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The role of androgens in follicular development in the ovary. I. A quantitative analysis of oocyte ovulation.

In an attempt to understand more fully processes that control the selection or recruitment of follicles for ovulation, the superovulation paradigm in combination with the androgen, 5 alpha-dihydrotestosterone, or the antiandrogens, cyproterone or cyproterone acetate, was used in the immature mouse to alter the developmental potential of follicles destined to ovulate or to become atretic. Quantitative analysis of the numbers of eggs ovulated after one or more rounds of stimulation by pregnant mare's serum gonadotrophin followed by human chorionic gonadotrophin (PMSG-hCG), revealed a dose-dependent ovulation response to exogenous androgen and antiandrogen. Low dosages of androgen improved the ovulation response significantly. Large dosages of cyproterone and cyproterone acetate (100 mg/kg body weight) generally decreased the ovulation number in gonadotrophin-injected mice, suggesting a role for androgen in preovulatory events that occur within the ripened follicle after the ovulatory stimulus (hCG) has been received. Low dosages of cyproterone, particularly 25 mg/kg, significantly enhanced the ovulatory response, a phenomenon not observed for cyproterone acetate at this dosage. Radioimmunoassays of serum LH suggested that the differential response of the ovary to the two antiandrogens was probably related to endogenous LH release. Experiments in which the time of administration of hCG +/- cyproterone was varied after PMSG priming suggested that cyproterone at a dosage of 25 mg/kg had a "rescuing" effect on follicles destined to become atretic for up to 96 hr after PMSG priming. Cyproterone at a dosage of 100 mg/kg had no such effect, and actually decreased the magnitude of the ovulatory response at all time points tested, suggesting that follicular atresia was accelerated by this treatment. Experiments in which the time of administration of cyproterone (100 mg/kg) was varied after hCG suggested that whatever the important androgen-mediated events preceding ovulation, these events occur within 2 to 3 hr after the hCG signal. By quantitating the numbers of eggs over several superovulation cycles, it could be shown that hormonal treatment in one induced cycle could affect significantly the ovulation response in subsequent cycles, suggesting that androgens influence the development of classes of follicles other than preovulatory follicles. These studies suggest that the process through which follicles are selected for ovulation is extremely sensitive to the androgenic environment and that the developmental pathways leading to ovulation or preovulatory follicular atresia are closely linked.

Animals↗

Horizontal cell processes in teleost retina.

Contacts between horizontal and bipolar cells are described in the retina of the teleost Eugerres plumieri. A single, long expansion observed in the external cone horizontal cells makes contact by means of a terminal button with the cell body of a bipolar. It represents the only contact between this class of horizontal cell and the bipolar soma. On the other hand, the medial and internal cone horizontal cells and the rod horizontal cells, which lack such a single, long expansion, display instead numerous short and fine expansions that terminate by means of a terminal knob on a bipolar cell body. The bipolar-destined, short expansions of the rod horizontal cell make contact with large bipolar cell bodies, whereas corresponding short expansions of cone horizontal cells contact small bipolar cell bodies. It is suggested that the ascending horizontal cell process forms presynaptic terminals in the photoreceptor triad complex, and that the single, long and the multiple, short bipolar-destined expansions are postsynaptic to the bipolar cell body.

Animals↗

Changes in intra-axonal calcium distribution following nerve crush.

We used the oxalate-pyroantimonate method to demonstrate the ultrastructural distribution of calcium within rat sciatic nerve 4 h after a crush injury. In normal nerve there are discrete gradients of axoplasmic calcium precipitate with the amount of precipitate decreasing in the axoplasm beneath the Schmidt Lantermann clefts and in the paranodal regions at the node of Ranvier. Near the crush site a marked increase in endoneurial and intra-axonal calcium precipitate correlated with morphologic evidence of axonal degeneration. More distant from the crush site, both in the distal segment destined to degenerate and in the proximal segment destined to regenerate, the most prominent finding was a loss of the normal gradient of precipitate beneath the Schmidt Lantermann clefts. The calcium influx at the crush site corresponds to the known role of calcium in triggering degeneration. The alterations in the distal axon may be an early stage leading to degeneration. Alteration in calcium distribution in the proximal nerve stump may play a role in the regulation of the response to injury.

Animals↗

Involvement of the Golgi apparatus in sorting of materials to opposite ends of frog rod retinal photoreceptors.

We have studied the rod cells of retinas of Rana pipiens by phosphatase cytochemistry and immunocytochemistry. We find that the Golgi apparatus of these cells, although different in its intracellular distribution from that of other neurons, has a cis-trans organization like that of other neurons as regards morphological features and the distribution of phosphatase activities. Antibodies against opsin bind to several sacs of the rod Golgi apparatus, especially those at the trans side of the Golgi stack. This suggests that Golgi involvement in the packaging of opsin for eventual delivery to the photoreceptive outer segments of the cell involves passage through trans Golgi systems. Proteins destined for the opposite end of the cell--the presynaptic terminal--also seem to pass through trans Golgi systems, as is indicated both by immunocytochemical localization of the synaptic vesicle protein p38 (synaptophysin) and by the presence of thiamine pyrophosphatase activity in some of the synaptic vesicles. Our findings suggest that sorting of membrane proteins destined for opposite ends of the photoreceptor takes place in systems at or near the trans Golgi face.

Animals↗

Synaptic arrangements between inner hair cells and tunnel fibers in the mouse cochlea.

Hair cells, the sensory cells of the organ of Corti, receive afferent innervation from the spiral ganglion neurons and efferent innervation from the superior olivary complex. The inner and outer hair cells are innervated by distinctive fiber systems. Our electron microscopical studies demonstrate, however, that inner hair cells, in addition to their own innervation, are also synaptically engaged with the fibers destined specifically to innervate outer hair cells, within both the afferent and efferent innervation. Serial sections of the afferent tunnel fibers (destined to innervate outer hair cells) in the apical turn demonstrate that, while crossing toward the tunnel of Corti, they receive en passant synapses from inner hair cells. Each inner hair cell (in a series of five in the apical turn) was innervated by two tunnel fibers, one on each side. We show here for the first time that, in the adult, the afferent tunnel fibers receive a ribbon synapse from inner hair cells and form reciprocal contacts on their spines. Vesiculated efferent fibers from the inner pillar bundle (which carries the innervation to outer hair cells) form triadic synapses with inner hair cells and their synaptic afferent dendrites; the vesiculated terminals of the lateral olivocochlear fibers from the inner spiral bundle synapse extensively on the afferent tunnel fibers, forming triadic synapses with both afferent tunnel fibers and their synaptic inner hair cells. This intense synaptic activity involving inner hair cells and both afferent and efferent tunnel fibers, at their crossroad, implies functional connections between both inner and outer hair cells in the process of hearing.

Animals↗

Pattern formation in the developing mammalian forebrain: selective adhesion of early but not late postmitotic cortical and striatal neurons within forebrain reaggregate cultures.

The mammalian cerebral cortex and striatum exhibit spatially restricted distributions of neurons. These neuronal collectives correlate with the age at which the neurons become postmitotic. We investigated in vitro the role of cell adhesion in the organization of like-birthdated neurons within the rat telencephalon. Specifically, the ability of neurons of similar birthdate to reassociate with one another within either striatal or cortical reaggregates was observed. Early postmitotic neurons (destined for the striatal patch compartment and cortical deep layers) or later born neurons (destined for the striatal matrix compartment and cortical superficial layers) were labeled in vivo with [3H]-thymidine or bromodeoxyuridine (Brdu) on Embryonic Day (E) 13 or 18, respectively. Two or seven days later, the striatum and cortex were separately removed, dissociated, and reaggregated in suspension cultures for 5 days. Within both striatal and cortical reaggregates, E13 [3H]thymidine-labeled cells were observed to clump together toward the center of the reaggregates. Conversely, reaggregates containing cells labeled on E18 with a single [3H]thymidine injection or with two separate Brdu injections contained labeled cells which were dispersed with respect to each other, but showed an overall distribution toward the periphery of the reaggregates. These results suggest that early, but not late, postmitotic striatal and cortical neurons selectively associate with one another within their respective structures. Dissociated embryonic striatal and cortical neurons were then co-reaggregated to examine if a single adhesive mechanism is shared by both tissues. Early born neurons within these reaggregates clustered with each other regardless of tissue type. Later born cortical and striatal neurons were found dispersed in relation to each other and the early born neurons. However, the selective adhesion of early born striatal and cortical neurons is not an attribute of all early postmitotic forebrain neurons, because dissociated early born septal-basal forebrain neurons were found dispersed within reaggregates of septal-basal forebrain tissue or when cocultured with striatal tissue. These results suggest that the organization of cortical and striatal neuronal groups may depend on a common adhesive mechanism that crosses tissue-type boundaries.

Animals↗

The contribution of both forebrain and midbrain crest cells to the mesenchyme in the frontonasal mass of mouse embryos.

Migration of cranial neural crest cells is a crucial event in the formation of facial organs such as the frontonasal mass and branchial arches. However, the source of the populating crest cells that occupy the frontonasal mass remains unclear in mammalian embryos. To elucidate this, we performed focal DiI injections at various sites in the prosencephalon (forebrain, including the future telencephalon and diencephalon), mesencephalon (midbrain), and the anterior part of the rhombencephalon (hindbrain) separated posteriorly by the preotic sulus (i.e., rhombomere A; future rhombomere 1 and 2) of cultured mouse embryos from the 3- to 10-somite stage. Results directly revealed that during these stages the lateral edge of the prosencephalon produced crest cells which migrated to the frontonasal mass. On the other hand, labeled cells at the anterior neural ridge in the prosencephalon contributed mainly to the head epithelium, including the nasal placode, Rathke's pouch, and oral epithelium. As for the crest cells of the mesencephalon and rhombomere A, their destinations were significantly dependent on the injection site and somite stage. At the 3- to 4-somite stage, the crest cells emigrating from both the mesencephalon and rhombomere A migrated to the first branchial arch. Moreover, the mesencephalic region, but never rhombomere A, produced another group of crest cells that migrated to the frontonasal mass. In the 5- to 10-somite stage, the destinations of late-emigrating crest cells were restricted depending on their premigratory positions, i.e., the region producing crest cells migrating toward the frontonasal mass was restricted to the anterior portion of the mesencephalon, and the crest cells from the posterior portion of the mesencephalon primarily migrated to the first branchial arch, while those from the rhombomere A predominantly migrated to the trigeminal ganglion. Migration toward the frontonasal mass from the mesencephalon ceased at the earliest in the 7-somite stage, followed by termination of mesencephalic and rhombencephalic crest cell migration toward the first branchial arch at the 8-somite stage, whereas the contribution from rhombomere A to the trigeminal ganglion continued even at the 10-somite stage. This behavior suggests that both the prosencephalic and mesencephalic crest contribute to the mesenchymal cells in the frontonasal mass and also that the migration patterns of crest cells released from the prosencephalon, mesencephalon, and rhombencephalon depend on their axial level and developmental stage at initial emigration.

Animals↗

Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila.

A new monoclonal antibody, specific to an epitope in the carboxyl terminus of the Drosophila collagen IV molecule (basement membrane collagen) was identified. The distributions of collagen IV, laminin, and an additional extracellular molecule, the 2G2 antigen (2G2-Ag), were followed immunocytochemically during early wing development. In late third instar larvae, collagen IV and laminin surround the entire wing disc, whereas the 2G2-Ag is limited to the region of the future wing pouch. For the first few hours following eversion of the disc, all three ECM components line the basal surfaces of all epithelial cells in the wing pouch, both those destined to line the wing veins and those destined to become tightly apposed in the large intervein regions. Collagen IV and laminin persist on these cells during the two initial rounds of apposition of dorsal and ventral wing surfaces; later, they become restricted to the cells lining the veins. The 2G2-Ag disappears completely quite early in the pupal period. Collagen IV appears to be synthesized at least twice, once in the larva and a second time in the pupa; in between it is enzymatically cleaved and may be eliminated, probably by hemocytes. In an extreme allele of blistered the wing is ballooned to form a single internal space. Collagen IV and laminin line all basal wing cell surfaces early in pupal development as they do in the wild type. Later, however, they continue to line the entire cavity of the mutant wing rather than assuming a restricted distribution. In a completely veinless wing (rhomboidveinletvein), collagen IV and laminin are also present generally on basal surfaces at early times, but are completely absent between the tightly apposed wing layers later. The ECM distributions both in wild type wings and in mutants suggest that the matrix plays a role in the establishment of the wing venation pattern. One possibility, strengthened by recent findings regarding ECM receptors in Drosophila, is their involvement in dorsal-ventral wing layer adhesion. Our findings also lead us to suggest that certain sets of features which distinguish vein from intervein cells may be linked during cell differentiation and thus help to define these cell phenotypes. The features include cytoskeletal specializations and certain cell surface and ECM molecules.

Animals↗

The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain.

In the mammalian forebrain most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles. These neurons become postmitotic before they undergo migration to their final destinations. In this study we examined the proliferative and migratory properties of cells destined for the olfactory bulb that arise postnatally from progenitor cells situated at the anterior extent of the subventricular zone (SVZa). The SVZa-derived cells migrate along a stereotypical pathway to the olfactory bulb where they become interneurons. Using lineage tracers and the cell proliferation marker BrdU, we have demonstrated that SVZa-derived cells in the rat retain the capacity for division after migrating away from their initial site of generation. These cells also express a neuron-specific tubulin, recognized by the antibody TuJ1. These results suggest that, unlike other immature neurons, these SVZa-derived cells have made a commitment to become neurons before becoming postmitotic.

Animals↗

Neural crest apoptosis and the establishment of craniofacial pattern: an honorable death.

During development of the vertebrate head neural crest cells emigrate from the hindbrain and populate the branchial arches, giving rise to distinct skeletal elements and muscle connective tissues in each arch. The production of neural crest from the hindbrain is discontinuous and crest cells destined for different arches, carrying different positional cues, are separated by regions of apoptosis centered on rhombomeres (r) 3 and r5. This cell death program is under the interactive control of the neighboring hindbrain segments. Both r3 and r5 produce large numbers of crest cells when freed from their flanking rhombomere, but when conjoined with their neighbor the cell death program is restored. Two key components of this program are Bmp 4 and msx-2, both of which are expressed in the apoptotic foci of r3 and r5 and which are also regulated by neighbor interactions. Importantly, the addition of recombinant Bmp 4 to isolated cultures of r3 and r5 induces the expression of Bmp 4 and msx-2 and restores the cell death program. This early neural crest segregation is maintained during development and it has profound effects upon the final craniofacial pattern. Even though crest cells from different axial origins will contribute to compound skeletal elements, these distinct populations do not intermingle. Furthermore head muscle connective tissues are exclusively anchored to skeletal domains arising from neural crest from the same axial level. Thus the discontinuous production of neural crest sculpts the crest into nonmixing streams and consequently ensures the fidelity of patterning.

Animals↗

The neuronal progenitor cells of the forebrain subventricular zone: intrinsic properties in vitro and following transplantation.

During the development of the central nervous system, progenitor cells, located within distinct germinal zones, produce presumptive neurons that migrate to their destinations and differentiate. Recent studies have demonstrated that a discrete region of the anterior part of the postnatal subventricular zone (SVZa) comprises neuronal progenitor cells whose progeny are fated to become the interneurons of the olfactory bulb. The SVZa is of particular interest because it is one of few germinal zones to persist postnatally and may be the only postnatal germinal zone to give rise exclusively to neurons. To the extent that the SVZa is unique among proliferative zones, the SVZa progeny are unique among neurons. First, unlike most cortical neurons, the SVZa-derived cells do not rely on radial glia-assisted migration when traveling to their target region. Second, the SVZa progeny continue to proliferate as they migrate to their target region. And third, the SVZa progeny express early neuron-specific antigens prior to their final division and, therefore, prior to reaching their destination where they will terminally differentiate. To better understand the capacity of the SVZa progeny to concurrently proliferate, migrate, and differentiate, we studied the cells in vitro and following transplantation into the neonatal SVZa and adult striatum. In each setting, we found that the SVZa cells continue both to proliferate and to differentiate into neurons. In addition, after homotopic and heterotopic transplantation, we found that the SVZa cells maintain their ability to migrate. These results suggest that the unique features of the SVZa progeny are specified intrinsically rather than by their extrinsic environment.

Animals↗

Cardiac looping in the chick embryo: the role of the posterior precardiac mesoderm.

Grafts of mesoderm taken from the precardiac region of quail embryos of stages 5-7 were inserted into the precardiac mesoderm of chick embryos of stages 5-7. The experiments were of four types and were code named to indicate the origin and the destination of the graft. QACP: tissue from the anterior end of the quail precardiac area was inserted into the posterior end of the chick precardiac mesoderm; QPCA: tissue from the posterior end of the quail precardiac area was inserted into the anterior end of the chick precardiac mesoderm; QACA: tissue from the anterior end of the quail precardiac area was inserted into the anterior end of the chick precardiac mesoderm; QPCP: tissue from the posterior end of the quail precardiac area was inserted into the posterior end of the chick precardiac mesoderm. In no case was precardiac tissue removed from the host. Three main-types of anomaly were obtained: inverted hearts, in which looping took place to the left rather than to the right; compact hearts, in which no looping occurred, and hearts in which extra tissues or regions were apparent. The incidence of compact hearts was significantly greater with QPCA than with any other category of experiment. When older donors were used (stages 8-9), the incidence of compact hearts fell. No variations in the origin of the graft, nor in its ultimate destination in the host, were found to affect the frequency of any of the anomalies. Sections showed that quail hearts tended to have thicker walls than chick hearts; although quail tissues were often incorporated into the host chick hearts, they retained the histological characteristics of the donors. The fact that no compact hearts resulted from the experiment QACA, or from the mock operations, leads us to conclude that failure to loop in the compact hearts was not due to mechanical trauma caused by the operation, but to some specific difference between grafts taken from the anterior and posterior precardiac mesoderm. The fact that compact hearts were obtained when chick donors were used instead of quails, shows that the effect is not species-specific. We propose that a morphogen is secreted by the posterior end of the precardiac mesoderm and this plays a role in controlling the cessation of looping.

Animals↗

The total number, time or origin and kinetics of proliferation of neurons comprising the deep cerebellar nuclei in the rhesus monkey.

