Biomedical subjects

D Maier

Publications and source records attributed to D Maier.

At least 37 records · Page 2Linked to original sources

PubMed1999

Intracytoplasmic sperm injection overcomes previous fertilization failure with conventional in vitro fertilization.

OBJECTIVE: To evaluate the outcome of intracytoplasmic sperm injection (ICSI) in patients with previous idiopathic fertilization failure (< or =20% fertilization rate) after conventional IVF. DESIGN: Retrospective analysis. SETTING: IVF program at a university medical center. PATIENT(S): Twenty-five patients who underwent 38 ICSI cycles after experiencing unexplained fertilization failure with conventional IVF (group A) and 87 patients who underwent 118 ICSI cycles for male factor indications during the same period (group B). INTERVENTION(S): Intracytoplasmic sperm injection was performed in a subsequent cycle after fertilization failure with conventional IVF. MAIN OUTCOME MEASURE(S): Outcomes of IVF were compared between groups A and B. RESULT(S): Fertilization was achieved with ICSI in all patients with previous fertilization failure. The mean (+/- SD) fertilization rate (68%+/-21% vs. 64%+/-22%), implantation rate per embryo (22.6% vs. 20%), and delivery rate per cycle (47.3% vs. 49.1%) did not differ significantly between groups A and B. Overall, 72% of patients with previous unexplained fertilization failure had a successful pregnancy after ICSI. CONCLUSION(S): Intracytoplasmic sperm injection can overcome unexplained fertilization failure caused by a potentially occult gamete abnormality, with the same fertilization, implantation, and pregnancy rates as are seen in patients with abnormal sperm parameters.

Adult↗

PubMed1999

Subcellular localization of Hairless protein shows a major focus of activity within the nucleus.

Hairless, a major antagonist of the Notch signaling-pathway in Drosophila (Bang and Posakony, 1992; Maier et al., 1992), associates with Suppressor of Hairless [Su(H)], thereby inhibiting trans-activation of Notch target genes (Brou et al., 1994). These molecular interactions could occur either at the step of signal transduction in the cytoplasm or during implementation of the signal within the nucleus. We examined the subcellular distribution of Hairless, showing that it is a low abundant, ubiquitous protein that is cytosolic as well as nuclear. High levels of Hairless cause nuclear retention of Su(H), loss of Hairless reduces the amount of Su(H) in the nucleus.

Animals↗

PubMed1999

Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines.

In this study we established the simultaneous status of TP53, p16, p14ARF and PTEN tumor suppressor genes in 34 randomly chosen human glioma cell lines. Nine cell lines (26.4%) harbored mutations or deletions in all four tumor suppressor genes and 22 cell lines (64%) had alterations in at least three. Mutations/deletions were found at the following frequencies: TP53 (76.5%), p14ARF (64.7%), p16 (64.7%), PTEN (73.5%). Thus, there was a high incidence of alterations in the cellular pathways involving the p53 transcription factor (94.1%), the retinoblastoma protein (64.7%) and the PTEN phosphatase (73.5%) and 91% of cell lines carried mutations in two or more pathways. This provides the first clear genetic evidence that these tumor suppressors participate in biological pathways which are functioning separately/independently in glioma cells. The status of the gene alterations did not correlate with tumorigenicity in immunocompromized mice or any clinical parameters. Although the mutation rate was higher in glioma cell lines than that reported for glioma tissues, the alterations were molecularly representative of those found in adult de novo glioblastoma. This study highlights the importance of developing therapeutic approaches applicable to tumors with a broad range of genetic alterations and also provides an invaluable panel of glioma cell lines to make this possible.

Adult↗

PubMed1999

Lesbian couples as therapeutic donor insemination recipients: do they differ from other patients?

Reports were based on 23 lesbian couples seeking therapeutic donor insemination (TDI). Seventeen single women and 14 heterosexual couples with known infertility, due to vasectomy, were recipient controls. No group differences were found on self-esteem, psychiatric symptomatology or dyadic adjustment, except that lesbians reported greater dyadic cohesion than heterosexuals. Lesbians and single women were likely to disclose their use of TDI to others and had planned to disclose this to any child conceived; married couples were divided on this issue. Groups were alike in what they wanted to know about the donor (principally health variables and medical history), and in their concerns about the use of TDI (genetic and medical history). Groups differed in the reasons they elected to use TDI, with lesbian couples and single women choosing TDI affirmatively, and married couples accepting it as a last resort.

Adaptation, Psychological↗

PubMed1998

Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas.

