35 results on '"Sharp RM"'
Search Results
2. NZ's Iron and Steel Industry - an Historical Perspective
- Author
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Sharp, RM, Cann, NK, and McFadzean, D
- Published
- 1990
3. Cutting the Cost of Corrosion
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Sharp, RM
- Published
- 1991
4. Foreword
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Sharp, RM
- Published
- 1994
5. The Application of a Multistylus Recorder to the Energy Dispersive Analysis of Paint Flakes in the Scanning Electron Microscope
- Author
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Meinhold, RH and Sharp, RM
- Abstract
Paint flakes occur as evidence in a wide variety of crimes. Here we shall confine ourselves to the examination of vehicle paints, although the methods are equally applicable to other types of paint.
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- 1978
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6. The Corrosion of Carbon Steel and Stainless Steel in Simulated Geothermal Media
- Author
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Pound, BG, Abdurrahman, MH, Glucina, MP, Wright, GA, and Sharp, RM
- Abstract
The corrosion rates of low-carbon steel, and 304, 316 and 410/420 stainless steels in simulated geothermal media containing hydrogen sulfide have been measured by means of the polarization resistance technique. Good agreement was found between weight-loss and polarization resistance measurements of the corrosion rate for all the metals tested. Carbon steel formed a non-adherent film of mackinawite (Fe1+xS). The lack of protection afforded to the steel by the film resulted in an approximately constant corrosion rate. The stainless steels also exhibited corrosion rates that were independent of time. However, the 410 and 420 alloys formed an adherent film consisting mainly of troilite ( FeS ) which provided only limited passivity. In contrast, the 304 and 316 alloys appeared to be essentially protected by a passive film which did not seem to involve an iron sulfide phase. However, all the stainless steels, particularly the 410 and 420 alloys, showed pitting, which indicated that some breakdown of the passive films occurred.
- Published
- 1985
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7. Electrochemical Phase Diagrams for the Fe/S/H2O System under Geothermal Conditions
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Pound, BG, Wright, GA, and Sharp, RM
- Abstract
Previously published electrochemical phase (potential-pH) diagrams for the Fe/S/H2O system at elevated temperatures are assessed. It is concluded that the potential-pH equations derived by Biernat and Robins1 can be used to provide reliable diagrams over the temperature range 298-573 K. These equations were used to derive a set of diagrams relevant to geothermal fluids in general terms, so that the corrosion products of iron and ferrous alloys immersed in these fluids may be predicted. In addition, diagrams are presented for geothermal fluids in the Broadlands and Wairakei fields in New Zealand. The significant changes in the E-pH diagrams as the temperature increases over the range 298-573 K are that the region of stability for Fe(OH)3- widens and the regions of stability for FeS2 and Fe3O4 and, at higher temperatures, FeS, shrink in size.
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- 1985
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8. Genetics of atherosclerosis risk factors in Mexican Americans.
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MacCluer JW, Stern MP, Almasy L, Atwood LA, Blangero J, Comuzzie AG, Dyke B, Haffner SM, Henkel RD, Hixson JE, Kammerer CM, Mahaney MC, Mitchell BD, Rainwater DL, Samollow PB, Sharp RM, VandeBerg JL, and Williams JT
- Published
- 1999
9. Lead (Pb) Bioaccessibility and Mobility Assessment of Urban Soils and Composts: Fingerprinting Sources and Refining Risks to Support Urban Agriculture.
- Author
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Sharp RM and Brabander DJ
- Abstract
While the presence of legacy lead (Pb) in urban soil is well documented, less is known about the bioaccessibility, transport, and exposure pathways of urban soil Pb. We study Pb bioaccessibility in Roxbury and Dorchester, MA, urban gardens to assess exposure risk and identify remediation strategies, applicable locally and in urban gardens across the country. We work in partnership with The Food Project, which brings the goals and perspectives of local farmers to the center of the research process and enables efficient local application of results to reduce Pb exposure. We measure changes in Pb bioaccessibility as a function of growing material, grain size, and Pb source. In comparison to soils, compost has lower total Pb concentrations, has lower Pb solubility in gastric fluid, and limits fine particle resuspension. The mean bioaccessible Pb concentration of compost is 265 mg/kg, nearly an order of magnitude lower than that of soils, and compost contains 14% higher carbon content than soils, which may account for the observed 19% lower Pb bioaccessibility in compost. For all matrices (soil, raised bed fill, and compost) grain sizes <37 μm contain a disproportionate fraction of the total pool of bioaccessible Pb. Furthermore, the isotopic composition of Pb in the size fractions linked with resuspension and elevated blood lead levels is indicative of leaded gasoline and leaded paint even decades removed from the primary deposition of these sources., Competing Interests: The authors declare no conflicts of interest relevant to this study., (©2017. The Authors.)
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- 2017
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10. Natural pathology of the captive chimpanzee (Pan troglodytes): A 35-year review.
- Author
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Kumar S, Laurence H, Owston MA, Sharp RM, Williams P, Lanford RE, Hubbard GB, and Dick EJ Jr
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- Animals, Ape Diseases epidemiology, Ape Diseases etiology, Biopsy veterinary, Incidence, Ape Diseases pathology, Pan troglodytes
- Abstract
We present the spontaneous pathological lesions identified as a result of necropsy or biopsy for 245 chimpanzees (Pan troglodytes) over a 35-year period. A review of the pathology database was performed for all diagnoses on chimpanzees from 1980 to 2014. All morphologic diagnoses, associated system, organ, etiology, and demographic information were reviewed and analyzed. Cardiomyopathy was the most frequent lesion observed followed by hemosiderosis, hyperplasia, nematodiasis, edema, and hemorrhage. The most frequently affected systems were the gastrointestinal, cardiovascular, urogenital, respiratory, and lymphatic/hematopoietic systems. The most common etiology was undetermined, followed by degenerative, physiologic, neoplastic, parasitic, and bacterial. Perinatal and infant animals were mostly affected by physiologic etiologies and chimpanzee-induced trauma. Bacterial and physiologic etiologies were more common in juvenile animals. Degenerative and physiologic (and neoplastic in geriatric animals) etiologies predominated in adult, middle aged, and geriatric chimpanzees., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2017
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11. Alopecia in Outdoor Group- and Corral-Housed Baboons (Papio hamadryas spp.).
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Lutz CK and Sharp RM
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- Alopecia epidemiology, Animals, Female, Male, Seasons, Sex Factors, Alopecia veterinary, Housing, Animal, Monkey Diseases epidemiology, Papio hamadryas
- Abstract
Alopecia has been reported to occur in several species of captive NHP. Much of this research has focused on macaque monkeys; whether other primate species such as baboons are affected similarly is unknown. Because alopecia can be a focus of inspectors and a possible marker of wellbeing, the purpose of the current study was to survey the occurrence of alopecia in 2 baboon populations and to identify potential risk factors. Subjects were 262 group-housed and 279 corral-housed baboons. Alopecia was assessed cage-side (group-housed) and on sedated animals (corral-housed). Although alopecia was mild in both populations, there were significant effects of season and sex. Alopecia was greater in the winter (group-housed) and the fall (corral-housed) and in female baboons. In addition, the group-housed baboons showed a significant negative effect of age and a lesser effect of group size on alopecia. These results demonstrate that variables other than those associated with animal management practices can affect hair loss in baboons.
- Published
- 2015
12. Mortality in captive baboons (Papio spp.): a-23-year study.
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Dick EJ Jr, Owston MA, David JM, Sharp RM, Rouse S, and Hubbard GB
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- Animals, Female, Male, Seasons, Texas epidemiology, Animals, Laboratory, Monkey Diseases mortality, Papio
- Abstract
Background: We report the causes of mortality for 4350 captive baboons that died or were euthanized due to natural causes during a 23 year period at the Southwest National Primate Research Center., Methods: Necropsy records were retrieved and reviewed to determine a primary cause of death or indication for euthanasia. Data was evaluated for morphological diagnosis, organ system, and etiology., Results: The 20 most common morphologic diagnoses accounted for 76% of the cases, including stillborn (10.8%); colitis (8.6%); hemorrhage (8.4%); ulcer (5.2%); seizures (4.7%); pneumonia (4.2%); inanition (4.1%); dermatitis (3.8%); spondylosis (3.3%); and amyloidosis (3.0%). The digestive system was most frequently involved (21.3%), followed by the urogenital (20.3%), cardiovascular (12.2%), and multisystem disease (10.3%). An etiology was not identified in approximately one-third of cases. The most common etiologies were trauma (14.8%), degenerative (9.5%), viral (8.7%), and neoplastic/proliferative (7.0%)., Conclusion: This information should be useful for individuals working with baboons., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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13. Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).
- Author
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Lutz CK, Williams PC, and Sharp RM
- Subjects
- Animals, Animals, Laboratory, Appetitive Behavior, Blood Specimen Collection adverse effects, Blood Specimen Collection veterinary, Female, Laboratory Animal Science, Male, Self-Injurious Behavior epidemiology, Sex Factors, Social Behavior, Texas, Behavior, Animal, Housing, Animal, Papio hamadryas psychology, Risk Factors, Stereotyped Behavior
- Abstract
Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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14. Correlation between presence of Trypanosoma cruzi DNA in heart tissue of baboons and cynomolgus monkeys, and lymphocytic myocarditis.
- Author
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Mubiru JN, Yang A, Dick EJ Jr, Owston M, Sharp RM, VandeBerg JF, Shade RE, and VandeBerg JL
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- Animals, Chagas Cardiomyopathy pathology, Chagas Cardiomyopathy veterinary, Female, Lymphocytes pathology, Macaca fascicularis, Male, Monkey Diseases parasitology, Myocarditis parasitology, Myocarditis pathology, Myocarditis veterinary, Papio hamadryas, Polymerase Chain Reaction, Retrospective Studies, Texas, Trypanosoma cruzi isolation & purification, Chagas Cardiomyopathy parasitology, DNA, Kinetoplast analysis, Trypanosoma cruzi genetics
- Abstract
Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi. In this study, we retrospectively reviewed cases of animals that were diagnosed with lymphocytic myocarditis and used a polymerase chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues. We show that the PCR method is applicable in archived frozen and FFPE tissues and the sensitivity is in the femtogram range. A positive correlation between PCR positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is shown. We also show epicarditis as a common finding in animals infected with T. cruzi.
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- 2014
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15. Trichobezoars in baboons.
