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Biomedical subjects

J Shan

Publications and source records attributed to J Shan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Area postrema ablation attenuates activation of neurones in the paraventricular nucleus in response to systemic adrenomedullin.

Adrenomedullin (ADM) is a potent vasodilator in the periphery which also acts centrally to increase blood pressure and inhibit drinking, feeding and salt appetite. This study was designed to study the effects of circulating ADM on neuronal activation in autonomic centres in the rat brain and to examine whether neuronal nitric oxide (NO) may participate in these processes. We identified activated neurones 1 h after intravenous (i.v.) injections of ADM (2 nmol/kg) using immunohistochemistry for Fos. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical reaction was used to localize putative NO-producing neurones and double labelling for Fos and NADPH-d was used to identify activated NO producing neurones. To separate baroreceptor-induced neuronal activation in autonomic centres by ADM from other effects which it may have, i.v. infusions of sodium nitroprusside (NP) were used to mimic the hypotensive effects of ADM in control rats. Significantly greater numbers of activated neurones were found in the paraventricular nucleus of the hypothalamus (PVN) and especially in the dorsolateral medial parvocellular division, the nucleus of the solitary tract, and the area postrema (AP) of ADM-treated rats compared to control rats. In addition, the number of activated NO-producing neurones in the PVN was significantly higher in ADM-treated rats compared to rats treated with NP. To determine whether AP is one of the possible routes through which systemic ADM enters the brain to exert its central effects, the APs of rats were ablated by aspiration. One hour after i.v. injections of ADM, significantly fewer PVN neurones were activated in AP ablation rats compared to AP sham ablation rats. Similarly, the number of activated NO-producing neurones in the PVN was significantly lower in AP ablation rats compared to AP sham ablation rats. In conclusion, our results suggest that systemic ADM gains access to the brain through the AP to regulate neuronal activity in autonomic centres and that neuronal NO might be involved in central autonomic and/or neuroendocrine regulation by ADM.

Adrenomedullin↗
PubMed2000

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study.

A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

Adolescent↗
PubMed2000

The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast: a comparison in sinus rhythm and atrial fibrillation patients.

OBJECTIVE: To investigate the relationship between spontaneous echo contrast (SEC) and left atrial appendage (LAA) blood flow velocity using transesophageal echocardiography (TEE) during percutaneous balloon mitral valvotomy (PBMV) in patients with atrial fibrillation and sinus rhythm. METHODS: Thirty-five patients (21 in sinus rhythm and 14 in atrial fibrillation) with rheumatic mitral stenosis underwent PBMV with intraoperative transesophageal echocardiography monitoring. We measured LAA blood flow velocities and observed the left atrium for various grades of SEC (from 0 = none to 4 = severe), before and after each balloon inflation. RESULTS: Left atrial appendage maximal emptying velocity (LAA MEV) was reduced from 35 +/- 14 cm/s to 6 +/- 2 cm/s at peak balloon inflation and increased to 40 +/- 16 cm/s after balloon deflation. Comparison of the values before balloon inflation and after balloon deflation showed that LAA velocities were significantly lower (P < 0.001). During balloon inflation, both maximal emptying velocity (MEV) and maximal filling velocity (MFV) were significantly decreased, compared to those before inflation and after balloon deflation (P < 0.01). And both MEV and MFV were significantly higher after balloon deflation relative to those before balloon inflation. Patients with atrial fibrillation had significantly lower MEV and MFV before and during balloon inflation and after balloon deflation than patients with sinus rhythm. At peak balloon inflation, new or increased SEC grades were observed during 54 of 61 (88%) inflations and unchanged during 7 (12%) inflations. SEC grades were reduced after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%) and remained unchanged after 6 deflations (10%). At peak balloon inflation, left atrium spontaneous echo contrast (LASEC) grade 4 was observed during 14 of 27 (93%) inflations in the atrial fibrillation patients, significantly higher than in patients with sinus rhythm (8 of 34, 24%; P < 0.05). LASEC completely disappeared after 16 of 34 deflations (47%) in the patients with sinus rhythm, significantly higher than in the atrial fibrillation patients (2 of 27 deflations; P < 0.01). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) correlated with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Both the time to lowest LAA velocity and the time to highest LASEC were significantly longer in the patients with sinus rhythm than in the atrial fibrillation patients (2.6 +/- 1.1 s vs 1.7 +/- 1.0 s, P < 0.05 and 2.8 +/- 1.4 s vs 1.9 +/- 1.3 s, P < 0.05, respectively). Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) correlated with the mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). Both intervals are significantly shorter in the patients with sinus rhythm than in the atrial fibrillation patients (2.0 +/- 1.6 s vs 3.5 +/- 1.5 s, P < 0.01 and 2.2 +/- 1.7 s vs 3.6 +/- 1.6 s, P < 0.05). CONCLUSION: Reducing the blood flow velocity in the human left atrium by balloon occlusion of the mitral valve may enhance SEC, whereas restoring blood flow after balloon deflation would cause enhanced echogenic blood to disappear or decrease in both groups of patients. Patients with atrial fibrillation demonstrate more severe blood stagnation of the left atrial body and appendage during transient balloon inflation at mitral valve orifice and slower recovery from the stagnation, decreasing to a lesser extent after balloon deflation, when compared to patients with sinus rhythm.

