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H Nizze

Publications and source records attributed to H Nizze.

At least 55 records · Page 3Linked to original sources
PubMed1998

Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.

The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted into pre-established tumours derived from human pancreatic cells. Cytochrome P450 2B1 converts the chemotherapeutic agent ifosfamide to toxic metabolites. Administration of ifosfamide to tumour-bearing mice that were recipients of implanted encapsulated cells results in partial or even complete tumour ablation. These results suggest that in situ chemotherapy with genetically modified cells in an immunoprotected environment may prove useful for application in man.

Adenocarcinoma↗
PubMed1998

Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis.

The oxidative metabolism of xenobiotics is effected mainly by cytochrome P450 enzymes (CYP), which are expressed as a family of genetically related enzymes primarily in hepatocytes. The pancreas is among the extrahepatic tissues expressing CYP, and it has been suggested that intermediates generated by them might be of pathogenetic significance for diseases of the pancreas such as chronic pancreatitis. We studied 10 surgical resection specimens by immunohistochemistry with polyclonal antibodies against recombinant human CYP 1A1, 1A2, 2C9, 2E1, and 3A and used tissues from 11 normal pancreata as controls. In addition, we assayed microsomal preparations for their capacity to metabolize verapamil. In normal pancreata weak to moderate expression of all enzymes was demonstrated immunohistochemically in up to 50% of duct epithelia, acinar cells, and islet cells. In contrast, in chronic pancreatitis an up-regulation was observed, with immunohistochemical positivity in some cases in up to 100% of duct epithelia and acinar cells. The oxidative capacity of microsomal preparations from chronic pancreatitis was higher than that of preparations obtained from control tissues; compared to liver microsomes, however, it was low. The up-regulation of CYP may have pathogenetic significance for chronic pancreatitis. Yet considering the pancreas' capacity for conjugation reactions, conceivably low levels of reactive intermediates could effectively undergo inactivation.

Adult↗
PubMed1998

Morphometric measurements to quantify the cerulein induced hyperstimulatory pancreatitis of rats under the protective effect of lectins.

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+ release and alpha-amylase secretion in vitro as well as on pancreatic secretion of intact rats in vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 microg/kg/h i.v. or 10 microg/kg/h i.p.) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum alpha-amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous i.p. administration of cerulein and WGA or UEA in a dosage of 125 microg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1+/-2.0 microm (cerulein) to 7.5+/-1.1 microm (cerulein + WGA) or 7.2+/-1.3 microm (cerulein + UEA). The serum amylase activity was reduced from 63.7+/-15.8 mmol/l x min (cerulein) to 37.7+/-11.8 (cerulein + WGA) or 39.4; +52.9; -31.1 (cerulein + UEA-I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.

Amylases↗
PubMed1998

The influence of ethanol on long-term effects of dibutyltin dichloride (DBTC) in pancreas and liver of rats.

The present study was done to determine the additional influence of daily ethanol intake (15% in drinking water ad libitum) on long-term toxic effects of a single administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and liver of rats. Pathohistological changes in pancreas, bile duct and liver as well as pathobiochemical parameters of pancreatitis (amylase and lipase activity), liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute interstitial pancreatitis as well as acute bile duct and liver lesions in the early experimental phase. Later on, the acute inflammatory processes in pancreas and liver took a chronic course resulting in pancreatic fibrosis and liver cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks, ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct epithelium as well as the formation of obstructive ductal plugs by necrotic cell debris. The obstruction and cholestasis in the DBTC/ethanol-group were significantly stronger as in the DBTC-group. The significant increase of hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated rats after 12 to 24 weeks was connected with a more severe chronic inflammatory fibrosis in pancreas and liver in comparison to the DBTC-treated group.

Administration, Oral↗
PubMed1998

[Steroid hormone receptor status and other immunohistochemical prognostic markers in benign and malignant diseases of the breast].

In addition to classical morphological prognosis factors of breast carcinoma (pTNM stage, tumor grading, histological typing), many other immunohistochemical markers of different prognostic value exist.--The comparative estrogen (ER) and progesterone receptor (PR) analysis of normal and pathological breast tissue showed a gradually inverse biological correlation between the decrease of ER+PR+ and the increase of ER-PR-frequency from benign breast changes to noninvasive and invasive breast carcinomas. In benign breast epithelium, ER+PR+ and ER-PR+ might be regarded as low-risk phenotype, whereas ER+PR- and ER-PR- could be estimated as high-risk phenotype in view of a later dedifferentiation and possible malignization.--During carcinogenesis, the initial loss of epithelial growth factor receptor (EGF-R) as well as its later neoexpression could be regarded as a progression maker.--The proliferation rate (Ki67) in breast cancer significantly correlates with increasing grading and apoptosis rate, whereas the expression of bcl-2-protooncogene is inverse to increasing grading. As for the prognostic value of the single factors, it is supposed that they mostly might represent "one piece of a larger puzzle" [13].

