Na K)-ATPase (NKA) plays an im- portant role in ion homeostasis and regulates cardiac contraction... more Na K)-ATPase (NKA) plays an im- portant role in ion homeostasis and regulates cardiac contraction. To understand the molecular basis of its cardiac regulatory functions, we investigated whether the primary structure of the H1-H2 domain in -1 (1) subunit of the enzyme plays a role in myocardial contractile regulation. Here we show that site-specific binding to this 1 H1-H2 domain
DISTURBANCES in gastrointestinal motor activity are seen frequently in patients with progressive ... more DISTURBANCES in gastrointestinal motor activity are seen frequently in patients with progressive systemic sclerosis (scleroderma).1 2 3 4 5 6 7 8 9 10 11 12 Although the esophagus is involved most often, abnormalities of the small intestine leading to stasis and bacterial overgrowth ...
Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-i... more Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown. The role of CC10 in the regulation of T(H)2 cytokine expression was investigated. The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting. In vitro, a significant, dose-dependent suppressive effect of CC10 was found on T(H)2 cytokine expression, but not IFN-gamma, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4(+) T(H)2 cells, but not in naive CD4(+) T cells. In contrast, CC10 was able to induce IFN-gamma expression in naive CD4(+) T cells, but not in polarized T(H)1 cells. Furthermore, the suppression of T(H)2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of T(H)2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo, reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of T(H)2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia. These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses.
International Archives of Allergy and Immunology, 1991
We have addressed the hypothesis that the excitability of peripheral neurons is affected during i... more We have addressed the hypothesis that the excitability of peripheral neurons is affected during immediate hypersensitivity reactions. Guinea pigs were actively sensitized to ovalbumin. The electrical membrane properties of neurons within the superior cervical ganglion, bronchial parasympathetic ganglion and nodose ganglion were evaluated before, during and after antigen challenge. In all preparations, antigen stimulation induced the release of histamine and arachidonic acid metabolites. Our results support the hypothesis that the excitability of sympathetic, parasympathetic and sensory C-type neurons may be increased during immediate hypersensitivity reactions.
Biochemical and Biophysical Research Communications, 2002
Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic subunit of (Na(+) ... more Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic subunit of (Na(+) + K(+))-ATPase was investigated using a specific antibody directed against this peptide in cultured African green monkey kidney CV-1 cells. Immunofluorescence staining of frozen cell sections shows that an anti-KRQPRNPKTDKLVNE antibody (SSA95) interacts with its antigenic site and binds to the extracellular side of the cell membrane. Indirect immunofluorescence and flow cytometric analyses confirmed the presence of this epitope on intact cell surfaces. These results suggest that the KRQPRNPKTDKLVNE region of the (Na(+) + K(+))-ATPase is expressed on the cellular membrane surface.
Recent reports of and our own experience with biochemical alterations of liver function secondary... more Recent reports of and our own experience with biochemical alterations of liver function secondary to salicylate therapy stimulated this prospective study. Thirty-four children with juvenile rheumatoid arthritis, 6 children with acute cartilagenous necrosis of the hipfollowing slipped capital femoral epiphysis, and 2 children with ulcerative colitis and hip disease who were on salicylates were followed over a period of 1-27 months with serial determinations of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, and serum salicylate. Prothrombin time was measured in 14 children. Twenty-two of 34 children with rheumatoid arthritis and none of the 8 controls demonstrated abnormalities of various liver functions at serum salicylate levels between 7.0 and mg%. Three children demonstrated severe abnormalities characterized by marked elevation of SGOT, SGPT, LDH, and AP, prolongation of prothrombin time, and epistaxis. This type of reaction occurred within 5-14 days of initiation of aspirin therapy and occurred at serum salicylate levels between 18 and 43 mg%. Moderate changes in various liver function tests were observed in 19 other children. None of those children who were tested showed prolongation of prothrombin time. The serum salicylate level in this group varied between 7.0 and 38.2 mg%. The abnormal liver function tests returned to normal in 6 children upon withdrawal of aspirin and in 12 others even when salicylates were continued. Therefore, despite the occurrence of biochemical abnormalities following chronic salicylate therapy, it does not appear to be necessary to discontinue their use except in those children who develop bleeding.
A patient with fever, myalgias, and acute polyarthritis in whom echovirus 9 was isolated from thr... more A patient with fever, myalgias, and acute polyarthritis in whom echovirus 9 was isolated from throat and rectal swab specimens is described. All symptoms resolved spontaneously over a one week period except for the arthritis which required three months for complete recovery. A mildly inflammatory synovial fluid and histologic picture were observed. Attempts to isolate the virus from synovial fluid and synovium during acute illness were unsuccessful.
