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Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 73 records · Page 4Linked to original sources
PubMed1997

[The heart in infection and MODS (multiple organ dysfunction syndrome)].

Dysfunctioning of the heart forms part of the multiple organ dysfunction syndrome (MODS) in sepsis and SIRS. This acute septic cardiomyopathy is often underestimated in degree and relevance, although yet in fact 10% of all sepsis fatalities are due to intractable heart failure. This potentially reversible cardiomyopathy is characterized by a considerable pump failure, is not primarily ischemic, coronary blood flow being normal or even enhanced; left and right ventricle are enlarged as a consequence of an increased ventricular compliance. Damage of the heart can further be aggravated in case of an additional right ventricular impairment due to pulmonary hypertension in ARDS. SIRS-cardiomyopathy in non-infectious MODS has common traits with acute septic cardiomyopathy. The pathogenesis of heart disease in sepsis and SIRS is multifactorial, the endotoxin/TNF-alpha/NO/cGMP-cascade representing a main negative inotropic axis. Therapy of acute septic cardiomyopathy and SIRS-cardiomyopathy at present still is mainly symptomatic (volume substitution, inotropic/vasoactive agents), causal therapeutic principles are, however, put to test in the context of a comprehensive concept of causal sepsis treatment.

Cardiomyopathies↗
PubMed1996

Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.

Airway Obstruction↗
PubMed1996

Specific immunohistochemical detection of cardiac/fetal alpha-actin in human cardiomyocytes and regenerating skeletal muscle cells.

We describe three murine monoclonal antibodies (mAbs) raised against a synthetic decapeptide representing the aminoterminal sequence of the cardiac/ fetal isoform of sarcomeric alpha-actin. When used for immunoblotting or histological immunolocalization, these mAbs distinguish cardiac/fetal alpha-actin from skeletal muscle alpha-actin, and also from all other actin isoforms. We show, by immunofluorescence and immunoperoxidase microscopy of tissue sections, that cardiac/fetal alpha-actin can be localized not only in cardiomyocytes but also in skeletal muscles and their satellite cells during regeneration. These mAbs are potentially valuable in developmental biology, for the characterization of tissue and cultured myogenic cells, in pathology, and for serodiagnosis.

Actins↗
PubMed1996

Symplekin, a novel type of tight junction plaque protein.

Using a monoclonal antibody we have identified and cDNA-cloned a novel type of protein localized, by light and electron microscopy, to the plaque associated with the cytoplasmic face of the tight junction-containing zone (zonula occludens) of polar epithelial cells and of Sertoli cells of testis, but absent from the junctions of vascular endothelia. The approximately 3.7-kb mRNA encodes a polypeptide of 1142 amino acids (calculated molecular weight 126.5 kD, pI 6.25), for which the name "symplekin" (from Greek sigma upsilon mu pi lambda epsilon kappa epsilon iota, nu, to tie together, to weave, to be intertwined) is proposed. However, both the mRNA and the protein can also be detected in a wide range of cell types that do not form tight junctions or are even completely devoid of any stable cell contacts. Careful analyses have revealed that the protein occurs in all these diverse cells in the nucleoplasm, and only in those cells forming tight junctions is it recruited, partly but specifically, to the plaque structure of the zonula occludens. We discuss symplekin as a representative of a group of dual residence proteins which occur and probably function in the nucleus as well as in the plaques exclusive for either tight junctions, adherens junctions, or desmosomes.

Amino Acid Sequence↗
PubMed1996

Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque.

Using antibodies and recombinant DNA techniques, we have identified plakophilin 2, a novel desmosomal plaque protein of M(r) 100,000 (estimated from SDS-PAGE), which is a member of the arm-repeat family of proteins and can occur in two splice forms (2a and 2b) because of the insertion of a 44 amino acid (aa)-encoding exon. In its aa sequence (837 and 881 aa, calculated pIs: 9.33 and 9.38, mol wts 92,750 and 97,410 kD), it is conspicuously related to the 80-kD plakophilin 1, with which it shares a central region of 9 repeats of the arm-motif, preceeded by a long head region and followed by a very short (11 aa) carboxy-terminal sequence. Plakophilin 2 and its mRNA have been detected in a wide range of tissues and cell types, including cells devoid of desmosomes. By light and electron microscopical immunolocalization, plakophilin 2 has been localized to plaques of desmosomes of one-layered ("simple") and complex epithelia, carcinomas, diverse epithelium-derived cell culture lines, as well as cardiac tissue and the dendritic reticulum cells of lymphatic germinal centers, i.e., desmosomes in which plakophilin 1 is not detected. However, plakophilin 2 has also been localized in the desmosomes of certain but not all stratified epithelia where it coexists with plakophilin 1. Remarkably, plakophilin 2 is also enriched in the karyoplasm of a wide range of cell types, including many that lack desmosomes and in which, therefore, the nuclear state is the only locally enriched form of plakophilin 2 present. We conclude that plakophilins 2a and 2b are basic nuclear proteins that in certain cell types additionally assemble with other proteins to form the desmosomal plaque and serve general nuclear functions as well as a function specific to many but not all desmosomes.

