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Biomedical subjects

K Langner

Publications and source records attributed to K Langner.

At least 19 recordsLinked to original sources

A multivalent HIV-vaccine: development of a plasmid DNA for the expression of HIV envelope glycoproteins with hypervariable V3-loop domains.

The third hypervariable (V3) loop of the HIV-1 envelope glycoprotein gp120 plays an essential role in the process of viral entry. It contributes to the tropism, coreceptor usage and immune-escape of the virus. We generated a monovalent plasmid DNA and demonstrated the expression of HIV-1 clade B subtype NL4-3 gp120 and gp160 in comparison to a multivalent plasmid DNA encoding for a variety of V3-variants. In contrast to the membrane-anchored gp160, preliminary data demonstrate the monovariant gp120 is expressed in and presented on a human dendritic cell (DC) line, due to a HIVenv-specific re-stimulation of naïve T-cells detected by IFNgamma-ELISPOT assay.

AIDS Vaccines↗

[Neoadjuvant therapy in non-small cell lung cancer. Prognostic impact of "mediastinal downstaging"].

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.

Adenocarcinoma↗

Ossification in atherosclerotic carotid arteries.

BACKGROUND: Heterotopic ossification as newly formed bone in extraosseous tissue is an uncommon finding in atherosclerotic lesions. The exact mechanisms and development of bone formation in regard to late stage calcified atherosclerosis still remains under debate. METHODS: We studied 400 autopsy carotid probes and 306 samples of atherosclerotic carotid endatherectomy. Radiographic analysis and classification of calcification was performed followed by light microscopy. In probes with detected ossifications further analysis using immunohistochemistry, scanning electron microscopy (SEM) and energy dispersive x-ray micro-analysis (EDX) including calcium mapping was performed. RESULTS: Ossification in atherosclerotic carotid arteries was a finding in only a minority of samples (5%) and occurred at sites of large calcific deposits. Histomorphology of bone formation equaled skeletal bone showing osteoblastic cells, osteocytes included in osteoid matrix, bone marrow and osteolytic giant multinucleated cells. Closely related to newly formed bone zones of neovascularization were found. Development of ossification seemed to occur in five stages (lipidous plaque, fibrous cellular plaque, fibrous acellular plaque, calcified plaque and osteogenesis). The environment of sites of ossification was characterized by a varying texture of extracellular fibrous matrix, foam cells, smooth muscle cells, fibroblasts and calcified deposits. CONCLUSIONS: Heterotopic ossifications of atherosclerotic plaques seem to be a specific differentiation of fibrous plaques. Components of atherosclerotic lesions like vascular wall cells, neovessels and matrix structures seem to be involved in the process of transformation to mature bone tissue.

Arteriosclerosis↗

Grading of tumor regression in non-small cell lung cancer : morphology and prognosis.

OBJECTIVE: Different types of multimodality therapy, including chemoradiotherapy and surgery, increasingly are being used for the treatment of patients with locally advanced non-small cell lung cancer (NSCLC; stages IIIA and IIIB). In this context, the applicability of a morphologic regression grading and its prognostic value were investigated. PATIENTS AND METHODS: In a multicenter phase II trial, 54 patients with locally advanced NSCLC received neoadjuvant bimodality treatment (ie, two cycles of ifosfamide, carboplatin, and etoposide, followed by twice-daily radiation up to 45 Gy with simultaneous administration of carboplatin and vindesine). Forty patients underwent resections. Using the corresponding resection specimens of the primary and regional lymph nodes, the following regression grading was established: grade I, no regression or only spontaneous tumor regression; grade II, morphologic evidence of therapy-induced tumor regression with at least 10% (grade IIa) or < 10% (grade IIb) vital tumor tissue; and grade III, complete tumor regression with no evidence of vital tumor tissue. Regression grading then was correlated with the survival time. RESULTS: Three tumors were classified as regression grade I, 10 were classified as regression grade IIa, 20 were classified as regression grade IIb, and 7 were classified as regression grade III. Patients with tumors of regression grades IIb or III showed significantly longer survival times than those with tumors of regression grades I or IIa (median survival time, 36 vs 14 months, respectively; 3-year survival rate, 52% vs 9%, respectively; p = 0.02). These survival times were also compared for patients who had undergone complete resection (median survival time, not reached vs 23 months, respectively; 3-year survival rate, 56% vs 11%, respectively; p = 0.03). The presurgical clinical response after patients had received neoadjuvant multimodality therapy had no predictive value in assessing the extent of therapy-induced tumor regression in the resection specimen. CONCLUSIONS: After neoadjuvant therapy of patients with NSCLC, the proposed tumor regression grading was of predictive value for long-term survival. Beyond the achievement of complete tumor resection (R0), a therapy-induced tumor regression of < 10% of vital tumor tissue is pivotal for superior long-term outcomes.

