Ultrastructural organization of the human lamellar bone tissue mineral component in aged and elderly

The lamellar bone mineral component in mature and senile age was studied using the methods of transmission electron microscopy and cryofractography. This component was shown to be formed by crystals (13-4 x 7-8 x 3-4 nm) of the prismatic shape that formed coplanar units (29-3 x 18-21 x 3-4 nm). The peculiarities of mineral particle distribution inside and between the collagen fibrils, as well as on the completely formed areas of bone surface, were detected. It was established that the length and the width of coplanar crystal aggregates was significantly higher in senile age as compared to similar linear parameters defined in persons of mature age (by 17-20 and 5-9%, respectively).     

A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

Background  

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Legionnaires disease: results of 25-years of studying infections, problems and perspectives of research

The paper summarizes the results of 25-year study of Legionnaires' disease (Legionnaire's bacillus infection) in its epidemiology, diagnosis, and prevention, the taxonomy and biology of the causative organism. Emphasis is laid on the contribution of the Russian school of investigators in studying this problem. Despite the intensive efforts in investigating the infection and its causative organism, there are still many problems in predicting and preventing the epidemics of Legionnaires' disease, which annually occur in different countries of the world. Legionnaires' disease is a typical example of technogenic infections: active industrial and domestic uses of closed water circulating systems in industry and aerosol sources promote the spread of the infection caused by Legionnaire's bacillus and make its control in these systems. Despite the introduction of current immunological and molecular genetic methods, diagnosis is effective only for L. pneumophila, serogroup 1. The sensitivity and specificity of methods for diagnosis and identification for other 15 L. pneumophila serogroups and 41 species of L. bacilli are far from being perfect. L. bacilli are also a most popular object for studying the biochemical and genetic aspects of its intracellular parasitism.     

Role of alpha-interferon in regulation of apoptosis in cells of the hypothalamo-hypophyseal-adrenocortical system of old mice in oxidative stress

The aim of this work was to demonstrate the role of interferon alpha (IA) in apoptosis control of cells of hypothalamohypophysial adrenocortical system (HHAS) in young and old mice under conditions of hyperoxia. The increase of functional activity of neurosecretory cells of hypothalamic paraventricular nucleus in old mice treated with IA was demonstrated, while no effect was found in young mice. This differences could be associated with aging changes in HHAS in intact old animals. Oxidative stress caused an increase in the number of cells synthesizing proapoptotic c-fos protein in paraventricular nucleus of mice of both age groups. However, the protective action of IA against the stress is expressed more actively and in more early stage of apoptosis in young mice. Thus, the degree of IA participation in the control of programmed cell death of hypothalamic cells depends on the age of the animal. In the adrenal zona fasciculata of young mice the number of apoptotic cells was significantly increased after IA administration while after hyperoxia or its combination with IA it remained at control level. In the adrenal gland of old mice the proportion of apoptotic cells was not different from that found in young mice and remained unchanged after all experimental challenges.     

Scar formation in the liver

The review examines the current data on the cellular and tissue mechanisms of scar formation in the liver. On the basis of the analysis of the literature, authors conclude that to minimize the destructive processes in the liver, the most advisable and promising method during the operations on this organ is the use of laser surgical devices. However, the problems of the selection of the optimal regimes of laser radiation and of the methods of conducting these operations to promote reliable and rapid healing of postoperative wound of the liver.     

Immunohistochemical profile of endometrioid adenocarcinoma of the uterus: ER, PR, HER-2, Ki-67 and their prognostic value

76 endometrioid adenocarcinomas of the uterine body were studied. Expression of the above markers is of essential value together with metastatic involvement of regional lymph nodes, stage of the disease and pathogenetic variant for determining prognosis of carcinoma aggressiveness and disease outcome. Positive hormonal-receptor status of the tumor is characterized by well-differentiated tumor cells, small depth of invasion, rare metastases to regional lymph nodes and higher survival (5 year--81%) of patients comparing with cases where ER and PR were not determined (53%). On the contrary, overexpression of oncoprotein HER-2 and Ki-67 higher than median (42%) was associated with high tumor aggression resulting finally in a significant fall in the survival (from 75% to 58% and from 79% to 60%, respectively). Combination of HER-2 overexpression with a high level of Ki-67 is particularly unfavourable (5-year survival--43%).     

The characteristics of digital electron optical systems for x-ray diagnosis

The paper deals with the specific features of X-ray diagnostic units that have no screen-filming device for film X-ray study, with the requirements for hardware and software of these units. It gives data on specific systems for digital X-ray study.     

Models of radiation dispersion in medical laser tomographic system

The prospects for developing a new noninvasive medical diagnostic technique, such as optical (laser) tomography of biological tissues largely depend on the feasibility of designing an adequate mathematical model for the reconstruction of images of the spatial structure of objects that are in the highly scattering medium (HSM). The basic difficulty is that it is necessary to effectively describe the physical properties and the propagation pattern of photons of different types in such a medium. This review considers methods for describing the distribution of laser ultrashort pulses in HSM with particular emphasis on a new nonstationary two-flux model of radiation transfer.