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Biomedical subjects

K Klingler

Publications and source records attributed to K Klingler.

At least 19 recordsLinked to original sources
PubMed2000

[Inpatient rehabilitation in inpatients with chronic obstructive lung diseases (COPD): effect on physical capacity for work, psychological wellbeing and quality of life].

Success of inpatient rehabilitation for patients with chronic obstructive pulmonary disease (COPD) was assessed in a prospective study of 39 patients (mean age = 71 years). Six months after hospital stay (mean duration 22.4 days), physical endurance as assessed by the 6-minute walk distance remained unchanged. Subjective health measures improved (SF36 21 vs 29%; p < 0.05), MRC-dyspnoea was reduced (2.61 vs 2.19; p < 0.05) and measures of global quality of life also improved (56.1 vs 67.5; p < 0.05). Meanwhile, anxiety symptoms were reduced (7.7 vs 6.0; p < 0.05); no changes in depression scores were observed (6.8 vs 6.2; p = 0.271). A novel visual method to assess the burden of suffering, PRISM (Pictorial Representation of Illness and Self Measure), was applied for the first time in COPD patients. PRISM scores improved significantly (6.3 vs 12.2; p < 0.001). In conclusion, inpatient pulmonary rehabilitation improved subjective physical health measures and reduced anxiety levels.

Aged↗
PubMed1999

Downregulation of c-kit (stem cell factor receptor) in transformed hematopoietic precursor cells by stroma cells.

We show a dramatic downregulation of the stem cell factor (SCF) receptor in different hematopoietic cell lines by murine stroma. Growth of the human erythroid/macrophage progenitor cell line TF-1 is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). However, TF-1 cells clone and proliferate equally well on stroma. Independent stroma-dependent TF-1 clones (TF-1S) were generated on MS-5 stroma. Growth of TF-1S and TF-1 cells on stroma still requires interaction between c-kit (SCF receptor) and its ligand SCF, because antibodies against c-kit inhibit growth to less than 2%. Surprisingly, c-kit receptor expression (RNA and protein) was downregulated by 2 to 3 orders of magnitude in TF-1S and TF-1 cells grown on stroma. This stroma-dependent regulation of the kit receptor in TF-1 was also observed on exposure to kit ligand-negative stroma, thus indicating the need for heterologous receptor ligand interaction. Removal of stroma induced upregulation by 2 to 4 orders of magnitude. Downregulation and upregulation of c-kit expression could also be shown for the megakaryocytic progenitor cell line M-07e and was comparable to that of TF-1, indicating that stroma-dependent regulation of c-kit is a general mechanism. Downregulation may be an economic way to compensate for the increased sensitivity of the c-kit/ligand interaction on stroma. The stroma-dependent c-kit regulation most likely occurs at the transcriptional level, because mechanisms, such as splicing, attenuation, differential promoter usage, or mRNA stability, could be excluded.

Animals↗
PubMed1998

Valvular endocarditis due to Mycobacterium tuberculosis.

Granulomas due to Mycobacterium tuberculosis are rarely observed in valvular structures. When observed, they are associated with disseminated tuberculosis in immunocompromised patients. We report the first case of tuberculous valvular endocarditis isolated in an immunocompetent patient. The patient had severe mitral valve regurgitation due to a perforation of the anterior leaflet of the mitral valve. M. tuberculosis was cultured from the vegetations and no other tuberculous foci were identified. This case exemplifies the protean manifestations of M. tuberculosis infections.

Endocarditis, Bacterial↗
PubMed1997

Effects of mycobacteria on regulation of apoptosis in mononuclear phagocytes.

Since apoptosis is observed in tuberculous granulomata, we investigated the molecular mechanisms underlying the apoptotic pathway in an in vitro model of mycobacterial infection of mononuclear phagocytes. We postulated that Mycobacterium tuberculosis could trigger the apoptotic pathway in macrophages, resulting in death of the microorganism by modulating the expression of bcl-2, bax, bcl-xL, and bcl-xS. We found that the mRNA of bcl-2, an inhibitor of apoptosis, was downregulated in peripheral blood monocytes (PBM) between 2 and 6 h following infection with M. bovis BCG or induction with heat-killed M. tuberculosis H37Ra. Western analysis showed a downregulation of the Bcl-2 protein, with a half-life of 24 h. At the same time points, there was no change in the expression of Bax or Bcl-xS, inducers of apoptosis, but Bcl-xL, another inhibitor of apoptosis, was minimally upregulated by BCG. To determine if apoptosis could be a mechanism for growth inhibition in vivo, we obtained alveolar macrophages by bronchoalveolar lavage from involved sites in patients with active pulmonary tuberculosis. Using the TUNEL (terminal deoxynucleotidyltransferase mediated nick end labeling) technique, we observed significantly more apoptosis in involved segments of five tuberculosis patients (14.8 +/- 1.9%) than in those of normal controls (<1%, P = 0.02) or in uninvolved segments (4.3 +/- 0.9%, P < 0.05). We conclude that apoptosis of mononuclear phagocytes induced by M. tuberculosis occurs in vivo and that in an in vitro model of mycobacterial infection, apoptosis may be mediated by downregulation of Bcl-2.

