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Biomedical subjects

U Klein

Publications and source records attributed to U Klein.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Hyponatremia and lung edema in endometrium ablation with rollerball ablation].

OBJECTIVE: Absorption of hypotonic irrigating solution with consecutive severe hyponatremia is a potential risk of the endometrial rollerball ablation procedure. MATERIAL AND METHODS: We report the case of a 45-year-old female, who underwent an endometrial rollerball ablation procedure. RESULTS: After irrigating the uterine cavity for 45 min with 10 1 of 2.7% Sorbitol and 0.54% Mannitol she developed clinical signs of pulmonary edema with severe hyponatremia. CONCLUSIONS: A TUR-like syndrome as a potential risk of the rollerball ablation procedure is discussed briefly. Strategies to minimize the risk and to early detect the TUR-like syndrome are suggested.

Dilatation and Curettage↗
PubMed1998

Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells.

Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM+IgD+ B cells. IgM+IgD+CD27(+) B cells resemble class-switched and IgM-only memory cells in terms of cell phenotype, and comprise approximately 15% of PB B lymphocytes in healthy adults. Moreover, a very small population (<1% of PB B cells) of highly mutated IgD-only B cells was detected, which likely represent the PB counterpart of IgD-only tonsillar germinal center and plasma cells. Overall, the B cell pool in the PB of adults consists of approximately 40% mutated memory B cells and 60% unmutated, naive IgD+CD27(-) B cells (including CD5(+) B cells). In the somatically mutated B cells, VH region genes carry a two- to threefold higher load of somatic mutation than rearranged Vkappa genes. This might be due to an intrinsically lower mutation rate in kappa light chain genes compared with heavy chain genes and/or result from kappa light chain gene rearrangements in GC B cells. A common feature of the somatically mutated B cell subsets is the expression of the CD27 cell surface antigen which therefore may represent a general marker for memory B cells in humans.

Adult↗
PubMed1998

BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci.

The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown, but it is commonly believed that this mechanism is restricted to the Ig loci. B cell lymphomas commonly display multiple somatic mutations clustering in the 5'-regulatory region of BCL-6, a proto-oncogene encoding for a POZ/Zinc finger transcriptional repressor expressed in germinal center (GC) B cells and required for GC formation. To determine whether BCL-6 mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism, we screened single human tonsillar GC B cells for mutations occurring in the BCL-6 5'-noncoding region and in the Ig variable heavy chain sequences. Thirty percent of GC B cells, but not naive B cells, displayed mutations in the 742 bp region analyzed within the first intron of BCL-6 (overall frequency: 5 x 10(-4)/bp). Accordingly, an expanded survey in lymphoid malignancies showed that BCL-6 mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying mutated Ig variable heavy chain sequences. These results indicate that the somatic hypermutation mechanism active in GC B cells physiologically targets non-Ig sequences.

B-Lymphocytes↗
PubMed1998

Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease.

Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged VH region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found in naive B cells, approximately 4% of in-frame and >40% of out-of-frame rearrangements of GC B cells harbored deletions and/or insertions of variable length. The pattern of deletions/insertions and their restriction to mutated V genes strongly suggests that they result from somatic hypermutation. Deletions and insertions account for approximately 6% of somatic mutations introduced into rearranged VH region genes of GC B cells. These deletions/insertions seem to be the main cause for the generation of heavy chain disease proteins. Furthermore, it appears that several types of oncogene translocations (like c-myc translocations in Burkitt's lymphoma) occur as a byproduct of somatic hypermutation within the GC-and not during V(D)J recombination in the bone marrow as previously thought.

B-Lymphocytes↗
PubMed1998

Changes in pulmonary mechanics after fiberoptic bronchoalveolar lavage in mechanically ventilated patients.

