Showing papers by "University of Duisburg-Essen published in 1996"

Human Papillomavirus Infections in Nonmelanoma Skin Cancers From Renal Transplant Recipients and Nonimmunosuppressed Patients

Abstract: Background : Nonmelanoma carcinomas of the skin represent the most frequent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. Purpose : We analyzed tumors obtained from both immunosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. Methods : Twenty-nine specimens of nonmelanoma carcinomas of the skin were obtained from 19 renal allograft recipient patients ; these included 20 specimens of squamous cell carcinoma (SCC) from 11 patients, five specimens of basal cell carcinoma (BCC) from four patients, and four specimens of carcinoma in situ (CIS) from four patients. Forty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients ; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four keratoacanthoma (benign epithelial tumor) specimens from four patients. A polymerase chain reaction method involving use of degenerate oligonucleotide primers, in which the conserved region of the open reading frame of the HPV L1 (major capsid protein) gene is amplified, was used to amplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions ; different primer combinations were used in order to increase the sensitivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specific DNA was either sequenced directly after elution from the gel or amplified with semi-nested, degenerate primers, after which the products were cloned and sequenced. Sequences were compared with all known papillomavirus sequences. Results : Thirteen (65%) of the 20 SCC specimens and three of the five BCC specimens from immunosuppressed (renal allograft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malignant tumor specimens from this patient group revealed faint signals upon amplification and hybridization ; the origin of these signals has not been identified in the present study. In nonimmunosuppressed patients, eight (31%) of 26 SCC specimens and four (36%) of 11 BCC specimens contained sequences of HPV types. Two putative novel HPV sequences could be identified in this group. Faint signals of yet undetermined origin were observed in eight of the SCC specimens and in two of the BCC specimens. Two of four keratoacanthoma specimens contained sequences of known HPV type. (Keratoacanthoma is a nonmalignant lesion for which the natural history has not been defined.) The spectrum of HPV types in both groups of patients differed substantially. Conclusions : These data point to the frequent presence of HPV sequences in SCCs and BCCs of the skin. The etiologic relationship of these infections to the respective malignant tumors remains to be evaluated. Implications : The presence of HPV DNA in a large percentage of specimens of nonmelanoma carcinomas of the skin from immunosuppressed patients, as well as from nonimmunosuppressed patients, renders a papillomavirus infection as a possible factor in the etiology of this disease

Observer-based supervision and fault detection in robots using nonlinear and fuzzy logic residual evaluation

Abstract: A high degree of automation in flexible production units require powerful tools for supervision and fault detection to maintain quality and productivity. In this paper, an observer-based fault detection method is proposed which makes use of non-measurable process information instead of installing as many sensors as possible. The detection method is reviewed and applied to the fault detection problem in an industrial robot, using a dynamic robot model. The robot model is enhanced by the inclusion of nonlinear friction terms. A new residual evaluation approach of model-based fault detection methods is investigated for processes which exhibit unstructured disturbances, arising from model simplification. The present analytical approaches are applicable only to structured approaches. In this paper a fuzzy-logic approach is presented which is capable to address unstructured disturbances as well. Finally, some practical results for an industrial robot example are presented.

Novel Stable Silenes via a Sila-Peterson-type Reaction. Molecular Structure and Reactivity

Abstract: The first stable silene was synthesized only in 19811 after decades of intensive unsuccessful attempts.2 Despite intensive recent research, the study of silenes is still in its infancy.2 For example, only two methods for the synthesis of stable silenes are currently known1,3 and the X-ray structures of only 2 silenes, (Me3Si)2SidC(OSiMe3)Ad (1)4 and Me2SidC(SiMe3)SiMe(tBu)2 (2),5 have so far been determined. More recently West et al. reported the first X-ray structure of a 1-silaallene, R2SidCdCR2. We report here an important new synthetic method for preparing stable silenes having a novel substitution pattern and report the X-ray structure for one of these silenes. We7a and others7b have reported recently that transient silenes can be synthesized via a sila-Peterson-type reaction (eq 1). For

Early age-dependent growth impairment in chronic renal failure

Abstract: We report early linear growth in 73 children (51 boys, 22 girls) with early onset of chronic renal failure (CRF). The inclusion criteria was onset of CRF before 6 months of age, two or more height measurements during the 1st year of life, follow-up for at least 3 years and continuously impaired renal function with a glomerular filtration rate below 50 ml/min per 1.73 m2 at 1 year or later. Only height measurements taken during conservative treatment or dialysis were included. The data were analysed in terms of the infancy-childhood-puberty growth model. There was an age-dependent growth failure in early life leading to an attained height of −3 standard deviation score (SDS) at 3 years of age. Approximately one-third of the reduction in height occurred during fetal life and one-third during the first postnatal months. Between 0.75 and 1.5 years of age height also decreased by 1 SD as a consequence of a delayed onset of the second, the “childhood’, phase of growth in 36% of the patients and by an ‘offset childhood’ growth pattern — i.e. a return to the infancy phase pattern after onset of the childhood phase — in 60% of the patients. Growth between 0.25–0.75 and 1.5–5 years of age was generally percentile parallel and thus less likely to be affected in CRF with early disease onset. The glomerular filtration rate was not related to the height gain in early life. We speculate that the growth failure during fetal life and the first postnatal months reflects metabolic and/or nutritional influences and the impaired growth at 0.75–1.5 years of age is related to a partial insensitivity to growth hormone.

Influence of moderate alcohol consumption on obstructive sleep apnoea with and without AutoSet nasal CPAP therapy

Abstract: Snoring worsens with high alcohol consumption. It is unclear whether moderate alcohol intake worsens sleep and breathing in subjects with obstructive sleep apnoea syndrome (OSAS), and whether alcohol increases the pressure requirement for nasal continuous positive airway pressure (CPAP). Fourteen adult males with untreated OSAS but without heart or lung disease were studied (age 53+/-9 yrs, body mass index (BMI) 33+/-5 kg x m(-2) (mean+/-SD). The subjects underwent overnight polysomnography on four occasions: control, alcohol, CPAP, and alcohol + CPAP. On the alcohol nights, the subjects drank 1.5 mL x kg(-1) body weight (BW) vodka (40% alcohol by volume) (blood alcohol with and without CPAP 0.45+/-0.1 and 0.47+/-0.2 mg x mL(-1) (mean+/-SD)). On the CPAP nights, the pressure required to prevent apnoea, snoring, and silent inspiratory airflow limitation was determined using an autotitrating nasal CPAP system (ResCare AutoSet). Alcohol and control nights were performed in random order. Without CPAP, alcohol produced a small non-significant decrease in the percentage of rapid eye movement (REM) sleep (control 11+/-2 vs alcohol 8+/-1% (mean+/-SEM)), but with CPAP there was no such effect (control 15+/-2 vs 17+/-2%; CPA x alcohol interaction p=0.015). With CPAP, slow-wave sleep in the first 2 h increased slightly with alcohol (control 39+/-6 vs alcohol 51+/-4%; p=0.004). Arousal index without CPAP increased slightly with alcohol (control 43+/-5 vs alcohol 49+/-6 events x h(-1); p=0.02). There was little or no effect of alcohol on other sleep stages, arousal index, apnoea index, apnoea/hypopnoea index, mean or longest event duration, mean or worst arterial oxygen saturation, with or without CPAP, either for the full night or for the first 2 h. There was no change in the pressure requirement for CPAP (full night: control 11.9+/-0.9 vs alcohol 12.5+/-0.9 cm H2O; first 2 h: 10.9+/-0.6 vs 11.1+/-0.8 cm H2O). Moderate alcohol intake (in the form of vodka) has little effect on breathing or saturation during sleep in subjects with mild-to-severe obstructive sleep apnoea, and no effect on the pressure required for continuous positive airway pressure in order to prevent apnoea, snoring, and flow limitation. These results cannot be extrapolated to other doses or forms of alcohol, or to subjects with concurrent heart or lung disease.

Synthesis and catalytic properties of large ligand stabilized palladium clusters

Abstract: Ligand stabilized palladium clusters in the size range of 3–4 nm on various supports are used as catalysts in gas phase and liquid phase hydrogenation reactions. 1,10-Phenanthroline and O2 form the ligand shell for a mixture of seven- and eight-shell clusters. ( Pd 7 8 (phen)), on TiO2, Al2O3, and CaCO3. The gas phase hydrogenation of 1,3-butadiene under various conditions gives results like established metal catalysts, i.e. low selectivities. In contrast with these observations liquid phase reactions show high selectivities which can additionally be influenced by variation of the ligand shell. Semihydrogenation of 2-hexyne with Pd 7 8 (phen) on TiO2 in n-octane results in 93% of cis-2-hexene. If 3-n-butyl or 3-n-heptyl-phenanthroline is used instead of the unsubstituted ligand the selectivity is about the same, however, the formation of daughter products such as isomers or n-hexane is almost completely suppressed. The hydrogenation of a series of unsaturated carbonic acids again shows the influence of the nature of the ligands on the products. Here, phenanthroline and (−)-cinchonidine are compared. Finally, the hydrogenation of acetophenone is studied using di-2,9-(2-methyl-butyl)-1,10-phenanthroline and (−)-cinchonidine for comparison. The isopentyl substituted phenanthroline enforces high activities, whilst cinchonidine prevents the same reaction almost quantitatively. TEM and STM studies of the clusters have been performed and will be described.

Adjustment of bronchoalveolar lavage volume to body weight in children

Abstract: To define the amount of epithelial lining fluid (ELF) that is recovered during bronchoalveolar lavage (BAL) in the pediatric age group, we measured albumin and urea concentrations in serum and BAL fluid (BALF) of 37 children aged 3-15 years without bronchopulmonary disease. The children were studied while undergoing elective surgery for non-pulmonary illnesses using a BAL protocol adjusted to body weight. ELF increased with age in proportion to increases in lavage volume. When corrected for the child's weight, approximately 20 mu l ELF/kg body weight were recovered throughout the age range. ELF derived by determining albumin or urea concentrations in BALF were significantly correlated; however, considerable variability was observed in older children when the urea method was used. This was likely due to the increase in dwell time that is known to affect urea concentrations in BALF. In children ELF/100 ml BALF was higher than in adults, suggesting a greater permeability of the alveolar membrane in children. These data show that a BAL protocol adjusted to body weight will yield constant fractions of ELF in children aged 3-15 years. These results should facilitate the comparison of BALF constituents in children of different age groups.

Analytic wavelets generated by radial functions

Abstract: In this paper, we deal with a class of non-stationary multiresolution analysis and wavelets generated by certain radial basis functions. These radial basis functions are noted for their effectiveness in terms of “projection”, such as interpolation and least-squares approximation, particularly when the data structure is scattered or the dimension of ℝ s is large. Thus projecting a functionf onto a suitable multiresolution space is relatively easy here. The associated multiresolution spaces approximate sufficiently smooth functions exponentially fast. The non-stationary wavelets satisfy the Littlewood-Paley identity so that perfect reconstruction of wavelet decompositions is achieved. For the univariate case, we give a detailed analysis of the time-frequency localization of these wavelets. Two numerical examples for the detection of singularities with analytic wavelets are provided.

Relevance of asbestos bodies in sputum

Abstract: The presence of asbestos bodies (ABs) in sputum specimens of individuals with occupational asbestos exposure has been well-documented. The aim of this study was to determine their clinical relevance in comparison to the concentration of AB in bronchoalveolar lavage (BAL) and lung tissue. Subjects were included following a well-documented exposure of asbestos history (n = 93) or BAL fluid analysis positive for ABs (n = 42). The subjects with a well documented history of AB exposure were divided into three groups: heavy (Group 1, n = 29); moderate (Group 2, n = 31); or occasional exposure (Group 3, n = 33). BAL fluid was available from all subjects, and lung tissue from 21 subjects. To assess the variability, 10 sputum positive subjects collected subsequent sputum on days 2, 7, 14, 30 and 90. ABs were determined by light microscopy after membrane filtration of specimen digests. The mean sputum AB content was highest in Group 1 (2.4 +/- 5.5 AB.mL-1), lower in Group 2 (0.2 +/- 0.3 AB.mL-1) and lowest in Group 3 (0.1 +/- 0.1 AB.mL-1) suggesting a correlation with cumulative exposure. However, many negative sputum samples were noted, when BAL specimens were positive. The AB content of sputum and BAL specimens did not correlate. ABs were found in sputum of all subjects with a tissue content of > 1,000 AB-cm-3, but in none with contents of < 1,000 AB-cm-3. Substantial variability of ABs was found in the five sequentially collected sputa of 10 initially positive patients (coefficient of variation 28-93%), but only two false negatives were found in these 50 samples. Thus, sputum analysis for asbestos bodies is an insensitive method for assessing the lung asbestos burden, much less sensitive than bronchoalveolar lavage fluid analysis. However, a sputum sample positive for asbestos bodies is suggestive of a high lung asbestos burden.

