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Biomedical subjects

M Heinemann

Publications and source records attributed to M Heinemann.

At least 37 records · Page 2Linked to original sources

Guanosine 3',5'-bis(diphosphate) (ppGpp)-dependent inhibition of transcription from stringently controlled Escherichia coli promoters can be explained by an altered initiation pathway that traps RNA polymerase.

An in vitro analysis was performed to investigate the inhibitory mechanism of the global regulatory substances guanosine 3',5'-bis(diphosphate) (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp) during initiation of transcription. Three promoters with well known differential ppGpp sensitivities in vivo were studied: the Escherichia coli rrnB P2 promoter that is only weakly ppGpp dependent; a P2 base change variant (P2F) that confers both stringent and growth rate regulation; and the completely unregulated PtacI promoter. The in vivo ppGpp dependency for all three promoters was verified in vitro in multiple round transcription reactions, reflecting a combination of the effects at initiation, promoter clearance, and elongation. In the main part of our study, we concentrated on the contribution of initiation complex formation to the overall inhibition of transcription. Kinetic measurements of complex association and dissociation revealed that at sensitive promoters (p)ppGpp triggered an alternative initiation pathway by RNA polymerase. This involved the stabilization of the initial closed complexes, and impeded open complex formation. Subsequently formed ternary complexes were structurally altered. Based on the above findings, we propose a model which suggests that ppGpp-altered RNA polymerases are preferentially bound and enter the alternative pathway. Thus, discrimination is obtained at early steps of initiation, which causes efficient inhibition at later steps of the transcription cycle probably involving promoter clearance and elongation.

Collodion↗

[Tricuspid valvulectomy in antibiotic-refractory right-heart endocarditis].

HISTORY AND CLINICAL FINDINGS: A 19-year-old man, known to be addicted to intravenous heroin, was admitted because of respiratory failure with a septic fever up to 40.0 degrees C. An abscess at the site of intravenously heroin injection on the right arm had been previously opened. At examination he was pale and his general condition was poor. There were numerous puncture sites over lower arm veins, some of them thrombosed. There were no signs of septic emboli to the skin and to visible mucosae. The spleen was not palpable. INVESTIGATIONS: There was leucocytosis with shift to the left, thrombocytopenia (54,000/microliter), anaemia (haemoglobin 7.9 g/dl) and markedly raised C-reactive protein (202 mg/dl). Blood culture grew Staphylococcus aureus. Transthoracic and transoesophageal echocardiography revealed a large vegetation on the tricuspid valve, confirming infectious endocarditis involving the tricuspid valve. Chest radiogram showed an infiltrate and pleural effusion of the left lung. TREATMENT AND COURSE: Infectious emboli to the lung necessitated artificial ventilation. The septic process could not be controlled by antibiotics. The whole of the tricuspid valve was therefore removed, followed by high doses of antibiotics (vancomycine, gentamicine, rifampicine). This successfully controlled the infection and a postoperative sacroileitis. Postoperative echocardiography revealed severe tricuspid regurgitation with marked enlargement of the right ventricle, paradoxical movement of the interventricular septum and a dilated inferior vena cava. 7 months postoperatively there were no clinical signs of severe right heart failure. CONCLUSION: Removal of the tricuspid valve without valve replacement can be successfully undertaken to control the infection in intravenously heroin addicts in whom the valve has been destroyed by infectious endocarditis.

Acute Disease↗

Infection of Acanthamoeba castellanii by Chlamydia pneumoniae.

