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Biomedical subjects

C Unger

Publications and source records attributed to C Unger.

At least 73 records · Page 4Linked to original sources
PubMed1997

Premature contractions: possible influence of sonographic measurement of cervical length on clinical management.

In a retrospective case control study with historical controls, the influence of the introduction of vaginal sonographic cervical length measurement on the utilization of hospital services and pregnancy outcome of gravid women at risk of preterm delivery was examined. Prior to the introduction of vaginal ultrasonography to measure cervical length, we registered 76 hospitalizations totalling 1827 hospitalization days due to premature cervical ripening and/or premature labor in 1991 and 1992. In 1994 and 1995, after vaginal ultrasonography was introduced and intravenous tocolysis was limited to cases with cervical shortening to less than 3 cm, there were 64 admissions resulting in just 869 hospitalization days. Long-term hospitalizations (over 10 days) were reduced from 55 to 25 cases (p < 0.0001) and the median length of hospital stay decreased from 18 to 8 days (p < 0.0001). The number of preterm births (< or = 37 weeks) remained stable: 12 cases in 1991-1992 and 13 cases in 1994-1995. In conclusion, vaginal sonographic measurement of cervical length provides an objective criterion for cervical shortening with premature labor. The method could therefore be a suitable means of reducing unnecessary therapeutic interventions in gravid women with premature contractions and/or cervical dilatation. A prospective randomized trial to confirm these findings is suggested.

Case-Control Studies↗
PubMed1997

Phase I study of paclitaxel administered as a 1-hour infusion: toxicity and pharmacokinetics.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most important new drugs used in the treatment of solid tumors. Use of paclitaxel, however, is associated with some toxicity. The main adverse side effects include myelotoxicity, neurotoxicity, hypersensitivity reactions, and asthenia. Toxicity seems to be schedule dependent. Currently, paclitaxel is routinely administered via 3- or 24-hour infusions. This study was performed to evaluate the toxicity and pharmacokinetics of a 1-hour infusion. Thirty-four patients with incurable solid tumors were included. Dose levels were escalated from 150 to 250 mg/m2. Thirty-four patients received a total of 105 courses of paclitaxel. The dose-limiting toxicity was World Health Organization grade 3 neuropathy at a dose of 250 mg/m2 in two of three patients. Two patients were not evaluable for dose-limiting toxicity because treatment was stopped after fewer than three courses due to disease progression. Neither had experienced a dose-limiting toxicity. Other toxicities were World Health Organization grade 1/2 neutropenia, asthenia, myalgia, arthralgia, and grade 1 hypersensitivity. Twenty-one patients were evaluable for preliminary anticancer efficacy. A partial response was observed in five patients (24%), stable disease in three (14%), and progressive disease in 13 (62%). The maximum tolerated dose was established at 250 mg/m2. A dose of 225 mg/m2 is recommended for further phase II trials. There was considerable interindividual and some intraindividual variability in pharmacokinetic parameters. Paclitaxel pharmacokinetics were linear up to 225 mg/m2, while a slightly overproportional increase in the peak plasma concentration and the area under the concentration-time curve was observed at 250 mg/m2, suggesting that paclitaxel's pharmacokinetic characteristics may be nonlinear at higher doses.

Adolescent↗
PubMed1996

Current concepts of treatment in medical oncology: new anticancer drugs.

General principles for anticancer drug development include traditional drug-screening methods in biological test systems. Today, testing of a drug in a panel of selected human tumor xenografts in mice is assumed to have the best predictive value for clinical efficacy. Chemical modification of well-known antitumor drugs from compound groups such as purine analogs, vinca alkaloids, antifolates and platinum analogs are carried out to increase anticancer activity, to reduce toxic side-effects and to improve pharmacokinetic properties of the drugs. In the last decade the enormous development in molecular techniques has led to the discovery of key proteins that are intimately involved in the regulation of cancer growth control. Cell growth inhibitors could be developed by structure-based design, creating small organic molecules ("peptide mimetics") to target crucial enzymes, oncogenes or oncogene products, tumor-suppressor genes and their products as well as growth factors and their corresponding receptors. Drugs representing new leading structures, like alkylphosphocholines, topoisomerase I inhibitors, taxoids and suramin, have already entered the clinic. Novel therapeutic approaches may provide substantial progress in cancer treatment in the very near future. Examples are the concept of high-dose chemotherapy with hematopoietic stem cell support, the various strategies of gene therapy, the modulation of multi-drug resistance of cancer cells, and strategies to inhibit tumor angiogenesis.

Animals↗
PubMed1996

Axillary lymphadenectomy--just how radical should it be?

UNLABELLED: To determine whether local axillary recurrences correlate with the number of lymph nodes extirpated, 779 cases of breast cancer were analysed in retrospect. RESULTS: The number of lymph nodes extirpated varied between 1 and 42 per axilla. The axillary recurrence rate of 5.5% showed a minimal correlation between the frequency of these recurrences and the number of lymph nodes removed. There is an equally insignificant correlation between the percentage of positive histological findings and the number of lymph nodes extirpated: The trend analysis shows that with fewer than five lymph nodes extirpated, 40% of positive histological findings can be expected, whereas with over 20 lymph nodes extirpated the percentage is 45%. CONCLUSION: The number of lymph nodes extirpated is an unsuitable indicator as to how radical axillary clearance is. Surgeons should rely on anatomical boundaries rather than focusing on the number of lymph nodes removed.

Adult↗
PubMed1996

Does labor start too late?

To determine the optimal time of delivery, in terms of lowest risk of peripartum complications, the relative incidences of the parameters. Abnormal cardiotocogram (CTG), operative vaginal delivery, Apgar < 7 at 1 and 5 min, artery cord blood pH < 7.20, blood loss > 500 ml, epidural anesthesia, and Cesarean section, were retrospectively analysed with regard to mode of labor onset (spontaneous, induced) and gestational age in all deliveries between gestational weeks (GW) 35 + 0/7 and 42 + 6/7 from 1986 through 1993 at Zurich University Hospital (n = 11,834) and additionally with regard to birth weight in the same population from 1987 through 1993 (n = 10,346). The distribution of most parameters was parabolic with nadirs at GW 37-38; the incidence of low Apgar scores and Cesarean sections, however, was lowest nearer term (GW 39-40). Mode of labor onset had little effect (< or = 1 week) on the time of lowest incidence. The birth weight associated with the fewest complications was 3000 g, with the optimal time of delivery being GW 37-38, assuming a birth weight normal for gestational age.

Anesthesia, Epidural↗
PubMed1995

[Are there alternative forms of therapy in breast carcinoma? Status and perspectives for the treatment of metastasized breast carcinoma].

The emergence of new cytotoxic agents and techniques for treatment of systemic disease as single modalities or in combination with irradiation and surgery will impact on the use of such agents in the management of systemic breast cancer. Metastatic breast carcinoma, unlike other solid tumors, is highly responsive to chemotherapy, response rates of 50 to 70% have been reported consistently, although there has not been a significant improvement on long-term survival of these patients in the last ten years. New therapeutic approaches include cytotoxic and hormonal agents, growth and differentiation factors, monoclonal antibodies, hematopoietic stem cell support, conquest of tumor cell resistance by MDR-modulation, genetic manipulation, identification of new targets on the tumor surface, synthesis of target-oriented designer-drugs and inhibition of tumor angiogenesis. In breast cancer the tumor growth correlates with vascularization and angiogenesis. Tumor angiogenesis is stimulated by the vascular endothelial growth factor (VEGF). Microvessel density is a significant predictor of survival among node-negative women, who are at risk for having occult metastases at presentation. These patients could then be given systemic adjuvant therapy. Animal experiments show promising inhibition of tumor growth in nude mice after application of antibodies against VEGF. Other methods of manipulation of molecular mechanisms of angiogenesis are under investigation.

Breast Neoplasms↗
PubMed1995

Effects of hexadecylphosphocholine on membrane phospholipid metabolism in human tumour cells.

