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Biomedical subjects

A Hermann

Publications and source records attributed to A Hermann.

At least 73 records · Page 4Linked to original sources

Expression and cellular localization of kininogens in the human kidney.

Human high (H) and low (L) molecular weight kininogens are encoded by distinct mRNAs derived by alternative splicing from a single kininogen gene. Previous studies have demonstrated the presence of L-kininogen but not of H-kininogen in the distal nephron structures of the kidney. Using the highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) we have been able to demonstrate the expression of both H-kininogen mRNA and L-kininogen mRNA in kidney and liver. The presence of H- and L-kininogen antigen was shown immunohistochemically by applying specific antibodies that discriminate between the two types of kininogens. Immunoreactive kininogens were localized in the cortical and medullary collecting ducts. Our results indicate that both types of kinin-bearing kallikrein substrates are expressed in the human kidney where they might contribute to the suggested roles of the kallikrein-kinin system in the regulation of renal blood flow and electrolyte excretion.

Amino Acid Sequence↗

Modulation of ganglion cell activity in the pineal gland of the rainbow trout: effects of cholinergic, catecholaminergic, and GABAergic receptor agonists.

Second order neurons within intact isolated pineal glands of the rainbow trout were explored by extracellular recordings to investigate modulatory effects of putative intrapineal neurotransmitters. Acetylcholine, dopamine, and norepinephrine were found to increase ganglion cell activity in a majority of cells tested. The excitatory effects of acetylcholine, dopamine, and norepinephrine were mimicked by muscarinic, dopamine D2, and beta-adrenergic receptor agonists and significantly increased with the applied light intensity, resulting in an attenuation of the ganglion cell response to light. GABA decreased discharge activity in most cells tested. This effect, which could be mimicked with the GABAA receptor agonist piperidine, was independent from the adaptive status. Acetylcholine and GABA were still active if applied during synaptic blockade with low Ca++ high Mg(++)-perfusion medium, whereas dopamine and norepinephrine exhibited no effects if applied during synaptic blockade, suggesting a differential cellular distribution of neurotransmitter receptors in the trout pineal gland. These data demonstrate that ganglion cell activity in the trout pineal gland is under the influence of several neurotransmitters, including acetylcholine, dopamine, norepinephrine, and GABA, which is in contrast to the originally proposed simple bineuronal transduction pathway from photoreceptors onto ganglion cells. Since the above-mentioned neurotransmitters are believed to be released from pineal interneurons, we may conclude that ganglion cell activity in the teleost pineal gland is, similarly to the retina, the product of photoreceptor signals and a modulatory active interneuronal system.

Action Potentials↗

Role of calcium in photodynamically induced cell damage of human fibroblasts.

Photodynamically induced changes in the cytoplasmic free calcium concentration ([Ca2+]i) and its role in cell damage were investigated in human skin fibroblasts using confocal laser microscopy. Fluorescence and absorbance spectrophotometry measurements indicate that the photosensitizer aluminum phthalocyanine tetrasulfonate (AIPcS4) binds to the plasma membrane and only after irradiation is able to enter the cells, causing massive morphologic alterations. Upon irradiation of sensitizer-treated cells, the increase in [Ca2+]i is related to the amount of light and extracellular [Ca2+]e. The increase in [Ca2+]i was substantially reduced in the absence of [Ca2+]a. Cell damage or death after photodynamic treatment was prevented and shifted toward higher fluence by increasing [Ca2+]i at high [Ca2+]e and was greater at low [Ca2+]e. Application of Ca2+ channel blockers, such as Co2+, Cd2+ or verapamil, could not prevent the increase of [Ca2+]i. Our results indicate that activation of the photosensitizer, AIPcS4, causes an influx of Ca2+, which protects cells from, photodamage. At low [Ca2+]e and high fluence values, release of Ca2+ from internal stores probably as a protective measure occurs in order to increase the [Ca2+]i.

Calcium↗

Distribution and seasonal variation of vasoactive intestinal (VIP)-like peptides in the nervous system of Helix pomatia.

