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Biomedical subjects

M Wilhelm

Publications and source records attributed to M Wilhelm.

At least 163 records · Page 9Linked to original sources
PubMed1994

Hyperthermic isolated limb perfusion with cis-diamminedichloro-platinum. II. An experimental study in dogs with a balloon-occlusion technique for repeated high-dose treatment.

Isolated organ perfusion is attractive for regional high-dose chemotherapy because of its advantage to reduce whole body toxicity. Intraoperative hyperthermic isolated perfusion procedures involving a heart-lung machine have been developed, but repeated treatments carry a high risk of vessel and tissue damage. Therefore, a study of isolated hyperthermic limb perfusion in four dogs was conducted using a balloon-occlusion technique including a hyperthermia unit, two low-flow rotary pumps, a bubble oxygenator, and two polyurethane balloon catheters. After 15 min infusion of cisplatinum the concentrations of serum platinum (Pt) in the isolated limb and in the whole body were measured by atomic absorption spectroscopy. Regional exposure to Pt was more than 10-fold higher than systemic exposure. After 60 min isolated limb perfusion, the area under the curve (AUC) of Pt concentrations in the isolated limb showed values between 767.4 and 1055.6 micrograms/l x 60 min, whereas in the whole body values between 59.8 and 75.9 micrograms/l x 60 min were obtained. Repeated isolated limb perfusions with the balloon-occlusion technique were performed in three dogs without systemic side effects. This model of regional chemotherapy may be useful for preoperative chemotherapy in malignant tumors of the limbs.

Animals↗
PubMed1994

Gold kinetics under long-term treatment with gold(I) disodium thiomalate: a comparison in three different mouse strains.

Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.

Animals↗
PubMed1994

An in vitro model for the expansion of V gamma 9 delta 2 T lymphocytes during development.

The gamma/delta T lymphocytes represent a minority of T lymphocytes in human peripheral blood. Although there have been reports of reactivity against (myco-) bacterial antigens and heat shock proteins, their function and antigen specificity remain ill defined. The biological role of gamma/delta T cells has been related to functions within the 'first line of defense'. Similar to gamma/delta T lymphocytes in the T-cell compartment, CD5 positive B cells represent a small subset of B lymphocytes, which is thought to be involved in the maintenance of natural immunity and autoimmunity. We provide evidence for the cooperation of gamma/delta T cells and CD5 positive B cells in the proliferative response of gamma/delta T cells to bacterial antigens. Our data indicate a strong proliferation of V gamma 9 delta 2 T cells in response to gram-negative bacteria, which is dependent upon the presence of CD5 positive B-CLL or activated normal B lymphocytes. The selective stimulation of the V gamma 9 delta 2 subpopulation by gram-negative bacteria is also confirmed by analysis of different gamma/delta T-cell clones. The interaction of gamma/delta T cells with activated B cells and gram-negative bacteria may prove to be a useful model similar to the expansion of the V gamma 9 delta 2 subpopulation during development. In addition, our in vitro system should provide new insights in the interaction of CLL B cells with the immune system and the antigens recognized by gamma/delta T cells.

Antigens, Bacterial↗
PubMed1994

Quantitative synaptology of the inner plexiform layer of the retina of Bufo marinus.

We have performed a quantitative electron microscope study on the inner plexiform layer (IPL) of Bufo marinus retina in order to reveal the types, morphological features, densities and distributions of synapses and compare these parameters to samples derived from the visual streak area and the retinal periphery. The IPL has been subdivided into five sublayers (SLs) and the data were analysed accordingly. The density of synapses was found to be about 140.000/mm2 and was not significantly different between the central and peripheral retina. In both locations, SL3 contained the smallest number of synapses. The amacrine:bipolar presynaptic profile ratio was about 7, both in the centre and at the periphery. Amacrine-amacrine interactions greatly outnumbered other types of synapses and occurred most frequently in SL2 and 4. Bipolar cell outputs are directed mostly to amacrine-amacrine dyads, and the inputs to bipolar terminals from amacrine cells somewhat outnumber those of the outputs. The largest number of synapses directed to ganglion cells was observed in SL1 and derived from amacrine cells. The correlation between the stratification of neurochemically and morphologically characterised amacrine cells, and the morphologically and physiologically characterised ganglion cell types in the IPL are discussed.

