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Biomedical subjects

T Kiviluoto

Publications and source records attributed to T Kiviluoto.

At least 19 recordsLinked to original sources
PubMed2001

In vivo glucose-stimulated amylin secretion is increased in nondiabetic patients with pancreatic cancer.

The incidence of diabetes is increased in patients with pancreatic cancer, but the mechanisms underlying this association are not clear. Alterations in beta-cell function, such as formation of amyloid from excessive production of amylin and reduced expression of GLUT2, have been suggested to be possible mechanisms. We compared in vivo secretory responses of amylin and insulin (n = 37) and expression of GLUT2 in pancreata (n = 10) obtained at surgery between diabetic and nondiabetic patients with and without pancreatic tumors. Fourteen had pancreatic adenocarcinoma, 7 had diabetes (duration 6 +/- 3 years) and a pancreatic tumor, 8 had type 2 diabetes (duration 6 +/- 2 years), and 8 were normal subjects. First (0 to 10 minutes) and second (10 to 120 minutes) phase insulin and amylin secretion were characterized using the hyperglycemic clamp technique. Both amylin and insulin concentrations followed a biphasic pattern in nondiabetic subjects. In nondiabetic patients with pancreatic cancer, total, as well as nonglycosylated amylin concentrations, were increased compared with nondiabetic subjects without pancreatic cancer. Both first- and second-phase plasma amylin and serum immunoreactive insulin concentrations were low in all patients with diabetes, ie, both in type 2 diabetes and in those patients with diabetes and pancreatic tumors. At surgery, specimens were obtained for characterization of GLUT2 expression in beta cells, which was unaltered in nondiabetic (n = 7) and diabetic (n = 3) patients. Amyloid staining was similarly negative in diabetic and nondiabetic pancreata independent of pancreatic carcinoma. In conclusion, plasma amylin, but not insulin concentrations, are increased in nondiabetic patients with pancreatic cancer, but low in all patients with diabetes. These data support the potential of using an increase in the ratio of circulating amylin to insulin as a marker for pancreatic cancer in nondiabetic patients.

Adenocarcinoma↗
PubMed2001

Expression of inducible and endothelial nitric oxide synthases in pouchitis.

To study the induction of nitric oxide synthase (NOS) in different forms of pouchitis, we divided patients in five groups: 1) ulcerative colitis, no pouch; 2) no-pouchitis; 3) chronic asymptomatic pouchitis; 4) chronic active pouchitis; and 5) acute pouchitis. Ileal biopsies were scored for NOS-2 (inducible) and NOS-3 (endothelial) immunoreactivity and acute inflammation. In group 1, most specimens lacked NOS-2 immunoreactivity. In group 2, some specimens showed NOS-2 immunoreactive epithelium. In group 3, areas of NOS-2-immunoreactive epithelium were consistently observed in most specimens. In groups 4 and 5, most specimens showed moderate-to-extensive epithelial NOS-2 staining. NOS-2 immunoreactivity scores of groups 1-5 were 0.25 +/- 0.16, 0.67 +/- 0.19, 1.19 +/- 0.40, 2.0 +/- 0.23, and 2.18 +/- 0.12, respectively. Corresponding acute inflammation scores were 0, 0.53 + 0.17, 1.00 +/- 0.33, 1.80 +/- 0.20, and 1.64 +/- 0.15. NOS-2 score correlated with acute inflammation score (p < 0.0001), indicating that NOS-2 induction correlates with both the clinical degree of pouchitis and the severity of acute inflammation. NOS-3 immunoreactivity increased in all pouchitis groups.

Colitis, Ulcerative↗
PubMed2001

HCl causes less intracellular acidification in Necturus gastric mucosa surface epithelial cells than other acids.

