Biomedical subjects
Publications and source records attributed to D N Robinson.
We present case reports of five patients with severe forms of mucopolysaccharidoses who developed postobstructive pulmonary oedema during anaesthesia. The difficulties of anaesthesia in these patients and the particular predisposition that these patients exhibit for the development of postobstructive pulmonary oedema is discussed.
Nanospheres of poly(methacrylic acid-grafted-poly(ethylene glycol)) were prepared by solution/precipitation polymerization. As colloidal drug delivery carriers, they present unique properties that render them promising candidates for oral protein delivery. The polymerization was carried out in water and the resulting suspension was freeze-dried. As with many colloidal systems, the freeze-dried suspension showed strong agglomeration after drying. The effects of preparation conditions on the particle size and redispersion were investigated using photon correlation spectroscopy. Furthermore, the ability of different types and concentrations of stabilizers (cryoprotectants and steric stabilizers) in preventing this phenomenon was addressed. Pluronics, block copolymers widely used as nonionic surfactants, were the most effective in stabilizing the particles during the freeze-drying process. Pluronic P123, however, increased significantly the particle size of the nanospheres. On the other hand, lyophilizates obtained in the presence of Pluronic F68 had good redispersion properties and no change in particle size was observed.
Technical advances are providing new insights into the mechanical properties of cells. Now, by combining genetic and biochemical studies with high-resolution mechanical measurements from atomic force microscopy, the biochemical bases of mechanical processes such as cytokinesis should be discernible.
Sigmund Koch's legacy is not merely a record of robust criticism aimed at (now mostly failed) dominant perspectives in psychology. Rather, his prescient and tutored thought captured particular habits of mind and institutionalized modes of inquiry likely to retard progress in psychology indefinitely. In important respects, it is Koch's critical assessments of his own earlier commitments and enthusiasms that exemplify his project for any "scientific" psychology worth having. It is in these self-criticisms that Koch discloses both the source and the costs of trimming and reducing reality merely to prosecute research of the approved type. Furthermore, it is in these self-criticisms that Koch exemplifies the integrity and disinterested judiciousness so characteristic of science at its best.
We have developed a system for performing interaction genetics in Dictyostelium discoideum that uses a cDNA library complementation/multicopy suppression strategy. Chemically mutagenized cells were screened for cytokinesis-deficient mutants and one mutant was subjected to library complementation. Isolates of four different genes were recovered as modifiers of this strain's cytokinesis defect. These include the cleavage furrow protein cortexillin I, a novel protein we named dynacortin, an ezrin-radixin-moesin-family protein, and coronin. The cortexillin I locus and transcript were found to be disrupted in the strain, identifying it as the affected gene. Dynacortin is localized partly to the cell cortex and becomes enriched in protrusive regions, a localization pattern that is similar to coronin and partly dependent on RacE. During cytokinesis, dynacortin is found in the cortex and is somewhat enriched at the poles. Furthermore, it appears to be reduced in the cleavage furrow. The genetic interactions and the cellular distributions of the proteins suggest a hypothesis for cytokinesis in which the contraction of the medial ring is a function of spatially restricted cortexillin I and myosin II and globally distributed dynacortin, coronin, and RacE.
In this review, we focus on recent discoveries regarding the molecular basis of cleavage furrow positioning and contractile ring assembly and contraction during cytokinesis. However, some of these mechanisms might have different degrees of importance in different organisms. This synthesis attempts to uncover common themes and to reveal potential relationships that might contribute to the biochemical and mechanical aspects of cytokinesis. Because the information about cytokinesis is still fairly rudimentary, our goal is not to present a definitive model but to present testable hypotheses that might lead to a better mechanistic understanding of the process.
The anatomy of the caudal (sacral extradural) space was studied in 41 children, using magnetic resonance imaging. The distance from the upper margin of the sacrococcygeal membrane to the dural sac, the length of the membrane and the maximum depth of the caudal space were each measured. Age, height, weight and body surface area were recorded and, using multiple linear regression (stepwise technique), equations predicting the length of the membrane and the distance between its upper margin and the lower limit of the dural sac were obtained. Wide variability limits the clinical usefulness of these equations. In all patients, the maximum depth of the caudal space was found to be at the upper margin of the sacrococcygeal membrane. No correlation was found between this maximum depth and the age, height, weight or body surface area of the child.
The philosophy of psychology at the turn of the century was an amalgam of perspectives and commitments--experimental science, Darwinian theory, positivism--forged partly out of achievements in experimental science and partly in response to transcendentalist (Hegelian) challenges. The amalgam itself appeared as an early version of the positivism that became developed and dominant early in the 20th century. For many psychologists at the turn of the century, experimental science, as practiced chiefly in physics and chemistry, was tantamount to a philosophy of science and one stripped of what were taken to be distracting and useless metaphysical quibbles. The assets and liabilities of this allegiance were recognized even as it was forming.
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Forty healthy children, aged between two and 12 years of age undergoing elective surgery where the anaesthetic technique involved tracheal intubation followed by spontaneous ventilation were studied. Induction of anaesthesia was with either alfentanil 15 micrograms.kg-1 or remifentanil 1 microgram.kg-1 followed by propofol 4 mg.kg-1 to which lignocaine 0.2 mg.kg-1 had been added. Intubating conditions were graded on a four point scale for ease of laryngoscopy, vocal cord position, degree of coughing, jaw relaxation and limb movement. All children were successfully intubated at the first attempt. There were no significant differences in the assessments of intubating conditions between the two groups. Arterial blood pressure and heart changes were similar in the two groups with both alfentanil and remifentanil attenuating the haemodynamic response to tracheal intubation. The time taken to resumption of spontaneous ventilation was similar in both groups.