Apoptosis↗
PubMed1995

[How safe is laparoscopic colon surgery?].

Like any new technique, laparoscopic colon surgery must display results of the same or even better quality than established methods. In this hospital every laparoscopic colon operation has been registered since 1993. Patients were informed orally or in writing that the laparoscopic procedure is a new surgical technique and that, in particular, long term results in colon carcinoma are lacking. Patients who did not undergo the laparoscopic method were those who did not agree to this type of surgery, had tumor infiltrations without extensive liver metastases, or tumor sizes where laparotomy to retrieve the specimen is not much smaller than the open surgery incision. All operations without exception were performed by two laparoscopically skilled abdominal surgeons. We used four 12 mm Troicarts placed in a diamond position, the criteria for mobilization and resection strictly following those of open surgery. In rectosigmoid resection the specimens were extracted suprapubically, with simultaneous implantation of the anvil, in the other cases at appropriate sites. The anastomoses were created either by the double stapling technique or with a single layer running suture. 88 patients underwent operation. The change to open surgery was 11%. The reasons for the change were chiefly inflamed, bleeding diverticulitis tumor, carcinoma infiltrations and, in one case, bleeding. The anastomosis failure rate of the descendorectostomy, and in all laparoscopic colon operations, was 4% and compares favourably with the literature. This was also true of stenosis incidence. The wound infection rate is on the whole the same as for open surgery. The complication in the descendorectostomy is reduced by half in the laparoscopic procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Lineage-restricted recruitment of immature hematopoietic progenitor cells in response to Epo after normal hematopoietic cell transfection with EpoR.

The receptor for erythropoietin (EpoR) is normally restricted in its expression to the relatively mature cells of the erythroid and megakaryocytic lineages. Using retrovirus-mediated gene transfer, the wild-type EpoR and a constitutively activated mutant of the EpoR, EpoRR129C, were expressed in primary hematopoietic cells. Retroviral infection of day-12 murine fetal liver, followed by stimulation with Epo as a single stimulus, generated day-8 erythroid colonies resembling colonies derived from burst-forming units-erythroid (BFU-E). Similarly, murine post-5 fluorouracil (5-FU) bone marrow cells or fetal liver cells, induced to express EpoR and stimulated by Epo, displayed a significant enhancement of megakaryocyte colony formation, particularly of the BFU-megakaryocyte (BFU-Mk) colony type. Cultures of bone marrow cells transduced with the EpoR retrovirus and stimulated by Epo contained macrophage colonies but very few granulocyte colonies. Experiments to culture single clones demonstrated direct action of Epo on megakaryocyte and macrophage clones but failed to demonstrate a direct action on granulocyte precursors. A similar pattern of lineage-restricted effects was demonstrated in unstimulated cultures of cells infected with the EpoRR129C retrovirus. In summary, we have demonstrated Epo-induced recruitment of immature erythroid and megakaryocyte precursors induced to express the EpoR. Furthermore, we have also demonstrated lineage-restricted cell proliferation in response to Epo by normal myeloid hematopoietic cells transduced with the EpoR.

Animals↗
PubMed1993

Upregulation of lineage specific receptors and ligands in multipotential progenitor cells is part of an endogenous program of differentiation.

Multipotent hematopoietic progenitor cell lines (FDCP-Mix) infected with a retroviral vector expressing the GM-CSF gene show functional downregulation of the GM-CSF receptor when maintained in IL-3 and activation of the receptor resulting in synchronous differentiation into mature granulocytes and macrophages on withdrawal of IL-3. This system has now been used to investigate whether or not receptors for some of the other growth factors are also influenced as a consequence of differentiation. We show here the lineage specific receptors for M-CSF, G-CSF and erythropoietin are all upregulated, regardless of whether or not differentiation is induced by GM-CSF or by other conditions. Concomitant induction of the mRNA coding for the ligands M-CSF and G-CSF, but not for erythropoietin, suggests that M-CSF and possibly G-CSF facilitate macrophage or granulocyte differentiation by an autocrine stimulation of the lineage specific receptors. FDCP-Mix mutants that are blocked in their ability to differentiate on exposure to GM-CSF, but that still require GM-CSF for proliferation, do not express increased levels of M-CSF receptor nor M-CSF. Based on these data, we suggest that expression of these lineage specific receptors is part of the intrinsic endogenous program of myeloid differentiation.