OBJECTIVE: We prospectively assessed the impact of bronchoalveolar lavage (BAL) on respiratory mechanics in critically ill, mechanically ventilated patients. STUDY DESIGN: Mechanically ventilated patients underwent BAL of one lung segment using 5 x 20 ml of sterile, physiologic saline with a temperature of 25-28 degrees C. The fractional inspired oxygen was increased to 1.0, but ventilator settings were otherwise left unchanged. Static pulmonary compliance, pulmonary resistance, alveolar ventilation, and serial dead space were measured 60 min and 2 min before and 8, 60, and 180 min after BAL to assess the consequences of the procedure. In addition, blood gases [partial pressure of carbon dioxide in arterial blood (PaCO2) and arterial oxygen tension (PaO2)], hemodynamic variables (heart rate, systolic and diastolic blood pressure), and body temperature were recorded at the same time points. SETTING: Intensive care unit of a university hospital. PATIENTS: 18 consecutive critically ill, mechanically ventilated patients. RESULTS: Pulmonary compliance decreased by 23% (p < 0.05) and pulmonary resistance increased by 22% (p < 0.05) shortly after BAL. The changes in pulmonary compliance and resistance were more than 30% in one third of the patient population. One hour after the procedure, PaO2 was significantly lower and PaCO2 significantly higher than before the procedure. Three hours after the procedure, pulmonary resistance returned to pre-BAL values but compliance remained 10% below baseline values (p < 0.05). CONCLUSION: BAL in mechanically ventilated patients is associated with deterioration of pulmonary mechanics and function.

Adult↗
PubMed1998

Lung flooding--a new method for complete lung sonography.

A sonographic examination of the lung has so far been impossible because of sound reflection. In conjunction with video-assisted thoracoscopic surgery, lung sonography would be helpful to make up for the lack of direct palpation. Animal experiments with pigs were performed to find out whether lung sonography becomes possible following bronchoalveolar flooding with a suitable liquid. The lung was filled with whole electrolyte solution through the left leg of a double-lumen endotracheal tube after resorption atelectasis (method 1) or compressive atelectasis (method 2). As an alternative, liquid perfluorocarbon was used (method 3). Under atelectasis, the lung thus flooded was investigated by ultrasound applied transpleurally and endobronchially. The first results proved that lung flooding is possible if certain prerequisites are fulfilled. Perfluorocarbon flooding led to total sound absorption which prevented sonography, whereas flooding with whole electrolyte solution made complete lung sonography possible, making visible the intrapulmonary vessels, bronchi and peribronchial lymphatic nodes. Measurements proved that the unilateral flooding caused no significant changes in the arterial and central venous pressure nor in transcutaneous oxygen saturation.

Animals↗
PubMed1998

Role of fiberoptic bronchoscopy in conjunction with the use of double-lumen tubes for thoracic anesthesia: a prospective study.

BACKGROUND: Fiberoptic bronchoscopy has been recommended to verify the position of double-lumen tubes (DLT), but this remains controversial. The authors studied the role of bronchoscopy for placing and monitoring right- and left-sided DLTs after blind intubation and after positioning the patient. METHODS: Two hundred patients having thoracic surgery requiring DLT insertion were prospectively studied. "Blind" tracheal intubations were done with 163 left-sided and 37 right-sided disposable polyvinyl chloride Robertshaw tubes. Bronchoscopy was performed by a different anesthesiologist after intubation and conventional clinical verification of correct placement and after patient positioning for thoracotomy. A DLT was considered malpositioned when it had to be moved >0.5 cm to correct its position. Critical malpositions were those that might have affected patient safety or influenced the surgical procedure if left uncorrected. RESULTS: After "blind" DLT intubation, clinical evidence of malpositioning was found in 28 patients. This was confirmed by fiberoptic assessment. In 172 patients in whom placement was judged correct by clinical assessment, malpositioning was detected by bronchoscopy in 79 cases, 25 of which were critical. After patient positioning, DLTs were found to be displaced in 93 patients, 48 of which were critical. Right-sided DLTs were significantly more likely to be malpositioned than were left-sided DLTs. Two complications were related to unsatisfactory lung separation in the 200 patients studied. CONCLUSIONS: After blind intubation and patient positioning, more than one third of DLTs required repositioning. Routine bronchoscopy is therefore recommended after intubation and after patient positioning.

Adolescent↗
PubMed1998

Somatic hypermutation in normal and transformed human B cells.

