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Biomedical subjects

U Krüger

Publications and source records attributed to U Krüger.

At least 37 records · Page 2Linked to original sources
PubMed1996

The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease.

The dissemination of cancer cells is a prerequisite in the development of micrometastases and solid metastases. Our previous examinations of these cells were based on immunocytological staining of tumor-associated antigens and cytokeratins. We have now developed a highly sensitive and specific detection method based on a nested reverse-transcriptase-polymerase-chain reaction (RT-PCR) of cytokeratin-20 (CK-20) mRNA. Using this method, we examined the bone marrow of 57 patients with colorectal cancer and detected increasing numbers of CK-20-positive samples, depending on the UICC stage. Some 35% of all bone-marrow samples tested positive for CK-20: none were found in colorectal cancer stage 1, 24% were in stage II, 31% in stage III and 71% in stage IV. Investigation of bone-marrow specimens of patients with pancreatic cancer showed that 4 out of 11 patients were positive for CK-20 mRNA. To confirm that sample positivity for CK-20 expression was due to disseminated tumor cells, we examined bone marrow from a control group (n = 16) without apparent carcinoma. In this group, 15 out of 16 donors were CK-20-negative, while one donor with familial adenomatous polyposis showed a CK-20-specific signal.

Base Sequence↗
PubMed1996

Generation of lymphocyte cell lines coexpressing CD4 and wild-type or mutant HIV type 1 glycoproteins: implications for HIV type 1 Env-induced cell lysis.

To gain more insight into the processes leading to HIV-1 Env-induced cell death, we aim to coexpress stably wild-type and relevant mutant variants of both HIV-1 Env and human CD4 in lymphocyte cell lines. Here we report on the generation and characterization of several cell lines inducibly or constitutively expressing wild-type or cleavage-defective HIV-1 glycoproteins and human CD4 either singly or in combination. Coexpression of CD4 and wild-type Env led to the formation of multinucleated syncytia, to growth arrest and cell death, effects that all could be prevented by cultivation in the presence of monoclonal antibodies that inhibit cell surface membrane fusion. Cell lines coexpressing CD4 and mutated, noncleavable Env, detectable at the cell surface and still retaining CD4-binding capacity, were not retarded in their growth and cytolysis did not occur. These results indicate that cell lysis requires cell surface interaction of CD4 and gp120/41 and cleavage of gp160 to gp120 and gp41.

B-Lymphocytes↗
PubMed1995

The absence of Emp24p, a component of ER-derived COPII-coated vesicles, causes a defect in transport of selected proteins to the Golgi.

Emp24p is a type I transmembrane protein that is involved in secretory protein transport from the endoplasmic reticulum (ER) to the Golgi complex. A yeast mutant that lacks Emp24p (emp24 delta) is viable, but periplasmic invertase and the glycosylphosphatidyl-inositol-anchored plasma membrane protein Gas1p are delivered to the Golgi apparatus with reduced kinetics, whereas transport of alpha-factor, acid phosphatase and two vacuolar proteins is unaffected. Oligomerization and protease digestion studies of invertase suggest that the selective transport phenotype observed in the emp24 delta mutant is not due to a defect in protein folding or oligomerization. Consistent with a role in ER to Golgi transport, Emp24p is a component of COPII-coated, ER-derived transport vesicles that are isolated from a reconstituted in vitro budding reaction. We propose that Emp24p is involved in the sorting and/or concentration of a subset of secretory proteins into ER-derived transport vesicles.

Amino Acid Sequence↗
PubMed1995

[Immunocytologic detection of micro-metastatic cells in patients with gastrointestinal tumors].

The success of surgical treatment of gastric-, colorectal- and pancreatic cancer is often limited due to local recurrence, the development of metastases or peritoneal carcinosis by cells which have been seeded already at the time of operation. Immunocytological methods enable the detection of disseminated cancer cells before their clinical manifestation as demonstrated by this study. Lavage samples from the peritoneal cavity and bone marrow samples from 147 patients with an adenocarcinoma of the stomach, colon and pancreas were investigated with a panel of six different monoclonal antibodies against tumor-associated antigens (CEA, CA-19-9, 19-1A, C-54-0, Ra96) and cytokeratin, respectively. Additionally, 43 patients with benign diseases were investigated as a control group. Micrometastatic cells were detected either in the bone marrow or the peritoneal cavity in 51% of the cancer patients (gastric cancer: 51%, colorectal cancer: 40%, pancreatic cancer: 72%). The occurrence of stained cells in the peritoneal cavity and bone marrow samples correlated with the tumor stage and showed even in about 30% of patients with a stage I tumor positive bone marrow and/or peritoneal cavity samples. No unspecific reactions were found in the control group. The 2-year follow up shows a significant correlation between tumor cell detection and the survival. Our study strongly indicates a clinical benefit of this method in adjuvant therapy concepts.

