CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence.

Transforming growth factor-α (TGF-α)-induced proliferation and transforming growth factor-ß (TGF-ß)-mediated quiescence are intricately balanced in normal lung-tissue homeostasis but are deregulated during neoplastic progression of lung cancer. Here, we show that Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a novel MYC-interacting transcriptional modulator, responds to TGF-α induction and TGF-ß suppression to orchestrate cellular proliferation and quiescence, respectively. Upon TGF-α induction, CITED2 was induced by MYC and further modulated MYC-mediated transcription in a feed-forward manner. CITED2 recruited p300 to promote MYC-p300-mediated transactivation of E2F3, leading to increased G1/S cell cycle progression. Moreover, CITED2 inhibited cellular quiescence by enhancing MYC-mediated suppression of p21(CIP1). CITED2 interacted with histone deacetylase 1 (HDAC1) and potentiated MYC-HDAC1 complex formation. TGF-ß stimulation provoked downregulation of CITED2, which abrogated MYC-HDAC1-mediated p21(CIP1) suppression, causing cellular quiescence. Ectopic CITED2 expression enhanced tumor growth in nude mice; furthermore, CITED2 knockdown caused tumor shrinkage and increased overall host mouse survival rates. Expression of CITED2/MYC/E2F3/p21(CIP1) signaling molecules was associated with poor prognosis of lung cancer patients. Thus, CITED2 functions as a molecular switch of TGF-α and TGF-ß-induced growth control, and MYC-CITED2 signaling axis provides a new index for predicting clinical outcome.

Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma.

Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 µg (10)B/mL medium of BA treatment, the boron concentration in UMR-106 cells was higher than that in L929 cells. The biodistribution and pharmacokinetics of BA in Sprague-Dawley (SD) rats were studied by administrating 25 mg (10)B/kg body weight to SD rats. Blood boron level decreased rapidly within one hour after BA injection. Boron concentration in the long bone was 4-6 time higher than that of blood. Results of this study suggest that BA may be a potential drug for BNCT for osteosarcoma.

Rotavirus infection increases the risk of bacteremia in children with nontyphoid Salmonella gastroenteritis.

To evaluate whether there is any impact of rotavirus infection on nontyphoid Salmonella (NTS) gastroenteritis, a total of 207 diarrheal children who had positive stool culture for NTS and also a stool examination for the rotavirus antigen were retrospectively analyzed. According to the positivity of the stool rotavirus antigen, patients were divided into two groups and compared with regard to demographic data, clinical features, laboratory findings, and complications. The results showed that there were no significant differences between the two groups of patients with regard to demographic data, clinical features, and laboratory findings, except that vomiting was more common in patients with a coinfection of rotavirus (70.4% vs 40.0%, P = 0.003). Complication by bacteremia occurred more frequently in patients with coinfection of rotavirus (32% vs 9.3%, P = 0.004), but none of them developed extraintestinal focal infections, which were observed only in patients with isolated NTS infection. Our study indicated that concomitant rotavirus infection increased the risk of bacteremia in children with NTS gastroenteritis, although the prognosis remained favorable.

Deleterious effects of short-term, high-intensity exercise on immune function: evidence from leucocyte mitochondrial alterations and apoptosis.