Luminal acid causes intracellular acidification in the gastric epithelium, but the mechanism by which H(+) enters surface cells remains obscure. This study addressed the problem by assessing how different acids affect intracellular pH in gastric surface cells. Isolated Necturus maculosus antral mucosa was exposed to HCl, HNO(3), H(2)SO(4), and H(3)PO(4) at pH 2.30. Intracellular pH was measured with microelectrodes. The physicochemical interaction of a synthetic model of gastric phospholipids with the different acids was studied using Langmuir film balance. Exposure to luminal HNO(3), H(2)SO(4), or H(3)PO(4) caused significantly larger intracellular acidification than exposure to HCl. The degree of acidification was not dependent on the valence or nature of the anionic counterion of the acid but significantly correlated with the amount of molecular acid. By Langmuir film balance, subphases acidified with HNO(3), H(2)SO(4), or H(3)PO(4) caused more close packing of phospholipid molecules than those acidified with HCl, possibly allowing hydrogen bonding between head groups to facilitate H(+) movement across the phospholipid membrane. HCl causes significantly less intracellular acidification in gastric epithelium than HNO(3), H(2)SO(4), or H(3)PO(4). This may be caused by the lower amount of molecular HCl in solution and possible hydrogen bonding between the head groups of phospholipid molecules and the other acids.

Acids↗
PubMed2001

Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers.

Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine-N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O2(-*) was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O2(-*) generators and ameliorated by O2-(8) scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O2(-*). or peroxynitrites may be involved.

Animals↗
PubMed2001

Quantitative comparison of growth-associated protein-43 and substance P in ulcerative colitis.

The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis. Tissue samples from normal colon and regions of ulcerative colitis colon were obtained at surgery and immunostained for substance P, vasoactive intestinal polypeptide (VIP), somatostatin, calcitonin gene-related peptide (CGRP), enkephalin, galanin, GAP-43, and neuron-specific enolase (NSE). Visual examination and semiquantitative analysis revealed a clear increase in the immunoreactivity for substance P in ulcerative colitis, whereas no differences were observed in the distribution of the other peptides. Therefore, quantitative analysis was performed only for substance P immunoreactivity in the lamina propria, circular muscle layer, and myenteric ganglia. In the lamina propria, the score of total intensity of substance P immunoreactivity was 0.55 +/- 0.15 (mean +/- SEM) in normal colon, 1.30 +/- 0.35 (p = 0.087) in least affected colon, and 2.22 +/- 0.28 (p < 0.001) in moderately affected colon, whereas no significant differences were observed in immunoreactivities for GAP-43. Similar results were obtained for the mean substance P- or GAP-43-immunoreactive area. In the circular muscle layer, the number, density, total intensity, and perimeter of substance P- and GAP-43-immunoreactive fibers were essentially similar in normal colon, and in mild or moderately affected colon. We conclude that ulcerative colitis does not change the density of gut innervation as a whole. However, the density of substance P-containing nerves is specifically increased, probably due to increased peptide synthesis leading to better visibility of the fibers.

Adult↗
PubMed2001

Changes in distribution of three isoforms of nitric oxide synthase in ulcerative colitis.

BACKGROUND: Nitric oxide (NO) has an important role both in normal physiology and pathological events of the colon. Our aim was to study possible changes of the three nitric oxide synthases in ulcerative colitis (UC). METHODS: Tissue samples from normal colon and least and moderately affected regions of ulcerative colitis colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP-43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was performed on the circular muscle layer. RESULTS: NOS-1-immunoreactive fibers in the muscularis mucosae disappeared in least affected and moderately affected UC colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular muscle showed no differences between normal and diseased colon. NOS-2 immunoreactivity appeared apically in the epithelial cells. In normal colon some specimens showed immunoreactivity in lower parts of crypts. NOS-2 immunoreactivity increased according to the severity of UC. NOS-3 immunoreactivity was exclusively localized in the vascular endothelium. The difference in NOS-3 staining intensity between the lamina propria and submucosa observed in normal tissue disappeared in moderately affected UC colon. The number of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC colon. CONCLUSIONS: All three NOS isoforms show specific changes in UC colon.

