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Papers by Sumit Singh

Research paper thumbnail of Safety of 5914 intravitreal ziv-aflibercept injections

The British journal of ophthalmology, Jan 11, 2018

To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retin... more To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke an...

Research paper thumbnail of Discrepancy in current central serous chorioretinopathy classification

The British journal of ophthalmology, Jan 12, 2018

To report the discordance in central serous chorioretinopathy (CSCR) classification among practis... more To report the discordance in central serous chorioretinopathy (CSCR) classification among practising retina specialists. The study conducted was a multicentre survey. Multimodal retinal images along with relevant clinical details of 100 cases diagnosed as CSCR (from six centres) were circulated among six retina specialists across the globe. The image sets included colour fundus photographs, fundus autofluorescence images, optical coherence tomography b-scans, fluorescein and indocyanine green angiography of the study and fellow eyes. The graders were asked to classify the disease of study eye, according to their own criteria. The graders were masked to the responses of other graders. The final analysis of the pooled response data was done based on the diagnosis of study eye only. The main outcome measure was degree of agreement between six independent observers using Fleiss Kappa statistics. Grading for 100 eyes of 100 patients (men, 93%) was included in the analysis. 20 patients ha...

Research paper thumbnail of Wide Field choroidal vascularity in healthy eyes

American journal of ophthalmology, Jan 26, 2018

To report variation of choroidal vascularity index (CVI) in macular and mid-equator areas in heal... more To report variation of choroidal vascularity index (CVI) in macular and mid-equator areas in healthy subjects using wide field optical coherence tomography (WF-OCT). Prospective, cross-sectional study. SETTING: Two centers study. Twenty eyes of 20 healthy subjects OBSERVATION PROCEDURE: Single high-definition scan passing through the fovea in both vertical and horizontal meridian were studied. Images were taken in primary and extremes of gaze and a manual montage was created. Previously reported semi automated algorithm was used to calculate the CVI in macular, superior, inferior, temporal and nasal quadrants. Difference in CVI in macular and four quadrants RESULTS: Twenty eyes from 20 subjects were enrolled in the study. The mean age was 28.85±6.29 years with males comprising 9/20 (45.0%).The refractive error(spherical equivalent) ranged from -3.00 D to +0.75 D. The average CVI in the macular area (40.01±7.67) was significantly smaller than in any of the other fundus areas (all p&l...

Research paper thumbnail of Surgical Outcomes After Inverted Internal Limiting Membrane Flap Versus Conventional Peeling for Very Large Macular Holes

Retina (Philadelphia, Pa.), Jan 23, 2018

To evaluate the anatomical and visual outcomes of inverted flap technique of peeling of internal ... more To evaluate the anatomical and visual outcomes of inverted flap technique of peeling of internal limiting membrane (ILM) versus standard peeling of ILM for macular holes of basal diameter more than 800 μm. Patients with very large idiopathic macular holes more than 800 μm in basal diameter (ranging from 243 μm to 840 μm in minimum diameter) were retrospectively included in the study. In Group A, 18 eyes of 18 patients underwent ILM peeling using the inverted flap technique. In Group B, 18 eyes of 18 patients underwent conventional ILM peeling. The primary endpoint was the rate of hole closure at 6 months after surgery. The secondary outcome measure was the change in best-corrected visual acuity at 6 months after surgery. There were no significant differences in ocular characteristics of the study groups at baseline except for the age distribution. Mean macular hole diameter was 1,162.8 ± 206.0 μm and 1,229.6 ± 228.1 μm in Group A and Group B, respectively. The hole closure rate was ...

Research paper thumbnail of Retinal pigment epithelium rip following single intravitreal ziv-aflibercept injection

Indian journal of ophthalmology, 2018

Manuscript received: 12.09.17; Revision accepted: 17.11.17 A 40‐year‐old male presented with dimi... more Manuscript received: 12.09.17; Revision accepted: 17.11.17 A 40‐year‐old male presented with diminished vision (visual acuity 20/30) in the right eye for 4 years. Fundus examination revealed hard drusen with subretinal hemorrhage inferior to fovea [Fig. 1a]. Autofluorescence showed punctate hyperautofluorescence due to drusen and hypoautofluorescence due to subretinal hemorrhage [Fig. 1b]. Fluorescein angiography showed the presence of pooling in the area of retinal pigment epithelium detachment (PED) with temporal leakage suggestive of the occult choroidal neovascular membrane (CNVM). Swept‐source optical coherence tomography (SS‐OCT) showed the presence of large PED and irregular RPE folds (thick arrow) with the presence of hyperreflectivity (thin arrow) at sub‐RPE level [Fig. 1c]. The patient was advised intravitreal ziv‐aflibercept (IVZ) injection (1.25 mg/0.05 ml) under standard protocol. At 1 month, vision had dropped to 20/80. Fundus showed the increased area of subretinal hemorrhage with visible deeper choroidal vessels (arrows) [Fig. 2a]. Autofluorescence showed the presence of hypoautofluoresecence nasally and temporally (asterisk) with central hyperautofluorescence suggestive of double RPE rip [Fig. 2b]. SS‐OCT showed the presence of irregular RPE folds with RPE rip (arrow) [Fig. 2c].

