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Biomedical subjects

B Ruebner

Publications and source records attributed to B Ruebner.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Adenocarcinoma, Mucinous↗
PubMed1997

Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland immunohistochemistry.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Nearly 93% of patients with PBC exhibit evidence of focal sialoadenitis. In an earlier study, we reported evidence of aberrant expression of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had Sjogren's syndrome. At the time of the previous study, data was not yet available regarding patients with PBC without sicca complaints. Therefore, to investigate the extent of salivary gland involvement in PBC, we collected lip biopsy sections from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or histologic features of Sjogren's syndrome and 9 PBC patients with established Sjogren's syndrome. Using immunohistochemical staining with both a murine monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined the ducts of these salivary glands for the presence of the characteristic aberrant staining pattern found in patients with PBC. We report that 6/9 PBC patients fulfilling established Sjogren's syndrome criteria and 6/9 PBC patients lacking features of Sjogren's syndrome showed intense staining of the ductal epithelial cells of the salivary gland. These data suggest that the PBC-specific antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed aberrantly in the salivary gland in 66% of patients with PBC, independent of Sjogren's syndrome. This finding suggests a common disease process in these two tissues. Further, expression of this molecule may be an early marker of salivary gland involvement in patients with PBC.

Animals↗
PubMed1996

Bile ductule formation in fetal, neonatal, and infant livers compared with extrahepatic biliary atresia.

The cell of origin of intrahepatic bile ducts during fetal development remains a subject of controversy, although there has been recent evidence that they form from hepatocytes. However, the origin of neoductules and ducts in the setting of liver disease has not been extensively investigated in humans. Using anticytokeratins characteristic of hepatocytes and bile ducts, we repeated earlier studies of fetal development to compare ductule formation in normal developing and newborn livers with the ductules formed during extrahepatic biliary atresia. We utilized an antibody to proliferating cell nuclear antigen (PCNA) staining to determine which cells were in active DNA synthesis (S phase) during fetal development and liver disease progression. The results indicated that hepatocytes undergo a phenotypic switch (metaplasia) to form ductular cells during fetal development. There was no ductular cell replication in the fetal livers. In contrast, both bile ductular metaplasia and proliferation were observed in biliary atresia. Therefore, both a limiting plate phenotypic switch to ductules and replication of ductular cells play a role in the increase in the ductules seen in the progression to biliary cirrhosis. Bile ductular proliferation in biliary atresia, however, was less than that seen in hepatocytes, whereas the number of bile ductules increased and the relative proportion of hepatocytes diminished as the accompanying periductular fibrosis progressed to cirrhosis.

Bile Ducts↗
PubMed1995

Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics.

The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg). The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity. Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v. terbutaline, i.v. piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin. Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v. piperacillin or with a combination of FUT-175 plus i.v. terbutaline, plus i.v. piperacillin compared to controls.

Acute Disease↗
PubMed1995

Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease.

The pathogenesis of alcohol-induced liver disease involves the adverse effects of ethanol metabolites and oxidative tissue injury. Previous studies indicated that covalent protein adducts with reactive aldehydes may be formed in alcohol consumers. To study the role of such protein adducts in the development of liver injury, we examined the sequential appearances of adducts of the ethanol metabolite acetaldehyde (AA) and of two products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenol (HNE), in ethanol-fed micropigs. Immunohistochemical stainings using specific antibodies that recognize epitopes of each adduct were performed from liver biopsy specimens obtained at 1, 5, and 12 months from micropigs fed either control diet (n = 5) or ethanol-containing diets (n = 5). After 1 month on the ethanol diet, AA and MDA adducts were observed primarily in the perivenous regions co-localizing with each other and coinciding with increased concentrations of serum aminotransferase markers of liver injury. HNE adducts were usually less intense and more diffuse, and were also seen in some biopsy specimens from control animals. Although the most intense staining reactions at 5 months remained in zone 3, a more widespread distribution was usually seen together with increased evidence of steatonecrosis and focal inflammation. In terminal biopsies at 12 months, perivenous fibrosis was present in three of five biopsy specimens. More extensive pericentral and intralobular fibrosis was noted in one micropig fed ethanol for 21 months. These studies demonstrate that covalent adducts of proteins with reactive aldehydes are formed in early phases of alcohol-induced liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1995

Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis.

