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Biomedical subjects

D Jacobson

Publications and source records attributed to D Jacobson.

8 recordsLinked to original sources

Morphometric analysis of heterozygote dancer mice predisposed to 6-aminonicotinamide-induced cleft lip.

Mid-facial development is an extremely complex process involving coordinated events and precise timing. Cleft lip (CL) may result from the failed fusion of the lateral and medial nasal processes in the developing embryo. It has been postulated that spontaneous CL in the A/J strain of mice may be due to a predisposing face shape (Trasler, '68). This hypothesis was examined in mutant mice susceptible to teratogen-induced CL. Mice carrying the dancer (Dc) mutation in the heterozygous state rarely develop CL, whereas 90% of homozygotes (Dc/Dc) develop CL. Outcrossed heterozygotes show elevated susceptibility to 6-aminonicotinamide (6AN)-induced CL (Trasler et al., '84) and these were used to investigate face shape as a predisposing factor. Dc/+ and +/+ males were mated to R stock females, and embryos were collected on day 10/21 hr, when the nasal placodes are approximately at the oblong or crescent stage. Total nasal process areas and volumes, medial and lateral process areas and volumes, and medial jut lengths were measured from histological sections, and comparisons made between the two populations. The results indicate that compared to +/+ control, heads of embryos from the Dc/+ cross have significantly smaller mean total process areas and volumes (P less than 0.005), mean lateral process areas and volumes (P less than 0.005), mean medial process area and volumes (P less than 0.01), mean maximum head diameter (P less than 0.02), but similarly sized medial juts and crown rump lengths. Correlations between maximum head diameter and process size indicate that the Dc mutation may hinder normal development of the nasal processes. These reduced nasal processes may explain the underlying predisposition to 6AN-induced CL.

6-Aminonicotinamide

Genes necessary for directed axonal elongation or fasciculation in C. elegans.

The outgrowth of single axons through different cellular environments requires distinct sets of genes in the nematode C. elegans. Three genes are required for the pioneering circumferential outgrowth of identified motor neuron axons between the lateral hypodermal cell membrane and the basal lamina. Three other genes are required for the longitudinal outgrowth of these axons along preexisting axon bundles as well as for the fasciculation of axons within these neuron bundles. Five additional genes are required for circumferential outgrowth, longitudinal outgrowth, and fasciculation; mutations in three of these genes disrupt axon ultrastructure, suggesting that they function in axon formation rather than in axon guidance.

Animals

Ligand-activated T cell growth factor-induced proliferation: absorption of T cell growth factor by activated T cells.

The fate in culture of the T cell growth factor (TCGF), which is required for continued growth of human cultured T cells (CTC) in vitro, was studied. TCGF activity was stable for 7 days at 37 degrees C. However, it was no longer detectable after incubation with actively growing CTC at 37 degrees C for 3 days. This loss of TCGF activity also occurred quite rapidly and was detectable within 1 hr of incubation of 0.3 ml supernatant with 2 to 5 x 10(7) CTC at 23 degrees C. 2 x 10(8) mononuclear peripheral blood leukocytes were not effective in removing TCGF activity, and incubation with similar numbers of cells from B and T cell lines had no effect. Three-day-old concanavalin A and phytohemagglutinin blasts were very reactive with TCGF, so that 10(7) or 2 x 10(7) cells consistently removed TCGF activity. These experiments suggested specific absorption of TCGF by activated T cells, and led us to develop a model of ligand-activated TCGF-induced proliferation of T cells: Ligands induce production of TCGF by T-producer cells and deliver a first signal to the T-responder cells. This causes a receptor for TCGF to appear on T-responder cells. Only then does TCGF deliver the obligatory second signal that is needed to drive the T-responder cells into proliferation.

Absorption

Expectancy theory prediction of the preference to remain employed or to retire.

Vroom's (1964) expectancy theory model was used to predict older workers' choices between continued employment or immediate retirement. It was hypothesized that a person's preference for one of the two alternatives would be a function of the differences between the instrumentality of employment and the instrumentality of retirement for the attainment of outcomes, multiplied by the valence of each outcome, summed over outcomes. To test this, 290 Israeli male workers, aged 57 to 64, were interviewed. Measures included: preference for employment or retirement; valences of 35 outcomes; perceived instrumentalities of employment and retirement. The results supported the hypothesis (R = .40; p less than .01). It is suggested that further research along these lines could equip organizations with a tool for assisting older employees in the transition to retirement or for encouraging those who are still capable of making a significant contribution to remain employed.

Decision Making

Is Far a Hox mutation?

The mouse First arch mutation, Far, causes a severe syndrome of craniofacial defects described previously. All of the known defects are derived from the anterior first arch, and to a very small extent, the dorsal second arch. Recently Far has been shown to be closely linked to Ulnaless on chromosome 2, and therefore in the vicinity of the Hox-4 gene cluster. This paper reports the results of several studies focused on the development origin of the most consistently expressed dominant effect caused by Far, an abnormal major bifurcation of the maxillary nerve. Nerve-stained whole-mount preparations of day 12 embryos showed that in Far mutants the maxillary nerve appears to have a central wedge missing from the normal single-stalked fan shape, and that the nerve defect in Far/Far and +/Far may be equally severe. The effect of retinoic acid on the development of the maxillary nerve was tested. Maternal treatment with 5 mg/kg retinoic acid on day 9 of gestation had no detectable effect on the maxillary nerve of +/Far embryos, and similar treatment with a teratogenic dosage (20 mg/kg) on day 8 or 9 produced no Far-like maxillary nerve defects in genetically normal embryos. The neural crest cells that give rise to nerves and mesenchyme of the first arch originate from specific rhombomeres, discrete segments of the developing head. The rhombomeres of 15 embryos at the 14-23 somite stages, of which 75% are expected to be +/Far or Far/Far, were examined. There was no detectable defect in segmentation or morphology of the rhombomeres compared with controls. The significance of ectopic cartilage in the palate of Far/Far mutants in relation to nerve bifurcation was explored. In histological studies, five out of six Far/Far day-15 fetuses had a rod of ectopic cartilage lateral to the posterior palate, running parallel to, and morphologically similar to, Meckel's cartilage, and lying between the two trunks of the abnormally bifurcated maxillary nerve. None of six +/Far day-15 fetuses examined had detectable ectopic cartilage in this region. We hypothesize that the maxillary nerve defects in Far mutants may be explained by the presence of an ectopic precartilaginous blastema that does not always further develop into detectable cartilage. The ectopic cartilage found in Far/Far resembles the epibranchial cartilage expressed in more posterior branchial arches and in the first arch of lower organisms, and therefore may represent an atavistic posteriorization of the anterior first arch in Far mutants.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Multiple