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Biomedical subjects

M Kirsch

Publications and source records attributed to M Kirsch.

At least 127 records · Page 7Linked to original sources

Early salt stress effects on the differential expression of vacuolar H(+)-ATPase genes in roots and leaves of Mesembryanthemum crystallinum.

In Mesembryanthemum crystallinum, the salt stress-induced metabolic switch from C3 photosynthesis to Crassulacean acid metabolism is accompanied by major changes in gene expression. However, early effects of salt exposure (i.e. prior to Crassulacean acid metabolism induction) on genes coding for vacuolar transport functions have not yet been studied. Therefore, the expression of vacuolar H(+)-ATPase genes was analyzed in different organs of 4-week-old plants stressed with 400 mM NaCl for 3, 8, or 24 h. Partial cDNAs for the subunits A, B, and c were cloned and used as homologous probes for northern blot analysis. In control plants, the mRNA levels for the different subunits showed organ-specific differences. In fully expanded leaves, subunit c mRNA was very low but increased transiently during the light period. Plant organs also differed in their salt-stress response. In roots and young leaves, mRNA levels for all three subunits increased about 2-fold compared to control plants, whereas in fully expanded leaves only subunit c mRNA responded to salt. The results indicate that the expression of vacuolar H(+)-ATPase genes does not always involve a fixed stoichiometry of mRNAs for the different subunits and that the mRNA level for subunit c is particularly sensitive to developmental and environmental changes.

Amino Acid Sequence↗

Relationship of amiodarone to postoperative complications of transthoracic implantation of automatic implantable cardioverter defibrillators.

The purpose of this study is to report the results and complications associated with transthoracic placement of an implantable defibrillator and their relationship to amiodarone, and to identify clinical predictors of complications. There were 159 men and 41 women. The mean patients age was 61 +/- 11 years, and the mean ejection fraction was 0.33 +/- 0.14. Fifty one percent of patients developed complications including death in 14 patients (7%). Variables which differed in patients who died and those that did not were age, ejection fraction and New York heart failure classifications. Postoperative mortality was unrelated to amiodarone therapy. Twenty patients (10%) developed pneumonia and 15 patients (7.5%) developed respiratory failure. Clinical variables associated with the development of respiratory failure were age, amiodarone therapy and a prior history of pulmonary disease. Patients receiving amiodarone had a higher incidence of an elevated defibrillation threshold (> or = 25 joules) as compared with those not being treated with amiodarone. Clinical factors associated with an elevated defibrillation threshold were a history of a myocardial infarction, prior bypass surgery, and amiodarone. The results of this study demonstrate that placement of an implantable defibrillator using a transthoracic approach is associated with a high incidence of complications. Amiodarone therapy is associated with an increased incidence of pneumonia, respiratory failure, and elevated defibrillation thresholds.

Adolescent↗

Esophageal lichen planus: a forgotten diagnosis.

Esophageal lichen planus (ELP), an infrequent cause of dysphagia, is associated with various mucosal lesions of the proximal esophagus. In a patient with oral lichen planus, with dysphagia and proximal esophageal lesions, the correct diagnosis of ELP was delayed for 10 years after dysphagia first occurred. This case report illustrates how the diagnosis of ELP in a symptomatic patient eluded experienced clinicians, even in the presence of oral lichen planus.

Aged↗

Ciliary neurotrophic factor promotes chick photoreceptor development in vitro.