We have studied 40 infants with a post-conceptual age of less than 60 weeks undergoing general anaesthesia for herniotomy. Patients were anaesthetized with 1 MAC equivalent values for age and agent and allocated randomly to receive halothane, savoflurane or thiopental for induction, and halothane, sevoflurane or desflurane for maintenance of anaesthesia. At induction, both time to acceptance of a face mask and loss of eyelash reflex were recorded. Emergence times were noted by a blinded observer. Induction and emergence times were similar between the halothane and sevoflurane groups but were consistently shorter in the desflurane group compared with the halothane or sevoflurane groups. There were no problems at extubation or significant apnoea in any group. Induction of anaesthesia in this population was no quicker with sevoflurane than with halothane and the method used for induction did not influence recovery time. Maintenance of anaesthesia with desflurane resulted in a shorter recovery time in infants in whom anaesthesia was induced with halothane or thiopental. Desflurane maintenance may be particularly beneficial in the neonate.
Drosophila kelch has four protein domains, two of which are found in kelch-family proteins and in numerous nonkelch proteins. In Drosophila, kelch is required to maintain ring canal organization during oogenesis. We have performed a structure-function analysis to study the function of Drosophila kelch. The amino-terminal region (NTR) regulates the timing of kelch localization to the ring canals. Without the NTR, the protein localizes precociously and destabilizes the ring canals and the germ cell membranes, leading to dominant sterility. The amino half of the protein including the BTB domain mediates dimerization. Oligomerization through the amino half of kelch might allow cross-linking of ring canal actin filaments, organizing the inner rim cytoskeleton. The kelch repeat domain is necessary and sufficient for ring canal localization and likely mediates an additional interaction, possibly with actin.
In Drosophila oogenesis, the development of a mature oocyte depends on having properly developed ring canals that allow cytoplasm transport from the nurse cells to the oocyte. Ring canal assembly is a step-wise process that transforms an arrested cleavage furrow into a stable intercellular bridge by the addition of several proteins. Here we describe a new gene wc named cheerio that provides a critical function for ring canal assembly. Mutants in cheerio fail to localize ring canal inner rim proteins including filamentous actin, the ring canal-associated products from the hu-li tai shao (hts) gene, and kelch. Since hts and kelch are present but unlocalized in cheerio mutant cells, cheerio is likely to function upstream from each of them. Examination of mutants in cheerio places it in the pathway of ring canal assembly between cleavage furrow arrest and localization of hts and actin filaments. Furthermore, this mutant reveals that the inner rim cytoskeleton is required for expansion of the ring canal opening and for plasma membrane stabilization.
The Drosophila ovary provides a favorable model system in which to study cellular morphogenesis. The development of a mature egg involves a syncytium of 16 germline cells and over 1000 somatically derived follicle cells. Intercellular transport, stable intercellular bridges, cell migrations, cell shape changes, and specific subcellular localization of many embryonic patterning determinants contribute to egg development and require a dynamic cytoskeleton. We discuss many of the recent genetic and cell biological studies that have led to insights into how the actin cytoskeleton is assembled and regulated during the morphogenesis of the Drosophila egg.
The Drosophila kelch gene produces a single transcript with a UGA stop codon separating two open reading frames (ORF1 and ORF2). From the transcript, 76 kDa ORF1 and 160 kDa full-length (ORF1 + ORF2) proteins are made. The expression of these two proteins is regulated in a tissue-specific manner causing the ratio of full-length to ORF1 protein to vary in different tissues. The only detected defect for kelch mutants is female sterility, and kelch protein is localized to the ovarian ring canals. kelch mutant ring canals are disorganized and have partly occluded lumens, causing a failure to transport cytoplasm. ORF1 and full-length kelch proteins co-sediment with ring canals suggesting that both proteins are found in the ring canals. Transgenetic analysis reveals that ORF1 kelch protein is sufficient to rescue ring canal morphology and fertility. In addition, we have mutated the UGA stop codon to a UAA stop codon and to three sense codons that allow constitutive readthrough. Analysis of these mutants reveals that a full-length kelch protein can partially compensate for the loss of endogenous kelch, but the residue included at the stop codon is critical for function. Finally, these studies suggest that the mechanism of stop codon suppression of kelch is by tRNA suppression.
A wide variety of intercellular junctions that are involved with cell adhesion or signal transduction have been described in recent years. A widespread but less well-characterized type of intercellular junction is the stable intercellular bridge. Several organisms use stable intercellular bridges as cytoplasmic connections, probably to allow rapid transfer of information and organelles between cells. Here, the authors take a detailed look at the assembly of intercellular bridges called ring canals in the Drosophila germline and discuss how examination of mutants that disrupt Drosophila ovarian ring canal assembly indicates that these bridges are required for intercellular transport of cytoplasm.
We analyzed the structure of cytoplasmic bridges called ring canals in Drosophila egg chambers. Two mutations, hu-li tai shao (hts) and kelch, disrupt normal ring canal development. We raised antibodies against the carboxy-terminal tail of hts and found that they recognize a protein that localizes specifically to ring canals very early in ring canal assembly. Accumulation of filamentous actin on ring canals coincides with the appearance of the hts protein. kelch, which is localized to the ring canals hours after hts and actin, is necessary for maintaining a highly ordered ring canal rim since kelch mutant egg chambers have ring canals that are obstructed by disordered actin and hts. Anti-phosphotyrosine antibodies immunostain ring canals beginning early in the germarium before hts and actin and throughout egg chamber development. The use of antibody reagents to analyze the structure of wild-type and mutant ring canals has shown that ring canal development is a dynamic process of cytoskeletal protein assembly, possibly regulated by tyrosine phosphorylation of some ring canal components.