Biomedical subjects

A P King

Publications and source records attributed to A P King.

At least 19 recordsLinked to original sources

PubMed2001

The rat approximates an ideal detector of changes in rates of reward: implications for the law of effect.

Rats responded on 2 levers delivering brain stimulation reward on concurrent variable interval schedules. Following many successive sessions with unchanging relative rates of reward, subjects adjusted to an eventual change slowly and showed spontaneous reversions at the beginning of subsequent sessions. When changes in rates of reward occurred between and within every session, subjects adjusted to them about as rapidly as they could in principle do so, as shown by comparison to a Bayesian model of an ideal detector. This and other features of the adjustments to frequent changes imply that the behavioral effect of reinforcement depends on the subject's perception of incomes and changes in incomes rather than on the strengthening and weakening of behaviors in accord with their past effects or expected results. Models for the process by which perceived incomes determine stay durations and for the process that detects changes in rates are developed.

Animals↗

PubMed2001

Cultural transmission of vocal traditions in cowbirds (Molothrus ater) influences courtship patterns and mate preferences.

In this study, the authors tested the cultural transmission of vocal traditions in cowbirds (Molothrus ater). Young cowbirds from a South Dakota (SD) population were housed over winter with adults of the SD population or with adults from an Indiana (IN) population. Song differences between the original SD and IN adult models were acquired by South Dakota culture (SDC) and Indiana culture (INC) males, respectively, and were transmitted to a 2nd cultural generation of birds. During playback tests of SDC and INC songs, SD females gave more copulatory responses to SDC songs. Finally, males with SD-like songs courted SDC females preferentially in breeding season tests, whereas males with IN-like songs courted INC females preferentially. These results indicate that the transmission of vocal traditions plays a fundamental role in the courtship patterns and mating decisions of cowbirds.

Animals↗

PubMed2001

Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases.

The authors report a series of 10 low-grade neoplasms arising in the midline anteriorly in the region of the septum pellucidum with many of the histologic features of dysembryoplastic neuroepithelial tumor (DNT). The patients (five female, five male) ranged in age from 6 to 35 years (mean age, 21.5 years). The most common presenting symptoms were headache, nausea and vomiting, and visual disturbances. Radiographically, the tumors extended into the lateral ventricles from the septal region and obstructed the foramen of Monro. Varying degrees of hydrocephalus were present. The lesions were lobular, well-delineated, hypointense to brain on T1-weighted magnetic resonance imaging, and hyperintense on T2-weighted images. They were uniformly nonenhancing or showed only minimal peripheral enhancement. The tumors, in aggregate, had the histologic features of DNT. These included a mucin-rich background, oligodendrocyte-like cells, "floating neurons," and a "specific glioneuronal element." Seven patients underwent gross total resection and two underwent subtotal resection. No patients received adjuvant chemotherapy or radiotherapy. On follow-up (n = 6; median, 14 months), all tumors had either not recurred or were radiologically stable. On the basis of both neuroimaging and histopathology, DNT-like lesions should be considered in the differential diagnosis of midline intraventricular tumors in children and young adults. Distinction from more aggressive neoplasms is essential because these tumors appear to behave in a benign fashion.

Adolescent↗

PubMed2000

Locking acrylic resin dental stent for image-guided surgery.

This article presents a procedure for fabricating a locking acrylic resin dental stent for use in image-guided base-of-skull surgery and neurosurgery. The stent offers advantages over conventional bone screw-anchored systems to surgeons and patients. In view of the increasing use of image guidance in base-of-skull surgery and neurosurgery, prosthodontists will meet a growing demand for this type of device in the future.

Acrylic Resins↗

PubMed2000

Design and evaluation of a system for microscope-assisted guided interventions (MAGI).

The problem of providing surgical navigation using image overlays on the operative scene can be split into four main tasks--calibration of the optical system; registration of preoperative images to the patient; system and patient tracking, and display using a suitable visualization scheme. To achieve a convincing result in the magnified microscope view a very high alignment accuracy is required. We have simulated an entire image overlay system to establish the most significant sources of error and improved each of the stages involved. The microscope calibration process has been automated. We have introduced bone-implanted markers for registration and incorporated a locking acrylic dental stent (LADS) for patient tracking. The LADS can also provide a less-invasive registration device with mean target error of 0.7 mm in volunteer experiments. These improvements have significantly increased the alignment accuracy of our overlays. Phantom accuracy is 0.3-0.5 mm and clinical overlay errors were 0.5-1.0 mm on the bone fiducials and 0.5-4 mm on target structures. We have improved the graphical representation of the stereo overlays. The resulting system provides three-dimensional surgical navigation for microscope-assisted guided interventions (MAGI).

