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PubMed1998

[Effects of the combined deficiency of selenium and iodine on thyroid function].

Recent studies reported the role of several trace elements in health and disease. The role of iodine deficiency in thyroid dysfunction is well known. Also the selenium deficiency has been reported to be correlated to thyroid dysfunctions. In fact, although the major role of selenium is related to the glutathione peroxidase system, which protects cellular structures from oxidative damages, selenium plays also an important role in thyroid hormone metabolism as an essential component of the three deiodinase. These regulate inter-conversion of active and inactive forms of iodothyronines. Several studies have been carried out to establish the role of combined selenium and iodine deficiency. This review aims to provide information on the relationship between selenium and iodine intake and thyroid function. Furthermore, the state of art on the effects of the combined deficiency of selenium and iodine is also provided.

Cysteine↗
PubMed1998

[Pathomorphological evaluation of the extraocular muscles during strabismus].

PURPOSE: An analysis of the histopathological picture of extraocular muscles removed in the operation of strabismus. MATERIAL AND METHODS: Light microscopy analysis included 131 fragments of rectus muscles, with the majority of lateral, collected from patients with concomitant squint of different angles and disease durations. RESULTS: Normotopic cross-striated muscle fibres were observed in 40 (30.6%) studied muscles, while pathological changes appeared in 91 (69.4%) muscles with a prevailance of fibrous atrophy. A correlation was found between the histopathological picture of the examined muscles and the extent of strabismus. CONCLUSIONS: Pathomorphological changes were observed with the majority of the extraocular muscles in the microscopic picture. The observed changes in the cellular structure of the extraocular muscles influenced the extent of the squint angle, affecting the result of surgery.

Adolescent↗
PubMedDate not supplied

[Adriamycin induced chronic cardiotoxicity: a morphological ultrastructural study on ventricular myocardium and conducting system of rabbit heart (author's transl)].

The administration of high doses of adriamycin in rabbits causes morphologically evident alterations of cardiac myocites, such as cellular structure disorganization, myofilaments disappearance and vacuolar degeneration through the cytoplasm. The less damaged myocites show protein synthesis activation with newly produced myofilaments. Macrophages and fibroblasts are seen in the interstitium among markedly injured cells. As a response to the toxic damage induced by adriamycin, it would be seen an hypertrophic compensatory response in the well preserved cells and interstitial fibrosis. The conducting system shows similar but less extensive lesions as the ventricular myocardium.

Animals↗
PubMed1999

[Stable oxygen and carbon isotopes in biological studies].

Biogenic chemical elements in the Earth biosphere are presented both by light and heavy stable isotopes (16O and 18O, 12C and 13C). Because of inequality of these isotopes the light ones dominate in the exchange processes between the animate and inanimate nature and this leads to changes in the ratios of isotope modifications in the environment. A comparatively constant isotopic composition of the Earth atmosphere is primarily maintained by water. It is the heavy carbon isotope that inputs to the most isotope-heavy compounds such as marine carbonates within the atmosphere--hydrosphere system. As in nature, biogenic isotopes fractionate inside hermetically sealed habitats with the regenerative life-support systems; however, the mechanism of relative stability of the isotope composition is unknown. The problem of providing the best isotopic composition of biogenic chemical elements aboard manned space vehicles was first raised by Yu.Ye.Sinyak and A.I. Grigoriev in 1996. The review contains the data on the levels of oxygen isotopes and photosynthetically generated oxygen in water pools in different regions of the Earth. discussion of the ratios of the oxygen and carbon isotopes in the atmospheric carbon dioxide, and the range of isotopes variations and presumed "sites" of isotopes fractionating in cellular structures of autotrophs. The wealth of literary findings effectuates the conclusion that artificial environments for humans should reproduce the natural relationships and variations of biogenic isotopes. Yet, what biogenic isotopes ratios are desirable aboard manned space vehicles can be determined in extensive investigations of the effects of various modifications of stable isotopes on humans with due account for the unfavourable factors of space flight.

