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Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

At least 307 records · Page 17Linked to original sources

Role of interstimulus and stimulus-hemisphere compatibility in the process of interhemispheric integration.

Normal subjects had to name German compound nouns which were presented tachistoscopically. The compound nouns were displayed either unilaterally to the left or right visual field, or bilaterally with one element to the left and one to the right visual field. A distinction was made between the bilateral conditions as to whether the representation of the elements, printed and/or pictorial, included a high or low interstimulus and a high or low stimulus-hemisphere compatibility. Analysis indicated firstly a superiority of the left hemisphere for the naming of compound nouns in mixed print and pictorial representation. Secondly, the performance in the bilateral conditions was moderated by stimulus-hemisphere compatibility. In the process of interhemispheric integration stimulus-hemisphere compatibility proved more crucial than interstimulus compatibility. Analyses of errors further illustrated hemispheric behaviour.

Adult↗

Heavy water (D2O)-induced shape changes, movements and F-actin redistribution in human neutrophil granulocytes.

Heavy water (D2O) induces characteristic shape changes and a distinct type of movement in human neutrophil granulocytes. In contrast to front-tail polarity as evoked by chemotactic peptides and microtubule-disassembling agents, D2O-based media produce non-polar neutrophils with many small or long surface projections. This phenotype is similar to that elicited by both phorbol myristate acetate and diacylglycerols, but the surface projections are smaller and more densely placed and are often associated with a single large projection. D2O-induced non-polar cells with surface projections perform continuous shape changes without front-tail polarity and without the unidirectional movement and cytoplasmic streaming seen in cells with front-tail polarity. Some of the cells show circus movements of a large projection indicating circular polarity. In neutrophils suspended in D2O, F-actin is shifted to the cell periphery, mainly into the surface projections of activated cells. The D2O-induced effects are reversed in H2O-based medium. D2O is dominant over the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), colchicine and taxol in that the combined action of D2O with any of these agents results in the D2O-induced phenotype. In contrast, cytochalasin B alone and in combination with fMLP induces a considerable decrease of non-polar cells and an increase of spherical cells similar to non-stimulated cells in H2O-based medium. Earlier studies indicated that D2O acts on microtubules. Our results suggest that D2O may act on the microfilament system. Neutrophils suspended in D2O-based medium may represent a useful model to study the relationship between shapes, movements, and particular functions of these cells.

Actins↗

Production and immunohistochemical characterization of monoclonal antibodies directed against renal basement membranes of rats.

Basement membranes were separated from rat glomeruli and purified by mild procedures, which led to a highly enriched basement membrane fraction. Here, the production and characterization of five monoclonal antibodies against tubular and glomerular basement membranes are described. These antibodies were analyzed immunohistochemically on frozen sections of rat, bovine, and human kidneys as well as on rat embryos. One monoclonal antibody (BM O II) exclusively recognized the glomerular basement membranes, another one (BM O VII) bound to tubular basement membranes and to Bowman's capsule. Three antibodies (BM O IV, BM M II, BM M III) recognized their antigens in both glomerular and tubular basement membranes as well as in mesangial cells. The BM O II antibody showed a stringent species specificity and bound only to glomerular basement membranes of the rat. The other four antibodies cross-reacted with human and bovine glomerular basement membrane and mesangial antigens; they also bound to other tissues in the developing rat embryo. Antibody binding to specific purified components of the basement membranes such as collagen type IV, laminin, heparan sulphate proteoglycan, and fibronectin was investigated by enzyme-linked immunosorbent assay (ELISA). None of these antibodies reacted with any of these known basement membrane components, indicating that the antibodies may serve as useful tools in future investigations of so far unidentified components of basement membranes.

Animals↗

[Pion radiotherapy of unresectable soft tissue sarcomas at the Swiss Institute for Nuclear Research].

