Arthrodesis of knee joint by vascularized fibular graft

Knee arthrodesis has been performed in 17 patients using vascularized fibular graft (VFG); 15 of them could be followed more than 1 year. Twelve were bone defect following tumor resection, two were traumatic bone defect, and one was intractable traumatic non-union. Three types of graft were performed; single VGF as supplement (Type I) in 5 cases, double VFG for femoral defect (Type II) in 8 cases, and double VFG for tibial defect (Type III) in 4 cases. Bone union was achieved in all cases except one. The average time to primary bone union was 4.7 months. Hypertrophy of the graft was observed significantly in some of Type II and in all of Type III. VGF is a useful method for knee fusion in patients with a large bone defect or with an intractable non-union. © 1996 Wiley-Liss, Inc.     

Nanoarchitectonics on living cells

In this review article, the recent examples of nanoarchitectonics on living cells are briefly explained. Not limited to conventional polymers, functional polymers, biomaterials, nanotubes, nanoparticles (conventional and magnetic ones), various inorganic substances, metal–organic frameworks (MOFs), and other advanced materials have been used as components for nanoarchitectonic decorations for living cells. Despite these artificial processes, the cells can remain active or remain in hibernation without being killed. In most cases, basic functions of the cells are preserved and their resistances against external assaults are much enhanced. The possibilities of nanoarchitectonics on living cells would be high, equal to functional modifications with conventional materials. Living cells can be regarded as highly functionalized objects and have indispensable contributions to future materials nanoarchitectonics.

We can introduce functional structures with various components on a living cell as if architectures were constructed on material surfaces.     

Effects of α1-adrenergic receptor antagonists on the development and progression of urothelial cancer

We recently demonstrated that silodosin, a selective α₁-blocker often prescribed for the symptomatic treatment of benign prostatic hyperplasia (BPH), could inactivate a c-fos proto-oncogene regulator ELK1 in bladder cancer cells possessing a functional androgen receptor (AR). However, the clinical impact of α₁-blockers on the development and progression of bladder cancer remained poorly understood. In the present study, we investigated if α₁-blockers clinically used, including silodosin, tamsulosin, and naftopidil, could prevent the neoplastic/malignant transformation and cell growth, using non-neoplastic urothelial SVHUC sublines with carcinogen/MCA challenge and bladder cancer lines, respectively. Bladder cancers in men treated with silodosin, tamsulosin, or naftopidil for their BPH were then compared. Silodosin at 1-10 µM significantly inhibited the neoplastic transformation of MCA-SVHUC-AR cells, but not that of AR-negative MCA-SVHUC-control cells. In MCA-SVHUC-AR, silodosin significantly reduced the expression levels of oncogenes (c-fos/NF-κB1) and induced those of tumor suppressors (p27/PTEN). However, tamsulosin (up to 1 µM) or naftopidil (up to 10 µM) failed to significantly inhibit the neoplastic transformation of AR-positive or AR-negative urothelial cells. Similarly, cell proliferation/migration of AR-positive bladder cancer lines was considerably inhibited only by silodosin. Meanwhile, the incidence of bladder cancer in patients with silodosin [49/540 (9.1%)] was marginally lower, compared to those with tamsulosin [64/523 (12.2%); P=0.094] or tamsulosin or naftopidil [64+28/523+236 (12.1%); P=0.082]. There were no significant differences in tumor grade/stage among the 3 cohorts. Outcome analysis revealed lower risks for disease progression of non-muscle-invasive bladder tumors in the silodosin group than in the naftopidil group (P=0.011) or tamsulosin+naftopidil groups (P=0.035). Similarly, silodosin patients with muscle-invasive tumor had lower risks for disease progression, compared with tamsulosin (P=0.006) or tamsulosin+naftopidil (P=0.028) patients. Multivariate analysis further showed that silodosin treatment in those with non-muscle-invasive tumor was associated with improved progression-free survival, compared with naftopidil (hazard ratio=0.086; 95% confidence interval=0.008-0.905; P=0.041) or tamsulosin/naftopidil (hazard ratio=0.128; 95% confidence interval=0.016-1.036; P=0.054) treatment. Our in vitro studies thus indicate that both urothelial tumorigenesis and tumor growth are inhibited by silodosin, but not by tamsulosin or naftopidil. Clinical data further suggest that even pharmacological doses (e.g. 0.1 µM) of silodosin contribute to preventing bladder cancer progression.     

