Search PubMed⌕ Search

Biomedical subjects

R W Pelton

Publications and source records attributed to R W Pelton.

At least 19 recordsLinked to original sources
PubMed2001

Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities.

PURPOSE: To describe the successful management of rhino-orbital mucormycosis without the use of orbital exenteration. METHOD: Case report. RESULTS: The patient had successful eradication of the fungal infection with retention of normal vision and ocular function. CONCLUSIONS: The use of multiple treatment modalities including aggressive surgical debridement guided by intraoperative frozen section monitoring, intravenous liposomal amphotericin B, intraorbital regular amphotericin B and hyperbaric oxygen may allow complete resolution of orbital phycomycosis and spare the patient from the blindness and disfigurement associated with exenteration.

Adult↗
PubMed2001

Superomedial lid crease approach to the medial intraconal space: a new technique for access to the optic nerve and central space.

PURPOSE: To present clinical and cadaver studies of a new approach to the medial intraconal space. METHODS: We retrospectively review our clinical results by using a new technique to gain access to the medial intraconal space through a superomedial lid crease incision. We also use cadaver dissection studies to compare this new approach with the medial transconjunctival approach, the lateral orbitotomy without bone-flap, and the lateral orbitotomy with bone-flap. RESULTS: Access to the medial intraconal orbital space through the superomedial lid crease incision allowed optic nerve sheath fenestration or biopsy in 18 eyes with few postoperative complications. One case of tonic pupil, one case of transient vertical diplopia, and two cases of transient medial ptosis were seen. Five cavernous hemangiomas were removed from the intraconal space with this approach, with one case of transient vertical diplopia and one case of transient medial ptosis. The cadaver studies showed that when the superomedial lid crease approach is used, the tangent angle with the optic nerve and the incision-to-nerve distance measurements compare favorably with the medial transconjunctival and the lateral orbital approaches. CONCLUSIONS: The superomedial lid crease approach to the medial intraconal space has a number of advantages over the medial transconjunctival and lateral orbital approaches, including ease of dissection, incision-to-nerve distance, and angle of approach to the optic nerve. This technique allows for optic nerve sheath fenestration or tumor removal from the central space with few complications.

Adolescent↗
PubMed2000

Burn scar malignancies of the eyelids.

PURPOSE: To study the clinicopathologic characteristics and treatment of eyelid carcinomas developing in thermal burn scars. METHODS: A review of eight cases of eyelid burn scar malignancies: two from our own experience and six from published reports. RESULTS: Reported cases of burn scar malignancy of the eyelid are short-latency basal cell carcinomas. All carcinomas arose from small superficial burns. These potentially aggressive tumors respond well to local excision. CONCLUSION: As with other areas of the body, eyelid burn scars may undergo neoplastic degeneration. These carcinomas are predominately short latency basal cell carcinomas, rather than long-latency squamous cell carcinomas that are more common elsewhere in the body, including the head and neck region. Clinicians should be diligent in the long-term surveillance of all eyelid burns.

Adult↗
PubMed1999

Bilateral optic disk edema caused by sarcoidosis mimicking pseudotumor cerebri.

PURPOSE: To present a case of retrobulbar optic nerve and chiasm sarcoidosis that mimicked pseudotumor cerebri. METHODS: A 34-year-old, thin, black woman presented with transient visual obscurations, normal visual acuity, bilateral optic disk edema, and enlarged blind spots. Clinical, medical, and radiologic evaluations were consistent with pseudotumor cerebri. The patient improved while taking acetazolamide, but 6 months later her symptoms worsened. Neuroimaging disclosed enhancement of the optic nerve and chiasm. RESULTS: Despite administration of intravenous corticosteroids, the patient's vision worsened. Bilateral optic nerve sheath fenestrations were performed, and pathology disclosed sarcoidosis. CONCLUSION: Sarcoidosis of the optic nerves and chiasm may mimic pseudotumor cerebri.

Adult↗
PubMed1997

[Schnyder corneal dystrophy and juvenile, systemic hypercholesteremia].

BACKGROUND: Central crystalline dystrophy of Schnyder is characterized by the deposition of unesterified cholesterol crystals and lipids in the central and paracentral corneal stroma. Classically, this disease has been described as autosomal dominantly inherited and non-progressive with cholesterol deposits found in the anterior one third of the cornea. In recent years, however, rare sporadic cases and individuals with progressive, panstromal Schnyder's dystrophy have been described. Furthermore, an association has been made between some patients with Schnyder's dystrophy and a region on the coast in southwest Finland. Among the stromal dystrophies, this disease is unique with its occasional association with genu valgum and systemic hyperlipidemia. The role of high serum cholesterol in the pathogenesis of this disorder is still unclear. PATIENT: A ten-year-old white male presented with a one year history of ocular irritation made worse by bright sunlight. His past medical history was significant only for attention deficit disorder for which he received methylphenidate. A brother died at four months of age secondary to an unexplained cardiac abnormality. The ocular examinations of the patient's mother and father were normal and no history of eye disease among the grandparents could be elicited. The patient's visual acuity was 20/20 +2 in the right eye and 20/15 -3 in the left eye. The external examination showed no xanthelasmas. Slit-lamp biomicroscopy revealed bilateral ring-shaped corneal opacities extending into the midperiphery but sparing the limbal zone. The ring was composed of a fine, lacy garland of crystals present primarily in the anterior aspect of the stroma just beneath Bowman's membrane. The anterior chamber and iris showed no signs of inflammation. Intraocular pressures were 20 mm Hg and the ocular examination was otherwise unremarkable. Physical exam demonstrated no genu valgum. Blood testing showed a total cholesterol of 201 mg/dl with a low density lipoprotein cholesterol (LDL-C) of 156 mg/dl. Retesting four months later revealed a total cholesterol level of 245 mg/dl and an LDL-C of 192 mg/dl. The patient was referred to the pediatric gastroenterology service where he was put on diet therapy for further management of his hypercholesterolemia. CONCLUSIONS: This case appears to represent one of the rare sporadic examples of Schnyder's corneal dystrophy. The patient's family history is negative for ocular problems and the parents deny any Scandinavian ancestry. This patient is also unique for his presentation with ocular irritation. Most patients with Schnyder's dystrophy are initially seen for diagnosis of asymptomatic cloudy corneas or for gradual, painless loss of vision although glare in bright sunlight is noted by some individuals. Perhaps the most significant finding concerning this patient are his serum cholesterol levels. The association between total and LDL cholesterol and atherosclerotic vascular disease are well known and the literature suggests that regression of coronary artery disease is possible with aggressive treatment of hypercholesterolemia. Intervention in children should be considered if total cholesterol exceeds 170 mg/dl or LDL-C exceeds 110 mg/dl. Thus, early detection may eliminate significant morbidity and mortality. We therefore advocate evaluating all patients with Schnyder's corneal dystrophy and their immediate family members for systemic hypercholesterolemia.

Child↗
PubMed1994

Expression of transforming growth factor-beta mRNAs and proteins in pulmonary vascular remodeling in the sheep air embolization model of pulmonary hypertension.

Transforming growth factor-beta (TGF-beta) has been suggested as one of the mediators of vascular remodeling in chronic pulmonary hypertension. We have previously shown a transient early increase in TGF-beta levels in lung lymph during the development of sustained pulmonary hypertension in a sheep model (12 days of air embolization). The present study examines expression and cellular localization of mRNA and protein of the three mammalian isoforms of TGF-beta in lung biopsy tissue taken during the development of pulmonary hypertension (0, 1, 4, 8, and 12 days of embolization). In control tissue, immunohistochemical techniques localized each of the TGF-beta proteins in an identical pattern in large preacinar airways--bronchial epithelium and subepithelial cells--and in the medial wall of muscular vessels; no protein was detected in intraacinar regions. Following air embolization, immunoreactivity appeared in peripheral lung. At day 1, immunoreactivity for TGF-beta 1 and TGF-beta 3 proteins was seen in edema fluid, in perivascular cells associated with nonmuscular intraacinar arteries, and in alveolar walls; no increased immunoreactivity was detected for TGF-beta 2. After 4, 8, and 12 days of embolization, immunoreactivity for all three TGF-beta proteins was associated with newly muscularized intraacinar arteries. With in situ hybridization, the three TGF-beta mRNAs co-localized in lung tissue from both control and air-embolized animals. In control tissue, hybridization was seen around preacinar airways and muscular vessels; no hybridization seen in intraacinar regions of the lung. After 1 day of embolization, the pattern of hybridization was similar to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

TGF beta 1 inhibits branching morphogenesis and N-myc expression in lung bud organ cultures.

Lung buds isolated from 11.5 days post coitum mouse embryos survive and undergo branching morphogenesis in culture. This organ culture system was used to examine the role of TGF beta 1 and N-myc expression in lung branching morphogenesis. By 24 hours, TGF beta 1 reversibly inhibited branching morphogenesis in a concentration-dependent manner. N-myc is known to be expressed during embryonic development in epithelial cells involved in branching morphogenesis and homozygous null N-myc mice have defects in lung development. In the present study, TGF beta 1 was shown to inhibit the steady-state level of N-myc RNA 3- to 4-fold at 14 and 48 hours of treatment as measured by northern blot and RNase protection analysis. Suppression of N-myc expression in epithelium was confirmed by in situ hybridization. Since inhibition of N-myc occurred prior to the observed changes in morphology and previous genetic studies have demonstrated and important role for N-myc in lung development, a model is proposed in which TGF beta 1 inhibits tracheobronchial development by inhibiting expression of N-myc.

