Limb reduction defects in Emilia Romagna, Italy: epidemiological and genetic study in 173,109 consecutive births.

Epidemiological and genetic variables in limb reduction defects (LRD) were analysed during the years 1978 to 1987 in a case control study in Emilia Romagna, northern Italy. During the observation period, 83 neonates out of 173,109 consecutive births had LRD (4.8 per 10,000). Cases were divided into five subgroups: transverse, intercalary, longitudinal, split, and multiple types of LRD. Of all cases, 64% were upper limb, 21% lower limb, and 15% both. Coexisting non-limb malformations were found in 10 cases (12%), five with recognised syndromes and five with other associated defects. About 7.2% of first degree relatives had defects involving the skeletal system. In two cases the mother had the same type of LRD (a split). No recurrence among sibs was observed. Risk factors correlated with LRD were found to be low birth weight (2500 g or less), vaginal bleeding, and threatened abortion.     

Failure of oocyte maturation: possible mechanisms for oocyte maturation arrest

For human IVF, the patient's ovaries are hormonally stimulated to ensure the collection of fully matured oocytes that are at the metaphase II stage. Only these oocytes can be successfully fertilized either when mixed with sperm or after ICSI. Nevertheless, in some cases immature or maturing oocytes are recovered from follicles. Surprisingly, sometimes these oocytes do not complete maturation when cultured in vitro, for unknown reasons. In this article we discuss some possible mechanisms that may be responsible for those atypical arrests.     

The role of relative osteoneural growth in the gross morphogenesis of the skeleton: A hypothesis

Summary A unifying concept of gross skeletal (neurocranial, neurospinal and appendicular) morphogenesis is proposed. It is based on a close developmental relationship of bone and the nervous tissue, most evident in the neurocranium. The neurospinal developmental interrelationship is modified by the neurovertebral growth differential, which appears to influence the development of spinal curvatures and the gross morphological features of the individual vertebrae. Disproportion in osteoneural growth, as a general biological phenomenon, would be expected to affect the development of the appendicular skeleton. The gross shape of the long bones (physiological curvature and epimetaphyseal widening/modelling) appear to result from a buildup of rapidly forming skeletogenic material adjacent to slower growing nervous trunks, as is the case with the enchondrally developing vertebral body.Pathological accentuation of vertebro-osteoneural growth disproportion, brought about mainly by inhibition of the vulnerable neural growth, will result in abnormal gross features of the skeleton, i.e., pathological curvatures, terminal or general thickening and shortening of bones, or dislocation of joints. Experimental and clinical deformities, such as idiopathic scoliosis, achondroplastic conditions, congenital dislocation of the hip joint, and some other bone dysplasias confined in their onset and progression to the growth period of life, seem to be related to the suggested mechanism. For the above-mentioned skeletal disorders the term osteoneural growth pathology is proposed.

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Le rôle de la croissance relative ostéo-neurale dans la morphogénèse du squelette. Une hypothèse

Résumé On propose une conception unitaire de la morphogénèse normale et pathologique du squelette axial et appendiculaire, à partir des relations les plus étroites existant entre la croissance des systèmes osseux et nerveux; la région neurocraniale en est la manifestation la plus expressive. La disproportion de croissance neuro-vertébrale en longueur exerce une influence décisive sur l'installation des courbures vértébrales physiologiques et sur les caractères morphologiques de chacune des vertèbres, aussi bien dans les dimensions des corps vértébraux que la forme du trou vertébral et des trous de conjugaison. Evoquant un phénomène biologique général, la disproportion de croissance ostéo-neurale agit de même sur le développement du squelette des membres. La forme, c'est-à-dire leurs courbures physiologiques et le modelage de la région épi-métaphysaire peuvent aussi être rattachés à un phénomène d'amassement de tissus osseux proliférant plus rapidement le long des troncs nerveux périphériques.L'accentuation pathologique de la disproportion de croissance ostéo-neurale, du fait principalement de l'inhibition de la croissance des structures nerveuses peut aboutir à des modifications des parties correspondantes du squelette avec effets de raccourcissement, de courbures pathologiques, d'élargissement partiel ou total et éventuellement, de dislocation articulaire. La conception proposée s'appuie sur des observations expérimentales de croissance ostéo-neurale chez des embryons d'oiseaux et d'amphibiens. On peut expliquer certaines déformations du squelette expérimentales ou cliniques comme la scoliose idiopathique, l'achondroplasie et la dysplasie congénitale de hanche par un même mécanisme d'adaptation des os en croissance à des troubles du développement des structures nerveuses avoisinantes. Une dénomination commune est proposée pour ces troubles de la croissance: pathologie de la croissance relative ostéo-neurale.

