The immunomodulatory effects of regulatory T cells: implications for immune regulation in the skin

Regulatory T cells are thought to have a critical role in the suppression of immune responses. In addition to the prevention of the development of autoimmunity, they are also thought to have a role in the prevention of allergic responses to environmental allergens, immune responses to tumours and the development of memory responses to chronic infections. They have been isolated within the skin and have been shown to express surface markers that enable skin-specific migration, suggesting that regulatory T cells have a functional role in the skin. There is accumulating evidence to suggest that regulatory T cells may be involved in numerous skin disorders and may also be modified by various therapeutic agents used to treat these disorders. We review the evidence for the presence of this T-cell subset in humans, the suppressive effects of regulatory T cells, and their role in the skin.     

Tendon graft fixation in ACL reconstruction: in vitro evaluation of bioabsorbable tenodesis screw

BACKGROUND: Conventional ACL reconstruction requires sufficient tibial bone quality for secure graft fixation. We evaluated the mechanical characteristics of a supplemental tenodesis screw in cadaveric specimens. MATERIAL AND METHODS: One group of 7 specimens from 7-paired tibiae was randomly assigned to undergo tibialis anterior tendon graft-bone tunnel fixation with a bioabsorbable interference screw, using conventional ACL reconstruction techniques. The other group of 7 specimens underwent the same procedure supplemented with a bioabsorbable tenodesis screw. All specimens were subjected to pullout testing on a servo hydraulic device. RESULTS: Specimens in the supplemental fixation group had double the load to failure (tenodesis = 467 (SD 184) N, control group = 223 (SD 66) N, p = 0.02) and were also one-third stiffer (tenodesis = 31 (SD 13) N/mm, control group = 21 (SD 6) N/mm, p = 0.03) than the specimens in the conventional fixation group. INTERPRETATION: Supplemental bioabsorbable tenodesis screw fixation may be advantageous for primary reconstruction in patients with low tibial bone mineral density or during revision procedures. By providing secure soft tissue graft-tibia fixation during the early phase after ACL reconstruction, supplemental tenodesis fixation may enable patients to participate safely in more intense, early rehabilitation.     

Screening for hepatocellular carcinoma

Liver cancer remains one of the most common causes of cancer death globally, and its cure rate has not improved for the past 20 years. Hepatocellular carcinoma develops in patients with cirrhosis of any etiology. Patients with cirrhosis are thus usually included in screening program aiming to achieve early detection and effective treatment for HCC. Only those patients diagnosed with HCC who would benefit with the available treatment, should undergo the screening procedure. This is based on ultrasonography and alpha-fetoprotein every 3-6 months based on the prevalence and economic status of the community being tested.     

Influence of HLA on progression of optic neuritis to multiple sclerosis: results of a four-year follow-up study

BACKGROUND: Genetic predisposition in multiple sclerosis (MS) has always been a critical concern in aetiology and progress of the disease. The present study looks into the relations between human leukocyte antigen (HLA), optic neuritis (ON) and MS in the Iranian population. METHODS: Patients with potential diagnosis of acute ON underwent a standardized clinical examination for confirming the diagnosis. Selected patients were gathered for HLA typing and clinical follow up. RESULTS: Of the 55 patients, 46 (83.6%) were female. The mean age was 25(+/-7.3) with a range of 12-43. Twenty of the 55 (36%) were confirmed for the diagnosis of clinically definite MS (CDMS). Results show that A23, B21, A11 and B51 alleles were present in 4 (20%), 6 (30%), 2 (10%) and 1 (5%) of the CDMS patients, respectively. Ten (50%) and 17 (85%) CDMS patients were positive for HLA class II alleles, DR2 and DQ1, correspondingly. CONCLUSIONS: The study strongly suggests the association among DR2, A23 and B21 allele and the evolution of ON to MS. High prevalence of A23 and DR2 alleles in CDMS patients compared with the normal population may suggest an important role for these alleles in the development of MS. The study suggests B51 as a protective factor against development of ON in the normal population. In addition, results do not confirm previous studies considering A11 as a predisposing factor. The present study finally evokes that different classes of HLA have different roles in susceptibility to MS and confirms disease heterogeneity as an important emerging concept in MS.     

T lymphocyte mediated lysis of mitomycin C treated Tenon's capsule fibroblasts

AIMS: To evaluate the effect of T cell co-culture on mitomycin C treated and untreated Tenon's capsule fibroblasts. METHODS: IL-2 dependent allogeneic T cells were incubated over a monolayer of mitomycin C treated or control fibroblasts. Fibroblast numbers were evaluated by direct counts using phase contrast microscopy. To determine whether T cell mediated lysis was a consequence of MHC mismatch, co-culture experiments were repeated with autologous T cells. The effect of Fas receptor blockade was established by co-incubation with a Fas blocking (M3) antibody. RESULTS: T cell co-culture resulted in a dramatic reduction in fibroblast survival compared to mitomycin C treatment alone (p = 0.032). T cell killing required fibroblast/lymphocyte cell to cell contact and was observed in both allogeneic and autologous co-culture experiments. Fas blocking antibodies did not significantly inhibit T cell killing (p = 0.39). CONCLUSION: T cells augment mitomycin C treated fibroblast death in vitro. Similar mechanisms may contribute to the cytotoxic effect of mitomycin C in vivo and account for the largely hypocellular drainage blebs that are observed clinically.     

