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D Hicks

Publications and source records attributed to D Hicks.

At least 91 records · Page 5Linked to original sources
PubMed1993

Acidic fibroblast growth factor is expressed abundantly by photoreceptors within the developing and mature rat retina.

In order to further understand the role(s) of fibroblast growth factors (FGFs) in the development, differentiation and function of the central nervous system, we analysed the expression of the mRNA, and the presence and tissue distribution of the translated product, of one member of the FGF family, acidic FGF (aFGF), within the mammalian retina. Firstly, the relative abundance of aFGF mRNA was assayed in embryonic (between 14 and 17 days of gestation), postnatal (between 1 and 17 days after birth) and adult rat retina by quantitative reverse transcription-coupled polymerase chain reaction amplification using specific aFGF oligonucleotides. The level of expression remained uniformly low throughout the embryonic period and until postnatal day 7. Therefore the quantity of aFGF mRNA increased rapidly, reaching 80% of adult levels by eye opening (postnatal day 13). Adult levels were three-fold higher than at early developmental times. In situ hybridization of adult rat retina using specific antisense aFGF riboprobes revealed labelling in all cellular layers. Antisera raised against recombinant human aFGF revealed very little labelling of 4-day postnatal retina, but by postnatal days 8 and 17 immunoreactive aFGF was localized mainly within the photoreceptor cell bodies. Western blots of retinal extracts derived from 17-day embryonic, 4-day postnatal and adult retina probed with the same antibody revealed a single immunoreactive band of the expected molecular weight (18 kDa) in all extracts. Thus aFGF is mostly transcribed and translated within the retina subsequent to the major steps of cell birth, migration and differentiation, and seems to be abundantly expressed by maturing photoreceptor cells.

Animals↗
PubMed1993

Presence and foveal enrichment of rod opsin in the "all cone" retina of the American chameleon.

The retinal photoreceptors of the eye of the American chameleon, Anolis carolinensis, have been considered to be exclusively cones. Its retina is unusual for possessing two foveas (areas associated with heightened visual acuity), with the major, central fovea deeply incised and very densely packed with photoreceptors. Immunoblotting and light- and electron microscopic-immunocytochemistry, using several opsin monoclonal antibodies previously found specific for rods, demonstrated the presence and localization of this protein in the Anolis retina. This visual pigment appears sparsely in a subpopulation of photoreceptors in the periphery but overwhelmingly in the central fovea. Complementary results with cone-specific antibody and lectin binding corroborated this spatial organization. These results, as well as those with geckos, suggest that photoreceptor morphology is not an accurate guide among the lacertilians to visual pigment content, and that this phylogenetic grouping may constitute a crossroads in vertebrate photoreceptor evolution.

Animals↗
PubMed1993

Fibroblast growth factor receptor deficiency in dystrophic retinal pigmented epithelium.

The retinal pigmented epithelium (RPE) is known to be the site of the primary lesion in inherited retinal dystrophy in the Royal College of Surgeons (RCS) rat, a model for retinitis pigmentosa. Although the only functional defect so far detected in these cells is their failure to efficiently phagocytose shed photoreceptor outer segment debris, the actual cause of photoreceptor cell death is still unknown. Recently the possibility of "trophic factors" important in photoreceptor survival produced by normal RPE but not by dystrophic RPE has been suggested. Hence we decided to investigate the presence and abundance of two candidate diffusible factors, the acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), as well as their high affinity cell surface receptors (FGF-R). mRNA was isolated from primary cultures of purified normal and dystrophic RPE and analyzed by PCR amplification using specific oligonucleotide primers for aFGF and bFGF: the size and abundance of amplified fragments was similar for both cell types. Also, aFGF protein, detected by immunocytochemistry using specific antisera, appeared to be present in approximately equal amounts and distributed in a similar pattern. However, scatchard analysis of radio-labelled bFGF binding to primary cultures of normal and dystrophic rat RPE revealed that dystrophic RPE possess only 29% the number of surface receptors compared to congenic normal cells. Furthermore, the level of expression of FGF-R2 mRNA, but not that of FGF-R1, was significantly different. Other parameters measured (receptor affinity, profile of ligand internalization and degradation, receptor molecular weight and mitogenic activity) did not show any significant differences between normal and dystrophic RPE. The precise role of FGF-R deficiency in the etiology of the disease hence remains to be determined, but it indicates the importance of trophic factors in the normal functioning of the retina.

