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Biomedical subjects

R C Rose

Publications and source records attributed to R C Rose.

At least 37 records · Page 2Linked to original sources
PubMed1998

Human papillomavirus type 11 recombinant L1 capsomeres induce virus-neutralizing antibodies.

The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain HPV genotype-restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R. C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study, HPV-11 virion-neutralizing monoclonal antibodies H11.F1 and H11.H3, previously characterized as recognizing two distinct HPV-11 capsid-neutralizing antigenic domains (S. W. Ludmerer, D. Benincasa, and G. E. Mark III, J. Virol. 70:4791-4794, 1996), were each found to be highly immunoreactive with trypsin-generated capsomeres in an enzyme-linked immunosorbent assay (ELISA). Capsomeres were used to generate high-titer polyclonal immune sera that demonstrated HPV genotype-restricted reactivity by ELISA. The capsomere antisera were then tested in an in vitro infectivity assay and found to neutralize HPV-11 virions. In this assay, HPV-11 capsomere polyclonal antisera exhibited neutralization titers (10(-5) to 10(-6)) comparable to those obtained with a virion-neutralizing antiserum raised previously against intact HPV-11 VLPs (R. C. Rose, R. C. Reichman, and W. Bonnez, J. Gen. Virol. 75:2075-2079, 1994). These results indicate that highly immunogenic, genotype-restricted HPV capsid-neutralizing antigenic domains are contained entirely within capsomeres. Thus, capsomeres may be viable vaccine candidates for the prevention of HPV disease.

Animals↗
PubMed1998

Ocular oxidants and antioxidant protection.

Oxidative damage and antioxidant protection in ocular tissues has not been reviewed recently. Metabolism in the eye is of increasing interest because the organ is highly susceptible to damage by sunlight, oxygen, various chemicals, and pollutants. Interest is expected to increase because of an aging Western world population and a continued depletion of stratospheric ozone. Hydrogen peroxide is discussed because it is both a byproduct and a source of free radical reactions and is normally present in the aqueous humor. The metabolism of reactive oxygen species by enzymes, nutrients, pigments, and low molecular weight scavengers is evaluated. Ascorbic acid, because of its high concentration in the eye, is thought to be a primary substrate in ocular protection; progress in determining the mechanisms by which it is recycled and maintained in the useful, reduced state is discussed. Recent information is included about antioxidants not previously known to be present in the eye, and some importance is placed on the properties of the vitreous humor and tear fluid because of the previous lack of emphasis on these.

Animals↗
PubMed1997

Age distribution of antibodies to human papillomavirus in children, women with cervical intraepithelial neoplasia and blood donors from South Africa.

Sera from 95 women with cervical intraepithelial neoplasia (CIN), 95 age-matched female blood donors, and 155 children aged between 1 and 12 years were tested by enzyme-linked immunosorbent assay (ELISA) for levels of serum IgG to three human papillomavirus (HPV) peptides (HPV-16 E2 [E2-16], HPV-18 E2 (E2-18], HPV-16 L1 [L1-16]), as well as HPV-16 virus-like particles (VLP-16) and bovine papillomavirus type 1 virus-like particles (BPV-VLP). In the adult group antibodies to E2-16 and VLP-16 were significantly associated with CIN when compared to the blood donor controls (P = .039 and P = .002, respectively). In women with CIN there was an increase in seropositivity to E2-16 and a decrease in seropositivity to VLP-16 with age. Antibodies to HPV-16 E2 could therefore be an important marker of CIN in women over 40 years of age, whereas antibodies to VLP-16 could be a marker for CIN in younger women. There was no correlation with CIN and antibodies to E2-18, L1-16, and BPV-VLP. In the children's sera antibodies were detected to E2-16 (44.5%), E2-18 (18.7%), L1-16 (20%), VLP-16 (4.5%), and BPV-VLP (5.1%). Between the ages of 3 and 12 years the prevalence of antibodies to E2-16 decreased with age. The presence of antibodies to HPV-16 in young children indicated infection with either HPV-16 or a related virus. HPV DNA isolation from children could help resolve this question.

Adult↗
PubMed1997

Properties of electrochemically active components in mammalian vitreous humor.

