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Biomedical subjects

A Hess

Publications and source records attributed to A Hess.

At least 73 records · Page 4Linked to original sources
PubMed1989

Neuropathological changes in the caudate nucleus elicited by MPTP and their prevention by monoamine oxidase inhibition.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin producing parkinsonism, causes an obvious reduction in tyrosine hydroxylase (TH) activity in the caudate nucleus. This depletion of TH activity is due to degeneration of TH-positive punctate dopaminergic terminals. The disappearance of these terminals unmasks the presence of long branching, varicose preterminal fibers, which may be sprouting after degeneration of their terminal arborizations. Glial cells, normally sparse with delicate processes, undergo intense increase in number and a robust hypertrophy. All of these changes are prevented completely by administration of deprenyl, a monoamine oxidase inhibitor, before and after MPTP. These neuropathological effects are additional manifestations of the dopaminergic neurotoxicity induced by MPTP. The metabolism of MPTP, which is blocked by monoamine oxidase inhibition, is apparently necessary for the expression of toxicity in the brain by this neurotoxin.

Animals↗
PubMed1989

Host resistance to cyclosporine induced syngeneic graft-versus-host disease. Requirement for two distinct lymphocyte subsets.

Cyclosporine is crucial for the prevention of organ allograft rejection and allogeneic graft-vs-host disease (GVHD). Despite its potent immunosuppressive activity, cyclosporine elicits a T cell-mediated autoimmune syndrome after autologous or syngeneic bone marrow transplantation, which has been termed syngeneic GVHD (SGVHD). Recent studies have shown that for disease manifestation, a cytoxan and radiation-sensitive T cell dependent host resistance mechanism must be eliminated, allowing the clonal expansion of autoreactive cells. This report characterizes the autoregulatory lymphocyte population, present in normal animals, capable of inhibiting the adoptive transfer of SGVHD. First, twice the number of unfractionated splenocytes from normal animals to those from autoimmune donors ensured complete inhibition of the adoptive transfer of immune reactivity. Second, the phenotype of this host resistance mechanism in normal splenocytes involves dual regulatory T cell subsets. A helper/inducer subset (W3/25+) must be cotransferred with a cytotoxic/suppressor subset (OX8+) in a ratio that approximates the normal ratio in normal unfractionated splenocytes in order to affect inhibition of the transfer of SGVHD. Moreover the specific inducer regulatory activity resides in the OX22-, W3/25+ subset of Th cells.

Animals↗
PubMed1988

Human immunodeficiency virus induces phosphorylation of its cell surface receptor.

AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population. The causative agent of this disease is the human immunodeficiency virus, HIV, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.

Antigens, Surface↗
PubMed1987

Lymphocyte populations with different sensitivity to cyclosporin have different plasma membrane potentials.

Cyclosporin A (CsA), a clinically potent immunosuppressive agent, shows preferential biologic activity against certain lymphocyte subsets. To investigate this activity, we used flow cytometry to separate two distinct lymphocyte populations from unfractionated human peripheral blood lymphocytes, based on their different binding affinity for a biologically active fluorescent, dansylated cyclosporin (dans-CsA) derivative. The separate lymphocyte populations demonstrated different resting plasma membrane potentials. The two lymphocyte populations also had different levels of interleukin-2 (IL-2) receptors and shifted plasma membrane potential differently upon treatment with cyclosporin and lymphokine IL-2. The cell population that bound more dans-CsA contained the cells which possessed IL-2 receptors and responded to CsA and IL-2 with changes in membrane potential. The cell population that did not effectively bind dans-CsA lacked IL-2 receptors and did not respond to CsA or IL-2 with immediate membrane potential changes. Furthermore, stimulation studies of these separated two lymphocyte populations with phytohemagglutinin in the presence and absence of CsA revealed that only the population which binds a low level of dans-CsA shows a marked difference in membrane potential between the cells stimulated in the presence and absence of CsA. We concluded that ion flux changes caused by CsA affect the activation process of naive lymphocytes but not that of already stimulated ones. It can also be postulated that the ion flux changing property of CsA could constitute its primary or main mode of action.

