through laws that establish science-based regulatory programs such as the Food, Drug, and Cosmetic Act, and the Toxic Substances Control Act. In setting priorities Congress relies on information, analysis, and advice from the four congressional support agencies, particularly the Office of Technology Assessment (OTA). OTA has undertaken a number of studies in recent years which address aging and nutrition issues. It is useful to try to devise mechanisms to encourage the establishment of national and international long-range goals and near-term priorities for research on aging and nutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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↗