[Vesicosigmoid fistula associated with bladder carcinoma: report of a case].
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Humans↗
Biomedical subjects
M Di Girolamo
Publications and source records attributed to M Di Girolamo.
Evidence that the 50-kDa substrate of brefeldin A-dependent ADP-ribosylation binds GTP and is modulated by the G-protein beta gamma subunit complex.
Brefeldin A, a fungal metabolite that inhibits membrane transport, induces the mono(ADP-ribosyl)ation of two cytosolic proteins of 38 and 50 kDa as judged by SDS/PAGE. The 38-kDa substrate has been previously identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We report that the 50-kDa BFA-induced ADP-ribosylated substrate (BARS-50) has native forms of 170 and 130 kDa, as determined by gel filtration of rat brain cytosol, indicating that BARS-50 might exist as a multimeric complex. BARS-50 can bind GTP, as indicated by blot-overlay studies with [alpha-32P]GTP and by photoaffinity labeling with guanosine 5'-[gamma-32P] [beta,gamma-(4-azidoanilido)]triphosphate. Moreover, ADP-ribosylation of BARS-50 was completely inhibited by the beta gamma subunit complex of G proteins, while the ADP-ribosylation of GAPDH was unmodified, indicating that this effect was due to an interaction of the beta gamma complex with BARS-50, rather than with the ADP-ribosylating enzyme. Two-dimensional gel electrophoresis and immunoblot analysis shows that BARS-50 is a group of closely related proteins that appear to be different from all the known GTP-binding proteins.
Adenosine Diphosphate Ribose↗
The transport of lysine across monolayers of human cultured intestinal cells (Caco-2) depends on Na(+)-dependent and Na(+)-independent mechanisms on different plasma membrane domains.
To characterize the mechanisms involved in the intestinal absorption of the essential amino acid L-lysine from the diet, the transepithelial transport of L-lysine was studied in monolayers of cultured human intestinal cells (Caco-2) grown and differentiated on microporous membrane supports. L-lysine was transported mainly in the apical (AP) to basolateral (BL) direction and the BL to AP transport was approximately one order of magnitude lower at all concentrations tested. Non-linear regression analysis of the transport in the AP to BL and the BL to AP direction identified, in both cases, single saturable components with similar Km but different Vmax and a nonsaturable diffusional component. The AP to BL L-lysine transport was highly energy- and sodium-dependent and was unaffected by an unfavorable concentration gradient. Selective replacement of sodium ions in the AP or the BL compartment and determination of both AP to BL transport and the intracellular soluble lysine pool showed that uptake occurs via a sodium-independent mechanism, not significantly influenced by membrane potential, whereas efflux is a sodium-dependent process. Competition experiments showed that L-lysine uptake is highly stereospecific and is shared by cationic and large neutral amino acids. This study demonstrates the presence of a sodium-dependent mechanism of lysine efflux across the BL membrane of intestinal cells, which may be essential for lysine transport into the blood circulation. Overall, these results support the use of the Caco-2 cell model for studies of intestinal nutrient transport.
Adenocarcinoma↗
[Magnetic resonance angiography of the intracranial circle using magnetization transfer contrast (MTC)].
Magnetic Resonance Angiography (MRA) is becoming an accurate technique to study vascular conditions, especially when the intracranial circulation is involved. Nevertheless, the contrast-to-noise (C/N) ratio in MRA images is often inadequate to obtain diagnostic images. C/N ratio can be increased by using magnetization transfer contrast (MTC), the technique which allows to reduce the signal from the stationary tissues surrounding vascular structures. To demonstrate the value of MTC, 10 healthy volunteers and 10 patients with different cerebral vascular conditions were examined. All exams were performed using 3D MOTSA (Multiple Overlapping Thin Slab Acquisition) Time of Flight sequences, with and without MTC. A quantitative analysis was carried out in the images with and without MTC, measuring the signal intensity value in the regions of interest at the vascular and stationary structures. A qualitative analysis was also carried out with a double blind study by two independent radiologists. Our results showed that MTC allows to reduce stationary tissues signal intensity, without affecting flowing blood signal intensity. Therefore, the C/N ratio is increased, thus allowing better depiction of smaller peripheral branches. In conclusion, MTC applied to intracranial MRA allows image quality to be markedly improved, with an overall increase in the diagnostic accuracy of this technique.