Animals↗
PubMed1993

Potential risk factors for rape in three ethnic groups.

This article describes the frequency of possible risk factors that emerged during a cross-cultural study of psychosocial response to sexual assault among African-American, Hispanic, and non-Hispanic white women presenting for treatment at a major urban rape treatment center. Of 881 victims screened, 51% had no observable risk factors while 49% fell into categories of variables that previous research has associated with increased vulnerability. Included were mental disability (psychiatric or developmental), a prior history of rape or incest, tourist or visitor status (site unfamiliarity), and homelessness. Ethnic groups differed significantly in these categories, suggesting socioeconomic and cultural variables that may affect rape statistics and that should be taken into account in rape prevention programs in the community.

Adolescent↗
PubMed1993

Cultural beliefs about rape and victims' response in three ethnic groups.

Cultural definitions of rape were assessed among 101 African-American, Hispanic, and non-Hispanic white female rape victims and 89 nonvictims matched for ethnicity, age, marital status, and socioeconomic status. Hispanics scored highest and whites lowest both in perceived community victim-blaming and in victims' psychological distress. Social and treatment implications are discussed.

Adaptation, Psychological↗
PubMed1993

Complications of laryngeal framework surgery (phonosurgery).

The rising popularity of surgery involving the laryngeal framework (surgical medialization of immobile vocal folds, vocal fold tightening, pitch variation, etc.) has resulted in increasing case experience. Little has appeared in the literature regarding complications or long-term results of this type of surgery. Several years' experience in a major referral center with various types of laryngeal framework surgery has led to a small number of complications. These have included late extrusion of the prosthesis and delayed hemorrhage. A review of these complications and recommendations for modification of technique to minimize them in the future are discussed.

Adult↗
PubMed1992

Coincident Kaposi sarcoma and T-cell lymphoma in a patient with the Wiskott-Aldrich syndrome.

A 24 year old male with a history of eczema, recurrent mild infections, and thrombocytopenia consistent with the Wiskott-Aldrich syndrome (WAS) presented with a mediastinal mass, generalized lymphadenopathy, splenomegaly, and severe thrombocytopenia. Studies of immune function including immunoglobulin levels and T-cell subsets were normal. Furthermore, his T lymphocytes proliferated normally in response to phytohemagglutinin, concanavalin A, and the combination of neuraminidase/galactose oxidase. However, their proliferative responses to anti-CD43 antibody and periodate were diminished, consistent with the clinical diagnosis of WAS. An initial inguinal lymph node biopsy surprisingly revealed Kaposi sarcoma. However, following splenectomy to increase the platelet count, biopsy of the mediastinal mass revealed T-cell large cell lymphoma. Studies of biopsied tissue for the presence of Epstein-Barr virus and cytomegalovirus were negative, as were studies of blood, including the polymerase chain reaction, for the presence of the human immunodeficiency virus (HIV). This is the first report of Kaposi sarcoma arising in a patient with a congenital immunodeficiency syndrome. Although Kaposi sarcoma can arise in the face of the severe immunosuppression that follows allograft transplantation and in patients infected with HIV, we postulate that longevity in the face of mild immunosuppression was the major factor in the development of Kaposi sarcoma in this patient.

Adult↗
PubMed1992

Analysis of opsin mRNA and protein expression in adult and regenerating newt retina by immunology and hybridization.

