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Pilocarpine HCl for treatment of salivary gland hypofunction in primary Sjogren's syndrome
600
Abstracts
12-14 kd. After electrophoresis on SDS polyacrylamide gels, the peptide was transThe partial sequence obtained demonstrated ferred to PVDF membranes and sequenced. cl<,se homology to the predicted amino acid sequence from the human 60 kd Ro/SSA This sequence began about 13 kd from the carboxyl terminus of the Ro/SSA protein. These results suggest that there is a major epitope in the C-terminal protein. portion of the bovine Ro/SSA protein.
PILOCARPINE HCl FOR TREATMENT OF SALIVARY GLAND HYPOFUNCTION IN PRIMARY SJOGREN'S SYNDROME. Phili C. Fox, Jane C. Atkinson, Alice A. Macynski, and Bruce J. Baum. CIPCB,NIDR.&a, MD USA. Diminished salivary output, as a consequence of the chronic inflammatory infiltrate of the salivary glands, is a hallmark of Sjogren's syndrome (SS). In addition to the subjective complaint (xerostomia), patients lacking adequate saliva In an suffer a number of functional disturbances of oral hard and soft tissues. effort to correct their oral dryness, 15 individuals with primary SS were enrolled in a 6 month trial of the parasympathomimetic drug pilocarpine HCl (PILO), 5 mg capsules, tid. A 1 month placebo period was assigned in a double-blinded fashion. Salivary dysfunction was assessed by unstimulated and stimulated saliva output from individual parotid and submandibular glands and by histopathologic examination of labial minor glands. All subjects had evidence of some remaining functional acinar tissue as demonstrated by technetium pertechnetate uptake. At each monthly visit, unstimulated saliva was collected on 5 occassions. and heart rate, blood pressure and ECG were recorded. Daily patient diaries recorded subjective responses and any side effects. One individual withdrew due to an unrelated illness. Thirteen of the 14 subjects (93%) noted subjective improvement in oral dryness while on active drug. Ten of these 13 (77%) had measurable increases in unstimulated saliva output following PILO. Maximal responses were seen 1 hour after drug. Objective responses did not change during the 6 months. Subjective improvement was progressive, with greater ease in speaking, eating and swallowing reported during the initial 2-4 weeks of PILO. Heart rate, blood pressure and ECG were stable in all participants. Mild, transient sweating (usually 30 min after PILO) was noted by 8 of the 14 subjects. One month PILO after stopping PILO, saliva had returned to pre-treatment levels in all cases. is a safe and effective treatment for stimulation of salivary output in SS.
A CROSS REACTIVE IDIOTYPE ON RHEUMATOID FACTOR IS FOUND IN SJOGREN'S SYNDROME PATIENTS IN DIFFERENT PARTS OF THE WORLD. g1 Fox*, FV Howell*, PP Chen*, DA Carson*, TJ Kipps*, zhang Nai Zheng**, Dong Yi**, H Moutsopolist, and S Sugaitt, *Research Institute Clinic of Scripps Clinic, La Jolla, CA (USA); **Peking Union Medical College, Beijing, PRC; tIoanna Medical College, Ioanna, Greece; ttKanazawa Medical College, Ishikawa, Japan. Monoclonal antibody 17.109 (MoAb 17.109) detects a cross reactive idiotype (CRI) located on kappa light chains of the V-kappa IIIb sub-subclass. The MoAb 17.109+ is encoded by the germ lined encoded gene HumkV325 that is expressed with little (or no) somatic diversification. We have previously found this CR1 on rheumatoid factor (RF) from American patients with Sjogren's syndrome (SS), especially among patients with RF paraproteins and mixed cryoglobulinemia. To determine whether this CR1 was found among different popularions, we examined sera with paraproteins from SS patients from Greece, Japan, and China. We found high levels of MoAb 17.109 reactive RF in 22/31 samples. In comparison, we used a different monoclonal antibody (MoAb 686) that detects a distinct idiotype located on kappa light chains of the V-kappa IIIa sub-subclass. Only l/31 SS sera samples contained RF reactive with MoAb 6B6. In summary, we have found preferential utilization of a particular human kappa variable region gene (HumkV325) in SS patients of different ethnic origin. We are currently investigating genetic factors (i.e. enhancer/promoter regions of the kappa gene) that are present in SS patients and may play a role in pathogenesis by promoting transcription of particular variable region genes.
GENETIC POLYMORPHISMS AND DNA SEQUENCES OF T-CELL ANTIGEN RECEPTORS AND HISTOCOMPATIBLE ANTIGEN GENES IN PRIMARY SJOGREN'S SYNDROME. p1 Fox*, BD Freimark", B Servenius*, C Shun-le**, P Concannon***, *Research Institute of Scripps (X&&z, La Jolla, CA (USA),; California Institute of **Second Shanghai Medical University, Shanghai, PRC; Technology, Pasadena, CA (USA). In order to understand genetic factors that predispose to Sjogren's syndrome (SS), we have used Southern blot analysis to study genetic polymorphisms involving the T-cell antigen receptor fl chain (Tip) and histocompatibility HLA-D region encoded genes. We
Abstracts
12-14 kd. After electrophoresis on SDS polyacrylamide gels, the peptide was transThe partial sequence obtained demonstrated ferred to PVDF membranes and sequenced. cl<,se homology to the predicted amino acid sequence from the human 60 kd Ro/SSA This sequence began about 13 kd from the carboxyl terminus of the Ro/SSA protein. These results suggest that there is a major epitope in the C-terminal protein. portion of the bovine Ro/SSA protein.
