[INFECTIONS CAUSED BY EPSTEIN-BARR VIRUS IN HIV-INFECTED PATIENTS].

The review is dedicated to features of clinical manifestations of infections caused by Epstein- Barr virus (EBV) in HIV-infected patients, problems of diagnostics and execution of antiviral therapy in the case of combination of these infections. Individuals at AIDS stage develop tumors, associated with EBV: non-Hodgkin's lymphomas, including Berkitt's,lymphoma, primary B-cell lymphoma,of CNS, nasopharyngeal carcinoma. Formation of lymphoid interstitial pneumonitis and leukoplakia is known to be associated with EBV. A large list of preparations that are inhibitors of EBV replication are currently known, however, there is no clear pathogenetically justified therapy scheme for patients with this infection against the background of HIV-infection.

The Variation of Peripheral Inflammatory Markers in Vocal Leukoplakia before and after Recurrence and Canceration.

BACKGROUND: This retrospective study aims at comparing the variation of peripheral inflammatory markers in recurrent and cancerous vocal fold leukoplakia (VFL) and at exploring the potential connection with pathological outcomes. METHODS: The patients undergoing carbon dioxide laser surgery with postoperative pathological diagnosis of recurrent vocal fold leukoplakia in the last 5 years were included. The clinical data were collected, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocytes-to-lymphocyte ratio (MLR) before and after recurrence and canceration were calculated. Related comparison with two-grade pathological classification was made to evaluate their potential connection with postsurgical histopathology and clinical events. RESULTS: The data of 193 patients were engaged into research, as 111 in the recurrence group (Group A) and 82 in canceration group (Group B). The NLR, PLR, and MLR were significantly increased in canceration event compared to the first (P = 0.009, 0.004, 0.007, respectively) and penultimate (P = 0.013, 0.041, 0.006, respectively) time when the previous pathologies were leukoplakia. When redividing the Group A according to the two-grade pathological classification, the high-risk groups showed statistically higher NLR and PLR values than low-risk groups in the subgroups with grade changing (P = 0.016, 0.005, 0.007, 0.005, respectively) and subgroups without grade changing (P = 0.020, 0.027, 0.030, 0.029, respectively). CONCLUSIONS: NLR, PLR, and MLR are reliable biomarkers in the circulation system which show significantly interrelation with the pathological progression of vocal fold leukoplakia. Presurgical evaluation of NLR, PLR, and MLR may have potential values to indicate the following treatment in clinical practice.

Premalignant and malignant oral lesions are associated with changes in the glycosylation pattern of carbohydrates related to ABH blood group antigens.

The distribution of carbohydrate structures related to the ABO(H) blood group antigen system was studied in biopsies from eight squamous cell carcinomas, and eight erythroplakias with epithelial dysplasia. Twenty oral lesions without histological evidence of malignancy (13 lichen planus lesions and 7 homogeneous leukoplakias) were also examined. The distribution of Lex, Ley, H type 2 chain, and N-acetyllactosamine, all type 2 chain carbohydrate structures, was investigated by immunohistological staining using monoclonal antibodies with selected specificity. The histological pattern of expression of these antigens in the benign lesions was similar to that of normal oral mucosa, i.e. expression of: N-acetyllactosamine on basal cells, H antigen on parabasal cells, and Lex and Ley on spinous cells. However, lesions with epithelial dysplasia showed H antigen on all spinous cells, and often also on basal cells, with expression of Lex and Ley restricted to the most superficial part of the epithelium above the H-positive cell layers. In carcinomas most cells were negative for H antigen but were positive for Ley and Lex in 5 out of 8 cases.

Influence of beta-carotene on immune functions.

Recent reports have demonstrated that beta-carotene, a nontoxic carotenoid, is able to stimulate immune functions in humans. The purpose of this study is to understand the mechanisms of immunoenhancement by carotenoids in order to explain their anticancer effects. We have evaluated the clinical efficacy of beta-carotene, given 30 mg/day orally, for treatment of oral leukoplakia patients. Patients who responded to beta-carotene treatment showed increased plasma levels of TNF-alpha. Epithelial cells from these patients were characterized in vitro. These results may lead to a better understanding of the therapeutic use of beta-carotene in humans.

[Bcl-2, p53, Ki-67 and apoptotic index in cancerous and precancerous lesions of the oral mucosa]. / Bcl-2, p53, Ki-67 ed indice aptoptico nelle lesioni preneoplastiche e neoplastiche della mucosa orale.

