Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice

Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice. We examined whether the retroviral envelope antigen, gp70, is a major nephritogenic antigen in ddY mice, a murine model of spontaneous mesangial glomerulonephritis associated with IgA and IgG deposition. Immunofluorescence microscopy revealed that the mesangial gp70 deposition increased with age in mice over 24 weeks old, as did the IgG and IgA deposits. Immunoelectron microscopy demonstrated the reaction products of gp70 superimposed on the electron dense deposits in the mesangial matrix. Various amounts of serum gp70 were detected in mice as young as 12 weeks without any apparent increase with age. There was no correlation between the serum level of gp70 and the extent of the glomerular gp70 deposition, whereas mice with heavier IgA deposition had higher mean levels of serum IgA. The absorption test demonstrated that significant amounts of serum gp70 composed immune complexes in 40 week-old ddY mice developing glomerulonephritis; however, this bound form of gp70 was not observed in 12 week-old mice without glomerulonephritis. Systemic examinations by immunofluorescence staining showed that gp70 was mainly localized in various lymphoid tissues. These findings suggest that the gp70 antigen, mostly derived from lymphoid cells, may circulate as immune complexes and accumulate in the mesangial area, thus contributing to the development of glomerulonephritis in these mice. In addition, the pathogenic role of the increased IgA production in these mice was discussed

Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change

Beneficial effect of donor-specific blood transfusions (DST) on living-related kidney allograft survival.

The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.</p

The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases

Misfolding and abnormal aggregation of proteins in the brain are implicated in the pathogenesis of various neurodegenerative diseases including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. In the polyQ diseases, an abnormally expanded polyQ stretch triggers misfolding and aggregation of the disease-causing proteins, eventually resulting in neurodegeneration. In this paper, we introduce our therapeutic strategy against the polyQ diseases using polyQ binding peptide 1 (QBP1), a peptide that we identified by phage display screening. We showed that QBP1 specifically binds to the expanded polyQ stretch and inhibits its misfolding and aggregation, resulting in suppression of neurodegeneration in cell culture and animal models of the polyQ diseases. We further demonstrated the potential of protein transduction domains (PTDs) for in vivo delivery of QBP1. We hope that in the near future, chemical analogues of aggregation inhibitor peptides including QBP1 will be developed against protein misfolding-associated neurodegenerative diseases

Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears

BACKGROUND: Rotator cuff tears (RCTs) are often associated with severe shoulder pain. Non-steroidal anti-inflammatory drugs, not recommended for long-term use, do not effectively manage RCT-induced pain, resulting in reduced quality of life. To improve management, a better understanding of the fundamental properties of RCT pain is needed. Here, we aimed to compare the expression levels of nerve growth factor (NGF) and cyclooxygenase-2 (COX-2) mRNA in the synovial tissues of patients with RCT-induced pain and patients with non-painful recurrent shoulder dislocation (RSD). METHODS: The study included 32 patients with RCT who underwent arthroscopic rotator cuff repair and 28 patients with non-painful RSD who underwent arthroscopic Bankart repair. Synovial tissue samples were harvested from subacromial bursa and rotator interval of RCT patients and from the rotator interval of RSD patients. Samples were analyzed quantitatively expression levels for NGF and COX2 mRNA and NGF protein. RESULTS: NGF mRNA and protein levels were significantly higher in the rotator interval of RCT patients than in the rotator interval of RSD patients (p = 0.0017, p = 0.012, respectively), while COX2 mRNA levels did not differ significantly between the two patient groups. In RCT patients, COX2 mRNA was more highly expressed in the rotator interval than in the subacromial bursa (p = 0.038), whereas the mRNA and protein levels of NGF did not differ between the two tissues. The expression of NGF mRNA in the synovium of the rotator interval was significantly correlated with the numeric rating scale of pain (ρ = 0.38, p = 0.004). CONCLUSION: NGF mRNA and protein levels were elevated in patients with painful RCT compared with those in patients with non-painful RSD, whereas COX-2 levels were comparable in the two patient groups. These findings provide insights into novel potential strategies for clinical management of RCT

Sensing applications of synthetic transport systems

This feature article offers a comprehensive account of a decade of research devoted to the combination of the grand sensing principles with synthetic transport systems that act in lipid bilayers. Differential sensing, that is pattern generation and pattern recognition, is exemplified with an artificial nose. The aptamer version of immunosensing is realized with sticky-end polymers of DNA double helices for both signal generation and signal transduction. Biosensing, that is the use of enzymes for signal generation, is exemplified first with an artificial tongue and then expanded to analytes such as cholesterol, phytate or polyphenols. Enjoyable also for the general reader, we hope that this account will inspire supramolecular organic as well as analytical, physical and biological chemists