Binding and Repair of O6-Ethylguanine in Double-Stranded Oligodeoxynucleotides by Recombinant Human O6-Alkylguanine-DNA Alkyltransferase do not Exhibit Significant Dependence on Sequence Context

Abstract: Double-stranded (ds) oligodeoxynucleotides (29mers) containing an O6-ethylguanine (O6-EtGua) flanked 5' and 3' by different bases (5'..TGT..3'; 5'..CGG..3', 5'..GGT..3'; 5'..GGG..3'; 5'..GGA..3') were synthesized to investigate the binding and repair characteristics of recombinant human O6-alkylguanine-DNA alkyltransferase (AT) in vitro. The apparent association constant (KA(app)) of AT to the oligomers and the repair rate constant for O6-EtGua (k) respectively, were determined by gel retardation and a monoclonal antibody-based filter binding assay. When ds- or single-stranded (ss) oligomers with or without O6-EtGua were used, no major differences in KA(app) values were observed with either substrate: KA(app) values for native AT were 7.1 and 8.4 x 10(5) M(-1) respectively, for unmodified and [O6-EtGua]-containing ds-oligomers. The corresponding values for ss-oligomers were 1.0 and 4.9 x 10(5) M(-1). The N-terminal first 56 amino acids of AT only exert a limited influence on DNA binding; the KA(app) values for an N-terminally truncated AT protein (1.1 x 10(5) M(-1)) and native AT were of the same order. Moreover, KA(app) was hardly affected by Cys(145)-methylated AT (2.0 x 10(5) M(-1)). The k-values (6.5-11.5 x 10(6) M(-1)s(-1)) were not significantly dependent on nucleotide sequence. k-values of 5.3 and 4.0 x 10(6) M(-1)s(-1) respectively, were obtained with the N-terminally truncated AT protein and for repair of the postreplicative mispair [O6-EtGua]: T by native AT. The low KA(app), the negligible influence on O6 of ethylation, and the minor modulation KA(app) and k by varying the bases flanking O6-EtGua, all indicate that the binding of AT to DNA is non-specific and mediated mainly by ionic interactions [reduced KA(app) and k-values at increased ionic strength]. Surplus DNA reduces the rate of O6-EtGua repair in ds-oligomers by competitive binding of AT molecules. The reaction mechanism of AT with DNA in vivo requires further investigation.

Molecular studies of chimerism and minimal residual disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation.

Abstract: We investigated 23 patients for their chimerism status who underwent allogeneic transplantation using peripheral blood progenitor cells (PBPCT) for chronic myelogenous leukemia (CML) (n = 14), acute myelogenous leukemia (AML) (n = 5), acute lymphoblastic leukemia (n = 1), myelodysplasia (MDS) (n = 1), and Hodgkin's disease (HD) (n = 2). These data were compared with those of patients after allogeneic BMT after matching them for disease and disease stage, sex of donor and recipient, GVHD prophylaxis, conditioning therapy and degree of HLA disparity. Patients were studied monthly up to 16 months post-transplant. In 11 of 23 (48%) patients who were transplanted with PBPCs and in 18 of 23 (78%) patients after BMT a mixed chimerism was detected at 1 month post-transplant. After 3 months, six of 21 (29%) evaluable patients after PBPCT remained mixed chimeric as opposed to 12 of 21 (57%) patients after BMT. We also assessed minimal residual disease using detection of the chimeric BCR/ABL transcripts by PCR of CML patients in this study. In four of 14 (29%) patients who underwent PBPCT, the BCR/ABL chimeric transcript was detected, while after BMT eight of 14 (57%) CML patients remained BCR/ABL positive. In two of these BMT patients, a cytogenetic relapse developed subsequently, and one other patient suffered a hematological relapse, whereas one of the CML patients relapsed after PBPCT. The present data may indicate that after PBPCT the incidence of leukemic relapse is similar or even lower than after BMT.