The 10q25-26 region between the dinucleotide markers D10S587 and D10S216 is deleted in glioblastomas and, as we have recently shown, in low-grade oligodendrogliomas. We further refined somatic mapping on 10q23-tel and simultaneously assessed the role of the candidate tumor suppressor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for partial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of eight (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively target 10q25-26. We did not find a tumor only targeting 10q23.3, and most tumors (23/32, 72%) showed large deletions on 10q including both regions. The sequence analysis of PTEN/MMAC1 revealed nucleotide alterations in 1/8 (12.5%) low-grade gliomas in a tumor with LOH at l0q21-qtel and in 5/21 (24%) high-grade gliomas displaying LOH that always included 10q23-26. Our refined mapping data point to the 10q25-26 region as the primary target on 10q, an area that also harbors the DMBT1 candidate tumor suppressor gene. The fact that we find hemizygous deletions at 10q25-qtel in low-grade astrocytomas and oligodendrogliomas - two histologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.

Amino Acid Substitution↗

PubMed1997

New deletion in low-grade oligodendroglioma at the glioblastoma suppressor locus on chromosome 10q25-26.

Loss of heterozygosity on chromosome 10 is considered to be associated with the progression of glioblastomas. Two closely related regions have recently been proposed to contain the glioblastoma suppressor locus on chromosome 10q25-26; a 1 cM region between the polymorphic (CA)n-repeat markers D10S587 and D10S216, and an area of 5 cM between the markers D10S221 and D10S209. To confirm and further delineate this region, we analyzed 51 glioblastomas and 11 intermediate and low-grade gliomas for loss of heterozygosity on chromosome 10. 47/62 mostly malignant gliomas displayed complete loss of chromosome 10 and nine tumors were unaltered, whereas four glioblastomas and two low-grade oligodendrogliomas had partial loss on distal 10q. With these six tumors, we constructed a deletion map with increased marker density at 10q25-26 which shows two centromeric breakpoints at the markers D10S587 and D10S216, thus only confirming the distal, but not the proximal candidate glioblastoma suppressor locus. Two out of four low-grade oligodendrogliomas displayed partial deletions on 10q25-26. This suggests that deletion on chromosome 10 is not merely a late event in the progression of glioblastomas, but could play a role earlier in the development of gliomas.

Brain Neoplasms↗

PubMed1997

Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos.

When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium ions, they develop with a loss of anterior structures. In the current study, we have characterized the neural defects produced by either Xwnt-8 or lithium and have examined potential cellular mechanisms underlying this anterior truncation. We find that the primary defect in embryos exposed to lithium at successively earlier stages during gastrulation is a progressive rostral to caudal deletion of the forebrain, while hindbrain and spinal regions of the CNS remain intact. Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain. Our results demonstrate that lithium and Wnts can act upon either prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a loss of anterior pattern. Specifically, ectodermal cells isolated from lithium- or Wnt-exposed embryos are unable to form anterior neural tissue in response to inductive signals from normal dorsal mesoderm. In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm. Taken together, our results are consistent with a model in which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal cells to produce a dominant posteriorizing morphogen which respecifies anterior neural tissue as posterior.

Animals↗

PubMed1997

In vivo structure-function analysis of Drosophila Hairless.

Hairless plays an important role as the major antagonist in the Notch signalling pathway in Drosophila. It appears to be a direct inhibitor of the signal transducer Su(H). Hairless encodes a pioneer protein which was dissected in a structure-function analysis; a series of deletion constructs was tested for wild type and gain of function activity in the fly as well as for Su(H) binding. Thereby, the Hairless protein was subdivided into the absolutely essential Su(H)-binding domain, similarly important N- and C-terminal domains and a central antimorphic domain. Therefore, Hairless protein might have additional functions apart from Su(H) binding and may antagonize Notch mediated cell-cell communication in a more complex way than currently anticipated.

Animals↗

PubMed1996

A comparison of single and married recipients of donor insemination.

There has been some controversy surrounding the use of donor insemination (DI) for single women. The purpose of the present study was to compare psychological characteristics of married versus single women who were DI recipients. A total of 17 single women and 17 married women completed psychological questionnaires regarding psychiatric symptomatology, self-esteem, and their attitudes towards DI prior to treatment. There were no significant differences between the groups in psychiatric symptomatology or level of self-esteem. A significant difference was found in the amount of time taken to decide to use DI with single women waiting longer. There were no significant differences between groups in reported concerns about the child. There were significant differences in attitudes towards disclosure with more single than married women reporting that they would tell the child about using DI to conceive.

Adult↗

PubMed1995

Bronchogenic carcinoma presenting as a pseudopregnancy.

A young woman with an occult bronchogenic carcinoma presented with secondary amenorrhea and an elevated beta subunit of human chorionic gonadotropin that was mistakenly attributed to pregnancy. Physicians should be aware that this carcinoma may present solely with an elevated beta human chorionic gonadotropin value, and the potential exists for confusion with a pregnancy state in women of childbearing age.

Adult↗

PubMed1994

In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases, from the adaptor protein SHC and from GTPase-activating protein in Ramos B cells.

Antigen receptors of B lymphocytes transmit their activation signal to the cell interior by associating with and activation of specific non-receptor tyrosine kinases. Most of these kinases as well as other cytoplasmic effectors contain at least one Src homology 2 (SH2) domain, known to bind tyrosine-phosphorylated proteins. We examined the binding specificity of SH2 domains from different signaling molecules in B cells and found that each of the SH2 domains tested bound distinct subsets of stimulation-dependent phosphoproteins in vitro. SH2 domains from Src-like tyrosine kinases bound predominantly to the HS1 phosphoprotein. The tandem SH2 domains of the ZAP-70 tyrosine kinase bound to phosphorylated Ig-beta but only weakly to Ig-alpha. Also the SHC-derived SH2 domain formed complexes with the tyrosine-phosphorylated Ig-alpha/beta heterodimer, while the C- and N-terminal SH2 domains of GTPase-activating protein displayed completely different binding preferences. These results suggest that cytoplasmic effector molecules can be recruited to the activated B cell receptor in an SH2-phosphotyrosine-mediated manner. The data also provide a possible explanation for the notion that Ig-alpha and Ig-beta might couple to different biochemical pathways.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors.

OBJECTIVES: The objectives were to determine (1) if sera from women with histories of spontaneous abortions were teratogenic to cultured embryos more often than were sera of nonaborters, (2) if the teratogenicity could be corrected by adding nutrients to the sera, and (3) if these findings were relevant to reproductive outcomes. STUDY DESIGN: Rat embryos were cultured for 48 hours on sera from 102 subjects who had experienced spontaneous abortions. Samples from 48 were retested with nutrients added and 10 took dietary supplements, were again tested with embryo cultures, and reported on their pregnancy outcomes. RESULTS: The frequencies of teratogenic sera increased with numbers of spontaneous abortions (0 to > or = 5) in a manner that did not deviate from linearity (27% to 89%) (chi 2 p > 0.957). Nutrient supplements were added to 48 samples, and 40 were corrected and 10 subjects were given dietary supplement. Sera from six showed improved embryo cultures, and these women completed their pregnancies. CONCLUSIONS: Rat embryo cultures may provide unique insights into the causes and treatment of spontaneous abortions.

Abortion, Habitual↗

PubMed1994

A prospective study of donor insemination recipients: secrecy, privacy, and disclosure.

OBJECTIVES: To study prospectively the attitudes and behaviors of heterosexual couples undergoing donor insemination. DESIGN: Couples undergoing donor insemination completed psychological questionnaires before treatment regarding psychiatric symptoms, self-esteem, marital adjustment, and their attitudes about privacy or disclosure. PARTICIPANTS: Forty-one of 82 heterosexual couples participated. MEASURES: A donor insemination questionnaire, a self-esteem scale, the Brief Symptom Inventory, and the Dyadic Adjustment scale were used. RESULTS: Psychiatric symptoms, self-esteem, and marital adjustment were all in the normal range. The amount of time taken by the couple to decide to do donor insemination was not related to reported psychiatric symptoms, self-esteem, marital adjustment, or marital satisfaction. Ninety-five percent of the couples believed a psychological consultation should be a mandatory part of the donor insemination treatment. The greatest concern the couples had about the donor child was its genetic and medical background. Thirty-eight percent of the couples did tell or planned to tell others about using donor insemination to conceive, and only 27% of the couples planned to tell the child of his or her donor origin. CONCLUSIONS: The results of this study support those of others, which have indicated that the majority of donor recipients are psychologically well adjusted and have average marital adjustment. In addition, this prospective study replicated the findings of other retrospective studies, indicating that most donor insemination recipients do not plan to tell the child of his or her donor origin. Additional prospective studies are needed to determine if attitudes and behavior regarding disclosure change over time.

Adaptation, Psychological↗

PubMed1994

Laparoscopic management of appendiceal intussusception associated with villous adenocarcinoma.

The authors present a case of appendiceal intussusception, a rare finding that can be associated with appendiceal neoplasms. A 74-year-old woman with right lower quadrant abdominal pain was found to have an appendiceal intussusception associated with a villous adenocarcinoma and was managed with a laparoscopic assisted right hemicolectomy. This case is presented along with a review of the symptoms, diagnosis, classification, and appropriate management of this entity via laparoscopy.

Adenocarcinoma↗

PubMed1993

Drosophila evolution challenges postulated redundancy in the E(spl) gene complex.