Cerebrovascular Circulation↗
[Magnetic resonance cholangiopancreatography. A new method of noninvasive biliopancreatic diagnosis].
Magnetic Resonance cholangiopancreatography (MRCP) is a new noninvasive imaging technique for the visualization of the biliary ducts with cholangiographic images similar to those obtained with ERCP and PTC, but with no contrast agent injection. In this paper, we report on our preliminary experience with a mild-field strength magnet (0.5T) and TSE sequences, acquired with respiratory compensation. The images were compared with ERCP images to compare diagnostic quality. Eighteen patients were examined: the biliary tract was dilated because of chronic pancreatitis in 3 patients, because of choledochal stones in 9, of carcinoma of the pancreatic head in 4, of lymphadenopathy in one patient. A patient submitted to choledochoduodenostomy and waiting for cholecystectomy was also examined. MRCP was performed with a superconductive magnet at 0.5T. Volumetric images on coronal planes were acquired; a T2-weighted TSE sequence (TR = 5000, TE = 244, Nex = 4, ETL = 45; acquisition time = 14 min 10 s) with respiratory compensation was also performed. The images were reconstructed on coronal planes at different angles with the MIP algorithm. All patients were then submitted to ERCP and one to PTC. In all patients, the intrahepatic biliary tracts, hepatic ducts and choledochus were completely demonstrated, with very good image quality in 16 cases and good in 2. The Wirsung duct was always visualized in all the 9 patients with mild to severe dilation. In conclusion, MRCP can be considered a valuable alternative to diagnostic ERCP. Further studies are necessary for better assessment of the potential advantages and pitfalls of this technique.
Adult↗
[Identification of pancreatic insulinomas. The role of magnetic resonance].
Insulinomas are the most common endocrine tumors of the pancreas. Although their clinical and biochemical diagnosis is extremely accurate, these lesions must be correctly located preoperatively to plan the best possible treatment. Many different noninvasive diagnostic techniques have been proposed, with only partially satisfying results. For many years such non-invasive modalities as arteriography have been considered the most reliable and accurate diagnostic tools. Recently, however, MRI has been proposed for best pancreas imaging, especially for tumor detection, and its results have been excellent especially thanks to its optimal contrast resolution. Fat-suppressed and turbo-spin-echo (TSE) sequences now yield even better results. In our study we examined 21 patients, whose symptoms were typical of insulinoma, using two different 0.5T magnets, one of which with 15 mT/m gradients. We used T1-weighted spin-echo (SE) sequences with and without respiratory compensation, SE ad TSE T2-weighted and fat-suppressed T1-weighted SE sequences. In 16 patients the lesions were correctly diagnosed and located, as confirmed at surgery. In the other 5 patients, MRI failed to locate the insulinomas. Three of these 5 patients were submitted to surgery, during which palpation and intraoperative US findings were also negative for a solid mass. The remaining 2 patients underwent clinical follow-up. Our study demonstrated that MRI, especially with fat-suppressed and T2-weighted TSE sequences, is a very accurate modality to detect pancreatic insulinomas and can therefore be proposed as the only preoperative technique.
Adolescent↗
[Carcinoma of the pancreas. Typical and atypical aspects using midfield-strength magnetic resonance].
Until few years ago, MR assessment of pancreatic carcinoma was thought to be feasible only with high-strength equipment, but today also low- and midfield units allow pancreatic lesion detection, thanks to parameter optimization. The authors retrospectively analyzed the MR findings of 57 patients examined with a midfield MR unit; all the patients had clinically suspected pancreatic carcinoma, which was confirmed in 54 cases. The lesions were more easily detected using T1-weighted sequences, thanks to their high intrinsic contrast, while T2-weighted sequences often confirmed the glandular changes already depicted by T1-weighted sequences. MRI correctly depicted vascular and lymph node involvement and detected liver metastases with no i.v. contrast agent injection. The only limitations of this technique are the unfeasibility of MR exams of diagnostic value in uncooperative patients (5% of cases) and the very similar MR features of parenchymal scars, due to previous acute pancreatitis, to those of pancreatic carcinoma. In conclusion, CT remains the gold standard in the study of pancreatic cancers, but midfield strength MRI, if correctly performed, can be proposed as a complementary tool to CT, especially in questionable cases and in the patients with known reactions to iodinated contrast agents.
