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Biomedical subjects

V Seitz

Publications and source records attributed to V Seitz.

17 recordsLinked to original sources
PubMed2006

Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.

Runx2 is an essential factor for skeletogenesis and heterozygous loss causes cleidocranial dysplasia in humans and a corresponding phenotype in the mouse. Homozygous Runx2-deficient mice lack hypertrophic cartilage and bone. We compared the expression profiles of E14.5 wildtype and Runx2(-/-) murine embryonal humeri to identify new transcripts potentially involved in cartilage and bone development. Seventy-one differentially expressed genes were identified by two independent oligonucleotide-microarray hybridizations and quantitative RT-PCR experiments. Gene Ontology analysis demonstrated an enrichment of the differentially regulated genes in annotations to terms such as extracellular, skeletal development, and ossification. In situ hybridization on E15.5 limb sections was performed for all 71 differentially regulated genes. For 54 genes conclusive in situ hybridization results were obtained and all of them showed skeletal expression. Co-expression with Runx2 was demonstrated for 44 genes. While 41 of the 71 differentially expressed genes have a known role in bone and cartilage, we identified 21 known genes that have not yet been implicated in skeletal development and 9 entirely new transcripts. Expression in the developing skeleton was demonstrated for 21 of these genes.

Animals↗
PubMed2003

Evolution of classic Hodgkin lymphoma in correlation to changes in the lymphoid organ structure of vertebrates.

In order to integrate evolutionary concepts into lymphoma research we mapped features of classic Hodgkin lymphoma (a disease which has been recently described to be derived from germinal center B-cells) onto a phylogenetic tree of vertebrates. Secondly, we matched the phylogenetic occurrence of classic Hodgkin lymphoma to the changes in the lymphoid organ structure during vertebrate evolution. According to our analysis, classic Hodgkin lymphoma evolved exclusively at the developmental stage of mammals. Interestingly the appearance of Hodgkin lymphoma is correlated to the evolution of germinal centers in mammals. This lends some credit to the hypothesis that genes specific to the germinal center reaction are involved in the pathogenesis of Hodgkin lymphoma. However, as evolution did not stop at the developmental stage of the mammalian stem-species, to a certain extent species with specific differences of classic Hodgkin lymphoma can be expected. One such difference is that classic Hodgkin lymphoma occurs with a significantly higher frequency in humans than in all other mammals. This could be partially due to Epstein-Barr virus (EBV) infection in approximately 40%-50% of Hodgkin disease cases, that is associated with an expression of the EBV-encoded oncogen LMP-1. In conclusion we propose that the mapping of lymphoma related characteristics onto a phylogenetic tree is a valuable new tool in lymphoma research.

Animals↗
PubMed2003

Identification of immunorelevant genes from greater wax moth (Galleria mellonella) by a subtractive hybridization approach.

In this study we have analyzed bacterial lipopolysaccharide (LPS) induced genes in hemocytes of the Lepidopteran species Galleria mellonella using subtractive hybridization, followed by suppressive PCR. We have found genes that show homologies to molecules, such as gloverin, peptidoglycan recognition proteins and transferrin known to be involved in immunomodulation after bacterial infection in other species. In addition, a few molecules previously not described in the innate immune reactions were detected, such as a RNA binding molecule and tyrosine hydroxylase. Furthermore, the full-length cDNA of a LPS-induced molecule with six toxin-2-like domains is described to be a promising candidate to further elucidate the relationship between toxin- and defensin-like domains in arthropod host defense.

Amino Acid Sequence↗
PubMed2003

A single amphioxus and sea urchin runt-gene suggests that runt-gene duplications occurred in early chordate evolution.

Runt-homologous molecules are characterized by their DNA binding runt-domain which is highly conserved within bilaterians. The three mammalian runt-genes are master regulators in cartilage/bone formation and hematopoiesis. Historically these features evolved in Craniota and might have been promoted by runt-gene duplication events. The purpose of this study was therefore to investigate how many runt-genes exist in the stem species of chordates, by analyzing the number of runt-genes in what is likely to be the closest living relative of Craniota-amphioxus. To acquire further insight into the possible role of runt-genes in early chordate evolution we have determined the number of runt-genes in sea urchins and have analyzed the runt-expression pattern in this species. Our findings demonstrate the presence of a single runt-gene in amphioxus and sea urchin, which makes it highly likely that the stem species of chordates harbored only a single runt-gene. This suggests that runt-gene duplications occurred later in chordate phylogeny, and are possibly also associated with the evolution of features such as hematopoiesis, cartilage and bone development. In sea urchin embryos runt-expression involves cells of endodermal, mesodermal and ectodermal origin. This complex pattern of expression might reflect the multiple roles played by runt-genes in mammals. A strong runt-signal in the gastrointestinal tract of the sea urchin is in line with runt-expression in the intestine of nematodes and in the murine gastrointestinal tract, and seems to be one of the phylogenetically ancient runt-expression domains.

