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Liver-expressed antimicrobial peptide 2 (LEAP-2) is a cationic peptide that plays an important role in innate immunity for host defense. The aim of this study was to characterize the LEAP-2 gene in the Japanese quail (Coturnix japonica). Japanese quail LEAP-2 (CjLEAP-2) was identified from the Japanese quail draft genome database by a local BLAST analysis using chicken LEAP-2 (GgLEAP-2). The exon-intron structure of CjLEAP-2, analyzed from three quails, is composed of three exons, as is the chicken LEAP-2 homolog (GgLEAP-2). An analysis of the coding sequence revealed that CjLEAP-2 is 231 bp long, like GgLEAP-2, and 93% identical to GgLEAP-2 at the nucleic acid level. The predicted amino acid sequence of CjLEAP-2 contained the liver-expressed antimicrobial peptide 2-precursor domain and four cysteine residues characteristic of the LEAP-2 protein. The amino acid sequence of the mature peptide of CjLEAP-2 was 100% identical to that of GgLEAP-2. We confirmed that CjLEAP-2 was transcribed in at least seven tissues, including the digestive system. Additionally, the mature peptide region of CjLEAP-2 exhibited no polymorphisms in 99 quails from six strains. Taken together, these findings indicate that CjLEAP-2 is non-polymorphic and therefore, it likely plays an important role in the innate immunity of quail as it does in chicken., (© 2016 Japanese Society of Animal Science.)

Isoleucyl-tRNA synthetase (IARS) c.235G > C (p.V79L) is a causative mutation for a recessive disease called IARS disorder in Japanese black cattle. The disease is involved in weak calf syndrome and is characterized by low birth weight, weakness and poor suckling. The gestation period is often slightly extended, implying that intrauterine growth is retarded. In a previous analysis of 2597 artificial insemination (AI) procedures, we suggested that the IARS mutation might contribute toward an increase in the incidence of prenatal death. In this study, we extended this analysis to better clarify the association between the IARS mutation and prenatal death. The IARS genotypes of 92 animals resulting from crosses between carrier (G/C) × G/C were 27 normal (G/G), 55 G/C and 10 affected animals (C/C) (expected numbers: 23, 46 and 23, respectively). Compared to the expected numbers, there were significantly fewer affected animals in this population (P < 0.05), suggesting that more than half of the affected embryos died prenatally. When the number of AI procedures examined was increased to 11 580, the frequency of re-insemination after G/C × G/C insemination was significantly higher at 61-140 days (P < 0.001). The findings suggested that the homozygous IARS mutation not only causes calf death, but also embryonic or fetal death., (© 2016 Japanese Society of Animal Science.)

Here we report the complete mitochondrial genome of the Bornean banteng Bos javanicus lowi (Cetartiodactyla, Bovidae), which was determined using next-generation sequencing. The mitochondrial genome is 16,344 bp in length containing 13 protein-coding genes, 21 tRNAs and 2 rRNAs. It shows the typical pattern of bovine mitochondrial arrangement. Phylogenetic tree analysis of complete mtDNA sequences showed that Bornean banteng is more closely related to gaur than to other banteng subspecies. Divergence dating indicated that Bornean banteng and gaur diverged from their common ancestor approximately 5.03 million years ago. These results suggest that Bornean banteng might be a distinct species in need of conservation.

It is thought that strong electron correlation in an insulating parent phase would enhance a critical temperature (Tc) of superconductivity in a doped phase via enhancement of the binding energy of a Cooper pair as known in high-Tc cuprates. To induce a superconductor transition in an insulating phase, injection of a high density of carriers is needed (e.g., by impurity doping). An electric double-layer transistor (EDLT) with an ionic liquid gate insulator enables such a field-induced transition to be investigated and is expected to result in a high Tc because it is free from deterioration in structure and carrier transport that are in general caused by conventional carrier doping (e.g., chemical substitution). Here, for insulating epitaxial thin films (∼10 nm thick) of FeSe, we report a high Tc of 35 K, which is 4× higher than that of bulk FeSe, using an EDLT under application of a gate bias of +5.5 V. Hall effect measurements under the gate bias suggest that highly accumulated electron carrier in the channel, whose area density is estimated to be 1.4 × 10(15) cm(-2) (the average volume density of 1.7 × 10(21) cm(-3)), is the origin of the high-Tc superconductivity. This result demonstrates that EDLTs are useful tools to explore the ultimate Tc for insulating parent materials.

Objective: Endovascular repair for retrograde type A aortic dissection with an entry in the descending aorta (RAAD) is challenging. We present early and mid- term results of endovascular repair for acute phase of RAAD by using commercially-available device., Methods: From April 2012 to June 2014, 10 consecutive patients with acute phase of RAAD underwent endovascular repair in our hospital. Of them, 9 patients had emergency surgery within 24 hours after the onset. The other one patient had urgent surgery 3 days after the onset. In all patients, the entry tear was covered with TAG or conformable TAG., Results: Technical success was achieved in all patients. No in-hospital mortality was experienced. In all patients, follow-up computed tomography images showed significant remodeling in the ascending aorta 3 months after surgery. During a median follow-up period of 19.5 months, no patients died and no re-intervention occurred., Conclusions: In patients with acute phase of RAAD, endovascular repair with commercially-available device can be safely performed and it provides sufficient remodeling in the ascending aorta early after surgery. This technique is an alternative to open repair in these patients.

In this study, we identified a cluster of 14 avian β-defensins (AvBD; approximately 66 kbp) in the Japanese quail, Coturnix japonica. Except for AvBD12 (CjAvBD12) and -13, the CjAvBDs coding sequences exhibited greater than 78.0% similarity to the respective orthologous chicken AvBD genes (GgAvBD). The putative amino acid sequence encoded by each CjAvBD contained six cysteine residues and the GXC (X1-2) motif considered essential for the β-defensin family. Each CjAvBDs also formed a sub-group with the respective orthologous genes of various bird species in a phylogenetic tree analysis. Synteny between the CjAvBD cluster and GgAvBD cluster was confirmed. The CjAvBD cluster was mapped on the long-arm end of chromosome 3 by linkage analysis based on single nucleotide polymorphisms (SNPs) of CjAvBD1 and CjAvBD12 (approximately 46 kbp), as well as GgAvBD cluster. We also confirmed that CjAvBD1, -4, -5, -9, and -10 are transcribed in 20 tissues, including immune and digestive tissues. However, our experimental data indicated that the CjAvBD cluster lacks the AvBD3 and -7 loci, whereas the CjAvBD101α, -101β, and -101θ loci arose from gene duplication of the AvBD6 orthologous locus in the CjAvBD cluster after differentiation between Coturnix - Gallus., (© 2015 Japanese Society of Animal Science.)

