Giri Venkatraman - Academia.edu (original) (raw)

Papers by Giri Venkatraman

Research paper thumbnail of Dosing of sublingual immunotherapy for allergic rhinitis: evidence-based review with recommendations

International forum of allergy & rhinology, Jan 11, 2015

Since the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increas... more Since the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increased. However, 1 of the primary barriers to providing SLIT is lack of a published dosing recommendations. The purpose of this work is to provide a range of effective SLIT dosing based upon a rigorous review of the existing evidence base. An appendix with SLIT dosing recommendations is also included. A comprehensive search of the past 25 years of the medical literature using PubMed was performed for specific antigens. Inclusion criteria for articles included: randomized, placebo-controlled studies of SLIT, studies with clinical allergic rhinitis outcomes, and dosing units available to determine the micrograms per month of major allergen administered. The extracted data was used to compile a range of effective SLIT dosing for individual antigens. Seventy-five articles met the inclusion criteria, providing a range of effective dosing for some allergens. There was commonly a wide range in dose...

Research paper thumbnail of Retroviral manipulation of the expression of bone morphogenetic protein receptor Ia by SVZa progenitor cells leads to changes in their p19INK4d expression but not in their neuronal commitment

International Journal of Developmental Neuroscience, 2001

Bone morphogenetic proteins (BMPs), a group of cytokines in the TGF-b superfamily, have complex r... more Bone morphogenetic proteins (BMPs), a group of cytokines in the TGF-b superfamily, have complex regulatory roles in the control of neural proliferation and cell fate decision. In this study, we analyzed the potential role(s) of BMP signaling on the regulation of the proliferation and differentiation of the unique progenitor cells of the neonatal anterior subventricular zone (SVZa). Unlike other progenitor cells of the brain, SVZa progenitor cells have the capacity to divide even though they express a neuronal phenotype. In order to augment or inhibit endogenous BMP signaling, we injected into the neonatal rat SVZa replication-deficient retroviruses encoding for either the wild-type BMP receptor subtype Ia (wt-BMPR-Ia) or a mutated dominant-negative version of BMPR-Ia (dn-BMPR-Ia) in conjunction with a reporter gene, human alkaline phosphatase (AP) and perfused the pups 1, 4 and 7 days post injection. We analyzed whether changing the expression of BMPR-Ia has an effect on the spatial-temporal expression pattern of the cyclin dependent kinase inhibitor, p19 INK4d , or on the phenotype of SVZa derived cells. The results of our study confirmed and extended our previous findings that in control (non injected) animals, the rostral migratory stream (RMS), traversed by the SVZa-derived cells en route to the olfactory bulb, exhibits an anterior high -posterior low gradient of p19 INK4d expression; p19 INK4d expression is essentially absent in the SVZa and highest in the subependymal zone in the middle of the olfactory bulb. However, SVZa progenitor cells encoding the wt-BMPR-Ia gene express p19 INK4d within the SVZa, suggesting that the BMPs induce SVZa cells to ectopically undergo cell cycle exit within the SVZa. Furthermore, unlike striatal SVZ progenitor cells, which acquire an astrocytic phenotype when exposed to BMPs, SVZa progenitor cells retain their neuronal commitment under augmented BMP signaling.

Research paper thumbnail of Neuronal Restricted Precursors

Stem Cells and CNS Development, 2001

Research paper thumbnail of Macrolide Therapy for Chronic Rhinosinusitis: A Meta-analysis

Otolaryngology -- Head and Neck Surgery, 2013

The objective of this study was to systematically review patient-reported outcomes of long-term m... more The objective of this study was to systematically review patient-reported outcomes of long-term macrolide therapy, compared with any other treatment, for adults with chronic rhinosinusitis. EMBASE and PubMed databases were searched in October 2011. A total of 1216 citations were screened initially by a single author, 23 full-text manuscripts were evaluated by 2 authors using structured data abstraction forms to assess for inclusion criteria and study quality, and 3 studies were included in the final review. This review finds that 3 prospective clinical studies have evaluated the effect of macrolide therapy for chronic rhinosinusitis. Based on the limited data, there is limited scientific evidence to support the use of long-term macrolide therapy for chronic rhinosinusitis. Further clinical research is needed to determine whether there may be a subgroup effect based on the underlying inflammatory disease process.