Adolescent↗
PubMed2000

[Clinical and pathological characteristics of gastric stump cancer and recurrent gastric stump cancer].

OBJECTIVE: To study early diagnosis and rational treatment of gastric stump cancer and recurrent gastric stump cancer. METHODS: The data of 27 patients with gastric stump cancer and 23 patients with recurrent gastric stump cancer were analysed retrospectively during the past 20 years based on their clinical and pathological findings. RESULTS: The onset time was 10 years or more for gastric stump cancer and less than 10 years for recurrent gastric stump cancer after gastrectomy. Gastroscopy was better than double contrast radiography in diagnosis. Partial resection of gastric stump was performed for patients with early cancer at the anastomotic stoma of gastrojejunostomy. Total resection of gastric stump was made for other patients. Lymph node of the mesojejunum were dissected routinely because their metastasis rate was about 40.0% in patients with cancer of anastomotic stoma. The effect of surgical treatment was poor for patients with advanced cancer. CONCLUSIONS: Regular gastroscopy is useful in detecting gastric stump cancer in patients with gastric cancer after gastrectomy, or in those years after removal benign. Malignancy was more evident in recurrent gastric stump cancer than in primary gastric cancer. Prognosis is good for early stage cases and poor for late stage cases after surgical treatment.

Adult↗
PubMed2000

[The relationship between angiotensin converting enzyme gene polymorphism and risk factors for coronary heart disease].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene polymorphism and risk factors for coronary heart disease (CHD). METHODS: 148 patients with CHD and 159 unrelated healthy individuals were studied using polymerase chain reaction (PCR) and genetic methods. Risk factors of CHD were assessed by standard questionnaire, physical examination and blood tests. RESULTS: (1) There were no significant differences among genotypes in terms of years, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL), HDL(2), HDL(3), apolipoprotein (Apo) AI, ApoB, and lipoprotein (a) [Lp (a)]. The prevalence rates of hyperlipidemia, hypertension (HT), cigarette smoking, diabetes mellitus (DM) and obesity were similar in the ACE genotypes (P > 0.05). (2) The DD genotype frequencies in low CHD risk groups, as defined by ApoB < 125 mg/dl and BMI <or= 24 kg/m(2), or TC < 230 mg/dl, TG < 200 mg/dl, LDL < 160 mg/dl and BMI <or=24 kg/m(2) without HT and DM were significantly higher than that in normal subjects (0.257, 0.315, 0.273 vs 0.157, chi(2) = 3.98, 7.80, 4.01, P < 0.05). CONCLUSION: There was no correlations between ACE gene polymorphism and the classic CHD risk factors noticed. ACE DD genotype seemed to be an independent risk factor for CHD in the Chinese population.

