Increased prostaglandin H synthase-1 expression and activity level in stably Harvey-ras transfected C3H10T1/2 cells

In these studies, prostaglandin H synthase activity was increased in stably Harvey-ras transfected C3H10T1/2 cells. The level of total prostaglandin H synthase protein was two-fold higher in stably Harvey-ras transfected C3H10T1/2 cells than in control cells with no difference in prostaglandin H synthase-2 level. Prostaglandin H synthase-1 mRNA level was two-fold higher in transfected than in control cells, while prostaglandin H synthase-2 was not significantly different. Thus, prostaglandin H synthase-1, but not prostaglandin H synthase-2, expression was increased in Harvey-ras transfected C3H10T1/2 cells.     

Disease type-associated increases of the plasma levels and ligand expression for natural alpha- or beta-galactoside-binding immunoglobulin G subfractions in patients with lung cancer

The presence of natural carbohydrate-binding antibodies may play a role in host defence against malignant cells in addition to elicitation of an immune response by artificial carbohydrate antigens. Human serum contains immunoglobulin G(2) (IgG) fractions with selectivity to alpha- and to beta-galactosides, respectively, irrespective of the type of blood group of the donor. To determine whether these naturally occurring subfractions may have any relevance for tumor disease control, their binding to malignant cells was ascertained by cytofluorimetric assays in vitro with a number of human tumor cell lines of different histogenetic origin. The affinity of cell binding was comparable to that of binding to lactosylated or melibiosylated neoglycoconjugates as model ligands in solid-phase assays and K-D values were found to be in the range of 5-300 nM. Cross-reactivity of the anomer-selective subfractions to the other type of ligand was observed to be rather low. When the IgG contents of plasma samples of patients with diverse types of lung cancer were assessed, the concentrations of both galactoside-binding immunoglobulin G subfractions were significantly increased in association with presence of small cell lung carcinoma and of metastatic lesions to the lung without any marked change in the overall IgG plasma level. Such an apparently general enhancement was seen for patients with adenocarcinoma and included both subfractions with no impact on their percentage in the total IEC content. When detergent extracts of tumor and tumor-free specimens of the same patient were analyzed with the affinity purified antibody subfractions to comparatively determine ligand presentation, increases in sugar-inhibitable binding were especially noted for the tumor tissue of small cell lung carcinomas and apparently tumor-free samples of cases with lung metastasis. Material from other types of lung cancer revealed no significant indication for disease-related alterations with the exception of carcinoids. These data demonstrate that plasma levels and ligand expression for two types of natural galactoside-binding immunoglobulin G fractions can show nonuniform responses in patients within the class of lung cancer. They encourage to deliberately monitor these parameters of the natural carbohydrate-directed antibody fractions in cancer patients with various types of disease to clarify the clinical significance of respective malignancy-associated changes.     

Health seeking behaviour and household health expenditures in Benin and Guinea: the equity implications of the Bamako Initiative

Curative and preventive care utilization in Bamako Initiative health centres in Guinea and Benin increased significantly. Service based data and household survey results are compared and interpreted to evaluate the equity aspects of the Bamako Initiative programmes in these settings. Improvements in the use of preventive services are shared by the richer and poorer groups of the population. Inequities are more apparent regarding curative area. An important part of the population is not using Bamako Initiative Health Centres for financial reasons. However, the poor were found to use these Health Centres relatively more than richer socio-economic groups. Challenges of the future are identified and recommendations made as to how to tackle the problem of true indigence.     

Cardiopulmonary indications for endothelin receptor antagonists: review of recent efficacy trials

Recent clinical and experimental animal trials indicate that endogenously produced endothelin-1 (ET-1) contributes to the abnormal systemic and pulmonary vascular resistance associated with congestive heart failure (CHF) and pulmonary hypertension (PH). In experimental CHF, the chronic blockade of ET-1 actions by ET receptor antagonists clearly improves haemodynamic status, and improves cardiac structure and survival. The latter is based on limited results. In experimental PH there are consistent reports of prevention and reversal of PH, pulmonary vascular remodelling and right ventricular hypertrophy, independent of the inciting mechanisms. These results in experimental animals illustrate the potential efficacy of the ET receptor antagonists in future clinical trials. With five ET receptor antagonists in clinical development, and more on the way, their potential will soon be realised.     