Alternative Splicing↗
PubMed1996

Massage therapy reduces anxiety and enhances EEG pattern of alertness and math computations.

Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in the massage chair for 15 minutes, two times per week for five weeks. On the first and last days of the study they were monitored for EEG, before, during and after the sessions. In addition, before and after the sessions they performed math computations, they completed POMS Depression and State Anxiety Scales and they provided a saliva sample for cortisol. At the beginning of the sessions they completed Life Events, Job Stress and Chronic POMS Depression Scales. Group by repeated measures and post hoc analyses revealed the following: 1) frontal delta power increased for both groups, suggesting relaxation; 2) the massage group showed decreased frontal alpha and beta power (suggesting enhanced alertness); while the control group showed increased alpha and beta power; 3) the massage group showed increased speed and accuracy on math computations while the control group did not change; 4) anxiety levels were lower following the massage but not the control sessions, although mood state was less depressed following both the massage and control sessions; 5) salivary cortisol levels were lower following the massage but not the control sessions but only on the first day; and 6) at the end of the 5 week period depression scores were lower for both groups but job stress score were lower only for the massage group.

Adult↗
PubMed1996

Cocaine-exposed preterm neonates show behavioral and hormonal differences.

OBJECTIVE: Prematurity has been associated with prenatal cocaine exposure, but most studies on the behavioral effects of prenatal cocaine exposure have been restricted to full-term infant samples. The current study focused on behavioral and hormonal responses in preterm cocaine-exposed infants compared with a cohort of non-cocaine-exposed infants of similar gestational age. METHODOLOGY: A comparison between 30 cocaine-exposed and 30 non-cocaine-exposed preterm neonates suggested that the cocaine-exposed neonates were born to mothers who had higher parity and more obstetric complications. In addition, mothers of cocaine-exposed preterm neonates visited, touched, held, and fed their infants less frequently than mothers of nonexposed infants. RESULTS: The cocaine-exposed infants had smaller head circumferences at birth, spent more time in the neonatal intensive care unit, and had a greater incidence of periventricular-intraventricular hemorrhages. They also had inferior Brazelton cluster scores, including lower state regulation and range-of-state scores, and greater depression. During sleep-wake behavior observations, they showed difficulty maintaining alert states and self-regulating their behavior, and they spent more time in indeterminate sleep and had decreased periods of quiet sleep and increased levels of agitated behavior, including tremulousness, mouthing, multiple limb movements, and clenched fists. Finally, higher urinary norepinephrine, dopamine, and cortisol levels and lower plasma insulin levels were noted in the cocaine-exposed preterm neonates. CONCLUSIONS: These findings highlight the need for follow-up assessments and early intervention.

Case-Control Studies↗
PubMed1995

Dichloromethane as an inhibitor of cytochrome c oxidase in different tissues of rats.

Based on the metabolism of dichloromethane (DCM) to carbon monoxide (CO), a process mediated by cytochrome P-4502E1 (CYP2E1), cytochrome c oxidase activity was determined in different tissues of rats after DCM exposure. It is likely that binding of CO to cytochrome c oxidase is significant at low carboxyhemoglobin levels, because intracellular effects of CO depend on CO partial pressures in the tissues. Two methods of exposure were used: (1) administration of DCM, 3.1, 6.2, and 12.4 mmol/kg p.o. in Oleum pedum tauri, 10% (v/v), producing a maximum of 10% COHb 6 h after gavage, and (2) accidental scenario, i.e. rats were exposed nose-only to DCM, 250,000 ppm for 20 s, producing 3-4% COHb after 2 h. Cytochrome c oxidase activity was reduced 6 h after the high oral DCM dose in brain, lung, and skeletal muscle by 28-42% and 20 min after inhalative uptake of DCM in the brain, liver, kidney, and skeletal muscle by 42-51%. COHb formation due to DCM, 6.2 mmol/kg p.o., was completely prevented after treatment of rats with the mechanism-based inhibitor of CYP2E1, diethyl-dithiocarbamate (DDTC), using an oral dose of 32 mumol/kg. The decrease in cytochrome c oxidase activity after exposure to DCM was not evident in rats treated with this dose of DDTC. Therefore, it seems that the effect of DCM is produced by the DCM metabolite CO.

