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C Berg

Publications and source records attributed to C Berg.

At least 91 records · Page 5Linked to original sources

Methods for studying xenoestrogenic effects in birds.

The embryonated bird egg provides a simple whole organism test system that allows examination of xenoestrogenic effects at different levels of biological organisation. Test compounds are injected into the yolk, the albumen or the air chamber at defined stages of embryonic development. Bioavailability and embryonic exposure may be determined by autoradiography and image analysis. Females represent the heterogametic sex (ZW) and estrogens determine differentiation into the female phenotype in birds. Xenoestrogenic effects can be examined by markers of gene expression and anatomical or histological characterization of the gonads and tubular sex organs. Chicks may be raised to sexual maturity and examination of sexual behaviour and reproductive physiology performed. The Japanese quail is a suitable test organism due to its small size and early sexual maturation.

Abnormalities, Drug-Induced↗

Sources of bias in a dietary survey of children.

OBJECTIVE: To compare non-responders and responders to a dietary survey with respect to demographic variables and intention to choose selected breakfast foods, and to examine if there was any systematic change in number of food items reported during a 7 d recording period. DESIGN: Cross-sectional survey. SETTING: Mölndal, Sweden. SUBJECTS: All pupils in 5th, 7th and 9th grades in the municipality were asked to complete a questionnaire during school hours. All those present (n = 1584, 92% of total) answered questions about lifestyle factors and about intentions, attitudes and beliefs concerning high-fibre bread and milk with varying fat content. All subjects in the initial sample were asked to fill in a 7 d record of food consumed. Acceptable food records were completed by 69% of the initial participants. RESULTS: Subjects not completing the food record differed significantly from participants with respect to demographic, lifestyle and dietary factors. Dropout was more common among those who reported not usually eating breakfast and among those intending to drink whole milk for breakfast. A decline in reported food items during the recording period was also observed. CONCLUSIONS: Two sources of bias were observed here, one indicating significant differences between non-participants and participants, the other suggesting the presence of a time-dependent trend in number of recorded foods. It is likely such biases are present in other dietary surveys involving schoolchildren, and should be taken into consideration in the design, analysis and interpretation of such studies.

Adolescent↗

Molecular pathology in basal cell cancer with p53 as a genetic marker.

Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 samples were analysed. Direct DNA sequencing of exons 5-8 was performed, haplotypes were determined after cloning of p53 exons and loss of heterozygosity (LOH) ascertained by microsatellite analysis. All tumors had p53 mutations and in a majority both p53 alleles were affected, commonly through missense mutations. Microdissection of small parts (50-100 cells) of individual tumors showed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation. Samples from normal immunohistochemically negative epidermis always showed wild type sequence, except for a case of previously unknown germline p53 mutation. Our analysis also included p53 immunoreactive patches i.e. morphologically normal epidermis with a compact pattern of p53 immunoreactivity. Mutations within those were never the same as in the adjacent BCC. This detailed study of only one gene thus uncovered a remarkable heterogeneity within a tumor category famous for its benign clinical behavior.

Aged↗

Length of maternal hospital stay for uncomplicated deliveries, 1988-1995: the impact of maternal and hospital characteristics.

OBJECTIVES: To determine the independent association of selected maternal and hospital characteristics with length of maternal hospital stay for uncomplicated vaginal deliveries. METHOD: Linear regression analysis using National Hospital Discharge Survey data from 1988 to 1995. Independent variables were year, maternal age and race, method of payment, and hospital ownership, size, and geographic location. The outcome measure was length of maternal hospital stay for uncomplicated vaginal deliveries. RESULTS: Length of stay was independently associated with year, geographic region, payment method, and hospital size. From 1988 to 1995, the mean length of stay fell from 2.1 to 1.5 days. The rate of decrease was similar for all regions, methods of payment, and hospital size. Women in the West had a shorter mean length of stay (1.5 days) than women in the Northeast (2.2 days). The difference by method of payment was smaller. Length of stay was shortest for women without insurance (1.8 days) and longest for women covered by Blue Cross (2.1 days). Maternal age and race and type of hospital ownership were not independently associated with the length of stay. CONCLUSIONS: Significant variations existed in the length of time women are hospitalized for normal childbirth. These variations are primarily associated with where a woman lives and whether she is insured. Given the current public debate on the impact of shortened hospital stays, these variations need to be explored and their effects on maternal and infant well-being clarified.

Adolescent↗

Evaluation of prenatal care information on birth certificates.

