Serum Levels Of Elastase Research Articles

Abstract 3122: A strategy for detecting high-risk groups for pancreatic cancer with glycol-biomarkers

Abstract (Aim) Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers, showing a high potential for invasive activity and high recurrence rates. One of the reasons for poor prognosis of PDAC is a difficulty in an early diagnosis. When pancreatic tumors are detected by CT or MRI examinations, most cases are at the advanced stage even if tumor size is within 2 cm. To make an early diagnosis for PDAC truely, we should make a targeting of high-risk groups for developing PDAC like chronic hepatitis followed by hepatocellular carcinoma. Aberrant glycosylation is a promising target for cancer biomarkers. Several kinds of glyco-biomarkers are clinically used for PDAC diagnosis like CA19-9. We have reported that fucosylated haptoglobin (Fuc-Hpt) is a novel type of glyco-biomarker for PDAC. Serum Fuc-Hpt levels are dramatically increased at the stage IV of PDAC as well as a few cases of Stage I-III. In the present study, we performed pathological analysis of surrounding tissues around pancreatic cancer as well as normal pancreas in autopsy cases and investigated the clinical usefulness of glycol-biomarkers for chronic pancreatitis and pancreatic cancer (Subjects and Methods) 88 cases of pancreatic cancer patients and 100 cases of other diseases are enrolled in this study. Inflammation, fibrosis and fatty changes were investigated in these pancreatic tissues by 2 independent researchers in blind way. Serum fucosylated haptoglobin (Fuc-Hpt) levels in patients with chronic pancreatitis and pancreatic cancer were measured with lectin-antibody ELISA, using Aleuria aurantia lectin (AAL) and Pholiota squarrosa lectin (PhoSL). AAL recognizes all types of fucosylation and PhoSL recognizes core fucosylation. (Results) Pancreatectomy specimens showed a higher ratio of positive change in fibrosis (86% vs. 42%), fatty degeneration (72% vs. 44%), and inflammatory cell infiltration (14% vs. 3%) than control samples. Multivariate analyses demonstrated that each histological change was a significant, independent determinant for PDAC. In contrast, AAL-reactive Fuc-Hpt levels were increased in patients with pancreatic cancer and AAL-reactive Fuc-Hpt was though to be produced in the liver metastasis of pancreatic cancer. In contrast, PhoSL-reactive Fuc-Hpt levels were increased in patients with chronic pancreatitis, compared to pancreatic cancer. Correlations of PhoSL-reactive Fuc-Hpt levels and other biochemical parameters such as serum amylase, lipase, and elastase levels were not observed. The investigation of mechanisms underlying an increase of serum PhoSL-reactive Fuc-Hpt in patients with chronic pancreatitis is underway. (Conclusion) Cryptogenic pancreatitis might be a premalignant disease for pancreatic cancer and dramatic changes in fucosylation linkage on Fuc-Hpt were observed in pancreatic carcinogenesis. These findings give us a possibility of preventing or diagnosing pancreatic cancer at earlier stage, chronic pancreatitis. Citation Format: Eiji Miyoshi, Tomohiro Maekawa, Makiko Ueda, Mayuka Shimomura, Shinji Takamatsu, Kotarosumitomo Nakayama, Yoshihiro Kamada, Yasuhiko Tomita. A strategy for detecting high-risk groups for pancreatic cancer with glycol-biomarkers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3122.

A Rare Pancreatic Tumor That Underwent a Change in Morphology and Histopathologic Features During Chemotherapy

