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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 127 records · Page 7Linked to original sources
PubMed1999

Will GnRH antagonists provide new hope for patients considered 'difficult responders' to GnRH agonist protocols?

We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.

Clomiphene↗
PubMed1999

Relationship with Family of Origin Scale (REFAMOS). Interrater reliability and associations with childhood experiences.

BACKGROUND: Family relationships in the transition from childhood to adult life may be important mediators of risk and resilience for adult psychopathology. AIMS: To develop a reliable and valid measure of the quality of relationships with each parent in young adults. METHOD: Interrater reliability of the Relationship with Family of Origin Scale (REFAMOS) was assessed from audio-taped interviews with 59 subjects. Age-related trends and associations with recalled childhood relationships were examined in survivors of childhood cancer and their controls (n = 178). RESULTS: Intraclass correlation coefficients were in the range 0.69-0.95, and kappa values 0.80-0.82. Indices of current closeness to mothers were negatively correlated with age of subject and positively correlated with recalled maternal care in childhood. Negative qualities in current relationships were correlated with recalled overprotection. CONCLUSIONS: The REFAMOS has good interrater reliability, and shows the predicted age-related trends in scores and associations with recalled childhood relationships.

Adolescent↗
PubMed1999

The Oct-2 POU domain gene in the neuroendocrine brain: a transcriptional regulator of mammalian puberty.

POU homeodomain genes are transcriptional regulators that control development of the mammalian forebrain. Although they are mostly active during embryonic life, some of them remain expressed in the postnatal hypothalamus, suggesting their involvement in regulating differentiated functions of the neuroendocrine brain. We show here that Oct-2, a POU domain gene originally described in cells of the immune system, is one of the controlling components of the cell-cell signaling process underlying the hypothalamic regulation of female puberty. Lesions of the anterior hypothalamus cause sexual precocity and recapitulate some of the events leading to the normal initiation of puberty. Prominent among these events is an increased astrocytic expression of the gene encoding transforming growth factor-alpha (TGF alpha), a tropic polypeptide involved in the stimulatory control of LHRH secretion. The present study shows that such lesions result in the rapid and selective increase in Oct-2 transcripts in TGF alpha-containing astrocytes surrounding the lesion site. In both lesion-induced and normal puberty, there is a preferential increase in hypothalamic expression of the Oct-2a and Oct-2c alternatively spliced messenger RNA forms of the Oct-2 gene, with an increase in 2a messenger RNA levels preceding that in 2c and antedating the peripubertal activation of gonadal steroid secretion. Both Oct-2a and 2c trans-activate the TGF alpha gene via recognition motifs contained in the TGF alpha gene promoter. Inhibition of Oct-2 synthesis reduces TGF alpha expression in astroglial cells and delays the initiation of puberty. These results suggest that the Oct-2 gene is one of the upstream components of the glia to neuron signaling process that controls the onset of female puberty in mammals.

Alternative Splicing↗
PubMed1999

Hepatic triglyceride lipase promotes low density lipoprotein receptor-mediated catabolism of very low density lipoproteins in vitro.

We demonstrate here that hepatic triglyceride lipase (HTGL) enhances VLDL degradation in cultured cells by a LDL receptor-mediated mechanism. VLDL binding at 4 degrees C and degradation at 37 degrees C by normal fibroblasts was stimulated by HTGL in a dose-dependent manner. A maximum increase of up to 7-fold was seen at 10 microg/ml HTGL. Both VLDL binding and degradation were significantly increased (4-fold) when LDL receptors were up-regulated by treatment with lovastatin. HTGL also stimulated VLDL degradation by LDL receptor-deficient FH fibroblasts but the level of maximal degradation was 40-fold lower than in lovastatin-treated normal fibroblasts. A prominent role for LDL receptors was confirmed by demonstration of similar HTGL-promoted VLDL degradation by normal and LRP-deficient murine embryonic fibroblasts. HTGL enhanced binding and internalization of apoprotein-free triglyceride emulsions, however, this was LDL receptor-independent. HTGL-stimulated binding and internalization of apoprotein-free emulsions was totally abolished by heparinase indicating that it was mediated by HSPG. In a cell-free assay HTGL competitively inhibited the binding of VLDL to immobilized LDL receptors at 4 degrees C suggesting that it may directly bind to LDL receptors but may not bind VLDL particles at the same time. We conclude that the ability of HTGL to enhance VLDL degradation is due to its ability to concentrate lipoprotein particles on HSPG sites on the cell surface leading to LDL receptor-mediated endocytosis and degradation.

Animals↗
PubMed1998

Napsins: new human aspartic proteinases. Distinction between two closely related genes.

cDNA sequences were elucidated for two closely related human genes which encode the precursors of two hitherto unknown aspartic proteinases. The (pro)napsin A gene is expressed predominantly in lung and kidney and its translation product is predicted to be a fully functional, glycosylated aspartic proteinase (precursor) containing an RGD motif and an additional 18 residues at its C-terminus. The (pro)napsin B gene is transcribed exclusively in cells related to the immune system but lacks an in-frame stop codon and contains a number of polymorphisms, one of which replaces a catalytically crucial Gly residue with an Arg. Consideration is given to whether (pro)napsin B may be a transcribed pseudogene or whether its putative protein product undergoes rapid intracellular degradation.

Amino Acid Sequence↗
PubMed1998

Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance.

A reliable, nontoxic method of inducing transplantation tolerance is needed to overcome the problems of chronic organ graft rejection and immunosuppression-related toxicity. Treatment of mice with single injections of an anti-CD40 ligand antibody and CTLA4Ig, a low dose (3 Gy) of whole body irradiation, plus fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT) reliably induced high levels (>40%) of stable (>8 mo) multilineage donor hematopoiesis. Chimeric mice permanently accepted donor skin grafts (>100 d), and rapidly rejected third party grafts. Progressive deletion of donor-reactive host T cells occurred among peripheral CD4(+) lymphocytes, beginning as early as 1 wk after bone marrow transplantation. Early deletion of peripheral donor-reactive host CD4 cells also occurred in thymectomized, similarly treated marrow recipients, demonstrating a role for peripheral clonal deletion of donor-reactive T cells after allogeneic BMT in the presence of costimulatory blockade. Central intrathymic deletion of newly developing T cells ensued after donor stem cell engraftment had occurred. Thus, we have shown that high levels of chimerism and systemic T cell tolerance can be reliably achieved without myeloablation or T cell depletion of the host. Chronic immunosuppression and rejection are avoided with this powerful, nontoxic approach to inducing tolerance.

Abatacept↗
PubMed1998

Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights.

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

Animals↗
PubMed1998

Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death.

Centromere protein C (CENPC) is a key protein that has been localized to the inner kinetochore plate of active mammalian centromeres. Using gene targeting techniques, we have disrupted the mouse Cenpc gene and shown that the gene is essential for normal mouse embryonic development. Heterozygous mice carrying one functional copy of the gene are healthy and fertile, whereas homozygous embryos fail to thrive. In these embryos, mitotic arrest and gross morphological degeneration become apparent as early as the morula stage of development. The degenerating embryos demonstrate highly irregular cell and nuclear morphologies, including the presence of a large number of micronuclei. Mitotic chromosomes of these embryos display a scattered and often highly condensed configuration and do not segregate in an ordered fashion. These results describing the phenotype of the mutant mouse embryos indicate that CENPC has a direct role in the mitotic progression from metaphase to anaphase.

Animals↗
PubMed1998

Malignant intraperitoneal neoplasms of childhood.

OBJECTIVE: The purpose of this paper is to review and categorize the CT appearances of primary and secondary intraperitoneal neoplasms in children. MATERIALS AND METHODS: We retrospectively reviewed the CT images of 14 cases of intraperitoneal neoplasms. They were reviewed for bowel wall thickening, mesenteric nodules, ascites, calcification, peritoneal nodules, omental caking, and contrast enhancement. RESULTS: Computed tomography images of 14 cases of intraperitoneal neoplasms were evaluated: rhabdomyosarcoma (5), lymphoma (3), neuroblastoma (2), germ cell tumor (1), mesothelioma (1), Wilms tumor (1), and hepatocellular carcinoma (1). Nodular enhancement was seen in all cases, ascites in most, significant bowel wall thickening only with lymphoma, and calcification only with germ cell tumors. Omental caking was present both with rhabdomyosarcoma and lymphoma. CONCLUSIONS: While rare in pediatrics, intraperitoneal neoplasms occur in children, and CT is useful in identifying these peritoneal neoplasms.

Child↗
PubMed1998

Operative outcomes of minimally invasive saphenous vein harvest.

BACKGROUND: The longest incision used in surgery is the standard incision for harvesting the greater saphenous vein for arterial grafting. This long incision is associated with significant pain and morbidity. We present a comparative study between two relatively less invasive techniques: the standard bridge technique (BT) and the endoscopic saphenous vein harvest (ESVH). PATIENTS AND METHODS: This is a prospective, nonrandomized, case-matched study of contemporaneous minimally invasive saphenous vein harvest in patients undergoing multiple vessel coronary artery bypass grafting (CABG). Data points include operative time, total wound length, length of vein harvested, intraoperative complications, conversions to open, injury to the graft, postoperative complications and hospital length of stay. Follow-up continued for 8 weeks postdischarge. RESULTS: Within a 10-month period (July 1996 to May 1997), 60 saphenous vein harvests were performed, with 29 by BT and 31 by ESVH. Patient demographics were well matched, except for a larger number of patients with peripheral vascular disease in the ESVH group. ESVH only required 2.3 incisions versus 5 for the BT (P = 0.000001), whereas ESVH produced on average longer veins of 53.9 cm versus 47.7 cm for BT (P = 0.05). Harvest times were comparable in the two groups. However, mean vein preparation times, incision closure times, and total vein operative times for the BT were, respectively, 18.5 minutes, 35.1 minutes, and 94 minutes versus significantly less times of 11.3 minutes (P = 0.009), 10.6 minutes (P = 0.000001), and 73 minutes (P = 0.0001), respectively, for ESVH. The early, minor wound complication rate was 32% for the ESVH group versus 3% for the BT group (P = 0.0048). However, excluding small wound hematomas, the wound complication rate in the ESVH group fell to 13%. Graft quality was acceptable in both groups. CONCLUSIONS: ESVH was demonstrated to be a useful procedure to harvest saphenous veins for CABG surgery. The ESVH technique allowed the harvesting of a longer vein, via shorter and fewer incisions and in less time. However, for maximum operating room efficiency with the new technology, staff education is essential. There was a greater incidence of minor wound complications in the ESVH group; however, the majority of these ESVH complications were small wound hematomas, which did not occur as surgeon experience with the technique increased.

Aged↗