77歳,女性.顕微鏡的血尿を伴うネフローゼ症候群を呈した.光顕上,膜性増殖性糸球体腎炎(MPGN)の像を呈し,糸球体係蹄壁を中心に単クローン性免疫グロブリン(IgG3-κ鎖)の沈着を認め,電顕では糸球体係蹄内皮下に細顆粒状沈着物を認めた.本例の臨床・病理学的特徴は,Proliferative Glomerulonephritis with Monoclonal IgG Deposits(PGNMID)の疾患概念に合致し,ステロイドおよびMizoribineの併用による免疫抑制療法が有効であった点である.

The BK virus is a double-stranded DNA virus to which 90% of adults have been exposed. BK virus infections typically result in an oral or respiratory infection; however, BK virus reactivation is an infectious disease of concern in kidney transplant recipients. The prevalence of BK virus nephropathy (BKN) in kidney transplant recipients is approximately 5%, and most cases occur within one yr after kidney transplantation. Graft survival of BKN is reported to be 3060%, and the standard treatment strategy for BKN is reducing immunosuppressive therapy and close monitoring for rejection. Viral infection is most common in the early post-transplantation phase, and BKN or acute rejection is one of the major factors involved in graft loss. However, in this report, we describe the successful management of BKN and cytomegalovirus infection concurrent with plasma cellrich acute rejection.

症例は61歳，男性．胃原発mucosa associated lymphoid tissue（MALT）リンパ腫の切除後の再発時にネフローゼ症候群を発症しクリオグロブリン陽性の膜性増殖性糸球体腎炎（MPGN）+半月体形成性糸球体腎炎の診断を得た．腎不全進行により透析療法を開始したがRituximabを含めた多剤化学療法を行ったところ，MALTの退縮と同時に腎機能の回復が得られ，透析離脱が可能となった．本症例のMPGN発症機序として腫瘍B細胞が深く関わっていた可能性が示唆された．

Here, we report the successful treatment of a 38-yr-old Japanese man diagnosed with recurrent immunoglobulin A nephropathy (IgAN) with chronic active antibody-mediated rejection (CAAMR), three yr after undergoing living-related donor kidney transplantation. Immediately after transplantation, the allograft function was well maintained with a serum creatinine (S-Cr) level of < 1.8 mg/dL. About three yr after transplantation, urine protein excretion had reached 4.59 g/d, and the S-Cr level had increased to more than 2.0 mg/dL. Based on the allograft biopsy, we diagnosed nephrotic syndrome because of recurrence of IgAN with CAAMR. Subsequently, we performed a tonsillectomy, administered three sessions of steroid pulse therapy, and added losartan for the recurrence of IgAN. We also changed his immunosuppressant from mizoribine to mycophenolate mofetil to treat the CAAMR. The nephrotic syndrome improved with the multiple therapeutic approaches; however, the S-Cr level did not decrease below 2.0 mg/dL. We possibly could have performed additional treatments such as rituximab and intravenous immunoglobulin for the CAAMR, but therapeutic strategies for CAAMR have not yet been established.

A 31-yr-old Japanese man with end-stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent living related kidney transplantation at the age of 26 yr. The allograft functioned well immediately after surgery, and we did not observe histological findings of rejection and recurrent FSGS in protocol biopsies at two months and one yr after transplantation. Four years after transplantation, the urine protein excretion reached 11 g/d, and the serum creatinine increased over 2.5 mg/dL. We diagnosed nephrotic syndrome due to recurrent FSGS with graft dysfunction and confirmed FSGS lesions with severe endothelial injury with an allograft biopsy, associated with calcineurin inhibitor (CNI) nephrotoxicity. Thereafter, we performed plasmapheresis and steroid therapy with subsequent low-density lipoprotein adsorption, combined with the reduction of tacrolimus. The nephrotic syndrome improved dramatically with the multiple therapeutic approaches. Primary FSGS recurs frequently in patients immediately after kidney transplantation. Post-transplant FSGS has various causes, such as recurrent primary disease, obesity, hyperfiltration, donor-related nephrosclerosis, and CNI-induced arteriolopathy. In the case of nephrotic syndrome after kidney transplantation, we should consider not only recurrent FSGS, but also CNI-induced nephrotoxicity to determine the optimal treatment.

