Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpinet

Laipcarpine (LC), a pyorrolizidine alkaloid, is able to inducea series of chronic and progressive lesions in rat liver, includingalong-lasting block in the cell cycle, the appearance of enlargedhepatocytes (megalocytosis), fibrosis, cirrhosis and malignantneoplasms. In this study the effect of transplantation of normalhepatocytes on the development of LC (80 µmol/kg i.p.).Four weeks later all animals were subjected to 2/3 paroticlhepatectomy (PH). In addition, at the time of PH one group ofrats were transplanted with normal hepatocytes isolated froma syngeneic donor (10⁶ cells/rat via the portal vein), whilethe other group received only the culture medium. All rats werekilled 14 weeks after the operation. Grossly, the liver of ratsexposed to LC followed by PH with no transplantation of normalhepatocytes was small in size (% liver wt/body wt 1.66 ±0.08) and exhibited a few whitish nodules. Histologically,     

Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors

Insulin-like growth factor II (IGF-II) is a mitogen for manycell types and an important modulator of muscle growth and differentiation.IGF-II gene is prevalently expressed during prenatal developmentand its gene activity is regulated by genomic imprinting, inthat the allele inherited from the father is active and theallele inherited from the mother is inactive in most normaltissues. IGF-II expression is activated in several types ofhuman neoplasms and an alteration of IGF-II imprinting has beendescribed in Beckwith–Wiedemann syndrome and Wilms' tumour.Here we show that monoallelic expression of IGF-II gene is conservedin normal adult muscle tissue whereas two or more copies ofactive IGF-II alleles, arising by either relaxation of imprintingor duplication of the active allele, are found in 9 out of 11(82%) rhabdomyo-sarcomas retaining heterozygosity at 11p15,regardless of the histological subtype. Since IGF-II has beenindicated as an autocrine growth factor for rhabdomyosarcomacells, these findings strongly suggest that acquisition of adouble dosage of active IGF-II gene is an important step forthe initiation or progression of rhabdomyosarcoma tumorigenesis.Among different types of muscle tumors, relaxation of imprintingseems to arise prevalently in rhabdomyosarcomas, since we havedetected only one case of partial reactivation of the maternalIGF-II allele out of 7 lelomyosarcomas tested.     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

Regional effect of estradiol on rat caudate-putamen dopamine receptors: lateral-medial differences

The effect of a chronic 17 beta-estradiol (10 micrograms, b.i.d.) treatment of 2 weeks to ovariectomized rats was investigated on lateral and medial caudate-putamen dopamine receptors. Dopamine D2 receptors were assayed with [3H]spiperone binding to caudate-putamen homogenates or by autoradiography of forebrain sections. Estradiol treatment leads to a significant increase in the density of lateral caudate-putamen dopamine receptors while for the medial dopamine receptors the increase is non-significant. This effect is observed when plasma levels of 17 beta-estradiol and prolactin are increased. These results indicate that the effect of estradiol on striatal dopamine receptors is heterogeneous and that those in the lateral part are more susceptible to this steroid.     

A physiological dose of progesterone affects rat striatum biogenic amine metabolism

Ovariectomized rats injected with progesterone (50 micrograms s.c.) showed a peak in striatum dopamine (DA) concentration after 15 min followed by a decrease at 60-75 min and a return to control values 90 min after the steroid injection. The DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased after the progesterone injection, with a peak at 45 min and a return to control values after about 2 h. Striatum serotonin (5-HT) concentrations remained unchanged after the progesterone injection while its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was increased at 45 min and returned to control values after 2 h. The peak plasma progesterone concentration occurred 15-30 min after the steroid injection while estradiol concentrations were unchanged indicating no significant conversion of progesterone into estradiol. A similar experiment was performed in male rats. As with female rats, a progesterone injection led to a progesterone peak at 30 min while plasma estradiol levels remained unchanged. Male rats responded to the progesterone injection with a maximal increase of DA, DOPAC and HVA concentrations as soon as after 15 min and these amines remained elevated up to 75 min after the steroid injection. 5-HT and 5-HIAA remained unchanged after the progesterone injection. Thus, very small physiological doses of progesterone can increase striatum dopaminergic activity in rats of both sexes while serotonergic activity is influenced only in female rats. This effect is seen within minutes and is relatively short. It is probably non-genomic, presynaptic and similar to the effect of a small dose of a DA releasing agent.     

Two-dimensional echocardiography in the diagnosis of intracardiac masses: A prospective study with anatomic validation

The accuracy of two-dimensional echocardiography in the detection of intracardiac masses was verified in 334 patients who underwent cardiac catheterization in our laboratory over 21 consecutive months. A complete two-dimensional echocardiographic (2DE) examination was performed a day before catheterization. The presence or absence of a mass was verified at surgery in 77 patients who successively underwent mitral or aortic valve replacement (51), left ventricular aneurysmectomy with or without myocardial revascularization (25), and resection of atrial myxoma (2). In 32 patients 2DE revealed the presence of a mass-left or right atrial thrombi in 12, left atrial myxoma in 2, left ventricular thrombi in 16, and endocardial vegetations in 2. The other 45 patients were free of intracardiac masses on 2DE. Anatomic verification at surgery revealed the presence of an intracardiac mass in 34 patients. In 30 (true positives) of these, 2DE revealed the mass as well, and in 4 (false negatives) the presence of a mass had not been identified by 2DE. In 2 patients (false positives) the predicted mass was not found at surgery. Absence of a mass was correctly predicted by 2DE in 41 patients (true negatives). Thus 2DE detected intracardiac masses with sensitivity of 88.2% and a specificity of 95.3%. We recommend that 2DE be performed in all patients prior to hemodynamic study and/or cardiac surgery to enable safer management of patients with intracardiac masses during cardiac catheterization and/or cardiac surgery.     

Automated assessment of cervical dystonia.

We developed an automated and objective method to measure posture and voluntary movements in patients with cervical dystonia using Fastrack, an electromagnetic system consisting of a stationary transmitter station and four sensors. The junction lines between the sensors attached to the head produced geometrical figures on which the corresponding aspects of the head were superimposed. The head position in the space was reconstructed and observed from axial, sagittal, and coronal planes. Four patients with cervical dystonia and 6 healthy subjects were studied. Each patient was representative of one of the typical patterns of cervical dystonia. The study allowed the authors to collect quantitative data on posture and range of motion of the head. This pilot study demonstrates the efficacy of the Fastrack system to objectively measure the head position in cervical dystonia patients.