RESUMEN
Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti-obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥ 2 kg or body mass index (BMI) reduction ≥ 0.5 kg/m(2) . Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective 'risk ratio' (RR) of 1.84 (95% CI: 1.37-2.46) and 2.14 (95% CI: 1.58-2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22-5.85) and 2.76 kg (95% CI: 1.61-3.83) and a mean difference in BMI reduction of 1.32 kg m(-2) (95% CI: 0.78-1.85) and 2.02 kg m(-2) (95% CI: 0.94-3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96-1.28) and 1.14 (95% CI: 1.03-1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: -0.58 to 0.74) and 0.65 kg (95% CI: -0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m(-2) (95% CI: -0.39 to 0.75) and 0.83 kg m(-2) (95% CI: 0.29-1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti-obesity drugs but with fewer reported adverse effects. However, these conclusions were limited by small sample size and low quality of methodologies.
Asunto(s)
Terapia por Acupuntura/métodos , Medicina Tradicional China/métodos , Obesidad/terapia , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/uso terapéutico , Terapias Complementarias , Humanos , Resultado del TratamientoRESUMEN
A set of variant human hemoglobins, each with an Ala or Gly substitution at a single residue, has been prepared, and the kinetics of their reactions with carbon monoxide have been measured. This reaction is rate-limited by the binding of the first CO to the deoxygenated T state of the protein. The magnitudes of the effects of the mutations on CO combination vary widely, and, with the exception of beta Y145, the residues with the most significant effects on these kinetics are found in the hinge region of the alpha 1 beta 2 interface. Mixed-metal hybrids, with zinc protoporphyrin IX in place of heme on both alpha or both beta subunits, were prepared for beta W37E, beta W37A, alpha Y140G, and alpha Y140A, hinge region variants causing large kinetic changes, and for beta Y145G. Such hybrids permit measurements of the kinetics of CO binding to only the heme-containing alpha or beta subunits within the unliganded hemoglobin tetramer. Mutations at beta 37 and alpha 140 have global effects on the T state, increasing the rates of CO binding to both types of subunits. Mutation of beta Y145 has a large effect on the beta subunits in the deoxygenated T state, but very little effect on the alpha subunits. Oxygen equilibria measurements on the crystalline T state of beta W37E also indicate large affinity increases in both subunits of this variant. The overall oxygen equilibria of the variant hemoglobins in solution are sensitive to numerous variables besides the properties of the deoxygenated T state. In contrast to CO combination kinetics, the residues whose alterations cause the largest changes in overall oxygen equilibria in solution are scattered seemingly randomly within the alpha 1 beta 2 interface.
Asunto(s)
Hemoglobinas/química , Hemoglobinas/genética , Mutación , Sustitución de Aminoácidos , Monóxido de Carbono/metabolismo , Dimerización , Globinas/química , Globinas/genética , Globinas/metabolismo , Hemoglobina A/química , Hemoglobina A/genética , Hemoglobina A/metabolismo , Hemoglobinas/metabolismo , Humanos , Técnicas In Vitro , Hierro/química , Cinética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Oxígeno/metabolismo , Estructura Cuaternaria de Proteína , Subunidades de Proteína , Protoporfirinas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Zinc/químicaRESUMEN
Because Tyr35beta is located at the convergence of the alpha1beta1, alpha1beta2, and alpha1alpha2 interfaces in deoxyhemoglobin, it can be argued that mutations at this position may result in large changes in the functional properties of hemoglobin. However, only small mutation-induced changes in functional and structural properties are found for the recombinant hemoglobins betaY35F and betaY35A. Oxygen equilibrium-binding studies in solution, which measure the overall oxygen affinity (the p50) and the overall cooperativity (the Hill coefficient) of a hemoglobin solution, show that removing the phenolic hydroxyl group of Tyr35beta results in small decreases in oxygen affinity and cooperativity. In contrast, removing the entire phenolic ring results in a fourfold increase in oxygen affinity and no significant change in cooperativity. The kinetics of carbon monoxide (CO) combination in solution and the oxygen-binding properties of these variants in deoxy crystals, which measure the oxygen affinity and cooperativity of just the T quaternary structure, show that the ligand affinity of the T quaternary structure decreases in betaY35F and increases in betaY35A. The kinetics of CO rebinding following flash photolysis, which provides a measure of the dissociation of the liganded hemoglobin tetramer, indicates that the stability of the liganded hemoglobin tetramer is not altered in betaY35F or betaY35A. X-ray crystal structures of deoxy betaY35F and betaY35A are highly isomorphous with the structure of wild-type deoxyhemoglobin. The betaY35F mutation repositions the carboxyl group of Asp126alpha1 so that it may form a more favorable interaction with the guanidinium group of Arg141alpha2. The betaY35A mutation results in increased mobility of the Arg141alpha side chain, implying that the interactions between Asp126alpha1 and Arg141alpha2 are weakened. Therefore, the changes in the functional properties of these 35beta mutants appear to correlate with subtle structural differences at the C terminus of the alpha-subunit.
Asunto(s)
Sustitución de Aminoácidos , Hemoglobinas/química , Hemoglobinas/metabolismo , Mutagénesis Sitio-Dirigida , Sitios de Unión , Monóxido de Carbono/metabolismo , Cristalografía por Rayos X , Hemoglobinas/genética , Humanos , Cinética , Modelos Moleculares , Mutación , Oxígeno/metabolismo , Fotólisis , Estructura Cuaternaria de Proteína , Subunidades de Proteína , Termodinámica , Tirosina/genética , Tirosina/metabolismoRESUMEN
We have compared the photoinitiated electron-transfer (ET) reaction between cytochrome b(5) (b(5)) and zinc mesoporphyrin-substituted hemoglobin [(ZnM)Hb] and Hb variants in order to determine whether b(5) binds to the subunit surface of either or both Hb chains, or to sites which span the dimer--dimer interface. Because the dimer--dimer interface would be disrupted for monomers or alpha beta dimers, we studied the reaction of b(5) with alpha ZnM chains and (ZnM)Hb beta W37E, which exists as alpha beta dimers in solution. Triplet quenching titrations of the ZnHb proteins with Fe(3+)b(5) show that the binding affinity and ET rate constants for the alpha-chains are the same when they are incorporated into a Hb tetramer or dimer, or exist as monomers. Likewise, the parameters for beta-chains in tetramers and dimers differ minimally. In parallel, we have modified the surface of the Hb chains by neutralizing the heme propionates through the preparation of zinc deuterioporphyrin dimethyl ester hemoglobin, (ZnD-DME)Hb. The charge neutralization increases the ET rate constants 100-fold for the alpha-chains and 40-fold for the beta-chains (but has has little effect on the affinity of either chain type for b(5), similar to earlier results for myoglobin). Together, these results indicate that b(5) binds to sites at the subunit surface of each chain rather than to sites which span the dimer-dimer interface. The charge-neutralization results further suggest that b(5) binds over a broad area of the subunit face, but reacts only in a minority population of binding geometries.
Asunto(s)
Citocromos b5/química , Hemoglobinas/química , Proteínas de la Membrana/química , Animales , Sitios de Unión , Bovinos , Deuteroporfirinas/química , Dimerización , Transporte de Electrón , Esterificación , Compuestos Férricos/química , Humanos , Metaloporfirinas/química , Fotólisis , Estructura Terciaria de Proteína , Volumetría , Zinc/químicaRESUMEN
We describe an operating theater blood transaction system (OTBTS) that is a novel computer software system incorporating electronic crossmatch and the concept of a "self-service" blood banking system in the operating theater. Through this system, the surgeons and the anesthetists can issue blood units for intraoperative transfusion for the patients with a negative antibody screen without the need for a porter service or pneumatic tube system. Since implementation of the OTBTS, the time for obtaining compatible blood for intraoperative transfusion has been reduced from 20 to 30 minutes to around 1 minute. Furthermore, the crossmatch-transfusion ratio was reduced to 1.05. The 23% of patients who required extra blood units (i.e., more than originally anticipated) during surgery further benefited from the system. The blood stock reserved for patients undergoing surgery was reduced by 20%. Therefore, the OTBTS is a system that can greatly enhance the efficiency and safety of intraoperative transfusion and can also save workforce resources.
Asunto(s)
Transfusión Sanguínea/métodos , Procedimientos Quirúrgicos Operativos/métodos , Terapia Asistida por Computador/instrumentación , Bancos de Sangre/normas , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Humanos , Cuidados IntraoperatoriosRESUMEN
Human hemoglobin produced in the Escherichia coli coexpression system of Hernan et al. [(1992) Biochemistry 31, 8619-8628] has been transformed into a functionally homogeneous protein whose properties closely approximate those of normal hemoglobin A. Both of the alpha and beta chains of this hemoglobin contain a valine-methionine substitution at position 1 in order to accommodate the difference in specificity of the protein-processing enzymes of procaryotes. Despite extensive purification, functional homogeneity of the E. coli expressed hemoglobin was achieved only by the complete disassembly of the hemoglobin into its component alpha and beta globins and their reassembly in the presence of hemin. The kinetics of CO combination and the thermodynamics of O2 binding and cooperativity of the reassembled alphaV1M-betaV1M hemoglobin closely approximate those of HbA. The alpha globin obtained from the E. coli expressed hemoglobin was also combined with normal human beta chains and hemin to form the alphaV1M variant. The alpha+M variant of HbA, in which the normal N-terminal valine of the alpha chains is preceded by a methionine residue, was prepared by the same procedure. The kinetics of the reactions of CO with the alphaV1M and alpha+M variants are similar to those for HbA. The equilibria of oxygen binding to alphaV1M and HbA are similar whereas alpha+M exhibits a significantly higher oxygen affinity. The three-dimensional structures of alphaV1M and alpha+M offer an explanation for the latter affinity difference. Although the structures of alphaV1M and HbA, which have been determined by X-ray crystallography, are virtually indistinguishable except at the N-terminal residues, that of alpha+M indicates the displacement of a solvent molecule, possibly a chloride ion, from arginine 141alpha. Such an alteration in an anion binding site could result in increased oxygen affinity.
Asunto(s)
Escherichia coli/genética , Hemoglobinas/química , Hemoglobinas/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Cristalización , Cristalografía por Rayos X , Hemoglobina A/química , Hemoglobina M/química , Hemoglobinas/genética , Humanos , Metionina/genética , Modelos Moleculares , Fragmentos de Péptidos/química , Proteínas Recombinantes/aislamiento & purificación , Valina/genéticaRESUMEN
Four variants of human beta globin in which the Trp at position 37 has been replaced with a Tyr, Ala, Gly, or Glu have been expressed in Escherichia coli. These globins have been combined with normal human alpha chains and heme to form tetrameric hemoglobin molecules. A technique for the preparation of alpha chain dimers, which are cross-linked between their alpha99 lysine residues, has been developed, and these alpha dimers were combined with two of the beta globins, betaW37G and betaW37E, to form the corresponding cross-linked variants. The kinetics of CO binding to the deoxygenated derivatives following rapid mixing and of CO rebinding following flash photolysis have been examined as functions of pH in the presence and absence of the organic phosphate inositol hexaphosphate, IHP. The kinetic measurements indicate that replacement of the tryptophan with other residues destabilizes the hemoglobin tetramer, resulting in considerable dissociation of even the deoxygenated hemoglobins into alphabeta dimers at micromolar protein concentrations. Substitutions at beta37 also alter the properties of the deoxygenated hemoglobin tetramer. The alteration of the functional properties of the T states of these variants as well as the tendency of the deoxygenated derivatives to dissociate into alphabeta dimers increases in the order HbA < betaW37Y < betaW37A < betaW37G < betaW37E. Stabilizing the betaW37G or betaW37E tetramers by addition of IHP or by cross-linking does not restore the normal functional properties of the T state. Measurements of the geminate rebinding of CO establish a kinetic difference between the normal R state tetramer and the alphabeta dimer consistent with quaternary enhancement, the greater affinity of oxygen for the R state tetramer than for the alphabeta dimer. Kinetics of geminate rebinding also suggest that quaternary enhancement may be altered by substitutions at the beta37 position.
Asunto(s)
Hemoglobina A/metabolismo , Conformación Proteica , Sustitución de Aminoácidos , Monóxido de Carbono/metabolismo , Monóxido de Carbono/efectos de la radiación , Reactivos de Enlaces Cruzados/química , Escherichia coli/metabolismo , Globinas/biosíntesis , Globinas/química , Globinas/genética , Globinas/metabolismo , Hemoglobina A/biosíntesis , Hemoglobina A/química , Hemoglobina A/genética , Humanos , Concentración de Iones de Hidrógeno , Cinética , Espectrometría de Masas , Mutación , Fotólisis , Ácido Fítico/metabolismo , Unión Proteica , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triptófano/genéticaRESUMEN
The effects of chloride ion concentration on the rate constants for association of carbon monoxide with human hemoglobin A and a synthetic form of the mutant hemoglobin Rothschild (beta 37 Trp-->Arg) have been investigated by stopped-flow techniques. Previous studies of the structure [Kavanaugh et al. (1992) Biochemistry 31, 4111] and functional properties [Rivetti et al. (1993) Biochemistry 32, 2888] of hemoglobin Rothschild crystallized in the T state have demonstrated that the mutant arginine residues create new chloride ion binding sites and that chloride ions act to lower the oxygen affinity of hemoglobin Rothschild in these crystals. The studies reported here demonstrate a parallel effect of chloride ions on the rate of CO association with deoxygenated hemoglobin Rothschild in solution. Although the kinetics of CO binding to this hemoglobin in solution exhibit a Bohr effect, the chloride effect is independent of pH. In addition, we find that other halide ions have similar effects on the rate constants for the association of CO with this hemoglobin variant.