Animals↗
PubMed1993

Distinct classes of factor-independent mutants can be isolated after retroviral mutagenesis of a human myeloid stem cell line.

Retroviral insertion mutagenesis has been used extensively in vivo but not in vitro to induce and identify critical mutations during oncogenic progression and differentiation. We have developed a tissue culture system using the human, growth factor-dependent, hematopoietic precursor cell line TF-1 that permits the use of retroviral vectors to induce a large (up to 28-fold) increase in the mutation frequency to growth factor independence and thus the isolation of many mutants. The mutation frequency, as expected, is directly proportional to the number of retroviral insertions (2.2 x 10(-7) mutants per insertion). The mutant phenotypes can be subdivided into mutants that release growth factors and those that do not ("autonomous" mutants). The majority of growth factor-producing mutants release an unidentified ligand. A subset of the autonomous mutants shows alterations in expression of the alpha subunit of either the GM-CSF or the IL-3 receptor. One mutant expresses neither GM-CSF nor IL-3 alpha receptor chains, thus showing coordinate regulation of the alpha receptor subunits.

Cell Line↗
PubMed1990

[Callus distraction by an internal bone transport system in unilateral fixation].

The problem of the treatment of bone defects can be solved by distraction osteogenesis as developed by ILIZAROV. This study shows how the bone transport technique can be adapted to every common external fixator while using a new internal distraction system. In 20 dogs a bone defect of 6 cm was performed at the femur. The femur was stabilized with an unilateral frame. A proximal or distal corticostomized bone fragment (length 2.5 cm) was descended through the bone defect (1 mm day). In 15 dogs a new regeneration of bone was observed. The quality of the regenerated bone depends upon stability of the fixation. In 5 dogs with osteotomy and rapid dislocation of the transported fragment no bone bridging was found.

Animals↗
PubMed1989

Conversion of factor-dependent myeloid cells to factor independence: autocrine stimulation is not coincident with tumorigenicity.

It has been postulated that the disruption of the normal hormonal regulation of blood cell formation and proliferation leads to the autonomous growth of hematopoietic progenitors or stem cells and thus to leukeamia. We have utilized established hematopoietic cell lines to establish the different mechanism by which growth autonomy is acquired. The analysis of thirteen spontaneous factor-independent mutants revealed that the majority (12/13) secreted a factor that stimulated growth of the parental cell line. Thus, autocrine stimulation may be a important mechanism by which normal growth control is disrupted. This is supported by the observation of Young and Griffin (1987) that some cells isolated from patients with acute myeloblastic leukemia (AML) autogenously produce growth factor. In the majority of Dind mutants more closely examined, growth factor gene activation was due to the juxtapostion of a retrotransposon. Although the exact nature of the involvement of human retroviruses in inducing leukemia has not been elucidated, one could envisage that altered growth factor regulation due to integration of the virus may play an important role. The existence of a second class of Dind mutants that have obtained factor-independence by a mechanism not involving factor production concurs with the acquisition of factor-independent growth in hematopoietic cells after introduction of some oncogenes. Several models have been proposed to explain how oncogenes may "short circuit" and thus activate the normal signal transduction pathway by mimicking the active receptor, transducer, or effector (Weinberg, 1985). To investigate more closely the role of autocrine stimulation in the induction of growth autonomy and tumorigenicity, retroviral vectors expressing either GM-CSF or IL3 were introduced into factor-dependent hematopoitic cell lines. Non-linear clonability of infected cell lines in the absence of exogenous growth factor and inhibition of proliferation by antiserum supported a model of autocrine stimulation. However, a secondary event, correlated with amount of factor released, often occurred that abrogated the requirement for secreted CSF. Growth of cells in which this alteration had occured was cell-density independent and could not be blocked by antibody. It has been postulated that autogenous factor may react with its receptor intracellularly (Lang et al., 1985). The results presented here cannot exclude that the secondary events may allow the internal interaction of receptor and factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

[Indications for and results of interlocking nailing in lower leg fractures].

