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Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 127 records · Page 7Linked to original sources
PubMed1989

Identification of the collagen-producing cells in healing flexor tendons.

A monoclonal antibody to procollagen type I (anti-pC) which specifically stains cells synthesizing collagen was used to study the healing of chicken flexor tendons in vivo. Healing was assessed using routine hematoxylin and eosin histology and immunoperoxidase staining with anti-pC. Studies showed that epitenon cells proliferate 3 days after injury and are producing collagen by 7 days after injury. Tenocytes do not begin producing collagen until 14 to 21 days after injury. From 3 to 5 weeks, the entire substance of the tendon becomes filled with collagen-synthesizing cells. These cells may have originated from the tendon sheath, the epitenon, or the endotenon; however, the evidence presented in this study suggests that the epitenon is a major source of these cells.

Animals↗
PubMed1989

Cytokeratins and cytokeratin filaments in subpopulations of cultured human and rodent cells of nonepithelial origin: modes and patterns of formation.

Using immunofluorescence microscopy, we observed that in several established cell culture lines derived from different nonepithelial tissues and species, cells spontaneously emerge, usually at low frequencies, which contain cytoplasmic structures decorated by antibodies specific for cytokeratins 8 and 18. This phenomenon was further examined at both the protein (gel electrophoreses of cytoskeletal proteins, followed by immunoblotting) and the RNA (Northern blots, "nuclear run-on" analysis, in situ hybridization) level. Positive cell lines included simian virus (SV40)-transformed human fibroblasts (HF-SV80, WI-38 VA13), human astrocytic glioma cells (U333 CG/343MG), rat (RVF-SMC) and hamster (BHK-21/13) cells derived from vascular smooth muscle and murine sarcoma MS-180 cells. In two cell lines (HF-SV80 and BHK-21/13), the frequency of the cytokeratin-containing cells and of the cytokeratin fibril arrays per cell was drastically increased upon treatment with 5-azacytidine. The structural appearance of the cytokeratins was variable in the different cell lines but could also differ among cells of the same culture: While small granular or comma-shaped structures or bizarrely shaped filament arrays prevailed in WI-38, RVF and normally grown BHK-21 cells, most of the other lines revealed extended normal-looking, fibrillar arrays. In one line (MS-180), the appearance of cytokeratins was associated with a morphological change, as it was only found in a subpopulation of cells that had lost their typical elongated and spindle-shaped phenotype and assumed a rounded ("coccoid") shape. Our results show that the expression of the genes encoding cytokeratins 8 and 18 is not necessarily restricted to programs of epithelial differentiation and that factors stochastically effective appear in cultured cell lines that allow the synthesis of these cytoskeletal components. Mechanisms possibly involved in this spontaneous and selective advent of cytokeratins 8 and 18 and implications for tumor diagnosis are discussed.

Animals↗
PubMed1989

An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis.

Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing "cellular" fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.

Antibodies, Monoclonal↗
PubMed1988

Autonomous healing of chicken flexor tendons in vitro.

A monoclonal antibody to procollagen type I, which specifically stains cells actively secreting collagen, was used to study the healing of chicken flexor tendons in vitro. Healing was assessed with histology, immunohistologic staining, and autoradiography. Studies showed that epitenon cells proliferate 2 days after injury and are producing collagen 4 days after injury. Endotenocytes remain dormant during this time period. Tendons in vitro demonstrate active collagen synthesis and thus the capacity for autonomous repair.

Animals↗
PubMed1988

Infants of depressed mothers show "depressed" behavior even with nondepressed adults.

To determine whether the "depressed" behavior (e.g., less positive affect and lower activity level) of infants noted during interactions with their "depressed" mothers generalizes to their interactions with nondepressed adults, 74 3-6-month-old infants of "depressed" and nondepressed mothers were videotaped in face-to-face interactions with their mothers and with nondepressed female strangers. "Depressed" mothers and their infants received lower ratings on all behaviors than nondepressed mothers and infants. Although the infants of "depressed" versus nondepressed mothers also received lower ratings with the stranger adult, very few differences were noted between those infants' ratings when interacting with their mother versus the stranger, suggesting that their "depressed" style of interacting is not specific to their interactions with depressed mothers but generalizes to their interactions with nondepressed adults as early as 3 months of age.

Adolescent↗
PubMed1988

Biotin stores in rodent lungs: localization to Clara and type II alveolar cells.

Biotin is a cofactor for carboxylases used in fatty acid synthesis, gluconeogenesis, and energy production by the citric acid cycle. Although lung has low levels of this vitamin overall, high concentrations were demonstrated histochemically in Clara cells of mouse, rat, hamster, and guinea pig using avidin conjugated to peroxidase. Lesser concentrations were found in type II cells of mouse, rat, and hamster but not guinea pig. By electron microscopy, biotin stores in mouse Clara cells were localized to mitochondria, while those in type II cells were present in both mitochondria and the cytoplasmic matrix. Biotin stores in type II cells are probably used mainly in fatty acid synthesis but also in gluconeogenesis and energy production. The reason for particularly high concentrations in the mitochondria of Clara cells is unknown.

Animals↗
PubMed1988

Action of metal chelators on lipoxygenases, cyclooxygenase and on inflammation-induced vasodepression.

Metal complexing agents could exert antiinflammatory activity by inhibition of oxygen radical production, by inhibition of eicosanoid synthesis and by inhibition of metalloenzymes. We found a moderate antiedema activity of the iron (II)/iron (III)-chelator combination, o-phenanthroline/desferrioxamine, which could refer to an involvement of iron ions in the inflammatory reaction. The newly synthetized complexing agent ethylene-diimino-dibutyric acid caused weak antiedema and antivasodepressor effects which remain to be explained. Altogether, the in vivo effects of the metal chelators were rather weak. In vitro, only desferrioxamine produced a remarkable inhibition of two lipoxygenases.

Animals↗
PubMed1988

Action of cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors as well as of oxygen free radical scavengers (OFRS) in the inflammation-induced vasodepression.

Vasoprotective activity of COX inhibitors (diclofenac, piroxicam, indomethacin, aspirin) and of LOX inhibitors (nordihydroguaiaretic acid, propyl gallate, oxphaman) or of both (BW 755c) as well as of OFRS (mannitol, ethanol, thiourea, vitamin E) was investigated ex vivo in the isolated perfused hindlegs of the animals after in vivo u.v.-irradiation and antigen-provocation in mice and rats, respectively. The results show that vasodepression is mainly prevented by OFRS, antioxidants/LOX inhibitors and aspirin, but not by other COX inhibitors.

Animals↗
PubMed1987

Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting.

Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.

Endocrine System Diseases↗
PubMed1987

Biochemical and immunological characterization of the duck hepatitis B virus envelope proteins.

To examine the envelope proteins of duck hepatitis B virus (DHBV), which are encoded by the pre-S/S open reading frame of the viral genome, an antiserum was raised in rabbits against a fusion protein comprising most of the pre-S coding segment. By using this antiserum, viral particles could be precipitated from serum, and two pre-S proteins with molecular sizes of approximately 35 and 37 kilodaltons were detected in the sera and livers of DHBV-infected ducks after Western blotting and after biosynthetic labeling of a primary duck liver cell culture. In serum, the pre-S proteins were shown to exist predominantly in DHBV-DNA-free particles associated with a 17-kilodalton protein which, by N-terminal amino acid sequence analysis, was shown to represent the viral S protein which is encoded by the 3' proximal segment of the DHBV pre-S/S open reading frame. To compare the immunogenic potential of the S and pre-S proteins, serum particles and gel-purified S protein were used to immunize rabbits. In neither case was a significant immune response against the DHBV S protein observed. However, a good antibody titer against DHBV pre-S was obtained even after immunization with small amounts of the pre-S antigen.

Amino Acid Sequence↗
PubMed1987

Endocrine consequences of perinatal methadone exposure.

In summary, we have shown that marked acute responses as well as persistent changes in hypothalamopituitary responsivity to opiate challenge result from perinatal opioid addiction. We have also shown that different endocrine systems and opioid receptor subtypes develop at different rates, and that the responses of these systems depend upon the relative timing of the treatment regimen and the functional development of the particular opioid system involved. It should be emphasized that these studies have investigated only a single developmental window. The additional critical question of how opioid neuron function is affected by treatment during the period of active neuronal differentiation has not yet been answered. However, these studies do demonstrate the utility of this neuroendocrine model in assessing opioid function following chronic treatment regimens. By using neuroendocrine function as an end point, multiple systems can be studied simultaneously in the same animal. This has a particular advantage in studying the effects of chronic drug exposure on the developing nervous system, because hormone secretion is an easily quantifiable and early maturing functional index which can be used to identify vulnerable (and resistant) systems. Endogenous opioid systems appear to be particularly important in neuroendocrine regulation during the early phase of development, when other neural controls have not yet matured. Our preliminary results suggest that specific opioid systems that mature early may be especially important in the specific neuroendocrine effects of perinatal opiate addiction.

Aging↗
PubMed1986

Synaptophysin: a marker protein for neuroendocrine cells and neoplasms.

Synaptophysin is an integral membrane glycoprotein (Mr 38,000) that occurs in presynaptic vesicles of neurons and in similar vesicles of the adrenal medulla. By using a monoclonal antibody to this protein (SY38), we have found, by immunohistochemistry and immunoblotting, that an identical or similar protein is also expressed in neuroendocrine tumors of neural type, such as pheochromocytomas and paragangliomas. In addition, this protein occurs in certain neuroendocrine epithelial cells, such as pancreatic islet cells; in a variety of neuroendocrine epithelial tumors, including isletcell adenomas and carcinomas and several carcinoids and neuroendocrine carcinomas of the gastrointestinal and the bronchial tracts; and in medullary carcinomas of the thyroid. Our results show that synaptophysin, and the vesicles that contain it, can occur in normal and neoplastic neuroendocrine cells of neural type, as demonstrated by colocalization with neurofilaments, as well as in those of epithelial type, as shown by colocalization with cytokeratin filaments and desmoplakins. We conclude that synaptophysin is expressed independently of other neuronal differentiation markers and propose that it be used as a differentiation marker in tumor diagnosis.

Adrenal Medulla↗
PubMed1986

Pharmacologic evaluation of dopaminergic receptor blockade by metoclopramide.

The occurrence of adverse extrapyramidal effects following metoclopramide (MCP) therapy has been well documented in humans. In rats, MCP produced catalepsy and inhibited apomorphine-induced stereotypy, locomotor activity, and rotational behavior. MCP also accelerated dopamine turnover, potently stimulated prolactin release, and, at high concentrations, inhibited [3H]spiperone binding to striatal membranes. These behavioral and biochemical effects induced by MCP were similar to those observed with haloperidol. We conclude that MCP possesses most of the pharmacological properties of neuroleptic agents.

Animals↗
PubMed1986

The biochemical pathogenesis of chronic obstructive pulmonary diseases: protease-antiprotease imbalance in emphysema and diseases of the airways.

Emphysema is believed to result from destruction of elastic fibers due to an imbalance between proteases and their inhibitors in the lung. The imbalance can arise from a primary failure of secretion of the inhibitors, as occurs in hereditary alpha-1-protease inhibitor deficiency, or as the result of complex interactions of environmental agents with the lung. Environmental agents may produce their effects by stimulating degradation of elastic fibers by neutrophils and macrophages, damaging protease inhibitors by oxidative or proteolytic mechanisms or by impairing the biosynthetic repair of damage to the connective tissue. Protease excess has also been consistently observed in purulent sputum. Since experimentally administered proteases stimulate secretion of mucus and damage mucociliary clearance, protease-antiprotease imbalance might be involved in the pathogenesis of bronchitis and bronchiectasis as well as emphysema. Because the protease inhibitors of bronchial mucus are distinct from those of the acinar units, and no hereditary deficiencies are known, there is no direct proof of this hypothesis in man.

Animals↗