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Biomedical subjects

M Ebert

Publications and source records attributed to M Ebert.

At least 37 records · Page 2Linked to original sources
PubMed1995

Differential distribution of human epidermal growth factor receptor family in acute pancreatitis.

Using northern blot analysis and immunohistochemistry, we assessed the expression and distribution of human epidermal growth factor receptor-1 (HER-1), HER-2, and HER-3 in pancreatic tissues obtained from patients with acute pancreatitis (AP). Overall, HER-1, HER-2, and HER-3 mRNA levels were similar in the normal pancreas and in the pancreas of AP patients. However, three patients exhibited a significant increase in HER-1 mRNA levels. Furthermore, the distribution of the receptors differed with respect to the various cell types in the human pancreas. In the normal pancreas, moderate HER-1 and strong HER-3 immunoreactivity was present predominantly in the cytoplasm of acinar cells and to a lesser extent in the ductal cells, whereas strong HER-2 immunoreactivity was present in the islet cells. In the AP tissues, there was a marked increase in HER-1 immunoreactivity in acinar and ductal-like cells, whereas HER-3 immunoreactivity was less prominent in acini and increased in ductal-like cells. HER-2 immunoreactivity was again mainly evident in islet cells, but was also present in the ductal-like cells. These findings indicate that there is altered distribution of HERs in the pancreas following AP and raise the possibility that HERs may be involved in the process of pancreatic regeneration during recovery from AP.

Acute Disease↗
PubMed1995

Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography.

The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p < 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation.

Adult↗
PubMed1995

[Chronic pancreatitis with inflammatory enlargement of the pancreatic head].

A number of patients with chronic pancreatitis develop an inflammatory enlargement of the head of the pancreas leading to complications such as common bile duct, duodenal, pancreatic duct, and/or vascular obstruction. The duodenum preserving pancreatic head resection has been developed to treat these lesions and to avoid a Whipple procedure in chronic pancreatitis. Between 1972 and 1992 280 patients (231 male, 49 female, mean age 44, range 22-76 years) underwent a duodenum preserving pancreatic head resection for chronic pancreatitis. The indication to operate was a cholestases syndrome in 50% of the patients, a duodenal compression in 36% and an obstruction of the portal vein in 16% of the patients. 94% suffered from pain, 53% had recurrent severe pain attacks and 72% had daily pain. Hospital mortality was 1.1% (3/280). Pancreatic fistula, leakage of pancreatic anastomosis and postoperative bleeding occurred in 4.6%, 1.8% and 3.2% of the patients, respectively. A relaparotomy needed 16 patients (5.7%). With respect to glucose tolerance in the early postoperative period 88% of the patients, showed no change in comparison with the preoperative glucose tolerance analysis. In a long-term follow-up (mean follow-up time was 3.7 years (3 months to 18 years)) 219 patients were included. The late mortality within the follow-up period was 5.0% (11/219). 90% of the patients had no or rare pain in the long-term follow-up. 63% of the patients were full rehabilitated professionally. The duodenum preserving pancreatic head resection represents a new standard procedure which solves most surgical problems in chronic pancreatitis. It does not lead to diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer.

The c-met proto-oncogene encodes a transmembrane tyrosine kinase receptor (MET) that has the capacity to modulate cell proliferation and differentiation; it is activated by the hepatocyte growth factor. Using a highly specific anti-MET antibody we found mild MET immunoreactivity in acinar, ductal, and islet cells in the normal human pancreas and intense MET immunoreactivity in many of the duct-like cancer cells in 14 of 16 human pancreatic adenocarcinomas. Intense MET immunoreactivity was also evident in the ductal cells in regions adjacent to the cancer cells. Northern blot analysis of total RNA revealed that, by comparison with the normal pancreas, pancreatic cancers exhibited a 7-fold (P < 0.01) increase in c-met mRNA levels. Hepatocyte growth factor mRNA levels were increased 10-fold (P < 0.05) in the same cancers. The concomitant over-expression of c-met and hepatocyte growth factor in human pancreatic cancers suggests that there is excessive activation of c-met-dependent signaling pathways that may contribute to pancreatic cancer cell growth in vivo.

Adolescent↗
PubMed1994

Molecular cloning and sequence analysis of two novel fission yeast casein kinase-1 isoforms.

The cDNAs for two casein kinase-1 homologs, hhp1 and hhp2, have been isolated from Schizosaccharomyces pombe and characterized. Their corresponding genes reside on chromosomes II and I, respectively, and encode approximately 42-46 kDa proteins that are related structurally to the HRR25 gene product of budding yeast. On the basis of multiple sequence alignment, the CK1 family appears to consist of three main branches. We predict that the branch containing the hhp genes encodes nuclear kinases involved in the regulation of DNA metabolism.

Amino Acid Sequence↗
PubMed1994

Induction and expression of amphiregulin in human pancreatic cancer.

The epidermal growth factor receptor is activated by a family of polypeptides that includes the growth factor amphiregullin (AR). Using Northern blot analysis and the polymerase chain reaction, we now report that AR mRNA is expressed in human pancreatic cancer cell lines, and that this expression is enhanced in several of these cell lines by tetradecanoyl phorbol acetate and transforming growth factor alpha. AR was also expressed in normal and malignant pancreatic tissues. However, in the normal pancreas, AR immunostaining was most evident in the nuclei of ductal cells. In contrast, in many carcinomas, AR was also present in the cytoplasm of the ductal-like cancer cells. Cytoplasmic localization of AR was associated with a more advanced clinical stage. These findings suggest that AR may contribute to aberrant activation of the epidermal growth factor receptor in human pancreatic cancer, and may enhance disease progression.

Amino Acid Sequence↗
PubMed1994

Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features.

BACKGROUND: Carcinoid tumors of the gastrointestinal tract are most common localized in the appendix, followed by the small intestine, the rectum, and the stomach. The localization of these tumors at the ampulla of Vater is extremely seldom. METHODS: In the present study the authors describe two patients with carcinoid tumors of the ampulla Vater and review 71 previously published cases. RESULTS: Most patients presented with jaundice, but without carcinoid syndrome. Because the tumor grows submucosally, preoperative diagnosis was correct only in 15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver was present in 45%. Standard treatment is Whipple resection or local excision in small tumors. CONCLUSIONS: Carcinoid tumors of the ampulla of Vater are an extremely rare clinical entity. Generally, the prognosis is good with a 5-year survival period of 90%.

Adult↗
PubMed1994

Inhibition of pancreatic secretion under long-term octreotide treatment in humans.

The somatostatin analogue octreotide (SMS 201-995) is a potent inhibitor of human exocrine pancreatic secretion. In the present study we analyzed the effect of octreotide (3 x 100 micrograms, daily) given over a time period of 7 days on hormone-stimulated exocrine pancreatic secretion in 6 healthy volunteers using a secretin-ceruletide test. The secretin-ceruletide test was carried out before, following the first injection of octreotide (day 1) and after a 7-day treatment with 3 x 100 micrograms octreotide daily. Duodenal fluid was collected over 30 min without stimulation, over 60 min following a bolus injection of 1 U/kg body weight secretin, and over 60 min during a continuous infusion of secretin and ceruletide. Following the first injection of octreotide and following 7 days of octreotide treatment secretin/ceruletide-stimulated amylase secretion was significantly reduced. Trypsin and chymotrypsin secretion was significantly reduced after the first injection of octreotide when pancreatic secretion was stimulated by secretin and ceruletide simultaneously. However, secretin and ceruletide-induced trypsin and chymotrypsin secretion was not inhibited after 7 days of octreotide treatment. Baseline, secretin and secretin/ceruletide-stimulated bicarbonate output were not influenced by octreotide either following the first injection of octreotide or the 7 days' treatment. Octreotide is a potent inhibitor of secretin/ceruletide-stimulated pancreatic amylase, trypsin and chymotrypsin secretion. However, following a 7-day treatment with octreotide this inhibition is only persistent for pancreatic amylase secretion.

Adult↗
PubMed1994

Role of octreotide in the treatment of pancreatic cancer.

Prognosis in patients with advanced pancreatic cancer is dismal. There has been no effective therapy for these patients so far. Somatostatin and its analogues have been proven to be potent inhibitors of experimental pancreatic cancer. Tumor inhibition is supposed to be mediated directly by somatostatin-binding sites or indirectly by suppression of growth factors. In two trials the value of the new somatostatin analogue octreotide in a low-dose (3 x 100 micrograms/day) and a high-dose (3 x 2,000 micrograms/day) protocol was evaluated in patients with advanced pancreatic cancer. Median survival of the patients with a low-dose protocol was 3 months. However, the treatment of pancreatic cancer with a high-dose protocol revealed a median survival of 6 months and stable disease in 4/10 patients. According to quality of life scoring 4 patients showed values comparable to healthy controls. Octreotide therapy with a high-dose protocol is a promising experimental therapeutic approach to advanced pancreatic cancer.

Female↗
PubMed1994

Portal films for relative exit dose determinations.

Portal films are radiographic images taken regularly in external photon beam radiotherapy in order to verify geometrical set-up. However, they also contain quantitative dose information. Absolute dosimetry with film is possible but the desired accuracy of +/- 5% is difficult to achieve. However, relative dosimetry with film would be useful in combination with a point determination of absolute dose, though a dose response linearisation is required for relative dosimetry over the range of doses given to portal films in routine clinical practice. For this purpose, a technique for the rapid dose response linearisation of portal films is investigated in simulated treatment situations and evaluated in terms of the ability to yield relative exit dose distributions from the portal films. A combination of such distributions with a single determination of radiation transmission with diodes should generate full two-dimensional transmission information. Distributions obtained from two anthropomorphic phantoms provided results consistent with distributions obtained from a treatment planning system to generally within +/- 5%, and most often within +/- 2%. It is concluded that the extraction of exit dose information from portal films would be useful for mantle, compensated, or other unusual treatment situations.

Calibration↗
PubMed1993

Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival.

BACKGROUND: Transforming growth factor beta s (TGF-beta s) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-beta expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-beta expression in human pancreatic cancer. METHODS: The distribution of TGF-beta isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques. RESULTS: Immunohistochemical analysis showed the presence of TGF-beta 1 (47% of tumors), TGF-beta 2 (42% of tumors), and TGF-beta 3 (40% of tumors) in the cancer cells. The presence of TGF-beta 2 was associated with advanced tumor stage (P < 0.05). Furthermore, there was a significant correlation between the absence of TGF-beta s in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P < 0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells. CONCLUSIONS: These findings show that human pancreatic cancers show increased levels of TGF-beta isoforms and enhanced TGF-beta mRNA expression and suggest that the presence of TGF-beta s in pancreatic cancer cells may contribute to disease progression.

Adenocarcinoma↗
PubMed1993

Enzyme treatment after gastrointestinal surgery.

After gastrointestinal surgery, patients often suffer from maldigestion. The extent of this maldigestion syndrome depends on the type of surgical procedure performed. After total pancreatectomy, subtotal left resection, resection for chronic pancreatitis. Whipple operation with ductal occlusion, and total gastrectomy, patients need obligatory enzyme treatment. After partial pancreatectomy without duct occlusion or partial gastrectomy, enzyme treatment should be initiated when exocrine pancreatic insufficiency occurs.

Chronic Disease↗
PubMed1987

[Surgery in chronic pancreatitis. II. Late results following non-resection operations].

Between 1966 and 1985, 994 patients with chronic pancreatitis were treated at a University Surgical Department, 346 by drainage or diversion procedure, 339 by resection and 309 conservatively. The most frequent non-resecting procedures were: pancreatic pseudocyst drainage in 146, biliary-digestive tract anastomosis in 80, gastro-enterostomy in 15, biliary-tract revision in 58 and pancreatic duct drainage in 7 patients. More than half the patients had previously been operated on at least once. Overall postoperative death rate was 6.6%. Of those operated on up to 1983, whose subsequent course was analysed retrospectively, 16% had died (mean observation period 4.6 years). As many as 29% of patients had further bouts of pancreatitis. Weight remained steady or increased in 82%, the number of those with diabetes increased by 6%. All but 12% remained free of pain postoperatively or had only minor and occasional symptoms. Alcohol abuse decreased markedly. If alcohol consumption remained moderate (less than 50 g daily), late mortality rate was definitely decreased. Drainage or diversion procedures and pancreas resection are not competitive but complementary methods in chronic pancreatitis. Imaging techniques have helped the trend towards more conservative management.

