Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis

The aim of this study was to investigate the relationship between the biochemical markers of arthritis and the radiographic grading of osteoarthritis (OA) in knees. Seventy-one women aged 49–85 years with knee OA were studied. Anterior–posterior knee radiographs and hand radiographs were taken in all patients. The radiographic grading of OA in the knee was performed by using the Kellgren–Lawrence criteria and the joint space width. The 71 patients with knee OA were divided into two groups: 37 patients exhibiting generalized osteoarthritis (GOA) and 34 non-GOA patients, according to the grading of their hand radiograph. C-reactive protein (CRP), urinary pyridinoline, YKL-40, plasma matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were measured as the biochemical markers of arthritis. The radiographic grading with the Kellgren–Lawrence scale revealed a significant relationship to the joint space width (P = 0.003): the joint space width decreased with increasing Kellgren–Lawrence grade. All biochemical markers had negative correlations with the joint space width, but only urinary pyridinoline had a significant correlation (P = 0.039). Pyridinoline (P = 0.034) and TIMP-1 (P = 0.017) also exhibited a significant relationship to the Kellgren–Lawrence grade. In GOA evaluations, the joint space width did not differ between GOA and non-GOA patients. CRP, pyridinoline, YKL-40 and MMP-3 levels were significantly greater in GOA patients than in non-GOA patients. CRP, pyridinoline, YKL-40, MMP-3 and TIMP-1 levels each related to at least one of the radiographic gradings. Furthermore, pyridinoline related to every type of radiographic grading examined in the present study

〈Original Papers〉Continuous heavy precipitation with a winter occluding cyclone captured by GPM satellite in central Japan

A fifth highest event of two-day accumulation precipitation in Honsyu area (Jan. 17-18, 2016) was nominated during the 10 winters since 2006 (Anzai and Ueno, 2018). Then, using Global Precipitation Measurement (GPM) dual-frequency precipitation radar (DPR) products, a case study was conducted to reveal the three-dimensional and synoptic scale structures of a precipitation system associated with a cyclone the mature stage. The disturbance in the front was composed of wide-ranging stratiform precipitation with a maximum of more than 2 km level by a poleward-ascending warm airstream moving over an easterly cold air mass. Subsequent convective precipitation was associated with an upper front due to dry intrusion over the warm conveyor belt. Successions of the stratiform to areas of convective precipitation were confirmed by surface weather radar images. We clarify that the combination of stratiform and convective precipitation was dependent on the conveyor belt structure of the cyclone toward the occluding stage and caused exceptional slow-moving heavy precipitation in central Japan

Cutting error prediction by multilayer neural networks for machine tools with thermal expansion and compression

In training neural networks, it is important to reduce input variables for saving memory, reducing network size, and achieving fast training. This paper proposes two kinds of selecting methods for useful input variables. One of them is to use information of connection weights after training. If a sum of absolute value of the connection weights related to the input node is large, then this input variable is selected. In some case, only positive connection weights are taken into account. The other method is based on correlation coefficients among the input variables. If a time series of the input variable can be obtained by amplifying and shifting that of another input variable, then the former can be absorbed in the latter. These analysis methods are applied to predicting cutting error caused by thermal expansion and compression in machine tools. The input variables are reduced from 32 points to 16 points, while maintaining good prediction within 6 ﾎｼm, which can be applicable to real machine tools

Predictors of Hypotension after Adrenalectomy for Pheochromocytoma

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

The molecular mechanisms involved in the terminal differentiation of erythroblasts have been elucidated by comparing enucleation and cell division. Although various similarities and differences between erythroblast enucleation and cytokinesis have been reported, the mechanisms that control enucleation remain unclear. We previously reported that dynein and microtubule-organizing centers mediated the polarization of nuclei in human erythroblasts. Moreover, the accumulation of F-actin was noted during the enucleation of erythroblasts. Therefore, during enucleation, upstream effectors in the signal transduction pathway regulating dynein or actin, such as cell division control protein 42 homolog (Cdc42), may be crucial. We herein investigated the effects of the Cdc42 inhibitor, CASIN, on cytokinesis and enucleation in colony-forming units-erythroid (CFU-Es) and mature erythroblasts (day 10). CASIN blocked the proliferation of CFU-Es and their enucleation in a dose-dependent manner. Dynein adopted an island-like distribution in the cytoplasm of non-treated CFU-Es, but was concentrated near the nucleus as a dot and co-localized with gamma -tubulin in CASIN-treated cells. CASIN blocked the accumulation of F-actin in CFU-Es and day 10 cells. These results demonstrated that Cdc42 plays an important role in cytokinesis, nuclear polarization and nuclear extrusion through a relationship with dynein and actin filament organization during the terminal differentiation of erythroblasts

Bortezomib Reduces the Tumorigenicity of Multiple Myeloma via Downregulation of Upregulated Targets in Clonogenic Side Population Cells

Side population (SP) cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11) express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2 gamma nul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3) express genes involved in the cell cycle and mitosis (e. g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM), polycomb (e. g., EZH2, EPC1) and ubiquitin-proteasome (e. g., UBE2D3, UBE3C, PSMA5) more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680) and a proteasome inhibitor (bortezomib) with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3) and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems

Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P < .0001). In conclusion, the new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions. © 2013 Elsevier Inc. All rights reserved

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations