PubMed Health⌕ Search

Biomedical subjects

F Farina

Publications and source records attributed to F Farina.

At least 37 records · Page 2Linked to original sources

The KlPMR1 gene of Kluyveromyces lactis encodes for a P-type Ca(2+)-ATPase.

A novel P-type Ca(2+)-ATPase gene has been cloned and sequenced in the yeast Kluyveromyces lactis. The gene has been named KlPMR1 and is localized on chromosome I. The putative gene product contains 936 residues and has a calculated molecular weight of 102,437 Da. Analysis of deduced amino acid sequence (KlPmr1p) indicated that the encoded protein retains all the highly conserved domains characterizing the P-type ATPases. KlPmr1p shares 71% amino acid identity with Pmr1p of S. cerevisiae, 62% with HpPmr1p of Hansenula polymorpha, 56% with Y1Pmr1p of Yarrowia lipolytica and 52% with the Ca(2+)-ATPase encoded for by the SPCA1 gene of Rattus norvegicus; these similarities place KlPmr1p in the SPCA group (secretory pathway Ca(2+)-ATPase) of the P-type ATPases. The K. lactis strain harbouring the Klpmr1 disrupted gene is not able to grow in presence of low calcium concentrations and shows hypersensitivity to high concentrations of EGTA in the medium. These defects are relieved by PMR1 of S. cerevisiae on a centromeric plasmid, demonstrating that KlPMR1 encodes for a functional Pmr1p homologue.

Animals↗

Defective apoptosis as potential mechanism in the tumorogenesis of myelolipoma.

Apoptosis is considered an important mechanism of selective deletion that occurs during hematopoiesis. Myelolipoma is a rare benign tumor composed of adipose tissue and hematopoietic cells. The pathogenesis of this benign tumor is still unclear. Analysing the structural levels and apoptosis of normal human bone marrow (NHBM) and human myelolipoma (HM), the apoptotic events resulted abundantly present in NHBM compared to HM, which showed a small number of apoptotic cells. By contrast, Fas expression was strongly present both in NHBM and HM. These findings suggest that an altered function of Fas in myelolipoma is not able to trigger the apoptotic machinery. In conclusion, we hypothesize that drastic reduction of apoptosis in myelolipoma can be considered one of the growth regulatory mechanisms.

Adrenal Gland Neoplasms↗

Involvement of Fas/FasL system in the pathogenesis of autoimmune diseases and Wilson's disease.

The interaction of Fas with FasL has been demonstrated to be implicated in the pathogenesis of several autoimmune and liver diseases. Recently, attention has been focused on the hypothesis that thyrocytes and beta cells undergo massive Fas/FasL-mediated apoptosis during autoimmune response. Similarly, hepatocyte cell death occurring following copper accumulation points towards the same mechanism.

Diabetes Mellitus, Type 1↗

Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma.

Cholesterol is used by cells for biosynthetic processes and for steroid synthesis. Although the role of cholesterol in tumorigenesis is not clear it is known that steroids are important factors in human carcinogenesis. A polypeptide, diazepam binding inhibitor (DBI), which is an endogenous ligand for peripheral benzodiazepine receptors enhances steroidigenesis by promoting cholesterol delivery to the inner mitochondrial membrane which represents the rate-limiting step of steroid biosynthesis. We have assayed the total cholesterol (TC) and the DBI plasma concentrations in patients with liver cirrhosis complicated by hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver cirrhosis. TC and DBI levels have been studied in 73 cirrhotic patients and in 23 patients with HCC. Both TC and DBI levels were higher in HCC patients when compared with age, sex and Child-Pugh class matched cirrhotic controls. The values (mean+/-S.D.) in patients in Child-Pugh class B and C with and without HCC were respectively 128+/-30 mg/dl vs. 106+/-27 mg/dl (P < 0.01) and 2.05+/-0.78 pmol/ml vs. 0.78+/-0.84 pmol/ml (P < 0.0001). The data may be the result of the metabolic influence of tumors that enhances steroid biosynthesis during tumor proliferation.

Adult↗

Up-regulation of peripheral benzodiazepine receptor system in hepatocellular carcinoma.

Increased number of peripheral benzodiazepine receptors (PBRs) have been found in some tumors outside the liver. The present study was to verify whether the PBR system is altered in hepatocellular carcinoma (HCC). The levels of endogenous benzodiazepine-like compounds (BZDs), measured by radioreceptor binding technique after HPLC purification and the endogenous ligand for PBRs, termed diazepam binding inhibitor (DBI), measured by radioimmunoassay utilizing a specific antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver cirrhosis and 10 patients with HCC. The levels of BZDs in serum were increased hundred fold in liver cirrhosis patients and slightly elevated in HCC patients. DBI was found to be increased in HCC patients. The binding recognition sites for PBRs (Bmax) were increased 4 to 7 fold in HCC tissue in comparison with that found in non-tumoral liver tissue (NTLT). On the contrary the concentrations of DBI were found to be significantly decreased in HCC tissue in comparison with the respective NTLT. These results seem to suggest an implication of PBRs and of their putative endogenous ligands in the metabolism of these neoplastic cells and possibly in their proliferation. The up-regulation of PBRs found in HCC tissue seems to indicate an increased functional activity of these receptors and opens up the possibility of new pharmacological and diagnostic approaches while the changes in the circulating endogenous ligands for the above receptors might be envisaged as early markers of tumorigenesis in liver cirrhosis.

Adult↗

Benzodiazepine-like compounds in the plasma of patients with fulminant hepatic failure.

BACKGROUND: Benzodiazepine-like compounds have been implicated in the pathogenesis of encephalopathy after fulminant hepatic failure. METHODS: The levels and the nature of benzodiazepine-like compounds were determined in six cases of fulminant hepatic failure during the course of the disease. Blood samples were collected on admission and a few days later, when the neurologic status had improved in five cases and immediately before death in one case. The compounds were measured in sera with a binding technique after high-performance liquid chromatography purification and analyzed with mass spectrometry. RESULTS: Their levels were highly variable in those with severe encephalopathy and were still increased on awakening in some cases. Diazepam and N-desmethyldiazepam were inconsistently present. CONCLUSIONS: The inconsistent presence of benzodiazepine-like compounds in encephalopathy after fulminant hepatic failure and their persistence, in some cases, at high levels on awakening from coma seem to indicate that the encephalopathy is not strictly dependent on the levels of these compounds.

Adult↗

Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy.

BACKGROUND/AIM: Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. SUBJECTS: Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. METHODS: Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. RESULTS: Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. CONCLUSIONS: Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.

Aged↗

Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis.

Benzodiazepine-like compounds are present in trace amounts in the blood of normal subjects and increase in liver cirrhotic patients with or without encephalopathy. Their increased presence may, however, represent an occasional precipitating factor of hepatic encephalopathy. The source of these compounds is still unknown, but they are constituents of our diet since benzodiazepine receptor ligands have been described in plants, vegetables and in animals. They may also be synthesized, at least in part, by intestinal bacterial flora. In this article we report that the level of these compounds in the blood decreased by 40% after therapy with rifaximin, which reduces the aerobic and anaerobic intestinal bacterial flora. This observation indicates that intestinal bacterial flora is involved in the production of these compounds and that repeated short-term medications with this non-absorbable antibiotic may be useful in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis.

Aged↗

Changes in endogenous benzodiazepine-like compound levels during the course of fulminant hepatic failure: potential effects of decreased renal function.

The pathogenetic agents which cause encephalopathy due to fulminant hepatic failure are still under debate. Ammonia and benzodiazepine-like compounds are two of the most important agents considered, so far. Herein, we report the levels of benzodiazepine-like compounds in serum and in urine and of venous ammonia measured during the course of the disease (30 days). The patient rapidly developed stage IV encephalopathy with high levels of ammonia and with only a slight increase of benzodiazepine-like compounds. At that moment, the levels of these compounds were similar to those recorded in the blood when the patient regained full consciousness 28 days later. During the course of the disease, there was a 10-fold increase of benzodiazepine-like compounds in serum which was recorded in parallel with an impaired excretion due to oliguria. This observation seems to indicate that encephalopathy may develop in the absence of significantly increased levels of these compounds and that their episodic increase during fulminant hepatic failure may be an epiphenomenon linked with several factors such as impaired renal function.

Adult↗

Hepatic encephalopathy in liver transplant recipients precipitated by benzodiazepines present in transfused blood.

The observation that there are episodes of encephalopathy in liver cirrhosis patients after orthotopic liver transplantation, despite a well functioning graft and despite the lack of cerebral complications, prompted us to investigate the potential role of circulating benzodiazepine-like compounds in these episodes. The plasma levels of benzodiazepines were examined in 14 liver cirrhotic patients before and after transplantation. The benzodiazepines in the fluids infused during surgery and in individual bags of blood administered after surgery to 4 of these patients were also assayed. Herein we report that benzodiazepines accumulating in the blood of some transplanted patients appear to derive from blood transfusions utilized during surgery. The analysis of the types of benzodiazepines present in the blood utilized for transfusions suggests the use of commercial benzodiazepines by the donors. These compounds seem to be able to precipitate hepatic encephalopathy in patients with preexisting encephalopathy. Hence we suggest not using benzodiazepine consumers as blood donors, at least for patients with encephalopathy undergoing to liver transplantation.

Adult↗

Management and follow-up of 78 giant haemangiomas of the liver.

The natural history and appropriate treatment of giant liver haemangioma remain poorly defined. The diagnostic strategy and the results of a longitudinal study of 78 such lesions are described. Sixteen resected patients and 62 with asymptomatic giant haemangiomas were entered into a follow-up programme consisting of clinical assessment and abdominal ultrasonography every 6 months. Resection was considered only for symptomatic patients (14 cases) and rapidly growing lesions (two cases). The mean follow-up was 36 months for the resected patients and 55 months for the observed group. Surgery permanently relieved symptoms. No recurrence of haemangioma was observed. Some 32 of 36 unresected lesions followed up remained stable in size. Minor changes were observed in four of 36. None ruptured or became symptomatic. It is concluded that asymptomatic large haemangiomas can be managed safely by observation. However, the occasional occurrence of rapid growth might represent a further indication for resection and justifies strict imaging follow-up. The pattern of growth, rather than absolute size, of a lesion is suggested for selection of asymptomatic patients who might benefit from preventive surgical excision. When feasible, the authors prefer enucleation to remove giant haemangiomas.

Adult↗

Multi-frequency bioelectric impedance measurements for predicting body water compartments in patients with non-ascitic liver cirrhosis.

We assessed total body water (TBW) and extracellular water (ECW) in thirty-four non-ascitic cirrhotics and twenty healthy controls by 2H2O and Br dilution. In the same subjects, bioelectric impedance (BI) was recorded at multiple frequencies. Body hydration was similar for controls (mean 55.6 (SD 6.7)), less-severe cirrhotics (Child-Pugh classification A; CPA; n 21, mean 56.2 (SD 6.2)) and moderately-severe cirrhotics (Child-Pugh classification B; CPB; n 13, mean 57.2 (SD 5.4)). However, intracellular water standardized per litre TBW was significantly higher in CPB subjects (mean 27.0 (SD 7.5); P < 0.01) compared with CPA (mean 21.3 (SD 10.6)) and control subjects (mean 18.0 (SD 9.8)). Published formulas for predicting TBW and ECW from BI at multiple frequencies were applied to the cirrhotics. These formulas gave accurate predictions of TBW and ECW, although standard errors of estimates were higher for CPB subjects (TBW < or = 2.5 and ECW < or = 2.1 l) than those for CPA (TBW < or = 2.0 and ECW < or = 1.8 l) and control (TBW 1.4 and ECW 0.9 l) subjects.

Body Water↗

[Pancreatic harvesting from multiorgan donors for islet transplantation].

The result of human islet isolation procedures to transplant in type I insulin-dependent diabetic patients is significantly conditioned by the technique used for pancreas procurement from multiorgan donor. In fact, during multiorgan procurement, an improper handling of the gland could result in edema or degranulation of the acinar tissue, detrimental for the islet purification step. The surgical technique used by our surgical team, includes some important refinements to obtain the largest quantity and the best quality of purified endocrine material.

Adolescent↗

Characterization of the MN gp120 HIV-1 vaccine: antigen binding to alum.

PURPOSE: The characterization of recombinant MN gp120/alum vaccine requires the study of the gp120-alum interaction for the successful formulation of an alum-based HIV-1 vaccine. METHODS: Several observations suggest that the gp120-alum interaction is weak, wherein buffer counterions such as phosphate, sulfate, bicarbonate may cause the desorption of gp120 from alum. Comparison of gp120 with other proteins using particle mobility measurements shows that the weak binding of gp120 to alum is not an anomaly. Serum and plasma also cause desorption of gp120 from alum with a half-life of only a few minutes, wherein this half-life may be faster than the in-vivo recruitment of antigen presenting cells to the site of immunization. RESULTS: Immunization of guinea pigs, rabbits and baboons with gp120 formulated in alum or saline demonstrated that alum provides adjuvant activity for gp120, particularly after early immunizations, but the adjuvant effect is attenuated after several boosts. CONCLUSIONS: These observations indicate that both the antigen and the adjuvant require optimization together.

AIDS Vaccines↗

Zinc and magnesium in liver cirrhosis.

The Authors determined zinc (Zn) and magnesium (Mg) in the plasma, urine, erythrocytes (RBCs), mono- and polymorphonuclear cells (MNCs and PMNs) of patients with overt alcoholic and non-alcoholic liver cirrhosis. In order to obtain a clearer clinical picture, biochemical and nutritional parameters (retinol, tocopherol, six different carotenoids, creatinine-height index and tricipital skinfold), as well as markers of portal hypertension (spleno-portal size and platelet count) were also evaluated. The plasma levels of Zn and Mg were found to be reduced, as were the urine levels of Mg. Urine Zn, on the other hand, was higher than normal. Plasma Zn correlated inversely, and urine Zn directly, with the severity of the disease, rather than with alcohol consumption or treatment with diuretics. Protein metabolism impairment would appear to affect the plasma transport of Zn rather than its overall availability in the organism; the opposite was found in the case of Mg, the availability of which appeared to be reduced. Determination of the two elements in RBCs, MNCs and PMNs suggested that a true nutritional deficit cannot be demonstrated. MNCs, rather than RBCs or PMNs seem better to reflect tissue status of trace elements.

Erythrocytes↗

[Lymphovenous anastomosis in severe ascites].

The authors dealt with 37 patients suffering from advanced liver cirrhosis with ascites. Eighteen patients out of them underwent Denver peritoneum-jugular shunt as a first choice procedure, the other 19 patients underwent lymphovenous anastomosis. The extremely advanced hepatic damage and the general conditions of these patients discouraged us to perform a portocaval shunt. In the 19 patients who underwent lymphovenous anastomosis we had no mortality rate. Two patients showed post-operative complications: 1 patient complained which hoarseness regressed in 5 months and the other patient suffered from a spleno-mesenteric-portal thrombosis with digestive hemorrhage from gastro-esophageal varices. In 6 patients out of 19 who underwent lymphovenous anastomosis, we did not obtain any immediate positive effects on ascites. In 4 patients, after 3 months, the ascites came back ingravescent and in the other 9 patients the positive effects on ascites were still evident after 1 year. Despite failure to obtain very comforting results, they suggest to employ this technique at any rate, as the first procedure, to make ascites more "manageable", because of its safety.

Anastomosis, Surgical↗

[The Denver peritoneojugular shunt. Current indications].

Personal experience of 31 patients suffering from intractable ascites due to advanced liver cirrhosis between 1978 and 1987 is reported. Seventeen patients were selected for a peritoneojugular shunt: in 3 patients the Le Veen shunt was performed and in 14 the Denver shunt was preferred. The high postoperative morbidity and mortality due to liver failure, DIC, hepatorenal syndrome, bleeding, sepsis and cerebral thrombosis is pointed out. Careful selection of patients to be submitted to this surgical procedure is essential because of the high morbidity due to ascites reinfusion. DIC has to be diagnosed as soon as possible and, when severe, the prompt interruption of the peritoneojugular shunt is mandatory.

Adult↗