Initial experience with laser retinal surgery

The authors describe 21 cases with resection of the retinal rupture valve with Nd:YAG laser impulse, performed to reduce the vitreoretinal tractions. Resection of the 'dump' rupture valve has been carried out in 10 cases, in the rest 11 the operation has been performed in the presence of a detachment of the retina. Anatomic success (detachment of the valve from the retina) has been achieved in 16 cases. The technique of the surgery is described, as are indications and contraindications to the operation.     

Quinacrine inhibits the epidermal dendritic cell migration initiating T cell-mediated skin inflammation

Quinacrine (QC) is an anti-inflammatory drug that has been used for the treatment of malaria and rheumatoid diseases. The mechanism(s) underlying the anti-inflammatory activity of QC remains poorly understood. We recently reported the QC-mediated inhibition of the NF-kappaB pathway using an in vitro model. To test this potential mechanism in vivo, we used the contact hypersensitivity response (CHS) to chemical allergen sensitization and challenge in mice as a model of skin inflammation. The results indicated that QC treatment inhibited NF-kappaB activation in the skin during allergen sensitization. This inhibition was reflected by decreased mRNA expression and protein production of the NF-kappaB-dependent cytokines TNF-alpha and IL-1beta and the chemokine CCL21 in the skin. The decreases in these cytokines resulted in reduced migration of allergen-presenting dendritic cells from the skin into skin-draining lymph nodes and markedly decreased activation of effector CD8+ T cells for the CHS response to allergen challenge (inhibitory concentration 50% or IC50 was 55 mg/kg). These findings reveal a previously unrecognized mechanism of QC-mediated inhibition of inflammation.     

Accumulation in “normal” lungs of live tumorigenic cells during sub-cutaneous growth of weakly and highly metastasizing tumors and their In vitro sensitivity to growth regulation by normal fibroblasts

The main purposes of the study were: (I) in vivo comparison of accumulation of live tumorigenic cells (LTC) in macroscopcally normal lungs of animals bearing 6 s.c. Syrian hamster sarcomas differing in spontaneous metastasizing activity (SMA); (2) in vitro examination of the sensitivity of these cell strains to the growth-regulating signals of normal fibroblasts. Cell strains used differed in SMA from very weak (WM) to extremely high (HM). The numbers of LTC doses in “normal” lung tissue of tumorbearing animals were determined in s.c. transplantation tests by titrating single-cell suspensions prepared from the lung tissues of 5 tumor-bearing animals, for each cell strain, every 5 days during 30 days of s.c. tumor growth, until the appearance of the first spontaneous lung metastases. The sensitivity of WM and HM cells to growth-regulating signals of normal hamster embryo fibroblasts (HEFs) was examined by in vitro co-culturing during 6 days with daily determination of ³H-TdR incorporation in the WM and HM cells grown with or without contact with HEFs. The data presented demonstrate (I) the surprisingly similar efficiency in the occupation of macroscopically normal lung tissues by live tumorigenic cells of WM and HM strains, disseminating spontaneously from the s.c. tumors; (2) the significantly lower sensitivity of HM cells, in contrast to WM, to growth inhibition by contact with HEFs and especially their marked ability to usurp the growth-stimulating signals of normal HEFs. © 1994 Wiley-Liss, Inc.     

A fifteen-month survey of directly observed therapy--short course and antibiotic drug resistance in the region of Plovdiv

OBJECTIVE: This study addresses the issue of antituberculosis drug resistance in a cohort of 213 patients from Plovdiv included in the pilot phase of a DOTS based project for a 15-month period. Between July 1. 1998 and September 30, 1999, ninety three culture-positive patients participated in the study. 89 of them were tested for drug susceptibility to rifampicin, izoniazid, etambutol, and streptomycin. RESULTS: Resistance to at least one antituberculosis drug was established in 24.7% of the patients. Monoresistance was found in 13.5% of the cases. The median prevalence of combined resistance to rifampicin and isoniazid was 6.7%. The prevalence of resistance to rifampicin or isoniazid was 21.4%. Drug susceptibility testing results were obtained within 67 days. In 33% of the patients continuation treatment phase was initiated before drug susceptibility data were available. CONCLUSIONS: During the observed period a considerably high rate of drug resistant tuberculosis was registered among the patients included in the pilot phase of the program based on Directly Observed Therapy--Short Course. The percentage of resistance to R and/or I gives better information about the risk of inadequate treatment during the continuation treatment phase. The high percentage of this pattern of resistance in our region requires the continued use of four first-line drugs for therapy until the results of drug-susceptibility testing are received.     

AKT2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival

Amplification or overexpression of the HER-2/neu gene in breast cancers is associated with aggressive behavior and resistance to therapeutic regimens. The molecular mechanisms that contribute to therapeutic resistance/survival of HER-2/neu-overexpressing tumor cells have not been well defined. To determine if phosphatidylinositol 3-kinase/AKT signaling contributes to cell survival in HER-2/neu-positive breast cancers, we performed immunohistochemical analyses to evaluate expression of HER-2/neu and AKT in a series of 52 breast carcinomas. Elevated expression of HER-2/neu was found to correlate with overexpression of AKT2 protein and activation of AKT kinase. HER-2/neu-overexpressing breast cancer cell lines were resistant to apoptosis induced by UV treatment and hypoxia, which was suppressed in the presence of the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin, indicating a link between AKT activation and stress resistance in HER-2/neu-overexpressing cells. These observations suggest that AKT signaling augments resistance to stress-induced apoptosis in breast cancer cells overexpressing HER-2/neu.