Hexadecylphosphocholine (HePC) is an analogue of the antiproliferative alkyllysophospholipids (ALP). As these lipid-like compounds interfere with membrane lipid metabolism at several sites, we studied the effects of HePC on uptake and metabolism of inositol and choline, two important phospholipid precursor molecules in two sensitive cell lines, Raji and KB, and in a resistant variant of KB cells, KBr. HePC substantially inhibited the membrane uptake of inositol and of choline in KB and Raji. Inositol uptake of KBr cells was constitutively low and was not further decreased by HePC. In all three cell lines, uptake inhibition of choline was less pronounced. Uptake inhibition showed characteristics of a non-specific effect, probably due to the physicochemical properties of HePC as a "lyso" structure. Decreased uptake of inositol did not affect phosphoinositide synthesis. Cellular phosphatidylcholine (PC) metabolism seemed to be affected through inhibition of choline incorporation and enhancement of PC degradation in the two sensitive cells. In KBr cells, these effects were not observed.

Antineoplastic Agents↗
PubMed1995

Anti-pneumococcal antibody levels three to seven years after first booster immunization in children with sickle cell disease, and after a second booster.

We measured pneumococcal antibody levels in 55 patients (ages 7 to 20 years) with sickle cell disease 3 to 7 years after the first booster immunization. Only 6 of the children had protective levels of antibodies (> 300 ng/ml) against all 12 serotypes tested. Thirty-two children (58%) had suboptimal levels against 1 to 3 serotypes; 17 had suboptimal levels against 4 to 10 serotypes. Ten patients from the latter group (ages 13 to 17 years) received a second booster 6 to 8 years after the first booster immunization, and had a marked increase in antibody levels against all serotypes with the exception of serotypes 3 and 4 in two patients and serotype 6A in one patient.

Adolescent↗
PubMed1995

Biochemical, physiological, and molecular characterization of sucrose synthase from Daucus carota.

Sucrose synthase (EC 2.4.1.13) from carrot (Daucus carota) is a tetramer with a molecular mass of 320 kD and subunits of 80 kD. The enzyme has a pH optimum of 7.0 (cleavage direction). Maximal activities were measured at 55 degrees C. The Km for Suc was estimated as 87 mM and for UDP as 0.39 mM. Fructose acts as a noncompetitive inhibitor with an inhibition constant of 17.2 mM. In contrast, glucose inhibits carrot sucrose synthase uncompetitively with an inhibition constant of 4.3 mM. cDNA clones encoding a single class of sucrose synthase polypeptide were isolated and sequenced. DNA gel blot analysis also indicated the occurrence of only one to two genes. The deduced amino acid sequence of the carrot enzyme is highly homologous to the sucrose synthase sequences of tomato, potato, and bean. A comparison of the cDNA-derived amino acid sequence with the SS1- and SS2-type sucrose synthase sequences of the monocot plants maize, rice, and barley showed that the carrot enzyme is neither of the SS1 nor of the SS2 type. High enzyme activity was found in roots and petioles of developing carrot plants, with maximal activity in roots at the transition of primary roots to tap roots. Enzyme activity was highly correlated with both polypeptide and transcript levels, indicating that gene expression is regulated mainly at the mRNA level in the different tissues and organs of developing carrot plants.

Amino Acid Sequence↗
PubMed1994

Gamma-irradiation-induced micronuclei from mouse hepatoma cells accumulate high levels of the tumor suppressor protein p53.

The p53 tumor suppressor protein plays an important role in the G1 arrest of cells treated with DNA-damaging agents. Mouse hepatoma cells with wild-type or mutated p53 genotype were gamma-irradiated and the time course of p53 expression was determined by immunocytochemical staining. In p53 wild-type cells, gamma-irradiation led to a transient accumulation of the protein in the nuclei, whereas no such accumulation occurred in p53-mutated cells. Micronuclei were induced by gamma-irradiation in both wild-type and mutated cells in a dose- and time-dependent manner, but only micronuclei from p53 wild-type cells demonstrated a strongly positive staining reaction for p53 protein. This accumulation of p53 protein in micronuclei was not associated with a block in DNA synthesis as evidenced by bromodeoxyuridine labeling experiments.

Animals↗
PubMed1994

Pharmacokinetic behavior and antineoplastic activity of liposomal hexadecylphosphocholine.

