<p>Plasma samples collected at indicated timepoints following intragastric administration o... more <p>Plasma samples collected at indicated timepoints following intragastric administration of <sup>D3</sup>33-mer to FH09 (in remission) were analyzed by 3Q LC-MS/MS, monitoring for the <i>m/z</i> 979.5<sup>4+</sup>→263.4<sup>+</sup> transition in the positive ion SRM mode. Peak intensities are scaled relative to the highest peak in each chromatogram. Absolute intensities are indicated to the right of the ordinate axis. A <sup>D3</sup>33-mer peptide reference exhibits the same retention time and ion transitions as the peptide detected in the 180 min plasma sample.</p
<p>(A) Gastrointestinal symptoms in gluten-sensitive FH09 improve with sequential administr... more <p>(A) Gastrointestinal symptoms in gluten-sensitive FH09 improve with sequential administration of reduced gluten and gluten-free diets, but return upon reintroduction of dietary gluten (diet changes indicated by vertical arrows). Criteria that were used in clinical scoring of gluten sensitivity in the juvenile macaque FH09 were scaled relative to the healthy, age-matched control, FR26 (score 1, indicated by dotted line). Score 2 corresponded to beginning of diarrhea, e.g. pasty stools. Score 3 corresponded to semi-liquid stools and decreased activity. Score 4 corresponded to liquid stools, decreased activity, moderate dehydration and “balloon” stomach. Score 5 corresponded to liquid stools, depression, severe dehydration and balloon stomach. Score 6 would correspond to a moribund animal where prompt euthanasia is recommended. Each datapoint represents the mean of 7 daily measurements taken over the course of the indicated week. Standard deviations are indicated by error bars. (B) Anti-gliadin IgG (blue; open circles) and IgA (red; open squares) return to baseline with dietary exclusion of gluten, but are elevated following reintroduction of dietary gluten. The level of anti-gliadin IgG (blue; closed circle) and IgA (red; closed square) in control FR26 are shown for comparison. Each datapoint represents the mean of triplicate measurements. Standard deviations are indicated by error bars.</p
<p>(A) Morphometric analysis of villus height:crypt depth ratios from at least 4 different ... more <p>(A) Morphometric analysis of villus height:crypt depth ratios from at least 4 different areas of distal duodenum in gluten-sensitive FH09 and control FR26 following dietary changes. Administration of a gluten-free diet increased the V:C ratio in FH09 at week 27 to a level that is statistically equivalent to that in FR26 (constant at all time points). Reintroduction of dietary gluten resulted in a drop in V:C ratio in FH09 (week 37) relative to that in FH09 on a gluten-free diet (week 27) and to that in FR26. *P<0.05. (B–C) H&E-stained duodenum at week 37 following 10 weeks of a gluten-containing diet. 100× magnification. (B) Control macaque FR26 exhibits normal villus architecture. (C) Gluten-sensitive macaque FH09 exhibits villus blunting. (D–E) Highlighted sections in B–C were examined by immunohistochemistry. 400× magnification. (D) Anti-CD3 staining in FR26 shows few CD3+ IELs (dark brown dots in epithelium). (E) Anti-CD3 staining in FH09 shows intraepithelial lymphocytosis.</p
<p>Gluten-sensitive FH45 (A-C) and control FI96 (D-F) were switched from a gluten-containin... more <p>Gluten-sensitive FH45 (A-C) and control FI96 (D-F) were switched from a gluten-containing to a gluten-free diet at week 0, re-challenged with the gluten-containing diet from week 10.4 to 11.4, and then returned to a gluten-free diet for the remainder of the experiment. During week 22.9-30.9, the gluten-free diet was supplemented with a daily slice of wheat bread. FH45 additionally received a daily dose of EP-B2 glutenase during the first half of this period (week 22.9-26.9). Clinical scores (A,D), anti-gliadin antibodies (B,E), and anti-TG2 antibodies (C,F) were monitored over the course of the experiment. Levels of IgG (blue; open circles) and IgA (red; open squares) antibodies are provided on the left and right ordinates, respectively. Clinical score criteria are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001857#s2" target="_blank">Methods</a>.</p
ABSTRACT Background A 4.5-month-old male colony-bred Indian rhesus macaque was presented for pres... more ABSTRACT Background A 4.5-month-old male colony-bred Indian rhesus macaque was presented for presumed trauma to the right eye. The globe was centrally distended 5 mm, with apparent hyphema and moderate to severe corneal edema. Surgical enucleation was performed. The initial histopathology report concluded chronic keratitis. Nearly 3 years later, a diagnosis of goniodysgenesis was made. The eye was sent to a veterinary ocular pathologist for definitive diagnosis. Conclusions Final conclusions were anterior segment and corneal defects. Based on the retinal pathology and optic nerve pathology, there was evidence of optic nerve atrophy, a recently described condition in macaques.
Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radic... more Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). Results ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues we...
