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Biomedical subjects

G Russo

Publications and source records attributed to G Russo.

At least 55 records · Page 3Linked to original sources

Ras family genes: an interesting link between cell cycle and cancer.

Ras genes are evolutionary conserved and codify for a monomeric G protein binding GTP (active form) or GDP (inactive form). The ras genes are ubiquitously expressed although mRNA analysis suggests different level expression in tissue. Mutations in each ras gene frequently were found in different tumors, suggesting their involvement in the development of specific neoplasia. These mutations lead to a constitutive active and potentially oncogenic protein that could cause a deregulation of cell cycle. Ras protein moderates cellular responses at several mitogens and/or differentiation factors and at external stimuli. These stimuli activate a series of signal transduction pathways that either can be independent or interconnected at different points. Recent observations begin to clarify the complex relationship between Ras activation, apoptosis, and cellular proliferation. A greater understanding of these processes would help to identify the factors directly responsible for cell cycle deregulation in several tumors, moreover it would help the design of specific therapeutic strategies, for the control on the proliferation of neoplastic cells. We summarize here current knowledge of ras genes family: structural and functional characteristics of Ras proteins and their links with cell cycle and cancer.

Animals↗

[Helicobacter pylori and gastric cancer. The incidence of infection in personal experience].

BACKGROUND: Helicobacter pylori is an identified carcinogen for gastric cancer, but the underlying mechanisms remain to be defined. The aim of this study is to analyze the incidence of Hp infection in our series of patients with gastric carcinoma. METHODS: Between 1988 and 1998, 60 patients with diagnosis of gastric adenocarcinoma underwent partial or total gastrectomy. Forty-one were males and 19 females with an average age of 62 years (range 36-79). Twenty-seven cancers (45%) were localized in the lower third of the stomach, 17 (28%) in the middle third and eight (13%) in the upper third or cardias. In six patients (10%) the tumor was multicentric, while a recurrence on gastric stump after subtotal gastrectomy was present in two cases (3%). According to Lauren's criteria 39 cancers (65%) were of intestinal type, 16 (27%) of diffuse type and five (8%) of mixed type. The histologic preparations have been re-examined in order to verify the presence or not of Hp on gastric mucosa around neoplasm. RESULTS: Hp was found in 35 (58%) of the analyzed specimens and therefore a significant percentage of patients was Hp-positive at the time of diagnosis and surgery. Between 35 Hp-positive samples, 24 were adenocarcinomas of intestinal type, nine of diffuse type and two of mixed type, with a prevalence of Hp in intestinal type cancer. CONCLUSIONS: This study confirmed the high incidence of Hp infection in patients with gastric carcinoma, particularly in those with intestinal type cancer.

Adenocarcinoma↗

[Lipothymia and syncope in adolescents].

Syncope is the transient loss of consciousness and postural tone resulting from inadequate cerebral perfusion. The most common type of syncope in healthy children and adolescents is the vasovagal syncope, which is a benign and transient condition. The evaluation of syncopal children or adolescents is on a detailed history and physical examination. ECG is mandatary, other laboratory tests must be guided by pertinent positives or negatives in the history and physical examination. The pathology of syncope seems to follow a common pathway with many inciting stimuli. Cerebral perfusion is compromised by a transient decrease in cardiac output caused by vasomotor changes decreasing venous return, primary dysrhythmia, or impairment of cerebral vascular tone. Tilt table testing can be useful in selecting therapy by demonstrating the physiologic response leading to syncope in an individual patient. Treatment is usually targeted to those in whom syncope is recurred or has been associated with physical injury. In others, treatment involves removal or avoidance of agents that predispose to hypotension or dehydration, including alcohol, vasodilating anti-hypertensive medications, and diuretics. However, when these measures fail to prevent the recurrence of symptoms, pharmacologic therapy is usually recommended. The efficacy of beta blockers, midodrine and SRIs have been confirmed in randomized, prospective clinical trials. In addition to these 3 agents, there is also considerable clinical experience suggesting the value of fludrocortisone.

Adolescent↗

Homoclinic gluing bifurcations during the light induced reorientation in nematic-liquid-crystal films.

An s-polarized laser beam that impinges at small incidence angle on a homeotropically aligned nematic liquid crystal produces very interesting nonlinear phenomena. In this paper, we show that, due to the symmetry of the system, a cascade of successive homoclinic gluing bifurcations is responsible for the transition towards a stochastic regime in the experiment. We compare the experimental results with a model describing a sequence of gluing bifurcations.