Research paper thumbnail of Assessing analytical comparability of biosimilars: GCSF as a case study

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 21, 2016

The biosimilar industry is witnessing an unprecedented growth with the newer therapeutics increas... more The biosimilar industry is witnessing an unprecedented growth with the newer therapeutics increasing in complexity over time. A key step towards development of a biosimilar is to establish analytical comparability with the innovator product, which would otherwise affect the safety/efficacy profile of the product. Choosing appropriate analytical tools that can fulfil this objective by qualitatively and/or quantitatively assessing the critical quality attributes (CQAs) of the product is highly critical for establishing equivalence. These CQAs cover the primary and higher order structures of the product, product related variants and impurities, as well as process related impurities, and host cell related impurities. In the present work, we use such an analytical platform for assessing comparability of five approved Granulocyte Colony Stimulating Factor (GCSF) biosimilars (Emgrast, Lupifil, Colstim, Neukine and Grafeel) to the innovator product, Neupogen(®). The comparability studies in...

Research paper thumbnail of Should charge variants of monoclonal antibody therapeutics be considered critical quality attributes?

Electrophoresis, Sep 8, 2016

Charge variants, namely acidic and basic variants, are typically found in monoclonal antibody the... more Charge variants, namely acidic and basic variants, are typically found in monoclonal antibody therapeutics. Charge heterogeneity is typically not regarded to affect safety and efficacy of the product. As a result, the commonly followed approach involves assignment of a specification for the variants based on statistical analysis of variability in levels that is seen during commercial manufacturing. This is followed by monitoring of product quality to demonstrate consistency. This paper aims to demonstrate that this perception of charge variants warrants a more in-depth investigation to evaluate the role charge variants play in safety and efficacy of a monoclonal antibody therapeutic. In addition, a novel procedure has been suggested for making this assessment and alleviate the problems that are traditionally faced when isolating these variants for characterization. The suggested procedure utilizes the principles of bioseparations, cell biology, and statistics and it is demonstrated ...

Research paper thumbnail of Case Report Of Solitary Eccrine Spiradenoma Of Eyelid

European Ophthalmic Review, 2015

Eccrine spiradenoma, a sweat gland tumor, is rarely found in the eyelid. We encountered a 73-year... more Eccrine spiradenoma, a sweat gland tumor, is rarely found in the eyelid. We encountered a 73-year-old man with a nodular growth in his left upper eyelid, which had developed over the last 12 years. He had developed mild pain in the past. Excision was carried out under local anesthesia in a pentagon fashion with clear margins. The histopathology was suggestive for a benign eccrine spiradenoma.

Research paper thumbnail of Case Report of Isolated Schwannoma—A Rare Eyelid Tumor

US Ophthalmic Review, 2014

Schwannoma (neurilemmoma) is a benign tumor of the peripheral nerve arising from Schwann cells th... more Schwannoma (neurilemmoma) is a benign tumor of the peripheral nerve arising from Schwann cells that form the neural sheath. Schwannoma of ophthalmic interest is rare. Although it has been reported in relation to the orbit, and less frequently with the uveal tract and conjunctiva, instances of eyelid Schwannoma are extremely uncommon. We report a case of a 18-year-old male who developed eyelid Schwannoma. The mass was surgically removed by excisional biopsy. The histopathologic examination showed Schwannoma.

