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Biomedical subjects

G Rossi

Publications and source records attributed to G Rossi.

At least 433 records · Page 24Linked to original sources

Bet2p and Mad2p are components of a prenyltransferase that adds geranylgeranyl onto Ypt1p and Sec4p.

Three different prenyltransferases have been identified in yeast and higher cells, the farnesyltransferase and the type I and type II geranylgeranyltransferases (GGTase). The farnesyltransferase and GGTase-I modify peptides in vitro with the CAAX (C, Cys; A, aliphatic residue; X, terminal amino acid) consensus motif. These enzymes are heterodimers that have different beta-subunits and a shared alpha-subunit. In yeast, the RAM2 gene encodes this alpha-subunit. RAM2 is also homologous to MAD2, a yeast gene whose product has been implicated in the feedback control of mitosis. We have shown that Bet2p is a component of the yeast GGTase-II (refs 6, 12) that geranylgeranylates Ypt1p, a small GTP-binding protein that mediates transport from the endoplasmic reticulum to the Golgi complex. Here we report that Mad2p is a component of this enzyme. Bet2p forms a complex with Mad2p that appears to bind geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. The efficient transfer of geranylgeranyl onto small GTP-binding proteins requires the presence of an additional activity.

Alkyl and Aryl Transferases↗

Processing of complex between urokinase and its type-2 inhibitor on the cell surface. A possible regulatory mechanism of urokinase activity.

Complexes between the urokinase-type plasminogen activator (uPA) and its type-2 inhibitor (PAI-2) are bound by a cell-surface receptor for uPA and rapidly cleaved into two fragments of 70 and 22 kDa. The 70-kDa fragment contains the active site of uPA and PAI-2, while the 22-kDa species was identified as the amino terminal fragment of uPA, that binds specifically to the receptor. When the experiment is performed at 4 degrees C, both fragments remain bound to the cell surface and can be eluted by acid treatment. We therefore postulate that after the binding of the uPA-PAI-2 complex, a new binding site for the 70-kDa species becomes available. This additional binding favours the cleavage of the complex into the 70-and 22-kDa fragments; the 70-kDa species is endocytosed or released, while the 22-kDa fragment remains on the cell surface to prevent the binding of intact uPA.

Cell Line↗

Apomorphine test for dopaminergic responsiveness: a dose assessment study.

The clinical diagnosis of idiopathic Parkinson's disease (IPD) remains difficult and is supported by a favorable response to levodopa, while failure to respond represents an exclusion criterion. Recently, the response to subcutaneous apomorphine has been suggested as a tool in predicting levodopa responsiveness in parkinsonian syndromes. We administered apomorphine at doses of 10, 50, and 100 micrograms/kg subcutaneously against placebo over two consecutive days in 37 patients with parkinsonism and evaluated the motor response for 90 min after each dose. Subsequently, we compared the motor response with the follow-up response to levodopa therapy and to a final diagnosis. Twenty-seven patients of 37 showed a positive response to apomorphine, and 10 had a negative response. All positive responses to the apomorphine test were obtained with 50 or 100 micrograms/kg doses. Because of the high frequency of side effects with the dose of 100 micrograms/kg, 50 micrograms/kg seems more useful. After an adequate period of levodopa/carbidopa therapy (12-month follow-up), 29 patients improved; 25 of these had demonstrated a positive response to the apomorphine test. The final diagnosis of IPD, made on the basis of an exhaustive clinical and neuroradiological evaluation and on the response to chronic levodopa therapy, was in good agreement with the response to the apomorphine test (predictivity of diagnosis, 86.4%). Our data indicate that subcutaneous apomorphine at the dose of 50 micrograms/kg is a useful tool in the differential diagnosis of parkinsonian syndromes.

Aged↗

Circumferential choledochoplasties with autologous venous and arterial grafts.

Circumferential choledochoplasties with vascular grafts have rarely been attempted either experimentally or in clinical practice. In this study, choledochoplasties using autologous venous and arterial grafts were performed in rats. Sixty-four rats were randomly selected into five treatment groups: A) venous interpositional graft replacement of a choledochus gap without a stent; B) venous graft with prolene stent; C) venous graft with polyethylene stent; D) arterial graft; E) a control group with simple resection between ligatures in the choledochus. The operative mortality in treatment groups B, C, D, and E, was 0, and 13% in group A. At 12 weeks follow-up, all the rats in group E had died, whereas, 52.2% (P < .05) of the rats in group A, 30% of the rats in group B, 57% of the rats in group C, and 92.8% of the rats in group D survived treatment. Surviving animals were sacrificed at 3 months for further examination. The morphology and caliber of the common bile duct of these rats were normal in 25% of the rats in group A, 33% of the rats in group B, 25% of the rats in group C, and 84.6% of the rats in group D. Proximal dilations were found in the rats presenting with abnormal morphology. The dilations were less marked in the group treated by arterial choledochoplasties. Laboratory and clinical cholestatic parameters were within normal ranges in the presence of common bile duct dilations less than four times the normal duct caliber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatitis C virus infection in liver allograft recipients.

The impact of HCV infection after liver transplantation remains a topic of discussion. The aims of this study were to define the prevalence of anti-HCV antibodies in liver donors; the risk of acquired HCV infection and HCV re-infection according to the pre-transplant anti-HCV status; the prevalence of HCV infection in post-transplant chronic hepatitis. Sera from 42 recipients with follow up longer than 6 months and their donors were tested for anti-HCV. By results at pre-transplant time patients were classified as follows: donor (D) negative and recipient (R) negative (D-/R-) 31; D-/R+ 9; D+/R- 1; D+/R+ 1. Twenty-one patients with sustained hepatic dysfunction underwent liver biopsy. In group D-/R-, 5 patients showed anti-HCV positivity and 3 (9.7%) of them had acquired HCV hepatitis. In group D-/R+, 6 patients showed persistent anti-HCV positivity and 4 (44.4%) of them had recurrent HCV hepatitis; of these 2 died due to liver failure. The 2 patients of groups D+/R- and D+/R+ had normal liver function. Anti-HCV negative hepatitis was found in 2 patients. The prevalence of anti-HCV positivity in liver donors appeared low (3.2%). Acquired HCV infection rate was 9.7%. Pre-transplant HCV infection led to a high incidence of recurrence (44.4%). HCV was the major etiological agent in post-transplant chronic hepatitis (77.8%).

Adolescent↗

Social class and mood disorders: clinical features.

We examined clinical features in 877 in- and outpatients affected by depression who were enrolled in psychopharmacological trials, subdivided according to Hollingshead's method into five social classes. The results showed that social class correlated significantly with the subtypes of mood disorders, with bipolar disorder being more frequent amongst the upper than the lower social classes. Furthermore, as already reported in other countries, social class appeared to influence the psychopathological pattern of depressive symptoms: somatization and anxiety were more frequent amongst the lower social classes, while psychic and cognitive symptoms were more common amongst the upper classes.

Adult↗

Laser nephelometric evaluation of albumin, IgG and alpha 2-macroglobulin: applications to the study of alterations of the blood-brain barrier.

Cerebrospinal fluid and serum levels of albumin, immunoglobulin G and alpha 2-macroglobulin were determined by laser nephelometer in various pathological conditions: Guillain-Barré syndrome amyotrophic lateral sclerosis, lumbar disc herniation. These proteins are different due to their molecular weight, spacial conformation, CSF and serum concentrations and their CSF/serum quotient reflects the status of the blood-brain barrier. In the subjects group comparisons, albumin quotient and IgG quotient show a significant differentiations. The linear regression of albumin quotient compared to alpha 2-macroglobulin quotient behaves differently in the individual groups. The protein CSF/serum quotients are helpful in distinguishing the causes of alterations in the blood-brain barrier.

Adolescent↗

Gamma-aminobutyric acid mediation of the inhibitory effect of endogenous opioids on the arginine vasopressin and oxytocin responses to nicotine from cigarette smoking.

Previous studies have demonstrated that naloxone exerts positive effects on the responsiveness of arginine vasopressin (AVP) and oxytocin (OT) to nicotine, suggesting inhibitory actions of endogenous opioids. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in the regulation of naloxone-sensitive endogenous opioid action. AVP and OT secretory patterns after (two nonfilter) cigarette smoking were examined in seven normal male subjects with (experimental test) and without (control test) concomitant treatment with naloxone (4 mg in an intravenous bolus plus 6 mg infused over 2 hours), the GABAergic agent sodium valproate (600 mg in three divided doses orally), or the combination of naloxone and sodium valproate. Cigarette smoking increased by 2.4-fold (peak v baseline) the plasma concentrations of AVP without modifying OT levels. In the presence of naloxone, plasma AVP and OT levels in response to nicotine were significantly higher than those in the control test. In the naloxone plus nicotine test, AVP levels increased 4.2-fold (peak v baseline) and OT concentrations increased 1.6-fold (peak v baseline). Pretreatment with sodium valproate changed neither AVP nor OT secretory patterns during the cigarette-smoking test. In contrast, sodium valproate abolished the facilitating effect of naloxone on both AVP and OT responses to nicotine. In the sodium valproate plus naloxone plus nicotine test, plasma AVP and OT levels were not significantly higher than those obtained during the nicotine test. These data indicate a GABAergic mediation of the inhibitory modulation by endogenous opioids of the AVP and OT responses to nicotine.

