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Papers by Arup Roy-Burman

Research paper thumbnail of Anti-N-methyl D-Aspartate Receptor Encephalitis Mimics Viral Encephalitis

The Pediatric Infectious Disease Journal, 2012

Research paper thumbnail of Anti-N-methyl-D-aspartate receptor encephalitis complicating ovarian teratomas: a case report

American Journal of Obstetrics and Gynecology, 2011

Research paper thumbnail of Generalised cranial artery spasm in human rabies

Developments in biologicals, 2008

In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This surv... more In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This survivor and another patient with dog-associated rabies were found to have developed deficiencies of tetrahydrobiopterin (BH4) and associated neurotransmitters. BH4 is also essential for neuronal nitric oxide synthase (nNOS), so rabies is predicted to cause constriction of cerebral arteries. We assume that rabies virus, which almost exclusively targets neurons, would disproportionately affect cerebral over systemic perfusion by disrupting nNOS and lead to generalised cerebral artery spasm. Cranial artery vasospasm, therefore, was actively sought in two rabies patients, with the intention to specifically treat with BH4 and L-arginine when necessary. Flow velocities and resistive (RI) or pulsatility indices (PI) of middle cerebral arteries (MCA) were obtained by transcranial doppler ultrasound (TCD). A survival analysis of 8 attempts at the MP is presented. Of these, two cases are reported her...

Research paper thumbnail of Human rabies-Indiana and California, 2006 (Reprinted from MMWR, vol 56, pg 361-365, 2007)

Research paper thumbnail of Nucleotide Sequence and Phylogenetic Classification of Human Papillomavirus Type 59

Virology, 1994

From a basal cell carcinoma (BCC) the complete genome of candidate human papillomavirus (HPV) typ... more From a basal cell carcinoma (BCC) the complete genome of candidate human papillomavirus (HPV) type 92 was characterized. Phylogenetically, the candidate HPV 92 was relatively distantly related to other cutaneous HPV types within the B1 group. By quantitative real time PCR, 94 viral copies were present per cell in the BCC and another BCC contained 1 viral copy per cell. Lower copy numbers were found in two solar keratoses (1 copy per 33 cells and 1 copy per 60 cells) and two squamous cell carcinomas (1 copy per 436 cells and 1 copy per 1143 cells). The high viral load of HPV 92 in two BCCs differs from the low amount of HPV DNA reported from nonmelanoma skin cancers.

Research paper thumbnail of Rhinovirus Associated With Severe Lower Respiratory Tract Infections in Children

The Pediatric Infectious Disease Journal, 2009

By D7 after a single booster dose, all subjects elicited a rapid increase in RVNA concentrations.... more By D7 after a single booster dose, all subjects elicited a rapid increase in RVNA concentrations. A significant lower response in the ID groups at all time points is in accordance to previous studies with PCECV and PVRV. 5, A recent study in Thailand demonstrated the safety and immunogenicity of 2 or 3 ID doses of PCECV in school children and an anamnestic immune response after 2 simulated PEP booster doses. Studies with other rabies vaccines have reported long term immunity against rabies virus after a pre-exposure series followed by a single booster dose after 1 year. In our study, all children in the half-IM group even had RVNA concentrations Ͼ100 IU/mL on Y1 ϩ 7days. No evidence that either route or dose of concomitant administration of PCECV had an impact on JE antibodies at 1:10 serum dilution was detected.

Research paper thumbnail of Phage versus Phagemid Libraries for Generation of Human Monoclonal Antibodies

Journal of Molecular Biology, 2002

Non-immune (naïve) phage antibody libraries have become an important source of antibodies for rea... more Non-immune (naïve) phage antibody libraries have become an important source of antibodies for reagent, diagnostic, and therapeutic use. To date, reported naïve libraries have been constructed in phagemid vectors as fusions to pIII, yielding primarily single copy (monovalent) display of antibody fragments. For this work, we subcloned the single chain Fv (scFv) gene repertoire from a naïve phagemid antibody library into a true phage vector to create a multivalently displayed scFv phage library. Compared to monovalently displayed scFv, multivalent phage display resulted in improved efficiency of display as well as antibody selection. A greater number of antibodies were obtained and at earlier rounds of selection. Such increased efficiency allows the screening for binding antibodies after a single round of selection, greatly facilitating automation. Expression levels of antigen-binding scFv were also higher than from the phagemid library. In contrast, the affinities of scFv from the phage library were lower than from the phagemid library. This could be overcome by utilizing the scFv in a multivalent format, by affinity maturation, or by converting the library to monovalent display after the first round of selection.

