Functional status of the articularis genus muscle in individuals with knee osteoarthritis.

OBJECTIVES: To clarify the functional status of the articularis genus muscle (AGM) in individuals with knee osteoarthritis (OA) and to analyze the muscle's relationship with knee OA. METHODS: Fifty-two individuals with knee OA (mean age, 73.4 years), 50 elderly individuals without knee OA changes (mean age, 71.2 years) and 75 young individuals (mean age, 20.2 years) were observed the AGM using ultrasonography. The thickness of the AGM, the anteroposterior distance of the suprapatellar bursa, and moving distance of the muscle insertion were measured both at rest and during isometric contraction, and values during contraction were expressed as percentages of the values at rest (%Muscle-Increase, %Bursa-Increase). RESULTS: Muscle thickness at rest, %Muscle-Increase, %Bursa-Increase, and moving distance of the muscle insertion were significantly lower and anteroposterior distance of the suprapatellar bursa was significantly higher in the OA group than in the controls (p<0.001, all). In the OA group, these values for the AGM were significantly correlated with knee range of motion, knee pain, and Kellgren and Lawrence grade. CONCLUSIONS: Individuals with knee OA exhibited atrophic changes and dysfunctions of the AGM, and these were associated with symptoms. Atrophic changes and dysfunctions of the AGM may be specific changes associated with knee OA.

Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT.

The effects of macrophage activation on the outcome of allogeneic hematopoietic SCT (allo-HSCT) have yet to be fully examined. A total of 70 adult patients who received a first allo-HSCT for hematological diseases were studied. We counted the number of hemophagocytic cells in BM clot sections on day +14±7, and analyzed its impact on subsequent outcome. In all, 23 patients were diagnosed as having increased numbers of hemophagocytic cells (HP group), whereas 47 were not (non-HP group). The HP group was not associated with an increased incidence of acute or chronic GVHD, but was associated with worse hematopoietic recovery than the non-HP group. The 2-year OS for the HP group and the non-HP group was 30 and 65% (P<0.01), respectively, and 2-year non-relapse mortality was 48% and 27% (P<0.01), respectively. Multivariate analysis confirmed that the HP group was associated with a lower OS (hazard ratio (HR)=2.3; 95% confidence interval (CI), 1.0-5.4; P=0.048) and higher non-relapse mortality (HR=4.0; 95% CI, 1.6-9.9; P<0.01). The HP group had higher incidences of death due to graft failure (P<0.01) and endothelial complications, such as sinusoidal obstruction syndrome and transplant-associated microangiopathy (P=0.01). Macrophage activation is a previously unrecognized complication with negative impact on outcome of allo-HSCT.

Eosinophilia predicts better overall survival after acute graft-versus-host-disease.

The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P=0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P=0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P=0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P=0.03) and lower NRM (P=0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P=0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.

Rapid microRNA (miRNA) detection and classification via surface-enhanced Raman spectroscopy (SERS).

microRNAs (miRNA) are recognized as regulators of gene expression during development and cell differentiation as well as biomarkers of disease. Development of rapid and sensitive miRNA profiling methods is essential for evaluating the pattern of miRNA expression that varies across normal and diseased states. The ability to identify miRNA expression patterns is limited to cumbersome assays that often lack sensitivity and specificity to distinguish between different miRNA families and members. We evaluated a surface-enhanced Raman scattering (SERS) platform for detection and classification of miRNAs. The strength of the SERS-based sensor is its sensitivity to detect extremely low levels of analyte and specificity to provide the molecular fingerprint of the analyte. We show that the SERS spectra of related and unrelated miRNAs can be detected in near-real time, that detection is sequence dependent, and that SERS spectra can be used to classify miRNA patterns with high accuracy.