Adenocarcinoma↗
PubMed1994

[Diagnosis of adrenal cortex insufficiency in steroid-dependent bronchial asthma--the CRH test in comparison with diurnal cortisol profile in serum and cortisol in 24-hour urine].

In 50 patients with bronchial asthma requiring systemic treatment with glucocorticoid preparations, a CRH test has been performed in addition to the conventional determination of cortisol in the serum and 24-h urine in order to evaluate the function of the hypothalamo-pituitary-cortico-adrenal axis. According to the CRH test, 19 of the 50 patients were suffering from corticoadrenal insufficiency, whereas both the conventional tests had yielded a high percentage of false-positive and false-negative findings. There was no indication for the assumption that development of insufficiency of the corticotropic axis was in any way dependent on the glucocorticoid preparation or on the dosage or duration of treatment.

Adrenal Cortex↗
PubMed1994

[Immunocytologic detection of disseminated tumor cells in the peritoneal cavity and bone marrow in patients with pancreatic carcinoma].

Despite radical surgical treatment, the prognosis of patients with pancreatic cancer is poor. The success of surgical treatment is often limited due to local recurrence and especially the development of metastases and peritoneal carcinosis by cells which have been seeded already at the time of operation. Immunocytological methods enabled the detection of disseminated cancer cells before their clinical manifestation as demonstrated by this study. Lavage samples from the peritoneal cavity and bone marrow samples from 34 patients with an adenocarcinoma of the pancreas were investigated with a panel of six different monoclonal antibodies against tumor-associated antigens (CEA, CA-19-9, 17-1A, C-54-0, Ra96) and cytokeratin, respectively. Additionally, 43 patients with benign diseases were investigated as a control group. By this method, micrometastases were detected either in the bone marrow or the peritoneal cavity in 76% of pancreatic cancer patients. The occurrence of stained cells in the peritoneal cavity and bone marrow samples correlated with the tumor stage and showed even in early stages (I and II) a detection rate of 43% (bone marrow) and 33% (peritoneal cavity), respectively. No unspecific reactions were found in the control group. The 1-year follow-up shows a significant correlation between tumor cell detection and the survival (p = 0.03). Our study demonstrates that in most patients pancreatic cancer is a disseminated disease at time of diagnosis. It underlines the need for adjuvant postoperative therapy concepts.

Adenocarcinoma↗
PubMed1993

Sequence-specific resonance assignments of the 1H-NMR spectra of a synthetic, biologically active EIAV Tat protein.

The equine infectious anemia virus (EIAV) trans-activating (Tat) protein is a close homologue of the human immunodeficiency virus (HIV) Tat protein. Both of these proteins bind to an RNA trans-activation responsive element (TAR). We synthesized chemically a protein with the sequence of the 75 amino acid Tat protein from EIAV. The chemically synthesized protein was shown to be biologically active. Circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectroscopy were used to structurally characterize the synthetic protein. We obtained nearly complete resonance assignments in the 2D-NMR spectra of the protein at pH 3.0. There is at least some evidence from the experimental data that the basic TAR binding domain of the synthetic protein has a tendency to form a helix, but our experiments also indicate that the protein probably does not have an overall stable tertiary structure in aqueous solution at this pH. CD spectroscopy suggested that the protein adopts a more stable, predominantly alpha-helical structure in a trifluoroethanol/water solution.

Amino Acid Sequence↗
PubMed1993

[Chronic obstructive lung disease and alpha-2-macroglobulin deficiency in serum--case report].

The protease-antiprotease concept has contributed substantially to the pathogenetic understanding of different internistic disease patterns including the generalised, histologically mostly panlobular pulmonary emphysema. Attention is presently focused on alpha-1-antitrypsin protease inhibitor deficiency for which substitute solutions are already available. We present a case report on a patient of 40 years of age suffering from a severe, basally located pulmonary emphysema (as was evident on x-ray examination) with respiratory global insufficiency and an obstructive component that was only partially reversible under medication. Laboratory chemistry revealed that this was associated with an alpha-2-macroglobulin deficiency. Possibly the deficiency in this protease inhibitor of low specificity but broad spectrum of action may contribute to a better understanding of some of the types of emphysema that had so far been subclassified as cryptogenic although bearing traits of "proteinase inhibitor deficiency".

Adult↗
PubMed1992

(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate.

[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Intraperitoneal hepatocyte transplantation: morphological results.

The value of isolated intraperitoneal hepatocyte transplantation as a temporary support in acute hepatic failure is controversial since the functional capacities and survival rate of auxiliary transplanted liver cells are uncertain. It was the aim of this study to investigate the survival rate of intraperitoneally (i.p.) transplanted hepatocytes and microcarrier attached hepatocytes. In 25 rats (group A) an i.p. hepatocyte transplantation and in 30 rats (group B) an i.p. microcarrier attached hepatocyte transplantation was performed and the animals were killed at 3 h, 12 h, 24 h, 3 and 7 days (group A) and 1, 2, 3, 7, 14 and 28 days (group B) after transplantation. Histological investigation showed that transplanted hepatocytes undergo complete cell necrosis within 3 days (groups A and B). Liver cell necrosis was followed by a peritoneal reaction resulting in granuloma formation in both groups. Since liver cell necrosis occurred soon after transplantation and could not be avoided by attachment of liver cells to microcarriers, it can be concluded that metabolic support from transplantation cannot be expected in acute hepatic failure.

