Lack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomas

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and panctopenia. Interferons (IFNs), specifically of the α subtypes have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN-α is still rather limited. The mechanisms responsible for the beneficial action of IFN-α in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-α, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-α and are commonly used as a model cell to test anti-proliferative effect of IFN-α. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we overexpresed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-α. These results let us to suggest that IFN-α sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.     

Gender Dysphoria and Perceived Social Support: A Matched Case-Control Study

BackgroundIn people diagnosed with Gender Dysphoria (GD), low perceived social support from their families and society has been suggested to be associated with poor quality of life and mental well-being.AimTo compare the perceived social support in individuals with GD with that in individuals without GD matched for age and gender.MethodsThe study group (n = 50) consisted of individuals diagnosed with GD via psychiatric evaluation. A control group (n = 50) was created by matching volunteers without GD by age and gender. Sociodemographic data form, Structured Clinical Interview Form for DSM-IV TR Axis I Disorders (SCID-I), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to gather data from participants.Outcomescomparing the perceived social support, the total and subscale MSPSS scores of groups were calculated.ResultsThe presence of at least 1 psychiatric disorder was significantly higher in the GD group than in the control group, either lifetime or during evaluation (P < .001 and P = .025, respectively). The total MSPSS and family support subscale scores were found to be significantly lower in the GD group than in the control group (P = .001 and P ≤ .001, respectively). When the groups formed on the basis of gender identity (32 trans men vs 32 cis men and 18 trans women vs 18 cis women) were compared, only the family support subscale score was found to be lower in trans men than cis men (P = .005). In addition, comparisons within the groups formed based on sex assigned-at-birth revealed lower total, friend, and family support in those assigned female-at-birth and lower total and family support in those assigned male-at-birth in the GD group. A multiple linear regression analysis revealed that the presence of GD was significantly associated with total and family support MSPSS subscale scores.Clinical ImplicationsThe findings show that perceived social support in people diagnosed with GD is lower, even when the presence of psychiatric disorders is included in the analysis.Strengths and LimitationsThe matched case-control design was the major study strength, whereas the sample size was the major limitation.ConclusionClinical care of people diagnosed with GD should include the evaluation of diverse sources of social support, efforts to strengthen family and friend support, maintenance of interpersonal relationships, and support of mental well-being.Kaptan S, Cesur E, Ba?ar K, et al. Gender Dysphoria and Perceived Social Support: A Matched Case-Control Study. J Sex Med 2021;18:812–820.     

Large Lipomatous Hypertrophy of the Interventricular Septum

We present the case of a 58-year-old woman who had large lipomatous hypertrophy of the interventricular septum, a condition that is reported very infrequently. Preoperative cardiac magnetic resonance images revealed an inhomogeneous, infiltrating mass that was suppressed in fat-suppression mode. The extensive mass was causing right ventricular dysfunction, so we excised it through a right ventricular approach. The findings on histologic analysis of the mass were consistent with lipomatous hypertrophy. The patient died of septic shock on the 28th postoperative day. In addition to the patient''s case, we discuss the characteristics and diagnosis of this rare entity.     

Distinct responses of Gulf of Mexico phytoplankton communities to crude oil and the dispersant corexit® Ec9500A under different nutrient regimes

This study examines the potential effects of exposure to South Louisiana sweet crude oil (LSC), Corexit^® EC9500A, and dispersed oil on enclosed phytoplankton communities under different nutrient regimes. Three distinct microcosm experiments were conducted for 10 days to assess changes to the structure of natural communities from the Gulf of Mexico as quantified by temporal changes in the biomasses of different phytoplankton groups. Concentration of NO₃, Si and PO₄ were 0.83, 0.99 and 0.09 μM for the unenriched treatments and 14.07, 13.01 and 0.94 μM for the enriched treatments, respectively. Overall, the contaminants LSC and Corexit^® EC9500A led to a decrease in the number of sensitive species and an increase in more resistant species. Phytoplankton communities showed more sensitivity to LSC under nutrient-limited conditions. The addition of nutrients to initially nutrient-limited treatments lessened the inhibitory effect of LSC in the short term. Centric diatoms benefited most from this enrichment, but pennate diatoms demonstrated considerably greater tolerance to crude oil at low crude oil concentrations in nutrient-enriched treatments. Dinoflagellates showed relatively higher tolerance in nutrient-limited treatments and high crude oil concentrations. Corexit^® EC9500A inputs significantly increased the toxicity of crude oil. Corexit^® EC9500A alone had a highly inhibitory effect at 63 ppm on phytoplankton communities. This study highlights the fact that different nutrient regimes play a major role in determining the shifts of the phytoplankton community in response to exposure to different concentrations of crude oil and dispersant. Determination of the functional equivalence of shifted phytoplankton groups could complement our research and allow for more pertinent extrapolation to real world conditions.     