NK-lysins are cationic peptides that play important roles in host protection, and are an important constituent of innate immunity. We identified nine single-nucleotide polymorphisms (SNPs) in the NK-lysin open reading frame (ORF) from 32 Japanese quails in six strains: A, B, ND, K, P, and Y. The G to A substitution at nucleotide position 272 in the ORF resulted in a Gly (G) to Asp (D) amino acid substitution (Cj31G and Cj31D alleles). The Cj31D allele was detected in P (frequency 0.76) and Y (frequency 0.03) strains. We compared the antimicrobial activities of four synthetic peptides from the helix 2-loop-helix 3 region of avian NK-lysins against Escherichia coli: Cj31G and Cj31D from quail and Gg29N and Gg29D from chicken. The antimicrobial activities of the four peptides decreased in the following order: Gg29N > Cj31G > Gg29D > Cj31D (P < 0.05). Although there were no differences in the predicted secondary structure of the Cj31G and Cj31D, the net charge of the Cj31G was higher than that of Cj31D. These data indicated that the antimicrobial activity of CjNKL is influenced by net charge, similar to that which has been observed in chicken., (© 2015 Japanese Society of Animal Science.)

To establish a rational molecular design for bisphosphonate (BP)-modified proteins for efficient bone targeting, a pharmacokinetic study was performed using a series of alendronate (ALN), a nitrogen-containing BP, modified proteins with various molecular weights and varying degrees of modification. Four proteins with different molecular weight-yeast glutathione reductase (GR; MW: 112,000 Da), bovine serum albumin (BSA; MW: 67,000 Da), recombinant human superoxide dismutase (SOD; MW: 32,000 Da), and chicken egg white lysozyme (LZM; MW: 14,000 Da)-were modified with ALN to obtain ALN-modified proteins. Pharmacokinetic analysis of the tissue distribution of the ALN-modified and unmodified proteins was performed after radiolabeling them with indium-111 (111In) by using a bifunctional chelating agent. Calculation of tissue uptake clearances revealed that the bone uptake clearances of 111In-ALN-modified proteins were proportional to the degree of ALN modification. 111In-GR-ALN and BSA-ALN, the two high-molecular-weight proteins, efficiently accumulated in bones, regardless of the degree of ALN modification. Approximately 36 and 34% of the dose, respectively, was calculated to be delivered to the bones. In contrast, the maximum amounts taken up by bone were 18 and 13% of the dose for 111In-SOD-ALN(32) and LZM-ALN(9), respectively, because of their high renal clearance. 111In-SOD modified with both polyethylene glycol (PEG) and ALN (111In-PEG-SOD-ALN) was efficiently delivered to the bone. Approximately 36% of the dose was estimated to be delivered to the bones. In an experimental bone metastasis mouse model, treatment with PEG-SOD-ALN significantly reduced the number of tumor cells in the bone of the mice. These results indicate that the combination of PEG and ALN modification is a promising approach for efficient bone targeting of proteins with a high total-body clearance.

The surgical strategy for coexisting lung cancer and aneurysm is controversial owing to the risk of aneurysm rupture during the perioperative period of pulmonary resection. We performed simultaneous pulmonary resection and endovascular repair in 2 patients with coexisting lung cancer and aneurysm. Case 1:A 74-year-old man presented at our hospital with cT2aN0M0 lung cancer and a 5.0 cm abdominal aortic aneurysm. Because computed tomography indicated the possibility of advanced lung cancer, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right lower lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. Case 2:A 72-year-old man presented at our hospital with cT2aN1M0 lung cancer, a 5.0 cm left internal iliac artery aneurysm, and right renal cell carcinoma( RCC). Because the lung cancer was advanced and the patients needed following surgical treatment for RCC, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right upper lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 11.

Objective: To estimate the frequency of deep vein thrombosis (DVT) among non-surgical inpatients, and to evaluate the D-dimer assay as a screening tool for DVT., Methods: Subjects were non-surgical inpatients aged 20 years or older who had been bedridden for at least 24 hours and had moderate-to-high risk factors for DVT. We assessed the presence of DVT by venous ultrasonography. Patients who received a diagnosis of venous thromboembolism (VTE) before admission, who had symptoms or findings of VTE at admission, or who had surgery or trauma within the past 3 months before admission were excluded., Results: DVT was confirmed in 96 of 525 patients (18.3%). In a logistic regression analysis, longer duration of hospitalization, higher D-dimer value, and history of cancer surgery were significantly associated with the occurrence of DVT. The D-dimer assay showed high sensitivity (96.1%) and high negative predictive value (97.6%)., Conclusion: Non-surgical inpatients with a long-term hospitalization or history of cancer surgery have a risk for DVT, and need to be considered for added DVT preventive measures as recommended in the prevention guidelines. In addition, the D-dimer assay is beneficial for the screening of DVT in medical practice.

We report herein a rare case of endocardial blood cyst (EBC) in an adult patient. A 63-year-old asymptomatic woman underwent echocardiography, which incidentally detected a cardiac tumor in the right atrium. On echocardiography, the tumor was revealed to be a 30-mm round mass with thin, hyperechogenic walls and heterogeneously hypoechogenic contents. The lesion was attached to the septum. On computed tomography, the tumor appeared partly calcified and showed poor contrast-enhancement. On magnetic resonance imaging, the lesion appeared isointense or slightly hyperintense in T1 and T2-weighted sequences. Myxoma was strongly suspected based on these preoperative imaging findings. The tumor was successfully excised under cardiopulmonary bypass. Gross examination confirmed that the cyst was filled with blood. The cystic walls comprised thin-layered fibrous tissue lined with endocardial cells. No tumor cells were found. The diagnosis of EBC was confirmed based on histopathological examination, and the postoperative course was uneventful.