Biomarkers, Tumor↗
PubMed1997

[Fatal chronic oxalosis after sublethal ethylene glycol poisoning].

A 36-year-old man known as chronic alcohol abuser presently suffered from arthralgia and showed bilateral petriefied kidneys by sonography and computed tomography. Because of an unclear renal failure a kidney biopsy was performed and presented typical chronic renal oxalosis with massive oxalate crystal deposits, tubular atrophy and interstitital fibrosis. Since the man had never shown signs of hyperoxaluria in his life before, a secondary oxalosis was supposed. The subsequently prompted exploration established a three to four times abuse of rocket fuel with cola lemonade 12 years before during the patient's army time as a marine soldier. Such fuels contain ethylene glycol (glysantin) as antifreeze commonly known to cause in toxic doses acute renal tubular necrosis with hyperoxaluria. The presented case, however, suggests a rare sublethal ethylene glycol poisoning with initial renal tubular damage, oxalate crystal deposition and subsequent chronic interstitial oxalate nephritis with tubular atrophy, interstitial fibrosis and chronic renal failure. Undergoing chronic hemodialysis, the patient died 5 months after the kidney biopsy diagnosis by acute heart failure. At autopsy, progressed chronic renal oxalosis could be confirmed. Decompensated oxalate cardiomyopathy with disseminated myocardial oxalate crystal deposits caused acute heart failure promoted by myocardial hypertrophy in renal hypertension.

Adult↗
PubMed1997

Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride.

BACKGROUND & AIMS: Regulatory mechanisms in chronic pancreatitis finally resulting in pancreatic fibrosis cannot be studied sufficiently in human pancreas. Results of a new pancreatitis model in rats suitable for investigation of the processes leading to pancreatic fibrosis are presented. METHODS: Experimental pancreatitis was induced by intravenous application of 8 mg/kg body wt dibutyltin dichloride. Pancreatitis was characterized by histology, serum parameters, and immunohistochemistry, detecting inflammatory cells. Gene expression of collagen type I and transforming growth factor beta1 was shown by Northern blot analysis. RESULTS: Dibutyltin dichloride induced an acute edematous pancreatitis within 24 hours. Extensive infiltration with mononuclear cells could be observed after day 7 followed by the development of fibrosis. Parallel to the cell infiltration, an upregulation of messenger RNA-encoding collagen type I and transforming growth factor beta1 could be shown. An active inflammatory process could be shown until the end of the observation period, i.e., 2 months. CONCLUSIONS: The findings suggest that dibutyltin dichloride-induced pancreatitis in rats is suitable to study cellular interactions and mediators involved in the development of pancreatic fibrosis.

Animals↗
PubMed1997

Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions.

Dibutyltin dichloride (DBTC; 6 mg/kg body weight, i.v.) induced acute interstitial pancreatitis in rats. The course of the pancreatitis was examined within 28 days by light and electron microscopy as well as by pathobiochemistry (amylase, lipase, alkaline phosphatase, and bilirubin in serum; tin concentration in biliopancreatic juice, tissue, and concretions). The pathogenesis of the DBTC-induced pancreatitis in rats was studied by different experimental designs (in intact animals, after bile duct ligation, after surgical bypass of the bile duct). DBTC caused toxic necrosis of the biliopancreatic duct epithelium, which is then shed into the duct and forms obstructing plugs in the distal common bile duct. Interstitial pancreatitis occurred during the first 4 days, accompanied by significantly increased activities of serum alpha-amylase and lipase. After 7 days extensive infiltration of the pancreatic interstitium with mononuclear cells was observed. Twenty-eight days after administration of DBTC one-third of the rats showed periductal and interstitial fibrosis as well as an active inflammatory process in the pancreas. The findings suggest a twofold pathogenesis of the DBTC-induced pancreatitis: first, the cytotoxic effects on the biliopancreatic duct epithelium lead to epithelial necrosis with obstruction of the duct, subsequent cholestasis, and interstitial pancreatitis; and second, the hematogenic DBTC effects cause direct injury of pancreatic cells (mitochondrial damage, autophagy, cell necrosis) followed by interstitial edema and inflammation. Both processes lead to this special type of DBTC-induced acute pancreatitis with a tendency to a chronic course, when the obstruction of the duct and cholestasis persist.

Acute Disease↗
PubMed1997

Santorini's duct--risk factor for acute pancreatitis or protective morphologic variant? Experiments in rabbits.

