Recent advances in video‐assisted thoracoscopic surgery for lung cancer

As a result of increased use of CT in both screening and daily practice, the number of early lung cancers has increased enormously. Surgeons pursue both curativity and reduced invasiveness in treating patients with early stage lung cancer; therefore, minimally invasive operations, such as video‐assisted thoracoscopic surgery (VATS) lobectomy are now being routinely performed. Most previous reports have shown that there is no difference in mortality and local recurrence between open surgery and VATS in stage I patients. However, surgeons' improved technical experience and patients' demands could soon make VATS lobectomy the operative method of choice for early stage lung cancer. Moreover, the indications for VATS are expanding to encompass complex procedures such as segmentectomy or sleeve resection. Training and dissemination of the technique and the monitoring of outcomes are necessary.     

Lymph node lesion in infectious mononucleosis showing geographic necrosis containing cytologically atypically B-cells. A case report

Lymph node lesions in infectious mononucleosis (IM) show a marked histological diversity and may occasionally be confused with malignant lymphoma. We report on a rare case of IM showing geographic lymph node necrosis as well as angiocentric lymphoproliferative lesions, and containing numerous centroblasts, immunoblasts and Reed-Sternberg (RS)-like cells. The patient was a 40-year-old Japanese man with signs and symptoms of classical IM. This was later confirmed serologically, but the necrotic area comprised 50% of a cervical lymph node. The large lymphoid cells, including RS-like cells, were CD3-, CD5-, CD15-, CD20+, CD30+, CD45RO-, CD79a+, LMPI+, and EBNA2+. In situ hybridization study also disclosed that these cells were associated with Epstein-Barr virus (EBV). The patient was disease free during a follow-up of 15 years. Although the classical IM syndrome rarely shows a close resemblance to lymphomatoid granulomatosis of the lymph node or to EBV+ B- cell lymphoproliferative disorders associated with an immunodeficient state on histology, it is important for pathologists to be aware of this type of lesion in diagnostic practice.     

Brain lipid hydroperoxide level increases in senescence-accelerated mice at an early age

We previously reported that the levels of lipid hydroperoxides, one of oxidative stress markers, in the brain and peripheral organs such as liver, heart, and lung are significantly higher in senescence accelerated-prone 8 mice (SAMP8) than in their controls, senescence accelerated-resistant mice (SAMR1), at 3, 6, and/or 9 months of age. To ascertain the exact age at which the lipid hydroperoxide levels increase in SAMP8, we measured them in the brain and liver of SAMP8 and SAMR1 at both 1 and 2 months of age. At 1 month of age, there was no significant inter-strain difference in the levels in brain or liver. However, in SAMP8 both levels were significantly greater at 2 months of age than at 1 month of age, but no such difference was detected for SAMR1. The present results suggest that SAMP8 are exposed to elevated levels of oxidative stress from an early age (2 months old), and that this may be a cause of the senescence-related impairments and degeneration in the brain and peripheral tissues (such as liver, heart, and lung) seen in this strain.     

Stenosis of the bicuspid aortic valve with systemic lupus erythematosus

We herein present a rare case of severe aortic valve stenosis with a bicuspid valve in a patient with systemic lupus erythematosus. The symptoms resulted from aortic valve stenosis, such as chest pain, dyspnea and syncope, which subsided after the insertion of an intra-aortic balloon pump. Thereafter, a calcified bicuspid aortic valve was successfully replaced with a mechanical valve. The pathological findings of the resected valve included irregular fibrotic thickening and marked calcification without any vegetation or thrombus formation. The efficacy of an intra-aortic balloon pump for the relief of symptoms associated with severe aortic valve stenosis indicates its usefulness for such critically ill patients prior to undergoing valvular surgery.     

Critical role of activation-inducible lymphocyte immunomediatory molecule/inducible costimulator in the effector function of human T cells: a comparative in vitro study of effects of its blockade and CD28 blockade in human beings and monkeys

Activation-inducible lymphocyte immunomediatory molecule (AILIM; also referred to as inducible costimulator, ICOS) is the third homolog of the "professional" costimulatory molecule, CD28. To date, the characteristics and role of AILIM/ICOS, especially in effector function of T cells, have been determined through numerous studies in vitro and in vivo using mice. Considering potential differences among species, whether the AILIM/ICOS blockade acts as an efficacious immunomodulator for human diseases remains to be elucidated. In the present study, ability of AILIM/ICOS blockade to modulate immune responses of human and monkey cells was investigated using a fully human antibody (JTA-009), comparing the effect of CD28 blockade. JTA-009 blocked the response of human and monkey T cells co-stimulated with anti-CD3 and AILIM/ICOS ligand, B7h. AILIM/ICOS and CD28 blockade both inhibited human mixed lymphocyte reaction in different fashions, as well as cytokine production in T helper (Th) 1-/Th2-type recall responses. In monkeys however, CD28 blockade by CTLA4-Ig effectively prevented mixed lymphocyte reaction to a greater extent than AILIM/ICOS blockade. These results suggest that AILIM/ICOS blockade is valuable for suppressing both primary allogenic response and recall responses of T cell in human beings, and that there are differences between human and monkey use preferences for costimulatory molecules.     

Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism

Huntington's disease (HD) is a fatal neurodegenerative disorder. Despite a tremendous effort to develop therapeutic tools in several HD models, there is no effective cure at present. Acidosis has been observed previously in cellular and in in vivo models as well as in the brains of HD patients. Here we challenged HD models with amiloride (Ami) derivative benzamil (Ben), a chemical agent used to rescue acid-sensing ion channel (ASIC)-dependent acidotoxicity, to examine whether chronic acidosis is an important part of the HD pathomechanism and whether these drugs could be used as novel therapeutic agents. Ben markedly reduced the huntingtin-polyglutamine (htt-polyQ) aggregation in an inducible cellular system, and the therapeutic value of Ben was successfully recapitulated in the R6/2 animal model of HD. To reveal the mechanism of action, Ben was found to be able to alleviate the inhibition of the ubiquitin-proteasome system (UPS) activity, resulting in enhanced degradation of soluble htt-polyQ specifically in its pathological range. More importantly, we were able to demonstrate that blocking the expression of a specific isoform of ASIC (asic1a), one of the many molecular targets of Ben, led to an enhancement of UPS activity and this blockade also decreased htt-polyQ aggregation in the striatum of R6/2 mice. In conclusion, we believe that chemical compounds that target ASIC1a or pharmacological alleviation of UPS inhibition would be an effective and promising approach to combat HD and other polyQ-related disorders.