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PubMed2004

Relative importance of birth size and postnatal growth for women's educational achievement.

BACKGROUND: Child undernutrition, commonly measured by growth failure, is associated with functional disadvantages later in life. AIMS: To assess relationships between child growth and women's educational achievement (EA). STUDY DESIGN AND SUBJECTS: Women from four ladino Guatemalan villages were measured as children (1969-1977) and again at ages 20-29 years (1996-1999). The anthropometric measurements analyzed were weight, length, and head circumference (HC) at birth and 2 years and height at adulthood. Sample sizes were 120 at birth, 133 at 2 years, and 145 at adulthood; 108 cases had data at all three points. OUTCOME MEASURES: Women's EA was computed based on five educational tests and was categorized into quintiles. Analysis was based on a proportional odds model. Generalized estimating equations were used to account for sibling clustering. Multiple Stage Least Squares analyses were used to assess the relative importance of birth size and of early (birth to age 2 years) and late postnatal growth (2 years to adulthood). RESULTS: Size at 2 years (HC and length) but no indicator at birth was positively associated with women's EA. Schooling was a strong, positive predictor of women's EA (odds ratio (OR)=13.7, 95% confidence interval (CI) [6.1, 30.6]). Early postnatal growth but not birth size or late postnatal growth was associated with women's EA (OR with 1 standard deviation (S.D.) increment in length=1.5, 95% CI [1.05, 2.2]). CONCLUSIONS: Growth in length and HC from birth to 2 years of age, but not birth size or growth after 2 years, is an important predictor of women's EA.

Adult↗
PubMed2004

Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task.

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.

Adult↗
PubMed2006

Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: proteomic characterization.

The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor beta (TGFbeta) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFbeta treatment, or co-treatment with TGFbeta inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFbeta signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFbeta signaling pathway in breast cancer cells.

Antineoplastic Agents↗
PubMed1992

Intraretinal xenografts of differentiated human retinoblastoma cells integrate with the host retina.

We report on the successful use of chemically modified Y79 human retinoblastoma cells for intraretinal xenografting into damaged adult mammalian eyes. Y79 cells were exposed in vitro to retinoic acid/butyrate to induce differentiation. Using a multisite transplantation method, the suspension was injected into the subretinal space of Fischer 344 rats. The survival, integration, and differentiation potential of these cells was studied, following their return to the intraocular milieu from which the progenitor cells originated. The grafted cells survived and differentiated into immature photoreceptor elements in the subretinal and intraretinal locations, as multiple clusters of rosette-forming cells intimately attached to the host neuroretina. The differentiation process included development of synaptic connectivity of the ribbon type with the surrounding neuropil. No signs of renewed cell division were found within grafts performed on 42 rat eyes, and there was no indication of cell-mediated host reaction against the transplants. This study indicates that tumorigenicity can be suppressed in mitotically arrested Y79 cells, and that these cells are capable of undergoing differentiation in vivo. This provides evidence of the remarkable differentiation properties of human retinoblastomas while indicating that Y79 cells may ultimately be able to substitute for fetal cells in experimental retinal transplantation.

Animals↗
PubMed1999

Identification of linear surface epitopes on the guinea pig sperm membrane protein PH-20.

The sperm plasma membrane protein PH-20 has previously been shown to be an effective immunogen for protection against fertilization in guinea pigs. To identify immunodominant regions on gpPH-20 that may be related to this contraceptive effect, we used several high-titer immune sera obtained from animals rendered infertile by gpPH-20 injections to screen a set of overlapping peptides that cover the entire 494-residue sequence. Multiple clusters of peptide sequences exhibited specific reactivity. Some of these sequences were then constructed as octameric synthetic peptides and tested for immunogenicity in female guinea pigs. Our results indicated two regions (res. 94-119 and res. 424-444) to be highly immunogenic and both are surface accessible when native gpPH-20 is in solution or anchored on sperm surface. Both anti-peptide antibodies are specific for gpPH-20 and one of them inhibited hyaluronidase activity partially. These monospecific antibodies should be useful probes for further molecular definition of gpPH-20 structure-function relationships.

Amino Acid Sequence↗
PubMed1996

Characterization of mutations induced by 300 and 320 nm UV radiation in a rat fibroblast cell line.

The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelengths (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo and HSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely fit some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge at 320 nm from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers and C oligomers as predominant targets at both wavelengths; (2) increased incidence of relatively large deletions at 300 nm; and (3) greatly increased frequency of tandem double mutations at both wavelengths and of clustered multiple mutations at 320 nm. These results suggest the involvement of distinct mechanisms specifically operating, or becoming evident, in UV-mediated mutagenesis at these different wavelengths in mammalian cells.

Acyclovir↗
PubMed1996

The gamma 2 subunit of the GABAA receptor is concentrated in synaptic junctions containing the alpha 1 and beta 2/3 subunits in hippocampus, cerebellum and globus pallidus.

The gamma 2 subunit is necessary for the expression of the full benzodiazepine pharmacology of GABAA receptors and is one of the major subunits in the brain. In order to determine the location of channels containing the gamma 2 subunit in relation to GABA-releasing terminals on the surface of neurons, a new polyclonal antipeptide antiserum was developed to the gamma 2 subunit and used in high resolution, postembedding, immunoelectron-microscopic procedures. Dual immunogold labelling of the same section for two subunits, and up to three sections of the same synapse reacted for different subunits, were used to characterize the subunit composition of synaptic receptors. The gamma 2 subunit was present in type 2, "symmetrical" synapses in each of the brain areas studied, with the exception of the granule cell layer of the cerebellum. The gamma 2 subunit was frequently co-localized in the same synaptic junction with the alpha 1 and beta 2/3 subunits. The immunolabelling of synapses was coincident with the junctional membrane specialization of the active zone. Immunolabelling for the receptor often occurred in multiple clusters in the synapses. In the hippocampus, the gamma 2 subunit was present in basket cell synapses on the somata and proximal dendrites and in axo-axonic cell synapses on the axon initial segment of pyramidal and granule cells. Some synapses on the dendrites of GABAergic interneurones were densely labelled for the gamma 2, alpha 1 and beta 2/3 subunits. In the cerebellum, the gamma 2 subunit was present in both distal and proximal Purkinje cell dendritic synapses established by stellate and basket cell, respectively. On the soma of Purkinje cells, basket cell synapses were only weakly labelled. Synapses on interneuron dendrites were more densely labelled for the gamma 2, alpha 1 and beta 2/3 subunits than synapses on Purkinje or granule cells. Although immunoperoxidase and immunofluorescence methods show an abundance of the gamma 2 subunit in granule cells, the labelling of Golgi synapses was much weaker with the immunogold method than that of the other cell types. In the globus pallidus, many type 2 synapses were labelled for the gamma 2 subunit together with alpha 1 and beta 2/3 subunits. The results show that gamma 2 and beta 2/3 subunits receptor channels are highly concentrated in GABAergic synapses that also contain the alpha 1 and beta 2/3 subunits. Channels containing the gamma 2 subunit are expressed in synapses on functionally distinct domains of the same neuron receiving GABA from different presynaptic sources. There are quantitative differences in the density of GABAA receptors at synapses on different cell types in the same brain area.

Animals↗
PubMed2002

Characterisation of immunoglobulin light chain cDNAs of the Atlantic salmon, Salmo salar L.; evidence for three IgL isotypes.

By screening a cDNA library and analysis of DNA produced by a combined 3'RACE/5'-anchored PCR, we have isolated three isotypes of IgL in the Atlantic salmon. Two of the isotypes were homologous to rainbow trout IgL1 and L2 sequences, while the third represents a previously uncharacterised salmonid IgL. The novel type 3 CL region is homologous to spotted wolffish c1 and yellowtail sequences, while the VL region is more similar to channel catfish F class than to any other fish VL sequences. Southern analysis indicates that the gene segments of all three isotypes are organised in multiple clusters. In addition, the VL gene segments of type 3 are arranged in opposite orientation relative to the JL and CL segments, while gene segments in type 2 clusters are all in the same orientation. Although transcripts of type 1 and 3 were readily found in the spleen and head kidney, only minute amounts of type 2 transcripts were seen. The majority of type 3 messages were truncated, suggesting that spliced and full-length transcripts of this isotype probably are present at a low level compared to type 1 transcripts. The uniqueness of the type 3 VLJL sequences suggests that this isotype offers additional diversity to the antigen-binding site of Atlantic salmon immunoglobulins.

Amino Acid Sequence↗
PubMed1999

Aspergillus mycetoma in a secondary hydroxyapatite orbital implant: a case report and literature review.