The Swiss Institute for Nuclear Research SIN at Villigen is one of the three centres in the world (LAMPF, Los Alamos; TRIUMF, Vancouver) where pion therapy is possible. A dynamic, tumour conforming spot scan technique for the treatment of deep-seated tumours has been in use since November 1981. With this technique with a favorable integral dose distribution, curative irradiation also of advanced tumours in the retroperitoneum and pelvis is possible. Only at SIN, the treatment of non-resectable soft tissue sarcomas with pions is part of the clinical program. Between 1983 and 1985 totally nine patients were treated, 1/9 with three manifestations, 1/9 with palliative intent. In 20 fractions over five weeks (four fractions a week) total doses of 30 to 36 Gy (90% isodose) were applied. In a follow-up period of eleven to 43 months (median 18 months) only 1/10 tumour manifestations treated with greater than or equal to 30 Gy failed locally. The two-year survival rate (Kaplan-Meier) is 56%. Metastases were the cause of death in 3/5 patients, 1/5 heart disease, 1/5 local tumour progression. Even though 9/11 tumours were located in the retroperitoneum or pelvis, no radiogenic morbidity of the bowel was found. These preliminary results stimulate the intensification of this clinical program. 1986 the same number of patients with non-resectable soft tissue sarcomas was treated as in the whole period 1982 to 1985 before.

Adolescent↗

[Fulminant hepatitis in Listeria septicemia].

We report on a 44-year-old male patient admitted with acute severe icteric hepatitis. Listeria monocytogenes was isolated from blood cultures. The further course was complicated by meningitis and the patient finally died of multiorgan failure. Autopsy revealed nodular cirrhosis of the liver with cholestatic hepatitis and focal subacute liver dystrophy, as well as granulating meningitis. The case is discussed in the context of five previously published observations on hepatitis due to Listeria monocytogenes.

Adult↗

Nerve growth factor (NGF) receptor expression in chicken cranial development.

In order to map the expression of receptors for nerve growth factor (NGF) during brain and cranial ganglia development, iodinated NGF (125I beta NGF) was used as a probe in an autoradiographical analysis performed between embryonic day 3 (E3) and posthatching day 3 (P3) of chicken development. Heavy autoradiographic labelling was observed at the classical NGF target sites, the proximal cranial sensory ganglia and the sympathetic superior cervical ganglion, throughout development and after hatching. In contrast, only weak labelling could be detected during a restricted time span in the vestibulocochlear (E4-E8) and the distal cranial sensory ganglia (E4-E10), the neurons of which originate from the otic and epibranchial placodes. Specific 125I beta NGF binding was also observed in various brain regions during early brain development. NGF receptor expression there followed a characteristic pattern. The neuroepithelial layer displayed very low levels of specific 125I beta NGF binding, while strong 125I beta NGF labelling was found in the mantle layer. Brainstem somatomotor nuclei, visceromotor columns, brainstem alar plate, cerebellar anlage, tectum, and basal forebrain (epithalamus, striatum) were found to be transiently labelled by 125I beta NGF in early development (E4-E12). Non-nervous tissues such as parts of the otic vesicle epithelium and skeletal muscle anlagen of the head were also labelled. These results, showing specific binding of 125I beta NGF to cranial cells of different origin (neural tube, neural crest, placode, and possibly mesoderm) strengthen the concept that NGF may have diverse functions in growth and differentiation of various tissues and cell types.

Animals↗

Nerve growth factor (NGF) in serum: evaluation of serum NGF levels with a sensitive bioassay employing embryonic sensory neurons.