We identified an antimicrobial cationic peptide that was expressed in the natural killer cells and cytotoxic T-lymphocytes of Japanese quail. The gene, designated CjNKL, was located downstream of AEBP1L and POLD2 in a region syntenic with the chicken genome. CjNKL comprised four exons, as does chicken GgNKL. The coding sequence in CjNKL was 411 bp long and exon 3 of CjNKL lacked 9 bp when compared to chicken GgNKL, but CjNKL and GgNKL were 81% identical at the nucleic acid level. The saposin like type-B domain of CjNKL contained the six essential cysteines, one proline, 15 cationic amino acids residues, and an antibacterial region that are characteristic of NKL proteins. The 5' flanking region of CjNKL contained positive regulatory elements, an activator protein-1 binding site and two nuclear factor (NF)-κB binding sites, and a negative regulatory element, CAAT/enhancer binding protein β (C/EBPβ) binding site. However, the number of NF-κB sites and C/EBPβ sites within CjNKL are fewer than the number within GgNKL. Additionally, we confirmed that CjNKL was transcribed in at least 18 tissues, including immune and digestive tissues. These data indicated that transcriptional activation of CjNKL differed slightly from those of GgNKL., (© 2013 Japanese Society of Animal Science.)

We describe a case of patent ductus arteriosus (PDA) in a 76-year-old woman with a history of stroke, atrial fibrillation, and chronic obstructive pulmonary disease. Cranial diffusion-weighted imaging (DWI) performed for preoperative assessment showed a hyperintense lesion in the left cerebellum. Preoperative transesophageal echocardiography (TEE) demonstrated two highly mobile masses approximately 5 mm in diameter adherent to the left and non-coronary cusps of the aortic valve. We performed transpulmonary patch closure of PDA under hypothermic circulatory arrest. Subsequently, two frond-like masses were completely shaved off the cusps, preserving the native aortic leaflets. Pathological examination confirmed the diagnosis of papillary fibroelastoma (PFE). To our knowledge, this is the first report of PDA associated with PFE. Perioperative use of TEE is an effective tool for management of cardiovascular patients with suspected cardiogenic embolism.

After the Great East-Japan Earthquake, the prevalence of deep vein thrombosis (DVT) in disaster shelters in Ishinomaki (Pacific coast, Miyagi, Japan) was found much higher than that ever reported in Japan. In Ishinomaki, twelve patients were found to have pulmonary thromboembolism for one month since the earthquake and DVT was found in 10 of those patients. The calf DVT was examined using ultrasonography in the shelters (from March to July 2011) and in temporary emergency housings (from August to December 2011). Calf DVT was found in 190 of 701 evacuees. DVT prevalence was higher in the tsunami-flooded shelters (34.2%) than in that in the non-flooded shelters (19.1%). This indicated that deteriorated and crowded condition in the tsunami-flooded shelters might induce thrombogenesis in calf veins. Therefore, evacuees were recommended to leave tsunami-flooded areas. DVT prevalence in the shelters was gradually reduced, however, that was still higher in the temporary emergency housings (8.9%) than in the non-disaster area in Japan (2.2% in Yokohama city). The risk of calf DVT in the temporary emergency housings was increased because of reduced blood flow in the calf veins caused by immobility. The residents of the housings were required to be physically active to avoid calf DVT. (English translation of Jpn J Phlebol 2013; 24: 380-384).

Background: This study aimed to investigate whether left atrial appendage (LAA) dysfunction evaluated by transesophageal echocardiography (TEE) during sinus rhythm is predictable of paroxysmal atrial fibrillation (PAF) as an embolic source in the acute stage of stroke., Methods and Results: We measured and analyzed LAA flow velocity (LAA-FV) and LAA ejection fraction (LAA-EF) in 300 acute ischemic stroke patients by TEE. We divided the acute ischemic stroke patients into 3 groups. The atrial fibrillation (AF) group (n=58) comprised patients whose TEE was performed during AF rhythm. The PAF group (n=42) comprised patients with a history of AF but with normal sinus rhythm when TEE was performed. The normal sinus (sinus) group (n=200) did not have any history of AF. We found that mean LAA-FV and LAA-EF values in the PAF group were significantly lower than those in the sinus group (P<.001). The diagnostic accuracy of LAA-FV for the diagnosis of PAF calculated as the area under receiver operating characteristic curves was low (.582, 95% confidence interval [CI]=.498-.665) but that of LAA-EF was modest (.721, 95% CI=.653-.789), with an optimal cutoff point of 49.1%., Conclusions: LAA dysfunction as determined by TEE (LAA-EF<49.1%) in the acute stage of stroke is predictive of PAF with moderate accuracy. Long-term electrocardiographic monitoring is recommended for cryptogenic stroke patients with LAA dysfunction., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Based on sequences of two cosmid clones from Japanese quail (Coturnix japonica, Coja), we confirmed that the syntenic cluster, GNB2L1∼BTN1∼BTN2, is located in the quail TRIM subregion of the quail major histocompatibility complex (MHC Coja) region. These cosmids also included four CjBG loci and one CjLEC locus; therefore, the quail TRIM subregion was thought to be adjacent to the BG/LEC subregion. We then identified three polymorphic markers - CjHEP21, CjTRIM39.2 and CjBTN2 - in the TRIM subregion that may be useful for the functional analysis of the MHC-Coja region. We examined MHC-Coja sequences from 321 individual quails sampled from 11 inbred strains, and we found eight alleles for each of the three genes - CjHEP21, CjTRIM39.2 and CjBTN2. These polymorphisms represent the first avian DNA markers in the TRIM subregion. Additionally, we discovered a quail-specific VNTR (variable number of long tandem repeats, 133-137 bp) in intron 7 of CjBTN2. We identified 25 haplotypes in the sample of 321 quail; these haplotypes comprised combinations of all 24 alleles of the three polymorphic genes. We suggest that there are two recombination hotspots, one between each pair of adjacent loci. All strains, except AMRP, contained multiple haplotypes; the AMRP strain contained a single, apparently fixed haplotype., (© 2012 Japanese Society of Animal Science.)

