Showing papers by "University of Zurich published in 1986"

Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex.

Abstract: gamma-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. In the cerebral cortex, GABA-containing cells represent a subpopulation of interneurons. With semithin frozen sections, it is possible to demonstrate that most GABA neurons in the rat somatosensory cortex contain the calcium-binding protein parvalbumin and that parvalbumin is found virtually only in GABA neurons. Parvalbumin seems to influence the electrical properties and enzymatic machinery to modulate neuronal excitability and activity. The specific role of parvalbumin in GABA-containing cortical cells may be related to controlling the effectiveness of their inhibitory action.

Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus.

Abstract: Regional cerebral protein synthesis was investigated in the Mongolian gerbil during recovery from forebrain ischemia produced by bilateral common carotid artery occlusion for 5 min. At various recirculation periods up to 72 h animals received a single dose ofl-(3,5-3H)tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique. During the initial 30 min of recirculation autoradiographs revealed an almost complete inhibition of protein synthesis in all forebrain structures with the exception of the medio-dorsal thalamic nuclei. Between 30 min and 12 h of recirculation amino acid incorporation was completely restored in neurons of the cerebral cortex, basal ganglia, hippocampal CA3 and CA4 zones and the dentate gyrus. In CA1, early (90-min postischemia) and progressive recovery of a few irregularly dispersed neurons was observed, but the vast majority of pyramidal cells never regained their normal biosynthetic activity. Between 3 and 6 h of recirculation CA1 neurons showed faint labeling, followed by a secondary deterioration resulting in complete lack of incorporation within 12 h after restoration of blood flow. Autoradiographs at all subsequent time points exhibited persistent inhibition of protein synthesis in CA1 until neuronal necrosis occurred 2–3 days later. Thus, in contrast to ischemia-resistant cell populations with rapid progressive and complete restoration of protein synthesis, hippocampal neurons undergoing delayed necrosis are characterized by an early incomplete recovery immediately followed by a secondary persistent inhibition.

The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology.

Abstract: In order to test its potential application to surgical neuropathology, the monoclonal antibody Ki-67 was used to demonstrate immunohistochemically the proliferating cells in 40 neoplasms of the nervous system. The antibody, which reacts with a nuclear protein expressed in the G1, G2, S, and M phases of the cell cycle, was demonstrated in frozen sections of all lesions. The highest incidence of stained nuclei was found in a metastatic carcinoma (57%). The percentage of stained cells in gliomas was in general agreement with the histologic grade and known biologic behavior of the lesions, ranging from 0.6% in a pilocytic astrocytoma to 12.4% in a glioblastoma multiforme. In the fibrillary astrocytic neoplasms of low cellularity, there were good correlations between the percentages of stained cells and the degrees of nuclear pleomorphism and chromatin density. In meningiomas, schwannomas, and a cerebellar hemangioblastoma, the fractions of labeled nuclei were less than 1%. The percentage of stained cells in pituitary adenomas showed considerable variation among the four cases (0.2-1.5%), the biologic significance of which is unknown. In four of the above cases, Ki-67 staining was performed on air-dried squash preparations with excellent visualization of immunoreactive nuclei. In one case, a hemangioblastoma, no stained nuclei were seen. The results confirm that Ki-67 staining is technically suitable as a diagnostic method, with good correlations between frozen sections and smear preparations. Determination of the replicating cell fraction could become an important additional criterion to predict the biologic behavior of nervous system neoplasms.

The interferon genes.

Abstract: Publisher Summary This chapter discusses the types, effects, and properties of interferons (IFN). Interferons are classified into two types, I and II, on the basis of distinct biological, biochemical, and serological properties. Type II IFN, which is acid-labile, is secreted by T lymphocytes after immune or mitogenic stimulation. Analyses at the genomic level have revealed only one gene for type II IFN, namely—IFN-γ, which shows no clear relationship to the genes of type I IFN and is located on a different chromosome than the latter. Type I IFNs are induced by viral infection or the treatment of a variety of cells with poly(I)·poly(C) and are usually acid-stable. The genes encoding type I IFNs are the members of a superfamily. All are located on one chromosome and comprise the IFN-β and IFN-α families, which diverged 200-300 million years ago or more. In ungulates, the IFN-β family comprises several genes and in man and mouse, only one. The recently described IFN-β 2 , while cross-reacting with IFN-β antibodies, is apparently not related to the IFN-β at the genetic level. The IFN-α family comprises at least two subfamilies, IFN-α I and IFN-α II , which diverged 120 million years ago or more, clearly before the mammalian radiation.

A regularized decomposition method for minimizing a sum of polyhedral functions

Abstract: A problem of minimizing a sum of many convex piecewise-linear functions is considered. In view of applications to two-stage linear programming, where objectives are marginal values of lower level problems, it is assumed that domains of objectives may be proper polyhedral subsets of the space of decision variables and are defined by piecewise-linear induced feasibility constraints. We propose a new decomposition method that may start from an arbitrary point and simultaneously processes objective and feasibility cuts for each component. The master program is augmented with a quadratic regularizing term and comprises an a priori bounded number of cuts. The method goes through nonbasic points, in general, and is finitely convergent without any nondegeneracy assumptions. Next, we present a special technique for solving the regularized master problem that uses an active set strategy and QR factorization and exploits the structure of the master. Finally, some numerical evidence is given.

Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I.

Abstract: Insulin-like growth factor I (IGF-I) and insulin stem from a common precursor, are structural homologues, act through similar receptors and elicit insulin-like and growth-promoting effects in vitro and in vivo1,2. Serum IGF-I levels are controlled by growth hormone1, insulin3–6 and nutrition6–10. Insulin-deficient growth-arrested diabetic animals have reduced serum IGF-I levels which are restored towards normal by insulin but not by growth-hormone treatment3–6. Here we show that normal growth of diabetic rats is restored by infusion of recombinant human (rh)IGF-I without normalization of the blood sugar level and that insulin acts via an increase of IGF-I synthesis on growth of diabetic rats. We describe a new mechanism of endocrine control of growth in which IGF-I is the major stimulator at the cellular level. Growth hormone and insulin act mainly by modulating the hepatic synthesis of IGF-I.

Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain.

Abstract: Using antibodies to neuropeptide Y (NPY) in combination with immunohistochemical techniques we have studied the distribution of cell bodies and nerve terminals containing NPY immunoreactivity (-i) in the hippocampal region of rats and monkeys (cynomolgus). In colchicine-pretreated rats a large number of NPY-positive cells are present in all areas of the hippocampal region. The NPY-i cells range in size from small (diameter across soma: 10-15 micron) to large (approximately 20 micron). Most of the NPY-i cells are situated in the hilus, in the subgranular zone of the area dentata, and in the stratum oriens of Ammon's horn. A majority of these are polymorphic cells but cells of different morphology are present in these layers as well. These include small spheroid cells and dentate pyramidal basket cells that are distinct from the polymorphic cells in the subgranular zone. The subicular complex (e.g., the subiculum, pre-, and parasubiculum) and the entorhinal area contain fewer NPY-i cells than the rest of the hippocampal region. In the dorsal parts of the pre- and parasubiculum numerous small cells are scattered throughout all layers, while in the entorhinal area the NPY-stained cells are situated primarily in the deep layers (V and VI). In the ventral part of the lateral entorhinal area large multipolar and bitufted cells are found in layers II-VI. In the untreated monkey brain NPY-positive cells are found in the hilus of the area dentata and in the deep (IV through VI) layers of both the medial and lateral entorhinal area. Fewer NPY-stained cells are present in the subicular complex and in the entorhinal area. In the monkey as well as in the rat, NPY-stained cells are present in the angular bundle and in the alveus. A dense network of NPY-i fibers innervates the entire hippocampal region in both the rat and the monkey. The hippocampal NPY-i preterminal processes are present primarily in stratum moleculare of Ammon's horn and in the outer one-third of this layer in the area dentata. The NPY-positive innervation of the dentate molecular layer is far more prominent in the monkey than in the rat brain. Numerous NPY-stained fibers are scattered in other areas as well. In all retrohippocampal structures, and in particular the entorhinal area, the NPY-i fibers form a massive network that innervates all layers to about the same extent, with the exception of the molecular layer, which is more densely innervated than the other layers.

Polarization vision in bees

Abstract: A solution to the long-standing problem of how honey bees detect polarized light from the sky is presented. The mechanism involves the transformation of polarization information into modulations of perceived brightness while the bee scans the sky by rotating its field of view. Using this technique the bee needs only a very simple strategy to read compass information from the polarization patterns in the sky.

Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes.

Abstract: Schwann cells (SC) isolated from neonatal rat sciatic nerves are shown to immunogenically present foreign and exogenous autoantigen to antigen-specific syngeneic T line cells in vitro. The antigen-presenting SC express Ia antigens on their membranes upon treatment with interferon gamma and contact with syngeneic T line cells. Monoclonal antibodies against Ia block specific antigen presentation, but not polyclonal mitogenic T cell activation. The antigen-presenting SC bind antibodies specific for astrocytic glial fibrillary acidic protein and may thus be related to the nonmyelinating glia cells of the peripheral nerve. Furthermore, SC isolated from 6-day-old rats activate rat myelin basic protein (MBP)-specific syngeneic T line cells in the absence of exogenous MBP. In contrast, they activate purified protein derivative of tuberculin (PPD)-specific T cells only in the presence of PPD. Since the MBP-specific T line cells are not activated by syngeneic professional antigen-presenting cells in the absence of MBP, endogenous MBP produced in the 6-day-old sciatic nerves appears to be presented by autochthonous SC to the autoreactive T cells. The Clinical Research Unit for MS is supported by funds of the Hermann-and-Lilly-Schilling Foundation.

