Conjoined twins: theoretical embryologic basis.

A theoretical basis for the embryology of conjoined twins was formulated from clinical experience with ten cases and extensive review of pertinent embryologic and clinical literature, including over 500 cases. Regarding the age old question of fusion or fission, it is concluded that there is no known embryologic process by which conjoined twins can be formed by fission but firm evidence to support fusion in all cases. Whether the fusion occurs between embryos on one embryonic disc or on two is of no consequence since they are all monovular. Intact ectoderm will not fuse to intact ectoderm, and all seven types of conjoined twins are explained by seven possible sites of union in the early embryo. One new term is proposed: parapagus, from the Greek para, meaning "side," combined with pagus, meaning "fixed"; this is the group formerly called dicephalus or diprosopos. These anterolaterally united parapagus twins must result from two nearly parallel notochords in close proximity; craniopagi and pygopagi from fusion at the cranial and caudal neuropores, respectively; cephalopagi and ischiopagi from union at the pharyngeal and cloacal membranes, respectively; thoracopagi from merging of the cardiac anlage; and omphalopagi from fusion of the umbilicus or of the edges of two embryonic discs in any area not including the above sites. Parasitic twins result from embryonic death of one twin, leaving various portions of the body vascularized by the surviving autosite. The rarity of cases (2) not easily explained by the above theories, and the nearly 6% of twins with two umbilical cords arising from the placenta would seem to support these conclusions. Should one wish to learn the methods of a conjurer, he might vainly watch the latter's customary repertoire, and, so long as everything went smoothly, might never obtain a clue to the mysterious performance, baffled by the precision of the manipulations and the complexity of the apparatus; if, however, a single error were made in any part or if a single deviation from the customary method should force the manipulator along an unaccustomed path, it would give the investigator an opportunity to obtain a part or the whole of the secret.(ABSTRACT TRUNCATED AT 400 WORDS)     

Conjoined hemoglobins. Loss of cooperativity and protein-protein interactions

Hemoglobin cross-linked as a bis(isophthalamide) of the epsilon-amino groups of lysine 82 of each beta-subunit binds and releases oxygen with a Hill coefficient indicative of cooperative oxygen binding (typically approximately 2.0). However, connecting two such cross-linked tetramers with a relatively short covalent linkage produces cross-linked bis-tetramers that bind oxygen with Hill coefficients near unity. To separate the effect of the linkages from the effects of protein-protein interactions in the conjoined proteins, reagents (1 and 2) were used to produce bis-tetramers (A and B). These have a considerably greater distance between cross-linked tetramers than earlier examples. Yet, the bis-tetramers (A and B) bind oxygen with minimal cooperativity (n(50) = 1.4, 1.2). To assess the effect of the linkage itself, cross-linked tetramers (Cand D) were prepared from reactions with the same reagents. These bind oxygen with cooperativity similar to that of cross-linked tetramers without the extended chain (C, n(50) = 2.0; D, n(50) = 1.8). Other tetramers (E and F) with flexible, saturated hydrocarbon appendages were also prepared. These also showed cooperativity in oxygen binding (E, n(50) = 1.7; F, n(50) = 1.8) despite their high degree of hydrophobicity. Thus, the intertetrameric linkages themselves do not induce the loss of cooperativity, leading to the conclusion that solution effects of the tetramers upon one another are the source of the decline in cooperativity: protein-protein interactions are most significant in disrupting the cooperativity of the bis-tetramers, regardless of the span or composition of the linker. This suggests that effects of oligomerization of hemoglobin within red cell substitutes should be considered in terms of such interactions.     

The Importance of Monitoring During Operations on Conjoined Twins

Besides complete and careful preoperative investigation of thoracopagus conjoined twins, monitoring of the various parameters, such as arterial blood pressure, central venous pressure, blood pH, and temperature, are most essential for accurate blood replacement, maintenance of normal body chemistry and thermoregulation. Equally important is continued monitoring in the postoperative period when assisted ventilation may be required as well.Twin “A” returned from the operating room in excellent condition, breathing spontaneously through an endotracheal tube. Twin “B” returned on positive-pressure-assisted ventilation; this was to prove a poor prognostic sign as this twin died eight hours postoperatively.     

Conjoined twins in a rhesus monkey (Macaca mulatta)

Conjoined twinning is an extremely rare occurrence among human and nonhuman primates. The current report describes a case of minimally conjoined omphalopagus rhesus monkey twins that were observed in the breeding colony at the California Regional Primate Research Center. The full-term nonviable male twins were morphologically normal and united in the umbilical region, involving the liver, xiphoid, umbilicus, body wall, and skin. The umbilical cords were separate, but closely aligned, within an ensheathing amnion; each cord contained two arteries and a vein. The closely associated cords were centrally inserted on a large bidiscoid placenta. There were no gross or histologic abnormalities in the viscera, with the exception of enlargement of the left central liver lobes, which constituted the area of attachment. The cause of death was attributed to asphyxia and trauma experienced during parturition.     

Conjoined Use of EM and NMR in RNA Structure Refinement

More than 40% of the RNA structures have been determined using nuclear magnetic resonance (NMR) technique. NMR mainly provides local structural information of protons and works most effectively on relatively small biomacromolecules. Hence structural characterization of large RNAs can be difficult for NMR alone. Electron microscopy (EM) provides global shape information of macromolecules at nanometer resolution, which should be complementary to NMR for RNA structure determination. Here we developed a new energy term in Xplor-NIH against the density map obtained by EM. We conjointly used NMR and map restraints for the structure refinement of three RNA systems — U2/U6 small-nuclear RNA, genome-packing motif (Ψ^CD)₂ from Moloney murine leukemia virus, and ribosome-binding element from turnip crinkle virus. In all three systems, we showed that the incorporation of a map restraint, either experimental or generated from known PDB structure, greatly improves structural precision and accuracy. Importantly, our method does not rely on an initial model assembled from RNA duplexes, and allows full torsional freedom for each nucleotide in the torsion angle simulated annealing refinement. As increasing number of macromolecules can be characterized by both NMR and EM, the marriage between the two techniques would enable better characterization of RNA three-dimensional structures.