Research paper thumbnail of Object oriented modelling and development of a dispatching algorithm for automated guided vehicles

The International Journal of Advanced Manufacturing Technology, 2004

The main problem for an automated guided vehicle (AGV) dispatching system is to assign vehicles t... more The main problem for an automated guided vehicle (AGV) dispatching system is to assign vehicles to transport demands which optimise some predetermined objectives of a manufacturing shop. This paper presents a framework for an AGV dispatching system based on an object oriented approach using the unified modelling language (UML), and the development of a dispatching algorithm to facilitate a human controller to dispatch efficiently a fleet of AGVs in response to calls from any shop floor (or machine) operator. The main reason for this work is to model an AGV dispatching system as well as to develop a dispatching algorithm which can record details of the AGV position and movement and ensure their allocation of new orders. The provision of both immediate and pre-booked orders for an AGV is also incorporated in the proposed AGVs dispatching system. The underlying AGV dispatching system and algorithm are capable of dispatching a vehicle automatically to handle a call at the required time. In order to overcome difficulties associated with tackling immediate orders, pre-booked orders, and processing of information related to AGVs, a comprehensive dispatching algorithm is developed which aims to minimise lateness, traveling time and distance of empty vehicles in a simulated jobshop scenario. The effectiveness of the proposed framework for an AGV dispatching system is shown through a test problem.

Research paper thumbnail of Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis

British Journal of Dermatology, 2013

Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly t... more Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly through enhanced sensory nerve-skin mast cell interaction. Cell adhesion molecule 1 (CADM1) is a mast-cell adhesion molecule that mediates the adhesion to, and communication with, sympathetic nerves. To investigate the role of mast cell CADM1 in the pathogenesis of AD, CADM1 expression levels by comparing between lesional and nonlesional skin mast cells of an AD mouse model, which was developed by repeated application of trinitrochlorobenzene, and to examine, in cocultures, how the alterations in CADM1 detected in lesional mast cells might affect the sensory nerve-mast cell interaction. AD-like lesional and nonlesional skin mast cells were collected separately by laser capture microdissection. CADM1 expression was examined by reverse transcription-polymerase chain reaction and CADM1 immunohistochemistry. In cocultures, adhesion between dorsal root ganglion (DRG) neurites and IC2 mast cells was analysed by loading a femtosecond laser-induced impulsive force on neurite-attendant IC2 cells, while cellular communication was monitored as the IC2 cellular response ([Ca(2+)]i increase) after nerve-specific stimulant-induced DRG activation. AD-like lesional mast cells expressed three-fold more CADM1 transcripts than nonlesional cells. This was supported at the protein level, shown by immunohistochemistry. In coculture, CADM1 overexpression in IC2 cells strengthened DRG neurite-IC2 cell adhesion and doubled the population of IC2 cells responding to DRG activation. A function-blocking anti-CADM1 antibody abolished these effects in a dose-dependent manner. Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced mouse model of AD.

Research paper thumbnail of Safety of 5914 intravitreal ziv-aflibercept injections

The British journal of ophthalmology, Jan 11, 2018

To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retin... more To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke an...

Research paper thumbnail of Discrepancy in current central serous chorioretinopathy classification

The British journal of ophthalmology, Jan 12, 2018

To report the discordance in central serous chorioretinopathy (CSCR) classification among practis... more To report the discordance in central serous chorioretinopathy (CSCR) classification among practising retina specialists. The study conducted was a multicentre survey. Multimodal retinal images along with relevant clinical details of 100 cases diagnosed as CSCR (from six centres) were circulated among six retina specialists across the globe. The image sets included colour fundus photographs, fundus autofluorescence images, optical coherence tomography b-scans, fluorescein and indocyanine green angiography of the study and fellow eyes. The graders were asked to classify the disease of study eye, according to their own criteria. The graders were masked to the responses of other graders. The final analysis of the pooled response data was done based on the diagnosis of study eye only. The main outcome measure was degree of agreement between six independent observers using Fleiss Kappa statistics. Grading for 100 eyes of 100 patients (men, 93%) was included in the analysis. 20 patients ha...

Research paper thumbnail of Wide Field choroidal vascularity in healthy eyes

American journal of ophthalmology, Jan 26, 2018

To report variation of choroidal vascularity index (CVI) in macular and mid-equator areas in heal... more To report variation of choroidal vascularity index (CVI) in macular and mid-equator areas in healthy subjects using wide field optical coherence tomography (WF-OCT). Prospective, cross-sectional study. SETTING: Two centers study. Twenty eyes of 20 healthy subjects OBSERVATION PROCEDURE: Single high-definition scan passing through the fovea in both vertical and horizontal meridian were studied. Images were taken in primary and extremes of gaze and a manual montage was created. Previously reported semi automated algorithm was used to calculate the CVI in macular, superior, inferior, temporal and nasal quadrants. Difference in CVI in macular and four quadrants RESULTS: Twenty eyes from 20 subjects were enrolled in the study. The mean age was 28.85±6.29 years with males comprising 9/20 (45.0%).The refractive error(spherical equivalent) ranged from -3.00 D to +0.75 D. The average CVI in the macular area (40.01±7.67) was significantly smaller than in any of the other fundus areas (all p&l...