American Journal of Respiratory and Critical Care Medicine, 2000
Immunohistochemistry was combined with retrograde tracing techniques to characterize the effect o... more Immunohistochemistry was combined with retrograde tracing techniques to characterize the effect of nerve growth factor (NGF) on substance P (SP) producing vagal neurons innervating the guinea pig trachea. Fast blue dye instilled into the trachea retrogradely labeled nerve cell bodies located in the nodose and jugular ganglia. In untreated guinea pigs > 99% of the SP-containing neurons labeled with fast blue were located in the jugular ganglia. The SP-positive neurons were small in diameter (23 +/- 1 microm) and were negative for neurofilament immunoreactivity. The fast-blue-positive neurons in the nodose ganglia, by contrast, were large in diameter (40 +/- 3 microm) and were negative for SP immunoreactivity and positive for neurofilament immunoreactivity. After NGF-beta injections into the tracheal wall, approximately 10% of the large-diameter nodose neurofilament-positive neurons projecting fibers to the trachea became SP-positive (p < 0.05). We previously demonstrated that nodose nerve endings supplying the trachea are exquisitely mechanically sensitive, but capsaicin- and bradykinin-insensitive. These results suggest that NGF not only increases SP expression in airway neurons, but changes the neuronal phenotype such that large, capsaicin-insensitive nodose neurons with fast-conducting "Adelta" fibers provide a component of the tachykinergic innervation.
... that there is no consistent pattern of a relationship between SUA levels and casual blood pre... more ... that there is no consistent pattern of a relationship between SUA levels and casual blood pressure determinations de-spite some suggestive trends. ... AMERICAN JOURNAL OF MEDICINE Serum Uric Acid, Coronary Heart Disease Myers et al. ... Pub. Health Rep., 76: 963, 1961. ...
... Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; O. Choi: Affiliation... more ... Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; O. Choi: Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; HS Lee: Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; Z. Zhu: Affiliations. ...
American journal of physiology. Gastrointestinal and liver physiology, Jan 15, 2015
TRPA1 is a newly defined cationic ion channel, which selectively expressed in primary sensory aff... more TRPA1 is a newly defined cationic ion channel, which selectively expressed in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays the important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by in vivo OCT imaging, histological stains, and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole-cell patch clamp recordings in Dil-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esoph...
Proceedings of the National Academy of Sciences, 2014
Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral r... more Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.
Na K)-ATPase (NKA) plays an im- portant role in ion homeostasis and regulates cardiac contraction... more Na K)-ATPase (NKA) plays an im- portant role in ion homeostasis and regulates cardiac contraction. To understand the molecular basis of its cardiac regulatory functions, we investigated whether the primary structure of the H1-H2 domain in -1 (1) subunit of the enzyme plays a role in myocardial contractile regulation. Here we show that site-specific binding to this 1 H1-H2 domain
DISTURBANCES in gastrointestinal motor activity are seen frequently in patients with progressive ... more DISTURBANCES in gastrointestinal motor activity are seen frequently in patients with progressive systemic sclerosis (scleroderma).1 2 3 4 5 6 7 8 9 10 11 12 Although the esophagus is involved most often, abnormalities of the small intestine leading to stasis and bacterial overgrowth ...
Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-i... more Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown. The role of CC10 in the regulation of T(H)2 cytokine expression was investigated. The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting. In vitro, a significant, dose-dependent suppressive effect of CC10 was found on T(H)2 cytokine expression, but not IFN-gamma, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4(+) T(H)2 cells, but not in naive CD4(+) T cells. In contrast, CC10 was able to induce IFN-gamma expression in naive CD4(+) T cells, but not in polarized T(H)1 cells. Furthermore, the suppression of T(H)2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of T(H)2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo, reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of T(H)2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia. These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses.
International Archives of Allergy and Immunology, 1991
We have addressed the hypothesis that the excitability of peripheral neurons is affected during i... more We have addressed the hypothesis that the excitability of peripheral neurons is affected during immediate hypersensitivity reactions. Guinea pigs were actively sensitized to ovalbumin. The electrical membrane properties of neurons within the superior cervical ganglion, bronchial parasympathetic ganglion and nodose ganglion were evaluated before, during and after antigen challenge. In all preparations, antigen stimulation induced the release of histamine and arachidonic acid metabolites. Our results support the hypothesis that the excitability of sympathetic, parasympathetic and sensory C-type neurons may be increased during immediate hypersensitivity reactions.
