Extent Of Mononuclear Cell Infiltration Research Articles

Comparison of three different dosages of low-level laser therapy on expression of cell proliferation and inflammatory markers following ovariohysterectomy in rats

The objective of the current study was to evaluate Low-level laser therapy (LLLT) on the healing of incisional wounds following ovariohysterectomy in rats, by means of subjective histopathological and immunohistochemical analysis. A total of 72 female Wistar rats were categorised into four treatment groups (Group I; sacrification 4 hours following only one LLLT application, Group II; sacrification 7 days following only one LLLT application, Group III; sacrification 4 hours after two LLLT applications, and Group IV; sacrification 7 days after two LLLT applications). Each group was further divided into four different doses subgroups (Group Control [C, off mode LLLT application], L1 [1 J/cm2], L3 [3 J/cm2], and L6 [6 J/cm2]), with equal representation in each subgroup. Ovariohysterectomy was employed using two 2-cm-length midline abdominal incisions in the left and right sides of line alba. The Group C was assigned to the left side incision to each rat in the study. After irradiation, the tissue was subjected to histopathological analysis to determine the extent of mononuclear cell infiltration, edoema, and epithelialization. Additionally, immunohistochemical analysis was performed to evaluate the expression of proliferating cell nuclear antigen (pCNA) and inducible nitric oxide synthase (iNOS). Group L1 and L3 significantly decreased mononuclear cell infiltration compared with Group C in all treatment groups (p < 0.05). Group L3 significantly decreased edoema compared with Group C in all groups except for treatment Group I (p < 0.05). Group L2 and L3 significantly increased epithelization in treatment Group IV (p < 0.05). Moreover, Group L2 and L3 significantly increased pCNA in all groups, while L2 and L3 significantly decreased iNOS expression in treatment Group II, III, and IV (p < 0.05). However, no statistical difference was found between subgroups of treatment Group I in iNOS expiration (p > 0.05). The results of the current examination demonstrated that LLLT can modulate mononuclear cell infiltration and edoema, and improve epithelization, as well as increase pCNA expression, whereas decrease iNOS expression during the wound healing process, therefore enhancing wound healing following ovariohysterectomy in rats.

A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of Sjögren’s syndrome

Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs). We included 44 primary Sjögren's syndrome (pSS) patients and 15 NCs in this study; we found that the expression of NOS2 and CD68 was elevated in all of the SG of SS patients. Additionally, the serum and saliva levels of IL-6, IL-17A, and NO were higher in the pSS patients, compared with the NCs. Furthermore, the NOS2-induced excess NO was associated with the extent of the MNC infiltration, and thereby with tissue injury. It is also important to note that there were correlations between the levels of IL-6, IL-17A, and NO. Such findings indicate that through the effects of NO, IL-17A participates in the pathophysiology of the disease. With the purpose of improving both the diagnosis and prognosis, IL-6, IL-17A, and NO should be assayed in the serum and saliva of patients suspected of SS.

Multifaceted Assessment of Chronic Gastritis: A Study of Correlations between Serological, Endoscopic, and Histological Diagnostics

Aim. Chronic gastritis was assessed serologically, endoscopically and histologically to identify correlations between these methods. Methods. Subjects comprised 319 patients who had provided informed consent. Serological assessment of chronic gastritis was based on the pepsinogen test method. Endoscopic gastritis and histological gastritis were assessed and scored according to the Kimura-Takemoto classification system and the updated Sydney classification system respectively, and correlations between these three methods were studied. Results. Pepsinogen I/II ratio showed a significant correlation to the extent of mononuclear cell infiltration of the gastric corpus. When histological gastritis was divided, on the basis of the distribution of mononuclear cell infiltration, into gastritis limited to the antrum and corpus gastritis, these types were distinguished with high accuracy using a pepsinogen I/II ratio of 3 as the cutoff. A good correlation was also seen between pepsinogen I/II ratio and development of atrophy in endoscopic gastritis, where groups with and without advanced atrophy were also distinguished with high accuracy using a cutoff value of 3. Conclusion. Significant correlations exist between serum pepsinogen levels, endoscopic gastritis, and histological gastritis. Pepsinogen I/II ratio allows prediction of the existence of endoscopic gastritis and histological gastritis, or the extent of their development, with high accuracy.

