Deficiency of immunoreactive somatostatin in the median eminence of Snell dwarf mice

Snell dwarf mice (dw/dw) are characterized by a genetically determined, congenital lack of pituitary GH, TSH and prolactin. Given that hypothalamic somatostatin is involved in the regulation of pituitary GH and TSH release, it was decided to investigate the content of immunoreactive somatostatin (IRS) in the median eminence of dw/dw and phenotypically normal mice of the same strain. The content of IRS in the pyloric antrum and pineal gland of these animals was also examined. The effects of ovariectomy and of hyperprolactinemia (induced by a pituitary graft under the kidney capsule) on the median eminence content of IRS were also studied in both normal and dwarf mice. Median eminence IRS content was significantly lower in the dw/dw (23.6 +/- 1.8 ng) than in normal mice (57.4 +/- 7.1 ng); no difference was found in the pyloric IRS content of dw/dw (16.9 +/- 1.6 ng/mg of protein) and normal animals (13.8 +/- 1.9 ng/mg of protein), nor in the pineal content of IRS (639.4 +/- 64.4 pg/gland in the dw/dw; 732 +/- 265 pg/gland in normals). Neither ovariectomy nor hyperprolactinemia were found to affect the IRS content in the tissues studied in normal or dwarf mice. Treatment of an additional group of 9 dwarf mice with L-thyroxine (L-T4 2 micrograms/48 h. s.c. for 2 weeks) significantly increased the animals weight (10.2 +/- 0.4 g versus 7.4 +/- 0.3 g) and produced maturation of facial features; however, it did not change the IRS content in any of the tissues studied. It is concluded that the content of IRS in the median eminence of mice with a congenital lack of GH, TSH and prolactin is significantly reduced and that this is unlikely to be related to the deficiency of thyroid hormones in these animals.     

Study of the dynamics of neutralization escape mutants in a chimpanzee naturally infected with the simian immunodeficiency virus SIVcpz-ant.

Here we report on the use of spectral map analysis of time-paired sequential neutralization data of 11 serum samples of a chimpanzee naturally infected with a simian immunodeficiency virus (SIVcpz-ant) and 8 primary consecutive SIVcpz-ant isolates, taken at about 4-month intervals. The analysis reveals the existence of three SIVcpz-ant isolate and serum neutralization clusters. Each cluster groups virus isolates and/or sera based on similarities of their neutralization spectra. On average, neutralization escape mutants emerged after 15 months and mounted a neutralization response approximately 8 months later. The entire gp160 regions of eight consecutive isolates were sequenced and analyzed by a new statistical method called polygram, which allowed the deduction of amino acid sequence motifs of gp160 which were specific for SIVcpz-ant isolates belonging to the same isolate neutralization clusters. Changes in specific amino acid quadruplets in V1, V2, C3, V4, V5, and CD4 domains of gp120 and gp40 were seen to correlate with the neutralization clusters with most of the specific changes occurring in the V4 region. This method of analysis may facilitate an understanding of the study of the dynamic interplay between human immunodeficiency virus (HIV) and host neutralization responses as well as providing possible insights into mechanisms of persistence of HIV-1-related lentiviruses in their natural hosts.     

Melatonin-induced suppression of the pinealectomy-stimulated rat adrenal cortex mitotic activity

Pineal involvement in the regulation of adrenocortical mitotic activity has recently been suggested. It has been shown that melatonin (Mel) decreased the mean mitotic activity rate (MMAR) of the adrenal cortex both in vivo and in organ culture. The goal of the present study was to test the influence of pinealectomy (PX) and/or Mel-treatment on the MMAR of adrenocortical cells, as well as on the adrenal weight in rats. The stathmokinetic method was used in the study. It was found that PX significantly increased the MMAR of the adrenocortical cells. Moreover, Mel suppressed the proliferogenic effect of PX on the rat adrenocortical cells. Melatonin alone did not significantly affect the mitotic activity of the adrenal cortex. None of the three experimental procedures, i.e. Mel, PX and Mel-treatment of pinealectomized animals significantly affected the adrenal weight. The present data suggest that Mel may be involved in the inhibitory control of adrenocortical cell proliferation.     