Animals↗
PubMed1993

Immunocytochemical identification of serotonin-synthesizing neurons in the vertebrate retina: a comparative study.

Serotonin-synthesizing neurons in the retinas of goldfish, axolotl, turtle, chick, rabbit and cat were identified using double labelling with anti-serotonin and anti-phenylalanine hydroxylase antibodies. The latter antibody recognizes tryptophan 5-hydroxylase, one of the synthesizing enzymes for serotonin. Neurons labelled by both markers were considered to be serotonin-synthesizing neurons, while those only with serotonin-immunoreactivity were assumed to be serotonin-accumulating neurons. In the goldfish and chick retinas, all serotonin-immunoreactive amacrine cells (S1) were positive for phenylalanine hydroxylase. In the axolotl and turtle retinas, all the S1 amacrine cells, and only 52.8% and 40.5% of S2 amacrine cells were double-labelled. Although serotonin-immunoreactive bipolar cells were observed in the turtle and chick retinas, the synthesizing enzyme for serotonin could not be detected in these cells. In the rabbit and cat retinas, tryptophan hydroxylase could not be revealed in any cell type with immunocytochemistry. In control experiments SLI neurons in the raphe nuclei of the brain stem always exhibited PH-LI in all species examined, including mammals, indicating that our anti-PH antibody is able to recognize tryptophan hydroxylase across vertebrate classes. These results indicate that the majority of serotonin-immunoreactive amacrine cells are able to synthesize serotonin and are the source of endogenous serotonin in the non-mammalian retina, while some serotonin-immunoreactive amacrine and bipolar cells possibly only accumulate serotonin. We also suggest that serotonin may not be a primary neurotransmitter in the serotonin-accumulating bipolar and amacrine cells of the non-mammalian retina.

Ambystoma mexicanum↗
PubMed1993

Morphology and distribution of Müller cells in the retina of the toad Bufo marinus.

We have previously shown that an antibody against neuron-specific enolase (NSE) selectively labels Müller cells (MCs) in the anuran retina (Wilhelm et al. 1992). In the present study the light- and electron-microscopic morphology of MCs and their distribution were described in the retina of the toad, Bufo marinus, using the above antibody. The somata of MCs were located in the proximal part of the inner nuclear layer and were interconnected with each other by their processes. The MCs were uniformly distributed across the retina with an average density of 1500 cells/mm2. Processes of MCs encircled the somata of photoreceptor cells isolating them from each other by glial sheath, except for those of the double cones. Some of the photoreceptor pedicles remained free of glial sheath. Electron-microscopic observations confirmed that MC processes provide an extensive scaffolding across the neural retina. At the outer border of the ganglion cell layer these processes formed a non-continuous sheath. The MC processes traversed through the ganglion cell layer and spread beneath it between the neuronal somata and the underlying optic axons. These processes formed a continuous inner limiting membrane separating the optic fibre layer from the vitreous tissue. Neither astrocytic nor oligodendrocytic elements were found in the optic fibre layer. The significance of the uniform MC distribution and the functional implications of the observed pattern of MC scaffolding are discussed.

Animals↗
PubMed1993

Inactivation by ionizing radiation of ion channels formed by polyene antibiotics amphotericin B and nystatin in lipid membranes: an inverse dose-rate behavior.

The phenomena reported are part of a study about the effects of ionizing radiation on membrane transport. We found that the conductance of lipid membranes in the presence of the polyene-antibiotics nystatin or amphotericin B is reduced to virtually zero following irradiation. Ion channels formed by these substances seem to represent extremely sensitive structures being inactivated by radiation doses in the range of a few Centigray (1 cGy = 1 rad) at sufficiently small dose rates. Inactivation shows a so-called inverse dose-rate behavior, i.e., at constant radiation dose the effect increases with decreasing dose rate. Similar to radiation-induced lipid peroxidation the phenomenon may be understood on the basis of a radical chain mechanism initiated by free radicals of water radiolysis. The process--via peroxidation of the polyene part of the molecules--is suggested to modify the hydrophobic exterior and to destabilize the barrel-like structure of the ion channels.