Considerable controversy surrounds the question of whether or not nerve growth factor (NGF) or a related nerve growth-promoting factor is present in serum. Recently, supporting its role as a local neuronotrophic factor, the presence of NGF in glial cells and its production in target tissues of NGF-responsive neurons were demonstrated [Rush: Nature 312:364-367, 1984; Heumann, Korsching, Scott, Thoenen: EMBOJ 3:3183-3189, 1984; Shelton and Reichardt: Proc Natl Acad Sci USA 81:7952-7955, 1984]. At the same time, the concept that NGF may play a role as a humoral factor has been questioned, since careful analyses of serum with specific and sensitive radioimmunoassays [Suda, Barde, Thoenen: Proc Natl Acad Sci USA 75:4042-4046, 1978; Korsching and Thoenen; Proc Natl Acad Sci USA 80:3513-3516, 1983; Furukawa, Kamo, Furukawa, Akazawa, Satoyoshi, Itoh, Hayashi: J Neurochem 40:734-744, 1983] as well as bioassays [Skaper and Varon: Exp Neurol 76:655-665, 1982] have not confirmed earlier reports [Levi-Montalcini and Booker; Proc Natl Acad Sci USA 46:373-391, 1960; Banks, Banthorpe, Charlwood, Pearce, Vernon: Nature 246:503-504, 1973; Hendry: Biochem J 128:1265-1272, 1972] on NGF's representation in serum. In this study serum from mouse, rat, and man was analyzed with an in vitro bioassay system which employs sensory neurons from chicken embyro dorsal root ganglia and which allows the measurement of NGF concentrations as low as 0.8 pM. It was found that sera from all these species contained neuronotrophic activity (S-NGF). The target cell spectrum as well as characteristic parameters of the neuronal growth response of S-NGF and of NGF were identical. S-NGF of mouse serum was completely inhibitable by polyclonal and monoclonal antibodies to mouse submandibular gland beta NGF. On polyacrylamide isoelectric focussing gels mouse and human S-NGF could be recovered from the same position as NGF as well as from the region where alpha 2-macroglobulin and serum albumin focused. In newborn and adult male and female mice basal S-NGF levels were equivalent to 10-50 pM NGF. A fraction of the serum samples of male mice showed elevated S-NGF levels. The incidence of high S-NGF levels was more frequent in NMRI and C57BL/6 males than in BALB/c males. Following sialectomy of male mice only basal S-NGF levels were observed up to 5 weeks after the operation. This indicates that although the submandibular gland may contribute to S-NGF levels in serum under certain conditions that appeared to be stress related, it cannot be the only source of S-NGF.

Animals↗

Re-acceleration of the down-regulated contraction kinetics in the rat tracheal smooth muscle.

The contraction kinetics of smooth muscle show a down-regulation after the transient rise found during sustained contraction. We tried to find out therefore if the contraction kinetics of rat tracheal smooth muscle can be re-accelerated during sustained activation. A 2 s length vibration (100 Hz sinusoidal; amplitude = 6% of the muscle length) produces an immediate fall in the force developed by the activated muscle. A biexponential function was fitted to the force recovery. The reciprocal of the time constant, t2, describing the slow component of force recovery, reflects the kinetics of contraction. The contraction kinetics reach their highest levels (t2 = 4.9 +/- 0.1 s,n = 166) about 30 s after the onset of electrical field stimulation. Three experimental groups were activated by either 10 microM serotonin (5-HT), 100 microM acetylcholine (ACh), or by 2 microM ACh for 50 min. Approximately 10 vibrations were applied to each preparation after an 8 min activation in order to observe stabilized down-regulated contraction kinetics. t2 values were calculated from the force recovery after vibration and averaged 11.2 +/- 0.2 s (n = 141), 11.5 +/- 0.2 s (n = 137), and 11.1 +/- 0.3 s (n = 84), respectively. After 50 min of continuous chemical activation, the preparation was stimulated additionally by the neurogenic release of acetylcholine. The t2 of post-vibration force recovery, as measured after 30 s of neural activation, showed no change in the specimens basically activated by 100 microM ACh (11.0 +/- 0.4 s, n = 51).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Accumulation of anthracotic particles along lymphatics of the human lung: relevance to "hot spot" formation after inhalation of poorly soluble radionuclides.

Large lung sections of humans of advanced adult age revealed a markedly nonuniform retention pattern of dense anthracotic particle aggregates, with an impressive accumulation of this material along pulmonary lymphatics, i.e. the deep (peribronchial), septal (perivenous) and superficial (pleural) networks. Conversely, the alveolar parenchyme contained only occasional, small aggregates of macrophages heavily loaded with carbon, representing little more than 2% of this material in lung tissue. Although translocation kinetics of anthracotic particles cannot readily be compared to those of highly toxic alpha-emitting, poorly soluble radionuclides such as 239PuO2, lymphatic drainage of the latter over the years may also be expected to lead to a concentration of radioactive material along lymph vessels. Since human data on the effects of inhaled 239PuO2 are virtually lacking, the above distribution pattern is apt to help in identifying cells and other tissue components most heavily at risk. Findings are also relevant to the problem of "hot spot" formation in vivo and its possible sequelae. The latter are briefly discussed with regard to both stochastic and non-stochastic effects.

Cell Aggregation↗

Aminopyrine N-demethylation by rats with liver cirrhosis. Evidence for the intact cell hypothesis. A morphometric-functional study.

The intact cell hypothesis states that a reduced number of intrinsically normal hepatocytes, together with hemodynamic alterations, explains decreased drug metabolism in cirrhosis. We explored this hypothesis by comparing results of the aminopyrine breath test with in vitro measurements of aminopyrine N-demethylation and morphometrically determined liver cell volume in a rat model of cirrhosis. Aminopyrine N-demethylation in vivo (ABT-k) was 0.98 +/- 0.10/h (mean +/- SD) in controls. The cirrhotic rats were separated into those with normal (NCR) and those with abnormal ABT-k (PCR). Microsomal aminopyrine N-demethylase averaged 2.08 +/- 0.77 and 2.09 +/- 0.54 mumol/min in controls and NCRs, respectively; it was reduced to 1.00 +/- 0.81 mumol/min (p less than 0.02) in PCRs. Morphometrically determined hepatocellular volume was 18.8 +/- 2.8, 17.1 +/- 1.9, and 11.6 +/- 6.1 ml in controls, NCRs, and PCRs, respectively, PCRs being lower than controls (p less than 0.01) and NCRs (p less than 0.05). When N-demethylase and cytochrome P450 were related to hepatocellular volume (in milliliters), no significant difference between the three groups was apparent. We conclude that reduced aminopyrine N-demethylation in progressed cirrhosis is mainly due to a loss of liver cell volume. The function per liver cell volume remains constant, however, thus favoring the intact cell hypothesis for the handling of slowly metabolized compounds such as aminopyrine.

Aminopyrine↗

Liver fibrosis in carbamoylphosphate synthetase deficiency.

Structural sequelae of inherited defects of the urea cycle in general, and their liver pathology in particular, are still not well understood. This holds true especially for the possible late effects in involved organs of patients now surviving longer because of more effective therapy. Some urea cycle defects may result in chronic and progressive liver damage, as has been reported. A peculiar type of liver fibrosis was observed in a girl with carbamoylphosphate synthetase deficiency, who survived for 1 year and 7 months. Hepatic fibrosis, or even cirrhosis, has been observed in argininosuccinic aciduria. Long-term survivors with urea cycle disorders may form a group at risk for the development of chronic fibrosing liver disease.

Carbon-Nitrogen Ligases↗

Extensive glomerular immaturity associated with renal tubular acidosis, nephrogenic diabetes insipidus and nephrocalcinosis.

Neonatal renal failure and glomerular immaturity have been described in 1983. The present paper describes 3 cases with the same histological features. However, follow-up of the patients during 14, 18 and 4 years, respectively, showed the following: The histologic immaturity may be followed by maturation. Thus, late maturation may be a term more suitable to designate this constellation. Renal failure may not necessarily ensue, at least not during early infancy. In the 3 cases presented in this report, the histological finding is associated with renal tubular acidosis, renal diabetes insipidus and nephrocalcinosis. The association of transient glomerular immaturity (or late glomerular maturation) and renal tubular acidosis may enhance the development of nephrocalcinosis.

Acidosis, Renal Tubular↗

Atrial natriuretic peptide protects against acute ischemic renal failure in the rat.

Because of its ability to increase glomerular filtration, antagonize the actions of vasoconstrictors, and produce vasodilation, alpha human atrial natriuretic peptide (alpha-hANP) was evaluated for its potentially beneficial effects in experimental ischemic renal failure induced by 45-60 min of renal artery occlusion in bilaterally or unilaterally renally intact Sprague-Dawley rats. After ischemia, a 4-h intrarenal infusion of alpha-hANP restored 14C-inulin clearances in bilaterally and unilaterally intact animals from 0.05 +/- 0.006 and 0.05 +/- 0.01 ml/min per 100 g to 0.314 +/- 0.04 and 0.25 +/- 0.01 ml/min per 100 g, respectively (P less than 0.001, n = 8), compared with normal values of 0.49 +/- 0.023 ml/min per 100 g. Histologically, there was a progressive decrease in medullary hyperemia and prevention of intratubular cell shedding and granulocyte margination as a result of the 4-h alpha-hANP infusion such that after 24 and 48 h the histological appearance of the tissue was essentially normal. The results show that a 4-h intrarenal infusion of alpha-hANP after renal ischemia can preserve glomerular filtration rate and reduce renal tissue damage.