Question: A 63-year-old man visited our hospital because of epigastric discomfort. He had no family history of pancreatic cancer, and abdominal examination was unremarkable. Serum levels of elastase 1 (1199 ng/dL; normal 100–400) and DUPAN2 (190 U/mL; normal <150) were elevated; however, serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, pancreatic polypeptide, gastrin, insulin, and vasoactive intestinal peptide were normal. Abdominal computed tomography (CT) showed a well-marginated round mass, 6 cm in diameter, in the pancreatic head, as well as a dilated caudal main pancreatic duct. Contrast-enhanced CT showed heterogeneous enhancement that was weak at the periphery of the tumor and almost absent in the center (Figure A). Diagnostic endoscopic ultrasound-guided fine-needle aspiration (FNA) showed trabecular growth patterns with acinar formations within a solid tumor. The tumor cells contained cytoplasmic periodic acid Schiff-positive zymogen granules and relatively large, eccentrically located nuclei. Immunohistochemistry showed strong expression of trypsin and chymotrypsin but no expression of chromogranin A or synaptophysin, suggesting acinar cell carcinoma. Because direct tumor invasion into the proper hepatic artery was suspected, we administered chemotherapy consisting of gemcitabine and S-1. After 4 courses, we observed a remarkable change in tumor morphology, including a clear demarcation of hypervascular and hypovascular areas (Figure B, white arrow). The tumor size was essentially unchanged. The disease was considered stable and stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, a surgical specimen of the tumor had a mosaic-like pattern with partial necrosis (Figure C). Microscopically, the tumor had 2 distinct components (Figure D). The hypovascular area encompassed most of the tumor and comprised of acinar epithelial cells with prominent nucleoli and pale eosinophilic cytoplasm resembling the specimen obtained by FNA (Figure E). This area was positive for trypsin and chymotrypsin, but negative for chromogranin A and synaptophysin. The Ki-67 labeling index was approximately 20%. The hypervascular

Non‐surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis

Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. Overall, 31 ChP and 29 AgP were examined clinically prior to and 12weeks after SRP (subgingival scaling of all pockets within 2days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. At baseline, serum elastase, CRP, and LBP were significantly (p<0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p<0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p<0.001). A significant difference was observed regarding change of serum elastase 12weeks after SRP between AgP and ChP (p=0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. SRP results in serum elastase reduction in AgP but not in ChP.

Haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms

Haptoglobin (Hp) polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases and atherosclerosis. Circulating neutrophils and neutrophil-associated proteases are an important initial component of experimental abdominal aortic aneurysm (AAA) formation. Elastase and C-reactive protein (CRP) levels are elevated in patients with AAAs. This study assessed the relationship between AAA expansion and Hp phenotypes, neutrophil count, elastase, and CRP levels. Eighty-three consecutive AAA patients underwent annual ultrasound scans. Three major Hp phenotypes (1-1, 2-1, and 2-2) were determined, and the neutrophil count, serum elastase, and high-sensitivity (hs) CRP levels were measured at the initial examination. After initial screening, patients were rescanned at 6- to 12-month intervals up to a period of 2 to 7 years. The mean yearly growth of the AAA largest transverse diameter was estimated for each group of Hp patients. The results are presented as median (interquartile range). Hp 2-1 patients had a significantly higher growth rate (3.69 [2.40] mm/y) of AAA compared with patients with Hp 2-2 (1.24 [0.79], P < .00001) and Hp 1-1 (1.45 [0.68], P = .00004). This association remained significant in the multivariate analysis. Elevated elastase serum activity was also evident in AAA patients with Hp 2-1 (0.119 [0.084] arbitrary units) in contrast to Hp 2-2 (0.064 [0.041], P < .00001) and Hp 1-1 (0.071 [0.040], P = .0006) patients. CRP serum levels (mg/L) were significantly higher in patients with Hp 2-1 (7.2 [7.1]) than in Hp 2-2 (3.4 [3.1], P = .0058) and Hp 1-1 (2.8 [4.1], P = .044). The neutrophil count was not significantly different among Hp groups. The Hp 2-1 phenotype showed a strong association with increased rates of the expansion of AAAs and may be a useful independent predictor of growth rate. Further large follow-up studies will be needed to investigate the pathomechanisms of association and the role of elastase and inflammation in the progression of AAA.

Serum elastase and antithrombin-3 levels after umbilical cord blood transplantation or bone marrow transplantation

The severity of graft-versus-host disease (GVHD) was compared after cord blood transplantation (CBT) and bone marrow transplantation (BMT). The severity of GVHD was also analyzed in relation to serum elastase and antithrombin-3 (AT-3) levels. There was no significant difference in the average grade of acute GVHD between 49 BMT patients and 20 CBT patients (X2-test). However, there was a lower incidence of patients without acute GVHD (grade 0) or patients with severe acute GVHD (grade 3 or 4) in CBT compared with BMT group. Linear regression analysis found no significant correlation between the serum elastase level and the grade of acute GVHD, between the serum AT-3 level and the grade of acute GVHD, or between the serum levels of elastase and AT-3 before conditioning and after engraftment. The AT-3 level after engraftment was significantly higher in the CBT group than in the BMT group and it did not fail along with the elevation of elastase in the CBT group (p < 0.01 by the Mann–Whitney U-test vs. the BMT group). In conclusion, the lower risk of severe acute GVHD in the CBT group may have been related to the smaller decrease of AT-3 after transplantation.