Asunto(s)
Cloruros/metabolismo , Hemoglobinas Anormales/metabolismo , Sitios de Unión , Monóxido de Carbono/metabolismo , Cloruros/química , Hemoglobinas Anormales/química , Humanos , Cinética , Concentración Osmolar , SolucionesRESUMEN
The overexpression of a nonfusion product of human beta-globin in Escherichia coli from its cDNA sequence has been accomplished for the first time. Expression of beta-globin from its native cDNA required the use of the strong bacteriophage T7 promoter. In this system, beta-globin accumulated to approximately 10% of total E. coli proteins. alpha-Globin was not expressed in the T7 system using the native cDNA. For the expression of alpha-globin, synthetic genes containing optimal E. coli codons were constructed. Neither synthetic alpha- nor beta-globin gene alone was expressed from the lac or tac promoter. Globin expression was achieved when the two synthetic alpha- and beta-globin genes were combined as an operon downstream of the lac promoter. The two proteins combined intracellularly with endogenous heme, which was concomitantly overproduced to yield tetrameric hemoglobin as roughly 5-10% of total E. coli protein. Cloning the alpha- and beta-globin cDNAs in a construct identical with the lac promoter did not yield globin production, establishing the requirement for optimal codon usage. The recombinant beta-globin from the T7 expression system was purified and reconstituted in vitro with heme and native alpha chains. N-terminal analyses showed that the beta-globin produced in the T7 system and the tetrameric hemoglobin produced from the synthetic genes contained an additional beta 1 methionine residue. Two additional mutants, beta 1 Val----Met and beta 1 Val----Ala were produced using the T7 system. Functional and structural properties of the purified hemoglobins will be discussed in the following papers.
Asunto(s)
Hemoglobinas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Codón/genética , Escherichia coli/genética , Genes Sintéticos , Globinas/biosíntesis , Globinas/genética , Hemoglobinas/biosíntesis , Humanos , Datos de Secuencia Molecular , Mutagénesis , Operón , Regiones Promotoras Genéticas/genética , Ingeniería de Proteínas/métodos , Procesamiento Proteico-Postraduccional , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Fagos T/genéticaRESUMEN
The relation of human erythrocyte Rh0(D) to Du sites is an important unresolved question in the field of immunohematology. To compare the immunological reactivity of Rh0(D)-positive and Du erythrocytes, the binding characteristics of two anti-Rh0(D) antisera to human Rh0(D)-positive and Du ("low-grade") erythrocytes were studied. 14C-Protein A and direct antibody-labeled techniques were used to generate binding curves and to derive double-reciprocal plots. The results show that the number of antigen sites differ by a factor of 10 to 15 between the Rh0(D)-positive and Du red cells, but that the dissociation constants between anti-Rh0(D) and the Rh0(D) and Du antigens are indistinguishable when studied by the two labeling methods and two different anti-Rh0(D) antibodies. The extent of binding to 112 different Du samples showed a normal distribution and was independent of apparent phenotype. These data suggest immunologic identity of Rh0(D) and Du ("low-grade") sites and that the difference between the antigens of Rh0(D) and Du cells is quantitative only. The data are incompatible with the "missing mosaic" and gene interaction theories of mechanism.
Asunto(s)
Eritrocitos/inmunología , Isoanticuerpos/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Reacciones Antígeno-Anticuerpo , Humanos , Inmunoglobulina G/inmunología , Papaína/farmacología , Fenotipo , Proteína Estafilocócica A/inmunologíaRESUMEN
Previous studies have suggested a membrane phospholipid requirement for Rho(D) antigen activity. Isolated erythrocyte membranes incubated with phospholipase A2 from both bee venom and porcine pancreas undergo loss of Rh antigen activity. The mode of attenuation of this antigen activity as indicated by double-reciprocal binding plots suggests substantial loss of sites accompanied by an apparently increased association constant. In the presence of anti-Rho(D), but not anti-A, bound to group A Rho(D)-positive membranes prior to hydrolysis, there is marked protection: almost complete preservation of sites at the expense of a decreased association constant. This pattern of protection is not seen with phospholipase C, which cleaves the polar headgroup in contrast to the A2-enzymes, which hydrolyze the fatty acid in the 2-position. Analysis of the products of digestion shows a trend to protection of bulk phospholipids of all major classes in the presence of bound specific antibody. The hydrophobic fatty acid chain may be the site with which the bound anti-Rho(D) antibody is in closest proximity.
Asunto(s)
Membrana Eritrocítica/efectos de los fármacos , Isoanticuerpos/inmunología , Fosfolipasas/farmacología , Fosfolípidos/metabolismo , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Animales , Venenos de Abeja , Humanos , Fosfolipasas A/farmacología , Fosfolipasas A2 , Porcinos , Fosfolipasas de Tipo C/farmacologíaRESUMEN
Radiation inactivation was used to determine the molecular size of the RhO(D) antigen of isolated membranes and of the intact human erythrocyte. Isolated membranes were frozen and irradiated at -50 degrees C. After thawing, the bound 14C-anti-D was measured and the log residual Rh(D) antigen activity was plotted against the radiation dose. A mol. wt of 60,000 was calculated. Intact human erythrocytes frozen in the presence of cryoprotective reagents were also studied. Rh(D) antigen inactivation occurred as a single exponential function of radiation dose which also yielded a mol. wt of approx. 56,000 upon analysis by classical target theory.
Asunto(s)
Eritrocitos/inmunología , Sistema del Grupo Sanguíneo Rh-Hr , Relación Dosis-Respuesta en la Radiación , Membrana Eritrocítica/inmunología , Membrana Eritrocítica/efectos de la radiación , Eritrocitos/efectos de la radiación , Congelación , Humanos , Técnicas In Vitro , Peso MolecularRESUMEN
Hemolysis resulting from a warm-to-cold temperature shift in a hypertonic environment (hypertonic cryohemolysis) is studied with the use of phospholipases as membrane probes of the phospholipids of the outer leaflet of the bilayer. Bee venom phospholipase A2 which attacks only phosphatidylcholine (PC) in the intact erythrocyte results in inhibition of cryohemolysis produced by both hypertonic sodium chloride and sucrose. In both cases, about 25% of the loss of PC occurs before any such inhibition, suggesting the possibility of functionally separate domains of PC in the outer leaflet of the bilayer. Sphingomyelinase also attacks only sphingomyelin in the intact erythrocyte and results in inhibition of cryohemolysis due to hypertonic sodium chloride but not of that due to sucrose. In each case, inhibition of the enzymatic hydrolysis by EDTA abolished the effect on cryohemolysis. It is postulated that cryohemolysis is inhibited when phospholipid interaction with membrane (cytoskeletal) proteins are abolished, but present knowledge of membrane structure does not permit a detailed mechanism to be proposed.
Asunto(s)
Frío , Hemólisis , Fosfatidilcolinas/sangre , Membrana Eritrocítica/metabolismo , Humanos , Técnicas In Vitro , Lípidos de la Membrana/sangre , Proteínas de la Membrana/sangre , Concentración Osmolar , Solución Salina Hipertónica , Esfingomielinas/sangre , SacarosaRESUMEN
The relation of the human erythrocyte Rho(D) antigen to its chimpanzee counterpart is currently unresolved. To explore this relation, we prepared 14C protein A to compare the binding parameters between human anti-Rho(D) and Rho(D)-positive human and chimpanzee erythrocytes. Double reciprocal plots of the binding in each case exhibited a straight line with intercepts indicating approximately the same numbers of Rho(D) binding sites for human and chimpanzee erythrocytes but an affinity that was 20 times greater for the human. This would indicate that the human and chimpanzee each have a single class of sites whose primary structure is very similar but sufficiently different to give the large divergence in affinity as measured by the human isoimmune antiserum.
Asunto(s)
Membrana Eritrocítica/inmunología , Eritrocitos/inmunología , Pan troglodytes/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Animales , Humanos , Especificidad de la Especie , Proteína Estafilocócica ARESUMEN
Two of four chimpanzees developed a moderately strong positive direct Coombs test after injection of stroma of their autologous erythrocytes that had been treated with alpha-methyldopa in the presence of diethyldithiocarbamate. Similar experiments with rabbits were unsuccessful. The results are concluded to be a demonstration that the first step in the development of autoantibody in alpha-methyldopa therapy is interaction of the oxidized drug with certain, as yet unidentified, peptides of the erythrocyte membrane.