Potentiation of the propunishment, but not the convulsant action of the beta-carboline DMCM by naltrexone

The ability of naltrexone (NTX) to potentiate the propunishment and convulsant properties of DMCM, a benzodiazepine receptor inverse agonist, was studied in mice. Doses (0.39 and 1.56 mg/kg) of DMCM which were below the threshold for propunishment effects showed a marked ability to enhance the suppressive effects of punishment on locomotor activity in the presence of naltrexone (0.5 or 2.5 mg/kg IP), higher doses of DMCM and NTX (3.13 mg/kg and 10 mg/kg, respectively) had a depressant effect of their own on both punished and unpunished locomotor activity. DMCM given alone induced clonic convulsions (ED50: 5.7 mg/kg IP) but this activity was not changed in the presence of naltrexone. These results suggest an interaction of BZ receptors and opioid systems in the control of anxiety.     

PLASMA PHOSPHOLIPASE A2 ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION

1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain.     

CT of pancreatic neoplasms Part II: The unusual tumors

The pancreas gives rise to a remarkable variety of neoplasms other than ductal adenocarcinoma. Although no individual type of tumor in this category is prevalent enough to qualify as common, most types are currently encountered with a frequency far greater than that in decades of the recent past. This change is largely the result of the expanded use of contemporary abdominal imaging. The unusual tumors of the pancreas vary greatly in their biologic behavior and, accordingly, in their clinical consequences and therapeutic requirements. Accurate diagnosis, therefore, can be of considerable clinical relevance. Not only is it worthwhile to distinguish one type of unusual pancreatic tumors from another, it is perhaps of even greater consequence to distinguish the unusual tumors from ordinary pancreatic adenocarcinomas. The goals of this discussion are to expand radiologic awareness of these uncommon but interesting pancreatic neoplasms and to increase familiarity with their diagnostically salient features.     

Physical activity and mental health in the United States and Canada: evidence from four population surveys

Secondary analysis of four surveys was carried out in order to examine the association of physical activity and various aspects of mental health in the household populations of the United States and Canada. Level of physical activity was shown to be positively associated with general well-being, lower levels of anxiety and depression, and positive mood. This relationship is independent of the effects of socioeconomic status and physical health, and described younger and older members of both sexes. The association is particularly strong for women and persons age 40 years and over. The robustness of this conclusion stems from the nature of the data sources: four population samples in two countries over the span of 10 years in which physical activity levels were assessed by four techniques and psychological status was assessed by six distinct scales. Although the surveys are cross-sectional, the most plausible explanation for the results is that physical activity enhances mental health in certain respects. Data on the comparative effects of recreation and housework suggest that quality of time, and not mere energy expenditure, must be taken into account in attempts to explain the psychological benefits of physical activity.     

Cystic pancreatic tumors: CT and sonographic assessment

Thirty-five CT scans and 23 sonograms of 45 pathologically proved pancreatic cystic neoplasms (16 microcystic adenomas, 17 mucinous [macrocystic] cystadenomas, and 12 mucinous [macrocystic] cystadenocarcinomas) in 43 patients were retrospectively and blindly reviewed. Radiologic findings and their usefulness in differentiating microcystic from mucinous subtypes were assessed. The number of cysts within the tumors (more than six in microcystic adenomas and six or fewer in mucinous cystadenomas and cystadenocarcinomas) and the diameter of the majority of cysts within the tumor (less than or equal to 2 cm in microcystic adenomas and greater than 2 cm in mucinous tumors) were the most helpful radiologic findings in differentiating tumor types. Calcification was present in 38% of microcystic adenomas, 18% of mucinous cystadenomas, and 8% of mucinous cystadenocarcinomas by CT. Calcification was not definitely identified on any of the sonograms. A central scar was identified in only two (13%) of 16 microcystic adenomas. Blind retrospective review was often able to correctly classify tumors as either microcystic (CT, 93%; sonography, 78%) or mucinous (CT, 95%; sonography, 93%). All tumors with a typical appearance on either CT or sonography were categorized correctly. Cystic pancreatic tumors may be difficult to prospectively separate from other types of pancreatic cysts. Assuming a cystic neoplasm is present, it often can be classified correctly as microcystic or mucinous (macrocystic) by using the above criteria.     

Autoimmune progesterone dermatitis: absence of contact sensitivity to glucocorticoids, oestrogen and 17-α-OH-progesterone

Autoimmune progesterone dermatitis is a rare condition, characterized by recurrent premenstrual exacerbations of a dermatosis, in which sensitivity to progesterone can be demonstrated. The sensitizing mechanism is unknown. The aim of this study was to test the hypothesis that cross-sensitivity between steroid groups could induce allergy to endogenous progesterone in these patients. 5 patients with autoimmune progesterone dermatitis and 1 with oestrogen-sensitive dermatitis have been patch tested with a corticosteroid series, conjugated oestrogen 1% in petrolatum (pet.), and 17-α-OH-progesterone 2% pet. There were no immediate or delayed reactions at 2 and 4 days to any steroid group. We have therefore been unable to demonstrate steroid cross-sensitivity, or a use for 17-α-OH-progesterone in the investigation of oestrogen - and progesterone-sensitive dermatoses.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.     

The ranking of facial attractiveness.

A method of assessing facial attractiveness is described in which facial photographs were ranked by adults in order from the most to the least attractive. The rankings of a group of normal 10-year-old children were compared to those given to a group of similarly aged patients with repaired clefts. Most previous methods have grouped patients into categories, but this tends to obscure individual differences in facial attractiveness: patients with small differences in appearance are generally placed in the same group. In the ranking technique described in this paper these individual differences were not obscured. Those individuals with repaired clefts were consistently judged as being less attractive than those in the normal group. It is suggested that this method could be further developed to assess the cosmetic benefit produced by treatment of facial deformity.     

Retinal pigment epithelial cells secrete urokinase-type plasminogen activator and its inhibitor PAI-1.

Secretion of plasminogen activators and their inhibitors was examined in cultures of human retinal pigment epithelial (RPE) cells. The methods employed were zymography and reverse zymography, solid-phase immunocapture assay, metabolic labeling followed by immunoprecipitation, and immunofluorescence. The results showed that these cells produce urokinase-type plasminogen activator (u-PA) and a plasminogen activator inhibitor (PAI) which is immunologically and biochemically similar to PAI-1. Tissue-type plasminogen activator activity (t-PA) was not detected, but we detected small amounts of t-PA in an inactive complex with inhibitor in RPE cell-conditioned media. We conclude that RPE cells have the potential to utilize u-PA-catalyzed plasminogen activation which is subject to regulation by PAI-1. These results may have a bearing on the pathogenesis of proliferative retinal diseases.