Antioxidants are considered to have important roles in protecting the eye against radiation, oxygen toxicity and other threats. Several water-soluble electrochemically-active compounds that might function as antioxidants in vitreous humor of rabbit, rat and bovine eyes were identified and quantitated. In that the rat is a nocturnal animal species and the other two are diurnal, the results allow a tentative evaluation on the comparative physiology of light-dark behavior patterns that influence this ocular fluid. All analyses were performed by HPLC with electrochemical detection. The utility of this approach is that components of vitreous humor can be identified by their retention time and by their characteristic response when the voltages of the two sensing electrodes are progressively brought together. Four compounds regarded as functional antioxidants in the animal kingdom were identified and quantitated. Other antioxidants known to be present in several biological fluids are not present at detectable or significant levels in vitreous humor; metabolites or precursors of these might be present in trace quantities.

Animals↗
PubMed1997

Serological and T-helper cell responses to human papillomavirus type 16 L1 in women with cervical dysplasia or cervical carcinoma and in healthy controls.

In a cross-sectional study we have investigated serological and T-helper (Th) cell responses to human papillomavirus type 16 (HPV-16) L1 in women with HPV-16 related diseases and related them to cervical histology and HPV DNA status. Using a virus-like particle (VLP) based ELISA to detect antibodies to the HPV-16 L1 capsid protein, 45% (33/73) of women with cervical dysplasia, 40% (2/5) of women with cervical cancer, 36% (4/11) of healthy adult female controls and 6% (2/35) of healthy children were found to be seropositive. Amongst women with cervical dysplasia, the highest levels of seropositivity were found in those who were HPV-16 DNA positive (60%, 15/25) or positive for any of the "high-risk' HPV types, 16/18/33 (58%, 18/31), when compared with those with HPV type "X' (25%, 5/20) or with healthy children (6%, 2/35; P < 0.05 for all comparisons). There was a trend for women with cervical dysplasia to show an increased level of seropositivity with increasing grade of lesion. There was no direct correlation found between seropositivity and Th cell responses in all groups studied. However, a combined analysis of each individual's Th and B cell responses suggests that a Th1 pattern of response is predominant amongst healthy adult controls (80% of responders) but reduced in women with cervical dysplasia (55% of responders). A trend towards a decrease in Th1 type responses was also noted with increasing grade of dysplastic lesion. These findings provide further evidence for the importance of the Th response in the control of genital HPV infections.

Adult↗
PubMed1997

Expression of the human papillomavirus type 11 L1 capsid protein in Escherichia coli: characterization of protein domains involved in DNA binding and capsid assembly.

The L1 major capsid protein of human papillomavirus type 11 (HPV-11) was expressed in Escherichia coli, and the soluble recombinant protein was purified to near homogeneity. The recombinant L1 protein bound DNA as determined by the Southwestern assay method, and recombinant mutant L1 proteins localized the DNA-binding domain to the carboxy-terminal 11 amino acids of L1. Trypsin digestion of the full-length L1 protein yielded a discrete 42-kDa product (trpL1), determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, resulting from cleavage at R415, 86 amino acids from the L1 carboxy terminus. Sucrose gradient sedimentation analysis demonstrated that trpL1 sedimented at 11S, while L1 proteins with amino-terminal deletions of 29 and 61 residues sedimented at 4S. Electron microscopy showed that the full-length L1 protein appeared as pentameric capsomeres which self-assembled into capsid-like particles. The trpL1 protein also had a pentameric morphology but was unable to assemble further. In an enzyme-linked immunosorbent assay, the trpL1 and L1 capsids reacted indistinguishably from virus-like particles purified after expression of HPV-11 L1 in insect cells. The carboxy terminus of L1 therefore constitutes the interpentamer linker arm responsible for HPV-11 capsid formation, much like the carboxy-terminal domain of the polyomavirus VP1 protein. The trypsin susceptibility of HPV-11 L1 capsids suggests a possible mechanism for virion disassembly.

Amino Acid Sequence↗
PubMed1996

An apparatus for ultraviolet B irradiation of small volumes of biological fluid under controlled oxygen tension.

BACKGROUND: The design, construction, and calibration of a unique apparatus for ultraviolet (UV) B irradiation of small volumes of biological fluid under temperature-controlled open atmospheric or closed cell conditions of defined Po2 is described. METHODS: The apparatus consists of a custom designed UV transmissible quartz silica 3 port spectrophotometric cuvette coupled to a deuterium UV B source by UV transmissible fiber optics. Fluid movement, temperature regulation, dosimetry, and miniaturized biosensors for oxygen, pH, and temperature are described along with a preliminary experiment. RESULTS: The apparatus produces a known photochemical effect using an endogenous aqueous humor UV B photosensitizer-L tryptophan. UV B radiation is contained, thus protecting laboratory personnel. The system provides a continuous spectral UV B dose of 30 mJ/cm2/hr, which is equivalent to approximately 5.5 UV sunlight hours reaching an aliquot of mammalian aqueous humor. CONCLUSIONS: This biophysical apparatus can be used to investigate antioxidant protective systems in ocular fluid (aqueous/vitreous humors and tears), and is also applicable to evaluating the interaction of radiation with ocular and nonocular tissue cell homogenate.

