[Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)"].

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

[Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)].

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

Zirconia crowns--an esthetic and resistant restorative alternative for ECC affected primary teeth.

The present report discusses briefly the problem of ECC in very young children and the recommended approaches for prevention and treatment. The esthetic restoration of the maxillary incisors with Zirconia Nu Smile crowns is described. It is also stressed that the luxation injury two months after placement did not damage the appearance nor the stability of the crowns.

Minimal intervention dentistry procedures: a ten year retrospective study.

UNLABELLED: Minimal Intervention Dentistry (MID) is an effective treatment approach with increasing acceptance among dental professionals. OBJECTIVE: This study aimed to evaluate the MID impact on Dentistry by analyzing procedures performed on patients treated at a Pediatric Dentistry Graduate Program clinic which implemented MID. STUDY DESIGN: The number of procedures including sealants, modified atraumatic restorative treatment (mART), resin crowns, direct pulp capping, pulpotomy, pulpectomy, and deciduous/ permanent extractions from 333 pediatric patients treated between the years 2001 to 2003 and 2008 to 2010 in Distrito Federal, Brazil were analyzed. Statistical analysis involved chi-square and G Williams tests. RESULTS: 783 procedures were analyzed and demonstrated that there was a significant reduction of sealant placement in the last triennium when compared to the first one (p<0.0001). Moreover, there was a significant increase in the amount of mART (p<0.0001). This increase in mART procedures resulted in a significant reduction in procedures with pulp involvement: direct pulp capping (p=0.0014), pulpotomy (p=0.0014) and pulpectomy (p=0.0002). CONCLUSIONS: Based on the results, MID represented a positive impact on the intervention on caries lesions in patients, mainly reflected by the significant reduction in the number of direct pulp capping, pulpotomy and pulpectomy.

Esthetic restorative options for pulpotomized primary molars: a review of literature.

OBJECTIVE: The goal of this manuscript was to review the existing literature in regards to esthetic options to restore pulpotomized primary molars. STUDY DESIGN: A pubmed literature search has been performed and all relevant studies were assessed. RESULTS: Two laboratory, 3 restrospective and 4 prospective clinical studies were found, reviewed and analyzed. CONCLUSIONS: Based on the limited information available, we concluded that tooth colored and bonded restorations showed promising results as alternative materials to replace stainless steel crowns after pulpotomies in primary molars. Hybrid composites tend to perform better than compomers. Resin modified glass ionomer cements demonstrated excellent marginal seal and retention. More long-term follow up studies are necessary until more definitive recommendations can be made.

A randomised controlled clinical trial comparing pure Portland cement and formocresol pulpotomies followed from 2 to 4 years.

PURPOSE: The purpose of the present prospective randomised clinical control trial was to evaluate the long-term clinical and radiographic success rate of pulpotomies in primary molars using pure Portland cement versus formocresol. Pure Portland cement has shown a high rate of success in pulpotomy treatments, with no side effects. METHODS: Healthy 3- to 11-year-old children were treated with pulpotomies on primary molars as part of their scheduled dental treatment. Pulp dressing alternated randomly between pure Portland cement and formocresol. Data were analysed at follow-up periods up to 48 months. RESULTS: 68 (50%) teeth with pure Portland cement and 68 (50%) teeth with formocresol in 136 healthy children (59 boys and 77 girls) were followed. The overall success rate of the pulpotomies in this study was 95.6%. Pure Portland cement was successful in 100% of the cases (68 out of 68), and formocresol in 91.1% (62 out of 68). No association was found between success and type of tooth or time range from treatment to last follow-up. CONCLUSION: Based on this study's results, it can be concluded that there is no superiority of one material over the other and pure Portland cement can be used in primary molar pulpotomies.

Impaired Kupffer cell function precedes development of secondary amyloidosis.

It has been demonstrated previously that the acute phase reactant, serum amyloid A (SAA), is subject to degradation by surface membrane-associated proteinases of peripheral blood monocytes. However, monocytes obtained from the blood of patients with amyloidosis degraded SAA incompletely, leaving a cleavage product that, biochemically and immunologically, resembled the amyloid protein A (AA) deposited in their tissues. To investigate the role of fixed macrophages in amyloidogenesis and to establish more definitively that amyloid deposition is attributable to faulty processing of the precursor protein rather than aberrant synthesis, secondary amyloidosis was induced in C57BL/6J mice by serial injections of casein. Kupffer cells (KC) were isolated from livers of mice that had received 0, 8, 13, 18, and greater than 30 injections of the stimulant. The cells were cultured with SAA for 4, 8, and 18 h and then subjected to electron microscopy and enzyme analyses. The medium was analyzed by SDS-PAGE to determine the amount of residual SAA and/or the appearance of AA. KC of healthy animals degraded SAA completely whereas KC of stimulated mice showed increasing amounts of residual SAA and the appearance of the AA cleavage product. The AA peptide appeared in KC cultures early during the course of casein injections and before any amyloid could be demonstrated in the organs of the stimulated mice. The addition of KC isolated from healthy mice to cultures that had produced AA eliminated the abnormal peptide. The results, indicate that defective KC function precedes amyloidosis. The abnormal AA cleavage product formed by such cells is still susceptible to hydrolysis by normal cells. In addition, ultrastructural evidence is presented that suggests that KC may also play a role in fibrillogenesis of the AA protein.

Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages.

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.

[Assessment of pulps vitality for children and adolesents].

Accurate assessment of pulp status is one of the greatest diagnostic challenges in clinical practice. This may be further complicated in children and adolescent where the practitioner is faced with different situations such as: primary teeth, developing permanent dentition, traumatized teeth, patients undergoing orthodontic treatment. In addition, the dentist is frequently faced with young children who have limited ability to recall a pain history or cooperate with the test itself. A variety of pulp testing approaches exist, and there may be a confusion as to their validity in different clinical situations. Sensitivity tests include thermal testing and Electric Pulp Test. Their limitation is the possibility to get false positive or false negative results. Their primary limitation lies in the fact that they test the sensory response of the tooth, which can be temporarily lost after dental trauma. A more accurate assessment of pulp vitality would be made by determining the presence of a functioning blood supply with the use of Laser Doppler Flowmetry or Pulse Oximetry. This paper provides the clinician with a comprehensive review of current pulp testing methods and allow greater insight into the interpretation of pulp testing results, especially in young patients.

Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds.

Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino-terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces.

Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts.

Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpressed in many carcinomas. CEA has been shown to function in vitro as a homotypic intercellular adhesion molecule. This correlation of overproduction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation. Using stable CEA transfectants of the rat L6 myoblast cell line as a model system of differentiation, we show that fusion into myotubes and, in fact, the entire molecular program of differentiation, including creatine phosphokinase upregulation, myogenin upregulation, and beta-actin downregulation are completely abrogated by the ectopic expression of CEA. The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage. The adhesion function of CEA is essential for this effect since an adhesion-defective N domain deletion mutant of CEA was ineffective in blocking fusion and CEA transfectants treated with adhesion-blocking peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose division potential with differentiation similarly to the parental cell line. Thus the expression of functional CEA on the surface of cells can block terminal differentiation and maintain proliferative potential.

Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen.

Carcinoembryonic antigen (CEA) expression is perhaps the most prevalent of phenotypic changes observed in human cancer cells. The molecular genetic basis of this phenomenon, however, is completely unknown. Twenty-seven CEA cDNA clones were isolated from a human colon adenocarcinoma cell line. Most of these clones are full length and consist of a number (usually three) of surprisingly similar long (534 base pairs) repeats between a 5' end of 520 base pairs and a 3' end with three different termination points. The predicted translation product of these clones consists of a processed signal sequence of 34 amino acids, an amino-terminal sequence of 107 amino acids, which includes the known terminal amino acid sequence of CEA, three repeated domains of 178 amino acids each, and a membrane-anchoring domain of 27 amino acids, giving a total of 702 amino acids and a molecular weight of 72,813 for the mature protein. The repeated domains have conserved features, including the first 67 amino acids at their N termini and the presence of four cysteine residues. Comparisons with the amino acid sequences of other proteins reveals homology of the repeats with various members of the immunoglobulin supergene family, particularly the human T-cell receptor gamma chain. CEA cDNA clones in the SP-65 vector were shown to produce transcripts in vitro which could be translated in vitro to yield a protein of molecular weight 73,000 which in turn could be precipitated with CEA-specific antibodies. CEA cDNA clones were also inserted into an animal cell expression vector and introduced by transfection into mammalian cell lines. These transfectants produced a CEA-immunoprecipitable glycoprotein which could be visualized by immunofluorescence on the cell surface.

Sensitivity of human carcinoma cell lines to lysis by blood natural killer cells correlating with surface expression of carcinoembryonic antigen.