Mononuclear cell infiltration in clear‐cell renal cell carcinoma independently predicts patient survival

The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P < .001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC.

Possible mechanisms of elevation of serum transaminase levels during interferon-beta therapy in chronic hepatitis C patients.

Serum transaminase levels are frequently elevated in patients with chronic hepatitis C who are receiving interferon (IFN)-beta therapy, despite hepatitis C virus (HCV)-RNA being eradicated from the serum. We examined liver histology to determine the reason for this elevation. Patients with chronic hepatitis C, diagnosed by liver histology and positive serum HCV-RNA, were given intravenous injections of IFN-beta, at a daily dose of 6 MU, every day for periods of 6 to 12 weeks. When serum alanine transaminase (ALT) levels during the therapy were higher than three times the levels before the therapy, liver biopsy was performed. Histological findings on light microscopy were compared in liver biopsy specimens obtained before and during the therapy. An increase in serum ALT levels was found in 19 of the 102 patients who received the IFN-beta therapy. Autoimmune hepatitis was not contributory in any of these 19 patients, because serum antinuclear antigen was negative and IgG levels were not increased. Liver histology was examined in 10 of these 19 patients. The period between the start of IFN-beta therapy and the biopsy during the therapy ranged from 14 to 46 days. In 2 patients, the extent of mononuclear cell infiltration in the liver and hepatocyte necrosis was less than the extent before the therapy. In the remaining 8 patients, the grade of chronic hepatitis was unchanged during,the therapy, but vacuole formation and apoptotic nuclei in hepatocytes were found in 2 patients, and centrilobular necrotic areas in 1 patient. The elevation of serum ALT levels during IFN-beta therapy in chronic hepatitis C patients was not a result of increased hepatitis activity. Degenerative, apoptotic, and necrotic changes in hepatocytes, probably a result of the cytotoxic effects of IFN-beta, may have contributed to this elevation of ALT levels. However, such changes were absent in most of the patients, suggesting that decisions on the discontinuation of IFN-beta therapy must be made in accordance with liver histology findings.

Oral, perioral and systemic pathosis in HgCl2-induced autoimmunity in the BN rat.

Male BN rats were repeatedly skin-injected with HgCl2 solution and sacrificed after 6, 9, 14, 21, 28 or 24 days. Mononuclear cell infiltrates were observed in the oral mucosa and in lacrimal, salivary and thyroid glands from 6-9 days onwards, with a peak at 14-21 days. Immunohistochemistry identified these cells as predominantly T cells with some NK cells but very few B cells. Reversible parenchymal changes were observed but there was no obvious persistent tissue destruction. Serum titers of IgE, IgG1, anti-laminin and anti-DNP, but not IgG2a antibodies, were raised and peaked at 14-21 days. However, there was no correlation, within animals, between these titers and the extent of mononuclear cell infiltration. Mercury was histochemically detected within dendritic cells/macrophages in the connective tissue stroma of the glands and in the oral mucosa, but no correlation was found between the distribution of mercury and the degree of inflammation. We conclude that the accumulation of mononuclear cells in oral and perioral tissues of HgCl2-treated BN rats does not represent a local immune response to tissue-retained Hg. Instead, we propose that the extravasation represents an epiphenomenon that is not necessarily deleterious to the infiltrated organ.

Human Interferon-Inducible Protein-10 Induces Mononuclear Cell Infiltration in Mice and Promotes the Migration of Human T Lymphocytes Into the Peripheral Tissues of Human Peripheral Blood Lymphocytes-SCID Mice