Research paper thumbnail of Type III Protein Secretion Is Associated with Death in Lower Respiratory and Systemic Pseudomonas aeruginosa Infections

The Journal of Infectious Diseases, 2001

The ability of Pseudomonas aeruginosa to secrete specific toxins using the type III-mediated path... more The ability of Pseudomonas aeruginosa to secrete specific toxins using the type III-mediated pathway has been reported. To determine the association of this phenotype with human illness, immunoblot analysis was used to detect expression of type III secretory proteins in P. aeruginosa isolates from respiratory tract or blood cultures of 108 consecutive patients. Relative risk of mortality was 6-fold greater with expression of the type III secretory proteins ExoS, ExoT, ExoU, or PcrV. Phenotype was independently correlated with toxicity in cellular and murine models. Prevalence of this phenotype was significantly higher in acutely infected patients than in chronically infected patients with cystic fibrosis. These results suggest that the type III protein secretion system is integral to increased P. aeruginosa virulence. A positive phenotype is a predictor of poor clinical outcome. In the future, such analyses may help distinguish potentially lethal infection from colonization and help determine appropriate therapy for critically ill patients.

Research paper thumbnail of Generation and Characterization of a Protective Monoclonal Antibody to Pseudomonas aeruginosa PcrV

The Journal of Infectious Diseases, 2002

Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung inju... more Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung injury and the development of sepsis depend largely on the expression of type III secretion system (TTSS) virulence. TTSS functions as a molecular syringe to deliver toxins directly to the cytosol of cells, inhibit innate immune mechanisms, and prevent bacterial clearance. Polyclonal antibodies that bind to PcrV of P. aeruginosa inhibit the delivery of type III toxins and enhance the clearance of bacteria during acute lung infections. PcrV is a homologue of LcrV, a protective antigen in the Yersinia TTSS and an integral component of TTSS. In this study, a murine monoclonal antibody (MAb) to PcrV was generated: MAb 166, which is protective against P. aeruginosa when coinstilled with the bacterial inoculum or intraperitoneally transferred to mice. Fab fragments from MAb 166 prevent sepsis and death. The epitope bound by MAb 166 was mapped to the carboxyl-terminus of PcrV.

Research paper thumbnail of Novel HPV types present in oral papillomatous lesions from patients with HIV infection

International Journal of Cancer, 1996

Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatou... more Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69.

Research paper thumbnail of Failure of the Milwaukee Protocol in a Child With Rabies

Clinical Infectious Diseases, 2011

Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring... more Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.

Research paper thumbnail of Anti-N-methyl D-Aspartate Receptor Encephalitis Mimics Viral Encephalitis

The Pediatric Infectious Disease Journal, 2012

Research paper thumbnail of Anti-N-methyl-D-aspartate receptor encephalitis complicating ovarian teratomas: a case report

American Journal of Obstetrics and Gynecology, 2011

Research paper thumbnail of Generalised cranial artery spasm in human rabies

Developments in biologicals, 2008

In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This surv... more In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This survivor and another patient with dog-associated rabies were found to have developed deficiencies of tetrahydrobiopterin (BH4) and associated neurotransmitters. BH4 is also essential for neuronal nitric oxide synthase (nNOS), so rabies is predicted to cause constriction of cerebral arteries. We assume that rabies virus, which almost exclusively targets neurons, would disproportionately affect cerebral over systemic perfusion by disrupting nNOS and lead to generalised cerebral artery spasm. Cranial artery vasospasm, therefore, was actively sought in two rabies patients, with the intention to specifically treat with BH4 and L-arginine when necessary. Flow velocities and resistive (RI) or pulsatility indices (PI) of middle cerebral arteries (MCA) were obtained by transcranial doppler ultrasound (TCD). A survival analysis of 8 attempts at the MP is presented. Of these, two cases are reported her...

Research paper thumbnail of Human rabies-Indiana and California, 2006 (Reprinted from MMWR, vol 56, pg 361-365, 2007)

Research paper thumbnail of Nucleotide Sequence and Phylogenetic Classification of Human Papillomavirus Type 59

Virology, 1994

From a basal cell carcinoma (BCC) the complete genome of candidate human papillomavirus (HPV) typ... more From a basal cell carcinoma (BCC) the complete genome of candidate human papillomavirus (HPV) type 92 was characterized. Phylogenetically, the candidate HPV 92 was relatively distantly related to other cutaneous HPV types within the B1 group. By quantitative real time PCR, 94 viral copies were present per cell in the BCC and another BCC contained 1 viral copy per cell. Lower copy numbers were found in two solar keratoses (1 copy per 33 cells and 1 copy per 60 cells) and two squamous cell carcinomas (1 copy per 436 cells and 1 copy per 1143 cells). The high viral load of HPV 92 in two BCCs differs from the low amount of HPV DNA reported from nonmelanoma skin cancers.