Computer Simulation↗

PubMed2000

Functional expression of L-, N-, P/Q-, and R-type calcium channels in the human NT2-N cell line.

The biophysical and pharmacological properties of voltage-gated calcium channel currents in the human teratocarcinoma cell line NT2-N were studied using the whole cell patch-clamp technique. When held at -80 mV, barium currents (I(Ba)s) were evoked by voltage commands to above -35 mV that peaked at +5 mV. When holding potentials were reduced to -20 mV or 5 mM barium was substituted for 5 mM calcium, there was a reduction in peak currents and a right shift in the current-voltage curve. A steady-state inactivation curve for I(Ba) was fit with a Boltzmann curve (V(1/2) = -43.3 mV; slope = -17.7 mV). Maximal current amplitude increased from 1-wk (232 pA) to 9-wk (1025 pA) postdifferentiation. Whole cell I(Ba)s were partially blocked by specific channel blockers to a similar extent in 1- to 3-wk and 7- to 9-wk postdifferentiation NT2-N cells: 10 microM nifedipine (19 vs. 25%), 10 microM conotoxin GVIA (27 vs. 25%), 10 microM conotoxin MVIIC (15 vs. 16%), and 1.75 microM SNX-482 (31 vs. 33%). Currents were completely blocked by 300 microM cadmium. In the presence of nifedipine, GVIA, and MVIIC, approximately 35% of current remained, which was reduced further by SNX-482 (7-14% of current remained), consistent with functional expression of L-, N-, and P/Q-calcium channel types and one or more R-type channel. The presence of multiple calcium currents in this human neuronal-type cell line provides a potentially useful model for study of the regulation, expression and cellular function of human derived calcium channel currents; in particular the R-type current(s).

Calcium Channel Blockers↗

PubMed1999

A system for microscope-assisted guided interventions.

We present a system for surgical navigation using stereo overlays in the operating microscope aligned to the operative scene. This augmented reality system provides 3D information about nearby structures and offers a significant advancement over pointer-based guidance, which provides only the location of one point and requires the surgeon to look away from the operative scene. With a previous version of this system, we demonstrated feasibility, but it became clear that to achieve convincing guidance through the magnified microscope view, a very high alignment accuracy was required. We have made progress with several aspects of the system, including automated calibration, error simulation, bone-implanted fiducials and a dental attachment for tracking. We have performed experiments to establish the visual display parameters required to perceive overlaid structures beneath the operative surface. Easy perception of real and virtual structures with the correct transparency has been demonstrated in a laboratory and through the microscope. The result is a system with a predicted accuracy of 0.9 mm and phantom errors of 0.5 mm. In clinical practice errors are 0.5-1.5 mm, rising to 2-4 mm when brain deformation occurs.

Bone Cysts↗

PubMed1999

kappa- and mu-Opioid inhibition of N-type calcium currents is attenuated by 4beta-phorbol 12-myristate 13-acetate and protein kinase C in rat dorsal root ganglion neurons.

In rat dorsal root ganglion neurons, activation of kappa- and mu-opioid receptors decreases N-type calcium current, whereas a constitutively active form of protein kinase C (PKC; i.e., PKM, a PKC catalytic subunit fragment) increases N-type calcium current. PKC also attenuates inhibition of calcium current by several G protein-linked neurotransmitter systems. We examined the effects of activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) and dialysis of cells with PKM and a pseudosubstrate inhibitor PKC(19-31) (PKC-I) on kappa- and mu-opioid-mediated inhibition of calcium current, calcium current amplitude, and rundown. PMA modestly increased peak calcium current and substantially reduced calcium current "rundown," effects blocked by PKC-I. In contrast, PKC-I decreased calcium current and increased current rundown. PMA attenuated morphine-, dynorphin A-, and U50, 488- but not pentobarbitol-related inhibition of calcium current. Similar effects were seen with intracellular dialysis of PKM. Intracellular PKC-I did not block opioid inhibition of calcium current but did reverse PMA and PKM effects on opioid receptor coupling to calcium channels. Because neither PMA nor PKM changed the proportion of omega-CgTX-inhibited current, their effects were not due to a decrease in the proportion of N-type current. After omega-CgTX treatment, there were no differences in the dynorphin A effects on control and PMA- or PKM-treated neurons, suggesting that PKC primarily affected coupling to N-type calcium channels. These data suggest that in acutely dissociated rat dorsal root ganglion neurons, endogenous PKC is required for maintenance of calcium current, may play a role in regulation of neuronal calcium channels, and could be involved in tolerance and/or cross-talk inhibition of opioid responsiveness.