Rod photoreceptor cells were analysed in adult and regenerating Notophthalmus viridescens retinae using a combination of immunochemical and molecular biological approaches. Monoclonal anti-rhodopsin antibody (Rho-4D2) labelled rod but not cone photoreceptors in adult newt retinae. The antibody bound to the entire cell body, from the synaptic ending through to the outer segment, as examined by light and electron immunocytochemistry. The antibody labelled two bands of 35 and 56 kDa in Western blots of urodele retinal preparations separated by gel electrophoresis. In situ hybridization with radiolabelled anti-sense riboprobes specific for bovine opsin revealed intense patches of silver grains overlying approximately 50% of photoreceptor inner segment myoid regions; no signal above background was detected elsewhere in the retina, or with radiolabelled sense riboprobe controls. Northern blot analysis using the probe on poly A(+) mRNA of adult newt retinae indicated a single band of 1.5 kb, corresponding to the opsin transcript. Following surgical removal of the original retina in test animals, retinal regeneration was studied by sampling tissue from 0-50 days post-surgery. The reappearance of opsin immunoreactivity was examined by light microscopical techniques. No opsin expression was detected in regenerating tissue prior to 16 days. Subsequent to this time, rho-4D2 bound to cells in central areas in which substantial lamination of the new retina had already occurred, and was limited to the scleral border. At no time was any immunoreactivity observed in more peripheral undifferentiated tissue. Thus the reformation of a functional retina seems to follow the same control mechanisms as during development, photoreceptor redifferentiation being at least partly governed by positional or environmental cues.

Animals↗
PubMed1992

Diabetic mastopathy: a distinctive clinicopathologic entity.

Insulin-dependent diabetics may manifest evidence of autoimmune diseases involving endocrine or other organs. Rare cases of a peculiar fibrous and inflammatory lesion of the breast in diabetic patients have been previously described; however, the pathologic and clinical features that uniquely characterize these cases have not been defined or distinguished from other chronic inflammatory and fibrosing conditions in the breast. We studied eight patients with breast masses and longstanding insulin-dependent diabetes and compared them with 36 nondiabetic or short-duration diabetic patients with fibrosis and chronic mastitis. The longstanding diabetic patients presented with clinical breast masses ranging in size from 2 to 6 cm. Six of the eight patients had documented diabetic nephropathy, retinopathy, or neuropathy. Pathologically, these lesions showed lymphocytic lobulitis and ductitis, lymphocytic vasculitis (predominantly B cell), and dense keloid-like fibrosis that in many cases (six of eight) contained peculiar epithelioid cells embedded in dense fibrous stroma. We have provisionally labeled these cells "epithelioid fibroblasts" (EFBs). Although the features of lymphocytic lobulitis, ductitis, and/or vasculitis may occasionally be encountered in nondiabetic breast biopsies, EFBs appear to be unique to the diabetic condition. Control cases of chronic mastitis in nondiabetic or short-duration diabetes patients failed to show the complete constellation of lymphocytic lobulitis and ductitis, vasculitis, keloidal fibrosis, and EFBs. Diabetic mastopathy may represent an immune reaction to abnormal matrix accumulation. A hypothesis is presented.

Adult↗
PubMed1992

Creation of disc displacement in human temporomandibular joint autopsy specimens.

The purpose of this study was to investigate the possibility of iatrogenically creating disc displacement in the human temporomandibular joint (TMJ). Fourteen fresh TMJ autopsy specimens with superior disc position were selected for the study. The upper and lower joint spaces were exposed via a preauricular incision and two to three superficial mediolateral incisions were made in the inferior surface of the posterior disc attachment (ie, retrodiscal tissue). After these incisions were made it was possible to manually displace the disc anteriorly. To maintain the disc in the anterior position the condyle was positioned against the posterior disc attachment in a manner corresponding to the closed mouth position. The joints were then fixed in this relationship and magnetic resonance imaging (MRI) was repeated using the same scanning plane and scanning parameters as before intervention. After imaging, the joints were cryosectioned to show the degree of disc displacement. Histologic analysis was made of the posterior disc attachment. Postoperative MR images and cryosections showed the disc to be displaced anteriorly in 12 of the 14 joints. Displacement of the disc was complete in eight joints (the entire mediolateral dimension of the joint) and partial (only in the lateral part of the joint) in four joints. The disc remained in a superior position in two joints. Cryosections and histologic analysis showed the incisions in the inferior aspect of the posterior disc attachment to be superficial. The results of this study suggest that the integrity of the inferior aspect of the posterior attachment of the disc to the condyle is essential for keeping the disc in its position superior to the condyle.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Survey of colposcopy service provided by genito-urinary medicine in England and Wales.