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Mejido DC, Dick EJ Jr, Williams PC, Sharp RM, Andrade MC, DiCarlo CD, and Hubbard GB
- Subjects
- Animals, Bezoars etiology, Bezoars pathology, Female, Male, Monkey Diseases etiology, Trichotillomania complications, Bezoars veterinary, Gastrointestinal Tract pathology, Monkey Diseases pathology, Papio
- Abstract
Background: There is little information available concerning trichobezoars in the non-human primate literature., Methods: We evaluated 118 cases of trichobezoar in baboons over a 29-year period at the Southwest National Primate Research Center., Results: The anatomic locations affected in decreasing order were the stomach, small intestine, cecum, esophagus and colon. The most common clinical history was weight loss. The most frequent associated pathology included gastrointestinal inflammation and ulceration, emaciation, peritonitis, intussusception, pneumonia, and aspiration. Trichobezoars were the cause of death in nine baboons and the reason for euthanasia in 12. Females were 2.14 times more likely than males to be affected. The greater the percentage of group housing time, the more likely the baboon is to develop trichobezoars., Conclusions: The baboon may present a useful model to evaluate the etiology, genetic predisposition, physiopathology, neurobiology, and treatment response of trichobezoars.
- Published
- 2009
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16. Endometrial and cervical polyps in 22 baboons (Papio sp.), 5 cynomolgus macaques (Macaca fascicularis) and one marmoset (Callithrix jacchus).
- Author
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Bennett MW, Dick EJ Jr, Schlabritz-Loutsevitch NE, Lopez-Alvarenga JC, Williams PC, Sharp RM, and Hubbard GB
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- Animals, Callithrix, Female, Macaca fascicularis, Papio, Polyps pathology, Uterine Cervical Diseases pathology, Uterine Diseases pathology, Monkey Diseases pathology, Polyps veterinary, Uterine Cervical Diseases veterinary, Uterine Diseases veterinary
- Abstract
Background: Endometrial and cervical polyps are masses of endometrium or cervical epithelium that bulge into the uterine or cervical lumen. The physiopathology and contributing factors of endometrial polyps development are still unknown., Methods: Clinical and pathology records of 28 non-human primates with histologically confirmed endometrial and cervical polyps were reviewed. Twenty-one baboons with endometrial polyps were evaluated for age at diagnosis, body weight, menstrual cycle length, presence of endometriosis and adenomyosis and number of offspring, cesarean sections, and stillbirths., Results: Endometrial polyps in baboons were associated with increased age, decreased menstrual cycle lengths, endometriosis, and decreased parity. No differences were found for weight, adenomyosis, or number of cesarean sections or stillbirths., Conclusions: Baboons are a promising model for the study of endometrial polyps because of their similarity to humans in both the development of endometrial polyps and association of many of the same risk factors.
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- 2009
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17. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter.
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Shearer WT, Lee BN, Cron SG, Rosenblatt HM, Smith EO, Lugg DJ, Nickolls PM, Sharp RM, Rollings K, and Reuben JM
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- Antarctic Regions, Humans, Interleukin 1 Receptor Antagonist Protein, Interleukin-10 blood, Interleukin-12 biosynthesis, Sialoglycoproteins blood, Interferon-gamma blood, Interleukin-10 antagonists & inhibitors, Seasons, Sialoglycoproteins antagonists & inhibitors
- Abstract
Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.
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- 2002
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18. Best cases from the AFIP: gastrointestinal stromal tumor. Armed Forces Institute of Pathology.
- Author
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Sharp RM, Ansel HJ, and Keel SB
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- Aged, Humans, Male, Radiography, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms pathology
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- 2001
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19. N-(4-hydroxyphenyl)retinamide (4-HPR) decreases neoplastic properties of human prostate cells: an agent for prevention.
- Author
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Sharp RM, Bello-DeOcampo D, Quader ST, and Webber MM
- Subjects
- Cell Count, Cell Division drug effects, Cell Line, Transformed cytology, Cell Line, Transformed drug effects, Cell Line, Transformed metabolism, Dose-Response Relationship, Drug, Humans, Immunoenzyme Techniques, Keratins metabolism, Male, Neoplasm Invasiveness prevention & control, Phenotype, Prostate cytology, Prostate metabolism, Prostatic Neoplasms, Retinoblastoma Protein metabolism, Tumor Cells, Cultured, Tumor Suppressor Protein p53 metabolism, Vimentin metabolism, Anticarcinogenic Agents pharmacology, Cell Transformation, Neoplastic drug effects, Fenretinide pharmacology, Prostate drug effects
- Abstract
The development of prostate cancer through a multistep process of carcinogenesis may have a long latent period of 20-30 years. It is possible that progression to a malignant state could be blocked or reversed during this time. This study focuses on the ability of the synthetic retinoid, N-(4-hydroxyphenyl)-retinamide (4-HPR), to reverse changes associated with malignant transformation and tumor progression, towards a normal phenotype. To examine the responsiveness of cells at different steps of prostate carcinogenesis, three immortalized, but non-tumorigenic (RWPE-1, WPE1-7 and WPE1-10), and one human prostate carcinoma cell line (DU-145), were used. The effects of 4-HPR on cell proliferation, expression of intermediate filament proteins cytokeratin 18 and vimentin, and tumor suppressor proteins p53 and pRb were examined by immunostaining and compared. Results show that 4-HPR caused inhibition of growth in all cell lines in a dose-dependent manner. 4-HPR induced an increase in staining for cytokeratin 18, a marker of differentiation for prostate epithelial cells. While all cell lines showed strong immunostaining for vimentin, treatment with 4-HPR for 8 days caused a marked decrease in staining for vimentin in all cell lines. In an in vitro assay, 4-HPR also caused inhibition of invasion by DU-145 cells in a dose-dependent manner. Furthermore, 4-HPR treatment was effective in significantly decreasing the abnormal nuclear staining for the tumor suppressor proteins p53 and pRb. Because 4-HPR decreased invasion-associated vimentin expression, inhibited invasion, and normalized p53 and pRb immunostaining, we propose that 4-HPR may be an effective agent for secondary and tertiary prevention, i.e. promotion and progression stages, respectively, of prostate cancer.
