Evaluating the Long-Term Outcomes of Periodontal Surgery vs. Non-Surgical Treatment in Aggressive Periodontitis.

Background: Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate. Materials and Methods: A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures. Results: A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group (P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years (P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications. Conclusion: This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment.

PROMs in post-mastectomy care: Patient self-reports (BREAST-Q™) as a powerful instrument to personalize medical services.

One of the goals of immediate breast reconstruction (IBR) is to satisfy the patient's outcome. Recent studies therefore tended to focus on the patient's perception of the care and on the impact on quality of life using patients-reported-outcome-measures (PROMs), able to measure the health status directly without the clinician's interposition. We present a preliminary prospective study on 333 patients who underwent mastectomy with IBR in a two-year period, in a single Italian centre, using a dedicated PROMs, the BREAST-Q™, to determine the patient's satisfaction. We studied two groups of IBR: Group A (two-step with tissue-expander) and Group B (one-step: prosthesis/mesh) and conducted a pre- and post-operative comparison for each group to evaluate score-gain over time, and a group-score comparison to determine whether differences were significant between reconstruction types. Two-hundred-and-nine were actually enrolled and 132 completed all the questionnaires. The response rate was 62.8% and the compliance rate (completion of all the questionnaires) was 63.1%. In both groups all the analyzed domains worsened comparing the pre and post-operative period; the differences were statistically significant only for physical and sexual-wellbeing. In the comparison between the two groups, none of the detected differences reached the statistical significance. According to our experience, we can state that PROMs could improve the health concept redefining the variables to be monitored even if data is still insufficient to draw any definitive conclusion. PROMs can help surgeons and patients decide the most appropriate surgery for a particular patient-profile and to identify those who require further support.

Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential.

Epithelial-mesenchymal transition (EMT) is a critical process for embryogenesis but is abnormally activated during cancer metastasis and recurrence. This process enables epithelial cancer cells to acquire mobility and traits associated with stemness. It is unknown whether epithelial stem cells or epithelial cancer stem cells are able to undergo EMT, and what molecular mechanism regulates this process in these specific cell types. We found that epithelial-ovarian cancer stem cells (EOC stem cells) are the source of metastatic progenitor cells through a differentiation process involving EMT and mesenchymal-epithelial transition (MET). We demonstrate both in vivo and in vitro the differentiation of EOC stem cells into mesenchymal spheroid-forming cells (MSFCs) and their capacity to initiate an active carcinomatosis. Furthermore, we demonstrate that human EOC stem cells injected intraperitoneally in mice are able to form ovarian tumors, suggesting that the EOC stem cells have the ability to 'home' to the ovaries and establish tumors. Most interestingly, we found that TWIST-1 is constitutively degraded in EOC stem cells, and that the acquisition of TWIST-1 requires additional signals that will trigger the differentiation process. These findings are relevant for understanding the differentiation and metastasis process in EOC stem cells.

Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells.

Chronic hepatitis C virus (HCV) infection frequently develops into liver disease and is accompanied by extra-hepatic autoimmune manifestations. The tetraspanin CD81 is a putative HCV receptor as it binds the E2 envelope glycoprotein of HCV and bona fide HCV particles. Here we show that HCV E2 binding to CD81 on human cells in vitro lowers the threshold for IL-2 receptor alpha expression and IL-2 production, resulting in strongly increased T cell proliferation. HCV E2-induced co-stimulation also enhances the production of IFN-gamma and IL-4 and causes increased TCR down-regulation. This suggests that binding of HCV particles to CD81 on T cells in vivo may lead to activation by otherwise suboptimal stimuli. Therefore, co-stimulation of autoreactive T cells by HCV may contribute to liver damage and autoimmune phenomena observed in HCV infection.

Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes.

Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.

Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C.

The healthy liver of adult humans has little or no lymphocyte component and the histological finding of intrahepatic lymphocytes (IHL) is evidence of liver pathology. In a liver injured by chronic hepatitis C, the most common chronic liver disease, most IHL are activated/pro-inflammatory cells, which are particularly enriched for effectors of innate immunity (natural killer (NK), natural T, and other NK-like T cells). IHL do not undergo clonal expansion in the liver but migrate from extrahepatic sites to the chronically infected liver, where they display effector function and subsequently die, suggesting that maintenance of the IHL pool depends on continuous lymphocyte migration. The cytotoxic and inflammatory functions of these IHL have three potential outcomes: 1) they could be helpful in clearing the virus (a rare case in hepatitis C virus (HCV) infection); 2) they could be useless and have no effect on the infection; or 3) they could be harmful, whereby overaggressive lymphocyte responses destroy the liver in a continuous and unsuccessful attempt to clear the virus. Unfortunately, we do not know as of yet which of these possibilities is the case and, therefore, a more complete picture of the intrahepatic immune response will be relevant to the development of new therapeutic strategies against HCV. Additionally and from a more general perspective, due to the availability of biopsied material and the high prevalence (approximately 3%) of HCV infection worldwide, studying the chronically inflamed liver of hepatitis C patients is an ideal model to investigate the poorly understood processes of lymphocyte trafficking, activation and death to non-lymphoid sites of chronic inflammation in man.

Activation of the human P-glycoprotein ATPase by trypsin.

The human MDR1 gene product, P-glycoprotein (Pgp), a tandemly duplicated molecule containing two putative ATP- and perhaps two drug-binding sites, is responsible for multidrug resistance in tumors. In this report, we characterized the effects of trypsinization of Pgp on its ATPase function. Incubation of Pgp-containing membranes with trypsin at a ratio of 1000:1 (w/w) resulted in a gradual increase in the basal- and the drug-stimulated ATPase activities of Pgp in a time-dependent manner. The maximal basal-, verapamil-, and vinblastine-stimulated ATPase activities of the trypsinized Pgp were approximately 1.8-, 1.5-, and 1.75-fold higher than the activities of the native Pgp, respectively. Increased basal- and drug-stimulated ATPase activities of the Pgp were also observed when the ratio of membrane protein to trypsin in the incubation mixtures was raised to 10:1 (w/w). Immunoblotting analysis of Pgp tryptic digests using Pgp-specific NH(2)11, C219, and C494 antibodies together revealed the degradation of full-length Pgp and formation of at least eight peptides migrating in the 36-60 kDa range. Immunoprecipitation reactions using NH(2)11 and C494 antibodies have suggested that the peptides originating from the NH(2) half of Pgp are in strong association with the COOH half of the peptide. These findings suggest that while Pgp fragments together exhibit the ATPase functional characteristics, Pgp possesses a cleavage activation site or region, and its cleavage leads to the activation of basal ATPase function of Pgp.

[T-cell interferon-gamma, tumor necrosis factor-alpha and interleukin-6 receptor binding in patients with multiple sclerosis. Effects of interferon-beta-1b treatment]. / Las uniones a los receptores para el interferón-gamma, el factor de necrosis tumoral-alpha y la interleucina-6 en linfocitos T de pacientes con esclerosis múltiple. Resultado del tratamiento con interferón-beta 1b.

INTRODUCTION: Multiple sclerosis (MS) is a T-cell-mediated demyelinating disease of the central nervous system (CNS), in which the cytokine network may be deranged. Interferon (IFN)-gamma, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are cytokines with several effects on the neuroimmune system. Specific IFN-gamma, IL-6, and TNF-alpha receptors have been found on human lymphocytes and other cell types. PATIENTS AND METHODS: We assayed IFN-gamma, TNF-alpha, and IL-6 binding on peripheral blood T cells from MS patients, as compared with healthy subjects. T cells from MS patients have significantly less IFN-gamma receptors, and more TNF-alpha and IL-6 receptors than those from controls. Such receptors are of the same type in patients and healthy subjects. By comparing MS patients' subgroups with each other, significant differences in mean Bmax values have been found between patients in a stable phase and those in relapse, and between stable patients and those in an evolutive phase. As far as IL-6 binding is concerned, significant differences in mean Bmax values were observed only between patients in stable phase and those in relapse. RESULTS: T lymphocytes from untreated MS patients, which had significantly smaller amounts of IFN-gamma receptors than those from controls, and more TNF-alpha and IL-6 receptors than controls showed a significant increase in IFN-gamma binding, and a significant decrease in TNF-alpha and IL-6 binding after a 3-month IFN-beta 1b treatment. T-cell IFN-gamma Bmax values were even higher, and those of TNF-alpha and IL-6 were lower after 6 months. CONCLUSION: We discuss these results in terms of MS immunopathophysiology, since activated T cells have decreased IFN-gamma, and increased TNF-alpha and IL-6 receptor amounts.

CD4+/CD45RA+ 'naive' T cells and immunological response to influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a high frequency of infections, including those of viral aetiology. Previous reports have demonstrated a specific immunologic response to influenza virus vaccine in B-CLL patients with normal IgG levels. In this study, we have evaluated different immunophenotypically defined B and T cell subsets in 18 B-CLL patients before immunization with killed-influenza-virus vaccine. A correlation between immunological response to vaccination and both absolute numbers of CD4+/CD45RA+ naive T cells and CD5- B cells was found. These data may suggest a supporting role of the CD4+/CD45RA+ T cell subset in the specific antibody response to vaccination with influenza virus vaccine in B-CLL patients.

p56lck plays a key role in transducing apoptotic signals in T cells.

The CD4 receptor synergizes with the T-cell antigen receptor (TCR) in helper T-cell activation. However CD4 cross-linking in the absence of simultaneous TCR engagement leaves the cells primed to activation dependent apoptosis. To assess the role of the CD4 associated protein tyrosine kinase p56lck in CD4 priming to apoptosis we have constructed Jurkat T-cell lines stably transfected with a constitutively active form of p56lck. These cells were constitutively primed to undergo apoptosis upon TCR crosslinking with specific antibodies. In addition the Jurkat JCaM1 line, which is defective for p56lck expression, was resistant to TCR induced apoptosis. These data indicate that p56lck is required for T-cell apoptosis and that CD4 priming of T-cells for antigen dependent apoptosis is due to inappropriate or partial activation of the p56lck signal transduction pathway.

Adhesion of Bordetella pertussis to eukaryotic cells requires a time-dependent export and maturation of filamentous hemagglutinin.

Bordetella pertussis, the human pathogen of whooping cough, when grown at 22 degrees C is nonvirulent and unable to bind eukaryotic cells. In response to a temperature shift to 37 degrees C, the bacterium acquires the ability to bind eukaryotic cells in a time-dependent fashion. By studying in vitro the temperature-induced transition, from the nonvirulent to the virulent state, we found that binding to CHO cells is mediated by the Arg-Gly-Asp-containing domain of filamentous hemagglutinin (FHA), a protein with multiple binding specificities. This protein is synthesized as a 367-kDa polypeptide within 10 min after temperature shift, but requires 2 hr before it is detected on the bacterial cell surface and starts to bind CHO cells. Mutations affecting the cell surface export of FHA abolish bacterial adhesion to CHO cells, while mutations in the outer membrane protein pertactin strongly reduce binding. This suggests that multiple chaperon proteins are required for a correct function of FHA. Finally, several hours after maximum binding efficiency is achieved, the N-terminal 220-kDa portion of FHA that contains the binding regions is cleaved off, possibly to release the bacteria from the bound cells and facilitate spreading. The different forms of FHA may play different roles during bacterial infection.

Multianalytic study on cervical HPV lesions.

Nowadays new sophisticated techniques of molecular biology based on the principles of hybridization between nucleic acids, allow a correct diagnosis of genital HPV infection. In the present paper, beside traditional diagnostic methods, we used In Situ Hybridization (ISH) and Polymerase Chain Reaction (PCR) to detect the presence of HPV types 6, 11, 16, 18, 31 and 33. We tested ten patients affected by cervical lesions of high histological atypias associated with HPV, who underwent surgical conization. Types 6 and 11, at low risk of evolution, are less frequent than 31 and 33, at medium grade of evolution, and than 16 and 18 which are at high risk of evolution.

Differential effect of adenosine on DNA synthesis in lymphoid and myeloid cell lines.

In this report, the effects of adenosine on the promyelocytic cell line HL-60 and on T-lymphocytic clones are compared. According to previous reports, adenosine induces a dose-dependent inhibition of DNA synthesis in T-lymphocytes. Conversely, adenosine dose-dependently enhances DNA synthesis in HL-60 cells, as documented with [3H]thymidine uptake studies and flow cytometric cell-cycle analysis. Unlike its effect on lymphocytes, the adenosine effect on HL-60 cells does not seem to be mediated by receptor binding, but it appears to be correlated with an intracellular mechanism following active uptake. Despite the different effects exerted by adenosine on lymphocytes and myeloid cells, a purinergic pathway appears to be more generally involved in the regulation of some phases of cell growth.

Flow cytometric analysis of DNA ploidy pattern from deparaffinized formalin-fixed gastric cancer tissue.

Histologically processed tissue from gastric cancers has been analyzed by flow cytometry in an attempt to correlate DNA ploidy pattern and behavior of the tumor. Of the mucosal and submucosal cancers (so-called early, all stage I in the present series), 62.7% show a diploid DNA pattern and 37.3% show a single aneuploid pattern. Of the deeply infiltrating (beyond the submucosa) cancers (stage II and III), 52.1% are single aneuploid and 47.9% are multiploid. While stage-I patients are all alive at the end of the follow-up period (6 years), in stage II and III cases Cox's regression model shows that the hazard function depends on DNA pattern: survival is negatively influenced by multiploidy. On this basis, it may be assumed that the DNA pattern is a useful prognostic indicator of gastric cancer. As expected, in Cox's regression model an even more important negative correlation exists between survival and stage: single aneuploid cases in stage II have a better prognosis than those in stage III. Instead, no correlation is found between histological cancer subtype (Laurén and WHO classifications), grade and DNA pattern.

Flow-cytometric assessment of DNA index and percent S phase cells in bronchogenic epidermoid carcinoma.

The DNA index and percent S phase cells were assessed in 45 bronchogenic epidermoid carcinomas from paraffin-embedded retrieved material by flow cytometry. Previously, a comparison between flow cytometric findings from fresh and from paraffin-embedded material was made. The DNA index and the percent S phase cells from fresh and paraffin-embedded material were strongly correlated. Only 3 of the 45 cases were diploid. The DNA index was significantly lower in grade 1 than in grade 2-3 tumors. No correlations were found between DNA index and presence of lymph node metastases, but the percent S phase cells was significantly higher in lymph-node-positive tumors.