The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline

A 28-year-old woman was referred to us to undergo 131I therapy who had multiple pulmonary metastases from papillary thyroid carcinoma after total thyroidectomy. There was no increased accumulation of a tracer in the pulmonary metastatic foci on whole-body scanning using a 111 MBq diagnostic dose of 131I. However, the pulmonary metastases were gradually decreased in size, and then clearly reduced 8 months after the start of TSH suppression therapy, which was maintained by T3 instead of T4 to bring down the serum TSH level below 0.1 microU/ml. Reduction rates of the foci were 33-76% on chest X-ray. The reduction was confirmed and no new lesions were found on the serial CT scans. Serum thyroglobulin level was lowered 80 to 25 ng/ml by this suppression therapy and progression of disease was not observed under a 54 months' T3 treatment. Thus, TSH suppression therapy might improve survival of patients with differentiated thyroid cancer.     

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for > or = 40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.     

Failure of thrombolytic therapy in patients with myocardial infarction is associated with high plasma levels of factor VII antigen

Thrombolytic therapy in acute myocardial infarction fails to re-establish coronary blood flow in a significant number of patients. One reason for this may be haemostatic imbalance. We investigated whether coagulation factor VII antigen (FVIIag), fibrinogen and protein C were related to reperfusion. Plasma from 45 patients was drawn before treatment and reperfusion assessed by means of continuous, on-line, vector-ECG analysis. Among the 17 patients with no reperfusion, FVIIag levels were significantly higher than among the 28 with signs of reperfusion (560 vs. 410 microg/l median, p = 0.006). Protein C levels where higher in the group with successful reperfusion (1.10 vs. 1.01 U/ml median, p = 0.03), whereas no difference was seen in fibrinogen levels. The findings were not influenced by plasma-triglycerides, body-mass index, age or time between onset of chest pain and thrombolytic therapy. The results suggest that FVII is of importance for the formation as well as resolution of coronary clots.     

The sociopsychological importance of food in hospital. Evaluation of a new meal system in a children's cancer ward

Malnutrition of patients in hospitals is a subject that is fairly well described in the medical literature, but less attention has been paid to the social significance of food in hospitals. This article describes a study of the social and psychological impact of the introduction of a new meal delivery system in a children's cancer ward. A traditional centralized meal system was replaced by a staffed local kitchen. The evaluation involved questionnaires to the children, parents and staff members; qualitative, indepth, semi-structured interviews with subgroups; observations of meals. Children, staff and parents greatly preferred the new meal system, which changed the significance of food and meals in the hospital: from an arena of conflict and problems to one with a greatly enhanced social status. The article underlines that it is important to integrate socio-psychological and nutritional aspects of food and eating if malnutrition in hospitals is to be overcome.     

Novel spironucleosides: 1",3"-thiazolidine-2"-spiro-3'-3'-deoxyuridine derivatives

Reaction of 2',5'-di-O-TBDMS-3'-ketouridine 1 with L-cysteine yielded in good yield a resolvable mixture of the two expected epimeric spironucleosides 2 and 3. Amidification of their carboxylic group took place readily and the ribo carboxamide 4 was oxidized to the corresponding sulfoxide 6. Despite their similarity to TSAO derivatives these compounds did not exhibit usable anti-HIV activity.     

Bladder carcinoma with lymphoepithelioma-like differentiation: a report of 9 cases

Both an antibody that catalyzes metal insertion into porphyrins and the corresponding enzyme, ferrochelatase, are shown by resonance Raman spectroscopy to induce distortion in the bound porphyrin substrate. It was found that the enzyme-induced distortion is different from that induced by the antibody; the catalytic antibody produces a distortion which is similar to the one present in the hapten, N-methylmesoporphyrin IX (N-MeMP). Activation of specific out-of-plane vibrational modes reveal that the antibody induces an alternating up-and-down tilting of the pyrrole rings, while ferrochelatase induces tilting of all four pyrrole rings in the same direction (doming). Both distortions are effective in catalyzing metal insertion. The distortion induced in the enzyme is only seen when an inhibitory metal ion is also bound. This observation suggests an allosteric mechanism, in which a conformational change which distorts the porphyrin toward the transition state geometry, is induced by metal binding at an adjacent site. In contrast, the antibody does not have a metal binding site and appears to function largely through binding interactions with the porphyrin.     

The effect of phospholipase C on human blood platelets

The effect of phospholipase C (EC 3.1.4.3) on human blood platelets has been studied. Phospholipase C from Bacillus cereus was purified to homogeneity as judged by analytical and sodium dodecyl sulphate disc gel electrophoresis and by immunoelectrophoresis. Human platelets isolated from platelet-rich plasma by gel filtration or by centrifugation and washing were incubated with phospholipase C. A loss of 20-45% of the total platelet phospholipid was observed, whereas 88% was hydrolyzed when platelet homogenates were submitted to identical enzyme treatment. Intact platelets lost 50-75% phosphatidylethanolamine, 20-50% phosphatidylcholine, and 20-25% phosphatidylserine. Sphingomyelin was not a substrate for the enzyme under the conditions used. The platelets contained no detectable endogenous phospholipase C activity. The loss of phospholipid was not accompanied by aggregation of the platelets, nor did the platelets lose their ability to aggregate with ADP or thrombin. Total platelet factor 3 releasable by freezing and thawing was reduced. Measurements of releasable platelet factor 4 and the efflux of serotonin showed that no release reaction was triggered even when up to 45% of the total phospholipid in the platelets was hydrolyzed. When sphingomyelinase was added together with, before, or after phospholipase C, aggregation occurred. Sphingomyelinase alone gave no aggregation. The gel-filtered platelets also aggregated upon addition of purified phospholipase C from Clostridium perfringens. The distribution of phospholipids in the platelet membrane is discussed.     

The evolution of enzymatic interesterification in the oils and fats industry

Immobilised lipases have now become accepted as a mainstream technology for fat modification. This paper presents the development of this technology in particular for the production of trans‐free fats. One of the factors influencing this development has been concern for health, which has made trans fats a major issue for food manufacturers and consumers. Enzymatic interesterification is a relatively new method for producing trans‐free alternatives for fats used in conventional margarines and shortenings. The development of this technology is examined from the perspective of an eventual industrial application rather than operation only at the laboratory scale. This paper also covers the practical means of operating immobilised enzyme columns and gives examples of how formulations can be adapted to match existing specifications. There are environmental benefits when choosing enzyme technology in comparison with chemical‐based routes. Life cycle assessments have been used to quantify the differences in environmental impact of this new technology. The final process is both capable of providing fats with the correct melting properties but without trans fats and of reducing the environmental impact of fat processing. Finally, the future developments that are anticipated in the applications of this technology are considered.     

The P9 pocket of HLA-DQ2 (non-Aspbeta57) has no particular preference for negatively charged anchor residues found in other type 1 diabetes-predisposing non-Aspbeta57 MHC class II molecules

Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno-pathogenic peptides. Recent studies in man and mouse have revealed that some type 1 diabetes-predisposing non-Aspbeta57 class II molecules (i.e. DQ8, DR4Dw15 and I-Ag7) preferentially bind peptides with a negatively charged anchor residue at P9. It has been suggested that this is a common feature of type 1 diabetes-predisposing class II molecules. The molecular explanation for such a phenomenon could be that class II beta chains with Aspbeta57 form a salt bridge between Aspbeta57 and a conserved Arg of the a chain, whereas in non-Aspbeta57 molecules the Arg is unopposed and free to interact with negatively charged P9 peptide anchor residues. We have investigated the specificity of the P9 pocket of the type 1 diabetes-associated DQ2 molecule and in particular examined for charge effects at this anchor position. Different approaches were undertaken. We analyzed binding of a high-affinity binding ligand and P9-substituted variants of this peptide, and we analyzed the binding of a set of synthetic random peptide libraries. The binding analyses were performed with wild-type DQ2 and a mutated DQ2 with Ala at beta57 substituted with Asp. Our results indicate that the wild-type DQ2 (non-Aspbeta57) prefers large hydrophobic residues at P9 and that there is no particular preference for binding peptides with negatively charged residues at this position. The specificity of the P9 pocket in the mutated DQ molecule is altered, indicating that the beta57 residue contributes to determining the specificity of the P9 pocket. Our data do not lend support to the hypothesis that all non-Asp beta57 class II molecules predispose to development of disease by binding peptides with negatively charged P9 anchor residues.