Inhibitory effects of FUT-175, a new synthetic protease inhibitor, on intravascular hemolysis by human serum in mice

Effects of FUT-175, a new protease inhibitor, on intravascular hemolysis of mouse erythrocytes caused by intravenous injection of human serum was studied in mice. In in vitro experiments, unsensitized erythrocytes obtained from various species of animals were lysed with sera in EGTA-GVB-Mg++. After heat inactivation of sera at 50 degrees C for 30 min, hemolysis in EGTA-GVB-Mg++ was abolished, indicating loss of activity of the alternative complement pathway. FUT-175 inhibited the alternative complement pathway-mediated hemolysis with IC50 values of 1.3 X 10(-7) to 4.0 X 10(-7) M. Intravenous injection of human serum caused intravascular hemolysis of mouse erythrocytes in mice. No remarkable change was observed in the mice that were injected with heat-inactivated (56 degrees C, 30 min) human serum. Intravenous administration of FUT-175 at a dose of 3 or 10 mg/kg inhibited intravascular hemolysis of mouse erythrocytes regardless of whether it was administered before or after injection of human serum. These results indicated that FUT-175 prevents intravascular hemolysis of mouse erythrocytes through the inhibitory effect of both alternative and classical complement pathway.     

Inhibitory effect of bestatin on the growth of human lymphocytes.

Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes.     

Medium-term oncological and functional outcomes of hemi-gland brachytherapy using iodine-125 seeds for intermediate-risk unilateral prostate cancer

PURPOSETo examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer.METHODSWe recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2–3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated.RESULTSMedian follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease.CONCLUSIONSHemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer.     

Einfluss des Parasympathicusreizenden Giftes „Acetylcholin“ auf das Knochenmark

Ohne Zusammenfassung     

Reliability and validity of the Japanese Orthopaedic Association hip disease evaluation questionnaire (JHEQ) for patients with hip disease

BackgroundThe Japanese Orthopaedic Association hip disease evaluation questionnaire (JHEQ) was developed to evaluate the quality of life (QOL) in patients with hip disease. This questionnaire consists of three subscales: pain; movement; and mental. The purpose of this study was to assess the reliability and validity of the JHEQ for use as a clinical evaluation tool.MethodsWe investigated patients who visited the outpatient department at our hospital and affiliated hospital between April and May 2010. The study population comprised 286 patients (239 women) with a mean age of 56.8 years. The diagnosis was osteoarthritis of the hip in 230 patients, avascular osteonecrosis of the femoral head in 49 patients, and other conditions in 7 patients. The JHEQ questionnaire, the SF-36 questionnaire as a generic QOL scale, and the Oxford hip score (OHS) as a disease-specific scale, were filled out by the patient while waiting in the outpatient department.ResultsPearson’s correlation coefficients of 0.6 were observed between JHEQ pain and SF-36 bodily pain (BP) subscales, and between JHEQ movement and SF-36 physical functioning (PF) subscales. The JHEQ mental subscale correlated with SF-36 social functioning (SF) and BP subscales. A strong negative correlation was seen between JHEQ pain and OHS pain subscales (r = ?0.817). JHEQ movement subscale also showed a strong negative correlation with the OHS function subscale (r = ?0.715). These results indicated the convergent validity of JHEQ. The internal consistency of pain, movement, and mental subscales of JHEQ was satisfactory, indicated by Cronbach’s α coefficients of 0.92, 0.91, and 0.94, respectively. Each subscale also showed high test–retest reliability with intra-class correlation coefficients of 0.89, 0.93, and 0.85, respectively.ConclusionsWe determined the reliability and validity of JHEQ as a self-administered questionnaire that evaluates hip disease. JHEQ is useful as a tool for evaluating patients with hip disease.     

In vivo kinematics of mobile-bearing total knee arthroplasty during deep knee bending under weight-bearing conditions

Purpose  

Little is known about the in vivo kinematics of mobile-bearing total knee arthroplasty, especially at deep knee flexion under weight-bearing conditions.     

Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10)

An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs mapped to chromosomes 1 and 7 as probes. We found that the signal intensities of 2 centromere alphoid probes, D1Z7 on chromosome 1 and D7Z1 on chromosome 7, were almost invariably reduced on the derivative chromosome compared with those on their normal counterparts. These results suggest that this translocation results from the recombination between the 2 alphoids, which was further confirmed by fiber FISH experiments. Because the relative reduction in the intensities of D1Z7 and D7Z1 signals on the derivative chromosomes was highly variable among patients, it was estimated that the breakpoints in these patients were randomly distributed over several megabase pairs within each alphoid cluster except for its extreme end to the short arm. Our results provide a novel insight into the structural basis for generation of this translocation as well as its leukemogenic roles.     

Merosin-positive congenital muscular dystrophy with early orthopaedic problems in relation to Ullrich's disease

We report three patients with sporadic merosin-positive congenital muscular dystrophy (CMD) with torticollis and/or developmental dislocation of the hip in early childhood. Diagnosis of merosin-positive CMD was based on their clinical and dystrophic muscle biopsy findings. At the age 13 months, patient 1 was found to have developmental dislocation of both hips, which was surgically treated at 5 years. Patient 2 had severe torticollis and contracture of both hip joints which had been present since the neonatal period, and underwent repair of the torticollis at 2 years. Patient 3 was found to have developmental dislocation of the left hip at one month of age. Although she had generalized muscle hypotonia she learned to walk at 23 months. She had no facial muscle involvement nor contracture of joints, but had hyperlaxity of distal joints. Her muscle biopsy showed complete collagen VI deficiency immunohistochemically. In contrast to merosin-deficient CMD, merosin-positive CMD appears to be a group of heterogeneous diseases. Since collagen VI was reported to be defective in Ullrich's disease, patient 3 may be diagnosed as having Ullrich's disease but had no typical clinical characteristics of the disease. Further study is needed to identify the pathogenetic mechanism of congenital muscular dystrophy with early joint abnormalities to determine whether there is a primary abnormality of the connective tissue including collagen VI.