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Biomedical subjects

C Schulze

Publications and source records attributed to C Schulze.

At least 55 records · Page 3Linked to original sources
PubMed1998

Endothelium-dependent microvascular vasomotion and its correlation with vasoactive mediators early after cardiac transplantation in humans.

Endothelial dysfunction precedes and predicts transplant vasculopathy. We investigated the relationship between endothelial dysfunction and the vasoactive mediators nitric oxide and endothelin, 33.7 +/- 2.0 days after heart transplantation. Coronary flow was measured in 18 patients to determine the endothelial microvascular vasomotor response to acetylcholine. Endomyocardial biopsies were taken to determine the levels of gene expression of isozymes of endothelin and nitric oxide synthases (NOS). Blood samples from the coronary sinus and aorta were withdrawn for measurement of endothelin, nitrite and cytokines. Five patients (30%) showed an impaired coronary flow reserve response to acetylcholine, significantly higher inducible NOS gene expression and significant transcardiac nitrite production. Plasma nitrite correlated with tumour necrosis factor-alpha levels in coronary sinus and a transcardiac net extraction of endothelin was noted in all patients. In conclusion, 30% of patients develop endothelial dysfunction early after heart transplantation; this correlates with the expression and activation of vasoactive and immunomodulatory mediators, which may predict the development of transplant vasculopathy.

Endothelin-1↗
PubMed1998

Minimally invasive coronary artery bypass grafting: port-access approach versus off-pump techniques.

BACKGROUND: Within the past 5 years several surgical techniques have been developed for less invasive surgical treatment of coronary artery disease. The aim of this study was to define specific indications for the various minimally invasive coronary artery surgical procedures. METHODS: Minimally invasive direct coronary artery bypass grafting through a minithoracotomy was performed in 67 patients. The left internal mammary artery was anastomosed on the beating heart with the use of a pressure or suction stabilizer without the use of extracorporeal circulation. In 58 other patients with multivessel disease, the off-pump coronary artery bypass grafting technique through a sternotomy was applied with a left internal mammary artery to left anterior descending artery and additional vein grafts without extracorporeal circulation. In a third group, Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting was performed through a left minithoracotomy with the use of an endovascular extracorporeal circulation system and cardioplegic arrest. Angiographic follow-up was complete in 64% of the patients. RESULTS: There was minimal perioperative or postoperative mortality (0.5%). The medium surgical procedure time for all minimally invasive and off-pump procedures was 2.5 hours; it was 4.5 hours for Port-Access procedures. The median postoperative intensive care unit stay was 1.0 days, and the median hospitalization was 5.0 days. Overall graft patency was 97.3%; in 8 patients (4.1%) a stenosis either at or distal to the graft anastomosis was dilated with coronary angioplasty. CONCLUSIONS: For single-vessel disease of the left anterior descending artery, the minimally invasive coronary artery bypass grafting procedure can be performed safely without the use of extracorporeal circulation. In case of hemodynamic instability or anatomic variation, the Port-Access procedure can be applied without additional necessity for sternotomy. For multivessel disease, the off-pump bypass grafting procedure with sternotomy can be recommended depending on the coronary arteries involved. In case of necessary grafts to the lateral marginal or circumflex branches, Port-Access grafting can be recommended and may play an important role in the future for the development of fully endoscopic robot-assisted coronary artery bypass grafting.

Adult↗
PubMed1998

Nitric oxide and endothelin in the development of cardiac allograft vasculopathy. Potential targets for therapeutic interventions.

Extensive research has been carried out in recent years to discover the potential risk factors contributing to cardiac allograft atherogenesis. Injury to endothelial cells has been regarded as an important early mechanism in the development of transplant atherosclerosis; it leads to the manifestation of epicardial and microvascular endothelial dysfunction and development of intimal hyperplasia. Moreover, continuous minor endothelial cell damage contributes to endothelial dysfunction which reflects one of the first measurable steps in the cascade of atherogenesis without macroscopic evidence of vascular lesions. The discovery of two important vasoactive substances nitric oxide (NO) and endothelin (ET) has brought new insights but also new unsolved questions regarding the mechanisms leading to atherosclerosis. To date it is known that both substances play a major role in both prevention and development of atherosclerosis. NO appears to be protective in low concentrations by inhibiting leukocyte and platelet activation/adherence and smooth muscle cell proliferation. Impaired endothelial NO production, as one cause of endothelial dysfunction may occur in early stages of atherosclerosis before macroscopic lesions are evident. In addition, increased endothelin release also results in endothelial dysfunction by inducing vasoconstriction; it promotes vascular lesion formation due to endothelial- and vascular smooth muscle cell proliferation. Direct and indirect manipulation of both the NO and ET signal transduction systems may provide novel preventive and therapeutic approaches for limiting transplant atherogenesis and to treat native atherosclerosis. This review summarizes important experimental and clinical evidence which points to nitric oxide and endothelin as potential therapeutic targets in the process of cardiac allograft vasculopathy.

Animals↗
PubMed1998

Amino acid sequence of the D-galactose binding lectin II from the sponge Axinella polypoides (Schmidt) and identification of the carbohydrate binding site in lectin II and related lectin I.

The sponge Axinella polypoides contains several D-galactose binding lectins. One of the main components, lectin I was sequenced earlier, the complete sequence of the other major constituent of saline extracts, lectin II has been determined by amino acid sequencing and mass spectrometry. Both lectins have a homology of 65% to each other and both possess a disulfide loop between positions 4 and 46. As long as this loop is closed in both lectins, they can be boiled in the presence of SDS or treated with 6 mol guanidine hydrochloride without losing their hemagglutinating activity. Incubation with beta-mercaptoethanol alone does not effect the carbohydrate binding capacity either. However, reduction of the disulfide bond under chaotropic conditions destroys the activity irreversibly. This disulfide loop is also an immunologically dominant epitope in both lectins, as was revealed with monospecific polyclonal antisera. Thus, sponge lectins seem to be of different origins, since three completely different structures were described: the structure of Geodia cydonium, related to the mammalian S-type lectins with one SH-group, the Axinella lectins with one disulfide loop and the Aaptos lectins I and II with 11 cysteine residues/subunit.

Amino Acid Sequence↗
PubMed1998

Renal dysplasia in three young adult Dutch kooiker dogs.

Chronic renal failure as consequence of renal dysplasia was diagnosed in three young adult Dutch kooiker dogs (Dutch decoy dogs). Two animals were anorectic from an early age and were thinner than healthy dogs of the same breed. All three were presented because of apathy and weakness. Laboratory examination revealed anaemia and uraemia. One dog was presented with severe dehydration and died during emergency treatment. One dog was euthanatised because of a poor prognosis, and one was given a low-protein diet. This dog survived for 7 months after the diagnosis of chronic renal failure. At necropsy all three animals had shrunken, pale, and firm kidneys that showed microscopical lesions characteristic of canine renal dysplasia, such as asynchronous differentiation of nephrons, persistent immature mesenchyme, persistent metanephric ducts, and adenomatoid proliferation of the tubular epithelium. Secondary degenerative and inflammatory changes consisted of interstitial fibrosis and predominantly lymphocytic/plasmacytic inflammation. This is the first report of renal dysplasia in the Dutch kooiker dog. The disease should be included in the differential diagnosis in young Dutch kooiker dogs with signs of chronic renal failure. The presentation of three cases of this rare disease in this breed, which is based on a rather small gene pool, suggests that it is a familial or hereditary nephropathy.

Animals↗
PubMed1998

Generalized AA-amyloidosis in Siberian tigers (Panthera tigris altaica) with predominant renal medullary amyloid deposition.

Generalized amyloidosis with predominant renal medullary amyloid deposition was found in four closely related Siberian tigers (Panthera tigris altaica) suffering from end stage kidney diseases. Only minimal to mild amounts of amyloid were deposited in various organs outside the kidneys with individually variable organ involvement. The Congo red staining affinity of amyloid deposits was sensitive to potassium permanganate oxidation. The deposits were further characterized as being of the amyloid-A (AA) type by immunohistochemistry using the mouse monoclonal antibody mc4 directed against a conserved region of the human AA-protein. A combination of immunohistochemistry and Congo red staining was much more sensitive for the diagnosis of amyloid deposits than Congo red staining alone. With this combination, even minimal amyloid deposits were detected that had been missed in the first reading using Congo-red-stained slides alone. Since no common primary cause was identified, the amyloidosis was classified as idiopathic generalized AA-amyloidosis with a potential familial predisposition.

Amyloidosis↗
PubMed1998

Nested polymerase chain reaction and in situ hybridization for diagnosis of canine herpesvirus infection in puppies.

The usefulness of two nucleic acid detection systems in suspected cases of spontaneous canine herpesvirus (CHV) infection in puppies was evaluated. Formalin-fixed, paraffin-embedded tissues from seven 1-3-week-old naturally infected puppies with lesions characteristic of CHV infection were investigated in a retrospective study. Nested polymerase chain reaction (PCR) and nonradioactive in situ hybridization (ISH) were used to detect nucleotide sequences of the CHV thymidine kinase (TK) gene. According to the original necropsy reports, CHV was isolated in four of the seven puppies using primary canine lung and/or kidney cells. In all seven puppies, gross and histologic lesions consisted of disseminated focal necroses and hemorrhages predominantly in kidneys, lung, liver, and spleen. In addition, few small amphophilic intranuclear inclusion bodies were detected by light microscopy mainly in epithelial cells of kidney, lung, and liver. ISH was performed with a 111-base-pair (bp) digoxigenin-labeled double-stranded DNA probe. Viral DNA was detected in the nuclei of cells near and within lesions. Various cell types, including bronchiolar and alveolar epithelial cells, hepatocytes, renal tubular epithelial cells, neurons, fibrocytes, cardiac myocytes, and endothelial cells, were positive for viral DNA. PCR amplification products of the expected length of 168 bp containing the expected cleavage site for the restriction enzyme EcoRI, derived from paraffin blocks containing lung, kidney, and liver tissues, were detected in all seven puppies. The specificity of the obtained amplicon was further confirmed by Southern blot analysis. ISH and PCR are both useful methods for diagnosing CHV infection in formalin-fixed, paraffin-embedded tissues and are highly specific and sensitive methods for further investigations of the pathogenesis of CHV-induced lesions.

Animals↗
PubMed1998

3D-video- and robot-assisted minimally invasive ASD closure using the Port-Access techniques.

BACKGROUND: Video-assisted minimally invasive surgical methods with endovascular-based femoral cardiopulmonary bypass (CPB) and balloon occlusion of the aorta (Port-Access technique) were used to close an ostium-secundum atrial septal defect (ASD) in 7 patients. METHODS: Minor modifications were made to the system to provide drainage of the superior vena cava. The surgery was performed through a small (3.5-5cm) right anterolateral thoracotomy with 3D video and robotic arm assistance. RESULTS: The operative procedures were completely uneventful and the patients were discharged four days postoperatively in good condition and with excellent cosmesis. CONCLUSION: Using the modifications described, the Port-Access surgical method can be recommended for minimally invasive closure of an ASD.

Adolescent↗
PubMed1998

Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection.

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.

Administration, Oral↗
PubMed1997

1-(5-phospho-beta-D-ribosyl)2'-phosphoadenosine 5'-phosphate cyclic anhydride induced Ca2+ release in human T-cell lines.

