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Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 109 records · Page 6Linked to original sources

Asymptomatic large hypothalamic hamartoma associated with polydactyly in an adult.

A hypothalamic hamartoma is a congenital tumor-like neural malformation. It is usually seen in children and is associated with neuroendocrinological symptoms, seizures, or psychological impairments. An asymptomatic hypothalamic hamartoma in an adult is extremely rare. This report describes an asymptomatic adult with a large hypothalamic hamartoma associated with polydactyly in his feet. Both polydactyly and hamartoma are rare lesions; therefore, this may not be a coincidental presentation. It is thought to have occurred in the embryonic period presumably between 37 and 40 gestational days.

Adult↗

Theoretical study of rectangular pulse electrical stimulation (RPES) onskin cells (in vivo) under conforming electrodes.

Our previous in vivo experimental results have shown RPES can enhance skin wound healing by using conforming electrodes. Based on an equation of polarization transmembrane voltage [Cole, K. S. 1972], two equations were derived to describe the peak RPES intensity on skin cells in vivo: (1) U = 1.5 a J/sigma, (2) Jm = 1.5 a (J/sigma) (Cm/tau). Where U: polarization transmembrane voltage. a: radius (R) for spherical cells or semi-length (L) for long fibers parallel to the electrical field. J: external imposed pulse current density under the electrode. sigma: average conductivity of skin tissue. Jm: transmembrane displacement current density. Cm: membrane capacitance per unit area and tau: time constant. Calculations indicated that the sensory fibers (SF) would receive the strongest stimulation compared to other cells in skin since generally LSF > or = 100 R. The sensitivity of SF to the stimulation could enhance skin wound healing as well as protect normal skin cells from harmful electroporation. From these theoretical calculations. We proposed a theoretical range of the pulse current density as: U1 sigma/(1.5 L) < or = J < or = U2 sigma/(1.5 L), where U1 and U2 are the excitation threshold voltage (about 0.01 V) and polarization electroporation voltage (about 0.1 V) for a SF respectively, for RPES to enhance skin wound healing.

Electric Conductivity↗

Schrodinger equation, Maxwell-Bolzmann distribution and a single channel current.

The dual nature, wave and particle, of ions in the biological system was considered. A theoretical model, based on the steady state Schrodinger equation and Maxwell-Bolzmann distribution of energy, is proposed to describe passive transport of ions through a biological membrane channel in a time independent field. Constant height (V2) and length(L) of the potential energy barrier and effective mass of ions are used in the model. This model shows that an ion may go through or be reflected from a channel whether its energy is lower or higher than the barrier. This is a departure from classical theory. Based on a published I-Vm (channel current-transmembrane voltage) curve from an activated K+ channel in a human erythrocyte membrane [Palle Christophersen, 1991], calculations with our model show that more than 99% of the channel current is contributed by ions with higher energy than the potential barrier. The current can be amplified 10,000 times while V2 is reduced from 0.45 eV (channel closed) to 0.20 eV (channel opened) at Vm = 0.07 V. In contrast, the current changes only 1.5% while L is narrowed from 90 A to 30 A at Vm = 0.07 V, V2 = 0.20 eV. The energy barrier: V2 = 0.16 + 0.43 Vm (eV), at r = 0.99, for 0.02 V < or = Vm < or = 0.12 V.

Biological Transport↗

Columns for visual features of objects in monkey inferotemporal cortex.

At early stages of the mammalian visual cortex, neurons with similar stimulus selectivities are vertically arrayed through the thickness of the cortical sheet and clustered in patches or bands across the surface. This organization, referred to as a 'column', has been found with respect to one-dimensional stimulus parameters such as orientation of stimulus contours, eye dominance of visual inputs, and direction of stimulus motion. It is unclear, however, whether information with extremely high dimensions, such as visual shape, is organized in a similar columnar fashion or in a different manner in the brain. Here we report that the anterior inferotemporal area of the monkey cortex, the final station of the visual cortical stream crucial for object recognition, consists of columns, each containing cells responsive to similar visual features of objects.

Animals↗

PMA-sensitive protein kinase C is not necessary in TRH-stimulated prolactin release from female rat primary pituitary cells.

