Biomedical subjects

R P Green

Publications and source records attributed to R P Green.

At least 19 recordsLinked to original sources

PubMed2001

Male-to-female sex reversal in mice lacking fibroblast growth factor 9.

Fgfs direct embryogenesis of several organs, including the lung, limb, and anterior pituitary. Here we report male-to-female sex reversal in mice lacking Fibroblast growth factor 9 (Fgf9), demonstrating a novel role for FGF signaling in testicular embryogenesis. Fgf9(-/-) mice also exhibit lung hypoplasia and die at birth. Reproductive system phenotypes range from testicular hypoplasia to complete sex reversal, with most Fgf9(-/-) XY reproductive systems appearing grossly female at birth. Fgf9 appears to act downstream of Sry to stimulate mesenchymal proliferation, mesonephric cell migration, and Sertoli cell differentiation in the embryonic testis. While Sry is found only in some mammals, Fgfs are highly conserved. Thus, Fgfs may function in sex determination and reproductive system development in many species.

Animals↗

PubMed2001

Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains.

Fibroblast growth factor receptors (FGFR) 1 and 3 have distinct mitogenic activities in vitro. In several cultured cell lines, FGFR1 transmits a potent mitogenic signal, whereas FGFR3 has little or no mitogenic activity. However, in other in vitro assays the FGFR3 intracellular domain is comparable with that of FGFR1. In vivo, FGFR3 negatively regulates chondrocyte proliferation and differentiation, and activating mutations are the molecular etiology of achondroplasia. By contrast, FGFR1 transmits a proliferative signal in various cell types in vivo. These observations suggest that inhibition of the proliferating chondrocyte could be a unique property of FGFR3 or, alternatively, a unique property of the proliferating chondrocyte. To test this hypothesis, FGFR1 signaling was activated in the growth plate in cells that normally express FGFR3. Comparison of transgenic mice with an activated FGFR1 signaling pathway with an achondroplasia-like mouse that expresses a similarly activated FGFR3 signaling pathway demonstrated that both transgenes result in a similar achondroplasia-like dwarfism. These data demonstrate that suppression of mitogenic activity by FGFR signaling is a property that is unique to growth plate chondrocytes. Surprisingly, we observed that in transgenic mice expressing an activated FGFR, some synovial joints failed to develop and were replaced by cartilage. The defects in the digit joints phenocopied the symphalangism that occurs in Apert syndrome and the number of affected joints was dependent on transgene dose. In contrast to the phenotype in the growth plate, the joint phenotype was more severe in transgenic mice with an activated FGFR1 signaling pathway. The failure of joint development resulted from expanded chondrification in the presumptive joint space, suggesting a crucial role for FGF signaling in regulating the transition of condensed mesenchyme to cartilage and in defining the boundary of skeletal elements.

Animals↗

PubMed1999

Fibroblast growth factor receptor 3 gene transcription is suppressed by cyclic adenosine 3',5'-monophosphate. Identification of a chondrocytic regulatory element.

Signaling through fibroblast growth factor receptors (FGFRs) is critical for the development and patterning of the vertebrate skeleton. Gain-of-function alleles of fgfr2 and fgfr3 have been linked to several dominant skeletal disorders in humans, while null mutations in fgfr3 result in the overgrowth of long bones in a mouse model system. Interestingly, the expression pattern of fgfr3 in growth plate chondrocytes overlaps that of the parathyroid hormone (PTH)-related peptide (PTHrP) receptor, a signaling molecule that also regulates endochondral ossification. The coincident expression of these two receptors suggests that their signaling pathways may also interact. To gain insight into the regulatory mechanism(s) that govern the expression of the fgfr3 gene in chondrocytes, we have identified a cell-specific transcriptional regulatory element (CSRh) by measuring the activity of various promoter fragments in FGFR3-expressing (CFK2) and nonexpressing (RCJ) chondrocyte-like cell lines. Furthermore, we demonstrate that activation of PTH/PTHrP receptors, either by stimulation with PTH or through the introduction of activating mutations, represses CSRh-mediated transcriptional activity. Finally, the transcriptional repression of the CSRh element was mimicked by treatment with forskolin, 8-bromo-cAMP, and 3-isobutyl-1-methylxanthine or by overexpression of the catalytic subunit of protein kinase A. Together, these data suggest that protein kinase A activity is a critical factor that regulates fgfr3 gene expression in the proliferative or prehypertrophic compartment of the epiphyseal growth plate. Furthermore, these results provide a possible link between PTHrP signaling and fgfr3 gene expression during the process of endochondral ossification.

1-Methyl-3-isobutylxanthine↗

PubMed1996

Retinal detachment in U.S. Air Force flyers.