Aged↗
PubMed2000

Laminin alpha1-chain shows a restricted distribution in epithelial basement membranes of fetal and adult human tissues.

Two novel monoclonal antibodies were raised and used to study the expression of laminin (Ln) alpha1-chain in developing and adult human tissues. In both fetal and adult kidney, a distinct immunoreactivity was seen in basement membranes (BM) of most proximal tubules but not in the distal tubular or glomerular BM or in the basal laminae of blood vessels. Immunoprecipitation of metabolically labeled cultured human renal proximal tubular cells showed an abundant production and deposition of Ln alpha1-chain to the extracellular matrix, suggestive of an epithelial origin of kidney Ln-1. Quantitative cell adhesion experiments with JAR choriocarcinoma cells showed that purified human Ln-1 is a good substrate for cell adhesion that it is differently recognized by integrin receptors when compared to mouse Ln-1. In fetal and adult testes immunoreactivity was solely confined to BM of the seminiferous epithelium. In the airways BM-confined reaction was only seen in fetal budding bronchial tubules (16-19 weeks) at the pseudoglandular stage of development. In the skin a distinct immunoreactivity was confined to BM of developing hair buds but not in epithelial BMs of adult epidermis or of epidermal appendages. In other adult tissues, immunoreactivity was found in BMs of thyroid, salivary, and mammary glands as well as in BMs of endometrium and endocervix, but not of ectocervix or vagina. No immunoreactivity was found in BMs of most of the digestive tract, including the liver and pancreas, except for BMs of esophageal submucosal glands and duodenal Brunner's glands. In fetal specimens, BMs of the bottoms of the intestinal and gastric glands were positive. Basal laminae of blood vessels were generally negative for Ln alpha1 chain with the exception of specimens of both fetal and adult central nervous system in which immunoreactivity for Ln alpha1 chain was prominently confined to capillary walls. The results suggest that outside the central nervous system, Ln alpha1 chain shows a restricted and developmentally regulated expression in BMs of distinct epithelial tissues.

Adult↗
PubMed2000

Fatal cardiac tamponade after emergency tension-free repair of a large paraesophageal hernia.

Paraesophageal hernia is an unusual disorder of the esophageal hiatus that may be associated with life-threatening mechanical problems. We report a case of a large paraesophageal hernia that presented with acute thoracic herniation and incarceration of the stomach. The patient underwent laparoscopic operation, including reduction of an intrathoracic stomach, hernial sac removal, and tension-free repair of the hiatus with polytetrafluoroethylene (PTFE) mesh. The mesh was fixed with a straight hernia stapler. Postoperatively the patient developed a fatal cardiac tamponade secondary to a coronary vein laceration due to fixation of the mesh with the stapler. Different operative techniques and possibilities for prevention of the complication are discussed.

Aged↗
PubMed2000

Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for alpha3beta1 integrin.

Interplay between laminin-5 (Ln-5) and its integrin (Int) receptors alpha2beta1, alpha3beta1 and alpha6beta4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immunoreactivity for chains of Ln-5 (alpha3-beta3-gamma2) and Ln-10 (alpha5-beta1-gamma1), as well as for type VII collagen, in basement membranes (BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln al chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for alpha2, alpha6, beta1 and beta4 Ints was found in all tumors and that for alpha3 Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the gamma2 chain of Ln-5 was present as typical Mr 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to alpha3 and beta1 Int subunits, but not those to Int alpha2 or alpha6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the alpha3beta1 Int complex for adhesion to Ln-5.

Adenoma↗
PubMed2000

Superior mesenteric and portal vein thrombosis following laparoscopic nissen fundoplication.

This case report describes superior mesenteric and portal vein thrombosis after laparoscopic Nissen fundoplication. As a thromboembolic prophylaxis, 2,500 IU of dalteparin was given preoperatively. After postoperative day 19, the patient experienced gradually increasing abdominal pain, mostly related to meals. Physical examination and laboratory tests were normal. CT scan revealed a portal and superior mesenteric vein thrombosis. Dalteparin and warfarin treatment was started, and symptoms relieved rapidly. In a control Doppler ultrasound 1 month after the onset of the treatment, a good flow in the portal and superior mesenteric vein was seen. Possible mechanisms are discussed.

Abdominal Pain↗
PubMed1999

Renal cell carcinomas and pancreatic adenocarcinomas produce nidogen in vitro and in vivo.

The production of nidogen by four renal cell carcinoma (RCC) and three pancreatic adenocarcinoma (PAc) cell lines has been studied in cell culture and in xenografted tumours in nude mice. In RCC cells, immunoreactivity for nidogen was seen only after exposure to monensin to induce cytoplasmic accumulation of secretory proteins. In PAc cells, immunoreaction was also detectable in control cells. Immunoblotting of control and monensin-exposed cells and immunoprecipitation of culture media of radioactively labelled cells demonstrated the production of nidogen polypeptide of Mr ca. 150000 by six of the seven cell lines. Basement membranes (BMs) and stroma of the xenografted tumours derived from these six cell lines demonstrated immunoreactivity for both human and mouse nidogen, as revealed with species-specific antibodies. The ability of the cells to produce nidogen in vitro and deposit in vivo was positively correlated with high histological grade of the xenografted tumours, although the small number of cell lines studied calls for further studies to confirm this. The distribution of nidogen in human RCC and PAc specimens was also studied by immunohistochemistry. There was strong immunoreactivity for nidogen in tumour stroma, BM of carcinoma cell nests, and endothelial basal lamina, but no conclusions could be drawn regarding histological grade and immunostaining patterns, because stromal production could not be ruled out. The results show that nidogen is produced by human carcinoma cells both in vitro and in vivo.

Adenocarcinoma↗
PubMed1999

Expression of SPARC (secreted protein, acidic and rich in cysteine) in healing intestinal anastomoses and short bowel syndrome in rats.

Due to the proposed functions in soft tissue repair, we evaluated the spatial and temporal distribution of SPARC, a counteradhesive, matricellular glycoprotein in healing intestinal anastomoses and short bowel syndrome (SBS) in rats. Intestinal anastomoses were performed in the jejunum of male Wistar rats. SBS was induced by resecting 70% of the small bowel. In situ hybridization was performed to localize SPARC mRNA and immunohistochemical studies for locating the SPARC protein. The granulation tissue in the anastomotic area exhibited immunoreactivity for SPARC at all time points. The level of expression was maximal at seven to nine days. Endothelial cells of capillaries, smooth muscle cells, fibroblastic cells, and macrophages, as well as mesothelial cells on the serosal surface, were stained. The immunoreactivity was mostly intracellular. SPARC mRNA transcripts were localized to the edges of the anastomotic area at days 1 and 4 and on the newly formed granulation tissue later. The expression of SPARC mRNA was maximal at seven days and decreased thereafter. Both in normal controls and in SBS, SPARC was expressed in endothelial cells of submucosal capillaries and in smooth muscle cells but not in epithelium. Based on the restricted temporal and spatial distribution during the healing of intestinal anastomoses and in SBS we propose that SPARC plays a significant role in intestinal repair and adaptation.

Anastomosis, Surgical↗
PubMed1998

Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for elective cholecystectomy, but controversy persists over use of this approach in the treatment of acute cholecystitis. We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy (OC) in patients with acute cholecystitis. METHODS: 63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The primary endpoints were hospital mortality and morbidity, length of hospital stay, and length of sick leave from work. Analysis was by intention to treat. Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography (LC group) or intraoperative cholangiography (OC group). FINDINGS: The two randomised groups were similar in demographic, physical, and clinical characteristics. 48% of the patients in the OC group and 59% in the LC group were older than 60 years. 13 patients in each group had gangrene or empyema, and one in each group had perforation of the gallbladder causing diffuse peritonitis. Five (16%) patients in the LC group required conversion to OC, in most because severe inflammation distorted the anatomy of Calot's triangle. There were no deaths or bile-duct lesions in either group, but the postoperative complication rate was significantly (p=0.0048) higher in the OC than in the LC group: seven (23%) patients had major and six (19%) minor complications after OC, whereas only one (3%) minor complication occurred after LC. The postoperative hospital stay was significantly shorter in the LC than the OC group (median 4 [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7). INTERPRETATION: Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality rate, and the morbidity rate seems to be even lower than that in OC. However, a moderately high conversion rate must be accepted.

Acute Disease↗
PubMed1998

Cholesterol metabolism and serum and biliary noncholesterol sterols in gallstone patients during simvastatin and ursodeoxycholic acid treatments.

Effects of long-term high-dose ursodeoxycholic acid (UDCA) and simvastatin treatments on cholesterol metabolism and biliary lipid compositions were compared in patients with cholesterol gallstones. Absorption and synthesis of cholesterol, serum and biliary noncholesterol sterols and lipids were determined in 14 patients randomized to UDCA (23-25 mg/kg/d) or simvastatin (40 mg/d) for 1 year. Simvastatin reduced serum low-density lipoprotein cholesterol by 55%, and UDCA, by 9%. Cholesterol absorption was decreased (35%) by UDCA, but nonsignificantly increased by simvastatin (P < .05 for difference of changes caused by the two drugs). Whole-body synthesis and biliary output of cholesterol were both significantly decreased only by UDCA. In addition, UDCA inconsistently increased the proportions of serum and biliary precursor sterols of cholesterol, known to reflect cholesterol synthesis, but did not affect their biliary secretions. Simvastatin, however, dramatically reduced serum and also biliary cholesterol precursor sterol proportions and their biliary secretions and increased proportions of serum and biliary plant sterols and cholestanol, known to reflect cholesterol absorption, but had no effect on their biliary secretion. Only UDCA significantly decreased the molar percentage of cholesterol, the lithogenic index, and the cholesterol/phospholipid (CH/ PL) ratio in bile, whereas both treatments inconsistently decreased the vesicular CH/PL ratio (P < .07 in both groups). It is concluded that both drugs decreased serum cholesterol and inhibited cholesterol synthesis, but had a differing influence on precursor sterols and the absorption of cholesterol. UDCA had more beneficial effects than simvastatin on the antilithogenic properties of bile.

Anticholesteremic Agents↗
PubMed1998

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Adaptation, Physiological↗
PubMed1998

Laparoscopic Nissen fundoplication: a prospective analysis of 200 consecutive patients.

Nissen fundoplication is now the most common antireflux operation for gastroesophageal reflux disease. This study is a report on the laparoscopically performed floppy Nissen procedure. Two hundred consecutive patients were analyzed (84 women, 116 men, mean age 49 years, mean duration of symptoms 5 years) after laparoscopic Nissen fundoplication between 1992 and 1996. The main indications for surgery were daily heartburn, retrosternal pain, and regurgitation demanding continuous medical therapy. Eight patients (4%) had esophageal stricture, and 21 (11%) had Barrett's esophagus with intestinal metaplasia. All patients underwent upper gastrointestinal endoscopy, 24-h esophageal pH monitoring, and esophageal manometry before and 3 months after the operation. In addition, a questionnaire was completed an average of 2.2 years (range 1.0-4.6) after the operation. The results of the study were as follows: mortality was zero, and the morbidity rate was 5%. The mean hospital stay was 3.8 +/- 2.8 days, and sick leave was 14.3 +/- 10.4 days. Postoperatively, esophagitis was healed or significantly improved in all but 4 patients (98%), and 24-h pH and lower esophageal sphincter pressure were normal. After 2 years, 87% of the patients had Visick scores of I-II. It is concluded that laparoscopic floppy Nissen fundoplication provides an efficient and safe alternative for surgical treatment of gastroesophageal reflux disease.

Adult↗
PubMed1997

Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane.

We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1 integrin receptor recognizing laminin-5.

Adenocarcinoma↗