Animals↗

PubMed1999

Stereo augmented reality in the surgical microscope.

We present an augmented reality system that allows surgeons to view features from preoperative radiological images accurately overlaid in stereo in the optical path of a surgical microscope. The purpose of the system is to show the surgeon structures beneath the viewed surface in the correct 3-D position. The technical challenges are registration, tracking, calibration and visualisation. For patient registration, or alignment to preoperative images, we use bone-implanted markers and a dental splint is used for patient tracking. Both microscope and patient are tracked by an optical localiser. Calibration uses an accurately manufactured object with high contrast circular markers which are identified automatically. All ten camera parameters are modelled as a bivariate polynomial function of zoom and focus. The overall system has a theoretical overlay accuracy of better than 1 mm. Implementations of the system have been tested on seven patients. Recent measurements in the operating room conformed to our accuracy predictions. For visualisation the system has been implemented on a graphics workstation to enable high frame rates with a variety of rendering schemes. Several issues of 3-D depth perception remain unsolved, but early results suggest that perception of structures in the correct 3-D position beneath the viewed surface is possible.

Depth Perception↗

PubMed1997

A brain of her own: a neural correlate of song assessment in a female songbird.

The song control region in the avian forebrain is a series of discrete, interconnected nuclei mediating song learning and production. It has been studied in males or in species where both sexes sing. Little is known about the neural correlates of song perception in nonsinging females, often the intended recipients of song. We studied cowbirds (Molothrus ater), a species in which only males sing but in which females discriminate between males on the basis of song. We focused on nucleus lMAN because it has been implicated in early song acquisition, a stage relevant to both sexes to choose among competing acoustic models. We found that volume of lMAN was monomorphic in cowbirds. Moreover, the volume and neuronal number of female lMAN were positively correlated with selectivity of copulatory responding. The results provide strong evidence of nonsinging female's use of "song" control nuclei for song perception without the possibility of song production.

Animal Communication↗

PubMed1997

Imaging and pathological features of primary malignant rhabdoid tumours of the brain and spine.

In this article two cases of primary malignant extrarenal rhabdoid tumour are described. In the affected children the brain and the spinal cord were the primary sites of origin of the tumour. The imaging findings are presented and the pathology discussed. Although the imaging features are non-specific, rhabdoid tumour should be included in the differential diagnosis of childhood intracranial and spinal neoplasms.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Distinct cytoplasmic domains of the growth hormone receptor are required for glucocorticoid- and phorbol ester-induced decreases in growth hormone (GH) binding. These domains are different from that reported for GH-induced receptor internalization.

Glucocorticoids inhibit growth in children and antagonize the growth-promoting action of GH in peripheral tissues. Recently, they have been shown to decrease GH binding. In this study we examine the molecular mechanisms by which the glucocorticoid dexamethasone (DEX) and the phorbol ester phorbol myristate acetate (PMA) decrease cellular GH binding. In 3T3-F442A fibroblasts, DEX and PMA decrease the number of GH receptors (GHRs) capable of binding GH by 50% (t1/2 = 6 h) and 70% (t1/2 = 15 min), respectively. Neither appear to decrease the total number of cellular GHR. Rather, they appear to redistribute GHRs away from the plasma membrane or inactivate GHRs on the membrane such that they cannot bind GH. DEX and PMA also decrease GH-induced tyrosyl phosphorylation of GHR and JAK2 with a magnitude and time course correlating with that of inhibition of GH binding. DEX- and PMA-induced reductions of GH binding are also observed in a Chinese hamster ovary (CHO) cell line stably transfected with a rat liver GHR cDNA, further arguing that DEX and PMA act post-translationally on GHR. Using mutant GHRs stably expressed in CHO cells, amino acids 455-506 and tyrosines 333 and/or 338 of GHR were shown to be required for maximal DEX-induced inhibition of GH binding. DEX decreased GH binding to a GHR mutant F346A, which is reported to be deficient in ligand-induced internalization, suggesting that DEX decreases GH binding by a mechanism distinct from that of ligand-induced GHR internalization. PMA reduced GH binding to CHO cells expressing all GHR mutants tested. However, deletion of the C-terminal 132 amino acids decreased this effect, suggesting that at least one component of PMA action on GHR requires amino acids 507-638. These data suggest that distinct pathways mediate the effects of GH, DEX, and PMA on GHR number in the plasma membrane.

