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Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

The presence of psychological distress has a negative impact not only on cancer patients' quality of life but also on the course of the disease, with slower recovery and increased morbidity. These issues are of particular importance in melanoma patients (MP), who remain at risk of disease progression for many years after diagnosis. This study aimed to investigate psychological distress, coping strategies, and their possible relationships with demographic-clinical features in patients with early-stage melanoma in follow-up. The investigation focused in particular on whether the psychological profile differed between patients at different melanoma stages. Data of 118 patients with melanoma in the Tis-Ia stages (MP_Tis-Ia) and 86 patients with melanoma in the Ib-IIa-IIb stages (MP_Ib-II) were gathered through a self-administered survey and compared using a cross-sectional design. The results evidenced a high percentage of anxiety (25%) and distress symptoms (44%), whereas depressive symptoms seemed less frequent (8%). Psychological distress was higher in women than in men, and in patients with a higher educational level. Nevertheless, no significant differences were found between MP_Tis-Ia and MP_Ib-II. With respect to coping style, the patients in this sample adopted predominantly positive and active strategies. Correlational analyses showed that maladaptive coping strategies such as behavioral disengagement, denial, self-distraction, and self-blame were most strongly related to increased levels of psychological distress. The high presence of anxiety and distress symptoms, their relationship, and the use of negative coping strategies underline the importance of psychological distress screening also in early-stage MP, including at long-term follow-up.

Microfluidic flow focusing devices (mFFD) are currently used to produce microdroplets and emulsions. Recently, it has been demonstrated that they are well adapted to the encapsulation of biologic objects like proteins and cells. Liquids used for encapsulation are most of the time dilute polymeric solutions with relatively low viscosity. However, investigations have started to assess the possibility of encapsulation with more concentrated solutions, like semi-dilute solutions of alginates. In this work, we analyze the behavior of highly viscous alginate solutions in pressure actuated FFDs. Experiments have been performed using alginate solutions with a viscosity up to 2600 times that of water. In parallel, an analytical model of the flow in the different branches of the FFD has been derived that explains the limits of the droplet regime. This model can be used to produce scaling rules for FFDs, facilitating the dimensioning of FFDs according to the desired size of the capsules. Finally, an example of encapsulation of Jurkat cells in a high viscosity Keltone alginate capsule is given.

We report a case of a melanoma arising after about 10 years after a burn injury. This is an uncommon example of a carcinogenetic event that could be prevented or diagnosed early. Usually, the mutagenic event clinically appears many years after the burn especially if it was not treated correctly with a careful surgical approach. The average time of latency could be found in literature as 46.5 years from the burn, whereas our case was only 10. A frequent and very long follow-up of the burn scars could represent a valid prophylactic option to avoid neoplastic proliferation if the tumor appears.

Proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β (IL1β) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1β and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1β effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. Furthermore, IL1β has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the striatum. To better detail the synaptic action of IL1β, and to clarify its complex interaction with the ECS, here we investigated the possible interplay between IL1β and CB1Rs controlling glutamate transmission (CB1Rs(glu)), other critical elements of the ECS. Our results show that the sensitivity of CB1Rs(glu) is fully blocked in the presence of IL1β in corticostriatal brain slices, and that the protein kinase C/TRPV1 pathway is involved in this effect. IL1β failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1β-CB1Rs(GABA) but not IL1β-CB1Rs(glu) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-β-cyclodextrin all blocked IL1β-mediated inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1β in the striatum.

We report the first related case of a metastasis from melanoma appeared on a pacemaker device pocket. The stadiation exams showed that this is the only localization of the pathology. The integrated management from both cardiologic and dermatologic surgery was described. It was composed by two interventions, a first time for the implant of a new device contralaterally, and later by the surgical intervention, with exeresis of the lesion, radical lymph node dissection of the axilla and plastic reconstruction. The previous pacemaker implant may hypothetically create a favourable environment for metastatic cells ingrowth. This could be explained by a chronic inflammatory reaction and capsule formation around the device as previously reported, or by a blockage of lymphatic drainage in this specific site.

