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Biomedical subjects

R An

Publications and source records attributed to R An.

At least 19 recordsLinked to original sources

Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells.

The transcription factor PDX-1 (pancreatic duodenal homeobox-1) is required for normal pancreatic development and for the function of insulin-producing islet beta-cells in mammals. We have shown previously that glucose regulates insulin gene expression in part through the activation and translocation of PDX-1 from the nuclear periphery to the nucleoplasm. We have also found that PASK [PAS (Per-Arnt-Sim) kinase], a member of the nutrient-regulated family of protein kinases, is activated in response to glucose challenge in beta-cells and is involved in the regulation of expression of PDX-1. Purified PASK efficiently phosphorylated recombinant PDX-1 in vitro on a single site (Thr-152). To determine the impact of phosphorylation at this site, we generated wild-type and mutant (T152A, T152D and T152E) forms of PDX-1 and examined the distribution of each of these in clonal MIN6 beta-cells by immunocytochemical analysis. Unexpectedly, only the T152D mutation significantly affected subcellular distribution, increasing the ratio of nuclear/cytosolic labelling at low and high glucose concentrations, suggesting that phosphorylation at Thr-152 inhibits nuclear uptake in response to glucose. Based on these results, experiments to examine the contribution of Thr-152 to the overall phosphorylation of PDX-1 in intact cells will be undertaken.

Cell Nucleus↗

A new naphthoquinone from Pyrola japonica.

A new naphthoquinone, 5,8-dihydro-2,7-dimethyl-[1,4]naphthoquinone (1), which was named 5,8-dihydrochimaphilin, isolated from an ethyl acetate soluble fraction from the root of Pyrola japonica, together with chimaphilin (2). Compound 1 was transformed rapidly to 2 upon exposure to air by HPLC analysis. This fact supported that chimaphilin (2) may be an artifact from 1.

Antineoplastic Agents, Phytogenic↗

[Diagnostic value of pentavalent 99mTc-dimercaptosuccinicacid ([V]-DMSA) in head and neck tumors].

The purpose of this investigation was to assess the biodistribution of 99mTc-[V]-DMSA in human being, and its diagnostic value in patients with head and neck tumours. 20 patients with histologically confirmed head and neck tumours were examined with planar as well as SPECT scintigraphy. Whole body scintigraphy in different time after injection of 99mTc-[V]-DMSA was performed to assess the major sequential organ biodistribution. Our results showed that the blood clearance of 99mTc-[V]-DMSA was bi-exponential. All organs except kidneys showed a relatively rapid elimination of 99mTc-[V]-DMSA. The kidneys showed a increasing accumulation in the first 2 h, which is probably due to the tubular reabsorption of 99mTc-[V]-DMSA. In 15 of 20 patients, 19 lesions could be proven by means of planar scintigraphy (corresponding sensitivity of 75%). 29 lesions in 18 patients could however be detected by the application of SPECT (corresponding sensitivity of 90%). Except primary tumours and local lymphadenmetastases in 5 patients distant metastases (3 thorax wall, 1 liver and 1 inguinal/paravesicle) were found. Altogether a sensitivity of 76.9% and a specificity of 71.4% were calculated for the detection of primary tumour. The sensitivity and specificity for the exploration of lymphadenmetastases were 75% and 100%. In conclusion, this study show that 99m Tc-[V]-DMSA, particularly with SPECT imaging, is useful in localising the primary tumours and lymphadenmetastases as well as distant metastases of head and neck tumours. The possible therapeutic application of 188/186Re-[V]-DMSA is also evaluated.

Adult↗

Beta2-adrenergic receptor overexpression in the developing mouse heart: evidence for targeted modulation of ion channels.