Research paper thumbnail of BMP mRNA and protein expression in the developing mouse olfactory system

The Journal of Comparative Neurology, 2002

The bone morphogenetic proteins (BMPs) play fundamental roles during the organization of the cent... more The bone morphogenetic proteins (BMPs) play fundamental roles during the organization of the central nervous system. The presence of these proteins has also been demonstrated in regions of the adult brain that are characterized by neural plasticity. In this study, we examined the expression of BMP4, 6, and 7 mRNAs and proteins in the murine olfactory system. The olfactory system is a useful model for studying cell proliferation and neural differentiation because both of these processes persist throughout life in the olfactory epithelium (OE) and olfactory bulb (OB). Our results demonstrate a differential expression of BMP4, 6, and 7 in the embryonic, postnatal, and adult olfactory system. In particular, BMP4 and BMP7 showed similar immunostaining patterns, being expressed in the olfactory region from the earliest stages studied (embryonic day 15.5) to adulthood. During development BMPs were expressed in the OE, olfactory bulb nerve layer, glomerular layer (GL), mitral cell layer (MCL), and subventricular zone. During the first postnatal week of life, BMP4 and 7 immunoreactivity (-ir) was particularly evident in the GL, MCL, and in the subependymal layer (SEL), which originates postnatally from the subventricular zone. In adults, BMP4 and 7 immunostaining was present in the GL and SEL. Within the SEL, BMP4 and 7 proteins were expressed primarily in association with the astrocytic glial compartment. BMP6-ir was always found in mature olfactory receptor neurons and their axonal projections to the OB. In summary, these data support the hypothesis that BMPs play a role in the morphogenesis of the olfactory system during development and in its plasticity during adulthood.

Research paper thumbnail of Expression of Coxsackie-Adenovirus receptor (CAR) in the developing mouse olfactory system

Journal of Neurocytology, 2005

Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use o... more Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use of adenoviruses (AdV) as gene delivery vectors. OSNs are the first order neurons in the olfactory system and the initial site of odor detection. They are highly susceptible to adenovirus infection although the mechanism is poorly understood. The Coxsackie-Adenovirus receptor (CAR) and members of the integrin family have been implicated in the process of AdV infection in various systems. Multiple serotypes of AdV efficiently bind to the CAR, leading to entry and infection of the host cell by a mechanism that can also involve integrins. Cell lines that do not express CAR are relatively resistant, but not completely immune to AdV infection, suggesting that other mechanisms participate in mediating AdV attachment and entry. Using in situ hybridization and western blot analyses, we show that OSNs and olfactory bulbs (OB) of mice express abundant CAR mRNA at embryonic and neonatal stages, with progressive diminution during postnatal development. By contrast to the olfactory epithelium (OE), CAR mRNA is still present in the adult mouse OB. Furthermore, despite a similar postnatal decline, CAR protein expression in the OE and OB of mice continues into adulthood. Our results suggest that the robust AdV infection observed in the postnatal olfactory system is mediated by CAR and that expression of even small amounts of CAR protein as seen in the adult rodent, permits efficient AdV infection and entry. CAR is an immunoglobulin domain-containing protein that bears homology to cell-adhesion molecules suggesting the possibility that it may participate in organization of the developing olfactory system.