Psicosis cicloides: a propósito de un caso / Cycloid psychosis: a propos of a case

El concepto de psicosis cicloide se ha ido desarrollando y modificando a lo largo de los años. A pesar de que actualmente no se contempla como tal en los manuales diagnósticos al uso, hay numerosos pacientes que podrían ser incluidos en este diagnóstico controvertido. Se presenta el caso de una paciente que cumpliría los criterios clásicos de psicosis cicloide. Se realiza un repaso sobre esta entidad desde los puntos de vista diagnóstico y pronóstico. Se debate, además, la necesidad de instaurar un tratamiento antipsicótico y eutimizante en las fases agudas y de mantenimiento de la enfermedad (AU)

Effective extracellular trehalose production by Cellulosimicrobium cellulans.

A bacterium isolated from a petal of Casa Blanca Lily (ST26 strain) produced a marked amount of extracellular trehalose (alpha- d-glucopyranosyl-[1,1]-alpha- d-glucopyranose) in culture medium containing glucose. 16S rDNA-based phylogeny showed that ST26 belongs to, or is related to, Cellulosimicrobium cellulans, a close relative of Cellulomonas spp. Various Cellulomonas strains obtained from culture collections also showed extracellular trehalose productivity, suggesting that trehalose production is a common property of this bacterial genus. ST26 accumulated trehalose in medium supplied with glucose but not with sucrose, glycerol or maltose. Effective extracellular trehalose production by ST26 was achieved by supplying 0.5-1% ammonium sulfate and 0.5-1% CaCO(3). The addition of CaCO(3) adjusted the pH of the culture to around 5.0. The optimized culture conditions yielded trehalose from glucose at a conversion rate of 61%. The addition of ammonium sulfate greatly reduced the dry cell weight of ST26 and intracellular content of trehalose, which suggests that the addition of ammonium sulfate makes ST26 cells leak trehalose into the medium. ST26 effectively propagated in minimal medium containing trehalose as a sole carbon source, which suggests that trehalose serves as a carbohydrate reserve of this organism.

Involvement of MAPK activation in bacterial endotoxin-inducible tissue factor upregulation in human monocytic THP-1 cells.

BACKGROUND: Monocytic tissue factor (mTF) hypercoagulation leading to thrombotic complications is commonly observed following sepsis. OBJECTIVE: We herein study the intracellular mechanism of mTF upregulation in human model monocytic THP-1 cells in response to bacterial endotoxin (lipopolysaccharide, LPS; Escherichia coli O111:B04), determining if mitogen-activated protein kinase (MAPK) activation is involved in the signaling. METHODS: We assessed mTF upregulation by its cell surface expression, protein synthesis, and functional activity based on flow cytometry, Western blotting analysis, and a single-stage clotting assay, respectively. RESULTS: A 3-h challenge with LPS (100 ng/ml) drastically induced mTF functional activity, accompanied by elevated surface mTF expression and synthesis. The suppression by genistein (G) of LPS-inducible mTF upregulation implied the involvement of protein tyrosine kinase activation in mTF upregulation. LPS activated MAPK, which was significantly depressed by G, SB 203580 (SB), and PD 98058 (PD). Interestingly, inclusion of SB and PD also markedly diminished LPS-inducible mTF upregulation. The parallelism between MAPK and mTF activities revealed the involvement of MAPK activation in such mTF upregulation. Based on the ability of SB and PD to respectively block LPS-inducible tyrosine phosphorylation of p38 MAPK and Erk1/2, it was evident that tyrosine phosphorylation of MAPKs is required for mediating LPS-inducible mTF synthesis and upregulation. Contrasting with the established prevention of mTF upregulation by these inhibitors, failure to offset the already LPS-induced mTF activity seemed to be consistent with the view that LPS readily activated MAPK responsible for mTF synthesis. CONCLUSION: Our data suggest that the tyrosine phosphorylation of MAPKs (p38 and Erk1/2) leading to their activation could be a prerequisite for LPS induction of mTF synthesis contributing to the upregulation of mTF-initiated extrinsic coagulation.

Effect of dietary seal and fish oils on lipid metabolism in hamsters.