Animals↗
PubMed1991

[Necroses and hematomas--two local complications in intraoral conduction anesthesia. Case report].

According to the literature vascular lesions are reported in 6% of intraoral conduction anesthesia. A possible consequence is the intraarterial injection of catecholamin added local anesthetic. Due to a long lasting angiospasm necrosis of local mucosae and extraoral skin are possible. In a young female patient extraoral necrosis of parts of the skin of the lower lip and intraoral mucosa appeared, following intraoral conduction anesthesia. Subsequently a scar persisted needing a plastic cicatricotomy. Moreover sensitivity in the area of distribution of the mental nerve was deranged.

Adult↗
PubMed1991

[Laparoscopic cholecystectomy. An alternative procedure in the treatment of symptomatic cholecystolithiasis].

The authors report about their first experiences concerning the treatment of gallbladder stones using a laparoscopic approach. 40 patients (33 female, 7 male) were treated with this new method. The age of the patients, who had undergone this procedure, varied from 24 to 76 years, the average age was 42 years. Our current indication is the symptomatical chronic gallbladder lithiasis. The average time of operation was 60 to 90 minutes. The mortality rate was zero. Slight operative bleeding from an accessory artery and vein occurred in two cases. This was controlled by electrocoagulation. We observed no complications in the postoperative phase. The patients were dismissed from the hospital on the 3. to 5. day. This method is very favourable with regard to the operative strain on the patients.

Adult↗
PubMed1991

[Intraperitoneal hepatocyte transplantation: morphologic findings and clinical relevance].

In order to evaluate if intraperitoneal hepatocyte transplantation could include a therapeutic approach in acute hepatic failure, isolated hepatocytes as well as microcarrier attached hepatocytes were transplanted intraperitoneally and the survival rates of transplanted cells were evaluated morphologically. The histological investigations showed, that the transplanted hepatocytes undergo complete cell necrosis within 3 days due to a lack of substrate, which also cannot be avoided by an attachment to microcarriers. Liver cell necrosis is followed by a peritoneal reaction resulting in granuloma formation. Because liver cell necrosis occurred early after i.p. hepatocyte transplantation a functional support in acute hepatic failure cannot be expected.

Animals↗
PubMed1990

[Determination of a prececal N-absorption from natural feed by 15N-labeled laboratory rats using the isotope dilution method].

60 Wistar rats (5 animals/group) received 12 different feedstuffs over a period of 7 days and were simultaneously labelled with 15N (orally by means of 15NH4Cl in the feed). In the subsequent 5 days faeces were collected in order to determine the apparent and true digestibility of crude protein. On the 13th experimental day the animals were killed 3 hours after the intake of half the daily ration and the atom-% 15N excess (15N') was determined in the TCA-soluble and TCA-precipitable fractions of the blood plasma and the digesta of the 2nd and 3rd thirds of the small intestine. Precaecal N-absorption was calculated with the help of the quotient [formula: see text] the blood plasma and the digesta The following values (in %) were registered in comparison to true N-digestibility (in the following in brackets): casein = 95.8 (99.2), whole egg = 92.1 (97.5), fish meal = 85.8 (93.4), dried skimmed milk = 98.4 (96.1), soybean meal = 79.6 (90.6), assay protein = 94.2 (98.9), wheat = 92.9 (90.7), barley = 84.3 (84.8), yeast, grown on molasses = 85.6 (87.2), yeast, grown on whey = 86.1 (88.5), biomass of liquid manure = 43.6 (68.9), activated sludge = 54.4 (64.1). One can conclude that the isotope dilution technique demonstrated here as an evaluation method is very well suited for the characterization of the N-digestibility of a feedstuff in the small intestine.

Animal Feed↗
PubMed1989

Determination of epitope specificities and affinities of monoclonal antibodies in solution phase using biotin-labeled carcinoembryonic antigen and avidin as precipitating agent.

A generally applicable method for the selective precipitation of antigens from solution phase is presented. The method is based on the rapid and quantitative binding of avidin to biotin-labeled antigen in the presence of biotinylated carrier protein. Using carcinoembryonic antigen (CEA) as a model antigen biotin-labeled CEA was precipitated to greater than 97% at amounts of up to 5000 ng/tube. The method was applied to the determination of epitope specificities and affinities of monoclonal anti-CEA antibodies in solution phase. Non-specific precipitation did not exceed 2% for radiolabeled Fab fragments and 6% for radiolabeled IgG. Because antigen-antibody binding takes place in solution, artifacts introduced by the immobilization of reactants to solid supports are omitted.

Animals↗