NephrologyVolume 10, Issue s6 p. A438-A438 Role of lymphangiogenesis for long-term renal survival in advanced IgA nephropathy KEITA HIRANO, KEITA HIRANO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorYOUICHI MIYAZAKI, YOUICHI MIYAZAKI Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorYASUNORI UTSUNOMIYA, YASUNORI UTSUNOMIYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorTETSUYA KAWAMURA, TETSUYA KAWAMURA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorTATSUO HOSOYA, TATSUO HOSOYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this author KEITA HIRANO, KEITA HIRANO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorYOUICHI MIYAZAKI, YOUICHI MIYAZAKI Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorYASUNORI UTSUNOMIYA, YASUNORI UTSUNOMIYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorTETSUYA KAWAMURA, TETSUYA KAWAMURA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this authorTATSUO HOSOYA, TATSUO HOSOYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, JapanSearch for more papers by this author First published: 09 December 2005 https://doi.org/10.1111/j.1440-1797.2005.00520.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume10, Issues6December 2005Pages A438-A438 RelatedInformation

The firing rates of cortical neurons change in time; yet, some aspects of their in vivo firing characteristics remain unchanged and are specific to individual neurons. A recent study has shown that neurons in the monkey medial motor areas can be grouped into 2 firing types, "likely random" and "quasi-regular," according to a measure of local variation of interspike intervals. In the present study, we extended this analysis to area TE of the inferior temporal cortex and addressed whether this classification applies generally to different cortical areas and whether different types of neurons show different laminar distribution. We found that area TE did consist of 2 groups of neurons with different firing characteristics, one similar to the "likely random" type in the medial motor cortical areas, and the other exhibiting a "clumpy-bursty" firing pattern unique to TE. The quasi-regular type was rarely observed in area TE. The likely random firing type of neuron was more frequently found in layers V-VI than in layers II-III, whereas the opposite was true for the clumpy-bursty firing type. These results show that neocortical areas consist of heterogeneous neurons that differ from one area to another in their basic firing characteristics. Moreover, we show that spike trains obtained from a single cortical neuron can provide a clue that helps to identify its layer localization.

NephrologyVolume 9, Issue s2 p. A52-A52 Prognostic impact of widened peritubular capillaries associated with compensatory tubular hypertrophy in advanced IgA nephropathy Keita HIRANO, Keita HIRANO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTetsuya KAWAMURA, Tetsuya KAWAMURA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTakashi YOKOO, Takashi YOKOO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorYouichi MIYAZAKI, Youichi MIYAZAKI Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorYasunori UTSUNOMIYA, Yasunori UTSUNOMIYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTatsuo HOSOYA, Tatsuo HOSOYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this author Keita HIRANO, Keita HIRANO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTetsuya KAWAMURA, Tetsuya KAWAMURA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTakashi YOKOO, Takashi YOKOO Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorYouichi MIYAZAKI, Youichi MIYAZAKI Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorYasunori UTSUNOMIYA, Yasunori UTSUNOMIYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this authorTatsuo HOSOYA, Tatsuo HOSOYA Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of medicine, Tokyo, JapanSearch for more papers by this author First published: 23 December 2004 https://doi.org/10.1111/j.1440-1797.2004.00278.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume9, Issues2December 2004Pages A52-A52 RelatedInformation

