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Biomedical subjects

B Jarvis

Publications and source records attributed to B Jarvis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Yeast vitality during cider fermentation: assessment by energy metabolism.

In an apple juice-based medium, an ethanol-tolerant Australian wine-yeast used for cider manufacture produced more than 10% ethanol over a 5 week period. Growth of the inoculum (10(6) organisms ml(-1)) occurred to a population of 3.1 x 10(7) ml(-1) during the first few days; at the end of the fermentation only 5 x 10(5) yeasts ml(-1) could be recovered as colony-forming units on plates. Respiratory and fermentative activities were measured by mass spectrometric measurements (O2 consumption and CO2 and ethanol production) of washed yeast suspensions taken from the cider fermentation at intervals. Both endogenous and glucose-supported energy-yielding metabolism declined, especially during the first 20 days. Levels of adenine nucleotides also showed decreases after day 1, as did adenylate energy charge, although in a prolonged (16.5 week) fermentation the lowest value calculated was 0.55. AMP was released into the medium. 31P-NMR spectra showed that by comparison with aerobically grown yeast, that from the later stages of the cider fermentation showed little polyphosphate. However, as previously concluded from studies of 'acidification power' and fluorescent oxonol dye exclusion (Dinsdale et al., 1995), repitching of yeast indicated little loss of viability despite considerable loss of vitality.

Adenine Nucleotides↗
PubMed1999

Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages < or = 500 microg/day in adults and adolescents with mild to moderate asthma.

UNLABELLED: Fluticasone propionate is a corticosteroid with comparatively high receptor affinity and topical activity. Inhaled fluticasone propionate < or =500 microg/day provided effective corticosteroid maintenance treatment in patients with mild to moderate asthma in randomised, controlled clinical studies of 4 to 24 weeks in duration. Dosages of 50 to 250 microg twice daily produced consistent improvement in spirometric measures of lung function, reduced the frequency of as-needed beta2-agonist bronchodilator use, asthma symptom scores and night-time wakenings, and prevented asthma exacerbations compared with placebo. Fluticasone propionate < or =250 microg twice daily provided significantly greater improvements in lung function than nedocromil 4 mg 4 times daily, theophylline (5 to 15 mg/L) or zafirlukast 20 mg twice daily. Health-related quality of life improved significantly with fluticasone propionate 88 microg twice daily, but not zafirlukast 20 mg twice daily or placebo. In comparative trials in which fluticasone propionate was given at half the dosage of beclomethasone dipropionate, budesonide or flunisolide, fluticasone propionate < or =250 microg twice daily produced equivalent or greater improvement in spirometric parameters and equivalent reductions in the use of as-needed beta2-agonists than beclomethasone dipropionate, budesonide or flunisolide. Fluticasone propionate 250 microg twice daily was generally more effective than triamcinolone acetonide 200 microg 4 times daily in two 24-week trials. The combination of inhaled fluticasone propionate < or =250 plus salmeterol < or =50 microg twice daily allowed for the use of lower dosages of the inhaled corticosteroid. The incidence of adverse events in patients receiving inhaled fluticasone propionate 50 to 250 microg twice daily was similar to that in beclomethasone dipropionate 168 to 500 microg twice daily and budesonide 100 to 600 microg twice daily recipients and greater than that in recipients of triamcinolone acetonide 200 microg 4 times daily in comparative trials. The incidence of oral candidiasis was < or =8% in patients treated with fluticasone propionate < or =250 microg twice daily or other agents. There was no evidence of clinically significant hypothalamo-pituitary-adrenal (HPA) axis suppression with fluticasone propionate < or =250 microg twice daily in comparative trials. CONCLUSIONS: Inhaled fluticasone propionate < or =500 microg/day is an effective antiinflammatory therapy for mild to moderate asthma in adolescents and adults. The drug is more effective than nedocromil, theophylline or zafirlukast and is at least as effective as other inhaled corticosteroids administered at twice the fluticasone propionate dosage. The addition of inhaled salmeterol allows the use of lower maintenance dosages of fluticasone propionate. The drug is well tolerated and there is no evidence of a clinically significant effect of this dosage on HPA axis function. Hence, fluticasone propionate < or =500 microg/day is a particularly suitable agent for patients with mild to moderate asthma.