Effects of 4-nonylphenol on phytoplankton and periphyton in aquatic microcosms

The effects of nonylphenol (NP) on phytoplankton and periphyton were studied in 230 L outdoor microcosms. Phytoplankton cell density and biomass, phytoplankton and periphyton diversity, and assemblage composition were analyzed during a four-week preapplication period, followed by six weeks of NP treatment via controlled release and a six weeks postapplication period. Changes in species richness and diversity were not correlated with NP concentrations. However, changes in phytoplankton cell densities during the first week of the postapplication period were related to previous exposure. In the controls and the lowest-dosed microcosm. Conjugatophyceae constituted most of the biomass during the dosing and the postapplication period. In contrast, Dinophyceae dominated the biomass during the dosing and the postapplication period at higher NP concentrations. Principal response curves revealed changes in phytoplankton assemblage composition during the dosing and the postapplication period. Dinophyceae and most Cyanophyceae were more abundant at intermediate and higher NP concentrations, whereas Conjugatophyceae were less abundant compared to controls. Assemblages only partly recovered during the postapplication period. Periphyton taxon richness, diversity, and assemblage change was not related to NP concentrations. At the lowest and intermediate concentration, assemblages were significantly different from the controls and the higher concentrations, which were similar during the treatment period.     

Defective antigen-presenting capacity of murine dendritic cells during starvation

Significant impairments of several aspects of immunity have been described in acute and chronic nutritional deficiencies; however, there have been few studies on antigen-presenting cells during starvation. We examined the antigen-presenting capacities of mouse dendritic cells (DCs) from lymphoid organ (spleen DCs) and non-lymphoid tissue (liver DCs) during starvation. The total numbers of spleen DCs and liver DCs were significantly fewer in starved mice than in control mice. Functional analysis showed that the proliferative activities of spleen DCs and liver DCs were significantly impaired in starved mice compared with control mice. In particular, liver DCs from starved mice were unable to induce interferon-gamma. Liver DCs from starved mice were unable to induce proliferation of antigen-specific memory lymphocytes. These data indicated that one major cause of impairment of immunologic responses during starvation may be mediated through DCs.     

Popliteal artery injuries: the Kashmir experience

BACKGROUND: Popliteal artery injuries pose a serious threat to limb survival. Blunt trauma appears to be associated with a higher amputation rate than penetrating trauma, probably because of the more extensive nature of the injuries. METHODS: Two hundred seventy-two cases of popliteal artery injury were studied retrospectively from 1989 to 2001, a warlike period in Kashmir. Preoperative angiography was not performed. Thirty-two percent of patients had associated venous injury and 24.6% of patients had associated bone fracture. RESULTS: Overall morbidity was 55%, with the most common complication being infection (24%). Secondary amputation had to be performed in 16 patients (5.5%). The amputation rate was not influenced by cause of injury and type of repair or the presence of venous injury, but associated bone fracture significantly increased the risk of amputation (p < 0.05). The patients who underwent repair more than 12 hours after sustaining injury had a significantly greater amputation rate (p < 0.05). CONCLUSION: Prompt resuscitation, vascularization, and proper technique appear to be the only correctable factors that improve limb salvage.     

Combination therapy with interferon alpha and beta to chronic hepatitis C

To increase the sustained response (SR) rate in chronic hepatitis C (CHC), we tried a combination therapy with interferon (IFN) alpha and beta. Fifty patients were grouped into 4 groups: group 1H (n=9), HCV serotype 1 and high HCV-RNA titer (over 6 log copies/ml); group 1L (n=11), HCV serotype 1 and low HCV-RNA titer (less than 6 log copies/ml); group 2H (n=23), HCV serotype 2 and high HCV-RNA titer; group 2L (n=7), HCV serotype 2 and low HCV-RNA titer. They were given a total dose of 768 MIU which included natural IFN beta (6 MIU) once daily for 28 consecutive days and then natural IFNalpha (10 MIU) three times a week for 20 weeks. Forty-nine patients with CHC receiving IFN alpha at total dose of 480 MIU served as single therapy group. In combination group, SR rate was achieved in 62%, 44% in 1H, 45% in 1L, 70% in 2H, and 86% in 2L, respectively. In single group, SR rate was achieved in 45, 14, 58, 60, and 82%, respectively. There was no significant difference for SR rate between combination group and single group. However, in patients with HCV-RNA titer between 6-7 log copies/ml of 1H group, SR rate in combination group (67%, 4/6) was significantly higher than that of single group (18%, 3/17) (p<0.05). These data suggest the usefulness of combination therapy with IFN alpha and beta in CHC with serotype 1 having moderately high HCV-RNA titer.