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Biomedical subjects

H Zimmermann

Publications and source records attributed to H Zimmermann.

At least 235 records · Page 13Linked to original sources

The electromotor system of the electric catfish (Malapterurus electricus): a fine-structural analysis.

The electromotor system of the electric catfish (Malapterurus electricus) consists of two large ganglion cells situated in the spinal cord, two single axons containing electric nerves and two large electric organs with several million electroplaque cells. The small, irregularly stacked electroplaque cells possess at their center a crater-like indentation from which a stalk like protrusion arises. Many synaptic contacts derived from a single axon collateral are carried on lobe-like protrusions at the terminal knob of this stalk. The electric nerve consists of a large myelinated axon (diameter: 25 micron) surrounded by many layers of connective tissue cells. The two ganglion cells (200 micron in diameter) are rich in elements of the rough endoplasmic reticulum, Golgi apparatus and lysosomal structures. The cytoplasm of the soma changes its appearance towards the voluminous axon hillock (50 micron in diameter) which these organelles do not enter. The cell soma is perforated in a tunnel-like manner by blood capillaries, axons and processes of glial cells. The cell soma and dendrites are covered with two types of synapse. One type forms mixed chemical and electrical (gap junctions) contacts with intermediate attachment plaques. The other type is only chemical in nature. This system may be useful in the study of an identified vertebrate giant neuron.

Animals↗

[Cholinergic nerve endings: cellular function and molecular structure].

Progress made in the study of the cellular and molecular function of cholinergic nerve terminals suggests that the textbook schemes need to be extended. Vesicles contained in cholinergic nerve terminals not only store acetylcholine but also ATP and Ca2+ as well as peptides. These substances when co-released by exocytosis may modulate transmission both pre- and postsynaptically.

Acetylcholine↗

Synapsin I is associated with cholinergic nerve terminals in the electric organs of Torpedo, Electrophorus, and Malapterurus and copurifies with Torpedo synaptic vesicles.

Using an affinity-purified monospecific polyclonal antibody against bovine brain synapsin I, the distribution of antigenically related proteins was investigated in the electric organs of the three strongly electric fish Torpedo marmorata, Electrophorus electricus, Malapterurus electricus and in the rat diaphragm. On application of indirect fluorescein isothiocyanate-immunofluorescence and using alpha-bungarotoxin for identification of synaptic sites, intense and very selective staining of nerve terminals was found in all of these tissues. Immunotransfer blots of tissue homogenates revealed specific bands whose molecular weights are similar to those of synapsin Ia and synapsin Ib. Moreover, synapsin I-like proteins are still attached to the synaptic vesicles that were isolated in isotonic glycine solution from Torpedo electric organ by density gradient centrifugation and chromatography on Sephacryl-1000. Our results suggest that synapsin I-like proteins are also associated with cholinergic synaptic vesicles of electric organs and that the electric organ may be an ideal source for studying further the functional and molecular properties of synapsin.

Animals↗

Ectonucleotidase activities associated with cholinergic synaptosomes isolated from Torpedo electric organ.

Intact synaptosomes isolated from the electric organ of the electric ray Torpedo marmorata contain, at their surface, enzyme activities for the hydrolysis of externally applied nucleoside phosphates. The diazonium salt of sulfanilic acid, as a low-molecular-weight, slowly permeating, covalent inhibitory agent, selectively blocks these enzyme activities and leaves intracellular lactate dehydrogenase intact. The ectoenzymes comprise both a nucleoside triphosphate and diphosphate phosphohydrolase, as well as a 5'-nucleotidase. Activity of nonspecific ectophosphatases is absent. The nucleoside triphosphatase hydrolyzes almost equally well ATP, GTP, CTP, UTP, and ITP and is activated to a similar degree by Mg2+ or Ca2+. It has a high affinity for ATP (Km for ATP in the presence of Mg2+, 75 microM; in the presence of Ca2+, 66 microM). Maximal rates in the presence of Mg2+ and Ca2+ were very similar (34.8 and 32.5 nmol of Pi/min/mg of synaptosomal protein, respectively). Either Mg-ATP or Ca-ATP can act as a true substrate. ADP inhibits hydrolysis of ATP, but AMP is without effect. The nucleoside triphosphatase is not inhibited significantly by a number of inhibitors of mitochondrial Mg2+-ATPase or of Ca2+ + Mg2+-ATPases. It is, however, considerably inhibited by filipin and quercitin. The capacity of intact synaptosomes to hydrolyze also extracellular ADP, GDP, AMP, GMP, and IMP suggests that the nucleoside triphosphatase is part of an enzyme chain that causes complete hydrolysis of the respective nucleoside triphosphate to the nucleoside. We conclude that the cholinergic nerve terminals of the Torpedo electric organ can hydrolyze ATP released on coexocytosis with acetylcholine via an ectonucleoside triphosphatase activity that is different from known endogenous nerve terminal ATPases. The final product of the hydrolysis, adenosine, can then be salvaged by the nerve terminal for resynthesis of ATP. Other possible physiological functions of the ectonucleotidases are discussed.