Aged↗
Immunoresponsiveness of cancer patients: effect of blood transfusion and immune reactivity of tumor infiltrating lymphocytes.
The immunoreactivity of cancer patients submitted to surgery and perioperatively transfused was investigated. Peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL) were tested for the natural killer (NK) cytotoxic activity, for the in vitro synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). The serum levels and the production of PGE2 by PBMC were significantly higher in patients than in controls, whereas no significant differences in the tested immunological variables emerged between the two groups of subjects. Instead, TIL produced significant larger amounts of spontaneous PGE2 (p < 0.001) and significant lower amounts of IFN-gamma (p < 0.001) and TNF-alpha (p < 0.001) than autologous PBMC, suggesting an involvement of PGE2 in the impairment of the host immunoreactivity at the tumor site. To evaluate the immunomodulating effect of blood transfusion, the patients were reexamined 8 to 20 days after surgery. No differences were found in the NK cytotoxic activity, lymphokine synthesis, serum levels, and production of PGE2 between transfused and untransfused patients. These results do not support the hypothesis that blood transfusions negatively affect the immune response of neoplastic patients.
Adult↗
Stimulation of endogenous ADP-ribosylation by brefeldin A.
Brefeldin A (BFA) is a fungal metabolite that exerts profound and generally inhibitory actions on membrane transport. At least some of the BFA effects are due to inhibition of the GDP-GTP exchange on the ADP-ribosylation factor (ARF) catalyzed by membrane protein(s). ARF activation is likely to be a key event in the association of non-clathrin coat components, including ARF itself, onto transport organelles. ARF, in addition to participating in membrane transport, is known to function as a cofactor in the enzymatic activity of cholera toxin, a bacterial ADP-ribosyltransferase. In this study we have examined whether BFA, in addition to inhibiting membrane transport, might affect endogenous ADP-ribosylation in eukaryotic cells. Two cytosolic proteins of 38 and 50 kDa were enzymatically ADP-ribosylated in the presence of BFA in cellular extracts. The 38-kDa substrate was tentatively identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The BFA-binding components mediating inhibition of membrane traffic and stimulation of ADP-ribosylation appear to have the same ligand specificity. These data demonstrate the existence of a BFA-sensitive mono(ADP-ribosyl)transferase that may play a role in membrane movements.
ADP Ribose Transferases↗
[The role of intraoperative echography in laparoscopic cholecystectomy].
On the basis of recent technological improvements, the laparoscopic approach has become the method of choice during cholecystectomy. This surgical procedure, however, needs that cholangiography be performed simultaneously to better define the anatomy of the biliary ducts and the possible presence of choledochus stones. The use of intraoperative US during cholecystectomy is nowadays advocated for the unquestionable advantages offered by this technique--i.e., its non-invasiveness, high spatial resolution and no need of contrast agent administration. In this study, we examined 30 patients with cholelithiasis who underwent laparoscopic cholecystectomy and were submitted to endolaparoscopic US besides routine intraoperative cholangiography. In all cases, both techniques allowed optimal visualization of the biliary tree, clearly demonstrating choledochus stones in 2 cases. Intraoperative US proved to be more accurate in two cases. In one case which was positive at intraoperative cholangiography, the method allowed the biliary duct filling defect to be referred to an artifact caused by the presence of an air bubble. In another case, the lack of opacification of the hepatic ducts at cholangiography was referred, after US, to extrinsic gallbladder compression. US also allowed the adjacent parenchymal organs, such as the liver and the head of pancreas, to be studied. A limitation of this technique was represented by the difficult assessment of the choledochus in the patients with anatomical abnormalities or adhesions of the intestinal loops of the upper abdomen. In conclusion, endolaparoscopic US proved to be a reliable technique in the intraoperative study of the biliary ducts and can be considered as a procedure complementary to intraoperative cholangiography.