Retinal detachment is a serious ocular condition, even though 85% can be repaired permanently. Long-term complications include decreased or loss of vision, redetachment, visual field changes, and proliferative vitreoretinpathy. To assess the effect of retinal detachment on flying careers, we reviewed the records of all aviators with a rhegmatogenous retinal detachment who were examined by the Ophthalmology Branch of the Aerospace Medicine Directorate at the Armstrong Laboratory (formerly the USAF School of Aerospace Medicine) from 1967-1986. Of the 19 flyers, 12 were returned to flying duties; only 2 were disqualified for ocular reasons alone. In 10 flyers, the detachments were previously undiagnosed. Associated vitreoretinal pathology was common in both eyes (42%). All received some type of treatment. Redetachment occurred in 4 flyers, but the overall final reattachment rate was 95%. Final posttreatment visual acuities were 20/20 or better in 16 flyers. Treatment-induced myopia was common. Many flyers enjoyed long flying careers after detachment repairs.

Adult↗

PubMed1994

A physical comparison of chromosome III in six strains of Saccharomyces cerevisiae.

We have tested the clones used in the European Yeast Chromosome III Sequencing Programme for possible artefacts that might have been introduced during cloning or passage through Escherichia coli. Southern analysis was performed to compare the BamHI, EcoRI, HindIII and PstI restriction pattern for each clone with that of the corresponding locus on chromosome III in the parental yeast strain. In addition, further enzymes were used to compare the restriction maps of most clones with the map predicted by the nucleotide sequence (Oliver et al., 1992). Only four of 506 6-bp restriction sites predicted by the sequence were not observed experimentally. No significant cloning artefacts appear to disrupt the published sequence of chromosome III. The restriction patterns of six yeast strains have also been compared. In addition to two previously identified sites of Ty integration on chromosome III (Warmington et al., 1986; Stucka et al., 1989; Newlon et al., 1991), a new polymorphic site involving Ty retrotransposition (the Far Right-Arm transposition Hot-Spot, FRAHS) has been identified close to CRY1. On the basis of simple restriction polymorphisms, the strains S288C, AB972 and W303-1b are closely related, while XJ24-24a and J178 are more distant relatives of S288C. A polyploid distillery yeast is heterozygous for many polymorphisms, particularly on the right arm of the chromosome.

Artifacts↗

PubMed1994

A survey of U.S. Air Force flyers regarding their use of extended wear contact lenses.

We reviewed the USAF Tactical Air Command's (TAC) contact lens database for the period July 1989 through June 1991. An anonymous survey was mailed to 396 TAC aircrew members in February 1992 to assess their experiences using extended wear soft contact lenses (EWSCL). Analysis was performed on those responses to compare differences between aviators who currently wear (CW), those who discontinued wear (DCW), and flyers who wore EWSCL while deployed to S.W. Asia for Desert Shield/Desert Storm. Of the 396 surveyed, 284 (72%) returned the survey and demonstrated that the daily use of EWSCL to be logistically practical and physiologically safe. No ocular malady was reported that would preclude continued use by aircrews. Desert Shield/Storm experiences documented that the use of EWSCL by USAF aircrews in a desert environment was possible. Logistical difficulties for the small number who either deployed with inadequate supplies or required replacement lenses were shown to be the primary challenge to the wear of EWSCL during Desert Shield/Storm. Subjectively, aircrews expressed strong beliefs that EWSCL contributed to their abilities as combat aviators.

Adult↗

PubMed1994

Retinal vein occlusions: case reviews of USAF aviators.

Retinal vein occlusions are primarily a disease of the elderly, frequently with permanent visual abnormalities. However, both branch and central retinal vein occlusions occur rarely in young individuals. Reported here are a series of retinal vein occlusions in USAF aviators. Seven cases were identified from records of the USAF Armstrong Laboratory Aeromedical Consultation Service from 1976-91. Four cases of central retinal vein occlusions and three cases of branch occlusions are summarized. Initial visual acuity ranged from 20/15 to 20/400. All seven aviators recovered 20/15 vision and returned to flying status. Hyperlipidemia was found in four of the seven aviators, and hypertension was diagnosed in two aviators. Included is a discussion of current concepts in the natural history, associated systemic conditions, treatment options, and aeromedical implications of retinal vein occlusions.

Adult↗

PubMed1993

Chimeric-transgenic mice represent a powerful tool for studying how the proliferation and differentiation programs of intestinal epithelial cell lineages are regulated.

