Biomedical subjects

Martin Langer

Publications and source records attributed to Martin Langer.

24 records · Page 2Linked to original sources

PubMed2002

Preferential binding of the anticancer drug rViscumin (recombinant mistletoe lectin) to terminally alpha2-6-sialylated neolacto-series gangliosides.

Production of biochemically defined recombinant mistletoe lectin was achieved by cloning and separate expression of the single catalytically active A-chain and the B-chain with carbohydrate binding properties in Escherichia coli, yielding an active heterodimeric protein named rViscumin (Eck et al. [1999] Eur. J. Biochem., 265, 788-797). Employing solid phase binding assays, rViscumin was shown to preferentially bind to terminally alpha2-6-sialylated neolacto-series gangliosides IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer isolated from human granulocytes. Only marginal binding of rViscumin to galactose-terminated neutral GSLs was determined, whereas reinvestigation of ricin specificity demonstrated this lectin as a galactose-binding protein. Human promyelotic HL-60 cells exhibited an IC(50) value (half maximum cytotoxicity) of 1.16 pM and human bladder carcinoma 5637 cells of 12.1 pM rViscumin; CHO-K1 cells were resistant to rViscumin treatment up to a concentration of 5.26 nM tested. Quantification of the predominant receptor ganglioside IV(6)Neu5Ac-nLc4Cer by means of a specific anti-Neu5Acalpha2-6Galbeta1-4GlcNAc-R antibody revealed 3.68 x 10(6) and 1.54 x 10(6) receptor molecules per HL-60 and 5637 cell, respectively; CHO-K1 cells were negative, lacking alpha2-6-sialylated gangliosides. The data imply a direct correlation of rViscumin cytotoxicity and the expression of receptor ganglioside. Moreover, CHO-K1 cells were rendered susceptible toward rViscumin cytotoxicity after exogenous application of human granulocyte gangliosides. Thus, (1) rViscumin has to be considered as a sialic acid-specific rather than a galactose-specific type II ribosome-inactivating protein, and (2) neolacto-series gangliosides with Neu5Acalpha2-6Galbeta1-4GlcNAc-terminus are true functional and physiologically relevant rViscumin receptors.

Animals↗

PubMed2002

Immunoadsorption and plasma exchange in pregnancy.

BACKGROUND: During pregnancy, familial hyperlipidemia or systemic lupus erythematosus (SLE) can exacerbate having devastating consequences for both mother and fetus. Immunoadsorption is established for removal of pathogenic proteins lipoproteins or autoantibodies, but this procedure has only rarely been used in pregnancy. METHODS: We evaluated retrospectively 126 extracorporeal treatments during six pregnancies. Forty low-density lipoprotein immunoadsorptions, 6 sole plasma exchanges and 36 combined procedures (plasma exchange followed by immunoadsorption) were performed for severe hypertriglyceridemia, complicated by acute pancreatitis. Forty-four IgG immunoadsorptions were executed in 2 pregnant women suffering from SLE with a disastrous course during prior pregnancies. RESULTS: In hyperlipidemic pregnant women, mean triglyceride levels prior to treatment were 3,841 +/- 2,076 mg/dl (mean +/- SD) and total cholesterol was 617 +/- 354 mg/dl. Until delivery, a 27% reduction of triglycerides could be achieved. Clinical and serological signs of pancreatitis disappeared after initiation of extracorporeal therapy. Four healthy babies were delivered (birthweights between 2,250 and 3,360 g). In 1 woman suffering from SLE, intrauterine fetal death occurred in the 22nd week of gestation despite a reduction of cardiolipin antibodies by 69%. The second case (a twin pregnancy) was complicated by steroid-resistant antibody-mediated anemia. Due to frequent immunoadsorptions, red blood cell count improved (reduction of antierythrocyte antibodies by 66.6%) and 2 healthy babies (birthweights 2,120 and 2,350 g) were delivered by cesarean section. CONCLUSION: Long-term antibody-based immunoadsorption has been demonstrated to be safe and well tolerated in pregnant women and enables normal intrauterine/fetal development. Although rarely indicated during pregnancy, this treatment modality might be a promising new technique for removal of autoantibodies and lipoproteins in patients with serious gestational complications without sufficient response to conventional therapy.

Adsorption↗

PubMed2002

Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury.

