Search PubMed⌕ Search

Biomedical subjects

K Moberg

Publications and source records attributed to K Moberg.

11 recordsLinked to original sources
PubMed2004

Relationship between illness-associated absence in day-care children and weather parameters.

This 5-year study demonstrated a statistically significant correlation between morbidity among children attending day-care centres and various weather parameters. The study was undertaken in south-central Sweden, where sharp seasonal contrasts in climatic and weather conditions occur. Illness-associated absence (IAA) decreased significantly when the weather was bright, sunny and warm, determined using average monthly weather parameters analysed over 60 months. This may be because good weather encourages outdoor activities which, in turn, reduce the risk of spreading respiratory tract infections as outdoor play areas are larger, body contact is less frequent, and any bacteria and viruses present will be readily dispersed. In multiple regression analysis, outdoor temperature was the most prominent parameter linked with IAA. This may reflect the behaviour of the staff with regard to various weather conditions. It is therefore to be recommended that children attending day-care centres should be allowed and encouraged to play outdoors when conditions allow.

Absenteeism↗
PubMed2003

European experience with a novel noninvasive sensor for intra-amniotic or extra-amniotic evaluation of fetal oxygen saturation.

OBJECTIVE: We evaluated the feasibility of a new instrument for continuous fetal pulse oximetry during labor. The measuring sensor can be placed on the fetal back before or after rupture of membranes. METHODS: One hundred adult women who had completed 32 weeks of gestation and had an anticipated duration of labor greater than 30 minutes were included in the study. Patients with premature rupture of membranes for 24 hours or more, low placental localization, placenta previa or abruption, vaginal bleeding, acute infection, polyhydramnios, oligohydramnios, or uterine or congenital abnormalities were excluded. RESULTS: All sensors were placed successfully. The mean continuous recording time was 276 minutes. Peripheral oxygen saturation as measured by pulse oximeter values were obtained during a median of 64.05% of the recording time. No chorioamnionitis or endometritis was noted. CONCLUSION: The new sensor instrumentation was safe for mother and fetus and was well accepted by parents and physicians.

Adolescent↗
PubMed2001

Computed assisted detection of interval breast cancers.

OBJECTIVES: To examine interval cancer detection rate for a system of computer assisted detection (CAD) and its influence on radiologists' sensitivity/specificity in a screen-like retrospective review situation. MATERIALS AND METHODS: Three screening radiologists reviewed previous screen images of 59 interval cancers mixed with other screening mammograms (ratio 1:5) and non-mixed. Mixed interval cases were interpreted both without and with aid of CAD. RESULTS: CAD detected a number of 14 interval cancers while the three radiologists detected 17, 12 and 11 without and 16, 10 and 13 with CAD. Although CAD specificity was low (38%) no reduction in radiologists' specificity occurred using CAD (73%, 82% and 89% without and 78%, 90% and 92% with CAD). Non-mixed reading increased radiologists' detection rate to 21, 17 and 19 interval cancers respectively. CONCLUSION: Despite sufficiently high sensitivity for CAD alone no increase in radiologist sensitivity (or decrease in specificity) occurred with CAD. Improving CAD specificity, with unaffectedly high sensitivity, should make radiologists more inclined to revise interpretations according to CAD. The potential sensitivity increase, noted when using CAD as a double reader, could be realised in this way.

Aged↗
PubMed2000

Radiological review of incidence breast cancers.

OBJECTIVES: To examine the rate of incidence cancers detectable on review of previous screening mammograms using two reviewing methods. To compare the results with a previous study of interval cancers using the same reviewing methods. SETTING: Almost 50000 women are regularly invited for service screening at Stockholm Söder Hospital. From 1989 to 1993, 119 women were identified with breast cancer detected at screening and the previous round attendance (incidence cancer). METHODS: Screening mammograms, obtained before detection of the incidence cancers, were reviewed first mixed with other screening images (ratio 1:8) and then non-mixed. Reviewers from the screening unit responsible for the mammograms as well as reviewers from other units interpreted all images by both single and double reading. RESULTS: The proportion detected on retrospective review varied between 5% and 50% depending on the review method used and the number of reviewers included to classify a case as truly identified. Generally more cancers were detected when non-mixed samples of mammograms were reviewed than when mixed samples were reviewed (mean increase 23%) and when interpreted by double reading compared with single reading (mean increase 14%). CONCLUSIONS: In an experimental retrospective set up, fewer incidence cancers were identified in mixed than in non-mixed review. Generally more incidence cancers were identified on review (22%) than previously reported for interval cancers (14%), probably reflecting differences in tumour biology and growth. How many women with potentially visible incidence cancers would have benefited from earlier tumour detection still needs to be evaluated.