BACKGROUND: Although moderate exercise can benefit health, acute and vigorous exercise may have the opposite effect. Strenuous exercise can induce alterations in the physiology and viability of circulating leucocytes, which have a causal relationship with exercise-induced immune distress. OBJECTIVES: To investigate the use of mitochondrial transmembrane potential (MTP), a functional marker of the energy and viability status of leucocytes, for monitoring the immunomodulating effects of short-term, high-intensity exercise. METHODS: 12 healthy volunteers with a mean Vo(2)max of 70.4 ml/kg/min carried out 3 consecutive days of high-intensity exercise (85% of Vo(2)max for 30 min every day). Blood samples were collected at multiple time points immediately before and after each exercise session and at 24 and 72 h after the completion of exercise. Leucocyte MTP, apoptosis and circulatory inflammation markers were measured by flow cytometry and enzyme-linked immunosorbent assays. RESULTS: MTP of peripheral blood leucocytes had declined immediately after the first exercise session and remained subnormal 24 h later. It did not normalise until 72 h after exercise. The sequential changes in MTP were consistent among the three leucocyte subpopulations (polymorphonuclear neutrophils, lymphocytes and monocytes) and were significant (p<0.05). Leucocytes displayed a gradual and incremental change in their propensity for apoptosis during and after exercise. Similarly, plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand were raised during the exercise sessions and had not normalised by 72 h after the completion of exercise. Correlation between changes in leucocyte MTP and plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand was variable, but significant for polymorphonuclear neutrophils and lymphocytes (p<0.05). CONCLUSIONS: Short-term, high-intensity exercise can lead to a significant and prolonged dysfunction of the mitochondrial energy status of peripheral blood leucocytes, which is accompanied by an increased propensity for apoptosis and raised pro-inflammatory mediators. These results support the immunosuppressive effects of excessive exercise and suggest that MTP is a useful marker of these effects.

Detection of C-reactive protein based on immunoassay using antibody-conjugated magnetic nanoparticles.

We report a detection method for C-reactive protein (CRP) based on competitive immunoassay using magnetic nanoparticles under magnetic fields. Functional magnetic nanoparticles were prepared and conjugated with anti-CRP for immunoassay. Magnetic nanoparticles labeled with anti-CRP were flowed through a separation channel to form depositions for selective capture of CRP under magnetic fields. Free CRP and a fixed number of CRP-labeled particles were used to compete for a limited number of anti-CRP binding sites on the magnetic nanoparticles. The deposited percentages of CRP-labeled particles at various concentrations of free CRP were determined and used as a reference plot. The determination of CRP in the unknown sample was deduced from the reference plot using the deposited percentages. The running time was less than 10 min. The CRP concentration of serum sample was linearly over the range of 1.2-310 microg/mL for deposited percentages of CRP-labeled particles. The detection limit of this method was 0.12 microg/mL which was approximately 8-fold lower than the typical clinical cutoff concentration (1 microug/mL). This method can provide a fast, simple, and sensitive way for protein detection based on competitive immunoassay using magnetic nanoparticles under magnetic fields.

Outcomes of HIV-infected children with tuberculosis who are started on antiretroviral therapy in Malawi.

SETTING: Mzuzu Central Hospital, in the northern region of Malawi, which provides free antiretroviral therapy (ART) to human immunodeficiency virus (HIV) infected adults and children, including those with tuberculosis (TB). OBJECTIVES: To compare outcomes in HIV-infected children who have been started on ART because of 1) active TB, 2) a past history of TB in the last 2 years and 3) a non-TB diagnosis. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July 2004 and September 2006, 439 (11%) children of a total 3908 patients were started on ART. There were 29 with active TB, 56 with a past history of TB in the last 2 years and 354 with a non-TB diagnosis. The three groups were similar in nutritional indices and CD4-lymphocyte percentages. The 6-month probability of survival was 0.86 in the active TB group, 0.94 in the past history of TB group and 0.89 in the non-TB group. 12-month survival probability for the same groups was 0.86, 0.86 and 0.88, respectively. CONCLUSION: HIV-infected children with active and previous TB who are started on ART have good outcomes that are similar to those of children started on ART due to a non-TB diagnosis.

Neural-network hybrid control for antilock braking systems.

The antilock braking systems are designed to maximize wheel traction by preventing the wheels from locking during braking, while also maintaining adequate vehicle steerability; however, the performance is often degraded under harsh road conditions. In this paper, a hybrid control system with a recurrent neural network (RNN) observer is developed for antilock braking systems. This hybrid control system is comprised of an ideal controller and a compensation controller. The ideal controller, containing an RNN uncertainty observer, is the principal controller; and the compensation controller is a compensator for the difference between the system uncertainty and the estimated uncertainty. Since for dynamic response the RNN has capabilities superior to the feedforward NN, it is utilized for the uncertainty observer. The Taylor linearization technique is employed to increase the learning ability of the RNN. In addition, the on-line parameter adaptation laws are derived based on a Lyapunov function, so the stability of the system can be guaranteed. Simulations are performed to demonstrate the effectiveness of the proposed NN hybrid control system for antilock braking control under various road conditions.

Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise.

Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.

Age-related changes in the mitochondrial depolarization induced by oxidative injury in human peripheral blood leukocytes.

Aging is associated with impaired immunity and reduced host defenses. Mitochondrial bioenergetic dysfunctions and reduced antioxidative ability of immunocompetent cells may contribute to this phenomenon. In this study, 60 healthy volunteers of different age groups donated their blood after overnight fasting. Leukocytes were subjected to oxidative injuries by exposure to t-butylhydroperoxide, and were labeled with fluorochromes for measuring mitochondria transmembrane potential (delta psi m), membrane peroxidation and mitochondrial oxidant formation. delta psi m declined after t-butylhydroperoxide exposure, and the change was more prominent in leukocytes from older individuals. Cyclosporin A partly restored delta psi m, implying the contributing role of mitochondrial permeability transition pores. The mitochondrial depolarization was accompanied by increased oxidant formation and oxidation of pyridine nucleotides, which were more prominent in older subjects. The results support the view that the bioenergetic functions of mitochondria are more susceptible to oxidative injury in aged individuals. The decreased ability of leukocytes to resist oxidative stress may contribute to immunosenescence in humans.

The effectiveness of single and multiple applications of triple dye on umbilical cord separation time.

UNLABELLED: The effectiveness of single and multiple applications of triple dye for umbilical cord care in the umbilical cord separation time (UCST) was evaluated in 180 neonates. Seven neonates were excluded, three where the cord stump separation time was uncertain and four to whom contact was lost. The participating neonates were randomly assigned to two groups. Group 1, 101 neonates, were treated with a regimen of a single application of triple dye. Group 2, 79 neonates, were treated with multiple applications of triple dye. Complete information was obtained from 97 neonates (96.2%) in group 1 and 76 (96%) in group 2. The UCST was 12.6 +/- 0.45 (mean +/- SE) days in group 1 and 16.68 +/- 0.65 days in group 2 (P < 0.0001) and showed no significant association with infants' gender, mode of delivery, gravidity, gestational age, birth weight, or hospital stay. CONCLUSION: A single application of triple dye may be a more favourable regimen with a similarly antimicrobial effect, a shorter UCST and may be more cost effective than multiple applications of triple dye in umbilical cord care.

Trichosporon beigelii causing oral mucositis and fungemia: report of one case.

A 23-month-old boy, a victim of acute myelomonocytic leukemia (AML), was admitted for chemotherapy. On the eighth hospital day, he started a one-week course of chemotherapy with agents of epirubicin and cytosine arabinoside. Unfortunately, persistent neutropenia, deteriorating diarrhea and intermittently spiking fever developed from the sixteenth hospital day. Initially, ceftazidime and amikacin were empirically utilized. Blood culture yielded Klebsiella pneumoniae and the fever subsided for one day. Unfortunately, oral mucositis and catheter-induced phlebitis developed subsequently. Subsequently, oral nystatin and intravenous oxacillin were added. The results of cultures from both blood and oral mucosal tissue yielded a fungus. Trichosporon beigelii. We changed from an oral antifungal agent to intravenous amphotericin B on the twenty-fourth hospital day. He presented signs of septic shock with disseminated intravascular coagulopathy and expired on the twenty-fifth hospital day after failure to respond to aggressive resuscitation. We report this case to emphasize that in cytotoxic chemotherapy-induced granulocytopenic AML patients who have compromised immune systems, and who may manifest some signs or symptoms of infection, and at the same time poorly respond to interventional antibiotic treatment, the possibility of T. beigelii infection can not be neglected.

MR findings of Werdnig-Hoffmann disease in two infants.