5'-Nucleotidase↗

Acetylcholine, ATP, and proteoglycan are common to synaptic vesicles isolated from the electric organs of electric eel and electric catfish as well as from rat diaphragm.

Cholinergic synaptic vesicles were isolated from the electric organs of the electric eel (Electrophorus electricus) and the electric catfish (Malapterurus electricus) as well as from the diaphragm of the rat by density gradient centrifugation followed by column chromatography on Sephacryl-1000. This was verified by both biochemical and electron microscopic criteria. Differences in size between synaptic vesicles from the various tissue sources were reflected by their elution pattern from the Sephacryl column. Specific activities of acetylcholine (ACh; in nmol/mg of protein) of chromatography-purified vesicle fractions were 36 (electric eel), 2 (electric catfish), and 1 (rat diaphragm). Synaptic vesicles from all three sources contained ATP in addition to ACh (molar ratios of ACh/ATP, 9-12) as well as binding activity for an antibody raised against Torpedo cholinergic synaptic vesicle proteoglycan. Synaptic vesicles from rat diaphragm contained binding activity for the monoclonal antibody asv 48 raised against a rat brain 65-kilodalton synaptic vesicle protein. Antibody asv 48 binding was absent from electric eel and electric catfish synaptic vesicles. These antibody binding results, which were obtained by a dot blot assay on isolated vesicles, directly correspond to the immunocytochemical results demonstrating fluorescein isothiocyanate staining in the respective nerve terminals. Our results imply that ACh, ATP, and proteoglycan are common molecular constituents of motor nerve terminal-derived synaptic vesicles from Torpedo to rat. In addition to ACh, both ATP and proteoglycan may play a specific role in the process of cholinergic signal transmission.

Acetylcholine↗

[Auxiliary liver transplantation in an animal experiment--a novel surgical model].

At the problem of the auxiliary liver transplantation has been worked for about 30 years. Extensive series of tests with animals with a novel transplantation model justify these promises well of a successful clinical use. Laboratory chemical, histologic, angiographic and nuclearmedical examinations prove the fitness of this method. Basic supposition for a success is the preservation of physiological conditions at the donor liver with sufficient perfusion of the recipient liver.

Abdomen↗

Elevated pancreatic glucagon in obesity.

Because of conflicting reports on plasma levels of total immunoreactive glucagon (IRG) in obesity, we investigated, by gel filtration, the individual IRG fractions in grossly obese patients (N = 16; BMI 40 +/- 2) as compared with normal weight subjects (N = 18). Mean total IRG was 142 +/- 12 pg/ml in normal subjects and 190 +/- 15 pg/ml (P less than 0.02) in obese subjects. IRG3500 was 16 +/- 2 pg/ml in normal subjects and 34 +/- 5 pg/ml (P less than 0.005) in the obese subjects. Obese patients with normal glucose tolerance demonstrated 30 +/- 5 pg/ml IRG3500 (N = 11; P less than 0.01) as compared with those who were obese with impaired glucose tolerance (42 +/- 12 pg/ml, N = 5; P less than 0.0025), although the total IRG of the latter group (173 +/- 31 pg/ml) was not different from that of normal subjects. IRG90000 was of comparable magnitude in the entire groups of obese and normal subjects. A wide variability of big plasma glucagon levels was found in all three groups, mean levels not being significantly different. These data suggest that plasma IRG3500 levels are elevated in grossly obese patients, particularly in those patients with impaired glucose tolerance, a finding that may be masked by mere measurements of total plasma IRG.

