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Biomedical subjects

M Monti

Publications and source records attributed to M Monti.

At least 37 records · Page 2Linked to original sources

A novel zinc finger transcriptional repressor, ZNF224, interacts with the negative regulatory element (AldA-NRE) and inhibits gene expression.

The interaction between the negative cis-element (AldA-NRE) and p97 repressor nuclear protein is a key step in modulating transcription of the human and mouse aldolase A (AldA) gene during the cell cycle and differentiation. In an attempt to clarify the role of transcriptional repression in regulating gene expression, we purified, from HeLa cells, the nuclear protein that specifically binds to the AldA negative regulatory element (NRE). Matrix-assisted laser desorption ionization-time of flight analysis and examination of protein profiles from the SwissProt database revealed that the previously defined p97 repressor is ZNF224, a zinc finger protein. We demonstrate that ZNF224, a Kruppel-like zinc finger transcription factor, is the repressor protein that specifically binds to the negative cis-element AldA-NRE and affects the AldA-NRE-mediated transcription.

Amino Acid Sequence↗

Sexual functions after high-dose chemotherapy in survivors of germ cell tumors.

We investigated the changes in sexual function in male patients with germ cell tumor continuously disease free after one or two courses of high-dose chemotherapy with hematopoietic stem cell support. A questionnaire was mailed to 35 patients, and 30 patients sent it back. Sexuality was considered a problem by 10 patients (33%), but no patients considered sexuality a major problem. Erection was more difficult to achieve in seven patients (23%) and 10 patients (33%) experienced increased difficulty in maintaining an erection. Eight patients (27%) had the experience of less intensive and less frequent orgasm. In all, 13 patients (43%) thought that both the disease and treatment had worsened their sexual capacity, but 20 patients (67%) were satisfied with their sex life. Most of the patients (63%) considered that insufficient information and counselling had been given by their physicians about the sexual sequelae of therapy. However, the amount of information about the disease and treatment was considered good by 77 and 80% of the patients, respectively. This study shows that 27% of patients were not content with their ability to attain sexual satisfaction due to the illness or its treatment. Communication is an important issue and better information tools could lead to improved compliance in these patients.

Adolescent↗

Cytotoxic gamma/delta subcutaneous panniculitis-like T-cell lymphoma: report of a case with pulmonary involvement unresponsive to therapy.

Peripheral subcutaneous panniculitis-like T-cell lymphoma (PSPTCL) is a rare form of cutaneous lymphoma recently proposed as a distinct clinicopathological entity. It usually presents with multiple indurated subcutaneous plaques or tumours, most commonly located on the extremities and trunk and clinically mimicking lobular panniculitis. Associated constitutional symptoms due to haemophagocytic syndrome may advance or, more often, complicate the clinical course in about 40-70% of cases. Finding of TIA-1+ and perforin + cytolytic granules in atypical pleomorphic lymphocytes suggests PSPTCL origin from granular cells of T-cell or natural killer cell phenotype. Cells have a CD3+ CD4+ CD8- or CD3+ CD4- CD8+ T-cell phenotype. Moreover, these lymphomas can express natural killer cell associated antigens, such as CD56, especially in gamma/delta variants. PSPTCL following an indolent clinical course with recurrent self-healing lesions have been described. The prognosis of most PSPTCL is poor even when treated with aggressive chemotherapy. This paper reports a case of PCTCL in a young woman with T-cytotoxic differentiation, with rapid progression unresponsive to several treatments.

Adult↗

Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.

Administration, Oral↗

Doxorubicin, paclitaxel and gemcitabine: a Phase I study of a new sequential treatment in stage III B - IV breast cancer.

Based on the synergistic interactions of the sequence doxorubicin-paclitaxel-gemcitabine obtained in our preclinical study, a Phase I trial was conducted to evaluate the feasibility of this new sequence in breast cancer. Patients with stage IIIB-IV breast cancer received doxorubicin on day 1, paclitaxel on day 2 and gemcitabine on day 6 and 13 (steps IIa, III and V) in cohorts of 3 patients. From March 1999 to December 2000, 9 patients were treated. The most important toxicity was hematological. The maximum tolerated dose was reached at the second level because dose-limiting toxicity occurred in 3 patients. Non hematological toxicities were alopecia, diarrhea, asthenia, nausea, mucositis, paresthesia and myalgia. A Phase II trial is ongoing to further investigate the activity of this new sequential treatment with doxorubicin (50 mg/m2 day 1), paclitaxel (160 mg/m2 day 2) and gemcitabine (800 mg/m2 day 6) in advanced breast cancer.

Adult↗

Introducing colposcopy and vulvovaginoscopy as routine examinations for victims of sexual assault.

