Induction of Apoptosis Reduces Immunogenicity of Human T-Cell Lines in Mice

Apoptotic cells, e.g. postinflammatory neutrophils, were reported to be engulfed by phagocytes without induction of an inflammatory response. We investigated the humoral immune response of BALB/c mice after repeated injection of viable or apoptotic human T cells. Following interleukin-2 (IL-2) deprivation, phytohaemagglutinin (PHA)/IL-2 expanded human T-cell lines were irradiated with UV-B light to induce apoptosis, confirmed by propidium iodide staining of Triton X-100-lysed cells. Indirect immunofluorescence was used to detect antilymphocyte antibodies 7 days after each injection. We found high levels of antilymphocyte antibodies in all animals immunized with viable T cells, whereas animals injected with apoptotic cells showed a significantly reduced humoral immune response. We conclude that apoptotic cells induce poor xenoreactive T-cell responses when compared with viable cells.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.      

Renale und enterale Elimination der Koproporphyrin-Isomeren bei Rotor-Syndrom

Summary Urinary and fecal total, isomer I, and isomer III coproporphyrin excretion of a Rotor's syndrome patient and his family were determined. The proprositus showed increased urinary total coproporphyrin excretion (248 µg/24 h) and a shift of the coproporphyrin isomer I/III relation (70%/30%). The propositus's father and two siblings also had elevated renal excretion of coproporphyrin I. Total coproporphyrin excretion was enhanced only in the propositus's father and one sibling, while being normal in another sibling. All family members that could be investigated showed considerably decreased fecal porphyrin excretion. In Rotor's syndrome porphyrin excretion is mainly renal. The coproporphyrin isomer I/III relation is shifted towards isomer I. Phenotypically normal relatives with normal bilirubin plasma levels may have alterations in both their renal and enteral coproporphyrin excretion.

Herrn Professor Dr. med. N. Zöllner zum 65. Geburtstag gewidmet     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.