OBJECTIVE: The authors describe the first case report of a fungal abscess within a hydroxyapatite orbital implant in a patient who had undergone straightforward secondary hydroxyapatite implant surgery. DESIGN: Case report and literature review. INTERVENTION: Four months postoperatively after pegging and 17 months after original implant placement, chronic discharge and socket irritation became evident. Recurrent pyogenic granulomas were a problem, but no obvious area of dehiscence was present over the implant. The peg and sleeve were removed 31 months after pegging (44 months after original placement of the implant). The pain and discharge did not resolve, and the entire hydroxyapatite orbital implant was removed 45 months after sleeve placement and 58 months after initial implant placement. The pain and discharge settled rapidly. MAIN OUTCOME MEASURES: Cultures and histopathology. RESULTS: Results of bacterial cultures were negative. Results of histopathologic examination of the implant disclosed intertrabecular spaces with multiple clusters of organisms consistent with Aspergillus. CONCLUSIONS: Persistent orbital discomfort, discharge, and pyogenic granulomas after hydroxyapatite implantation should cause concern regarding potential implant infection. The authors have now shown that this implant infection could be bacterial or fungal in nature. This is essentially a new form of orbital Aspergillus, that of a chronic infection limited to a hydroxyapatite implant.

Abscess↗
PubMed2003

Controlling Echinococcus multilocularis-ecological implications of field trials.

Two field trials to reduce the prevalence of Echinococcus multilocularis in foxes have been conducted in recent years. Although both trials reduced prevalence considerably, they failed to eradicate the parasite in the study region. Following the control trial in northern Germany, prevalence recovered unexpectedly and rapidly, reaching pre-control levels five quarters (15 months) after the end of control. To understand the internal dynamics of the parasite-host system's reaction to control, we developed a spatially explicit simulation model, Echi. The simulation model incorporates the information available concerning fox tapeworm population dynamics. Using epidemiological parameters to adjust pre-control prevalence, the model predicts the temporal evolution of the prevalence of E. multilocularis in controlled foxes without departing from the range of uncertainty of the field data. However, the model does not predict the rapid pre-control recovery observed in the field trial. The deviation of the model's prediction from field data indicates the involvement of processes not yet taken into account. We modified the model step by step to mimic processes with the potential to cause the rapid post-control recovery of the prevalence of E. multilocularis in foxes. Neither the longevity of tapeworm eggs nor the migratory behaviour of foxes showed any influence on the post-control reaction of the parasite-host system. However, landscape structures leading to a heterogeneous distribution of infected foxes have the potential to alter the system's reaction to control. If infected foxes are concentrated in multiple clusters in the landscape, the model prediction tallied with the range of uncertainty of the field data. Such spatial distribution of infected foxes may be caused by differential abiotic conditions influencing the survival of tapeworm eggs. The model was found to comply best with field data if the foxes acquire partial immunity by being exposed to the fox tapeworm. Both hypotheses explaining the rapid post-control recovery of the prevalence of E. multilocularis observed in the fox population were supported by field data. Both hypotheses have far-reaching consequences for future control trials. The spatial aggregation of infected foxes would enable control efforts to be concentrated on these highly infected areas. However, the acquisition of immunity acts as a buffer to control, necessitating intensified control measures.

Animals↗
PubMed2003

Independent component analysis of nondeterministic fMRI signal sources.

Neuronal activation can be separated from other signal sources of functional magnetic resonance imaging (fMRI) data by using independent component analysis (ICA). Without deliberate neuronal activity of the brain cortex, the fMRI signal is a stochastic sum of various physiological and artifact related signal sources. The ability of spatial-domain ICA to separate spontaneous physiological signal sources was evaluated in 15 anesthetized children known to present prominent vasomotor fluctuations in the functional cortices. ICA separated multiple clustered signal sources in the primary sensory areas in all of the subjects. The spatial distribution and frequency spectra of the signal sources correspond to the known properties of 0.03-Hz very-low-frequency vasomotor waves in fMRI data. In addition, ICA was able to separate major artery and sagittal sinus related signal sources in each subject. The characteristics of the blood vessel related signal sources were different from the parenchyma sources. ICA analysis of fMRI can be used for both assessing the statistical independence of brain signals and segmenting nondeterministic signal sources for further analysis.

Artifacts↗
PubMed2001

Characterization of human bone morphogenetic protein (BMP)-4 and -7 gene promoters: activation of BMP promoters by Gli, a sonic hedgehog mediator.

Among the bone morphogenetic protein (BMP) family, which plays a crucial role not only in bone formation but also in development, BMP-2, -4, and -7 participate predominantly in various aspects. To undertake complex tasks, their expression is strictly controlled. In this study we isolated and analyzed the 5'-flanking regions of the human BMP-4 and -7 genes to elucidate the mechanism of their temporally and spatially specific expression. As for BMP-4 expression, a reverse transcription-polymerase chain reaction (RT-PCR) assay with specially designed sets of primers demonstrated that osteoblastic SaOS-2 and Hos cells expressed two types of transcripts comprising one of the 5'-untranslated first exons, whereas MG63 cells displayed only the transcript with the BMP-4 proximal first exon. Likewise, RT-PCR revealed that Hos and MG63 cells expressed BMP-7. Subsequent 5'-RACE confirmed an alternative usage of the BMP-4 first exons with clustered multiple transcription start sites in the distal exon and the sole start site in the proximal exon. The transcription start site of the BMP-7 gene was found to be far upstream (764 bp) of the initiation ATG codon. We constructed a series of deletion mutants of fusions between these BMP promoters and the luciferase gene and examined their activity by transient transfection into osteoblastic Hos and renal COS-7 cells. The degree of distal and proximal BMP-4 promoter activity was in accordance with the expression level of the corresponding transcripts. Both distal and proximal BMP-4 promoters possessed suppressor elements that are operative only in Hos cells. The positive and negative elements identified in the BMP-7 promoter were more remarkably effective in Hos cells. The activities of the respective BMP-4 promoters and BMP-7 promoter were all stimulated upon the cotransfection of a potential sonic hedgehog (SHH) mediator, Gli1 or Gli3 into COS-7 cells, providing direct evidence that the Gli proteins are capable of inducing the BMP expression. Our systems are helpful for assessment of the complicated interactions of molecules involved in the skeletogenesis and developmental processes.

Animals↗
PubMed1987

Molluscum contagiosum: characterization of viral DNA and clinical features.

Restriction endonuclease analysis of molluscum contagiosum virus DNA revealed two subtypes. In a study of 46 isolates from 41 patients, some with no other disorder and some with atopic dermatitis, the ratio of MCV I isolates to MCV II was 34:12. Multiple clustered lesions removed at the same time from an individual patient yielded only one type of MCV. Lesions induced by MCV I or MCV II were indistinguishable on the basis of size and form. Neither subtype was associated exclusively with lesions at certain sites or with other clinical features. Heterogeneity of DNA restriction endonuclease cleavage patterns amongst isolates of the same subtype was observed, this being greatest for MCV II.

Adolescent↗
PubMed1998

Multiple risk factors in the development of externalizing behavior problems: group and individual differences.

The aim of this study was to test whether individual risk factors as well as the number of risk factors (cumulative risk) predicted children's externalizing behaviors over middle childhood. A sample of 466 European American and 100 African American boys and girls from a broad range of socioeconomic levels was followed from age 5 to 10 years. Twenty risk variables from four domains (child, sociocultural, parenting, and peer-related) were measured using in-home interviews at the beginning of the study, and annual assessments of externalizing behaviors were conducted. Consistent with past research, individual differences in externalizing behavior problems were stable over time and were related to individual risk factors as well as the number of risk factors present. Particular risks accounted for 36% to 45% of the variance, and the number of risks present (cumulative risk status) accounted for 19% to 32% of the variance, in externalizing outcomes. Cumulative risk was related to subsequent externalizing even after initial levels of externalizing had been statistically controlled. All four domains of risk variables made significant unique contributions to this statistical prediction, and there were multiple clusters of risks that led to similar outcomes. There was also evidence that this prediction was moderated by ethnic group status, most of the prediction of externalizing being found for European American children. However, this moderation effect varied depending on the predictor and outcome variables included in the model.

Black or African American↗
PubMed1977

Comparative study of hen yolk phosvitin and plasma vitellogenin.

Vitellogenin, the only phosphoprotein detectable in the plasma of laying hens, is present at an approximate concentration of 1 mg/mL and can be isolated by chromatography on diethylaminoethylcellulose. Vitellogenin has a molecular weight of 235 000--240 000 and contains approximately 3% phosphorus by weight. Evidence that this protein is the precursor of phosvitins includes its ability to act as an acceptor for phosphate with a phosvitin specific kinase, the generation of a peptide similar to phosvitin by trypsinization, and the presence of distinctive peptides of multiple clustered phosphoserine upon partial acid hydrolysis. This partial sequence similarity between phosvitins and vitellogenin has not been previously reported. The phosphorus content and amino acid composition of vitellogenin are consistent with a model which contains two phosvitins and one lipovitellin. The total molecular weights of these proteins (28 000 + 34 000 + 170 000 = 232 000) are close to that of vitellogenin.

Amino Acids↗
PubMed1993

A simple network model simulates hippocampal place fields: parametric analyses and physiological predictions.

Hippocampal place cells may be the computational units of a neuronal cognitive mapping system. A network model trained to compute locations from distal cues simulated the defining properties of hippocampal place cells (i.e., place-specific activation). The model produced units with detailed properties of place cells, including multiple subfields, "silent" and "noisy" cells, fields that persisted after cue removal, and groups of simulated fields that overlapped in multiple clusters. Quantitative variants of the model showed that different properties of the fields were influenced by the complexity of the visual input (the number of spatial cues), the available computational resources (the number of hidden units), and the output encoding used to represent location. The simulations provide a framework for testing relationships between place field properties, variations in spatial environments, and the integrity of the hippocampal system.

Animals↗
PubMedDate not supplied

The class I major histocompatibility antigen gene activated in a line of SV40-transformed mouse cells is H-2Dd, not Qa/Tla.

We have previously described several complementary DNA clones isolated because they correspond to messenger RNAs present at higher levels in the simian virus 40 (SV40)-transformed BALB/c 3T3 cell line SV3T3 Cl38 than in the normal, parental BALB/c 3T3 line. One of these clones, pAG64, hybridizes to RNAs which, while present in BALB/c 3T3 cells, are 10-20-fold more abundant in SV3T3 Cl38 and are found at high levels in a wide variety of transformed cell lines. Nucleotide sequence analysis showed that pAG64 encodes a class I antigen of the major histocompatibility complex. To ascertain the identity of pAG64, we compared its sequence with the available sequences of d haplotype class I antigen genes [K locus, L locus, D locus and the Qa gene defined by genomic clone 27.1] and found that it showed multiple clustered differences from each of these sequences. We therefore concluded that it was not derived from the H-2Kd, H-2Ld or H-2Dd genes and thus must correspond to one of the other class I antigen genes, namely those of the Qa/Tla complex, although it was clearly not the Qa gene defined by the genomic clone 27.1. We now report subsequent findings which indicate that pAG64 in fact corresponds to the H-2Dd gene and not to a Qa/Tla gene.

Animals↗
PubMed2002

Induction of vasculogenesis in breast cancer models.

Recently, there have been reports of postnatal vasculogenesis in cases of ischaemia models. The aim of the present study is to provide evidence of postnatal vasculogenesis in breast-cancer-bearing mice. Based on cell surface antigen expression, we isolated endothelial precursor cells from bone marrow, peripheral blood and tumour-infiltrating cells from mice that had received six human breast cancer xenografts. In all three areas (bone marrow, peripheral blood and tumour-infiltrating cells), endothelial precursor cell population was elevated in all transplanted mice. Differentiation and migration activities of endothelial precursor cells were measured by comparing levels of the endothelial precursor cell maturation markers Flk-1, Flt-1, Tie2, VE-cadherin and CD31 among these three areas. The endothelial precursor cell population was 14% or greater in the gated lymphocyte-size fraction of the inflammatory breast cancer xenograft named WIBC-9, which exhibits a hypervascular structure and de novo formation of vascular channels, namely vasculogenic mimicry (Shirakawa et al, 2001). In vitro, bone marrow-derived endothelial precursor cells from four human breast cancer xenografts proliferated and formed multiple clusters of spindle-shaped attaching cells on a vitronectin-coated dish. The attaching cells, which incorporated DiI-labelled acetylated low-density lipoprotein (DiI-acLDL) and were negative for Mac-1. The putative bone marrow derived endothelial precursor cell subset, which was double positive of CD34 and Flk-1, and comparative bone marrow derived CD34 positive with Flk-1 negative subset were cultured. The former subset incorporated DiI-acLDL and were integrated with HUVECs. Furthermore, they demonstrated significantly higher levels of murine vascular endothelial growth factor and interleukin-8 in culture supernatant on time course by enzyme-linked immunosorbent assay. These findings constitute direct evidence that breast cancer induces postnatal vasculogenesis in vivo.

Animals↗