Research paper thumbnail of Surgical Outcomes After Inverted Internal Limiting Membrane Flap Versus Conventional Peeling for Very Large Macular Holes

Retina (Philadelphia, Pa.), Jan 23, 2018

To evaluate the anatomical and visual outcomes of inverted flap technique of peeling of internal ... more To evaluate the anatomical and visual outcomes of inverted flap technique of peeling of internal limiting membrane (ILM) versus standard peeling of ILM for macular holes of basal diameter more than 800 μm. Patients with very large idiopathic macular holes more than 800 μm in basal diameter (ranging from 243 μm to 840 μm in minimum diameter) were retrospectively included in the study. In Group A, 18 eyes of 18 patients underwent ILM peeling using the inverted flap technique. In Group B, 18 eyes of 18 patients underwent conventional ILM peeling. The primary endpoint was the rate of hole closure at 6 months after surgery. The secondary outcome measure was the change in best-corrected visual acuity at 6 months after surgery. There were no significant differences in ocular characteristics of the study groups at baseline except for the age distribution. Mean macular hole diameter was 1,162.8 ± 206.0 μm and 1,229.6 ± 228.1 μm in Group A and Group B, respectively. The hole closure rate was ...

Research paper thumbnail of Retinal pigment epithelium rip following single intravitreal ziv-aflibercept injection

Indian journal of ophthalmology, 2018

Manuscript received: 12.09.17; Revision accepted: 17.11.17 A 40‐year‐old male presented with dimi... more Manuscript received: 12.09.17; Revision accepted: 17.11.17 A 40‐year‐old male presented with diminished vision (visual acuity 20/30) in the right eye for 4 years. Fundus examination revealed hard drusen with subretinal hemorrhage inferior to fovea [Fig. 1a]. Autofluorescence showed punctate hyperautofluorescence due to drusen and hypoautofluorescence due to subretinal hemorrhage [Fig. 1b]. Fluorescein angiography showed the presence of pooling in the area of retinal pigment epithelium detachment (PED) with temporal leakage suggestive of the occult choroidal neovascular membrane (CNVM). Swept‐source optical coherence tomography (SS‐OCT) showed the presence of large PED and irregular RPE folds (thick arrow) with the presence of hyperreflectivity (thin arrow) at sub‐RPE level [Fig. 1c]. The patient was advised intravitreal ziv‐aflibercept (IVZ) injection (1.25 mg/0.05 ml) under standard protocol. At 1 month, vision had dropped to 20/80. Fundus showed the increased area of subretinal hemorrhage with visible deeper choroidal vessels (arrows) [Fig. 2a]. Autofluorescence showed the presence of hypoautofluoresecence nasally and temporally (asterisk) with central hyperautofluorescence suggestive of double RPE rip [Fig. 2b]. SS‐OCT showed the presence of irregular RPE folds with RPE rip (arrow) [Fig. 2c].

Research paper thumbnail of Assessing analytical comparability of biosimilars: GCSF as a case study

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 21, 2016

The biosimilar industry is witnessing an unprecedented growth with the newer therapeutics increas... more The biosimilar industry is witnessing an unprecedented growth with the newer therapeutics increasing in complexity over time. A key step towards development of a biosimilar is to establish analytical comparability with the innovator product, which would otherwise affect the safety/efficacy profile of the product. Choosing appropriate analytical tools that can fulfil this objective by qualitatively and/or quantitatively assessing the critical quality attributes (CQAs) of the product is highly critical for establishing equivalence. These CQAs cover the primary and higher order structures of the product, product related variants and impurities, as well as process related impurities, and host cell related impurities. In the present work, we use such an analytical platform for assessing comparability of five approved Granulocyte Colony Stimulating Factor (GCSF) biosimilars (Emgrast, Lupifil, Colstim, Neukine and Grafeel) to the innovator product, Neupogen(®). The comparability studies in...

Research paper thumbnail of Should charge variants of monoclonal antibody therapeutics be considered critical quality attributes?

Electrophoresis, Sep 8, 2016

Charge variants, namely acidic and basic variants, are typically found in monoclonal antibody the... more Charge variants, namely acidic and basic variants, are typically found in monoclonal antibody therapeutics. Charge heterogeneity is typically not regarded to affect safety and efficacy of the product. As a result, the commonly followed approach involves assignment of a specification for the variants based on statistical analysis of variability in levels that is seen during commercial manufacturing. This is followed by monitoring of product quality to demonstrate consistency. This paper aims to demonstrate that this perception of charge variants warrants a more in-depth investigation to evaluate the role charge variants play in safety and efficacy of a monoclonal antibody therapeutic. In addition, a novel procedure has been suggested for making this assessment and alleviate the problems that are traditionally faced when isolating these variants for characterization. The suggested procedure utilizes the principles of bioseparations, cell biology, and statistics and it is demonstrated ...