Intraarticular injection of dexamethasone (DEX) accelerates cartilage degradation due to the suppression of chondrocyte proliferation and extracellular matrix formation. The present study first demonstrated the interaction between DEX and TGF beta, a potent growth factor for cultured rat articular chondrocytes (CRAC), and then investigated the molecular mechanism by which DEX counteracts TGF beta-induced chondrocyte proliferation and differentiation through the regulation of AP-1 activity. DEX reduced serum-deprived and TGF beta-stimulated cell growth and [(3)H]-thymidine incorporation of CRAC. DEX also inhibited the expression of (alpha)1 type II collagen with concomitant suppression of the promoter activity. Transfection studies using a reporter vector with AP-1 responsive elements showed that DEX reduced TGF beta-activated but not basal luciferase activities. Activation of 3TP-luc, another AP-1 responsive element containing reporter was also blocked by DEX. GAL4-Elk1 studies revealed that DEX suppressed TGF beta-induced ERK activation which led to c-fos gene expression followed by increase in AP-1 complex formation, whereas the Smad pathway was not involved in DEX-dependent negative regulation of AP-1 in a reporter assay that requires FAST1-Smad2 for the activation. DEX also eliminated TGF beta-induced c-fos mRNA expression and ERK activation in Northern analysis and in vitro kinase assay, respectively. Further, DNA synthesis and transactivation of type II collagen by TGF beta were inhibited by PD98059, an inhibitor of MEK. Our results indicate that DEX suppressed TGF beta-induced chondrocyte proliferation and type II collagen expression, probably through selective inhibition of ERK integrated AP-1 activation.

OBJECTIVE To investigate the involvement of Tie-1 and Tie-2, receptor tyrosine kinases required for angiogenesis, in synovial proliferation and angiogenesis of rheumatoid arthritis (RA). METHODS Synovial tissues from 10 patients with RA and three control subjects were analysed by double immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS Expression of Tie-1 and Tie-2 was seen in all synovia, but predominantly in papillary projected portions. In synovial lining cells, Tie-2 was expressed mainly in the basal layer and frequently colocalised with vimentin and proliferating cell nuclear antigen (PCNA), whereas Tie-1 was also expressed in the superficial layer. In stromal cells, Tie-2 immunoreactivity was restricted to vimentin positive fibroblast—but not macrophage derived cells, whereas Tie-1 expression was not dependent on the phenotype. Tie receptors were also highly expressed in the endothelium and surrounding pericytes of capillaries scattered over the papillary proliferated synovium without notable difference in the expression of the two receptors. Furthermore, Tie positive vessels often overexpressed PCNA. In normal synovia, expression of Tie receptors was restricted to the capillary endothelium. RT-PCR confirmed the expression of Tie-1 and Tie-2 in RA synovial tissues and also in the cultured synoviocytes. CONCLUSION The results suggest the possible involvement of overexpressed Tie-1 and Tie-2 in synovial lining and stromal cells in the pathophysiology of RA synovitis, probably through distinct mechanisms. Furthermore, expression of Tie receptors in actively growing vasculature may reflect the direct involvement of these receptors in angiogenesis and subsequent vascularisation.

A second mammalian ornithine decarboxylase antizyme was discovered. The deduced protein sequence of the human antizyme2 is 54% identical and 67% similar to human antizyme1 but 99.5% identical to mouse antizyme2. Polyamine-regulated programmed ribosomal frameshifting is used in decoding antizyme2 mRNA as it is for antizyme1 mRNA. The mRNA signals for the programmed frameshifting are similar in the mRNAs for the two antizymes. However, in the stimulatory pseudoknot 3′ of the shift site, while the sequences of the stems are highly conserved, the sequences of the loops are divergent. Functional distinctions between antizymes seem likely, but no distinction in the tissue distribution of human antizyme1 and 2 mRNAs was distinguished, though antizyme2 mRNA is 16-fold less abundant than its antizyme1 counterpart. In addition to the previously characterized human antizyme1 mRNA, a second antizyme1 mRNA with an additional 160 nucleotides at its 3′ end was identified, and it has a tissue distribution different from that of the shorter antizyme1 mRNA.

The difference in resistance to bacterial invasion into the dentinal tubules between vital and nonvital teeth has not been determined. This study was conducted to clarify the effect of vital pulp on bacterial invasion into the dentinal tubules. The specimens were 19 intact pairs of bilateral upper third molars of 19 healthy, young adult male volunteers. In each case, 30 or 150 days before extraction, pulpectomies and root canal fillings were carried out unilaterally and a class V cavity involving the dentin was made on the palatal surface of both the pulpectomized tooth and the nonpulpectomized opposite tooth. The cavities were left unprotected to expose them to oral flora until the extractions were done, and the extracted teeth were examined histologically. When extraction followed 150-day exposure to the oral flora, there was a statistically significant difference in the bacterial invasion rate between the vital and nonvital teeth. It was postulated that vital teeth were much more resistant to bacterial invasion into the dentinal tubules than were nonvital teeth, thereby suggesting that the vital pulp plays some important role in this process.

An ornithine decarboxylase antizyme cDNA was obtained from Xenopus laevis liver and its sequence was determined. The cDNA consists of two major open reading frames as found in mammalian antizymes, which require +1 ribosomal frameshifting for its translation. Sequences important for frameshifting, namely the frameshift site and downstream stimulatory pseudoknot determined in the rat mRNA, are conserved.

Rat antizyme gene expression requires programmed, ribosomal frameshifting. A novel autoregulatory mechanism enables modulation of frameshifting according to the cellular concentration of polyamines. Antizyme binds to, and destabilizes, ornithine decarboxylase, a key enzyme in polyamine synthesis. Rapid degradation ensues, thus completing a regulatory circuit. In vitro experiments with a fusion construct using reticulocyte lysates demonstrate polyamine-dependent expression with a frameshift efficiency of 19% at the optimal concentration of spermidine. The frameshift is +1 and occurs at the codon just preceding the terminator of the initiating frame. Both the termination codon of the initiating frame and a pseudoknot downstream in the mRNA have a stimulatory effect. The shift site sequence, UCC-UGA-U, is not similar to other known frameshift sites. The mechanism does not seem to involve re-pairing of peptidyl-tRNA in the new frame but rather reading or occlusion of a fourth base.

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importance of antizyme we examined the effect of forced expression of antizyme on cellular ODC and polyamine levels and cell growth. Antizyme almost completely abolished the induction of ODC by growth stimuli. This may have been caused by antizyme-induced rapid degradation of newly synthesized ODC, since the half-life of ODC complexes with antizyme was less than 5 min. Forced expression of antizyme caused reductions of cellular putrescine and spermidine levels, and inhibited cell growth, which was partially restored by the addition of putrescine. These observations suggested a critically important role of antizyme in polyamine metabolism.

Degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis, is accelerated by the binding of antizyme, an ornithine decarboxylase inhibitory protein induced by polyamines. In the present study, we examined the effects of a series of deletion mutants of rat antizyme. The results indicated that two regions of antizyme, one internal (amino acids 122-144) and the other near the C-terminus (amino acids 211-218) are necessary for its binding to ornithine decarboxylase and inhibition of its activity, and an additional internal region (amino acids 88-118, especially 113-118) is necessary for its destabilization.