High prevalence of deep vein thrombosis (DVT) in disaster shelters has been reported in the aftermath of earthquakes in Japan. Calf DVT was examined using sonography in the shelters after the Great East Japan earthquake on March 11, 2011. By the end of July 2011, 701 out of 8,630 evacuees suspected with calf DVT, judged by inspections or medical interviews, were examined in 32 shelters, and 190 evacuees were confirmed to have calf DVT. The prevalence of DVT was 2.20%, which was 200 times higher than the usual incidence in Japan. The DVT prevalence seemed to decrease with time. By the end of May, a significantly higher prevalence of DVT was found in tsunami-flooded shelters (109 of 3,871 evacuees; 2.82%) than in non-flooded shelters (53 of 3,155 evacuees; 1.68%). After June, its prevalence was still higher (18/541; 3.33%) in tsunami-flooded shelters than in non-flooded shelters (10/1063; 0.94%). The cause of the high prevalence of DVT was supposed to be dehydration due to the delay in supplying drinking water, vomiting, and diarrhea experienced by the evacuees because of a shortage of clean water to wash their hands. Dehydration was especially noticed in women because they restricted themselves of water intake to avoid using unsanitary toilet facilities. Moreover, crowded shelters restricted the mobility of elderly people, which would exacerbate the prevalence of DVT. Those deteriorated and crowded shelters were observed in tsunami-flooded areas. Therefore, long-term shelters should not be set up in flooded areas after tsunami.

An 86-year-old man was admitted for abdominal pain. Dissected descending thoracic aortic aneurysm and infrarenal abdominal aortic aneurysm were observed under computed tomographic (CT) scan. Hematologic studies revealed low platelet count and an increase in fibrin degradation products (FDP), and disseminated intravascular coagulation( DIC) associated with dissecting aortic aneurysm was highly suspected. Platelet transfusion was performed and gabexate mesilate was administered, however, no improvement of DIC could be obtained. An increase in aortic diameter was observed under CT scan and surgery was performed. The infrarenal aneurysm was replaced with a bifurcated prosthetic graft under open repair. Simultaneously, an endovascular stent-graft was delivered from the left limb of the abdominal graft and implanted into the descending thoracic aorta. The postoperative recovery was uneventful but platelet count did not improve in this case.

We present a case of floating thrombus originating from an almost normal thoracic aorta in a 54-year-old man who presented with acute arterial occlusion of his left leg. Transesophageal echocardiography (TEE), computed tomography, and magnetic resonance imaging showed two masses in an almost normal aorta after embolectomy for the acute arterial occlusion. Although the embolus was thrombus histologically, malignant tumors could not be ruled out. The masses did not decrease in size after 7 days of anticoagulant therapy, so they were extirpated under cardiopulmonary bypass (CPB) and TEE guidance. Frozen section examination during CPB indicated that there was no evidence of malignancy in the removed mass. TEE played an important role in the diagnosis and surgery of this condition, and it was useful when deciding on a surgical strategy. Because the treatment strategy for this disease remains controversial, further studies are needed.

Bortezomib is a potent agent for multiple myeloma (MM); however, severe treatment-related toxicities such as peripheral neuropathy have been observed in conjunction with its use. In this study, we present the cases of 9 patients with refractory MM whose administration schedule was modified from twice weekly to an interval of once weekly or longer mainly due to adverse events. The average duration from diagnosis to the time of bortezomib induction was 56 months. The schedule was changed to the modified administration according to the physician's discretion. The average duration of modified treatment was 16 months. Six patients with IgG or IgA subtype showed more than a minor response. One patient with BJP had stable disease for 3 years, and the other BJP-type patient with extramedullary plasmacytomas showed remarkable tumor regression. The treatment-related toxicities of this strategy were mild and tolerable. To our knowledge, this is the first report of the administration of bortezomib at intervals longer than once weekly., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Unfractionated heparin (UFH) is the standard drug for the initial treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) in Japan, whereas fondaparinux is the standard drug in Europe and the United States. Here, we examine the efficacy and safety of fondaparinux in Japanese patients., Methods and Results: In 2 randomized, open-label, multicenter studies, 80 Japanese patients with acute PE or DVT received either subcutaneous fondaparinux or intravenous UFH as a non-comparative reference, in a 3:1 ratio, for 5-10 days. Concomitant warfarin therapy was continued until Day 90. Multidetector-row computed tomography-based assessment showed that 57.9% and 45.9% of the patients with acute PE and acute proximal DVT had proximal DVT and PE as a complication, respectively. There was no recurrence of symptomatic venous thromboembolism. In the fondaparinux group, the respective improvement rates at the end of the initial treatment and follow-up periods were 71.4% and 86.8% for 42 patients with PE, and 57.8% and 83.3% for 46 patients with DVT; similar results were noted in the UFH group. One patient in the fondaparinux group experienced major bleeding during the initial treatment, but no such episode in the UFH group., Conclusions: Once-daily, subcutaneous fondaparinux is as effective and safe without monitoring as adjusted-dose intravenous UFH for the initial treatment of acute PE and DVT in Japanese patients.

The expression of YB-1 has been reported to predict poor clinical outcome in many human malignancies, including hematopoietic malignancies. In this study, we investigated the correlations between YB-1 expression and the clinicopathological features of patients with diffuse large B-cell lymphoma (DLBCL) in a single institution. The expression of YB-1 was analyzed in 168 cases by immunohistochemistry. Fifteen out of 168 cases (8.9%) showed cytoplasmic expression of YB-1. The expression of YB-1 was significantly associated with 5-year overall survival (OS) (p = 0.023). Rituximab plus CHOP therapy (n = 94) improved the 5-year survival rate in both YB-1-positive and -negative patients. In conclusion, the data presented in this report provide evidence that the cytoplasmic expression of YB-1 is a poor prognosis factor in DLBCL treated with CHOP therapy, whereas rituximab improves the survival of both YB-1-positive and -negative patients with DLBCL.

In the current study, we describe four novel members of the 90 kDa heat shock protein (HSP90) family expressed in Japanese quail, Coturnix japonica. The coding regions of the genes, CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1, exhibited more than 94% similarity to their related genes in chicken. The putative proteins encoded by these quail genes contained motifs considered essential for HSP90 gene function. In addition, the predicted proteins were more similar to HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 proteins expressed in vertebrates than they were to other members of the HSP90 family. Exon numbers of CjHSP90AA1 (11), CjHSP90AB1 (12) or CjTRAP1 (18) are the same as the chicken and mammalian orthologs. Furthermore, gene order in the regions surrounding CjHSP90AB1 and CjTRAP1 has been preserved, providing evidence that the genomic regions were orthologous to HSP90-containing regions in the chicken genome. The promoter regions of the genes also contained conserved motifs identified in related genes of chicken. However, the nucleotide sequences of the 5'-flanking region of these genes were highly polymorphic. We also found that CjHSP90AA1 exhibited a robust response to heat shock treatment. Taken together, the data suggest that CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1 encode orthologs of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1, respectively.

An 83-year-old woman had been suffering from palpitations and fatigue for a month. An annual screening test revealed an increased WBC count so she was referred to our hospital. CBC showed extremely elevated WBC count (186,300/microl), in which the population of blastic eosinophils was over 90%. The eosinophils expressed CD7/13/33/34/DR, and the karyotype demonstrated 47,XX,+8. The fusion gene of FIP1-LP/PDGFRalpha in peripheral blood was negative. As plural effusion due to the underlying disease progressively worsened, she was given prednisolone and hydroxyurea, but the effect was limited. Steroid pulse therapy and imatinib (100 mg/day) were administrated. As a result, a prompt response was observed. The WBC count rapidly decreased, but tumor lysis syndrome led to acute renal failure and disseminated intravasucular coagulation appeared. Supportive therapies such as artificial dialysis and transfusions were conducted, but unfortunately she died because of alveolar hemorrhage.

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA.

The Mhc is a highly conserved gene region especially interesting to geneticists because of the rapid evolution of gene families found within it. High levels of Mhc genetic diversity often exist within populations. The chicken Mhc is the focus of considerable interest because of the strong, reproducible infectious disease associations found with particular Mhc-B haplotypes. Sequence data for Mhc-B haplotypes have been lacking thereby hampering efforts to systematically resolve which genes within the Mhc-B region contribute to well-defined Mhc-B-associated disease responses. To better understand the genetic factors that generate and maintain genomic diversity in the Mhc-B region, we determined the complete genomic sequence for 14 Mhc-B haplotypes across a region of 59 kb that encompasses 14 gene loci ranging from BG1 to BF2. We compared the sequences using alignment, phylogenetic, and genome profiling methods. We identified gene structural changes, synonymous and non-synonymous polymorphisms, insertions and deletions, and allelic gene rearrangements or exchanges that contribute to haplotype diversity. Mhc-B haplotype diversity appears to be generated by a number of mutational events. We found evidence that some Mhc-B haplotypes are derived by whole- and partial-allelic gene conversion and homologous reciprocal recombination, in addition to nucleotide mutations. These data provide a framework for further analyses of disease associations found among these 14 haplotypes and additional haplotypes segregating and evolving in wild and domesticated populations of chickens.

We here report the case of a young Japanese woman diagnosed with chronic active Epstein-Barr virus (EBV) infection. Intensive therapy with the CHOP regimen was partially able to control virus expansion, but various central nervous system symptoms appeared and gradually progressed. EBV-encoded RNA, detected using in situ hybridization, disclosed the presence of EBV in liver and bone marrow tissue, and real-time PCR revealed the presence of EBV in the cerebrospinal fluid (CSF) and serum. CD3+CD4+CD8-CD56- T-cell expansion in the peripheral blood (PB) and CSF was also observed. Atrophic brain changes were progressive, and the patient died of central nervous system disturbance and pulmonary hemorrhage a year after diagnosis. Autopsy revealed that EBV-infected T lymphocytes with a phenotype similar to those seen in PB and CSF had infiltrated multiple organs: the lymph nodes, bone marrow, endocardium, pericardium, myocardium, spleen, liver, and spinal cord. There have been few previous reports of severe degenerative changes in the myocardium, liver, and spinal cord in patients with EBV infection. Although EBV occasionally infiltrates the central nervous system and brain, atrophic changes mediated by EBV are rare. The autopsy results of this case suggest the possibility of EBV-mediated, severe degenerative changes in multiple organs.

Left ventricular assist devices (LVADs) have become more important than ever for patients with terminal heart disease. The chronic shortage of donors for heart transplantation may enhance the importance of LVADs as destination therapy. To prevent cerebral complications, the evaluation of high-intensity transient signals (HITS) of transcranial Doppler (TCD) ultrasound is important. In the present study, HITS were measured on seven occasions in patients supported with LVADs. The high-frequency counts in HITS were greater than the low-frequency counts (47 +/- 42 vs. 9 +/- 9 in 3 min, P = 0.025), and declined further with oxygen delivery to the patient. The high frequency of signals may imply air microemboli, and the counts may increase with time.

We investigated chromosome (Chr) aberrations in the process of replicative senescence and immortalization of cultured bovine oviduct epithelial cells (BOEC) before and after transfecting vectors SV40 large T or human telomerase reverse transcriptase (hTERT). We found that a gradual increase in the number of metacentric chromosomes occurred during replicative senescence but not immortalization of BOEC. The accumulation of metacentric chromosomes was concomitant with decreases in the number of acrocentric autosomes, strongly suggesting that Robertsonian (Rb) translocation frequently occurred in cultured BOEC. The process was also correlated with an accumulation of extremely shortened telomeres (<4 kb). The maximum number of metacentric chromosomes reached a plateau (8.75 +/- 0.53) in the senescent BOEC (approximately 48 population doublings), and the value was stably maintained in all immortalized lines. These results suggest that not all autosomes may be involved in Rb translocation. Fluorescence in situ hybridization analysis using probes specific for Chr1, Chr29, telomeres, and x-chromosomes of bovine confirmed the presence of t(1;29) with other unidentified fused chromosomes. There was no evidence for duplication of sex chromosomes. Because no detectable fluorescence in situ hybridization signals at the centromere for telomeres were indicative of no direct integration of telomere sequences in the Rb translocated chromosomes, these results raise a possibility that Rb translocation between certain autosomes of bovine cells is partly but critically dependent upon a physical state of telomere attrition. The cells and cell lines established in this study could provide a promising system for further studies on the mechanisms of chromosomal translocation because of centromeric fusion in bovine cells.

