Teneurin proteins possess a carboxy terminal sequence with neuromodulatory activity

We have previously shown that a bioactive neuropeptide-like sequence is present at the carboxy-terminus of the teneurin transmembrane proteins. We have subsequently called this peptide 'teneurin C-terminal associated peptide' (TCAP). The sequence encodes a peptide 40 or 41 amino acids long flanked by a cleavage motif on the amino terminus and an amidation motif on the carboxy terminus, characteristic of bioactive peptides. This sequence is highly conserved in all vertebrates. A TCAP-like sequence is encoded by each of the four teneurin genes. We have therefore examined the neurological role TCAP-1 may play in mice and rats. In situ hybridization studies showed that the teneurin-1 mRNA containing the TCAP-1 sequence is expressed in regions of the forebrain and limbic system regulating stress and anxiety. A synthetic version of amidated mouse/rat TCAP-1 was prepared by solid-phase synthesis and used to investigate the in vitro and in vivo activity. TCAP-1 induces a dose-dependent change in cAMP accumulation and MTT activity in immortalized mouse neurons. Administration of synthetic TCAP-1 into the basolateral amygdala significantly increases the acoustic startle response in low-anxiety rats and decreases the response in high-anxiety animals in a dose-dependent manner. When 30 pmol TCAP-1 is administered into the lateral ventricles each day for 5 days, the sensitization of the rats to the acoustic startle response is abolished. These data indicate that TCAP may possess functions that are independent of the teneurin proprotein and together, the teneurins and TCAP, may represent a novel system to regulate neuronal function and emotionality.     

A novel activation-induced cytidine deaminase gene mutation in a Tunisian family with hyper IgM syndrome

Mutations in activation-induced cytidine deaminase can cause an autosomal recessive form of hyper-IgM syndrome. We have examined a Tunisian family composed of six members: two healthy parents, their two healthy daughters and two affected sons. We found a homozygous transversion G to T in the two sons while heterozygosity for the mutation was found in all other family members. This alteration is localised in intron 2 at the +1 position resulting in defective splicing. Use of various intronic cryptic splice-sites led to expression of various aberrant mRNA species. Conclusion:This is a novel mutation found in the gene encoding for activation-induced cytidine deaminase in a Tunisian family with hyper-IgM type 2 syndrome. This alteration leads to the use of two cryptic splicing sites causing the formation of two different mRNA species.C. Fiorini and S. Jilani contributed equally to this work.     

Intermittent low-dose finasteride is as effective as daily administration for the treatment of hirsute women

In a prospective randomized study 38 women with idiopathic hirsutism or polycystic ovary syndrome (PCOS) received 2.5 mg of finasteride every day or every 3 days. Intermittent low-dose administration of finasteride was as effective as continuous administration in reducing hirsutism score and was accompanied by a lower incidence of side effects.     

Evaluation of complications and long-term results after surgery for gynaecomastia

In an attempt to evaluate ten years of surgical treatment of gynaecomastia, we analysed the incidence of complications and the quality of the results in a group of patients classified according to Simon. Over the decade 1992-2002, 107 patients with gynaecomastia aged from 17 to 79 years were treated. The prevalent surgical approach was subcutaneous mastectomy. In 71 patients the surgical approach was via a periareolar inferior incision, superior in 15, inferior with bilateral extensions in 10; using a complete circumareolar approach (according to Padron) in 8 patients and a subcutaneous transareolar mastectomy in 3. No immediate complications were observed. Ten patients presented a modest postoperative haematoma. Only in one diabetic patient with chronic bronchitis and grade III gynaecomastia did partial dehiscence of the surgical wound occur. Most patients achieved good results. We judged the results excellent in 94 patients, good in 11, and unsatisfactory in 2. On the basis of our experience and in agreement with the literature data, we can affirm that the best results were obtained by subcutaneous mastectomy with a periareolar incision.     

Hematological malignancies in the island of Sardinia, 1974-1993: age and sex distributions and temporal changes in incidence

We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984-1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia.     

Alzheimer disease risk associated with APOE4 is modified by STH gene polymorphism

The association of the STH gene polymorphism with Alzheimer disease (AD) is debated. In the analysis of two genetically and diagnostically distinct groups of Alzheimer patients from the USA and Italy, the authors did not find an association with the STH polymorphism. However, the APOE-4-associated risk of AD greatly increased if the STH-G allele was also present. The STH-G allele appears to be a risk modifier for AD.     

Heterogeneity of response to imatinib-mesylate (glivec) in patients with hypereosinophilic syndrome: implications for dosing and pathogenesis

Four cases of hypereosinophilic syndrome (HES) treated with the tyrosine-kinase inhibitor imatinib-mesylate are reported. The drug was effective in three patients, but a prolonged clinical and hematological remission was obtained only in one patient, due to appearance of resistance or poor tolerability in the other cases. The dose of imatinib necessary to achieve a response ranged from 100 to 600 mg/d. One patient with evidence of a clonal T-cell population did not respond at all. We confirm the efficacy of imatinib in HES, but we also underline that type and duration of response may be variable. This could be due to different pathogenetic mechanisms of the disease in single patients.     

Possible multiple myeloma dedifferentiation following thalidomide therapy: a report of four cases

Thalidomide has been shown to be effective in approximately 30% of patients with refractory or advanced multiple myeloma (MM). Here we report on 4 cases of patients treated with thalidomide for refractory MM showing dedifferentiation of the neoplasm. In these cases thalidomide treatment despite reduction of M-component-was followed by disease progression and a very poor clinical outcome which was paralleled by bone marrow plasmacytosis showing marked signs of dedifferentiation, inducing us to speculate on a potential role of thalidomide on dedifferentiation of myeloma cells. In our opinion, a possible dedifferentiation of MM should therefore be taken into account in MM patients treated with thalidomide when clinical course deteriorates despite reduction of M-component.