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Biomedical subjects

A M Kenney

Publications and source records attributed to A M Kenney.

At least 19 recordsLinked to original sources
PubMed2000

Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors.

Sonic hedgehog (Shh) signal transduction via the G-protein-coupled receptor, Smoothened, is required for proliferation of cerebellar granule neuron precursors (CGNPs) during development. Activating mutations in the Hedgehog pathway are also implicated in basal cell carcinoma and medulloblastoma, a tumor of the cerebellum in humans. However, Shh signaling interactions with cell cycle regulatory components in neural precursors are poorly understood, in part because appropriate immortalized cell lines are not available. We have utilized primary cultures from neonatal mouse cerebella in order to determine (i) whether Shh initiates or maintains cell cycle progression in CGNPs, (ii) if G(1) regulation by Shh resembles that of classical mitogens, and (iii) whether individual D-type cyclins are essential components of Shh proliferative signaling in CGNPs. Our results indicate that Shh can drive continued cycling in immature, proliferating CGNPs. Shh treatment resulted in sustained activity of the G(1) cyclin-Rb axis by regulating levels of cyclinD1, cyclinD2, and cyclinE mRNA transcripts and proteins. Analysis of CGNPs from cyclinD1(-/-) or cyclinD2(-/-) mice demonstrates that the Shh proliferative pathway does not require unique functions of cyclinD1 or cyclinD2 and that D-type cyclins overlap functionally in this regard. In contrast to many known mitogenic pathways, we show that Shh proliferative signaling is mitogen-activated protein kinase independent. Furthermore, protein synthesis is required for early effects on cyclin gene expression. Together, our results suggest that Shh proliferative signaling promotes synthesis of regulatory factor intermediates that upregulate or maintain cyclin gene expression and activity of the G(1) cyclin-Rb axis in proliferating granule neuron precursors.

Animals↗
PubMed1998

Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo.

One of the earliest documented molecular events after sciatic nerve injury in adult rats is the rapid, long-term upregulation of the immediate early gene transcription factor c-Jun mRNA and protein in lumbar dorsal root ganglion (DRG) neurons, suggesting that c-Jun may regulate genes that are important both in the early post-injury period and during later peripheral axonal regeneration. However, neither the mechanism through which c-Jun protein is increased nor the level of its post-injury transcriptional activity in axotomized DRGs has been characterized. To determine whether transcriptional activation of c-Jun occurs in response to nerve injury in vivo and is associated with axonal regeneration, we have assayed axotomized adult rat DRGs for evidence of jun kinase activation, c-Jun phosphorylation, and activator protein-1 (AP-1) binding. We report that sciatic nerve transection resulted in chronic activation of c-Jun amino-terminal kinase-1 (JNK) in L4/L5 DRGs concomitant with c-Jun amino-terminal phosphorylation in neurons, and lasting AP-1 binding activity, with both c-Jun and JunD participating in DNA binding complexes. The timing of JNK activation was dependent on the distance of the axotomy site from the DRGs, suggesting the requirement for a retrograde transport-mediated signal. AP-1 binding and c-Jun protein returned to basal levels in DRGs as peripheral regeneration was completed but remained elevated in the case of chronic sprouting, indicating that c-Jun may regulate target genes that are involved in axonal outgrowth.

Animals↗
PubMed1998

Rescue of alpha-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo.

Small (18-25 microm diam) dorsal root ganglion (DRG) neurons are known to express high levels of tetrodotoxin-resistant (TTX-R) sodium current and the mRNA for the alpha-SNS sodium channel, which encodes a TTX-R channel when expressed in oocytes. These neurons also preferentially express the high affinity receptor for nerve growth factor (NGF), TrkA. Levels of TTX-R sodium current and of alpha-SNS mRNA are reduced in these cells after axotomy. To determine whether NGF participates in the regulation of TTX-R current and alpha-SNS mRNA in small DRG neurons in vivo, we axotomized small lumbar DRG neurons by sciatic nerve transection and administered NGF or Ringer solution to the proximal nerve stump using osmotic pumps. Ten to 12 days after pump implant, whole cell patch-clamp recording demonstrated that TTX-R current density was decreased in Ringer-treated axotomized neurons (154 +/- 45 pA/pF; mean +/- SE) compared with nonaxotomized control neurons (865 +/- 123 pA/pF) and was restored partially toward control levels in NGF-treated axotomized neurons (465 +/- 78 pA/pF). The V1/2 for steady-state activation and inactivation of TTX-R currents were similar in control, Ringer- and NGF-treated axotomized neurons. Reverse transcription polymerase chain reaction revealed an upregulation of alpha-SNS mRNA levels in NGF-treated compared with Ringer-treated axotomized DRG. In situ hybridization showed that alpha-SNS mRNA levels were decreased significantly in small Ringer-treated axotomized DRG neurons in vivo and also in small DRG neurons that were dissociated and maintained in vitro, so as to correspond to the patch-clamp conditions. NGF-treated axotomized neurons had a significant increase in alpha-SNS mRNA expression, compared with Ringer-treated axotomized cells. These results show that the administration of exogenous NGF in vivo, to the proximal nerve stump of the transected sciatic nerve, results in an upregulation of TTX-R sodium current and of alpha-SNS mRNA levels in small DRG neurons. Retrogradely transported NGF thus appears to participate in the control of excitability in these cells via actions that include the regulation of sodium channel gene expression in vivo.

Animals↗
PubMed1997

Temporal variability of jun family transcription factor levels in peripherally or centrally transected adult rat dorsal root ganglia.

Enhanced chemiluminescent (ECL) immunoblotting was used to quantitatively assess the initial changes in jun family transcription factor protein levels in adult rat lumbar dorsal root ganglia (DRG) after peripheral axotomy and dorsal root transection, and to study the effects of neurotrophic factor administration on these changes. Transection of central (dorsal root) or peripheral (spinal nerve) branches of DRG neurons resulted in rapid elevation of c-jun protein levels, which was transient after dorsal root transection but sustained, though slightly attenuated, after spinal nerve transection. These results suggest that injury-induced c-jun elevation is biphasic, consisting of an early, transient, injury-initiated phase and a more prolonged secondary phase specific to peripheral target disconnection. c-jun protein changes were not modulated by administration of NGF or BDNF. Immunohistochemistry was used to localize c-jun protein induction to DRG neurons. Using ECL immunoblotting, we also observed temporally regulated increases in junD protein levels after both injuries. A transient up-regulation of junB was detected by immunoblotting 5 days after peripheral axotomy, coincident with a slight decrease in c-jun protein levels.

Animals↗
PubMed1997

Timing of c-jun protein induction in lumbar dorsal root ganglia after sciatic nerve transection varies with lesion distance.

In situ hybridization and immunohistochemical studies have shown that sciatic nerve crush or transection induces upregulation of the immediate early gene c-jun mRNA and protein in lumbar dorsal root ganglion neurons. Here we have used enhanced chemiluminescent (ECL) immunoblotting as a sensitive and quantitative way of measuring the time of course of c-jun protein induction following sciatic nerve transection at two distances from the L4 and L5 dorsal root ganglia. c-Jun protein was first detected within 3 h of proximal sciatic nerve transection and within 6 h of distal nerve transection. These results indicate substantially earlier increases in c-jun protein after nerve injury than previously reported, which can be attributed to the sensitivity of this detection method. The earlier induction of c-jun after proximal as compared to distal nerve transection supports the hypothesis that the c-jun response to sciatic nerve injury involves a distance-dependent signalling mechanism.

Animals↗
PubMed1979

Copulatory behavior and the initiation of pregnancy in California voles (Microtus californicus).

The copulatory behavior of Microtus californicus and its effect on pregnancy initiation were examined in two experiments. In experiment 1 18 males and 18 females which had received exogenous hormones participated in 54 tests of copulatory behavior, each continued to a satiety criterion of 30 min with no copulations. The basic pattern involved no lock, intravaginal thrusting, ejaculation possible on a single insertion and multiple ejaculation. Ejaculation frequency ranged from 1 to 5, with a mean of 2.2. In experiment 2, it was found that all females receiving satiety tests of copulatory behavior while in male-induced estrus ovulated and became pregnant. Whereas all 10 females receiving one ejaculation ovulated, only 60% became pregnant. Thus, it appears that copulation beyond one ejaculation functions in increasing the likelihood of pregnancy. By comparing different species of Microtus it is proposed that copulatory patterns in which males persist for many thrusts and ejaculations may have evolved in conjunction with ornate penile morphology, large litter sizes, and high stimulus requirements for the initiation of ovulation and a funtional luteal phase.

Animals↗
PubMed1977

Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys.

The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys.

Age Factors↗
PubMed1977

Effects of vaginal-cervical stimulation in seven species of muroid rodents.

Six species of muroid rodents (Peromyscus californicus, P. eremicus, P. gossypinus, Mesocricetus auratus, Rattus norvegicus and R. rattus) were given artificlal vaginal-cervical stimulation in an attempt to induce pseudopregnancy. Some females of each species became pseudopregnant, but it was not clear that stimulation patterns mimicking the copulatory patterns of conspecific males were more effective than other patterns of stimulation. In the non-domesticated species (Peromyscus and R. rattus) a few females responded to a variety of stimulus conditions, and no species differences in responsiveness among the wild species were evident. The established laboratory rodents (R. norvegicus, M. auratusy were markedly more responsive to artificial stimulation, suggesting possible effects of domestication on fecundity and reactions to handling- Microtus ochrogaster, an induced ovulator, ovulated in response to vaginal-cervical stimulation only if one intromission from a male was also provided. No other differences in the responses of reflex and spontaneous ovulators were apparent.

Animals↗
PubMedDate not supplied

Expanding Medicaid coverage for pregnant women: estimates of the impact and cost.

An estimated 361,000 pregnant women are expected to be newly eligible for Medicaid coverage when all states raise the income ceiling for such coverage to 100 percent of the federal poverty level by 1990, as Congress has mandated. According to a methodology for projecting the effects of recent congressional changes in the Medicaid program, about 64 percent of these women would be otherwise uninsured, at least for maternity care, and the rest would have some insurance, so Medicaid would be the payer of last resort. Congress has also given states the option to cover pregnant women with incomes from 100 to 185 percent of poverty. If all states were to do so, another 552,000 women would become eligible, 29 percent of whom would otherwise have no insurance coverage for maternity care. The estimate of newly eligible women with incomes below 185 percent of poverty represents 24 percent of the 3.8 million women who give birth in the United States each year. Under the 100-percent-of-poverty ceiling, the estimated number of poor women eligible for coverage ranges from 4,000 or fewer in 18 states and the District of Columbia to 41,000 in California and Texas. At 185 percent of poverty, the number ranges from 4,000 or fewer in 11 states and the District of Columbia to more than 90,000 in California and Texas. Eight states have already elected to extend Medicaid coverage to the 185-percent-of-poverty ceiling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Sex education and AIDS education in the schools: what states and large school districts are doing.

Four-fifths of the states either require or encourage the teaching of sex education in the public schools, and nearly nine in 10 large school districts across the United States support such instruction. All but four states and virtually every large school district support the provision of AIDS education, and backing for instruction about sexually transmitted diseases and about abstinence is nearly as widespread. Fewer states and districts (two-thirds and four-fifths, respectively) require or encourage the schools to teach about pregnancy prevention. Examination of state and district curricula indicates that large school districts tend to be bolder than the states in the range of sex-related topics covered, especially in the area of pregnancy prevention. Districts also offer local educators more support (through curricula, training and other activities) than do the states. Finally, AIDS education appears to be receiving more attention and funding from both the states and the local school districts than is sex education.

Acquired Immunodeficiency Syndrome↗