OBJECTIVE: To investigate the expansion of colposcopy services within genito-urinary medicine (GUM) in England and Wales since 1985. DESIGN: Data collected by postal and verbal communication from 189 genito-urinary medicine clinics in England and Wales in January 1990. SUBJECTS: Consultant and junior genito-urinary physicians practising colposcopy. MAIN OUTCOME MEASURES: Number of clinics providing colposcopy service; indication for colposcopy, treatment facilities available, waiting lists and training opportunities, compared with that in 1985. RESULTS: Of the 189 genito-urinary medicine clinics contacted, 60 provided a colposcopy service and 55 of these returned completed questionnaires. There has been a 67% increase in the number of colposcopies in use and over 50% of clinics have the facilities to treat cervical pathology. Waiting lists were minimal for both examination and treatment. Both men and women are examined with the colposcope for a variety of indications. At present, 52% of career grade GUM physicians practise colposcopy compared to 24% in 1985 and 94% of senior registrars compared with 42% in 1985 were in training or trained in colposcopy.

Colposcopy↗
PubMed1992

Fibroblast growth factor stimulates photoreceptor differentiation in vitro.

Dissociated newborn rat retinal cells were maintained in monolayer culture for periods of up to 11 d. When grown in the absence of exogenous growth factors, 1-2% of the total neuronal population expressed opsin (the photopigment that is specific for maturing photoreceptors). Addition of a single dose of 10 ng/ml basic fibroblast growth factor (bFGF) to the culture medium induced an average increase of sixfold in the numbers of neurons expressing opsin. This supplementation had little effect on the total number of differentiated neurons or of glial cells when measured at the same time points. Furthermore, another specific class of retinal neurons, the amacrine cells, showed no changes following exposure to this growth factor. Two other growth factors known to exert neurotrophic effects, epidermal and nerve growth factor, were without effect. The effect of bFGF was dose dependent, with highly significant differences being observed with as little as 100 pg/ml, and with 700 pg/ml eliciting half-maximal stimulation; maximal effects were observed at 10 ng/ml. Induction of opsin expression by low concentrations of bFGF was blocked completely by an antiserum directed specifically against bFGF, but not by preimmune serum immunoglobulins. This increase in the number of photoreceptors expressing opsin following exposure to bFGF could have been due to either increased cell survival, increased proliferation of progenitor cells, or increased differentiation of immature photoreceptors. There was no increase in overall cell survival under the experimental conditions used, and double labeling immunocytochemistry combined with autoradiographic analysis of 3H-thymidine uptake showed that proliferation of neuronal precursors was not enhanced by the addition of bFGF. In contrast to these observations, cultures established from older (postnatal day 3) retina revealed large numbers of opsin-expressing photoreceptors in all culture plates, with or without added growth factors. This reduction in the stimulatory effects of bFGF with increasing postnatal age is consistent with the period of sensitivity being limited to the cycling of neuronal precursors. It is possible that a bFGF-like molecule is secreted by neighboring cells such as the retinal pigmented epithelium, to participate in retinal development and differentiation. To our understanding, this molecule is the first protein identified to influence specifically the differentiation of photoreceptor cells.

Aging↗
PubMed1991

Localization of acidic fibroblast growth factor in proliferative vitreoretinopathy membranes.