RIASSUNTO Nonostante gli sforzi per diffondere e implementare le raccomandazioni nutrizionali per il trattamento del diabete, la loro applicazione nella pratica clinica è ancora largamente insufficiente. Tra le possibili ragioni va considerato il fatto che le abitudini alimentari risentono molto delle tradizioni gastronomiche locali. Lo studio si propone di valutare le abitudini alimentari delle persone con diabete in tre macroaree geografiche italiane, nord, centro e sud, per studiare in che misura le tradizioni gastronomiche locali possano influenzare l'adesione alle raccomandazioni nutrizionali. Sono stati studiati 1786 pazienti diabetici di tipo 2; le abitudini alimentari sono state indagate con un questionario alimentare semiquantitativo di frequenza validato (EPIC, European Prospective Investigation on Cancer and Nutrition). L'introito energetico è sovrapponibile nelle 3 macroaree geografiche, ma gli alimenti che contribuiscono alla composizione della dieta sono diversi a seconda della locazione geografica: al nord si osserva un maggiore consumo di carne, salumi e grassi animali; al sud, un maggiore consumo di pane integrale e legumi. Questo si traduce in una differente composizione in nutrienti della dieta: il consumo di grassi totali, grassi saturi e polinsaturi risulta significativamente più basso al sud e al centro rispetto al nord (p < 0,05); il contrario si osserva, invece, per i carboidrati totali e la fibra alimentare (p < 0,05). Infine, la proporzione di pazienti che aderiscono alle raccomandazioni nutrizionali è generalmente scarsa sia per il consumo di fibra, mediamente inferiore rispetto a quanto raccomandato, sia per il consumo di grassi saturi, mediamente superiore ai livelli consigliati. In conclusione, le raccomandazioni nutrizionali sono scarsamente seguite su tutto il territorio nazionale; si osservano, tuttavia, significative differenze geografiche verosimilmente dovute all'influenza delle tradizioni gastronomiche locali che vanno tenute in conto per migliorare l'adesione dei pazienti alle raccomandazioni dietetiche.

The knowledge of factors modulating the behaviour of bone mass is crucial for preventing and treating osteoporotic disease; among these factors, body weight (BW) has been shown to be of primary importance in postmenopausal women. Nevertheless, the relative effects of body composition indices are still being debated. Our aim was to analyze the relationship between body mass index (BMI), fat and lean mass and bone mineral density (BMD) in a large population of women. Moreover, this study represents a first important report on reference standard values for body composition in Italian women.Between 2005 and 2008, weight and height of 6,249 Italian women (aged 30-80 years) were measured and BMI was calculated; furthermore BMD, bone mineral content, fat and lean mass were measured by dual-energy X-ray absorptiometry. Individuals were divided into five groups by decades (group 1, 30.0-39.9; group 2, 40.0-49.9; group 3, 50.0-59.9; group 4, 60.0-69.9; group 5, 70.0-79.9). Differences among decades for all variables were calculated using a one-way analysis of variance (ANOVA) and Bonferroni test by the SPSS programme.Mean BW was 66.8±12.1 kg, mean height 159.1±6.3 cm and mean BMI 26.4±4.7 kg/m(2). According to BW and BMI, there was an increase of obesity with age, especially in women older than 50 years (p0.001). Lean mass increased until 50 years of age but significantly decreased after this age (p0.001). The percentage of osteopenia and osteoporosis in the examined population was 43.0% and 16.7%, respectively.Our data show that obesity significantly decreased the risk for osteoporosis but did not decrease the risk for osteopenia. It is strongly recommended that a strong policy regarding prevention of osteopenia and osteoporosis be commenced. An overall examination of our results suggests that both fat and lean body mass can influence bone mass and that their relative effect on bone could be modulated by their absolute amount and ratio to total BW.

Aims and Background The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. Methods and Study Design In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors >2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. Results We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patients showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. Conclusions At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.

Objective: The present investigation was aimed to evaluate the effect of subclinical hypothyroidism and obesity on bone mineral content (BMC) in different body segments. Methods: Thirty-two premenopausal women (age: 37 ± 9.9 years), with a wide range in body mass index (BMI), were studied. Subclinical hypothyroidism was defined by a basal TSH ≧4 µU/l and/or a TRH-stimulated peak ≧30 µU/l. For each subject, weight, height, BMI (weight/height2) and the waist/hip ratio were measured. Total BMC, total bone mineral density (BMD), leg BMC, leg BMD, trunk BMC, trunk BMD, arm BMC and arm BMD were determined using dual-energy X-ray absorptiometry. Thyroid function (basal and TRH-stimulated TSH, free T3 and free T4) were determined from fasting blood samples for all subjects. Results: Anova was conducted within all the groups to observe the effect of thyroid status and/or obesity on BMC and BMD. There was no statistical difference for age. Total BMC was affected by obesity (p < 0.05) but not by thyroid status, BMD of the legs was significantly influenced both by thyroid function and obesity (p < 0.01); total BMD was affected by hypothyroid status (p < 0.05). A direct relationship between leg BMD and TSH was demonstrated. Conclusion: Subclinical thyroid hypofunction and obesity seem to affect BMD differently in the body segments. An influence of gravitational force seems necessary in order to make evident the effect of subclinical hypothyroidism on bone. A condition of subclinical hypothyroidism should be considered when evaluating subjects for osteoporosis, since a BMD measured at the femoral neck may induce underestimation of initial osteoporosis.

Molecular scanning of insulin receptor substrate-1 (IRS-1) revealed several amino acid substitutions. The most common IRS-1 variant, a Gly to Arg972 change, is more prevalent among type 2 diabetic patients. In this study we overexpressed wild-type and Arg972IRS-1 variant in L6 skeletal muscle cells and examined the functional consequences of this polymorphism on insulin metabolic signaling. L6 cells expressing Arg972-IRS-1 (L6-Arg972) showed a decrease in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity compared with L6 cells expressing wild-type IRS-1 (L6-WT) as a consequence of decreased binding of p85 subunit of PI 3-kinase to IRS-1. L6-Arg972 exhibited a decrease in both basal and insulin-stimulated glucose transport due to a reduction in the amount of both GLUT1 and GLUT4 translocated to the plasma membrane. Both basal and insulin-stimulated Akt phosphorylations were decreased in L6-Arg972 compared with L6-WT. Basal glycogen synthase kinase-3 (GSK-3) activity was increased in L6-Arg972 compared with L6-WT, and insulin-induced inactivation of GSK-3 was also reduced in L6-Arg972. This change was associated with a significant decrease in insulin-stimulated glucose incorporation into glycogen and glycogen synthase activity in L6-Arg972 compared with L6-WT. These results indicate that the Arg972-IRS-1 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI 3-kinase/Akt/GSK-3 signaling pathway. The present data indicate that the polymorphism at codon 972 of IRS-1 may contribute to the in vivo insulin resistance observed in carriers of this variant.

It has been previously demonstrated that pituitary adenylate cyclase-activating polypeptide (PACAP) regulates insulin secretion. PACAP exerts its biological action by binding to at least three different receptor subtypes coupled to different signal transduction mechanisms. The signaling pathways underlying the insulinotropic effect of PACAP involve mainly the activation of adenylate cyclase to form cAMP, which directly and indirectly, through increased intracellular Ca2+, stimulates insulin exocytosis. In the present study we have characterized the functional and molecular expression of PACAP/vasoactive intestinal polypeptide receptors isoforms and subtypes and its isoforms in a beta-cell line and in isolated rat pancreatic islets. Although insulinoma cells express the messenger RNA encoding PAC1 (-R and -hop variants), VPAC1 and VPAC2, binding experiments indicate the preponderance of PAC1 over VPAC 1-2 receptors. We have also shown that the main signaling pathway of PACAP in beta-cells is mediated by adenylate cyclase, whereas the inositol 1,4,5-trisphosphate pathway is almost inactive. Furthermore, we have demonstrated that PACAP exerts long-term effects on beta-cells, such as transcriptional regulation of the insulin gene and genes of the glucose-sensing system (GLUT1 and hexokinase 1).

We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P0.01) and positively correlated with IGF-I binding (r = 0.92; P0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P0.002) and body mass index (r = 0.71; P0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

We report a clinical case of a double primitive tumour (right kidney clear cell carcinoma and gastric carcinoma) in two brothers. There is no history of cancer in the parents. Both patients were previously affected by gastric ulcer. No report of association between the two neoplasms was found in literature. The age of the patients (61 and 70 years) and the singleness of the kidney tumour seem to exclude the case of a familial kidney cancer. The neoplastic transformation of the gastric ulcer is instead a quite frequent report with an incidence of about 1%. Alterations of oncogenes or tumour suppressor genes shared from both neoplasm are at present still unknown. Nevertheless molecular analysis of patients' neoplastic genome could point out typical chromosome translocations/deletions or gene mutations.