Chlamydia pneumoniae is an intracellular respiratory pathogen, which, similar to Legionella, might have developed mechanisms to escape the intracellular bactericidal activity of both human host cells and amoeba. We therefore investigated the intracellular growth and survival of C. pneumoniae in Acanthamoeba castellanii by using cell culture, immunofluorescence microscopy, and electron microscopy. A castellanii was incubated with purified elementary bodies of C. pneumoniae TW 183 at a concentration of 10(6) inclusion-forming units (IFU)/ml to give a ratio of approximately 1 IFU of C. pneumoniae per amoeba. Quantitative determination of chlamydial growth within A. castellanii revealed viable and infective C. pneumoniae in the range of 10(4) to 10(5) IFU/ml between days 7 and 14 postinfection. Immunofluorescence analysis and transmission electron microscopy with subsequent immunogold staining confirmed evidence of infection of the amoebae by C. Pneumoniae and additionally revealed that C. pneumoniae entered the typical growth cycle. Our results show that amoebae allow the survival of C. pneumoniae, suggesting that amoebae may serve as an additional reservoir for Chlamydia or Chlamydia-related organisms.

Acanthamoeba↗

Isolation and long-term culture of primary ocular human immunodeficiency virus type 1 isolates in primary astrocytes.

Vitreous specimens from 14 HIV-1 infected persons undergoing medically indicated vitrectomy were assayed for the presence of infectious HIV-1 and viral tropism. Human primary fetal astrocytes, adult lymphocytes, or macrophages were exposed to vitreous in culture and and cells were then assayed for HIV-1 DNA by polymerase chain reaction amplification. We found that 11 of 14 patients tested carried ocular HIV-1 which replicated in one or more primary cell types; of the 13 vitreous samples tested in astrocytes, eight contained transmissible HIV-1. The three patients with no culturable ocular virus were in antiviral therapy at the time of vitrectomy. Comparison of envelope V3 sequences from astrocytes infected in culture to that in uncultured blood cells revealed 21% sequence divergence indicating that ocular HIV-1 transmitted to astrocytes was not recently derived from virus present in the blood. Two ocular samples transmissible to astrocytes were tested further and found capable of sustained replication by serial passage to uninfected astrocytes. However, the viral structural proteins produced by infected astrocytes were abnormal, p24 was absent and higher molecular weight Gag proteins were present. We conclude that the eye is a central nervous system compartment which frequently contains HIV-1 capable of replication in human astrocytes.

Acquired Immunodeficiency Syndrome↗

The genes of lepA and hemN form a bicistronic operon in Bacillus subtilis.

The IepA operon of Bacillus subtilis was found to be bicistronic and to consist of the two genes IepA and hemN, which encode a putative GTP-binding protein and an oxygen-independent coproporhyrinogen III oxidase, respectively. The IepA operon is located immediately upstream of the dnaK operon. Both operons are transcribed in the same direction and are not separated by an obvious transcription-terminator-like structure. The IepA operon is preceded by a potential vegetative promoter, and there is a putative strong intergenic terminator between IepA and hemN. Northern blot experiments revealed only a transcript corresponding to IepA, but expression of hemN was demonstrated in slot-blot and immunoblot experiments using antibodies raised against His-tagged HemN. The data suggest that most of the transcripts originating at the potential vegetative promoter are terminated at the intergenic terminator. Readthrough transcription into the downstream dnaK operon was not found.

Amino Acid Sequence↗

Growth of Chlamydia pneumoniae induces cytokine production and expression of CD14 in a human monocytic cell line.

Chlamydia pneumoniae was able to survive and to multiply in the human monocytic cell line Mono Mac 6. Growth of C. pneumoniae induced production of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6, as well as up-regulation of the CD14 molecule in a time-dependent manner. Infection of monocytic cells and a proinflammatory cytokine response may be important in C. pneumoniae pathogenesis.

Cell Line↗

A model of genital Chlamydia trachomatis infection using human xenografts in severe combined immunodeficiency mice.