Research paper thumbnail of Multiplanar Computed Tomographic Analysis of Frontal Recess Cells

Archives of Otolaryngology–Head & Neck Surgery, 2005

Frontal recess anatomy can be very complex, with accessory cells such as frontal, agger nasi, and... more Frontal recess anatomy can be very complex, with accessory cells such as frontal, agger nasi, and intersinus septal cells encroaching on the frontal recess and possibly contributing to obstruction of the frontal sinus. In this study, we determined the prevalence of these cells and their relationship to frontal sinusitis in patients who have (revision group) and have not (primary group) had previous sinus surgery. Multiplanar computed tomographic images were reconstructed on a computer workstation to determine the presence of frontal, agger nasi, and intersinus septal cells and frontal sinusitis. We also measured the diameter and area of the frontal isthmus for each sinonasal cavity. We were able to retrieve 106 of 117 images from a surgical database encompassing the previous 2 years. Tertiary care academic practice of the senior author. Frontal cells were found in 25.5% of frontal recesses, including 29.6% of sides in the primary group and 21.9% of sides in the revision group. We identified 33.0% of patients as having unilateral or bilateral frontal cells. Type I cells were the most common cell (18.4% of primary sinuses). The presence of frontal sinusitis and the diameter and area of the frontal isthmus were not significantly different for those patients with compared with patients without frontal cells. Intact agger nasi cells were identified in 86.7% of primary sinuses and 53.5% of revision sinuses. There was no increased incidence of frontal sinusitis in patients with persistent agger nasi cells in the revision group. When we evaluated multiplanar reconstructions, we identified frontal cells in 33.0% of patients overall, which was more common than previously reported. The findings of agger nasi cells indicated that these cells were likely addressed in less than half of previous sinus procedures. However, frontal cells and retained agger nasi cells were not associated with a higher incidence of frontal sinusitis, and there was no association between the size of the frontal isthmus and the presence of frontal sinusitis. Although anatomic variations in the frontal recess are likely to play a role in frontal sinusitis, mucosal inflammatory processes are likely to be a much more important etiologic factor.

Research paper thumbnail of External Auditory Canal Wall Cholesteatoma: A Complication of Ear Surgery

Acta Oto-laryngologica, 1997

Primary external auditory canal wall cholesteatomas are usually present in the inferior portion o... more Primary external auditory canal wall cholesteatomas are usually present in the inferior portion of the canal lateral to the tympanic membrane. Small inclusion cysts are a common finding along incision lines after ear surgery. This report details 5 cases of large canal wall cholesteatomas after prior ear surgery. The middle ear or mastoid was not directly involved in any of the cases. The largest of these presented 8 years after the initial procedure and eroded in the middle and temporal fossae. A common feature among these patients was an extended period in which the patient was lost to follow-up after surgery. This experience reinforces the need for vigilant long term follow up even in the asymptomatic postoperative patient.

Research paper thumbnail of NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression

European Journal of Neuroscience, 2000

Nuclear factor I (NFI) proteins are DNA-binding transcription factors that participate in the tis... more Nuclear factor I (NFI) proteins are DNA-binding transcription factors that participate in the tissue speci®c expression of various genes. They are encoded by four different genes (NFI-A, B, C, and X) each of which generates multiple isoforms by alternative RNA splicing. NFI-like binding sites have been identi®ed in several genes preferentially expressed in olfactory receptor neurons. Our prior demonstration that NFI binds to these elements led to the hypothesis that NFI is involved in the regulation of these genes. To analyse the role of NFI in the regulation of olfactory neuron gene expression we have performed transient transfection experiments in HEK 293 cells using constructs that place luciferase expression under the control of an olfactory marker protein (OMP)-promoter fragment containing the NFI binding site. In vitro mutagenesis of this site revealed a negative modulation of luciferase expression by endogenous NFI proteins in HEK 293 cells. In addition, we have used in situ hybridization to analyse the tissue and cellular distribution of the four NFI gene transcripts during pre-and postnatal mouse development. We have simultaneously characterized the expression of Pax-6, and O/E-1, transcription factors known to regulate the phenotype of olfactory receptor neurons. We demonstrate that all of these transcription factors vary in speci®c spatio±temporal patterns during the development of the olfactory system. These data on NFI activity, and on transcription factor expression, provide a basis to understand the role of NFI in regulating gene expression in olfactory receptor neurons.

Research paper thumbnail of Dosing of sublingual immunotherapy for allergic rhinitis: evidence-based review with recommendations

International forum of allergy & rhinology, Jan 11, 2015

Since the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increas... more Since the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increased. However, 1 of the primary barriers to providing SLIT is lack of a published dosing recommendations. The purpose of this work is to provide a range of effective SLIT dosing based upon a rigorous review of the existing evidence base. An appendix with SLIT dosing recommendations is also included. A comprehensive search of the past 25 years of the medical literature using PubMed was performed for specific antigens. Inclusion criteria for articles included: randomized, placebo-controlled studies of SLIT, studies with clinical allergic rhinitis outcomes, and dosing units available to determine the micrograms per month of major allergen administered. The extracted data was used to compile a range of effective SLIT dosing for individual antigens. Seventy-five articles met the inclusion criteria, providing a range of effective dosing for some allergens. There was commonly a wide range in dose...

Research paper thumbnail of Retroviral manipulation of the expression of bone morphogenetic protein receptor Ia by SVZa progenitor cells leads to changes in their p19INK4d expression but not in their neuronal commitment

International Journal of Developmental Neuroscience, 2001

Bone morphogenetic proteins (BMPs), a group of cytokines in the TGF-b superfamily, have complex r... more Bone morphogenetic proteins (BMPs), a group of cytokines in the TGF-b superfamily, have complex regulatory roles in the control of neural proliferation and cell fate decision. In this study, we analyzed the potential role(s) of BMP signaling on the regulation of the proliferation and differentiation of the unique progenitor cells of the neonatal anterior subventricular zone (SVZa). Unlike other progenitor cells of the brain, SVZa progenitor cells have the capacity to divide even though they express a neuronal phenotype. In order to augment or inhibit endogenous BMP signaling, we injected into the neonatal rat SVZa replication-deficient retroviruses encoding for either the wild-type BMP receptor subtype Ia (wt-BMPR-Ia) or a mutated dominant-negative version of BMPR-Ia (dn-BMPR-Ia) in conjunction with a reporter gene, human alkaline phosphatase (AP) and perfused the pups 1, 4 and 7 days post injection. We analyzed whether changing the expression of BMPR-Ia has an effect on the spatial-temporal expression pattern of the cyclin dependent kinase inhibitor, p19 INK4d , or on the phenotype of SVZa derived cells. The results of our study confirmed and extended our previous findings that in control (non injected) animals, the rostral migratory stream (RMS), traversed by the SVZa-derived cells en route to the olfactory bulb, exhibits an anterior high -posterior low gradient of p19 INK4d expression; p19 INK4d expression is essentially absent in the SVZa and highest in the subependymal zone in the middle of the olfactory bulb. However, SVZa progenitor cells encoding the wt-BMPR-Ia gene express p19 INK4d within the SVZa, suggesting that the BMPs induce SVZa cells to ectopically undergo cell cycle exit within the SVZa. Furthermore, unlike striatal SVZ progenitor cells, which acquire an astrocytic phenotype when exposed to BMPs, SVZa progenitor cells retain their neuronal commitment under augmented BMP signaling.

Research paper thumbnail of Neuronal Restricted Precursors

Stem Cells and CNS Development, 2001

Research paper thumbnail of Macrolide Therapy for Chronic Rhinosinusitis: A Meta-analysis

Otolaryngology -- Head and Neck Surgery, 2013

The objective of this study was to systematically review patient-reported outcomes of long-term m... more The objective of this study was to systematically review patient-reported outcomes of long-term macrolide therapy, compared with any other treatment, for adults with chronic rhinosinusitis. EMBASE and PubMed databases were searched in October 2011. A total of 1216 citations were screened initially by a single author, 23 full-text manuscripts were evaluated by 2 authors using structured data abstraction forms to assess for inclusion criteria and study quality, and 3 studies were included in the final review. This review finds that 3 prospective clinical studies have evaluated the effect of macrolide therapy for chronic rhinosinusitis. Based on the limited data, there is limited scientific evidence to support the use of long-term macrolide therapy for chronic rhinosinusitis. Further clinical research is needed to determine whether there may be a subgroup effect based on the underlying inflammatory disease process.

