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Biomedical subjects

C Frye

Publications and source records attributed to C Frye.

At least 19 recordsLinked to original sources

Maternal oral contraceptive use and atopic diseases in the offspring.

BACKGROUND: This study examined the association of maternal oral contraceptive (OC) use - before and after birth - and atopic manifestations in the offspring. METHODS: A total of 2754 East German children aged 5-14 years participated in a cross-sectional survey in 1998-99. The standardized parental questionnaire in 1998-99 included data on atopic diseases, socio-economic factors, parental atopy and maternal OC use. Specific immunoglobulin E against common inhalant allergens was measured by radioallergosorbent test (RAST). RESULTS: Maternal OC use before birth was associated with a higher risk of atopic diseases in the offspring compared with children of mothers who had never taken OC [asthma: odds ratio (OR) 1.6; 95% confidence interval (CI): 0.9-3.0; allergic rhinitis: OR 1.5; CI: 0.96-2.2; atopic eczema: OR 2.6; CI: 1.6-4.3; atopic sensitization: OR 1.5; CI: 0.97-2.2]. However, the effect estimates for maternal OC use after birth compared with the never users showed quite similar effects for these atopic conditions. No relations were observed between the prevalences of atopic diseases and maternal age at beginning of OC use, the duration of OC use, the type of contraceptive or maternal age at birth. CONCLUSION: This study raises doubts in a true biological association between OC use and atopic diseases.

Adolescent↗

Trends and predictors of overweight and obesity in East German children.

OBJECTIVE: Childhood overweight and obesity seem to be increasing at an alarming rate throughout the Western world. During the 1990's, tremendous socioeconomic changes have taken place in East Germany, and studies about the prevalence and trends of childhood overweight and obesity in Central Eastern European countries are rare. Therefore, we analyzed trends in overweight and obesity in East German school children. DESIGN AND SUBJECTS: We examined 5- to 7-y-old school entrants, 8- to 10-y-old third graders and sixth-grade school children aged 11-14 y in three consecutive surveys performed in 1992-93, 1995-96, and 1998-99 in Eastern Germany. In total, we received 7611 questionnaires. Information about height and weight was available for 6650 children. RESULTS: Overweight and obesity showed a significant increasing trend for 11- to 14-y and 8- to 10-y-old children but not for the school entrants aged 5-7 y. After adjustment for age, sex, season and area, the risk of being overweight in 1998-99 compared to 1992-93 was 1.6 (CI 1.4-1.9) and 1.9 (CI 1.4-2.5) for obesity, respectively. Low birth weight and higher parental education were protective factors for overweight and obesity. Breast feeding was protective with regard to obesity. This effect was stronger if the children were exclusively breast-fed. CONCLUSIONS: In conclusion, our data provide further evidence that the prevalence of overweight and obesity increases. These results might suggest that preventive actions should start as early as possible and children from disadvantaged families might be considered as a susceptible subgroup.

Adolescent↗

Vaccination against Haemophilus influenzae type b and atopy in east German schoolchildren.

INTRODUCTION: Although routine childhood immunisations are known to prevent severe diseases there is an ongoing discussion on possible side effects in later life. In this paper we investigated the association of Haemophilus influenzae type b (Hib)-vaccination and atopic diseases and allergic sensitisation in children in Eastern Germany. METHODS: From 1998-1999 a cross-sectional survey of school children aged 5 to 14 years on long-term health effects of air pollution was conducted in three regions of Eastern Germany. Atopic outcome was defined by parental reporting of wheezing and doctor's diagnosed asthma (including asthma-like bronchitis), hay fever and eczema. Specific serum IgE against 5 aeroallergens were analysed by RAST-technique. Vaccination status was assessed by vaccination records from the respective local health authorities. Analysis is restricted to 1943 children with complete information on age, gender, place of residence, parental education and 1676 children with available blood data. RESULTS: Lifetime prevalence were 4.9% for asthma, 21.1% for wheezing, 6.6% for hay fever, 11.4% for eczema. 32% of the children had at least one specific IgE RAST>0. Hib-vaccination coverage was 42 % overall, 93 % in 5-7 yr olds, 59 % in 8-10 yr olds and 11 % in 11-14 yr olds. Odds Ratios adjusted for age, gender, place of residence, and parental education were 1.86 (1.05-3.32) for asthma, 1.55 (0.95-2.54) for hay fever, 1.03 (0.70-1.50) for eczema and 1.25 (0.94-1.67) for at least 1 specific IgE RAST>0. CONCLUSION: We found little evidence for an association between Hib-vaccination and some atopic outcomes and causality cannot be ascertained. Our findings do not give sufficient support to question the value of Hib vaccination given the substantial contribution of mass immunisations to public health. Specific research on possible long-term effects of vaccines is needed to enable final conclusions on this topic.

Adolescent↗

Allergic sensitization owing to 'second-hand' cat exposure in schools.

BACKGROUND: Environmental allergen loads play an important role in triggering symptoms in atopic individuals. While a number of previous studies have shown that cat allergens (Fel d 1) can be found in school dust samples, no study has provided evidence that public places contribute to increased atopic sensitization rates in children. METHODS: We employed data collected in a health survey of school children living in Germany in order to examine the association between the proportion of class- and schoolmates reporting cat contact and sensitization rates in children. RESULTS: Among 1893 children, 8.7% were sensitized to cats. Those sensitized were 5-7 times more likely to have received an asthma diagnosis or to have reported wheezing. Pupils without regular contact with cats were twice as likely to test positive for major cat allergen when the proportion of schoolmates with cat contact was high. No such relation was observed amongst children reporting regular cat contact. CONCLUSIONS: Our study suggests that allergens in school environments contribute to allergic sensitization and atopic diseases such as asthma. Thus, methods to reduce the allergen load in classrooms should be considered.

Adolescent↗

[European Community Respiratory Health Survey in Adults (ECRHS)].

The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma, allergy, and allergic sensitization in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140 000 individuals aged 20 - 44 years from 22 countries. The aim of this review is to summarize the results of the ECRHS and to present the specific contribution of the German centers in Hamburg and Erfurt. The prevalence ranged from 2.0 - 11.9 % for asthma, 9.5 - 40.9 % for allergic rhinitis, 4.0 - 32.0 % for wheeze, 3.4 - 27.9 % for bronchial hyperreactivity, and 16.2 - 44.5 % for allergic sensitisation against common aeroallergens. Although the prevalence of these atopic disorders were found to be consistently higher for the Hamburg center compared to the Erfurt center, strong regional differences in the prevalences were also found within several other European countries. Overall Europe, the lowest prevalences were seen in the Eastern and Middle European countries with the center Erfurt, followed by the Mediterranean region. The highest prevalences were reported for all English speaking centers. Strong geographic variation was reported for medication for asthma. Asthma seems to be undertreated in several countries. Environmental exposures and in particular indoor factors, and exposures at the workplace are playing a major role for asthma in adulthood. Furthermore, protective effects on atopy were found for exposures to pets (dogs) and a large number of siblings in early childhood. In conclusion, the ECRHS has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and likely due to environmental factors.

Adult↗

[Environmental surveys in the areas of Bitterfeld, Hettstedt and a comparative area in 1992-2000].

The aim of the environmental epidemiological study was to determine possible adverse effects on the health of children in the environmentally polluted areas of Bitterfeld and Hettstedt compared to the less polluted area of Zerbst (Eastern Germany). The changes of the health parameters were recorded together with the environmental changes during the time period of 6 years. The study design consisted of three repeated regional cross-sectional studies in 1992/93, 1995/96 and 1998/99. In total, 7,611 questionnaires could be analysed (participation rate: 89%, 75% and 75%). Children living in the most polluted area of Hettstedt had a noticeable higher risk for non-allergic respiratory diseases and symptoms compared to children living in the control area of Zerbst. From 1992 to 1999 a statistically significant decrease in the prevalences of these health outcomes was found. Children without indoor pollutants in their homes had the greatest benefit by the improvement of ambient air quality. The increase in lung function (FVC, FEV1) also underlines the improvement of the respiratory health. Children living in the polluted areas reported allergies more often (physician's diagnosis, allergy specific antibodies). The prevalence of asthma, the bronchial hyperreactivity and atopic eczema was increased within the observational period of 6 years. An increased prevalence was also shown for more severe allergic sensitisation (RAST classes > 17.5 kU/l), while the prevalence of hay fever increased slightly on a non-significant level. The burden with lead and cadmium was higher in children living in polluted areas and decreased during the study period except for 1997 where the lead concentration in blood increased according to the higher lead concentration in settled dust in Hettstedt at that time.

Adolescent↗

Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany.