Cell Membrane↗
PubMed1986

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice.

The administration to mice of 1-methyl-4-(2'-methylphenyl)-1,2,3, 6-tetrahydropyridine (2'-CH3-MPTP), a substituted analog of the dopaminergic neurotoxin MPTP caused even more dopaminergic toxicity than MPTP itself. Under conditions in which MPTP was relatively ineffective (i.e. two injections per day of 0.113 mmol/kg at an interval of 6 h for one or two days), 2'-CH3-MPTP caused a very large decrement in the neostriatal content of dopamine and its metabolites and a corresponding decrement in the capacity of a neostriatal synaptosomal preparation to take up [3H]dopamine. Moreover, 2'-CH3-MPTP administration (as few as four injections) caused a virtually complete loss of nerve cells in the zona compacta of the substantia nigra. This compound, like MPTP, may prove to be a valuable research tool.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

5'-Nucleotidase of cerebellar molecular layer: reduction in Purkinje cell-deficient mutant mice.

The molecular layer of the cerebellar cortex contains high levels of the enzyme 5'-nucleotidase (EC 3.1.3.5), localized predominantly to Bergmann glia. In the present study, histochemical methods have been employed to examine the distribution of cerebellar 5'-nucleotidase in mice of two separate mutant strains in which Purkinje cells are eliminated selectively. In homozygous 'Purkinje cell degeneration' (pcd) and 'nervous' (nr) mice, molecular layer 5'-nucleotidase is greatly reduced and residual enzyme activity in colocalized with surviving Purkinje cells. These results suggest strongly that the expression of 5'-nucleotidase activity by Bergmann glia is under the inductive influence of their associated Purkinje cells.

5'-Nucleotidase↗
PubMed1985

Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in the mouse: relationships between monoamine oxidase, MPTP metabolism and neurotoxicity.

Mice treated with MPTP had a marked decrement in their neostriatal content of dopamine and its metabolites compared to controls and a severe loss of nerve cells in the zona compacta of the substantia nigra. Furthermore, neostriatal synaptosomal preparations from MPTP-treated mice had a greatly diminished capacity to take up 3H-dopamine compared to control. These biochemical and histological changes seen in MPTP-treated mice are similar to those observed in Parkinson patients. In mice treated with the specific MAO-B inhibitor deprenil prior to MPTP, these changes were not observed. It thus follows that deprenil is able to protect against the MPTP-induced dopaminergic neurotoxicity in mice. These data suggest a critical role for MAO-B in MPTP-induced neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Data reduction for electron isodose measurements.

Recent developments in computer technology enable the use of direct measured data without complex calculations for the isodose generation of electron fields of a 42 MeV Betatron. To reduce the time necessary for measuring the isodose data, different procedures to measure and generate electron matrices are investigated. Different methods to reduce the amount of data necessary for the isodose-generation are introduced. Under certain circumstances isodose data for numerous field sizes can be generated from a set of data of one field with sufficient accuracy.

Electromagnetic Fields↗
PubMed1985

Clinical results after therapy with fast neutrons (DT, 14 MeV) since 1976 in Hamburg-Eppendorf.

In Hamburg since 1976 to 1980 we have treated 328 patients with fast neutron (DT, 14 MeV) and after reconstruction of the generator further 69 patients in 1984. The therapy with DT-neutrons had the best curative effect on high differentiated tumors. With the standard dose of 16 Gy in four weeks or--treating tumors in radiosensitive organs like brain and intestine--with a photon-neutron schedule, we have seen no necroses in normal tissues. The rate of medium or slight subcutaneous fibroses is not more than 10%. The local effect on tumors in our pilot study has been better than with megavoltage therapy in invasive thyroid cancer, prostate cancer stage C, soft tissue sarcoma and also in rectum-carcinoma. The best results have been achieved with neutrons only, but a photon-neutron schedule may be more effective as megavoltage therapy only. With our DT-neutrons we find some indications for better results than with megavoltage therapy if we use sophisticated treatment planning and if we strictly observe the tolerance dose of the different tissues and organs. The therapeutic index of our monoenergetic DT-neutrons is higher than with cyclotron-produced neutrons.