人眼小梁细胞体外表达表皮生长因子mRNA和表皮生长因子受体

目的 了解培养的小梁细胞分泌表皮生长因子（ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＥＧＦ）及细胞膜上表皮生长因子受体（ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ,ＥＧＦＲ）的情况。方法 进行人眼小梁细胞体外培养。用ＥＧＦ ｃＤＡＮ探针,α＾－３２ｐ同位素标记及斑点杂交放射自显影法,检测小梁细胞分泌ＥＧＦｍＲＮＡ的情况。结果 人眼小梁细胞体外培养成功。免疫组化染色显示小     

Primary liver tumors in China

Until now, no large series studies on the clinicopathological features of primary liver tumors (PLTs) in mainland China have been reported. The authors retrospectively investigated 3,160 cases of PLTs surgically resected at Shanghai Oriental Hospital of Hepatobiliary Surgery between January 1982 and January 1996. Most of them are true neoplasms, others are tumor-like lesions. The 3,160 cases of PLTs could be divided into 3 groups of 25 types arising from three germinal layers, of which tumor-like lesions (Group 1) were of 4 types involving 112 cases (3.5%), benign PLTs (Group 2) were of 10 types involving 499 cases (15.8%) and malignant PLTs (Group 3) were of 11 types involving 2,549 cases (80.7%). The most common type of lesion in each group was solitary necrotic nodule, cavernous hemangioma and hepatocellular carcinoma (HCC), accounting for 73.2%, 74.3% and 96.6% of their respective groups. The patients ranged in age from 5 months to 79 years (mean, 45.7 years), but the age distribution and sex ratio varied reciprocally from group to group and from lesion to lesion. For example, the mean age of the patients in Group 1 was 39.1 years of age, whereas in Group 2 and Group 3, it was 45.9 years and 49.6 years, respectively. The sex ratio of men to women was 2.6:1 in Group 1, 1:1.1 in Group 2 and 7.7:1 in Group 3. The rates of serum HBsAg positivity and concomitant liver cirrhosis in the patients with HCC were 74.4% and 72%, respectively, and the concomitant rate of cirrhosis in small HCC (<3 cm in diameter) was as high as 83.3% (P<0.05), demonstrating a close relationship of HCC with HBV infection and liver cirrhosis. HCC amounts to 78.4% of the total 3,160 PLTs in this series, indicating that HCC is the most common malignant tumor of the liver in China.     

Emergency medical services systems in the United States and China: a developmental comparison

International emergency medical services (EMS) consultation requires many sensitivities to cross-cultural issues. Contemporary EMS models in developed countries have, by necessity, a systems framework. This study compares evolving EMS systems in the United States and China. It is concluded, that, no matter what the potential and cultural differences might be, a systems framework inherently will emerge in EMS development. As such, the EMS components recognized often will expose an evolving systems approach with more similarities than differences and can reveal strategies for improvement. Providing a developmental comparison process is a necessary first phase in analysis of a country's systems development or restructuring.     

Acute systemic and antiischemic effects of epanolol in patients with coronary artery disease

Summary Antiischemic effects of ₁-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial ₁-agonistic activity, although useful in preserving cardiac function, may counteract such antischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective ₁-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p<.05), whereas cardiac output fell temporarily by 9% (p<.05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p<.05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16±7% vs. –7±8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p<.05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional ₁-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its ₁-antagonistic profile.     

Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor andα 2 adrenoceptor blockade on naloxone-induced antinociception

Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature=51.5 ± 0.5°C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or ₂ adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5–10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT₁ or 5-HT₃ receptors by methiothepin or MDL 72222, respectively, or by the ₂ adrenoceptor blocker idazoxan. None of the 5-HT or ₂ adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT₂ receptors in the antinociception induced by opioid receptor blockade is discussed.     

Solubility Enhancement of Nucleosides and Structurally Related Compounds by Complex Formation

Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excipients were studied as solubilizing agents for poorly water-soluble adenine (nucleic acid base), guanosine (nucleoside), and structurally related drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was appreciably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (K _a ) values were measured at 25°C in pH 7 phosphate buffer using phase solubility analysis. The effect of combination ligands on substrate solubility was also studied. Additive solubility enhancement was obtained for several ligand pairs.