We report two infants with Werdnig-Hoffmann disease diagnosed by means of spinal MR imaging, histopathologic examination of muscle biopsy specimens, cloned DNA analysis, electrophysiological examination, and clinical history. The MR findings were consistent with previous histopathologic reports.

Recurrent acute suppurative thyroiditis in a child: case report.

A 23-month-old girl presented with a history of persistent fever and growing left anterior neck mass following an upper respiratory tract infection. Laboratory studies revealed leukocytosis, elevated levels of the erythrocyte sedimentation rate and C-reactive protein, and a mild impairment of thyroid function. Thyroid scan showed a decreased radioactive iodine uptake of the left thyroid gland. Culture of the thyroid aspirate grew the mixed flora, viridans streptococci, Prevotella spp, and Peptostreptococcus magnus. She was discharged after a surgical drainage and a 14-day course of penicillin-G therapy. Unfortunately, she was readmitted for the resembling problems, the fever and progressing left anterior neck mass 3 months later. Culture of thyroid aspirate also grew the viridans streptococci. She recovered after a 14-day course of penicillin-G therapy. A left pyriform sinus fistula was found by barium esophagogram. A selective operation was performed 8 weeks later.

Cat scratch disease in a child.

We report a case of a 9-year-old girl scratched on the right side of her neck by a kitten about one month prior to admission. She was well until three weeks later when she developed enlarged right neck masses, a pustula on the scratch site, right injected conjunctiva, headache, general malaise and fever, thus fulfilling the clinical criteria for CSD. Initially, she was treated by a practicing physician but the manifestations persisted for one week. After admission, leukocytosis and a mildly elevated erythrocyte sedimentary rate were noted. The serum IgG titer to Bartonella henselae was performed by means of indirect fluorescent antibody (IFA) test at the National Institute of Preventive Medicine. The serum titer of anti-B, henselae Ig G was 1:256 and greater (> or = 1:256). The positive serum titer(negative titer being < 1:64) to B, henselae, the organism thought to be responsible for CSD, also supports this diagnosis. She was treated with a 7-day course of intravenous gentamicin and the fever subsided within 24 hours. Following this, she improved clinically and was discharged one week later. One month after discharge, she remained well with no palpable neck masses.

Epididymo-orchitis in an infant resulting from Escherichia coli urinary tract infection.

Epididymo-orchitis (EO) is said to be extremely rare in infants and children. It is usually diagnosed after scrotal exploration for symptoms which mimic manifestations between EO and torsion of the cord and its appendage. The pathophysiologic mechanisms for the development of EO are not well known. Although some causative agents of EO have been reported, in most cases there was no clear etiology. We report a 3-month-old male infant who had been well until the day prior to admission when irritability, left testicular swelling, scrotal erythema with a hot sensation were noted by his mother. He was treated medically after excluding the possibility of an emergent surgical condition (such as torsion of the cord and its appendage, or incarcerated hernia) by means of physical examinations, abdominal and inguino-scrotal sonography, laboratory studies, and testicular radionuclide scintigraphy. A catheterized sample of urine for culture yielded Escherichia coli. There was the possibility that the EO was caused by hematogenous rather than local spread from an infection of the urinary tract. He was treated with a 10-day course of intravenous cefazolin and amikacin. Following this, he improved clinically and a repeat catheterized urine sample remained sterile on culture. In addition, a bilateral inguinal hernia and hydrocele were detected by inguino-scrotal sonography and were operated on the 11th hospital day. He was discharged on the 16th day of hospitalization and remained well 11 months after discharge.

Androgen receptor protein binding properties and tissue distribution of 2-selena-a-nor-5alpha-androstan-17beta-ol in the rat.

2-selena-A-nor-5alpha-androstan-17beta-ol was studied in vitro and in vivo in the rat prostate gland. The data demonstrates the ability of this compound to selectively complex with the specific receptors of 5alpha-dihydrotestosterone (5alpha-DHT) in the cytosol and to be retained in the nuclei in an unaltered form. Studies with selenium-75 labeled material suggests that the uptake and localization is similar to endogenous 5alpha-dihydrotestosterone.