The genesis of the neurons that form the cerebellar nuclei was studied by autoradiographic methods in 30 postnatal rhesus monkeys which were exposed to 3H-thymidine at various embryonic (E) and postnatal (P) ages. As a basis for this quantitative analysis, five 2-3 month old monkeys were used for cell counting and estimation of the total number of neurons in each of the cerebellar nuclei. The results show that the cerebellar nuclei on each side contain 131,000 neurons. There are 68,000 neurons in the dentate nucleus, 25,000 neurons in the posterior interposed nucleus, and 19,000 neurons in both the anterior interposed the fastigial nuclei. All of the neurons comprising the deep nuclei are generated during the first half of the 165 days gestation period in this species. Although neurogenesis lasts from E30 through E70, approximately 81% of the neuron population is generated during a one week period between E36 and E40, with the peak of proliferation occurring at E36. Before E45 both large (maximum diameter greater than 35 micrometers) and small (maximum diameter 35 micrometers or less) neurons are produced simultaneously; after this period only small neurons are generated. Although no clearcut spatio-temporal gradients of neurogenesis could be discerned along any of the cardinal axes, each cerebellar nucleus has a somewhat distinctive developmental history in terms of the onset and cessation of neurogenesis and the tempo of cell proliferation. Thus, genesis of neurons destined for the dentate nucleus begins earlier and ends later than proliferation of the neurons that ultimately comprise the fastigial nucleus. Generation of the neurons destined for the anterior and posterior interposed nuclei follows an intermediate time course. The present data on neurogenetic sequences in the deep nuclei could not be correlated with the zonal pattern of reciprocal axonal connections that link the deep nuclei and overlying cerebellar cortex.

Aging↗

Neuronal injury and expression of 72-kDa heat-shock protein after forebrain ischemia in the rat.

We evaluated the relationship between the induction of the 72-kDa heat-shock protein (hsp 72) and the presence of necrotic neurons in the rat hippocampus, 48 h after an 8-min episode of forebrain ischemia in eight rates. Hsp 72 was detected using the monoclonal antibody C92 on vibratome brain tissue sections. Hematoxylin and eosin (H&E) staining on adjacent paraffin-embedded sections was used to determine histopathological features. All morphologically intact CA1/2 neurons, 70% of which are destined to become necrotic 7 days after ischemia, exhibited intense hsp 72 staining, while necrotic or damaged neurons were devoid or low in hsp 72. Hsp 72 was also detected in CA3 neurons destined to survive 7 days after ischemia. Blood vessels positive for hsp 72 were detected in focal brain regions, in which severely damaged neurons were either devoid or low in hsp 72 staining. Occasional glial cells expressed hsp 72 in both normal and damaged brain regions. Hsp 72 response to a transient forebrain ischemia seemingly reflects differences in the selective ischemic vulnerability of CA1/2 and CA3 neurons. Further, the presence of hsp 72 within a neuron is likely only a marker of stress and is not necessarily indicative of eventual neuronal survival.

Animals↗

Divergent regulation of muscarinic binding sites and acetylcholinesterase in discrete regions of the developing human fetal brain.

The expression of muscarinic acetylcholine binding sites and of cholinesterases was studied in extracts prepared from discrete regions of the human fetal brain, between the gestational ages of 14 and 24 weeks. The specific binding of [3H]N-methyl-4-piperidyl benzilate [( 4H]-4NMPB) to muscarinic binding sites ranged between 0.05 and 1.30 pmol/mg protein in the different brain regions, with Kd values of 1.2 +/- 0.2 nM. Binding of the cholinergic agonist oxotremorine fitted, in most of the brain regions examined, with a two-site model for the muscarinic binding sites. The density of muscarinic binding sites increased with development in most regions, with different rates and onset times. It was higher by about sixfold in some areas destined to become cholinergic, such as the cortex and midbrain, than in noncholinergic areas such as the cerebellum. In other areas destined to become cholinergic, such as the hippocampus and the caudate putamen, the receptor density remained low. Average density values increased from 0.1 +/- 0.1 at 14 weeks up to 0.7 +/- 0.4 pmol/mg protein at 24 weeks. The variability in the specific activities of cholinesterase was relatively low, and extracts from different brain regions hydrolyzed from 5 to 30 nmol of [3H]acetylcholine/min/mg protein. These were mostly "true" acetylcholinesterase (EC 3.1.1.7) activities, inhibited by 10(-5) M BW284C51, with minor pseudocholinesterase (EC 3.1.1.8) activities, inhibited by 10(-5) M iso-OMPA. The enzyme from different brain regions and developmental stages displayed similar Km values toward [3H]acetylcholine (ca. 4 X 10(-4) M-1). The ontogenetic changes in cholinesterase specific activities had no unifying pattern and/or relationship to the cholinergic nature of the various brain areas. In most of the brain regions, the arbitrary ratio between the specific activity of cholinesterase and the density of muscarinic binding sites decreased with development, with average values and variability ranges of 83 +/- 50 and 19 +/- 19 at 14 and 24 weeks, respectively. Our findings suggest divergent regulation for cholinergic binding sites and cholinesterase in the fetal human brain and imply that the expression of muscarinic receptors is related to the development of cholinergic transmission, while acetylcholinesterase is also involved in other functions in the fetal human brain.