Trends in prevalence of atopic diseases and allergic sensitization in children from Eastern Germany during the 1990s were analysed. The study consisted of three regional cross-sectional surveys of a total of 7,632 children (aged 5-14 yrs) in 1992-1993, 1995-1996, and 1998-1999. Information was gathered on atopic diseases and potential predictors by a parental questionnaire. Allergic sensitization for birch, grass, mite, cat, and cladosporium were assessed by radioallergosorbent test (RAST). After adjustment for age, sex and the study area of the participants, prevalence increased between the first and third survey for hay fever, for asthma and for atopic eczema. The adjusted prevalence of allergic sensitization (RAST > 0.35 kU x L(-1)) showed a decrease, whereas the prevalence of strong sensitization (RAST > or = 17.5 kU x L(-1)) increased significantly, specifically in cohorts born after 1989. Further adjustment for possible determinants of these atopic diseases did not change the trend estimates. A clear increase in the prevalence of atopic diseases, with the exception of hay fever, was observed as well as a shift towards a stronger allergic sensitization, which might affect the onset of clinical manifestations of atopic diseases. Differences in the epidemiology of respiratory symptoms, illnesses and allergies between populations living in the former East Germany and those living in the former West Germany have been reported. Among East German children, lower prevalence rates of asthma, and positive skin-prick tests were observed compared to West German children in the early 1990s. Similarly, among East German adults, lower specific immunoglobulin (Ig) E levels and lower prevalence rates of asthma, wheezing, positive methacholine-challenge tests, allergic rhinitis, and positive skin-prick tests have been reported compared to those of West German adults.

Adolescent↗

Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model.

BACKGROUND: - Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6) with cardiac-specific overexpression of TNF-alpha develop congestive heart failure. METHODS AND RESULTS: To determine the effect of anti-TNF-alpha therapy in this model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type mice treated with saline, and TNF1.6 mice treated with TNF-alpha neutralizing antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to compare cardiac hypertrophy, function, and catecholamine response at 12 weeks of age versus baseline (6 weeks). cV1q treatment did not limit cardiac hypertrophy, but it significantly improved basal fractional shortening and responsiveness to beta-adrenergic stimulation, and it limited development of cardiac dilation. CONCLUSIONS: Blockade of TNF-alpha bioactivity by antibody therapy may both preserve cardiac function and partially reverse pathological changes in congestive heart failure.

Adrenergic beta-Agonists↗

Early antibiotic treatment and later asthma.

The reasons for the asthma epidemic are poorly understood. As the asthma prevalence follows the geographical and temporal trend of antibiotic use into clinical medicine, we examined a possible association in a population-based study of 2,512 children age 5-14 in East Germany. Wheezing was associated with increasing number of antibiotic courses (never versus one time odds ratio 1.9, P = 0.012, 2 to 5 times odds ratio 3.0, P<0.001 and more than 5 times, odds ratio 6.9, P<0.001) which was also seen for asthma diagnosis. The risk increased with earlier administration (never versus second year odds ratio 4.6, month 7-12 odds ratio 5.4 and birth until month 6 odds ratio 7.9, all P<0.001). Also non pulmonary treatment indication was associated with later wheezing (odds ratio 3.9, P<0.001). The most likely possible explanation is reverse causation indicating that frequent upper respiratory infections, an early symptom of asthma, are treated with antibiotics. Antibiotic therapy could also be a proxy of another closely associated genetic or environmental factor. The high dose effect, the time dependency of the administration and the effect by non-pulmonary indications raises the possibility that early antibiotic treatment could itself be related to later asthma.

Adolescent↗

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗

Margarine consumption and allergy in children.

Dietary fat consumption is hypothesized to influence atopy development by modulation of IgE production. The aim of our study was to assess whether margarine consumption is associated with allergic sensitization and diseases in children. Data of a cross-sectional health survey in 1998-1999 comprising 2,348 children age 5 to 14 yr were analyzed. Information on type of fat used as spread during the past 12 mo, children's health, and sociodemographic factors were gathered by questionnaire. Allergic sensitization to common aeroallergens was assessed by specific serum IgE. Compared with butter consumption, margarine consumption was associated with allergic sensitization (adjusted odds ratio 1.30 [95% confidence interval: 1.01 to 1.67]) and with rhinitis symptoms during the past 12 mo (1.41 [1.01 to 1.97]). Sex-stratified analysis showed that these associations were limited to boys (boys: sensitization 1.57 [1.12 to 2.20], rhinitis symptoms 1.76 [1.12 to 2.78]; girls: sensitization 0.99 [0.67 to 1.46], rhinitis symptoms 1.03 [0.63 to 1.70]). No statistically significant relation was observed between exclusive margarine consumption and ever physician-diagnosed hay fever or asthma in all children. In conclusion, the sex difference in the association of margarine consumption with allergic sensitization was in accordance with the higher IgE concentrations and atopy prevalence in boys compared with girls. Increased intake of certain polyunsaturated fatty acids might further stimulate IgE production in boys.

Adolescent↗

Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany. Bitterfeld Study Group.

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8-14 yrs from three communities in East Germany were carried out in 1992-1993 and 1995-1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed. The prevalence of BHR increased from 6.4%, in 1992-1993 to 11.6% in 1995-1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3-3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95-2.3) after adjustment for several indoor factors. In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.

Asthma↗

Embryonic hemoglobins are expressed in definitive cells.