The HCT-8R clone of the HCT-8 human colon tumor line, which expresses increased quantities of carcinoembryonic antigen (CEA) on its surface, was discovered to have an enhanced susceptibility to lysis by natural killer (NK) cells in human peripheral blood. This increase in susceptibility to lysis by peripheral blood mononuclear cells was not explained by stimulation of interferon release by HCT-8R cells but rather was found to be attributable to an increased susceptibility of HCT-8R cells to lysis by those NK cells that bind to sheep erythrocytes (E-RFC). Cold target competition experiments and single-cell assay for cytotoxic cells suggested that the presence of surface CEA did not increase lysis of HCT-8R by facilitating "recognition" by E-RFC-type cytotoxic cells but by rendering HCT-8R cells more susceptible to the lytic mechanism of NK cells. The magnitude of expression of surface CEA by a variety of human carcinoma cell lines with a few exceptions and subclones of HCT-8 also correlated with increased susceptibility to lysis by blood mononuclear cells. The possible clinical significance of these findings was discussed.

Epitopes of carcinoembryonic antigen defined by monoclonal antibodies prepared from mice immunized with purified carcinoembryonic antigen or HCT-8R cells.

A library of 18 monoclonal antibodies (MAbs) reactive with purified carcinoembryonic antigen (CEA) has been prepared. The specificity of these MAbs was tested and they have been separated into nine subgroups, each recognizing a different region of the CEA molecule. Seven MAbs from four of the groups also react with the nonspecific cross-reacting antigen. Some of the MAbs are directed against conformational determinants: three of the MAb groups bind poorly to sodium dodecyl sulfate-treated CEA, while five of the groups are not reactive with reduced and alkylated CEA. Three of the groups react with purified CEA but not with the cell surface CEA of HCT-8R cells, while the other groups react with both forms. The MAbs were tested for binding to fragments of CEA obtained by chemical cleavage and the groups of MAbs were found to react with different subsets of such fragments.

Specificity of anti-carcinoembryonic antigen monoclonal antibodies and their effects on CEA-mediated adhesion.

The carcinoembryonic antigen (CEA) domain specificities of a library of monoclonal anti-CEA antibodies were determined to investigate the mechanisms of homophilic binding involved in CEA-mediated intercellular adhesion. Using an indirect immunofluorescence cell surface staining technique, the reactivities of these antibodies were tested systematically on Chinese hamster ovary cells stably transfected with constructs of CEA gene family members CEA, nonspecific cross-reacting antigen, CGM6, and biliary glycoprotein, as well as on stable Chinese hamster ovary transfectants expressing truncated CEA and CEA/nerve cell adhesion molecule chimeric proteins. Epitopes for these antibodies were thus localized on the CEA molecule as follows: monoclonal antibody groups 1, 2, and 6 react with epitopes in the N-terminal domain of CEA, whereas groups 3, 5a, 5b, and 9 react with determinants found in the internal repeating domains located in the C-terminal part of the CEA molecule. Groups 4 and 8 appear to react with a repeating epitope in the internal domains of CEA and in all CEA subfamily members. Fab fragments of monoclonal antibody group 1 block aggregation of CEA transfectant cells, indicating that a region in the N domain is involved in CEA homophilic interaction. Fab fragments of monoclonal antibody group 9 recognize an epitope dependent on the B2 and A3 domains and stimulate aggregation. These results support the recently reported CEA-CEA homophilic reciprocal binding model in which anti-parallel molecules are bound by 2 bonds between the N domain of one molecule and the A3B3 domain of the interacting partner.

Studies on the control of gene expression of the carcinoembryonic antigen family in human tissue.

The control of expression of genes of the carcinoembryonic antigen family was investigated in 22 specimens of malignant and nonmalignant human colonic tissues. These surgical specimens included seven colonic adenocarcinomas that were compared with normal adjacent colonic mucosal tissues from the same individual. mRNA preparations from all colonic tissues expressed three bands of 3.5, 3.0, and 2.6 kilobases on Northern blots probed with carcinoembryonic antigen (CEA) complementary DNA probe while normal liver and spleen were negative. The major band of 3.0 kilobases was 6 to 10 times more intense in the colon tumor specimens than in the matched normal mucosa. However, the tumor/normal ratios of immunoreactive CEA in these pairs varied from 2- to greater than 100-fold. Furthermore, there was no direct proportionality between mRNA levels and gene product expression, suggesting that the known variations in CEA expression in human colonic tissues result from both transcriptional and posttranscriptional control mechanisms. Southern blots of DNA from these specimens did not reveal any gene rearrangements or amplifications accompanying expression. Finally, Southern blots of DNA digested with methylation-sensitive endonucleases and probed with a genomic DNA fragment upstream of CEA gene coding regions demonstrated that CEA expression is correlated with a decreased level of methylation in the 5' region of the CEA gene.

Monoclonal antibodies to human lung tumor antigens demonstrated by immunofluorescence and immunoprecipitation.