Adult↗

Ecto-adenosine triphosphatase activity at the cholinergic nerve endings of the Torpedo electric organ.

Synaptosomes isolated from the electric organ of Torpedo marmorata contain activity of an ATPase which is located at the extracellular face of the plasma membrane. Ecto-ATPase activity can be stimulated independently and to a similar extent by either Ca-2+ or Mg-2+. Apparent Km-values for ATP are 79 microM and 53 microM for Ca-2+ and Mg-2+ respectively. Apparent Km-values for Ca-2+ and Mg-2+ at 1 mM ATP are 0.71 mM and 0.61 mM respectively. The enzyme is also activated by Mn-2+ and GTP can replace ATP as a substrate. Presence of 5'- nucleotidase activity suggests that adenosine is the final hydrolysis product. Thus hydrolysis of nucleotides released during exocytosis of synaptic vesicle contents and purine salvage must be a major role of this ecto-enzyme. We furthermore suggest that the ecto-ATPase may provide the key to understanding the storage of the high energy compound ATP in cholinergic synaptic vesicles. On depolarization of the nerve terminal and exocytosis, ATP represents the signal for activating the ATPase whereby concentrations of Ca-2+ and Mg-2+ are already saturating. Following depolarization induced Ca-2+ influx, a possible function of the ATPase may be the outward transport of Ca-2+ from the nerve terminal.

Adenosine Monophosphate↗

Enrichment of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate in cholinergic axon terminals of the Torpedo electric organ.

On fractionation of intact electric organ, cAMP and cGMP are enriched in the synaptosome fraction by factors of 14 and 6 respectively. For all regions of the electromotor neuron the absolute contents of nucleotides are in the order ATP greater than cAMP greater than cGMP. However, the molar ratios of cAMP/cGMP vary between tissues. Specific contents of both cyclic nucleotides are lowest in the nerve. For cAMP, specific contents in the axon terminal and in the perikaryal region are similar. As compared to this, cGMP is considerably enriched in the presynaptic nerve ending. This points to a physiological role of cGMP in presynaptic function.

Adenosine Triphosphate↗

Binding of cationized and native ferritin to cellular structures of the electric organ of Torpedo marmorata.

The distribution of polycationic and polyanionic binding sites in the electric organ of Torpedo marmorata was investigated by incubation of tissue with native (NF) ferritin. 1) Collagen fibrils from the electric organ carry rosettes of polyanionic sites on their surface with a periodicity of 60 nm, corresponding to the pattern of crossbanding in collagen fibrils. The CF-binding sites are abut 30 nm in size and project 20 nm beyond the surface of the fibril. 2) As revealed by incubation of tissue homogenates, CF heavily stains the intraperiod line of the axonal myelin and also tubular structures in the axonal cytoplasm. 3) Neither the extracellular aspects of the pre- nor the postsynaptic membrane became labeled with either NF or CF. After incubation of tissue homogenates. labeling of the electron-dense material of the cytoplasmic aspect of the postsynaptic membrane was observed with NF and, in particular, with CF. The ventral basal lamina of the electroplaque cell revealed uniform labeling with NF. In contrast, CF-binding sites were distributed in the lamina densa of the basal lamina as a lattice of discrete binding sites, approximately 45 nm in diameter. The presence of polyanionic sites in the basal lamina, which also proceeds through the synaptic cleft, suggests the existence of a diffusion barrier for the released neurotransmitter acetylcholine. It is proposed that this facilitates hydrolysis of acetylcholine in the synaptic cleft and recirculation of the products of hydrolysis to the axon terminal.

Animals↗

Glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report.

The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. Plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.

Adrenal Insufficiency↗

[Therapy of progressive interstitial lobar emphysema].

Progressive pulmonary interstitial lobar emphysema is a complication of artificial ventilation in infants with RDS. Several types of conservative approaches are suggested. In 3 of our cases the rapid progression of emphysema makes lobectomy necessary.

Female↗