Spontaneous tumor development in bone marrow-rescued DNA-PKcs(3A/3A) mice due to dysfunction of telomere leading strand deprotection.

Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at the Thr2609 cluster is essential for its complete function in DNA repair and tissue stem cell homeostasis. This phenomenon is demonstrated by congenital bone marrow failure occurring in DNA-PKcs(3A/3A) mutant mice, which require bone marrow transplantation (BMT) to prevent early mortality. Surprisingly, an increased incidence of spontaneous tumors, especially skin cancer, was observed in adult BMT-rescued DNA-PKcs(3A/3A) mice. Upon further investigation, we found that spontaneous γH2AX foci occurred in DNA-PKcs(3A/3A) skin biopsies and primary keratinocytes and that these foci overlapped with telomeres during mitosis, indicating impairment of telomere replication and maturation. Consistently, we observed significantly elevated frequencies of telomere fusion events in DNA-PKcs(3A/3A) cells as compared with wild-type and DNA-PKcs-knockout cells. In addition, a previously identified DNA-PKcs Thr2609Pro mutation, found in breast cancer, also induces a similar impairment of telomere leading-end maturation. Taken together, our current analyses indicate that the functional DNA-PKcs T2609 cluster is required to facilitate telomere leading strand maturation and prevention of genomic instability and cancer development.

Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.

BACKGROUND AND PURPOSE: The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity. EXPERIMENTAL APPROACH: Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. KEY RESULTS: The results showed that of (+)-antroquinonol (100 µM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. CONCLUSIONS AND IMPLICATIONS: Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity.

Epidemiological investigation of a case of nosocomial Legionnaires' disease in Taiwan: implications for routine environmental surveillance.

An epidemiological investigation with Legionella and molecular subtyping was conducted to determine the source of a case of nosocomial Legionnaires' disease (LD) who was hospitalized in three hospitals within a month. Legionella pneumophila serogroup 3, an uncommon serogroup for infection, was isolated from the patient's sputum. Environmental surveillance revealed Legionella colonization in all three hospitals; the patient isolate matched the isolate from the first hospital by molecular typing. Culturing the hospital water supply for Legionella is a pro-active strategy for detection of nosocomial LD even in hospitals experiencing no previous cases.

Efficacy of point-of-entry copper--silver ionisation system in eradicating Legionella pneumophila in a tropical tertiary care hospital: implications for hospitals contaminated with Legionella in both hot and cold water.

A medical centre in Southern Taiwan experienced an outbreak of nosocomial Legionnaires' disease, with the water distribution system thought to be the source of the infection. Even after two superheats and flush, the rate of Legionella positivity in distal sites in hospital wards and intensive care units (ICUs) was 14% and 66%, respectively. Copper-silver ionisation was therefore implemented in an attempt to control Legionella colonisation in both hot- and cold-water systems. Environmental cultures and ion concentration testing were performed to evaluate the efficacy of ionisation. When the system was activated, no significant change in rate of Legionella positivity in the hospital wards (20% vs baseline of 30%) and ICUs (28% vs baseline of 34%) of the test buildings over a three-month period was found, although all Legionella positivity rates were below 30%, an arbitrary target for Legionnaires' disease prevention. When ion concentrations were increased from month 4 to month 7, however, the rate of Legionella positivity decreased significantly to 5% (mean) in hospital wards (P=0.037) and 16% (mean) in ICUs (P=0.037). Legionella positivity was further reduced to 0% in hospital wards and 5% (mean) in ICUs while 50% sites were still positive for Legionella in a control building. Although Legionella was not completely eradicated during the study period, no culture- or urine-confirmed hospital-acquired Legionnaires' disease was reported. Ionisation was effective in controlling Legionella for both hot and cold water, and may be an attractive alternative as a point-of-entry systematic disinfection solution for Legionella.

[Infusion speed as a factor to influence the analgesic level of spinal anesthesia--hypobaric solution of tetracaine].

In spinal anesthesia, as known, the injection speed of local anesthetic drug is a factor which influences the analgesic level. For study it, automatic infusion apparatus was available to control as 5 kinds of infusion speed (0.02-0.51 mL/s), and 78 patients were divided into 6 groups. The results of the painless level was discussed by T-test and distribution analysis (F-test). The mean of painless level in each group was found to be no significant difference as discussed by T-test. But the largest distribution was found in the group of 0.04 mL/s, and high analgesic level as rise up to T6 was occasionally found in groups of 0.04 mL/s & 0.02 mL/s. It means, the infusion speed is not an important factor, but extremely slow infusion is more dangerous than high speed infusion, which will take a risk of high level spinal anesthesia.

Mastitis neonatorum.

Eleven cases of neonatal mastitis diagnosed at National Taipei College of Nursing Health Center, since 1983, have been reviewed by chart retrospectively. All 11 cases occurred in full-term infants 1-4 weeks postnatally. Female predominated with male: female ratio of 1: 1.75. The mastitis of these cases were confined to unilateral side and did not spread systemically. Gram stain smear of the purulent material got from aspiration, incision or spontaneous rupture of abscess were attempted in ten cases and Gram positive cocci were observed in nine of whom pus culture yield staphylococcus aureus later in eight. We feel Gram stain is one of the rapid and useful diagnostic method. Treatment was given by appropriate antibiotics parenterally followed by surgical incision or drainage when fluctuation was present. The prognosis of neonatal mastitis is excellent. In general, these our clinical observation are similar to those described in the literatures since 1950s.