Administration, Inhalation↗
PubMed1999

Salmeterol/fluticasone propionate combination.

Current evidence suggests that addition of the long-acting beta2-agonist salmeterol to an inhaled corticosteroid in patients with persistent asthma symptoms provides greater clinical benefit than doubling the dosage of the inhaled corticosteroid. Fixed combination salmeterol/fluticasone propionate in 3 different fluticasone propionate dosage strengths administered via the Diskus powder inhaler does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles - including the influence of the corticosteroid on plasma cortisol levels. Administration of fixed combination salmeterol/ fluticasone propionate to both adults and children with persistent asthma provides greater improvements in lung function than either agent alone, and at least equal effectiveness to the same dosages of the 2 agents given by separate powder inhalers. Preliminary reports indicate that combination therapy has also demonstrated superior efficacy to budesonide (fluticasone propionate dosages were 25% those of budesonide). The most commonly encountered adverse effects in clinical trials with combined salmeterol/fluticasone propionate therapy have been oropharyngeal candidiasis. hoarseness/dysphonia, throat irritation, headache, tachycardia/palpitations, tremor and dizziness (all in < or =5% of patients).

Administration, Inhalation↗
PubMed1999

Etanercept: a review of its use in rheumatoid arthritis.

UNLABELLED: Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-alpha and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis. In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with > or = 1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures. A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by <25% in patients treated with placebo. In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years. Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time. Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged > or =4 years with refractory juvenile rheumatoid arthritis. Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept- than placebo-treated patients, but did not bias the results of any study. CONCLUSIONS: When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.

Animals↗
PubMed1999

Lamivudine. A review of its therapeutic potential in chronic hepatitis B.

UNLABELLED: Lamivudine is a deoxycytidine analogue that is active against hepatitis B virus (HBV). In patients with chronic hepatitis B, lamivudine profoundly suppresses HBV replication. Clinically significant improvements in liver histology and biochemical parameters were obtained with lamivudine in double-blind, randomised, trials in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B and compensated liver disease. After 52 weeks of treatment, relative to placebo (< or = 25%), significantly more Chinese (56%) or Western patients (52%) treated with lamivudine 100 mg/day had reductions of > or = 2 or more points in Knodell necro-inflammatory scores. Moreover, significantly fewer lamivudine 100 mg/day than placebo recipients had progressive fibrosis in liver biopsies (< or = 5 vs > or = 15%) and fewer lamivudine- than placebo-treated patients progressed to cirrhosis (1.8 vs 7.1%). More lamivudine 100 mg/day than placebo recipients acquired antibodies to HBeAg after 52 weeks (16 vs 4% in Chinese patients and 17 vs 6% in Western patients). ALT levels normalised in significantly more lamivudine than placebo recipients enrolled in these trials. In HBeAg-negative, HBV DNA positive patients with compensated liver disease enrolled in a double-blind, randomised study, HBV DNA levels were suppressed to below the limit of detection (< 2.5 pg/ml) and ALT levels normalised in 63% and 6% of patients treated with lamivudine 100 mg/day or placebo for 24 weeks. Clinically significant improvements in liver histology were obtained in 60% of patients treated with lamivudine for 52 weeks in this study. Lamivudine 100 mg/day for 52 weeks produced similar or significantly greater improvements in liver histology and ALT levels than 24 weeks' treatment with lamivudine plus interferon-alpha. In liver transplant candidates with chronic hepatitis B and end-stage liver disease, lamivudine 100 mg/day alone, or in combination with hepatitis B immune globulin, generally suppressed HBV replication and appeared to protect the grafted liver from reinfection. Lamivudine 100 mg/day suppressed viral replication and improved liver histology in liver transplant recipients with recurrent or de novo chronic hepatitis B. Lamivudine 300 or 600 mg/day reduced HBV replication in HIV-positive patients. The incidence of adverse events in patients with chronic hepatitis B and compensated liver disease treated with lamivudine 100 mg/day or placebo for 52 to 68 weeks was similar. 3.1- to 10-fold increases in ALT over baseline occurred in 13% of patients during treatment with lamivudine 100 mg/day or placebo for 52 weeks. Post-treatment ALT elevations were more common in lamivudine than placebo recipients; however, these generally resolved spontaneously; < or = 1.5% of lamivudine- or placebo-treated patients experienced hepatic decompensation. CONCLUSION: Lamivudine inhibits HBV replication, reduces hepatic necro-inflammatory activity and the progression of fibrosis in patients with chronic hepatitis B, ongoing viral replication and compensated liver disease including HBeAg-negative patients. The drug also suppresses viral replication in liver transplant recipients and HIV-positive patients. Thus, lamivudine is potentially useful in a wide range of patients with chronic hepatitis B and ongoing viral replication.

