Biomedical subjects

F Mantovani

Publications and source records attributed to F Mantovani.

At least 19 recordsLinked to original sources

PubMed2001

Networked seduction: a test-bed for the study of strategic communication on the Internet.

One of the emerging features of the Internet is its relational and communicative nature: the initial centrality of the information exchange is moving to the building of online relationships, from friendship to romantic and even sexual relationships. The main goal of this paper is to define a theoretical model for the study of seductive processes on the Internet. In particular, taking up the perspective of the user, a shift of focus is proposed: from the description of the development of interpersonal attraction to the investigation of seduction, considered as a strategic communication process. According to the presented model, the key effort of the subjects involved in a computer-mediated seductive interaction is the negotiation of the meaning of the situation they are involved in. This process usually requires two tasks: the analysis of the characteristics of the communicative environment in which the play of interpersonal attraction develops, and the exploitation of the affordances offered by the communicative environment according to specific strategic goals. The main features of the model are both the focus on the communicative tools employed by the users to reach their relational goals, and the ergonomic characteristics of the networked environment. This approach can be used as a test-bed for the definition of specific hypotheses concerning the development of seductive interaction online.

Communication↗

PubMed2001

[Erectile dysfunction after non-nerve sparing radical pelvic surgery. Therapeutical experience with sildenafil and L-arginine evaluated by Buckling test].

BACKGROUND: Patients undergoing radical pelvic floor surgery are often find that sexual function is impaired. In this research hypothesis, we evaluated the efficacy of alternative therapy to conventional PGE 1 injections, such as the association of Sildenafil and L-Arginine. This association is based on the principle that L-Arginine, the precursor of nitric oxide, improves the effect of Sildenafil, which is effective in the presence of nitric oxide. METHODS: The experimental plan was to make a comparative study between 2 random groups of patients selected from those undergoing radical cystectomies and prostatectomies over the past three years. 116 patients were eligible (64 prostatectomies and 52 cystectomies). The first random group was treated with Sildenafil alone and the second with Sildenafil and L-Arginine. The efficacy of treatment was evaluated using the Buckling test (pressure threshold of cavernous flexation at penile axial rigidity) once after ambulatorial administration and then by telephone interview (subjective evaluation) after administration at domicile. RESULTS: The starter dose was 50 mg and was inefficient in both groups (Buckling test between 0 and 250). 100-mg doses gave significant results (Buckling test >500) in both groups, especially the second. Cardiopathic patients, diabetics and patients with retinal disorders or who were unmotivated were excluded from the study. The mean age of patients was 65. CONCLUSIONS: The resumption of relatively satisfactory sexual activity was demonstrated using non-invasive pharmacological treatment.

Aged↗

PubMed2000

Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins.

A general theme that has emerged from studies of DNA tumor viruses is that otherwise unrelated oncoproteins encoded by these viruses often target the same important cellular factors. Major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 oncoproteins, respectively, and although otherwise unrelated, both of these viral proteins possess a functional PDZ domain-binding motif that is essential for their transforming activity and for binding to the PDZ domain-containing and putative tumor suppressor protein DLG. We report here that the PDZ domain-binding motifs of Ad9 E4-ORF1 and high-risk HPV-18 E6 also mediate binding to the widely expressed cellular factor MUPP1, a large multi-PDZ domain protein predicted to function as an adapter in signal transduction. With regard to the consequences of these interactions in cells, we showed that Ad9 E4-ORF1 aberrantly sequesters MUPP1 within the cytoplasm of cells whereas HPV-18 E6 targets this cellular protein for degradation. These effects were specific because mutant viral proteins unable to bind MUPP1 lack these activities. From these results, we propose that the multi-PDZ domain protein MUPP1 is involved in negatively regulating cellular proliferation and that the transforming activities of two different viral oncoproteins depend, in part, on their ability to inactivate this cellular factor.

3T3 Cells↗

PubMed2000

Immunohistochemical and quantitative study of mast cells in La Peyronie's disease.

OBJECTIVE: In order to investigate the possible association between mast cells (MCs) and the fibrous plaque of La Peyronie's disease, the number of MCs in normal penile tissue and in the fibrous plaque was determined. METHODS: The control group consisted of 5 total and 3 partial penectomies with no fibrotic lesions, while the study group consisted of 23 excisional biopsies from cases of La Peyronie's disease dating back to at least 2 years earlier and with no signs of activity. The biopsies included tissues from the tunica albuginea (TA), the areolar tissue (Br) between the tunica and the erectile tissue (CC) and from the latter. The number of MCs was counted with the aid of an image analysis program following staining the antibody antitryptase. RESULTS: In the cases of La Peyronie's disease the number of MCs/mm(2) was significantly higher in the TA and Br but lower in the CC. The MCs were related to fibroblasts and vasculonervous channels in the TA, and were concentrated around the fibrous plaques and granulation tissue between the TA and BR and between the latter and the CC. CONCLUSION: Our data indicate that MCs have a role in the genesis of the fibrous plaque in the TA and in the persistent inflammation in the Br. Medical treatment aimed at repressing MC activation and proliferation locally might be useful in La Peyronie's disease.

