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Biomedical subjects

C C Muscoplat

Publications and source records attributed to C C Muscoplat.

At least 19 recordsLinked to original sources

Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.

BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.

Adult↗

Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S.

6-Hydroxymethylacylfulvene (HMAF; MGI 114) is a novel semisynthetic antitumor agent derived from the sesquiterpene mushroom toxin illudin S. In vitro cytotoxicity determinations produced IC50 concentrations (concentrations required for 50% inhibition of growth) ranging from 160 nM in sensitive MCF-7 human mammary carcinoma cells to 17 microM in relatively insensitive murine B16 melanoma cells. In vivo antitumor activity was consistent with in vitro sensitivity. HMAF was very effective in human tumor xenograft models, including MX-1 breast carcinoma, MV522 lung adenocarcinoma, and HT-29 colon carcinoma, but not murine B16 melanoma or P388 leukemia. Excellent responses were observed in animals bearing MX-1 tumors administered i.v. or i.p. doses of 3-7.5 mg/kg daily for 5 days, with complete regression recorded in 29 of 30 animals administered i.v. HMAF. Extensive tumor shrinkage was also observed with MV522, and significant tumor growth inhibition was obtained with HT-29 when animals received 5 daily i.p. doses ranging from 3.75 to 7.5 mg/kg. Complete regressions were also observed in individual animals with MV522 and HT-29. The excellent activity of HMAF in several human solid tumor xenografts, including the more refractory MV522 and HT-29 models, warrants the further investigation of this novel agent in clinical trials.

Animals↗

Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer.

BACKGROUND AND METHODS: We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks. RESULTS: We studied 207 patients who had each received > or = 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine. CONCLUSIONS: Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating.

Administration, Oral↗

A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients.

PURPOSE: To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer. PATIENTS AND METHODS: One hundred sixty-two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry. RESULTS: Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups. CONCLUSION: It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.

Administration, Oral↗

Immunization against bovine papillomavirus infection.

The two large open reading frames denoted L1 and L2 in the non-transforming region of the bovine papillomavirus type 1 (BPV-1) genome have been molecularly cloned to expression in Escherichia coli. Antisera against the E. coli-derived L1 and L2 protein reacted with BPV-1 in both enzyme-linked immunosorbent assays and immunoprecipitation reactions. Neutralization of BPV-induced transformation of mouse C127 cells was demonstrated most consistently with antisera against the L1 protein. E. coli-derived L1 protein protected calves against BPV-1 challenge after vaccination.

Animals↗

Adjuvant enhancement of humoral immune response to chemically inactivated bovine viral diarrhea virus.

Potentiation of the antibody response to inactivated bovine viral diarrhea virus by immunological adjuvants was studied in guinea pigs and cattle. The inactivated bovine viral diarrhea virus alone was demonstrated to be a weak immunogen. Addition of either 2 mg per mL diethylaminoethyl-dextran or 5% alhydrogel to inactivated bovine viral diarrhea virus did not or only slightly stimulated the antibody response; the combined adjuvants induced a significantly higher titer. A higher concentration (20 mg per mL) of diethylaminoethyl-dextran, on the contrary, suppressed the immune potentiation by the dual adjuvants. Combination of Bordetella bronchiseptica and alhydrogel adjuvants stimulated a high titer of antibody. The titer was further elevated upon revaccination and was significantly higher than that induced by alhydrogel alone. In cattle, alhydrogel enhanced the immune response and the additional inclusion of diethylaminoethyl-dextran did not cause a significant potentiation of the immunity. However, the antibody decay rate was significantly slower when stimulated by the combined adjuvants.

Adjuvants, Immunologic↗

Development and characterization of a hybridoma-derived antibody (Aby 1A1) with specificity to canine thymocytes and peripheral T lymphocytes.

