Severe congenital absence of skin in a preterm infant

A severe case of aplasia cutis congenita in a preterm infant is described. Although major problems with thermoregulation and fluid balance were anticipated, these parameters were relatively easy to control once the patient was stabilized. Meticulous skin care and rapid formation of a membranous-like fibrous tissue layer covering the denuded areas probably played an important role in minimizing excessive fluid and heat loss. The prognosis in aplasia cutis congenita is determined by the underlying associated anomalies, the severity of skin lesions and, in our case, the maturity of the infant who died from complications of prematurity.     

Inhibition of histone deacetylases sensitizes glioblastoma cells to lomustine

Purpose

Glioblastoma (GBM) ranks among the deadliest solid cancers worldwide and its prognosis has remained dismal, despite the use of aggressive chemo-irradiation treatment regimens. Limited drug delivery into the brain parenchyma and frequent resistance to currently available therapies are problems that call for a prompt development of novel therapeutic strategies. While only displaying modest efficacies as mono-therapy in pre-clinical settings, histone deacetylase inhibitors (HDACi) have shown promising sensitizing effects to a number of cytotoxic agents. Here, we sought to investigate the sensitizing effect of the HDACi trichostatin A (TSA) to the alkylating agent lomustine (CCNU), which is used in the clinic for the treatment of GBM.

Methods

Twelve primary GBM cell cultures grown as neurospheres were used in this study, as well as one established GBM-derived cell line (U87 MG). Histone deacetylase (HDAC) expression levels were determined using quantitative real-time PCR and Western blotting. The efficacy of either CCNU alone or its combination with TSA was assessed using various assays, i.e., cell viability assays (MTT), cell cycle assays (flow cytometry, FACS), double-strand DNA break (DSB) quantification assays (microscopy/immunofluorescence) and expression profiling assays of proteins involved in apoptosis and cell stress (Western blotting and protein array).

Results

We found that the HDAC1, 3 and 6 expression levels were significantly increased in GBM samples compared to non-neoplastic brain control samples. Additionally, we found that pre-treatment of GBM cells with TSA resulted in an enhancement of their sensitivity to CCNU, possibly via the accumulation of DSBs, decreased cell proliferation and viability rates, and an increased apoptotic rate.

Conclusion

From our data we conclude that the combined administration of TSA and CCNU eradicates GBM cells with a higher efficacy than either drug alone, thereby opening a novel avenue for the treatment of GBM.

     

A mutant human IgG molecule with only one C1q binding site can activate complement and induce lysis of target cells

There are potentially two binding sites for C1q on IgG, one on each C(H)2 domain of the gamma heavy chains, close to the lower hinge region. It is not clear whether the presence and involvement of both the C1q binding sites is necessary to induce the activation signal of human IgG. In order to clarify this issue, we made a hybrid mutant IgG1/IgG3 molecule where the IgG1 half of the molecule was made unable to activate complement through the introduction of a P329A mutation. The IgG3 half of the molecule was mutated to harbor a hinge region identical to that of IgG1, and for detection a peptide tag derived from p21ras was introduced into the FG loop of the C(H)1 domain. The hybrid IgG1P329A/IgG3h1-ras molecules were isolated by Protein A affinity chromatography and shown to activate complement and induce complement-mediated lysis at the same levels as wild-type IgG1 and IgG3h1-ras molecules. Thus, one C1q binding site per IgG is sufficient to induce activation. Wild-type human IgG molecules might also normally expose only one C1q binding site as already shown for interaction with FcgammaR, were IgG expose one binding site per molecule.     

Thin newborns are more insulin resistant at 10 years of age

Aims: To investigate the relation between ponderal index or birth weight and insulin resistance in late childhood. Methods: An observational study of 92‐term appropriate‐for‐gestational age infants was carried out. Weight and length were measured at birth and at 9 months and duration of breast feeding was noted at 9 months. Follow‐up examinations at 10 years of age included measurement of weight, height, pubertal status, fasting insulin and glucose concentrations. Results: Ponderal index at birth was negatively (B ± SE = ?0.05 ± 0.02; p = 0.025) and current BMI was positively (B ± SE = 0.14 ± 0.02; p < 0.001) associated with insulin resistance measured as homeostasis model assessment (HOMA) at 10 years of age adjusted for gender and pubertal stage. Current BMI and ponderal index at birth were still significant after adjusting for weight at 9 months. Birth weight and weight at 9 months was not correlated with HOMA (p = 0.58) adjusted for current BMI, gender and pubertal stage. HOMA was higher in the tertile with the lowest ponderal index than in the two remaining tertiles (p = 0.024). Conclusion: Relative thinness at birth, but neither birth weight nor weight gain from 0–9 months, was associated with higher insulin resistance at 10 years of age in this cohort with a low prevalence of overweight at 10 years of age and normal birth weight.     

Polysaccharides from the roots of Entada africana Guill. et Perr., Mimosaceae, with complement fixing activity

Entada africana is a tree used in traditional medicine in Mali. The root is, for example, used for wound-healing. Since polysaccharides from other plants are thought to play a role in the wound-healing process, we wanted to study the polysaccharides present in the root of this species. The polysaccharides were extracted with water at 50 and 100 degrees C and were further separated by anion exchange chromatography. The acidic fractions were finally purified by affinity chromatography on a Con A column. The fraction denoted Ea100 acidic I had the highest activity in the complement fixation test system, while the other acidic fractions had minor activities and the neutral fractions were almost negative. Ea100 acidic I has a structure resembling the arabinogalactan-protein type II polymer, which also was demonstrated by the abilities to precipitate with the Yariv reagent. The biological activity was reduced considerably after removal of arabinofuranoside residues by weak acid hydrolysis. The main core of the other polysaccharides extracted with 100 degrees C were pectins resembling the rhamnogalacturonan type I. These fractions also contain arabinogalactan type II structures, shown by the formation of precipitates with the Yariv reagent.     