Adult↗

[Changes in differentiation of small cell lung cancer after chemotherapy].

We reexamined biopsy and resection specimens from seven patients with histologically established primary diagnosis of small-cell lung cancer (SCLC) which showed previously undetected adenocarcinomatous differentiation after chemotherapy. Adenocarcinoma was diagnosed in the same part of the lung as was SCLC before treatment in five cases and in contralateral location in two. Two tumors showed heterogeneous differentiation with small-cell and adenocarcinomatous components, and five had only adenocarcinoma. The interval between histological evidence of SCLC and adenocarcinoma was 3 months-5 years. From the specific findings in the respective patients we can offer two possible explanations for changing differentiation in SCLC after chemotherapy: (a) a primarily heterogeneously differentiated tumor with selection of adenocarcinomatous component under chemotherapy, and (b) an independently developed adenocarcinoma after successful chemotherapy of SCLC, as patients with treated SCLC are known to have an increased risk of non-SCLC. However, therapy-induced alteration of differentiation seems much more unlikely. These findings should be considered in diagnosis and therapy of SCLC to allow early and appropriate reaction to non-SCLC components.

Adenocarcinoma↗

[Synovial sarcoma of the pericardium].

A precordial tumor of the pericardium was radiologically diagnosed as the cause of an untypical clinical picture of heart disease in a 41-year-old soldier. As the patient had an increased asbestos exposure due to his profession, he was admitted to operation under the tentative diagnosis of a pericardial mesothelioma and the question of an occupational disease (BK 4105). Microscopic and immunohistochemical findings are compatible with the diagnosis of a synovial sarcoma of the pericardium. The present immunohistochemical marker spectrum allowed a reliable differentiation between synovial sarcoma and pericardial mesothelioma, which is more frequent than synovial sarcoma. The epithelioid component was determined using the following antibodies: MNF 116, CK 19, CK 7, EMA and Ber EP-4 were positive while Factor VIII, Calretinin, S100, Vimentin, CEA, CD 31, bcl-2 and HBA-71 were negative. The sarcomatous component was determined with antibodies to Vimentin, bcl-2 and HBA-71 which were positive, and to MNF 116, CK 19, CK 7, Factor VIII, Calretinin, S100, EMA, CEA, Ber EP-4 and CD 31 which were negative. Synovial sarcomas of the pericardium in the lower anterior mediastinum or the myocardium are exceedingly rare. A causal relationship between tumor formation and an increased asbestos exposure--similar to the epidemiologically based experiences with pericardial mesothelioma--is not likely. Primary extrapericardial synovial sarcoma could be excluded.

Adult↗

Differential expression of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 in experimental glomerulonephritis.