We developed a new model of human genital Chlamydia trachomatis infection in order to characterize the pathogen-host relationship in a clinically relevant system using a human strain of C. trachomatis instead of the commonly employed mouse biovar (MoPn). Human endometrial tissue was xenografted into the skin of mice homozygous for the mutation severe combined immunodeficiency and inoculated with C. trachomatis serovar K. C. trachomatis efficiently infected the endometrium as shown by cell culture and immunofluorescence microscopy and persisted for more than 6 weeks. Chlamydial inclusions detected by direct immunofluorescence and electron microscopy appeared to be smaller than those produced by in vitro cell culture-grown chlamydiae. A pattern of localized mild infection prevailed, and infiltrative uncontrolled spread of chlamydiae was observed in only 1 of 10 infected grafts. This might correspond to the well-known tendency of the agent to cause asymptomatic infections. This model allows the study of a human genital infection resembling the clinical situation and offers the possibility to better characterize the host-parasite relationship with respect to pathogenicity and therapy.

Animals↗

[Current problems of pediatric audiology. Part II. Fitting of hearing aids, cochlear implants and care of the child with hearing loss].

Principles of fitting of hearing aids in infants and small children with special regard to limitation in fitting, measurements in situ, precision and efficiency in hearing aids choice are described. Author presented current results of the questionnaire investigations concerning early detection of children hypoacusis, preschool and public school education. Own examinations results of speech and language acquisition in deaf children as well as authors opinion on cochlear implants were presented.

Audiology↗

[Transfemoral fenestration and stent implantation in aorto-iliac dissection].

Subacute left lower limb ischemia developed in a patient with aortic dissection. Angiography revealed a dissection of the aorta abdominalis and a severe stenosis of the left common iliac artery. The patient underwent successful percutaneous fenestration and intravascular stent placement. The patient is currently (4 month post-intervention) ambulating without any signs of the leg ischemia. Percutaneous balloon fenestration and, if necessary, stent placement should be considered as a treatment option and a alternative to surgery in selected cases.

Aortic Dissection↗

[The long-term functional results following velopharyngoplasty as a speech-improving measure].

Forty three out of 148 patients who had undergone velopharyngeal flap graft between 1980 and 1992 to treat velopharyngeal insufficiency, and for whom pre- and postoperative data were available, were studied for the purpose of determining the long term morphological functional results of the treatment. Almost all of the 43 patients (93.5%) had received a velopharyngeal flap graft according to Sanvenero-Rosselli. The remaining 4.7% had received a velopharyngeal adhesion according to Stellmach. Four physicians from the fields of oral surgery, orthodontics, phoniatrics, and logopedics evaluated the pre- and postoperative data as well as the results of the follow-up examination according to subjective criteria from their respective disciplines. All four physicians judged that following velopharyngeal flap graft a gradual improvement in the ability to speak had been achieved in 86% of the patients in the follow-up study. At the time of the follow-up examination 70% of these cases were judged to have achieved a "good" qualitative level of articulation and 21% were judged to have achieved a "usefull" level. The best results were obtained in patients who had been operated on before the age of six. The reason is that in these young patients muscular malfunction and pathological movement patterns can be more easily modified than in older patients. In many cases additional speech improvement was achieved through logopedic therapy following the velopharyngeal flap graft. In the most difficult cases intensive therapy while the patients were still hospitalized proved to be especially effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Cleft Lip↗

Pulmonary artery sling with tracheal stenosis: primary one-stage repair in infancy.

Pulmonary artery sling is often associated with tracheal stenosis. In many cases repair of the vascular anomaly alone does not relieve dyspnea. Primary one-stage repair with long segment tracheal resection (2.4 cm) and relocation of the left pulmonary artery using cardiopulmonary bypass and deep hypothermic circulatory arrest is described in a 6.5-month-old girl weighing 6.5 kg. This technique resulted in normal ventilation and pulmonary flow distribution.

Bronchi↗

Advances in aortic arch surgery.