Adult↗

Dichloroacetic acid accelerates initial development of 2-cell murine embryos in vitro.

Preimplantation embryos up to the 8-cell stage of development use lactate and pyruvate but not glucose or Krebs cycle intermediates to support growth, development, and cleavage. The dominant effect of dichloroacetic acid (DCA) is the irreversible stimulation of pyruvate dehydrogenase (PDH) activity, thus accelerating the oxidative metabolism of pyruvate and lactate. To test the hypothesis that early induction of oxidative metabolism in 2-cell murine embryos accelerates preimplantation embryo cleavage rates, female B6C3F1 mice at 6 to 8 weeks of age were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated. All 2-cell stage embryos were randomly assigned to culture media with or without 130 micrograms/mL DCA. The developmental stage of all embryos was then noted every 24 hours for a total of 72 hours. Chi-square analysis and the method of average rank sum were used to compare the distribution of embryos at each observation point. At 24 hours, DCA-exposed embryos had achieved an advanced stage of growth and development relative to controls (average rank sum, P = .026; chi-square distribution, P = .047). Subsequently, at 48 and 72 hours, neither the average rank sum nor the chi-square distribution was different. Our data suggest that DCA accelerates early growth and development of murine embryos before implantation, possibly through the early induction of oxidative metabolism.

Animals↗

Abnormal serotonergic control of prolactin and cortisol secretion in patients with seasonal affective disorder.

The effects of the serotonergic agent d,l-fenfluramine (60 mg PO) or a placebo on serum prolactin (PRL) and cortisol levels were evaluated in seven patients (five men and two women) with seasonal affective disorders (SAD) and in eight normal controls (eight men and two women). Both groups were tested in fall/winter when patients with SAD suffered depressive symptoms and in spring/summer, when patients were euthymic. Spring/summer and fall/winter tests gave similar results. PRL and cortisol patterns were similar in all subjects after placebo, whereas both hormonal responses to d,l-fenfluramine were significantly lower in patients with SAD than in normal controls. Correlation studies between the two hormonal responses revealed that on both periods the amplitudes of PRL and cortisol increments were significantly and positively correlated in patients with SAD. These data show diminished serotonergic responsiveness in SAD regardless of the actual depressive status of the patients. They are consistent with a decrease of central serotonergic activity in SAD.

Adult↗

Cochlear interdependence and micromechanics in man and their relations with the activity of the medial olivocochlear efferent system (MOES).

Following stimulation of one ear with white noise (WN) or 0.5, 1 and 2 kHz tone bursts a statistically valid mean reduction in the amplitude of delayed evoked otoacoustic emissions (DEOE), elicited from the contralateral ear by bursts of the same frequencies, was observed in 10 people (19-23-years-old) with normal hearing. This reduction only appeared in response to a contralateral stimulus delivered 7, 8 and 9 ms earlier than that used to produce the DEOE. This inhibitory effect was just referable to the activity of the medial olivocochlear efferent system (MOES). This research has shown that: (i) the cochlear interdependence is linked to activation of the MOES; (ii) in man the activity of MOES is inhibitory and only appears for a stimulus of the same frequency or (for WN) including that used to elicit DEOE; (iii) the cochlear interdependence is frequency selective and the MOES thus establishes a direct functional interdependence between homologous sectors of the organs of Corti on the two sides; (iv) DEOE would appear to be no more than partly generated by outer hair cells (OHC) of the organ of Corti in relation to the frequency of the stimulus employed, thus substantiating the hypothesis that in their production the effects of an 'active' mechanism, represented by the 'slow' contractile activity of the OHC, is overlain by those of a 'passive' mechanism formed by the oscillations induced by the movements of the stapes in the basilar membrane (BM) or in the set of membranes and liquids of cochlear canal.

Adolescent↗