RESUMO
BACKGROUND: Incorporation of routine clinical testing for neutralizing antibodies (NAbs) to interferon (IFN)-ß has remained problematic. With increasing treatment choice for patients, routine NAb testing should be incorporated to aid therapeutic decisions. OBJECTIVE: We sought to improve interpretation of NAb results by combining the luciferase NAb assay (luciferase gene expression assay under control of interferon-stimulated response element) and in-vivo biomarker (myxovirus A protein, MxA) induction in patients with MS. METHODS: Blood samples (serum and PAXGene(®) for RNA) were obtained pre-injection and 12 hours post-injection of IFN-ß from 144 subjects. Sera were tested for NAbs using the luciferase assay. MxA expression was quantified by real-time polymerase chain reaction (PCR). RESULTS: 26% of samples were NAb positive (titre > 20 NU). There was no difference in NAb titres in the pre- or post-dose sera (p = 0.643). MxA expression was inhibited in a dose-dependent fashion in NAb positive samples. Mean MxA level post-IFN-ß: NAb negative 2330 (95% CI 1940-2719), NAb 20-99 NU 1533 (95% CI 741-2324), NAb 100-600 NU 832 (186-1478) and NAb > 600 NU 101 (95% CI 0-224). NAb titre and MxA level correlated strongly: MxA pre- (Spearman r = -0.72, p < 0.0001), MxA post- (Spearman r = -0.79, p < 0.0001) and MxA induction (Spearman r = -0.67, p = 0.0004). CONCLUSION: A single, 12-hour post-injection sample should be used to test for NAbs using the luciferase assay and IFN-ß bioactivity (MxA) in the clinical setting.
Assuntos
Anticorpos Neutralizantes/sangue , Bioensaio/métodos , Monitoramento de Medicamentos/métodos , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/genética , Genes Reporter , Humanos , Fatores Imunológicos/imunologia , Interferon beta-1a , Interferon beta/imunologia , Londres , Luciferases/biossíntese , Luciferases/genética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteínas de Resistência a Myxovirus , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Elementos de Resposta , Fatores de Tempo , Transfecção , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Cerebrospinal fluid (CSF) spectrophotometry for bilirubin is a highly sensitive test in the diagnostic work up of a suspected subarachnoid hemorrhage (SAH). CASES: We report two cases suffering from an aneurysmal SAH in which extraventricular drainage for acute hydrocephalus was required. Longitudinal analyses of the CSF samples demonstrated that CSF bilirubin was detectable in all cases during the first week, becoming undetectable in one case in the second week. Importantly, CSF ferritin levels rose substantially (>1,000 ng/ml) after 6 days, peaking around 3,000 ng/ml after 2 weeks (normal upper reference range 12 ng/ml). In both cases blood was visible on the initial CT brain scan, disappearing on a later scan. CONCLUSION: CSF ferritin levels may be an important additional laboratory test in the diagnostic work-up of patients with a suspected SAH. CSF ferritin levels may prove particularly helpful in cases with late presentation if the CT brain scan is normal and CSF bilirubin level is undetectable.
Assuntos
Bilirrubina/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Ferritinas/líquido cefalorraquidiano , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/diagnóstico por imagem , Espaço Subaracnóideo/metabolismo , Tomografia Computadorizada por Raios XRESUMO
Few regional and seasonal Guillain-Barré syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.
Assuntos
Autoanticorpos/líquido cefalorraquidiano , Glicoesfingolipídeos/imunologia , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/genética , Cadeias beta de HLA-DQ/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Infecções por Campylobacter/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença/genética , Alemanha , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/genética , Índice de Gravidade de Doença , Adulto JovemRESUMO
Abnormal proteins synthesized in rabbit reticulocytes in response to (i) the lysine analogue aminoethylcysteine and (ii) puromycin, form high molecular weight aggregates prior to degradation. Inhibitors of ATP synthesis partially inhibit catabolism of the aminoethylcysteine-induced abnormal protein; degradation of puromycin peptides synthesized after incubation with 25 micrograms/ml puromycin was not inhibited. Catabolism of the analogue-induced high molecular weight aggregate of abnormal protein in cell-free extracts was markedly stimulated by ATP, whereas proteolysis of the aggregated puromycin-peptides was ATP-independent. The ability of the reticulocytes to degrade the puromycin-peptide aggregates was found to decrease with cellular maturity. It is suggested that the energy-dependency for proteolysis is in some way related to the chain length of the abnormal protein synthesized.