In the human, most IgM+IgD+ as well as CD5+ peripheral blood B cells express unmutated V genes and thus can be assigned to a pre-germinal centre (GC) stage of development. The memory B-cell compartment generated in the GC reaction and characterized by cells bearing somatically mutated V-region genes consists not only of class-switched cells, but also of IgM-only B cells and perhaps a subset of IgM+IgD+B cells expressing the CD27 antigen. Comparison of the rearranged V-region genes of human B-cell lymphomas with those of the normal B-cell subsets allows the identification of the progenitor cells of these tumours in terms of their stage of maturation. On this basis, most B-cell non-Hodgkin lymphomas, and in addition Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD), are derived from B cells at a GC or post-GC stage of development. The mutation pattern indicates that the precursors of the tumour clones have been stringently selected for expression of a functional antigen receptor with one notable exception: HRS cells in classical (but not lymphocyte-predominant) HD appear to be derived from "crippled" GC B cells. Sequence analysis of rearranged V genes amplified from single tonsillar GC B cells revealed that the somatic hypermutation process introduces deletions and/or insertions into V-region genes more frequently than indicated by previous investigations. Presumably, this feature of the hypermutation mechanism is often responsible for the generation of heavy chain disease, and also several types of chromosomal translocations of oncogenes into immunoglobulin loci in human B-cell lymphomas.

Animals↗
PubMed1998

Endogenous fluctuations of DNA topology in the chloroplast of Chlamydomonas reinhardtii.

DNA supercoiling in the chloroplast of the unicellular green alga Chlamydomonas reinhardtii was found to change with a diurnal rhythm in cells growing in alternating 12-h dark-12-h light periods. Highest and lowest DNA superhelicities occurred at the beginning and towards the end of the 12-h light periods, respectively. The fluctuations in DNA supercoiling occurred concurrently and in the same direction in two separate parts of the chloroplast genome, one containing the genes psaB, rbcL, and atpA and the other containing the atpB gene. Fluctuations were not confined to transcribed DNA regions, indicating simultaneous changes in DNA conformation all over the chloroplast genome. Because the diurnal fluctuations persisted in cells kept in continuous light, DNA supercoiling is judged to be under endogenous control. The endogenous fluctuations in chloroplast DNA topology correlated tightly with the endogenous fluctuations of overall chloroplast gene transcription and with those of the pool sizes of most chloroplast transcripts analyzed. This result suggests that DNA superhelical changes have a role in the regulation of chloroplast gene expression in Chlamydomonas.

Animals↗
PubMed1998

[Value of aspiration of tracheal secretions and bronchoalveolar lavage in diagnosis of nosocomial pneumonia in ventilated patients].

The diagnostic value of endotracheal aspirates with quantitative assessment and bronchoalveolar lavage (BAL) was investigated in 104 mechanically ventilated patients in an anaesthesiologic/surgical intensive care unit. Patients were either considered as "pneumonia positive" (77 patients) according to clinical, radiological or laboratory criteria or "pneumonia negative" (27 patients). Using a threshold of 10(5) colony forming units (cfu) per ml for endotracheal aspirates and 10(4) cfu/ml for BAL-fluid, the results were similar for both techniques (sensitivity 74% and 77% respectively; specifity 63%). In our investigation, in 80% of the cases microbial growth was observed in either both or neither of the techniques. Therefore 20% of the patients had positive results in only one of the two diagnostic procedures. As a consequence of the presented study, quantitative assessment of endotracheal aspirates as a cost-effective, low-invasive and simple technique could be helpful in diagnosing nosocomial pneumonia in mechanically ventilated patients. Performance of BAL is indicated in patients with clinical signs of nosocomial pneumonia and negative results in endotracheal aspirates (< 10(5) cfu/ml). Nevertheless, diagnostic uncertainty will remain in about 15% of all cases, even when both techniques are applied. The primary use of invasive bronchoscopic techniques, such as BAL, in diagnosis of nosocomial pneumonia has to be considered critically.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Molecular single-cell analysis reveals that CD5-positive peripheral blood B cells in healthy humans are characterized by rearranged Vkappa genes lacking somatic mutation.

