Marked changes in the ribonuclease activity of mature and immature gonads of sea urchins Hemicentrotus pulcherrimus and Anthocidaris crassispina

It is generally impossible to sort male and female sea urchins before they reach maturity, i.e., while they are still in the immature stage. The ribonuclease (RNase) activity of the gonads of immature stage sea urchins consistently shows a constant activity level. Comparison of the RNase activity of the gonads of mature male and female Hemicentrotus pulcherrimus and Anthocidaris crassispina species at pH 5.0 showed that while its mean specific activity in the immature stage of female H. pulcherrimus increased rapidly from 7.35 to 62.79 units/mg, its activity in male H. pulcherrimus decreased from 7.35 to 1.90 units/mg. The same phenomenon was observed in A. crassispina. Based on its optimal pH, substrate specificity, and heat stability the RNase that exhibited these changes was determined to be an enzyme of the RNase T2 type. This enzyme is also thought to exert an influence on sex determination in sea urchins.     

Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy

Background

Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736–742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities.

Materials and methods

As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy.

Results

A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800–2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 ± 6.8 versus 5.3 ± 5.2 years; P = 0.02), amount of proteinuria (1.5 ± 1.6 versus 0.8 ± 0.8 g/day; P < 0.0001), serum creatinine (0.99 ± 0.40 versus 0.87 ± 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.’s prognostic score (37.4 ± 17.8 versus 28.1 ± 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(?0.0330) × (age) + (0.4772) × log (amount of proteinuria) ? (0.0273) × (hematuria grade: 0, 1, 2, and 3) + (0.7604) × (pathological grade: 1, 2, 3, and 4) ? 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than ?0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76).

Conclusion

TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.     

Association of TP53 and MDM2 polymorphisms with survival in bladder cancer patients treated with chemoradiotherapy

Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy- and radiotherapy-associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine > proline) and MDM2 (SNP309, T > G) were genotyped using PCR-RFLP, and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T / G + G / G genotypes had improved cancer-specific survival rates after CRT ( P  =   0.009). In multivariate analysis, the MDM2 T / G + G / G genotypes, and more than two of total variant alleles in TP53 and MDM2 , were independently associated with improved cancer-specific survival ( P  =   0.031 and P  =   0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy-free survival ( P  =   0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy. ( Cancer Sci 2009; 100: 2376–2382)     

Two cases of inflammatory bowel disease with multiple myeloma

A significant increase has been reported in reticuloendothelial neoplasms in patients with inflammatory bowel diseases. We present two rare cases of multiple myeloma in patients with inflammatory bowel diseases. One was in a 58-year-old woman with ulcerative colitis, and the other was in a 59-year old woman with Crohn's disease. In both patients, multiple myeloma occurred during long-term observation of inflammatory bowel disease and during the inactive stage of intestinal inflammation. The multiple myeloma appeared to have resulted from monoclonal gammopathy of undertermined significance in both patients, and was diagnosed by characteristic serum and bone marrow findings. Our findings suggested that multiple myeloma should be particularly considered in women of middle or advanced age with ulcerative colitis or Crohn's colitis and serum monoclonal gammopathy. Received: October 29, 1998 / Accepted: April 4, 1999     

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema

Purpose  

To evaluate the geographic pattern of central retinal sensitivity and its resolution shortly after intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME).