Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer.

Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin-expressing TRM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.

Harvesting, Coupling, and Control of Single-Exciton Coherences in Photonic Waveguide Antennas.

We perform coherent nonlinear spectroscopy of individual excitons strongly confined in single InAs quantum dots (QDs). The retrieval of their intrinsically weak four-wave mixing (FWM) response is enabled by a one-dimensional dielectric waveguide antenna. Compared to a similar QD embedded in bulk media, the FWM detection sensitivity is enhanced by up to 4 orders of magnitude, over a broad operation bandwidth. Three-beam FWM is employed to investigate coherence and population dynamics within individual QD transitions. We retrieve their homogenous dephasing in a presence of low-frequency spectral wandering. Two-dimensional FWM reveals off-resonant Förster coupling between a pair of distinct QDs embedded in the antenna. We also detect a higher order QD nonlinearity (six-wave mixing) and use it to coherently control the FWM transient. Waveguide antennas enable us to conceive multicolor coherent manipulation schemes of individual emitters.

Transurethral microwave thermotherapy: first experiences in Poland.

OBJECTIVE: To present early experiences in Poland with high-energy transurethral microwave thermotherapy (HeTUMT), considered as a serious alternative to surgery in managing benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: Sixty-one patients were treated in two centres using a commercial TUMT system. The patients were assessed at 5-6 weeks, 3 and 6 months after treatment, evaluating subjective complaints, the International Prostate Symptom Score (IPSS), urinary flow rate and postvoid residual volume. RESULTS: A complete follow-up was available in 44 patients; most had symptomatic improvement 3 months after HeTUMT but it was slightly less pronounced after 6 months. The improvement in objective variables increased up to 6 months after HeTUMT. There was > or = 50% improvement in subjective complaints in 43% of the patients, in urinary flow rate in 25% and in residual urine in half. Two patients required re-treatment for a urethral stricture and ineffective HeTUMT. CONCLUSIONS: HeTUMT may be a useful treatment for BPH but the outcome for an individual patient seems to be unpredictable. The indications for TUMT should be reviewed individually for each patient.

ESWL in hemophiliac patients.

OBJECTIVE: To assess ESWL treatment of urolithiasis in patients with hemophilia, the frequency of hemorrhagic complications, and to determine the treatment outline. PATIENTS AND METHODS: From 1991 to 1997, eleven patients with hemophilia were treated by ESWL for urolithiasis. Substitution of deficient coagulation factors was started on the day of treatment. Ultrasound examination was performed in all cases on the 1st day after the procedure in order to discover any potential hemorrhagic complications. Substitution withdrawal depended on the patients' general status, lack of hematuria and the absence of signs of hemorrhage. Preliminary results were evaluated after 7-10 days on the basis of plain abdominal X-ray of the kidney, ureter and bladder and ultrasonography. RESULTS: In total, 25 ESWL sessions were performed, 1-6/patient. Nine patients (81.8%) discharged stones, and 2 patients are being followed up. No hemorrhagic complications were observed. CONCLUSIONS: Substitution of deficient coagulation factors makes ESWL a safe method of urinary stone management in hemophiliacs. No hemorrhagic complications were seen in our patients. Substitution withdrawal may be based on the patients' good general status, lack of hematuria and absence of signs of hemorrhage.

Some pink yeasts associated with softening of olives.

Pink yeasts identified as Rhodotorula glutinis var. glutinis, R. minuta var. minuta, and R. rubra produce polygalacturonases which cause a slow softening of olive tissue. Both pectin methyl esterase and polygalacturonase are produced when cultures are grown in appropriate media. Crude, cell-free dialyzed enzyme preparations measured viscosimetrically exhibited optimal activity on sodium polygalacturonate at pH 6.0 and 40 C, and were active in the range of pH 4.0 to 9.0 and 10 to 50 C. Cultures grown in sterilized olives and brine at pH 4.0 with sterile glucose added aseptically caused a slow softening of tissue as measured with a Christel texturometer. Similar results were obtained when crude, cell-free enzyme preparations were added to olives in buffer solution at pH 6.0 with Merthiolate. Commercial control of these yeasts is easy if anaerobic conditions can be provided. Otherwise, the industry has to resort to manual removal of the film from the brine surface, either by skimming or by flagellation.