Previous in vitro studies have convincingly demonstrated the involvement of diffusible factors in the regulation of photoreceptor development. We now provide evidence that ciliary neurotrophic factor (CNTF) represents one of these regulatory molecules. In low density monolayer cultures prepared from embryonic day 8 chick retina, photoreceptor development was studied using the monoclonal antiopsin antibody rho-4D2 as a differentiation marker. The number of cells acquiring opsin immunoreactivity, determined after 3 days in vitro, was increased up to 4-fold in the presence of CNTF to maximally 10.5% of all cells. Basic fibroblast growth factor or taurine both of which have been reported to stimulate opsin expression in rat retinal cultures and other neurotrophic factors tested (nerve growth factor, brain derived neurotrophic factor) had no effect. The EC50 of the CNTF effect (2.6 pM) was virtually identical to that measured for other CNTF receptor mediated cellular responses. Conditioned medium produced by cultured retinal cells (most likely glial cells) exhibited opsin stimulating activity identical to that of CNTF. Stimulation of opsin expression was specific for morphologically less mature photoreceptors and obviously restricted to rods, since changes in the number of identifiable cone photoreceptors expressing opsin immunoreactivity (10% of all cones) were not detectable. Measurement of the kinetics of the CNTF response revealed that the factor acted on immature opsin-negative progenitors and that CNTF effects were unlikely to reflect enhanced cell survival. Proliferation of photoreceptors was also unaffected, as demonstrated by [3H]thymidine autoradiography. With prolonged culture periods a gradual decrease in the number of opsin-positive cells was observed both in controls and in the continuous presence of CNTF. This decrease could be partly prevented by the addition of 1 mM taurine. Our results suggest that CNTF acted as an inductive signal for uncommitted progenitor cells or during early stages of rod photoreceptor differentiation, whereas other extrinsic stimulatory activities seemed to be required for further maturation.

Animals↗

[Hypokalemic myopathy in cats].

Clinical signs, laboratory findings and the course of hypokalemic myopathy in ten cats are described. One of these cats needed continuing potassium substitution; in the other nine cats hypokalemia was a temporary phenomenon as a result of severe diabetic ketoacidosis and its therapy. In these patients normokalemia was achieved after potassium substitution for three to seven days. The clinical signs of hypokalemic myopathy already resolved after one to four days. Etiologic factors contributing to hypokalemic myopathy in these patients are discussed.

Animals↗

Differential expression of L-selectin, VLA-4, and LFA-1 on CD34+ progenitor cells from bone marrow and peripheral blood during G-CSF-enhanced recovery.

To examine mechanisms of mobilization and homing of hematopoietic progenitor cells, coexpression of CD34 and the adhesion molecules L-selectin (CD62L), VLA-4 (alpha 4 beta 1-integrin, CD49d/CD29), and LFA-1 (alpha L beta 2-integrin, CD11a/CD18) was evaluated. Samples from leukapheresis (LP) products and bone marrow (BM) were obtained on the same day from patients who received granulocyte colony-stimulating factor (G-CSF) after cytotoxic chemotherapy. The proportion of CD34+ cells expressing L-selectin tended to be greater in LP products compared with BM. In samples from both sources, the mean fluorescence intensity of CD34 was significantly greater on CD34+/L-selectin-positive cells compared with the CD34+/L-selectin-negative cell subset. Three-color immunofluorescence showed that early CD34+/HLA-DRdim or CD34+/HLA-DR- progenitor cells were strongly positive for L-selectin, whereas L-selectin-negative cells were only found in the CD34+HLA-DRbright subset. The mean fluoresence intensity of VLA-4 and LFA-1 was significantly greater on CD34+ cells from BM compared with LP products. Moreover, a distinct population of CD34dim/VLA-4bright and CD34dim/LFA-1bright cells was found only in samples from BM. This subset may be enriched for myeloid progenitor cells, since the cloning efficiency of CD34+ cells for CFU-GM was significantly greater in BM samples than in LP products. Binding of CD34+ cells to endothelial cells was partially inhibited by a blocking antibody to beta 2-integrin. In conclusion, L-selectin is expressed in significant amounts on more primitive CD34+ cells which circulate in considerable numbers in the peripheral blood. This suggests that L-selectin plays a role in redistribution and homing of hematopoietic progenitor cells to the bone marrow following cytotoxic damage. Conversely, strong expression of VLA-4 and LFA-1 was mainly found on lineage-committed progenitor cells of the bone marrow.

Adult↗

Expression of ciliary neurotrophic factor receptor mRNA and protein in the early postnatal and adult rat nervous system.