Acetylcholine↗

The inferior alveolar artery in its bony course.

Based on the dissection of 30 hemi-mandibles, the authors report a study of the inferior alveolar artery in its intraosseous course. On morphologic considerations they propose a classification of the collaterals into two groups: the principal collaterals destined for the teeth and the bony alveolar tissue and the secondary collaterals destined for the sheath and the nerve as well as the bony tissue around the canal. Loss of the teeth and absorption of the alveolar bone modify the caliber of the inferior alveolar arterial axis, the distribution of its collaterals and possibly its mode of termination. These facts suggest a consideration of the vascularization of the mandible in terms of four sectors. They arrive at practical conclusions that may be drawn from this study in stomatology.

Aged↗

Effects of extra- and intracellular calcium concentration on DNA replication, lateral growth, and differentiation of human epidermal cells in culture.

Variation in the extra- and intra-cellular concentration of calcium ([Ca]e and [Ca]i) affected the 3H-thymidine labeling pattern of sorted S-phase cells in human epidermal cultures. A lowering of [Ca]e resulted in retarded lateral growth but, unless [Ca]e was extremely low, caused an increase in the proportion of strongly labelled (rapidly cycling) S-phase cells. An increased desquamation of superficial cells due to a reduced cellular cohesiveness was also observed in low calcium medium. Thus, a lowering of [Ca]e might stimulate the proliferation of a pool of cycling cells destined for rapid terminal differentiation and tissue regeneration, whereas proliferation destined for lateral growth is inhibited. Attempts to decrease the [Ca]i with the calcium chelator quin-2 at low [Ca]e seemed to elevate the proportion of strongly labelled S-phase cells, whereas an increased [Ca]i obtained with the ionophore A23187 caused a dramatic decrease in the proportion of S-phase cells that showed strong 3H-thymidine incorporation. This implies that variation in both [Ca]i and [Ca]e may play a role in the regulation of proliferation and differentiation, in keratinocytes.

Aminoquinolines↗

Welfare reform and interstate migration of poor families.

The thesis of this study is that as a result of increased inequalities in welfare rules, the 1996 welfare reform act not only enhanced incentives for poor families to move but also (and perhaps more important) created disincentives for them to stay in "race to the bottom" states. In testing this thesis, we evaluated the mediating and moderating roles of state economic development and family structure. We merged data from three main sources: the 1996-1999 panel of the Survey of Income and Program Participation, the Urban Institute's Welfare Rules Database, and state economic data from the Bureau of Labor Statistics. Modeling both destination (pull) and departure (push) effects of welfare policy measures and selected covariates in a nested discrete-time event-history migration analysis, we found robust support for the thesis that stringency in state welfare-eligibility and behavior-related rules stimulated interstate out-migration of poor families in the United States. However poor families were not drawn to states with relatively more-lenient welfare rules, although stringency in state welfare dollar benefits inhibited in-migration and state unemployment patterns may have conditioned the migration effects of welfare-reform rules on the choice of destination. Single mothers were not more directly affected by welfare-eligibility and behavior-related rules than were poor married couples.

Data Collection↗