Transannular patch repair of double-outlet right ventricle, {s,d,l}, and single right coronary artery

AbstractJ Thorac Cardiovasc Surg 1999;117:622-

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS <it>in vivo</it>

Abstract Background An episode of peripheral immune response may create long-lasting alterations in the neural network. Recent studies indicate a glial involvement in synaptic remodeling. Therefore it is postulated that both synaptic and glial changes could occur under the peripheral inflammation. Results We tested this possibility by in vivo two-photon microscopy of dendritic spines after induction of a peripheral immune response by lipopolysaccharide (LPS) treatment of mice. We observed that the spines were less stable in LPS-treated mice. The accumulation of spine changes gradually progressed and remained low over a week after LPS treatment but became significantly larger at four weeks. Over eight weeks after LPS treatment, the fraction of eliminated spines amounted to 20% of the initial population and this persistent destabilization resulted in a reduction of the total spine density. We next evaluated glial activation by LPS administration. Activation of microglia was confirmed by a persistent increase of Iba1 immunoreactivity. Morphological changes in microglia were observed two days after LPS administration and were partially recovered within one week but sustained over a long time period. Conclusions These results indicate long-lasting aggravating effects of a single transient peripheral immune response on both spines and microglia. The parallel persistent alterations of both spine turnover and the state of microglia in vivo suggest the presence of a pathological mechanism that sustains the enhanced remodeling of neural networks weeks after peripheral immune responses. This pathological mechanism may also underlie long-lasting cognitive dysfunctions after septic encephalopathy in human patients.</p

Impaired Urea Accumulation in the Inner Medulla of Mice Lacking the Urea Transporter UT-A2

Urea transporter UT-A2, the major urea transporter of the thin descending limb of the loop of Henle in short loop nephrons, has been implicated in urea recycling in the medulla, thereby producing concentrated urine. To investigate the physiological role of UT-A2 in vivo, we generated UT-A2-selective knockout mice by deleting the UT-A2 promoter. Western analysis, immunohistochemistry, and quantitative reverse transcription-PCR were used to confirm the specific deletion of UT-A2 with preservation of other UT-A transporters. Compared to wild-type mice, differences in the urine outputs of UT-A2(−/−) mice consuming a normal protein diet (20% protein) were not observed under normal conditions or with dehydration. Likewise, impairment of urea accumulation in the inner medulla of UT-A2(−/−) mice was not observed. On a low-protein diet (4% protein), however, significantly reduced maximal urine osmolality was observed in dehydrated UT-A2(−/−) mice compared to wild-type littermates (2,500 mosmol versus 3,450 mosmol, respectively). A significant reduction in urea accumulation in the inner medulla was also observed in UT-A2(−/−) mice; however, differences in Na(+) and Cl(−) accumulation were not observed. Thus, UT-A2 is important for maintaining a high concentration of urea in the inner medulla when urea supply to the kidney is limited

Management of future liver remnant: strategies to promote hepatic hypertrophy

The resectability of hepatocellular carcinoma (HCC) has been assessed based on the liver functional test, the liver volume of the future liver remnant (FLR), and, more recently, the functional liver volume of FLR. Liver volume is estimated via multi-detector computed tomography and three-dimensional image visualization technologies, and functional liver volume is investigated via 99mTc-galactosyl human serum albumin scintigraphy, 99mTc-mebrofenin hepatobiliary scintigraphy, and gadoxetic acid-enhanced magnetic resonance imaging. Several special techniques have been developed to promote FLR hypertrophy, thus allowing for safe hepatectomy. As an interventional technique, portal vein embolization (PVE) is essential, and, along with transarterial chemoembolization or hepatic vein embolization, this is beneficial in promoting a much larger FLR. Dual embolization is recommended for patients with very small FLR or with PVE failure. Radioembolization by Yttrium-90 microspheres (i.e., radiation lobectomy) can help in achieving FLR hypertrophy and has an anticancer effect on HCC. Transarterial chemoembolization on PVE has a similar anticancer effect. Surgical procedures, such as two-stage hepatectomy as well as associated liver partition and portal vein ligation for staged hepatectomy, are somewhat invasive. Therefore, they should be applied as a salvage procedure for patients with HCC who had inadequate response to the interventional approach. However, the best approach should be selected mainly based on the functional volume of FLR and the patients’ condition; in addition, the resources of each facility should be considered

肺に広範なCa沈着をきたした1症例

長期血液透析療法の合併症の1つにCa代謝異常があり，腎性骨異栄養症とよばれる骨軟化症，線維性骨炎，骨多孔症と転移性石灰化がみられたりする。この転移性石灰化は骨や関節内および周囲組織にかぎらず, 動脈，角膜，心，腎，肝，胃粘膜などの軟部組織にも起りうる。今回頑固な咳敗を主訴とした26歳の男子透析患者に，99mTc-polyphosphate をつかつて全身のシンチグラフィを行なったところ，肺実質部で一様な高度の99mTc-polyphosphateのとりこみがみられた.胸部X線像に注意すると気管支幹，末梢気管支，さらに肺胞部にも点状石灰化病変が広範にみられ，これが頑固な咳嗽の原因となったと考えられた. 血清Ca，P濃度をふりかえって調べたところ血清Ca値は10.4-9.3mg %と正常値であったが，血清P値は10.5-9.8mg% と上昇していたことが判明した.直ちにアルミゲル3.0g，3 x 分の経口投与を開始したところCa値は1l.4-10.2 mg%と僅かに上昇したが, p値は4.4-3.0mg % と著明に正常化し， 投与開始後2カ月で咳歎も消失し左手関節周囲の疾痛，腫張も消失した。その後経過をみてきたが，肺実質部の点状石灰化陰影大幅に消失改善し, 1975年9月には正常男子の出生をえて1978年9月現在，週3回の血液透析で元気に社会復帰している1症例を報告し文献的検討を行なった。Recent progress in the treatment of chronic renal failure such as hemodialysis and renal transplantation have made the longer survival and rehabilitation of the patients possible. On the other hand, various complications have become the matter of problem in which metabolic disorder is one of the importants. Here reported is a case of diffuse interstitial pulmonary metastatic calcification