We have used reverse transcription/polymerase chain reaction (RT-PCR) and Western blotting with an anti-peptide antibody to study the expression of the alpha-component of the receptor for ciliary neurotrophic factor (CNTFR alpha) in rat nervous tissue. At the early postnatal stage CNTFR alpha protein could be detected in all parts of the nervous system studied (and also in muscle and liver). It was particularly abundant in pons, cerebellum, spinal cord, retina and sciatic nerve. In adult tissues the content was dramatically reduced except for olfactory bulb and cortex, where CNTFR alpha protein was upregulated during development. Only in part of the tissues, expression of CNTFR alpha mRNA and its developmental regulation paralleled that of the protein. These differences are partly explainable by the different cellular localization of mRNA and the membrane associated receptor protein, but, in addition, they suggest the existence of different regulatory mechanisms for CNTFR alpha. Our results support the idea that CNTF plays an important role during the development of the nervous system and that CNTF actions may be found in many brain regions and target cells.

Animals↗

A new familial glomerulonephropathy in Bernese mountain dogs.

Between 1989 and 1992, 22 Bernese mountain dogs (18 females and four males) aged between two and seven years, which had been suffering for some weeks from weight loss, anorexia, apathy, vomiting, polydipsia and polyuria, were examined. All of them had high blood urea nitrogen and serum creatinine concentrations, and many had hyperphosphataemia, hypercholesterolaemia, hypoproteinaemia and nonregenerative anaemia. All the dogs had very high protein: creatinine ratios in the urine, and macroproteinuria was identified by sodium dodecyl sulphate gel electrophoresis. The immunofluorescent titres against Borrelia burgdorferi, measured in 19 of the dogs, ranged between 256 and 32,768. In all cases, membrano-proliferative glomerulonephritis with concomitant interstitial nephritis was diagnosed. From an analysis of the dogs' pedigree it was concluded that the glomerulonephritis of these Bernese mountain dogs was inherited as an autosomal recessive trait and that its expression was influenced by a second gene locus with a sex-linked dominance exchange.

Animals↗

Activated monocytes kill malignant brain tumor cells in vitro.

The purpose of our study was to investigate the susceptibility of human glioblastoma multiforme (GBM) cells to lysis by human peripheral-blood monocytes following activation with biological response modifiers (BRM) and to lysis by various BRMs directly. Cytotoxic effects were determined using a monocyte-/BRM-mediated tumor cytotoxicity assay. Human peripheral-blood monocytes from healthy donors were activated in vitro by incubation for 24 h with different BRMs such as gamma- and beta-interferon (gamma, beta-IFN), lipopolysaccharide (LPS), muramyldipeptide (MDP) and tumor necrosis factor-alpha (TNF-alpha) in varying concentrations and combinations. Seven human GBM cell lines as well as an adenocarcinoma brain metastasis cell line and a malignant melanoma cell line served as target cells. Radiolabeled target cells were cocultivated with activated monocytes or with BRMs directly. Cytotoxicity was calculated after 72 h of cocultivation. High levels of cytotoxicity were mediated by monocytes activated with beta-IFN in six out of eight brain tumor cell lines and with TNF-alpha in five cell lines. The combination of two BRMs, in particular the combination of gamma-IFN + beta-IFN and gamma-IFN + TNF-alpha, was associated with an enhanced monocyte mediated lysis exceeding LPS control, whereas the combination of gamma-IFN + MDP was very effective against the metastasis cell line. Monocyte-mediated cytotoxicity against tumor target cells was up to ten fold higher than direct cytotoxicity of soluble BRMs. Our data indicate that BRM-stimulated peripheral-blood monocytes exert cytotoxic properties against human glioblastoma cells in vitro, which exceed those of BRMs alone up to ten fold. The higher tumoricidal activities observed after stimulation with combined BRMs suggest mutual promoting mechanisms of BRMs acting on the stimulation of lyctic activity in human peripheral blood monocytes.

Acetylmuramyl-Alanyl-Isoglutamine↗

Drug-induced ileal disease: a new entity in the differential diagnosis of Crohn's disease.

Ileal disease in the United States is usually caused by Crohn's disease. Accumulating reports, however, show that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause ileal and colonic inflammation and strictures that may mimic inflammatory bowel disease and other conditions. A patient is described with weight loss, loose stools, and terminal ileal disease, all of which resolved after discontinuing an NSAID. Clinicians must become familiar with the expanding clinical and radiological spectrum of NSAID gastrointestinal tract toxicity.