OBJECT: The aim of this study was to investigate the effects of moderate hyperventilation on intracranial pressure (ICP), jugular venous oxygen saturation ([SjvO2], an index of global cerebral perfusion), and brain tissue PO2 (an index of local cerebral perfusion). METHODS: Ninety-four tests consisting of 20-minute periods of moderate hyperventilation (27-32 mm Hg) were performed on different days in 36 patients with severe traumatic brain injury (Glasgow Coma Scale score < or = 8). Moderate hyperventilation resulted in a significant reduction in average ICP, but in seven tests performed in five patients it was ineffective. The response of SjvO2 and brain tissue PO2 to CO2 changes was widely variable and unpredictable. After 20 minutes of moderate hyperventilation in most tests (79.8%), both SjvO2 and brain tissue PO2 values remained above the lower limits of normality (50% and 10 mm Hg, respectively). In contrast, in 15 tests performed in six patients (16.6% of the studied population) brain tissue PO2 decreased below 10 mm Hg although the corresponding SjvO2 values were greater than 50%. The reduction of brain tissue PO2 below 10 mm Hg was favored by the low prehyperventilation values (10 tests), higher CO2 reactivity, and, possibly, by lower prehyperventilation values of cerebral perfusion pressure. In five of those 15 tests, the prehyperventilation values of SjvO2 were greater than 70%, a condition of relative hyperemia. The SjvO2 decreased below 50% in four tests; the corresponding brain tissue PO2 values were less than 10 mm Hg in three of those tests, whereas in the fourth, the jugular venous O2 desaturation was not detected by brain tissue PO2. The analysis of the simultaneous relative changes (prehyperventilation - posthyperventilation) of SjvO2 and brain tissue PO2 showed that in most tests (75.5%) there was a reduction of both SjvO2 and brain tissue PO2. In two tests moderate hyperventilation resulted in an increase of both SjvO2 and brain tissue PO2. In the remaining 17 tests a redistribution of the cerebral blood flow was observed, leading to changes in SjvO2 and brain tissue PO2 in opposite directions. CCONCLUSIONS. Hyperventilation, even if moderate, can frequently result in harmful local reductions of cerebral perfusion that cannot be detected by assessing SjvO2. Therefore, hyperventilation should be used with caution and should not be considered safe. This study confirms that SjvO2 and brain tissue PO2 are two parameters that provide complementary information on brain oxygenation that is useful to reduce the risk of secondary damage. Changes in SjvO2 and brain tissue PO2 in opposite directions indicate that data obtained from brain tissue PO2 monitoring cannot be extrapolated to evaluate the global cerebral perfusion.

Adolescent↗

PubMedDate not supplied

Metagenomics: an inexhaustible access to nature's diversity.

The chemical industry has an enormous need for innovation. To save resources, energy and time, currently more and more established chemical processes are being switched to biotechnological routes. This requires white biotechnology to discover and develop novel enzymes, biocatalysts and applications. Due to a limitation in the cultivability of microbes living in certain habitats, technologies have to be established which give access to the enormous resource of uncultivated microbial diversity. Metagenomics promises to provide new and diverse enzymes and biocatalysts as well as bioactive molecules and has the potential to make industrial biotechnology an economic, sustainable success.

Biodiversity↗

PubMedDate not supplied

A new technique for reconstruction of the common bile duct by an autologous vein graft and a biodegradable endoluminal stent.

The incidence of severe bile duct injuries has significantly increased since the introduction of laparoscopic cholecystectomy. The ideal reconstruction procedure for traumatic defects of the bile duct should be technically simple and should preserve both the physiological passage of bile and the sphincter of Oddi. In this article we describe a new technique for bile duct reconstruction in a pig model by means of an autologous vein graft that is splinted by a endoluminal biodegradable polylactate acid stent. In 12 pigs the external jugular vein was removed and used as an autologous vein graft. After performing a median laparotomy a 2-cm segment was resected from the bile duct. The common bile duct was reconstructed by a venous interponate that had been endoluminally stented by a biodegradable polylactate acid stent. For the examination of stent degradation, 2 pigs were sacrificed at 3, 4, and 5 months (stent degradation group) and the remaining 6 pigs at 6 months (survival group). All the pigs in the survival group survived for 6 months before being sacrificed. After 4 months the stent material had been completely broken down and the vein graft had been relined with bile duct epithelium. Thus, this new technique for bile duct reconstruction using an autologous vein graft with an endoluminal stent is simple to perform and reliable, and constitutes an interesting alternative to bilodigestive anastomosis due to the preservation of the papilla of Vateri.

Animals↗

PubMedDate not supplied

Binding of recombinant mistletoe lectin (aviscumine) to resected human adenocarcinoma of the lung.

BACKGROUND: Lectins, carbohydrate proteins, bind to glycoconjugates of all mammalian cells, including cancer cells. Aberrant glycosylation, detected by lectin histochemistry, can predict outcome in some tumour entities. One such lectin is aviscumine (recombinant mistletoe lectin). Aviscumine has cytotoxic effects and can therefore be used as anti-tumour therapy. MATERIALS AND METHODS: Lectin histochemistry with aviscumine was performed on primary tumour sections from resected adenocarcinoma of the lung. Staining results were then correlated with the clinical course of the patients. RESULTS: Most of the adenocarcinomas (92.5%) bound aviscumine. Kaplan-Meier analysis revealed no correlation between aviscumine binding and progression-free survival or overall survival. CONCLUSION: These results suggest that for the selected group of patients with adenocarcinoma of the lung aviscumine binding activity can not serve as a prognostic factor. More strikingly, however, aviscumine binds to malignant cells in 92.5% of the patients. This is an indicator for the use of aviscumine as a possible target for tumour therapy.

Adenocarcinoma↗