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L Sommer

Publications and source records attributed to L Sommer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cell lineage determination and the control of neuronal identity in the neural crest.

The molecular mechanisms underlying the determination of neuronal identity in the vertebrate peripheral nervous system are only just beginning to come into focus. Many of these mechanisms, such as the involvement of cascades of bHLH transcription factors and lateral inhibition via the Notch-Delta system, appear to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993). The way in which these genetic circuits are controlled by instructive growth factors, and the manner in which they lead to expression of a particular neuronal identity, is far from clear. This process is being elucidated by studies of neurogenesis in the peripheral autonomic lineage, which is arguably the best-understood neurogenic lineage in vertebrates. Emerging evidence is beginning to suggest that neuronal diversity within the autonomic and sensory lineages may be generated by related, but distinct, mechanisms. All autonomic progenitors express a common bHLH protein, MASH1, which appears to be induced by members of the BMP2 subfamily secreted by the tissues to which these progenitors migrate. Additional signals may then act on these progenitors in different locations to induce the expression of other transcription factors, which act in conjunction with MASH1 to specify the final phenotypes of the different autonomic neuron subtypes (sympathetic, parasympathetic, and enteric). Although different classes of autonomic neurons develop in very different locations within the body, different classes of sensory neurons are located together in dorsal root ganglia. The finding that distinct but related subtypes of bHLH proteins, the neurogenins, are expressed by different classes of sensory neuron precursors early in development suggests that sensory neuron diversity, in contrast to autonomic neuron diversity, may be pre-specified at or before the time neural crest cells begin their emigration from the neural tube.

Animals↗
PubMed1996

neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS.

We recently identified neurogenin (ngn), a neuroD-related bHLH gene, whose Xenopus homolog functions as a neuronal determination factor and upstream activator of XneuroD (Ma et al. Cell 87: 43-52, 1996). Here we identify two additional ngn's, ngn2 and ngn3, which together define a novel subfamily of atonal-related mouse genes. Comparative analysis of ngn expression indicates that these three genes define distinct progenitor populations in the developing CNS and PNS, exhibiting nonoverlapping expression in some areas and partial overlap in others. The expression of the ngn's spatially overlaps and often temporally precedes that of neuroD, suggesting that (as in Xenopus) the ngn's and neuroD function in a cascade. Thus, as in myogenesis, different bHLH determination factors may activate a common bHLH differentiation factor in different sublineages. The ngn's therefore represent both a family of putative mammalian neuronal determination genes and useful markers of the origins of neuronal diversity.

Amino Acid Sequence↗
PubMed1996

Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence.

Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase. If this precursor pool is eliminated in vitro by complement-mediated lysis, enteric neurons continue to develop; however, none of these are serotonergic. In the mouse, the Mash-1-/- mutation, which eliminates sympathetic neurons, also prevents the development of enteric serotonergic neurons. Other enteric neuronal populations, however, including those that contain calcitonin gene related peptide are present. Enteric tyrosine hydroxylase-containing cells co-express Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons. Serotonergic neurons are generated early in development, while calcitonin gene related peptide-containing enteric neurons are generated much later. These data suggest that enteric neurons are derived from at least two progenitor lineages. One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and generates early-born enteric neurons, some of which are serotonergic. The other is Mash-1-independent, does not express sympathoadrenal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.

Animals↗
PubMed1995

The cellular function of MASH1 in autonomic neurogenesis.

Using primary cultures and immortalized multipotential stem cell lines derived from wild-type and Mash1 mutant neural crest cells, we have analyzed the cellular function of MASH1 in autonomic neurogenesis. We present evidence for the existence of a precursor expressing MASH1 and neuronal markers such as neurofilament, neuron-specific tubulin, and tetanus toxin receptor. This cell has a nonneuronal morphology. Differentiation of this precursor to neurons that express markers such as SCG10, peripherin, and neuron-specific enolase is dependent upon MASH1 function. These data imply that the differentiation of autonomic neurons from uncommitted neural crest cells occurs in several sequential steps. Moreover, they suggest that MASH1 does not commit multipotent cells to a neural fate, like its Drosophila achaete-scute counterparts, but rather promotes the differentiation of a committed neuronal precursor.

Animals↗
PubMed1995

Effects of the gonadotropin-releasing-hormone agonist, D-Trp-6-GnRH, on prolactin secretion in healthy young men.

The objective of this study was to examine the changes in basal plasma gonadotropin, alpha-subunit, sex steroids, and prolactin levels and the prolactin and luteinizing hormone (LH) secretion pattern before, during and 161 days after treatment with a depot preparation of D-Trp-6-GnRH in young men. Gonadotropins, alpha-subunit, sex steroids, and prolactin were measured in pooled plasma samples. Additionally, before treatment, several times during its course and on day 161 after treatment, blood samples were drawn for 8 h every 15 min for prolactin and LH measurements. After initial stimulation of the pituitary, administration of a depot preparation of D-Trp-6-GnRH resulted in a constant decrease in gonadotropin and sex steroid concentrations with LH and testosterone concentrations remaining within the limits of prepubertal levels from days 16 to 48. Alpha-Subunit concentrations (0.4 +/- 0.09 IU/l; mean +/- SE) increased after application of D-Trp-6-GnRH, and remained elevated until day 48. Basal prolactin levels (3.5 +/- 0.25 microgram/l) did not change significantly during treatment but afterwards increased consistently with maximal levels at day 141 (15.3 +/- 3.8 microgram/l); they had decreased at day 161 to 10.3 +/- 1.8 microgram/l which is significantly higher than before treatment (p < 0.05). On day 161, prolactin pulse amplitude was significantly higher than before and during treatment (p<0.05), while no significant changes in pulse frequency occurred. No significant temporal coupling between LH and prolactin release could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Secretion pattern of immunoreactive inhibin in men.

Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24-27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1-32 amino acids of the alpha-subunit of human inhibin. The normal range for men was 0.79-3.1 U/l x 10(-3), the sensitivity of the assay was 0.1 U/l x 10(-3) (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45-3.20 U/l x 10(-3). During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20-1.86 U/l x 10(-3). Highest testosterone levels were observed in the morning (20.5-36.6 pmol/l), lowest concentrations were detected at night (7.35-12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation.2+ volunteers follow a clear diurnal rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Seven-day administration of the gonadotropin-releasing hormone antagonist Cetrorelix in normal cycling women.

In contrast to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists do not show any stimulatory effect on the pituitary but their clinical usage was precluded by severe side effects and high dose requirements. We report here on a 7-day treatment using the potent GnRH antagonist Cetrorelix ([Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]GnRH) on five women 23-33 years old. All women were ovulatory and were studied during three consecutive cycles: a control cycle, a treatment cycle and a post-treatment control cycle. Throughout the control cycles blood samples were obtained daily during cycle days 8-18 and on days 21 and 23 during the remainder of the control cycles. On the eighth day of the treatment cycle women were hospitalized at 07.00 h for 26 h. Repeated blood samples were drawn at 15-min intervals during the entire period. Subjects received 3 mg of Cetrorelix sc for the first time at 09.00 h on the eighth day of the cycle and daily at 08.00 h for the following 6 days. Blood samples were obtained daily over a period of 25 days and every third day throughout the remainder of the treatment cycle. Twenty-four hours after the first application of Cetrorelix, luteinizing hormone (LH) and estradiol were in the subnormal range and remained subnormal until the end of medication. The suppressive effect of Cetrorelix compared to pretreatment values lasted at least 6 days for LH and FSH and 11 days after the last Cetrorelix injection for estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Direct measurement of immunoreactive renin during changes of posture in man.

For several years, it has been possible to determine renin by a direct RIA. In the present study, plasma active renin concentration (PRC) was related to plasma renin activity (PRA) and aldosterone as a function of a standardized posture test. Using PRC, our target was to define the shortest necessary test duration. The three parameters were examined in 10 healthy male subjects (22-34 years old). Salt balance was determined in 24-hour urine, and plasma potassium and sodium were measured. Volunteers were hospitalized for 1 night, and at 8 a.m. the next morning they were subjected to the following postural changes: 3 h active orthostasis and 3 h recumbency. Frequent blood samples were taken. Orthostasis induced a significant rise in PRC, PRA and aldosterone already after 15 min. PRC and PRA reached a maximum level after 90 min of orthostasis and remained relatively stable, while aldosterone reached its highest level already after 30 min and then gradually decreased. Significant correlations were found between PRA and PRC (p < 0.001), between PRC and aldosterone (p < 0.001), and between PRA and aldosterone (p < 0.001). The PRC/PRA ratio changed during the course of the test, especially in supine subjects. When subjects returned to the supine position, all the parameters measured began a continual decrease. There were no significant changes in serum potassium and sodium levels throughout the duration of the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Nuclear targeting of the transcription factor PTF1 is mediated by a protein subunit that does not bind to the PTF1 cognate sequence.