Preparation of bronchoalveolar lavage fluid with microscope slide smears

Abstract: The method of preparation of bronchoalveolar lavage fluid (BALF) for cytological examination can significantly affect the results of cellular quantitation. Investigations have shown that cytocentrifugation leads to an underestimation of the number of lymphocytes and membrane filter preparation to an underestimation of the number of neutrophils. As a simple alternative to these two techniques, BALF cells could be prepared by the microscope slide smear technique, which is familiar as the means for preparing peripheral blood for differential counts. In order to compare cell differentials determined by microscope slide technique with differentials resulting from cytocentrifugation, cells were isolated from 35 BALF samples using standard methods, and counted using a haematocytometer. Forty thousand cells in 200 microL were prepared by cytocentrifugation (3 min, 57 x g; Cytospin 2) and 5 x 10(5) cells in 5 microL by microscope slide smear. Both samples were air-dried, stained using May-Grunwald Giemsa stain, and 600 cells were counted to obtain differentials. To test the adequacy of sampling by the microscope slide smear technique, known quantities of lymphocytes or neutrophils were added to fixed numbers of BALF cells, microscope slide smears prepared, and differentials determined on 600 cells. The resulting differentials were compared to the calculated differentials. Preparation of BALF cells with the microscope slide smear technique yielded well-preserved cell morphology. Compared to cytocentrifugation, microscope slide smear preparations had significantly higher percentages of lymphocytes. The microscope slide smears for the samples with predetermined numbers of cells yielded lymphocyte and neutrophil percentages which did not differ from the calculated differentials (59.6 +/- 1.5 vs 59.6 +/- 5.2% and 54.6 +/- 6.0 vs 53.1 +/- 6.0%, respectively). Varying the number of cells counted from 100 to 800 confirmed the reproducibility of the counts for counting 600 cells. Using 5 x 10(5), 2.5 x 10(5), or 1 x 10(5) cells per preparation demonstrated that adequate specimens could be obtained from as few as 1 x 10(5) cells. Thus, microscope slide smear preparation is a simple and accurate method for the quantitation of bronchoalveolar lavage fluid cytology.

Transsternal transpericardial operations in the treatment of bronchopleural fistulas after pneumonectomy.

Abstract: Between 1972 and 1993, 19 patients (15 males and 4 females) with bronchopleural fistulae and pleural empyema after pneumonectomy were treated with transsternal transpericardial operations and closure of the fistula. The underlying malignant disease was a non-small cell carcinoma in 12, a malignant epithelial mesothelioma in two, and an atypical carcinoid tumor in one case. One patient each presented with tuberculosis, chest trauma, and lung destroyed by bronchiectasis. Fistulas affected the right bronchial stump in 17, and the left in 2, cases after pneumonectomy. The time between pneumonectomy and transsternal transpericardial operation ranged between 1 month and 4 years. All patients were submitted to drainage and irrigation of the empyema cavity (2-4 weeks). In 16 patients a long bronchial stump was sutured or stapled, in three cases resection of a short stump with the distal trachea was followed by anastomosis of the trachea and left main stem bronchus. Irrigation of the pneumonectomy cavity was continued in all patients for 2 weeks. Transsternal transpericardial operation was successful in 15 patients. Two patients died in the first 30 days, of renal or respiratory failure without fistula recurrence. In two cases the fistula recurred; definitive healing was achieved using a great omentum flap and endoscopic application of fibrin glue and bone spongiosa. Transsternal transpericardial management of bronchus stump fistula after pneumonectomy is highly effective and offers advantages over the direct approach through the infected empyema cavity.

Microsatellite instability and loss of heterozygosity at the hMLH1 locus on chromosome 3p21 occur in a subset of nonsmall cell lung carcinomas.

Abstract: Microsatellite alterations observed in tumor specimens may reflect genomic instability due to defective mismatch repair genes. To investigate whether this occurs in human nonsmall cell lung carcinomas we have analyzed microsatellite instability at 5 marker loci and loss of heterozygosity (LOH) at the hMLH1 locus on chromosome 3p21 using the polymerase chain reaction. Of a total of 49 nonsmall cell lung carcinomas examined, 43% (13 of 30 informative cases) showed LOH at 3p21 and 29% (14 of 49) exhibited microsatellite instability at one or multiple loci. LOH of the mismatch repair gene hMLH1 at 3p21 occurred in 82% (9 of 11 informative cases) of the tumors with microsatellite instability. This suggests that defects in the mismatch repair gene hMLH1 at 3p21 may be involved in microsatellite instability and tumorigenesis of a subset of nonsmall cell lung carcinomas. However, in those nonsmall cell lung carcinomas without microsatellite instability LOH at 3p21 probably involved another tumor suppressor gene(s) in this chromosomal region.