Administration, Inhalation↗
PubMed1995

Maintenance of cell-type-specific cytoskeletal character in epithelial cells out of epithelial context: cytokeratins and other cytoskeletal proteins in the rests of Malassez of the periodontal ligament.

We have determined the patterns of synthesis of cytokeratins and other epithelial marker proteins in the "rests of Malassez" of the periodontium of rabbits and humans, by immunofluorescence microscopy of cryosections prepared from fixed and decalcified rabbit teeth with attached ligament or from manually isolated human periodontal ligaments. Proteins of the major cell structures characterizing epithelial differentiation are present in Malassez cells: a complex set of cytokeratins as well as desmosomal, hemidesmosomal and basal lamina proteins. In addition, we have shown these cytoskeletal and extracellular matrix structures by electron microscopy. The cytokeratin complement of Malassez cells was found to be highly complex, as 8 of the total of 20 known epithelial cytokeratins were detected (nos. 5, 7, 8, 14, 15, 17, 18, 19). This pattern, together with the presence of the desmosomal cadherins Dsg2 and Dsc2 and the cytoplasmic desmosome plaque-associated protein plakophilin 1, indicates that the cells of the rests of Malassez are derived from the basal cell layer of a stratified squamous epithelium rather than from simple epithelial or neuroendocrine epithelial cells. Our observations show that Malassez cells retain the major characteristics of epithelial cells throughout their differentiation from the root sheath epithelium into the rests of Malassez, even though the surface location and the polar tissue architecture that typify epithelial are lost during this process. From this study we further conclude that the specific cytoskeletal complement of the Malassez cells represents an intrinsic gene expression program that neither depends on nor causes the formation of a stratified epithelium. We also compare the specific cytoskeletal features of Malassez cells with those of other persisting epithelial residues and discuss the potential value of these findings in relation to the histogenesis and diagnostic classification of dental and periodontal cysts and tumors.

Adolescent↗
PubMed1995

Cytokeratin 20 is a general marker of cutaneous Merkel cells while certain neuronal proteins are absent.

Merkel cells are difficult to identify in tissue sections. Previous studies have used cytokeratins (CK) 8, 18, and 19 as histologic markers of Merkel cells. However, these CKs are also expressed in some outer root sheath keratinocytes and some early fetal epidermal cells and thus are not truly specific of Merkel cells in general. Using selective antibodies against a newly described CK, number 20--originally found in intestinal epithelium and Merkel cell carcinomas--in comparison to a key protein of neuroendocrine cells, chromogranin A, we established CK 20 as a specific Merkel cell marker in skin of humans, pigs, and mice. CK 20 seems to be an even more general and sensitive Merkel cell marker as compared to CgA. In double-labeling experiments with stratified-squamous epithelial CK (numbers 5 and 13-17) and simple epithelial CK (numbers 8, 18, and 20) antibodies evaluated by confocal laser scanning microscopy, no cell expressing CKs of both types (i.e., no cell of so-called "transitional" character between Merkel cells and keratinocytes) was identified in human skin. In addition, various neuronal markers present in Merkel cell carcinomas including neurofilaments, peripherin, nerve growth factor receptor, and neuronal cell adhesion molecule appear to be absent in normal Merkel cells. Thus, Merkel cells exhibit a distinct and unique marker profile, with CK 20 being of particularly high value in various species.

Adult↗
PubMed1995

Peripherally inserted central catheters in children.

PURPOSE: To assess the feasibility and complications of peripherally inserted central catheters (PICCs) in pediatric patients. MATERIALS AND METHODS: The authors attempted to place PICCs in 122 patients aged 9 days to 19 years (mean, 6.82 years; median, 5 years). Catheters were placed to allow prolonged administration of antibiotics or chemotherapeutic agents (n = 50), provide total parenteral nutrition (n = 41), and establish prolonged intravenous access for blood draws and fluid administration (n = 31). Silicone catheters measuring 3, 4, and 5 F were inserted in either basilic or cephalic veins and positioned at the junction of the superior vena cava and right atrium under fluoroscopic guidance. Patients were monitored for complications until devices were removed. RESULTS: Fluoroscopically guided PICC placement was successful in 137 of 148 attempts. Postinsertion complications included mechanical defects of the catheter, PICC-related infection, occlusion of the PICC, and venous stasis. Complications occurred at a rate comparable to those seen with blind insertion. CONCLUSION: Fluoroscopically guided PICC placement is feasible and safe in pediatric patients.