3T3 Cells↗

PubMed1996

Social malleability in cowbirds: new measures reveal new evidence of plasticity in the eastern subspecies (Molothrus ater ater).

The social experiences of young Molothrus ater ater cowbirds were manipulated in a 2-year study. In the 1st year, males were housed with pairs of canaries. The males were tested in 3 social contexts. Also, vocal repertoires were recorded and played back to females. In contrast to a previous study of the M. a. artemisiae subspecies, the males did not vocalize to the canaries in courtship tests (T. M. Freeberg, A. P. King, & M. J. West, 1995) but showed incompetent courtship of female cowbirds. In their 2nd year, half of the males were housed with older males and female cowbirds, and half were housed with only females. Those exposed to older males courted much more successfully than did those deprived of such experience. All males developed new repertoires, and song potencies did not correlate across years. The data reveal intraspecific variation in the ontogeny of mate recognition but intraspecific dependence on social learning to acquire courtship skills.

Animals↗

PubMed1996

Signalling pathway of GH.

GH has long been known as a regulator of body growth and metabolism, yet its mechanism of action at the cellular level has been elusive. We have recently shown that GH promotes the rapid association of GH receptor with the tyrosine kinase JAK2, activates JAK2, and promotes the tyrosyl phosphorylation of both JAK2 and GH receptor. This suggests that the initial signalling event in GH action is the activation of JAK2 which in turn phosphorylates tyrosines within JAK2 and GH receptor. We have identified a number of proteins that appear to bind to these phosphotyrosines in GH receptor/ JAK2 complexes. These proteins in turn become phosphorylated on tyrosines, resulting in their activation. These proteins include: 1) the signal transducers and activators of transcriptions (Stats) 1, 3 and 5 which have been implicated as regulators of transcription of a variety of genes; 2) the insulin receptor substrates (IRS) 1 and 2, which are believed to mediate some of the metabolic effects of GH; and 3) Shc proteins which lie upstream of Ras and the mitogen activator kinases (MAP) designated ERKs 1 and 2, proteins implicated in the regulation of cellular growth and/or differentiation. These various proteins work in concert with each other and with other signalling molecules to elicit the diverse effects of GH. Other hormones and growth factors also activate JAK kinases. Specificity in signalling was investigated by determining whether signalling pathways for particular ligands may be selectively inhibited by hormones or growth factors. Glucocorticoids were found to selectively decrease binding and cellular signalling in response to GH. This decrease appeared to be due to a decrease in the number of GH receptors in the plasma membrane. Using truncated and mutated GHR, two regions of the GH receptor were identified required for the inhibitory effect of glucocorticoids. Interestingly, they appeared to differ from the region required for GH-induced internalization. Hence, a large amount of insight into signalling by GH has been obtained during the 3 years since JAK2 was identified as a signalling molecule for GH and other ligands that bind to members of the cytokine receptor family. This new insight, and the insight that will continue to be gained in the next few years should enable the design of new and better therapeutic uses of GH and the other ligands that bind to JAK kinase-linked receptors.

Animals↗

PubMed1995

Biphasic synovial sarcoma in the small intestinal mesentery.

BACKGROUND: A 46-year-old man presented with recurrent anemia and polyarthralgia. Investigations revealed a mass in the ileal mesentery, which was resected. Results of routine histologic examination suggested a diagnosis of synovial sarcoma, a rare malignancy usually not reported at this site. METHODS: Tissue was examined immunohistochemically, ultrastructurally, and by fluorescent in situ hybridization to confirm the diagnosis. RESULTS: Immunohistochemical studies revealed widespread labeling for cytokeratins and focal labeling for desmin and vimentin in the epithelial component, with labeling for epithelial membrane antigen in the epithelial and spindle-cell components. Fluorescent in situ hybridization analysis showed the characteristic t(X;18) translocation of synovial sarcoma. CONCLUSIONS: This is a unique case of synovial sarcoma in the small intestinal mesentery. Immunohistochemical labeling confirmed the diagnosis, although, to the authors' knowledge, the pattern of desmin labeling has not been described previously. The clinical association with polyarthralgia, which resolved after removal of the neoplasm, also has not been described previously.

