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Biomedical subjects

J Lenz

Publications and source records attributed to J Lenz.

At least 55 records · Page 3Linked to original sources

Transcriptional activity of core binding factor-alpha (AML1) and beta subunits on murine leukemia virus enhancer cores.

Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates the DNA binding activity of CBF alpha. One of the genes that encodes a CBF alpha subunit is AML1, also called Cbf alpha 2. This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias. An exogenously expressed Cbf alpha 2-encoded subunit (CBF alpha 2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells. Activity was mediated through the core elements. Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer. The longest form, CBF beta-187, increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells, although it had no effect in P19 cells. Transcriptional activation by CBF beta required binding to the CBF alpha subunit, as a form of CBF beta that lacked binding ability, CBF beta-148, failed to increase activity. These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits. They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores. We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv. This difference strongly affects transcription in T cells and leukemogenicity of SL3. However, no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays. Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated.

Animals↗

The personal telemedicine system. A new tool for the delivery of health care.

An inexpensive home telemedicine system has been developed, comprising a personal telemedicine unit in the patient's home connected by ordinary telephone lines to a central nursing station. Using this system a nurse or other health-care professional at the central station was able to make a 'video visit' to the patient's home. In a preliminary trial, patients were referred by the patient's physician or by a home-care nurse. All 12 patients learned to use the personal telemedicine unit easily and effectively, and there were no complications related to its use. A significant finding was a reduction in the number of home-care visits in seven of the 12 patients (58%). Telecare using the personal telemedicine system was significantly cheaper than care delivered by conventional routes. The average charge was about $15 for a video visit by a nurse, compared with about $90 for a real visit.

Adolescent↗

[Thoracic actinomycosis].

Thoracic actinomycosis is a rare disease without characteristic clinical signs. Approximately 90% of patients suffering from thoracic actinomycosis have undergone diagnostic and therapeutic procedures based on a wrong diagnostic hypothesis (malignancies 35-44%, other pulmonary disorders 33-35%). The opportunities for a timely and adequate diagnosis by the use of clinical examination, laboratory studies, microbiology studies, radiologic imaging or invasive measures are limited. In 85%, thoracic actinomycosis has not been identified prior to thoracotomy, open biopsy and histological examination. Based on a wrong diagnostic hypothesis, resective thoracic surgery according to the principles of oncologic surgery can hardly be avoided. We report on a 43-year-old male suffering from actinomycosis of the left hemithorax. Clinical signs, differential diagnosis, treatment and clinical course are described. The role of surgery in the treatment protocol of thoracic actinomycosis is discussed. In pulmonary and pleural disorders of unknown origin, differential diagnosis should include thoracic actinomycosis as early as possible. Due to the considerably high mortality rate of untreated disease, the outcome of thoracic actinomycosis can only be improved by a timely and combined employment of surgical and antibiotic therapy.

Actinomycosis↗

[Treatment of pilonidal sinus with excision and primary suture using a local, resorbable antibiotic carrier. Results of a prospective randomized study].

The excision of a pilonidal sinus with wound healing by second intention, often results in a long duration of treatment. On the other hand, primary suture after excision has a high rate of abscess formation. In a randomized study we treated 40 patients with excision of pilonidal sinus, insertion of a collagen sponge containing Gentamicin and primary suture (group 1) to prevent this abscess formation. Another 40 patients were treated in the same way but without applying the Gentamicin-collagen sponge (group 2). There had been no significant differences as to the history and duration of the disease, the wound size, the degree of inflammation, the weight of the patients or the amount of hair near the sinus. In group 1 only 7.5% of the patients had a postoperative abscess formation, in contrast to group 2, with an abscess rate of 52.5% and consecutive surgery (p less than 0.001). One year after the operation the recurrence rate was 0 in both groups. Considering the results mentioned, surgical excision of the pilonidal sinus in combination with insertion of a resorbable antibiotic sponge we recommend this therapy.

Abscess↗

DNA binding properties of YB-1 and dbpA: binding to double-stranded, single-stranded, and abasic site containing DNAs.

A number of eukaryotic DNA binding proteins have been isolated by screening phage expression libraries with DNA probes containing the binding site of the DNA-binding protein. This methodology was employed here to isolate clones of the factor that interacts with the W box element of the human major histocompatibility complex HLA-DQB gene. Surprisingly, several cDNA clones of YB-1, a cDNA clone that was previously isolated with a CCAAT element-containing sequence were found. Independently, the screening of phage expression libraries with depurinated DNA resulted in the isolation of YB-1 and dbpA, a previously isolated cDNA that has homology to YB-1. Additional characterization of YB-1 showed that it bound a wide variety of DNA sequences and suggested that the binding of this protein is promiscuous. Furthermore, we show that both YB-1 and dbpA bind to depurinated DNA better than undamaged DNA and that the extent of specificity of binding is influenced by Mg2+. Due to the lack of sequence specificity and high degree of binding to depurinated DNA, we suggest that these proteins might be involved in chromosome functions such as maintenance of chromatin structure or DNA repair that do not require sequence-specific binding.