Asian People↗
PubMed2000

[Study on the quality standard of changan oral solution].

OBJECTIVE: To study the quality standard of Changan oral solution. METHOD: Thin layer chromatography was used for identification pig's bile plaster. TLC scanning was used for the determination of hyodeoxycholic acid. RESULTS: The TLC identification was highly specific and the spots was clear and concentrated. Linear regression for hyodeoxycholic acid was over the range of 3.50-12.25 micrograms. The average recovery of hyodeoxycholic acid was 100.5%, RSD was 3.2%. CONCLUSION: This standard was capable to effectively control the quality of Changan oral solution.

Administration, Oral↗
PubMed1999

Isolation of a novel gene, TSP50, by a hypomethylated DNA fragment in human breast cancer.

A novel gene, testes-specific protease 50 (TSP50), was isolated from a human testes cDNA library by using a genomic DNA probe, BR50. BR50 was isolated by a modified representational difference analysis (RDA) technique due to its hypomethylated feature in a breast cancer biopsy. This altered DNA methylation status was also detected by BR50 in other breast and some ovarian cancer tissues. The TSP50 gene product is a homologue to several human proteases, which indicates that it may encode a protease-like protein. Northern analysis of 16 different types of normal human tissues suggests that TSP50 was highly and specifically expressed in human testes, which indicates that it might possess a unique biological function(s) in that organ. Methylation status analysis in normal human testes and other tissues showed a correlation between DNA methylation and gene expression. Most importantly, reverse transcription-PCR analysis of 18 paired breast cancer tissues found that in 28% of the cancer samples, the TSP50 gene was differentially expressed. The possibility that TSP50 may be an oncogene is presently under investigation.

Amino Acid Sequence↗
PubMed1999

Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa.

We have previously elucidated the opiate-like action of mitragynine, an active principle isolated from the Thai medicinal plant Mitragyna speciosa. In the present study, effects of the related compound, mitragynine pseudoindoxyl on electrically stimulated contraction in guinea pig ileum and mouse vas deferens, and on its binding affinity in the guinea pig brain membranes were studied. Mitragynine pseudoindoxyl inhibited the electrically stimulated ileum and mouse vas deferens contractions in a concentration-dependent manner. In the ileum, the effective concentration is in an nM order, being nearly equivalent to reported concentrations of the micro-opioid receptor agonist [D-Ala2, Met-Phe4, Gly-ol5] enkephalin (DAMGO), and is 100- and 20-fold smaller than those of mitragynine and morphine, respectively. In the vas deferens, it is 35-fold smaller than that of morphine. The inhibitory action of mitragynine pseudoindoxyl in the ileum was antagonized by the non-selective opioid receptor antagonist naloxone and the micro-receptor antagonist naloxonazine. It was also antagonized by the delta-receptor antagonist naltrindole in the vas deferens. Mitragynine pseudoindoxyl showed a similar binding affinity to DAMGO and naltrindole at micro- and delta-receptors, respectively. However, the affinity at kappa-receptors was negligible. The present study demonstrates that mitragynine pseudoindoxyl, a novel alkaloid structurally different from other opioid agonists, acts on opioid receptors, leading to a potent inhibition of electrically stimulated contraction in the ileum through the micro-receptors and in mouse vas deferens through delta-receptors.

Analgesics↗
PubMed1999

Identification of the deoxyribonucleic acid-binding site of a regulatory protein involved in prostate-specific and androgen receptor-dependent gene expression.