Animals↗
PubMed1996

The potential role of speech production models in automatic speech recognition.

This paper investigates the issues that are associated with applying speech production models to automatic speech recognition (ASR). Here the applicability of articulatory representations to ASR is considered independently of the role of articulatory representations in speech perception. While the question of whether it is necessary or even possible for human listeners to recover the state of the articulators during the process of perceiving speech is an important one, it is not considered here. Hence, the authors refrain from posing completely new paradigms for ASR which more closely parallel the relationship between speech production and human speech understanding. Instead, work aimed at integrating speech production models into existing ASR formalisms is described.

Humans↗
PubMed1996

Intestinal absorption of water-soluble vitamins.

Vitamin utility is a scientific/medical topic that appears to be pursued as ardently by the lay public as by scientists and medical practitioners. A group of epidemiologists evaluates the effects on health of vitamin intake in the natural diet and by supplementation. The role in ocular disease, cancer of the breast or colon, and cardiovascular disease are a few of the concerns. The results and recommendations concerning dietary vitamin intake will likely continue to change. However, the processes by which dietary vitamins are delivered from intestinal chyme to the blood are more certain. The concept of homeostasis might apply to various of the vitamins as it does to minerals, water, etc. This review will discuss some common methods used to study vitamin absorption and the proposed mechanisms of absorption, and will conclude with a section about dietary regulation.

Animals↗
PubMed1996

Hidden Markov models for speech and signal recognition.

Hidden Markov methods have become the most widely accepted techniques for speech recognition and modeling. They are based on parametric statistical models which have two components. The first is a Markov chain which produces a sequence of states. This sequence of states characterizes the evolution of a non-stationary process like speech through a set of "short-time" stationary events. The sequence of states is "hidden" from the observer by the second component of the model, a set of output distributions, which governs the manner in which the sequence of states is converted into a sequence of speech observations. The purpose of this paper is first, to describe hidden Markov models (HMMs) as a general signal modeling procedure, second, to describe the application of HMMs to speech recognition and modeling, and, third, to describe other problems to which HMMs have been successfully applied. It is hoped that this discussion will inspire other applications, especially in the area of modeling biological processes represented as continuous waveforms, such as the electroencephalogram (EEG).

Humans↗
PubMed1995

Analysis of water-soluble antioxidants by high-pressure liquid chromatography.

The measurement of endogenous substances that function as biological antioxidants is of importance because the values obtained might be an index of future health. We quantified three water-soluble antioxidants by high-pressure liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). Current-voltage relationships made at various settings of the D2 porous graphite electrode help to identify ascorbic acid, glutathione and uric acid. The antioxidants are determined simultaneously and without need for derivatization. The method is seen to be useful for comparison of normal rat liver with liver that had undergone oxidative stress through ischaemia. Antioxidant levels in liver, kidney, pancreas and intestinal mucosa are presented and compared with literature values. Endogenous contents of oxidized forms of ascorbic acid and glutathione become apparent following exposure of tissue samples to a strong reductant such as 2-mercapthoethanol.

Animals↗
PubMed1994

Human papillomavirus (HPV) type 11 recombinant virus-like particles induce the formation of neutralizing antibodies and detect HPV-specific antibodies in human sera.

Recombinant human papillomavirus type 11 (HPV-11) virus-like particles (VLPs) were tested for their ability to induce the formation of neutralizing antibodies, and were also tested for serodiagnostic capabilities in an ELISA in comparison with HPV-11 whole virions. VLPs, purified by CsCl density gradient centrifugation from the cell-free supernatant of Ac11L1-infected Sf9 suspension cell cultures, were used to immunize rabbits and anti-VLP antibodies were tested in the athymic mouse model of HPV-11 infection. Pretreatment of infectious HPV-11 virions with the immune serum of VLP-treated animals caused a marked reduction of graft growth (P < 10(-4)) and viral gene expression (P < 10(-4)), similar to the effects obtained using whole virion postimmune serum, and consistent with immune neutralization. To assess the serodiagnostic capabilities of VLPs, a VLP ELISA was developed and used to analyse sera that were tested previously in an HPV-11 whole virion ELISA. Specific antibodies were detected in 49% of patients' sera (P = 2 x 10(-4)), and individual VLP seroreactivities correlated with those previously obtained using whole virions as the antigen (r = 0.87; P < 10(-6)). These results indicate that recombinant VLPs can be used to elicit a neutralizing antibody response, and can substitute faithfully for native virions in the development of HPV-serodiagnostic immunoassays.