Breast Neoplasms↗
PubMed1999

Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation.

In mammalian cells, activation of certain checkpoint pathways as a result of exposure to genotoxic agents results in cell cycle arrest. The integrity of these arrest pathways is critical to the ability of the cell to repair mutations that otherwise might compromise viability or contribute to deregulation of cellular growth and proliferation. Here we examine the mechanism through which DNA damaging agents result in a G1 arrest that depends on the tumor suppressor p53 and its transcriptional target p21. By using primary cell lines lacking specific cell cycle regulators, we demonstrate that this pathway functions through the growth suppressive properties of the retinoblastoma protein (pRB) tumor suppressor. Specifically, gamma-irradiation inhibits the phosphorylation of pRB at cyclin-dependent kinase 2-specific, but not cyclin-dependent kinase 4-specific, sites in a p21-dependent manner. Most importantly, we show that pRB is a critical component of this DNA damage checkpoint. These data indicate that the p53 --> p21 checkpoint pathway uses the normal cell cycle regulatory machinery to induce the accumulation of the growth suppressive form of pRB and suggest that loss of pRB during the course of tumorigenesis disrupts the function of an important DNA damage checkpoint.

Animals↗
PubMed1999

Two models for radiological reviewing of interval cancers.

OBJECTIVES: To compare two different review methods of examining how many of our interval cancers could be regarded as missed cases (overlooked and misinterpreted owing to observer's error). SETTING: A mass screening programme in Stockholm 1989-91, performed at five independent screening units. 107,846 women attended for screening (70.6% of those invited), and 207 women with interval breast cancers were identified. Interval cancers from two of the units, 104 cases, are reviewed in this study. METHODS: Screening examinations preceding the interval cancer diagnoses were reviewed both mixed with other screening images in a ratio 1:8 and non-mixed. Both internal reviewers (from the two units responsible for the screening mammograms) and external reviewers (from the other units) took part in the study. RESULTS: The proportion regarded as missed cases varied between 7% and 34%, depending on what review method was used, and on the number of reviewers included to identify a case as missed. Mixed reviewing reduced the number identified as missed cases by 50% compared with non-mixed reviewing. Whether the reviewer was internal or external made no difference to the results. CONCLUSIONS: Comparing the rate of missed cases from different studies may be misleading unless the same review method is used. No difference in detection rate could be shown whether the radiologist reviewed images from his/her own screening unit or not. Most of our interval cancers were not regarded as missed cases by either of the two methods.

Breast Neoplasms↗
PubMed1998

E2F-6, a member of the E2F family that can behave as a transcriptional repressor.

The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription of genes that direct the process of cell division. All previously identified E2F proteins can act in a similar manner; depending on whether or not they are associated with the cell cycle inhibitors the retinoblastoma protein (pRB), p107, or p130, they can either repress or activate the transcription of E2F-responsive genes. We now report the cloning and characterization of another E2F family member, E2F-6, whose structure is reminiscent of the dominant inhibitors of other transcription factor families. The dimerization and DNA binding properties of E2F-6 are similar to those of the other E2F family members. However, it is not regulated by pRB, p107, or p130, and it is unable to activate transcription. Instead, it can act to repress the transcription of E2F responsive genes by countering the activity of the other E2F complexes via a pRB-, p107-, or p130-independent mechanism.

Amino Acid Sequence↗
PubMed1997

E2F activity is regulated by cell cycle-dependent changes in subcellular localization.