Assuntos
Trifosfato de Adenosina/farmacologia , Proteínas Sanguíneas/biossíntese , Envelhecimento Eritrocítico , Reticulócitos/metabolismo , 2,4-Dinitrofenol , Animais , Proteínas Sanguíneas/isolamento & purificação , Sistema Livre de Células , Dinitrofenóis/farmacologia , Peso Molecular , Polirribossomos/efeitos dos fármacos , Polirribossomos/metabolismo , Puromicina/sangue , Coelhos , Reticulócitos/efeitos dos fármacos , Cianeto de Sódio/farmacologia , Fluoreto de Sódio/farmacologiaRESUMO
The ability of rabbit reticulocytes to degrade puromycin-peptides and aminoethylcysteine-induced aberrant polypeptides decreased during cellular maturation. Cell-free studies indicate that the fall in proteolytic activity is not a consequence of accumulation of proteinase inhibitors or the conversion of all of the abnormal protein into undegradable forms. A decrease in peptidase activity using seven dipeptides and one tripeptide as substrates was also found to accompany reticulocyte maturation. Addition of the aminopeptidase B inhibitor bestatin to reticulocyte extracts did not inhibit the conversion of acid-precipitable puromycin-peptides to acid-soluble products; bestatin did induce the accumulation of very low molecular weight material (possibly di- or tripeptides) within the acid soluble fraction.
Assuntos
Endopeptidases/sangue , Peptídeo Hidrolases/sangue , Reticulócitos/enzimologia , Animais , Cisteína/análogos & derivados , Cisteína/farmacologia , Leucina/análogos & derivados , Leucina/farmacologia , Puromicina/sangue , Coelhos , Reticulócitos/efeitos dos fármacosRESUMO
Malondialdehyde (MDA) and hypochlorite anions are deleterious products of oxygen free-radical metabolism. The effects of carnosine, a naturally occurring dipeptide (beta-alanyl-L-histidine), on protein modification mediated by MDA and hypochlorite have been studied. MDA and hypochlorite induced formation of carbonyl groups and high molecular weight and cross-linked forms of crystallin, ovalbumin and bovine serum albumin. The presence of carnosine effectively inhibited these modifications in a concentration-dependent manner. It is proposed that relatively non-toxic carnosine and related peptides might be explored as potential therapeutic agents for pathologies that involve protein modification mediated by MDA or hypochlorite.
Assuntos
Carnosina/farmacologia , Ácido Hipocloroso/antagonistas & inibidores , Ácido Hipocloroso/toxicidade , Malondialdeído/antagonistas & inibidores , Malondialdeído/toxicidade , Proteínas/química , Proteínas/efeitos dos fármacos , Animais , Bovinos , Reagentes de Ligações Cruzadas , Cristalinas/química , Cristalinas/efeitos dos fármacos , Técnicas In Vitro , Peso Molecular , Ovalbumina/química , Ovalbumina/efeitos dos fármacos , Soroalbumina Bovina/química , Soroalbumina Bovina/efeitos dos fármacosRESUMO
We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. Autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.
Assuntos
Doença de Depósito de Glicogênio Tipo IV/genética , Hidropisia Fetal/patologia , Doenças Musculares/patologia , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Adulto , Idade de Início , Saúde da Família , Evolução Fatal , Feminino , Variação Genética , Idade Gestacional , Doença de Depósito de Glicogênio Tipo IV/enzimologia , Humanos , Hidropisia Fetal/genética , Músculo Esquelético/patologia , Músculo Esquelético/ultraestrutura , Doenças Musculares/congênito , Doenças Musculares/genética , GravidezRESUMO
Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts. Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules. Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.
Assuntos
Carnosina/farmacologia , Senescência Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Peptídeos beta-Amiloides/farmacologia , Animais , Células CHO , Células Cultivadas , Circulação Cerebrovascular , Cricetinae , Reagentes de Ligações Cruzadas , DNA/efeitos dos fármacos , DNA/metabolismo , Dano ao DNA , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Ácido Hipocloroso/farmacologia , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Malondialdeído/metabolismo , Fragmentos de Peptídeos/farmacologia , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , RatosRESUMO
Malondialdehyde (MDA) is a deleterious end-product of lipid peroxidation. The naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in brain and innervated tissues at concentrations up to 20 mM. Recent studies have shown that carnosine can protect proteins against cross-linking mediated by aldehyde-containing sugars and glycolytic intermediates. Here we have investigated whether carnosine is protective against malondialdehyde-induced protein damage and cellular toxicity. The results show that carnosine can (1) protect cultured rat brain endothelial cells against MDA-induced toxicity and (2) inhibit MDA-induced protein modification (formation of cross-links and carbonyl groups).
