Dihydrofolate reductase and thymidylate synthase in plants: an open problem

This review deals with recent findings in the purification and characterization of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) in plants. The few enzymes purified, which differ remarkably in regard to their structure. kinetic and molecular properties and subcellular location are described. The response of DHFRs to antifolic agents and the analysis of resistance mechanisms in isolated cell lines is also reported. Problems opened by recent studies of the enzymes isolated from plants are outlined.     

Hemorheological and coagulation aspects in plasmacytoma

We reported the main rheological and coagulative features in seven patients affected with monoclonal gammapathy: four of them presented IgA class paraprotein, two IgM class paraprotein and one IgG class paraprotein. All presented increased plasma and serum viscosity. The four patients affected with IgA monoclonal paraproteinaemia underwent one plasma volume plasmapheresis. This procedure has been demonstrated to be useful and effective in reducing both plasma and serum viscosity.     

Prolactin lowering effect of amphetamine in normoprolactinemic subjects and in physiological and pathological hyperprolactinemia

The effect on plasma prolactin (PRL) of d-amphetamine (Amph) was studied in normo- and hyperprolactinemic subjects. In normoprolactinemic women Amph failed to lower plasma PRL levels when infused intravenously over 1 h at the dose of 7.5 mg, but induced at the dose of 15.0 mg a modest inhibition of plasma PRL (maximum PRL inhibition 20 +/- 4.5% at 45 min). Likewise, in puerperal women Amph at the dose of 7.5 mg did not decrease significantly plasma PRL levels but it was active in this respect (maximum inhibition 37 +/- 10% at 120 min) at the dose of 15.0 mg. In subjects with presumptive evidence of a PRL-secreting adenoma, Amph at either the 7.5 mg or the 15.0 mg dose failed to alter baseline PRL levels. These results indicate that Amph is a poor PRL suppressor in either normo- or hyperprolactinemic subjects. It is proposed that this may be due to the drug's ability to effect release of dopamine mainly from a non-granular pool of the amine.     

Platelet factor 4 (PF4) and heparin released platelet factor 4 (HR-PF4) in diabetes mellitus. Effect of the duration of the disease

Several investigators have reported an altered platelet function in diabetes mellitus as measured by elevated levels of platelet specific proteins platelet factor 4 (PF4) and B-thromboglobulin (BTG). We studied 20 insulin dependent (IDD), 20 non insulin dependent (NIDD) diabetic males without overt clinical symptoms of cardiovascular disorders and 30 normal controls. We evaluated PF4, BTG and heparin released platelet factor 4 (HR-PF4) as measured 2.5 minutes after a bolus injection of 5,000 I.U. of a commercial mucous heparin. The patients showed normal levels of both PF4 and BTG. Furthermore HR-PF4 failed to show statistically significant variation between patients and controls. However when the diabetics were divided on the basis of the duration of the disease, the IDD had an increased HR-PF4 mean level and the trend became statistically significant when diabetes existed more than 17 years (patients HR-PF4 149.1 ng/ml, range 17.3-194; controls HR-PF4 110.9 ng/ml range 50-160, less than p less than 0.05). NIDD failed to reveal the same pattern. Although the significance of HR-PF4 is unknown, insulin dependent diabetes mellitus after many years could cause a potentially dangerous, silent vascular damage with enhanced platelet vessel wall interaction as measured by an elevated HR-PF4.     

Release of nucleotide-cleaving acid phosphatase from carrot cells grown in suspension culture

Carrot ( Daucus carota L. cv. Lunga di Amsterdam) cells grown in suspension culture release into the culture medium a phosphatase capable of converting deoxyribo- as well as ribonucleoside triphosphates into nucleosides. The enzyme activity requires acidic pH and allows a prompt utilization of phosphorylated DNA precursors as measured by tritiated dTTP incorporation. Such utilization is partially inhibited by inorganic phosphate and completely inhibited by ATP.     

Maintenance of a normal meal-induced decrease in plasma ghrelin levels in children with Prader-Willi syndrome.