The presence of antimitochondrial antibodies (AMA) is a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, the study of these autoantibodies has enabled much information to be accumulated about the specificity of this response. The autoantigens have been identified as components of a functionally related enzyme family, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E2 subunit (PDC-E2) has been determined to be the immunodominant autoantigen. Using a panel of mouse monoclonal antibodies and human combinatorial autoantibodies, it has been demonstrated that patients with PBC, but not controls, have an abnormal expression of either PDC-E2 or a cross-reacting molecule in the apical region of biliary epithelium. Others have shown a similar reaction using rabbit sera directed to PDC-E2. Our previous studies have concentrated on AMA-positive patients. In this study, the presence of PDC-E2, class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells of AMA-positive as well as AMA-negative patients is addressed. Most patients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region of the bile duct epithelial cells of "PDC-E2," increased IgA expression, and little major histocompatibility complex (MHC) class II staining in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E2 on the apical side of their biliary epithelium had anticentromere antibodies and Sjögren's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Role of fine needle aspiration cytology and endoscopic biopsy in the preoperative assessment of pancreatic and peripancreatic malignancies.

Sixty-seven of 207 patients with pancreatic and peripancreatic malignancies underwent preoperative fine needle aspiration cytology (FNA), and 24 patients underwent intraluminal endoscopic biopsies. All patients had confirmation of the diagnosis of malignancy either at operation, autopsy, or by clinical follow-up. FNA of liver metastases was positive for malignancy in 12 of 12 patients. FNA of the pancreas was performed on 44 patients with pancreatic adenocarcinoma and 11 patients with other pancreatic or peripancreatic malignancies. The diagnosis of cancer was established by FNA in 32 of 44 (72.4%) patients with pancreatic adenocarcinoma and 1 of 11 patients (9.1%) with other pancreatic or peripancreatic malignancies. In the patients with pancreatic adenocarcinoma, 17 of 18 patients (94.4%) who had no operative intervention, 12 of 18 (66.7%) patients who had palliative bypass procedures, and 3 of 8 (37.5%) patients resected had positive FNA. Eighteen of 24 patients (75%) who underwent intraluminal endoscopic biopsies, and 11 of 15 (73.3%) with ampullary carcinoma were positive. We believe that FNA is of limited value in the diagnosis of small resectable tumors of the pancreas as it identified cancer in only 3 of 8 patients in whom it was employed. False negative FNA may delay the diagnosis and treatment of pancreatic malignancies. Patients in whom there is a high index of suspicion of pancreatic or peripancreatic malignancy based on clinical presentation, CT scan, or ERCP assessment do not require preoperative, histologic proof of malignancy prior to pancreaticoduodenectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗
PubMed1993

Centrilobular distribution of acetaldehyde and collagen in the ethanol-fed micropig.

We established a new animal model of alcoholic liver disease in the micropig, a species that consumes ethanol voluntarily in the diet. Ten micropigs were pair-fed diets containing 40% of calories as ethanol or cornstarch with identical amounts of fat, protein and micronutrients for 12 mo. Liver histopathology in the ethanol-fed pigs included steatonecrosis in all five and interstitial and perivenous fibrosis in three. Electron microscopy showed Ito-cell transformation with perisinusoidal collagen accumulation. Acetaldehyde adducts were found by immunofluorescence in the centrilobular region and were focused in perivenous zone 3 of all ethanol-fed animals. Protein and triglyceride levels were increased, whereas vitamin A and iron levels were decreased in liver homogenates from ethanol-fed animals. Thus, in this new animal model of alcoholism, ethanol feeding produced the features of alcoholic liver disease concurrent with hepatic deficiency of selected nutrients. Histological and immunofluorescent studies provide in vivo evidence that perivenous collagen deposition is linked to ethanol metabolism and acetaldehyde production.

Acetaldehyde↗
PubMed1992

Role of bacterial infection in diet-induced acute pancreatitis in mice.

This study was performed to elucidate the role of bacterial infection in acute pancreatitis in young female mice fed a choline-deficient diet supplemented with 0.5% DL-ethionine (CDE diet). Mice were randomly classified into two groups: one had been fed CDE diet alone (nonantibiotic group), the other was fed a CDE diet with oral administration of antibiotics (antibiotic group). Survival rates at 96 and 144 h after introduction of the CDE diet were significantly improved in the antibiotic group, 25.0 and 19.4%, respectively, as compared with 3.6 and 0% in the nonantibiotic group (p, 0.05). Aerobic and anaerobic bacterial cultures of blood, ascites, spleen, and pancreas were taken from living mice 72 h after introduction of the CDE diet. Positive bacterial growth from one or more of the specimens occurred in 29.4% of the nonantibiotic group, and in 10.0% of the antibiotic group. Mice with pancreatic necrosis had a higher positive culture rate, 62.5% in the nonantibiotic group vs 20.0% in the antibiotic group. These results suggest that reduction of intestinal flora in mice inhibits secondary infection caused by bacterial translocation and improves survival in diet-induced hemorrhagic pancreatitis. We believe the development of bacterial infection of gut origin may be a factor influencing mortality in severe pancreatitis.

Acute Disease↗
PubMed1992

Effect of protease inhibitor FUT-175 on acute hemorrhagic pancreatitis in mice.

The effect of FUT-175, a new synthetic trypsin inhibitor, was evaluated in a lethal model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented diet (CDE diet). When FUT-175 was given prophylactically at doses of 20 mg/kg body wt, the survival rate was significantly improved (p less than 0.05). The serum amylase concentration and trypsin activity in serum were also significantly diminished (p less than 0.05). Prophylactic administration of 5 mg/kg body wt of FUT-175 showed a statistically significant decrease in the serum trypsin activity, but it did not improve the survival rate. Therapeutic administration of FUT-175 showed no favorable effect. FUT-175 showed protective effects on the course of severe acute pancreatitis only when given prophylactically at the beginning of the pancreatitis induced by the CDE diet.

Acute Disease↗
PubMed1989

Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis.

The availability of recombinant mitochondrial autoantigens may permit the experimental study of the pathophysiology of primary biliary cirrhosis. Previously, we demonstrated that high-titer antibodies to the 74 kD mitochondrial autoantigen dihydrolipoamide acetyltransferase could be generated when BALB/c mice were immunized with purified recombinant protein. Based on these data, we attempted an 8-month study to induce antibodies and liver dysfunction by immunizing AKR/J, C3H/J and CBA/HeJ mice as well as rats, guinea pigs, rabbits and rhesus monkeys with purified recombinant human dihydrolipoamide acetyltransferase. Antibodies to dihydrolipoamide acetyltransferase were readily induced and detected in all species of experimental animals with species and strain differences in the titer of the responses. Of particular interest, rabbits and guinea pigs produced antibodies which were specifically reactive with the functional site of dihydrolipoamide acetyltransferase, whereas the other strains and species produced antibodies to other epitopes on the molecule. Finally, similar to data on humans with primary biliary cirrhosis, the pyruvate dehydrogenase enzyme pathway was inhibited in the presence of immunized animal sera. These data imply that features other than simply an antibody response to mitochondrial enzymes are required for the development of primary biliary cirrhosis. Further studies will be necessary to determine the mechanisms by which mitochondrial proteins elicit an immune response.