In this study, we used a 5'-flanking region (-426/+28) of the rat prostatic probasin (rPB) gene shown to be sufficient to direct prostate-specific expression in transgenic mice in identifying the exact DNA-binding site of a putative prostate-specific transcription factor. Chloramphenicol acetyl transferase (CAT)-reporter gene analyses revealed that the construct pCAT PB -244/+52 was equally well induced by androgens in both prostatic LNCaP and nonprostatic COS-1, MCF-7, HEC-1, and HEP-1 cell lines, indicating that although the probasin gene region -244/+52 was important for androgen regulation, it was not regulated in a prostate-specific manner. Further studies suggested that the region -278/-240 was most crucial for prostate-specific expression. The sequence -426/-279 could be considered a silencer area, especially in nonprostatic cells. In deoxyribonuclease I footprinting, a protected 12-bp region was found between the nucleotides -251 and -240 only with nuclear extracts of prostatic origin. Deletion of this area decreased androgen induction significantly (P < 0.05) in transient transfections of prostatic cells compared with the wild-type reporter construct. Glucocorticoids were incapable of increasing the induction of the pCAT PB -278/+52 reporter construct compared with that of pCAT PB -244/+52 in the prostatic cell line LNCaP, suggesting that the putative prostate-specific protein acts as an inducer only when androgen and androgen receptor are present.

Androgen-Binding Protein↗
PubMed1999

Augmentation of diabetes-associated renal hyperfiltration and nitric oxide production by pregnancy in rats.

We tested the hypothesis that pregnancy might increase diabetes-associated nitric oxide (NO) production and renal hyperfiltration. Two weeks following i.v. streptozotocin (40 mg/kg), mean arterial pressure (MAP) was not modified by diabetes; glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF) were higher in pregnant than in virgin controls and increased by diabetes to a greater extent in pregnant than in virgin rats. Urinary volume (UV), creatinine, albumin and sodium (UNaV) were significantly increased by diabetes. Diabetes led to an increase in renal, cardiac, aortic and uterine but not in placental NO synthase activities. Infusion of NG-nitro-l-arginine (l-NA) caused a dose-dependent reduction in GFR, RPF, plasma NO2-/NO3-, UV and UNaV; in general, diabetes increased these effects to a greater extent in pregnant than in virgin rats. l-NA increased MAP in all groups of rats but did not alter FF. Diabetes did not alter responses of thoracic aorta rings to vasoconstrictor effects of phenylephrine and the vasorelaxant effects of sodium nitroprusside but increased endothelium-dependent relaxant effects of acetylcholine. In general the effects of diabetes of 7 days duration were similar to those described above for diabetes of 14 days duration. These data suggest that diabetes-associated renal hyperfiltration and NO production are augmented by pregnancy.

Acetylcholine↗
PubMed1999

Vasorelaxing action of rutaecarpine: effects of rutaecarpine on calcium channel activities in vascular endothelial and smooth muscle cells.

Rutaecarpine (Rut) has been shown to induce hypotension and vasorelaxation. In vitro studies indicated that the vasorelaxant effect of Rut was largely endothelium-dependent. We previously reported that Rut increased intracellular Ca2+ concentrations ([Ca2+]i) in cultured rat endothelial cells (ECs) and decreased [Ca2+]i in cultured rat vascular smooth muscle (VSMCs) cells. The present results showed that the hypotensive effect of Rut (10-100 microgram/kg i.v.) was significantly blocked by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine. In aortic rings, Rut (0. 1-3.0 microM)-induced vasorelaxation was inhibited by Nomega-nitro-L-arginine and hydroquinone but not by antagonists of the various K+ channels, 4-aminopyridine, apamin, charybdotoxin, or glibenclamide. Rut (0.1 and 1.0 microM) inhibited the norepinephrine-induced contraction generated by Ca2+ influx and at 1.0 microM increased cyclic GMP (cGMP) production in endothelium-intact rings and to a lesser extent in endothelium-denuded rings. In whole-cell patch-clamp recording, nonvoltage-dependent Ca2+ channels were recorded in ECs and Rut (0.1, 1.0 microM) elicited an opening of such channels. However, in VSMCs, Rut (10.0 microM) inhibited significantly the L-type voltage-dependent Ca2+ channels. In ECs cells, Rut (1.0, 10.0 microM) increased nitric oxide release in a Ca2+-dependent manner. Taken together, the results suggested that Rut lowered blood pressure by mainly activating the endothelial Ca2+-nitric oxide-cGMP pathway to reduce smooth muscle tone. Although the contribution seemed to be minor in nature, inhibition of contractile response in VSMCs, as evidenced by inhibition of Ca2+ currents, was also involved. Potassium channels, on the other hand, had no apparent roles.

