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Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 91 records · Page 5Linked to original sources

Omniplane transesophageal echocardiography imaging planes exploration.

One hundred and twenty-four patients with heart disease were examined by omniplane TEE in order to systematically research every views of omniplane TEE, and further explore anatomy and image feature of each view. The result showed that omniplane TEE transducer can be rotated in probe from 0 degree to 180 degrees, obtain many views at various angles behind the heart and fully demonstrate the structure and pathology of the heart and great vessels. It was useful for clinical diagnosis because of getting more information about the heart and great vessels. As omniplane TEE probe was little rotated in esophagus, it lessened esophagus stimulation. Meanwhile, it was suitable for three-dimensional reconstruction of left ventriculum.

Adolescent↗

Clinical application of Omniplane transesophageal echocardiography.

One hundred and twenty-four patients with heart disease (75 cases of rheumatic heart disease, 26 cases of congenital heart disease, 13 cases of aortic disease and 10 cases of other disease) were examined by Omniplane transesophageal echocardiography (TEE). The result showed that Omniplane TEE transducer can be rotated from 0 degree to 180 degrees in probe and had the advantages of broader scope, obtaining more information, less stimulation to esophagus and easy to manipulate. It suggests that Omniplane TEE is a efficient technique in clinical diagnosis and can be extensively used in the future.

Adolescent↗

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

Administration, Oral↗

Ethanol potentiates interleukin-1 beta-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells.

Experiments were performed to examine the effect of ethanol on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in the release of nitrite and in the intracellular accumulation of L-citrulline. In parallel with this, IL-1 beta increased inducible nitric oxide synthase (iNOS) mRNA and protein. Ethanol (6.5-650 mM) potentiated the IL-1 beta-mediated stimulation of iNOS mRNA production, the appearance of iNOS protein and the generation of nitrite and L-citrulline from smooth muscle cells in a concentration-dependent manner. In the absence of IL-1 beta, ethanol failed to induce iNOS expression. These results demonstrate that pharmacologically relevant concentrations of ethanol enhance the IL-1 beta-induced expression of the iNOS gene in vascular smooth muscle. The ability of ethanol to augment the release of the platelet inhibitor and vasodilator nitric oxide may, in part, contribute to the beneficial cardiovascular effects associated with moderate alcohol consumption.

Amino Acid Oxidoreductases↗

Human cortical regions activated by wide-field visual motion: an H2(15)O PET study.

1. Several areas in the monkey dorsal visual pathway, including the dorsal part of the medial superior temporal area, have been found to contain cells responding to movements of a wide visual field and are suggested to be involved in analyzing self-induced motion information. In the present study, positron emission tomography was used to localize human cortical regions responding to wide-field visual motion. Changes in regional cerebral blood flow (rCBF) were measured when subjects maintained fixation and viewed low-contrast (0.15 log units brighter than the background) dots subtending 80 x 80 degrees and moving either coherently or incoherently. Brain foci were localized after activity in a fixation-only paradigm was subtracted from that in the two moving dot paradigms. 2. Both the coherent and incoherent movements significantly activated the primary/secondary visual cortex and surrounding visual areas in the cuneus and superior occipital gyrus. Subtraction of images between the coherent and incoherent movements showed that the activity caused by the two types of movement was comparable in these early visual cortical regions. 3. In the lateral occipitotemporoparietal cortex, the coherent movement specifically activated two separate areas; a posterior focus was located at the border of the right occipitotemporal gyri, and a dorsoanterior focus was located bilaterally in the temporoparietal cortex. The incoherent movement did not activate these regions. 4. A fine anatomic localization using individual magnetic resonance images was performed for the bilateral activation in the temporoparietal cortex, which was found to be located mainly in the depth of the inferior parietal lobule and a small portion of the superior and middle temporal gyri. 5. Both the coherent and incoherent movements activated a part of the superior parietal lobule located within the intraparietal sulcus (Brodmann area 7). The bilateral foci activated by the coherent movement were located more anteriorly than the focus activated by the incoherent movement. Subtraction images between the coherent and incoherent movements, however, did not reveal any significant rCBF increases in the superior parietal lobule. 6. Several other cortical regions known to be involved in visuospatial and visuomotor functions were also activated by the coherent movement, including the frontal eye field (Brodmann area 8) and premotor cortex (Brodmann area 6) in the frontal lobe. 7. The posteriorly located activation at the border of occipito-temporal gyri corresponds to the homologue of the middle temporal area reported in previous activation studies using small to medium-sized motion stimuli. The bilateral activation in the inferior parietal lobule appeared to rely on wide-field motion stimulation.

Adult↗

Cyclic nucleotide regulation of interleukin-1 beta induced nitric oxide synthase expression in vascular smooth muscle cells.

Experiments were performed to examine the effect of cyclic nucleotides on the expression of inducible nitric oxide synthase (iNOS) activity by interleukin-1 beta (IL-1 beta) treated rat aortic smooth muscle cells (SMC). Treatment of vascular SMC with IL-1 beta stimulated iNOS mRNA expression and the subsequent release of nitrite, a stable oxidation product of nitric oxide (NO). Similarly, lipophilic analogues of cAMP also induced both iNOS mRNA expression and nitrite release. The addition of IL-1 beta and cAMP derivatives resulted in a synergistic enhancement of both iNOS mRNA production and of nitrite formation. In contrast, lipophilic analogues of cGMP did not induce iNOS expression. The addition of cGMP derivatives modestly increased IL-1 beta-induced SMC nitrite generation without affecting the production of iNOS mRNA. The capacity of cyclic nucleotides to positively modulate the induction of iNOS activity may play an important role in regulating the release of NO in vivo.

Amino Acid Oxidoreductases↗

A novel 3-substituted benzazepinone growth hormone secretagogue (L-692,429).

The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype compound of a novel class of compounds that stimulate release of growth hormone (GH). The molecule evolved from efforts to identify a non-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by sequential attachment of dimethyl-beta-alanine and 2'-biphenylyltetrazole side chains to a chiral 3-aminobenzolactam nucleus. Comparison of the biological activity of 1 with the corresponding six- and eight-membered lactam analogs shows the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of the structurally diverse GH secretagogues, L-692,429 and GHRP-6, was performed.

Amino Acid Sequence↗

Comparison of neuronal selectivity for stimulus speed, length, and contrast in the prestriate visual cortical areas V4 and MT of the macaque monkey.

1. Prestriate area V4 and the middle temporal area (MT) compose the first stage in which the ventral and dorsal visual cortical pathways are segregated. To better known the functional dichotomy between the two pathways at this level, we recorded cell responses from V4 and MT using anesthetized, immobilized macaque monkeys and compared the selectivity for speed of stimulus motion and stimulus length and the sensitivity to luminance contrast between the two areas. 2. V4 cells were as selective as MT cells for speed. The sharpness of tuning was not different between the two populations. The optimal speed varied widely in both areas, but both of the two distributions showed peaks at 32 degrees/s. 3. V4 and MT cells were similar in that about one-half of the cells (45% in V4 and 48% in MT) showed inhibition by long (16 degrees) bars. However, V4 cells preferred stimuli whose lengths were distributed around the lengths of the receptive field, whereas an overwhelming majority of MT cells preferred stimuli whose lengths were much shorter than the lengths of the receptive field. 4. The cutoff contrast at which one-half the maximum response was elicited was distributed widely in both areas, and the two distributions considerably overlapped. MT cells as a whole, however, were slightly more sensitive to the luminance contrast than V4 cells. 5. There was a tendency toward local clustering for cells with similar speed preferences in MT but not in V4. Pairs of MT cells recorded within 400 microns had smaller difference in the optimal speed than that of cell pairs taken randomly from the whole sample of MT cells.

Animals↗

Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells linked with cell cycle arrest in G1 phase.

The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle alterations in human malignant glioma cell lines, SF-188 and LN-382, were investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN-382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase increased, while the percentage of cells in the S phase decreased. LN-382 cells did not show any marked change in cell kinetics. TNF arrests certain human glioma cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid synthesis in the subsequent S phase, suppressing the proliferation pathway.

Brain Neoplasms↗

Pituitary adenylate cyclase activating polypeptide-induced desensitization on growth hormone release from rat primary pituitary cells.

Pituitary adenylate cyclase activating polypeptide (PACAP38) stimulated growth hormone release as well as cAMP accumulation in a static rat primary pituitary cell culture in a dose-dependent manner with EC50 values of 1.9 +/- 0.4 nM (n = 13) and 0.9 +/- 0.3 nM (n = 5), respectively. The maximal GH response was observed between 5 to 15 min. Prolonged incubation (3 to 4 hrs) markedly reduced the stimulatory effect of PACAP38. The effect of PACAP38 on GH release was desensitized by pretreatment of the cells with PACAP38 or GRF, but not with PMA. The PACAP38-induced desensitization appeared to be time- and dose-dependent. Somatostatin (20 nM) inhibited PACAP-stimulated GH release through a cAMP-independent pathway.

Animals↗

A nonpeptidyl growth hormone secretagogue.

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

Amino Acid Sequence↗

A novel non-peptidyl growth hormone secretagogue.

Direct screening of preselected compounds in a rat primary pituitary cell culture assay, followed by chemical modification of selected pharmacophores led to the identification of a novel non-peptidyl class of GH secretagogues (substituted benzolactams). The prototype compound of this class, L-692,429, stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner with an EC50 value of 60 nM. Under the same conditions, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GH-releasing peptide, GHRP-6) and GH-releasing factor (GRF) had EC50 values of 10(-8) and 5 x 10(-10) M, respectively. L-692,428, the S-enantiomer, of L-692,429, was inactive at a concentration as high as 2 microM. GH release induced by L-692,429 was inhibited by somatostatin as well as by GHRP-6 and substance P antagonists but not by GRF or opiate antagonists. L-692,400, which is structurally related to L-692,429 but biologically inactive, inhibited GH response not only to L-692,429 but also GHRP-6. Like GHRP-6, L-692,429 alone had no effect on intracellular cAMP levels; however, it synergized with GRF to further increase both the accumulation of cAMP and the release of GH. Maximal effects of L-692,429 and GHRP-6 on GH release were comparable. Interestingly, when presented together in maximal concentrations, L-692,429 and GHRP-6 did not cause an additional GH release when compared with either secretagogue alone. L-692,429 had a small effect on prolactin release but not adrenocorticotropin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue.

L-692,429, a benzolactam derivative, stimulated GH release from rat primary pituitary cells in a dose-dependent manner. The concentration of L-692,429 required for half-maximal stimulation were 59.6 +/- 7.3 nM. Under the same conditions, GHRP-6 and GRF had EC50 values of 10.3 +/- 1.9 nM and 0.47 +/- 0.09 nM, respectively. L-692,428, the enantiomer of L-692,429, was inactive at a concentration as high as 2 microM. Like GHRP-6, L-692,429 had no effect on intracellular cAMP level; however, it synergized with GRF to further increase not only the accumulation of cAMP but also the release of GH. The magnitude of GH release stimulated by maximal concentrations of L-692,429 and GHRP-6 was comparable. Interestingly, when presented together in maximal concentrations, L-692,429 and GHRP-6 did not cause additional GH release when compared with either secretagogue alone. The L-692,429-stimulated GH release was completely inhibited by 20 nM somatostatin. To our knowledge, L-692,429 is the first non-peptidyl GH secretagogue which has a direct effect on the release of growth hormone from rat primary pituitary cells. Its effect is most likely mediated through a mechanism which is similar to that of GHRP-6.

Animals↗

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↗