Competitive exclusion,or species aggregation?

Summary There is a long-standing dispute over whether the analysis of species co-occurrence data, typically on islands in an archipelago, can disclose the forces at work in structuring a community. Here we present and utilise three scores S, C and T. S gives the mean number of islands shared by a species pair in the presence/absence data under study. The scores C and T are based on the way that a pair of species occurs on a pair of islands. When each species occurs on a different island, this adds to the checkerboard score C; if they occupy the same island, this increases the togetherness score T.In judging whether observed values of S, C and T are compatible with a null hypothesis assuming no species interaction, we follow Connor and Simberloff (1979) in generating a control group of (constrained) simulated incidence patterns.Presence/absence matrices can have paradoxical features, in combining a high mutual exclusion by species (checkerboardedness) with a degree of species aggregation that is also high. We show that this is in fact inevitable — that, given the usual contraints, C and T can differ only by a constant. This means that extreme checkerboardedness can be produced by forces making for species aggregation, just as well as by those making for avoidance.If we restrict our attention to a subset of species, the constraints are less rigid and the S, C and T scores are somewhat freer to vary. We consider the confamilial subsets in the Vanuatu archipelago as likely candidates for revealing any competition forces at work. Calculating the actual S, C and T scores for these subsets, we compare them with the corresponding scores in a sample of simulated colonization patterns.The actual species-distributions differ significantly from what we would expect if the colonization choices of different species were uncorrelated (save for some biological constraints). The confamilial species of the real world share more islands, and occur in a pattern less checkerboarded, and more aggregated, than their simulation counterparts. This suggests that competition pressures, if they exist, are overcome by countervailing factors.The method used is applicable in other ways, and to a wider class of problems, in analysing the forces behind community structure.     

Classification of dopamine-antagonists from pharmacological data

A graphical method is described that allows to classify the dopamine- antagonists on the basis of three pharmacological observations. The so-called spectral map represents the relative affinities of these drugs for three receptor sites.     

Using genetic algorithms for the construction of phylogenetic trees: application to G-protein coupled receptor sequences

Many different phylogenetic clustering techniques are used currently. One approach is to first determine the topology with a common clustering method and then calculate the branch lengths of the tree. If the resulting tree is not optimal exchanging tree branches can make some local changes in the tree topology. The whole process can be iterated until a satisfactory result has been obtained. The efficiency of this method fully depends on the initially generated tree. Although local changes are made, the optimal tree will never be found if the initial tree is poorly chosen. In this article, genetic algorithms are applied such that the optimal tree can be found even with a bad initial tree topology. This tree generating method is tested by comparing its results with the results of the FITCH program in the PHYLIP software package. Two simulated data sets and a real data set are used.     

Protein-protein interactions as a target for drugs in proteomics

Protein-protein interactions play a central role in numerous processes in the cell and are one of the main fields of functional proteomics. This review highlights the methods of bioinformatics and functional proteomics of protein-protein interaction investigation. The structures and properties of contact surfaces, forces involved in protein-protein interactions, kinetic and thermodynamic parameters of these reactions were considered. The properties of protein contact surfaces depend on their functions. The contact surfaces of permanent complexes resemble domain contacts or the protein core and it is reasonable to consider such complex formation as a continuation of protein folding. Characteristics of contact surfaces of temporary protein complexes share some similarities with active sites of enzymes. The contact surfaces of the temporary protein complexes have unique structure and properties and they are more conservative in comparison with active site of enzymes. So they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations were undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or, on the contrary, to induce protein dimerization.     

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Immunotherapy with Bacillus Calmette–Guérin (BCG)—an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization—is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties, and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can lead to an over-stimulated immune system having dangerous side effects for the patient.     

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.