BACKGROUND: In this study an immunohistochemical analysis of both normal and pathological tissues was made to investigate the expression of some factors involved in genic regulation mechanisms of apoptosis. METHODS: In normal mucosa, in leukoplakia, in mild and severe dysplasia and in high, mild and low grade cancer a bcl-2, p53, and Ki 67 evaluation was made using immunostaining techniques; also an evaluation of apoptotic index was carried out. Seventy-two biopsies were made in 12 patients with normal mucosa, 12 affected by leukoplakia, 12 by dysplasia (6 mild, 6 severe), 12 by low grade, 12 by mild grade and 12 by high grade cancer. > t RESULTS: The immunohistochemical analysis pointed out that there was weak bcl-2 expression in normal mucosa and in preneoplastic lesions and less more in severe dysplasia while bcl-2 was discreetly detectable in oral tumors. P53 was not detectable in normal mucosa and weakly expressed in preneoplastic lesions, presenting a peak in severe dysplasia. These results showed an interesting inverse relation between bcl-2 and p53 expression in severe dysplasia. Ki 67 expression results to be weak in normal mucosa, in preneoplastic lesions and in mild dysplasia, while it reaches the maximum level in severe dysplasia and in tumors. CONCLUSIONS: In all the samples the apoptotic index expression showed the same features of the Ki 67 protein. These results were achieved through statistically analysis carried out with the U Mann Whitney test.

[Free stromal cells in dysplasias and cancer of the cervix uteri]. / Svobodnye kletki stromy pri displaziiakh i rake sheiki matki.

The content and distribution of lymphocytes and plasma cells in stroma was studied in 452 cases of different diseases of the cervix. As dysplastic changes of the epithelium advanced up to the microinvasive form of cancer, the number of lymphocytes was found to increase progressively and blast forms appeared. In intraepithelial cancer, infiltration of the stroma with lymphocytes and plasma cells was poor, whereas in deep invasive cancer no lymphocytic and plasma cell infiltration was observed. The changes in the content and distribution of the immunocompetent cells of the stroma in different structural and functional alterations of the epithelium indicates the active part of the mechanisms of local immunological defence in combined changes of the epithelium and connective tissue.

[Immunohistochemical examinations of dyskeratosis and exocervical neoplasia in gynecological pathology]. / Immunogistokhimicheskie issledovaniia diskeratoza i neoplasticheskikh izmenenii ékzotserviksa pri ginekologicheskoi patologii.

An immunohistochemical study was carried out with monoclonal antibodies to estrogen receptors (Ers), Ki-67, BCL-2, P53 and human papillomaviruses (HPV) of normal cervix (7 cases), cervical leukoplakia (5 cases), CIN I (7 cases) and CIN II-III (6 cases). Correlations were also investigated between hyperestrogenemia and molecular changes in the exocervix. About two thirds of patients with leukoplakia and precancerous changes had clinical signs of hyperestrogenemia which led to proliferation of estrogen-sensitive parabasal cells. Due to neoplastic epithelial transformation the number of cells with Ki-67, P53 and HPV positive reactions in the nuclei increased, while Ers and BCL-2 expression decreased. Because active proliferative parabasal cells are needed for HPV replication we consider hyperestrogenemia as a factor stimulating development of neoplastic changes in the uterine cervix.

[Immune serum globulin E in patients with leukoplakia (author's transl)]. / Serum-Immunoglobulin-E bei Leukoplakiepatienten.

Significant changes of humoral factors can occur during the development and growth of malignant tumors. Such can be observed by the periodic recording of immune serum globulin E levels if sensitive RIA methods are employed. Observations of normal persons show largely stable immune serum globulin E levels, and are comparable in patients with leukoplakia of the larynx as well as in patients whose malignant conditions were removed by oepration or radiotherapy. In three patients, a statistically significant increase in serum immune globulin E was recorded immediately before malignant degeneration of known leukoplakia occurred, and was also found in 22 control tumor patients who had experienced local relapses of disease.

Cell mediated and humoral immune responses in oral submucous fibrosis.

Cell-mediated and humoral immune responses were assessed in 50 patients with oral submucous fibrosis (OSMF) and the results were compared with those of 50 patients with oral-leukoplakia, 50 oral cancer patients, and 50 normal healthy adult controls. The number of high-affinity rosette-forming cells (HARFC) was found to be significantly decreased in OSMF and oral cancer, whereas the number of total rosette-forming cells (TRFC) remained unaltered. Levels of serum IgA, IgD, and IgE were found to be elevated both in OSMF and oral cancer. Immunologic derangements were found to be more pronounced in oral cancer than in OSMF. The enumeration of HARFC along with the estimation of serum levels of IgA, IgD, and IgE indicates that OSMF can be an intermediary stage in the malignant transformation of a normal cell, and that these parameters may serve as markers for the early detection of oral cancer.

Leukoplakia of oral mucosa: pathogenesis and possible correction with phytoadaptogen.