The human cytokine, interferon-inducible protein-10 (IP-10), is a small glycoprotein secreted by activated monocytes, T cells, keratinocytes, astrocytes, and endothelial cells and is structurally related to the alpha subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other alpha chemokines that induce neutrophil migration, IP-10 has been shown to chemoattract monocytes and T lymphocytes in vitro, suggesting a role in T-cell-mediated immune responses. We therefore examined the effects of human IP-10 after in vivo administration. IP-10 induces significant mononuclear cell infiltration after subcutaneous injections in normal mice. In an effort to study the in vivo effects of IP-10 on human leukocyte migration, we then examined the ability of recombinant human IP-10 (rhIP-10) to induce human-T-cell infiltration using a human/severe combined immune deficiency (SCID) mouse model. SCID mice received an intraperitoneal injection of human peripheral blood lymphocytes (10(8) cells), followed by a subcutaneous injection of rhIP-10 (1 micrograms/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhIP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhIP-10 again induced significant mononuclear cell accumulation 72 hours after injection. Immunohistologic evaluation determined that a significant number of human CD3+ T cells were recruited in response to rhIP-10 injections. These results show that rhIP-10 is capable of inducing human T-cell migration in vivo and may play an important role in monocyte and lymphocyte recruitment into inflammatory sites.

Expression of HLA ABC and DR antigens in thyroid neoplasia and correlation with mononuclear leukocyte infiltration

The rejection of tumor cells by the immune system depends on the production of tumor-associated antigens and the expression of HLA antigens on these cells. We therefore studied the expression of HLA ABC and DR antigens in malignant and benign thyroid disorders and correlated it with the types and extent of mononuclear cell infiltration. In the normal thyroid, HLA ABC expression was weak and focal, while it was diffusely present in benign disorders and in most but not all malignancies. HLA DR antigens, while absent or infrequently expressed in normal thyroid, were strongly but often focally expressed in all cases of autoimmune thyroid disease (AITD), as well as in most cases of malignant tumors and benign epithelium surrounding these tumors, and colloid nodule disease. There was a T cell predominance in all disorders, and the CD4+/CD8+ ratio was greater than 1 in most benign and malignant specimens. There was a direct correlation between the high expression of HLA antigens and dense inflammatory infiltration in AITD but not in most tumor specimens. Lack of such correlation suggests that the expression of HLA antigens is an autonomous event in tumors, independent of cellular infiltrate.

Prevention of experimental allergic encephalomyelitis by anterior hypothalamic lesion in rats.

Bilateral electrical lesions were performed in the anterior hypothalamus (AH) and hippocampus (HC) of female Lewis rats. AH but not HC lesions were found to inhibit the appearance of clinical signs typical of experimental allergic encephalomyelitis (EAE). The incidence of EAE was 17.2% and the duration was 1.33 +/- 0.07 days after AH lesions compared with an incidence of 85% and duration of 4.81 +/- 0.6 days in the controls. Destruction of the AH was followed by decreased levels of antibodies to myelin basic protein and increased reactivity of splenic lymphocytes to concanavalin A, but did not affect the extent of mononuclear cell infiltration within the brain and spinal cord.

Risk and prognostic factors in trophoblastic neoplasia

Three hundred and seventeen patients with gestational trophoblastic tumors were investigated and treated between 1957-1973. The risk of trophoblastic tumor was influenced by the outcome of the antecedent pregnancy (hydatidiform mole, non-mole abortion, term delivery) and the ABO blood groups of the mating couple; it was also influenced by the patient's age. The response to treatment with chemotherapy and , where appropriate, with surgery and radiotherapy, was influenced prfoundly by several factors. These included 1) the outcome of the antecedent pregnancy, 2) the total body burden of tumor at the time treatment stated as reflected by the urinary output of human chorionic gonadotrophin (CG), 3) the interval between the antecedent pregnancy and the start of chemotherapy, 4) the ABO groups of the mating couple, 5) the extent of mononuclear cell infiltration in the tumor, 6) the immunological status of the patient at the start of treatment, 7) the size of tumor masses, 8) the site of metastases and particularly the presence of intracranial metastases, and possibly by 9) the age and 10) the parity of the patient. A detailed study of the HLA antigens of the patient, her husband, and antecedent child has shown no positive effect on risk or prognosis. These data provide a basis for a scoring system that allows the prognosis to be defined at the time of diagnosis and facilitates tisk of drug resistance. Applied retrospectively to the cases from which the scoring system was generated, prognostic groups with survival rates ranging from 0-100% can be defined. Unfavorable prognostic factors combine so as to increase the probability of drug resistance.