The pathogenesis of proliferative vitreoretinopathy (PVR) membranes remains poorly understood. We have studied the presence of acidic fibroblast growth factor (aFGF), a potent mitogen for many cells, within these membranes. We have used affinity purified monospecific anti-aFGF polyclonal antibodies, in conjunction with highly sensitive immunofluorescence techniques. The labelling was exclusively localized to cell bodies and was absent from the extracellular matrix. Double labelling techniques revealed that all cytokeratin positive cells (probably pigmented epithelial cells) and macrophages contained aFGF-like immunoreactivity, whilst glial cells were unlabelled. Appropriate controls indicated the specificity of the antibodies. Hence, the presence of this mitogenic molecule within certain cell types constituting PVR membranes may contribute to the pathogenesis.

Animals↗
PubMed1991

[FGF and physiopathological implications].

The role of FGF in retinal pathologies can be considered in two respects: 1-as a causative agent (for instance, stimulating aberrant growth or abnormally affecting some aspects of cellular behaviour), or 2-as a possible therapeutic drug (for instance, its ability to rescue neuronal cells from programmed or surgically-induced death), there is evidence for both: the retina, particularly the photoreceptors (PR), seems to be highly succeptible to a host of genetic defects, for instance, in the rat mutant RCS a defect in the pigmented epithelial cells (RPE) leads to the destruction of the PR. Transocular injection of FGF into RCS rats reduces the rate of PR cell loss. On the other hand, we have recently identify a difference in FGF-Receptor cell biology in the RCS mutant which may underline this particular dystrophy. Cultures of purified RPE cells were established from the dystrophic RCS rat and its congenic normal sighted control, and the number and affinity of cell surface FGF-R determined by incubation with 125I-bFGF. Scatchard analysis of the bining data indicated that whereas affinites were in both strains around 60pM, there was a large reduction in receptor number, about 70% in the mutant. Analysis of other FGF/FGF-R criteria, such as mitogenic activity, receptor molecular weight and the profile of FGF degradatoin showed no significant differences between the strains. Thus, defects in the FGF/FGF-R regulating system may actually led to retinal degeneration (RCS rat). But, once again, the underlying principles of FGF mechanisms of action in vivo are at present too incompletely understood to permit rationalization of these various observations.

Animals↗
PubMed1991

Lithium induced renal toxicity--a review of the literature.

Lithium therapy is widely accepted as efficacious treatment for bipolar affective disorder. However, long term usage of lithium raises concern of side effects involving multiple organ systems, particularly renal function. A review of the literature indicates no significant effects on glomerular filtration rate. The main renal consequences of chronic lithium therapy are decreases in renal concentrating capacity. Treatment recommendations to diminish these renal toxic side effects of lithium therapy are reviewed.

Glomerular Filtration Rate↗
PubMed1990

Cell commitment and differentiation in explants of embryonic rat neural retina. Comparison with the developmental potential of dissociated retina.

The differentiation of presumptive neural retina following its isolation from rat embryos and growth in explant and monolayer culture has been studied to obtain information regarding the extent to which factors extrinsic and intrinsic to the retina participate in determining molecular and cytological differentiation. Explanted retinal epithelium retained the capacity for mitosis, as shown by [3H]thymidine incorporation, and from the undifferentiated neuroepithelium, retinal cell-types emerged and acquired a laminar organization resembling that in vivo. Characterization of rod photoreceptor cells at both the light and electron microscopic level showed that these cells exhibit differentiated structural features including inner segments, connecting cilia and membranous expansions suggestive of forming outer segments. Immunofluorescent labeling with an antibody to a synaptic vesicle protein, and electron microscopic identification of synaptic elements showed formation of synapses by the photoreceptor cells within the explant. Neurites extending from the explants exhibited growth on laminin, fibronectin and collagen substrates. Since the neurites immunolabeled with antibodies to the 140 kDa subunit of neurofilament and with antibodies to Thy-1, they could be identified as axons of ganglion cells. Antibodies to a variety of cell-type specific antigens showed that the cells expressed molecules associated with the fully differentiated cell. Furthermore, since our approach has been to explant embryonic retina at an age when the antigens are not yet expressed in vivo, the appearance of the antigens in culture represented de novo expression. In contrast, neural retinal cells in dissociated cultures did not exhibit de novo expression of differentiated molecular properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