Medical and dental records of Veterinary Dental Specialties and Oral Surgery were searched to ide... more Medical and dental records of Veterinary Dental Specialties and Oral Surgery were searched to identify dogs that received full metal prosthodontic crowns on canine teeth, using a feather or knife edge preparation between 2005 and 2017. A total of 160 teeth in 84 dogs were included in the study. Current follow-up by telephone, electronic mail, or electronic messaging was conducted, in addition to thorough record review for in-person recheck examinations. Treatment was considered successful if the prosthodontic crown was in place and no further or additional injury to the tooth had occurred at the time of reexamination, owner contact, or patient death. Tooth fracture apical to the prosthodontic crown occurred in 2 (1.25%) cases, bond failure between the tooth and the cement or the cement and the crown occurred in a single case (0.625%), and one metal crown required replacement after 3 years due to wear (0.625%), for an overall failure rate of 2.5%. These results suggest that feather p...
We explored the possibility of using normal adult rhesus macaques for the preclinical assessment ... more We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung. Our primary objective was to determine whether an intra-bronchial inoculum of at least 10(6)S. pneumoniae colony-forming units, or one as high as 10(8)-10(9) organisms, could detectably survive in rhesus macaques for a period longer than 1-2 weeks. If so, we hypothesized, it would be possible to observe signs of pneumonia commonly observed in humans, and discriminate between vaccinated/protected animals and controls. Infection was detectable in bronchoalveolar lavage fluids 3-5 weeks post-inoculation. The clinical course of disease mimicked aspects of that of human pneumococcal pneumonia. Signs of inflammation typical of the disease in humans, such as elevated concentrations of neutrophils and of pro-inflammatory cytokines in bronchoalveolar lavage fluids were also observed. These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.
Reports of transfusion-associated cases of West Nile virus (WNV) infection indicate the need for ... more Reports of transfusion-associated cases of West Nile virus (WNV) infection indicate the need for sensitive screening methods to identify WNV-infected blood products. We experimentally infected 5 rhesus macaques with WNV, to determine the level and duration of viremia, the kinetics of the humoral immune response, and the sensitivity of various assay systems for detecting WNV in blood. All macaques developed subclinical infections with low levels of viremia; nested reverse-transcription polymerase chain reaction was the most sensitive method for detecting virus or viral RNA in blood. Specific WNV antibodies appeared during the second week of infection; the results of an IgM enzyme-linked immunosorbent assay became positive on the ninth or tenth day after infection, followed in 1-2 days by hemagglutination-inhibiting and neutralizing antibodies. Our results suggest that both nucleic acid and serological testing may be needed to determine exposure to WNV and to identify potentially infected blood donors.
<p>Plasma samples collected at indicated timepoints following intragastric administration o... more <p>Plasma samples collected at indicated timepoints following intragastric administration of <sup>D3</sup>33-mer to FH09 (in remission) were analyzed by 3Q LC-MS/MS, monitoring for the <i>m/z</i> 979.5<sup>4+</sup>→263.4<sup>+</sup> transition in the positive ion SRM mode. Peak intensities are scaled relative to the highest peak in each chromatogram. Absolute intensities are indicated to the right of the ordinate axis. A <sup>D3</sup>33-mer peptide reference exhibits the same retention time and ion transitions as the peptide detected in the 180 min plasma sample.</p
<p>(A) Gastrointestinal symptoms in gluten-sensitive FH09 improve with sequential administr... more <p>(A) Gastrointestinal symptoms in gluten-sensitive FH09 improve with sequential administration of reduced gluten and gluten-free diets, but return upon reintroduction of dietary gluten (diet changes indicated by vertical arrows). Criteria that were used in clinical scoring of gluten sensitivity in the juvenile macaque FH09 were scaled relative to the healthy, age-matched control, FR26 (score 1, indicated by dotted line). Score 2 corresponded to beginning of diarrhea, e.g. pasty stools. Score 3 corresponded to semi-liquid stools and decreased activity. Score 4 corresponded to liquid stools, decreased activity, moderate dehydration and “balloon” stomach. Score 5 corresponded to liquid stools, depression, severe dehydration and balloon stomach. Score 6 would correspond to a moribund animal where prompt euthanasia is recommended. Each datapoint represents the mean of 7 daily measurements taken over the course of the indicated week. Standard deviations are indicated by error bars. (B) Anti-gliadin IgG (blue; open circles) and IgA (red; open squares) return to baseline with dietary exclusion of gluten, but are elevated following reintroduction of dietary gluten. The level of anti-gliadin IgG (blue; closed circle) and IgA (red; closed square) in control FR26 are shown for comparison. Each datapoint represents the mean of triplicate measurements. Standard deviations are indicated by error bars.</p
