Retrograde degeneration of thalamic neurons in the mediodorsal nucleus after neonatal and adult aspiration lesions of the medial prefrontal cortex in the rat. Implications for mechanisms of functional recovery

The behavioural consequences of neonatal lesions of the frontal cortex are limited as compared with similar lesions performed in adulthood. The present study has investigated, using unbiased quantitative methods with randomized systematic sampling, the total neuronal cell numbers in the mediodorsal nucleus of the thalamus after aspiration lesions of the medial prefrontal cortex performed in neonatal and in adult rats. It was found that the reduction in total cell numbers after neonatal prefrontal cortex lesions was similar to that found after adult cortex lesions. In neonatally lesioned animals the neuronal cell density was significantly increased by 13%, whereas in adult lesioned animals it was unchanged. On the other hand, the volume of the mediodorsal nucleus was reduced by 27% in neonatally, and 20% in adult lesioned animals. Total neuronal cell number of the mediodorsal nucleus was significantly decreased in neonatally as well as in adult lesioned rats, by 14% and 21%, respectively. These findings are discussed in the light of the previously proposed role of the thalamus as a neural substrate of functional sparing after neonatal cortical lesions.     

Issues in the design and interpretation of studies to evaluate the impact of community-based interventions

Increasingly, epidemiologists are faced with the need to evaluate the impact of an intervention that is delivered at the level of a community or cluster of individuals, rather than at the individual level. This has profound implications for the design and interpretation of a study to evaluate its impact. We start by discussing the issues arising in the extension of the randomized double-blind controlled trial methodology to the evaluation of interventions delivered to clusters of individuals, or to whole communities, where the unit of randomization is a cluster of individuals rather than an individual. We then consider alternative approaches to design, discuss their relative strengths and weaknesses and present a framework of design options. Finally we propose a pragmatic approach to evaluation design in this setting. We believe that the answer lies in the judicious selection of different design elements, combined in such a way that when the evidence from each is presented together, a clear picture of the impact of the intervention emerges. We illustrate this using an example from the recent literature.     

The Chlamydomonas reinhardtii ODA3 gene encodes a protein of the outer dynein arm docking complex

We have used an insertional mutagenesis/ gene tagging technique to generate new Chlamydomonas reinhardtii mutants that are defective in assembly of the uter ynein rm. Among 39 insertional oda mutants characterized, two are alleles of the previously uncloned ODA3 gene, one is an allele of the uncloned ODA10 gene, and one represents a novel ODA gene (termed ODA12). ODA3 is of particular interest because it is essential for assembly of both the outer dynein arm and the outer dynein arm docking complex (ODA-DC) onto flagellar doublet microtubules (Takada, S., and R. Kamiya. 1994. J. Cell Biol. 126:737- 745). Beginning with the inserted DNA as a tag, the ODA3 gene and a full-length cDNA were cloned. The cloned gene rescues the phenotype of oda3 mutants. The cDNA sequence predicts a novel 83. 4-kD protein with extensive coiled-coil domains. The ODA-DC contains three polypeptides; direct amino acid sequencing indicates that the largest of these polypeptides corresponds to ODA3. This protein is likely to have an important role in the precise positioning of the outer dynein arms on the flagellar axoneme.     

Results of the double stapling procedure in colorectal surgery

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprung's disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprung's disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprung's disease.     

Significance of a false-positive trisomy 18 multiple-marker screening test

We report our results in 24 children with malignant primary bone tumours of the distal femur treated with a Stanmore extendible endoprosthesis (SEER). This consists of a femoral component that can be lengthened, a constrained knee and an uncemented sliding tibial component which crosses the proximal tibial physeal plate perpendicularly. The average age of the patients at diagnosis was ten years and the mean follow-up was 4.7 years (2.5 to 7.9). The mean growth of the affected tibia was 76% (18 to 136) and of the fibula 83% (15 to 750) of the growth of the unaffected limb. Measurement of growth arrest lines showed that the mean growth of the proximal tibial physis on the affected side was 69% (43 to 100) of that of the normal side. The great variability in the growth of the physis cannot yet be explained.     

Dealing with difficult students in the classroom

Experiments on rat males (120-150 g b.weight) inhaling air with oxygen concentration 16, 14, 12, 10, 8 and 5.3% for an hour and placed at the altitudes 2000, 3500 and 3200 in above the sea level in the mountains demonstrated that adrenaline and noradrenaline concentrations in the brain tissues, adrenals, blood and urine depend on the intensity and duration of the exposure to low pO2 in the air. Adaptation to hypoxia provokes a significant increase of noradrenaline in the adrenals, cerebral cortex, hypothalamus and biological fluids.     

In vitro maintenance of Schistosoma japonicum and surgical transfer from donor to na?ve recipient pigs

The insulin receptor (IR) is a membrane-bound glycoprotein composed of alpha and beta subunits derived from a common precursor. This processing is observed for both subtypes A and B of the IR and its physiological importance is poorly understood. In order to investigate the functional consequences of the absence of IR precursor cleavage, using site-directed mutagenesis of the hIRB cDNA, we have produced two mutants replacing the sequence Arg-Lys-Arg-Arg by either His-Lys-His-Arg or Arg-Lys-Arg-Ser. These two mutants, stably expressed in CHO, were structurally and functionally characterized in comparison to the wild-type human IR. These mutations result in the production of uncleaved receptors which are expressed normally at the cell surface. These receptors bind insulin with a normal affinity and activate the tyrosine-kinase resulting in normal phosphorylation of the receptors. These uncleaved receptors can mediate both the metabolic and mitogenic effects of insulin. These results provide evidence for a fully functional uncleaved insulin receptor of the B subtype (exon 11 + ) in contrast to the uncleaved A subtype (exon 11 -) described in the literature, which shows a reduced affinity for insulin and cannot therefore correctly transduce the insulin signal.     

Assessment of accuracy of the Doppler pressure half-time method in the estimation of the mitral valve area immediately after balloon mitral valvuloplasty

AIM: The reliability of Doppler echocardiography in determining the mitral valve area after balloon mitral valvuloplasty has been questioned, as discrepancies were noted between measurements obtained by the pressure half-time method and those derived haemodynamically, immediately following completion of the procedure. Recent investigations, however, have indicated that these discrepancies may be attributable to the over-estimation of the mitral valve area by haemodynamic measurements, caused by the presence of the iatrogenic atrial septal defect complicating transseptal catheterization. The aim of the present study was to further test this hypothesis. METHODS AND RESULTS: Measurements of the mitral valve area by the Doppler pressure half-time method and the Gorlin formula were obtained and compared in 238 consecutive patients before and immediately after retrograde non-transseptal balloon mitral valvuloplasty, which does not involve puncture and/or dilatation of the inter-atrial septum. No significant difference was found between Doppler- and Gorlin-derived measurements, neither before (1.04 +/- 0.23 vs 1.03 +/- 0.23 cm2, P = ns) nor immediately after (2.14 +/- 0.47 vs 2.12 +/- 0.49 cm2, P = ns) valvuloplasty. Linear regression analysis demonstrated a high degree of correlation between Doppler and Gorlin measurements before (r = 0.778) and after (r = 0.886) the procedure. Good agreement was confirmed by the Bland-Altman method. CONCLUSION: Doppler echocardiography yields accurate measurements of the mitral valve area immediately after retrograde non-transseptal balloon mitral valvuloplasty. This finding supports the hypothesis that the creation of an iatrogenic atrial septal defect during transseptal catheterization may contribute to the poor agreement between Doppler and Gorlin data after balloon mitral valvuloplasty.     

Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.