- Published
- 2001
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20. Antibody responses to bacteriophage phi X-174 in human subjects exposed to the antarctic winter-over model of spaceflight.
- Author
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Shearer WT, Lugg DJ, Rosenblatt HM, Nickolls PM, Sharp RM, Reuben JM, and Ochs HD
- Subjects
- Adult, Antarctic Regions epidemiology, Antibodies, Viral immunology, Antibody Formation, Antigens, Viral immunology, Humans, Male, Middle Aged, Seasons, Space Flight, Bacteriophages immunology
- Abstract
Background: It has been proposed that exposure to long-term spaceflight conditions (stress, isolation, sleep disruption, containment, microbial contamination, and solar radiation) or to ground-based models of spaceflight will alter human immune responses, but specific antibody responses have not been fully evaluated., Objective: We sought to determine whether exposure to the 8-month Antarctic winter-over model of spaceflight would alter human antibody responses., Methods: During the 1999 Australian National Antarctic Research Expeditions, 11 adult study subjects at Casey, Antarctica, and 7 control subjects at Macquarie Island, sub-Antarctica, received primary and secondary immunizations with the T cell-dependent neoantigen bacteriophage phi X-174. Periodic plasma samples were analyzed for specific antibody function., Results: All of the subjects from Casey, Antarctica, cleared bacteriophage phi X-174 normally by 1 week after primary immunization, and all had normal primary and secondary antibody responses, including immunologic memory amplification and switch from IgM to IgG antibody production. One subject showed a high normal pattern, and one subject had a low normal pattern. The control subjects from Macquarie Island also had normal immune responses to bacteriophage phi X-174., Conclusions: These data do not support the hypothesis that de novo specific antibody responses of subjects become defective during the conditions of the Antarctic winter-over. Because the Antarctic winter-over model of spaceflight lacks the important factors of microgravity and solar radiation, caution must be used in interpreting these data to anticipate normal antibody responses in long-term spaceflight.
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- 2001
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21. Effects of iron loading on pathogenicity in hepatitis C virus-infected chimpanzees.
- Author
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Bassett SE, Di Bisceglie AM, Bacon BR, Sharp RM, Govindarajan S, Hubbard GB, Brasky KM, and Lanford RE
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- Alanine Transaminase blood, Animals, Biomarkers blood, Diet, Dietary Supplements, Ferritins blood, Hepatitis C blood, Humans, Iron administration & dosage, Iron blood, Male, Pan troglodytes, Time Factors, Transferrin metabolism, Virulence, Hepacivirus pathogenicity, Hepatitis C physiopathology, Iron pharmacology, Liver metabolism
- Abstract
Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)-infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV-infected chimpanzees. Iron was supplemented in the diets of four HCV-infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV-infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Although various degrees of iron loading occurred in all chimpanzees, HCV-infected animals exhibited increased loading in comparison with uninfected animals. The effects of iron loading on HCV disease expression was determined by comparing disease parameters during an extended baseline period before iron loading with the period during iron loading and immediately following iron loading. Iron loading did not influence the viral load, but did exacerbate liver injury in HCV-infected chimpanzees, as evidenced by elevated ALT and histological changes. Because all chimpanzees on high iron diets experienced iron loading, but pathological effects were only observed in HCV-infected chimpanzees, HCV infection appears to increase the susceptibility of the liver to injury following iron loading. These results confirm and extend previous observations made in human populations and serve to further validate the chimpanzee model of chronic hepatitis C.
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- 1999
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22. Modulation of the malignant phenotype of human prostate cancer cells by N-(4-hydroxyphenyl)retinamide (4-HPR).
- Author
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Webber MM, Bello-DeOcampo D, Quader S, Deocampo ND, Metcalfe WS, and Sharp RM
- Subjects
- Apoptosis, Carcinoma metabolism, Cell Division drug effects, Cell Movement drug effects, Epithelial Cells metabolism, Humans, Male, Neoplasm Invasiveness, Phenotype, Prostatic Neoplasms metabolism, Receptors, Retinoic Acid biosynthesis, Tumor Cells, Cultured, Up-Regulation drug effects, Vimentin biosynthesis, Carcinoma pathology, Fenretinide pharmacology, Prostatic Neoplasms pathology
- Abstract
A long latent period of 20 to 30 years may be involved in the multistep process of carcinogenesis represented by prostatic intraepithelial neoplasia (PIN) in the prostate. It is, therefore, possible that progression to a malignant state could be blocked or reversed during this time. Retinoids not only have the ability to block steps in the process of carcinogenesis but they may also modulate or reverse some malignant characteristics of cancer cells. This study focuses on the ability of N-(4-hydroxyphenyl)-retinamide (4-HPR), a synthetic retinoid, to reverse malignant characteristics towards a normal phenotype, using the human prostate carcinoma cell line DU-145. These malignant characteristics include abnormal cell proliferation, intermediate filament expression, motility, invasion, and cell survival. Results show that 1 microM and 10 microM 4-HPR caused 31% and 96% inhibition of growth, while all-trains retinoic acid (ATRA) produced similar effects at 10 and 100 microM, making 4-HPR ten times more effective than ATRA. While DU-145 cells show strong immunostaining for vimentin, treatment with 1 microM 4-HPR for eight days caused a marked decrease in vimentin staining. This was accompanied by a change from an elongated to an epithelial cell morphology. Densitometric analysis of Western blots for vimentin showed a 53% decrease in vimentin expression in 1 microM 4-HPR treated cells. Concomitant with the decrease in vimentin expression, cell motility and invasive ability also decreased by 32% and 52%, respectively. Growth inhibition was accompanied by DNA fragmentation and apoptosis. Exposure of cells to 1 microM 4-HPR caused a marked upregulation of nuclear retinoid receptors RARalpha and a detectable expression of RARgamma. These results suggest that inhibition of growth and vimentin expression, and induction of apoptosis by 4-HPR in prostate cancer cells may occur via a receptor-mediated mechanism involving transrepression of AP-1 by retinoid receptors. We propose that vimentin may serve as a useful intermediate marker for early detection of prostate cancer in biopsy specimens and that 4-HPR may be effective in blocking several steps in prostate carcinogenesis as well as the progression of PIN to invasive carcinoma.