Animals↗
PubMed1992

Negative regulation of gene expression by TGF-beta.

Stromelysin gene expression is transcriptionally activated by a number of growth factors (e.g., EGF and PDGF), tumor promoters (e.g., TPA), and oncogenes (e.g., ras, src) through an AP-1-dependent mechanism. TGF-beta repression of stromelysin induction is mediated at the level of transcription by an element located at position -709 in the rat stromelysin promoter referred to as the TGF-beta inhibitory element (TIE). A TIE-binding protein complex is induced by treatment of rat fibroblasts with TGF-beta. This protein complex contains the protooncogene c-fos, and induction of c-fos by TGF-beta is required for the repressive effects of TGF-beta on stromelysin gene expression. Interestingly, c-fos induction is also required for stimulation of stromelysin expression by EGF in rat fibroblasts. Preliminary studies suggest that differential regulation of members of the jun family of early-response genes may explain this apparent paradox and determine whether stromelysin is induced or repressed by growth factors. TGF-beta stimulation therefore initiates a cascade of events that results in a specific pattern of gene expression: the direct stimulation of early-response genes can lead to subsequent induction or repression of other genes. Growth factor regulation of matrix metalloproteinases appears to play a role in embryonic development in the morphogenesis of the murine lung. Treatment of embryonic lungs in organ culture with the growth factors EGF or TGF-alpha results in stimulation of growth and inhibition of branching morphogenesis. A similar inhibition of branching was observed when these lung rudiments were treated with the matrix metalloproteinase collagenase. Most interestingly, the effects of EGF and TGF-alpha can be completely reversed by the tissue inhibitor of metalloproteinases, TIMP. TGF-beta has the opposite effect on growth of murine lung rudiments--growth is inhibited in a dose-dependent manner. This example illustrates a potential role for growth factor regulation of matrix-degrading metalloproteinases in complex developmental processes.

Animals↗
PubMed1991

Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development.

Isoform-specific antibodies to TGF beta 1, TGF beta 2, and TGF beta 3 proteins were generated and have been used to examine the expression of these factors in the developing mouse embryo from 12.5-18.5 d post coitum (d.p.c.). These studies demonstrate the initial characterization of both TGF beta 2 and beta 3 in mammalian embryogenesis and are compared with TGF beta 1. Expression of one or all three TGF beta proteins was observed in many tissues, e.g., cartilage, bone, teeth, muscle, heart, blood vessels, lung, kidney, gut, liver, eye, ear, skin, and nervous tissue. Furthermore, all three TGF beta proteins demonstrated discrete cell-specific patterns of expression at various stages of development and the wide variety of tissues expressing TGF beta proteins represent all three primary embryonic germ layers. For example, specific localization of TGF beta 1 was observed in the lens fibers of the eye (ectoderm), TGF beta 2 in the cortex of the adrenal gland (mesoderm), and TGF beta 3 in the cochlear epithelium of the inner ear (endoderm). Compared to the expression of TGF beta mRNA transcripts in a given embryonic tissue, TGF beta proteins were frequently colocalized within the same cell type as the mRNA, but in some cases were observed to localize to different cells than the mRNA, thereby indicating that a complex pattern of transcription, translation, and secretion for TGF beta s 1-3 exists in the mouse embryo. This also indicates that TGF beta 1, beta 2, and beta 3 act through both paracrine and autocrine mechanisms during mammalian embryogenesis.

Animals↗
PubMed1991

Expression of transforming growth factor-beta 1, -beta 2, and -beta 3 mRNA and protein in the murine lung.

Evidence has accumulated suggesting that the various isoforms of beta-type transforming growth factors (TGF-beta s) regulate important functions in the lung; however, the cellular source of these proteins is not well defined. Northern blot analysis of murine lung tissue demonstrates that mRNA transcripts for all three TGF-beta isoforms are found from birth through adulthood. Although the level of expression for each TGF-beta is variable during the first 2 wk post partum, all three isoforms are equal in the adult lung. Using in situ hybridization and immunohistochemical analysis, we have localized both mRNA and protein expression for all three isoforms of TGF-beta in the adult murine lung. At low magnification, immunohistochemical localization of TGF-beta proteins appears coincident in their pattern of expression with TGF-beta mRNAs in the large proximal conducting airways of the lung. However, on closer analysis, protein expression of all three TGF-beta isoforms is confined to the bronchiolar epithelium, while TGF-beta mRNA transcripts for each of the TGF-beta genes are found in smooth muscle cells and connective tissue fibroblasts lying subjacent to the epithelium. Although the levels of both TGF-beta mRNA and protein expression are high in the proximal bronchiolar tree, their signal intensities completely disappear as the terminal bronchioles progress to respiratory bronchioles. Additionally, in the lung vasculature, there is very high expression of all three TGF-beta mRNA transcripts in the smooth muscle cells of the large vessels. TGF-beta2 and TGF-beta but not TGF-beta1 proteins are expressed in these same smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules.