Misclassification frequently leads to bias in epidemiological studies, and causes concern for perinatal epidemiologists interested in using birth certificates as a data source. We used a maximum likelihood method to estimate the classification probabilities (conditional probabilities that indicate the probability of classification in a particular category, given the person's true category) of two data sources for a three-category outcome of prenatal care. The probability that women receiving adequate or inadequate care were correctly classified was estimated to be greater than 90%. The probability was much lower (< 35%) that women receiving intermediate care were correctly classified. The misclassification women from the intermediate category resulted in poor predictive values (< 70%) of women classified as receiving either adequate or inadequate care. Because of these findings, we combined the adequate and intermediate categories to form a two-category classification system. This revision resulted in higher positive predictive values (> 90%) with only a slightly lower classification probability (> 85%) for the combined category. We conclude that the degree of accuracy for a two-category classification of prenatal care based upon birth certificate information is acceptable, but we question the accuracy of indices of prenatal care with more than two categories.

Birth Certificates↗

Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin.

Ultraviolet light, which is the major etiology of human skin cancer, will cause mutations in the p53 gene. We and others have found that such mutations occur in more than one-half of non-melanoma squamous cell cancer and precancer. Immunostaining for p53 has disclosed a characteristic compact pattern not only in cancer/precancer but also in areas of microscopically normal epidermis termed p53 patches. By microdissection, sequence analysis of the p53 gene, and analysis of loss of heterozygosity (LOH) at the site of this gene, we have now extended previous data to ascertain whether these p53 patches are precursors of simultaneously present squamous cell cancer or its morphologically recognized precancerous stages (dysplasia, carcinoma in situ). In none of 11 instances with co-existence of a p53 patch with dysplasia or in situ or invasive cancer were the mutations identical. We conclude that p53 patches, estimated to be approximately 100,000 times as common as dysplasia, have a very small or even no precancerous potential. Their common presence demonstrates that human epidermis contains a large number of p53 mutations apparently without detrimental effect. The only result of the mutation may be a clandestine benign clonal keratinocyte proliferation. The importance of p53 mutations for such benign cell multiplication on one band and malignant transformation on the other is unclear. Although the spectrum, type, and multiplicity of mutations were similar in both types of proliferative responses, there was a clear difference with respect to LOH. No LOH was found in 17 p53 patches. By contrast 11 of 30 precancers/cancers had LOH.

Carcinoma in Situ↗

Comparison of the pharmacokinetics of dolasetron and its major active metabolite, reduced dolasetron, in dog.

Dolasetron mesilate (Anzemet) ((2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1 H-indole-3-carboxylate monomethane-sulfonate) is a 5-HT3 receptor antagonist, which is in development for the treatment of chemotherapy-induced emesis. The ketone moiety of dolasetron is rapidly reduced by carbonyl reductase to form an alcohol, reduced dolasetron (red-dolasetron), which is the major pharmacologically active metabolite in humans. The pharmacokinetics of dolasetron and red-dolasetron were compared in dog, after single intravenous (i.v.) (2 mg/kg) and oral (p.o.) (5 mg/kg) administration of [14C]dolasetron or [14C]red-dolasetron. Pharmacokinetic parameters of dolasetron showed a terminal elimination half-life (t1/2) of 0.1 h, total body plasma clearance (Cltot) of around 109 mL/min/kg, apparent volume of distribution (aVd beta) of 0.83 L/kg, and bioavailability (F) of 7%. Pharmacokinetic parameters of red-dolasetron, calculated after dolasetron or red-dolasetron administration, were very similar. The t1/2 was around 4.0 h, Cltot 25 mL/min/kg, aVd beta 8.5 L/kg, and F around 100%. The apparent first-order formation rate constant (ki) of red-dolasetron was 7 h-1, which was similar to the first-order elimination rate constant (kel) of dolasetron. Cmax of red-dolasetron was similar, after po administration of either compound, but the median Tmax was 0.33 h after dolasetron, compared with 1.5 h after red-dolasetron. The first-order absorption rate constants (ka) of dolasetron and red-dolasetron were 14 h-1 and 2 h-1, respectively. Dolasetron transport across Caco-2 cell monolayers was also higher than that of red-dolasetron. Thus dolasetron was more quickly absorbed than red-dolasetron, and its administration led to the more rapid appearance of red-dolasetron in plasma. There appears to be no advantage in the direct administration of the metabolite, especially as in humans oral administration of dolasetron, 30 min before chemotherapy, has been shown to be effective in preventing emesis.

Animals↗

Intensive outpatient adjuvant therapy for breast cancer: results of dose escalation and quality of life.

