An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female

Hypergonadotropic hypogonadism is characterized by decreased gonadal function due to the inability of the gonads to respond to pituitary gonadotropins. Hypergonadotropic hypogonadism in females has many causes, among which are ovarian dysgenesis and abnormalities of the ovarian receptors for the pituitary gonadotropins. We evaluated a woman who presented with amenorrhea due to hypergonadotropic hypogonadism, but who had structurally normal ovaries. She is a sister of two previously identified 46,XY male pseudohermaphrodites with Leydig cell hypoplasia. Injection of hCG did not cause any change in plasma levels of estradiol or progesterone, suggesting complete ovarian resistance to LH. Analysis of the DNA sequence of the LH receptor gene revealed that the patient is homozygous for the same single base change as her two brothers. This mutation causes substitution of an alanine residue by a proline at position 593. In vitro analysis of the mutant LH receptor in cultured human embryonic kidney 293 cells documented that the receptor is unable to stimulate adenylyl cyclase in response to hCG. Plasma levels of estradiol and progesterone were low, whereas LH and FSH levels were increased. On histological analysis of the ovary, follicles were seen at all developmental stages. Nonetheless, primary amenorrhea had been present for 5 yr, and repeated measurements of plasma estradiol and progesterone indicate that ovulation does not occur. These results document the existence of inherited LH resistance as a cause of primary amenorrhea in women. The combined clinical and molecular observations are consistent with previous experimental data suggesting that in humans, LH is necessary for ovulation but follicular maturation can occur in the presence of FSH alone.     

Potential weekly intake of artificial food colours by 3-14-year-old children in Brazil.

The Potential Weekly Intake (PWI) of artificial food colours by 3-14-year-old children living in the District of Bar?o Geraldo, Campinas, S?o Paulo, Brazil, was estimated on the basis of average consumption data of artificially coloured food and analytically determined colour concentration in foodstuffs ingested. Coloured food consumption data were obtained through dietary recall interviews and collection of the packages and/or labels of the coloured foods consumed during a two-week period. Colours found in the individual types of foods detected through the consumption survey were identified and determined by methods that included wool dyeing and polyamide column extractions, ascending paper chromatography and spectrophotometry. The results showed that all artificial colours used in the composition of 83 commercial food products, including jellies, juices, soft drinks, syrups and 57 different candies, were permitted for use in food in Brazil the year the survey was conducted (1986), in amounts below those prescribed by law. Statistical analysis performed to compare the PWI for different population groups demonstrated that young male children, especially from lower social classes, were most exposed to artificial colours. Comparison of the estimated potential intakes with the toxicologically Acceptable Daily Intake (ADI) showed that consumption of Amaranth, Sunset Yellow, Indigotine and Tartrazine by all children in the study represented approximately 24%, 3%, 0.05% and 0.4%, of the actual ADI values, respectively.     

Rational polypharmacy in schizophrenia

Approximately 10 to 30% of patients with schizophrenia show poor response to neuroleptics alone. An initial evaluative and treatment approach to these patients is outlined, and the literature on adjunctive treatments, which seek to augment neuroleptic effects, is reviewed. The greatest evidence for efficacy has been shown for lithium, benzodiazepines, carbamazepine, reserpine, and electroconvulsive therapy, although individual patients may also respond to propranolol, clonidine, valproic acid, and L-dopa. Antidepressants may also be useful for treating comorbid depression in nonacutely psychotic patients. One general theme is that no one adjunctive treatment benefits all patients; indeed, only a minority of patients responds to any given agent. Therefore, the choice of specific treatments is best guided by the clinical characteristics of the individual patient. These observations raise the possibility that subgroups of schizophrenia exist; delineation of differences in clinical response to biochemically distinct agents may help elucidate such underlying differences between patient groups.     

In vitro study of the early membrane effects of C27-steroid hormone ecdysterone, immobilized on the nanodispersed magnetite surface]

The object of the study was to reveal the existence of receptor interactions of C27-steroid hormone ecdysterone with the surface of various cells (liver and spleen macrophages, thymus and spleen lymphocytes, erythrocytes and hepatocytes from rat organs) in experiments in vitro using ecdysterone immobilized on the nanodispersed iron surface (which did not penetrate the cell during observation) and the model of fast (during 15 s) activation of phospholipid signal system with ecdysterone. The parameters, which are characteristic of cell phospholipid signal system activation, were evaluated (the concentrations of free arachidonic acid, diene conjugates, tromboxane B2 and leukotriene C4) and its alteration in response to free and immobilized ecdysterone introduction in suspensins of intact cells and cells with the surface modified in vivo by pre-injection of antigen (human erythrocytes). Concurrent binding of immbilized ecdysterone with intact rat cells in the presence of free ecdysterone was also investigated. It was established that there are high-affinity ecdysterone-specific binding sites on the plasma membranes of all cells investigated, Kd estimated according to two different methods varied in the region of 10(-8)-10(-7) M. The characteristic features of the changes in parameters characteristic of phospholipid system activation were revealed to be queite similar in intact cells, as well as in cells with modified surfaces, under introduction of free ecdysterone and immobilized ecdysterone, which did not penetrate into cytosole. The data obtained point to the existence of ecdysterone receptors on the surface of cells plasma membranes and are indicative of the membrane effects as mechanisms of the early pregenomic phase of cells activation by ecdysterone.     

oriGNAI3: a narrow zone of preferential replication initiation in mammalian cells identified by 2D gel and competitive PCR replicon mapping techniques

The nature of mammalian origins of DNA replication remains controversial and this is primarily because two-dimensional gel replicon mapping techniques have identified broad zones of replication initiation whereas several other techniques, such as quantitative PCR, have disclosed more discrete sites of initiation at the same chromosomal loci. In this report we analyze the replication of an amplified genomic region encompassing the 3'-end of the GNAI3 gene, the entire GNAT2 gene and the intergenic region between them in exponentially growing Chinese hamster fibroblasts. These cells express GNAI3 but not GNAT2 . The replication pattern was first analyzed by two-dimensional neutral-alkaline gel electrophoresis. Surprisingly, the results revealed a small preferential zone of replication initiation, of at most 1.7 kb, located in a limited part of the GNAI3 - GNAT2 intergenic region. Mapping of this initiation zone was then confirmed by quantitative PCR. The agreement between the two techniques exploited here strengthens the hypothesis that preferred sites of replication initiation do exist in mammalian genomes.     

Effects of laser therapy on lipids and antioxidants in blood of patients with bronchial asthma

Laser therapy was assessed for effects on lipoperoxides and free radical catchers in blood lipids of patients with bronchial asthma (BA). When a group of 52 BA patients was compared to healthy donors by dienic conjugates, vitamin E and overall lipid-soluble antioxidants levels in the whole blood and plasma, these appeared higher in the asthmatics. Combination of laser therapy with conventional treatment returned these parameters close to normal.     

L-cystine-di-beta-naphthylamidase activity in plasma of the snake Bothrops jararaca after chronic challenges of water balance

Plasma protein, osmolality and L-cystine-di-beta-naphthylamidase activity were measured in Bothrops jararaca snakes submitted to normal hydration, water deprivation, water loading, salt loading or argvasotocin injections. Protein and osmolality were similar for male and female snakes in all treatments. Protein content was similar in all treatments, indicating the ability of the animals to maintain fluid balance between the vascular and extravascular compartment under osmotic challenges. Osmolality was increased in water-deprived and salt-loaded and was decreased in water-loaded animals compared with normally hydrated or argvasotocin-injected snakes. Enzymatic activity differed between males and females and was higher in salt-loaded females and in arg-vasotocin-injected females and males than in water-loaded snakes. A positive linear regression between osmolality and L-cystine-di-beta-naphthylamidase was obtained for female snakes (correlation coefficient = 0.6162, P < 0.01). The data show a role of arg-vasotocin in the consistent relationship between water balance and this sex-related aminopeptidase activity.     

Frequency of lyme borreliosis and diagnostic titers of antibodies to borrelia burgdorferi in patients with neurological diseases in endemic region of Russia

The frequency of diagnostic titers of antibodies to Borrelia burgdorferi in 289 examinees suffering from neurological diseases made up 10.4%, while in the population this figure was under 1.9%. Lyme-borreliosis was detected in 11 (3.8%) patients, 2 of them had mixed infection with tick-borne viral encephalitis. In 10 patients (3.5%) the diagnosis of neuroborreliosis required verification with other techniques. It is thought valid to perform serological screening for neuroborreliosis only in patients with tick-born encephalitis to identify mixed infection.