We surveyed anesthetic practices and the use of cerebral monitoring and brain protective therapies during cerebral aneurysm surgery by sending a questionnaire to 822 hospitals in Japan. Three hundred and fifty four hospitals responded. For induction, 51% used thiopental, 41% used propofol, and 94% supplemented induction with fentanyl. For maintenance 45% used isoflurane, 29% used sevoflurane, and 26% used propofol. Only 6% used EEG and/or evoked potentials in most of their patients. Specific brain protective measures were used in most of the hospitals. If used, 97% used mannitol, 43% used steroids and 23% used a certain level of induced hypothermia. When mild hypothermia was used, 39% used 33-34 degrees C, 59% used>34 degrees C, 2% used <33 degrees C, and only 4% used mild hypothermia in every patient. During temporary clipping, 18% kept the blood pressure equal to the level when awake, while 56% used induced hypotension. To control blood pressure during extubation, 72% used nicardipine or nitroglycerine. The use of intraoperative brain protective therapies were common but brain monitoring was not the standard.

We encountered 2 cases of pulmonary thromboembolism developed during refuge for Niigata Chuetsu earthquake in 2004. Case 1 was a 76-year-old woman who moved to the back seat of a car for refuge since the earthquake struck on October 23rd, 2004. When she emerged from the car on the morning of October 25th, she felt sudden dyspnea and lost consciousness. On arrival at the hospital, she had low blood pressure and hypoxemia, hypocapnia, and metabolic acidosis. Based on her clinical history and her symptoms, pulmonary thromboembolism was suspected and heparinization was begun immediately. In our hospital, the chest CT angiography proved the diagnosis. She was transferred to a university hospital for further treatment. Case 2 was a 79-year-old woman. She spent only one night in a car. Fifteen days after the earthquake, chest tightness and dyspnea occurred. Although her symptoms were improved and disappeared, she came to our hospital. Chest CT images confirmed pulmonary thromboembolism, and treatment with heparin was begun. We think this pulmonary thromboembolism was related to the knee-bending position she had assumed in the car and decreased activity during refuge. This is a clinical condition which could happen during disasters in the future. We should recognize the likelihood of pulmonary thromboembolisms in the disasters in the future.

We propose that the hidden order in URu₂Si₂ is an incommensurate octupole order, which is derived from a spin-1 XXZ model with XX octupole and Z dipole interactions based on the singlet-doublet crystal-field level scheme. The octupole moments break time-reversal invariance and give rise to finite hyperfine fields on the nuclei of the ligand Si and Ru ions. In order for the hyperfine fields to be observed as a nuclear magnetic resonance (NMR) linewidth, the order must be incommensurate, with the ordering vector determined so as to account for the ²⁹Si NMR linewidth data quantitatively.

Basophils play an important role in allergic inflammation and are pathologically related to hematological disturbances, such as iron deficiency anemia and myeloproliferative disorders; however, they are only rarely encountered in lymphoid malignancies. Here, we report the case of a 33-year-old man with a bulky mass of the small intestine, multiple paraaortic lymphoadenopathy, pleural effusion, and ascites, who was diagnosed as a case of de novo CD5+ diffuse large B cell lymphoma (DLBCL). This patient showed a marked elevation of the basophil count in the peripheral blood, which appeared to run in parallel with the tumor burden. High dose chemotherapy followed by autologous peripheral blood cell transplantation yielded complete remission, and the patient has remained disease free for 5 years. To the best of our knowledge, this is the first report of a case of de novo CD5+ DLBCL showing marked elevation of the PB basophil count., ((c) 2006 Wiley-Liss, Inc.)

Background: The quail and chicken major histocompatibility complex (Mhc) genomic regions have a similar overall organization but differ markedly in that the quail has an expanded number of duplicated class I, class IIB, natural killer (NK)-receptor-like, lectin-like and BG genes. Therefore, the elucidation of genetic factors that contribute to the greater Mhc diversity in the quail would help to establish it as a model experimental animal in the investigation of avian Mhc associated diseases. AIMS AND APPROACHES: The main aim here was to characterize the genetic and genomic features of the transcribed major quail MhcIIB (CojaIIB) region that is located between the Tapasin and BRD2 genes, and to compare our findings to the available information for the chicken MhcIIB (BLB). We used four approaches in the study of the quail MhcIIB region, (1) haplotype analyses with polymorphic loci, (2) cloning and sequencing of the RT-PCR CojaIIB products from individuals with different haplotypes, (3) genomic sequencing of the CojaIIB region from the individuals with the different haplotypes, and (4) phylogenetic and duplication analysis to explain the variability of the region between the quail and the chicken., Results: Our results show that the Tapasin-BRD2 segment of the quail Mhc is highly variable in length and in gene transcription intensity and content. Haplotypic sequences were found to vary in length between 4 to 11 kb. Tapasin-BRD2 segments contain one or two major transcribed CojaIIBs that were probably generated by segmental duplications involving c-type lectin-like genes and NK receptor-like genes, gene fusions between two CojaIIBs and transpositions between the major and minor CojaIIB segments. The relative evolutionary speed for generating the MhcIIBs genomic structures from the ancestral BLB2 was estimated to be two times faster in the quail than in the chicken after their separation from a common ancestor. Four types of genomic rearrangement elements (GRE), composed of simple tandem repeats (STR), were identified in the MhcIIB genomic segment located between the Tapasin-BRD2 genes. The GREs have many more STR numbers in the quail than in the chicken that displays strong linkage disequilibrium., Conclusion: This study suggests that the Mhc classIIB region has a flexible genomic structure generated by rearrangement elements and rapid SNP accumulation probably as a consequence of the quail adapting to environmental conditions and pathogens during its migratory history after its divergence from the chicken.