PURPOSE: A dose-escalation study was conducted to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cyclophosphamide (CY) in combination with granulocyte colony-stimulating factor (G-CSF0 and doxorubicin (DOX) given every 2 weeks for eight cycles as outpatient adjuvant therapy for node-positive breast cancer. A pilot study to assess quality of life (QOL) was performed. PATIENTS AND METHODS: From March 1991 to April 1993, 19 patients were entered. Patients received escalating doses of CY intravenously (i.v.) (1,000 mg/m2, 1,500 mg/m2, 2,000 mg/m2, or 2,500 mg/m2) with DOX 40 mg/m2, G-CSF 10 micrograms/kg/d on days 2 to 12, and mesna, every 2 weeks for eight cycles. QOL was measured by the Profile of Mood States (POMS), the Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), and a 27-item QOL scale. RESULTS: The CY dose of 2,500 mg/m2 every 2 weeks elicited toxicities that required dose reductions secondary to a combination of thrombocytopenia, hematuria, and anemia that required transfusion. The dose of 2,000 mg/m2 resulted in an acceptable toxicity profile. Ninety-two percent of cycles at the 2,000-mg/m2 dose were delivered on schedule and 77% without hospitalization. QOL assessments indicated high levels of distress measured by POMS in 47%, poor overall quality of life in 40%, and significant problems with physical symptoms in less than 27% of all patients for any given cycle. CONCLUSION: A dose of CY at 2,000 mg/m2 can be administered every 2 weeks with DOX and G-CSF for eight cycles in the outpatient setting with manageable toxicity. The majority of women described levels of physical symptoms and emotional distress as tolerable during treatment.

Adult↗

Stereoselectivity of the carbonyl reduction of dolasetron in rats, dogs, and humans.

The initial step in the metabolism of dolasetron or MDL 73,147EF [(2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H- quinolizin-8-yl 1H-indol-3-carboxylate, monomethanesulfonate] is the reduction of the prochiral carbonyl group to give a chiral secondary alcohol "reduced dolasetron." An HPLC method, using a chiral column to separate reduced dolasetron enantiomers, has been developed and used to measure enantiomers in urine of rats, dogs, and humans after dolasetron administration. In all cases, the reduction was enantioselective for the (+)-(R)-enantiomer, although the dog showed lower stereoselectivity, especially after iv administration. An approximate enantiomeric ratio (+/-) of 90:10 was found in rat and human urine. The contribution of further metabolism to this enantiomeric ratio was considered small as preliminary studies showed that oxidation of the enantiomeric alcohols by human liver microsomes demonstrated only minor stereoselectivity. Further evidence for the role of stereoselective reduction in man was obtained from in vitro studies, where dolasetron was incubated with human whole blood. The enantiomeric composition of reduced dolasetron formed in human whole blood was the same as that found in human urine after administration of dolasetron. Enantioselectivity was not due to differences in the absorption, distribution, metabolism, or excretion of enantiomers, as iv or oral administration of rac-reduced dolasetron to rats and dogs lead to the recovery, in urine, of essentially the same enantiomeric composition as the dose administered. it is fortuitous that the (+)-(R)-enantiomer is predominantly formed by carbonyl reductase, as it is the more active compound.

Administration, Oral↗

The moment of inertia of bird wings and the inertial power requirement for flapping flight

The agility and manoeuvrability of a flying animal and the inertial power required to flap the wings are related to the moment of inertia of the wings. The moments of inertia of the wings of 29 bird species and three bat species were determined using wing strip analysis. We also measured wing length, wing span, wing area, wing mass and body mass. A strong correlation (r2=0.997) was found between the moment of inertia and the product of wing mass and the square of wing length. Using this relationship, it was found that all birds that use their wings for underwater flight had a higher than average moment of inertia. Assuming sinusoidal wing movement, the inertial power requirement was found to be proportional to (body mass)0.799, an exponent close to literature values for both metabolic power output and minimum power required for flight. Ignoring wing retraction, a fairly approximate estimate showed that the inertial power required is 11&shy;15 % of the minimum flight power. If the kinetic energy of the wings is partly converted into aerodynamic (useful) work at stroke reversal, the power loss due to inertial effects may be smaller.

Journal Article↗

Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides.

Among the candidate cancer-prognostic genes is the p53 tumor suppressor gene, which, when mutated, plays an important role in the development of many types of cancers. To facilitate robust large-scale DNA analysis of microdissected tumor biopsies, we describe a multiplex/nested PCR approach for a simultaneous outer amplification of exons 4-9 of the human p53 gene with parallel amplification of the HLA-DQB1 locus, involving a total of 14 primers. This approach reduces the required number of cells for analysis and avoids any variation in the amplifications of the individual p53 exons during the common outer amplification step. The HLA sequencing allows sample identification because the DQB1 locus is highly polymorphic and is thereby patient-specific. The p53 and HLA amplicons are analyzed by solid-phase sequencing in a semiautomated format. To improve the DNA sequence quality, we used 2'-deoxyribonucleoside 5'-O-1-thiotriphosphates in the sequencing reactions.

Autoanalysis↗

Characterization of UDP-glucuronic acid transport in rat liver microsomal vesicles with photoaffinity analogs.

The endoplasmic reticulum (ER) of rat liver contains several well characterized UDP-glucuronosyltransferases (UGTs), membrane-bound proteins of 50-54 kDa, and also less well identified UDP-glucosyltransferases, with nucleotide binding sites located on the lumenal surface. There is evidence that the substrates for these enzymes, UDP-glucuronic acid (UDP-GlcUA) and UDP-glucose (UDP-Glc), biosynthesized in the cytosol, are transported into the lumen of the ER via unknown mechanisms, the characteristics of which are poorly defined. A new approach for the study of the transport process has been devised using two active-site directed photoaffinity analogs, [beta-32P]5-azido-UDP-GlcUA and [beta-32P]5-azido-UDP-Glc. Photoincorporation of these probes into the lumenally oriented UGTs of intact rat liver microsomal vesicles was used as an indicator of transport. In intact vesicles, [32P]5N3UDP-GlcUA was efficiently incorporated into UGTs in a time, temperature and concentration dependent manner. In contrast, [32P]5N3UDP-Glc apparently was not transported effectively; maximal photolabeling of the 50-54 kDa proteins by this probe was dependent on detergent disruption of the vesicles. Vesicular uptake of and subsequent photolabeling of the 50-54 kDa proteins by [32P]5N3UDP-GlcUA were inhibited by UDP-GlcUA and 5N3UDP-GlcUA while UDP-Glc, 5N3UDP-Glc, UDP-xylose and UDP-N-acetylglucosamine were less inhibitory, suggesting a high degree of specificity for the uptake/photolabeling process. The anionic transport inhibitors DIDS and SITS inhibited [32P]5N3UDP-GlcUA photoincorporation into UGTs in intact vesicles, but also inhibited photolabeling of these and other enzymes in detergent disrupted vesicles. These data suggest the presence in rat liver microsomal vesicles of a specific, carrier-mediated transport process for UDP-GlcUA which is distinct from the mechanism of UDP-Glc transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Microbiological collaborative studies for quality control in food laboratories: reference material and evaluation of analyst's errors.

Working groups of the Federal Health Office in Germany and of the International Dairy Federation (IDF) have developed a quality assurance system to assess the analyst performance for colony count methods. The experiment design consists of several dilution series produced from a homogeneous sample suspension. Each series contains a number of twofold dilution steps with parallel plates on each level. The structure of this design permits a detailed analysis of the total variance and identification of analysts' methodological errors as single effects. A computer-based interpretation aid may classify the laboratory as working in correspondence with good laboratory practice ('acceptable') or, otherwise, furnishing 'to good' or 'unacceptable' results. Some examples are given for deviation depending on individual faults. Both, internal quality assurance and collaborative studies demand suitable reference samples. The reference material used has to meet certain requirements concerning homogeneity, contamination level and microbiological stability during a period of storage and transport. A naturally contaminated sample material was prepared, which has been used successfully in microbiological collaborative studies.

Animals↗

IMPLICATIONS OF GILL ARCH MOVEMENTS FOR FILTER-FEEDING: AN X-RAY CINEMATOGRAPHICAL STUDY OF FILTER-FEEDING WHITE BREAM (BLICCA BJOERKNA) AND COMMON BREAM (ABRAMIS BRAMA)

Previous research shows that the reducible-channel model of filter-feeding can probably be applied to common bream, but not to white bream. According to this model, zooplankton are retained in the channels between the medial gill rakers; the mesh size of the sieve can be reduced by lowering the lateral rakers of the neighbouring gill arch into these channels. Gill arch movements may well disturb this mechanism; the depressed lateral gill rakers will move in and out of the medial channels and also shift out of their centre. We have quantified these disturbances by measuring the gill arch movements during filter-feeding in white bream and common bream, using dorsal X-ray films. In both species, the lateral rakers are long enough to bridge the gill slits. It was expected that common bream, which can reduce their channels, would have considerably less shift out of the channel centre than white bream, which cannot reduce their channels. However, the predicted shift is 40&shy;50 % of the channel width in white bream and 75 % in common bream. A new, dynamic retention mechanism is proposed for common bream. According to this hypothesis, once a particle is trapped in a reduced channel, the channel walls release mucus and the particle becomes sticky. Hence, particles need to be retained mechanically only during part of the gulping cycle. According to the hypothesis, this is achieved by sideways rotation of the lateral rakers in combination with their tapering shape. Retention mechanisms with interdigitating rakers are expected chiefly in facultative filter-feeders, because such mechanisms are easily disturbed by gill arch movements.

Journal Article↗