Eicosapentaenoic and docosahexaenoic acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerols and in the sn-2 position of fish oil triacylglycerols. Seal oil-rich or fish oil-rich fats having constant polyunsaturated (PUFAs)/monounsaturated/saturated fatty acids and n-6/n-3 PUFAs ratios were fed to hamsters for 3 weeks. The control fat contained linoleic acid as the sole PUFA. The concentration of triacylglycerols in the liver was significantly lower in the fish oil group than in the control group. Phospholipid concentration in serum was lower and that in the liver was higher in the seal oil group compared with the fish oil group. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and the malic enzyme were significantly lower in both the fish and seal oil groups than in the control group. Dietary seal oil more effectively reduced arachidonic acid content in liver phosphatidylcholine and phosphatidylethanolamine and serum phosphatidylcholine than fish oil. These results showed that different intramolecular distribution of n-3 PUFAs influenced glycerolipid metabolism and arachidonic acid content in serum and liver phospholipids of hamsters.

Crystallization and preliminary crystallographic studies of RhoGDI in complex with the radixin FERM domain.

The Rho guanine nucleotide-dissociation inhibitor (RhoGDI) is a general regulator that forms a complex with the GDP-bound form of Rho-family GTPases and suppresses their activation. The FERM domains of ERM (ezrin/radixin/moesin) proteins bind to RhoGDI and dissociate Rho from RhoGDI. The formation of a complex between RhoGDI and the FERM domain is an important step in the regulatory cycle of Rho activation. In this study, crystals of RhoGDI complexed with the FERM domain of radixin were obtained. The crystals of the binary complex belong to the space group P2(1)2(1)2, with unit-cell parameters a = 130.9 (2), b = 151.2 (2), c = 71.2 (1) A, and contain two protein complexes in the crystallographic asymmetric unit. A 2.9 A resolution data set was collected using synchrotron radiation at SPring-8.

c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro.

c-Jun is an oncoprotein that activates transcription of many genes involved in cell growth and proliferation. We studied the mechanism of transcriptional activation by human c-Jun in a human RNA polymerase II transcription system composed of highly purified recombinant and native transcription factors. Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)-associated factor (TAF) subunits of transcription factor IID (TFIID). Protein-protein interaction assays revealed that c-Jun binds with high specificity to the largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c-Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds to TBP and represses its interaction with TATA boxes, thereby decreasing DNA binding by TFIID. We hypothesized that c-Jun is capable of derepressing the effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of this hypothesis, we found that c-Jun increased levels of TFIID-driven transcription in vitro when added at high concentrations to a DNA template lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to revealing a mechanism by which c-Jun activates transcription, our studies provide the first evidence that an activator can bind directly to the N terminus of TAF(II)250 to derepress RNA polymerase II transcription in vitro.

Human Taf(II)130 is a coactivator for NFATp.

NFATp is one member of a family of transcriptional activators that regulate the expression of cytokine genes. To study mechanisms of NFATp transcriptional activation, we established a reconstituted transcription system consisting of human components that is responsive to activation by full-length NFATp. The TATA-associated factor (TAF(II)) subunits of the TFIID complex were required for NFATp-mediated activation in this transcription system, since TATA-binding protein (TBP) alone was insufficient in supporting activated transcription. In vitro interaction assays revealed that human TAF(II)130 (hTAF(II)130) and its Drosophila melanogaster homolog dTAF(II)110 bound specifically and reproducibly to immobilized NFATp. Sequences contained in the C-terminal domain of NFATp (amino acids 688 to 921) were necessary and sufficient for hTAF(II)130 binding. A partial TFIID complex assembled from recombinant hTBP, hTAF(II)250, and hTAF(II)130 supported NFATp-activated transcription, demonstrating the ability of hTAF(II)130 to serve as a coactivator for NFATp in vitro. Overexpression of hTAF(II)130 in Cos-1 cells inhibited NFATp activation of a luciferase reporter. These studies demonstrate that hTAF(II)130 is a coactivator for NFATp and represent the first biochemical characterization of the mechanism of transcriptional activation by the NFAT family of activators.