Hexadecylphosphocholine (HePC) shows remarkable antineoplastic efficacy in Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinoma. Unfortunately, this is accompanied by detrimental side effects that include gastrointestinal damage, body weight loss, and thrombophlebitis after i.v. injection, which has precluded the use of the HePC in humans, where nausea and vomiting can occur at noneffective dose levels. We have developed small unilamellar vesicles (SUVs) composed of HePC, cholesterol, and 1,2-dipalmitoyl-sn-gly-cero-3-phosphoglycerol, which can be given p.o. and i.v. In contrast to the free drug, the toxicity of liposomal HePC is shown to be greatly reduced, and there is no risk of thrombophlebitis. Single administration of equimolar HePC doses results in differing pharmacokinetic values for free HePC (p.o.) and HePC-SUVs (p.o., i.v.).

Administration, Oral↗
PubMed1994

Inhibition of calcium-dependent protein kinase C by hexadecylphosphocholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine do not correlate with inhibition of proliferation of HL60 and K562 cell lines.

We investigated the hypothesis that the antiproliferative effect of hexadecylphosphocholine (HePC) and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is mediated through the inhibition of cellular protein kinase C (PKC). In the sensitive HL60 cell line, ID50 and LD50 values of 5.6 and 5.3 microM, respectively (HePC), and of 3.8 and 4.2 microM, respectively (ET-18-OCH3) were obtained. In the more resistant K562 cell line, these values were 69.1 and > 97 microM, respectively (HePC) and 7.8 and 76.8 microM, respectively (ET-18-OCH3). Treatment of both cell lines with HePC and ET-18-OCH3 (25 microM) for 2 h did not lead to PKC translocation. However, a 30% reduction of PKC activity, mainly due to a decrease in the cytosolic compartment, was found. Half maximal stimulation of PKC translocation by phorbolester (TPA) in HL60 and K562 cells, which were pretreated for 2 h with 25 microM of the lipids, resulted in a 20-30% decrease of membrane-bound PKC, whereas the cytosolic form was found to be unchanged. In the same experimental setting, dioctanoylglycerol (DIC8)-stimulated PKC translocation was not affected by HePC or ET-18-OCH3. However, a 10-20% reduction of PKC enzyme activity in the membrane and in the cytosolic fraction was obtained. These findings indicate that HePC and ET-18-OCH3 do not interfere with PKC translocation but rather mediate a general decrease of the enzyme activity in the membrane and cytosol of the cells. Since the extent of PKC inhibition was somewhat similar in the sensitive HL60 and the resistant K562 cell line, inhibition of PKC is probably not a prerequisite for the antiproliferative action of HePC and ET-18-OCH3.

Antineoplastic Agents↗
PubMed1994

cDNA cloning of carrot (Daucus carota) soluble acid beta-fructofuranosidases and comparison with the cell wall isoenzyme.

Carrot (Daucus carota), like most other plants, contains various isoenzymes of acid beta-fructofuranosidase (beta F) (invertase), which either accumulate as soluble polypeptides in the vacuole (isoenzymes I and II) or are ionically bound to the cell wall (extracellular beta F). Using antibodies against isoenzyme I of carrot soluble beta F, we isolated several cDNA clones encoding polypeptides with sequences characteristic of beta Fs, from bacteria, yeast, and plants. The cDNA-derived polypeptide of one of the clones contains all partial peptide sequences of the purified isoenzyme I and thus codes for soluble acid beta F isoenzyme I. A second clone codes for a related polypeptide (63% identity and 77% similarity) with characteristics of isoenzyme II. These two soluble beta Fs, have acidic isoelectric points (3.8 and 5.7, respectively) clearly different from the extracellular enzyme, which has a basic isoelectric point of 9.9. Marked differences among the three nucleotide sequences as well as different hybridization patterns on genomic DNA gel blots prove that these three isoenzymes of carrot acid beta F are encoded by different genes and do not originate from differential splicing of a common gene, as is the case in the yeast Saccharomyces cerevisiae. All three carrot acid beta Fs, are preproenzymes with signal peptides and N-terminal propeptides. A comparison of the sequences of the soluble enzymes with the sequence of the extracellular protein identified C-terminal extensions with short hydrophobic amino acid stretches that may contain the information for vacuolar targeting.

Alternative Splicing↗