Interleukin-3 dependent c-myc protein expression during the cell cycle of murine mast cells.

Aim of the study was to evaluate the relationship between the mitogenic stimulus interleukin-3 to normal murine mast cells and the cell cycle dependent expression of the nuclear c-myc protein. In order to do that on a cell by cell basis, we measured the nuclear c-myc protein simultaneously by flow cytometry, via specific monoclonal antibodies, and the DNA content via the intercalating dye propidium iodide. When cells were deprived from interleukin-3 (IL-3), proliferation was inhibited and the majority of cells arrested in early G1 (G1A, characterized by low c-myc content). Readdition of IL-3 resulted in a slow transition of cells from G1A to late G1 (G1B, at higher c-myc content) before DNA synthesis started. G1A cells with low c-myc content do not undertake DNA synthesis. Using a stathmokinetic methodology we confirmed that the G1A cells are early postmitotic G1 phase cells. The low content of c-myc within these cells appears a direct consequence of reduced c-myc levels during mitosis. Cumulatively, the data suggest that c-myc protein levels of murine mast cells fall at mitosis and that these levels must rise before cells can traverse the G1 phase. Our data are compatible with a model in which c-myc protein content of G1 phase cells has to reach a critical threshold before the cells can move further into the cell cycle.     

Ovarian and uterine findings in pelvic sonography: comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty.

OBJECTIVE: To describe pelvic sonographic findings in girls as old as 7 years, to compare prepubertal girls with girls who had isolated thelarche or central precocious puberty, and to verify the accuracy of sonographic variables for distinguishing prepubertal girls from girls with central precocious puberty. METHODS: Ninety-six prepubertal girls and 2 reference groups (8 girls with isolated thelarche and 8 with idiopathic central precocious puberty) were included. Ovaries were classified morphologically as homogeneous, paucicystic, macrocystic, multicystic, and having isolated cysts. Receiver operating characteristic curves were used to choose the best cutoff points. RESULTS: Chronologic and bone age were correlated with uterine length, area, and volume and ovarian volume in prepubertal girls (P < .0001). Ovarian morphologic characteristics in prepubertal girls differed significantly from those of the reference groups (P < .0001). The best cutoff points were uterine length of 4.0 cm, uterine area of 4.5 cm2, uterine volume of 3.0 cm3, and ovarian volume of 1.0 cm3. CONCLUSIONS: Uterine and ovarian growth are proportional to age in prepubertal girls. Mean ovarian volume greater than 1 cm3 showed 100% sensitivity and specificity for discriminating between prepubertal girls and girls with central precocious puberty. Microcysts are common in prepubertal girls, but the presence of 6 or more follicles up to 10 mm in diameter may suggest central precocious puberty in girls younger than 8 years.     

Magnetic resonance in the staging of multiple myeloma]

The authors retrospectively reviewed the MR examinations of 46 patients with clinical and laboratory findings of monoclonal gammopathies (MG). All cases had been submitted to radiographic examination which had shown skeletal involvement in 22 cases and osteoporosis in 11, with rupture of the vertebral body in 3 patients. Scintigraphy had been performed on all patients and CT on 12; 36 patients were subsequently submitted to follow-up (at 6, 12 and 24 months). MR examinations were performed with dedicated coils and standard sequences for the subjects with skeletal localizations on X-ray images. The extant cases, with no radiographic evidence of skeletal involvement, were submitted to MRI of the spine, skull and pelvis. In agreement with clinical and laboratory findings and with follow-up results (in 36 patients), MRI diagnosed MG with no skeletal involvement in 13 cases, osteoporosis in 8 (with rupture of the vertebral body in 2), asymptomatic non-progressive myeloma in 4, solitary myeloma in 3, and multiple myeloma in 18 cases. The good identification of bone marrow and its multiplanarity make MRI the method of choice in the study of patients with suspected or known gammopathies. If compared with other modalities, MRI is more sensitive and accurate in depicting the tumor, its size and relationship to periskeletal tissues, and its possible multifocality. Moreover, the technique has proven to be a valid tool during the follow-up, showing tumor response to therapy.     

Cellular expression of somatostatin in MAM-induced microencephaly in the rat.

Methylazoxymethanol acetate (MAM) is a mitotic inhibitor that has been used to selectively destroy neuroblasts at specific times during gestation. The administration of MAM results in a dose-dependent microencephaly. Following MAM treatment at 15 days of gestation, we have noted an increase in the level of SS immunoreactivity in the neocortex, as determined by radioimmunoassay. Northern blot analysis for preproSS mRNA revealed an increase in MAM-treated cortex. The cellular distribution of SS has been determined using in situ hybridization and immunocytochemistry. There was a 30% increase in the density of SS-immunoreactive neurons in the cortex of the MAM-treated animals. These data suggest that SS neurons in the cortex are spared following MAM treatment at GD 15.     