We examined the relation between glomerular expression of chemokines from alpha-subfamily (macrophage inflammatory protein-2, MIP-2) and beta-subfamily (monocyte chemoattractant protein-1, MCP-1) and infiltration of neutrophils and monocytes in antibody mediated glomerulonephritis in rats. In the accelerated model of nephrotoxic nephritis (NTN), glomerular expression of MIP-2 and MCP-1 genes correlated with the sequential migration of neutrophil and monocyte influx, respectively. These relationships were investigated further in the heterologous phase of NTN by applying various treatments known to modulate the severity of injury. Pretreatment with bacterial lipopolysaccharide resulted in greater injury, MIP-2 expression increased 25- to 50-fold, and the glomerular neutrophil count increased two- to fourfold. Both MIP-2 mRNA levels and neutrophil infiltration were reduced by additional pretreatment with IL-6, IL-1 receptor antagonist, soluble IL-1 receptor or soluble TNF receptor (Spearman correlation coefficient r = 0.897, P < 0.005). In the heterologous phase of NTN, different pre-treatments only resulted in trivial changes in MCP-1 expression and monocyte infiltration. In conclusion, glomerular MIP-2 gene expression correlates with neutrophil infiltration both temporally during the evolution of nephritis, and when glomerular injury is modified by treatment. Glomerular MCP-1 gene expression correlates with monocyte influx. The data show chemokines of alpha- and beta-subfamilies co-operative to cause selective and sequential migration of different leukocyte subsets during development of antibody mediated glomerulonephritis.

Animals↗

Modulation of antibody-mediated glomerular injury in vivo by IL-1ra, soluble IL-1 receptor, and soluble TNF receptor.

The severity of glomerular injury in the heterologous phase of NTN is dependent on proinflammatory cytokines including TNF alpha and IL-1 beta, and can be enhanced by LPS. We have previously shown that passive immunization against IL-1 beta and TNF partially abrogated the LPS effect in this model. In the present work, we have assessed the effects on glomerular injury of blocking and binding of IL-1 to its receptor by rh IL-1 receptor antagonist (IL-1ra) and by neutralizing IL-1 and TNF with rm soluble IL-1 receptor type1 (sIL-1Rt1) and rh sTNF receptor (sTNFr p55), respectively. Pretreatment with either IL-1ra, sIL-1Rt1, or sTNFr partially abrogated the effects of LPS and reduced albumin excretion from 45 +/- 8, 66 +/- 9, and 101 +/- 17 mg/24 hr at 13 +/- 4 (P < 0.02), 14 +/- 4 (P < 0.001), and 21 +/- 7 mg/24 hr (P < 0.001), respectively. Similarly, these inhibitors reduced the prevalence of glomerular capillary thrombi and the intensity of glomerular neutrophil infiltration. Glomerular thrombosis was reduced from 18 +/- 3%, 28 +/- 5%, and 25 +/- 7% to 3 +/- 2% (P < 0.002), 6 +/- 2% (P < 0.001), and 3 +/- 2 (P < 0.001), respectively, and glomerular neutrophil infiltration was reduced from 46 +/- 3, 54 +/- 2, 59 +/- 8 to 19 +/- 2 (P < 0.001), 25 +/- 2 (P < 0.001), and 28 +/- 2 neutrophils/50 glomeruli in section, respectively. Coadministration of both soluble receptors of IL-1 and TNF caused a further decrease in glomerular injury. The protective effect was also noticed at four hours after induction of nephritis, and even when these inhibitors were administered after the LPS injection and at the same time of induction of nephritis. All three treatments reduced circulating TNF concentration (down to 20%, 34%, and 0%, respectively) but without detectable glomerular TNF gene expression. Glomerular IL-1 beta mRNA levels were also reduced by 41%, 53%, and 67%, respectively, when assessed by densitometric analysis of Northern blots. In contrast, the glomerular expression of IL-1ra was not affected by its exogenous administration but was mildly reduced by sIL-1Rt1 and sTNFr, which demonstrates the potential role for host derived IL-1ra as an endogenous negative feedback mediator in the glomerulus. These results confirm the direct involvement of IL-1 and TNF in LPS-enhanced hNTN and demonstrate the potency of these inhibitors in modulating injury even when administered after LPS and in time of induction of nephritis. They were more specific and effective than passive immunization with polyclonal antibodies, and this demonstrates their potential usefulness in the management of nephritis.

Animals↗

Autoantibodies in HIV-infected hemophilia patients against different epitopes on CD4+ lymphocytes and recombinant CD4.