A hybridoma (1A1)-producing antibody with reactivity to canine T-lymphocyte surface antigens was produced, using standard fusion techniques. Antibody secreted from this hybridoma was tested for specific anti-canine lymphocyte activity, using an enzyme-linked immunosorbent assay, an indirect-fluorescent antibody assay, and cytotoxicity assay. Antibody 1A1 reacted with canine T lymphocytes, but not with B lymphocytes, and with brain tissue and connective tissue. The antibody was also characterized. Its heavy chain had a molecular weight (mol wt) of 80,000 and its light chain was 28,000 mol wt. The Aby 1A1 is a monoclonal immunoglobulin M with a kappa light chain, and it binds poorly to Staphylococcus A.

Animals↗

Development and characterization of a monoclonal antibody (Aby 6C6) that distinguishes medullary from cortical thymocytes.

A hybridoma (6C6) producing antibodies with specificities to canine thymocyte surface antigens was produced using standard fusion techniques. The Aby 6C6 has affinity for medullary thymocytes, bone marrow cells, T- and B-peripheral lymphocytes, and monocytes. The Aby 6C6 appears to have 2 heavy chains with different molecular weights, an isoelectric focusing pattern consistent with monoclonality, and is an immunoglobulin G2b antibody with a kappa light chain.

Animals↗

Application of indomethacin as a potentiator of lymphocyte blastogenesis in Brucella abortus exposed cattle.

Lymphocytes from Brucella abortus field strain infected, strain 19 vaccinated, non-exposed and field strain infected, but immunologically unresponsive cattle were incubated with B. abortus antigen and indomethacin. There were significant increases (P less than 0.005) in the blastogenic responses, as measured by [3H] thymidine uptake, in cultures with indomethacin as compared to cultures without indomethacin. Lymphocyte blastogenic responses to B. abortus antigen were potentiated by indomethacin in both B. abortus exposed and non-exposed cultures. However, potentiation of sensitized lymphocyte blastogenic responses by indomethacin was significantly greater (P less than 0.005) than that in non-exposed lymphocytes. Additionally, indomethacin significantly potentiated Brucella-induced lymphocyte blastogenic responses in lymphocytes from anergic cattle.

Adjuvants, Immunologic↗

Protection of calves against fatal enteric colibacillosis by orally administered Escherichia coli K99-specific monoclonal antibody.

A monoclonal antibody (MCA) to enterotoxigenic Escherichia coli K99 antigen agglutinated K99+ enterotoxigenic E. coli strains B44 (O9:K30;K99;F41:H-) and B41 (O101:K99;F41:H-) grown at 37 degrees C but not at 18 degrees C. The MCA, which was characterized as immunoglobulin G1, reacted specifically with K99 antigen in an enzyme-linked immunosorbent assay and precipitated radiolabeled K99 antigen. A total of 45 colostrum-fed and colostrum-deprived calves were used in three separate trials to determine whether the orally administered K99-specific MCA would prevent diarrhea caused by strain B44. Twenty-eight calves were fed 1 ml of mouse ascitic fluid containing K99-specific MCA at 10 h of age and were orally challenged with strain B44 at 12 to 14 h of age. Control calves either received no placebo or were fed 1 ml of mouse ascitic fluid containing fibronectin-specific MCA at 10 h of age. There was no difference in the incidence of diarrhea between the two groups after challenge. However, the severity of diarrhea, as evaluated by the proportion of calves in each group that developed severe dehydration, the degree of clinical dehydration, the degree of clinical depression, the degree of weight loss, and the duration of diarrhea after challenge was significantly reduced in calves that received the K99-specific MCA. The mortality rate was also significantly lower (P less than 0.001) in the treated (29%) than in the control (82%) group. These results suggest that orally administered K99-specific MCA can prevent severe fatal enteric colibacillosis.

Animals↗

Immunoprophylaxis of an ocular solid malignant tumor in cattle.