Desmin↗

PubMed1995

Ultrastructure of rat pulmonary arterioles after neonatal exposure to hypoxia and subsequent relief and treatment with monocrotaline.

A group of rats was born in and spent the first 4 weeks of life at a simulated altitude of 3550 m. Two animals were killed immediately afterwards and the remaining 16 were allowed to recover for various times up to a maximum of 12 weeks at sea-level atmospheric pressure. On ultrastructural examination, the pulmonary arterioles of hypoxic rats showed muscularization, the new layer of mature smooth muscle cells containing abundant organelles and myofilaments. These cells were bounded by prominent elastic laminae. During the recovery period, the medial layer became progressively thinned, but the cells still retained some characteristics of smooth muscle by 12 weeks' recovery. When a similar group of ten hypoxic rats was allowed to recover for 12 weeks before being given monocrotaline, there was early enlargement of the residual smooth muscle cells in the media of pulmonary arterioles and within 5 weeks there was again a thick layer of medial smooth muscle. This was in contrast to the sparse, weakly muscularized arterioles seen in eight similarly treated rats born under normoxic conditions. The relevance is discussed of these findings to the rare occurrence of primary pulmonary hypertension in people who were born at high altitude but returned to sea-level during childhood.

Altitude↗

PubMed1995

Dexamethasone-induced antagonism of growth hormone (GH) action by down-regulation of GH binding in 3T3-F442A fibroblasts.

Supraphysiological levels of glucocorticoids, whether endogenous (Cushing's syndrome) or exogenous (glucocorticoid therapy), inhibit growth in children and immature animals. This effect has long been suspected to be due to glucocorticoid antagonism of GH action at the level of peripheral tissues. In the present study we demonstrate direct antagonism of GH action at the cellular level by the artificial glucocorticoid dexamethasone. Dexamethasone was found to inhibit the ability of GH to elicit several early events in GH signaling in 3T3-F442A fibroblasts. Dexamethasone (100 nM) for 24 h decreases by 50-75% GH-induced tyrosyl phosphorylation of mitogen-activated protein kinases ERK1 and ERK2, the transcription factor Stat3/APRF, the GH receptor-associated tyrosine kinase JAK2, and the GH receptor. These effects appear to be specific to GH. Dexamethasone does not inhibit induction of tyrosyl phosphorylation of ERK proteins by epidermal growth factor or phorbol myristate acetate, nor does it block induction of tyrosyl phosphorylation of Stat3/APRF by leukemia inhibitory factor or interleukin-6, or induction of JAK2 by leukemia inhibitory factor or interferon-gamma. Dexamethasone does not decrease the expression of ERK1 or -2, Stat3, or JAK2 proteins. Rather, the effects of dexamethasone on GH action appear to be due to a decrease in the number of GH receptors in the plasma membrane. Twenty-four-hour treatment with dexamethasone leads to a 50% decrease i GH binding, which Scatchard analysis suggests is due to a decrease in GH receptor number. These findings suggest that glucocorticoids antagonize cellular GH action by decreasing GH binding, suggesting a mechanism by which systemic glucocorticoids could antagonize GH action in peripheral tissues.

3T3 Cells↗

PubMed1993

Effect of TMB-8 on alpha-adrenoceptor agonist and KC1 induced-contractions in isolated rabbit aorta.

1. TMB-8 (10(-6) M-10(-4) M) depresses the contractile effect of the selective alpha 1-adrenoceptor agonists methoxamine and phenylephrine in the isolated rabbit aorta. 2. TMB-8 also depresses contractions evoked by 80 mM KCl in this tissue when used at similar concentrations. 3. The calcium antagonist nifedipine potentiates the inhibitory effect of TMB-8 on the alpha 1-contractions. 4. In preparations mounted in Ca-free solution containing 0.5 mM EGTA, 10(-4) M TMB-8 markedly depressed the contractions caused by both alpha 1-adrenoceptor agonists. 5. The Ca2+ agonist BAY K 8644 (10(-6) M) partially prevented the inhibitory effect of TMB-8 on 80 mM KCl contractions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