PILOCARPINE HCl FOR TREATMENT OF SALIVARY GLAND HYPOFUNCTION IN PRIMARY SJOGREN'S SYNDROME. Phili C. Fox, Jane C. Atkinson, Alice A. Macynski, and Bruce J. Baum. CIPCB,NIDR.&a, MD USA. Diminished salivary output, as a consequence of the chronic inflammatory infiltrate of the salivary glands, is a hallmark of Sjogren's syndrome (SS). In addition to the subjective complaint (xerostomia), patients lacking adequate saliva In an suffer a number of functional disturbances of oral hard and soft tissues. effort to correct their oral dryness, 15 individuals with primary SS were enrolled in a 6 month trial of the parasympathomimetic drug pilocarpine HCl (PILO), 5 mg capsules, tid. A 1 month placebo period was assigned in a double-blinded fashion. Salivary dysfunction was assessed by unstimulated and stimulated saliva output from individual parotid and submandibular glands and by histopathologic examination of labial minor glands. All subjects had evidence of some remaining functional acinar tissue as demonstrated by technetium pertechnetate uptake. At each monthly visit, unstimulated saliva was collected on 5 occassions. and heart rate, blood pressure and ECG were recorded. Daily patient diaries recorded subjective responses and any side effects. One individual withdrew due to an unrelated illness. Thirteen of the 14 subjects (93%) noted subjective improvement in oral dryness while on active drug. Ten of these 13 (77%) had measurable increases in unstimulated saliva output following PILO. Maximal responses were seen 1 hour after drug. Objective responses did not change during the 6 months. Subjective improvement was progressive, with greater ease in speaking, eating and swallowing reported during the initial 2-4 weeks of PILO. Heart rate, blood pressure and ECG were stable in all participants. Mild, transient sweating (usually 30 min after PILO) was noted by 8 of the 14 subjects. One month PILO after stopping PILO, saliva had returned to pre-treatment levels in all cases. is a safe and effective treatment for stimulation of salivary output in SS.
A CROSS REACTIVE IDIOTYPE ON RHEUMATOID FACTOR IS FOUND IN SJOGREN'S SYNDROME PATIENTS IN DIFFERENT PARTS OF THE WORLD. g1 Fox*, FV Howell*, PP Chen*, DA Carson*, TJ Kipps*, zhang Nai Zheng**, Dong Yi**, H Moutsopolist, and S Sugaitt, *Research Institute Clinic of Scripps Clinic, La Jolla, CA (USA); **Peking Union Medical College, Beijing, PRC; tIoanna Medical College, Ioanna, Greece; ttKanazawa Medical College, Ishikawa, Japan. Monoclonal antibody 17.109 (MoAb 17.109) detects a cross reactive idiotype (CRI) located on kappa light chains of the V-kappa IIIb sub-subclass. The MoAb 17.109+ is encoded by the germ lined encoded gene HumkV325 that is expressed with little (or no) somatic diversification. We have previously found this CR1 on rheumatoid factor (RF) from American patients with Sjogren's syndrome (SS), especially among patients with RF paraproteins and mixed cryoglobulinemia. To determine whether this CR1 was found among different popularions, we examined sera with paraproteins from SS patients from Greece, Japan, and China. We found high levels of MoAb 17.109 reactive RF in 22/31 samples. In comparison, we used a different monoclonal antibody (MoAb 686) that detects a distinct idiotype located on kappa light chains of the V-kappa IIIa sub-subclass. Only l/31 SS sera samples contained RF reactive with MoAb 6B6. In summary, we have found preferential utilization of a particular human kappa variable region gene (HumkV325) in SS patients of different ethnic origin. We are currently investigating genetic factors (i.e. enhancer/promoter regions of the kappa gene) that are present in SS patients and may play a role in pathogenesis by promoting transcription of particular variable region genes.
GENETIC POLYMORPHISMS AND DNA SEQUENCES OF T-CELL ANTIGEN RECEPTORS AND HISTOCOMPATIBLE ANTIGEN GENES IN PRIMARY SJOGREN'S SYNDROME. p1 Fox*, BD Freimark", B Servenius*, C Shun-le**, P Concannon***, *Research Institute of Scripps (X&&z, La Jolla, CA (USA),; California Institute of **Second Shanghai Medical University, Shanghai, PRC; Technology, Pasadena, CA (USA). In order to understand genetic factors that predispose to Sjogren's syndrome (SS), we have used Southern blot analysis to study genetic polymorphisms involving the T-cell antigen receptor fl chain (Tip) and histocompatibility HLA-D region encoded genes. We