Characterization of materials for optimal near-infrared and x-ray imaging of the breast

Development of a detector case for complete co-registration of images in a non-fiber-based combined near-infrared spectral tomography and digital breast tomosynthesis, required analysis to find materials that could support a breast under full mammographic compression without affecting the x-ray images or the quality of the near infrared measurements. Several possible solutions were considered, and many types of plastics were tested in the development of the detector case. Light channeling within the detector case changed the data obtained in resin and agarose phantoms, lowering recovered absorption values. Additional developments focusing on blocking stray light were successful and permitted a normal subject imaging exam.OCIS codes: (120.3890) Medical optics instrumentation, (170.0110) Imaging systems, (170.3830) Mammography     

Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

Abstract:  To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days −3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm² (day -3) vs 1477 mm² (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm² (day -3) vs 648 mm² (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation, and peaked after the day of graft infusion (day 0). sTNFRI levels at day 0 predicted changes in weight SDS (r = 0.65; p = 0.05), triceps skinfold SDS (r = 0.85; p = 0.007) and gastrointestinal dysfunction (r = 0.88; p = 0.004). Likewise, IL-1Ra levels at day 0 correlated with the gastrointestinal dysfunction (r = 0.83; p = 0.01) and with the change in weight SDS (r = 0.77; p = 0.03). This study suggests that pretransplant levels of inflammatory markers are associated with posttransplant symptoms of gastrointestinal dysfunction and loss of both fat and lean body mass. Future studies should adress if the use of conditioning regimens with limited proinflammatory cytokine inducing activity, anti-inflammatory agents, or more optimised nutritional support can reduce the burden of such posttransplant complications.     

Iron supplement in pregnancy and development of gestational diabetes—a randomised placebo-controlled trial

Objective  To test the hypothesis that iron supplement from early pregnancy would increase the risk of gestational diabetes mellitus (GDM).
Design  Randomised placebo-controlled trial.
Setting  A university teaching hospital in Hong Kong.
Population  One thousand one hundred sixty-four women with singleton pregnancy at less than 16 weeks of gestation with haemoglobin (Hb) level between 8 and 14 g/dl and no pre-existing diabetes or haemoglobinopathies.
Methods  Women were randomly allocated to receive 60 mg of iron supplement daily ( n = 565) or placebo ( n = 599). Oral glucose tolerance tests (OGTTs) were performed at 28 and 36 weeks. Women were followed up until delivery.
Outcome measures  The primary outcome was development of GDM at 28 weeks. The secondary outcomes were 2-hour post-OGTT glucose levels, development of GDM at 36 weeks and delivery and infant outcomes.
Results  There was no significant difference in the incidence of GDM in the iron supplement and placebo groups at 28 weeks (OR: 1.04, 95% confidence interval [CI]: 0.7–1.53 at 90% power) or 36 weeks. Maternal Hb and ferritin levels were higher in the iron supplement group at delivery ( P < 0.001 and P = 0.003, respectively). Elective caesarean section rate was lower in the iron supplement group (OR: 0.58, 95% CI: 0.37–0.89). Infant birthweight was heavier ( P = 0.001), and there were fewer small-for-gestational-age babies in the iron supplement group (OR: 0.46, 95% CI: 0.24–0.85).
Conclusion  Iron supplement from early pregnancy does not increase the risk of GDM. It may have benefits in terms of pregnancy outcomes.     

Living with Marfan syndrome I. Perceptions of the condition

We present data from an exploratory study of 174 adults with Marfan syndrome regarding their cognitive perceptions of the condition as postulated by the self-regulatory model (Leventhal H, Benyamini Y, Brownlee S et al. In: Petrie KI, Weinman JA, eds. Perceptions of Health and Illness: Current Research and Applications. Amsterdam, The Netherlands: Harwood Academic, 1997: 19-45; Leventhal H, Nerenz DR, Steele DJ. In: Baum A, Taylor SE, Singer JE, eds. Handbook of Psychology and Health. Hillsdale, NJ: Lawrence Erlbaum Associates, 1984: 219-252). The vast majority of the respondents had adequate general knowledge about Marfan syndrome. Eighty-three percent of the respondents perceived Marfan syndrome as having had significant adverse consequences on their lives. Having striae, pain (sore joints), and depression were each independently correlated with this view. Fifty-eight percent of the respondents indicated that they felt they had low to moderate control over their condition, demonstrating variability. History of aortic dissection, pain (sore joints), and depressive symptoms were each negatively correlated with the view that Marfan syndrome is a curable/controllable condition. Moreover, approximately 28% view the condition as a lethal condition, whereas 67% view it as a serious condition. Forty-four percent of the cohort were found to have significant symptomatology of depression independent of beta- and Ca2+-channel blockade use. Respondents cited both advantages and disadvantages of being affected. Genetic counseling that addresses patients' perceptions of Marfan syndrome, and its associated pain, fatigue, and depressive symptoms, may enhance patient adaptation to the condition.