Journal Article↗

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis.

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.

Aged↗

pRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus.

It has been recently reported that retinoblastoma family proteins suppress cell growth by regulating not only E2F-dependent mRNA transcription but also rRNA and tRNA transcription and, through HDAC1 recruitment, chromatin packaging. In the present study we report data showing that these various control strategies are correlated, at least in part, with nuclear compartmentalization of retinoblastoma proteins. In a first series of experiments, we showed that pRb2/p130 and p107 are not evenly distributed within the nucleus and that cell cycle-dependent binding with E2F4 changes also as a function of their subnuclear localization. Namely, in the nucleoplasm pRb2/p130-E2F4 complexes are more numerous during G0/G1 while in the nucleolus they increase in S phase. Partially different functions for p107 are suggested since p107-E2F4 complexes in the nucleoplasm are more numerous is S phase with respect to G0/G1 and no cell cycle change is observed in the nucleolus. In a second series of experiments we showed that pRb2/p130, p107, E2F4, and pRb2/p130-HDAC1 complexes are all inner nuclear matrix-associated proteins and localize to sites different from pRb/p105 ones. We provide further evidence of multiple and partially distinct retinoblastoma protein family functional roles during cell cycle. Moreover, our data support emerging evidence for functional interrelationships between nuclear structure and gene expression.

Cell Compartmentation↗

Gradients of expression of calcium and potassium currents in frog crista ampullaris.

In the present work we studied the intraregional expression of voltage-dependent Ca2+ and K+ currents in hair cells of frog crista ampullaris. The currents were recorded in situ from sensory cells of the peripheral region, the most populated region of the crista, by using the whole-cell variant of the patch-clamp technique. Voltage-clamp recordings revealed that the calcium current (I(Ca)) and the outward potassium currents of I(A), I(K) I(KCa) types and the inward rectifier potassium current of I(K1) type exhibited a significant gradient of density (pA/pF) along the region. I(A) density was maximal in cells located at the beginning of the peripheral region and decreased gradually becoming very small at the opposite end. All the other currents showed an opposite gradient of expression. Current-clamp experiments showed that the voltage behaviour of hair cells changed in relation to cell position. Cells located at the beginning of the peripheral region showed large depolarizations from the resting potential (close to -45 mV) which are consistent with the presence of small I(K) and I(KCa), and an I(A) largely inactivated at rest. These cells also exhibited slowly developing and large hyperpolarizations that approached passive ones, due to the lack of I(K1). In contrast, cells located at the opposite side of the region showed smaller depolarizations and hyperpolarizations from the resting potential (close to -65 mV), due to the presence of large I(K) and I(KCa), and I(K1), respectively. The possible role of the intraregional variation of Ca2+ and K+ currents in both hair cell function and afferent discharge properties is discussed.

Animals↗

The basal energy expenditure of female athletes vs. sedentary women as related to their family history of type 2 diabetes.

The purpose of this study was to investigate the basal metabolic rate (BMR) in 16 professional sportswomen (soccer players) versus 15 sedentary women, as related to the presence (FH+) or absence (FH-) of a family history of type 2 diabetes. The sportswomen, in toto, had a significantly higher BMR than expected from predictive equations (+14.92%). However, the difference was limited only to FH- sportswomen (+18.66%, p<0.0005). FH- sportswomen showed a significantly higher measured BMR than FH+ sportswomen (p<0.005), and FH+ (p=0.058) and than FH- (p<0.05) sedentary women. There were no other significant differences relative to physical, metabolic and plasmatic data between the groups. The sportswomen with familiarity to type 2 diabetes had a BMR lower than that of FH- sportswomen, and similar to that of sedentary sedentary women. It appears that FH+ sportswomen have a "sub-clinical metabolic inertia", representing a precocious signal in young diabetes-prone subjects, despite the modifications induced from activity on their body composition (increased FFM, even though marginally significant).

Adolescent↗

Thalidomide and its dermatologic uses.

This article reviews how the drug thalidomide can be used for various dermatologic disorders. Also included is a short discussion of the chemistry and physiologic mechanisms of thalidomide. Thalidomide, now available again in the United States, is another drug that can be considered by dermatologists for some severe, unusual disorders.

Acquired Immunodeficiency Syndrome↗

Effect of intragastric volume and osmolality on mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease.

OBJECTIVE: Both transient lower esophageal sphincter (LES) relaxations (TLESRs) and periods of low/absent LES pressure (LESP) are the main mechanisms of gastroesophageal reflux. These events are believed to be triggered by stimuli from different areas of the upper GI tract. We aimed at investigating the relationship between LESP profile and gastric emptying and distension after meals of different composition in 30 children with gastroesophageal reflux disease (median age 7.0 yr, range 12 months-12 yr). METHODS: Recordings of LESP and intraesophageal pH for 1 h fasting and for 2 postprandial h were performed with a perfused sleeve catheter and flexible electrode, respectively; gastric emptying and distension of antral area were simultaneously recorded with real-time ultrasonography. Ten patients had a standard meal (group A), 10 had a high-volume meal (group B), and 10 had a high-volume and osmolality meal (group C). RESULTS: Postprandial esophageal acid exposure was significantly higher in patients of groups B and C than in patients of group A (p < 0.01); it was also more prolonged in patients of group C than in subjects of group B (p < 0.05). A higher postfeeding rate of reflux episodes caused by TLESRs was detected in patients of groups B and C as compared with patients of group A (p < 0.01). This increase did not statistically differ in patients of groups B and C. Patients of group C exhibited a higher postprandial rate of reflux episodes associated with low/absent tone of the LES as well as a more prolonged gastric emptying time and a higher postfeeding gastric distension as compared with patients of groups A and B (p < 0.01). Finally, a significant correlation was only found between the postprandial rate of reflux events resulting from low/absent LESP and the degree of antral distension in patients of group C (p < 0.01). CONCLUSION: Gastroesophageal reflux is worsened by increasing the volume and osmolality of meals through significant changes of LESP. Meals of high volume and meals with high volume and osmolality cause a comparable increase of reflux episodes as a result of TLESRs. However, meals with high volume and osmolality cause the higher degrees of esophageal acid exposure than meals with high volume resulting from a higher rate of reflux episodes associated with low/absent LESP. This finding correlates with a high postfeeding antral distension.

Child↗

Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse.

Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Experimental evidence suggests that a defect in vascular endothelial growth factor (VEGF) regulation might be associated with wound-healing disorders. We studied the involvement of lipid peroxidation in the pathogenesis of altered VEGF expression in diabetes-related healing deficit by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/ db+ mice and their normal (db+/+m) littermates. Animals were then randomized to the following treatment: raxofelast (15 mg.kg(-1).day(-1) i.p.), an inhibitor of lipid peroxidation, or its vehicle (DMSO/NaCl 0.9%, 1:1 vol: vol). The animals were killed on different days (3, 6, and 12 days after skin injury), and the wounded skin tissues were used for histological evaluation, for analysis of conjugated dienes (CDs), as an index of lipid peroxidation and wound breaking strength. Furthermore, we studied the time course of VEGF mRNA expression throughout the skin-repair process (3, 6, and 12 days after skin injury), by means of reverse transcriptase-polymerase chain reaction, as well as the mature protein in the wounds. Diabetic mice showed impaired wound healing with delayed angiogenesis, low breaking strength, and increased wound CD content when compared with their normal littermates. In healthy control mice, a strong induction of VEGF mRNA was found between day 3 and day 6 after injury, while no significant VEGF mRNA expression was observed at day 12 after injury. In contrast, VEGF mRNA levels, after an initial increase (day 3), were significantly lower in diabetic mice than in normal littermates, and light induction of VEGF mRNA expression was also present at day 12 after injury. Similarly, the wound content of the angiogenic factor was markedly changed in diabetic mice. Administration of raxofelast did not modify the process of wound repair in normal mice, but significantly improved the impaired wound healing in diabetic mice through the stimulation of angiogenesis, re-epithelization, and synthesis and maturation of extracellular matrix. Moreover, raxofelast treatment significantly reduced wound CD levels and increased the breaking strength of the wound. Lastly, the inhibition of lipid peroxidation restored the defect in VEGF expression during the process of skin repair in diabetic mice and normalized the VEGF wound content. The current study provides evidence that lipid peroxidation inhibition restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and normalizes the defect in VEGF regulation associated with diabetes-induced skin-repair disorders.