Aged↗

Loin pain-hematuria syndrome with a distinctive vascular lesion and alternative pathway complement activation.

We describe a 48-year-old woman with loin pain-hematuria syndrome. Her renal abnormalities included conspicuous microaneurysmal and glomeruloid (plexiform) angiomatous changes. The deposition of both properdin and the C5b-9 complex, as well as the usual C3, in arterioles argues for complement activation. To our knowledge, neither of these features has been previously described. We speculate about the cause of loin pain-hematuria syndrome and note the uncommonness of this entity in the United States as opposed to Great Britain.

Complement Pathway, Alternative↗

The use of intravascular ultrasound in the management of thoracic outlet syndrome.

We have reviewed our early experience with intravascular ultrasound in the management of thoracic outlet syndrome. Eight patients presenting with symptoms of venous obstruction secondary to thoracic outlet syndrome have been evaluated by duplex ultrasound, contrast venography, and intravascular ultrasound (IVUS). IVUS was performed at the same time as venography, using the brachial venous access site. In all eight patients IVUS and venography were in agreement. IVUS was able to identify the etiology of the stenoses. Four of the six patients with abnormal IVUS studies have had surgery, and IVUS was used intraoperatively during three of these cases. Based on the demonstration of release of extrinsic compression by real time imaging, it was possible to limit the necessary dissection to two first rib resections alone and one resection of just the insertion of the pectoralis minor muscle. Three of the four patients have had complete resolution of their symptoms postoperatively. Currently, the average follow-up time is 13 months. One patient who was a current procedure has had a minor relapse at 6 months. There have been no complications. These results have shown that IVUS is a safe technique and is as accurate as venography in identifying the sites and degree of narrowing. IVUS provides additional data as well regarding the etiology of the underlying process. The intraoperative use of IVUS has proved helpful in decision-making to minimize the dissection necessary to release extrinsic venous compression. The operative results compare favorably with those found in the literature.

Adult↗

Correlation between scintigraphic evidence of regional sympathetic neuronal dysfunction and ventricular refractoriness in the human heart.

BACKGROUND: Denervation supersensitivity has been proposed as a mechanism for the relation between ventricular arrhythmias and the sympathetic nervous system. Evaluation of this phenomenon in humans has become feasible only recently with the development of noninvasive scintigraphic methods for evaluating the pattern of sympathetic innervation. The purpose of this study was to determine if scintigraphic evidence of sympathetic neuronal dysfunction correlates with measurements of ventricular refractoriness and to evaluate the phenomenon of denervation supersensitivity in humans. METHODS AND RESULTS: Eleven patients with a history of sustained ventricular tachycardia or sudden cardiac death who were referred for placement of an implantable defibrillator participated in this study (seven men and four women; age, 51 +/- 18 years). Preoperative scintigraphic evaluation of the pattern of sympathetic innervation was performed with 11C-hydroxyephedrine in conjunction with positron emission tomography. At the time of surgery, ventricular refractoriness was determined in regions of myocardium demonstrating normal and reduced 11C-hydroxyephedrine retention in the baseline state and during an infusion of norepinephrine. Scintigraphic evaluation demonstrated regions of reduced 11C-hydroxyephedrine retention in each patient. The effective refractory period in areas of myocardium that demonstrated reduced 11C-hydroxyephedrine retention was significantly longer than in areas of myocardium demonstrating normal 11C-hydroxyephedrine retention (273 +/- 32 versus 243 +/- 32 msec, p < 0.001). Norepinephrine shortened the effective refractory period in regions of myocardium demonstrating normal and reduced 11C-hydroxyephedrine retention to a similar degree. CONCLUSIONS: There is a correlation between scintigraphic evidence of sympathetic neuronal dysfunction and ventricular refractoriness in the human heart. These observations help validate the use of scintigraphic techniques for evaluation of sympathetic innervation and may assist in the further evaluation of the relation between the sympathetic nervous system and ventricular arrhythmias.

Carbon Radioisotopes↗