An in vivo system has been developed for examining the effects of wild-type or mutant proteins on cell fate determination in the mouse intestinal epithelium or on the proliferation and differentiation programs of its component epithelial lineages. This system takes advantage of the fact that at the conclusion of gut morphogenesis, each intestinal crypt is composed of a monoclonal population of cells descended from a single active multipotent stem cell, each villus is supplied by several monoclonal crypts, and the four principal cell types of the intestinal epithelium differentiate during a rapid, geographically well-organized migration along the crypt-to-villus axis. Embryonic stem (ES) cells (129/Sv origin) are initially transfected with recombinant DNAs consisting of a reporter of interest linked to transcriptional regulatory elements that control the cell lineage-specific, differentiation-dependent, and axial patterns of expression of fatty acid binding protein genes in the gut. Stably transfected ES cells are subsequently introduced into host C57BL/6 blastocysts to generate chimeric-transgenic mice. At the borders of ES cell-derived and host blastocyst-derived epithelium, intestinal villi are found that are supplied by both ES cell- and host blastocyst-derived crypts. These villi can be rapidly identified in fixed whole-mount preparations of intestine using the alpha-L-fucose-specific Ulex europaeus agglutinin type I (UEA-I) lectin. They appear striped because UEA-I recognizes a cell-surface carbohydrate polymorphism between the inbred strains used to generate the chimeric animals. The strength of this system derives from the fact that two gut epithelial populations can be compared and contrasted that occupy virtually identical positions along the crypt-to-villus and duodenal-to-colonic axes within the same animal and differ only by the presence or absence of a single gene product. The band of blastocyst-derived epithelium in these striped, polyclonal villi can be used as an internal control to assess the biological effect of the transfected gene product produced in the adjacent stripe of ES-derived cells. The system can be used for either gain-of-function or loss-of-function experiments.

Animals↗

PubMed1992

The pigmentary dispersion disorder in USAF aviators.

The pigmentary dispersion syndrome (PDS) can have serious ocular consequences. Visual changes due to glaucoma and the treatment required can threaten the high level of visual function necessary in military aviation. We reviewed the records of 50 aviators with PDS who were evaluated at the Aeromedical Consultation Service (formerly the USAF School of Aerospace Medicine) over the past 10 years. At last evaluation, 48 were still qualified to fly. Only two aviators were permanently removed from flying duties due to glaucoma. Initial intraocular pressures, cup-to-disc ratios, and refractions were not statistically correlated with progression to glaucoma, but sample sizes were small. At final evaluation, 20 of the 34 aviators with follow-up had glaucoma and required medication. Thirteen eyes underwent laser trabeculoplasty. With appropriate management, the majority of aviators with PDS were able to safely continue their flying careers.

Adult↗

PubMed1992

The medical acceptability of soft contact lens wear by USAF tactical aircrews.

Seventy-two Tactical Air Command (TAC) aircrew members completed one full year of soft contact lens (SCL) wear. A daily-wear regimen, using extended-wear lenses, was used to minimize corneal stress. Baseline measurements of visual acuity with SCLs and with spectacles after SCL removal and ocular indicator gradings were compared to measurements at 5-d, 10-d, 1-month, 3-month, 6-month, and 12-month examinations. Visual acuity did not decrease during the test. No aircrew member developed corneal ulcers or other serious complications requiring elimination from the test. Two aircrew members lost a total of 9 "duties not to include flying" (DNIF) days: one flyer was grounded for 1 d with a corneal abrasion and another for 8 d with epithelial microcysts. The TAC SCL Test, as designed, was generally successful. The conservative approach to SCL wear during the test and the meticulous follow-up care by United States Air Force eye care professionals most likely contributed to the low ocular complication rate.

Aerospace Medicine↗

PubMed1992

Prescribing spectacles for aviators: USAF experience.

This special report was written for USAF vision specialists to use as a guide when prescribing spectacles for military aviators and to extend to the civilian sector the knowledge gained from the USAF experience. Visual correction in aviators presents some unique problems, especially for presbyopes. The demands of each individual aircraft environment need to be well understood. Ophthalmologists and optometrists must consider all pertinent aeromedical factors before prescribing spectacles for ametropic aviators.

Adult↗

PubMed1992

Cataract surgery and intraocular lenses in military aviators.

We reviewed the medical records of 23 military aviators who were evaluated by the United States Air Force School of Aerospace Medicine (USAFSAM) after cataract extraction with intraocular lens implantation between 1979 and 1990. The 23 subjects were male Caucasians, with a mean age of 43 years. Of the subjects, 21 were pilots, and, of these, 8 were qualified in high-performance aircraft. There were a total of 28 operated eyes, 24 of which had received extracapsular cataract extractions (ECCE) with posterior chamber lenses. The best-corrected, postoperative vision was 20/20 or better in all eyes. Posterior capsule opacification occurred in 14 (60%) of the ECCE eyes, with five requiring Nd:YAG (Yttrium-Aluminum-Garnet) laser capsulotomies. One aviator was disqualified from flying duties because of ocular deficiencies, for a visually-qualified-to-fly rate of 96%. Eight aviators have actually flown since surgery. Although follow-up was short, the initial results are encouraging.