B cells expressing the CD5 cell surface antigen are involved in certain B cell malignancies and autoimmune diseases. From studies in the mouse, it emerged that CD5+ B cells represent a separate lineage of B lymphocytes that, in contrast to conventional (CD5-) B cells, are not driven into T cell-dependent immune responses in which rearranged variable (V) region genes are diversified by somatic hypermutation. Against this background it came as a surprise that human disease-involved CD5-positive autoreactive B cells as well as B cell chronic lymphocytic leukemias can harbor somatically mutated V region genes. Recent V gene analyses on CD5+ B cells in healthy adults did not give rise to a clear picture about the fraction of somatically mutated among all CD5+ B cells. In this work we used a molecular single-cell analysis to determine reliably the frequency of mutated CD5+ B cells in healthy humans: single, kappa light chain-expressing CD5+ peripheral blood B cells were isolated by flow cytometry, and rearranged Vkappa genes were amplified by PCR. From one donor, CD5+CD19+ B cells were analyzed. Since CD5+ B cells were found among IgM+IgD+ and IgM+IgD- cells (but almost not among class-switched cells) from two other donors, individual cells corresponding to these IgM-expressing subsets were investigated separately. The sequence analysis of rearranged Vkappa genes revealed that most if not all CD5+ B cells in healthy humans carry unmutated V region genes. From one of the donors, a novel polymorphic Jkappa2 gene segment was identified. To explain the discrepancy between the frequent occurrence of disease-associated somatically mutated CD5+ B cells and the low incidence or absence of somatic mutation in normal CD5+ B cells, we speculate that CD5+ B cells usually do not participate in germinal center reactions, but if they occasionally do so, they may be at an increased risk to become involved in autoimmune diseases or B cell malignancies.

Adult↗
PubMed1997

A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B.

The alpha-subunit of eukaryotic initiation factor 2B (eIF-2B), a guanine nucleotide exchange protein that functions in regulation of translation, was observed to associate with the carboxyl-terminal cytoplasmic domains of the alpha2A- and alpha2B-adrenergic receptors in a yeast two-hybrid screen of a cDNA library prepared from 293 cells. This protein association was confirmed in vitro by affinity chromatography and was shown to be specific for a subset of G protein-coupled receptors, including the alpha2A-, alpha2B-, alpha2C-, and beta2-adrenergic receptors, but not the vasopressin (V2) receptor. Association of these proteins in vivo was confirmed by specific co-immunoprecipitation of eIF-2Balpha with full-length beta2-adrenergic receptors expressed in transfected 293 cells and by fluorescence microscopy showing co-localization of these proteins in intact cells. Remarkably, eIF-2Balpha co-localized with receptors exclusively in regions of the plasma membrane that are in contact with the extracellular medium, but failed to associate with membranes making cell-cell contacts. Overexpression of eIF-2Balpha in 293 cells caused a small (approximately 15%) but significant enhancement of beta2-adrenergic receptor-mediated activation of adenylyl cyclase, without affecting forskolin or V2 receptor-mediated activation. These observations suggest a new role for a previously identified guanine nucleotide exchange protein in membrane biology and cell signaling.

Amino Acid Sequence↗
PubMed1997

The H+ pump in frog skin (Rana esculenta): identification and localization of a V-ATPase.

We here report on studies on the frog skin epithelium to identify the nature of its excretory H+ pump by comparing transport studies, using inhibitors highly specific for V-ATPases, with results from immunocytochemistry using V-ATPase-directed antibodies. Bafilomycin A1 (10 microM) blocked H+ excretion (69 +/- 8% inhibition) and therefore Na+ absorption (61 +/- 17% inhibition after 60 min application, n = 6) in open-circuited skins bathed on their apical side with a 1 mm Na2SO4 solution, "low-Na+ conditions" under which H+ and Na+ fluxes are coupled 1:1. The electrogenic outward H+ current measured in absence of Na+ transport (in the presence of 50 microM amiloride) was also blocked by 10 microM bafilomycin A1 or 5 microM concanamycin A. In contrast, no effects were found on the large and dominant Na+ transport (short-circuit current), which develops with apical solutions containing 115 mm Na+ ("high-Na+ conditions"), demonstrating a specific action on H+ transport. In immunocytochemistry, V-ATPase-like immunoreactivity to the monoclonal antibody E11 directed to the 31-kDa subunit E of the bovine renal V-ATPase was localized only in mitochondria-rich cells (i) in their apical region which corresponds to apical plasma membrane infoldings, and (ii) intracellularly in their neck region and apically around the nucleus. In membrane extracts of the isolated frog skin epithelium, the selectivity of the antibody binding was tested with immunoblots. The antibody labeled exclusively a band of about 31 kDa, very likely the corresponding subunit E of the frog V-ATPase. Our investigations now deliver conclusive evidence that H+ excretion is mediated by a V-ATPase being the electrogenic H+ pump in frog skin.

Animals↗
PubMed1997

Evidence for a large compartment of IgM-expressing memory B cells in humans.

