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Biomedical subjects

K K Miller

Publications and source records attributed to K K Miller.

33 records · Page 2Linked to original sources
PubMed1998

Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake.

Leptin is a protein encoded by the ob gene and expressed in adipocytes. A sensitive marker of nutritional status, leptin is known to correlate with fat mass and to respond to changes in caloric intake. Leptin may also be an important mediator of reproductive function, as suggested by the effects of leptin infusions to restore ovulatory function in an animal model of starvation. We hypothesized that leptin levels are decreased in women with hypothalamic amenorrhea and that leptin may be a sensitive marker of overall nutritional status in this population. We, therefore, measured leptin levels and caloric intake in 21 women with hypothalamic amenorrhea (HA) and 30 age-, weight-, and body fat-matched eumenorrheic controls. Age (24 +/- 5 vs. 24 +/- 3 yr), body mass index (20.6 +/- 1.3 vs. 21.1 +/- 1.5 kg/m2), percent ideal body weight (94.9 +/- 5% vs. 96.3 +/- 6.3%), and fat mass (14.2 +/- 3.6 vs. 15.5 +/- 2.9 kg, determined by dual energy x-ray absortiometry) did not differ between the groups. Leptin levels were significantly lower in the HA subjects compared with those in the controls (7.1 +/- 3.0 vs. 10.6 +/- 4.9 micrograms/L; P = 0.005). Total caloric intake (1768 +/- 335 vs. 2215 +/- 571 cal/day; P = 0.003), fat intake (333 +/- 144 vs. 639 +/- 261 cal/day; P < 0.0001), and insulin levels (5.6 +/- 1.2 vs. 7.4 +/- 3.2 microU/mL; P = 0.015) were lower in the women with HA than in the eumenorrheic controls. The difference in leptin levels remained significant after controlling for insulin (P = 0.023). These data are the first to demonstrate hypoleptinemia, independent of fat mass, in women with HA. The hypoleptinemia may reflect inadequate calorie intake, fat intake, and/or other subclinical nutritional disturbances in women with HA. The mechanism and reproductive consequences of low leptin in this large population of women remain unknown.

Adult↗
PubMed1997

Cholecystokinin increases GABA release by inhibiting a resting K+ conductance in hippocampal interneurons.

Cholecystokinin (CCK) is found co-localized with the inhibitory neurotransmitter GABA in interneurons of the hippocampus. Also, CCK receptors are found in abundance in this brain region. The possibility that CCK alters interneuron activity was examined using whole-cell current- and voltage-clamp recordings from visualized interneurons in the stratum radiatum of area CA1 in rat hippocampal slices. The effect of CCK on GABA-mediated IPSCs was also determined in pyramidal neurons. The sulfated octapeptide CCK-8S increased action potential frequency or generated inward currents in the majority of interneurons. These effects of CCK persisted in the presence of tetrodotoxin and cadmium, suggesting that they were direct. Current-voltage plots revealed that CCK-8S inhibited a conductance that was linear across command potentials and reversed near the equilibrium potential for K+ ions. The K+ channel blocker tetraethylammonium (10 mM) generated inward currents similar to those initiated by CCK, and it occluded the effect of the peptide. BaCl2 (1 mM) and 4-aminopyridine (2 mM) did not alter the effect of CCK. The CCKB receptor antagonist PD-135,158 completely blocked the inward currents generated by CCK-8S. CCK also resulted in an increase in spontaneous action potential-dependent IPSC frequency, but no changes in action potential-independent miniature IPSCs or evoked IPSCs in pyramidal neurons. These results provide evidence that CCK can depolarize hippocampal interneurons through the inhibition of a resting K+ conductance, leading to increased tonic inhibition of pyramidal neurons. This action of CCK may contribute to its anticonvulsant properties, as observed in limbic seizure models.

Animals↗
PubMed1997

Neuropeptide FF inhibition of morphine effects in the rat hippocampus.

