Biomedical subjects
Publications and source records attributed to D Maier.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The P3 component of a visual event related potential (ERP) was studied for five consecutive weeks in six women with normal menstrual cycles. Serum concentrations of luteinizing hormone (LH), estradiol (E2) and progesterone were studied during the same period. Increases in P3 amplitude, although nonsignificant, were noted in the week preceding onset of menses. No significant changes in reaction times to target/nontarget stimuli were noted over the same time period.
Hairless is a dominant loss of function mutation in Drosophila affecting the formation of adult sensory organs. In the mutants, neuronal precursor cells do not differentiate, suggesting that Hairless might be involved in specifying or realizing neuronal fate in the fly, similar to the 'pro-neural' genes of the achaete-scute complex. As highlighted by the manifold phenotypic interactions of Hairless with most of the neurogenic loci, the gene might play an important role in nervous system development. Therefore, we initiated a molecular analysis of the Hairless locus in order to elucidate the function of its gene product and gain insight into the biochemical nature of the observed genetic interactions in which it participates. Here, we report the molecular cloning of the Hairless locus, confirmed by breakpoint and transformation analysis. Unexpectedly, Hairless activity peaks during embryogenesis, where transcripts accumulate primarily in endo- and mesodermal cell layers, and is lowest during larval stages, the lethal phase of Hairless mutants. The putative Hairless protein deduced from DNA sequencing is extremely basic and highly enriched in serine residues. Hairless appears to encode a novel protein without compelling homology to other known proteins which function in specifying peripheral nervous system development in Drosophila.
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Antibodies to negatively charged phospholipids are associated with a predisposition to both arterial and venous thrombosis, recurrent fetal wastage, and thrombocytopenia. These associations have been reported in patients who do not fulfill criteria for connective tissue diseases. In this study, we determined the prevalence of antiphospholipid antibodies in 81 women who had had recurrent spontaneous abortion (3 or more fetal losses), in 88 women whose pregnancies were successful, and in 64 women who had never been pregnant. Antiphospholipid antibodies were found in 16% of women with recurrent spontaneous abortion, and at a statistically greater prevalence than in women who had successful pregnancies (7%) as well as those who had never been pregnant (3%). A false-positive VDRL and IgG anticardiolipin antibodies were more specific for fetal wastage than was either the lupus anticoagulant or IgM anticardiolipin antibodies.
OBJECTIVE: To survey a sample of couples who had completed therapeutic donor insemination (TDI) regarding several psychological variables. DESIGN: Couples who had conceived through TDI in the past 7 years completed a retrospective survey. PARTICIPANTS: Thirty-five of seventy couples returned completed questionnaires. MEASURES: Demographic questionnaire, TDI, and confidentiality questionnaire (created for this study), Dyadic Adjustment Scale. RESULTS: The majority of the subjects told at least one person about the TDI but 81% of subjects who told someone reported that, if they had to do it over again, they would tell no one. Eighty-six percent reported that they have not and will not tell the child. Time from diagnosis to beginning TDI was not correlated with marital adjustment after TDI. Overall, the couples reported average marital adjustment. For both men and women, the biggest concern was the genetic/medical history of the donor. Most couples did not have psychological counseling, but 39% thought it should be mandatory. CONCLUSIONS: Retrospectively, most couples regretted telling others about TDI. Most couples do not plan to tell the TDI child about its genetic origin. The major concern about TDI is the genetic and medical background of the donor. Psychological counseling should be available to couples undergoing TDI.
OBJECTIVE: Because of the psychologically demanding nature of infertility treatment, it has been recommended that psychological services be made available to infertile patients. However, no specific guidelines for the scope or usage of those services has been proposed. Our objective was to formulate guidelines to be used at our institution to provide psychological evaluations to infertility patients. DESIGN: The guidelines were formulated through discussions between the division psychologist and attendings and then presented to and modified by the University Ethics, Risk Management, Legal, and Institutional Review Board departments. SETTING: The University of Connecticut Health Center Division of Reproductive Endocrinology and Infertility provides tertiary level care to infertility patients. Services include assisted reproductive technologies and donor gamete programs. Surrogate parenting is not a provided service. RESULTS: Guidelines for the provision and use of psychological services for infertility patients were formulated. CONCLUSIONS: These guidelines are preliminary in nature and intended to provide a starting point for discussion among physicians, nurses, and mental health professionals regarding the psychological needs of infertility patients.
An evolutionary approach was applied to identify elements involved in the regulation of the segmentation gene fushi tarazu (ftz) by comparing the Drosophila melanogaster ftz gene with its Drosophila hydei homologue. The overall organization of the ftz gene is very similar in both species. Surprisingly, ftz proved to be inverted in the ANT-C of D. hydei with respect to D. melanogaster. Strong homologies extend over the entire 6 kb of the ftz upstream region with the best match in the 'upstream element'. We identified several highly conserved boxes embedded in unrelated sequences that correspond extremely well to two germ layer specific enhancers in the upstream element. Transformation experiments revealed that D. hydei ftz gene products can restore D. melanogaster ftz function and, furthermore, that trans-acting factors from D. melanogaster recognize and control D. hydei ftz regulatory elements. These findings indicate a conservation of the entire regulatory network among segmentation genes for several millions of years during the evolution of Drosophila.
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