Research paper thumbnail of Rhinovirus Associated With Severe Lower Respiratory Tract Infections in Children

The Pediatric Infectious Disease Journal, 2009

By D7 after a single booster dose, all subjects elicited a rapid increase in RVNA concentrations.... more By D7 after a single booster dose, all subjects elicited a rapid increase in RVNA concentrations. A significant lower response in the ID groups at all time points is in accordance to previous studies with PCECV and PVRV. 5, A recent study in Thailand demonstrated the safety and immunogenicity of 2 or 3 ID doses of PCECV in school children and an anamnestic immune response after 2 simulated PEP booster doses. Studies with other rabies vaccines have reported long term immunity against rabies virus after a pre-exposure series followed by a single booster dose after 1 year. In our study, all children in the half-IM group even had RVNA concentrations Ͼ100 IU/mL on Y1 ϩ 7days. No evidence that either route or dose of concomitant administration of PCECV had an impact on JE antibodies at 1:10 serum dilution was detected.

Research paper thumbnail of Phage versus Phagemid Libraries for Generation of Human Monoclonal Antibodies

Journal of Molecular Biology, 2002

Non-immune (naïve) phage antibody libraries have become an important source of antibodies for rea... more Non-immune (naïve) phage antibody libraries have become an important source of antibodies for reagent, diagnostic, and therapeutic use. To date, reported naïve libraries have been constructed in phagemid vectors as fusions to pIII, yielding primarily single copy (monovalent) display of antibody fragments. For this work, we subcloned the single chain Fv (scFv) gene repertoire from a naïve phagemid antibody library into a true phage vector to create a multivalently displayed scFv phage library. Compared to monovalently displayed scFv, multivalent phage display resulted in improved efficiency of display as well as antibody selection. A greater number of antibodies were obtained and at earlier rounds of selection. Such increased efficiency allows the screening for binding antibodies after a single round of selection, greatly facilitating automation. Expression levels of antigen-binding scFv were also higher than from the phagemid library. In contrast, the affinities of scFv from the phage library were lower than from the phagemid library. This could be overcome by utilizing the scFv in a multivalent format, by affinity maturation, or by converting the library to monovalent display after the first round of selection.

Research paper thumbnail of Type III Protein Secretion Is Associated with Death in Lower Respiratory and Systemic Pseudomonas aeruginosa Infections

The Journal of Infectious Diseases, 2001

The ability of Pseudomonas aeruginosa to secrete specific toxins using the type III-mediated path... more The ability of Pseudomonas aeruginosa to secrete specific toxins using the type III-mediated pathway has been reported. To determine the association of this phenotype with human illness, immunoblot analysis was used to detect expression of type III secretory proteins in P. aeruginosa isolates from respiratory tract or blood cultures of 108 consecutive patients. Relative risk of mortality was 6-fold greater with expression of the type III secretory proteins ExoS, ExoT, ExoU, or PcrV. Phenotype was independently correlated with toxicity in cellular and murine models. Prevalence of this phenotype was significantly higher in acutely infected patients than in chronically infected patients with cystic fibrosis. These results suggest that the type III protein secretion system is integral to increased P. aeruginosa virulence. A positive phenotype is a predictor of poor clinical outcome. In the future, such analyses may help distinguish potentially lethal infection from colonization and help determine appropriate therapy for critically ill patients.

Research paper thumbnail of Generation and Characterization of a Protective Monoclonal Antibody to Pseudomonas aeruginosa PcrV

The Journal of Infectious Diseases, 2002

Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung inju... more Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung injury and the development of sepsis depend largely on the expression of type III secretion system (TTSS) virulence. TTSS functions as a molecular syringe to deliver toxins directly to the cytosol of cells, inhibit innate immune mechanisms, and prevent bacterial clearance. Polyclonal antibodies that bind to PcrV of P. aeruginosa inhibit the delivery of type III toxins and enhance the clearance of bacteria during acute lung infections. PcrV is a homologue of LcrV, a protective antigen in the Yersinia TTSS and an integral component of TTSS. In this study, a murine monoclonal antibody (MAb) to PcrV was generated: MAb 166, which is protective against P. aeruginosa when coinstilled with the bacterial inoculum or intraperitoneally transferred to mice. Fab fragments from MAb 166 prevent sepsis and death. The epitope bound by MAb 166 was mapped to the carboxyl-terminus of PcrV.

Research paper thumbnail of Novel HPV types present in oral papillomatous lesions from patients with HIV infection

International Journal of Cancer, 1996

Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatou... more Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69.

Research paper thumbnail of Failure of the Milwaukee Protocol in a Child With Rabies

Clinical Infectious Diseases, 2011

Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring... more Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.