Application of Rhenium-186 Radiosynovectomy in Elbow Diffuse Pigmented Villonodular Synovitis. - A Case Report with Multiple Joint Involvement

After surgical therapy of diffuse pigmented villonodular synovitis (DPVNS), recurrence is seen in almost half of the patients. The effectiveness of radiosynovectomy (RSV) in preventing recurrence and complaints of DPVNS is well known. Elbow involvement in DPVNS is a very rare condition; therefore, RSV in elbow hasn’t been experienced widely. The aim of this case report is to show the effectiveness of RSV with rhenium-186 (Re-186) sulfide colloid. We applied Re-186 sulfide colloid to the elbow joint of DPVNS patients six weeks after arthroscopic synovectomy. As a result, the patient did not have any complaints, and our findings are compatible with residue or recurrence on magnetic resonance imaging (MRI) in sixth and twentieth month controls after administration. We concluded that Re-186 is an effective adjuvant therapy for the prevention of recurrence and complaints.     

Enhanced sensitivity to oxidant-induced micronucleus frequency in elderly individuals is not associated with glutathione S-transferase M1 (GSTM1) null genotype in lymphocytes

BACKGROUND: A large number of studies have demonstrated that various kinds of DNA damage accumulate during aging and that oxidative stress possibly contributes to this process. Glutathione S-transferase M1 (GSTM1) can prevent their possible effects on DNA via detoxification of reactive substances that induced oxidative stress. OBJECTIVE: To investigate the relationship between GSTM1 polymorphism and DNA sensitivity to oxidative stress with age, we used micronucleus (MN) frequency as a marker of DNA damage in lymphocytes from young and elderly subjects. Methods: This study was performed in 30 young (age range 20-36 years) and 30 elderly (age range 66-87 years) healthy individuals who were chosen on the basis of their GSTM1 genotype (15 GSTM1 null and 15 GSTM1 positive for each group). Lymphocytes were cultured after Ficoll isolation and treated for 48 h with a 30-muM dose of cumene hydroperoxide (CumOOH), a dose that does not decrease cell viability. RESULTS: There was no significant difference in the MN frequency observed in control cultures from young and elderly individuals. However, the MN frequency in CumOOH-treated cultures was significantly higher in the elderly group than the young group (p < 0.001). No association was found between the GSTM1 phenotype and CumOOH-induced MN frequency. CONCLUSIONS: The results suggest that lymphocytes of elderly individuals are more susceptible to in vitro MN induction by CumOOH. However, this difference in susceptibility is not explained by the lack of GSTM1.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

Effects of primary selective laser trabeculoplasty on anterior segment parameters

AIM:To investigate the effects of selective laser trabeculoplasty (SLT) on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG).METHODS: Pentacam measurements of 45 eyes of 25 (15 females and 10 males) patients (12 with OHT, 13 with POAG) before and after SLT were obtained. Measurements were taken before and 1 and 3mo after SLT. Pentacam parameters were compared between OHT and POAG patients, and age groups (60y and older, and younger than 60y).RESULTS: The mean age of the patients was 57.8±13.9 (range 20-77y). Twelve patients (48%) were younger than 60y, while 13 patients (52%) were 60y and older. Measurements of pre-SLT and post-SLT 1mo were significantly different for the parameters of central corneal thickness (CCT) and anterior chamber volume (ACV) (P<0.05). These parameters returned back to pre-SLT values at post-SLT 3mo. Decrease of ACV at post-SLT 1mo was significantly higher in younger than 60y group than 60y and older group. There was no statistically significant difference in Pentacam parameters between OHT and POAG patients at pre- and post-treatment measurements (P>0.05).CONCLUSION:SLT leads to significant increase in CCT and decrease in ACV at the 1^st month of the procedure. Effects of SLT on these anterior segment parameters, especially for CCT that interferes IOP measurement, should be considered to ensure accurate clinical interpretation.