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Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 109 records · Page 6Linked to original sources

The impact of three-dimensional structure on the expression of PlA alloantigens on human integrin beta 3.

We have compared the binding of affinity-purified anti-PlA1 IgG from seven nonrelated donors with chimeric integrin subunit beta 3 molecules expressed in the baculovirus-Spodoptera frugiperda insect cell system. Beta 3 chimeras were engineered to include segments of antigenic human beta 3 sequences spliced to intervening segments of nonantigenic Xenopus beta 3 sequence. Our results clearly show that antibodies from all seven donors will bind to nondenatured molecules containing the antigenic human beta 3 Cys26-Cys38 loop only when it is presented in a correct orientation that must be maintained by noncontiguous human sequences. Key downstream sequences are located within the region beta 3(288-490), flanking either side of the putative long-range disulfide at Cys435. Although our results confirm unambiguously that the Leu/Pro polymorphism at position 33 in human beta 3 is necessary for the expression of PlA epitopes, they also indicate that this polymorphic sequence alone is not sufficient. The requirement for additional human beta 3 sequence transcends the need to maintain a correct orientation within the Cys26-Cys38 loop itself, because the murine monoclonal antibody SZ21, which recognizes the sequence beta 3(28-35) contained within the Cys26-Cys38 loop, binds to all chimeras containing this loop, even if the same chimeras are not recognized by anti-PlA1. Our results indicate that additional noncontiguous residues encompassed by the sequence 288-490 either directly contribute to the composition of the PlA1 epitope or, more likely, maintain the Cys26-Cys38 loop in a proper orientation with respect to the remainder of the beta 3 molecule and thereby maintain proper antigenic presentation of the sequences in that loop.

Amino Acid Sequence↗

Binge eating in massively obese patients undergoing bariatric surgery.

Data on the prevalence of binge eating in a series of 92 massively obese patients undergoing bariatric surgery are presented. A semistructured clinical interview demonstrated that 63 individuals had problems with binge eating, 43 of these reporting episodes of binge eating more than twice a week and then meeting the diagnostic criteria for binge eating disorder. By comparison with their nonbinge eating counterparts, binge eaters demonstrated higher body weight, greater weight fluctuation due to reducing diets in their past lifetime, higher Three-Factor Eating Questionnaire Disinhibition and Hunger score, and an overall higher psychopathology as assessed by the Eating Disorder Inventory. The great prevalence of binge eating in these patients could be accounted for by the high body weight, by the characteristics of the patients, or by the context in which the eating behavior assessment was carried out.

Adolescent↗

Lack of concordant p53 mutations in some paired primary and metastatic mouse squamous cell carcinomas induced by chemical carcinogenesis.

We studied the frequency and pattern of p53 mutations in 16 mouse skin primary squamous carcinomas induced by chemical carcinogens and their 19 matched metastases. The molecular changes were analyzed by polymerase chain reaction-single-strand conformation polymorphism and subsequent direct sequencing analysis. Eleven mutations of the p53 gene were detected in a total of eight primary tumors, and 10 mutations were detected in nine metastases. Only four pairs had identical mutations in primary and paired metastatic tumors. Eight mutations in six pairs were detected in primary tumors but not in their metastases, and four mutations from three matched pairs were detected in metastases but not in primary tumors. The four pairs that contained the same mutations in both the primary and secondary tumors had lymph-node metastases, and all mutations occurred in exon 8. Conversely, five of six pairs with p53 mutations only in primary tumors had lung metastases, and only one of the mutations occurred in exon 8. None of the mutations found only in metastases were located in exon 8. These data indicate that p53 mutations are prevalent in lymph-node metastases and infrequent in lung metastases of mouse skin tumors and that primary tumors with exon 8 mutations may be more likely to metastasize to the lymph nodes.

Animals↗

Binge eating following biliopancreatic diversion for obesity.

The prevalence of binge eating disorder (BED) was assessed in 68 massively obese patients prior to and following biliopancreatic diversion (BPD) for obesity. The eating behavior and the psychological traits were evaluated by the Three Factor Eating Questionnaire and the Eating Disorder Inventory. Since after BPD the body weight regulation is substantially dependent on intestinal absorption, the individuals operated on have to be considered as absolutely free eaters. In this population, 30 patients were affected by BED and in 24 of them binge eating disappeared spontaneously following BPD, highlighting the main role of preoccupation with food, diet and overweight in causing or in maintaining BED.

Adolescent↗

Molecular cloning and analysis of nre, the major nitrogen regulatory gene of Penicillium chrysogenum.