Adult↗

PubMed1999

Sp1 and CTF/NF-1 transcription factors are involved in the basal expression of the Hmgi-c proximal promoter.

HMGI-C is a nuclear architectural factor which is expressed during embryogenesis but not in adult tissues while it becomes re-expressed following neoplastic transformation. In this paper we identify the promoter region of the mouse Hmgi-c gene and by stepwise deletion of the 5' sequences we map the promoter activity of the most abundant transcript to a very short fragment containing a long polypyrimidine/polypurine (ppyr/ppur) tract. We demonstrate that this tract is a multiple binding site for the transcription factors Sp1 and Sp3 and that in Drosophila SL2 cells, Sp1 activates the Hmgi-c promoter. In addition, another transcription factor, CTF/NF-1, binds the proximal promoter immediately downstream of this region and its mutation decreases transcription in NIH-3T3 cells. This study identifies factors responsible for the basal activity of Hmgi-c gene and provides a foundation for further analysis of the mechanism of its regulation.

Animals↗

PubMed1999

Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines.

The E6 proteins derived from tumour associated papillomavirus types target the cellular tumour suppressor protein p53 for ubiquitin mediated degradation. In cell lines derived from cervical tumours the p53 protein is present in very low amounts, but it can be activated by appropriate DNA damaging agents, indicating that functional p53 is present within these lines. Recent studies have also shown that different polymorphic forms of the p53 protein are differentially susceptible to E6 mediated degradation. Therefore we have been interested in analysing the effects of different HPV E6 proteins upon p53 levels in a variety of cervical tumour derived cell lines. We show that inhibition of E6 mediated degradation of p53 frequently results in increased levels of p53 expression. However, there are notable exceptions to this where increased p53 levels are only obtained following DNA damage and proteasome inhibition. We also show in E6 expressing cells, that as well as p53 being targeted for degradation, the localization of p53 to the nucleus is also inhibited, consistent with previous observations which indicate that degradation of p53 is not essential for E6 mediated inhibition of p53 function. These results have important implications for any potential therapies which might aim to block E6 mediated degradation of p53.

Acetylcysteine↗

PubMed1999

The interaction between p53 and papillomaviruses.

The p53 tumour suppressor is one of the host's principal defences against viral replication and subsequent cell transformation. The human papillomaviruses have evolved an elaborate strategy whereby the viral E6 proteins directly target p53 for ubiquitin mediated degradation and thus overcome the inhibitory effects of p53. However, a more detailed picture of the HPV*b1p53 interaction is now emerging in which there is a complex interplay between both positive and negative effectors of these interactions. This demonstrates the existence of a finely balanced virus*b1host relationship which, on rare occasion, fails and initiates the processes that ultimately lead to malignancy.

DNA Replication↗

PubMed1999

[Urgency-frequency syndrome in women: interstitial cystitis and correlated syndromes].

In our clinical practice we encountered urgency-frequency syndrome in female patients. Only in the 3.6% is possible to diagnose a typical interstitial cystitis (IC). In the 63.6% we observed only local trigonal squamous metaplasia (leucoplasia), it could be considered a paraphysiological condition present in 50-70% of fertile women, its rigid, not impermeable epithelium may offer an aethiological hypotesis for the dysuric syndrome. In the treatment of this lesion by endoscopic infiltration we had syntomatological results with 47.8% of patients even if only for a short period (one-two years). This treatment is simple and can be repeated, if the patient is responsive. We noticed that the results did not change even if we used different drugs probably due to the role of a physical detachment of leucoplasia from bladder trigon.

Adolescent↗

PubMed1998

Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.

The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

Alleles↗

PubMed1998

NF-kappaB mediated transcriptional activation is enhanced by the architectural factor HMGI-C.