The half-life of ornithine decarboxylase (ODC) in HMO, cells, a variant cell line derived from hepatoma tissue culture (HTC) cells, is markedly increased compared with that in the parental cell line. In the present study, we examined which of the three relevant factors is responsible for the ODC stabilization in HMO(A) cells, namely ODC itself, a regulatory protein antizyme and an ODC-degrading activity. SDS/PAGE analysis of radiolabeled ODC revealed that ODC from HMO, cells migrated somewhat faster than that from HTC cells, suggesting that HMO(A) ODC was structurally altered. Direct sequencing of reverse-transcription/polymerase-chain-reaction (RT-PCR) products of ODC mRNA from HMO(A) cells revealed a T to G replacement, causing a Cys441 --> Trp replacement near the C-terminus. No alteration was found in the whole coding region of antizyme mRNA. An authentic mutant ODC cDNA with the same replacement was transfected and expressed in C55.7 ODC-deficient Chinese hamster ovary cells. Upon cycloheximide treatment, the mutant ODC activity did not decrease appreciably for at least 3 h, whereas wild-type ODC activity decreased with a half-life of 1 h. In-vitro-synthesized mutant ODC with the Cys441 --> Trp (or Ala) replacement was also stable in a reticulocyte-lysate ODC-degradation system. Metabolically labeled and purified mouse ODC was degraded in HMO(A) cell extracts in the presence of ATP and antizyme as rapidly as in HTC cell extracts, indicating that HMO, cells have a normal ODC degrading activity. These results indicated that the single amino acid replacement, Cys441 --> Trp, is responsible for the stabilization of ODC in HMO(A) cells and that Cys441 is important for rapid ODC turnover.

Comminuted fractures of the distal end of the radius are difficult to align and reduction of the fracture is difficult to maintain. Since 1983 we have treated such cases by external pin fixation. Twelve patients were evaluated. In the roentgenographic evaluation final radial angle averaged 22.8°, radial length averaged 9.4mm, and ulnar variance averaged 3.3mm. These figures are close to the average of the uninjured side. Five patients showed dorsal angulation. Wrist dorsal flexion averaged 68.3°, and volar flexion averaged 63.8°. Supination and pronation were almost in the normal range. We used Saitou's point system to assess the patient and according to this five patients had excellent results: 6 patients, were good; and only one patients was assessed as fair. External pin fixation was very useful for treating comminuted fractures of the wrist.

The degradation of ornithine decarboxylase (ODC) is stimulated by polyamines in a protein synthesis-dependent manner. It has been suggested that antizyme, an ODC-inhibiting protein induced by polyamines, is involved in the process of polyamine-stimulated ODC decay. In this study, we investigated the direct effect of antizyme on ODC decay in hepatoma tissue culture (HTC) cells. A truncated rat antizyme cDNA, Z1, was inserted into an expression vector at a site under the control of a glucocorticoid-inducible promoter and transfected into HTC cells. In the transfected cells dexamethasone increased the amount of Z1 mRNA and induced active antizyme in the absence of exogenous polyamines. When dexamethasone was added to cells with a high level of ODC, rapid decays of ODC activity and protein were elicited after a lag time. Cycloheximide abolished the effect of dexamethasone. These effects of dexamethasone were not observed in control HTC cells transfected with the chloramphenicol acetyltransferase gene. This study indicated that, once induced, antizyme stimulated ODC degradation independently of polyamines and strongly supported our previous hypothesis that the ODC decay-accelerating action of polyamines is mediated by antizyme.

We cloned an ornithine decarboxylase antizyme-encoding gene (Oaz) from a rat liver genomic library. The entire gene was located on a 4367-bp EcoRI fragment, which corresponded to one of two fragments hybridizable with the antizyme-encoding cDNA, Z1, on Southern blot analysis. Sequence analysis of the cloned gene showed that it consisted of five exons which were identical with the cDNA. The transcription start points of the Oaz mRNA were located 75 and 76 nucleotides upstream from the first ATG codon, as determined by S1 nuclease protection and primer extension analyses. The 5'-flanking region of the gene contained typical promoter motifs, such as a TATA box and Sp1-binding sites. Introduction of a chimeric gene consisting of the 5'-flanking region and the bacterial cat gene into Chinese hamster ovary cells revealed a promoter activity in the region, which was comparable in strength to that of the simian virus 40 promoter. In addition, we isolated a 12-kb EcoRI fragment, the other sequence hybridizable to the cDNA. Sequence analysis showed that it represented a processed Oaz pseudogene and was not able to encode any active protein.