1. We studied the effect of overexpression of the beta2-adrenergic receptor (beta2-AR) in the heart on ion channel currents in single cells isolated from hearts of fetal and neonatal transgenic and wild-type mice. The beta2-AR transgene construct was under the control of the murine alpha-myosin heavy chain (alpha-MHC) promoter, and ion channel activity was measured at distinct developmental stages using whole-cell and perforated patch clamp techniques. 2. We found no change in L-type Ca2+ channel current (ICa) density in early embryonic stages (E11-13) of beta2-AR transgenic positive (TG+) mice, but significant increases in ICa density in intermediate (E14-16, 152 %) and late (E17-19, 173.7 %) fetal and neonatal (1 day post partum, 161 %) TG+ compared with transgenic negative (TG-) mice. This increase in ICa was accompanied by a negative shift in the peak of the current-voltage relationship in TG+ mice. 3. Transient (< 3 min) or prolonged (16-24 h) exposure of TG- neonatal stage myocytes to 8-Br-cAMP (300 microM) increased ICa density and caused a shift in the current-voltage relationship to a similar extent to that seen in TG+ mice. In TG+ myocytes, 8-Br-cAMP had no effect. Exposure of TG+ cells to Rp-cAMPS reversed both the shift in voltage dependence and reduced the peak current density observed in these myocytes. We concluded from these results that the L-type Ca2+ channel is maximally modulated by cAMP-dependent protein kinase (PKA) in TG+ mice and that the alpha-MHC promoter is functional in the ventricle as early as embryonic day 14. 4. In contrast, we found that slow delayed rectifier K+ channels were not changed significantly at any of the developmental stages studied by the overexpression of beta2-ARs compared with TG- mice. The sensitivity of murine slow delayed rectifier K+ channels to cAMP was tested by both transient and prolonged exposure to 8-Br-cAMP (300 microM), which increased the slow delayed rectifier K+ channel current (IK,s) density to a similar extent in both TG- and TG+ neonatal myocytes. In addition, we found that there was no difference in the concentration dependence of the response of ICa and IK,s to 8-Br-cAMP. 5. Thus, overexpression of the beta2-AR in the heart results in distinct modulation of ICa, but not IK,s, and this is not due to differences in the 8-Br-cAMP sensitivity of the two channels. Instead, these results are consistent with both compartmentalization of beta2-AR-controlled cAMP and distinct localization of L-type Ca2+ and slow delayed rectifier K+ channels. This cAMP is targeted preferentially to the L-type Ca2+ channel and is not accessible to the slow delayed rectifier K+ channel.

8-Bromo Cyclic Adenosine Monophosphate↗

[Evaluation of 99mTc(V)-DMSA imaging in patients with pharyngolaryngeal carcinoma].

OBJECTIVE: To evaluate the value of tumor-seeking agent 99mTc(V)-DMSA in patients with pharyngolaryngeal carcinoma and its biodistribution in human being. METHOD: Planar and SPECT scintigraphy with 99mTc(V)-DMSA were performed in 12 patients with histologically confirmed pharyngolaryngeal carcinoma. The dynamic distribution in patients was also analyzed. RESULT: 9 cases (11 lesions) showed increased uptake by planar imaging and 11 cases (19 lesions) were clearly demonstrated by SPECT images. Furthermore, distant metastatic lesions were showed in 5 patients. Biodistribution in patients showed the accumulation of 99mTc(V)-DMSA in kidney was significantly greater than other organs. CONCLUSION: These results could suggested the clinical utility of 99mTc(V)-DMSA, specially with SPECT, for detecting primary pharyngolaryngealcarcinoma and their metastatic lesions (both local and distant). 99mTc(V)-DMSA Tumor-seeking agent Pharyngolaryngeal carcinoma.

Aged↗

[The two-step three-photon resonant ionization of atom Cu].

This paper discusses the process of resonant laser ablation (RLA), where the two-step three-photon resonant ionization of copper is considered as the best scheme. The rate equations of resonant ionization of copper are calculated and the factors that affect the ionization efficiency are discussed. The results prove the potential advantages of RLA especially the low energy threshold.

English Abstract↗

Effects of captopril and nadolol on renal hemodynamics in patients with essential hypertension.

The randomized single-blind study was designed to compare the effects of captopril (Cap) and nadolol (Nad) on renal hemodynamics in 60 patients with essential hypertension. They were divided into two groups at random. Cap was given in dosage of 37.5-75 mg/d per os and Nad 40-80 mg/d. The results show that both drugs increase the blood volume distributed to the kidneys from cardiac output (renal blood flow/cardiac output), Cap increasing 10% (P < 0.05) and Nad 8% (P < 0.05). Renal vascular resistance (RVR) is lowered by the two drugs, 13% (P < 0.05) by Cap and 11% (P < 0.05) by Nad. These suggest that both drugs facilitate the maintenance of renal blood circulation in patients with essential hypertension, being beneficial for long-term treatment of hypertension.

Adult↗

Major pharmacological effects of 6-methoxytetrahydro-beta-carboline, a drug elevating the tissue 5-hydroxytryptamine level.

Major pharmacological effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-methoxytryptoline, 6-MeOTHBC) are described. It seemed to have a weak effect of its own on 5-HT-receptors. It is concluded that most of the effects, like the increase of rectal temperature after peripheral administration and decrease and then increase after intrahypothalamic application as well as the antagonism of the group toxicity of amphetamine without effect on norepinephrine toxicity or barbiturate sleeping time, can result from the increase of tissue 5-HT-concentration and/or inhibition of 5-HT-uptake.

Acute Disease↗