Animals↗
PubMed1999

Leflunomide: a review of its use in active rheumatoid arthritis.

UNLABELLED: A77 1726, the active metabolite of leflunomide, is an immunomodulator which inhibits cell proliferation in activated lymphocytes in patients with active rheumatoid arthritis. Because A77 1726 has a long half-life (approximately 2 weeks), treatment with oral leflunomide is initiated with a loading dose of 100mg once daily for 3 days and continued with 20mg once daily. Results of large randomised, double-blind, multicentre trials of up to 24 months' duration have shown that leflunomide is significantly superior to placebo and at least as effective as sulfasalazine in improving primary outcome measures, such as tender joint counts, swollen joint counts and physicians' and patients' global assessment, in adult patients with active rheumatoid arthritis. Whereas improvement in all primary outcome measures with leflunomide was similar to or significantly less than that with methotrexate after 12 months, the efficacy of both agents was similar after 24 months. The therapeutic effect of leflunomide appears earlier (at 4 weeks) than that of sulfasalazine or methotrexate, and reduction from baseline values in functional disability was significantly greater with leflunomide than with sulfasalazine, methotrexate or placebo at end-point. Leflunomide was at least as effective as sulfasalazine or methotrexate in delaying the rate of radiological progression of disease. The most common adverse events reported in patients receiving leflunomide in randomised double-blind, placebo-controlled trials were diarrhoea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), increased serum hepatic aminotransferases (10%), dyspepsia (10%) and alopecia (9%). Leflunomide was as well tolerated as sulfasalazine or methotrexate in clinical trials. Monitoring of serum hepatic enzyme levels is recommended in patients receiving leflunomide. The drug is not recommended in female patients who are or may become pregnant. Drug treatment should be discontinued, and hastened drug elimination procedure should be considered, in male patients wishing to father a child. 16 potential cases of pancytopenia and 9 cases of serious skin reactions have been associated with the use of leflunomide in 76,000 patients to date. CONCLUSIONS: Leflunomide is a disease-modifying antirheumatic drug which reduces the signs and symptoms of inflammatory arthritis and delays the radiological progression of disease in adult patients with active rheumatoid arthritis. The drug appears to be as effective and as well tolerated as sulfasalazine or methotrexate, and represents a suitable alternative to these agents in adult patients with active rheumatoid arthritis. Benefits with leflunomide are evident within 4 weeks and efficacy is maintained for durations of up to 24 months.

Adult↗
PubMed1998

Activation of p38MAPK in microglia after ischemia.

p38MAPK has been implicated in the regulation of proinflammatory cytokines and apoptosis in vitro. To understand its role in neurodegeneration, we determined the time course and localization of the dually phosphorylated active form of p38MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38MAPK and mitogen-activated protein kinase-activated protein 2 activity increased over 4 days after ischemia. Phosphorylated p38MAPK immunoreactivity was observed in microglia in regions adjacent to, but not in, the dying CA1 neurons. In contrast, neither c-Jun N-terminal kinase 1 nor p42/p44MAPK activity was altered after ischemia. These results provide the first evidence for localization of activated p38MAPK in the CNS and support a role for p38MAPK in the microglial response to stress.

Animals↗
PubMed1998

Nelfinavir. A review of its therapeutic efficacy in HIV infection.

UNLABELLED: Nelfinavir is a selective inhibitor of HIV protease, the enzyme responsible for post-translational processing of HIV propeptides. In the presence of the drug, immature, noninfectious virus particles are produced. Nelfinavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors and/or other protease inhibitors profoundly suppresses viral replication. Plasma HIV RNA levels (viral loan) rapidly fall below the limit of detection (LOD; usually 400 or 500 copies/ml in the majority of patients. When used in combination with NRTIs, nelfinavir 1250mg twice daily produced similar results to 3-times-daily nelfinavir at a range of total daily dosages. In an ongoing study > 70% of adults receiving a nelfinavir based combination regimen had plasma HIV RNA levels below the LOD (< 400 copies/ml) after 84 weeks. In addition, 73% of paediatric patients receiving nelfinavir plus at least 1 new NRTI had viral loads below the LOD (< 400 copies/ml) after 34 weeks. Furthermore, CD4+ cell counts generally increased in conjunction with reductions in viral load. Combination therapy with nelfinavir and saquinavir results in higher saquinavir plasma concentrations, make twice-daily administration of saquinavir feasible and may delay the emergence of resistant viral strains. A unique mutation at codon 30 (D30N) of the protease gene confers resistance to nelfinavir, but HIV with D30N mutation remains fully susceptible to indinavir, ritonavir and saquinavir in vitro. Nonetheless, in clinical use, significant cross-resistance is seen with all currently available protease inhibitors. Diarrhoea is the most frequently reported adverse event in patients receiving nelfinavir-based combination therapy and has been reported in up to 32% of nelfinavir recipients in randomised trials. Diarrhoea is generally of mild to moderate severity and does not result in weight loss. Rash, nausea, headache and asthenia were each reported in < or = 5% of patients. Approximately 5% of patients enrolled in an expanded access programme in the US discontinued nelfinavir because of adverse events. Nelfinavir is metabolised by the cytochrome P450 system. Several clinically significant pharmacokinetic drug interactions between nelfinavir and other drugs (i.e. ketoconazole, rifabutin, rifabutin, rifampicin), including other protease inhibitors (i.e. indinavir, ritonavir, saquinavir) have been documented. As with other available protease inhibitors, hyperglycaemia, hyperlipidaemia and abnormal fat distribution have been reported, albeit infrequently, in association with nelfinavir. CONCLUSION: Nelfinavir-based combination regimens are well tolerated and produce profound and prolonged suppression of HIV replication in adult and paediatric patients. Hence, nelfinavir is suitable for inclusion in antiretroviral regimens for initial therapy for HIV infection and, alternatively, in regimens for patients unable to tolerate other protease inhibitors.

Adult↗
PubMed1998

Rifapentine.

Rifapentine is a rifamycin antibiotic with antimycobacterial activity. Rifapentine is generally more active against Mycobacterium tuberculosis than rifampicin (rifampin), although strains resistant to rifampicin are usually cross-resistant to rifapentine. Sputum culture conversion rates were slightly higher after 6 months of rifapentine- versus rifampicin-based therapy in patients with pulmonary tuberculosis in a Western study; however, relapse rates were higher in rifapentine recipients during follow-up. The excess relapses in the rifapentine group appeared to be related to poor compliance with nonrifamycin antituberculosis drugs during the intensive phase (first 2 months) of therapy. Rifapentine- and rifampicin-containing regimens produced similar sputum culture conversion rates with low rates of relapse in 2 randomised clinical trials in patients with smear-positive tuberculosis in China. In one trial, there was no difference in sputum culture conversion rates in patients treated with rifapentine once weekly or rifampicin twice weekly in combination with isoniazid and ethambutol during the continuation phase of treatment. Hyperuricaemia, which was reported only during the intensive phase, elevated ALT and AST levels and neutropenia were the most common treatment-related adverse events reported in patients receiving rifapentine- or rifampicin-containing regimens for tuberculosis in 1 Western study.

Animals↗
PubMed1998

Mexiletine. A review of its therapeutic use in painful diabetic neuropathy.

UNLABELLED: Mexiletine is an orally active local anaesthetic agent which is structurally related to lidocaine (lignocaine) and has been used for alleviating neuropathic pain of various origins. Mexiletine has been evaluated in several randomised, placebo-controlled trials in patients with painful diabetic neuropathy. The drug decreased mean visual analogue scale (VAS) pain ratings in all studies that used this measure, although in only 2 studies was this effect significantly greater than the often substantial responses seen with placebo. The clinical significance of these decreases is not clear. Statistically significant (vs placebo) reductions in VAS pain ratings were observed in 16 patients receiving mexiletine 10 mg/kg/day for 10 weeks in 1 study and in nocturnal (but not diurnal) pain in 31 patients receiving mexiletine 675 mg/day for 3 weeks in another. Retrospective analysis of another study revealed that mexiletine recipients (225 to 675 mg/day) who described their pain as stabbing, burning or formication on the pain-rating-index-total instrument of the McGill Pain Questionnaire, experienced statistically significant reductions in VAS pain scores after 5 weeks, compared with placebo recipients. Mexiletine generally did not have a significant influence on the quality of sleep in patients with diabetic neuropathy. In Japanese patients, statistically significant reductions in subjective pain ratings were achieved with mexiletine 300 mg/day in 1 study and with 450 mg/day in a further study. In controlled trials, the frequency of adverse events in patients receiving mexiletine for painful diabetic neuropathy ranged from 13.5 to 50%. Gastrointestinal complaints, of which nausea was the most frequent, were the most common adverse events in mexiletine recipients. Central nervous system complaints were uncommon, but included: sleep disturbance, headache, shakiness, dizziness and tiredness. Serious cardiac arrhythmias have not been reported in patients receiving mexiletine for painful diabetic neuropathy; however, transient tachycardia and palpitations have been reported. There are significant differences in the metabolism of mexiletine between people who have cytochrome P450 2D6 [CYP2D6; extensive metabolisers (EMs)] and those who lack this isoenzyme [poor metabolisers (PMs)]. EMs, but not PMs, are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g. quinidine). Moreover, mexiletine inhibits CYP2D6-mediated metabolism of metoprolol and cytochrome P450 1A2-mediated metabolism of theophylline. Phenytoin and rifampicin (rifampin) induce the metabolism of mexiletine. Clearance of mexiletine is impaired in patients with hepatic, but not renal, dysfunction. Hence, dosage adjustments may be necessary in patients with liver disease. CONCLUSIONS: Tricyclic antidepressants (TCAs) are the agents of choice for painful diabetic neuropathy; however, they are ineffective in approximately 50% of patients and are generally not well tolerated. Mexiletine is an alternative agent for the treatment of painful diabetic neuropathy in patients who have not had a satisfactory response to, or cannot tolerate, TCAs and/or other drugs.

Diabetic Neuropathies↗
PubMed1996

Health and immunology study following exposure to toxigenic fungi (Stachybotrys chartarum) in a water-damaged office environment.

There is growing concern about adverse health effects of fungal bio-aerosols on occupants of water-damaged buildings. Accidental, occupational exposure in a nonagricultural setting has not been investigated using modern immunological laboratory tests. The objective of this study was to evaluate the health status of office workers after exposure to fungal bio-aerosols, especially Stachybotrys chartarum (atra) (S. chartarum) and its toxigenic metabolites (satratoxins), and to study laboratory parameters or biomarkers related to allergic or toxic human health effects. Exposure characterization and quantification were performed using microscopic, culture, and chemical techniques. The study population (n = 53) consisted of 39 female and 14 male employees (mean age 34.8 years) who had worked for a mean of 3.1 years at a problem office site; a control group comprised 21 persons (mean age 37.5 years) without contact with the problem office site. Health complaints were surveyed with a 187-item standardized questionnaire. A comprehensive test battery was used to study the red and white blood cell system, serum chemistry, immunology/antibodies, lymphocyte enumeration and function. Widespread fungal contamination of water-damaged, primarily cellulose material with S. chartarum was found. S. chartarum produced a macrocyclic trichothecene, satratoxin H, and spirocyclic lactones. Strong associations with exposure indicators and significant differences between employees (n = 53) and controls (n = 21) were found for lower respiratory system symptoms, dermatological symptoms, eye symptoms, constitutional symptoms, chronic fatigue symptoms and several enumeration and function laboratory tests, mainly of the white blood cell system. The proportion of mature T-lymphocyte cells (CD3%) was lower in employees than in controls, and regression analyses showed significantly lower CD3% among those reporting a history of upper respiratory infections. Specific S. chartarum antibody tests (IgE and IgG) showed small differences (NS). It is concluded that prolonged and intense exposure to toxigenic S. chartarum and other atypical fungi was associated with reported disorders of the respiratory and central nervous systems, reported disorders of the mucous membranes and a few parameters pertaining to the cellular and humoral immune system, suggesting a possible immune competency dysfunction.

Adult↗
PubMed1987

Phospholamban stoichiometry in canine cardiac muscle sarcoplasmic reticulum.

Treatment of cardiac sarcoplasmic reticulum with the crosslinking reagent dithiobis (succinimidyl propionate) in the presence of 125I-calmodulin, resulted in the formation of a 40,000-dalton affinity labeled component, consisting of a 1:1, phospholamban: 125I-calmodulin complex. In parallel experiments, sarcoplasmic reticulum was phosphorylated in the presence of calmodulin and [gamma-32P]ATP, and then treated with the crosslinking reagent to produce an affinity labeled component consisting of a 1:1, calmodulin: 32P-phospholamban complex. These experiments permitted determination of the amount of 125I and 32P incorporated into the 40,000-dalton complexes, as well as the amount of 32P incorporated into the 23,000-dalton form of phospholamban. If 1 mol of Ca2+-dependent ATPase phosphoprotein represents 1 mol of 100,000-dalton Ca2+-dependent ATPase monomer, then there are 4.88 +/- 1.33 mol Ca2+-dependent ATPase/mol of phospholamban. If there are 2 mol of Ca2+-dependent ATPase phosphoprotein/mol of 100,000-dalton Ca2+-dependent ATPase monomer, then there are 9.76 +/- 2.66 mol Ca2+-dependent ATPase/mol phospholamban.

Adenosine Triphosphatases↗
PubMed1987

Identification of the calmodulin-binding components in canine cardiac sarcolemma.

The covalent attachment of 125I-calmodulin to canine cardiac sarcolemma has been achieved using the crosslinker dithiobis(succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the crosslinked products revealed three 125I-calmodulin-labeled components of Mr = 125,000, 108,000 and 81,000. That the formation of these three components was Ca-dependent and inhibited by unlabeled calmodulin, or calmodulin antagonists, would indicate that the formation of these components was calmodulin-specific. The size of these 125I-labeled components was unchanged over a range of crosslinker or 125I-calmodulin concentrations indicating that they represent 1:1 complexes between 125I-calmodulin (Mr = 17,000) and Mr = 108,000, 91,000 and 64,000 sarcolemma components respectively. The labeling of these components with 125I-calmodulin was not enhanced when endogenous calmodulin was removed from sarcolemma. The possible identity of the 125I-calmodulin-labeled sarcolemma components is discussed.

Animals↗