Amino Acid Sequence↗
PubMed2001

Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type.

BCL-6 is essential for germinal center formation and thus for affinity maturation of immunoglobulin (Ig) genes by somatic mutations. The 5'-noncoding region of the BCL-6 gene is even a target for the mutation machinery. Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma. In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations, such as diffuse large B-cell lymphoma and follicular lymphoma, also carry BCL-6 mutations, some of which are recurrently detectable. Classic Hodgkin disease (cHD) is also derived from B cells with high loads of somatic mutations and thus a further candidate for BCL-6 mutations. To determine the presence and potential role of BCL-6 mutations in cHD, the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-Sternberg (HRS) cells from 6 cases of cHD and 6 cases of HD-derived cell lines was analyzed. All B-cell-derived HD cases and cell lines harbored BCL-6 mutations. In contrast, both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations. With only one exception, there were no lymphoma-specific recurrent BCL-6 mutations detected, and BCL-6 protein was absent from the HRS cells of most cases. In conclusion, (1) somatic BCL-6 mutations are restricted to cHD cases of B-cell origin, and (2) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for BCL-6 protein expression and the pathogenesis of cHD.

5' Untranslated Regions↗
PubMed2000

Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease.

Recent molecular single-cell studies have shown that in approximately 95% of cases, Reed-Sternberg cells of classic Hodgkin disease (HD) are derived from B cells of germinal center origin. Attempts to determine the cellular nature of the remaining cases have so far failed. To clarify whether they are derived from T cells, this study examined 791 single CD30(+) Hodgkin and Reed-Sternberg (HRS) cells from 13 T-cell marker-positive cases and from 6 cases with null-cell phenotype for rearranged T-cell receptor-gamma (TCR-gamma) genes by single copy polymerase chain reaction. Monoclonally rearranged TCR-gamma genes were detectable in 2 of the 13 classic HD cases with T-cell marker-positive HRS cells, with none detectable in the null-cell cases. Eight of the T-cell marker-positive cases and all 6 null-cell cases were also studied for rearrangements of immunoglobulin genes. Six of the 8 T-cell marker-positive cases harbored clonal immunoglobulin gene rearrangements. The 2 cases without rearranged immunoglobulin genes were those that contained clonal TCR-gamma rearrangements and lacked expression of the B-cell-specific activator protein. From these findings we conclude that cases of classic HD with T-cell-derived HRS cells definitely exist, although their overall incidence at 1% to 2% is very low. Even within the T-cell marker-positive cases only a minority (15%) were derived from T cells. The majority (85%) originated from B cells, indicating that the T-cell antigens expressed by HRS cells are, in contrast to those expressed in non-Hodgkin lymphoma, not lineage specific.

Adolescent↗
PubMed1994

Effects of a school for pregnant students on the incidence of low-birthweight deliveries.

To evaluate effects of an alternative public school for pregnant teenagers in New Haven, CT, medical and school records were reviewed for a 1-year birth cohort of 230 adolescent mothers. Nearly three-quarters of all school-aged primiparas who were enrolled in the city's public schools when they became pregnant attended the alternative school. Because of summer vacation, however, students who conceived in January through April began attending later in pregnancy than did those who conceived in May through December; these mothers were significantly more likely to deliver a preterm, low-birthweight infant. No such seasonal effects were found for other teenagers in the city who were not enrolled in public school at conception. Positive birth outcomes for early program attenders are similar to those reported for a nurse-home-visitation program. The results suggest that school programs have considerable potential to be an effective service delivery model for providing prenatal intervention to adolescents.

Adolescent↗
PubMed1994

Parent-focused intervention: diffusion effects on siblings.

This study examined whether intervention provided to parents of firstborn children produced delayed benefits for later-born children. We studied younger siblings of children in the Yale Child Welfare Project, a family support program previously shown to result in better school adjustment for the firstborns. Information was obtained from the siblings' teachers and school records for 3 academic years. As was true for the older children, intervention group siblings had better school attendance than did control group siblings, were less likely to need supportive or remedial services, and were more likely to be making normal school progress. The results suggest that changes in the caregiving environment resulting from early family support lead to benefits for all the family's children. Parent-focused programs thus appear to provide a particularly efficient strategy for intervention efforts.