Human embryonic zeta and epsilon globin chains are synthesized in yolk sac-derived primitive erythroid cells, and decrease rapidly during definitive erythropoiesis. Examination of zeta and epsilon globin expression at the cellular level using dual-color immunofluorescence staining with specific monoclonal antibodies showed that embryonic globin proteins are present in definitive erythroid cells. More than half of fetal erythrocytes were positive for zeta and approximately 5% for epsilon globin. Approximately one third of newborn red blood cells were zeta-positive and less than 1% epsilon-positive. Adult erythrocytes did not have embryonic globins. Erythroblasts that developed in liquid cultures also contained embryonic globin in amounts which declined with ontogenic age, and the proportion of positive cells in vitro was less than in the comparable erythrocytes that developed in vivo. Thus, embryonic globin chains are synthesized in definitive erythroid cells and decrease with ontogeny. Modulation of embryonic globin gene expression is not solely due to a switch from primitive to definitive erythropoiesis.

Adult↗

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

Brain Neoplasms↗

Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor.

Mitogen-activated protein kinases function in signal transduction pathways that are involved in controlling key cellular processes in many organisms. A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 to downstream stress-activated protein kinase/JNK1 and p38 mitogen-activated protein kinase. This mitogen-activated protein kinase pathway has been implicated in the signal transduction of cytokine- and stress-induced apoptosis in a variety of cell types. Here, we report that two human tumor cell lines, derived from pancreatic carcinoma and lung carcinoma, harbor homozygous deletions that eliminate coding portions of the MKK4 locus at 17p, located approximately 10 cM centromeric of p53. In addition, in a set of 88 human cancer cell lines prescreened for loss of heterozygosity, we detected two nonsense and three missense sequence variants of MKK4 in cancer cell lines derived from human pancreatic, breast, colon, and testis cells. In vitro biochemical assays revealed that, when stimulated by MEKK1, four of the five altered MKK4 proteins lacked the ability to phosphorylate stress-activated protein kinase. Thus, the incidence of coding mutations of MKK4 in the set of cell lines is 6 of 213 (approximately 3%). These findings suggest that MKK4 may function as a suppressor of tumorigenesis or metastasis in certain types of cells.

DNA, Neoplasm↗

Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.

Deletions involving regions of chromosome 10 occur in the vast majority (> 90%) of human glioblastoma multiformes. A region at chromosome 10q23-24 was implicated to contain a tumour suppressor gene and the identification of homozygous deletions in four glioma cell lines further refined the location. We have identified a gene, designated MMAC1, that spans these deletions and encodes a widely expressed 5.5-kb mRNA. The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin. MMAC1 coding-region mutations were observed in a number of glioma, prostate, kidney and breast carcinoma cell lines or tumour specimens. Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.

Amino Acid Sequence↗

Interleukin-1 beta inhibits phospholamban gene expression in cultured cardiomyocytes.

Phospholamban is a key regulatory protein that defines diastolic function. Proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) can depress contractility and intracellular Ca2+ currents and transients. An alteration in phospholamban expression is a possible pathway by which these cytokines modulate cardiac function. To test this hypothesis, primary cultures of neonatal rat cardiomyocytes were incubated with IL-1 beta, TNF-alpha, or both, and the level of phospholamban transcripts was examined by Northern blot analyses. Phospholamban transcript levels were decreased approximately equal to 50% (P < .0001) in cells exposed to 2 ng/mL IL-1 beta (20 hours), whereas TNF-alpha had no effect. Western blot analyses showed that IL-1 beta also reduced phospholamban protein levels (60% of control, P < .0001). The effects on transcript levels were gene specific; IL-1 beta induced transcripts for inducible NO synthase (iNOS), did not alter GAPDH transcripts, and reduced sarcoplasmic reticulum Ca(2+)-ATPase (65% of control, P < .001) transcripts. Cardiomyocytes treated with IL-1 beta showed no alterations in basal contractile parameters (maximum velocity of contraction and relaxation and maximal amplitude of contraction) but were unresponsive to beta-adrenergic stimulation. Studies performed in the presence of second-messenger inhibitors showed that the effect of IL-1 beta on phospholamban transcript levels was blocked by dexamethasone, was insensitive to inhibitors of iNOS, cyclooxygenase, or tyrosine kinases, but was enhanced by the addition of the protein kinase inhibitor staurosporine. These data demonstrate that IL-1 beta alters the expression of phospholamban, a key regulator of cardiac contractility, at both the transcript and protein levels. The results suggest novel mechanisms by which IL-1 beta may modify cardiac function.

Animals↗

Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13.

An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1. 0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. One large gene with a transcript size of 10.7 kb showed significant similarity to a gene predicted by the Caenorhabditis elegans genome and the Saccharomyces cerevisiae genome sequencing efforts, while another contained a motif sequence similar to the human 2',3' cyclic nucleotide 3' phosphodiesterase gene. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals.

BRCA2 Protein↗