[Anesthetic management for an adult patient with secundum atrial septal defect associated with a large left-to-right shunt].

We describe the case of a 68-year-old woman with secundum atrial septal defect associated with a large left-to-right shunt and congestive heart failure. The patient with a pancreatic tumor was scheduled for hepatic cholangiojejunostomy and cholecystectomy. To determine the ratio of pulmonary to systemic flow (Qp/Qs) as an indicator for the magnitude of left-to-right shunt, oxymetric catheters were placed in the superior vena cava and pulmonary artery. In addition, oxygen delivery was assessed using superior vena cava oxygen saturation (SsvcO2). Although the patient was anesthetized with high-dose fentanyl to supplement nitrousoxide and sevoflurane, the Qp/Qs markedly increased after skin incision. Epidural local anesthetic was then administered. The Qp/Qs decreased to the preoperative value and the hemodynamic condition was improved thereafter. The operative course was uneventful. This case illustrates the potential usefulness of continuous measurement of the Qp/Qs and SsvcO2 for anesthetic management of adult patients with secundum atrial septal defect.

[Anesthetic management of a patient with deep venous thrombosis using temporary inferior vena cava filter].

A patient with deep venous thrombosis caused by a huge uterine leiomyoma underwent abdominal hysterectomy. To prevent pulmonary thromboembolism, the patient received anticoagulant therapy until 6 hr before surgery and temporary inferior vena cava filter was placed. A combination of preoperative anticoagulant therapy and the filter placement during perioperative period enabled this patient to be successfully-managed.

[A case of free rupture of abdominal aortic aneurysm into the peritoneal cavity during posture change after induction of anesthesia].

We report a case in which posture change for radiography after induction of anesthesia caused free rupture of the abdominal aortic aneurysm (AAA) into the peritoneal cavity, resulting in shock, although in the patient an AAA had ruptured into only the retroperitoneal space and hemodynamics had been stable preoperatively. The massive bleeding was controlled with autotransfusion using a washing salvaging autotransfusion device and a roller pump for hemodialysis. In addition, international mild hypothermia was effective for protection of the brain from suspected ischemia during shock. Meticulous attention should be paid for anesthetic management of patients with ruptured AAA even if their hemodynamic status is stable.

Establishment and characterization of a prostatic small-cell carcinoma cell line (PSK-1) derived from a patient with Klinefelter syndrome.

BACKGROUND: Prostatic small-cell carcinoma (SMCC) is an extremely aggressive, rarely occurring tumor, and there has been no previous report of prostatic SMCC in association with Klinefelter syndrome. This study reports on the first such case and the establishment of the first cell line of SMCC from this tumor. METHODS: Prostatic SMCC tissue was derived from a 29-year-old man with Klinefelter syndrome. Characteristics of the culture tumor cells were evaluated with cell growth in vitro, neuron-specific enolase (NSE) secretion ability, tumorigenicity in nude mice, chemosensitivity to anticancer drugs, and karyotypic analysis. RESULTS: A culture cell line (PSK-1) was successfully established from prostatic SMCC with Klinefelter syndrome. PSK-1 cells had a polygonal epithelioid morphology and demonstrated loss of contact inhibition. These cells secreted NSE into the culture supernatant. Tumors produced in nude mice were histologically similar to the original SMCC. In a chemosensitivity test, PSK-1 cells were found to be sensitive in vitro to cisplatin, etoposide, and doxorubicin, but resistant to dacarbazine and 5-fluorouracil. Cytogenetic analysis showed that the PSK-1 cells at passage 35 revealed 76-84 chromosomes, with a mode of 82 chromosomes. CONCLUSIONS: PSK-1 cells could represent some properties of the original tumor cells, and could be used in studies on the etiology and treatment of this disease.