There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefecture after the earthquake. Cities, towns, and villages in the prefecture were classified into two areas (high evacuee rate area, and low evacuee rate area) due to the mean ratio of evacuees to the overall population during 1 week immediately after the earthquake. A rate of 5% and higher was encountered for the high evacuee rate area and a rate of < 5% was encountered for the low evacuee rate area. Ten out-of-hospital cases of APE (seven in the high evacuee rate area and three in the low evacuee rate area) were diagnosed within the first month after the earthquake. The relative risk of APE was high in the high evacuee rate area (13.09; P = 0.0002) and also higher in women (8.55; P = 0.04). All patients in the high evacuee rate area had stayed in their automobiles for long periods of time, but none had done so in the low evacuee rate area ( P = 0.008).

We experienced anesthetic management of an infant girl with Cloverleaf syndrome complicated with prenatal diagnosis of craniosynostosis. She received posterior-cranioplasty and foramen magnum decompression at the age of 44 days, ventricuro-peritoneal shunting at 80 days and cranioplasty at 149 days all under general anesthesia without serious complications. In all three occasions, we induced general anesthesia with oxygen, sevoflurane, nitrous oxide and thiopental with a facemask. After we made sure it was not impossible to maintain the airway and ventilation, we performed orotracheal intubation with vecuronium. We maintained anesthesia paying particular attention to intracranial pressure and possible massive hemorrhage particularly during cranioplasty. Postoperative course was uneventful. Anesthesiologists should keep in mind that this syndrome is characterized by severe skull deformity, facial bone abnormalities, hydrocephalus and increased intracranial pressure.

We mapped two different quail Mhc haplotypes and sequenced one of them (haplotype A) for comparative genomic analysis with a previously sequenced haplotype of the chicken Mhc. The quail haplotype A spans 180 kb of genomic sequence, encoding a total of 41 genes compared with only 19 genes within the 92-kb chicken Mhc. Except for two gene families (B30 and tRNA), both species have the same basic set of gene family members that were previously described in the chicken "minimal essential" Mhc. The two Mhc regions have a similar overall organization but differ markedly in that the quail has an expanded number of duplicated genes with 7 class I, 10 class IIB, 4 NK, 6 lectin, and 8 B-G genes. Comparisons between the quail and chicken Mhc class I and class II gene sequences by phylogenetic analysis showed that they were more closely related within species than between species, suggesting that the quail Mhc genes were duplicated after the separation of these two species from their common ancestor. The proteins encoded by the NK and class I genes are known to interact as ligands and receptors, but unlike in the quail and the chicken, the genes encoding these proteins in mammals are found on different chromosomes. The finding of NK-like genes in the quail Mhc strongly suggests an evolutionary connection between the NK C-type lectin-like superfamily and the Mhc, providing support for future studies on the NK, lectin, class I, and class II interaction in birds.

Left ventricular unloading and energy charge as effects of transaortic catheter venting (TACV) during venoarterial bypass (VAB) in normal and failing hearts has been reported previously. The aim of this study was to assess the effectiveness and safety of a special multipurpose catheter for TACV during percutaneous cardiopulmonary support (PCPS) in a preclinical setting. Six adult pigs underwent PCPS with or without the TACV. With standard hemodynamic monitoring, LV volume and function were assessed by direct ultrasonic cardiography (UCG) in each condition. PCPS was smoothly established and the TACV catheter was safely introduced in all cases. As compared with isolated PCPS, the TACV combined with PCPS maintained significant blood flow with LV venting and systemic perfusion: the heart rate of the native heart, systemic arterial pressure, and central venous pressure were stable. Also the additional TACV led to a significant reduction of LV preload during PCPS, and the reduction was 25-30% of LVDd and 20-35% of LVAd. The results of this investigation suggest that clinical application of the TACV technique with a clinical PCPS circuit would be feasible and additional TACV might be use-ful for LV recovery during PCPS in patients with severe heart failure.

Phlebosclerosis of the colon is a rare disease characterized by a thickening of the wall of the colon with fibrosis, hyalinization and calcification to the affected veins. These symptoms result in a type of ischemic colitis known as phlebosclerotic colitis. A case of phlebosclerotic colitis coincident with carcinoma in adenoma is reported. A 74-year-old Japanese woman was admitted to hospital because of a mass in her right lower abdomen. Abdominal computed tomography examination revealed linear calcifications in the wall of the cecum and the ascending colon. Colonoscopy revealed dark purple mucosa with multiple ulcers in the cecum and the ascending colon. Biopsy specimens showed a marked hyalinous thickening of the wall of small blood vessels in the mucosa. Phlebosclerotic colitis was suspected because of negative results with amyloid stain. Alternative ileocolic angiography showed the serpentine of the peripheral nature blood vessels and pooling at the late venous phase. Microscopic examination of the surgically resected colon revealed mucosal and submucosal fibrosis, and a thickening of the venous wall with fibrosis, hyalinization and calcification from the mucosa to the serosa, which caused a marked luminal narrowing. A small polypoid lesion was also found in the affected region and was diagnosed histologically as carcinoma in adenoma. To our knowledge, this is the first reported case of phlebosclerotic colitis complicated by carcinoma.

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially life-threatening side effect of heparin therapy, triggered by an immune response, and has been reported to be related not only to the therapeutic use of heparin but also to heparin-coated catheters. A 45-year-old woman with intrapelvic malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy despite prophylactic heparin use. Subsequent large doses of heparin for treatment of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4 complex antibody and heparin-induced platelet aggregation assay were positive, so the diagnosis was HITTS, and heparin was replaced by argatroban after carrying out thrombectomy. This therapy was successful, and the patient made favorable progress.

To clarify special imaging assessment that is useful for minimally invasive cardiac surgery (MICS), we examined 141 cases of MICS operations with ministernotomy or minithoracotomy. In the 141 patients, 62 valve, 42 coronary, 37 congenital heart, and 2 other procedures were successfully completed without conversion to full sternotomy. Preoperative chest x-ray, computed tomography, and/or magnetic resonance imaging were necessary for determining the level of ministernotomy, especially in aortic valve operations. Transthoracic echocardiography was useful for selecting procedures of mitral valve or intracardiac repair through the MICS approach. Intraoperative transesophageal echocardiography was essential for continuous monitoring of cardiac function, intracardiac flow, air bubbles, and so forth. The above results suggest that intensive imaging assessment might be very important for successful MICS operations with ministernotomy or minithoracotomy and that extensive indications for this technique exist for various cardiovascular diseases.