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

Animals↗
PubMed1990

Differential expression of genes encoding TGFs beta 1, beta 2, and beta 3 during murine palate formation.

Transforming growth factor beta 1 (TGF beta 1) has been shown to have multiple effects on primary cultures of palate-derived cell types. We report the analysis, by in situ hybridization, of RNA expression for three different TGF beta isoforms (TGF beta 1, beta 2, and beta 3) during murine embryonic palate development. Differential expression of the three TGF beta genes is seen in the palatal shelves in mesenchymal and epithelial cells known to be involved in the morphogenesis of this organ. Taken together, these results suggest that the TGF beta s act as endogenous factors involved in the formation of the mammalian palate.

Animals↗
PubMed1990

Transforming growth factor-beta. A family of growth regulatory peptides.

TGF beta, initially described as a factor that stimulates rodent fibroblast cell lines to proliferate in soft agar, has been shown to be active in several biological processes. The in vitro biological activities of the closely related molecules, TGF beta 1, TGF beta 2, and TGF beta 3, are comparable. Northern blot analyses of adult and embryonic tissues have shown the TGF beta mRNAs to be expressed in vivo, yet their patterns of expression appear somewhat different. In addition, even when all the TGF beta s are expressed in a tissue at the same time, the expression observed has been shown to be localized to different cells within the organ in some cases. This suggests that perhaps these molecules may have activities or functions in mice that are not apparent in vitro. Several members of the TGF beta family of genes have been mapped to mouse chromosome locations near loci previously assigned morphogenetic mutant loci. Although the relationship between the TGF beta genes and these loci have not been proven to be allelic, they may reveal important clues to the true activities of these molecules in vivo.

Animals↗
PubMed1990

The beta-type transforming growth factor. Mediators of cell regulation in the lung.

An increased interest in the role of growth factors in the regulation of processes concerning normal and pathologic lung physiology has spurred a flurry of research in this area. Peptide growth factors are known to control not only cell proliferation but other events such as differentiation, chemotaxis, and matrix deposition as well. The transforming growth factor beta (TGF beta) family of regulatory peptides serves as a prime example to illustrate the multiplicity of effects elicited by peptide growth factors in various lung-derived cell types. At present, the TGF beta family consists of at least 17 proteins and, based on sequence analysis, they can be divided into two groups: a cluster that shows very high sequence similarity to TGF beta 1, the closely related group, and a cluster that shows weaker sequence similarity to TGF beta 1, the distantly related group. The purpose of this brief review is to summarize the salient features of TGF beta structure and regulatory abilities of the closely related group. In addition, we will outline the evidence suggesting a role for TGF beta in normal lung development and physiology. Emphasis will be placed on studies with the closely related members TGF beta 1 and TGF beta 2 because, until recently, purified protein was available only for these two proteins.

Animals↗
PubMed1990

Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A).

Bone morphogenetic protein-2A (BMP-2A) is a member of the transforming growth factor beta (TGF beta) gene family that has been implicated in cartilage and bone formation. Here we use in situ hybridization to show that BMP-2A RNA is expressed in a variety of embryonic epithelial and mesenchymal tissues outside of the developing skeletal system, including cell populations known to play important roles in morphogenesis. Thus, high levels of transcripts are found in developing limb buds (ventral ectoderm and apical ectodermal ridge), heart (myocardium of the atrioventricular canal), whisker follicles (ectodermal placodes, hair matrix and precortex cells), tooth buds (epithelial buds, dental papilla and odontoblasts), and craniofacial mesenchyme, as well as a number of other sites. The expression patterns of BMP-2A are different from those of TGF beta-1, -2 and -3, and this is illustrated in detail in the developing whisker follicles. These results suggest that BMP-2A plays multiple roles in morphogenesis and pattern formation in the vertebrate embryo.

Animals↗
PubMed1990

In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2.

To date, three closely-related TGF beta genes have been found in the mouse; TGF beta 1, TGF beta 2 and TGF beta 3. Previous experiments have indicated that TGF beta 1 and TGF beta 2 may play important roles during mouse embryogenesis. The present study now reports the distribution of transcripts of TGF beta 3 in comparison to the other two genes and reveals overlapping but distinct patterns of RNA expression. TGF beta 3 RNA is expressed in a diverse array of tissues including perichondrium, bone, intervertebral discs, mesenteries, pleura, heart, lung, palate, and amnion, as well as in central nervous system (CNS) structures such as the meninges, choroid plexus and the olfactory bulbs. Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues.

Animals↗