<p>(A) Morphometric analysis of villus height:crypt depth ratios from at least 4 different ... more <p>(A) Morphometric analysis of villus height:crypt depth ratios from at least 4 different areas of distal duodenum in gluten-sensitive FH09 and control FR26 following dietary changes. Administration of a gluten-free diet increased the V:C ratio in FH09 at week 27 to a level that is statistically equivalent to that in FR26 (constant at all time points). Reintroduction of dietary gluten resulted in a drop in V:C ratio in FH09 (week 37) relative to that in FH09 on a gluten-free diet (week 27) and to that in FR26. *P<0.05. (B–C) H&E-stained duodenum at week 37 following 10 weeks of a gluten-containing diet. 100× magnification. (B) Control macaque FR26 exhibits normal villus architecture. (C) Gluten-sensitive macaque FH09 exhibits villus blunting. (D–E) Highlighted sections in B–C were examined by immunohistochemistry. 400× magnification. (D) Anti-CD3 staining in FR26 shows few CD3+ IELs (dark brown dots in epithelium). (E) Anti-CD3 staining in FH09 shows intraepithelial lymphocytosis.</p
<p>Gluten-sensitive FH45 (A-C) and control FI96 (D-F) were switched from a gluten-containin... more <p>Gluten-sensitive FH45 (A-C) and control FI96 (D-F) were switched from a gluten-containing to a gluten-free diet at week 0, re-challenged with the gluten-containing diet from week 10.4 to 11.4, and then returned to a gluten-free diet for the remainder of the experiment. During week 22.9-30.9, the gluten-free diet was supplemented with a daily slice of wheat bread. FH45 additionally received a daily dose of EP-B2 glutenase during the first half of this period (week 22.9-26.9). Clinical scores (A,D), anti-gliadin antibodies (B,E), and anti-TG2 antibodies (C,F) were monitored over the course of the experiment. Levels of IgG (blue; open circles) and IgA (red; open squares) antibodies are provided on the left and right ordinates, respectively. Clinical score criteria are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001857#s2" target="_blank">Methods</a>.</p
ABSTRACT Background A 4.5-month-old male colony-bred Indian rhesus macaque was presented for pres... more ABSTRACT Background A 4.5-month-old male colony-bred Indian rhesus macaque was presented for presumed trauma to the right eye. The globe was centrally distended 5 mm, with apparent hyphema and moderate to severe corneal edema. Surgical enucleation was performed. The initial histopathology report concluded chronic keratitis. Nearly 3 years later, a diagnosis of goniodysgenesis was made. The eye was sent to a veterinary ocular pathologist for definitive diagnosis. Conclusions Final conclusions were anterior segment and corneal defects. Based on the retinal pathology and optic nerve pathology, there was evidence of optic nerve atrophy, a recently described condition in macaques.
Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radic... more Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). Results ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues we...
Medical and dental records of Veterinary Dental Specialties and Oral Surgery were searched to ide... more Medical and dental records of Veterinary Dental Specialties and Oral Surgery were searched to identify dogs that received full metal prosthodontic crowns on canine teeth, using a feather or knife edge preparation between 2005 and 2017. A total of 160 teeth in 84 dogs were included in the study. Current follow-up by telephone, electronic mail, or electronic messaging was conducted, in addition to thorough record review for in-person recheck examinations. Treatment was considered successful if the prosthodontic crown was in place and no further or additional injury to the tooth had occurred at the time of reexamination, owner contact, or patient death. Tooth fracture apical to the prosthodontic crown occurred in 2 (1.25%) cases, bond failure between the tooth and the cement or the cement and the crown occurred in a single case (0.625%), and one metal crown required replacement after 3 years due to wear (0.625%), for an overall failure rate of 2.5%. These results suggest that feather p...
We explored the possibility of using normal adult rhesus macaques for the preclinical assessment ... more We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung. Our primary objective was to determine whether an intra-bronchial inoculum of at least 10(6)S. pneumoniae colony-forming units, or one as high as 10(8)-10(9) organisms, could detectably survive in rhesus macaques for a period longer than 1-2 weeks. If so, we hypothesized, it would be possible to observe signs of pneumonia commonly observed in humans, and discriminate between vaccinated/protected animals and controls. Infection was detectable in bronchoalveolar lavage fluids 3-5 weeks post-inoculation. The clinical course of disease mimicked aspects of that of human pneumococcal pneumonia. Signs of inflammation typical of the disease in humans, such as elevated concentrations of neutrophils and of pro-inflammatory cytokines in bronchoalveolar lavage fluids were also observed. These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.
Reports of transfusion-associated cases of West Nile virus (WNV) infection indicate the need for ... more Reports of transfusion-associated cases of West Nile virus (WNV) infection indicate the need for sensitive screening methods to identify WNV-infected blood products. We experimentally infected 5 rhesus macaques with WNV, to determine the level and duration of viremia, the kinetics of the humoral immune response, and the sensitivity of various assay systems for detecting WNV in blood. All macaques developed subclinical infections with low levels of viremia; nested reverse-transcription polymerase chain reaction was the most sensitive method for detecting virus or viral RNA in blood. Specific WNV antibodies appeared during the second week of infection; the results of an IgM enzyme-linked immunosorbent assay became positive on the ninth or tenth day after infection, followed in 1-2 days by hemagglutination-inhibiting and neutralizing antibodies. Our results suggest that both nucleic acid and serological testing may be needed to determine exposure to WNV and to identify potentially infected blood donors.
Uploads
Papers by Erin Ribka