4-Aminopyridine↗
PubMed1999

[Relationship between extent of tumor resection and prognosis: an evaluation in 533 cases of gastric cancer].

OBJECTIVE: To evaluate prognosis of patients with stomach cancer based on the extent of tumor resection. METHODS: Five hundred and thirty-three cases of gastric cancer resected from 1980 through 1990 were divided into 3 categories A, B, and C, in the order of decreasing completeness of tumor resection as set forth in the 12th edition of "Rules for Gastric Cancer in Japan". RESULTS: There were 157 cases in category A, 209 cases in category B and 167 cases in category C. Their survival rate was 80.9%, 34.9%, and 9%, respectively. In category A and B, the depth of tumor invasion and lymph node metastasis were the major factors affecting survival rate. In the presence of lymph node metastasis, prognosis was dependent on which station (D1-D3) of lymph nodes dissected. In category B, if dissection covered D3 but metastasis was limited to I or II, the 5-year survival rate was 48%; if lymph node dissection performed was limited to the same station of lymph nodes where metastasis occurred, the 5-year survival rate dropped to 22.4% (P < 0.05). In case cancer left over at the cutting edge, the completeness of resection might drop from category A or B to C, and the 5-year survival rate correspondingly decreased to 6% and 12.2%, respectively. CONCLUSION: In order to ensure completeness of tumor resection, lymph node station dissected should be farther than that with metastasis, and the distance between the tumor and the cutting edge should be long enough to prevent residual tumor left behind.

Adult↗
PubMed1999

[Effect of sotalol on systemic hemodynamics and electrophysiology in patients with life-threatening ventricular tachyarrhythmias].

OBJECTIVE: To evaluate the systemic hemodynamics and electrophysiology effect of intravenous and oral sotalol and its tolerance of long-term oral therapy in patients with life-threatening ventricular tachyarrhythmias. METHODS: Twenty-three patients, 17 with sustained ventricular tachycardias (VTs), 6 with ventricular fibrillation (VF) were studied. 16 patients were postmyocardial infarction, 4 were right ventricular dysplasia and 3 were dilated cardiomyopathy. RESULTS: Sotalol prevented the induction of arrhythmias in 34.3% with bolus intravenous injection (1 mg/kg body weight) and 60.8% with oral (160 mg twice daily for 10 to 14 days). Both intravenous and oral sotalol led to bradycardia, decreased in cardiac index, increased in left ventricular filling pressure as well as in systemic vascular resistance. The stroke volume increased significantly after sotalol intravenous, but not changed at peak action after oral sotalol. During a follow-up of 3 to 6 months, oral sotalol prevented the recurrent of arrhythmias in 12 of 16 patients who were response to electrophysiology testing. Congestive heart failure associated with a marked bradycardia developed in one patient. This patient was managed with a reduction in the dosage and with a regimen of digoxin and furosemide. CONCLUSION: Sotalol provided effective prophylaxis against life- threatening Ventricular tachyarrhythmias. It exerted significant negative hemodynamics effects but with quite good clinical tolerance, even in patients with compromised heart function.

Administration, Oral↗
PubMed1999

[Biologic behavior and prognosis of patients with gastric cancer in young persons].

OBJECTIVE: To explore the relationship between the biological behavior and prognostic factors in treating gastric cancer of young persons by various surgical methods. METHODS: 89 young patients with gastric cancer aged 35 years or less were analyzed. RESULTS: The resectable rate was 73.0% (65/89), radical resectable rate 48.3% (43/89), and palliative resectable rate 24.7% (22/89). The 5-year survival rate was 24.7% (22/89) and 48.8% (21/43) for the radical group. Biological characteristics included infiltrated, diffused growth, lymph node metastasis, female predominance. CONCLUSIONS: The biological behavior of gastric cancer in young persons is poor. Early management gastric cancer and radical operation combined with complex treatment are essential.