Research paper thumbnail of BMP mRNA and protein expression in the developing mouse olfactory system

The Journal of Comparative Neurology, 2002

The bone morphogenetic proteins (BMPs) play fundamental roles during the organization of the cent... more The bone morphogenetic proteins (BMPs) play fundamental roles during the organization of the central nervous system. The presence of these proteins has also been demonstrated in regions of the adult brain that are characterized by neural plasticity. In this study, we examined the expression of BMP4, 6, and 7 mRNAs and proteins in the murine olfactory system. The olfactory system is a useful model for studying cell proliferation and neural differentiation because both of these processes persist throughout life in the olfactory epithelium (OE) and olfactory bulb (OB). Our results demonstrate a differential expression of BMP4, 6, and 7 in the embryonic, postnatal, and adult olfactory system. In particular, BMP4 and BMP7 showed similar immunostaining patterns, being expressed in the olfactory region from the earliest stages studied (embryonic day 15.5) to adulthood. During development BMPs were expressed in the OE, olfactory bulb nerve layer, glomerular layer (GL), mitral cell layer (MCL), and subventricular zone. During the first postnatal week of life, BMP4 and 7 immunoreactivity (-ir) was particularly evident in the GL, MCL, and in the subependymal layer (SEL), which originates postnatally from the subventricular zone. In adults, BMP4 and 7 immunostaining was present in the GL and SEL. Within the SEL, BMP4 and 7 proteins were expressed primarily in association with the astrocytic glial compartment. BMP6-ir was always found in mature olfactory receptor neurons and their axonal projections to the OB. In summary, these data support the hypothesis that BMPs play a role in the morphogenesis of the olfactory system during development and in its plasticity during adulthood.

Research paper thumbnail of Expression of Coxsackie-Adenovirus receptor (CAR) in the developing mouse olfactory system

Journal of Neurocytology, 2005

Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use o... more Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use of adenoviruses (AdV) as gene delivery vectors. OSNs are the first order neurons in the olfactory system and the initial site of odor detection. They are highly susceptible to adenovirus infection although the mechanism is poorly understood. The Coxsackie-Adenovirus receptor (CAR) and members of the integrin family have been implicated in the process of AdV infection in various systems. Multiple serotypes of AdV efficiently bind to the CAR, leading to entry and infection of the host cell by a mechanism that can also involve integrins. Cell lines that do not express CAR are relatively resistant, but not completely immune to AdV infection, suggesting that other mechanisms participate in mediating AdV attachment and entry. Using in situ hybridization and western blot analyses, we show that OSNs and olfactory bulbs (OB) of mice express abundant CAR mRNA at embryonic and neonatal stages, with progressive diminution during postnatal development. By contrast to the olfactory epithelium (OE), CAR mRNA is still present in the adult mouse OB. Furthermore, despite a similar postnatal decline, CAR protein expression in the OE and OB of mice continues into adulthood. Our results suggest that the robust AdV infection observed in the postnatal olfactory system is mediated by CAR and that expression of even small amounts of CAR protein as seen in the adult rodent, permits efficient AdV infection and entry. CAR is an immunoglobulin domain-containing protein that bears homology to cell-adhesion molecules suggesting the possibility that it may participate in organization of the developing olfactory system.

Research paper thumbnail of Multiplanar Computed Tomographic Analysis of Frontal Recess Cells

Archives of Otolaryngology–Head & Neck Surgery, 2005

Frontal recess anatomy can be very complex, with accessory cells such as frontal, agger nasi, and... more Frontal recess anatomy can be very complex, with accessory cells such as frontal, agger nasi, and intersinus septal cells encroaching on the frontal recess and possibly contributing to obstruction of the frontal sinus. In this study, we determined the prevalence of these cells and their relationship to frontal sinusitis in patients who have (revision group) and have not (primary group) had previous sinus surgery. Multiplanar computed tomographic images were reconstructed on a computer workstation to determine the presence of frontal, agger nasi, and intersinus septal cells and frontal sinusitis. We also measured the diameter and area of the frontal isthmus for each sinonasal cavity. We were able to retrieve 106 of 117 images from a surgical database encompassing the previous 2 years. Tertiary care academic practice of the senior author. Frontal cells were found in 25.5% of frontal recesses, including 29.6% of sides in the primary group and 21.9% of sides in the revision group. We identified 33.0% of patients as having unilateral or bilateral frontal cells. Type I cells were the most common cell (18.4% of primary sinuses). The presence of frontal sinusitis and the diameter and area of the frontal isthmus were not significantly different for those patients with compared with patients without frontal cells. Intact agger nasi cells were identified in 86.7% of primary sinuses and 53.5% of revision sinuses. There was no increased incidence of frontal sinusitis in patients with persistent agger nasi cells in the revision group. When we evaluated multiplanar reconstructions, we identified frontal cells in 33.0% of patients overall, which was more common than previously reported. The findings of agger nasi cells indicated that these cells were likely addressed in less than half of previous sinus procedures. However, frontal cells and retained agger nasi cells were not associated with a higher incidence of frontal sinusitis, and there was no association between the size of the frontal isthmus and the presence of frontal sinusitis. Although anatomic variations in the frontal recess are likely to play a role in frontal sinusitis, mucosal inflammatory processes are likely to be a much more important etiologic factor.

Research paper thumbnail of External Auditory Canal Wall Cholesteatoma: A Complication of Ear Surgery

Acta Oto-laryngologica, 1997

Primary external auditory canal wall cholesteatomas are usually present in the inferior portion o... more Primary external auditory canal wall cholesteatomas are usually present in the inferior portion of the canal lateral to the tympanic membrane. Small inclusion cysts are a common finding along incision lines after ear surgery. This report details 5 cases of large canal wall cholesteatomas after prior ear surgery. The middle ear or mastoid was not directly involved in any of the cases. The largest of these presented 8 years after the initial procedure and eroded in the middle and temporal fossae. A common feature among these patients was an extended period in which the patient was lost to follow-up after surgery. This experience reinforces the need for vigilant long term follow up even in the asymptomatic postoperative patient.

Research paper thumbnail of NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression

European Journal of Neuroscience, 2000

Nuclear factor I (NFI) proteins are DNA-binding transcription factors that participate in the tis... more Nuclear factor I (NFI) proteins are DNA-binding transcription factors that participate in the tissue speci®c expression of various genes. They are encoded by four different genes (NFI-A, B, C, and X) each of which generates multiple isoforms by alternative RNA splicing. NFI-like binding sites have been identi®ed in several genes preferentially expressed in olfactory receptor neurons. Our prior demonstration that NFI binds to these elements led to the hypothesis that NFI is involved in the regulation of these genes. To analyse the role of NFI in the regulation of olfactory neuron gene expression we have performed transient transfection experiments in HEK 293 cells using constructs that place luciferase expression under the control of an olfactory marker protein (OMP)-promoter fragment containing the NFI binding site. In vitro mutagenesis of this site revealed a negative modulation of luciferase expression by endogenous NFI proteins in HEK 293 cells. In addition, we have used in situ hybridization to analyse the tissue and cellular distribution of the four NFI gene transcripts during pre-and postnatal mouse development. We have simultaneously characterized the expression of Pax-6, and O/E-1, transcription factors known to regulate the phenotype of olfactory receptor neurons. We demonstrate that all of these transcription factors vary in speci®c spatio±temporal patterns during the development of the olfactory system. These data on NFI activity, and on transcription factor expression, provide a basis to understand the role of NFI in regulating gene expression in olfactory receptor neurons.