Various studies have demonstrated the usefulness of monoclonal antibodies in recognizing discrete tumor antigenic determinants. The present study describes the tissue reactivity of monoclonal antibodies prepared against a squamous cell carcinoma of the lung. Antigens were purified from the tumor extract by anti-beta 2 microglobulin affinity chromatography. These beta 2-associated antigens demonstrated tumor specificity by the leukocyte adherence inhibition assay. Antibody-secreting hybridomas were generated by fusion of mouse myeloma cells with mouse spleen cells immunized with purified tumor antigens. Hybridomas were selected by a solid-phase tumor membrane-binding immunoassay. The target specificity of the secreted monoclonal antibodies was ascertained by radioimmunoprecipitation analysis and indirect immunofluorescence on various human tumor and normal tissue sections. Monoclonal antibody-secreting hybridomas 48.4.8 and 48.4.2 secreted immunoglobulin that selectively immunoprecipitated polypeptide fragments from human lung tumor membrane antigens. Hybridoma 9.2.2 secreted antibody that was strongly positive by indirect immunofluorescence on all tested lung squamous cell carcinomas. Adjacent or intervening normal lung tissue did not display significant immunofluorescence. Adenocarcinomas of the lung were negative or focally positive when focal squamous cell differentiation was present. Oat cell carcinomas were negative. The secreted antibody did not significantly stain three extrapulmonary tumors or a variety of normal tissues.

Transcription of genes of the carcinoembryonic antigen family in malignant and nonmalignant human tissues.

Normal and diseased human tissues were analyzed for the transcription of genes of the carcinoembryonic (CEA) family. Epithelial tissues of colonic origin, whether malignant or normal, all express two closely related mRNA species of 3.0- and 3.5-kilobase mRNA which code for CEA. Only tissues of colonic origin were found to express these CEA-specific transcripts. Colon carcinomas consistently express a 2.6-kilobase mRNA species as well which codes for nonspecific cross-reacting antigen. Nonneoplastic colon mucosas, on the other hand, express lower or nondetectable levels of this transcript. Most breast carcinomas produce only the nonspecific cross-reacting antigen mRNA, whereas leukocytes of chronic myelogeneous leukemia express both nonspecific cross-reacting antigen mRNA and a 2.3-kilobase mRNA corresponding to a yet undefined gene of the CEA family. Thus the multiple CEA-like products reported to be produced by these tissues correspond to only four different mRNA species coding for three different peptides. These data suggest a less complex organization of the CEA family than was previously suspected and point to posttranscriptional modifications, such as variable patterns of glycosylation, as the likely reason for much of the observed complexity in CEA-like glycoproteins.

A mouse analogue of the human carcinoembryonic antigen.

Functional human carcinoembryonic antigen (CEA)-like genes have been shown to be present in the mouse. Southern analyses of murine DNA using both human and murine CEA complementary DNA probes have revealed the presence of multiple CEA-like genes, while analyses of RNA from different mouse tissues showed CEA-like transcripts in adult colon and liver. Furthermore, a CEA-like protein, immunoprecipitable with a rabbit polyclonal serum raised against human CEA, has been detected in adult murine colon tissue. Several murine CEA complementary DNA clones have been isolated from a murine colon complementary DNA library, and characterization of one such clone demonstrates that both the N-terminal and the internal domains have been conserved between the two species. The existence of a murine counterpart of CEA strengthens the case for an essential function for this human tumor marker and provides an experimentally amenable system for elucidation of its biological properties.

Identification of elastases associated with purified plasma membranes isolated from human monocytes and lymphocytes.

Studies were carried out to understand the pathogenesis of amyloid formation and to localize the elastase-like enzymes postulated to be associated with the surface of human peripheral blood monocytes and lymphocytes. These enzymes are known to degrade serum amyloid A and amyloid A proteins. Pure plasma membrane preparations were obtained by allowing cells to attach to polyacrylamide beads, followed by their disruption. The purity of the membranes was monitored by electron microscopy and enzyme determinations. The extracted membrane enzymes which have molecular weights of 56000 and 30000, respectively, were inhibited by DFP, MeO-Suc-Ala-Ala-Pro-Val-CH2Cl, Ac-Pro-Phe-Arg-CH2Cl . HCl, and elastinal but were not inhibited by EDTA or epsilon-amino caproic acid, thus exhibiting the properties of elastases. These enzymes cleave serum amyloid A to amyloid protein A. In some individuals, cleavage stops at this point, while in others a second step occurs, resulting in complete protein degradation. This activity was comparable whether monocyte or lymphocyte plasma membranes were employed. Since lymphocyte dependent cytotoxicity has also been attributed to surface proteases, it is likely that a spectrum of membrane associated enzymes mediate important physiologic function of these mononuclear leukocytes.