The Japanese Cattle industry has been undergoing major changes for the past three decades. During the 1950's and 1960's mechanized power rapidly. The process of beef industry structure change accelerated in the 1970's as medium scale feedlots came into being, regional packing plants were established, and the beef marketing system matured. Economic forces, both within and external to the industry. A major objective of this book is to test the authors' hypothesis that beef production by Japan's cattle industry could become competitive with imported beef.
ABSTRACT. The active form of vitamin D is synthesized by 25-hydroxyvitamin D 1α-hydroxylase (1α-hydroxylase), which is expressed predominantly in renal proximal tubular cells. To clarify the mechanism of cell-specific gene expression of this enzyme, the 5′-flanking region of the mouse 1α-hydroxylase gene was investigated. Investigation began with mRNA expression of 1α-hydroxylase in cultured cells, including LLC-PK1, NIH/3T3, HepG2, MDCK, and OK cells. Expression of 1α-hydroxylase mRNA was restricted in LLC-PK1 cells. Several lengths of the 5′-flanking region of 1α-hydroxylase gene were linked to a pGL3-basic luciferase vector and introduced into these cells. Only LLC-PK1 cells had a substantial luciferase activity. Deletion analyses revealed that luciferase activity was detected in constructs extending from the transcription initiation site to −1652 to −105 bp, whereas further deletion to −80 bp resulted in a marked decrease in activity. The region from −105 to −80 bp contained two ternary complex factor-1 (TCF-1) sites, and mutations in the proximal TCF-1 site decreased the activity. Electrophoretic mobility shift assay demonstrated binding of LLC-PK1 nuclear proteins to this region. Tests of enhancer function in LLC-PK1 cells indicated that the 26-bp fragment behaved as a classical enhancer, i.e., independently of position and orientation. Moreover, a decoy oligonucleotide corresponding to this region substantially inhibited the promoter activity of 1α-hydroxylase gene. This study suggests that the −105 to −80 bp element of mouse 1α-hydroxylase gene contains an enhancer to be necessary for renal proximal tubular cell-specific expression.
hyperphosphatemia in patients with ESRD in the USA since 2005 and in Europe since 2006.The aim of this observational, post-marketing study was to examine the longterm safety of LaC in patients with ESRD in the USA (NCT00567723).METHODS: The study comprised two groups.Patients (18 years old) who provided informed consent and had received LaC for 12 consecutive weeks formed the exposed group; these patients were recruited from completed and ongoing trials of LaC, or patients who had been prescribed LaC during normal clinical practice.Patients who had been treated with any other phosphate binder were included in a comparator group and were identified from the USRDS using 1:4 matching (exposed:comparator). Patients were matched by age, sex, number of consecutive weeks of dialysis at screening (12), and first year of starting dialysis.Primary outcomes were incidence of and time to all-cause mortality and first bone fracture requiring hospitalization.Secondary outcomes were incidence of and time to gastrointestinal (GI) disease, liver disease, malignancy and major infectious episodes requiring hospitalization.We present the final analysis based on 5-year follow-up data from the 2015 USRDS.A Cox proportional hazards (CPH) model, adjusted for patient baseline characteristics, compared primary and secondary outcomes between groups.RESULTS: Overall, 2136 exposed patients were enrolled, of whom 2026 were included for analysis; the comparator group comprised 8094 matched patients.Baseline characteristics were similar between groups (Table 1).All-cause mortality was 51.8% and 54.4% and bone fracture rates were 6.3% and 7.2% for the exposed and comparator groups, respectively.Kaplan-Meier analysis showed that median 5-year survival (95% CI) was 51.7 (49.3-54.2) and 49.0 (47.5-50.3)months for patients in the exposed and comparator groups, respectively.Incidences of secondary outcomes were: GI disease, 17.8% vs 19.1%; liver disease, 5.1% vs 6.2%; malignancy, 1.1% and 1.4%; and infectious episodes, 46.2% vs 49.3% for the exposed and comparator groups, respectively.CPH model results are shown in Table 2. CONCLUSIONS: LaC was not associated with increased risk of all-cause mortality, first bone fracture requiring hospitalization or any of the secondary safety outcomes compared with patients receiving any other phosphate binder.These data support the positive long-term safety profile of LaC in patients with ESRD.
The anti-shore erosion measure in the Niigata West Coast has been passed over about 25 years. These measures have composed of submerged breakwater, a jetty and nourishment. The beach (800, 000 m3 nourishment sand has been used) has changed to a very large sandy beach and been utilized by citizen as the place of recreation and relaxation. The calculation result of the flow has been improved due to the addition of wind stress which was not applied in the past for the purpose of reproducing the flow around submerged breakwater located offshore. In addition to the above, the prediction of topographic change around submerged breakwater has been also improved by the incorporation of development pattern of waves in Niigata Beach into the calculation condition.
To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD).
METHODS
Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated.
RESULTS
Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive.
CONCLUSIONS
Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.
Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.
Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) and its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated within atherosclerotic lesions and are known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells (SMCs) plays a critical role in the development, progression, and end-stage clinical consequences of atherosclerosis, yet little is known regarding the effects of specific oxPLs on SMC phenotype. The present studies were focused on determining whether oxPLs regulate expression of SMC differentiation marker genes and the molecular mechanisms involved. Results showed that POVPC and PGPC induced profound suppression of smooth muscle (SM) alpha-actin and SM myosin heavy chain expression while simultaneously increasing expression of MCP-1, MCP-3, and cytolysin. OxPLs also induced nuclear translocation of Krüppel-like transcription factor 4 (KLF4), a known repressor of SMC marker genes. siRNA targeting of KLF4 nearly blocked POVPC-induced suppression of SMC marker genes, and myocardin. POVPC-induced repression of SMC marker genes was also significantly attenuated in KLF4 knockout SMCs. Taken together, these results suggest a novel role for oxPLs in phenotypic modulation of SMCs and indicate that these effects are dependent on the transcription factor, KLF4. These results may have important novel implications for the mechanisms by which oxPLs contribute to the pathogenesis of atherosclerosis.