Ghrelin is a 28-amino acid peptide recently identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Ghrelin is a potent stimulator of GH secretion. It was recently shown that circulating ghrelin levels in humans rise shortly before and fall shortly after every meal, and that ghrelin administration increases voluntary food intake. The hypothesis that ghrelin hypersecretion might contribute to genetic obesity has never been investigated. In this context, Prader-Willi syndrome is the most common form of human syndromic obesity. As ghrelin affects appetite as well as GH secretion and both are abnormal in PWS, it has been surmised that these alterations might be due to ghrelin dysregulation. The aim of the study was to investigate whether ghrelin is suppressed by the meals differently in PWS children than in PWS adults. Overnight circulating fasting ghrelin levels and ghrelin levels 120 min after breakfast were assayed in 7 PWS children (10.2 +/- 1.7 yr), 7 subjects with morbid obesity (10.3 +/- 1.3 yr), and 5 normal controls (8.4 +/- 1.4 yr). Because of the data spread, no statistical difference was observed in fasting ghrelin levels between PWS and control children (p = NS); anyway, fasting ghrelin levels were significantly lower in obese children than in the other groups (p < 0.05 vs. control and PWS children). Ghrelin levels were slightly suppressed by the meal in control subjects (mean fasting ghrelin: 160.2 +/- 82 pg/ml; after the meal, 141.2 +/- 57 pg/ml, p = NS); the meal failed to suppress ghrelin levels in obese children (mean fasting ghrelin: 126.4 +/- 8.5 pg/ml; after the meal, 119.1 +/- 8.3 pg/ml, p = NS). Interestingly, the meal markedly suppressed ghrelin levels in PWS children (mean fasting ghrelin: 229.5 +/- 70.4 pg/ml; after the meal, 155.8 +/- 34.2 pg/ml, p < 0.01). In conclusion, since a lack of decrease in circulating ghrelin induced by the meal was previously reported in PWS adults, the finding of a meal-induced decrease in ghrelin levels in our population of young PWS would imply that the regulation of the ghrelin system involved in the orexigenic effects of the peptide is operative during childhood, although it progressively deteriorates and is absent in adulthood when hyperphagia and obesity progressively worsen.     

Combined deficiency of factor V and factor VIII. A report of another case.

A patient with combined factor V and factor VIII deficiency is presented. The bleeding manifestations were: easy bruising, post-traumatic bleeding, bleeding after tooth extractions. The main laboratory feature was a prolonged partial thromboplastin time which was corrected by the addition of adsorbed normal plasma but not by the addition of normal serum, hemophilia A plasma of another patient with combined factor V and factor VIII deficiency. The thromboplastin generation test was clearly abnormal and was corrected by the addition of adsorbed normal plasma but not by addition of normal serum. Prothrombin consumption was also defective. Prothrombin time was slightly prolonged too, Thrombin time, platelet and vascular tests were within normal limits and there was no hyperfibrinolysis. Factor VIII was 8% of normal, whereas factor V was 14% of normal. Factor VIII associated antigen was normal. All other clotting factors were within normal limits. The parents of the propositus were consanguineous (first cousins) but had normal factor V and factor VIII activity and normal factor VIII antigen. The same was true for other family members. The hereditary transmission of the condition appears autosomal recessive.     

Behavioral Weight Control for Overweight Adolescents Initiated in Primary Care

Objective: This study evaluates the post-treatment and short-term follow-up efficacy of, as well as participant satisfaction for, a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact. Research Methods and Procedures: 44 overweight adolescents were randomly assigned to either a multiple component behavioral weight control intervention (Healthy Habits [HH]; n = 23) or a single session of physician weight counseling (typical care [TC]; n = 21). Weight, height, dietary intake, physical activity, sedentary behavior, and problematic weight-related and eating behaviors and beliefs were assessed before treatment, after the 4-month treatment, and at 3-month follow-up. Participant satisfaction and behavioral skills use were measured. Results: HH adolescents evidenced better change in body mass index z scores to post-treatment than TC adolescents. Body mass index z scores changed similarly in the conditions from post-treatment through follow-up. Behavioral skills use was higher among HH than TC adolescents, and higher behavioral skills use was related to better weight outcome. Energy intake, percentage of calories from fat, physical activity, sedentary behavior, and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition. The behavioral intervention evidenced good feasibility and participant satisfaction. Discussion: A telephone- and mail-based behavioral intervention initiated in primary care resulted in better weight control efficacy relative to care typically provided to overweight adolescents. Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth.