CBF beta-SMMHC, expressed in M4Eo AML, reduced CBF DNA-binding and inhibited the G1 to S cell cycle transition at the restriction point in myeloid and lymphoid cells

CBF beta-SMMHC is expressed from the inv(16) chromosome in M4Eo AML. Mice lacking CBF subunits or expressing the CBF beta-SMMHC or AML1-ETO oncoproteins failed to develop definitive hematopoiesis. To investigate these effects on hematopoiesis, we expressed CBF beta-SMMHC from the metallothionein promoter, in both 32D cl3 myeloid cells and Ba/F3 B-lymphoid cells. Addition of zinc increased CBF beta-SMMHC levels more than tenfold, with higher levels evident in Ba/F3 lines. Levels obtained in 32D cl3 cells were similar to those of endogenous CBF beta. Indirect immunofluorescence revealed zinc-inducible speckled, nuclear staining in Ba/F3 cells and diffuse nuclear staining in 32D cl3 cells. CBF beta-SMMHC reduced endogenous CBF DNA-binding fivefold in both cell types, increased cell generation time 1.9-fold, on average, in 32D cl3 cells and 1.5-fold in Ba/ F3 cells and decreased tritiated thymidine incorporation into DNA correspondingly. CBF beta-SMMHC increased the proportion of cells in G1 1.7-fold, on average, in 32D cl3 and Ba/F3 cells, and decreased the proportion of cells in S phase by a similar degree. CBF beta-SMMHC induced a marked increase in hypophosphorylated Rb, but did not alter IL-3 Receptor alpha or beta subunit levels. Neither apoptosis nor 32D differentiation was induced by zinc in IL-3 in these lines. Induction of CBF beta-SMMHC in 32D cl3 cells did not inhibit their differentiation to neutrophils or their expression of myeloperoxidase mRNA in G-CSF, and did not produce an eosinophilic phenotype. Additional, proliferative genetic changes in M4eo AMLs might potentiate inhibition of differentiation by CBF beta-SMMHC by allowing its increased expression.     

Laboratory aid and ultrasonography in the diagnosis of appendicitis in children

The purpose of this study was to evaluate the relationship between the number of yolk sacs and amnionicity in monochorionic twin pregnancies scanned early in the first trimester. We retrospectively reviewed images of all monochorionic twins scanned between 6 and 9.5 weeks' gestation and with pathologic or sonographic confirmation of chorionicity-amnionicity. Each film was reviewed for the number of yolk sacs present, as well as for the gestational age at which the amniotic membrane was first visualized. Twenty monochorionic-diamniotic pregnancies and two monochorionic-monoamniotic pregnancies met the criteria for inclusion in the study. In diamniotic pregnancies scanned at less than 8 weeks' gestation, only the yolk sacs were identified; none of the dividing amniotic membranes were detected. Two yolk sacs were identified in all but one case. In this case, although one yolk sac was seen at 6 weeks, follow-up scanning at 8 weeks revealed two yolk sacs. In each of the monochorionic-monoamniotic twin pregnancies, one yolk sac was seen at 9 weeks and a single amnion encircled both embryos. We conclude that the sonographic identification of two yolk scas in monochorionic twins enables us to make the diagnosis of diamniotic twins early in the first trimester, before the amniotic membrane can be imaged. The presence of one yolk sac should prompt a follow-up ultrasonogram to assign amnionicity definitively.     

Reversing the Lecture/Homework Paradigm Using eTEACH® Web‐based Streaming Video Software

A new online streaming video and multi‐media application called eTEACH, http:eTEACH.engr.wisc.edu was used to reform a large, lecture‐based computer science course for engineering majors. In‐class lectures were replaced with videotaped lectures and other materials that students viewed on the Internet on their own schedule, making it possible to use the live class periods for small, team problem‐solving sessions facilitated by the professors and a teaching assistant. By using the eTEACH application to transform course lectures into “homework” and free up the face‐to‐face class time for working on problems that were similar to homework assignments, the professors effectively reversed the lecture and homework paradigm of a typical large lecture course. A thorough course evaluation over two semesters showed that students who took the online lecture version of the course gave significantly higher ratings to all aspects of the course, including lecture usefulness, professor responsiveness, the course overall, and the instructor. Although a few students missed having the opportunity to ask questions during lectures, about two‐thirds of the 531 students surveyed felt it was easier to take notes and understand the lectures presented via eTEACH than it would have been while attending the same lecture live, and 78% of students appreciated the ability to view and review course lectures on their own schedule.     

