INTERLEUKIN 6 GENE-TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA: TUMOUR CELL GROWTH AND METASTATIC POTENTIAL

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5–7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis. © 1997 John Wiley & Sons, Ltd.     

Structural versatility of peptides from Cα,α-disubstituted glycines: crystal-state conformational analysis of peptides from Cα-methylhomophenylalanine, (αMe)Hph

The molecular and crystal structures of the C^α-tetrasubstituted, δ-branched α-amino acid C^α-methyl-homophenylalanine, H-d -(αMe)Hph-OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X-ray diffraction. The peptides are Z-l -(αMe)Hph-(l -Ala)₂-OMe, pBrBz-[d -(αMe)Hph]₃-OtBu and Ac-(Aib)₂-l -(αMe)Hph-(Aib)₂-OtBu. All the (αMe)Hph residues prefer φ,ψ torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a β-bend conformation stabilized by a 1→4 C = O?H-N intramolecular H-bond. The terminally blocked pentapeptide is folded in a regular 3₁₀-helix. In general, the relationship between (αMe)Hph α-carbon chirality and helix handedness is the same as that exhibited by protein amino acids. A comparison is also made with the conclusions extracted from published work on peptides from other types of C^α-alkylated aromatic α-amino acids. © Munksgaard 1996.     

Dentinogenesis imperfecta in children with osteogenesis imperfecta: a clinical and ultrastructural study

International Journal of Paediatric Dentistry 2010; 20: 112–118 Aim. The aim of this study was to assess the correlation between osteogenesis imperfecta (OI) and dentinogenesis imperfecta (DI) from both a clinical and histological point of view, particularly clarifying the structural and ultrastructural dentine changes. Design. Sixteen children (6–12 years aged) with diagnosis of OI were examined for dental alterations referable to DI. For each patient, the OI type (I, III, or IV) was recorded. Extracted or normally exfoliated primary teeth were subjected to a histological examination (to both optical microscopy and confocal laser‐scanning microscopy). Results. A total of ten patients had abnormal discolourations referable to DI: four patients were affected by OI type I, three patients by OI type III, and three patients by OI type IV. The discolourations, yellow/brown or opalescent grey, could not be related to the different types of OI. Histological exam of primary teeth showed severe pathological change in the dentin, structured into four different layers. A collagen defect due to odontoblast dysfunction was theorized to be on the base of the histological changes. Conclusions. There is no correlation between the type of OI and the type of discolouration. The underlying dentinal defect seems to be related to an odontoblast dysfunction.     

Hand movements at 3 months predict later hemiplegia in term infants with neonatal cerebral infarction

Aim The aim of this study was to explore the predictive value of quantitative assessment of hand movements in 3‐month‐old infants after neonatal stroke. Method Thirteen infants born at term (five females, eight males; mean gestational age 39.4wks, SD 1.19, range 37–41wks; mean birthweight 3240g, SD 203, range 2900–3570g) with neonatal arterial ischaemic cerebral infarction, and 13 healthy infants (mean gestational age 39.1wks, range 37–41wks, SD 1.26; mean birthweight 3190g, SD 259, range 2680–3490g) were enrolled in the study. The absolute frequency and the asymmetry of global hand opening and closing, wrist segmental movements, and independent digit movements were assessed from videotapes recorded at around 12 weeks. Neurological outcome was assessed when the infants were at least 18 months old using Touwen’s neurological examination. Results Five of the 13 infants with neonatal stroke had normal neurological development, and eight had hemiplegia. Asymmetry of wrist segmental movements and the absolute frequency of independent digit movements were significantly different between infants with and without hemiplegia (p=0.006 and p=0.008, respectively). No differences were found in global hand movements. Interpretation We propose that the observed abnormalities of hand movements are the result of two different mechanisms: direct disruption of the corticospinal projection to the spinal cord, and altered modulation of the central pattern generators of general movements.     

A promoter mutation, C → T at position -92, leading to silent /3-thalassaemia

Summary. This study describes the clinical phenotype of the C?→? T mutation at position – 92 of the β-globin gene. Excluding two cases with HbA2 levels within the range of the /3-thalassaemia carrier state, heterozygotes for this mutation showed normal or borderline red blood cells count, Hb levels, MCV, MCH and HbA2 values, and unbalanced globin chain synthesis. Compound heterozygotes for the - 92 C → T mutation and a β° thalassaemia mutation (β°39) (two cases) or severe β-thalassaemia (p⁺ IVSII nt 745) (two cases) developed thalassaemia intermedia. According to these characteristics, the –92 promoter mutation should be added to the list of silent β-thalassaemias.