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Biomedical subjects

D J Roberts

Publications and source records attributed to D J Roberts.

At least 91 records · Page 5Linked to original sources

Confined placental mosaicism and intrauterine growth retardation: a case-control analysis of placentas at delivery.

OBJECTIVE: Our purpose was to determine the frequency of confined placental mosaicism in newborns with unexplained intrauterine growth retardation compared with infants with appropriate in utero growth. STUDY DESIGN: Amnion, chorion, and villi from 12 growth-retarded infants and 24 appropriately grown, matched controls were karyotyped. Fluorescence in situ hybridization with chromosome-specific probes was then used to confirm the karyotypic abnormality at additional uncultured placental sites. RESULTS: Karyotype analysis revealed placental mosaicism involving either aneuploidy or polyploidy in three of 12 (25%) cases versus two of 24 (8.3%) controls. Fluorescence in situ hybridization confirmed the karyotypic abnormalities in the placentas from growth-retarded infants only. CONCLUSION: Confined placental mosaicism was identified three times more frequently from placentas of growth-retarded infants compared with those of newborns with appropriate growth. Molecular studies of the placentas suggested a wider distribution of cells with abnormal karyotypes in cases compared with controls and support a biologic influence of placental mosaicism on fetal growth.

Amnion↗

Photosensitization of the endometrium with topical 5-aminolevulinic acid.

Photosensitization of the endometrium was attempted in vitro and in vivo by intrauterine administration of 5-aminolevulinic acid, which is converted to the photosensitizer protoporphyrin IX. Protoporphyrin IX was found in both functional and basal layers of the endometrial glands at concentrations nine and 10 times higher than myometrium in in vitro and in vivo experiments, respectively. Selective endometrial photosensitization is possible with topical 5-aminolevulinic acid, but it might not be distributed sufficiently evenly for use as a sensitizing agent in photodynamic ablation.

Administration, Topical↗

Photodynamic therapy of primary skin cancer: a review.

The role of photodynamic therapy (PDT) in the treatment of primary non-melanoma skin cancer is examined. Prolonged systemic skin photosensitivity limits the usefulness of PDT using conventional photosensitisers such as Photofrin-II. However in exceptional circumstances, such as multiple or widespread basal cell carcinomas, this therapy provides a useful and seemingly effective alternative mode of treatment. For Bowen's disease, PDT using topical 5-aminolaevulinic acid (ALA) yields high response rates and excellent cosmetic results. For large lesions and those in anatomically difficult sites or in poorly vascularised skin, ALA-based PDT can be considered the treatment of choice. Recent pharmacological and technological developments may further enhance the efficacy and convenience of photodynamic therapy, and make it more generally available in non-specialist centres.

Aged↗

Response of a rodent fibrosarcoma to photodynamic therapy using 5-aminolaevulinic acid or polyhaematoporphyrin.

The effects of 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) on the growth of an intradermal rat fibrosarcoma have been determined following topical, intravenous, or intratumour application of ALA. The pattern of tumour growth was identical following each type of therapy and we conclude that the efficacy of ALA-PDT is independent of the route of drug administration, at least in this tumour system. We have also compared the efficacy of interstitial ALA-based PDT with similar therapy using a conventional photosensitizer, polyhaematoporphyrin (PHP). ALA-PDT was less effective than PHP-based therapy at inhibiting the growth of a subcutaneous rat fibrosarcoma at light doses over 300 J. It is suggested that protoporphyrin IX photo-bleaching may limit the effectiveness of treatment, whilst the more bleach-resistant PHP may continue to be effective at higher light doses.

Aminolevulinic Acid↗

Octreotide reduces perception of rectal electrical stimulation by spinal afferent pathway inhibition.

Octreotide reduces perception of rectal distension in normal volunteers and irritable bowel patients. To localize octreotide's site of action, perceptual and evoked potential responses to rectal electrical stimulation were tested in seven normal volunteers after double-blind octreotide (100 micrograms 2) or placebo. After octreotide, the currents needed to elicit threshold perception of square-wave impulses delivered to the rectum were 29% higher than after placebo. When electrical stimulation was delivered at constant currents 50% above threshold, rectal perception scores were significantly reduced after octreotide compared with placebo. Rectal electrical stimulation led to characteristic and reproducible cerebral evoked potentials. Octreotide had no effect on latencies, but reduced peak-to-peak amplitudes by 35% compared with placebo. Rectal electrical stimulation also led to characteristic and reproducible spinal evoked potentials. Octreotide had no effect on spinal latencies, but reduced peak-to-peak amplitudes by 51%. In conclusion, octreotide reduces perception of rectal electrical stimulation, which is associated with inhibition of cerebral and spinal evoked potential amplitude, indicating effects on spinal afferent pathways.

Adult↗

Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut.

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

Animals↗

Detection of a LFA-1-like epitope on the surface of erythrocytes infected with a strain of Plasmodium falciparum.

The adhesion of erythrocytes infected with Plasmodium falciparum (P. falciparum) is one of the major pathological features of severe malaria. Several potential receptors to endothelium for falciparum-infected erythrocyte on endothelium have been described. Recently, the malaria binding site on ICAM-1(CD54) has been mapped to a site distinct but overlapping with the LFA-1 (CD11a/CD18) site. We detected by flow cytometry, confocal laser microscopy and immunoprecipitation, a molecule expressed at the surface of erythrocytes infected with mature stages of the M96 strain of P. falciparum that was recognized by a monoclonal antibody (mAb) (TS1/22) directed against an LFA-1 epitope. However, this molecule was not recognized by mAbs directed against other epitopes of LFA-1 or against other integrins. Furthermore, the mAb TS1/22 partially inhibited cytoadherence of parasitized red blood cells to human-brain microvascular endothelial cells. The expression of a molecule sharing an epitope with human LFA-1 integrin on the parasitized erythrocyte surface could be involved in the sequestration of these cells and thus in the pathogenesis of severe disease.

Antigens, Protozoan↗

A second case of "chorangiocarcinoma" presenting in a term asymptomatic twin pregnancy: choriocarcinoma in situ with associated villous vascular proliferation.

We report a case of "chorangiocarcinoma" (choriocarcinoma in situ in association with a villous vascular proliferation) presenting in one of dichorionic diamniotic twin placentae at term in an asymptomatic pregnancy. This case is the second reported of chorangiocarcinoma in the literature and the first case of choriocarcinoma (in situ or otherwise) in a twin pregnancy. The lesion had the gross appearance of an infarct in the presenting twin placenta. Histologic sections revealed malignant villous trophoblast in eight microscopic fields within the placental infarct. The remainder of the placenta and that of the cotwin were normal. The mother and infants had no evidence of metastatic disease 3 months postpartum. This placenta is the fourth example in the English literature of isolated choriocarcinoma in situ.

Adult↗

Left ventricular echogenic focus in the fetal heart: pathologic correlation.

Echogenic foci within the left ventricle of the heart have been found in a minority of fetuses and generally are believed to be a normal variant. The cause and exact location of these foci have remained speculative, however. We identified three fetuses with this sonographic finding in whom pathologic correlation was available. The only consistent histologic finding present in all three fetuses was mineralization within a papillary muscle; the chordae tendineae were normal. One of the three fetuses had trisomy 21. Echogenic foci within the left ventricle of the fetal heart represent papillary muscle mineralization. Until more data are available to investigate any possible association with aneuploidy, an echogenic focus in the left ventricle should still be considered a normal variant.

Adult↗

Advances in the molecular biology of gestational trophoblastic disease.

Gestational trophoblastic diseases are a heterogeneous pool of clinically and histopathologically defined entities with two clinically relevant features: reproductive failure and a high neoplastic potential. Here we review recent advances in understanding the biology and natural history of the most common form of trophoblastic disease, hydatidiform mole, with an emphasis on the clinical implications for patient management. There are no reliable genetic markers for predicting which subset of moles will behave aggressively, nor are there molecular diagnostic methods at present that offer advances over traditional histopathology. The predominant genetic finding in complete and partial hydatidiform moles is an imbalance of parental chromosomes, completely androgenetic (paternal) in the former and an extra paternal haploid set in the latter. This lack or imbalance of a maternal genomic contribution probably changes the gene expression since there is no evidence of gene mutation in these lesions.

Animals↗

Pregnancy complicated by thrombocytopenia secondary to human immunodeficiency virus infection.

BACKGROUND: Human immunodeficiency virus (HIV)-positive pregnant women may manifest thrombocytopenia similar to that of immune thrombocytopenic purpura (ITP), putting the fetus at risk of thrombocytopenia and hemorrhage. Whereas the fetal platelet count can be assessed in cases of ITP, there is no safe way to evaluate it during HIV-positive pregnancy without risking fetal inoculation with HIV. CASE: A pregnant woman with HIV-associated autoimmune thrombocytopenia was treated on several occasions with immune globulin and prednisone. Because of the inability to assess the fetal platelet count owing to the risk of fetal inoculation with maternal HIV, a primary cesarean was performed at term. The neonate was thrombocytopenic at birth. CONCLUSION: Because of the risk of fetal thrombocytopenia and the inability to evaluate fetal platelet counts safely (without resorting to invasive procedures that may increase the risk of fetal HIV infection), women with HIV-associated autoimmune thrombocytopenia should be delivered by cesarean.

Adult↗

Clinical teratology counseling and consultation case report: two distinct anterior neural tube defects in a human fetus: evidence for an intermittent pattern of neural tube closure.

Human neural tube closure is believed to be a continuous process that begins in the cervical region and progresses both rostrally and caudally. In contrast, an intermittent pattern of anterior neural tube closure has been demonstrated in rodents. Based on individual case photographs, a similar pattern of anterior neural tube closure, with multiple sites of closure, may also exist in humans. We report a human fetus with two distinct anterior neural tube defects separated by a cutaneous and mesenchymal bridge. The two defects occurred within distinct closure sites predicted by the murine model, one falling within closure II and the second within closure IV. Although one defect had adherent amniotic bands, evidence is presented to support a primary dysraphy rather than disruption from an amniotic band. This case provides further evidence supporting an intermittent pattern of anterior neural tube closure in human embryogenesis.

Abortion, Therapeutic↗

Characteristics of structural heart defects in trisomy 9 and their relationship to those in trisomy 13, 18, and 21.

The hearts from two live-born full-term infants with nonmosaic trisomy 9 (one complete trisomy 9, one partial trisomy 9) were studied after death. Both demonstrated conal and valvular anomalies associated with ventricular septal defects. These specific malformations are discussed in relation to published cases of trisomy 9 and the cardiac defects of other autosomal trisomies (13, 18, and 21).

Chromosomes, Human, Pair 13↗