Adult↗

PubMed1991

The career impact of keratoconus on Air Force aviators.

Keratoconus causes progressive blurring and distortion of vision, which threatens the career of a military aviator. To assess the impact of keratoconus on flying careers, we reviewed the records of all aviators with keratoconus who have been examined at the United States Air Force School of Aerospace Medicine over the past 23 years. Of the 22 aviators observed for more than three years, 18 were still qualified to fly at their most recent examination. The remaining four aviators were permanently removed from flying duties because of visual dysfunction caused by keratoconus. Of the 22 aviators examined, 15 required hard contact lenses for optimal correction of vision. No aircraft accidents or incidents, attributable to visual factors, were documented. We concluded that the majority of aviators with keratoconus are able to continue their flying careers safely with the aid of spectacles or contact lenses.

Adult↗

PubMed1991

Analysis of a circular derivative of Saccharomyces cerevisiae chromosome III: a physical map and identification and location of ARS elements.

DNA was isolated from a circular derivative of chromosome III to prepare a library of recombinant plasmids enriched in chromosome III sequences. An ordered set of recombinant plasmids and bacteriophages carrying the contiguous 210-kilobase region of chromosome III between the HML and MAT loci was identified, and a complete restriction map was prepared with BamHI and EcoRI. Using the high frequency transformation assay and extensive subcloning, 13 ARS elements were mapped in the cloned region. Comparison of the physical maps of chromosome III from three strains revealed that the chromosomes differ in the number and positions of Ty elements and also show restriction site polymorphisms. A comparison of the physical map with the genetic map shows that meiotic recombination rates vary at least tenfold along the length of the chromosome.

Chromosomes, Fungal↗

PubMed1990

Force necessary to fracture the orbital floor.

Current thought on the pathophysiology of orbital wall fractures postulates either a "hydraulic" or a "buckling" mechanism. Evidence from cadaver, dried skull, and theoretical model studies supports both theories. No in vivo data, human or nonhuman primate, are available that quantitate the force necessary to fracture the orbital floor by either of the two mechanisms. We developed an apparatus that delivers quantifiable force only to the globe, without occluding the orbital opening or striking the orbital rim. We used it on 11 anesthetized Macaca fascicularis monkeys. Following a single bilateral application, the orbits were exenterated, and the orbital walls and orbital contents were examined to determine the extent of injuries. Fractures were described, diagrammed, and photographed. Fracture of the orbital floor was consistently produced at and above a force of 2.08 J. Posterior ruptures of five eyes occurred over the same range. We provide the first accurate measurements of the force required to produce orbital blow-out fractures in a live primate model. We show that orbital floor fractures can occur at low energies with direct ocular trauma only ("pure" hydraulic mechanism). Orbital wall fractures failed to protect the globe from rupture in 23% of cases.

Animals↗

PubMed1990

Survey of spectacle wear and refractive error prevalence in USAF pilots and navigators.

A retrospective survey of 5000 active aircrew records was performed at 12 United States Air Force (USAF) bases to obtain information about the prevalence of spectacle wear and refractive error. The data revealed that 27.4% of pilots and 51.5% of navigators/weapons systems operators (Nav/WSO) required spectacles when flying. Of the spectacle-wearing pilots, 12.4% required bifocals. Myopia was the predominant refractive error and a relatively large percentage of aircrew members had astigmatism of 0.75 D or more, e.g., 33.1% of pilots. At the time of entry into the USAF, refractive error data were clustered around emmetropia with a definite skew toward hyperopia.

Adult↗

PubMed1990

Tonsillectomy and adenoidectomy: changing trends.

A review of 1,722 tonsil and adenoid procedures performed between 1978 and 1986 is presented. Each year there has been a progressive decrease in the number of procedures performed; the incidence of adenoidectomy has declined particularly. Although infection remains the predominant indication for surgery, there has been a dramatic rise in obstructive sleep apnea as a significant indication, from 0% in 1978 to 19% in 1986. At present, this trend promises to continue as physicians become increasingly aware of the prevalence and seriousness of adenotonsillar hypertrophy as a cause of sleep apnea, particularly in the general pediatric population.

Adenoidectomy↗

PubMed1989

Superior rhinotomy for en bloc resection of bilateral ethmoid tumors.

Ethmoid sinus neoplasms have traditionally been associated with a poor prognosis. Their advanced stage at presentation and proximity to vital structures have made them difficult to treat. Bilateral ethmoidal tumors impinging on or actively infiltrating the cribriform plate have been particularly resistant to cure. We have used the superior rhinotomy in conjunction with a bifrontal craniotomy in three patients to effect an en bloc resection of both ethmoid labyrinths and cribriform plate in an oncologically acceptable fashion.

Adenocarcinoma↗