Twenty nurse-midwives in government service in the Sudan (health visitors) were trained to provide intrauterine contraceptives in a research project designed to evaluate the safety of insertion of IUDs by medical personnel who are not physicians. After training, they inserted 763 IUDs. Independent evaluation of 520 clients was conducted by obstetrician-gynecologists who found that only six (1.2%) had been incorrectly inserted. Outcomes for clients of the health visitors with respect to perforations, infections, expulsions, and pregnancies compared well with those of eight physicians who participated in the study. The research strongly supports the concept of nurse-midwife training for IUD insertions which would greatly expand the availability of family planning services and would conserve physician time and skills for problem cases.In 1986, 20 nurse-midwives (health visitors) inserted 763 IUDs at health centers belonging to the Ministry of Health in Khartoum, the Sudan. Gynecologists evaluated 520 insertions after 1 month. The health visitors' outcomes were compared with those of 8 gynecologists who inserted 69 IUDs. Evaluating gynecologists found 98.8% of insertions to be correct and 99% of pelvic conditions to be normal. 47 IUDs inserted by health visitors were removed compared to 12 removals for the gynecologists. Only 14.9% of health visitor patients did not return for a post exam compared to 20.3% for those of gynecologists. Indeed the outcome of health visitors' patients remained better than the outcome of the gynecologists' patients. For example, 2.9% of IUDs inserted by the gynecologists were expelled whereas only .8% of those inserted by the health visitors were expelled. In addition, only .6% became pregnant with a health visitor inserted IUD while 1.4% of gynecologist patients became pregnant. Side effects from the IUD occurred significantly more often in gynecologist patients (13%) than health visitor patients (2.2%). A possible reason for this difference may be that the health visitors better prepared clients for temporary discomforts they would experience than did the gynecologists. Moreover only .6% of health visitor inserted IUDs were not in situ compared to 2.9% of gynecologists inserted IUDs. The research demonstrated that the nurse-midwives could indeed safely insert IUDs and improve the availability of IUDs. Other advantages of using them to perform this service are they knew their clientele well and clients are more comfortable with a female.

The authors study a group of 61 patients treated for floor of the mouth neoplasms at the Istituto di Oncologia di Torino. They confirm a high incidence of deaths in the first 2 years after treatment in patients T greater than 2 N+, and better survival in patients with stage I-II tumours. The survival does not tend to fall between 5 and 10 years after treatment.

The authors study a group of 295 patients treated for tongue neoplasms at the Istituto di Oncologia di Torino. They point out the influence of many factors on survival particularly referring to tumour size, lymph nodes metastases and tumour stage at the time of first treatment.

In 1980, the Department of Community Medicine of the University of Khartoum designed an operations research project to test the possibility of getting village midwives to be involved in the delivery of maternal and child health and family planning (MCH/FP) services. From 1981-1983 the project was implemented by the University of Khartoum in cooperation with the Ministry of Health. The project area covered 100 km. It encompassed a largely agrarian population of 93,000 in 90 villages north of Khartoum along the banks of the Nile. The focus was on training and supervising village midwives. Information was provided on contraceptives for birth spacing, distribution of oral contraceptives, and referral for other methods. Also provided to midwives was information for mothers on oral rehydration therapy for children with diarrhea, and distribution of oral rehydration solution packets. Nutrition education was given midwives with emphasis on breastfeeding and weaning procedures. Information was also supplied about vaccination for children under 5 years of age (in collaboration with the Sudan Expanded Program on Immunization). The project was expensive, particularly regarding incentive payments for supervisors and midwives. The project had a very good start, but when incentive payments were withdrawn, it almost collapsed. At first, what midwives could do to provide maternal and child health services was targeted, but as the project went on, there was more concern for involvement of midwives in broader rural health delivery. The project area was a conservative, Islamic one. An extension area was selected 5 hours travelling time from Khartoum in Shendi District of Nile Province. The project was begun in 60 villages of 75,000 inhabitants. The land stretched for 120 km along both banks of the Nile. In the extension area, a small fee (US$.025) was charged per cycle, half going to the midwives, and half towards the health teams' expenses. 21 health zones were created, and a health team created for each. Registers of women aged 15-49 and children 3 years have been set up for each health zone. There have been very good results in the management of diarrhea.

The Sudan Community-Based Health Project, initiated by the University of Khartoum in cooperation with the Ministry of Health in 1980, sought to test the proposition that government-trained village midwives could provide maternal-child health and birth spacing services in addition to their ongoing obstetrical duties. The project area encompassed 92,000 people in 93 villages. The 120 midwives serving the project area received training in 4 interventions -- oral rehydration therapy, maternal and child nutrition, immunization, and birth spacing -- and introduced these services by means of 3 rounds of household visits over a 5-month period. Comparison of pre- and post-intervention survey data indicates that village midwives can indeed be used successfully to promote not only contraceptive use, but also health attitudes and practices that are positively associated with fertility regulation. Between the 2 surveys, the percentage of women who ever used contraception increased from 22% to 28%, while the percentage of current users rose from 10% to 13%. Parity was significantly related to current use; each child born multiplied the likelihood of contraceptive acceptance (by a factor of 0.76 in the post-intervention sample). Maternal education was the socioeconomic variable that most enhanced receptivity to contraceptive acceptance after the project's interventions. In terms of community-level variables, village location along the Nile and proximity to a paved road were significant correlates of contraceptive use. When variables related to the project itself were analyzed, women with vaccinated children were found to be twice as likely to contracept as those with nonvaccinated children and women who believed breast feeding should be continued during diarrhea episodes were 1.5 times more likely to use birth spacing than those who did not. Although midwives did not specifically emphasize contraceptive use, it appears women who were encouraged by midwives to take positive steps in the area of child health were also likely to become more innovative in terms of fertility regulation.

Mitochondria carry maternally inherited genetic material, called the mitochondrial genome (mtDNA), which can be defined as the 25th human chromosome. The chromosome-centric Human Proteome Project (c-HPP) has initially focused its activities addressing the characterization and quantification of the nuclear encoded proteins. Following the last International HUPO Congress in Boston (September 2012) it was clear that however small the mitochondrial chromosome is, it plays an important role in many biological and physiopathological functions. Mutations in the mtDNA have been shown to be associated with dozens of unexplained disorders and the information contained in the mtDNA should be of major relevance to the understanding of many human diseases. Within this paper we describe the Italian initiative of the Human Proteome Project dedicated to mitochondria as part of both programs: chromosome-centric (c-HPP) and Biology/Disease (B/D-HPP). The mt-HPP has finally shifted the attention of the HUPO community outside the nuclear chromosomes with the general purpose to highlight the mitochondrial processes influencing the human health. Following this vision and considering the large interest and evidence collected on the non-Mendelian heredity of Homo sapiens associated with mt-chromosome and with the microbial commensal ecosystem constituting our organism we may speculate that this program will represent an initial step toward other HPP initiatives focusing on human phenotypic heredity.

Organogenesis is a complex event, often dependent on inductive tissue interactions, that ultimately promote expression and activation of a combinatorial sequence of transcription factors which are involved in controlling migration, growth and differentiation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

After a wide analysis of the problems concerning biology and integration of autogenic transplantation of tooth germs, the Authors present a clinical case of monolateral agenesis of two premolars, with the transfer of the second premolar germ from one side to an other, suggesting some technical details in flap scalloping.

Translation of rat thyroid mRNA in a cell-free protein synthesis system derived from rabbit reticulocytes results in synthesis of a 300-kDa thyroglobulin polypeptide [C. G. Alvino et al. (1982) >FEBS Lett. 137, 307 – 313]. In the presence of dog pancreas microsomal membranes this polypeptide is segregated into the microsomal vesicles and core-glycosylated, as shown by increased protection against proteolytic treatment and binding to concanavalin-A - Sepharose. The segregation process appears to be strictly coupled to glycosylation, i.e. no detectable amounts of unglycosylated chains are found in the vesicles, and both processes only occur cotranslationally. The glycosylated protein exhibits lower electrophoretic mobility with respect to its non-glycosylated form and comi- grates with a glycosylated 330-kDa polypeptide found in rat thyroid epithelial cells cultured in vitro [F. S. Ambesi- Impiombato et al. (1980) Proc, Nat1 Acad. Sci. USA, 77, 3455-3459]. Both glycosylated and non-glycosylated forms are immunoprecipitated by antibodies to 19-S rat thyroglobulin. Some features of the tyroglobulin poly- peptide segregation and glycosylation have been studied by synchronized translation of rat thyroid mRNA : (a) the signal sequence seems to be located at the amino-terminal portion of the nascent polypeptide chain; (b) the distribution of the carbohydrate units is mostly clustered in the amino-terminal half of the protein as monitored by posttranslational analysis of the polypeptides synthesized in the presence of pancreatic membranes during competition experiments carried out with the detergent Nonidet P40.

Expression of mutated versions of the p53 gene deranged the differentiation program of thyroid cells and resulted in deregulated growth. Specifically, p53 mutants in several residues of the DNA-binding region induced thyrotropin (TSH) -independent growth and inhibition of the expression of thyroid-specific genes. The loss of the differentiated phenotype invariably correlated with the blockage of the expression of the genes coding for the thyroid transcriptional factors PAX-8 and TTF2. Conversely, thyroid cells transfected with a p53 gene mutated at codon 392, located outside the DNA-binding region, stimulated the expression of differentiation genes in the absence of the TSH, and induced TSH-independent growth. cAMP intracellular levels were higher in thyroid cells transfected with the p53 gene mutated at the 392 site than in the untransfected thyroid cells, but lower in the cells transfected with the other mutated p53 genes. Fra-1 and c-jun were induced by p53, resulting in increased AP-1 levels. The results of this study suggest that p53 exerts effects on cAMP transduction pathway in thyroid cells, which are exquisitely sensitive to cAMP.