In GH3 cells and other clonal rat pituitary tumor cells, TRH has been shown to mediate its effects on prolactin release via a rise of cytosolic Ca2+ and activation of protein kinase C. In this study, we examined the role of protein kinase C in TRH-stimulated prolactin release from female rat primary pituitary cell culture. Both TRH and PMA stimulated prolactin release in a dose-dependent manner. When present together at maximal concentrations, TRH and PMA produced an effect which was slightly less than additive. Pretreatment of rat pituitary cells with 10(-6) M PMA for 24 hrs completely down-regulated protein kinase C, since such PMA-pretreated cells did not release prolactin in response to a second dose of PMA. Interestingly, protein kinase C down-regulation had no effect on TRH-induced prolactin release from rat pituitary cells. In contrast, PMA-pretreated GH3 cells did not respond to a subsequent stimulation by either PMA or TRH. Pretreatment of rat pituitary cells with TRH (10(-7) M, 24 hrs) inhibited the subsequent response to TRH, but not PMA. Forskolin, an adenylate cyclase activator, stimulated prolactin release by itself and in a synergistic manner when incubated together with TRH or PMA. The synergistic effects of forskolin on prolactin release was greater in the presence of PMA than TRH. Down-regulation of protein kinase C by PMA pretreatment abolished the synergistic effect produced by PMA and forskolin but had no effect on those generated by TRH and forskolin. sn-1,2-Dioctanylglycerol (DOG) pretreatment attenuated the subsequent response to DOG and PMA but not TRH. The effect of TRH, but not PMA, on prolactin release required the presence of extracellular Ca2+. In conclusion, the mechanism by which TRH causes prolactin release from rat primary pituitary cells is different from that of GH3 cells; the former is a protein kinase C-independent process whereas the latter is at least partially dependent upon the activation of protein kinase C.

Animals↗

Evidence for a role of protein kinase-C in His-D-Trp-Ala-Trp-D-Phe-Lys-NH2-induced growth hormone release from rat primary pituitary cells.

We have recently reported that His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) synergizes with GH-releasing factor (GRF) to increase GH release and cAMP accumulation in rat pituitary cells in vitro. This study was undertaken to further investigate the mechanism of action of GHRP-6 on GH release, particularly the involvement of protein kinase-C. Forskolin (10(-5) M), A23187 (10(-6) M), and phorbol 12-myristate 13-acetate (PMA; 10(-7) M) all stimulated GH release. However, only PMA can mimic the synergistic effects of GHRP-6 on GRF-stimulated GH release and intracellular cAMP accumulation. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester, was unable to stimulate GH release or potentiate the effect of GRF. Extracellularly added phospholipase-C not only stimulated GH release in a dose-dependent manner, but also potentiated GRF-induced GH release. Phloretin, a protein kinase-C inhibitor, in a concentration range of 10-250 microM had very little or no effect on basal and GRF-stimulated GH release, but markedly inhibited the stimulatory effects induced by either PMA or GHRP-6. Incubation of rat pituitary cells with 10(-6) M PMA for 24 h completely down-regulated protein kinase-C, since such PMA-pretreated cells did not release GH in response to a second dose of PMA. The protein kinase-C-depleted cells had an attenuated GHRP-6 response, but they responded normally to GRF. Moreover, the synergistic effects of GHRP-6 and GRF on GH release and cAMP accumulation were also greatly inhibited by protein kinase-C down-regulation. These data suggest that the effects of GHRP-6 on GH release, either alone or together with GRF, are at least partially mediated via the activation of protein kinase-C.

Amino Acid Sequence↗

Insulin-like effects of ATP on adipocyte pyruvate dehydrogenase and phosphorylase.

Extracellular ATP stimulated adipocyte pyruvate dehydrogenase in a time- and dose-dependent manner with an EC50 of 0.1 mM. The maximal effect was observed at 0.5 mM ATP after a 15-min incubation with a lag period of about 5 min. Depletion of intracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid reduced the effect of ATP by 50% and completely abolished the stimulatory effect of vasopressin on adipocyte pyruvate dehydrogenase but had no effect on the stimulation induced by insulin or adenosine. The effects of insulin and ATP on pyruvate dehydrogenase were glucose-dependent whereas the effect of adenosine was glucose-independent. Furthermore, ATP, like insulin, partially blocked the stimulatory effect of isoproterenol on phosphorylase. Adenosine, at a concentration of 1 mM, did not affect either basal or isoproterenol-stimulated phosphorylase activities. It is concluded that ATP activates adipocyte pyruvate dehydrogenase by at least two separate mechanisms: one is Ca2(+)-dependent and the other is Ca2(+)-independent. However, neither is the result of the formation of adenosine from ATP through hydrolysis.

Adenosine↗

The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture.

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner. Stimulation was observed after a 15-min, but not a 4-h, incubation. The concentrations of GHRP-6 required for half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively. GH release induced by GHRP-6 was not affected by the addition of either naloxone or the GRF antagonist [N-Ac-Tyr1,D-Arg2]GRF-(1-29)-NH2. The latter inhibited GRF-stimulated GH release by shifting the dose-response curve to the right. His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2, an analog of GHRP-6, inhibited GH release stimulated by GHRP-6 without affecting that induced by GRF. When present together at maximal concentrations, GHRP-6 and GRF produced a synergistic effect on GH release. GHRP-6 had no effect on intracellular cAMP levels, whereas GRF increased intracellular cAMP concentrations by 3-fold. Combined treatment of pituitary cells with GRF and GHRP-6 resulted in a potentiation of the GRF-induced increase in cAMP levels. Basal GH release was reduced by 30% after pretreatment with GHRP-6 (10(-7) M) for 1 h. Pretreatment with GHRP-6 also decreased the subsequent response to GHRP-6, but not GRF. In contrast, pretreatment with GRF for 1 h had no effect on the subsequent action of GHRP-6 or GRF on GH release. The desensitization induced by GHRP-6 was completely reversed within 1 h after removal of the peptide. Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.

Animals↗

Timing light and tone signals in pigeons.

Pigeons' ability to time light and tone stimuli was examined in four experiments. In Experiment 1, two groups of pigeons were trained to discriminate between 2- and 8-s durations of lights or tones and then were transferred to reversal or nonreversal discriminations in the alternate modality. Pigeons learned the light discrimination faster than the tone discrimination and showed immediate positive intermodal transfer from tone to light but not from light to tone. In Experiments 2-4, the peak procedure was used to study birds' timing of 15- and 30-s fixed-interval light and tone signals. Peak times on empty trials under baseline conditions closely approximated the length of fixed-interval signals. When pigeons were tested with time-outs and intermodal switches introduced midway through an empty trial, they tended to reset the timing mechanism and begin timing again from 0 s. With both estimation and production procedures, pigeons were less accurate when timing the tone stimuli than when timing the light stimuli. A comparison of these data with data from timing experiments with rats suggests several possible differences in timing processes between pigeons and rats.

Animals↗

Some psychophysics of the pigeon's use of landmarks.

1. Three pigeons (Columba livia) were trained to find hidden food in a sunken well (3.3 cm in diameter) at a constant place within an (160 cm x 160 cm) experimental box (Fig. 1). After learning the location, the animals were tested occasionally with the well and food absent. Landmarks in the experimental box might be transformed on such tests. 2. Changing the height or width of a nearby landmark had no systematic influence on the position of peak search. Translating a nearby landmark, however, led to a shift in peak search position. All three birds then searched most somewhere between the original goal location, as defined by the unmoved landmarks, and the goal location as defined by the shifted landmark. Within a limited range of landmark shift, the peak shift as a function of landmark shift is linear (Fig. 3). 3. To explain the data (Fig. 7), the pigeon records at the location of the goal the algebraic vectors from a number of landmarks to the goal. These vectors have both a direction and a distance component. When searching for the goal again in the experimental box, it computes independently for each landmark a navigation vector. This is arrived at by vector-adding the algebraic vector from the bird's current position to the landmark in question, supplied by perception, to the corresponding landmark-goal vector in its record. The pigeon moves in the direction and distance specified by a weighted average of the independently calculated navigation vectors. For positive vector weights, vector geometry guarantees that the bird would search somewhere between the original goal and the goal according to the shifted landmark. The extent to which it shifts toward the shifted goal reflects the vector weight given to the shifted landmark.

Animals↗

Purification of complexes of nuclear oncogene p53 with rat and Escherichia coli heat shock proteins: in vitro dissociation of hsc70 and dnaK from murine p53 by ATP.

Oligomeric protein complexes containing the nuclear oncogene p53 and the simian virus 40 large tumor antigen (D. I. H. Linzer and A. J. Levine, Cell 17:43-51, 1979), the adenovirus E1B 55-kilodalton (kDa) tumor antigen, and the heat shock protein hsc70 (P. Hinds, C. Finlay, A. Frey, and A. J. Levine, Mol. Cell. Biol. 7:2863-2869, 1987) have all been previously described. To begin isolating, purifying, and testing these complexes for functional activities, we have developed a rapid immunoaffinity column purification. p53-protein complexes are eluted from the immunoaffinity column by using a molar excess of a peptide comprising the epitope recognized by the p53 monoclonal antibody. This mild and specific elution condition allows p53-protein interactions to be maintained. The hsc70-p53 complex from rat cells is heterogeneous in size, with some forms of this complex associated with a 110-kDa protein. The maximum apparent molecular mass of such complexes is 660,000 daltons. Incubation with micromolar levels of ATP dissociates this complex in vitro into p53 and hsc70 110-kDa components. Nonhydrolyzable substrates of ATP fail to promote this dissociation of the complex. Murine p53 synthesized in Escherichia coli has been purified 660-fold on the same antibody affinity column and was found to be associated with an E. coli protein of 70 kDa. Immunoblot analysis with specific antisera demonstrated that this E. coli protein was the heat shock protein dnaK, which has extensive sequence homology with the rat hsc70 protein. Incubation of the immunopurified p53-dnaK complex with ATP resulted in the dissociation of the p53-dnaK complex as it did with the p53-hsc70 complex. This remarkable conservation of p53-heat shock protein interactions and the specificity of dissociation reactions suggest a functionally important role for heat shock proteins in their interactions with oncogene proteins.

Adenosine Triphosphate↗

"Stable" effects of insulin and isoproterenol on adipocyte pyruvate dehydrogenase.

Insulin, at a concentration of 1 mU/ml, stimulated glycogen synthase and pyruvate dehydrogenase about threefold in isolated rat adipocytes. Upon the removal of insulin, glycogen synthase activity remained in the activated state for 10 min and thereafter rapidly returned to basal level. On the other hand, insulin-stimulated pyruvate dehydrogenase activity remained elevated for at least 30 min. Isoproterenol (10(-8) M) stimulated phosphorylase and inhibited pyruvate dehydrogenase through the activation of beta-adrenergic receptors. Addition of the beta-antagonist, propranolol (10(-5) M), after isoproterenol reversed the action of isoproterenol on phosphorylase but not its action on pyruvate dehydrogenase. Dibutyryl cyclic AMP, when added to intact adipocytes, produced an effect on pyruvate dehydrogenase similar to that induced by isoproterenol. Our results indicate that both insulin and the beta-agonist have a unique action on pyruvate dehydrogenase which is different from their effects on other enzymes such as glycogen synthase and phosphorylase.

Adipose Tissue↗

A putative mediator of insulin action which inhibits adenylate cyclase and adenosine 3',5'-monophosphate-dependent protein kinase: partial purification from rat liver: site and kinetic mechanism of action.

A novel putative mediator of insulin action which acts to inhibit adenylate cyclase and cAMP-dependent protein kinase has been purified from livers of insulin-treated streptozotocin-diabetic rats. It was increased by short term (5-min) insulin injections in vivo and purified several thousand-fold by Sephadex and HPLC. Its mol wt was somewhat larger (2500) than previous mediators identified, and it was more hydrophobic in character. Its mechanism of action or adenylate cyclase was determined and found to be chiefly directed against the catalytic subunit. Its action on the cAMP-dependent protein kinase was found to be competitive with regard to protein substrate, but noncompetitive with regard to ATP and cAMP. Its relationship to other putative insulin mediators and the mechanism of insulin action is discussed.

Adenosine Triphosphate↗

The total artificial heart as a bridge to transplantation. A report of two cases.

In 1985, at the University of Arizona, Tucson, two attempts were made to "bridge" patients from impending death to heart transplantation, using orthotopically positioned total artificial hearts. The first attempt, using an unapproved device on an emergency basis, failed after transplantation because of severe pulmonary edema and Pseudomonas pneumonia and the apparent transmission of a Pseudomonas infection from donor to recipient. The second experience, using a Jarvik-7 device, led to stable support for nine days with one major complication, a reversible neurologic deficit with no associated computed tomographic scan abnormality. This patient survived cardiac transplantation and, after being successfully treated for complications, has made a full recovery and returned to full-time work.

Adult↗