Vasopressin stimulation of NaCl transport in the medullary thick ascending limb of Henle's loop is decreased in aging mice

The maximal urinary osmolality that can be reached by the kidney is reduced with age. This may be due to impaired NaCl transport by the medullary thick ascending limb of Henle's loop, which is part of the renal concentrating mechanism and is modulated by antidiuretic hormone (ADH). We therefore tested in vitro a possible age-related change in the transport capacity and in the response of this nephron segment to ADH in young (1–2 months) and old (20–24 months) mice. The transepithelial potential difference (V _te) was significantly higher in young mice (+8.5±0.4 mV, n=13) than in old ones (+6.6±0.5 mV, n=17). Addition of 0.1 nmol.l^–1 ADH to the bath solution significantly increased V _te by 5.2±0.5 mV in the young and by 3.1±0.6 mV in the old animals. Application of dibutyryl-cAMP (0.1 mmol.1^–1) did not further increase the hormonal response in both groups. The ADH-mediated increase in the corresponding equivalent short-circuit current (I _SC = V _te/R_te) was twice as great in young mice as in old, indicating that the stimulation of NaCl transport by ADH across the medullary thick ascending limb is significantly reduced with age. These results suggest that the previously reported age-related defect in the urinary concentrating ability of the kidney is partly due to a decreased response of the medullary thick ascending limb to ADH.     

Real time endoscopic imaging of oxyradical generation in pig stomach during ischemia–reperfusion

BACKGROUND: Oxygen-free radicals generation is considered to be a major cause of gastric injury during reperfusion. Chemiluminescence has been used to assess real-time free radical release on the surface of isolated organs. AIMS: To evaluate the combined use of chemiluminescence and gastroendoscopy techniques and to assess the real-time production of free radicals during ischemic damage of the gastric wall in an animal model. PATIENTS AND METHODS: For the experiment, an optical junction was set up between a fibroendoscope and a luminograph apparatus. Three pigs were submitted to gastrofibroendoscopy before, during and after 30 min of clamping of the coeliac artery. Under basal conditions, at the end of the ischemic phase and at the beginning of reperfusion, 1 mM of lucigenin, a specific superoxide enhancer, was injected in the left gastric artery of the animal. The endoscopic live images and chemiluminescence emission were recorded and successively superimposed to measure rate and spatial distribution of photon emission (photons/s). RESULTS: Free radical production was not observed under basal conditions or during the ischemic phase, but significantly increased during reperfusion reaching a maximum peak after 15 min (0.6+/-0.2 photons x 10(5)/s) and decreased progressively thereafter. The superimposition of live and chemiluminescence images allowed the determination of the regional production rate and distribution of photons. CONCLUSIONS: Preliminary observations, in an animal model, on an innovative imaging system which allows the visualization of rate and spatial distribution of reactive oxygen species formation are presented. This new endoscopic technique could be useful for the assessment of oxidative gastric mucosal injury in several gastric diseases; however, further studies remain necessary to determine the applicability of this technique in humans.     

Total agenesis of the left pericardium. Description of a case

Total agenesia of the left pericardium is an uncommon congenital anomaly. The case of a 20-year-old male patient practising sports and complaining of atypical chest pain is described. The Authors point out the importance of the particular ECG and Rx findings obtained varying the patient's supine position. The fundamental role of chest CAT scanning as a non-invasive diagnosis technique is confirmed.     

LEMMA: A Language for Easy Medical Models Analysis

The quality of health care systems and processes is becoming a prominent problem and more and more efforts are devoted to define methodologies and tools to measure and assure quality of care. New methods are required to optimize health care processes to guarantee high quality standards within (limited) available resources. Resource optimizations able to preserve the quality of treatments require good models of medical processes. This paper presents LEMMA, a new notation to model medical processes. LEMMA provides physicians with intuitive graphical elements to design their models. At the same time a high level timed Petri net corresponding to the designed model is built automatically. In this way, LEMMA models are ascribed formal semantics and can be executed and analyzed automatically. The dual language approach followed in this paper allows physicians to gain all the benefits of formal methods without being proficient in them. Medical users manage simple graphical elements, while Petri nets ensure formality and validation capabilities. In this way LEMMA mixes formal and informal notations, overcoming the problems of both the approaches. The definition of the notation has been supported by the development of an environment to design LEMMA models. The environment, besides letting us experiment with the notation, has been employed to define and analyze real case studies.     

葛根对小白鼠免疫功能的影响

从免疫学方面探讨中药葛根的强身健体作用。方法 :用 10 0 %葛根水浸出液定期给小鼠灌胃 ,然后检测小鼠抗体产生能力、淋巴细胞转化率、巨噬细胞吞噬的功能。结果 :用药组小白鼠以上免疫学指标均有显著增强作用 ,与对照组相比有非常显著性差异 (P <0 .0 1)。未见有副作用。结论 :口服葛根可明显增强机体免疫功能。     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.