Opioids have an excitatory effect on CA1 pyramidal neurons in the hippocampus due to the inhibition of gamma-aminobutyric acid (GABA) release from interneurons. Electrophysiologically, this pyramidal cell excitation is mainfest as an increase in extracellularly recorded population spikes, while the reduction in synaptic GABA release is manifest as a decrease in the amplitude of intracellularly recorded inhibitory postsynaptic potentials (IPSPs). Recent studies suggest that some of the behavioral effect of opioids, such as antinociceptin, can be inhibited antiopioid peptides such as neuropeptide FF (NPFF). In the present study, we have used the hippocampal response to opioids to examine the potential interactions between morphine and NPFF in vitro. Morphine alone (20-200 microM) caused reversible concentration-dependent increases in population spikes and decreases in IPSPs. In extracellular experiments, NPFF (1 microM) alone had no effect on population spikes, but significantly and concentration-dependently inhibited the morphine-induced increases in these responses. Intracellular experiments indicated that while NPFF had no effect on IPSP amplitude, or other pyramidal neurons membrane properties (membrane potential, input resistance, afterhyperpolarization, action potential frequency), it significantly reduced the decrease in IPSP amplitude caused by morphine. These results demonstrate that NPFF can attenuate the effects of morphine on population spikes and IPSPs in the hippocampus, and suggest that this effect occurs at a presynaptic site, possibly involving GABAergic interneurons.

Action Potentials↗
PubMed1994

Morphine-induced excitation of pyramidal neurons is inhibited by cholecystokinin in the CA1 region of the rat hippocampal slice.

Opioids increase the excitability of CA1 pyramidal neurons in the hippocampus through the inhibition of gamma-aminobutyric acid release from interneurons. This can be observed extracellularly as an increase in population spike amplitude. The sulfated form of the neuropeptide cholecystokinin (CCK-8S) has been shown in a variety of in vivo models to inhibit the response to opioids. We have utilized the well-characterized hippocampal response to opioids to examine the potential interactions between morphine and the neuropeptide cholecystokinin (CCK) in vitro. Morphine (1-500 microM; EC50 = 22.1 microM, 95% confidence interval = 6.5-75.9 microM) alone caused concentration-dependent increases in CA1 population spike amplitudes that were reversible upon washout or application of the opioid antagonist naloxone (10 microM). In contrast to the morphine effect, CCK-8S (0.001-1 microM) had no effect alone on population spikes (99.1 +/- 1.6% of control, P > .05). However, when hippocampal slices were pretreated with CCK-8S (0.1-1 microM), the morphine-induced increase in population spike amplitudes was blocked in a noncompetitive, reversible manner (IC50 = 17.8 nM, 95% confidence interval = 9.5-33.7 nM). This antagonism of morphine action by CCK-8S was not seen when CCK-8S was added after the opiate had achieved its maximal effect, and was blocked completely by the application of the selective CCKB receptor antagonist PD-135, 158 (1.5 microM). The unsulfated form of CCK, unlike CCK-8S, did not antagonize the excitatory actions of morphine on population spikes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Effects of adenosine and cadmium on presynaptic fiber spikes in the CA1 region of rat hippocampus in vitro.

Adenosine was found to decrease the amplitude of presynaptic fiber spikes recorded in stratum radiatum of the CA1 region of the hippocampus following stimulation of the Schaffer collateral and commissural afferents. The presynaptic fiber spike reflects currents activated in the presynaptic fibers and nerve terminals of this projection. However, the effect of adenosine was largely the result of: (a) temporal overlap between the presynaptic fiber spike and the field EPSP response and (b) an indirect effect most likely related to the hyperpolarization of CA3 neurons giving rise to the Schaffer collateral fibers. When the CA3 region was separated by a knife cut from the CA1 region and the field EPSP blocked with 6,7-dinitroquinoxaline-2,3-dione, the effect of adenosine was markedly reduced, but was still significant (4.4 +/- 1.4% reduction in the amplitude of the presynaptic fiber spike). However, this action was not mimicked by the Ca2+ channel antagonist cadmium, suggesting that it did not reflect an inhibition of Ca2+ currents by adenosine. This effect was not observed in the presence of the K+ channel antagonists Ba2+ or diaminopyridine. These results suggest that adenosine may have a small hyperpolarizing effect on the presynaptic nerve terminals, but this is unlikely to be the mechanism by which adenosine modulates transmission in this brain region.

Adenosine↗
PubMed1991

Localization of an endoplasmic reticulum calcium ATPase mRNA in rat brain by in situ hybridization.

SERCA-2 is an endoplasmic reticulum Ca2+ ATPase present in brain [Gunteski-Hamblin A.-M. et al. (1988) J. biol. Chem. 263, 15032-15040]. We sought to map the distribution of this pump in the rat brain and investigate its relationship to Ca2+ uptake by brain endoplasmic reticulum. Using in situ hybridization and Northern blots with antisense oligonucleotide probes, we found that SERCA-2 is concentrated most densely in the cerebellum, especially in Purkinje cells, and in the hippocampus, with heavy labeling also in cortex, thalamus, pontine nuclei and the mitral cell layer of the olfactory bulb. 45Ca2+ uptake displayed a similar pattern with heaviest accumulation in cerebellum, hippocampus, cortex, thalamus and olfactory bulb. In corpus striatum and substantia nigra, relative 45Ca2+ accumulation was greater than SERCA-2 mRNA. Thus, SERCA-2 appears to be involved in Ca2+ uptake into endoplasmic reticulum in brain for release by inositol 1,4,5-trisphosphate and other agents.

Animals↗
PubMed1987

Stereoscopic contours and optokinetic nystagmus in normal and stereoblind subjects.

Moving stereoscopic contours in a dynamic random-dot stereogram have been previously shown to induce optokinetic nystagmus in subjects with normal stereopsis. For this to be validated as an objective test of stereopsis, stereoblind subjects must also be shown not to develop OKN, especially since it has been shown that the optomotor system of stereoblind individuals retains sensitivity to some cyclopean stimuli. In this report we verify that stereoblind subjects do not have an optomotor response to stereoscopic contours--regardless of the alignment angle at which the stereo image pair is presented.

Depth Perception↗
PubMed1986

Stereopsis in normal infants and infants with congenital esotropia.

We used electro-oculographic recordings of eye movement responses to a dynamic random-dot stereogram to assess stereopsis in normal infants and in infants with congenital esotropia. Normal infants showed an onset of stereopsis at about 4 months of age, consistent with previous reports. Four of nine infants with congenital esotropia demonstrated stereopsis when tested within two weeks of surgical alignment. No patient with congenital esotropia showed evidence of stereopsis when tested at a postoperative interval of more than two weeks.

Adult↗
PubMed1986

Vergence amplitudes with random-dot stereograms.

Random-dot stereograms were found to be capable of producing fusional vergence amplitudes in the absence of monocular contours. These vergence amplitudes are not an artefact of monocular contours provided by the target borders or test instrument and are comparable in range to vergence amplitudes measured clinically with second degree fusion targets in an amblyoscope. We conclude that diplopia of monocularly recognisable contours is not necessary for producing fusional vergence amplitudes.

Convergence, Ocular↗
PubMed1977

T1Wh, a promising mouse strain with chromosomal markers for cleft palate research.

Attainment of the horizontal position by the secondary palatal shelves and fusion in relationship to morphological and chronological ages in T1Wh, and albino strain of mice homozygous for a 5;19 Robertsonian translocation, was found to be late and slow in comparison to other strains previously investigated. Spontaneous and cortisone-induced cleft palate frequencies of 3.5% and 100% respectively, were found in this strain. Its slow and late palatal closure, high susceptibility to cortisone, obvious marker chromosomes, and good breeding performance promise to make T1Wh a useful strain for cleft palate research.

Abnormalities, Drug-Induced↗