The recent finding of somatically mutated mu heavy chain transcripts in human peripheral blood (PB) B lymphocytes suggests that T-dependent B-cell memory might not be restricted to class-switched cells. We provide here evidence that IgM-only PB B cells are likely to be the IgM-expressing counterpart of classical (IgM- IgD-) memory B cells in humans. As shown by molecular single cell analysis, most IgM-only cells carry mutated V region genes, like class-switched cells. Although both subsets represent populations of nonactivated, resting cells, they express higher levels of Ig mRNA than naive (IgM+ IgD+) B cells. IgM-only and class-switched cells are CD38- CD77-, and mostly CD23-, thus neither resembling germinal center nor naive B cells. Because many IgM-expressing B cells located in secondary lymphoid tissues resemble IgM-only PB B cells in terms of cell phenotype, we propose that the human lymphoid system contains a large compartment of IgM-expressing memory cells. Moreover, these cells seem to represent the nonmalignant counterparts of IgM-expressing tumor cells in sporadic Burkitt's lymphoma, MALT lymphoma, monocytoid B-cell lymphoma, and diffuse large-cell lymphoma that were found to harbor somatically mutated V genes.

B-Lymphocyte Subsets↗
PubMed1997

[Staphylococcus-associated blepharokeratoconjunctivitis. Clinical findings, pathogenesis and therapy].

BACKGROUND: Staphylococci represent an important source of external infections of the eye. In addition to acute staphylococcal conjunctivitis a spectrum of subacute or chronic disease may be found. According to Valenton und Okumoto, with this staphylococci-associated blepharo-kerato-conjunctivitis in culture-positive cases S. aureus is found in 31% and S. epidermidis in 69% of smears. Microbiallergic and toxic mechanisms are the underlying etiology. PATIENTS: We report on a series of 38 patients with "red eye" that were seen between 1992 and 1994 in the external disease clinic at the Department of Ophthalmology, University of Heidelberg. RESULTS: There were 17 female and 21 male patients. The mean age was 53 +/- 20 years. The patient's complaints included recurrent red eyes with discomfort and pain. Clinically, a squamous blepharitis (63%) and conjunctivitis (87%) were present. Upon biomicroscopic evaluation, a corneal involvement could be found in 80% of cases. In 66% of cases conjunctival swabs were positive for staphylococci. DISCUSSION: The blepharitis may be squamous or ulcerative. The underlying cause is a dermal irritation by staphylococcal toxins. As early as 1937, Thygeson and Allan postulated a toxin-induced skin irritation by a "dermonecrotic factor." In chronic cases a papillary conjunctivitis caused by a toxin reaction can be observed. Histologically, no lymph follicles or eosinophils are present. Several types of keratitis and corneal involvement are found. An epithelial keratitis is caused by toxic mechanisms. Marginal infiltrates and ulcers indicate an antigen-antibody reaction. Phlyctenulae indicate a delayed immune reaction (Gell and Coombs type IV). Complications include vascular pannus, corneal scarring, and rarely corneal melting and ulcers. Therapy depends on the severity of the inflammation and the underlying pathomechanism. This includes reduction of toxin-producing organisms by hygiene of the lid margins and application of topical disinfectants and antibiotics. With immunological phenomena topical steroids are required.

Adolescent↗
PubMed1997

[Risks and side effects of diagnostic bronchoalveolar lavage in ventilated patients].

Bronchoalveolar lavage is used increasingly often as a diagnostic tool in critically ill patients undergoing mechanical ventilation. Most patients, even those with haemodynamic instability or respiratory failure, tolerate the procedure without marked adverse effects. A relatively small proportion of patients, however, will experience potentially deleterious side effects like prolonged deterioration of pulmonary mechanics, oxygen desaturation or sepsis-like symptoms. Despite all precautions, it is not possible to date to identify increased-risk patients beforehand. The potential benefits, namely, early diagnosis of an aetiological agent who is responsible for infection, must therefore be carefully weighted against the risks.

Bronchoalveolar Lavage Fluid↗
PubMed1997

On-demand analgesia with piritramide in children. A study on dosage specification and safety.

The results of this study show that postoperative patient-controlled pain therapy in children with piritramide is - in a similar way as with adults - a safe method involving a low incidence of side effects. A special pump parameter setting is required with larger bolus dose sizes and longer lockout intervals, not very different from the experience gained with adults, and which is based on other values than those recommended up to now with morphine for paediatric PCA. Side effects were rarely observed. The fear of respiratory depression constitutes no rational reason to deny the younger patients this form of analgesia provided that monitoring is guaranteed.

Adolescent↗