We have isolated the Penicillium chrysogenum nre gene which is homologous to the major nitrogen regulatory genes areA from Aspergillus nidulans and nit-2 from Neurospora crassa. Overall, nre shows 60% identity to areA and 30% identity to nit-2 at the amino-acid level. The gene encodes a protein of 835 amino-acid residues and contains a single Cys2/Cys2-type zinc finger with an adjacent basic region and a putative acidic activation region. In the DNA-binding domain, 98% of the amino-acid residues are identical in nre, areA and nit-2. The nre gene has been shown to be functional in N. crassa by heterologous complementation of a nit-2 mutant. Growth tests indicated that transformants could utilize nitrate, amino-acids, purines and amides as sole nitrogen sources. Nitrate reductase activity assays performed with transformants demonstrated that nitrogen control was completely normal. Complementation of N. crassa nit-2 mutants with 5'-deletion clones of nre suggests the possible presence of an internal promoter within the coding region. Northern analysis and ribonuclease protection assays of total cellular RNA indicated that nre encodes a 3.2-kb transcript which is reduced in content under conditions of nitrogen repression.

Amino Acid Sequence↗

Gender does not influence acute myocardial infarction in adult dogs.

Mechanisms responsible for the well-documented "protection" against myocardial ischemia and infarction in young women and subsequent loss of protection after menopause remain speculative. One possibility is that gender-related variables (such as endogenous hormone levels or regular loss of stored iron) alter the susceptibility of the heart to ischemia: if so, then premenopausal women when compared with men may manifest endogenous protection against acute myocardial ischemic injury. Using the canine model we therefore sought to determine whether gender influences acute myocardial ischemia and infarction. Retrospective analysis was performed on data compiled from 60 mature adult dogs subjected to 1 hour of coronary artery occlusion and > or = 4 hours of reperfusion. We first compared the incidence of lethal ventricular fibrillation in the male and female cohorts and then for survivors compared collateral blood flow during coronary occlusion (by injection of radioactive microspheres), infarct size (assessed by tetrazolium staining and expressed as a percentage of the myocardium at risk), and regional wall motion (by somomicrometry) in the infarct-related area. The incidence of lethal ventricular fibrillation was 23% in the male dogs and 19% in the female dogs (p = 0.70, difference not significant). For survivors, the area at risk of infarction was comparable in males and females (23 +/- 2% and 22% +/- 1% of the total left ventricular weight), and the groups were equally ischemic during coronary occlusion, with collateral blood flow to the ischemic subendocardium averaging 0.05 +/- 0.02 and 0.07 +/- 0.01 ml/min/g tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Obese binge eaters: metabolic characteristics, energy expenditure and dieting.

The study was carried out in two groups of massively obese women with BMI values who were to undergo bariatric surgery. The patients were evaluated for weight variability and for the presence and the frequency of binge eating. Body composition, resting energy expenditure (REE) and metabolic parameters were also measured. When non-bingeing individuals were compared with patients who met Binge Eating Disorder criteria, no differences in body composition, fat distribution, REE values and concentrations of serum lipids, insulin and thyroid hormones were found. On the other hand, weight variability due to reduced diet in the subjects' lifetime was significantly higher. This study does not support the hypothesis that in massively obese women binge eating is somehow induced by a reduced energy expenditure.

Adipose Tissue↗

Interference of angiotensin-converting enzyme inhibition with vasoactive peptides in the coronary circulation of dogs.

The coronary effects of angiotensin-converting enzyme (ACE) inhibitors and their mechanisms of action are not well understood. Because these drugs may interfere with hormone systems other than the reninangiotensin system (RAS), we studied modulation of the coronary effects of neurotensin, neuropeptide Y (NPY), and endothelin-1 (ET-1) by pretreatment with captopril in anesthetized, open-chest dogs. The left anterior descending coronary artery (LAD) was cannulated and perfused at a pressure equal to mean aortic blood pressure. Coronary blood flow (CBF) was measured by an electromagnetic flowmeter, subendocardial segment length by ultrasonic crystals. ACE inhibition (captopril 0.25 mg/kg), as an intracoronary (i.c.) injection, followed by an intracoronary infusion (0.25 mg/kg/h) did not affect the relative vasoconstrictor effects of ET-1 (10(-4)-10(-1) micrograms/kg i.c.) or neuropeptide Y (10(-3)-1 microgram/kg i.c.). However preinjection flow of a second dose-response curve of ET-1 was significantly higher in captopril-treated as compared with control animals. The increase in CBF induced by neurotensin (10(-3)-1 microgram/kg i.c.) was potentiated by captopril (40 +/- 14% after vs. 20 +/- 9% before captopril, p < 0.01, at the highest dose used). Changes in hemodynamics or in regional myocardial function could not explain altered effects of neurotensin. We therefore conclude that ACE inhibition does not interfere with the acute vasoconstrictor effects of ET-1 or NPY in this canine model but may reverse the long-term tonic coronary constrictor effect of ET-1. Potentiation of the neurotensin effect on CBF might be due to prevention of hydrolysis of neurotensin or to a cyclooxygenase-dependent mechanism.

