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Biomedical subjects

M Hummel

Publications and source records attributed to M Hummel.

At least 289 records · Page 16Linked to original sources
PubMed1980

Epstein-Barr virus (B95-8) DNA VII: molecular cloning and detailed mapping.

Two of the Sal I fragments and all of the internal BamHI fragments (with the exception of BamHI c, a 0.6 x 10(6) dalton fragment) of Epstein-Barr virus (EBV) DNA have been cloned in pBR322. The termini and other parts of the DNA (including the EcoRI fragment which contains BamHI c) have been cloned as EcoRI fragments in bacteriophage Charon 4A. The cloned DNAs have been used to derive a complete map of the BamHI fragments of EBV DNA and to align the BamHI, EcoRI, HindIII, and SalI cleavage sites in EBV DNA.

Bacteriocin Plasmids↗
PubMedDate not supplied

Immunosuppression is not required for reactivation of latent murine cytomegalovirus.

We have shown, for the first time, that TNF induces expression of MCMV IE RNA in the lungs of latently infected mice in the absence of immunosuppression. These initial data suggest that TNF may play an important role in the reactivation of latent MCMV, in the absence of immunosuppression, and provide a provocative insight into the mechanisms of CMV reactivation. Studies are in progress to determine whether genes associated with later stages of the viral life cycle are induced by TNF and whether infectious virus is produced.

Animals↗
PubMedDate not supplied

Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway.

Glycoproteins modified with a sialyl-Le(x)-moiety are important sensors for extracellular signals regulating cellular recognition, adhesion and migration. The transduction pathways and signals mediated by these glycoproteins within the cell are largely unknown. In search of novel glycoproteins modified with sialyl-Le(x)-moiety, we screened a human colonic cDNA expression library with a rabbit antiserum produced against sialyl-Le(x)-positive mucins. The antiserum detected a new protein, named B2, which was cloned and characterised in detail. The analysis of the B2 gene revealed a 5.7 kb RNA transcript detectable in all investigated tissues and a complete coding sequence of 2778 bp. The B2 protein exhibited two putative PH (pleckstrin homology) domains and a leucine zipper motif but no homology to any known proteins. Monospecific antibodies against the B2-protein precipitated from the solubilised membrane fraction of the colon carcinoma cell line LS 174T a protein with an apparent Mr = 162 kDa and, additionally, a mucin-like glycoprotein with an apparent Mr = 220 kDa. Protein fractionation on a CsCl gradient, Western blots and sandwich ELISA showed that the 220 kDa mucin carries the sialyl-Le(x) moiety and is tightly bound to the 162 kDa protein. The expression of the recombinant B2-protein enhanced staurosporine-induced apoptosis in epithelial cancer cell lines. These data indicate that B2 is a novel, ubiquitously expressed protein with a putative adapter function. The protein has been named AP162 (adapter protein 162). In colon carcinoma cells B2-protein is tightly associated with a sialyl-Le(x)-positive mucin and has a potential for involvement in sialyl-Le(x)-mediated transduction of apoptotic signals.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Mechanical circulatory support and heart transplantation. Pre-operative status and outcome.

Between July 1988 and December 1993, 118 patients waiting for heart transplantation underwent mechanical circulatory support by an extracorporeal, pneumatically driven assist device (the Berlin Heart System) to maintain a sufficient circulation and to restore impaired organ function (109 patients requiring a biventricular assist device [BVAD], 9 patients requiring a left ventricular assist device [LVAD]). Before implantation, all patients were in severe cardiogenic shock, despite maximum inotropic support; all had end organ failure. The aim of a retrospective study in 70 patients (for whom pre-operative parameters were available) was to identify patients who would permit from this procedure and could undergo successful transplantation. After a mean bridging time of 34.8 days, 75 (63.5%) patients underwent transplant, and 52 (44.1%) were discharged. Pre-operative coagulation parameters (fibrinogen, antithrombin III, platelet count, and kinetics) were correlated to post-operative blood loss and outcome. Patients who had no or mild coagulation disorders because of a shorter phase of low cardiac output before implantation of the assist device proved to gain faster restitution of organ function and most underwent transplantation. As a result of these observations, implantation of an assist device before shock-induced coagulopathy could occur allowed a greater number of patients to undergo successful bridging and be discharged after heart transplantation.

Adolescent↗
PubMedDate not supplied

Fungal infections following heart transplantation.

Following heart transplantation (HTx), patients often suffer from mycoses due to the necessary immunosuppressive treatment to prevent rejection episodes. Oropharyngeal Candida infections which mostly occur after HTx under high-dose immunosuppressive therapy can be avoided and treated successfully by prophylactic medication to be started immediately after transplantation, either by using azoles (e.g. fluconazole) or amphotericin B suspension. Contrary to this, invasive aspergillosis, beginning in the upper respiratory tract and the lung and mostly followed by hematogenous dissemination into various organs, is always a serious disease with high mortality. To avoid this infection, specimens from the respiratory tract, serum and urine should be examined mycologically prior to HTx. After HTx, apart from prophylactic avoidance of exposure to airborne fungal spores, close mycological control is mandatory to detect colonizations by aspergilli early. Timely administration of amphotericin B and 5-flucytosine, i.e. as soon as invasive growth is suspected, enables curative treatment of the often lethal course of this disease, even under immunosuppressive therapy.

Aspergillosis↗
PubMedDate not supplied

Obstructive bronchial aspergillosis after heart transplantation.

Obstructive bronchial aspergillosis is a rarely observed consequence of Aspergillus infection. It occurs not only in patients with the acquired immunodeficiency syndrome (AIDS), but also after heart transplantation (HTx) if T cells are reduced markedly by the application of antithymocyte globulin (ATG) in addition to immunosuppression with corticosteroids. In contrast to invasive aspergillosis or Aspergillus tracheobronchitis, the course of this form of Aspergillus infection may not be accompanied by symptoms, because bronchial inflammation with pseudomembranes, ulcers or destruction of mucosa and intrapulmonary infiltrates are absent. To prevent invasive aspergillosis following HTx, intensive antifungal therapy is necessary in cases of bronchial obstructive aspergillosis, because this form of Aspergillus infection seems to represent a stage before recognizable invasive disease, as in other immunocompromised patients.

Aspergillosis↗
PubMedDate not supplied

CT of heart transplant recipients: spectrum of disease.

The emergence of heart transplantation as the ultimate treatment for end-stage heart failure has been accompanied by new diagnostic challenges. Computed tomography (CT) has emerged as an important diagnostic tool in the evaluation of heart transplant recipients because many infectious, ischemic-hemorrhagic, and neoplastic complications are amenable to early detection with this modality. In the early postoperative period, CT is mostly indicated in the evaluation of infectious complications or cerebral symptoms. Later, CT is mostly performed for staging of infectious or neoplastic disease. Infectious complications include mediastinitis, soft-tissue inflammation, abscess formation, cerebral infarction, and aspergillosis. Complications related to ischemia or hemorrhage include allograft rejection and coronary allograft vasculopathy, the latter being the leading long-term cause of death in heart transplant recipients. CT is also indicated in malignant disease (eg, lymphoma, visceral carcinoma, skin tumors), which is the second most important long-term cause of death. Moreover, CT is helpful in identifying disease caused by immunosuppressive therapy (eg, leukoencephalopathy, osteoporosis, thoracic lipomatosis). CT has proved superior to both ultrasound and magnetic resonance imaging in the evaluation of heart transplant recipients. It has become the diagnostic modality of choice for many transplant-related complications and may help improve postoperative treatment of affected patients.

Diagnosis, Differential↗
PubMedDate not supplied

Clinical heart transplantation without routine endomyocardial biopsy.

In a prospective clinical study, routine endomyocardial biopsy (EMB) for early detection of cardiac allograft rejection was replaced by two noninvasive diagnostic techniques. In 32 patients who underwent transplantation during a 6-month period, intramyocardial electrogram (IMEG) amplitude was recorded with the telemetry function of a dual-chamber pacemaker system. An amplitude decrease of more than 8% below the individual range of variability in overnight long-term recordings served as an indicator of rejection. A prolongation of the time interval Te--the time span between maximal posterior wall contraction and peak retraction velocity--of more than 20 msec was used as an additional indicator of rejection-related left ventricular dysfunction. For patient safety, routine EMBs were still performed but remained undisclosed to the transplantation team. The pathologist was asked to intervene in cases of discrepancies between biopsy results and medical decisions, but no such intervention was necessary. Twenty-seven rejection episodes were treated medically, of which 22 were diagnosed noninvasively. In four patients, EMB, ordered because noninvasive parameters remained inconclusive, led to medical treatment. No false negative IMEG results were observed. Retrospective correlation with rejection gave a 100% negative predictive value for IMEG and a 96.9% negative predictive value for echocardiographic diagnosis. We conclude that omission of a schedule of routine biopsies is justified, if the described techniques of IMEG and echocardiography are meticulously applied and indicate normal cardiac function. EMB remains indicated if noninvasive parameters are not conclusive or if false-positive IMEG results, which were observed in the presence of infection or arrhythmias, are suspected. The frequency of EMB can be reduced by 90%, compared to conventional routine biopsy schedules. Diagnostic safety is increased because the additional information gained from IMEG and echocardiography is helpful in the interpretation of EMBs.

Biopsy↗
PubMedDate not supplied

[Use of cardiotonic heterosides in pediatrics].

The indications for the administration of cardiotonic heterosides are quite similar in adults and children. However, their use in children raises several practical problems, generally related to differences in kinetics and/or tissular sensitivity. The pharmacodynamic properties and the kinetics of cardiotonic glycosides of digitalis are reviewed and therapeutic and toxicologic effects are discussed.

Age Factors↗
PubMedDate not supplied

Heart transplantation in patients with muscular dystrophy associated with end-stage cardiomyopathy.

Until now, patients with muscular dystrophy and concomitant cardiomyopathy have been accepted for heart transplantation only reluctantly, because of a higher perioperative risk caused by physical disability and a suspected rapid onset of cardiomyopathy of the transplanted heart. Of a total of 582 heart transplant recipients, six patients had muscular dystrophy associated with end-stage cardiomyopathy. In three patients, preoperative neurologic diagnostic investigation revealed type Duchenne muscular dystrophy (three male); one female patient had Emery-Dreifuss; one male patient had Becker-Kiener dystrophy, and the specific classification could not be established in one male patient. Mean age was 25 years, ranging from 9 to 45 years. The postoperative follow-up ranges from 10 months to 7 years, with a mean of 40 months. All patients received triple-drug immunosuppression, consisting of azathioprine, cyclosporine, and steroids. All patients had an uneventful postoperative course. Postoperative time of intubation was not prolonged in these patients compared to other patients. All patients are physically rehabilitated. One patient died suddenly 27 months after operation. Annual recatheterization studies showed normal left ventricular ejection fraction (59.5 +/- 13.4% SD). Signs of coronary artery disease could not be observed. No progression of preexisting muscular dystrophy could be diagnosed, until now.

Adult↗