We studied 684 sera obtained from 20 hemophilia patients with AIDS/AIDS-related complex (ARC), 89 asymptomatic HIV+, 76 HIV- hemophilia patients and 151 healthy controls for antibodies against recombinant CD4 (rCD4). Twenty-two percent of AIDS/ARC patients, 10% of asymptomatic HIV+ patients, 17% of HIV-patients, and 1% of healthy controls had anti-rCD4 antibodies. Purified anti-rCD4 antibodies did not react with human CD4+ lymphocytes. This may explain why formation of anti-rCD4 antibodies correlated neither with the occurrence of autoantibodies against CD4+ lymphocytes nor with a decrease in CD4+ cell counts. Antibodies that were eluted from CD4+ lymphocytes after sequential adsorption and elution with separated CD8+ and CD4+ cells reacted with CD4+ lymphocytes of only some healthy individuals, suggesting diversity of CD4 expression.

Acquired Immunodeficiency Syndrome↗

Effect of continuous lumbar epidural anaesthesia during labour on fetal transcutaneous carbon dioxide.

The effect of epidural anaesthesia during labour on fetal transcutaneous carbon dioxide (tcPCO2) was observed on 27 fetuses. Our results show that in the course of epidural anaesthesia there is an increase in fetal tcPCO2. We can see a slight increase even before administering the test dose, while preparatory measures are undertaken for the epidural anaesthesia. After administering the test dose and after giving the main dose there is a further increase in fetal tcPCO2, which continues for up to 30 min after the main dose has been given. The results suggest that it is important to consider any pathological conditions in the fetus, so as to avoid the possibility of additionally endangering the fetus during epidural anaesthesia.

Adult↗

The influence of oxygen administration to the mother during labor on the fetal transcutaneously measured carbon-dioxide partial pressure.

The aim of this study was to plot the course of the transcutaneously measured PCO2 (tcPCO2) in the fetus during oxygenation of the mother. In our examination 35 parturients with a suspicious or pathologic CTG were given pure oxygen for 10 minutes at a flow speed of 10 l/min. The fetal tcPCO2 was measured with a TCM 3 measuring device from Radiometer. The measuring temperature was 41 degrees C. The fetal tcPCO2 was 67.2 +/- 3.9 mmHg before the O2 application, during the O2 application it was 67.3 +/- 14.1 mmHg and for the period after the O2 application we found an average measurement of 66.7 +/- 13.9 mmHg. Further we investigated whether, depending on the original levels of the fetal tcPCO2 an O2 application to the mother had a measurable effect on the fetal tcPCO2 levels. The average levels of the tcPCO2 in the fetuses with pathological original levels of greater than or equal to 60 mmHg or with normal levels of less than 60 mmHg did not show any significant differences before, during or after the O2 application. Our own results and reports given in the literature about an increase in the fetal O2 partial pressure during maternal oxygenation lead to the conclusion that in cases with fetal hypoxia, the O2 application to the mother--in addition to other measures for intrauterine reanimation or speedy termination of labor--could be of advantage.

Blood Gas Monitoring, Transcutaneous↗

[Magnetoencephalography--current trends].

The review deals with the method of magnet-encephalography. The physical principles and the most important technical conditions to put into practice this method are mentioned. Comparing with the electroencephalography this method shows various advantages, what leads to its intensive use for the localisation of components of evoked potentials, for the magnet-encephalographic record of the brain activity of the human fetus, and for the localisation of epileptic foci in therapy resistant epileptics.

Brain Damage, Chronic↗

In-vivo NMR spectroscopy of the fetal lung in guinea-pigs.

We have been successful in achieving phosphorus NMR in-vivo spectra of the fetal lung in an animal model. We used pregnant guinea-pigs with a gestational age of 45 to 65 days. The spectra were recorded on a Bruker tomograph (BMT 24/30) with a field strength of 2.35 T. The spectra showed a typical pattern. After recording the animals were sacrificed and the lungs were prepared for electron microscopic examinations. In the spectra peaks were found which appeared to be phosphorylcholine and phosphatidylcholine. For one peak it could be observed that the relative signal intensity increased with increasing gestational age as well as with increasing lung maturity. This could not be observed for other peaks. So the lecithin of the surfactant in the tissue of the fetal lung appears to be directly accessible through phosphorus in-vivo NMR spectroscopy. The peaks found appear already before the lamellar bodies are present in the pneumocytes type II.

