Age-related differences in IgA nephropathy

To clarify age-related differences in the characteristics of IgA nephropathy, we investigated 117 patients of all ages. The number of patients in the second decade of age was larger than that in the other age decades. There was no difference in sex in all age brackets. About one half of the patients under ten years of age presented as acute nephritis, but their prognosis was favorable. Patients over 10 years, most of whom were detected by chance, tended to have a greater degree of proteinuria, a lesser degree of creatinine clearance, a higher frequency of hypertension, and a higher level of serum cholesterol with age. Although the intensity of mesangial cell proliferation was not changed, the grade of glomerulosclerosis, interstitial change, and arteriosclerosis increased and the prognosis became poor as age advanced. Treatment with corticosteroids and antiplatelet agents was less effective in adults, especially in the older age brackets than in children because the frequency of histologically chronic lesions increased. In these cases, lipid-lowering agents and angiotensin-converting enzyme inhibitors may be helpful in preventing the progression.     

More than 10 years of follow-up of two patients after total femur replacement for malignant bone tumor

One patient with osteosarcoma and one with Ewing’s sarcoma of the femur were in 1987 and 1988 treated with prosthetic replacement of the femur and chemotherapy. There has been no loosening of the prostheses and no recurrence of the tumor. The patients have maintained 60% and 63% limb function scores evaluated by ISOLS criteria.

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Résumé  Deux patients, l’un avec un ostéosarcome, l’autre avec un sarcome d’EWING, furent opérés en 1987–1988 avec remplacement prothétique du fémur, associéà une chimiothérapie. Ces patients ont été suivis sans qu’il soit noté de récidive. Il n’y a pas de descellement, ni de luxation de la prothèse. Un score fonctionnel évalué selon les critères de l’ISOLS, montre une conservation de 60% et 63% de la fonction du membre inférieur.

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Accepted: 17 March 2000     

Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma.

PURPOSE: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. EXPERIMENTAL DESIGN: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). RESULTS: Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. CONCLUSIONS: Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen.     

Effects of super-extended paraaortic lymphadenectomy (PAL) on biological responses in totally gastrectomized patients with T3 or T4 gastric cancer

Background. In Japan, much attention has recently been paid to super-extended paraaortic lymphadenectomy (PAL) for the treatment of advanced gastric cancer. However, it has been reported that PAL is associated with increased morbidity and mortality, as compared to conventional extended lymphadenectomy (D2 or D3). Therefore, an analysis of the effects of PAL on perioperative changes in the biological responses of patients essential for determining the potential utility of this procedure. Methods. The current non-randomized prospective study included evaluations of perioperative changes in parameters of surgical stress (series I; serum levels of antidiuretic hormone, interleukin-6, trypsin, and phospholipase A ₂ ) and immunocompetence (series II; phytohemagglutinin- and concanavalin A-induced blastogenesis, activity of natural killer cells and the ratio of CD4 cells to CD8 cells) in patients with advanced gastric cancer (T3 or T4), comparing groups treated with D3 plus PAL ( n = 12) and D3 ( n = 13), and a control group with early gastric cancer ( n = 16) treated with D1 lymphadenectomy (perigastric N1 nodes) between April 1995 and April 1997. Results. The duration of surgery and the amount of blood lost were longer and greater in the D3 plus PAL group than in the D3 and D1 groups. D3 plus PAL and D3 were associated with significant postoperative increases in parameters of surgical stress, as well as with significant postoperative immunosuppression, compared to results with D1. However, there were no significant differences in the respective parameters between the D3 plus PAL and D3 groups. Conclusions. Our results indicate that there are no essential differences in patients' biological responses between D3 plus PAL and D3 lymphadenectomy. It appears that PAL-associated morbidity can be minimized by very careful manipulation during the dissection of paraaortic lymph nodes. Received for publication on Feb. 10, 1998; accepted on Jun. 3, 1998     

Carcinoma of the cervix: Value of dynamic magnetic resonance imaging in assessing early stromal invasion

Background The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging) in the evaluation of preinvasive and early invasive cancer of the cervix. Methods Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated for tumor detection and compared with results of histologic examination of the surgical specimens. Results The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging, whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and 5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images. In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic MR imaging. Conclusion Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced MR imaging.     

Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.     

Profiling of proteins phosphorylated or dephosphorylated during hyperactivation via activation on hamster spermatozoa

Background and Aims  It has been widely accepted that sperm hyperactivation is regulated by protein phosphorylations. But, the sperm hyperactivation phosphorylation pathway is not well understood yet because several different proteins have been detected in other studies. In order to understand the phosphorylation pathway that regulates hyperactivation, we established how to extract sperm protein completely and detected proteins that were phosphorylated during hyperactivation. Methods  Protein phosphorylation of hamster spermatozoa was detected by western blotting using antiphospho-amino acid monoclonal antibodies or the SELDI ProteinChip system with IMAC-Ga(III). Results  We detected 75 protein/peptide phosphoryations using the method established in the present study. Tyrosine phosphorylations occurred during hyperactivation. Serine or threonine phosphorylations occurred for 30 min. Furthermore, four of the serine or threonine phosphorations were phosphorylated by A-kinase. As for peptides, 15 peptides were dephosphorylated for 30 min. Other peptides were phosphorylated during hyperactivation. Conclusions  Because most of the proteins detected in the present study have been described previously, we could detect comprehensive protein phosphorylations. Moreover, we also detected many novel phosphopeptides. Although we did not understand the role of peptide, it was likely that motility was basically regulated by serine/threonine phosphorylations and hyperactivation was mainly regulated by tyrosine phosphorylations. (Reprod Med Biol 2006; 5: 123–135)     

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.