Acute Kidney Injury↗

Effect of phorbol myristate acetate and the chemotactic peptide fNLPNTL on shape and movement of human neutrophils.

The results show that the distinct types of shape produced by phorbol myristate acetate (PMA) and by chemotactic peptides (fNLPNTL) are associated with distinct types of neutrophil movement. Whereas the chemotactic peptide can induce front-tail polarity characterized by an expanding front, a contracted tail and preferential unidirectional movements of intracellular organelles, PMA can only elicit non-polar movements characterized by random formation and retraction of projections all over the surface, intracellular movements of organelles being ill-defined and changing in direction. Combined stimulation of human neutrophils with PMA and fNLPNTL results in a suppression of peptide-induced polarity and the formation of non-polar motile cells resembling those stimulated with PMA alone. The results suggest that the diacylglycerol-protein kinase C pathway may be instrumental in transducing or modulating signals to the locomotor apparatus of the cell. PMA-treated cells are, however, still capable of developing directional responses when appropriately stimulated. The findings lead to the hypothesis that distinct types of neutrophil movements are preferentially associated with distinct functions.

Chemotaxis, Leukocyte↗

Interhemispheric integration of compound nouns: effects of stimulus arrangement and mode of presentation.

Normal subjects had to name German compound nouns which were presented tachistoscopically. The compound nouns were displayed either unilaterally to the left or right visual field or bilaterally with one element to each visual field. In the bilateral condition a distinction was made as to whether familiar or unfamiliar arrangement of the elements was used. Representation in print was compared with pictorial representation of the compound nouns. A right visual-field superiority was observed with printed representation, but no laterality effects with pictorial representation. Bilateral processing was superior to unilateral processing. Within the bilateral conditions, the familiar arrangement of the elements yielded a significantly better performance than unfamiliar arrangement. This difference can be explained by reading habits and/or by different styles of interhemispheric integration.

Adult↗

Shape, movement and function of neutrophil granulocytes.

Evidence that distinct types of shapes and movement can be induced by different neutrophil-activating agents like the chemotactic peptides and PMA is reviewed. Front-tail polarity seems to be preferentially associated with locomotion, whereas non-polar cells with surface projections show preferentially pinocytosis. The following partially hypothetical concept on neutrophil shape changes has been derived from these experiments: Neutrophils are capable to perform distinct types of movements depending on the stimulus or stimuli. Distinct movements are preferentially associated with distinct functions such as locomotion, pinocytosis or others. The underlying cytoskeletal changes may differ accordingly.

Animals↗

Locomotion of tumor cells as an element of invasion and metastasis.

Malignant tumor cells are endowed with the ability to invade host tissues and to produce metastases. In this review, tumor cell locomotion as an important pathogenic mechanism in the invasive process is discussed. The traffic of neoplastic cells along preformed or newly created tissue pathways will not only depend on cellular cues and/or extracellular stimulatory or inhibitory soluble factors, but also on the interactions of tumor cells with the invaded tissue. Normal tissue exerts its influence on tumor cell migration mainly by providing contact surfaces, as both the growth and locomotor phenomena of tumor cells depend on the cells ability to adhere to structures present along the invasion front. Migrating tumor cells are morphologically characterized by a cell shape change typical for locomoting cells, i.e. polarization. This locomotor phenotype is associated with altered functions of the cytoskeleton induced by agents acting on cell surface receptors, on the signal cascade, or on the cytoskeletal apparatus itself, or evoked by mutations of cytoskeletal proteins. The search for stop signals of tumor cell locomotion is of particular interest, as this may represent an approach to exert an influence on the invasive process.

Animals↗