     

Heart development in the spotted dolphin (Stenella attenuata)

Marine mammals show many deviations from typical mammalian characteristics due to their high degree of specialization to the aquatic environment. In Cetaceans, some of the features of limbs and dentition resemble very ancestral patterns. In some species, hearts with a clearly bifid apex (a feature normally present during mammalian embryogenesis prior to completion of ventricular septation) have been described. However, there is a scant amount of data regarding heart development in Cetaceans, and it is not clear whether the bifid apex is the rule or the exception. We examined samples from a unique collection of embryonic dolphin specimens macroscopically and histologically to learn more about normal cardiac development in the spotted dolphin. It was found that during the dolphin's 280 days of gestation, the heart completes septation at about 35 days. However, substantial trabecular compaction, which normally occurs in chicks, mice, and humans at around that time period, was delayed until day 60, when coronary circulation became established. At that time, the apex still appeared bifid, similarly to early fetal mouse or rat hearts. By day 80, however, the heart gained a compacted, characteristic shape, with a single apex. It thus appears that the bifid apex in the adult Cetacean heart is probably particular to certain species, and its significance remains unclear.     

Infrared spectra and sequence length distribution in free radical styrene/methacrolein copolymers

The method of azoisobutyronitrile (AIBN)-initiated bulk copolymerization of styrene (S) and methacrolein (M) was employed to determine the monomer reactivity ratios r_S = 0.15 and r_M = 0.55 (Q_M = 1.50, e_M = 0.78). Quantitative IR spectroscopy in the region of 4000–450 cm^?1 was used to elucidate the structure of copolymers. In addition to methacrolein units containing aldehyde groups, the copolymers may also contain cyclic hemiacetal structures formed by the reaction of the carbonyls of the neighboring methacrolein units. The carbonyl absorption at 1722 cm^?1 showed that, up to 30 mole-% methacrolein in the copolymer, almost all methacrolein units have free aldehyde groups. The number of cyclic structures increases with the concentration of methacrolein in the copolymer. The experimental data are in agreement with the statistical theory on the sequence length distribution. The shift of the styrene band at 540 cm^?1 to higher wavenumber was investigated and related to the shortening of sequence length of the styrene units. The intensity of the styrene band at 760 cm^?1 was related with the distribution of the MSM triads and the copolymer structure.     

Synectin/syndecan-4 regulate coronary arteriolar growth during development.

Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin.     

The effect of elevated intracranial pressure on the vibrational response of the ovine head

Although potentially fatal increases in intracranial pressure (ICP) can occur in a number of pathological conditions, there is no reliable and noninvasive procedure to detect ICP elevation and quantitatively monitor changes over time. In this experimental study, the relationships between ICP elevation and the vibrational response of the head were determined. An ovine animal model was employed in which incremental increases in ICP were elicited and directly measured through intraventricular cannulae. At each ICP increment, a vibration source elicited a flexural response of the animal's head that was measured at four locations on the skull using accelerometers. Spectral analysis of the responses showed changes in proportion to ICP change up to roughly 20 cm H₂O (15 mm Hg) above normal; a clinically significant range. Both magnitude and phase changes at frequencies between 4 and 7 kHz correlated well (γ>0.92) with ICP across the study group. These findings suggest that the vibrational response of the head can be used to monitor changes in ICP noninvasively.     

Phantoms for texture analysis of MR images. Long-term and multi-center study

The application of texture analysis (TA) in magnetic resonance imaging (MRI) requires the availability of texture phantoms for use in the standardization of in vivo measurements. The aims of our study were (a) to develop a new type of phantoms suitable for MRI and TA and test their long-term stability; (b) to optimize the choice of texture parameters describing the phantoms; (c) to compare different MR imagers according to texture parameters in a multi-center study. A long-term study performed at 4.7 T proved that the developed phantom based on polystyrene spheres and an agar gel solution is stable at least 12 months. This phantom, with nodular patterns, was found useful for the modeling of structural differences. The comparison of TA parameters at 4.7 and 7 T proved that the same parameters can be used for the separation of structures. The proposed algorithm of the selection of TA parameters shows that there exists a part of texture parameters which can be measured with high reproducibility (1-3%); on the other hand, their absolute values can differ by more than 30% if the textures differ. Results obtained from the multi-center study of whole body MR imagers show the wide variation in the misclassification rates at the different sites and point out the importance of the set up of MR sequences.     

Production and Characterization of Generic Antibodies Against s-Triazine and Sulfonylurea Herbicides

Two different hapten designs have been suggested for production of generic antibodies. The first approach was based on the immunogen prepared by conjugating simazine mimic to carrier proteins through the Cl position of the s-triazine herbicide. For sulfonylurea herbicides a single ring hapten strategy was designed in order to produce antibodies with dominant selectivity towards arylsulfonyl or triazine moieties of metsulfuron-methyl. The best monoclonal antibody raised against simazine-derived hapten mimic (clone B10/B8/D2) exhibited in direct ELISA a broad pattern for a group of methylthio and methoxy s-triazines. Cross-reactivities based on simazine ( = 100%) were 417, 125, 25, 50, 28, 42 and 11% for simetryn, ametryn, prometryn, terbutryn, aziprotryn, atraton and atrazine, respectively. The superiour generic pattern was found for monoclonal antibody raised against s-triazine moiety of metsulfuron-methyl herbicide (clone 2C8/C8). This antibody showed in indirect ELISA the cross-reactivity values 100, 142, 95, 60, 40, 167, 83 and 21% for metsulfuronmethyl, cinosulfuron, triasulfuron, primisulfuron-methyl, thifensulfuron-methyl, chlorsulfuron and prosulfuron and tribenuron-methyl, respectively. The assays using both monoclonal and polyclonal antibodies operated within the ppt-ppb calibration ranges.