Adolescent↗
PubMed1986

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Adrenocorticotropic Hormone↗
PubMed1985

Genetic brain polypeptide variants in inbred mice and in mouse strains with high and low sensitivity to alcohol.

Twelve genetically determined brain polypeptide charge variants were identified by comparing cerebellar vermis of 7 inbred mouse strains and of mice selectively bred from 8 strains closely related to these 7 ancestral strains and one other for acute behavioral sensitivity to the sedative effects of ethanol. The selectively bred ethanol-sensitive (LS, long sleep) and insensitive (SS, short sleep) mice exhibited different allelic variants at 6 of these 12 gene loci expressed in the cerebellum. Variant polypeptide A1 (81 kdalton, pI 5.6) was shown to be associated with the membrane of synaptosomal mitochondria and to exhibit a basic variant in SS mice that is determined by a dominant allele. Other variant polypeptides showed codominant inheritance in F1 crosses. However, the phenotype of no single one of these brain polypeptides consistently correlated with the ethanol behavioral sensitivity of the 7 inbred mouse strains nor of 8 recombinant inbred (B X D, C57BL X DBA) strains. This finding supports the hypothesis that a substantial amount of inbreeding, leading to random fixation of alleles independent of selection for ethanol sensitivity, occurred during the breeding of the SS and LS mice. The present findings of a lack of a strong association between sleep time and a brain polypeptide variant do not preclude the existence of a major gene effect contributing to variation in acute sensitivity to ethanol but are consistent with reports that multiple loci are responsible for the difference in ethanol sensitivity between SS and LS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Clinical findings in patients with anorexia nervosa and affective illness in their relatives.

The most prevalent psychiatric disorders in the families of patients with anorexia nervosa are bipolar and unipolar major affective disorder. The presence of affective disorder, self-induced vomiting, or bulimia in the patient is not predictive of affective illness in the relatives. Thus these features do not define genetic heterogeneity within anorexia nervosa. There may be genetic factors shared between anorexia nervosa and affective disorders.

Adult↗
PubMed1983

Abnormalities in plasma and cerebrospinal-fluid arginine vasopressin in patients with anorexia nervosa.

Previous studies have indicated that many patients with anorexia nervosa have defects in urinary concentration or dilution suggestive of abnormal secretion of the antidiuretic hormone arginine vasopressin. To explore this possibility, we examined the response of plasma vasopressin to intravenous hypertonic saline in anorexic patients before and after correction of their weight loss. We also measured basal levels of the hormone in the cerebrospinal fluid. In all four subjects studied before correction of weight loss, the response to hypertonic saline was abnormal: in one, the plasma level of arginine vasopressin increased subnormally relative to the plasma sodium level; in the other three, it fluctuated erratically, with no relation to plasma sodium. These defects persisted in the three patients studied three to four weeks after recovery of body weight. In two patients who were initially studied when they were underweight, the defects were gone six months after recovery; in five of seven other patients studied at least six months after recovery but not while they were underweight, the response was normal. Abnormalities in the osmoregulation of plasma arginine vasopressin were not accounted for by nonosmotic stimuli and were almost always associated with an absolute increase in the level of arginine vasopressin in the cerebrospinal fluid or a reversal of the normal (less than 1.0) cerebrospinal fluid/plasma ratio of arginine vasopressin. These results indicate that most if not all patients with anorexia nervosa have abnormal levels of arginine vasopressin in their plasma and cerebrospinal fluid that are corrected very slowly with weight gain. The cause and consequences of these abnormalities remain to be determined.

Adult↗