E2F directs the cell cycle-dependent expression of genes that induce or regulate the cell division process. In mammalian cells, this transcriptional activity arises from the combined properties of multiple E2F-DP heterodimers. In this study, we show that the transcriptional potential of individual E2F species is dependent upon their nuclear localization. This is a constitutive property of E2F-1, -2, and -3, whereas the nuclear localization of E2F-4 is dependent upon its association with other nuclear factors. We previously showed that E2F-4 accounts for the majority of endogenous E2F species. We now show that the subcellular localization of E2F-4 is regulated in a cell cycle-dependent manner that results in the differential compartmentalization of the various E2F complexes. Consequently, in cycling cells, the majority of the p107-E2F, p130-E2F, and free E2F complexes remain in the cytoplasm. In contrast, almost all of the nuclear E2F activity is generated by pRB-E2F. This complex is present at high levels during G1 but disappears once the cells have passed the restriction point. Surprisingly, dissociation of this complex causes little increase in the levels of nuclear free E2F activity. This observation suggests that the repressive properties of the pRB-E2F complex play a critical role in establishing the temporal regulation of E2F-responsive genes. How the differential subcellular localization of pRB, p107, and p130 contributes to their different biological properties is also discussed.

Animals↗
PubMed1997

Specific regulation of E2F family members by cyclin-dependent kinases.

The transcription factor E2F-1 interacts stably with cyclin A via a small domain near its amino terminus and is negatively regulated by the cyclin A-dependent kinases. Thus, the activities of E2F, a family of transcription factors involved in cell proliferation, are regulated by at least two types of cell growth regulators: the retinoblastoma protein family and the cyclin-dependent kinase family. To investigate further the regulation of E2F by cyclin-dependent kinases, we have extended our studies to include additional cyclins and E2F family members. Using purified components in an in vitro system, we show that the E2F-1-DP-1 heterodimer, the functionally active form of the E2F activity, is not a substrate for the active cyclin D-dependent kinases but is efficiently phosphorylated by the cyclin B-dependent kinases, which do not form stable complexes with the E2F-1-DP-1 heterodimer. Phosphorylation of the E2F-1-DP-1 heterodimer by cyclin B-dependent kinases, however, did not result in down-regulation of its DNA-binding activity, as is readily seen after phosphorylation by cyclin A-dependent kinases, suggesting that phosphorylation per se is not sufficient to regulate E2F DNA-binding activity. Furthermore, heterodimers containing E2F-4, a family member lacking the cyclin A binding domain found in E2F-1, are not efficiently phosphorylated or functionally down-regulated by cyclin A-dependent kinases. However, addition of the E2F-1 cyclin A binding domain to E2F-4 conferred cyclin A-dependent kinase-mediated down-regulation of the E2F-4-DP-1 heterodimer. Thus, both enzymatic phosphorylation and stable physical interaction are necessary for the specific regulation of E2F family members by cyclin-dependent kinases.

CDC2-CDC28 Kinases↗
PubMed1996

E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry.

The E2F transcription factor couples the coordinate expression of cell cycle proteins to their appropriate transition points. Its activity is controlled by the cell cycle regulators pRB, p107, and p130. These bind to E2F at defined but distinct stages of the cell cycle. Using specific antisera, we have identified the DP and E2F components of each of these species. Although present at very different levels, DP-1 and DP-2 are evenly distributed among each of these complexes. In contrast, the individual E2Fs have distinctly different binding profiles. Consistent with previous studies, E2F-1, E2F-2, and E2F-3 bind specifically to the retinoblastoma protein. In each case, their expression and DNA binding activity are restricted to post-G1/S fractions. Surprisingly, E2F-1 and E2F-3 make unequal contributions to the pRB-associated and free E2F activity, suggesting that these proteins perform different cell cycle functions. Most significantly, this study showed E2F-4 accounts for the vast majority of the endogenous E2F activity. In arrested cells, E2F-4 is sequestered by the p130 protein. However, as the cells pass the G1-to-S transition, the levels of pRB and p107 increase and E2F-4 now associates with both of these regulators. Despite this, a considerable amount of E2F-4 exists as free E2F. In G1 cells, this accounts for almost all of the free activity. Once the cells enter S phase, free E2F is composed of an equal mixture of E2F-4 and E2F-1.

Antibodies, Monoclonal↗