Assuntos
Lesões Encefálicas/prevenção & controle , Encéfalo/metabolismo , Carnosina/farmacologia , Malondialdeído/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cristalinas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio/efeitos dos fármacos , Glucose/metabolismo , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/metabolismo , RatosRESUMO
Palmitoyl-protein thioesterase (PPT) and tripeptidyl-peptidase I (TPP-I) activities were measured in leucocytes and fibroblasts. Fourteen patients were confirmed as having late infantile neuronal ceroid lipofuscinosis due to a deficiency of TPP-I activity. This included one patient with a milder and more protracted form of the disease. In addition this enzyme deficiency was found in a clinically normal younger sibling of a patient. Of particular importance was the finding of normal TPP-I activity in two patients who had been diagnosed as having classical late infantile neuronal ceroid lipofuscinosis. A deficiency of PPT was confirmed retrospectively in stored fibroblasts from two patients who had already died having been diagnosed with infantile neuronal ceroid lipofuscinosis. Palmitoyl-protein thioesterase or TPP-I activities were measured in chorionic villi and cultured chorionic villi cells in three pregnancies. The enzyme results were confirmed by mutational analysis if the mutations were known, or, in the case of the pregnancy at risk for infantile neuronal ceroid lipofuscinosis by electron microscopy of the chorionic villi. Our results show that assay of PPT and TPP-I is reliable in the diagnosis of patients with mutations in the CLN1 and CLN2 genes. It is imperative to assay these enzymes in all patients to confirm the diagnosis and ensure accurate genetic counselling of other family members. Once an enzyme deficiency has been confirmed reliable prenatal diagnosis is available even if both mutations have not been detected.
Assuntos
Endopeptidases/metabolismo , Lipofuscinoses Ceroides Neuronais/diagnóstico , Lipofuscinoses Ceroides Neuronais/enzimologia , Tioléster Hidrolases/metabolismo , Adulto , Aminopeptidases , Criança , Amostra da Vilosidade Coriônica , Dipeptidil Peptidases e Tripeptidil Peptidases , Feminino , Fibroblastos/enzimologia , Humanos , Leucócitos/enzimologia , Masculino , Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/genética , Peptídeo Hidrolases/genética , Gravidez , Serina Proteases , Tripeptidil-Peptidase 1RESUMO
The increasing use of alternative therapies that rely on organically grown foods has renewed interest in the relationship between agricultural methods and food quality. The purpose of this article is to review the literature produced over the last 50 years comparing the nutritional quality of organic with conventional crops. Whereas few studies have been conducted, there is a trend in the data indicating higher nutrient content in organically grown crops. This phenomenon is possibly due to a higher water content in conventional crops, which causes nutrient dilution. For individual nutrients, existing studies show that organic fertilization practices produce crops with higher levels of ascorbic acid, lower levels of nitrate, and improved protein quality compared with conventionally grown crops. Although a theoretical rationale exists for possible effects of herbicides on nutrient content, few studies have examined the effects of these or other pesticides. Animal studies showed better growth and reproduction in animals fed organically grown feed compared with those fed conventionally grown feed. Further research is required to confirm the trends seen in the existing data and to clarify the exact relationships between agricultural management and nutritional quality.
Assuntos
Produtos Agrícolas , Alimentos Orgânicos , Humanos , Valor Nutritivo , Praguicidas/efeitos adversosRESUMO
OBJECTIVES: To survey existing literature comparing nutrient content of organic and conventional crops using statistical methods to identify significant differences and trends in the data. DESIGN: Published comparative measurements of organic and conventional nutrient content were entered into a database for calculation. For each organic-to-conventional comparison, a percent difference was calculated: (organic - conventional)/conventional x 100. For nutrients where there was adequate data, the Wilcoxon signed-rank test was used to identify significant differences in nutrient content as represented by the percent difference. Mean percent difference values were also calculated for each significant nutrient by study and by vegetable for the most frequently studied vegetables. The nutrient content of the daily vegetable intake was calculated for both an organic and conventional diet. RESULTS: Organic crops contained significantly more vitamin C, iron, magnesium, and phosphorus and significantly less nitrates than conventional crops. There were nonsignificant trends showing less protein but of a better quality and a higher content of nutritionally significant minerals with lower amounts of some heavy metals in organic crops compared to conventional ones. CONCLUSIONS: There appear to be genuine differences in the nutrient content of organic and conventional crops.
Assuntos
Grão Comestível , Alimentos Orgânicos/análise , Frutas , Micronutrientes/análise , Verduras , Ácido Ascórbico/análise , Humanos , Ferro/análise , Magnésio/análise , Fósforo/análiseRESUMO
OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) has been suggested to be a possible cause of multiple sclerosis (MS). If the presumed mechanism of venous stasis-related parenchymal iron deposition and neurodegeneration were true, then upregulation of intrathecal iron transport proteins may be expected. METHODS: This was a cross-sectional (n = 1,408) and longitudinal (n = 29) study on CSF ferritin levels in patients with MS and a range of neurologic disorders. RESULTS: Pathologic (>12 ng/mL) CSF ferritin levels were observed in 4% of the control patients (median 4 ng/mL), 91% of patients with superficial siderosis (75 ng/mL), 73% of patients with a subarachnoid hemorrhage (59 ng/mL), 10% of patients with relapsing-remitting MS (5 ng/mL), 11% of patients with primary progressive MS (6 ng/mL), 23% of patients with secondary progressive MS (5 ng/mL), and 23% of patients with meningoencephalitis (5 ng/mL). In MS, there was no significant change of CSF ferritin levels over the 3-year follow-up period. CONCLUSION: These data do not support an etiologic role for CCSVI-related parenchymal iron deposition in MS.
Assuntos
Ferritinas/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Insuficiência Venosa/etiologia , Adulto , Estudos de Coortes , Estudos Transversais , Avaliação da Deficiência , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Insuficiência Venosa/diagnósticoAssuntos
Enzimas , Manuais como Assunto , Separação Celular , Clonagem Molecular , Humanos , Miocárdio/citologia , Papaína , Kit de Reagentes para Diagnóstico , Pesquisa , TripsinaRESUMO
Elevated plasma aspartylglucosaminidase activity was found in 21/25 cases of CDG Ia, in single cases of CDG Ib, Ic and If, and in 15/16 cases of CDG Ix. The CDG I patients in whom the activity was not raised were either atypical clinically (CDG Ia) or very young (CDG Ih).
Assuntos
Aspartilglucosilaminase/sangue , Erros Inatos do Metabolismo dos Carboidratos/sangue , Aspartilglucosilaminase/genética , Aspartilglucosilaminase/metabolismo , Fibroblastos/metabolismo , Glicosilação , Humanos , Leucócitos/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Manose-6-Fosfato Isomerase/genética , Oligossacarídeos/metabolismo , Fosfotransferases (Fosfomutases)/genética , Fatores de TempoRESUMO
Sixty-five to ninety percent of all scoliosis is of unknown origin or idiopathic. During the last 30 yr, researchers worldwide have found a variety of abnormalities in tissues throughout the body including peripheral muscle, skin, ligaments, platelets, bone, intervertebral discs, serum and urine. The primary defects appear to be related to collagen and proteoglycan synthesis. The systemic abnormalities seen in idiopathic scoliosis cannot be explained by the biomechanical effects of the curvature.
Assuntos
Doenças do Colágeno/metabolismo , Escoliose/metabolismo , Osso e Ossos/metabolismo , Colágeno/metabolismo , Doenças do Colágeno/complicações , Glicosaminoglicanos/biossíntese , Humanos , Músculos/metabolismo , Proteoglicanas/biossíntese , Escoliose/complicaçõesRESUMO
OBJECTIVE: The purpose of this review is to examine the evidence implicating poor nutrition as a causative factor in the etiology of idiopathic scoliosis. Interactions between nutrition and genetics and biochemistry are considered. DATA SOURCES: Articles published in American or European journals or conference proceedings from 1955-1990. STUDY SELECTION: Relevant studies or observations published between 1955 and 1990 are included. DATA EXTRACTION: Data presented were selected by independent extraction by two reviewers. DATA SYNTHESIS: There is strong evidence from an animal model for an interaction between poor nutrition and genetics. There are anecdotal data and limited study data for humans. The biochemical mechanisms, explaining the actions of nutritional factors on spinal and paraspinal tissue, are partially known. CONCLUSIONS: There is evidence that poor nutrition may play a role in the etiology of idiopathic scoliosis. This possibility should be examined further in humans.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Necessidades Nutricionais , Escoliose/metabolismo , Animais , Galinhas , Pré-Escolar , Cobre/deficiência , HumanosRESUMO
It is now recognized that dietary carbohydrate components influence the prevalence and severity of common degenerative diseases such as dental problems, diabetes, heart disease and obesity. Fructose and sucrose have been evaluated and compared to glucose using glucose tolerance tests, but few such comparisons have been performed for a "natural" sugar source such as honey. In this study, 33 upper trimester chiropractic students volunteered for oral glucose tolerance testing comparing sucrose, fructose and honey during successive weeks. A 75-gm carbohydrate load in 250 ml of water was ingested and blood sugar readings were taken at 0, 30, 60, 90, 120 and 240 minutes. Fructose showed minimal changes in blood sugar levels, consistent with other studies. Sucrose gave higher blood sugar readings than honey at every measurement, producing significantly (p less than .05) greater glucose intolerance. Honey provided the fewest subjective symptoms of discomfort. Given that honey has a gentler effect on blood sugar levels on a per gram basis, and tastes sweeter than sucrose so that fewer grams would be consumed, it would seem prudent to recommend honey over sucrose.
Assuntos
Glicemia/análise , Frutose/farmacologia , Mel , Sacarose/farmacologia , Adulto , Carboidratos da Dieta/metabolismo , Teste de Tolerância a Glucose , HumanosRESUMO
Rifampin inhibited the intracellular proteolysis of canavanine-induced, rapidly sedimenting protein complexes in Escherichia coli.