The pancreas-specific transcription factor PTF1 is a heterooligomer that exists as two variants, alpha and beta, both of which bind DNA. The nucleus contains exclusively alpha while the cytoplasm contains both forms. Alpha and beta differ in protein composition. Reconstitution of alpha in vitro requires, in addition to the DNA-binding subunits common to both forms, a 75 kd glycosylated protein that apparently does not bind DNA. Here we show that this protein is essential for targeting PTF1 to the nucleus. Upon injection into frog oocytes, alpha is translocated quantitatively to the nucleus while beta remains in the cytoplasm. However, if beta is coinjected with purified 75 kd protein or a particular size fraction of pancreatic mRNA, it can be converted to alpha and imported into the nucleus.

Animals↗
PubMed1990

Interaction in situ of the cytoskeletal protein vinculin with bilayers studied by introducing a photoactivatable fatty acid into living chicken embryo fibroblasts.

The cytoskeletal protein vinculin, a putative actin--plasma-membrane linker, has been shown by hydrophobic photo-labeling to interact in vitro directly with bilayers of acidic phospholipids [Niggli et al. (1986) J. Biol. Chem. 261, 6912-6918]. In order to demonstrate that such an interaction occurs also in intact cells, chicken embryo fibroblasts were incubated for 2 h with a 3H-labeled photoactivatable fatty acid, 11-(4-[3-(trifluoromethyl)-diazirinyl]phenyl)-[2-3H]undecanoic acid. This resulted in biosynthetic incorporation into cellular lipids of a fraction of the fatty acid added. Following photolysis, vinculin was immunoprecipitated from different subcellular fractions using a specific polyclonal anti-vinculin antibody. The protein was recovered from both the cytosolic and the crude membrane fraction. Vinculin from both fractions incorporated label, but the membrane-associated population was at least eight times more strongly photolabeled than the cytosolic protein. Moreover, photolysis increased only labeling of the membrane-bound but not of the cytosolic protein. These results suggest that the direct interaction of vinculin with the hydrophobic core of the phospholipid layer observed in vitro may also be relevant in intact cells, and may be involved in its function as a linker protein.

Animals↗
PubMed1986

Diabetes alters drug metabolism--in vivo studies in a streptozotozin-diabetic rat model.

The influence of experimental streptozotozin-induced diabetes on hepatic drug metabolism in vivo has been studied in rats, using 14CO2-exhalation after 14C-aminopyrine injection. Male diabetic rats showed a decreased (-18%), females an increased (+19%) 14CO2-exhalation compared to controls, indicating altered hepatic drug metabolism due to diabetes.

Aminopyrine↗
PubMed1980

Calcium antagonistic effects of terodiline in rabbit aorta and human uterus.

The possible calcium antagonistic action of the anti-anginal drug terodiline was investigated by two experimental techniques. In isolated preparations of rabbit aorta and pregnant human uterus exposed to a calcium-free medium and then depolarized by potassium, terodiline in concentrations of 4.5--36 microM inhibited contractions produced by cumulative addition of calcium to the extracellular medium. This effect of terodiline could be reversed by high concentrations of calcium. Within the same concentration range, terodiline also reduced potassium-induced 45Ca influx in isolated aorta without affecting calcium efflux. It is suggested that terodiline, which structurally has similarities to prenylamine and fendiline, like these drugs can be classified as a calcium antagonist.

Adult↗
PubMed1980

Anticholinergic and calcium antagonistic effects of terodiline in rabbit urinary bladder.

The effects of terodiline on contractions induced in isolated rabbit detrusor by carbachol and potassium, and by electrical field stimulation were investigated. Terodiline relaxed preparations contracted by carbachol and potassium and, when added 15 min before stimulation, decreased the contractile responses to these agents in a concentration-dependent way. Terodiline more effectively inhibited carbachol than potassium induced contractions. The "pure" calcium antagonist nifedipine had the opposite effect. Both atropine and terodiline caused a parallel shift to the right of the concentration-response curve to carbachol. The maximum contractile tension and slope were not affected, suggesting a competitive antimuscarinic effect within the concentration range used. Atropine was approximately 750 times more potent than terodiline. The maximum inhibitory effect of atropine and the calcium antagonist nimodipine on the electrically induced response were 40% and 69%, respectively. Terodiline caused complete inhibition of the response, as also did a combination of nimodipine and atropine. --The results suggest that terodiline in low concentrations has mainly an antimuscarinic action. To this, a calcium antagonistic effect is added at higher concentrations. The two-fold action of the drug makes it an effective inhibitor of bladder contraction, and an interesting tool for investigations of bladder contractility.

Animals↗