Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139-169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.     

Training for general practice: a national survey.

OBJECTIVES--(a) To compare current vocational training in general practice with that ascertained by a survey in 1980; (b) to compare the training of trainees in formal training schemes with that of trainees arranging their own hospital and general practice posts. DESIGN--National questionnaire survey of United Kingdom and armed services trainees who were in a training practice on 1 April 1989. Questionnaires were distributed by course organisers. SETTING--Research project set up after an ad hoc meeting of trainees at the 1988 national trainee conference. SUBJECTS--2132 Of the 2281 trainees (93%) known to be in a training practice on 1 April 1989. RESULTS--1657 Trainees returned the questionnaires, representing 73% of all trainees known to be in a training practice on 1 April 1989. Between 1980 and 1989 there were significant improvements in the trainee year, and there was also evidence of improvements in general practice study release courses. There was no evidence of improvement in other aspects of training. General practice trainees spent an average of three years in junior hospital posts, which provided very little opportunity for study related to general practice. Training received during tenure of hospital posts differed significantly between trainees in formal schemes and those arranging their own hospital posts. During the trainee year training was almost the same for those in formal schemes and those arranging their own posts. Regions varied significantly in virtually all aspects of general practice training. CONCLUSIONS--The trainee year could be improved further by enforcing the guidelines of the Joint Committee on Postgraduate Training for General Practice. The poor training in junior hospital posts reflected the low priority that training is generally given during tenure of these posts. A higher proportion of general practice trainees should be attached to vocational training schemes. More hospital trainees could attend general practice study release courses if these were designed specifically with the needs of hospital doctors in mind.     

Potency of L-364,718 as an antagonist of the behavioral effects of peripherally administered cholecystokinin

A new antagonist of the peripheral cholecystokinin receptor, L-364,718, was found to block the reductions in food intake and exploratory activity induced by intraperitoneal administration of cholecystokinin octapeptide sulfate. L-364,718 significantly reversed the cholecystokinin-induced reduction in feeding at doses of 10 micrograms/kg - 10 mg/kg i.p. L-364,718 significantly reversed the cholecystokinin-induced reduction in exploratory activity at doses of 500 ng/kg - 10 mg/kg i.p. The time course of antagonist activity of L-364,718 was immediate to 90 minutes after intraperitoneal administration. L-364,718 had no significant effect on food intake or exploratory activity when administered alone, over the dose range of 100 ng/kg-10 mg/kg i.p. This compound appears to be at least one hundred times more potent than proglumide or benzotript as an antagonist of the behavioral effects of peripherally administered cholecystokinin.     

UK-73,093: A non-peptide neurotensin receptor antagonist

UK-73,093 was identified in a screening program as a compound able to displace [³H]-neurotensin from its bovine brain receptor. We describe the discovery of this compound, species differences in receptor affinity and its characterization as a functional neurotensin antogonist in vitro and in vivo.     

Some population dynamics of the Bank vole, Clethrionomys glareolus and the Wood mouse, Apodemus sylvaticus in mixed woodland

The population dynamics of Clethrionomys glareolus Schr.and Apodemus sylvaticus (L.) in mixed woodland in County Durham, were studied from March 1963 to January 1965. Two areas of 0.9 ha (2.25 acres) each were trapped monthly and information was obtained on population size, reproduction, survival and growth from marked animals.
Clethrionomys populations increased from June to an autumn peak; then declined, at first rapidly, but then more slowly in winter, before reaching a spring trough. The breeding season of Clethrionomys was from May to December; juveniles were caught from mid-June to December. Survival was in general poor during the breeding season but good at other times. Survival of young born early in the summer was particularly good on one of the areas and some individuals lived long enough to breed in two successive years. On both areas young born early in the year matured rapidly and bred in the year of their birth. Young born in late summer and early autumn ceased growing at a weight of about 14.5 g, remained immature, and formed the bulk of the overwintering population. Growth was completed at the time of sexual maturation the following spring.
Trapping failed to provide adequate samples of juvenile Apodemus in summer to account for subsequent recruitment. The possibility that a substantial proportion of the adult population of this species was also either trap shy or had emigrated temporarily is discussed. Breeding occurred from April until the following January, but the numbers trapped remained very low throughout the early months of the breeding season. Large scale recruitment of young fecund animals into the trap-revealed population occurred during the autumn. Apodemus males continued to grow rapidly during the winter.     