High mobility group I proteins (HMGI, HMGY and HMGI-C) are a family of low molecular mass non-histone nuclear proteins which constitute an important component of the active chromatin structure. Two members of this family, HMGI and HMGY, have been demonstrated to contribute to the transcriptional regulation of several promoters by interacting with the DNA and with different transcription factors. On the contrary, very little is known about the third member, HMGI-C, which plays an important role during embryonic growth and in the process of cell transformation, its gene being rearranged in a large number of mesenchimal tumors. In this paper we show for the first time that HMGI-C is also able to function as architectural factor, enhancing the activity of a transcription factor, NF-kappaB, through the PRDII element of the beta-interferon enhancer. Moreover we show that this enhancement is absolutely dependent on the binding of HMGI-C to its target sequence. The demonstration that HMGI-C is able to modulate transcription is thus an important initial step in the identification of genes regulated by this factor.

3T3 Cells↗

PubMed1998

Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix.

The expression of nuclear proteins high mobility group (HMG) I and HMGY was investigated in intraepithelial and invasive lesions of the uterine cervix. Human carcinoma cell lines C-41, ME-180, and CaSki were used for testing protein expression in neoplastic cells from the cervix. Morphological grading of the dysplasias (CIN 1, CIN 2, and CIN 3) and invasive carcinomas from formalin-fixed paraffin-embedded samples parallels the degree of nuclear immunostaining obtained using a polyclonal antibody raised against the amino-terminal region of HMGI(Y) proteins. The immunostaining obtained with HMGI(Y) antibody was compared with that observed using the antibody Ki-67, and the results were similar. We suggest the use of HMGI(Y) antibody in clinical oncology as a useful marker of intraepithelial lesions and invasive carcinomas.

Antibodies, Monoclonal↗

PubMed1998

[Surgery in day hospital: scrotal surgery].

Actually scrotal ambulatory surgery represents a necessity for the surgeon because of the more and more greatest request to admittance and because of the impossibility to admit patients with less severe diseases. Ambulatory treatments allows psychological advantage, less discomfort, less hospital complications for the patients and a reduction of sanitary expense. Light general anaesthesia with concomitant administration of local anaesthesia is performed in our Institute. Surgical treatment must be short, with low haemorragic risk, scarcely algogenic and aseptic. Since January 1994 till December 1997, 484 patients underwent scrotal ambulatory surgery in our Institute. We reported one cardiac black and two lypothymia attacks associated with anaesthesia. Therefore combined general anaesthesia results a valid technique but unvoid of complications. Ambulatory surgery for scrotal surgery represents a sure advantage for patients and for the sanitary expense.

Adolescent↗

PubMed1998

[Male and female urinary incontinence: treatment in day surgery].

Incontinence isn't itself a disease but the feature of possible urinary tract alterations or outside of it. Incontinence is frequent above all in the elderly but it can be on charge of both sexes at every age. In Italy, according to recent evaluations, people affected with this disease would be more than 4 millions. Incontinence is therefore an important failure for its health aspects but also for economic and social ones. The problem is to evaluate if incontinence can't be prevented and as consequence needs only an assistance management, or it can be considered a preventable disease able to be cured, as we deeply believe, suggested also by the positive results of new therapeutical procedures, in association with traditional surgery and rehabilitation such as injectables or mini-invasive quick operations such as colpocleisis or percutaneous vaginal colposuspension (PVC), matters of this presentation and always performed according to correct diagnosis and indication. Bovine dermal collagen highly purified, poorly viscous and easily injectable, despite traditional rehabilitation and surgery, is a further procedure, endoscopic and minimally invasive to treat stress incontinence. Collagen is employed to perform a bladder neck plasty, increasing urethrosphincterial competence, to obtain continence without the creation of an obstruction. Genital prolapse, that is hysterocolpocele or simple vaginal vault prolapse, has course in high proportion (37%) in elderly (after 80 years). Surgical management of severe failures of continence and often also of the voiding function, such as: hyscuria with vesicoureteral reflux, obstinate constipation related to severe genital prolapse with allied rectocele is often hardly performed in elderly owing to the age and general health conditions: colpoclesis is a vaginal surgical approach that can be easily performed by the urologist too, it is an effective alternative to permanent catheterization or maxipad to be offered to the patient to improve her quality of life. In between the above maintained procedures takes place the percutaneous vaginal colposuspension (PVC). It is an original technique made up in our Institute to treat incontinence by the bladder neck resuspension to Cooper ligament according to a complete miniinvasive retropubic tension free transvaginal colposuspension, in local anaesthesia and complementary light narcosis in Day Surgery. Urinary incontinence is today a disturbance easy to be cured thanks to injectables and to miniinvasive surgical procedures as reported in this presentation concerning the most advanced approaches to its management.

Aged↗

PubMed1998

[Urethral implantation of collagen in the treatment of urinary incontinence. Comparison of transurethral and periurethral approach].

BACKGROUND: In mini-invasive surgery for the treatment of urinary incontinence injectable substances such as politef, autologous fat or bovine collagen, which can increase urethral resistance or support the sphincteric one are particularly used. It's a simple procedure in which patients may undergo local anesthesia, in short time and in "day hospital" regimen. Collagen, used as an injectable bulking agent, is the gold standard for this surgical technique because of complete biocompatibility, no evidences of adverse immunogenic effects, foreign-body reaction, migration of injected material, and because of higher fluidity which allows the use of thin needles compared to Politef (polytetrafluoroethylene) where an injection device is requested. Bovine collagen is partially reabsorbed within 24-36 months and a reinjection is often necessary. Although autologous fat is cheaper than bovine collagen, its injection shows more difficulties due to the need of higher needle diameter and time to store and prepare the material to inject. METHODS: The results obtained by two different approaches: transurethral injection of collagen and periurethral injection of collagen have been studied. A total of 48 patients underwent collagen injection for treatment of urinary incontinence: 24 treated by transurethral approach and 24 by periurethral approach. Follow-up at 6, 12, 24 months after treatment includes: objective exam, PAD test, functional evaluation, complete urodynamic evaluation (uroflow, cystomanometry, LPP, pressure/flow study, UPP). RESULTS: No clinical differences between peri/trans-urethral approach were found although collagen injection via transurethral technique need fewer material, reducing cost of treatment: an efficacy of treatment in 80% of patients and restoration of a complete urinary continence in 50% of patients was obtained. Although no clinical differences were demonstrated between the two different sites of injection, transurethral approach can be used similarly in both sexes even if without a modified resector as "injection device" it's more difficult to inject collagen in the right position, at the level of bladder neck submucosa. Perineal approach, exclusive of female sex, realizes the procedure without bleeding of urethral mucosa and no waste of collagen, though a longer period of training by surgeon is requested. After four years of experience the authors agreed that with an adequate injection device (modified resector), transurethral approach should be preferred, thus depending on the possibility to inject collagen in a correct position, just under bladder neck mucosa, which is possible to manage with this technique, in order to reduce reabsorption process of collagen and to obtain a longer efficacy of treatment reducing the number of reinjection and of course the cost of treatment. Collagen injection should be considered within an integrated therapeutical picture together with topic and systemic pharmacotherapy, physiotherapy, not excluding surgery techniques such as implantation of an artificial sphincter device in man or a sling procedure in woman. CONCLUSIONS: The urethral collagen injection for the treatment of urinary incontinence is a safe, durable and valid technique to improve urinary continence through a non obstructive effect increasing urethral resistance. Performed under local anesthesia this procedure allows the treatment of patients who may not be candidates suitable for general anesthesia and conventional surgery.

Adult↗

PubMed1998

[Correction of acquired penile curvatures].

Penile acquired curvatures are related to the effects of the evolution of Peyronie's disease or to the results of conservative treatments. All the others (post-traumatic, post surgical) are quite rare and often therapeutically similar. More than 50% of penile acquired curvatures can today take advantage from pharmacophysical managements thanks to the technological progresses of industry and of the personal experience (cavernopharmacoperfusion) both being clinically suitable application for the effective results: more than 60% of stop in progression with decrease of the recurvatum enough to resume comfortable sexual intercourse. Last, when erectile failure is present, we suggest prosthesis implant preferring flexible-malleable device such as AMS 600. More recently we started an effective experience with the new silicone elastomers of Subrini (Virilis II). Both implants never required complementary surgery of the plaque to achieve straightening and sexual activity of satisfactory level.

Calcinosis↗

PubMed1997

High mobility group I proteins interfere with the homeodomains binding to DNA.

Homeodomains (HDs) constitute the DNA binding domain of several transcription factors that control cell differentiation and development in a wide variety of organisms. Most HDs recognize sequences that contain a 5'-TAAT-3' core motif. However, the DNA binding specificity of HD-containing proteins does not solely determine their biological effects, and other molecular mechanisms should be responsible for their ultimate functional activity. Interference by other factors in the HD/DNA interaction could be one of the processes by which HD-containing proteins achieve the functional complexity required for their effects on the expression of target genes. Using gel-retardation assay, we demonstrate that two members of the high mobility group I (HMGI) family of nuclear proteins (HMGI-C and HMGY) can bind to a subset of HD target sequences and inhibit HDs from binding to the same sequences. The inhibition of the HD/DNA interaction occurs while incubating HMGI-C with DNA either before or after the addition of the HD. The reduced half-life of the HD.DNA complex in the presence of HMGI-C, and the shift observed in the CD spectra recorded upon HMGI-C binding to DNA, strongly suggest that structural modifications of the DNA are responsible for the inhibition of the HD.DNA complex formation. Moreover, by co-transfection experiments we provide evidence that this inhibition can occur also in vivo. The data reported here would suggest that HMGI proteins may be potential regulators of the function of HD-containing proteins and that they are able to interfere with the access of the HD to their target genes.

3T3 Cells↗

PubMed1996

Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue transgenic mouse mutation assay.

Three genotoxic mouse carcinogens, 4-chloro-o-phenylenediamine (4-C-o-PDA), 2-nitro-p-phenylenediamine (2-N-p-PDA), and 2,4-diaminotoluene (2,4-DAT), were tested in the Big Blue transgenic mouse mutation assay. Each experiment consisted of a vehicle control group with ten Big Blue C57BL/6 mice, five of either sex, and an equally sized group treated with a high dose of the test chemical. In addition, four animals were treated with the vehicle and six animals with the test compound for the measurement of bromodeoxyuridine (BrdU) incorporation to determine cellular proliferation. Prior to the mutagenicity experiments, the maximally tolerated dose of each compound was determined using nontransgenic C57BL/6 mice. Based on these results the doses used in the main study were 200 mg/kg/day for 4-C-o-PDA, 150 mg/kg/ day for 2-N-p-PDA, and 80 mg/kg/day for 2,4-DAT. Animals were treated for 10 days over a 2 week period and were killed 10 days after the ast treatment. In an additional experiment with 2,4-DAT, animals were killed 28 days after treatment. Since all three chemicals are liver carcinogens in the mouse, the DNA of the liver was analyzed using the standard procedures for the Big Blue assay. Hepatocyte proliferation was assessed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and, in some studies, by measuring BrdU incorporation. 4-C-o-PDA and 2-N-p-PDA did not induce an increase in PCNA expression when measured 10 days after the last treatment. There was no increase in BrdU incorporation immediately after treatment with 4-C-o-PDA or with 2,4-DAT. However, 10 days after the last treatment with 2,4-DAT, a strong mitogenic effect was found with both techniques, i.e., in the PCNA and BrdU assays. 4-C-o-PDA, a liver carcinogen in both genders of mice, induced a small, statistically significant increase of the mutant frequencies in females. No increase was found in males. 2-N-p-PDA, which has been reported to induce liver tumors only in females, was found positive in males and was clearly negative in females. 2,4-DAT, a liver carcinogen in female mice, was positive in females and negative in males when the animals were killed 10 days after the last treatment. After an expression time of 28 days, 2,4-DAT induced a statistically significant increase in both sexes. The effect in females was marginally stronger than after 10 days' expression time and almost identical to the effect observed in males under these test conditions. In conclusion, the experiments showed that the Big Blue assay detects the genotoxicity of the three carcinogenic monocyclic aromatic amines tested. However, it seems that the sex specificity of the carcinogenic effects of these compounds is not reflected by the mutagenicity data in Big Blue mice.

Animals↗

PubMed1996

[New trends in the surgical treatment of penile carcinoma].

With the current oncological emphasis on radical treatment allied to minimal invasiveness, choice of treatment relies on precise clinical staging. The corpora cavernosa of the penis represent a well defined anatomical structure distinct from the corpus spongiosum and the glans which are tightly connected to one another. In case of primary penile tumour the T.N.M. classification of the American Joint Committee on Cancer includes in the T2 stage both infiltration of the corpus spongiosum and of corpora cavernosa. Jackson's classification seems to be more pertinent as it limits to stage 1 cases involving the glans and corona and classifies as stage 2 cases limited to the corpora cavernosa. Partial penectomy can prove overly invasive, yet insufficiently radical, if the anatomical continuity of the spongious tissue is not considered. Carcinoma of the glandular corpus spongiosum without cavernosal involvement indicates glandulectomy with partial uretrectomy and apical cavernous-urethrostomy. Preserving the corpora cavernosa is an option of great relevance to the quality of life of the patient: erectile ability and stand-up micturition are not affected and the patient keeps complete sexual ability and orgasmic sensation. In case of scrotal or public involvement, emasculation with hemipelvectomy must be attempted; if indicated, it can be followed by radiotherapy. Perineo/abdominal reconstruction can be followed by urinary diversion with adjuvant chemotherapy. In selective cases neophallic reconstruction can be later attempted using the inferior abdominal rectum muscle.

Adult↗