- Published
- 1999
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23. Dietary and genetic effects on LDL size measures in baboons.
- Author
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Singh AT, Rainwater DL, Kammerer CM, Sharp RM, Poushesh M, Shelledy WR, and VandeBerg JL
- Subjects
- Animals, Female, Genotype, Lipoproteins, LDL blood, Lipoproteins, LDL drug effects, Lipoproteins, LDL genetics, Male, Papio, Phenotype, Sex Factors, Dietary Fats administration & dosage, Gene Expression Regulation drug effects, Lipoproteins, LDL analysis
- Abstract
Genetic and dietary effects on LDL phenotypes, including predominant LDL particle diameter, LDL size distribution, and non-HDL cholesterol and apoB concentrations, were investigated in 150 pedigreed baboons that are members of 19 sire groups. Baboons were fed a sequence of three defined diets differing in levels of fat and cholesterol. Increasing dietary fat had relatively little effect on two measures of LDL particle size. However, increasing the level of cholesterol in the diet resulted in larger increases of the predominant LDL particle diameters and in the proportion of stain on LDLs > 28 nm. As expected, apoB and non-HDL cholesterol concentrations significantly increased when levels of dietary fat and cholesterol were increased. Correlations among the LDL phenotypes suggested that several different aspects of the LDL phenotype were captured by the four LDL measures across the three diets. Genetic effects indicated by sire group membership were significant both for expression of the LDL phenotypes and for response to changes in diet.
- Published
- 1996
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24. Genetic and environmental contributions to cardiovascular risk factors in Mexican Americans. The San Antonio Family Heart Study.
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Mitchell BD, Kammerer CM, Blangero J, Mahaney MC, Rainwater DL, Dyke B, Hixson JE, Henkel RD, Sharp RM, Comuzzie AG, VandeBerg JL, Stern MP, and MacCluer JW
- Subjects
- Adult, Age Factors, Aged, Anthropometry, Apolipoproteins A blood, Blood Glucose, Blood Pressure, Cardiovascular Diseases complications, Cholesterol, HDL blood, Dehydroepiandrosterone Sulfate blood, Diabetes Complications, Diabetes Mellitus epidemiology, Family Health, Female, Humans, Insulin blood, Male, Middle Aged, Pedigree, Phenotype, Prevalence, Risk Factors, Sex Factors, Sex Hormone-Binding Globulin metabolism, Texas epidemiology, Cardiovascular Diseases epidemiology, Cardiovascular Diseases genetics, Mexican Americans
- Abstract
Background: The familial aggregation of coronary heart disease can be in large part accounted for by a clustering of cardiovascular disease risk factors. To elucidate the determinants of cardiovascular disease, many epidemiological studies have focused on the behavioral and lifestyle determinants of these risk factors, whereas others have examined whether specific candidate genes influence quantitative variation in these phenotypes., Methods and Results: Among Mexican Americans from San Antonio (Tex), we quantified the relative contributions of both genetic and environmental influences to a large panel of cardiovascular risk factors, including serum levels of lipids, lipoproteins, glucose, hormones, adiposity, and blood pressure. Members of 42 extended families were studied, including 1236 first-, second-, and third-degree relatives of randomly ascertained probands and their spouses. In addition to the phenotypic assessments, information was obtained regarding usual dietary and physical activity patterns, medication use, smoking habits, alcohol consumption, and other lifestyle behaviors and medical factors. Maximum likelihood methods were used to partition the variance of each phenotype into components attributable to the measured covariates, additive genetic effects (heritability), household effects, and an unmeasured environmental residual. For the lipid and lipoprotein phenotypes, age, gender, and other environmental covariates accounted in general for < 15% of the total phenotypic variance, whereas genes accounted for 30% to 45% of the phenotypic variation. Similarly, genes accounted for 15% to 30% of the phenotypic variation in measures of glucose, hormones, adiposity, and blood pressure., Conclusions: These results highlight the importance of considering genetic factors in studies of risk factors for cardiovascular disease.
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- 1996
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25. Effects of a major gene for apolipoprotein A-I concentration are thyroid hormone dependent in Mexican Americans.