At the clinic for Traumatology at the University Hospital of Zürich between 1981-1986 53 tibial fractures in 52 patients have been treated with interlocking nails. The system of Grosse and Kempf was utilized. The fractures were produced by a variety of mechanisms of injury, of which 70% were caused by traffic accidents. Associated injuries to other organ systems were sustained by 44% of the patients, overall there were 13% considered to have multiple trauma. 21% of the fractures were open. 21% required stable fixation, 17% were dynamized. The remaining 79% fractures were treated with dynamic nailings. A bridging callus was observed after an average of 6 weeks, and cortical bridging at 18 weeks following nailing. Complications included local infection around the proximal transversal screws in 2 and osteomyelitis in 1 case.

Adolescent↗
PubMed1989

[Effect of blood transfusions on the survival of patients with colorectal cancers].

Blood transfusion is reported to cause immunosuppression. An adverse relationship between perioperative blood transfusions and the risk of subsequent recurrence of cancer was reported recently. We reviewed the records of 282 patients and analyzed the interaction between blood tranfusion and the outcome of Dukes stages A, B and C colorectal cancers treated by radical resection during the years 1978-1985. 53 of these patients did not receive any blood transfusions. The actuarial survival analysis (Cutler and Ederer) showed no significant difference for the overall and recurrence-free survival. This study did not support the hypothesis that blood transfusions had an adverse effect on survival of patients with colorectal cancer.

Blood Transfusion↗
PubMed1989

[Indications and results of interlocking nailing of the femur].

Since the introduction of an interlocking nail in 1972, different systems have been developed for the management of unstable femoral fractures. At the Clinic for Traumatology at the University Hospital of Zürich, the system of Grosse and Kempf was utilized until 1986, after which the AO universal nail system has been and still is used. Between 1981 and 1987, 63 femoral fractures in 62 patients have been treated with interlocking nails. The fractures were produced by a variety of mechanisms of injury, of which 75% were caused by traffic accidents. Associated injuries to other organ systems were sustained by 73% of the patients, overall there were 33% considered to have multiple trauma. 25% of the fractures were open. 44% (n = 28) required stable fixation, 15 were dynamized. The remaining 35 fractures were treated with dynamic nailings, 8 proximal and 27 distal. 15% were open nailings. Following dynamic stabilization full weight bearing was obtained after 56 and stable fixation after 120 days. A bridging callus was observed after an average of 8 weeks, and cortical bridging at 26 weeks following nailing. Complications included displacement of transversal screws in 3, local infections around the distal or proximal transversal screws in 3 and osteomyelitis at the fracture site in 3 cases.

Adolescent↗
PubMed1988

Transformation of single myeloid precursor cells by the malignant histiocytosis sarcoma virus (MHSV): generation of growth-factor-independent myeloid colonies and permanent cell lines.

Direct single-cell assays for oncogenic transformation are available for fibroblasts but not for other cell types. Using malignant histiocytosis sarcoma virus (MHSV), a member of the ras family of retroviruses, in vivo-infected granulocyte/macrophage and macrophage precursor cells lost the requirement for externally added hematopoietic growth factors. Factor-independent growth was demonstrated by colony-transfer experiments. More than 25% of the independent colonies were established as permanent macrophage cell lines following a phase of adaptation to tissue culture conditions. Factor-independent colony growth was also obtained by in vitro infection of single cells. As many as 50% of all myeloid precursor cells were target cells for MHSV as measured by this assay. About 2 x 10(-3) of these colony-forming cells acquired growth factor independence and immortality after in vitro infection. Cell lines derived from these colonies did not require adaptation to tissue culture conditions.

Animals↗
PubMed1987

Macrophage cell lines transformed by the malignant histiocytosis sarcoma virus: increase of CSF receptors suggests a model for transformation.

The malignant histiocytosis sarcoma virus (MHSV) contains Ha-v-ras-related oncogenic sequences and rapidly transforms myeloid cells in vivo and in vitro. Myeloid cell lines can be derived which do not require growth factor for continued proliferation. We initiated this work to define the process of transformation leading to autonomy of cell growth in transformed myeloid cells. Five established cell lines were examined. All express macrophage-specific cell-surface antigens and exhibit several other properties typical for mature macrophages. Growth properties, growth factor release, and growth factor receptor presentation were examined: Release of growth factors is not a consistent feature. All cell lines show cell-density-independent colony formation and do not release self-stimulating factors, thus excluding autocrine stimulation as a model leading to transformation. All cell lines express unusually high levels of granulocyte-macrophage (GM)- and multi-CSF receptors and, except for one, M-CSF receptors. The high increase in GM-CSF and other growth factor receptors may be causally related to the transformed state of the cells. MHSV can be used as a tool to easily derive cell lines of the macrophage pathway as a model to study myeloid transformation, differentiation, and macrophage function.

Animals↗