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: Verification by optical coherence tomography

Background

Relationships between plaque morphology on optical coherence tomography (OCT) and biomarker levels in the patients with acute coronary syndrome (ACS) have not been fully investigated.

Methods

ACS patients (n = 128) were prospectively enrolled and their plasma levels of soluble lectin-like oxidized LDL receptor-1 (sLOX-1), high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity troponin T (hs-TnT) were measured. Another set of 20 patients with stable angina pectoris (SAP) without plaque rupture or erosion served as controls. Among 128 ACS patients, 75 patients underwent OCT procedure to evaluate culprit plaque morphology, and were categorized into two groups; ACS with plaque rupture (ruptured ACS; R-ACS, n = 54) and ACS without plaque rupture (non-ruptured ACS; N-ACS, n = 21).

Results

Levels of sLOX-1 (p < 0.001), hs-CRP (p = 0.048) and hs-TnT (p < 0.001) were significantly higher in R-ACS than SAP. Levels of sLOX-1 were also significantly higher in R-ACS than in N-ACS (p < 0.001); whereas levels of hs-CRP (p = 0.675), as well as those of hs-TnT (p = 0.055), were comparable between R-ACS and N-ACS. Comparison of receiver operating characteristic (ROC) curves among sLOX-1, hs-CRP and hs-TnT to differentiate R-ACS from N-ACS revealed that the area under the curve (AUC) values of sLOX-1, hs-CRP and hs-TnT were 0.782, 0.531 and 0.643, respectively. ROC curves, generated for these biomarkers, to differentiate ACS with thin-cap fibroatheroma (TCFA) from those without demonstrated that the AUC values of sLOX-1, hs-CRP and hs-TnT were 0.718, 0.506 and 0.524, respectively.

Conclusion

sLOX-1, but not hs-CRP or hs-TnT, can differentiate ACS with plaque rupture from those without, and ACS with TCFA from those without.     

The natural history of maternal immunization against foetal platelet alloantigens

Foetomaternal alloimmune thrombocytopenia (FMAIT) occurs when maternal antibodies of an antigen-negative mother cause destruction of sensitized foetal platelets. In Caucasian populations, 6-12% of human platelet antigen (HPA)-1a-negative women develop anti-HPA-1a, and the incidence of clinically affected cases is estimated to be 10-20% of immunized women. This study was performed in order to elucidate the rate of maternal immunization, incidence of FMAIT and the likely outcome of the condition in Asians. Excluding two or more pregnancies during the period, serum samples from 24 630 pregnant women, mainly Japanese, were screened for antibodies against platelet alloantigens by means of mixed passive haemagglutination (MPHA) (Anti-HPA-MPHA, Olympus, Tokyo). Antibodies were detected in 0.91% (223/24 630) of the women's samples and the immunization rate was correlated with the number of pregnancies. Antibody specificity included anti-HPA-4b (49), anti-HPA-5a (three), anti-HPA-5b (168), anti-HPA-4b + 5b (one) and anti-Nak(a) (CD36) (two). No alloimmunization was observed within the HPA-1, HPA-2, HPA-3 or HPA-6 systems. Among HPA-4b- or HPA-5b-negative women, 24% or 14% estimated, respectively, had antibodies and 26% (10/38) or 10% (12/125) of neonates, respectively, born to these mothers developed thrombocytopenia. Two neonates born to mothers having anti-HPA-4b developed generalized purpura. No cases of intracranial bleeding or death due to FMAIT were recorded. Generalized purpura due to FMAIT occurs in one in 9359 (95% CI: 1 in 77 519-1 in 2591) pregnancies solely because of HPA-4b incompatibility.     

Surgical management of tachyarrhythmias

In this study of surgical procedures for various tachyarrfiythmias, Wolff-Parkinson-White syndrome comprised most of the cases. An endocardial approach was used to ablate accessory pathways. Additional use of cryocoagulation after surgical incision of the atrium, previously routinely performed, is at present only done occasionally for septal accessory pathways.

Ventricular tachycardia (VT) was the next most frequent condition. The surgical procedures for ischemic and nonischemic VTs are completely different, although both are based on the principle of complete electrophysiologic mapping. For ischemic VT, surgery consists of resection of the left ventricular aneurysm and excision or cryocoagulation of the endocardium, or both. For nonischemic VT, either excision of the entire thickness of the myocardium (2.0 × 2.5 cm on average) at the earliest excitation site of the right ventricle and cryocoagulation of the area of delayed potential or only incision and cyrocoagulation of the left ventricle were performed to avoid reduction of the left ventricular cavity.

Ectopic atrial tachycardia was cured by excision of the earliest excitation site without use of a heart-lung machine, when the focus was located in the atrial free wall. Other successful treatments were of reentrant atrial tachycaroia by cryocoagulation, atrial flutter by cryocoagulation of impulse pathways at the coronary sinus and around the atrioventricular node, and a new surgery for atrial fibrillation and flutter, which retained sinus rhythm. Johnson's procedure was used for surgical ablation of atrioventricular nodal reentrant tachycardia.     

Localization of verotoxin receptors in nervous system

We use immunohistochemistry to show the existence of verotoxin receptor in small sensory neurons in DRG of human, rabbit, rat and mouse. In capillary in nervous system, the verotoxin receptor exists in human and rabbit, but the receptor could not be demonstrated in rat and mouse, by this method. The receptors in sensory neuron of rat and in capillary in rabbit brain are determined as galactosylglobotriaosylceramide (GalGb3) and globotriaosylceramide (Gb3,), respectively. Although verotoxin was reported to bind to glycolipid receptors that possess the terminal disaccharide Galalpha1-4Galbeta (galactobiose), the binding to toxin to galabiosylceramide was half of that of GalGb3 which has galactobiose internally.     

Pathogenic role of ganglioside metabolism in neurodegenerative diseases

Ganglioside metabolism is altered in several neurodegenerative diseases, and this may participate in several events related to the pathogenesis of these diseases. Most changes occur in specific areas of the brain and their distinct membrane microdomains or lipid rafts. Antiganglioside antibodies may be involved in dysfunction of the blood–brain barrier and disease progression in these diseases. In lipid rafts, interactions of glycosphingolipids, including ganglioside, with proteins may be responsible for the misfolding events that cause the fibril and/or aggregate processing of disease‐specific proteins, such as α‐synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease, and copper‐zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting ganglioside metabolism may represent an underexploited opportunity to design novel therapeutic strategies for neurodegeneration in these diseases. © 2014 Wiley Periodicals, Inc.     

The Asthma Control Test,Japanese Version (ACT-J) as a Predictor of Global Initiative for Asthma (GINA) Guideline-Defined Asthma Control: Analysis of a Questionnaire-Based Survey

BackgroundThe 2006 Global Initiative for Asthma (GINA 2006) guidelines emphasize the importance of evaluating the control rather than the severity of asthma. The Asthma Control Test (ACT) is well known to be an excellent tool for evaluating asthma control in the clinical setting. This study aimed to evaluate the ACT, Japanese version (ACT-J) as a predictor of asthma control as defined by the GINA 2006 guidelines in actual clinical practice.MethodsA cross-sectional analysis comparing the ACT-J score and GINA classification of asthma control among 419 patients of primary care physicians and specialists was performed using the data from a 2010 questionnaire-based survey conducted by the Niigata Asthma Treatment Study Group.ResultsThe optimal cut-off point of the ACT-J score for predicting GINA-defined asthma control was 23, with ACT-J scores of ≥ 23 and ≤ 22 predicting controlled and uncontrolled asthma with area under the receiver operating characteristics curve values of 0.76 [95% confidence interval (CI): 0.72-0.81] and 0.93 [95% CI: 0.900.97], respectively.ConclusionsACT scores of ≥ 23 and ≤ 22 are useful for identifying patients with controlled and uncontrolled asthma, respectively, as defined by GINA 2006, and the latter is more strongly predictive than the former. The reason for the higher cut-off point of the ACT-J relative to other versions of the ACT is unclear and warrants further investigation.