Wild type neu transgene counteracts mutant homologue in malignant transformation of rat Schwann cells.

Abstract: Mutational activation of the neu (erbB-2) receptor protein tyrosine kinase gene appears to be the triggering event in the process of oncogenesis induced by N-ethyl-N-nitrosourea (EtNU) in immature Schwann cells of the rat peripheral nervous system. Subsequent loss of the wild-type neu allele may represent a critical secondary step towards malignancy. Developmentally-regulated expression of a wild-type rat neu transgene (neu cDNA under the control of the rat Po promoter) in the Schwann cells of transgenic BDIX and Sprague-Dawley rats exposed to EtNU on postnatal day 1 results in a lower incidence of early atypical proliferates in the trigeminal nerve. Furthermore, re-introduction of the wild-type neu gene into homozygous neu mutant schwannoma cells counteracts the expression of the tumorigenic phenotype. The suppressive action of the wild-type gene over its mutationally activated oncogenic homologue underlines the critical function of the neu gene in the control of differentiation in the Schwann cell lineage, and provides evidence for the responsiveness of cellular phenotypes towards quantitative shifts in the dosage of wild-type vs mutant signal transducing molecules.

Wheat kernel ingestion protects from progression of muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy

Abstract: A simple, reproducible test was used to quantify muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy. The effect of bedding on wheat kernels and of dietary supplementation ofα-tocopherol on the progression of muscle weakness was investigated in mdx mice. When measured during the first 200 d of life,mdx mice developed muscle weakness, irrespective of bedding and diet. When kept on wood shavings and fed a conventional rodent diet,mdx mice showed progressive muscle weakness over the consecutive 200 d, and eventually showed a significant weight loss during the next 200-d observation period. Progression of muscle weakness and weight loss were almost completely prevented in mdx mice that were kept on wheat kernel bedding. In contrast, only incomplete maintenance of muscle strength and body weight was observed in mdx mice kept on wood shavings and fed theα-tocopherol-supplemented diet. It is concluded from these experiments that a component of wheat kernels other than α-tocopherol is essential to prevent the progression of muscle weakness in mdx mice.

The Reduction of Oxalic Amidines with Metallic Lithium: Preparation of Lithiated Bisamides [R″N(RR′N)C=C(NRR′)NR″]Li2 and Their Use as Intermediates in a Novel Synthesis of Tetraaminoethenes

Abstract: Redn. of the 1,4-diaza-1,3-butadiene substructure of hexasubstituted oxalic amidines with Li metal yields the new Li diamides [R2N(RR1N)C:C(NRR1)NR2]Li2 [R = Ph; R1 = Me; R2 = 4-MeC6H4 (I) and R = R1 = Et; R2 = 2,4,6-Me3C6H2]. Subsequent reaction of I with various electrophiles gives the corresponding tetraaminoethenes R2R3N(RR1N)C:C(NRR1)NR2R4 [R3 = R4 = Me; R3R4 = -(CH2)3-] and the acylated derivs. II and III, resp. The 1st SET step in this reaction is the formation of monolithium radical anions, which were detected by EPR spectroscopy. The second electron transfer leads to the deeply colored dianions. In the case of I [cis-I.3 Et2O], the x-ray crystal structure reveals the cisoid arrangement of the bidental ligand and 3 mols. of Et2O which are located in a 2:1 fashion in the first coordination sphere of Li+. The NMR 2D-1H,6Li-HOESY-investigations of I in [D10]Et2O/Et2O (8:1) show Li+ contacts to the H atoms of the ether mols. and to the ortho-H atoms of the aryl moieties. Results of semiempirical calcns. are throughout in acceptable agreement with the exptl. data and explain the unusual coordination pattern of Li+ in the Li diamides.

Comparison of guinea-pig, bovine and rat alpha 1-adrenoceptor subtypes.