- Author
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Blangero J, Williams-Blangero S, Mahaney MC, Comuzzie AG, Hixson JE, Samollow PB, Sharp RM, Stern MP, and MacCluer JW
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- Adult, Apolipoprotein A-I blood, Base Sequence, Female, Genetic Linkage, Haplotypes, Humans, Male, Mexican Americans, Molecular Sequence Data, Apolipoprotein A-I genetics, Gene Expression Regulation, Triiodothyronine blood
- Abstract
Apolipoprotein A-I (apoA-I) is the principal protein component of HDL cholesterol. The thyroid hormone triiodothryonine (T3) is known to be a potent mediator of expression of the apoA-I structural gene (APOA1). Using complex segregation analysis, we detected a major gene influencing plasma concentration of apoA-I and examined its interaction with T3 serum level in Mexican Americans participating in the San Antonio Family Heart Study. Strong evidence for a major locus with two alleles (A and a) determining apoA-I level was obtained when interaction with T3 was allowed. The major gene appears not to be linked to the APOA1 structural locus. Genotypes differed significantly in their relationships to T3 level. The AA and Aa genotypes showed a positive relationship with T3 level, while the rarer aa homozygote showed a strong negative relationship with T3. The relative variance in apoA-I concentration due to this major gene varied from 56% to 18%, depending on T3 level. On average, the major gene accounts for 30% of apoA-I variation, and shared-household effects account for an additional 11%. These findings suggest that thyroid hormone has an important role in the genetic control of lipoprotein metabolism.
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- 1996
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26. Triiodothyronine exerts a major pleiotropic effect on reverse cholesterol transport phenotypes.
- Author
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Comuzzie AG, Blangero J, Mahaney MC, Sharp RM, VandeBerg JL, Stern MP, and MacCluer JW
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Apolipoprotein A-I blood, Apolipoprotein A-II blood, Biological Transport, Cholesterol, HDL blood, Female, Humans, Lipoprotein(a) analogs & derivatives, Lipoprotein(a) blood, Male, Middle Aged, Multivariate Analysis, Osmolar Concentration, Phenotype, Sex Characteristics, Cholesterol genetics, Cholesterol metabolism, Triiodothyronine pharmacology
- Abstract
The thyroid hormone triiodothyronine (T3) is known to be a potent mediator of APOA1 gene expression. With the use of multivariate quantitative genetic analysis, we have assessed the magnitude of shared effects of T3 on plasma concentrations of apolipoprotein AI (apo AI) and three related phenotypes: HDL-C, apo AII, and LpAI (which is a concentration of apo AI that contains HDL particles). Maximum likelihood techniques were used to simultaneously estimate mean effects and variance components in large, extended Mexican American families living in San Antonio, Tex. We found that T3 accounted for 16%, 23%, 21%, and 37% of the additive genetic variance in HDL-C, apo AI, apo AII, and LpAI, respectively, while explaining virtually none of the random environmental variance in these phenotypes. T3 also has a pronounced effect on the pairwise genetic correlations among the four phenotypes: After the pleiotropic effects of T3 concentrations are controlled for, the genetic correlations are reduced by 6% in the case of HDL-C and apo AI and 97% for apo AII and LpAI. Thus, genes that influence T3 have a significant effect on HDL-C, apo AI, apo AII, and LpAI and also on the correlations among these phenotypes.
- Published
- 1996
- Full Text
- View/download PDF
27. A primate model of monotypism in atherosclerotic lesions.
- Author
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Henkel RD, Sharp RM, Galindo LV, Aivaliotis MJ, Carey KD, McGill HC Jr, and VandeBerg JL
- Subjects
- Alleles, Animals, Arteries enzymology, Arteries pathology, Arteriosclerosis enzymology, Cell Division, Disease Models, Animal, Glucosephosphate Dehydrogenase analysis, Glucosephosphate Dehydrogenase genetics, Heterozygote, Muscle, Smooth, Vascular enzymology, Muscle, Smooth, Vascular pathology, Arteriosclerosis pathology, Papio
- Abstract
We have characterized the expression of allelic variants of X-linked glucose 6-phosphate dehydrogenase (G6PD) in aorta from homozygous, hemizygous, and heterozygous baboons (Papio hamadryas). Fibrous plaques from heterozygous baboons fed a high cholesterol, saturated fat diet contained distributions of G6PD allelic variants that differed from those of normal arterial wall and fatty streaks. The skewed allelic expression patterns in fibrous plaques of heterozygotes reflect decreased cellular heterogeneity in advanced vascular lesions. The tendency toward cellular monotypism in fibrous plaques is similar to that present in advanced human atherosclerotic lesions. Our results suggest that G6PD heterozygous baboons are a unique primate model for investigating the cellular origin of proliferating smooth muscle cells in atherosclerotic plaques.
- Published
- 1993
- Full Text
- View/download PDF
28. Semiquantitative analysis of X-linked gene expression during spermatogenesis in the mouse: ethidium-bromide staining of RT-PCR products.