Unexplained Elevated Serum Pancreatic Enzymes: A Reason to Suspect Celiac Disease

The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in 19%. The frequency of elevated serum pancreatic enzymes observed was identical in the patients with "typical" and "atypical" CD symptoms and in the asymptomatic patients. Most of the elevated values were lower than 2-fold the threshold limits. Elevated pancreatic enzymes were not associated with alcohol consumption, drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound scan showed no abnormal findings in the pancreatic region in any of the CD patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and lipase in 2 cases; these patients had not strictly adhered to the GFD. We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.

Diagnostic value of serum elastase 1 in pancreatic disease

We studied serum elastase 1 concentrations in patients with pancreatic disease to assess its diagnostic value and compare its sensitivity and specificity with that of amylase and pancreatic isoamylase. Markedly raised concentrations of elastase 1 were found in all twenty-nine patients with acute pancreatitis (amylase was elevated in all but three and pancreatic isoamylase in all but one). Serial measurements of the three enzymes in acute pancreatitis showed that elastase remained elevated longer than amylase and pancreatic isoamylase. The majority of chronic pancreatitis patients studied during a painful relapse (16 out of 21, 76 per cent) had elastase concentrations above the upper normal limit. Amylase and pancreatic isoamylase were elevated in 11 (52 per cent) and in 13 (62 per cent), respectively. Most patients with chronic pancreatitis studied during clinical remission (39 out of 43) had serum elastase levels either within (n = 24) or below (n = 15) the control range. The latter had severe exocrine pancreatic insufficiency and steatorrhoea. In carcinoma of the pancrease, 20 out of 32 (63 per cent) had abnormal serum elastase concentrations; 16 were higher and 4 lower than the control range. Amylase was abnormal in 10 (31 per cent) (8 high, 2 low), and pancreatic isoamylase was abnormal in 16 (50 per cent) (11 high, 5 low). In 46 control patients with non-pancreatic abdominal pain, serum elastase concentrations were not significantly different from those in healthy controls. Elastase was slightly raised in two, whereas amylase and pancreatic isoamylase were elevated in seven and eight, respectively. We conclude that serum elastase 1 is a highly sensitive and specific indicator of pancreatic disease.

Increased gut permeability after multiple trauma.

Gut permeability was studied in multiply injured patients with respect to the development of multiple organ failure (MOF). Two groups were defined according to MOF score (threshold 10 points) as to whether MOF developed (group 1; n = 11, four deaths) or did not (group 2; n = 21, no death). Gut permeability was determined from the ratio of urinary excretion of enterally administered lactulose and mannitol. Serum elastase concentrations were also determined. Mean(s.e.m.) gut permeability was abnormal during the entire study (day 1: group 1--5.1(2.1) versus group 2--10.6(4.1) (P not significant; P < 0.001 versus normal volunteers, 0.56(0.24)). An increase on days 3 and 5 correlated with serum elastase levels only in patients in group 1 (rs = 0.71, P < 0.01). Severe injury leads to increased intestinal permeability, which is related to a systemic inflammatory response.

Serum elastase and antithrombin-3 in patients with acute graft-vs.-host disease after bone marrow transplantation

The mechanism by which inflammatory cytokines are involved in acute graft-vs.-host disease (GVHD) after hematopoietic stem cell transplantation has only been studied recently. We focused on the changes of serum elastase and antithrombin-3 (AT-3) from before pre-treatment until the leukocyte recovery period after transplantation. We examined the correlation between these two parameters and the grade of acute GVHD, as well as the mechanism of onset. We measured the serum elastase and AT-3 levels before pre-treatment and during the leukocyte recovery period in 49 consecutive patients receiving bone marrow transplantation. The severity of acute GVHD was divided into five grades (0-4). No significant differences of pre-transplantation elastase levels were observed among the GVHD grades, but the elastase level during the leukocyte recovery period showed a significant correlation with the grade of GVHD (p < 0.01). A significant inverse correlation was also observed (p < 0.05) between the pre-transplantation level of AT-3 and the grade of GVHD, as well as a significant correlation at the time of leukocyte recovery (p < 0.0001). Furthermore, a significant correlation (p < 0.0001) was observed between the elastase and AT-3 levels during the leukocyte recovery period. These results suggest that elastase levels during the leukocyte recovery period are related to the grade of acute GVHD and the mechanism appears to include vascular endothelial injury mediated via AT-3.

Potentiation of the extracellular release of equine neutrophil elastase and alpha‐1‐proteinase inhibitor by a combination of two bacterial cell wall components: fMLP and LPS

Lipopolysaccharide (LPS) and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-like peptides are Gram-negative bacterial cell wall components which, when released into the peripheral circulation in endotoxaemia, have the potential to activate leucocytes. In vitro, equine neutrophils require priming with LPS in order to generate reactive oxygen intermediates (ROI) in response to fMLP. The aim of this study was to examine whether the release of other neutrophil products is similarly dependent on prior priming with LPS. In particular, neutrophil elastase (NE), a potent proteolytic enzyme, and its major inhibitor, alpha-1 proteinase inhibitor, were investigated. Neutrophils were isolated from equine peripheral blood (n = 5) by discontinuous Percoll gradient preparative centrifugation and primed with LPS prior to stimulation with fMLP. ROI were measured by lucigenin dependent chemiluminescence (LDCL). Concentrations of NE and API were determined by ELISA on cell free supernatants taken at 0, 2, 10, 30, 60 and 90 mins post stimulus. Data was analysed by Kruskal-Wallis and Mann-Whitney Tests. Sequential exposure of Percoll purified equine blood neutrophils in vitro to LPS followed by fMLP resulted in the greatest release of NE from equine neutrophils and was required for ROI generation. However, LPS or fMLP stimulation alone resulted in an increase in NE release compared to unstimulated control cells. In contrast, significant API release was only induced by LPS stimulation or fMLP stimulation only after LPS priming, not fMLP on its own. These results suggest that different stimuli (fMLP or LPS) are capable of invoking similar responses from equine neutrophils with respect to NE release yet different ones with respect to API release. In addition, demonstration of elastase release induced by LPS and/or fMLP suggests that monitoring serum elastase levels is a potential diagnostic tool for detecting the early onset of endotoxaemia in the horse.

Elastin degradation in the superficial temporal arteries of patients with intracranial aneurysms reflects changes in plasma elastase.

alpha 1-Antitrypsin (AAT) and alpha 2-macroglobulin (AMG) are elastase inhibitors that bind the enzyme and reduce measured levels of free elastase. It was recently demonstrated that some patients with intracranial aneurysms have significantly elevated plasma elastase (PE) levels. Although this elevation is unrelated to plasma AAT, it is unknown whether abnormal AAT phenotypes or reduced AMG levels play a role. Moreover, the pathological significance of this elevation is not understood. Plasma from 24 patients with aneurysms (ruptured, n = 15; unruptured, n = 9) and 10 age-matched patients who comprised a control group was analyzed for PE and AMG levels by enzyme-linked immunosorbent assay and for AAT phenotype by isoelectric focusing. Sections of superficial temporal temporal artery obtained from these patients at the time of surgery were examined for evidence of elastin degradation by using a van Gieson stain, with scoring on a nine-point quantitative scale. Patients with aneurysms showed significantly elevated PE levels (119 +/- 28 versus 17 +/- 7 micrograms/ml, P < 0.05), but AMG levels were not decreased. AAT phenotypic abnormalities were observed in 10% (2 of 20) of the patients with aneurysms, but this was not different from the expected population incidence (7%). Elastin degradation scores were significantly higher in patients with aneurysms than in patients control group (4.26 +/- 0.54 versus 1.21 +/- 0.43, P < 0.05). In addition, patients with higher elastase levels (> 80 micrograms/ml) demonstrated 55% higher degradation scores than did those with lower elastase levels (< 80 micrograms/ml). These data suggest that high PE levels may play a role in systemic arterial elastin degradation seen in patients with intracranial aneurysms. These data also support the contention that elevated elastase levels are not the result of decreased protease inhibitor levels. Although PE levels were significantly higher for the entire group of patients with aneurysms, this assay has relatively low sensitivity for predicting the presence of unruptured aneurysms. Additional study is necessary to determine whether serum elastase levels greater than 80 micrograms/ml, in the setting of other risk factors, are useful in identifying asymptomatic patients for additional screening.

EFFECTS OF ANTIBIOTICS ON CHANGES IN CYTOKINES AND ACUTE-PHASE PROTEINS AFTER LIVER RESECTION

Cytokines and acute phase-proteins are important in infectious diseases and under surgical stress, especially in postoperative infections. To study the effects of antibiotics on changes in cytokines and acute-phase proteins after surgery, we measured serum levels of interleukin 6 (IL-6), elastase from granulocytes, pancreatic secretory trypsin inhibitor (PSTI), C-reactive protein (CRP), and fibrinogen after liver resection in 12 patients with hepatocellular carcinoma. In the six of the 12 patients (group A), flomoxef (FMOX, 4 g/day) was administered intravenously for 3 days after surgery. In six other patients (group B), imipenem-cilastatin (IPM/CS, 1g/day) was administered for the same period. Group A was comparable to group B in age distribution of patients, preoperative hepatic function, operating time, and intraoperative bleeding volume. No patients had postoperative complications. The mean changes in serum levels of IL-6 in group B were smaller than those in group A. The changes in serum levels of elastase, PSTI, CRP, and fibrinogen were also smaller than those in group A. These results suggest that IPM/CS suppressed the usual increases after major surgery in the levels of IL-6 and acute-phase proteins. This preparation may suppress the progress of hypercytokinemia in the systemic inflammatory response. The effects of antibiotics on cytokines and acute-phase proteins should be considered in the choice of antibiotics for severe infectious diseases.

Assessment of eosinophil and neutrophil participation in atopic dermatitis: Comparison with the IgE-mediated late-phase reaction

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflamamtory reactions. (J ALLERGY CLIN IMMUNOL 1994;94:120-8.)

Serial Changes in Serum Levels of Pancreatic Isoamylase, Trypsin and Elastase 1 after Surgical Interventions to the Pancreas

Serum levels of pancreatic isoamylase, trypsin and pancreatic elastase 1 were observed serially in 17 patients who underwent radical operation for gastric cancer with dissection of the anterior capsule of the pancreas and in 10 patients who underwent colorectal surgery (control group). Amylase and trypsin levels after gastrectomy were significantly higher than those in the control group on the 2nd and 4th postoperative days, but were not significantly different on the 7th postoperative day and thereafter. Elastase 1 levels were significantly higher than those in the control group from the 4th to 21 st postoperative day, but were not significantly different on the 2nd postoperative day. The serum level of elastase 1 increased more slowly and was late in returning to normal as compared with that of amylase after direct surgery on the pancreas.

Serum pancreatic enzymes in HIV-seropositive patients

Serum concentrations of trypsin and elastase I were determined in 109 HIV Ab-positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase I between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions.

Elastase/Antielastase Systems in Pulmonary Diseases

Levels of serum elastase 1 in a variety of respiratory diseases were studied. In patients with pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or pulmonary infections, including pneumonia and pulmonary tuberculosis, serum elastase 1 levels were greater than those of an age-matched control group. In lung cancer patients, however, the serum elastase 1 level was within normal limits. Although alpha 1-antitrypsin levels were significantly higher in patients with pulmonary infections and lung cancer than in the normal group, they were within normal limits in patients with pulmonary emphysema, pulmonary fibrosis, and bronchial asthma. Alpha 2-macroglobulin levels were slightly increased in patients with pulmonary emphysema and pneumonia. These results suggest that the increases in serum elastase 1 levels in these respiratory diseases may be mainly caused by an imbalance of elastase/antielastase system in the lung tissue and the bloodstream.

Elastase-1 vs trypsin, lipase and amylase serum levels in pancreatic diseases

Serum levels of elastase-1 were measured in 174 patients with pancreatic diseases and in 131 controls and were compared with the circulating levels of trypsin, lipase and amylase and with clinical data. In 48 patients with chronic pancreatitis serum enzyme levels were also compared with the pancreatic exocrine capacity. About 50% of the patients with chronic pancreatic disease showed increased levels of serum elastase, sometimes even in the face of long lasting pain-free periods, and/or of severe pancreatic impairment. On the contrary, serum trypsin and lipase were almost always either normal or below the normal range in the absence of painful relapses and/or in the presence of an impairment of the exocrine pancreatic function. A strict correlation was found between elastase-1 and trypsin (r = 0.778) and lipase (r = 0.834). However, controls and patients with chronic pancreatic diseases behaved differently, an increase in trypsin and in lipase levels being associated in the patients with chronic pancreatitis with an increase in elastase-1 values significantly larger than that observed in controls. These findings raise the hypothesis, at present unproven, that trypsin and lipase serum assays are more reliable indices of pancreatic exocrine function, whereas serum elastase-1 levels may indicate the presence of acute pancreatic episodes, even if subclinical, the importance of which, in the natural history of the disease, remains unknown.

Serum Elastase 1 and Immunoreactive Trypsin in Chronic Pancreatic Disease: Is There Any Relationship with Trypsin Inhibitors?

In order to investigate modifications of serum levels of elastase 1, immunoreactive trypsin, alpha 1-antitrypsin and alpha 2-macroglobulin in chronic pancreatic disease, and to speculate on the possible relationships among these parameters, the enzymes and inhibitors were assayed in the sera of 33 control subjects, 34 pancreatic cancer, 28 chronic pancreatitis and 36 extra-pancreatic diseases. An increase of elastase 1, alpha 1-antitrypsin and alpha 2-macroglobulin was detected in pancreatic cancer, chronic pancreatitis and extra-pancreatic diseases; no changes were found for serum immunoreactive trypsin. Multiple regression analyses showed that only 7% of elastase 1 was explained by inhibitors with alpha 1-antitrypsin playing a major role. Inhibitors did not influence immunoreactive trypsin. Our data indicate that the variations of the serum levels of proteases and antiproteases in chronic pancreatic disease are probably independent of each other.

1464 PROTEOLYTIC-ANTIPROTEOLYTIC HOMEOSTASIS IN THE VENTILATED NEWBORN

Endogenous proteolytic enzymes and their inhibitors have been identified as important factors in the normal, and certain pathologic, restructuring of pulmonary tissue. This study evaluates these substances in the ventilated newborn. Sera was obtained from 10 ventilator dependent newborns. Total elastase activity and alpha-1 antitrypsin concentration were determined by radial diffusion technique. Total elastase inhibitory capacity was quantitated on elastin agar. Similar control assays were performed on 10 normal unventilated newborns. Differences were evaluated for significance by T-test. Total serum elastase activity was markedly elevated in the ventilator dependent newborn as compared to controls (2.51 ± 0.27 versus 1.91 ± 0.12 units/ml, p < 0.001). Alpha-1 antitrypsin content was slightly elevated in the ventilator dependent group (341 ± 31 versus 287 ± 57 ml/dl, p < 0.02). These alterations, however, were not associated with any significant change in total elastase inhibitory capacity (3.79 ± 2.17 versus 3.04 ± 1.18 units elastase inhibited per ml, p = 0.35). Ventilation in the newborn results in elevated circulating serum elastase levels. This is associated with an increased antiproteolytic concentration (alpha-1 antitrypsin) but no significant change in total serum antiprotease activity. These alterations in proteolytic-antiproteolytic homeostasis may play a role in ventilation induced pulmonary changes in the neonate.

Serum elastase I levels in pancreatic disease

The radioimmunoassay for human elastase I used in this study is accurate, sensitive, and specific, which we have confirmed. The assay can be done within 4 hours, which is important for clinical purposes. A total of 103 subjects were examined, and levels of 99 to 370 ng/dl (mean 200) in normal human sera were determined. The serum elastase levels in acute, acute relapsing, and chronic relapsing pancreatitis were significantly higher than normal. Although serial determinations returned to normal within 5 days after the onset of the attack, they decreased gradually and remained high on the 7th, 10th, and 11th days in patients who still had residual signs of pancreatitis. The values in patients with chronic pancreatitis and various other diseases were normal. The values in patients with acute pancreatitis were significantly higher than in those with hyperamylasemia of non-pancreatic origin. Twelve of 19 patients with pancreatic cancer had abnormal serum elastase levels; this was especially true in patients with cancer of the pancreatic head. We believe that the measurement of serum elastase levels by radioimmunoassay will become a useful diagnostic method for pancreatic disease in the future.