Evaluation of the antireflux mechanism following laparoscopic fundoplication

BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastro-oesophageal reflux disease (GORD), but the underlying motility mechanisms that explain the success of this operation remain unclear. METHODS: Twenty patients with a history of GORD underwent stationary oesophageal manometry and prolonged ambulatory pH monitoring, both before and 3 months after fundoplication. RESULTS: Eighteen patients were completely cured of reflux symptoms and stopped all antireflux medication after operation. After fundoplication there was a significant increase (P < 0.01) in median resting lower oesophageal sphincter (LOS) pressure and length. Median residual LOS pressure during swallow-induced LOS relaxation also increased significantly after operation (P < 0.01). The number of reflux episodes decreased from a median of 48 to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from 5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months following laparoscopic antireflux surgery show improved symptoms. One of the mechanisms underlying the antireflux action of fundoplication is an increase in median residual LOS pressure at the gastro-oesophageal junction. This may be a purely mechanical effect of the fundic wrap extrinsic to the LOS.     

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.     

Prenatal diagnosis of partial monosomy 13q associated with occipital encephalocoele in a fetus

The pre- and postnatal findings of a fetus with a de novo del(13)(pter-->q21:) and an occipital encephalocoele are described. Maternal serum alpha-fetoprotein (AFP) screening at 19 weeks' gestation demonstrated a high level of 2.5 multiples of the median (MOM) and ultrasonography at 27 weeks' gestation showed severe intrauterine growth retardation, cardiomegaly, an occipital encephalocoele, and a calvarial defect. Genetic amniocentesis revealed a karyotype of 46,XX,del(13)(pter-->q21:). The proband postnatally displayed additional abnormalities such as microphthalmia, hypertelorism, large low-set ears, and micrognathia. We discuss the association of central nervous system (CNS) malformations with 13q deletions and emphasize that pregnancies with neural tube defects warrant cytogenetic analysis, especially when additional fetal abnormalities and neonatal dysmorphism are observed.     

Prediction of thermal expansion coefficients of plain weave fabric composites

Three plain weave fabric composite analysis models are presented for the prediction of the on-axes thermal expansion coefficients. These are two-dimensional models in the sense that the actual strand cross-sectional geometry, strand undulation and the presence of a gap between the adjacent strands are taken into account. In the first two models, termed refined models, the representative unit cell is discretised into slices and elements and analysed. In the third method, a closed-form solution is presented. In this case, the representative unit cell is idealised as a crossply laminate and analysed. The relative merits and demerits of the models are also discussed. The predicted results are compared with the experimental values. A good correlation is observed.     

Increased synthetic peptide specificity of tissue-CSF bound anti-MBP in multiple sclerosis

Free and bound hydrosoluble protein extracts were prepared from four anatomical areas of a multiple sclerosis (MS) cerebrum and from corresponding anatomical areas of a normal (non-MS) control. Increased levels of IgG and anti-myelin basic protein antibodies (anti-MBP) were detected in all MS samples and they were undetectable in the controls. IgG and anti-MBP from free (unbound) hydrosoluble protein extracts are defined as free IgG and free anti-MBP while IgG and anti-MBP from tissue bound protein extracts are defined as bound IgG and bound anti-MBP. IgG was purified from free protein extracts by protein G Sepharose affinity chromatography and anti-MBP was further isolated from purified IgG by antigen specific (MBP) Sepharose affinity chromatography. Free and bound anti-MBP were reacted with 20 synthetic peptides of human MBP prepared by the Fmoc method. Free anti-MBP, whether in the context of whole protein extracts, or as purified IgG or as purified antibody was completely neutralized by peptides #12, #15, #56 and #56* containing overall residues 75-106, partially neutralized by peptides #27, #16 and #21 containing overall residues 61-83 and did not react with the remaining 13 peptides. Tissue bound anti-MBP was completely neutralized only by peptides #12, #15, #56 and #56* (overall residues 75-106) and showed no reactivity towards the remaining 16 peptides including peptides #27, #16 and #21. Synthetic peptide specificity of free anti-MBP purified from MS cerebrum was identical to previously reported specificity of free anti-MBP from MS cerebrospinal fluid (CSF), while tissue bound anti-MBP, as well as bound anti-MBP from CSF had a more restricted synthetic peptide specificity than free anti-MBP. This suggests that the most likely epitope of anti-MBP is located between residues 84 and 95 of human MBP just proximal to the tri-proline sequence (99-101).     