Amphotericin B↗
PubMed1993

Colocalization of GABA-immunoreactivity in neuropeptide- and monoamine-containing amacrine cells in the retina of Bufo marinus.

Immunocytochemical study was performed in the Bufo marinus retina to reveal the localization of gamma-aminobutyric acid (GABA)-immunoreactivity in neuropeptide Y (NPY)-, substance P (SP)-, serotonin (5HT)-and tyrosine hydroxylase (TH)-immunoreactive amacrine cells. GABA-immunoreactivity was present in all NPY-, in some of the SP- and 5HT-containing amacrine cells, but not in TH-immunoreactive amacrine cells. Among the 5HT-immunoreactive amacrine cells, a population of 5HT-synthesizing and most of the 5HT-accumulating cells were GABA-immunoreactive. These results indicate that neuropeptide- and GABA-immunoreactivity are colocalized in amacrine cells of the anuran retina. We propose a possible co-transmission for two classical neurotransmitters (GABA and 5HT) in some of the 5HT-containing amacrine cells.

Animals↗
PubMed1993

Differential signal requirement for upregulation of HLA-class II molecules in human lymphoma B cells.

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymphoma cells by either membrane IgM cross-linking or phorbolester stimulation. The ability of phorbolesters to substitute for anti-IgM antibodies in the activation of normal and malignant human B cells has been taken as evidence for the involvement of protein kinase C (PKC) in signals transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells show a distinct regulation of HLA-class II expression. In certain lymphoma cases phorbol-myristate-acetate (PMA) not only fails to up-regulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 induced class II expression. This negative signal induced by PMA seems to operate specifically in HLA-class II regulation because PMA can induce other anti-IgM mediated events like blast transformation and induction of IL-4 responsiveness at the same time. Therefore these cells support the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM antibodies and phorbolesters influence the regulation of HLA-class II expression in a contrary direction.

Antibodies↗
PubMed1992

Failure to detect any effect of amalgam restorations on peripheral blood lymphocyte populations.

Dental amalgam has been considered to have adverse side effects on the immune system. Reports have been contradictory, indicating both an increase and a decrease in peripheral blood lymphocyte counts associated with amalgam restorations. We investigated two groups of patients, one of which was treated with amalgam restorations for the first time. In the other group, all existing amalgam fillings were removed. Prior to and after treatment, we determined the absolute and relative numbers of granulocytes, lymphocytes, monocytes, T cells, B cells, cytotoxic T cells, helper T cells and natural killer cells. In addition, functional investigations of T cells were performed. We failed to find any effect of amalgam restorations on the immune system in terms of the parameters investigated.

Adolescent↗
PubMed1992

Neuron-specific enolase-like immunoreactivity in the vertebrate retina: selective labelling of Müller cells in Anura.

Neuron-specific enolase (NSE) immunocytochemistry was carried out in retinae of goldfish, axolotl, clawed frog, cane toad, lizard, chick, guinea-pig, rabbit, rat, cat and human. With the exception of Anura, strong immunoreactivity was seen in the large ganglion, amacrine cells and horizontal cells of the retina in all of the other species. Photoreceptors were found to be labelled in the rat and human retina and only one cone type in rabbit. Photoreceptor pedicles and ellipsoids were stained in the goldfish and the somata and inner segments of some photoreceptors in axolotl. In the axolotl retina, besides neurons, Müller cells (MCs) were also immunolabelled. In the retina of the cane toad and the clawed frog MCs were the only stained elements. Similarly in other parts of the central nervous system of the cane toad, glial elements of the optic tectum and spinal cord were immunoreactive. In contrast, in the peripheral nervous system, neurons of the 1st sympathetic ganglion and the 2nd dorsal root ganglion were labelled. In double-labelling experiments, glial fibrillary acidic protein and NSE showed colocalisation both in the glial elements of the optic tectum and spinal cord and in MCs of the retina of the cane toad.

Ambystoma↗
PubMed1992

Microtubule-associated protein 2 (MAP2)-immunoreactive neurons in the retina of Bufo marinus: colocalisation with tyrosine hydroxylase and serotonin in amacrine cells.

Neuron populations in the retina of the toad, Bufo marinus, were labelled with a monoclonal antibody raised against microtubule-associated protein 2 (MAP2). A subpopulation of cones, probably corresponding to the blue-sensitive small single cones, large diameter amacrine cells in the most proximal row of the inner nuclear layer and some large ganglion cells in the ganglion cell layer were labelled. Double labelling experiments were carried out to establish the colocalisation of MAP2 with known putative transmitter substances of the anuran amacrine cells. MAP2 was colocalised in a subpopulation of serotonin-immunoreactive and in all tyrosine hydroxylase-immunoreactive amacrine cells. The results indicate, that the MAP2 content in the neurons of the anuran retina can be correlated with other well-defined neurochemical and/or physiological properties.

Animals↗
PubMed1992

Gamma/delta receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis.

Recently we described a cutaneous T-cell lymphoma expressing the gamma/delta T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating gamma/delta T-lymphoma cells we established T-cell clones bearing the gamma/delta T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these gamma/delta T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of alpha/beta T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-gamma, since it was detectable in high amounts in the SN of these gamma/delta T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN-gamma antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-gamma, which is secreted in high amounts from gamma/delta T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.

Bone Marrow Cells↗
PubMed1992

Single-dose toxicokinetics of aluminum in the rat.

The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12,000 micrograms Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12,000 micrograms Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12,000 micrograms/kg. At IV doses between 10 and 1000 micrograms/kg the terminal half-life of elimination from whole blood (t1/2 beta) increased from 29.9 +/- 7.8 to 209.3 +/- 32.6 min, and the total body clearance (CL) decreased from 2.45 +/- 0.64 to 0.28 +/- 0.03 ml min-1 kg-1. Following an IV bolus of 10 and 100 micrograms/kg the administered Al was recovered completely from urine (94.4% +/- 9.9% and 98.5% +/- 3.2%). Twenty-nine days after the IV dose of 1000 micrograms/kg daily renal excretion decreased to baseline values while only 55.1% +/- 8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 micrograms/kg Al accumulated in liver (28.1 +/- 7.7 versus 1.7 +/- 0.5 micrograms/g of control rats) and spleen (72.5 +/- 21.1 versus < 0.4 microgram/g). After the single 1000 micrograms/kg IG dose no absorption of Al was detectable. The IG dose of 12,000 micrograms/kg resulted in a maximum blood Al level of 47.9 +/- 12.4 micrograms/l after 50 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1992

The topographic organization of the retinal ganglion cell layer of the lizard Ctenophorus nuchalis.

The numbers of neurons of the ganglion cell layer (GCL) and their distribution in the retina of an Australian lizard Ctenophorus nuchalis were investigated. Retinal wholemounts and sections were prepared for light microscopic and optic nerves for electron microscopic study. Counts of cell numbers in the GCL from wholemounts varied from 200,000 to 380,000. Neurons in the GCL were non-uniformly distributed, forming a high cell density streak along the naso-temporal axis of the retina. Neurons of the GCL formed 2 to 9 layers in the visual streak and a single layer in the rest of the retina. The number of neurons of the GCL in this area was estimated at about 2,100,000. Although the visual streak represented only 16% of the total retinal surface area, it contained about 90% of all neurons of the GCL. Optic axon counts yielded 147,000 myelinated and 2,643,000 unmyelinated fibres. The estimated optic fibre number of 2,790,000 was 18.2% less than the total number of neurons counted from sections in the GCL of the same eye. The unexpected high number of neurons in the area of the visual streak indicates that cell numbers obtained only from wholemount preparations may vastly underestimate the total neuron numbers in the GCL of the lizard retina.

Animals↗