Analysis of Variance↗

Sports-related eye injuries.

At the University Eye Hospital of Lund 272 patients were treated following blunt trauma during a two and half year period. The number of cases related to sports activity were extracted. The major sports responsible for the injuries and the type of injuries were identified and also an investigation into the sex and age distribution was made. Forty percent of the total number of cases were sports-related. Floor ball was responsible for 46% of these cases.

Adolescent↗

Argon laser photocoagulation of cyclodialysis clefts after cataract surgery.

Three patients with cyclodialysis clefts, hypotony and hypotonic retinopathy subsequent to cataract surgery were treated with argon laser photocoagulation. The hypotony was reversed in each patient and their visual acuity was normalized. Laser photocoagulation is a noninvasive treatment that can be repeated easily and safely. The complications of the treatment are minor. A hypertensive episode commonly occurs in the early postoperative period.

Aged↗

Successful application of deltamethrin pour on to cattle in a campaign against tsetse flies (Glossina spp.) in the pastoral zone of Samorogouan, Burkina Faso.

1,500-2,000 head of cattle were treated with deltamethrin 1% Spot On in an area of high tsetse densities, notably of Glossina morsitans submorsitans. After four treatments at monthly intervals, the time between two treatments was increased to two months. 11 months after the commencement of the campaign the fly population had decreased from initially 54.2 flies/trap/day to densities varying between 0.06-2.0 flies/trap/day, mostly G. palpalis gambiensis. Blood-meal analysis showed that this species was surviving in limited areas, mainly feeding on monitor lizards; consequently it is unlikely that this species can be eradicated solely by the use of cattle treated with a pyrethroid. The resistance of Trypanosoma congolense to all commercially available trypanocides necessitated the epidemiological monitoring of calves which were born after the start of the campaign in order to reasses the real challenge. The risk of new infections was low, basically due to contracts between the cattle and tsetse outside the ranching area. A weight increase from 122.3 kg to 213.6 kg of calves aged 6-12 months was recorded from October 1993 to October 1994. An average daily weight gain of more than 400 g was observed from the end of April 1994 to the beginning of August 1994.

Animal Husbandry↗

Eating disorder inventory in the assessment of psychosocial status in the obese patients prior to and at long-term following biliopancreatic diversion for obesity.

Psychological traits of obese patients, assessed with the Eating Disorder Inventory (EDI), were compared to those of subjects in the long-term following biliopancreatic diversion for obesity (BPD), when body weight has been steadily normal for over 1 year and any preoccupation with dieting and weight has been completely abandoned. The overall results suggest that the stable body weight normalization on a completely free diet does confer considerable psychological benefit on obese individuals. On the basis of the EDI results, post-BPD subjects were divided into weight-preoccupied and not-weight-preoccupied individuals. In the not-weight-preoccupied subjects, the psychosocial status and emotional rectivity were closely similar to those observed in lean control persons, whereas the few weight-preoccupied subjects, in spite of completely normal body weight, showed residual body dissatisfaction and personality traits very similar to those of eating-disordered patients.

Adolescent↗

Single-photon emission tomography studies of rubidium-81 in the detection of ischaemic heart disease, using a stress-reinjection protocol.

The present study was designed to determine the feasibility of using single-photon emission tomography (SPET) imaging with rubidium-81 (T1/2 = 4.54 h) to detect ischaemic heart disease, using a stress-reinjection protocol and a specially constructed 511-keV hexagonal hole collimator for a standard gamma camera. The diagnostic performance of 81Rb SPET in detecting coronary artery disease (CAD) was investigated in 52 patients with a high prevalence of CAD. Coronary arteriography was performed in 34 patients, 25 of whom were classified as having significant stenosis (> or = 50%). At peak exercise (Cornell protocol), 111-222 MBq 81Rb was injected i.v. for stress imaging, and after 3 h of rest, 74-111 MBq was reinjected for rest imaging. The displayed short- and long-axis slices and the polar map images were interpreted qualitatively. In comparison to coronary arteriography, which served as the gold standard, the performance of 81Rb SPET revealed a sensitivity of 95% for the detection of CAD. Images of diagnostic quality were obtained in all patients, these being comparable to thallium-201 SPET images. In conclusion, these results indicate that the described method can be routinely used for the positron emitter 81Rb with a conventional gamma camera and special shielding. 81Rb has the well-known advantages of a potassium analogue and 81Rb SPET permits better visualization, particularly of the posterior wall of the myocardium, due to the higher photon energy. Considering the typical dose of 201Tl used for SPET (74-148 MBq), a 81Rb SPET scan imposes a significantly lower radiation burden on the patient.