Abstract: 1. To elucidate a possible role of species differences in the classification of alpha 1-adrenoceptor subtypes, we have characterized the alpha 1-adrenoceptors in guinea-pig spleen, kidney and cerebral cortex and in bovine cerebral cortex using concentration-dependent alkylation by chloroethylclonidine and competitive binding with 5-methlurapidil, methoxamine, (+)-niguldipine, noradrenaline, oxymetazoline, phentolamine, SDZ NVI-085, tamsulosin and (+)-tamsulosin. Rat liver alpha 1B-adrenoceptors were studied for comparison. Chloroethylclonidine-sensitivity and (+)-niguldipine affinity were also compared at cloned rat and bovine alpha 1a-adrenoceptors. 2. Chloroethylclonidine concentration-dependently inactivated alpha 1-adrenoceptors in all five tissues. While chloroethylclonidine inactivated almost all alpha 1-adrenoceptors in rat liver and guinea-pig kidney and brain, 20-30% of alpha 1-adrenoceptors in guinea-pig spleen and bovine brain were resistant to alkylation by 10 microM chloroethylclonidine. With regard to concentration-dependency guinea-pig kidney and brain were approximately 10 fold less sensitive than guinea-pig spleen or rat liver. 3. In rat liver, all drugs tested competed for [3H]-prazosin binding with steep and monophasic curves. Drug affinities were relatively low and resembled most closely those of cloned rat alpha 1b-adrenoceptors. 4. In guinea-pig spleen, all drugs tested competed for [3H]-prazosin binding with steep and monophasic curves. Drug affinities were relatively low and resembled most closely those of cloned rat alpha 1b-adrenoceptors. 5. In guinea-pig kidney most drugs tested competed for [3H]-prazosin binding with steep and monophasic curves and had relatively low drug affinities close to those of cloned rat alpha 1b- and alpha 1d-adrenoceptors. However, noradrenaline and tamsulosin had consistently biphasic competition curves recognizing 36-39% high and 61-64% low affinity sites. 6. In guinea-pig cerebral cortex, all drugs tested competed for [3H]-prazosin binding with shallow and biphasic curves. While most drugs recognized approximately 25% high affinity sites, tamsulosin and noradrenaline recognized approximately 50% high affinity sites. Drug affinities at the high and low affinity sites except those for tamsulosin and noradrenaline resembled those at cloned alpha 1a- and alpha 1b-adrenoceptors, respectively. 7. In bovine cerebral cortex all drugs tested except for noradrenaline competed for [3H]-prazosin binding with shallow and biphasic curves. All drugs recognized approximately 70% high affinity sites. Drug affinities at the high and low affinity sites resembled those at cloned alpha 1a- and alpha 1b-adrenoceptors, respectively. Noradrenaline competition curves in bovine cerebral cortex were steep and monophasic. 8. When cloned rat and bovine alpha 1a-adrenoceptors transiently expressed in COS cells were studied in a direct side-by-side comparison, both species homologues had similar chloroethylclonidine-sensitivity and (+)-niguldipine affinity. 9. We conclude that properties of bovine alpha 1A- and alpha 1B-adrenoceptors are very similar to those of other species such as rat. alpha 1-Adrenoceptor subtypes in guinea-pigs resemble alpha 1A- and alpha 1B-adrenoceptors in other species but chloroethylclonidine sensitivity and competition binding profiles of noradrenaline and tamsulosin are not compatible with previously established alpha 1-adrenoceptor subtype classification.

Bone marrow transplantation from partially HLA-matched related donors in adults with leukaemia: the experience at the University Hospital of Essen, Germany.

Abstract: The Seattle group has demonstrated that bone marrow transplantation (BMT) using partially HLA-mismatched related donors is feasible in principal. However, it was unclear whether these results can also be achieved at smaller-sized BMT units. Therefore a matched pair analysis enrolling 52 BMTs from partially HLA-mismatched relatives and 52 control BMTs from HLA-identical siblings was performed at the University Hospital of Essen. Overall survival (OS) and incidence of graft-versus-host disease (GVHD) did riot differ significantly after study and control BMTs (OS : 52% v 63%, 1 year, 46% v 48% 5 years post transplant ; acute GVHD : 37% v 35%, chronic GVHD : 67% v 55%). After study BMTs, however, therapy-related mortality (P = 0.018) and incidence of graft failure (P = 0.002) were increased, whereas relapse rate was reduced (11% v 27%). Two or three mismatches in HVG direction implied the same risk of graft failure as one mismatch. Therefore, (i) OS after BMT from one HLA antigen mismatched relative and from HLA-identical siblings does not differ significantly even when performed at a 'smaller' centre ; (ii) two or even three HLA mismatches in host-versus graft (HVG) direction might be acceptable in family BMT for leukaemia.