Biliary Tract↗
[Intraoperative digital cholangiography during laparoscopic cholecystectomy interventions].
In the last years, laparoscopic cholecystectomy has become the method of choice in the surgical treatment of gallbladder stones. Recently, the same laparoscopic approach has been used to remove choledochus stones. This surgical procedure needs the accurate intraoperative study of the biliary tree with diagnostic imaging modalities to better define the anatomy of the biliary ducts and the possible presence of choledochus stones. To this purpose, transcutaneous and endolaparoscopic US with dedicated probes and intraoperative cholangiography can be performed. In this study, we performed 30 laparoscopic cholecystectomies during which all the patients were submitted to intraoperative cholangiography with a digital fluoroscopic unit. The maneuvers for catheter insertion in the cystic duct and the examination as a whole took 3 to 5 minutes. Intraoperative cholangiography demonstrated choledochus stones in 3 patients, while preoperative US detected them in 2 patients only. In 8 cases the dynamic study, carried out with digital image acquisition, allowed to refer the biliary duct filling defects to artifacts caused by the presence of air bubbles. In conclusion, intraoperative cholangiography, also during endolaparoscopic cholecystectomy, plays a major role in the surgical assessment of the biliary tree. When the procedure was performed with a digital fluoroscopic unit, its diagnostic accuracy was higher and the images on the TV monitor were better visualized.
Cholangiography↗
[Cystic neurinoma of the axilla. A case report].
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Axilla↗
DNA hypomethylation and differentiation in Friend leukemia cell variants.
The occurrence, upon differentiation, of a transient DNA hypomethylation has been observed in Friend erythroleukemia cells. Treatment with hexamethylenebisacetamide (HMBA) induces within 24 h a 20% hypomethylation of newly synthesized DNA, that is followed by re-methylation before completion of the differentiative process, as measured by the appearance of benzidine-positive cells. We examined a series of mutant clones which continue to grow in the presence of an inducer. Methylcytosine content of DNA was measured by HPLC, after cell labeling with [3H]uridine. We found that one of these continuously growing clones, which was still capable of hemoglobin synthesis, showed the same degree of hypomethylation as the parental one. The re-methylation process did not occur, however, unless erythroid differentiation was reverted by the removal of the inducer. In another clone which had lost the capacity to synthesize hemoglobin, no DNA hypomethylation was detectable. These experiments show that DNA hypomethylation is an early event strictly related to cell differentiation but not to cell growth arrest.
Acetamides↗
[Hypermedia software for teaching anatomy of the upper abdomen with computerized tomography and magnetic resonance].
The authors have developed a hypermedia program for creating a tutorial of CT and MR anatomy of the upper abdomen. The program was created on a Mcintosh computer, with the Supercard software: it is made up of a series of windows, each of them containing images, texts, schematic representations and sound. Moreover, each window contains buttons which are activated with the mouse and allow different kinds of function, all created by the authors to be displayed. In particular, navigation buttons allow the users to move in the program either sequentially or non-linearly, according to their needs. The possibility of obtaining information and schematic representations is given by specific buttons. There are also multiple buttons hidden in the images which, when activated, allow the name of the selected organ to be displayed. In conclusion, this program can be especially helpful since it allows different data sets to be integrated to provide the user with complete information. Moreover, the program allows learning to be controlled, that is the user to be informed on timing and methods for more effective studying.
Abdomen↗
[Angiography with magnetic resonance of the ++carotid arteries. Evaluation of clinical results obtained with low magnetic field equipment].