Base Sequence↗

Transcriptional initiation and postinitiation effects of murine leukemia virus long terminal repeat R-region sequences.

Sequences within the R components of the long terminal repeats (LTRs) of several retroviruses are known to be involved at various steps in expression of the viral genomes. A series of experiments was performed to test whether sequences within the R regions of the murine leukemia viruses Akv and SL3-3 affect viral expression. By using plasmid clones of the viral LTRs linked to a reporter gene, deletion of the R region was found to decrease expression to variable extents in a series of mammalian cell lines, with the largest effects being detected in murine fibroblasts. R-region sequences from the human immunodeficiency virus type 1 LTR or a random sequence were unable to substitute for the murine leukemia virus sequences. Transcripts from the R-region-deleted templates were initiated at the proper site in the LTR, but their levels were decreased at least 10-fold. Nuclear run-on assays showed that the decrease caused by the R-region deletions was due, in part, to an effect on RNA polymerase loading, suggesting an effect on transcriptional initiation. The remainder of the activity was presumably due to a posttranscriptional effect. Analysis of the R-region sequences of murine leukemia viruses and related retroviruses led to the prediction of a conserved secondary structure in the transcribed RNA that might have a role in activity. We conclude that R-region sequences are of importance for the expression of a variety of retroviruses.

3T3 Cells↗

Analysis of the significance of two single-base-pair differences in the SL3-3 and Akv virus long terminal repeats.

Two single-base-pair differences between the long terminal repeats (LTRs) of the T-lymphomagenic murine retrovirus SL3-3 and nonleukemogenic Akv virus were tested for effects on activity of the LTRs. Evidence was obtained from electrophoretic mobility shift assays for the presence of at least one factor in both T and non-T cells that bound to the region of the viral enhancers that contained the differences. However, no significant differences in activity in expression assays were detected when the two base-pair differences were exchanged between the two LTRs. Therefore, they do not contribute to the higher activity of the SL3-3 LTR in T-lymphoma cell lines.

Animals↗

Construction of a replication-competent murine retrovirus vector expressing the human immunodeficiency virus type 1 tat transactivator protein.

A replication-competent Akv murine leukemia virus-based vector encoding the human immunodeficiency virus tat cDNA under control of the simian virus 40 early promoter sequences was constructed. The simian virus 40 tat sequences were placed within the U3 region of the 3' long terminal repeat. The resulting virus, derived by transfection, replicated efficiently in mouse NIH 3T3 cells and maintained the tat cDNA insert. It has been suggested that Tat function requires the presence of a human-specific cofactor, which is absent in murine cells. However, infection of murine cells with the Akv virus encoding tat resulted in significant transactivation of a human immunodeficiency virus long terminal repeat-driven reporter gene, indicating that human cofactors are not always required for Tat function. The vector system described may be useful for introduction of foreign genes in vivo and in whole animals when virus spread is required for efficient infection and levels of gene expression.

Animals↗

[Heparin-associated thrombocytopenia, thrombosis and embolism. Side effects of thromboembolism prevention with low molecular weight heparin enoxaparin?].

Heparin-associated thrombocytopenia (HAT) is a rarely described adverse reaction of systemic administration of heparin that may be complicated by thrombosis, embolism and bleeding. Unfractionated heparin as well as low molecular weight heparin may provoke HAT. A case of HAT complicated by thrombosis and pulmonary embolism is described that came about during preventive postoperative anticoagulation with the low molecular weight heparin enoxaparin. Pathogenesis, diagnosis, prophylaxis and therapy of HAT are discussed.

Aged↗

[Early management of the intrathoracic area].

The procedures of preclinical management of chest injuries are presented. Emphasis is put on the different aspects of "acute thorax": sucking chest wound, pericardial tamponade, oligemic shock and open thorax. The primary acute management includes the chest tube, intubation, ventilation, pericardiocentesis and surgical management of penetrating chest trauma. The different in the literature are discussed.

Drainage↗

[Correlation of lymph node size and metastatic involvement of lymph nodes in bronchial cancer].

For preoperative staging in lung cancer mediastinoscopy is in competition with X-ray, tomography, and computer-tomography (CT). Many authors certify a high sensitivity and specificity to CT in staging lung cancer preoperatively by measuring the diameter of the hilar and mediastinal lymph nodes. In this study we measured the diameter of 162 lymph nodes from 83 patients postoperatively. In view of staging we found no sufficient correlation between the diameter of the lymph nodes and their infiltration by cancer cells. Even 35.7% of the nodes with a diameter of more than 2 cm were not infiltrated. The data support the opinion that CT alone is not sufficient for preoperative staging in lung cancer.

Adenocarcinoma↗

Types and correlates of blood/injury-related vasovagal syncope.