Pathogenesis of Lethal Shock After Intravenous Staphylococcal Enterotoxin B in Monkeys

The pathogenesis of shock in the rhesus monkey given intravenous staphylococcal enterotoxin B (SEB) is not understood. Several cardiovascular changes produced by a highly purified preparation of SEB were studied after administration of doses ranging from 50 to 1,000 mug/kg. Irreversible arterial hypotension was found consistently at the higher doses. Arterial blood pressure and cardiac output declined substantially as shock developed. Total peripheral vascular resistance did not rise at any time, but showed a significant fall during the late stages of shock. Portal and central venous pressures remained essentially unchanged. Venous O(2) content and pO(2) declined gradually throughout the period of toxemia, but arterial O(2) content remained constant until just prior to death, when a slight fall was noted in some monkeys. These changes were consistent with a pooling of blood in the peripheral vascular beds and seemed to resemble cardiovascular responses reported to occur in monkeys during shock due to bacterial endotoxin. Epinephrine, administered in the late stages of shock, caused arterial pressure to increase almost immediately and cardiac output to return to normal about 1 min later. Although life could occasionally be prolonged for several hours by continuous or intermittent epinephrine infusions, this therapy never succeeded in reversing the lethal effects of high doses of SEB.     

Ig VH gene family repertoire of plasma cells derived from lupus-prone MRL/lpr and MRL/++ mice

VH gene family usage was determined in both spontaneous, in vivo activated plasma cells and LPS-induced plasma cells from individual MRL/lpr mice by using in situ hybridization. It was found that VH gene family expression in spontaneous plasma cells varied from mouse to mouse. Some mice expressed VH families in an apparently random manner similar to that obtained with polyclonal activation. Other mice showed an exaggerated expression of particular VH gene families. VH J558 was overrepresented most frequently, but overrepresentation of VH 7183, Q52, and 36-60 was also observed. Importantly, LPS-induced VH gene family expression in these same mice displaying biased VH family usage in spontaneous plasma cells, appeared normal with no evidence for similar biases in the LPS-induced repertoire. Anti-DNA antibody concentrations and the degree of glomerulonephritis were determined for each mouse to measure the severity of disease. The level of expression of the J558 family was positively correlated with disease severity. The results suggest that the initial autoantibody response is highly diverse but becomes more restricted as the disease progresses.     

Le Fort fractures without mobility

The Le Fort fracture without maxillary mobility constitutes 9 percent of maxillary fractures observed over a 3-year period. A high Le Fort (level II or III) injury exists as a one- or two-piece incomplete fracture. The degree of fracture is insufficient to permit mobility of the maxillary alveolus. Frequently, an obvious unilateral zygomatic fracture is present. Physical findings consist of bilateral eyelid ecchymosis and malocclusion. The occlusal disturbance may consist of either crossbite, open bite, maxillary rotation, or lack of proper dental intercuspation. On CT scan, fractures are best demonstrated in the posterior and medial maxillary walls at the Le Fort I level; they are most obvious unilaterally with contralateral fractures that may be subtle. Bilateral maxillary sinus fluid is consistently present on CT. Treatment usually consists of observation and traction elastics but may require mobilization of the fragments followed by open reduction and rigid fixation.     

Phylogeny of Greya (Lepidoptera: Prodoxidae), based on nucleotide sequence variation in mitochondrial cytochrome oxidase I and II: congruence with morphological data

The phylogeny of Greya Busck (Lepidoptera: Prodoxidae) was inferred from nucleotide sequence variation across a 765-bp region in the cytochrome oxidase I and II genes of the mitochondrial genome. Most parsimonious relationships of 25 haplotypes from 16 Greya species and two outgroup genera (Tetragma and Prodoxus) showed substantial congruence with the species relationships indicated by morphological variation. Differences between mitochondrial and morphological trees were found primarily in the positions of two species, G. variabilis and G. pectinifera, and in the branching order of the three major species groups in the genus. Conflicts between the data sets were examined by comparing levels of homoplasy in characters supporting alternative hypotheses. The phylogeny of Greya species suggests that host-plant association at the family level and larval feeding mode are conservative characters. Transition/transversion ratios estimated by reconstruction of nucleotide substitutions on the phylogeny had a range of 2.0-9.3, when different subsets of the phylogeny were used. The decline of this ratio with the increase in maximum sequence divergence among taxa indicates that transitions are masked by transversions along deeper internodes or long branches of the phylogeny. Among transitions, substitutions of A-->G and T-->C outnumbered their reciprocal substitutions by 2-6 times, presumably because of the approximately 4:1 (77%) A+T-bias in nucleotide base composition. Of all transversions, 73%-80% were A<-->T substitutions, 85% of which occurred at third positions of codons; these estimates did not decrease with an increase in maximum sequence divergence of taxa included in the analysis. The high frequency of A<-->T substitutions is either a reflection or an explanation of the 92% A+T bias at third codon positions.