Acetyltransferases↗
PubMed1988

Orientation of small, flat, frozen-section specimens.

A method for orienting small, flat, frozen-section specimens perpendicular to the plane of sectioning can be performed by double-embedding and freezing. The technique is fast, simple, and reliable; it requires no special equipment.

Biopsy↗
PubMed1987

Dissolution of gallstones using cholecystostomy tube in the pig.

Cholecystostomy catheters and human cholesterol gallstones were implanted surgically in the gallbladders of eight pigs. Through the catheters, mono-octanoin or sterile water (H2O) was infused from two to seven days. The mono-octanoin dissolved pure cholesterol gallstones smaller than 200 g. There was no stone dissolution with infusion of sterile water and only one stone larger than 250 g was dissolved with mono-octanoin. Side effects included moderate-to-severe inflammation and ulceration of the gallbladder with mono-octanoin instillation, which precludes its widespread use with the present treatment regimen. Infusion of water caused little gallbladder irritation.

Animals↗
PubMed1987

Cystic neoplasms of the pancreas.

Eight patients with cystic neoplasms of the pancreas were seen at four Northern California hospitals between the years 1978 and 1986. Three of the tumors were benign and five were malignant. Three females, whose average age was 61 years, had cystadenomas. Three females and two males, whose average age was 48 years, had mucinous cystadenocarcinomas. Clinical presentations were similar among all patients. Abdominal pain was a prominent feature. Anorexia, weight loss, nausea and vomiting with a palpable abdominal mass were seen in five of eight patients. Obstructive jaundice was seen in two of eight patients. Among patients with benign lesions, one lesion was in the head and two lesions were in the tail of the pancreas. The malignant lesions were in the head of the pancreas in three patients and in the tail or body in two. A presumptive diagnosis was made preoperatively on the basis of the clinical, laboratory and roentgenographic findings in seven of eight patients. Of the patients with benign tumors, two are alive and well at seven years and four months and one patient was lost to follow-up study at four years. Among the patients with a malignant condition who underwent operation, resection for cure was performed upon four patients. One patient died postoperatively and the other three patients are alive and well without evidence of a recurrence at three and one-half, four and four years after resection. Pancreaticoduodenectomy was performed upon two patients and distal pancreatectomy in another. Palliation was attempted in one critically ill patient with an unresectable tumor by longitudinal pancreaticojejunostomy. This procedure was not effective in providing pain relief because of obstruction of the pancreatic duct by the viscous mucoid secretion of the tumor. The preoperative diagnosis of these very rare tumors is usually possible roentgenographically, especially with the use of the computed tomography scan. The presence of a thick mucoid secretion of high viscosity is diagnostic of mucinous cystadenocarcinoma. Cystic neoplasms of the pancreas should always be resected, if possible, with the expectation of long term survival.

Adult↗
PubMed1985

Amebiasis presenting as rectal bleeding without diarrhea in childhood.

A 6-year-old boy with no history of foreign travel had presented with rectal bleeding without diarrhea for 2 months. Despite negative stool cultures, a diagnosis of intestinal amebiasis was made by colonoscopy with tissue biopsy. In cases of persistent rectal bleeding, even without diarrhea, a diagnosis of amebiasis should be considered. When routine stool parasite examinations are negative, unsuspected amebiasis may be diagnosed by sigmoidoscopy or colonoscopy with tissue biopsy.

Biopsy↗
PubMed1985

Esophageal granular cell tumor removed by endoscopic polypectomy.

Granular cell tumors are rare neoplasms that are generally benign. They are usually found in the tongue, subcutaneous tissues, and breast. Since Abrikossof first described the histology of this tumor in 1926, there have been 86 cases involving the esophagus discussed in the literature. There is a low likelihood of these tumors becoming malignant and recurrence after resection is rare. However, these tumors can be confused with more malignant lesions. We report an additional case involving the esophagus and offer new management guidelines in the era of fiberoptic endoscopy.

Adult↗