BACKGROUND AND AIMS: Gallstone pancreatitis is assumed to result from stone passage through the choledochoduodenal junction. Stone impactions may either result in the obstruction of the pancreatic duct or occur below the confluence of the biliary tract and the pancreatic duct and, thus, may favour bile reflux into the pancreatic duct. We studied effects of a patent Santorini's duct upon secretory flow and pancreas morphology under both conditions. METHODS: A catheter in the distal rabbit pancreatic duct created a second outlet for pancreatic juice and, thus, mimicked a patent Santorini's duct. A second catheter was introduced into the proximal pancreatic duct and into the common bile duct. This catheter mimicked a common channel behind a papillary obstruction. Clamping of this catheter mimicked a stone obstruction of the pancreatic duct. A catheter in the cystic duct allowed for the infection of bile with 10(7) Escherichia coli bacteria/ml. The flow direction of bile and pancreatic juice was directly observed. Pancreatic histology was analysed after 24 h. RESULTS: Pancreatic duct obstruction produced an oedema of the gland. Creation of a patent Santorini's duct prevented development of the histological changes caused by pancreatic duct obstruction. In rabbits in which a common channel obstruction was mimicked, Santorini's duct produced flow of bile along the pancreatic duct system. Flow of sterile bile along the duct did not cause pancreatic inflammatory lesions. Bile that was infected with E. coli bacteria produced an acute interstitial-oedematous pancreatitis. CONCLUSIONS: (1) A patient Santorini's duct protects the gland from the effects of main pancreatic duct obstruction; (2) Santorini's duct promotes biliary pancreatic reflux during obstruction of the common channel and subsequent development of pancreatitis caused by infected choledochal secretions; (3) Santorini's duct may thus be both a protective morphological variant and a risk factor for pancreatitis dependent upon the site of stone impaction within the choledochoduodenal junction.

Acute Disease↗
PubMed1996

Hyperthermia induces heat shock protein expression and protection against cerulein-induced pancreatitis in rats.

BACKGROUND & AIMS: Heat shock proteins (HSPs) are part of the cellular stress response machinery. HSPs are expressed in the pancreas, but their protective potential has not been thoroughly investigated. The aim of this study was to characterize the pancreatic heat shock response both in vitro and in vivo and to study whether this response has protective effects. METHODS: For in vitro experiments, rat pancreatic acini were exposed to heat and protein expression was analyzed through 35S-methionine labeling or Western blots. In vivo, cerulein pancreatitis was induced after whole body hyperthermia (42 degrees C). RESULTS: After thermal stress (42 degrees C), acini increasingly expressed five proteins of 92, 72, 59, 58, and 30 kilodaltons, with HSP. 70 the most strongly induced 72-kilodalton protein. In vivo, increased expression of four isoforms of pancreatic HSP-70 was found. Isoform-specific antibodies identified the inducible and constitutively expressed (HSC-70) isoform of HSP-70. HSP-60 was also weakly induced after hyperthermia. Concomitantly, cerulein-induced pancreatic organ damage was greatly reduced after whole-body hyperthermia. The time course and strength of HSP induction correlated well with the time course and degree of protection against cerulein-induced pancreatitis. CONCLUSIONS: A causal relation between hyperthermia-induced HSP expression and organ protection seems possible.

Animals↗
PubMed1996

Assessment of chronic rejection in permanent accepted renal allografts in anti-CD4 treated rats.

In rats, transient prophylactic anti-CD4 therapy with the nondepleting mAB RIB5/2 prevents acute rejection of MHC-mismatched allografted kidneys and induces long-lasting unresponsiveness. However, little is known about long-term benefits of this prophylactic anti-CD4 regimen. Here we report experimental results of permanently accepted rat renal allografts after prophylactic anti-CD4 treatment in regard to signs of chronic rejection. Kidneys from Wistar Furth donors were orthotopically grafted into bilateral nephrectomized BDIX recipients under the cover of anti-CD4 treatment (20 mg/kg b.w). Kidney function was serially monitored by measurement of serum creatinine and urine protein excretion. After 100 or 300 days respectively renal allografts were harvested, histologically and immunohistologically assessed and intragraft cytokine gene expression determined. Serum creatinine increased in few allografted rats. 30% of the 300-day-old grafts had an increased proteinuria and higher degrees of glomerular sclerosis. In these grafts cellular infiltration was more pronounced. However, no activated leukocytes (IL-2 receptor positive) were detected. Correspondingly, intragraft gene expression of CD3, IL-10 and IFN gamma was low. The results of our study indicate that a prophylactic anti-CD4 regimen diminishes chronic rejection to a level comparable to isografted or naive mass-reduced or ischemic kidneys. Thus, the signs of chronic rejection observed seem to be mainly caused by alloantigen-independent processes.

Animals↗
PubMed1995

[primary and secondary malignant liver tumors at autopsy, biopsy and cytology: frequency and problems of differential diagnosis].

The frequency and ratio of primary and secondary malignant liver tumours were evaluated in the autopsy, biopsy and cytology files from 1980 to 1994. In 1008 necropsies with hepatic malignancies, 91 primary liver carcinomas and 917 metastatic liver tumours were observed. In a total of 2537 malignant neoplasias at autopsy, the overall-rate of liver metastases amounted to 36%. The four most frequent primary carcinomas of liver metastases found at necropsy were bronchial, colorectal, pancreatic, and breast carcinomas. In 193 liver tumour biopsies, 27 hepatic carcinomas and 160 liver metastases were diagnosed histologically, whereas in 6 biopsies only a differential diagnosis between primary/secondary carcinomas could be made. Histologically, adenocarcinomas were observed in 65% of the liver metastases under biopsy. The four most frequent primaries of hepatic metastases registered at biopsy were colorectal, biliary system, pancreatic, and gastric carcinomas, so that metastasis formation of the portal vein type predominated in the biopsy series with 73% of the cases. In spite of supplementary immunohistological examinations, the primary tumour remained unknown in 13% of the metastases studied at liver biopsy. In 58 fine needle aspirations of clinically suspected liver tumours, 11 hepatocellular carcinomas and 29 liver metastases were found cytologically, whereas 18 specimen showed differential diagnostically inconsistent tumour findings. Gastrointestinal and breast carcinomas were the two most often primaries of liver metastases diagnosed cytologically. The primary/secondary liver tumour ratio amounted to 1:10 at autopsy and shifted to 1:6 in the biopsy series as well as to 1:3 in the cytology material.

Autopsy↗
PubMed1993

Preservation time dependent morphological changes in cold stored human donor pancreas.

Pancreatic transplantation is being used to treat insulin-dependent diabetes. An intact structure of the graft is a prerequisite for preserved function and we therefore monitored the light microscopic and ultrastructural changes in 30 human donor pancreases stored in the cold in University of Wisconsin preservation solution. Twenty-three pancreases were stored for less than 24 h and 7 for more than 30 h. All glands stored longer than 30 h displayed cytoplasmic vacuolisation in a variable proportion of acinar cells. In addition, the glands stored over 40 h showed focal acinar necrosis. Endocrine tissue was only slightly affected, while duct cells showed no changes. It is concluded that cold preserved pancreases stored for less than 24 h are best for transplantation purposes and that acinar cells are more sensitive to ischaemic damage than endocrine and duct cells.

Adenosine↗
PubMed1993

[The trend distribution quotient, a new tool for evaluating renal perfusion scintigraphy using 99mTc-DTPA following renal transplantation].

We developed a new quantitative concept in dynamic renal transplant imaging, the Trend Distribution Ratio, and tested its diagnostic usefulness in 137 examinations. This ratio is an expression of the distribution of blood flow velocity in different areas of the kidney. With regard to the differential diagnosis between acute tubular necrosis and the various forms of rejection we arrived at a sensitivity of 0.83 and a specificity of 0.54. A differentiation between the various histological types of rejection has not yet been possible.

Blood Flow Velocity↗
PubMed1992

[Histological classification of malignant non-Hodgkin's lymphomas and patient survival: the Kiel classification versus the working formulation].

In 163 out of 251 histologically classified malignant Non-Hodgkin's lymphomas, a comparison was made of the patient survival with respect to both histological type and malignant grade according to the Kiel Classification (KC) and the three prognostic groups of the Working Formulation (WF). As expected, the survival rate of 94 low-grade malignant lymphoma cases (KC) was significantly better than that of 69 high-grade cases (p < 0.0001). Similar results were found both for 46 low grade cases (WF) in comparison to 50 high grade cases (p < 0.001) and for 67 intermediate grade cases (WF) compared with the 50 high grade cases (p < 0.05). The survival rates of low and intermediate grade cases (WF), however, showed no statistically significant difference. The low- and high-grade malignant lymphoma entities of KC, which together constitute the intermediate grade of WF, differed significantly with respect to patient survival (p < 0.05). Therefore, it appears that an intermediate grade is not essential in the KC.

Humans↗
PubMed1991

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue.

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.

Adult↗
PubMed1991

[Late metastasis of a breast carcinoma to the uterine corpus and cervix].

In a 55-years-old woman 11 years after radical operation of a left-sided breast cancer a late metastasis in the uterine corpus was diagnosed and treated by subtotal hysterectomy. In the further course a carcinoma developed in the opposite breast, which may be most probably a second primary breast cancer. However a contralateral metastasis of the earlier treated breast cancer cannot certainly be excluded. Finally, a metastasis of the left sided-breast cancer was diagnosed in the uterine cervix. This case shows, that gynaecological bleedings also may be caused by atypical metastasis of a breast cancer.

Breast Neoplasms↗