Individual Hereford cows bearing benign precursor lesions of ocular squamous cell carcinoma were treated by intralesional injection of mycobacterial cell walls in an oil-in-water emulsion in an attempt to interrupt neoplastic progression. Thirty-one months after treatment, statistical analysis of data indicated that intralesional BCG cell wall vaccine can interrupt this process and provides effective immunoprophylactic prevention of malignant disease.

Animals↗

Tumor associated antigens of bovine cancer eye.

A study was conducted to determine the presence of surface antigens on cultured cells of bovine ocular squamous cell carcinoma (BOSCC) by serological testing. Serum from cattle with plaque and malignant stages of disease were tested for reactivity with surface antigens of cultured autologous and allogeneic cells. Indirect immune fluorescence assays were conducted to determine the presence of antibodies towards these tumor cells. It was found that sera tested possessed antibodies to the cultured tumor cells. Further, no surface reactivity was observed when these sera were tested for reactivity with normal epithelial cells. Reactive sera were analyzed by absorption tests with autologous and allogeneic cells. Absorbed sera showed no reactivity to surface antigens or allogeneic cells. This study suggests that there might be a shared antigen among the cells from plaque and malignant lesions.

Animals↗

Cytotoxic effect of Pasteurella haemolytica on bovine polymorphonuclear leukocytes and impaired production of chemotactic factors by Pasteurella haemolytica-infected alveolar macrophages.

Pasteurella haemolytica exerted a cytotoxic effect on bovine polymorphonuclear neutrophil leukocytes. This effect was less than that seen with cultured alveolar macrophages or peripheral blood monocytes. When alveolar macrophages were cultured with Pasteurella haemolytica, macrophages produced less chemotactic factors for polymorphonuclear leukocytes than did noninfected controls. This effect was reversible, in that removal of the bacteria permitted remaining macrophages to elaborate more chemotactic factors than was seen in controls. The possible consequences of this impairment of function of alveolar macrophages are discussed.

Animals↗

Detection of cell-surface antigens of bovine ocular squamous cell carcinoma.

A serologic study was conducted to identify surface antigens on cultured cells of bovine ocular squamous cell carcinoma. Sera from cattle with various stages of disease were tested for reactivity with surface antigens of cultured autologous and allogeneic cells. Radioiodine-labeled protein A assays were conducted to determine the presence of antibodies for tumor cells. It was found that all sera tested had antibodies at a high level to autologous cells, whereas the reactivity of allogeneic serum to cultured cells varied. Furthermore surface reactivity was not observed in these sera in tests for reactivity with normal epithelial cells. Reactive sera were analyzed by absorption tests with autologous and allogeneic cells. Absorbed sera showed no reactivity to surface antigens on autologous or allogeneic cells. Also, results of quantitative absorption studies indicated that absorption with precarcinoma cells eliminated the reactivity of sera from carcinoma- (cancer-) bearing animals toward cultured tumor cells. This indicates that there might be a shared antigen among the cells from precarcinoma and carcinoma lesions.

Animals↗

Levamisole potentiation of antigen specific lymphocyte blastogenic response in Brucella abortus exposed but nonresponsive cattle.

Incubation of Brucella abortus (field strain) infected and strain 19 vaccinated bovine peripheral blood lymphocytes with B. abortus antigen and levamisole caused a consistently significant increase in [3H] thymidine uptake when compared to cultures without levamisole. Levamisole did not potentiate B. abortus-induced blastogenic response of lymphocytes from non-exposed cattle. A dose response study showed that 10 micrograms/culture induced maximum potentiation of B. abortus-induced lymphocyte stimulation. Using the 10 micrograms/well concentration of levamisole, further studies were conducted to determine the net potentiation of the blastogenic responses in lymphocytes from B. abortus (field strain) infected cattle. B. abortus strain 19 vaccinated but nonresponsive and non-exposed cattle. Levamisole significantly potentiated the B. abortus-induced lymphocyte blastogenesis in lymphocytes from unresponsive cattle.

Animals↗