Animals↗
PubMed1994

Serological differentiation of human papillomavirus types 11, 16 and 18 using recombinant virus-like particles.

The L1 major capsid protein-coding sequences of human papillomavirus (HPV) types 11, 16 and 18 were expressed in the baculovirus system. Virus-like particles (VLPs) were purified from recombinant-infected Spodoptera frugiperda Sf9 cells and cell-free culture supernatants. Rabbits immunized with purified VLPs developed antibodies that reacted only with the specific VLP type used as the immunogen. In addition, rabbit antibodies raised against infectious HPV-11 virions only reacted with HPV-11 L1 VLPs and not with VLPs derived from either HPV-16 or HPV-18. These results suggest that HPV-11, HPV-16 and HPV-18 virions are antigenically distinct from one another. This observation should be considered in future studies of immune responses to HPV.

Animals↗
PubMed1994

Evaluation of temperature sensitivity of human papillomavirus type 11 by using the human xenograft severe combined immunodeficiency mouse model.

The temperature sensitivity of human papillomavirus type 11 was evaluated by using a human xenograft severe combined immunodeficiency mouse model. Incubation of the virus for 1 h at a temperature higher than 56 degrees C but lower than 72 degrees C was sufficient to inhibit the virally induced growth of infected human tissue. However, 100 degrees C was necessary to completely inactivate HPV type 11 genome expression.

Animals↗
PubMed1993

Cerebral metabolism of oxidized ascorbate.

The brain has a high level of ascorbic acid which is thought to act as a reducing agent, e.g. in protecting tissues against oxidative stress. The mechanism by which ascorbate is maintained in the useful, reduced state in the CNS is evaluated herein. Cerebrum from rat or calf was minced and homogenized in buffer. The endogenous levels of ascorbic acid, dehydro-L-ascorbic acid (DHAA) and reduced glutathione (GSH) were determined by HPLC with coulometric electrochemical detection. We also quantitated tissue capacity to regenerate ascorbic acid from DHAA, which is a product of electron transfer reactions of ascorbic acid. The homogenate was fractionated by centrifugation in steps up to 110,000 x g and dialyzed free of low molecular weight components. The activity for reducing DHAA was approximately equal in the various supernatants; resuspended pellets had little activity. The active component has several properties of a protein, including being precipitated by solid ammonium sulfate addition to the tissue extract; most activity appeared in the 40-80% saturated fraction. The activity was stable up to a temperature of 80 degrees C, but was lost at 95 degrees C. The protein was digested by trypsin. The results suggest that a cytosolic component of cerebrum regenerates ascorbic acid in a step that preferentially uses GSH and NADPH as reducing cofactors. At least one form of DHAA reductase exists in brain.

Animals↗
PubMed1993

Evolution of the antibody response to human papillomavirus type 11 (HPV-11) in patients with condyloma acuminatum according to treatment response.

To evaluate the variation over time of seroreactivity to human papillomavirus type 11 (HPV-11) according to disease outcome, we selected a sample of 42 condyloma acuminatum patients from a group of subjects enrolled in a placebo-controlled trial of three alpha-interferon preparations administered parenterally for the treatment of condyloma acuminatum. This sample included 14 subjects who were cured by the end of follow-up (cured group) and 28 subjects who were not (failed group). For each individual, the first and last sera collected in the study were tested with an intact HPV-11 virion-based enzyme linked immunosorbent assay (ELISA). The sera of 20 nuns with no lifetime sexual exposure served as controls. The median optical density (OD) value of the first serum samples (as well as that of the last samples) from the patients, 0.155, was higher than that of the control sera, 0.073 (P = 2 x 10(-4)). Sensitivity of the assay was 50%. To test if evolution of seroreactivity in the seropositive patients was related to disease outcome after treatment, we examined the average percentage of daily change in OD between the two serum collections. The median OD in the cured group (n = 7) dropped by 0.05% a day whereas in the failed group (n = 11) it increased by 0.07% a day, a highly statistically significant difference (P = 0.006). It is concluded that changes in the seroreactivity to HPV-11 virions are related to outcome of condyloma acumination after treatment. Therefore, improved serological assays may eventually contribute to the monitoring of HPV disease activity.

Adult↗
PubMed1993

Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model.

We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11-infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum.

Animals↗