The Enhancer of split [E(spl)] gene complex belongs to the class of neurogenic loci, which, in a concerted action, govern neurogenesis in Drosophila. Two genetically distinct functions, vital and neurogenic, reside within the complex defined by lethal mutations in the l(3) gro gene and by the typical neurogenic phenotype of deletions, respectively. Such deletions always affect several of the many embryonically active genes in the region, which cannot be mutated separately to lethality. Seven of these genes are extremely similar at the transcription and sequence level sharing the basic helix-loop-helix (bHLH) motif of transcriptional regulators. While these E(spl) bHLH genes seem to be required collectively for neurogenesis, they are nonessential individually, suggesting functional redundancy of the encoded gene products. No specific functions could yet be ascribed to any of the other genes located within the complex. One might expect these apparently dispensable genes, as well as the supposedly redundant bHLH genes, to be under little evolutionary constraint and, thus, to evolve most rapidly. However, we find the entire E(spl) gene complex highly conserved during Drosophila evolution, indicating that all the genes as well as their organization are of functional importance.

Amino Acid Sequence↗

PubMed1993

Conservation and change of the developmentally crucial fushi tarazu gene in Drosophila.

We have studied the evolutionary changes occurring in the noncoding regions around the developmentally important fushi tarazu (ftz) gene in a total of 11 species in the genus Drosophila. Previous molecular developmental studies have identified DNA elements both 3' and 5' to the coding region which are important in proper regulation of expression of the Drosophila melanogaster ftz gene. We show here that these same elements are the most evolutionarily conserved regions in the vicinity of the gene homologs. Parts of some control elements are more conserved than exonic sequences. Not only is there sequence conservation, but the relative position, orientation, and distances among the control elements remain conserved. One quite significant difference does exist between the two major subgenera studied, Sophophora and Drosophila: namely, an inversion of the ftz unit with respect to other genes in the Antennapedia complex, ANT-C. As a comparison, we applied similar analysis to a "housekeeping" gene-rosy (ry), or Xdh. In contrast, DNA sequences 5' to the ry coding region revealed little evolutionary conservation. These studies bear out the proposition that functionally important DNA sequences remain more conserved through evolutionary time than do less functionally important sequences. This proposition could be tested in the present case because we could predict a priori from the developmental studies which DNA regions should be most conserved.

Animals↗

PubMed1993

The irregular chiasm C-roughest locus of Drosophila, which affects axonal projections and programmed cell death, encodes a novel immunoglobulin-like protein.

The axonal projection mutations irregular chiasm C of Drosophila melanogaster comap and genetically interact with the roughest locus, which is required for programmed cell death in the developing retina. We cloned the genomic region in 3C5 by transposon tagging and identified a single transcription unit that produces a major, spatially and temporally regulated mRNA species of approximately 5.0 kb. Postembryonic expression is strong in the developing optic lobe and in the eye imaginal disc. The gene encodes a transmembrane protein of 764 amino acids with five extracellular immunoglobulin-like domains and similarity to the chicken axonal surface glycoprotein DM-GRASP/SC1/BEN. Both known irreC alleles reduce the level of transcription, whereas the roughestCT mutation disrupts the intracellular domain of the protein.

Alleles↗

PubMed1993

Placental and decidual histology in spontaneous abortion: detailed description and correlations with chromosome number.

OBJECTIVES: To determine the histopathology of failed pregnancy in clinically symptomatic women with no more than one prior pregnancy loss in order to provide baseline data, and to determine whether the histology of the conceptus in spontaneous abortions could predict a normal or abnormal chromosome number. METHODS: A review of all spontaneous abortions from which karyotypes were obtained between 1984-1991 yielded 224 cases in which maternal history indicated no more than one prior spontaneous abortion, a reliable date of last menstrual period (LMP), and available villous (221) and/or decidual/implantation site (175) pathology. Molar pregnancies were excluded. RESULTS: Multivariate logistic regression analysis showed a significant relationship between chromosome number and gestational age at loss as calculated from the LMP. Considering this confounder, a villous circulation indicating fetal life to 11 or more weeks, chronic intervillositis and villous infarcts (each P < .01), and decidual vasculitis (P < .05) were more frequent in chromosomally normal conceptions. Substituting possible variables into the logistic regression equation yielded predictions ranging from 88% likelihood of chromosomal abnormality to 97% likelihood of normal chromosome number. CONCLUSIONS: Histology can assist in assessing whether a spontaneous abortion is chromosomally normal or abnormal. There are many pathologic findings seen in spontaneous abortions regardless of karyotype; however, certain findings are more common in chromosomally normal abortions. These data provide a baseline for study of the histopathology of habitual abortion.

Abortion, Spontaneous↗