- Author
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McCarrey JR, Dilworth DD, and Sharp RM
- Subjects
- Actins genetics, Animals, Base Sequence, Male, Mice, Molecular Sequence Data, Oligonucleotides, Polymerase Chain Reaction, RNA analysis, Staining and Labeling, Transcription, Genetic, Ethidium chemistry, Gene Expression, Genetic Linkage, Spermatogenesis genetics, X Chromosome
- Abstract
We have used analysis of ethidium-bromide-stained reverse transcriptase-polymerase chain reaction (RT-PCR) products to assess the effects of X-chromosome inactivation during spermatogenesis in the mouse. RT-PCR was performed on total RNA from eight different spermatogenic cell types, including premeiotic spermatogonia, meiotic spermatocytes, and postmeiotic spermatids, to detect transcripts from five different X-linked structural genes (Pgk-1, Zfx, Pdha-1, Hprt, and Phka) and two autosomal genes (Pgk-2 and beta-actin). Relative intensities of ethidium-bromide-stained RT-PCR products representing transcripts from each gene in each cell type were analyzed by densitometry using the Image program (version 1.4, NIH), and normalized against beta-actin values. These results suggest a coordinate inactivation of the X-linked loci at the onset of meiosis, followed by variable rates of decline of corresponding transcript levels reflecting differential mRNA stabilities and/or leaky expression after inactivation. Technically, these results indicate that analysis of ethidium-bromide-stained RT-PCR products can be used to provide a "semiquantitative" indication of relative levels of specific transcripts in a developing cell lineage without using radioactive probes to quantitate these products.
- Published
- 1992
- Full Text
- View/download PDF
29. Production of baboon (Papio hamadryas) monoclonal antibodies by herpesvirus papio immortalized baboon lymph node cells.
- Author
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Sharp RM, Durocher CL, and Parmenter JL
- Subjects
- Animals, Antibodies, Monoclonal classification, Antibodies, Monoclonal immunology, Cell Line, Transformed, Enzyme-Linked Immunosorbent Assay, Herpesviridae, Immunoblotting, Lipoproteins, LDL immunology, Lymph Nodes cytology, Lymphocytes metabolism, Mice, Papio, Antibodies, Monoclonal biosynthesis, Apolipoproteins B immunology, Cell Transformation, Viral, Lymphocytes immunology
- Abstract
Baboon monoclonal antibodies specific for monomorphic determinants of baboon apolipoprotein B were produced from in vivo primed lymph node cells immortalized by herpesvirus papio (HVP). Two cell lines from the immortalized cells were readily stabilized and grew rapidly. Since Epstein-Barr virus (EBV) cannot be used to immortalize baboon or macaque cells, HVP expands the potential sources of monoclonal antibodies to include baboons, and is the immortalizing agent of choice for macaques as well.
- Published
- 1990
- Full Text
- View/download PDF
30. Familial rheumatoid arthritis: a kindred identified through a proband with seronegative juvenile arthritis includes members with seropositive, adult-onset disease.
- Author
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Rossen RD, Brewer EJ, Sharp RM, Yunis EJ, Schanfield MS, Birdsall HH, Ferrell RE, and Templeton JW
- Subjects
- Adolescent, Adult, Antibodies, Antinuclear genetics, Antigen-Antibody Complex genetics, Arthritis, Juvenile diagnosis, Arthritis, Juvenile immunology, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid immunology, Child, Preschool, Female, Genes, MHC Class II, Genetic Linkage, HLA-DR Antigens, Histocompatibility Testing, Humans, Lymphocyte Culture Test, Mixed, Male, Middle Aged, Pedigree, Rheumatoid Factor genetics, Arthritis, Juvenile genetics, Arthritis, Rheumatoid genetics
- Abstract
Segregation of chromosome #6 markers has been studied in a large family, identified by a proband with seronegative, juvenile-onset rheumatoid arthritis, which contains four other individuals with adult-onset rheumatoid arthritis (RA). Two of the adult-onset patients have classical seropositive RA. Sera from two healthy members of this family also contain rheumatoid factors (RF). Six family members had crossovers in the short arm of chromosome #6. Three individuals with recombinants between HLA-B and HLA-D were identified; three others had identifiable crossovers between HLA-D and GLO (Glyoxylase 1). Linkage analysis suggested that susceptibility to RA in this family was influenced by a dominant gene located centromeric to HLA-B. The highest lod score (1.64) was obtained for linkage to GLO at a recombination rate of zero. Inheritance of specific chromosome #6 or Gm immunoglobulin allotype markers did not appear to influence serum RF. These results agree with previous family studies which suggest that acquisition of childhood- and adult-onset RA is influenced by a common disease susceptibility gene, linked to the major histocompatibility gene complex.
- Published
- 1982
- Full Text
- View/download PDF
31. The utility of simplex sibships in the characterization of HLA-linked disease susceptibility genes.
- Author
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Sharp RM and Templeton JW
- Subjects
- Chromosome Mapping, Genotype, Humans, Probability, Genetic Linkage, Genetic Predisposition to Disease, HLA Antigens genetics, Models, Genetic
- Abstract
We demonstrate, by plotting the deviations from expected ratios of identity by descent (IBD) scores of sibling pairs having only one affected individual, that simplex pairs can, under certain constraints, provide a rich source of information concerning linkage relationships of a disease susceptibility gene. In addition, two statistical tests of significance are presented, one for a fixed sample size and a second for a sequential sampling approach.
- Published
- 1984
32. Familial rheumatoid arthritis: linkage of HLA to disease susceptibility locus in four families where proband presented with juvenile rheumatoid arthritis.