Magnetic Resonance Angiography (MRA) is the latest diagnostic technique for the noninvasive evaluation of cardiovascular conditions. This technique has proved to be especially useful in the study of carotid arteries. All the clinical studies reported to date have been obtained at high or medium field strength; our purpose is to assess the clinical value of MRA in the evaluation of carotid arteries at low field strength. All the exams were performed with an 0.2 T permanent magnet, using the 2D time of flight (TOF) technique, the only one which is currently available on our equipment. Forty-two patients with clinical diagnosis of cerebrovascular insufficiency were examined. In all cases MRA findings were confirmed with digital subtraction angiography (DSA), which was considered the gold standard. The double-blind evaluation of the results showed high agreement of the two techniques in 70 of 84 carotid arteries. A mild tendency to overestimation was observed in 4 normal cases considered as mild stenoses on MRA, in 2 cases with mild stenosis considered as discrete stenoses on MRA and in 1 case of severe stenosis considered as an occlusion on MRA. Underestimation was seen in 1 case of mild stenosis considered as normal on MRA, in 2 cases of discrete stenosis which appeared as mild stenoses on MRA and in 2 cases of occlusion considered as severe stenoses. Our study showed high agreement between MRA and DSA results, which means that high quality exams can be obtained even at low field strength. Further progress can be expected when 3D TOF and phase-contrast techniques will be introduced.
Adult↗
[Animal experimentation in radiology. Objectives, organizational and ethical problems].
The contribution of biomedical sciences to the scientific breakthroughs in the last years has benefitted also by experiments on animals. As for diagnostic imaging, the use of new contrast media for angiography, CT and MRI makes it necessary, according to the law, to perform preliminary animal studies to test efficacy, pharmacokinetics and pharmacodynamics of the contrast agents. Experimental animal studies of clinically well-established contrast agents are also justified by the need to implement new imaging modalities. The close relationship between medical research and animal experimentation has awakened public opinion, as well as the researchers themselves, to the ethical and legal problems related to animal testing. This paper reports on the regulations which are currently in use in this field.
Animals↗
Magnetic resonance angiography: current clinical applications.
Magnetic Resonance Angiography (MRA) is the newest non-invasive procedure for the evaluation of the vascular system. The basis to obtain images of vessels from Magnetic Resonance (MR) data rely upon the specific signal alteration determined by flowing blood. By using special techniques only these signals are evidenced, with cancelling of the surrounding stationary tissues. Clinical applications are reviewed in this paper. They include: Evaluation of intracranial vessels with important adjunct information to those obtained by conventional MR images; Definition of cerebrovascular disease including the carotid artery with good correlation with Digital Subtraction Angiography (DSA); Evidence of abdominal vessels, with clear imaging of abdominal aortic aneurysms; Definition of renal arteries; although problems exist, the technique may become useful in the future for the screening of renovascular hypertension; Visualization of peripheral vessels; initial results indicate a potential application in the evaluation of peripheral run-off distal to occlusions.
Carotid Artery Diseases↗
K-ras transformation greatly increases the toxin-dependent ADP-ribosylation of GTP binding proteins in thyroid cells. Involvement of an inhibitor of the ADP-ribosylation reaction.
The GTP binding (G) proteins of normal (FRTL5) and ras-transformed thyroid cells (KiKi) were characterized by cholera and pertussis toxin-induced ADP-ribosylation and immunoblot analysis. Two pertussis toxin substrates with molecular masses of 40 and 41 kDa were identified in normal cells as the alpha i2 and alpha i3 subunits. The molecular masses of the cholera toxin substrates were 42 and 45 kDa. The same cholera and pertussis toxin substrates were present in the K-ras-transformed cell line. However, the toxin-dependent ADP-ribosylation was markedly higher in KiKi than in normal cell membranes (more than 50-fold). The reason for this difference was investigated; it could not be explained by the relative amounts of G proteins in the two cell systems, since the levels of alpha i2 subunit as measured by quantitative immunoblot in K-ras-transformed cells were only slightly (65%) higher than in normal cells. The difference in ADP-ribosylation was not due to poly-ADP-ribosylation nor to a different degree of subunit dissociation of G proteins in the two cell lines. Rather, the enhanced ADP-ribosylation in K-ras-transformed cells appears to be due to the loss of an inhibitory factor present in the normal cells. Partial characterization indicates that such a factor is a peripheral membrane protein of less than 25 kDa capable of directly interfering with the ADP-ribosylation reaction.
Adenosine Diphosphate Ribose↗