Adult↗
PubMed1997

Total, LDL, and HDL cholesterol decrease with age in older men and women. The Rancho Bernardo Study 1984-1994.

BACKGROUND: The purpose of the present study was to study the effects of age, weight change, and covariates on lipid and lipoprotein levels cross-sectionally and prospectively in an elderly population. METHODS AND RESULTS: A community-based sample of 1041 men and 1303 women aged 50 to 93 years was studied cross-sectionally in 1984 to 1987, with follow-up of 372 men and 545 women 8 years later. In the cross-sectional study, levels of total cholesterol (TC) and LDL cholesterol (LDL-C) decreased and levels of HDL cholesterol (HDLC) increased with age in men (all P < .001) but not in women. In the prospective study, TC, LDL-C, and HDL-C levels all decreased in both men and women, in all age groups (50 to 64 years, 65 to 74 years, and > or = 75 years) and in all weight change groups (> 2.5-kg loss, change within 2.5 kg, and > 2.5-kg gain) and in all waist girth change groups, for an overall decrement of approximately 1% per year. In multiple linear regression models, change in weight was the most important independent and consistent predictor of changes in TC, LDL-C, and HDL-C. Similar results were obtained in analyses excluding subjects taking lipid-lowering drugs or estrogen and in analyses adjusted for changes in cigarette smoking, alcohol intake, physical activity, medication use, and incident myocardial infarction, cancer, or diabetes. CONCLUSIONS: Cross-sectional decrements in TC and LDL-C with age in men are not explained by survivor bias because they are also observed prospectively. Although weight change was the most important explanatory variable, TC, LDL-C, and HDL-C levels also decreased in those who lost or gained weight. Age was not an independent predictor of change. Other prospective studies are recommended to better define the causes and consequences of cholesterol and lipoprotein changes in old age.

Aged↗
PubMed1997

Retinoic acid accelerates embryonic stem cell-derived cardiac differentiation and enhances development of ventricular cardiomyocytes.

Pluripotent embryonic stem (ES) cells spontaneously differentiate via embryo-like aggregates into cardiomyocytes of pacemaker-, atrium- and ventricle-like type, which can be distinguished by their specific patterns of action potentials. It has been shown that retinoic acid (RA) treatment during ES cell differentiation increases the number of cardiomyocytes in a time- and concentration-dependent manner. In order to test the effect of RA on cardiomyocyte differentiation and specialization into ventricle-like cardiomyocytes, we studied gene expression of beta-galactosidase driven by the ventricular myosin light chain-2 (MLC-2v) promoter as an indicator for ventricular differentiation. Clones containing the stably integrated expression vector pGNA/MLC-2.1 were selected, which revealed an increase of beta-galactosidase activity in cardiomyocytes of embryoid bodies at day 7 + 16. RA, both, in the all-trans and in the 9-cis configuration resulted in a significant acceleration of cardiomyocyte differentiation and a transient increase of beta-galactosidase activity. To test whether this acceleration of cardiac differentiation and RA-induced increase of the MLC-2v promotor/beta-galactosidase activity reflects an increase of cardiac- and ventricle-specific gene expression, a semi-quantitative RT-PCR analysis was performed for alpha-cardiac myosin heavy chain (alpha-MHC) and MLC-2v genes. It was shown that both 10(-8) M and 10(-9) M RA resulted in an increased level of alpha-cardiac MHC and MLC-2v mRNA in embryoid bodies in early, but not in terminal developmental stages. This led us to the conclusion that the RA-induced accelerated expression of cardiac-specific genes results in an enhanced development of ventricular cardiomyocytes. An increased number of ventricle-like cells after RA treatment was also found by patch-clamp analysis. The number of cardiomyocytes with Purkinje- and ventricle-like properties was shown to be increased by RA, whereas the number of pacemaker- and atrium-like cells was reduced and early pacemaker cells were not quantitatively affected.

Alitretinoin↗