Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): effect of differential expression of melan-A/MART-1

We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-103), we noted that Melan-A/MART-1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell-lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.     

Outcome of Judet's quadricepsplasty for knee contractures and the effect of local infiltration of epinephrine on reducing blood loss

Objective: To evaluate the effectiveness of Judet''s quadricepsplasty for treatment of knee contractures and to identify the effect of local infiltration of epinephrine on blood loss associated with this procedure. Methods: A retrospective cohort study was conducted in which all cases of knee contractures managed with Judet''s quadricepsplasty from 1st January 2009 to 31st December 2013 were included and were divided into two groups. The epinephrine group included patients who were infiltrated with diluted epinephrine (1:400,000) along with xylocaine, around the operative field 15 min prior to the incision time, while the control group did not receive any infiltration. Judet''s outcome, blood loss, drop in hemoglobin and required blood transfusion were noted for all patients and compared between both groups. Results: Most common preceding pathology identified for the development of knee contractures was periarticular fracture while ilizarov application was the most common etiology. Both groups were found similar in all preoperative characteristics except preoperative flexion contracture (p=0.02). All functional outcome measures including Judet''s outcome were similar in both groups. In contrast, duration of surgery (p=0.01), blood loss (p=0.02), drop in hemoglobin (p=0.01) and number of transfusions (p=0.03) were significantly reduced in epinephrine group. Conclusion: Judet''s quadricepsplasty is a useful procedure to increase the range of motion of rigid knees and local infiltration of epinephrine is effective in decreasing the amount of subsequent blood loss and transfusion requirements.     

Cytotoxic and photocatalytic studies of hexagonal boron nitride nanotubes: a potential candidate for wastewater and air treatment

Boron nitride (BN) nanomaterials are rapidly being investigated for potential applications in biomedical sciences due to their exceptional physico-chemical characteristics. However, their safe use demands a thorough understanding of their possible environmental and toxicological effects. The cytotoxicity of boron nitride nanotubes (BNNTs) was explored to see if they could be used in living cell imaging. It was observed that the cytotoxicity of BNNTs is higher in cancer cells (65 and 80%) than in normal cell lines (40 and 60%) for 24 h and 48 h respectively. The influence of multiple experimental parameters such as pH, time, amount of catalyst, and initial dye concentration on percentage degradation efficiency was also examined for both catalyst and dye. The degradation effectiveness decreases (92 to 25%) as the original concentration of dye increases (5–50 ppm) due to a decrease in the availability of adsorption sites. Similarly, the degradation efficiency improves up to 90% as the concentration of catalyst increases (0.01–0.05 g) due to an increase in the adsorption sites. The influence of pH was also investigated, the highest degradation efficiency for MO dye was observed at pH 4. Our results show that lower concentrations of BNNTs can be employed in biomedical applications. Dye degradation properties of BNNTs suggest that it can be a potential candidate as a wastewater and air treatment material.

Photocatalytic degradation studies of methyl orange using BNNTs.     

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.     

Retrocaval ureter

Two cases of retrocaval ureter are reported. A 22 years old male patient presented to us with the complaints of right flank pain and hematuria and a child of 2 years referred to us for evaluation of right side moderate hydronephrosis detected on ultrasound. The diagnosis was confirmed on intravenous urography and retrograde pyelography. Both the ends were transected and anastomosed above a JJ stent in front of the inferior vena cava. Postoperatively the patients remained asymptomatic and the hydronephrosis improved.     

Prediction of CYP-mediated silybin A-losartan pharmacokinetic interactions using physiological based pharmacokinetic modeling

Journal of Pharmacokinetics and Pharmacodynamics - The concomitant use of herbal products and synthetic drugs necessitates the assessment of their interaction potentials. The herbal...