Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total duodenopancreatectomy was performed in a 36-year-old man because of global chronic pancreatitis. Islets cells were isolated by collagenase digestion from the resected pancreas and re-implanted into the liver via the portal vein. Until the sixth postoperative day the amount of insulin required fell from 54 IU initially to 10 IU per day. Serial insulin determination demonstrated secretion by the implanted cells.
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PMID:[Autotransplantion of Langerhans islets after total duodeno-pancreatectomy in a patient with chronic pancreatitis (author's transl)]. 10 66

Secretion of pancreatic enzymes is inhibited in rats by the presence of intraduodenal proteases via inhibition of CCK release. The existence of a similar feedback mechanism in man is discussed controversially. Thus, in chronic pancreatitis (cP), which leads to a decrease of digestive enzyme secretion, increases in plasma CCK may be postulated. However, food induced CCK release may be impaired in cP due to maldigestion. We studied, therefore, the influence of food with or without addition of pancreatic extracts on plasma CCK in 16 male patients with longstanding cP. Plasma CCK was measured by bioassay using pancreatic rat acini prepared by collagenase digestion. Plasma samples were processed through SEP-PAK cartridges and assayed for CCK-like activity by comparing the bioactivity of samples with those of standard curves of CCK8. Plasma CCK was measured in 20 healthy controls and in cP prior and 7.5, 15, 30, 45, 60, and 90 min after the application of a test meal made out of milk, cream, eggs, and cacao. In addition CCK was measured in 10 of the same patients with cP on a separate day but with the addition of pancreatic extracts to the test meal. Basal plasma CCK levels were similar in both groups (control: 1.3 +/- 0.2 vs. cP: 1.5 +/- 0.3 pMol/l). Both groups showed a similar steep increase of postprandial CCK with maximal values seen between 7.5 and 30 min (control: 4.6 +/- 0.6 vs cP: 4.8 +/- 1.3 pMol/l). The addition of pancreatic extracts to the liquid meal in cP caused a statistically significant slight increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma cholecystokinin level in chronic pancreatitis]. 260 4

Recently we reported that a kind of serine protease, SH protease, and collagenase might be involved in blister formation and, furthermore, that the cooperative action of these three proteases was essential for blister formation in recessive dystrophic epidermolysis bullosa. In this study we examined the inhibitory effect of clinically usable serine protease inhibitors for blister formation in organ culture and in clinical trials of recessive dystrophic epidermolysis bullosa patients. Camostat mesylate, a synthetic serine protease inhibitor that is available for the treatment of chronic pancreatitis, demonstrated a striking effect of inhibiting blistering in organ culture of normal human skin with recessive dystrophic epidermolysis bullosa blister fluids. Subsequently we administered camostat mesylate by topical application to four patients with recessive dystrophic epidermolysis bullosa to assess its ability to reduce blistering. Therapeutic response was favorable; a significant effect in decreasing the number of blisters was observed in three of four patients. These findings actually supported the hypothesis that a kind of serine protease had a close relationship with blistering in recessive dystrophic epidermolysis bullosa and that therapy with a clinically usable protease inhibitor was useful for the treatment of this disease.
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PMID:Protease inhibitor therapy for recessive dystrophic epidermolysis bullosa. In vitro effect and clinical trial with camostat mesylate. 338 39

Chronic pancreatitis ablates a large majority of the acinar tissue which otherwise is a troublesome contaminant in preparing islet cells from higher mammals. Chronic pancreatitis was induced by dividing all pancreatic attachments to the duodenum, including major and minor ducts, in six dogs. After 10 weeks, biopsy of the pancreas showed marked acinar cell atrophy and fibrosis with preservation and even proliferation of islet cells. Intravenous glucose tolerance testing revealed only a minor decrease in K value from 3.4 +/- 1.0 to 2.1 +/- 0.4 during 10 weeks. All dogs then underwent total pancreatectomy and islet autotransplantation. The pancreas was dispersed to a cell suspension by perfusing the pancreatic ducts with collagenase until tissue integrity failed. The digested tissue was then chopped, dissociated by shaking, and filtered. The average cell yield from the pancreas was 7.6 X 10(7) cells of which greater than 95% were islet cells. Acid alcohol-extracted insulin values suggested an average 7% recovery of insulin content and essentially complete elimination of amylase content was demonstrated.
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PMID:Islet recovery in chronic pancreatitis. 619 73

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.
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PMID:Transplantation of dispersed pancreatic islet tissue in humans: autografts and allografts. 676 13

A patient with chronic pancreatitis underwent 95% pancreatectomy and islet autotransplantation. The pancreatic tissue was prepared by mincing and collagenase digestion, and then embolized into the liver via the portal vein. The patient has been followed with metabolic studies for 1 year. Fasting normoglycemia returned 3 weeks following operation. Intravenous glucose tolerance tests revealed K values that were similar before operation (1.06), and 3 weeks (0.96) and 4 months (1.09) after operation. Four months after islet transplantation, peripheral, portal, and hepatic vein insulin levels were determined simultaneously following an infusion of glucose (0.25 gm/kg) into the portal vein. During a 10-minute interval, right hepatic vein insulin increased fourfold, left hepatic vein insulin increased twofold, and peripheral vein insulin doubled. During this time portal vein insulin remained constant. In addition, significant levels of pancreatic glucagon were present in both hepatic veins, but were undetectable in the portal vein. At 6 months the patient became hyperglycemic and subsequently has required insulin therapy. Restudy at 10 months following islet transplantation revealed a marked drop in K value (0.34), and no evidence of graft function in the liver. These studies represent convincing evidence of transplanted intrahepatic islet cell function for a 6-month period following operation. The grafts for unknown reasons ceased to function at 6 months.
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PMID:Metabolic studies following intrahepatic autotransplantation of pancreatic islet grafts. 676 46

Total or near total pancreatectomy is the surest way to relieve the pain of chronic pancreatitis but is rarely applied because the metabolic consequences are so severe. For most patients drainage procedures are applicable, but pancreatectomy may be the only alternative for small duct disease or where procedures to improve duct drainage have failed. Preservation of endocrine function is a major problem in patients who require pancreatectomy. Experiments in pancreatectomized dogs have shown that intrasplenic or intraportal transplantation of unpurified pancreatic islet tissue dispersed by collagenase digestion can prevent diabetes. We have applied this technique to ten patients with chronic pancreatitis, small ducts, and intractable pain. The entire pancreas of > 95% of the pancrease was excised, minced, dispersed by collagenase digestion and infused into the portal vein < 2 1/2 hours after removal. Mean (+/- SD) rise in portal pressure was 17 +/- 8 cm of water. Liver function tests were altered minimally. All patients were relieved of pain. One patient died of a complication not related to the islet autotransplant; viable islets were identified in the liver at autopsy. Of the remaining nine patients, three have been insulin independent for 1, 9, and 38 months. One patient was insulin indpendent for 15 months and now takes 12 units of insulin daily. Three have nonketosis prone diabetes (tested by insulin withdrawal) and take 15--30 units of insulin per day. C-peptide studies in these patients show that functioning islets are present. Two patients are diabetic and require 35 and 60 units of insulin per day. In eight of nine patients tested serum insulin concentrations fell to undetectable levels during the interval between pancreatectomy and islet transplantation. Serum insulin levels during the first few hours after islet transplantation predicted success. In the insulin independent or in the patients with mild diabetes, insulin levels were persistently greater than or equal to 6 microU/ml. In the other two patients, the increase in insulin concentration was not sustained. Islet tissue preparation from a diseased pancreas is difficult. The surgeon and the patient must still be willing to accept diabetes for relief of pain when performing this operation. In some patients, however, islet autotransplantation can prevent or partially ameliorate diabetes after pancreatectomy, and preservation of endocrine function is worthwhile.
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PMID:Total or near total pancreatectomy and islet autotransplantation for treatment of chronic pancreatitis. 677 3

During total pancreaticoduodenectomy for chronic pancreatitis, four patients received an intraportal pancreatic mixed-cell autograft prepared by collagenase digestion. The technique of this autotransplantation procedure was successfully developed using a normal canine pancreas, but has proved difficult to apply in the human chronic pancreatitis model. Our four patients became insulin-dependent, with proof of intrahepatic insulin production in only one patient. Three factors have contributed to the lack of graft success: 1) the preoperative endocrine status, 2) systemic hypotension and portal hypertension secondary to graft infusion, and 3) difficulty applying the successful technique in a normal dog pancreas to an extensively scarred human pancreas. The preoperative insulin response during a glucose tolerance test was blunted or delayed in the three patients tested. An immediate decrease in blood pressure and rise in portal pressure occurred in every patient and prevented infusion of the entire graft (30-50%) in three patients. Unfortunately, the patient with the most compromised insulin status was the only patient able to receive the entire graft. Our experience would indicate that further refinements in technique are necessary to prevent the vascular reaction and allow infusion of the entire graft. Furthermore, normal islet cell function is necessary before a successful graft can be expected.
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PMID:Human pancreatic cell autotransplantation following total pancreatectomy. 678 24

Of 12 patients operated on for intractable pain from chronic pancreatitis, only the three with adequate preoperative insulin reserve were selected to undergo islet-cell replantation after subtotal pancreatectomy. Fourteen, nine, and four months postoperatively, they require no therapy with insulin. Since most techniques for obtaining islet cells have been performed with normal pancreata, chronic pancreatitis was produced in ten dogs by ligating the main and accessory pancreatic ducts. These dogs 162.6 +/- 15.8 days later underwent total pancreatectomy. The scarred pancreatic fragments were dissociated with collagenase for 20 minutes in five dogs or subjected to two intermittent digestions of ten minutes in the other five dogs and were autotransplanted to the liver. One dog from each group became normoglycemic within one week of replantation, and their percent per minute decreases of serum glucose level were 2.72 and 3.46, respectively. Our experimental and clinical data suggest that (1) present techniques for dissociating fibrotic tissue are unsatisfactory and lead to a very low yield of islet cells; (2) postoperative assessment of islet-cell function involves complicated invasive procedures (portal and hepatic vein cannulation) to determine accurately the source of insulin; and (3) careful preoperative evaluation of beta-cell function is needed.
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PMID:Islet cell autotransplantation after pancreatectomy for chronic pancreatitis. Its limitations. 678 58

Chronic pancreatitis is characterized by proliferation of the extracellular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this study we analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic pancreatitis (n = 8) and control pancreas (n = 7) by northern blot analysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromelysin) and TIMP-1 were not detectable in chronic pancreatitis and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhanced in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels could not be correlated to the histologically detectable degree of inflammation and fibrosis or to the total amount of deposited collagen protein, which was high in all chronic pancreatitis tissue samples as determined by a standard colorimetric procedure. Increased steady state levels of transcripts encoding extracellular matrix proteins or extracellular matrix degrading proteases may thus reflect the activity of processes involved in the remodeling of the gland during chronic inflammation. The precise role of overexpression of MMP-2 and its inhibitor TIMP-2 will have to be elucidated in further studies.
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PMID:Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis. 801 97


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