Adult↗

A novel intergenic site for integration and expression of foreign genes in the genome of pseudorabies virus.

Restriction enzyme analysis of DNA of a number of Pseudorabies virus (PRV) single plaque isolates revealed in several cases the existence of a unique EcoRI cleavage site, which has not been observed in PRV DNA before. This EcoRI site was mapped to the right end of the unique long region of the PRV genome, in BamHI-fragment 6. Sequence analysis of this region demonstrated the presence of an 11 bp tandem repeat in variable copy numbers in different PRV strains, suggesting the creation of the EcoRI recognition site by a recombinational event. The occurrence of variable reiterations and Northern blot analysis indicated an intergenic region. We therefore, used this site for integration and expression of heterologous DNA (the multiple cloning site of phage M13 and the E. coli lacZ gene). Viable PRV recombinants could be obtained which showed no detectable differences in virus growth in vitro compared to wild-type PRV. The novel insertion site can be used for the construction of PRV recombinants expressing foreign genes without apparent impairment of PRV genes.

Base Sequence↗

Murine squamous cell carcinoma cell lines produced by a complete carcinogenesis protocol with benzo[a]pyrene exhibit characteristic p53 mutations and the absence of H-ras and cyl 1/cyclin D1 abnormalities.

In this report, we describe the isolation and characterization of six murine squamous cell carcinoma cell lines (BPCC) derived from carcinomas produced by a complete carcinogenesis protocol with benzo[a]pyrene (B[a]P). All six cell lines were tumorigenic to varying degrees in nude mice, and several were spontaneously metastatic to the lungs. The in vivo invasive potential of each BPCC cell line was determined using de-epithelialized tracheal xenotransplants into which cells were inoculated. This assay revealed positive association of tumor grade with in vivo invasiveness, yet no clear relationship to the spontaneous metastatic potential of the cell lines, suggestive that invasive potential is only one determinant of the overall metastatic phenotype. At the molecular level, all six BPCC cell lines revealed the absence of mutations in the H-ras oncogene and no amplification or rearrangement in the cycl 1/cyclin D1 putative oncogene. Analysis of the p53 tumor suppressor gene revealed a direct correlation between positive nuclear immunohistochemical staining of the p53 protein in four BPCC cell lines and the presence of p53 mutations identified by direct sequence analysis. The localization of mutations to exons 7 and 8 of the p53 gene and the detection of G to T transversions in two of the four cell lines bearing p53 mutations are in agreement with previous analyses of a large series of primary B[a]P-induced murine skin tumors. In addition, frameshift mutations were identified in two cell lines. The correlation of the biological and molecular properties of these BPCC cell lines with the known characteristics of primary squamous cell carcinomas induced by B[a]P indicates that these cell lines could be useful tools in elucidating the mechanisms of tumorigenesis of this important chemical carcinogen.

Animals↗

Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene.

Human tobacco-related cancers exhibit a high frequency of G to T transversions in the mutation hot spot region of the p53 tumor suppressor gene, possibly the result of specific mutagens in tobacco smoke, most notably benzo[a]pyrene (B[a]P). No in vivo animal model of B[a]P-induced tumorigenesis has been used, however, to substantiate these molecular epidemiological data experimentally. Direct DNA sequence analysis of the hot spot region (exons 5-8 inclusive) of murine p53 was performed in 20 skin tumors induced by a complete carcinogenesis protocol with B[a]P. Sequence analyses revealed numerous heterozygous missense mutations in carcinomas, specifically in exons 7 and 8 of the p53 gene, and targeting exclusively guanine residues. Moreover, 70% (5/7) of the mutations characterized were G to T transversions. In contrast, direct DNA sequence analysis of 36 skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in either a complete carcinogenesis protocol or in a two-stage carcinogenesis protocol revealed a 30% frequency of heterozygous p53 mutations, with the majority of mutations found in carcinomas, but only a single G to T transversion (1/8). Thus, while mutation frequencies are similar, the pattern and type of p53 mutations in B[a]P-induced skin tumors differs significantly from the mutation spectra in DMBA-induced squamous neoplasias. These in vivo findings in B[a]P-induced tumors lend support to in vitro and molecular epidemiological evidence, suggesting that the p53 tumor suppressor gene may be a selective target of metabolically activated B[a]P species etiologically associated with human tobacco-related cancers.

9,10-Dimethyl-1,2-benzanthracene↗