Research paper thumbnail of Case Report Of Solitary Eccrine Spiradenoma Of Eyelid

European Ophthalmic Review, 2015

Eccrine spiradenoma, a sweat gland tumor, is rarely found in the eyelid. We encountered a 73-year... more Eccrine spiradenoma, a sweat gland tumor, is rarely found in the eyelid. We encountered a 73-year-old man with a nodular growth in his left upper eyelid, which had developed over the last 12 years. He had developed mild pain in the past. Excision was carried out under local anesthesia in a pentagon fashion with clear margins. The histopathology was suggestive for a benign eccrine spiradenoma.

Research paper thumbnail of Case Report of Isolated Schwannoma—A Rare Eyelid Tumor

US Ophthalmic Review, 2014

Schwannoma (neurilemmoma) is a benign tumor of the peripheral nerve arising from Schwann cells th... more Schwannoma (neurilemmoma) is a benign tumor of the peripheral nerve arising from Schwann cells that form the neural sheath. Schwannoma of ophthalmic interest is rare. Although it has been reported in relation to the orbit, and less frequently with the uveal tract and conjunctiva, instances of eyelid Schwannoma are extremely uncommon. We report a case of a 18-year-old male who developed eyelid Schwannoma. The mass was surgically removed by excisional biopsy. The histopathologic examination showed Schwannoma.

Research paper thumbnail of Object oriented modelling and development of a dispatching algorithm for automated guided vehicles

The International Journal of Advanced Manufacturing Technology, 2004

The main problem for an automated guided vehicle (AGV) dispatching system is to assign vehicles t... more The main problem for an automated guided vehicle (AGV) dispatching system is to assign vehicles to transport demands which optimise some predetermined objectives of a manufacturing shop. This paper presents a framework for an AGV dispatching system based on an object oriented approach using the unified modelling language (UML), and the development of a dispatching algorithm to facilitate a human controller to dispatch efficiently a fleet of AGVs in response to calls from any shop floor (or machine) operator. The main reason for this work is to model an AGV dispatching system as well as to develop a dispatching algorithm which can record details of the AGV position and movement and ensure their allocation of new orders. The provision of both immediate and pre-booked orders for an AGV is also incorporated in the proposed AGVs dispatching system. The underlying AGV dispatching system and algorithm are capable of dispatching a vehicle automatically to handle a call at the required time. In order to overcome difficulties associated with tackling immediate orders, pre-booked orders, and processing of information related to AGVs, a comprehensive dispatching algorithm is developed which aims to minimise lateness, traveling time and distance of empty vehicles in a simulated jobshop scenario. The effectiveness of the proposed framework for an AGV dispatching system is shown through a test problem.

Research paper thumbnail of Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis

British Journal of Dermatology, 2013

Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly t... more Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly through enhanced sensory nerve-skin mast cell interaction. Cell adhesion molecule 1 (CADM1) is a mast-cell adhesion molecule that mediates the adhesion to, and communication with, sympathetic nerves. To investigate the role of mast cell CADM1 in the pathogenesis of AD, CADM1 expression levels by comparing between lesional and nonlesional skin mast cells of an AD mouse model, which was developed by repeated application of trinitrochlorobenzene, and to examine, in cocultures, how the alterations in CADM1 detected in lesional mast cells might affect the sensory nerve-mast cell interaction. AD-like lesional and nonlesional skin mast cells were collected separately by laser capture microdissection. CADM1 expression was examined by reverse transcription-polymerase chain reaction and CADM1 immunohistochemistry. In cocultures, adhesion between dorsal root ganglion (DRG) neurites and IC2 mast cells was analysed by loading a femtosecond laser-induced impulsive force on neurite-attendant IC2 cells, while cellular communication was monitored as the IC2 cellular response ([Ca(2+)]i increase) after nerve-specific stimulant-induced DRG activation. AD-like lesional mast cells expressed three-fold more CADM1 transcripts than nonlesional cells. This was supported at the protein level, shown by immunohistochemistry. In coculture, CADM1 overexpression in IC2 cells strengthened DRG neurite-IC2 cell adhesion and doubled the population of IC2 cells responding to DRG activation. A function-blocking anti-CADM1 antibody abolished these effects in a dose-dependent manner. Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced mouse model of AD.