Victims of sexual assault require appropriate care, follow-up and information regarding their legal rights. Clinicians are faced with the challenging responsibility of identifying victims and providing effective interventive and preventive counselling. The most pressing medical task is to confirm the assault and to undertake correct documentation and exhibition of biological traces. Performing colposcopy and vulvovaginoscopy does not allow us to diagnose a sexual assault trauma, but it can help us to identify those microscopic lesions (due to the enhanced visualization and the higher resolution under which the genital areas are examined) that may not be seen during a normal clinical examination. The colposcopic and vulvovaginoscopic examination starts from the vulvar region looking for superficial lacerations and ecchymosis; the labia majora and minor are examined scrupulously, then the posterior forchette, the perineum and the hymen where it is possible to report microulcerations, contusions and even possible scars due to a precedent defloration. Recent advances in clinical forensic medicine show that trained examiners using colposcopy obtain evidence of genital trauma in 87% to 92% of rape victims. Colposcopy and vulvovaginoscopy must be performed within 48 hours from the sexual assault, because most of the lesions heal rapidly. Colposcopy and vulvovaginoscopy may be seen as a stressful invasion of a woman who is already vulnerable and at risk of the rape trauma syndrome. Prior information about colposcopy may reduce the level of anxiety experienced by many women undergoing this procedure. Incorporating colposcopy and vulvovaginoscopy into the routine assessment of sexual assault victims could be a valid way of identifying genital injuries; moreover the medical report will be more detailed and precise.

Colposcopy↗

Vascular endothelial growth factor, interleukin-6 and interleukin-2 in serum and follicular fluid of patients with ovarian hyperstimulation syndrome.

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.

Adult↗

[Parietal implantation after thoracoscopic surgery: a case report].

The Authors report the case of a patient who underwent video-thoracoscopic resection of a solitary pulmonary metastasis. She presented, after about two years, a local relapse (implantation) in the trocar site. Pathogenesis and surgical therapeutic problems are discussed as well.

Carcinoma, Renal Cell↗

[Rare pathology of the breast: adenoma of the nipple].

Adenoma of the nipple is a benign pathology which histologically interests the epithelium of the galactophorous ducts. This pathology looks like Paget's disease both macroscopically and microscopically, therefore an exact differential histologic diagnosis is needed with the breast's carcinoma to undertake the most timely surgical therapy.

Adenoma↗

Pro-sequence assisted folding and disulfide bond formation of human nerve growth factor.

Nerve growth factor (NGF) is a member of the neurotrophin family. These growth factors support neuronal survival and differentiation. Neurotrophins are synthesized as pre-pro-proteins. Whereas the pre-sequences mediate secretion, the function of the pro-peptides is largely unknown. To test the role of the pro-sequence as a folding enhancer, recombinant human pro-NGF (rh-pro-NGF) was produced in Escherichia coli. The oxidative refolding of rh-pro-NGF and rh-NGF was studied using electrospray mass spectrometry (ESIMS) time-course analysis. This analysis permitted both the identification and quantification of intermediates present during the process. The disulfide bonds formed at different times of the refolding processes were characterized by proteolytic digestion followed by matrix assisted laser desorption ionization mass spectrometry (MALDIMS) analysis. Folding yields and kinetics of rh-pro-NGF were significantly enhanced when compared to the in vitro refolding of mature rh-NGF. These results suggest that the pro-sequence of NGF promotes folding of the mature part.

Alkylation↗

Assessing delirium in cancer patients: the Italian versions of the Delirium Rating Scale and the Memorial Delirium Assessment Scale.

To validate the Italian versions of the Delirium Rating Scale (DRS) and the Memorial Delirium Assessment Scale (MDAS), 105 cancer patients consecutively referred for neurological or psychiatric consultation for mental status change were evaluated using the Confusion Assessment Method (CAM), the DRS, the MDAS, and the Mini-Mental State Examination (MMSE). According to the CAM criteria and clinical examination, 66 patients were delirious, and 39 received diagnoses other than delirium. The DRS and the MDAS scores significantly distinguished delirious from non-delirious patients. The MDAS and the DRS were mutually correlated. When using the proposed cut-off scores for the two scales, the MDAS had higher specificity (94%) but lower sensitivity (68%) than the DRS (sensitivity = 95%, specificity = 61% for DRS cut-off 10; sensitivity = 80%, specificity = 76%, DRS cut-off 12). The MMSE showed high sensitivity (96%) and very low specificity (38%). Exploratory factor analysis of the DRS and the MDAS suggested a three-factor and two-factor structure, respectively. Both instruments in their Italian version proved to be useful for the assessment of delirium among cancer patients. Further research is needed to examine the use of the DRS and the MDAS in other clinical contexts.

Aged↗

A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges.

Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-597.

Adenine↗

Purification, characterization, and functional role of a novel extracellular protease from Pleurotus ostreatus.

A new extracellular protease (PoSl; Pleurotus ostreatus subtilisin-like protease) from P. ostreatus culture broth has been purified and characterized. PoSl is a monomeric glycoprotein with a molecular mass of 75 kDa, a pI of 4.5, and an optimum pH in the alkaline range. The inhibitory profile indicates that PoSl is a serine protease. The N-terminal and three tryptic peptide sequences of PoSl have been determined. The homology of one internal peptide with conserved sequence around the Asp residue of the catalytic triad in the subtilase family suggests that PoSl is a subtilisin-like protease. This hypothesis is further supported by the finding that PoSl hydrolysis sites of the insulin B chain match those of subtilisin. PoSl activity is positively affected by calcium. A 10-fold decrease in the K(m) value in the presence of calcium ions can reflect an induced structural change in the substrate recognition site region. Furthermore, Ca(2+) binding slows PoSl autolysis, triggering the protein to form a more compact structure. These effects have already been observed for subtilisin and other serine proteases. Moreover, PoSl protease seems to play a key role in the regulation of P. ostreatus laccase activity by degrading and/or activating different isoenzymes.

Amino Acid Sequence↗