Formation and persistence of O6-ethylguanine in genomic and transgene DNA in liver and brain of λlacZ transgenic mice treated with N-ethyl-N-nitrosourea

Abstract: LacZ transgenic mice are suitable for short-term mutagenicity studies in vivo. Mutagenicity in these mice is determined in the lacZ transgene. Since the lacZ gene is of bacterial origin the question has been raised whether DNA-adduct formation and repair in the transgene are comparable to those in total genomic DNA. Mice were treated with N-ethyl-N-nitrosourea (ENU) and killed at several time points following treatment. Some mice were pretreated with O6-benzylguanine to inactivate the repair protein O6-alkylguanine-DNA alkyltransferase (AGT). O6-ethylguanine (O6-EtG) was determined in lacZ in liver and brain by means of a monoclonal antibody-based immunoaffinity assay. In addition, O6-EtG and N7-ethylguanine (N7-EtG) were assayed in total genomic DNA of liver and brain with an immunoslotblot procedure. In liver, the initial O6-EtG level in total genomic DNA was 1.6 times that in lacZ. The extent of repair of O6-EtG during the first 1.5 h after treatment was 2.1 times that in lacZ. At later time points, O6-EtG repair was the same. N7-EtG repair in genomic DNA was evident. In contrast to the liver, little repair of O6-EtG in total genomic and lacZ DNA occurred in the brain while N7-EtG was repaired. No initial difference in O6-EtG levels were found in lacZ and genomic brain DNA. These findings indicate that in the liver, total genomic DNA is more accessible than lacZ to ENU and/or the AGT protein, during the first 1.5 h following treatment. Because the difference in O6-EtG levels in the transgene and genomic DNA in the liver is restricted to the first 1.5 h after treatment, while the fixation of mutations occurs at later time points, O6-EtG-induced mutagenesis most likely is also very similar in both types of DNA.

Off-resonance light scattering from Bose condensates in traps

Abstract: The density-density correlation function determining off-resonance light scattering in weakly interacting Bose-condensed gases in a trapping potential is calculated in the Bogoliubov approximation. The evaluation of the necessary matrix elements is carried out for positive scattering length in the WKB approximation using the Thomas-Fermi approximation for the condensate.

Construction of a consistent YAC contig for human chromosome region 3p14.1.

Abstract: Chromosomal deletions and translocations of human chromosome region 3p14 are observed in various human malignancies and suggest the existence of a tumor suppressor gene locus within this region. Tumors most frequently affected by these aberrations are small-cell lung cancer and renal-cell carcinoma. In continuation of our previously published YAC contig of chromosome region 3p14.2-p14.3, we report here on the construction of a YAC contig of at least 11 Mb that consisted of 171 YACs and covers the entire subregion 3p14.1. This contig includes the t(3;8) breakpoint of a hereditary renal-cell carcinoma localized in 3p14.2 and extends into human chromosome region 3p12-p13. It defines the order of 34 DNA probes in relation to reference markers D3S6 and D3S30 as well as the human protein tyrosine phosphatase-gamma gene. For 31 DNA probes we identified nonchimeric YACs by fluorescence in situ hybridization. The minimal tiling pathway consists of 16 yeast artificial chromosomes. As a prerequisite for identification of a putative tumor suppressor gene within this region, this contig renders human chromosome region 3p14.1 accessible to gene isolation.

Hypersurfaces with constant inner curvature of the second fundamental form, and the non-rigidity of the sphere

Abstract: We classify the hypersurfaces of revolution in euclidean space whose second fundamental form defines an abstract pseudo-Riemannian metric of constant sectional curvature. In particular we find such piecewise analytic hypersurfaces of classC2 where the second fundamental form defines a complete space of constant positive, zero, or negative curvature. Among them there are closed convex hypersurfaces distinct from spheres, in contrast to a theorem of R. Schneider (Proc. AMS 35, 230–233, (1972)) saying that such a hypersurface of classC4 has to be a round sphere. In particular, the sphere is notII-rigid in the class of all convexC2-hypersurfaces.

Scanning tunneling microscopy and spectroscopy study of nanometer-sized metal clusters

Abstract: We describe scanning tunneling microscopy and spectroscopy results on the ligand stabilized metal cluster Pt 309 Phen 36 * O 30 at 4.2 K. In these measurements we observed very clear charging effects. In addition to the regular Coulomb staircase, sometimes an irregular staircase pattern has been observed. This irregular staircase pattern is consistent with a discrete density of states of the cluster. However. also the unknown influence of the ligands has to be considered.