Cardiolipin, conformation, and respiratory complex-dependent oligomerization of the major mitochondrial ADP/ATP carrier in yeast.

The phospholipid cardiolipin has pleiotropic structural and functional roles that are collectively essential for mitochondrial biology. Yet, the molecular details of how this lipid supports the structure and function of proteins and protein complexes are poorly understood. To address this property of cardiolipin, we use the mitochondrial adenosine 5'-diphosphate/adenosine 5'-triphosphate carrier (Aac) as a model. Here, we have determined that cardiolipin is critical for both the tertiary and quaternary assembly of the major yeast Aac isoform Aac2 as well as its conformation. Notably, these cardiolipin-provided structural roles are separable. In addition, we show that multiple copies of Aac2 engage in shared complexes that are largely dependent on the presence of assembled respiratory complexes III and IV or respiratory supercomplexes. Intriguingly, the assembly state of Aac2 is sensitive to its transport-related conformation. Together, these results expand our understanding of the numerous structural roles provided by cardiolipin for mitochondrial membrane proteins.

Retrospective analysis of an efficient peripheral blood stem cell collection and the relation between infused cell dose and clinical outcome in patients with malignant lymphoma and multiple myeloma.

INTRODUCTION: Etoposide (VP16) is a drug used not only for the treatment of lymphoma but also for the collection of peripheral blood stem cells (PBSCs). We analysed the efficacy and adverse effects of collecting PBSCs and the relation between the infused cell dose and the clinical outcome in lymphoid malignancies. METHOD: Investigating 30 patients with non-Hodgkin's lymphoma, one patient with Hodgkin's lymphoma, and five patients with multiple myeloma, we compared the effects of several doses of etoposide with those of CHOP or CHOP-like treatments or salvage treatments. We also analysed the relation between the amount of CD34(+) cells collected (above or below 5.0 × 10(6) /kg/day) and prognosis of these patients. RESULTS: We found the collected cell count to be highest in patients treated with 500 mg/m(2) of VP16 and lowest in those not treated with VP16 (P = 0.0073). A CD34(+) cell count above 100/µL on the collection day indicates that the target amount of CD34(+) cells (4.0 × 10(6) /kg) can be readily obtained and was reached most rapidly by the patients who had received 500 mg/m(2) of VP16 (P = 0.01). The longer duration of neutropenia in those patients (P = 0.000006) resulted in longer antibiotic treatment (P = 0.0052). Both progression-free survival (PFS) and overall survival (OS) were better for the patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day (P = 0.087 for PFS and P < 0.033 for OS). CONCLUSION: We show here that 3 days of VP16 at 500 mg/m(2) was useful for the collection of PBSCs and that patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day survived longer than those who yielded less.

[Catamenial pneumothorax with breast cancer treated successfully by goserelin acetate].

A 47-year-old woman with 4 episodes of right pneumothorax related to onset of menstruation was reported. A month ago, she was undergone breast conserving resection for breast cancer. She had recurrent right pneumothorax a month later and operation was performed. Thoracoscopy revealed the presence of multiple fenestrations in the right diaphragm. Thoracoscopic partial resection of the diaphragm was performed. Histopathological findings of the lesion showed spindle cells with hemosiderosis. Immunohistochemistry showed that spindle cells were estrogen receptor (ER) positive and progesterone receptor (PgR) positive, compatible with endometriosis. She was treated by tamoxifen and goserelin acetate for breast cancer and endometriosis. Two years later, gonadotropin releasing hormone (GnRH) analogue was converted from goserelin acetate to leuprorelin acetate. She was diagnosed as having recurrence of right pneumothorax 17 months later and was treated with a chest tube. Additionally, GnRH analogue was re-converted to goserelin acetate. Since then, she has been asymptomatic free for 18 months. A catamenial pneumothorax is rare disease with difficulty of diagnosis and treatment We herein report a case of the disease that was treated successfully by goserelin acetate.

Lymphocyte responsiveness to phytohemagglutinin (PHA) and serum inhibitory effect in patients with gastric cancer.

The in vitro lymphocyte response to PHA was determined in patients with gastric cancer in various stages prior to the surgical treatment. The lymphocyte responsiveness in the presence of homologous pooled AB serum in patients of stages II, III and IV were markedly reduced as compared with that in healthy controls (stages II, III; p less than 0.05, stage IV; p less than 0.01). Inhibition of normal lymphocyte responsiveness to PHA by serum from patients in stages III and IV were statistically significant only in the advanced stage. It was concluded that the suppression of the immune response in the early stage of gastric cancer was mainly due to the impairment of lymphocyte itself, which advanced with the progress of the stage and was modified by the serum inhibitory effect in advanced stages. In patients with advanced cancer, the higher was the lymphocyte responsiveness to PHA and PWM prior to the initial treatment, the more effective was the immunotherapy. This shows that the indication of the immunotherapy in patients with advanced cancer could be initiated. Furthermore, the correlation between the lymphocyte responsiveness to PHA and the clinical results of immunotherapy was discussed.