Incidence of elevated procalcitonin and presepsin levels after severe trauma: a pilot cohort study.

Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries. Trauma patients with an Injury Severity Score of ≥16 from October 2013 to September 2015 were enrolled in our study. We examined PCT and PSEP levels and their positive rates on days 0 and 1. PCT and PSEP levels on days 0 and 1 were compared. Risk factors for increasing sepsis biomarker levels were identified by multivariate logistic regression analyses. In this study, 75 patients were included. PCT levels on days 0 and 1 were 0.1±0.4 and 1.8±6.3 ng/ml, respectively (P=0.02). PSEP levels on days 0 and 1 were 221±261 and 222±207 pg/ml, respectively (P=0.98). As per multivariate logistic regression analyses, packed red blood cell (PRBC) transfusion was the only independent risk factor for higher PCT levels on day 1 (P=0.04). Using PCT to diagnose sepsis in trauma patients on day 1 requires caution. PRBC transfusion was found to be a risk factor for increasing PCT levels. On the other hand, PSEP levels were not affected by trauma during the early phases.

Stress on a postpartum mother inhibits the secretion of growth hormone in the offspring and causes persistent growth impairment.

Children exposed to environmental stress in the early neonatal period often develop psychiatric or somatic diseases in adulthood. In the present study in mice, we examined how postpartum stress on the mother influences their pups and thus tried to provide new insight into the management of idiopathic short stature. The dams were exposed to daily 3-h immobilization stress (IS) only for 3 weeks from the day after delivery. When compared to the pups of nonstressed dams (control pups), those of the IS dams (IS pups) showed lower body weight and height, which persisted even into adulthood. Their nutritional status was normal. The IS pups also showed low serum concentrations of insulin-like growth factor I (IGF-I) and poor responses to growth hormone-releasing hormone (GHRH) stimulation on day 22 and were behaviorally hyperactive at 8 weeks. Immunohistochemical analysis demonstrated that the number of pituitary GH-positive cells in response to treatment with GHRH was markedly decreased in the IS pups compared to the control pups. The IS dams did not show apparent behavioral abnormalities except downregulation of glucocorticoid receptor (GR) gene expression in the hippocampus. These results suggest that the perturbation of GH secretion in the pituitary glands is involved in the lifelong growth impairment of the IS pups.

[Midterm survival of valve replacement with Carpentier-Edwards pericardial bioprosthesis in young adults].

Biologic prostheses are generally considered to have superior antithrombotic properties but lack durability. We recommend biologic prostheses to elderly patients aged over 65 years old. The purpose of this report is to evaluate the midterm outcomes of aortic or mitral valve replacement with Carpentier-Edwards Pericardial Bioprosthesis (CEP) in patients younger than 60 years old. We performed valve replacement with CEP in 17 patients, aged 60 years or youngers, in the past 10 years. The survival rate and freedom from cardiac death at 9 years was 73.2% and 87.8%, respectively. There was no valve-related thromboembolism, anticoagulant-related hemorrhage, prosthetic valve endocarditis, structual valve dysfunction or re-operation. The midterm durability of the CEP in young patients was excellent. In selection of valve prosthesis, it is important to consider factors such as risk of re-operation as well as taking warfarins, and the patient's life style and wishes.

Quorum sensing and microbial biofilms.

Some bacterial species engage in two well-documented social behaviors: the formation of surface-associated communities known as biofilms, and intercellular signaling, or quorum sensing. Recent studies have begun to reveal how these two social behaviors are related in different species. This chapter will review the role quorum sensing plays in biofilm formation for different species. In addition, different aspects of quorum sensing in the context of multispecies biofilms will be discussed.

Development of articular cartilage grafts using organoid formation techniques.

In order to develop articular cartilage grafts, one must control shape and safety. We have developed scaffold-free culture methods in which the cells form multicellular aggregates (organoids). In this study, we applied the organoid culture method to chondrocytes attempting to reconstitute articular cartilage grafts. Primary rat costal chondrocytes and subcultured human articular chondrocytes were immobilized in hollow fibers by centrifugation at a density of 3 x 10(8) cells/cm3 to induce the formation of cylindrical-shaped organoids. To improve convenience, we developed a culture device to form sheet-shaped organoids (organoid-sheet). Primary bovine articular chondrocytes were cultured in this device. These organoids were evaluated by histological and gene expression analyses. In the primary rat culture system, chondrocytes formed cylindrical organoids in hollow fibers. Histochemical analysis revealed the presence of extracellular matrix (collagen and proteoglycan). The organoid maintained cartilage-specific gene expression (type II collagen, aggrecan) for 1 month of culture. In the subcultured human chondrocyte system, the organoid regained the decreased cartilage-specific gene expression. In the primary bovine culture system, the cells formed a 300 microm thickness organoid-sheet including abundant extracellular matrix. In conclusion, our organoid formation method was effective to form cartilage-like tissue. This result suggested that the technique may be applicable for the development of an articular cartilage graft.

[Surgical treatment for the valvular disease through partial sternotomy].

213 patients who underwent surgical treatment for the valvular disease through partial sternotomy were studied. We started the minimally invasive valvular surgery in July 1997. All the valvular diseases were indicated for the minimally invasive surgery except for the annulo-aortic ectasia and the concomitant disease with coronary artery bypass surgery. Ascending aorta was selected as an arterial cannulation place if we could choice it through intraoperative echocardiography. Venous cannulae 22-24 Fr were inserted into the venae cavae directly or through right atrium. Negative pressure venous drainage (maximally 90 mmHg) was performed if necessarily. We did single approach as possible. Mortality rate was 3.8%. We could complete 96.2% of our series as a minimally invasive surgery. Post operative intensive care unit (ICU) stay and hospital stay through partial sternotomy were significantly shorter than those through full sternotomy.

Expression of neuronal growth inhibitory factor (metallothionein-III) in the salivary gland.

Metallothioneins (MTs) are metal-binding proteins that have been regarded as intrinsic factors for protecting cells and tissues from metal toxicity and oxidants. Among the three major classes of MTs, MT-III is different from other MTs because it has neuronal inhibitory activity and is only expressed in the central nervous system. Recent studies, however, have confirmed that MT-III is also expressed in organs other than the brain. These findings not only indicate that MT-III has a much wider tissue distribution than was originally thought, but also suggest that it might have other unknown activities. In the present study, we examined the human salivary and thyroid glands and demonstrated that the MT-III gene is also expressed in the salivary but not in the thyroid gland. While salivary ducts showed intense immuno-reactivity with anti-MT-III, weak immunoreactivity was observed in acinar cells. This, together with the findings that some neuromodulators (i.e. nerve growth factor, etc.) exist in the salivary gland and that MT-III may participate in the transport in renal tubules, suggest that MT-III may have other functions than cytoprotection in the salivary gland.

[Total removal of infected pacemaker lead with cardiopulmonary bypass; report of a case].

The incidence of infection after pacemaker implant has been reported to occur rarely but it's one of the severe complication. Pacemaker lead sometimes imbedded in the right atrial and ventricular wall, and it seemed to be difficult to remove the pacemaker lead by closed techniques. The optimal treatment is total removal generator and pacing lead, therefore, it is necessary to remove with cardiopulmonary bypass. Septicemia caused by infections retained pacemaker lead developed in an 87-year-old man. Following antibiotic therapy, the lead was successfully removed by cardiotomy on cardiopulmonary bypass. Total removal with cardiopulmonary bypass would be recommended.

Receptor signaling mechanisms underlying muscarinic agonist-evoked contraction in guinea-pig ileal longitudinal smooth muscle.

1 In guinea-pig ileal longitudinal muscle, muscarinic partial agonists, 4-(N-[3-chlorophenyl]-carbomoyloxy)-2-butynyl-trimethylammonium (McN-A343) and pilocarpine, each produced parallel increases in tension and cytosolic Ca(2+) concentration ([Ca(2+)]c) with a higher EC(50) than that of the full agonist carbachol. The maximum response of [Ca(2+)]c or tension was not much different among the three agonists. The Ca(2+) channel blocker nicardipine markedly inhibited the effects of all three agonists 2 The contractile response to any agonist was antagonized in a competitive manner by M(2) receptor selective antagonists (N,N'-bis[6-[[(2-methoyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride and 11-[[2-[(diethlamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4] benzodiazepine-6-one), and the apparent order of M(2) antagonist sensitivity was McN-A343>pilocarpine>carbachol. M(3) receptor selective antagonists, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide and darifenacin, both severely depressed the maximum response for McN-A343, while darifenacin had a similar action in the case of pilocarpine. Both M(3) antagonists behaved in a competitive manner in the case of the carbachol response. 3 McN-A343 failed to release Ca(2+) from the intracellular stores, and the Ca(2+)-releasing action of pilocarpine was very weak compared with that of carbachol. All three agonists were capable of increasing Ca(2+) sensitivity of the contractile proteins. 4 McN-A343 rarely produced membrane depolarization, but always accelerated electrical spike discharge. Pilocarpine effect was more often accompanied by membrane depolarization, as was usually seen using carbachol. 5 The results suggest that muscarinic agonist-evoked contractions result primarily from the integration of Ca(2+) entry associated with the increased spike discharge and myofilaments Ca(2+) sensitization, and that Ca(2+) store release may contribute to the contraction indirectly via potentiation of the electrical membrane responses. They may also support the idea that an interaction of M(2) and M(3) receptors plays a crucial role in mediating the contraction response.

Sonographic features of hepatic artery calcification in chronic renal failure.

PURPOSE: Little is known about radiological aspects of hepatic artery calcification. For this reason, the sonographic features of calcified hepatic arteries were studied in patients with chronic renal failure who frequently develop tissue calcification due to hyperparathyroidism. MATERIAL AND METHODS: Ultrasound was performed in 314 patients on dialysis who underwent examination of the liver, spleen and kidney twice in the past 4 years and were reevaluated with particular attention to acoustic shadowing. Abdominal CT was carried out in 219 of these 314 patients, and ultrasound findings were reevaluated with reference to CT findings. RESULTS: A large acoustic shadow was seen in the hilum that corresponded to the calcified hepatic artery on CT in 8 patients, and in another 9, a similar large shadow was seen in the hilum without CT confirmation. Acoustic shadows of various sizes were definitely or most likely due to arterial calcification within the liver in 36 patients. The strength of shadow depended on the angle at which the ultrasound beam hit the artery. Probable calcification of small arteries accompanying portal veins was seen in 70 patients. These changes are different from those due to pneumobilia and biliary tract diseases. CONCLUSION: Calcification of the hepatic artery can be identified by its acoustic shadow.

Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial.

Alternative medicine use has increased at a remarkable pace all over the world in recent years. Although herbal medicine for the treatment of asthma is becoming the focus of public attention, randomized studies had not been performed, even in Eastern countries including Japan. This study was designed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to (TJ-96) is effective for the treatment of atopic asthma, and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation. A double-blind, randomized, crossover design was used. Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine. Furthermore, eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. After 4 weeks of treatment with TJ-96, values of PC20 -methacholine significantly improved in the treatment with TJ-96. Also, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma.

Acute renal failure and hearing loss due to sodium bromate poisoning: a case report and review of the literature.

Acute renal failure with hearing loss due to sodium bromate intoxication is described. A 48-year-old woman who ingested permanent wave neutralizer in a suicide attempt and developed anuria was admitted to our hospital for hemodialysis. Bromate intoxication was suspected and hemodialysis was carried out; she required maintenance dialysis 3 times a week. Irreversible severe sensorineural hearing loss continued and peripheral polyneuropathy developed in the lower limbs. We measured the concentration of bromine in the serum before and after the first hemodialysis and found its removal rate to be 61.3%. This is the first report that proved the utility of hemodialysis for bromate intoxication in a clinical setting.

Amida predominantly expressed and developmentally regulated in rat testis.

Amida was first isolated from a rat hippocampal cDNA library as an Arc-associated protein. Previous studies showed that Amida is a nuclear protein and overexpression of Amida induces cell apoptosis. In this study, we found that Amida mRNA was expressed predominantly in rat testis by Northern blot analysis. During the development of testis, Amida mRNA was barely detectable until postnatal days 24 to 29 during which it increased to levels found in adults. However, Amida protein was not detected until postnatal day 32. Amida mRNA was found to be enriched in spermatocytes and less in round spermatids, but was undetectable in elongated spermatids by in situ hybridization. In addition, Amida protein was observed in the nucleus of spermatocytes and even in the elongated spermatids by immunohistochemistry. The development and cellular localization differences of Amida mRNA and protein implicates that Amida mRNA may undergo posttranscriptional regulation. Furthermore, Amida mRNA decreased significantly in the 8-day experimental cryptorchid testis when spermatogenesis was disrupted. Taken together, these data suggest that Amida is involved in spermatogenesis and may play an important role in development of testicular germ cells.

Rantes production during development of cardiac allograft vasculopathy.

BACKGROUND: RANTES (regulated on activation, normal T cell expressed and secreted) production has been shown to correlate with mononuclear cell recruitment and precede intimal thickening in cardiac allograft vasculopathy (CAV). However, the cells that produce RANTES in CAV are undefined. Therefore, in an MHC II-mismatched murine model of CAV, we sought to (1) define the cellular sources of RANTES and (2) determine the role of CD4+ lymphocytes in RANTES production during CAV development. METHODS: B6.CH-2bm12 strain donor hearts were transplanted heterotopically into wild-type (WT) or CD4 knockout (CD4KO) C57BL/6 mice (MHC II mismatch). No immunosuppression was used. Recipients were sacrificed at 7, 14, and 24 days. Intragraft RANTES gene expression and protein levels were determined with ribonuclease protection assay and ELISA, respectively. At days 7 and 24, RANTES production by graft-infiltrating cells was defined with intracellular RANTES staining and multicolor FACS analysis. Intimal thickening was quantitated morphometrically. In murine hearts and in six explanted human hearts with advanced CAV, RANTES was also localized immunohistochemically. RESULTS: NK, NKT, and gammadelta+ cells, in addition to CD4+, CD8+ lymphocytes, and CD11b+ macrophages, produced RANTES in early and late stages of CAV. RANTES-producing NK, NKT, and gammadelta+ cells tripled in number during CAV development; by day 24, NK and gammadelta+ cells each outnumbered CD4+ lymphocytes and CD11b+ macrophages. The presence of CD4+ lymphocytes was required for sustained RANTES production in allografts, which correlated with mononuclear cell recruitment and preceded intimal thickening. In murine and explanted human hearts with advanced CAV, RANTES immunolocalized with graft-infiltrating mononuclear cells and vessel wall cells. CONCLUSIONS: We present evidence that other cell types in addition to CD4+, CD8+ T lymphocytes, and CD11b+ macrophages contribute significantly to RANTES production in CAV. In this MHC II-mismatched murine model of CAV, sustained RANTES production requires CD4+ lymphocytes, correlates with mononuclear cell recruitment, and precedes intimal thickening. In experimental and human CAV, vessel wall cells may also produce RANTES. Interventions aimed at inhibiting RANTES production in CAV may need to target several types of cells, and neutralization of RANTES bioactivity may reduce mononuclear cell recruitment and CAV development.

Metallothionein-III antagonizes the neurotoxic and neurotrophic effects of amyloid beta peptides.

Metallothionein-III (MT-III) protects cerebral cortical neurons in established culture from the toxic effect of amyloid beta peptides (Abetas). Protection is concentration dependent and approaches 100% at 0.1 microM. The EC(50) value estimated at 5 microM Abeta(1-40) is 2 nM. At higher concentrations (>0.1 microM), MT-III also antagonizes the trophic effect of Abeta(1-40) on cerebral cortical neurons in early cultures. Because only the fibrillar, SDS-resistant form of Abeta aggregates are thought to be neurotoxic, we analyzed and compared Abeta(1-40) aggregates formed in the presence and absence of MT-III using SDS-PAGE. Results show that aggregates formed in the absence of MT-III are predominantly SDS-resistant whereas those formed in its presence are mostly SDS-soluble. Neither MT-I nor -II exhibits any of the effects of MT-III. On the basis of these results, we propose that MT-III alleviates Abetas' neurotoxic effect by abolishing the formation of toxic aggregates of Abetas and that it may play a specific and important role in protecting the brain from the deleterious effects of Abetas.

CD8+ lymphocytes augment chronic rejection in a MHC class II mismatched model.

UNLABELLED: Chronic rejection, or cardiac allograft vasculopathy (CAV), remains the leading cause of late death in heart transplant recipients. The precise role and contributions of T lymphocyte subsets to CAV development remains unknown. METHODS: Donor hearts from B6.C-H2bm12 mice were transplanted into T lymphocyte subset knockout recipients and T lymphocyte-reconstituted nude recipients. No immunosuppression was used. Intimal proliferation was measured morphometrically. In vitro studies were performed to analyze the donor-specific activation status of recipient CD8+ lymphocytes by examining cellular proliferation, interleukin-2 secretion, and interleukin-2Ralpha expression. Intracellular cytokine staining assay was performed to determine both the profile and source of intragraft cytokines. RESULTS: Hearts transplanted into wild-type recipients developed severe CAV by 24 days. Intimal lesions were absent in the hearts that were transplanted into nude and CD4-/- knockout mice (containing CD8+ lymphocytes). In contrast, the donor hearts in CD8-/- knockout recipients (containing CD4+ lymphocytes) developed CAV, but significantly less than in wildtype. Adoptive transfer of T lymphocyte subset populations into nude recipients confirmed that CAV was absolutely contingent on CD4+ lymphocytes, and that CD8+ lymphocytes played an additive role in intimal lesion progression in the presence of CD4+ lymphocytes. Although CD8+ lymphocytes alone did not cause CAV in vivo, we demonstrated that MHC class II disparate alloantigens activated CD8+ lymphocytes both in vivo and in vitro. Finally, both CD4+ and CD8+ lymphocytes contributed to the intragraft IL-2 and IFN-gamma production. CONCLUSIONS: In this MHC class II mismatched murine model, CAV is a T lymphocyte dependent event, and absolutely contingent on the presence of CD4+ lymphocytes. Furthermore, CD8+ lymphocytes (1) are activated by MHC class II disparate antigens and (2) play a significant role in the progression of lesion development. Finally, both CD4+ and CD8+ lymphocytes contribute to CAV development via secretion of IFN-gamma, a known mediator of CAV in this model.

Isoform-specific regulation of vascular endothelial growth factor (VEGF) family mRNA expression in cultured mouse brown adipocytes.

We have shown that brown adipose tissue (BAT), a thermogenic organ in mammals, expresses high levels of vascular endothelial growth factor (VEGF) mRNA in response to exposure to cold, which may contribute to angiogenesis associated with cold-induced hyperplasia of this tissue. In the present study, we examined mRNA expression of not only VEGF, but also VEGF-B and VEGF-C, recently cloned VEGF isoforms, in vitro using immortal brown adipocytes (HB2) isolated from mouse BAT. HB2 preadipocytes expressed detectable levels of VEGF, VEGF-B and VEGF-C mRNA, but a low level of VEGF. After HB2 cells differentiated into adipocytes, the VEGF mRNA level increased without a noticeable change in the VEGF-B and VEGF-C mRNA levels. When HB2 cells were stimulated by norepinephrine, the VEGF mRNA level increased without a change in that of VEGF-B, while the VEGF-C mRNA level decreased. A marked reduction of VEGF-C mRNA expression was also found when HB2 cells were treated with agonists of peroxisome proliferator-activated receptor gamma (PPARgamma, troglitazone), retinoic acid receptor (RAR, all-trans retinoic acid) and retinoid X receptor (RXR, 9-cis retinoic acid). These results suggest a specific adrenergic mechanism for up-regulation of VEGF expression different from those for other VEGF isoforms, and thereby the major contribution of VEGF to the cold-induced angiogenesis in BAT. In addition, the agonists of PPARgamma, RAR and RXR are suggested to be inhibitory to angiogenesis through the reduction of VEGF-C production.