Adolescent↗
PubMed1995

Immunolocalization of SPARC, tenascin, and thrombospondin in pulmonary fibrosis.

Several biochemically unrelated multifunctional extracellular proteins, SPARC, thrombospondin 1, and tenascin-C (TN), have been grouped as antiadhesive glycoproteins because they inhibit the spreading of cells on extracellular matrix in vitro. Migration of fibroblasts and epithelial cells into the air spaces to organize inflammatory exudate is a feature common to several fibrosing lung diseases. We hypothesized that migration would be facilitated by loosening the adhesive interactions between cells and the pericellular matrix components of the alveolar wall and that one or more of the anti-adhesive glycoproteins could be involved. Immunohistochemistry was used to localize SPARC, TN, and thrombospondin 1 in biopsies of organizing pneumonia, idiopathic pulmonary fibrosis (nine cases of usual interstitial pneumonia, one of desquamative interstitial pneumonia), and control lungs. Each antigen had a distinctive distribution. Only TN was expressed in control lungs, where it strongly stained the basement membrane of large bronchi and weakly stained alveolar entrance rings and small veins. In organizing pneumonia, TN was heavily stained through the entire extracellular matrix of the Masson bodies. In idiopathic pulmonary fibrosis, TN was abundant in the fibroblast foci of active fibrosis but was also present in the basement membrane regions beneath the metaplastic epithelium lining honeycomb cysts. TN was abundant in the interstitium in desquamative interstitial pneumonia. SPARC was observed only intracellularly where it occurred in the fibroblasts of Masson bodies of organizing pneumonia and the fibroblast foci of usual interstitial pneumonia. In desquamative interstitial pneumonia, expression of SPARC was minimal, in rare interstitial fibroblasts. Thrombospondin 1 was found consistently in organizing pneumonia but only infrequently in idiopathic pulmonary fibrosis. In both, it was localized in the extracellular matrix immediately beneath reparative epithelium. These results are consistent with a role for SPARC in fibroblast migration. TN may function in both fibroblast migration and the adhesion of metaplastic bronchial-type epithelium. However, these proteins also have other activities that may be important in pulmonary fibrosis. The localization of thrombospondin 1 suggests that it may be synthesized by regenerating epithelium where it may aid in the adhesion or migration of the epithelial cells.

Antibodies, Monoclonal↗
PubMed1995

Cocaine sensitization in periadolescent and adult rats.

Periadolescent rats have been reported to be affected differentially by catecholaminergic agents when compared with younger or adult animals. The present study evaluated the behavioral responsivity of periadolescent (34- to 39-day-old) and adult (60- to 70-day-old) Sprague-Dawley rats of both sexes to i.p. cocaine (Coc) administration (0, 10 or 20 mg/kg, once daily for 4 days). All animals received injections of both saline and Coc every day paired with a different context, with one-half of the animals receiving the drug in the home cage (Coc-Home) and the other half in the testing chamber (Coc-Test). Forty-eight hours after the last drug injection, all animals were challenged with 10 mg/kg i.p. of Coc, and their behavior in the test chamber was scored. As expected, acute Coc induced a prominent increase in a number of behaviors, and this response profile was less marked in periadolescent relative to adult animals. In contrast, Coc-Test animals of both ages showed a clear behavioral sensitization relative to the chronic saline group. No evidence of carry-over effects was found in Coc-Home animals. Females were in general more sensitive than males to acute Coc effects. The development of behavioral sensitization to Coc was a function of age-specific alterations in sensitivity to psychostimulants. Periadolescent rats of both sexes showed sensitization to the locomotor activating effects (matrix crossings) of Coc, whereas a consistent sensitization profile for both stereotyped head scanning and focused sniffing activities were found in adults but not in periadolescents. Chronic Coc reduced body weight and food consumption, particularly in adult males, whereas it did not affect periadolescent patterns. No evidence of sensitization to Coc was found in the hormonal parameters considered.

Adrenocorticotropic Hormone↗