Aged↗
PubMed1984

Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice.

1-Methyl-4-phenyl-1,2,5,6- tetrahydropyri dine ( MPTP ) is known to cause an irreversible destruction of the dopaminergic nigrostriatal pathway and symptoms of parkinsonism in humans and in monkeys. However, MPTP has been reported to act only minimally or not at all in several other animal species. When MPTP (30 milligrams per kilogram of body weight) was administered parenterally to mice, a decrease in concentrations of neostriatal dopamine and its metabolites, a decrease in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, and a disappearance of nerve cells in the zona compacta of the substantia nigra were observed. In contrast, MPTP administration had no effect on neostriatal concentrations of serotonin and its metabolites. MPTP administration thus results in biochemical and histological changes in mice similar to those reported in humans and monkeys and similar to those seen in Parkinson's disease in humans. The mouse should prove to be a useful small animal with which to study the mode of action of MPTP .

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Organization of the infraorbital nerve in rat: a quantitative electron microscopic study.

The normal organization of the rat's infraorbital (IO) nerve was studied using conventional electron microscopic (EM) methods. Just caudal to the infraorbital foramen, at the level of the anterior superior alveolar foramen, the nerve was composed of 18-25 fascicles which ranged from 575 to 87,923 micron2 in cross-sectional area. Complete axon counts from thin sections taken at this level demonstrated that the IO nerve contained an average of 19,740 (S.D. = 2054) myelinated and 13,319 (S.D. = 1159) unmyelinated axons. The average diameter (including the myelin sheath) for medullated fibers was 4.42 micron (S.D. = 1.76) and that for unmyelinated axons was 0.60 micron (S.D. = 0.16). The fiber diameter distributions for both myelinated and unmyelinated axons were essentially unimodal.

Animals↗
PubMed1984

Fear of flying: an Israeli Air Force short case report.

This paper outlines the brief psychological treatment of an Israel Air Force pilot presenting with the fear of flying disorder. An in-depth case report is described and a variety of issues are discussed, including presentation of symptoms and psychotherapeutic techniques utilized, as well as the complicated role of the Mental Health Officer treating the problem within the military system.

Adult↗
PubMed1982

Spectroscopic intercomparison at the German neutron therapy centers.

An intercomparison of neutron dosimetry at the German neutron therapy centers at Hamburg, Heidelberg and Essen has been performed in 1979 and 1980. This intercomparison was undertaken to compare the experimental procedures and techniques for fast neutron dosimetry applied by each group. Because of the energy dependence of the dosimeters, spectroscopic investigations were performed at positions in the phantom identical to those applied during the dosimetric measurements. A description of the experimental procedures and environments is given. The measured neutron spectra are presented and discussed with respect to the changes at different positions in the phantom. Individual kerma-ratios are calculated from the neutron and photon energy distributions. The comparison of these kerma-ratios gives considerable differences in values that are used with neutron-insensitive ionization chambers. We recommend that individual generated kerma-ratios should be applied for ionization chamber dosimetry.

Light↗
PubMed1982

Triple chamber technique for thermal neutron dose measurements in fast neutron beams.

Collimated fast neutron beams used in radiotherapy are always contaminated with photons and thermal neutrons. From foil activation measurements the relative dose contribution of thermal neutrons to the absorbed neutron dose in different depths in a tissue equivalent phantom was determined. The sensitivities of a TE-Chamber, a GM-counter with a 6Li-shield and an unshielded GM-counter to fast neutrons, thermal neutrons and photons are presented. The triple chamber technique using these three devices is compared to foil activation technique with respect to the determination of relative thermal neutron depth dose curves. Finally the triple chamber technique is applied for the determination of depth dose curves of fast neutrons, thermal neutrons and photons in a solid TE-phantom.

Fast Neutrons↗