From 1980 to January 1991, 130 patients (89 men and 41 women, aged 22 to 76 years; mean age, 52 years) underwent 133 interventions on the aortic arch. Aneurysm was diagnosed in 57 patients, whereas 29 had chronic and 44 acute aortic dissection. In 67 instances a partial and in 35 instances a total arch replacement was performed. The distal arch was approached through a left thoracotomy in 14 patients. Local interventions (n = 17) included surgical reconstruction and glue procedures. Additionally, 55 patients required aortic valve replacement, preferably with composite grafts (n = 46), whereas the valve was reconstructed in 14. Procedures were performed using hypothermia (nasopharyngeal temperature, 11 degrees to 25 degrees C) and circulatory arrest (mean time, 27 minutes). Early mortality was 13.9% at the first operation on the aortic arch. Early deaths included 7 of 57 patients with aortic aneurysm (12.3%), 2 of 29 patients with chronic dissection (6.9%), and 9 of 44 patients with acute dissection (20.5%). Neurological (n = 6) and cardiac events (n = 5) were the most common causes of early death. Since 1987, 7 of 88 patients have died for an overall mortality of 8.0%. With growing experience, proper indication, and adequate operative strategy including the use of circulatory arrest in hypothermia, operation on the aortic arch can be performed with an acceptable risk.

Adult↗

[Surgical aspects of acute aortic dissection].

This paper highlights some of the surgical aspects of acute aortic dissections such as: emergency diagnosis, indications for surgery, reconstructive operative techniques, malperfusion phenomena and necessity for follow-up. Aortic dissection is caused by an intimal tear, called the "entry", and subsequent splitting of the media by the stream of blood. Two lumina are thus created, which may communicate through "re-entries". As this creates severe weakness of the aortic wall, rupture and/or dilatation are the imminent dangers of acute aortic dissection. Acute aortic dissection type A, by definition involving the ascending aorta (Figures 1 and 2), is an absolute indication for emergency surgical treatment, because its natural history shows an extremely poor outcome (Figure 3). Due to impending (intrapericardial) aortic rupture, it may be necessary to limit diagnostic procedures to a minimum. Transesophageal echocardiography is the method of choice for establishing a quick, precise and reliable diagnosis (Figure 4). In stable patients, computed tomography gives additional information about aortic diameters or sites of extrapericardial perforation. Digital subtraction angiography (DSA) shows perfusion of the lumina and dependent organs. The surgical strategy in acute aortic dissection type A aims at replacement of the ascending aorta. Reconstructive techniques have to be considered, especially in aortic valve regurgitation without annuloectasia (Figures 5 and 6). In recent times, the use of GRF tissue glue has reduced the need for teflon felt. Involvement of the aortic arch should be treated aggressively up to the point of total arch replacement in deep hypothermic circulatory arrest as part of the primary procedure (Figure 7). Malperfusion phenomena of aortic branches remain risk-factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Long-term follow-up after separate replacement of the aortic valve and ascending aorta.

Between May 1974 and November 1991, 28 patients underwent a separate replacement of the aortic valve and the ascending aorta (20 male, eight female; 32 to 71 years old, x = 52 years). 23 patients were operated for ascending aortic aneurysm, three for chronic and two for acute aortic dissection type A. 17/18 patients living at the beginning of this study were re-investigated after a mean follow-up interval of 8.5 years postoperatively with DSA, thoraco-abdominal CT and echocardiography. 1/8 biological aortic valves and 1/20 mechanical valves had to be replaced (four years and two months postoperatively) for valve degeneration and paravalvular leakage respectively. Three patients developed a sinus of Valsalva aneurysm and were reoperated five, 9.2 and 9.3 years after primary repair. In all three patients histological signs of idiopathic degenerative media disease of the aorta were found. Two other patients presented with a perfused perigraft channel and therefore had to be reoperated. Patients with chronic aortic dissection type A and/or ascending aortic aneurysms presenting clinical or intraoperative signs of degenerative media disease of the aorta should undergo composite graft replacement to preclude formation of sinus Valsalva aneurysms.

Adult↗