IL-18, a potent IFN-gamma-inducing cytokine, is expressed by various nonimmune cells as well as macrophages, suggesting that it has important physiological and immunological roles. The present study focused on the mechanism of active IL-18 induction from human oral epithelial cells. The epithelial cells and the cell lines constitutively express IL-18 mRNA and the 24-kDa precursor form of IL-18. Bioactive IL-18 exhibiting IFN-gamma-inducing activity was detected in the supernatant of the cells on costimulation with neutrophil proteinase 3 (PR3) and LPS for 24 h after IFN-gamma-priming for 3 days. An active 18-kDa form of IL-18 was detected in lysate and supernatant of the cells only after the above treatment and the induction was inhibited by cycloheximide and by serine proteinase inhibitors. After the treatment, lactate dehydrogenase activity was not detected in the cell culture supernatant, and PR3 was detected only in the membrane and not in cytoplasm fractions of the cells. Caspase-1 was not detected in the cells even after the treatment and the IL-18 induction was not inhibited by a caspase-1 inhibitor. These results suggest that the PR3-mediated induction of bioactive IL-18 secretion from oral epithelial cells in combination with LPS after IFN-gamma-priming occurred via a caspase-1-independent pathway, and provide new insight into the possible involvement of a neutrophil proteinase in the induction of bioactive IL-18 in oral inflammation such as periodontitis.

A-37-year-old woman in shock condition was transferred to our hospital after cardiopulmonary resuscitation for ventricular fibrillation. She was unconscious and suspected of suffering ischemic brain damage, with pathologic reflexes and weak brain stem reflexes. Brain CT scan showed cerebral edema without hemorrhage or infarction and an electroencephalograph revealed slow alpha-theta waves. Chest CT scan and echocardiogram showed ascending aortic aneurysm with sever aortic regurgitation. An emergent operation was performed for progression of heart failure. There were no distortion or dilatation of the sinus of Valsalva and annuloaortic ectasia and aortic valve leaflets were almost normal. We considered that the aortic valve dysfunction was cause by dilatation of the sinotubular junction. Ascending aortic and aortic valve replacement were carried out to shorten cardiopulmonary bypass time and to prevent the progression of brain damage. Mild hypothermia was employed as a neuroprotective procedure for three days after surgery. The patient's neurological symptoms, which were right hemiparesis, facial apraxia and motor aphasia, improved and she was discharged from the hospital on foot without any neurological complications on the 47th postoperative day and returned to work after two months.

As a new trigger method for chronic drive control of a ventricular assist device (VAD), a direct cardiac potential trigger was assessed under various conditions in a chronic experimental model. A pneumatic pulsatile VAD was implanted as circulatory support between the left ventricular apex and the ascending aorta in 12 adult pigs. Hemodynamic parameters and pump output were continuously monitored. Two tips of a bipolar electrode were set on the RV anterior wall and the LV posterior wall for recording direct cardiac potential. Counterpulsation drive of the VAD was applied by using the R wave in a standard electrocardiogram (ECG) or the direct cardiac potential as an ECG trigger. As special conditions, various artifacts on ECG, electromusculogram, arrhythmia, irregular ventilation, and passive vibration (simulation of exercise) were set for assessing the ECG trigger modes. Artifacts of irregular ventilation and passive vibration made the drive control poor using a standard ECG trigger. In contrast, the direct cardiac potential trigger maintained the counterpulsation control of the VAD well in all conditions of this study, and was a safe and reliable support for the native heart. It also supported animals for up to 48 hours after operation. The above results suggested that the direct cardiac potential trigger might be useful for monitoring native heart beats and adjusting the support cycle to the native heart cycle as a chronic control method for various VADs.

A 50-year-old healthy woman was scheduled for surgery of the first thoracic vertebral (T 1) hemangioma accompanying rapidly aggravated neurological deficit in three months. Anesthesia was induced with intravenous fentanyl and propofol and maintained with isoflurane-oxygen-air inhalation, followed by propofol infusion combined with sevoflurane inhalation. Following posterior decompression of T 1 with fusion of C 6-T 3, consecutive total spondylectomy of T 1 with anterior fusion of C 7-T 2 was carried out. At the end of surgery, marked edema was noticed on her face, neck and bilateral upper extremities, possibly due to long manipulation around the left jugular angle. Next morning the edema spread to her whole body and the elevation of both diaphragms and the mediastinal expansion were recognized. Mechanical ventilation in the mode of IMV was performed until subsiding of edema on the fifth postoperative day. During this period, hypoxemia was frequently observed in spite of appropriate respiratory support. On the third postoperative day, bronchoscopic bronchial toilet was performed which brought the improvement of blood oxygenation. The occasional administration of furosemide was not effective to reduce general edema, but served for the acceleration of lymphatic drainage after the release of the thoracic duct obstruction and the patient was extubated uneventfully on the sixth postoperative day.

We examined the relationship in horses between osmotic fragility of erythrocytes (OFE) measured as the red cell haemolysis rates (HLR) in 0.56% NaCl and certain physiological characters. Animals were exercised on a treadmill: warmed up at 30% VO2max for 5 min or at 105% VO2max for 1 min, given an exercise test at 80 or 105% VO2max until fatigued, and then cooled down. The pH and temperature of the blood had a significant correlation for the HLR: r = 0.93 and 0.92 (P < 0.01) on arterial and mixed venous blood, respectively. In multiple regression analysis, heart rate and packed cell volume showed lower coefficients for the HLR. The present study suggested that, in exercising horses, 1) the increase of blood flow and release of erythrocytes from the spleen into the circulation have little effect on changes of OFE; 2) the decrease of blood pH promotes OFE; 3) the increase of the pH causes osmotic resistance in the cells and 4) an increase of blood temperature during exercise is associated with the decrease in the OFE.