Child↗
PubMed1993

Adolescent mothers and repeated childbearing: effects of a school-based intervention program.

This study examined the effectiveness of a public school program for pregnant teenagers in preventing rapid repeated childbearing. Students permitted to attend longer than seven weeks postpartum were much more likely to avoid having another child in the next five years than were students required to return to their regular schools. The results indicate the potential of school-based programs to improve life outcomes for adolescent mothers and their children.

Adolescent↗
PubMed1991

Effects of an intervention program for pregnant adolescents: educational outcomes at two years postpartum.

Examined postpartum effects of a school-based intervention program for pregnant adolescents. Interviews were conducted with 102 innercity black, low-income, school-aged mothers who had attended the program, and their academic and medical records were reviewed. For teenagers who had been poor students prior to becoming pregnant, a strong linear effect was found for duration of program attendance: with sufficient time in the program, poorer students became indistinguishable from better students in educational success. Most of the better students were educationally successful at 2 years postpartum, independent of their length of time in the program. For all students, longer durations of postnatal intervention were predictive of lower likelihood of subsequent childbearing. Numerous academic, medical, social, and demographic variables were ruled out as possible confounding factors that might have produced the positive educational outcomes for poorer students. The results suggest that adolescents who appear to have minimal academic promise prior to their pregnancy are nevertheless very responsive to school-based intervention.

Adolescent↗
PubMed1989

Imitation, recall, and imitativeness in children with low intelligence of organic and familial etiology.

Groups of noninstitutionalized organic and familial mentally retarded and borderline mentally retarded children at two CA levels were given tasks designed to assess imitation. In contrast to findings from studies of average IQ children, organic low IQ children showed as much imitativeness at the older as at the younger age levels. Consistent with expectations, etiology, independent of IQ, was found to be significant. Familial low IQ children showed more absolute imitation and recall, whereas organic children were more imitative and responsive to the irrelevant behaviors modeled. Findings are discussed in terms of the developmental approach to imitation.

Attention↗
PubMed1985

Effects of family support intervention: a ten-year follow-up.

The delivery to impoverished mothers of a coordinated set of medical and social services, including day-care for their children, had effects that were evident a decade after the intervention ended. Intervention mothers were more likely to be self-supporting, and they had higher educational attainment and smaller family sizes than did control mothers. Intervention children had better school attendance, and boys were less likely to require costly special school services than were corresponding control children. The financial implications of these results were considerable, totaling about $40,000 in extra estimated welfare costs and documented school service costs needed by the 15 control families in the single year in which these follow-up data were gathered. There were no indications that the intervention had lasting effects on the children's IQ scores. The results suggest that family support procedures, including quality day-care, have considerable promise as a general model for intervention programs.

Achievement↗
PubMed1982

Is an intervention program necessary in order to improve economically disadvantaged children's IQ scores?

The hypothesis was investigated that alleviation of negative motivational factors underlies much of the 10-point IQ increase commonly found in economically disadvantaged children's performance following a preschool intervention program. Head Start and non-Head Start groups were tested on IQ and motivational measures 3 times before and during the Head Start year (pretest, retest, posttest). Both groups showed comparable IQ gains on retesting, but only the Head Start group showed continued gain from retest to posttest. Parallel changes were found on a motivational measure of wariness of an unfamiliar examiner. The test-retest improvement of both groups was interpreted as resulting from increased familiarity with the testing situation. The continued improvement of the Head Start children was interpreted as reflecting changes in the children's motivational structures as a result of attending a preschool intervention program.

Child, Preschool↗
PubMed1975

On "an experimental evaluation of sensorimotor patterning": a critique.

A critique was presented of a study by Neman, Roos, McCann, Menolascino, and Heal (1975) in which a sensorimotor training method of treatment for retarded children was evaluated. They presented evidence which they interpreted as support for the effectiveness of this treatment method in benefiting their sample of retarded individuals. Many shortcomings of the Neman et al. study were pointed out in the areas of evaluating the theoretical rationale underlying the treatment, subject selection, procedure, statistical analyses, and interpretation of the findings. In addition, the problems raised by the premature release of the findings to the press were discussed. Special note was made of the potential harmful effects of this publicity on retarded children and their families. The important role and responsibility of the National Association for Retarded Citizens in endorsing and recommending treatment methods for retarded individuals was also discussed.

Adolescent↗