Animals↗

[Elastase of polymorphonuclear granulocytes. Determination in plasma in pregnancy and following premature rupture of the membranes].

Between May and October 1984 in the Department of Obstetrics of the Frauenklinik Berlin-Neukölln, 147 blood samples were taken from 106 women who were pregnant or already in labor. The purpose was to determine the concentration of the elastase of the polymorphonuclear leukocytes. Towards the end of pregnancy (from the beginning of the 28th gestational week till birth of the child), the range of 66 ng/ml-122 ng/ml with a median of 92 ng/ml was considered normal. It was shown that the concentration of elastase in the plasma of pregnant women is affected neither by the increasing gestational age nor by such pregnancy-associated diseases as the following: fetal hypotrophy, cervix insufficiency, premature onset of labor, or gestational diabetes. In addition, the elastase concentration in pregnant women who had had a premature rupture of the membranes was determined. The values were compared with other clinical and laboratory infection parameters, such as temperature, the total number of leukocytes as well as the number of rod-shaped leukocytes, and the duration of the opening of the membranes. The results indicated that under 135 ng/ml, there is most likely no infection present. Elastase concentrations between 135 ng/ml and 180 ng/ml lie in the pre-pathological range, concentrations above 180 ng/ml nearly always indicate the presence of an infection.

Female↗

Plasma immunoreactive beta-endorphin, ACTH and cortisol concentrations in mothers and their neonates immediately after delivery--their relationship to the duration of labor.

In 29 cases of vaginal delivery with normal outcome and 4 cases of cesarean section, the concentrations of beta-endorphin, ACTH and cortisol were determined in maternal venous and umbilical venous plasma immediately postpartum. According to duration of labor and mode of delivery the cases examined were classified into three groups: Group A (18 cases) = vaginal delivery of less than 10 hours' duration, Group B (11 cases) = vaginal delivery of more than 10 hours' duration of labor, Group C (4 cases) = cesarean section under general anesthesia. With the exception of one, the deliveries took place at term. The 33 neonates were in a very good clinical state 5 minutes after parturition (11 Saling points as median value). For measurement of the hormone concentrations radioimmunoassays were used. In Group a the mean beta-endorphin concentration in maternal plasma amounted to 150.9 +/- 16.3 pg/ml, that in neonatal plasma to 239.2 +/- 23.5 pg/ml (means +/- SEM). In Group B plasma beta-endorphin, both maternal and neonatal, was slightly higher than in Group A: 153.0 +/- 12.0 pg/ml (maternal) and 260.9 +/- 37.1 pg/ml (neonatal). The differences between maternal and neonatal beta-endorphin levels were statistically significant: Group A p less than 0.01, Group B p less than 0.05; chi 2-test. The mean ACTH concentrations in the plasma of the newborn infants were also found to be considerably higher compared with those in the plasma of their mothers: Group A 78.2 +/- 16.5 pg/ml (maternal) and 98.0 +/- 23.3 pg/ml (neonatal); Group B 98.0 +/- 20.1 pg/ml (maternal) and 165.8 +/- 39.6 pg/ml (neonatal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Measurement of transcutaneous pCO2 and pO2 in the fetus during labor.

We used newly developed transcutaneous electrodes to measure continuously the partial pressure of oxygen (tcpO2) and carbon dioxide (tcpCO2) in 34 fetuses during labor, having simultaneous cardiotocography (CTG) and temperature measurements. We observed that tcpO2 and tcpCO2 varied with contractions during the first and second stages of labor. In some cases changes in the transcutaneous values corresponded well with changes in the CTG, we also detected changes in the fetal gas metabolism that were not noticeable on the cardiotocographic tracing. We defined the characteristic of the tcpO2 and tcpCO2 during the second stage of labor and found that the tcpO2 decreased and the tcpCO2 rose at this time.

Carbon Dioxide↗