Leukoplakia of the oral mucosa is characterized by impairment of the epithelial differentiation program. The use of complex phytoadaptogen in the treatment of patients with leukoplakia normalized expression of Fas-APO-1 antigen and keratin 17; increased expression of CD54 attested to activation of immune effectors. The clinical effect manifested in involution or shrinkage and loosening of the pathological focus and complete epithelialization of erosive surfaces. The phytopreparation exhibited adaptogenic effects normalizing the immune and IFN status and improving the state of adaptation systems in the body.

[T lymphocytes, non-malignant and premalignant changes in the planocellular epithelium of the uterine cervix]. / T limfociti, nemaligne i premaligne promene plocastoslojevitog epitela grlica materice.

T lymphocytes play an important role in the immune response to both neoplasia and viral infection. Normally, about 60% of T lymphocytes in the peripheral blood are T4 (helper) lymphocytes, while 20-30% are T8(suppressor) lymphocytes. When this ratio is inverted, most significant changes occur. The aim of the study was to examine the T4/T8 lymphocyte ratio in the peripheral blood of patients with nonmalignant and premalignant changes of the cervical epithelium and to compare it with that in patients without any cytological or colposcopical cervical abnormality. The results show a significant decrease of the T4/T8 lymphocyte ratio in the peripheral blood of patients with leukokeratosis (1.55) and especially of those with cervical intraepithelial neoplasia (1.19), compared with the results of the control group (2.31). These findings, as well as the knowledge of the importance of immune response in the control of the onset of malignancy, that the determination of T4/T8 lymphocyte ratio might be helpful in the prediction of the degree of premalignant cervical chance and indicate patient's follow-up.

Neutralizing antibody to herpes simplex virus type 1 in patients with oral cancer.

Neutralizing antibody to Herpes simplex virus type 1 (HSV-1), type 2, and measles virus was measured in the serum of patients with oral cancer, patients with oral leukoplakia, and in control subjects who were smokers and nonsmokers. Significantly higher titers to HSV-1 were found in controls who smoked than in controls who did not smoke. Patients with untreated oral cancer had HSV-1 neutralizing titers similar to those of the controls who smoked, but those with later stage tumors had higher titers than those with earlier stage tumors. In patients who were tumor free after treatment for oral cancer, higher antibody titers to HSV-1 were associated with longer survival times. No association was found between clinical status and antibody to measles virus. The data are consistent with a role for both HSV-1 and smoking in the pathogenesis of oral cancer.

Autoantibodies in patients with oral lupus erythematosus, lichen planus and leukoplakia. An aid in diagnosis.

Of 35 patients with oral discoid lupus lesions, 9 (25%) were diagnosed as Systemic (SLE) and 26 as Discoid (dle) lupus erythematosus. Antibodies to whole nuclei (ANAL), dsDNA (anti-DNA ab) and extractable nuclear antigens (anti-RNP ab, anti-Sm ab) as well as serum immunoglobulin levels (Ig) were determined in these patients, in 20 patients with reticular oral lichen planus (LP) and 20 with homogeneous oral leukoplakia (LEUK). High IgG ANA titres were found in the SLE cases, highly increased anti-DNA ab in 6 SLE cases (67%) and one DLE case (4%), slightly increased anti-DNA ab in 9 DLE (35%) but only two (5%) of the LP nd LEUK cases. The prevalence of autoantibodies and increased anti-DNA ab did not differ significantly between DLE cases with oral lesions only and those with cutaneous lesions as well. Increased Ig were present in 6 SLE (67%), 8 DLE (31%), and 3 LEUK (15%) but none of the LP cases. High ANA titres and/or elevated anti-DNA ab disclosed 8 of the 9 SLE and one of 26 DLE cases. Slightly elevated anti-DNA ab and elevated Ig indicated the diagnosis in 9 and 8, respectively, of the 26 DLE cases. It is concluded that determination of ANA, anti-DNA ab and Ig is of diagnostic importance in patients with verified or suspected oral discoid lupus lesions.

Immunopathology of oral leukoplakia.

The lymphocyte transformation test was performed with autologous saline homogenates of leukoplakia. A negative correlation was established (P<0.05) between the (14)C thymidine uptake of lymphocytes in vitro and the non-pyroninophilic mononuclear cell infiltration in biopsies. A depression of lymphocyte transformation was revealed in patients with carcinoma or carcinoma in situ and some with epithelial atypia, as compared with those showing only hyperkeratosis and to a less extent those with acanthosis. A corresponding depression was not found when lymphocytes were stimulated with phytohaemagglutinin, Candida albicans or Herpes simplex antigens. The Pyroninophilic cell count was raised in biopsies with carcinoma or carcinoma in situ and in some with epithelial atypia or acanthosis. These result suggest that in leukoplakia the carcinomatous transformation may be associated with some immunological changes.