Biochemical and Biophysical Research Communications, 2002
Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic subunit of (Na(+) ... more Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic subunit of (Na(+) + K(+))-ATPase was investigated using a specific antibody directed against this peptide in cultured African green monkey kidney CV-1 cells. Immunofluorescence staining of frozen cell sections shows that an anti-KRQPRNPKTDKLVNE antibody (SSA95) interacts with its antigenic site and binds to the extracellular side of the cell membrane. Indirect immunofluorescence and flow cytometric analyses confirmed the presence of this epitope on intact cell surfaces. These results suggest that the KRQPRNPKTDKLVNE region of the (Na(+) + K(+))-ATPase is expressed on the cellular membrane surface.
Recent reports of and our own experience with biochemical alterations of liver function secondary... more Recent reports of and our own experience with biochemical alterations of liver function secondary to salicylate therapy stimulated this prospective study. Thirty-four children with juvenile rheumatoid arthritis, 6 children with acute cartilagenous necrosis of the hipfollowing slipped capital femoral epiphysis, and 2 children with ulcerative colitis and hip disease who were on salicylates were followed over a period of 1-27 months with serial determinations of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, and serum salicylate. Prothrombin time was measured in 14 children. Twenty-two of 34 children with rheumatoid arthritis and none of the 8 controls demonstrated abnormalities of various liver functions at serum salicylate levels between 7.0 and mg%. Three children demonstrated severe abnormalities characterized by marked elevation of SGOT, SGPT, LDH, and AP, prolongation of prothrombin time, and epistaxis. This type of reaction occurred within 5-14 days of initiation of aspirin therapy and occurred at serum salicylate levels between 18 and 43 mg%. Moderate changes in various liver function tests were observed in 19 other children. None of those children who were tested showed prolongation of prothrombin time. The serum salicylate level in this group varied between 7.0 and 38.2 mg%. The abnormal liver function tests returned to normal in 6 children upon withdrawal of aspirin and in 12 others even when salicylates were continued. Therefore, despite the occurrence of biochemical abnormalities following chronic salicylate therapy, it does not appear to be necessary to discontinue their use except in those children who develop bleeding.
A patient with fever, myalgias, and acute polyarthritis in whom echovirus 9 was isolated from thr... more A patient with fever, myalgias, and acute polyarthritis in whom echovirus 9 was isolated from throat and rectal swab specimens is described. All symptoms resolved spontaneously over a one week period except for the arthritis which required three months for complete recovery. A mildly inflammatory synovial fluid and histologic picture were observed. Attempts to isolate the virus from synovial fluid and synovium during acute illness were unsuccessful.
American Journal of Respiratory and Critical Care Medicine, 2000
Immunohistochemistry was combined with retrograde tracing techniques to characterize the effect o... more Immunohistochemistry was combined with retrograde tracing techniques to characterize the effect of nerve growth factor (NGF) on substance P (SP) producing vagal neurons innervating the guinea pig trachea. Fast blue dye instilled into the trachea retrogradely labeled nerve cell bodies located in the nodose and jugular ganglia. In untreated guinea pigs > 99% of the SP-containing neurons labeled with fast blue were located in the jugular ganglia. The SP-positive neurons were small in diameter (23 +/- 1 microm) and were negative for neurofilament immunoreactivity. The fast-blue-positive neurons in the nodose ganglia, by contrast, were large in diameter (40 +/- 3 microm) and were negative for SP immunoreactivity and positive for neurofilament immunoreactivity. After NGF-beta injections into the tracheal wall, approximately 10% of the large-diameter nodose neurofilament-positive neurons projecting fibers to the trachea became SP-positive (p < 0.05). We previously demonstrated that nodose nerve endings supplying the trachea are exquisitely mechanically sensitive, but capsaicin- and bradykinin-insensitive. These results suggest that NGF not only increases SP expression in airway neurons, but changes the neuronal phenotype such that large, capsaicin-insensitive nodose neurons with fast-conducting "Adelta" fibers provide a component of the tachykinergic innervation.
... that there is no consistent pattern of a relationship between SUA levels and casual blood pre... more ... that there is no consistent pattern of a relationship between SUA levels and casual blood pressure determinations de-spite some suggestive trends. ... AMERICAN JOURNAL OF MEDICINE Serum Uric Acid, Coronary Heart Disease Myers et al. ... Pub. Health Rep., 76: 963, 1961. ...
... Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; O. Choi: Affiliation... more ... Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; O. Choi: Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; HS Lee: Affiliations. Johns Hopkins Asthma and Allergy Center, Baltimore, MD. ,; Z. Zhu: Affiliations. ...
American journal of physiology. Gastrointestinal and liver physiology, Jan 15, 2015
TRPA1 is a newly defined cationic ion channel, which selectively expressed in primary sensory aff... more TRPA1 is a newly defined cationic ion channel, which selectively expressed in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays the important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by in vivo OCT imaging, histological stains, and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole-cell patch clamp recordings in Dil-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esoph...
Proceedings of the National Academy of Sciences, 2014
Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral r... more Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.
Uploads