- Author
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Rossen RD, Brewer EJ, Sharp RM, Ott J, and Templeton JW
- Subjects
- Adolescent, Adult, Aged, Arthritis, Juvenile immunology, Child, Female, Genes, Dominant, Genes, MHC Class II, Genetic Linkage, Humans, Male, Middle Aged, Pedigree, Recombination, Genetic, Arthritis, Juvenile genetics, HLA Antigens genetics
- Abstract
The occurrence of a chronic seronegative polyarthritis has been studied in four families in which the proband presented with some form of juvenile rheumatoid arthritis. In these families, histocompatibility testing suggested that susceptibility to arthritis was controlled by a dominant allele with variable penetrance and expressivity at the rheumatoid-like arthritis, first locus (RLA-1). The combined lod scores for the four families (2.70) indicated that the odds in favor of genetic linkage between the major histocompatibility complex and the postulated disease susceptibility gene, RLA-1, were 500:1. In one family, a recombinant event permitted localization of RLA-1 centromeric to HLA-D. Of major interest was the fact that there was significant pleomorphism in the clinical manifestations of arthritis in affected individuals. In some, symptoms first occurred in childhood and in others, in adult life. Even among those with childhood-onset arthritis, different types of juvenile rheumatoid arthritis were observed within the same family.
- Published
- 1980
- Full Text
- View/download PDF
33. Development of preferred orientation in the eggshell of the domestic fowl.
- Author
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Sharp RM and Silyn-Roberts H
- Subjects
- Animals, Chickens, Female, Models, Biological, X-Ray Diffraction, Egg Shell ultrastructure
- Abstract
Preferred orientation in the shell of the domestic fowl is shown by x-ray diffractometry to develop gradually throughout the shell, beginning immediately after the start of shell deposition and reaching a maximum at the exterior surface. Only 2 out of 20 shells examined exhibited a single preferred orientation: This was one in which the pole of the (001) plane lies parallel to the shell surface normal. The remaining shells had two preferred orientations present simultaneously, one in which the (001) pole is parallel and the other in which the (104) pole is parallel to the surface normal. Previous work has resulted in conclusions that are in conflict with these; they are discussed in relation to the present work.
- Published
- 1984
- Full Text
- View/download PDF
34. Genetic control of serum neutralizing-antibody response to rabies vaccination and survival after a rabies challenge infection in mice.
- Author
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Templeton JW, Holmberg C, Garber T, and Sharp RM
- Subjects
- Animals, Genes, Dominant, Genes, MHC Class II, Genes, Recessive, Genetic Linkage, H-2 Antigens genetics, Mice, Mice, Inbred Strains immunology, Neutralization Tests, Rabies genetics, Vaccination, Antibodies, Viral biosynthesis, Rabies immunology, Rabies virus immunology
- Abstract
Quantitative differences in serum neutralizing-antibody (SNAb) responses to rabies vaccination and survival after a rabies challenge infection between two inbred mice strains, C3H/J and C57BL/6J, were shown to be under genetic control. A 99% confidence limit calculated from the SNAb response titers of 14 C57BL/6J mice resulted in an upper limit for the SNAb response titer of C57BL/6J mice at 50.63. A SNAb titer less than or equal to 50.63 in response to rabies vaccination was assigned the phenotype of hyporesponder, and a SNAb titer greater than 50.63 in response to rabies vaccination was assigned the phenotype of hyperresponder in this study. The hyper-SNAb response to rabies vaccination and the higher frequency of survival after rabies challenge infection behave as Mendelian dominant alleles in F1 hybrids (C3H/J X C57BL/6J) and backcross (BC) (F1 [C3H/J X C57BL/6J] X C57BL/6J) progeny. Both a relatively hyper-SNAb response and a higher frequency of vaccine-inducible survival phenotypes occur in C3H/J mice. On the other hand, both the relatively hypo-SNAb response and a lower frequency of vaccine-inducible survival phenotypes behave as Mendelian recessive alleles and occur in C57BL/6J mice. C3H/J mice are H-2 Kk, and C57BL/6J mice are H-2 Kb. All three phenotypic traits (H-2 type, SNAb response, and survival after rabies challenge infection) segregate as independent (unlinked) monogenic traits in BC progeny (F1 [C3H/J X C57BL/6J] X C57BL/6J). The genetically controlled survival trait is inducible by rabies vaccination, but SNAb response is not a parameter that measures successful vaccine induction of preexposure protection from a rabies challenge infection in the BC progeny. The essential role of vaccination in developing preexposure protection in genetically responsive mice is confirmed, but indicates that in vitro measurements other than SNAb titers need to be developed to identify mice that have failed to achieve preexposure protection by rabies vaccination. This study confirms Lodmell's findings (D. L. Lodmell and B. Chesebro, J. Virol. 50:359-362, 1984; D. L. Lodmell, J. Exp. Med. 157:451-460, 1983) that susceptibility to rabies infection is genetically controlled in some mice strains. Additionally, this study indicates that conventional rabies vaccination even with more potent vaccines may not induce protection from infection in some genetically susceptible individuals.
- Published
- 1986
- Full Text
- View/download PDF
35. Use of monoclonal antibodies in genetic research with nonhuman primates.
- Author
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Sharp RM
- Subjects
- Animals, Research, Antibodies, Monoclonal, Primates genetics
- Abstract
Monoclonal antibodies, because of their specificity and unlimited availability, have become one of the most powerful experimental tools available to the biological sciences. It is possible to make monoclonal antibodies that bind to determinants that are monomorphic in one or more species or to determinants that are polymorphic within a species. Few monoclonal antibodies have been made using immunogens derived from nonhuman primates. However, some monoclonal antibodies that recognize monotypic markers in humans can be used to detect polymorphic markers in nonhuman primates. Thus, the rapid development of monoclonal antibodies specific for human proteins significantly increases the potential number of immunogenetic markers useful for studying phylogenetic relationships and for identifying genetic polymorphisms among nonhuman primates.
- Published
- 1987
- Full Text
- View/download PDF
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