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Biomedical subjects

F Marini

Publications and source records attributed to F Marini.

At least 37 records · Page 2Linked to original sources

Expression of CD95(FAS) by gene transfer does not sensitize K562 to Fas-killing.

CD95(FAS/Apo-1) belongs to the family of TNF receptor related molecules and is expressed on many benign and malignant types of cells. CD95 triggering is involved in the apoptotic death of lymphoid cells and may also be important in myelopoiesis. Myeloid leukemia cells are in most cases resistant to CD95 triggering despite expressing the antigen. We reasoned that myeloid leukemic cells can become sensitized to the Fas pathway of cell death if CD95 expression is restored by gene transfer. As a model, we utilized the cell line K562 which does not express CD95 on their cell surface. The gene for CD95 was introduced into K562 cells (by electroporation). As a control, the gene coding for beta-galactosidase was used. The CD95 transfected K562 cells stably expressed CD95, and had a growth pattern comparable to untransfected cells, but still remained resistant to Fas-triggering (tested using recombinant Fas-ligand). Our experiment shows that antigen expression is not a critical determinant of Fas-mediated apoptosis, but further down-stream mechanisms determine the fate of the cells. The transfected cells also had a comparable susceptibility to NK-mediated lysis which shows that the expression of CD95 does not interfere with NK-mediated lysis of target cells.

Annexin A5↗

Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.

SPK1/RAD53/MEC2/SAD1 of Saccharomyces cerevisiae encodes an essential protein kinase that is required for activation of replication-sensitive and DNA damage-sensitive checkpoint arrest. We have investigated the regulation of phosphorylation and kinase activity of Spk1p during the cell cycle and by conditions that activate checkpoint pathways. Phosphorylation of Spk1p is induced by treatment of cells with agents that damage DNA or interfere with DNA synthesis. Although only S- and G2-phase cdc mutants arrest with hyperphosphorylated Spk1p, damage-induced phosphorylation of Spk1p can occur in G1 and M as well. Hydroxyurea (HU) induces phosphorylation of kinase-defective forms of Spk1p, demonstrating that this regulated phosphorylation of Spk1p occurs in trans. HU-induced phosphorylation is associated with increased catalytic activity of Spk1p. Furthermore, overexpression of wild-type SPK1, but not checkpoint-defective alleles, delays progression through the G1/S boundary. Damage-dependent phosphorylation of Spk1p requires both MEC1 and MEC3, whereas MEC1 but not MEC3, is required for replication block-induced phosphorylation. These data support the model that Spk1p is an essential intermediate component in a signal transduction pathway coupling damage and checkpoint functions to cell cycle arrest. This regulation is mediated through a protein kinase cascade that potentially includes Mec1p and Tel1p as the upstream kinases.

Alkaline Phosphatase↗

[Corticosteroid therapy in the prevention of recurrent post-surgical nasal polyposis].

The purpose of this study was to evaluate, in a group of 30 patients, the results of a medical treatment combining an oral corticosteroid (Deflazacort) with a drug applied topically (Beclomethasone dipropionate) following a well-defined protocol, in the prevention of recurrent post-surgical nasal polyposis. In the follow-up at 6, 12 and 24 months, the possible recurrence of polyposis was evaluated as well as the nasal blockage and the olfactory function. After six months the disease recurrence was observed in 33% of the cases, always in its early stages, whereas after one year the percentage rose to 50% (15 patients, of whom only 3 displayed a severe form with considerable reduction of nasal ventilation). At 24 months recurrence was observed in 57% of the patients. However most cases did not show any sign of further progression. Throughout the entire follow-up period under observation only 6 patients (20%) had a severe recurrence which therefore required a revision surgery. The comparison with a control group not undergoing medical therapy after surgery highlighted the significance of the results obtained. Consequently the therapeutic protocol adopted proved to be reliable due to the very high tolerability in all cases and to the high percentage of good or very good short and medium term results observed. No clinical side effects of any importance were observed during the study.

Adrenal Cortex Hormones↗

PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus.

Transmission of mitogenic and developmental signals to intracellular targets is often mediated by inositol derivatives. Here we present the cloning and characterization of a gene from Saccharomyces cerevisiae, PIK1, encoding the enzyme that catalyses the first committed step in the production of the second messenger inositol-1,4,5-trisphosphate. PIK1 encodes a phosphatidylinositol 4-kinase (PI 4-kinase) essential for growth. Cells carrying PIK1 on a multicopy vector overexpress PI 4-kinase activity exclusively in a nuclear fraction, suggesting that PIK1 is part of a nuclear phosphoinositide cycle. Temperature-sensitive mutations, but not a null mutation, can be suppressed by high osmolarity or an elevated concentration of Ca2+. Conditional mutants have a cytokinesis defect as indicated by a uniform terminal phenotype of cells with large buds and fully divided nuclei. We suggest that PIK1 controls cytokinesis through the actin cytoskeleton.

1-Phosphatidylinositol 4-Kinase↗

The B subunit of the DNA polymerase alpha-primase complex in Saccharomyces cerevisiae executes an essential function at the initial stage of DNA replication.

The four-subunit DNA polymerase alpha-primase complex is unique in its ability to synthesize DNA chains de novo, and some in vitro data suggest its involvement in initiation and elongation of chromosomal DNA replication, although direct in vivo evidence for a role in the initiation reaction is still lacking. The function of the B subunit of the complex is unknown, but the Saccharomyces cerevisiae POL12 gene, which encodes this protein, is essential for cell viability. We have produced different pol12 alleles by in vitro mutagenesis of the cloned gene. The in vivo analysis of our 18 pol12 alleles indicates that the conserved carboxy-terminal two-thirds of the protein contains regions that are essential for cell viability, while the more divergent NH2-terminal portion is partially dispensable. The characterization of the temperature-sensitive pol12-T9 mutant allele demonstrates that the B subunit is required for in vivo DNA synthesis and correct progression through S phase. Moreover, reciprocal shift experiments indicate that the POL12 gene product plays an essential role at the early stage of chromosomal DNA replication, before the hydroxyurea-sensitive step. A model for the role of the B subunit in initiation of DNA replication at an origin is presented.

Alleles↗

[Postoperative ischemic ileocolitis in the elderly. Suggested therapy with intraluminal administration of oxygen and glutamine].

Ischaemic ileocolitis in postoperative course of major abdominal surgery is a great challenge for the surgeon: the mortality rate is very high, and therapeutic choices are poor. In the elderly patients ischaemic bleeding ileocolitis is often determined by low flow: sepsis and cytologic damage are primed by activation of endotoxins and chemical mediators, and bacterial translocation could develop across intestinal wall. In our case the patient (male, caucasian, 68 years old) underwent bilio-hepatic resection for hilar cholangiocarcinoma. In the postoperative period continuous enteric haemorrhage was determined by an ischaemic ileocolitis demonstrated by colonoscopy. Abdominal angiography did not show stenosis or occlusion of mesenteric vessels. We administered dopamine and dobutamine as vasodilator drugs for splanchnic circulation without any positive response. Surgical removal of the colon was unsuccessful to stop bleeding. ileostomy and sigmostomy were performed. Histologic samples of the specimen showed ischaemic ileocolitis. After a few days the patient bled again. As last therapeutic choice, we bubbled oxygen in a solution of L-glutamin 500 mml (3 liters/min for 5 min). We administered 500 mml of this solution three times a day by enteral sond, and 100 mml twice a day by sigmoidostomy and endoluminal oxygenation was performed twice a day (1l/min for 1-2 minutes) under continuous control. Bleeding was reducing during the next five days, until stopping. If glutamine and O2 can be considered the fuel of enterocytes, we hypothesized endoluminal oxygenation and glutamine enteral supply of the small intestine could feeding enterocytes, until a complete restoration of enteral mucosa and stopping of the haemorrhage.

Aged↗

Red cell and plasma ferritin in a group of normal fetuses at different ages of gestation.

Plasma and cell ferritin were determined in 47 normal fetuses at different gestational ages in order to evaluate fetal iron status. Plasma ferritin shows an increase during pregnancy (17.7 micrograms/l-mean geometrical value of fetuses between 18 and 20 weeks; 56.8 micrograms/l mean geometrical value of fetuses between 32 and 35 wk) and significantly correlates to hemoglobin and number of red blood cells. Red cell ferritin, too, increases throughout pregnancy (from 92.7 ag/cell to 265 ag/cell) and shows a better correlation to hemoglobin and number of red blood cells. Experimental evidence has been provided showing that the placenta takes up ferritin and is important in iron storage and transport (even against a concentration gradient). Our data support this theory and suggest a situation of positive balance between iron uptake and utilization during intrauterine life.

Erythrocytes↗

[The lithotripsy therapy center "Citta di Brescia". Our experiences with the first 400 treatments].

From September 1988 to April 1989, 400 patients with stones in the calyx (40%), in the renal pelvis (45%), in the ureter (15%) and with staghorn calculi (5%) underwent shock wave treatment. In the majority of patients therapy was carried out with general anesthesia. Disintegration was achieves in 95% of stones in the kidney and 44% of stones localized in the ureter following "in situ" ESWL. The ureteroscopy and stone push-up with replacement into the renal ampulla was performed in 56% of ureteral calculi. The average number of impulses to achieve disintegration was 1850. In 20 patients were necessary 4000 SW; we studied this patients with echography, TAC and RMN 48 hours after the treatment. The objective of this trial is the assessment of the efficacy and cost benefit relation of lithotripter TRIPTER X1.

Evaluation Studies as Topic↗

Computerized tomography and magnetic resonance imaging after ESWL. Comparison at over 4,000 shock waves.

Twenty patients who received more than 3,000 shock waves at 20 kV during single treatment for renal calculi with the Tripter X1, were studied retrospectively after 48 hours with CT scan and magnetic resonance imaging (MRI). In 15 cases (85%) both diagnostic procedures were negative. In 2 cases both revealed a subcapsular haematoma and in another case perirenal urinary extravasation. We conclude that no substantial differences have been noted in postoperative complications in patients treated with 4,000 shock waves compared with those who received a smaller number of waves.

Humans↗

[Biomechanico-clinical interpretation of firearm wounds. General problems (III). A propedeutic ABC on terminal ballistics].

The surgeon should have a comprehensive knowledge of firearms as thermochemico-ballistic machines in order to come to grips in an adequate manner with the wounds they inflict on the human body. The traces left on the body to all intents and purposes embrace a cultural "cul de sac" which risks being defrauded of most of its content by a lack of those propedeutics elements which painstaking reflection is capable of affording us. Only the interpretation of each individual ballistic phase, both as a complete phenomenon in itself and as a component in a single articulated complex, can offer such elements: credit is due at least for a wholehearted commitment in this direction, while never losing sight at any time of the clinical perspective of such wounds.

Forensic Medicine↗

[Biomechanico-clinical study of gunshot wounds (general problems--II)].

Whenever the surgeon finds himself face to face with a wound (probably this is the only opportunity for a meeting between physician and pathology which seems to be able to leave the "illness" on one side, almost forgotten, as it were), even when immersed in routine, he can hardly help making a number of considerations of a general nature, to which the sentence above in brackets is not entirely extraneous. In practice, we cannot help asking ourselves an apparently simple, almost banal, question: what exactly is trauma? This triggers off a whole series of secondary queries, such as, for instance, what the relationship is between trauma and classical pathology? In the first place, it should be pointed out that "traumatic" pathology is undoubtedly the only instance of pathology in which, as a rule, at least at the outset, one can justifiably talk about the "isolated" role of what can certainly be regarded as an out-of-body factor. If, then, we consider the specifically morphological and pathophysiological aspects of the period subsequent to the traumatic insult, we find ourselves in an even more embarrassing position: we are faced with irreparably devastated organ and body structures, or with a situation which is already on the way to convalescence. One last alternative is that the traumatic insult is merely a memory, a key finding in the case history, a past reality which to all intent and purposes has ceased to exist, and we are faced with extremely complex clinical pictures which we tend to label as complications. A few examples by way of explanation: shock, adult respiratory distress syndrome (ARDS), stress ulcer, acute post-traumatic cholecystitis, haemorrhagic pancreatitis, and problems caused by resolving the hypovolaemia-ischaemia situation and by implementing reperfusion (oxygen radicals). Trauma favours - and surgeons concerned with organ transplants are well aware of this - the only possibility of death which, perhaps with a grain of excessive optimism, we may even accept as fruitful, in that it occurs without all the destructive deterioration involved in the process of dying. The above consideration probably plays a major role in our attitudes of almost fatalistic resignation towards the youthful victims of trauma.(ABSTRACT TRUNCATED AT 400 WORDS)

Physical Phenomena↗

[Cardiac arrhythmia observed in 400 workers without obvious heart disease by Holter monitoring].

To obtain information on the cardiac rhythm characteristics of subjects without heart disease during their daily work, we examined the continuous 24-hour electrocardiographic recordings of 400 workers from 4 factories in Eastern France presenting with criteria of cardiac normality. Sex, age and socio-professional category were taken into account. Supraventricular extrasystoles were extremely common, being observed in 52 p. 100 of men and 39 p. 100 of women. In men, the frequency of these extrasystoles increased with age (p less than 0.001), and their number was less than 20 per 24 hours in 90 p. 100 of the cases. Ventricular extrasystoles were detected in 40 p. 100 of men and 32 p. 100 of women. They too were age-related, though not significantly. Their number was less than 10 per 24 hours in 68 p. 100 of the cases and 10 to 50 per 24 hours in 28 p. 100. These ventricular extrasystoles usually were monomorphous, regularly coupled (92 p. 100) and isolated. However, 2 attacks of tachycardia were discovered. Episodes of bradyarrhythmia (RR superior or equal to 1500 ms) were present in 25 p. 100 of men and 19 p. 100 of women. They occurred more frequently before the age of 35 than later (p less than 0.001) and the recordings confirmed that they were predominantly nocturnal. Recordings without "disorders of rhythm" were relatively rare (20 p. 100 of men, 28.5 p. 100 of women). Finally, there was no clear-cut correlation between the prevalence or characteristics of these various "rhythmic abnormalities" and the type of professional activity.

Adult↗

[Biomechanical and clinical study of gunshot wounds (general problems). I].

Above and beyond their effective epidemiological incidence, which is perhaps somewhat greater than is commonly imagined even outside the war context, gunshot wounds constitute a unique cultural opportunity for the traumatologist and for surgeons in general. The actual morphological and clinical features of such wounds, which bear precise, localized witness to, and reflect in a virtually mathematical manner, a programmed, and thus readily quantifiable, dimension of kinetic energy (rich in experimental implications), stand out against the backcloth of an extremely extensive involvement of the body in which, amongst other things, the intervention of a whole host of mediators may be seen to play a decisive role. Lastly, it should not be forgotten that it is precisely in field hospitals or their equivalents that surgery has found a precious opportunity to escape the environmental or "cultural" conditioning of the moment and play a leading role not only in terms of technological solutions but also in terms of reflection on the main leitmotive of pathophysiology, from shock to ARDS.

Biomechanical Phenomena↗