Animals↗

Sutureless skin closure in varicose vein surgery: preliminary results.

OBJECTIVE: To describe the preliminary results of a special method of wound closure in varicose vein surgery using the tissue adhesive butyl-2-cyanoacrylate. METHODS: Eighteen consecutive young women (mean age 23 years) underwent partial stripping of the greater saphenous vein for varicose veins of the lower limbs by an external phleboextractor. Their wounds were closed without sutures by means of the adhesive butyl-2-cyanoacrylate. The cutaneous edges were drawn together by linear traction between forceps and the adhesive was applied and allowed to set. Less than 0.5 ml of adhesive was required to complete the entire procedure. Wounds were evaluated at 7 days for infection, dehiscence, and tissue reactions. At 6 months all wounds were rated for cosmesis using a validated visual analog scale, that is, a 100 mm line with "worst scar" at the right end of the line and "best scar" at the left end. All patients were interviewed about their acceptance of tissue adhesive skin closure. RESULTS: The mean time required to close the epidermis with the adhesive was 117 seconds. All patients were followed up for 6 months. At 7 days no adverse outcomes had occurred. Results of wound evaluation at 6 months by the visual analog scale showed scores of 22.2 +/- 13.8 mm (optimal). The percentage of optimal scores was 94.4%, and only one patient (5.6%) had a suboptimal score. Inquiry into the patient's opinions suggested that this procedure was very acceptable. CONCLUSION: Preliminary results with sutureless skin closure in varicose vein surgery have been very encouraging. This fast and cosmetic method of wound repair can replace the need for skin sutures in varicose vein surgery.

Adult↗

Carotid endarterectomy: a retrospective analysis. Microendarterectomy and transcranial Doppler ultrasound monitoring.

BACKGROUND: Analyses of the results obtained following our protocol for the surgical therapy of carotid artery stenosis is the aim of this study. METHODS: Ninety-one procedures were performed on 84 patients by the same surgical team. Indications for carotid endarterectomy (CEA) were 50-70% internal carotid artery (ICA) stenosis in 8% of the patients (100% symptomatic), 70-90% stenosis in 67% (64% symptomatic) and 90-99% ICA stenosis in 25% of our patients (33% symptomatic). Carotid shunt during arterial cross-clamp was only used in 4 cases (4.4%) following trans-cranial Doppler ultrasound (TCD) intraoperative monitoring findings. Operative microscope or surgical loupes were used for the complete removal of atheroma and the direct suture of the arteriotomy. Heparin was only antagonised in selected cases. RESULTS: No mortality and no permanent deficit related to ischemic events were present in our patients; a transient neurological deficit occurred in 1 case (1.1%). Two patients died (2.2%): 1 due to myocardial infarction and the second one to bronchopneumonia. Transient peripheral nerve deficits were noted in 2 cases. CONCLUSIONS: In order to reduce to a minimum ischemic risks during CEA, our preliminary experience advises microsurgical technique for the complete removal of the atheroma and suture, TCD evaluation of collateral reserve during cross-clamping, and the use of randomised multicenter studies guidelines for the selection of patients. More attention must also be given to postoperative care, since hemodynamic instability represents the main risk for our patients. Overnight intensive care unit (ICU) surveillance in all patients may help to avoid fatal complications.

Aged↗

Ex vivo and in vitro effect of human immunodeficiency virus protease inhibitors on neutrophil apoptosis.

Polymorphonuclear leukocytes (PMNL) from human immunodeficiency virus (HIV)-infected patients exhibit accelerated apoptosis and impaired functional activity. HIV protease inhibitor-based therapy produces improvements in both acquired and innate immune responses. Ex vivo and in vitro effects of HIV protease inhibitors on apoptosis and chemotaxis of PMNL were evaluated. After therapy, there was a rapid and significant decrease of PMNL apoptosis, which correlated with increased chemotactic function. These findings were found both in patients with immunological and virological response and in control subjects who showed an increase in CD4(+) T cell counts but no concomitant decline in HIV load. After in vitro treatment with ritonavir or indinavir, apoptosis of both HIV-infected and -uninfected PMNL markedly decreased and correlated with significant enhancement of chemotaxis. These results suggest that HIV protease inhibitors may improve the PMNL function by reducing the apoptosis rate and that this effect may, at least in part, be independent of their antiviral activity.

Adult↗