The distribution of neuropeptides immunologically related to vasoactive intestinal peptide (VIP) and its precursor peptide preproVIP(111-122), as well as to other peptides of the VIP-family, was studied in the central and peripheral nervous and sensory system of the snail, Helix pomatia, by use of immunocytochemical methods. VIP and preproVIP immunoreactivity was present in somata and nerve fibres of all central ganglia. Hibernating snails contained on average a total of 670 VIP- and 763 preproVIP-immunoreactive neurons. The number of immunoreactive cells was substantially reduced by more than 50% in active snails during summer with an average of 289 VIP- and 356 preproVIP-immunoreactive neurons. Antiserum against VIP labelled nerve fibres next to blood vessels and smooth muscle cells, whereas preproVIP-like material was localized in nerve fibres and endocrine-like cells among dorsal body cells and in the connective tissue along fiber tracts. VIP-immunoreactive material was also found in accessory ganglia of small and large tentacles, ganglia of the lips, the sensory epithelium of the tentacles, free nerve endings between skin epithelial cells, neuronal cells in the retina and in the sensory epithelium of statocysts. The cell-specific distribution and the seasonal variation of VIP- and preproVIP-like peptides suggest that they may act as transmitters or modulators in the nervous and sensory system and may be involved in the physiological adaptation of central neurons during long-term resting periods of snails.

Animals↗

Acetylcholine modulates ganglion cell activity in the trout pineal organ.

In the teleost pineal organ light activates functional photoreceptors, which transmit electrical activity to the brain via axons of intermediate ganglion cells. To investigate whether acetylcholine plays a role in the transduction of pineal photoreceptor signals, extracellular recordings were performed from ganglion cells of intact superfused pineal organs of the rainbow trout. Bath-applied acetylcholine increased the spike discharge rate of 96% of achromatic ganglion cells in a dose-dependent manner. The light response curve of ganglion cells, which was obtained by plotting spike rate vs light intensity, was significantly shifted by acetylcholine to higher frequencies. Acetylcholine was also active if applied during synaptic blockade with low Ca2+/high Mg(2+)-medium, demonstrating the presence of cholinergic receptors at the ganglion cell level. These data represent the first demonstration of acetylcholine constituting a postsynaptic modulation of photoreceptor signals in the trout pineal organ.

Acetylcholine↗

Acute action of ethanol on rat hippocampal CA1 neurons: effects on intracellular signaling.

Ethanol has a concentration dependent dual effect on electrical activity of rat CA1 hippocampal neurons. Low concentrations of ethanol (0.001%) enhance whereas high concentrations (0.5%) suppress synaptic transmission. Ethanol has no effect on cell input resistance and orthodromic or somatic threshold of action potentials. Cholera toxin, an activator of stimulatory guanine nucleotide binding regulatory protein (Gs), prevented the ethanol effects on field excitatory postsynaptic potentials (EPSPs). Staurosporine, an inhibitor of protein kinases, bisindolylmaleimide, an inhibitor of protein kinase C, and phorbol-12,13-dibutyrate (PDBu), an activator of protein kinase C, blocked the effect of ethanol on field EPSPs. Our results show that ethanol at extremely low concentrations is able to affect synaptic transmission and suggest that the molecular mechanism of ethanol action involves the activation of Gs protein and protein kinase C.

Animals↗

Identification of immunoreactive tissue kallikrein in human ductal breast carcinomas.

Various proteases have been shown to be present in malignant breast tissue. Although the question of the involvement of tissue kallikrein, a serine protease, in the pathophysiology of tumours has been raised, the presence of this enzyme in human breast carcinoma has so far not been examined. In the present study, both neoplastic and normal human breast are scanned by immunocytochemistry for the presence and cellular localization of tissue kallikrein. In the healthy breast, tissue kallikrein was observed as a deposit of immunoreactive material that localized in the apical portion of duct cells. In the malignant breast tumours surveyed, the enzyme was observed only in ductal carcinomas, whereas lobular carcinomas were devoid of immunostaining. In ductal carcinomas, the immunoreactivity for tissue kallikrein appeared to be associated with gradations of malignancy, being absent in dedifferentiated tumours. The presence of tissue kallikrein in malignant breast tumours poses the question of the role of this enzyme in malignant breast tissue. The enzyme may participate within the tissue either in proteolytic processes (it has been shown to activate procollagenase) or by enhancing vascularity or mitogenicity by the generation of kinins.

Breast Neoplasms↗

Parvalbumin-immunoreactive proteins in the nervous system of planarians.

1. Using immunological methods, we have identified parvalbumin-like material in the triclade flatworms, Polycelis nigra, Polycelis auriculata, Crenobia alpina, Dugesia tahitiensis, and Dugesia polychroa. 2. Western immunoblot analysis of these five species revealed heat stable parvalbumin-immunoreactive proteins between 32 kD and 44 kD. 3. Proteins at 19 and 32 kD revealed intense labeling with 45Ca2+. 4. Double immunodiffusion of planarian supernatants showed complete fusion of precipitates, indicating immunological relatedness of the parvalbumin-like material among the species investigated. 5. Immunocytochemical studies exhibit parvalbumin-immunoreactive material exclusively in neurons supporting the notion of an early evolutionary appearance of these proteins in the nervous system.

Animals↗

Sarcoplasmic calcium-binding protein.

Sarcoplasmic calcium-binding proteins (SCPs) are members of the EF-hand calcium-binding protein family which are characterized by the presence of helix-loop-helix motifs in their amino acid sequence. SCPs have an M(r) of approximately 20,000, a pI of approximately 5 and interact with two to three calcium ions (Ca2+) with a KD of 10(-7) to 10(-8) M. Mg2+ ions antagonize Ca2+ ion binding in a complex manner so that these proteins are exquisitely fine-tuned to interfere with the Ca2+ signal. SCPs apparently fulfil no specific activatory function. They exhibit strong polymorphism, show a marked homology to coelenterate photoproteins (aequorin, luciferin) and have been found only in invertebrates, predominantly in muscle and neurons. In mollusks, SCPs are distributed in a tissue-specific manner, with immunoreactivity to SCP I-like isoforms localized in electrically silent neurons colocalized with serotonin, and immunoreactivity to SCP II-like isoforms exclusively present in muscle.

Animals↗

Lymphoid tissue in the kidney of the musk shrew, Suncus murinus.

We describe a lymphoid tissue in the kidney of the musk shrew, Suncus murinus. An anatomically well organised lymphoid tissue, resembling the mucosa-associated lymphoid tissue, is associated with the epithelium of the renal pelvis and the ureter, respectively. Lymphoid tissue distributed along the arcuate artery and arcuate vein is not structurally organised in centre and periphery. This tissue type is most prominently developed between blood vessels. Immunocytochemistry revealed S-100-immunoreactive dendritic cells in both, structurally organised and structurally non-organised lymphoid tissues. The lymphoid tissue is innervated by neurofilament-immunoreactive nerve fibres. Some of these nerve fibres are associated with glial fibrillary acidic protein-immunoreactive structures, indicating that they are myelinated.

Animals↗

Visualization of tissue kallikrein in human breast carcinoma by two-dimensional western blotting and immunohistochemistry.

Tissue kallikrein is well known to liberate the vasoactive peptide kallidin from L-kininogen. Recently it was reported to activate matrix degrading metalloproteinases in vitro and to be present in gastric carcinoma cells. By immunohistochemistry we localized tissue kallikrein in the cytoplasm of ductal breast cancer cells. In addition, two-dimensional Western blotting was used to further characterize its biochemical properties. By this method immunoreactive tissue kallikrein was found to have a molecular mass of 25 kDa and an isoelectric point close to pH 6. Furthermore its presence in human milk could be demonstrated.

Blotting, Western↗

Epidemiology of osteoporosis. Implications for drug therapy.

Osteoporosis represents a major health problem. Fractures secondary to decreased bone mass and disrupted bone structure vastly increase morbidity in postmenopausal women, and morbidity as well as mortality in elderly people of either sex. Prophylaxis is possible, and indeed appears to be vital to ensure a high peak bone mass. Peak bone mass is reached during the second or third decade of life, i.e. 20 to 50 years before the appearance of osteoporotic fractures. Exercise and a sufficient calcium intake are possible measures in the early years. During menopause, estrogen replacement therapy will delay the accelerated bone loss and, most likely, also osteoporotic fractures. In established osteoporosis, a number of well documented therapies are now available. Depending on the age of the patient, bisphosphonates, calcitriol or other vitamin D preparations, calcium and calcitonin may be employed. This article reviews the epidemiology of osteoporotic fractures with special reference to the therapeutic implications.

Calcium, Dietary↗

[Postoperative infusion therapy: electrolyte solution in comparison with hypocaloric glucose and carbohydrate exchange-amino acid solutions].

OBJECTIVES: Comparison of early postoperative hypocaloric nutrition with glucose or xylitol/sorbitol- amino acid solutions versus saline alone. Influence on substrate, especially protein metabolism. DESIGN: Prospective randomized study. SETTING: Intensive care unit of an university hospital. PATIENTS: 44 patients in three groups after major surgery with necessity of intensive care. RESULTS: Hypocaloric infusions were well tolerated immediately after operation and positively influenced functional proteins and N-balance. During saline infusion protein parameters deteriorated significantly already after 24 to 36 hours. Glucose was not inferior to the xylitol/sorbitol solution and both resulted in a stable metabolic state during four days. CONCLUSIONS: After major trauma or surgery hypocaloric nutrition should be started within 24 hours and can be given already directly after the operation period without metabolic deterioration.

Abdomen↗

Signal transmission in the photosensitive pineal organ of the rainbow trout: modulation of ganglion cell activity by intrinsic dopamine.

The photosensitive pineal organ of the rainbow trout (Oncorhynchus mykiss) transduces photic information into nycthemeral neuronal signals. To investigate origin, cellular localization, and functional significance of pineal catecholamines, we performed HPLC-analysis of catecholamines and tyrosine hydroxylase (TH) activity, as well as immunocytochemical and electrophysiological studies. In biochemical and immunocytochemical investigations, pineal cells were found to contain endogenous TH. Using HPLC-analysis, the presence of a catecholamine precursor (L-dopa), catecholamines (dopamine, norepinephrine, epinephrine), and a metabolite (DOPAC) was demonstrated. The release of L-dopa, dopamine and DOPAC from isolated pineal organs was shown by superfusion experiments. Extracellular recordings were used to monitor the action of dopaminergic drugs on electrical activity of ganglion cells. Dopamine increased the discharge activity of action potentials, whereas dopamine receptor antagonists resulted in a reduction of ganglion cell activity. Our data provide evidence for establishing dopamine as an intrinsic neurotransmitter or neuromodulator in the photosensitive pineal organ of the rainbow trout.

Action Potentials↗

Lipoprotein(a), plasmin modulation, and atherogenesis.

Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein however the mechanisms by which Lp(a) promote the atherosclerotic process are not clear. The apolipoprotein(a) portion of Lp(a) shares partial homology with plasminogen, a finding that has stimulated numerous studies. Lp(a) binds to fibrin and the affinity between fibrin surfaces and Lp(a) appears to be related to the state of oxidation of the lipoprotein particle. Lp(a) also effects fibrin-dependent plasminogen activation. Recent findings suggest that dependent plasminogen activation. Recent findings suggest that depending upon the in vitro conditions, Lp(a) either promotes or inhibits plasmin formation. Lp(a) also inhibits cell-surface dependent plasmin generation that is associated with an inhibition of transforming growth factor-beta (TGF-beta) production in cell coculture systems. Lp(a) stimulates smooth muscle cell migration and proliferation as a secondary response to this decrease in TGF-beta concentration. Studies in transgenic mice containing the human apolipoprotein(a) gene, document that both plasmin and TGF-beta formation in the media of the aorta is markedly decreased in the presence of apo(a). Thus the atherogenicity of Lp(a) may be mediated, in part, through its modulation of plasmin and TGF-beta production in the blood vessel wall.

Adult↗

S-100-immunoreactive protein in Helix neurons.

S-100 proteins are a versatile group of calcium-binding proteins which exert intracellular as well as extracellular functions in a variety of cells. Our immunocytochemical studies, using the central nervous system of the terrestrial snail, Helix pomatia, showed that S-100-like material is present exclusively in a restricted number of neurons distributed in the cerebral ganglia, the left parietal ganglion, and the visceral ganglion. Electrophysiological investigations showed that immunostained neurons spontaneously discharge action potentials in a beating or bursting mode. Voltage clamp experiments further revealed a pronounced N-shaped current-voltage relationship of outward currents, indicating a prominent calcium-activated potassium current in these cells. Extracellular application of the disulfidic form of S-100(s-s) results in suppression of spontaneous discharge activity accompanied by an increase of membrane conductance. The total outward current as well as the inward rectifier current were increased. After removal of the calcium-dependent outward current component, S-100 effects were abolished indicating that S-100 acts on the calcium-activated current component. Our results suggest that S-100-like proteins modulate electrical activity of neurons in the central nervous system of Helix pomatia.

Action Potentials↗

Annexins in the gastropod nervous system.

We studied immunologically the distribution of the phospholipid- and Ca(2+)-binding proteins annexin I and annexin V in the nervous system of the molluscs, Aplysia californica and Helix pomatia. Within the Aplysia central nervous system we identified annexin I-immunoreactive neurons in the cerebral, buccal and abdominal ganglia. Annexin V-like material is restricted to neurons in the pedal ganglia. The Helix central nervous system contains annexin I-immunoreactive neurons in cerebral, buccal, visceral, left and right parietal, and pedal ganglia. Annexin V-immunoreactive material is present in neurons of the pleural, left and right parietal, and visceral ganglia.

Animals↗