Two new p73 splice variants, gamma and delta, with different transcriptional activity.

p73 has been recently identified as a new structural and functional homologue of the transcription factor p53. It is expressed in either a full-length form, alpha, or a shorter beta mRNA variant, with exon 13 spliced out. Here we report the identification and functional characterization of two new p73 splicing variants, gamma (splicing out exon 11) and delta (splicing out exons 11, 12, and 13).

Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling.

Early events in the signalling of tumor necrosis factor-receptor 1 (TNF-R1), which is the main TNF receptor on most cell types, have been clarified recently. A multimolecular signal transducing complex from which several pathways originate rapidly forms upon TNF-induced aggregation of the receptor. Although fully capable of transducing apoptotic signals, which depend on the adapter Fas-associated death domain protein (FADD) and on the subsequent recruitment/activation of the apoptotic proteases, TNF-R1 usually does not kill cells; this is due to the induction of a complex cytoprotective response that requires TNF-receptor associated factor 2 (TRAF2), a signal transducer that couples TNF-R1 to both nuclear factor kappaB (NFkappaB)-dependent and NFkappaB-independent transcriptional events implicated in induction of genes protecting from TNF cytotoxicity.

Pyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-6-ones. II. Synthesis and in vitro antimicrobial evaluation.

A series of Pyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-6-ones (4a-p) was prepared by a simple synthetic procedure based on the reaction of hydroxylamine or methoxyamine with 2,3-substituted ethyl 7-dimethylaminovinyl pyrazolo[1,5-a]pyrimidin-6-carboxylates (3a-p). The antimicrobial activity of the obtained compounds was evaluated on a series of standard strains of Gram positive, Gram negative bacteria and fungi. None of the tested compounds showed significant activity.

[Intravascular surgery in the treatment of peripheral arteriopathies: our experience].

The Authors, through a review of their vascular surgery experience in the treatment of PAOD at the III General Surgery Institute directed by Prof. G. Di Matteo (University, of Rome), focus their attention on endovascular surgery.

White matter lesion detection in multiple sclerosis: improved interobserver concordance with multispectral MRI display.

An assessment of the detectability of white matter lesions and of concordance between observers with different levels of MRI reading experience was performed with comparative evaluation of spin-echo MRI images and of corresponding "multispectral" maps in 16 patients with definite multiple sclerosis (MS). Multispectral maps were obtained by means of a recently described post-processing technique based on the simultaneous display of MRI parameters and a standardized colour scale with red, green and blue coding for relaxation rates R1 and R2 and proton density, respectively. Spin-echo images on films and multispectral maps displayed on a personal computer were randomly rated at 2-month intervals.

Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2. Nuclear factor kappaB (NFkappaB)-inducing kinase requirement for activation of activating protein 1 and NFkappaB but not of c-Jun N-terminal kinase/stress-activated protein kinase.

Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF receptor 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with the p55 TNF-R1 cytoplasmic domain and recruits the Fas-associated death domain protein (which directly activates the apoptotic proteases), the protein kinase receptor interacting protein, and TNF receptor-associated factor 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription factor nuclear factor kappaB (NFkappaB) and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, which in turn stimulates transcription factor activating protein 1 (AP1) mainly via phosphorylation of the c-Jun component.

Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis.

Inherited mutations of the Fas/Apo1/CD95 gene, a cell-surface receptor involved in cell death signaling and in the control of self-reactivity, characterize the recently identified autoimmune lymphoproliferative syndromes. A patient with type 2 autoimmune hepatitis with the immunologic and genetic features of autoimmune lymphoproliferative syndrome is described. The clinical picture was dominated by liver disease with hepatosplenomegaly and positivity for anti-liver-kidney microsome 1 and anti-liver-cytosol 1 antibodies.

Supplementation of nicotinic acid for lactating Holstein cows under heat stress conditions.

Twenty-six lactating Holstein cows (90 d of lactation) were blocked according to milk production, parity, and days of lactation for assignment to one of two dietary treatments. Diets included a control diet with no supplemental niacin and a diet supplemented with increasing concentrations of niacin (12, 24, or 36 g/d per cow over three consecutive 17-d periods. Cows were housed in a covered free-stall barn and were fed and milked twice daily.

[Combined outpatient surgical-cryotherapeutic treatment of anal fissures. Our experience].

The authors describe their technique and their experience of ambulatory surgical-cryotherapeutic combined, treatment of anal fissure. The data were observed in 35 patients (medium age 37.5); in 16 cases, previous treatments gave no benefit.

[Analysis of ocular saccadic movements with a fatigue test and neostigmine in Graves' ophthalmopathy].

Background: Aim of this study was to investigate the frequency of association between Myasthenia Gravis (MG) and Graves Ophthalmopathy (GO) using the responses to diagnostic tests for MG (fatigue and neostigmine tests) by measuring horizontal saccadic eye movements (SEM).

Methods: For this paper a random investigation was performed on eleven patients, affected by Graves' disease (GD) at the department of Molecular and Clinical Endocrinology and Oncology and department of Neurology of University of Federico II of Naples, for one year. Eleven patients (11 F), were subjected to endocrinological and ophthalmological examinations (TSH IRMA, TT3-RIA, TT4-RIA, TgAb, TPOAb, orbit ultrasonography or computed tomographic scans) and computerized analysis of saccadic eye movements (SEM); the fatigue and neostigmine tests were performed by means of SEM analysis in seven of this patients.

[Clinico-diagnostic aspects and therapeutic considerations of the combined surgical and radiotherapeutic approach in 2 cases of sacrococcygeal chordoma: our experience].

Chordomas are rare tumours arising from embryonic notochord tissue remnants. The commonest affected segment is the sacrum. This localization may present diagnostic and therapeutic problems.

Relative sparing of extraocular muscles in myotonic dystrophy: an electrooculographic study.

We studied 40 patients with myotonic dystrophy (MD) to investigate whether saccadic eye movement (SEM) abnormalities have a central or peripheral origin. SEMs were recorded by electrooculography and analyzed by a computer system. Six patients were followed up to 2-7 years.

Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway.

Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation.

Elevated serum levels of 90K/MAC-2 BP predict unresponsiveness to alpha-interferon therapy in chronic HCV hepatitis patients.

Background: The clinical outcome of hepatitis virus infections is though to depend on the complex interplay between the host immune response profile and virus factors. 90K/MAC-2 BP is a novel member of the Scavenger Receptor Cysteine Rich protein superfamily that functions as a molecular alarm signal for the cellular immune system against both cancer cells and virus infections.

Methods: To assess the significance and the potential clinical usefulness of testing for serum levels of 90K/MAC-2 BP in chronic viral hepatitis patients we studied 115 consecutive patients with chronic HCV hepatitis, 28 HBsAg chronic hepatitis patients, 12 asymptomatic HCV carriers and 11 asymptomatic HBV carriers.

[Adenocarcinoma of the anal glands. Description of a clinical case and review of the literature].

Adenocarcinoma of the anal glands is a rare slow-growing tumor with a more favorable prognosis compared with colorectal adenocarcinoma, especially if an early diagnosis is established. Clinical symptoms of this disease, often associated with a fistula in ano as in the reported case, include: perianal pain, rectal bleeding and presence of perianal mass. Also perianal Paget's disease may be a not rare association with adenocarcinoma of the anal glands.

[Indications and methods for rhino-pharyngo-laryngeal fibroscopy in children].

Flexible rhinopharyngolaryngoscopy (RFL) has now definitively replaced rigid endoscopy in the diagnosis of VADS in children owing to its ease of use and handling, also in the case of patients who are not wholly cooperative. RFL also enables the morphology and laryngeal function to be evaluated in children without risks for the patient provided the operator complies with a few simple precautions during diagnosis. During elective diagnosis, the patient must be in a fasting state and must not present uncompensated coagulopathies.

Pyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-6-ones. I. Synthesis and in vitro antimicrobial evaluation.

A series of pyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-6-ones (9-36) was prepared by a simple synthetic procedure based on the reaction of ethyl 7-dimethylaminovinyl pyrazolo[1,5-a]pyrimidin-6-carboxylates (1-8) and reagents (a-n) containing a primary amino group. When this set of compounds was subjected to "in vitro" antimicrobial screening, it showed no significant activity.

[Sclerosing adenocarcinomas of the hepatic hilum].

The authors report their series of 7 adenocarcinomas of the hepatic hilum. Five patients with a stage IV tumor underwent palliative surgery while the remaining 2 patients underwent radical surgery. One patient died and 3 reported postoperative complications.

[Esophagectomy without thoracotomy: indications and our experience].

In this paper the Authors report their experience of Orringer operation in 12 patients with oesophageal cancer observed from 1978 to 1992, and stress the possibility to extend the indications to Akijama oesophagectomy without thoracotomy for the treatment of malignant tumors of the entire oesophagus.

[Therapeutic strategies in the treatment of esophageal cancer: our experience].

Esophageal cancer has a poor prognosis. The Authors in reviewing esophageal carcinogenis stress the importance of an early diagnosis to improve surgical results and compare their experience with those of other Authors.

New 2,3-substituted 4,7-dihydro-6-(1'H-pyrazol-3'-yl)pyrazolo[1,5-a] pyrimidin-7-ones and related compounds: synthesis and benzodiazepine receptor binding study.

The reaction between two series of 7-dimethylaminovinyl pyrazolo[1,5-a]pyrimidines 4(a-r) 7a, 7d, 7f, 7(h-j) and hydrazine in acetic acid is investigated. The structure of 4,7-dihydro-6-(1'H-pyrazol-3'-yl)pyrazolo[1,5-a]pyrimidin-7- ones 5(a-r) and 7-methyl-6-(1'H-pyrazol-3'-yl)pyrazolo[1,5-a]pyrimidines 8a, 8d, 8f, 8(h-j) are attributed to the isolated products and the pathway of this reaction is suggested. The in vitro benzodiazepine receptor (BzR) affinity of the title compounds are determined by testing their ability to displace 3H-flunitrazepam from its specific binding in bovine brain membranes.

[Role of surgery in the treatment of gastroduodenal ulcer].

Medical approach to gastroduodenal ulcer has dramatically changed with the advent of anti-H2 drugs. There is still a role for surgery, but it has been confined to the treatment of the complications (perforation, stenosis and some cases of haemorrhage). In this paper the Authors collected the data of 43 patients (27 males and 16 females, mean age 45), operated between July 1988 and December 1992; 12 patients were operated for pyloric stenosis, 16 for gastrointestinal bleeding and 15 for perforation.

Resistance to Fas-mediated apoptosis in human hepatoma cells.

CTLs- and lymphokine-induced apoptosis of infected hepatocytes during the course of chronic viral hepatitis is thought to be important for both disease termination and prevention of hepatocellular transformation. We therefore studied apoptosis induced by Fas (APO-1 or CD95)-a widely expressed cell surface receptor whose ligand is involved in lymphocyte cytotoxicity-in a set of human hepatoma cell lines. As normal hepatocytes, all of the human hepatoma cell lines tested do express detectable amounts of Fas on their surface.