1-(5-Phospho-beta-D-ribosyl)2'-phosphoadenosine 5'-phosphate cyclic anhydride [2'-phospho-cyclic ADP-ribose, cAdo(2')P(5')PP-Rib] was prepared enzymatically from NADP+ using ADP-ribosyl-cyclase from Aplysia californica. The product was purified by HPLC and characterized by NMR and mass spectroscopy, by conversion to 1-(5-phospho-beta-D-ribosyl)adenosine 5'-phosphate cyclic anhydride (cADP-Rib) by alkaline phosphatase and by resistance to snake venom phosphodiesterase. cAdo-(2')P(5')PP-Rib dose-dependently released Ca2+ from an intracellular, non-endoplasmic reticular Ca2+ pool of permeabilized Jurkat and HPB. ALL T-lymphocytes. In contrast, the closely related compounds 1-(5-phospho-beta-D-ribosyl)3'phosphoadenosine 5'-phosphate cyclic anhydride and 1-(5-phospho-beta-D-ribosyl)cyclic 2',3'-phosphoadenosine 5'-phosphate cyclic anhydride did not induce Ca2+-release from permeabilized T cells. The Ca2+ pool sensitive to cAdo(2')P(5')PP-Rib partially overlapped with the Ca2+ pool sensitive to cADP-Rib recently described in T cells [Guse, A. H., da Silva, C. P., Emmrich, F., Ashamu, G. A., Potter, B. V. L. & Mayr, G. W. (1995) Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+-release in T-lymphocyte cell lines, J. Immunol. 155, 3353-3359]. Control experiments suggest that the results were neither due to Ca2+ contaminations in the cADP-Rib preparation nor to catabolism of cAdo(2')P(5')PP-Rib to cADP-Rib.

ADP-ribosyl Cyclase↗
PubMed1997

Na+ channel modulation and force-frequency relationship in human myocardium.

The enhancement of force of contraction (FOC) following increasing frequencies of stimulation is an important mechanism of positive inotropy in human myocardium. The present study aimed to investigate the influence of alterations in Na+ influx on FFR in human myocardium. Isometric FOC of electrically stimulated right auricular trabeculae (AUT, n = 12) from human non-failing hearts (n = 8) was measured at different stimulation rates (0.5-3 Hz) under control conditions, after increasing Na+ influx by the addition of (+/-)BDF 9148 (BDF, 3 mumol l-1) and after decreasing Na+ influx by the addition of lidocaine (LIDO, 10 mumol l-1). Additionally, the rate dependent changes in diastolic tension (DT) were measured in all experiments. Under control conditions FOC increased with increasing frequencies of stimulation. The rate at which maximal FOC was observed (SFmax) was 2.0 +/- 0.2 Hz and maximal increase in FOC (PIEmax) by increasing frequency of stimulation was +1.5 +/- 0.5 mN. After increase of Na+ influx by BDF (3 mumol l-1) SFmax was decreased to 0.8 +/- 0.1 Hz (p < 0.05 versus control) and PIEmax was +0.1 +/- 0.3 mN (p < 0.05). When Na+ influx was diminished by LIDO (10 mumol l-1) SFmax and PIEmax were increased compared to control (2.4 +/- 0.1 Hz and +4.1 +/- 0.9 mN, p < 0.05 versus control). The diastolic tension (DT) of AUT at 3 Hz was not changed at higher rates in the control group and after application of LIDO (10 mumol l-1), whereas after enhancement of Na+ influx by BDF there was an increase in DT of +0.7 +/- 0.2 at 3 Hz (p < 0.05 versus control and LIDO). An enhanced Na+ influx leads to a decrease in the optimal frequency and to a smaller force potentiation by higher stimulation rates which could be at least partly due to incomplete relaxation at higher frequencies, whereas a reduced Na+ influx is followed by opposite alterations. It is concluded that besides Ca2+ handling also Na+ influx and Na+ homeostasis might determine the frequency-induced force potentiation in human myocardium. Thus, the negative FFR in diseased human myocardium might result from changes in cellular Ca2+ or Na+ regulatory sites.

Aged↗
PubMed1997

Identification of the major hepatic DNA adduct formed by the food mutagen 2-amino-9H-pyrido[2,3-b]indole (A alpha C).

2-Amino-9H-pyrido[2,3-b]indole (A alpha C) is among the most prevalent heterocyclic amines detected in grilled or panfried meat; it was shown to be carcinogenic in mice, to induce preneoplastic foci in rat liver, and to form covalent DNA adducts in vitro and in vivo. The corresponding nitro compound 2-nitro-9H-pyrido[2,3-b]indole (N alpha C) was prepared and shown to be a direct acting mutagen in the Salmonella assay, while the amino compound required external metabolic activation with rat liver homogenate (S9). When A alpha C was incubated with S9 in the presence of calf thymus DNA, one major DNA adduct spot was detected upon 32P-postlabeling analysis. This adduct comigrated on ion-exchange TLC and reversed-phase HPLC with the major adduct detected in primary hepatocytes treated with A alpha C. In DNA isolated from livers of male F344 rats treated with 800 and 160 ppm, the formation of the same major adduct was observed with relative adduct levels of 20.6 +/- 9.6 and 1.4 +/- 1.1 adducts/10(8), respectively, as determined with the butanol extraction variant of the 32P-postlabeling assay. No DNA adducts were detected in liver DNA from rats treated with 32 ppm A alpha C or control animals. The major adduct spot was eluted and hydrolyzed and the modified base characterized by chromatographic and UV spectral comparison with a synthetic standard synthesized from acetylated guanine N3-oxide and A alpha C. Electrospray mass spectrometry and 1H- and 13C-NMR spectroscopy provided further evidence for the major adduct as N2-(guanin-8-yl)-2-amino-9H-pyrido[2,3-b]indole. A alpha C is formed especially in high-temperature preparation of food and may contribute considerably to the human carcinogenic risk that might be imposed by heterocyclic amines.

Animals↗
PubMed1997

Lysophosphatidic acid increases tight junction permeability in cultured brain endothelial cells.

Brain capillary endothelial cells are coupled by a continuous belt of complex high-electrical-resistance tight junctions that are largely responsible for the blood-brain barrier. We have investigated mechanisms regulating tight junction permeability in brain endothelial cells cultured to maintain high-resistance junctions. The phospholipid lysophosphatidic acid (LPA) was found to cause a rapid, reversible, and dose-dependent decrease in transcellular electrical resistance in brain endothelial cells. LPA also increased the paracellular flux of sucrose, which, together with the resistance decrease, indicated increased tight junction permeability. Activation of protein kinase C attenuated the effect of LPA, suggesting that it was mediated by activation of a signalling pathway. LPA did not cause any obvious relocalization of adherens junction- or tight junction-associated proteins. However, it did stimulate the formation of stress fibres, the recruitment of focal adhesion components, and the appearance of tyrosine phosphorylated protein at focal contacts. Our study shows that LPA is a modulator of tight junction permeability in brain endothelial cells in culture and raises the possibility that it triggers blood-brain barrier permeability changes under (patho)physiological conditions.

Animals↗
PubMed1997

Tacrolimus: a superior agent to OKT3 for treating cases of persistent rejection after intrathoracic transplantation.

Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.

Actuarial Analysis↗
PubMed1997

[Investigations on clinical diagnosis and pathogenesis of otitis media et interna in swine].

A total of 25 pigs with a head tilt as clinical sign of otitis media et interna were examined. The majority were weaner-pigs with respiratory tract disorders. In lateral and ventrodorsal radiographic views of the bulla tympanica, there was an increased opacity, often accompanied by marginal destruction or thickening of the bulla wall. The findings confirmed the clinical diagnosis in each affected pig. In the case of leptomeningitis an examination of the cerebrospinal fluid revealed a drastic increase in the cell count. In 20 of 23 microbiologically examined empyemic bullae a polyinfection was seen. The results indicate that the route of infection of the middle ear is by the auditory tube. Mange on the other hand plays only a minor role in the pathogenesis of otitis media.

Animals↗