Persisting myocardial sinusoids of both ventricles as an isolated anomaly: Echocardiographic, angiographic, and pathologic anatomical findings

Abstract: The persistence of myocardial sinusoids in both ventricles as an isolated anomaly is described. A 21-year-old patient had progressive heart failure considered as cardiomyopathy of obscure etiology. Two-dimensional echocardiography demonstrated channel-like structures in the thickened myocardium of both hypokinetic ventricles. Angiography showed a honeycomblike inner contour in both ventricles. Autopsy proved the diagnosis of persistent sinusoids in a thickened myocardium.

In vitro release of endogenous excitatory sulfur-containing amino acids from various rat brain regions

Abstract: Efflux of various amino acids from rat brain slices was determined under resting or depolarizing conditions. Slices of neocortex, hippocampus, striatum, cerebellum, mesodiencephalon, pons-medulla, and spinal cord were depolarized by K+ (50 mM) or veratrine (33 micrograms/ml). The 4-N,N-dimethylamino-azobenzene-4'-isothiocyanate (DABITC) derivatization method of Chang [Biochem. J. 199, 537-545 (1981)] for HPLC was adapted for analysis of amino acids and peptides in superfusion solutions. It allowed the separation and simultaneous detection of the sulfur-containing amino acids cysteine sulfinic acid (CSA), cysteic acid (CA), homocysteine sulfinic acid (HCSA), and homocysteic acid (HCA) at the picomole level. All four were shown to be released on depolarization in a Ca2+-dependent manner from brain slices. CSA and HCSA were released from cortex, hippocampus, mesodiencephalon, and, for HCSA only, striatum. HCA release, observed in all regions, was most prominent in cortex and hippocampus. CA was slightly increased by depolarization in hippocampus and mesodiencephalon. These sulfur-containing amino acids have been shown to exert an excitatory action on CNS neurons. The fact that these sulfur-containing amino acids are released as endogenous substances from nervous tissue supports the hypothesis that they play a role in CNS neurotransmission.

Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients.

Abstract: Pancreatic specimens of nine patients suffering from multiple endocrine neoplasia type I (MEN I) were investigated with regard to tumor frequency and growth pattern, islet hyperplasia and endocrine cell neoformation, immunocytochemical hormone profile of the tumors, and correlation to clinical symptoms. The majority of the 201 tumors were microadenomas (diameter less than 0.5 cm), which frequently displayed a trabecular growth pattern. Microadenomatosis was considered the most distinct feature of the MEN I pancreas. Additional larger tumors (diameter greater than 1.0 cm) were found in five patients. Whereas islet hyperplasia appears not to belong to the spectrum of the pancreatic lesions in MEN I, nesidioblastosis was occasionally observed. Immunocytochemical screening revealed that among hormone-positive tumors (approximately 80% of the tumors), pancreatic polypeptide tumors (PPomas), glucagonomas, and insulinomas were the most frequent. The high incidence of PPomas in these pancreases probably accounts for the elevated serum PP levels found in many MEN I patients. Somatostatinomas, gastrinomas, vasoactive intestinal polypeptide tumors (VIPomas), and neurotensinomas were rare. Clinically overt hyperinsulinism, observed in two patients and associated with a large insulinoma, was cured by tumor resection. Eight of nine patients presented a Zollinger-Ellison's syndrome (ZES), but only in two patients were gastrin-producing tumors found. The source of gastrin in MEN I patients with a ZES, in whom no gastrinoma could be detected, remains unclear.

Insect optic lobe neurons identifiable with monoclonal antibodies to GABA.

Abstract: Five monoclonal antibodies aginst GABA were tested on glutaraldehyde fixed sections of optic lobes of three insect species, blowflies, houseflies and worker bees. The specificity of these antibodies was analyzed in several tests and compared with commercially available anti-GABA antiserum. A very large number of GABA-like immunoreactive neurons inncrvate all the neuropil regions of these optic lobes. Immunoreactive processes are found in different layers of the neuropils. The immunoreactive neurons are amacrines and columnar or noncolumnar neurons connecting the optic lobe neuropils. In addition some large immunoreactive neurons connect the optic lobes with centers of the brain. Some neuron types could be matched with neurons previously identified with other methods. The connections of a few of these neuron types are partly known from electron microscopy or electrophysiology and a possible role of GABA in certain neural circuits can be discussed.