Resurgence of derived stimulus relations

Resurgence has been shown in human and nonhuman operant behavior, but not in derived relational responses. The present study examined this issue. Twenty-three undergraduates were trained to make conditional discriminations in a three-choice matching-to-sample paradigm. The training resulted in three equivalence classes, each consisting of four arbitrarily configured visual stimuli. The same 12 stimuli were then reorganized, and the conditional discrimination training was repeated such that three new classes were possible. In a subsequent test of derived relations, most subjects showed response patterns that were consistent with the altered conditional discriminations. Subjects were then exposed to conditional discrimination trials under extinction. Most subjects continued to respond consistently with the most recently reinforced conditional discrimination trials. During the next phase, subjects were exposed to symmetry and equivalence trials. Responses consistent with the most recent training produced feedback saying that the responses were incorrect, whereas other responses produced no feedback. Most subjects showed a resurgence of responding that was consistent with their earlier training. Finally, subjects were exposed to conditional discrimination trials carried out in extinction. Most subjects continued to show a resurgence of responding that was consistent with their early training.     

Ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: toward metabolic sink therapy for gyrate atrophy

There is now strong evidence that the chorioretinal degeneration associated with ornithine-delta-aminotransferase (OAT) deficiency is a consequence of hyperornithinemia. Therefore development of a metabolic system for clearing ornithine from the circulation is being pursued as a potential treatment. The skin is considered an attractive location for such a metabolic system because autologous cells can be safely and easily utilized. This study was undertaken to determine the ornithine metabolizing capacity of epidermal keratinocytes expressing normal and superphysiologic amounts of OAT. The data show that overexpression of OAT in keratinocytes cultured from a gyrate atrophy patient restores ornithine metabolism and results in a rate of ornithine disappearance from the medium that is significantly higher than the rate of disappearance from the medium bathing normal keratinocytes. In addition, OAT activity determined in soluble protein prepared from sonicates suggests that the capacity to maintain plasma ornithine within the normal range is contained within an accomplishable graft of keratinocytes overexpressing OAT. However, the actual rate of ornithine disappearance from the media was significantly less than predicted from enzyme activity assays. Following ornithine metabolite production by intact cells suggests that ornithine metabolism is limited primarily by clearance of downstream metabolites, as opposed to substrate delivery.     

Efficient computation of unique input/output sequences in finitestate machines

This paper makes two contributions toward computing unique input/output (UIO) sequences in finite-state machines. Our first contribution is to compute all UIO sequences of minimal lengths in a finite-state machine. Our second contribution is to present a generally efficient algorithm to compute a UIO sequence for each state, if it exists. We begin by defining a path vector, vector perturbation, and UIO tree. The perturbation process allows us to construct the complete UIO tree for a machine. Each sequence of input/output from the initial vector of a UIO tree to a singleton vector represents a UIO sequence. Next, we define the idea of an inference rule that allows us to infer UIO sequences of a number of states from the UIO sequence of some state. That is, for a large class of machines, it is possible to compute UIO sequences for all possible states from a small set of initial UIOs. We give a modified depth-first algorithm, called the hybrid approach, that computes a partial UIO tree, called an essential subtree, from which UIO sequences of all possible states can be inferred. Using the concept of projection machines, we show that sometimes it is unnecessary to construct even a partial subtree. We prove that if a machine remains strongly connected after deleting all the converging transitions, then all of the states have UIO sequences. To demonstrate the effectiveness of our approach, we develop a tool to perform experiments using both small and large machines     

mRNA for cardiac calcium channel is expressed during development of skeletal muscle

During the early development of skeletal muscle, cardiac isotypes of several contractile proteins are known to be transiently expressed. We report here that skeletal muscle developing in vivo, as well as primary cultures derived from skeletal muscle, express mRNA encoding the cardiac dihydropyridine-sensitive calcium channel. The mRNA is detectable at high concentration at the earliest stage tested in vivo and diminishes rapidly in concentration as myofibers mature. The concentration of the cardiac calcium channel mRNA also diminishes during the in vivo development of skeletal muscle in a genetically paralyzed mouse (mdg), indicating that muscle contractile activity is not necessary for the down-regulation. In contrast, mRNA for the skeletal muscle-specific calcium channel accumulates gradually in developing skeletal muscle. A similar temporal pattern of expression is also seen in primary cultures of skeletal myotubes. These results raise the question of whether the cardiac calcium channel may be functionally important during the early development of skeletal myofibers.