Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors

Insulin-like growth factor II (IGF-II) is a mitogen for manycell types and an important modulator of muscle growth and differentiation.IGF-II gene is prevalently expressed during prenatal developmentand its gene activity is regulated by genomic imprinting, inthat the allele inherited from the father is active and theallele inherited from the mother is inactive in most normaltissues. IGF-II expression is activated in several types ofhuman neoplasms and an alteration of IGF-II imprinting has beendescribed in Beckwith–Wiedemann syndrome and Wilms' tumour.Here we show that monoallelic expression of IGF-II gene is conservedin normal adult muscle tissue whereas two or more copies ofactive IGF-II alleles, arising by either relaxation of imprintingor duplication of the active allele, are found in 9 out of 11(82%) rhabdomyo-sarcomas retaining heterozygosity at 11p15,regardless of the histological subtype. Since IGF-II has beenindicated as an autocrine growth factor for rhabdomyosarcomacells, these findings strongly suggest that acquisition of adouble dosage of active IGF-II gene is an important step forthe initiation or progression of rhabdomyosarcoma tumorigenesis.Among different types of muscle tumors, relaxation of imprintingseems to arise prevalently in rhabdomyosarcomas, since we havedetected only one case of partial reactivation of the maternalIGF-II allele out of 7 lelomyosarcomas tested.     

Nasal lavage leukotrienes in infants with RSV bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys-LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease.     

A case of double valve substitution in a female patient carrier of a factor X deficiency]

We present the clinical case of a patient affected by mitral and aortic valvular disease submitted to double valvular replacement. This patient was also affected by congenital deficiency of factor X. We describe the normal problems encountered in cardiac surgery and the specific implications of this clinical case.     

Isolated blunt liver trauma: is nonoperative treatment justified?

During the past 8 years 13 children with isolated blunt liver trauma were managed nonoperatively. All patients selected for this management were hemodynamically stable after initial resuscitation and were without signs of other associated intraabdominal injuries on ultrasonogram and/or computed tomography. Patients were observed in an intensive care unit for at least 48 hours with repeated clinical assessments, laboratory studies, and bed rest. One patient with type 3 injury was operated on 8 days after injury because of sudden intraperitoneal bleeding on ambulation. Five patients required blood transfusions of not more than 300 mL per patient. Laboratory values returned to normal from 7 to 21 days after injury. Resolution of hepatic injury on ultrasonogram took from 1 to 3 months. Complete bed rest was prescribed for at least 10 days depending on the type of injury, with restricted activities up to 3 months postinjury. No complications were seen in this series.     

Functional analysis of cytotoxic cells in patients with acute nonlymphoblastic leukemia in complete remission

In the current study, we investigated the cytotoxic ability of peripheral blood mononuclear cells (PBMC) recovered from patients with acute nonlymphoblastic leukemia (ANLL) in complete remission (CR) against natural killer (NK)-sensitive, NK-resistant, autologous and allogeneic leukemic target cells taken at diagnosis. Our purpose was to define the role played by cytotoxic mechanisms in the control of leukemic cell growth in ANLL. Experiments were carried out at resting conditions and after in vitro activation with recombinant interleukin-2 (rIL-2) and anti-CD3 monoclonal antibody (moAb). At resting conditions, PBMC recovered from ANLL patients displayed a NK function that was not significantly different from controls (mean +/- standard error of the mean [SEM]: 21.9% +/- 3.9% versus control values of 27.5% +/- 2.9%; the P value was not significant [NS]), but they were unable to show cytotoxic activity against autologous and allogeneic leukemic cells. After in vitro boosting with rIL-2, PBMC were able to generate lymphokine activated killer (LAK) cells, as demonstrated by an increased killing of NK-resistant Daudi targets (16.3% +/- 2.7%). Although LAK activity was quantitatively lower than in control subjects (mean +/- SEM: 16.3% +/- 2.7% versus control values of 79.8% +/- 3.1%; P less than 0.001), it still exerted a cytotoxic effect against autologous and allogeneic leukemic cells. Similar results were obtained when anti-CD3 moAb was used as a stimulus in vitro. Our data suggest that nonspecific cytotoxic cells may be triggered to exert an in vitro cytotoxic effect on leukemic cells, which could possibly play a key role in vivo in the control of leukemic cell growth regulation.