This study investigated by interview, the initial syncopal episode of 103 blood/injury-related vasovagal fainters in order to examine two competing hypotheses concerning their origins. Graham (Circulation, 23, 901-906, 1961) postulated that the faint resulted when sympathetic nervous system (SNS) activity ceased on termination of a threat, leaving parasympathetic nervous system (PNS) activation unopposed. Engel [Fainting (2nd edn), 1962; Annals of Internal Medicine, 89, 901-906, 1978] proposed that when in the face of threat with SNS activation, escape is blocked, the PNS becomes activated as the conservation-withdrawal response, leading to syncope. We found cases clearly conforming to each of these formulations as well as some with characteristics of both, and some who fainted in response to blood or injury but with no perception of threat. The Graham and Engel types did not differ in terms of fear or avoidance of blood, injury, or medically-related situations nor did they differ in the frequency with which their parents reported blood/injury-related syncopal episodes. It is proposed that both may be activated by a common psychological mechanism involving cessation of a defensive posture. In contrast, the non-threat fainters showed significantly less medically-related avoidance and had a greater percentage (94%) of parents with positive faint histories.

Adult↗

Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites.

Damage to DNA can have lethal or mutagenic consequences for cells unless it is detected and repaired by cellular proteins. Repair depends on the ability of cellular factors to distinguish the damaged sites. Electrophoretic binding assays were used to identify a factor from the nuclei of mammalian cells that bound to DNA containing apurinic sites. A binding assay based on the use of beta-galactosidase fusion proteins was subsequently used to isolate recombinant clones of human cDNAs that encoded apurinic DNA-binding proteins. Two distinct human cDNAs were identified that encoded proteins that bound apurinic DNA preferentially over undamaged, methylated, or UV-irradiated DNA. These approaches may offer a general method for the detection of proteins that recognize various types of DNA damage and for the cloning of genes encoding such proteins.

Animals↗

Relative importance of elements within the SL3-3 virus enhancer for T-cell specificity.

Elements within the enhancer of T-lymphomagenic SL3-3 virus were examined for their contributions to transcriptional activity in T lymphocytes and non-T cells. A region containing two sequences homologous to the enhancer core consensus sequence and a sequence homologous to the binding site for factor LVb was found to have the largest effect on activity. Evidence was obtained that suggests that the activity of this region was greater in T lymphocytes than in non-T cells and that multiple elements within it were necessary for activity. A second region, containing sequences homologous to the binding site of factor NF-I and the glucocorticoid response element, had about a twofold effect on transcription in both T lymphocytes and non-T cell lines. The twofold effect was seen whether the region containing the cores and LVb site was present or not. These results indicate that the most important region for the specificity of SL3-3 enhancer activity and, presumably, for viral leukemogenicity comprises the core elements and the LVb site. DNA-protein-binding studies demonstrated that one cellular factor, S/A-CBF, bound to both core elements, while a second cellular factor, S-CBF, bound to only one of them. In combination with earlier studies, this indicates that cells contain multiple factors that bind to the critical region.

Animals↗

[Poly-, multiple trauma and intra-abdominal injuries].

The present work deals with the problem of abdominal injuries in polytraumatized patients. The results were obtained from a retrospective study of the records of 530 polytraumatized patients treated at the Central Hospital of the German Federal Armed Forces (Bundeswehr). In all, 193 of these patients had abdominal injuries. The overall mortality was 23.8% (n = 126): mortality among the patients with abdominal injuries was 26% (n = 50). Abdominal injuries alone led to death in 9.1% (n = 1), but mortality increased to 18.4% when at least one extra-abdominal injuries was also present. A combination of abdominal injuries and two or more extra-abdominal lesion led to a mortality rate of 27%. Mortality was found to be age- and sex-related: in young children and patients over 55 years (especially those around 70) mortality was 33.3%-72%. Among the cases with fatal outcome there was a female-to-male ratio of 3:2. The most common causes of death were: hemorrhage shock (62.3%), head injuries (37.7%), septicemia (8.1%), pneumonia, and ARDS (5.4% each). Within the last eight years we have used the following supplementary examination methods: computed tomography, peritoneal lavage, and ultrasonography. The retrospective study has shown that CT is not the examination of choice. The reliability with lavage and ultrasonography was approximately the same, but lavage was found to be more dangerous. Therefore, we abandoned lavage and used sonography only. However, we are of the opinion that any surgeon should use the examination method that has yielded the best results for him or her, to ensure the best possible outcome for the patient.

Abdominal Injuries↗

[Detection of glycosphingolipids of ABH and Le antigens on thin-layer plates using the PAP method].

Stroma from hemolyzed erythrocytes of blood groups 0, A1, B and A1B were obtained and subjected to butanol/phosphate buffer extraction. This extract was separated using HPTLC, and the ABH and Le substances were detected on the chromatogram using the PAP technique. The staining of the bands allowed specific demonstration of the serologically active glycosphingolipids present in the ABH and Le blood group substances. The antigens of the AB0 system showed a 3- to 12-band pattern. Each of the antigens Lea and Leb presented 3 bands. The slight differences in the levels of glycosphingolipids of equal chain lengths are probably due to differences in their chemical structures.

ABO Blood-Group System↗