Dietary energy restriction does not inhibit pancreatic carcinogenesis by N-nitrosobis-2-(oxopropyl)amine in the Syrian hamster

Dietary energy restriction was previously shown to be effective in preventing a wide range of experimentally induced cancers. Studies were conducted to assess the influence on pancreatic carcinogenesis of dietary energy restrictions (reduced fat and carbohydrate) of 10%, 20% or 40% in comparison with control in Syrian hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Two carcinogenesis studies were conducted. One used a single treatment with 20 mg BOP/kg body weight and followed hamsters for 102 weeks following treatment, and the other used three weekly treatments of 20 mg BOP/kg body weight and followed hamsters for 45 weeks after treatment. Hamsters were fed control or energy restricted diet beginning the week following the last BOP treatment. Pancreatic carcinomas were induced in 9-18% of the hamsters in the first experiment and in 59-66% of the animals in the second. Dietary energy restriction did not influence carcinoma incidence in either study, and in the second experiment the multiplicity of tumors was higher in the 40% energy restriction (ER) group than in control hamsters. Plasma corticosterone was suppressed by BOP treatment, particularly in the 20% and 40% ER hamsters in the second experiment, and diet or BOP treatment did not significantly alter plasma cortisol. Pancreatic protein kinase Czeta measured by Western blot was highest in the cytosol and particulate fractions of the 40% ER hamsters in the first experiment. These results indicate that dietary energy restriction is not effective in the prevention of BOP induced pancreatic carcinogenesis in the Syrian hamster.     

Murine cytomegalovirus-inhibitory effects of ImuVert

ImuVert, a sterile preparation composed primarily of Serratia marcescens membrane vesicles and ribosomes, was significantly inhibitory to murine cytomegalovirus (MCMV) infections in BALB/c mice. Antiviral activity was manifested as increased survivor number and decreased recoverable virus titers in spleens, lungs and salivary glands. Treatments were intraperitoneal (i.p.) beginning 24 h pre, 4 h post- or 24 h post-virus inoculation and then repeated 4 days later. Doses of 5, 16 or 50 micrograms/mouse were effective; 160 micrograms/mouse, which caused host weight loss in toxicity controls, was not inhibitory to the infection. A single i.p. treatment of mice substantially augmented natural killer (NK) cell activity and increased total B-cells, while reducing total T- and T-helper cells. A late (48 h) decline in T-cell function and transient increases in B-cell function were observed in the treated animals. Serum interferon was not induced. Mice pretreated with anti-asialo GM1 antibody to reduce their NK cell populations, then infected with MCMV and treated with ImuVert were protected to the same degree as normal animals. Severe combined immunodeficient mice infected with MCMV and treated with ImuVert were not protected from the infection. These data suggest ImuVert to act by a mechanism other than NK cell activation in preventing MCMV infections.     

A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment of type II collagen induced arthritis in mice

OBJECTIVE: Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation and injury responses, with multiple effects upon cellular activities. Discrete peptide sequences of the PF-4 molecule have been shown to retain biological activity. Our aim was to examine the influence of the PF-4 derived octapeptide (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if this peptide exhibited antiinflammatory properties. METHODS: DBA/1 mice were treated with CT-112 from either the time of immunization with type II collagen or from the initial onset of arthritis. RESULTS: CT-112 both prevented the development of arthritis in mice treated prophylactically and reduced progression of disease in animals treated therapeutically, and was active when delivered by either subcutaneous injection or oral gavage. No marked immunosuppressive effects were observed during CT-112 treatment, with only moderate decrease in antibody levels and mitogen responses. A significant reduction of the circulating levels of IL-1 was a consistent finding in mice treated therapeutically with CT-112. CONCLUSION: These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.     

Bridge design with reserve and residual reliability constraints

System reliability is evolving as an important design method for selecting components and topology. It should be used to investigate the original intact structure behavior as well as providing sufficient reserve capacity under likely accident and damage scenarios. Highway bridges are an area of special concern since effort to optimize the cost of construction may not provide adequate redundant capacity. The paper describes an example in which a typical girder bridge structure is optimized (both size and girder spacing) to achieve target system performance. System reliability constraints are imposed on the behavior of the intact structure under highway loads. Also, residual system reliability constraints are imposed to control safety under specified accident scenarios corresponding to damage and “lost” members due to corrosion, fatigue, fire or accidental collisions. An optimal design framework for controlling safety under all these life cycle situations is thus provided.     

Effect of storage temperature on phenolics stability in hawthorn (Crataegus pinnatifida var. major) fruits and a hawthorn drink

The stability of five major phenolics, namely (−)-epicatechin (EC), procyanidin B₂ (PC-B₂), chlorogenic acid (ChA), hyperoside (HP) and isoquercitrin (IQ), in hawthorn fruits and a canned hawthorn drink were evaluated during 6 months of storage in the dark at three different temperatures (4, 23 and 40 °C). HPLC with a diode-array detector was used to determine the contents of the individual compounds. The results showed that the studied phenolics in the hawthorn fruits and the drink were both stable at 4 °C and relatively unstable at 23 and 40 °C with varied extents of degradation. At room temperature (23 °C), marked degradations of EC and PC-B₂ were observed in both the fruits and the drink with around 50% and 30% decrease after a 6-month storage, respectively. A more significant decrease of the phenolics was observed at 40 °C, especially for EC and PC-B₂, which were almost completely degraded after a 6-month storage. HP, IQ and ChA were relatively stable at 23 °C, but unstable at 40 °C. Therefore, low-temperature storage is recommended for maintaining the quality and efficacy of hawthorn fruits and its preparations.