Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1.

N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4-nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4-cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response.     

A fatal case of Mycoplasma hominis meningoencephalitis in a full-term newborn.

We report the case of a 20-day-old full-term baby, born to a mother who had had an uncomplicated pregnancy and delivery, who died 13 days after the onset of meningitis. Mycoplasma hominis was the sole agent repeatedly recovered from cerebrospinal fluid and from postmortem brain tissue.     

Vital capacity restitution curve: prognostic value in chronic decompensated respiratory insufficiency

From a series of 50 patients with acute decompensation of chronic obstructive lung disease (38 of whom were treated by mechanical ventilation), the authors demonstrate the prognostic value of an easily obtained parameter of respiratory function: the vital capacity restitution curve (VCRC). From daily measurements of vital capacity, beginning on the day of admission, a graph is constructed which shows an initial period of increase in the degree of restitution, followed by stabilization of the values. An analysis of the various parameters embodied in this graph provides information about the prognosis. Such graphs can be divided into 3 zones of prognostic value: a favourable zone, an intermediate zone (mediocre survival with or without mechanical ventilation) and an unfavourable zone (death during the acute phase). Although a favourable prognosis can be made after 4 days of observation and almost always by the 10th day, an unfavourable prognosis cannot be made before the 21st day.     

Relationship of HLA to schizophrenia not supported in multiplex families.

The role of the human histocompatibility complex (HLA) in the pathogenesis of schizophrenia has been suggested in previous reports. We conducted a genetic study in 33 new families. Our linkage analysis, which used the affected sib-pair method, did not provide evidence for nonrandom assortment. Moreover, the results of an association study using the "haplotype relative risk" method failed to confirm the positive association between HLA A9 and schizophrenia. Taken together, our data did not support any relationship of HLA type to schizophrenia.     

Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in brief no. 217. Online

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/ bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 9 families affected by severe hypophosphatasia. Fourteen distinct mutations were found, 3 of which were previously reported in the North American or Japanese populations. Seven of the 11 new mutations were missense mutations (M45L, R119H, G145V, C184Y and H154Y, D289V, E459K), the four others were 2 single nucleotide deletions (544delG and 1172delC), a mutation affecting donor splice site (862 + 5A) and a nonsense mutation (R411X).     

Menstrual cycle and appetite control: implications for weight regulation

Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.      

Presentation of antigen to suppressor cells by a dimethylbenz (a) anthracene-resistant, Ia-positive, Thy-1-negative, I-J-restricted epidermal cell

The epidermal layer of the skin contains class II major histocompatibility (MHC)-positive antigen-presenting cells (APC), the most well characterized population being Langerhans' cells (LC). The chemical carcinogen 7,12 dimethylbenz (a) anthracene (DMBA) depletes about two-thirds of these cells from murine epidermis, and contact sensitizers applied to DMBA-treated skin induce specific immunological tolerance. This tolerance results from epidermal cells migrating to local lymph nodes within 3-6 hr after contact with antigen where they present the antigen to suppressor cells. Here we demonstrate that this epidermal cell which activates suppressor cells is a class II MHC-positive. Thy-1-negative, I-J-restricted APC. Hence at least two types of class II MHC-positive epidermal cells migrate to local lymph nodes and present antigen to lymphocytes; LC, which are sensitive to the effects of DMBA and activate helper lymphocytes, and another, which is resistant to DMBA and activates suppressor cells in an I-J-restricted manner. During the early stages of carcinogenesis any antigen present in the epidermis would be presented only by the cells which activate suppressor lymphocytes, resulting in tolerance induction. This may enable neoplastic cells to avoid the initiation of anti-tumour immunity.     

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.