Orthogonal solid-phase synthesis of a monobiotinylated analog of Neuropeptide Y

Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl protective group strategy. Instead of Asn⁷ in the native scquence, Boc-Lys(Alloc)-OH was incorporated. At the end of the synthesis the Alloc group was selectively removed by palladium-catalyzed hydrostannolysis and biotin coupled to the e-amino group of Lys⁷. After cleavage and characterization with plasma desorption mass spectrometry the N^e-7-biotinyl-[Lys⁷]-NPY and the nonbiotinylated analog [Lys⁷]-NPY were investigated as ligands to the NPY receptor from rat cerebral cortex. Both analogs were found to be high affinity ligands to the NPY receptor and bound with essentially the same affinity as unmodified NPY.     

Frequency and prognostic value of HLA antigens in osteosarcoma patients

A homogeneous group of 53 Caucasian subjects with high-grade osteosarcoma (OS) was typed for HLA-A and B locus antigens. Although no significant differences in the distribution of these antigens were found in comparison with 425 local controls, a trend towards an increase of HLA-B18 and decrease of HLA-B21 was observed. All the patients underwent amputation plus adjuvant chemotherapy and among the 29 patients with a follow-up longer than one year, 9 out of 10 subjects with HLA-A3 antigens developed metastases within a few months. None of the OS patients had the HLA-A3, B7 haplotype which is present in linkage-disequilibrium in the control population.     

DIFFERENTIATION PATHWAYS IN PRIMARY INVASIVE BREAST CARCINOMA AS SUGGESTED BY INTERMEDIATE FILAMENT AND BIOPATHOLOGICAL MARKER EXPRESSION

The expression of intermediate filament proteins (IFPs) in 65 primary breast carcinomas was analysed by a panel of specific antibodies. Results were integrated with the oestrogen and progesterone receptor (ER and PGR) status, Ki-67 marking, and epidermal growth factor receptor (EGFr) expression. Invasive breast carcinomas could be divided into three main groups: group 1 revealed positivity only for ‘simple epithelial’ cytokeratins (CKs 7, 8, 18, and 19); group 2 also stained with the antibodies K8.12 and 34βE12; while group 3 showed co-expression of CKs 14 and 17, vimentin, and α-smooth muscle actin. Group 3 consistently comprised tumours with the highest Ki-67 levels, EGFr positivity, and ER-PGR negative status. On the other hand, groups 1 and 2 usually exhibited a positive hormonal status, lower proliferative activity, and EGFr negativity. The results of this study indicate that the determination of IFPs can significantly contribute to the identification of groups of patients with different biopathological settings and possibly different clinical behaviour.     

The effect of glycerol on the guinea-pig hydropic ear

The aim of this paper was to investigate the effect of glycerol on experimental endolymphatic hydrops in guinea-pigs. The right endolymphatic sac and duct were obliterated through an extradural posterior fossa approach. Some animals received a 3 g/kg dose of glycerol for a period of 7 days, whereas others received the same dose for 30 days. The activity of glycerol was studied by investigating the volumetric changes in the scala media determined with a computerized planimeter. Glycerol induced a significant reduction of the hydrops showing its effectiveness and suggesting a strial metabolic response.     

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L⁻¹ of urine (range: 0.17–546.31 pmol/L⁻¹. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary β 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.     

Thin Primary Cutaneous Melanoma in Childhood and Adolescence: Report of 12 Cases

Abstract:  Approximately, 1–4% of all new melanoma cases occur in patients younger than 20 years. The clinical presentation of melanoma in the young is often challenging. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. Study subjects were drawn from 1470 patients with histologically confirmed melanoma. From this group, melanoma developed in 12 patients younger than 19 years. For each melanoma diagnosed, histologic characteristics, treatment, and outcomes were evaluated. Of the 12 patients described in this study, four were men and eight were women. The average age was 15.6 years ranging from 11 to 18 years. Regarding invasive melanomas, Breslow thickness ranged from 0.15 to 0.66 mm with a mean thickness of 0.36 mm. Primary treatment of 12 patients included wide local excision of their primary lesions. In many cases reported in literature lesions are amelanotic, nodular, and resemble pyogenic granuloma. From our case studies it was found that the clinical characteristics detected in melanomas diagnosed in childhood and adolescence have been the same as those described in adults and that the ABCDE clinical criteria may be helpful basics of melanoma.     

Conformational preferences and self-association modes of two diastereomeric statine derivatives

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, ¹H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.     

Results of Delivered Therapy for VT or VF in Patients with Third-Generation Implantable Cardioverter Defibrillators

Third-generation implantable cardioverter defibrillators (ICDs) offer tiered therapy and can provide significant advantage in the management of patients with life-threatening arrhythmias. Three different types of ICDs were implanted in 21 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF). Arrhythmia presentation was VT(76%), VF(10%), or both (14%). The mean left ventricular ejection fraction for the group was 32.4 ± 7%. No surgical mortality occurred. Prior to discharge individual EPS determined the final programmed settings of the ICDs. During a mean follow-up of 13 ± 1.4 months (range 2–20) the overall patient survival was 85.7%. No sudden arrhythmic or cardiac death occurred. Twenty of 21 patients (95%) received therapy by their device. In 14 patients (67%) antitachycardia pacing (A TP) was programmed "on," 13 of which was self-adaptative autodecremental mode. There were 247 VT episodes, 231 of which were subjected to ATP with 97% success and 3% acceleration or failure. Low energy shocks reverted all other VT episodes. VF episodes were successfully reverted by a single shock (93%), two shocks (6%), or three shocks (1 %). We conclude that ATP therapy of VT is successful in the large majority of episodes with rare failures, and that VF episodes are generally terminated by a single ICD shock.