Biology↗
PubMed1999

Supporting cells contribute to control of hearing sensitivity.

The mammalian hearing organ, the organ of Corti, was studied in an in vitro preparation of the guinea pig temporal bone. As in vivo, the hearing organ responded with an electrical potential, the cochlear microphonic potential, when stimulated with a test tone. After exposure to intense sound, the response to the test tone was reduced. The electrical response either recovered within 10-20 min or remained permanently reduced, thus corresponding to a temporary or sustained loss of sensitivity. Using laser scanning confocal microscopy, stimulus-induced changes of the cellular structure of the hearing organ were simultaneously studied. The cells in the organ were labeled with two fluorescent probes, a membrane dye and a cytoplasm dye, showing enzymatic activity in living cells. Confocal microscopy images were collected and compared before and after intense sound exposure. The results were as follows. (1) The organ of Corti could be divided into two different structural entities in terms of their susceptibility to damage: an inner, structurally stable region comprised of the inner hair cell with its supporting cells and the inner and outer pillar cells; and an outer region that exhibited dynamic structural changes and consisted of the outer hair cells and the third Deiters' cell with its attached Hensen's cells. (2) Exposure to intense sound caused the Deiters' cells and Hensen's cells to move in toward the center of the cochlear turn. (3) This event coincided with a reduced sensitivity to the test tone (i.e., reduced cochlear microphonic potential). (4) The displacement and sensitivity loss could be reversible. It is concluded that these observations have relevance for understanding the mechanisms behind hearing loss after noise exposure and that the supporting cells take an active part in protection against trauma during high-intensity sound exposure.

Acoustic Stimulation↗
PubMed1999

[Angiotensin and arteriosclerosis: an approach from transgenic and knockout mice].

This brief review was designed to summarize the relationship between the renin-angiotensin system and arteriosclerosis. Tsukuba hypertensive mice (THM) carrying both the human renin and angiotensinogen genes and C57BL/6J control mice 2 to 3 months of age were fed with either a western or normal diet for 14 weeks. Compared with controls, microscopic analyses revealed accelerated damage of cellular structure in the aortic root in THM fed with the western diet. Remarkably, the surface area of arteriosclerotic lesion in THM was shown to be 4 times larger than that in C57BL/6J on the same western diet. These findings suggested that hypertension induced by the activated renin-angiotensin system is involved in the development of arteriosclerotic lesions.

Animals↗
PubMed1999

Marked alteration of sterol metabolism and composition without compromising retinal development or function.

PURPOSE: To evaluate the consequences of altering retinal sterol metabolism and composition on the development, histologic organization, and electrophysiological function of the retina, under conditions that mimic the biochemical hallmarks of the Smith-Lemli-Opitz (SLO) syndrome. METHODS: Pregnant Sprague-Dawley rats were fed cholesterol-free chow containing AY9944 (treated group), an inhibitor of 3beta-hydroxysterol delta7-reductase, from gestational day 6 through postnatal day (P)28. Control animals were fed the same chow, but without AY9944. In addition, progeny in the treated group were injected subcutaneously every other day from birth to P28 with an olive oil emulsion containing AY9944; control animals received olive oil emulsion alone. At various postnatal times, tissues from treated and control animals were harvested, and their sterol profiles were analyzed by reversed-phase high-performance liquid chromatography. Companion eyes from animals of both groups were examined histologically at P1. At P28, animals were evaluated by electroretinography; tissues were then harvested for biochemical analysis and companion eyes were subjected to histologic and ultrastructural analyses. RESULTS: Treatment of developing rats with AY9944 caused markedly abnormal accumulation of 7-dehydrosterols and severely reduced cholesterol levels in all tissues examined, relative to control animals. Despite this, treated animals exhibited normal retinal development and had no overt ocular defects or decrease in electroretinographic function, up to P28. CONCLUSIONS: These results were unexpected, given the known biophysical effects of such sterol alterations on membrane properties and the profound dysmorphic and cognitive abnormalities associated with genetic defects in 3beta-hydroxysterol delta7-reductase that have been linked to the SLO syndrome. The results suggest that 7-dehydrosterols can substitute functionally for cholesterol in the retina or perhaps can act synergistically with subthreshold levels of residual cholesterol to allow normal cellular structure and function to be achieved.

Animals↗
PubMedDate not supplied

[The effect of Aerococcus viridans on the properties of salmonellae and staphylococci in vitro].

According to electron microscopy the repeated contacts of Aerococcus viridans 167 (industrial strain for the probiotic Aerobact production) with Salmonella typhimurium and Staphylococcus aureus caused the deep changes of cellular structure, down to bacteriolysis. Remaining viable pathogenic cells gave posterity with changed biochemical properties and virulence. S. typhimurium completely lost typical biochemical properties, its mobility and ability to be agglutinated by O-specific Salmonella serum reduced after the fifth joint passage. Sharp decrease of the leucotoxic and loss of the lethal and necrotic activity of the S. aureus toxin were observed. The latter was characterized by the smaller number of protein fractions in comparison with control series on electrophoregrams and densitograms. Pathogenic bacteria, playing a role in formation of the pathological intestinal microbiocenosis (S. typhimurium) and being hospital infections (S. aureus) acquired increased sensitivity to antibiotics. The carried out researches open some mechanisms of bactericidal and bacteriostatic action of A. viridans (group 12, Bergey, 1994) and their metabolic products, causing antagonistic effect during direct action on infectious microorganisms.

Animals↗
PubMedDate not supplied

[Geothermal water as part of culture medium and morpho-physiological properties of Saccharomyces cerevisiae].

Morphophysiological changes in Saccharomyces cerevisiae gamma-503 cells cultivated in nutrient media containing geothermal water as a source of mineral substances were studied. The optimal mineralization of the medium was found to be 4.0 g/l, supplemented with 2.6 g/l (NH4)2HPO4. These conditions provided active growth and development of the culture with high yields of the biomass and the maximal enzymatic activity. Differences in cellular structures at certain stages of metabolism were demonstrated.

Culture Media↗
PubMedDate not supplied

Antioxidant status of erythrocytes from patients with cirrhosis.

BACKGROUND/AIMS: The aim of the present study was to investigate possible involvement of oxidant stress in the anemia of cirrhotic patients and to assess blood antioxidant status of these patients. METHODOLOGY: Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were measured in the erythroctes from patients with liver cirrhosis and from controls. Levels of thiobarbituric acid reagent substance were also measured in the erythrocyte (TBARSe) and plasma (TBARSp) samples of the groups. RESULTS: Lower activities of SOD and GSH-Px were established in the erythrocytes from patients compared with control subjects. No differences were found between erythrocyte TBARS levels of control and patient groups. Plasma TBARS levels were, however, found to be significantly higher in the patient groups compared with controls. CONCLUSIONS: Results suggest that although enzymatic antioxidant defense system is significantly reduced in the erythrocytes from cirrhotic patients, this does not lead to further peroxidative reactions in the erythrocytes, possible due to preoxidation of some cellular structures sensitive to peroxidative attacks. There was, however, an important indication of accelerated peroxidative reactions in the plasma of the cirrhotic patients, which possibly resulted from extracellular oxidant stress in these patients.

Adult↗
PubMed1999

Interferon-gamma up-regulates expression and activity of P-glycoprotein in human peripheral blood monocyte-derived macrophages.

P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, is expressed in a variety of normal tissues but very little is known about its expression and function in cells of the immune system. In this study, we investigated the effect of interferon-gamma (IFN-gamma) on the expression and activity of Pgp in human peripheral blood monocyte-derived macrophages (MDM). We report that IFN-gamma up-regulated Pgp expression in a dose- and time-dependent manner. We show that IFN-gamma slightly increased the accumulation of MDR1 mRNA and induced a polarized redistribution of Pgp, as well as of some cytoskeletal proteins (ie, ezrin, actin, and alpha-actinin) on cell pseudopodia. Notably, confocal microscopy studies showed that Pgp and ezrin colocalized in these cellular structures. The IFN-gamma-induced Pgp up-modulation was a specific response of primary macrophages, as IFN-gamma treatment of primary lymphocytes and monocytic cell lines did not result in any increase of Pgp expression. Finally, IFN-gamma stimulated the Pgp transport activity in MDM, as rhodamine 123-efflux increased in treated cells as compared with control cultures. These results indicate that Pgp expression and activity can be up-regulated in human MDM in response to IFN-gamma. We suggest that IFN-gamma may be involved in the induction of multidrug resistance in macrophages.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.

We report the amino acid sequence, genomic organization, tissue expression, and alternative splice patterns for the human kinase related protein (KRP) gene, as well as the discovery of a new CA repeat sequence polymorphic marker in an upstream intron of the myosin light chain kinase (MLCK) gene. The KRP/MLCK genetic locus is a prototype for a recently discovered paradigm in which an independently regulated gene for a non-enzymic protein is embedded within a larger gene for a signal transduction enzyme, and both classes of proteins are involved in the regulation of the same cellular structure. The MLCK/KRP gene cluster has been found only in higher vertebrates and is localized to human chromosome 3q21. The determination of the human KRP amino acid sequence through cDNA sequence analysis and its comparison to the exon/intron organization of the human KRP gene revealed an alternative splice pattern at the start of KRP exon 2, resulting in the insertion of a single glutamic acid in the middle of the protein. Examination of tissue distribution using Northern blot analysis revealed that the human expression pattern is more similar to the well-characterized chicken KRP gene expression pattern than to rodent or rabbit. Unexpected differences of the human gene from other species is the apparent expression of the human gene products in adult cardiac muscle, an observation that was pursued further by the production of a site-directed antiserum and immunohistochemistry analysis. The results reported here provide insight into the conserved and variable features of this late evolving genetic paradigm, raise new questions about the molecular aspects of cardiac muscle regulation, and provide tools needed for future clinical studies. The comparative analysis of the MLCK/KRP locus, combined with the recent discovery of a similar genomic relationship among other signal transduction proteins, suggest a diverse distribution of this theme among signal transduction systems in higher vertebrate genomes and indicate the utility of comparative genomics in revealing late evolving genetic paradigms.

Adult↗
PubMedDate not supplied

[Reinforcement of the sclera with new types of synthetic materials in progressive myopia].

The possibility of using a new synthetic material mersilene for scleroplastic operations has been evaluated in experiments and clinical trials were carried out in patients with progressive myopia subjected to sclera fortification. Morphological studies showed the formation of a connective tissue capsule round mersilene; new collagen fibers grow through its cellular structures, thus fortifying the strength of the sclera-graft complex. Clinical results indicate that sclera fortification by a mersilene graft arrested the progress of myopia in almost all (98%) patients by the end of the first year postoperation; by the end of the second year, myopic refraction stabilized in 92% patients. Hence, mersilene transplants are recommended for scleroplasty in progressive myopia.

Adolescent↗
PubMed1999

Understanding the coronary disease process and the potential for prevention: a summary.

This presentation describes the atherothrombotic processes leading to acute coronary syndromes based on the recent studies of vascular biology. It outlines the mechanism of action and the evolving impact of lipid-lowering therapy in stabilization and secondary prevention of such processes. The present understanding of the pathogenesis of each phase of progression and of the various lesions preceding myocardial infarction emphasizes the physical, structural, cellular, and chemical properties of "vulnerable or unstable plaques" prone to disruption.

Coronary Artery Disease↗
PubMed1999

[The eye and nutrition].

PURPOSE: To examine the effect of vitamins and trace elements on ocular tissue. MATERIALS AND METHODS: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. RESULTS: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. DISCUSSION: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. CONCLUSION: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.

Animals↗
PubMed2000

The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability.

The electrogenic sodium bicarbonate cotransporter (NBC) is expressed in glial cells in the brain and plays an important role in the regulation of both intracellular and extracellular pH. Differential vulnerability to acidosis between neurons and glia has been noted and may contribute to infarction after cerebral ischemia. Ionic substitution studies and inhibition of injury by 4, 4'-di-isothiocyanostilbene-2,2'-disulfonic acid suggest that NBC is involved in astrocyte vulnerability to acidic injury. Recently two NBC cDNAs differing in 5'-untranslated and N-terminal coding sequence have been cloned from kidney and pancreas. We cloned one of these cDNAs from rat brain and demonstrate here that the clone is functional by expression in Xenopus oocytes. We determined the developmental and regional expression of NBC in the brain by in situ hybridization. Expression was observed in the spinal cord at embryonic day 17, whereas expression in brain was first seen at approximately postnatal day 0 (P0), increased at P15, and persisted in the adult brain. Expression was widespread throughout the cerebellum, cortex, olfactory bulb, and subcortical structures. Cellular resolution of the in situ hybridization signal and double labeling for glial fibrillary acidic protein were consistent with a glial localization for NBC. Expression of NBC in 3T3 cells that do not normally express this transporter rendered them vulnerable to acid injury. The expression profile suggests that this transporter is critical during the later stages of brain development and could be one of the factors contributing to the different patterns of injury seen in perinatal versus adult cerebral ischemia.

3T3 Cells↗
PubMed2000

Exogenously added growth factors have no effect on formation of cell junctions and cytoskeleton in urothelial cells in culture.

To elucidate the effects of epidermal growth factor-EGF and transforming growth factor-TGFbeta1 on cellular structure, especially on cell junctions and cytoskeleton, the distribution of ZO1, E-cadherin and desmoplakin as well as the organization of actin and keratin filaments have been examined immunohistochemically. In EGF-treated cultures as well as in TGFbeta1-treated cultures, the distribution of adhesion proteins looked similar. On the sites where cells made contacts, the presence of ZO1, E-cadherin and desmoplakin was revealed seen as a continuous line around cells. EGF as well as TGFbeta1 treatment induced no difference in the presence and distribution of cytokeratin 20; this marker of terminal differentiation was limited to superficial urothelial cells only. Also, the distribution of actin filaments was not significantly altered by any of the growth factors used. This indicates that neither cell junctions nor cytoskeleton of urothelial cells were affected by exogenously added growth factors. This may result from the influence of stroma on the formation of urothelium during the first days of culture of urinary bladder explants and the production of growth factors in the culture itself.

Actins↗
PubMed2000

The effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-induced Ca2+ mobilization in freshly isolated and cultured mouse lacrimal acinar cells.

Earlier reports have shown a remarkable synergism between InsP(4) and InsP(3) [either Ins(1,4,5)P(3) or Ins(2,4,5)P(3)] in activating Ca(2+)-dependent K(+) and Cl(-) currents in mouse lacrimal cells [Changya, Gallacher, Irvine, Potter and Petersen (1989) J. Membr. Biol. 109, 85-93; Smith (1992) Biochem. J. 283, 27-30]. However, Bird, Rossier, Hughes, Shears, Armstrong and Putney [(1991) Nature (London) 352, 162-165] reported that they could see no such synergism in the same cell type. A major experimental difference between the two laboratories lies in whether or not the cells were maintained in primary culture before use. Here we have compared directly the responses to inositol polyphosphates in freshly isolated cells versus cells cultured for 6-72 h. In the cultured cells, Ins(2,4,5)P(3) at 100 microM produced a robust stimulation of K(+) and Cl(-) currents, as much as an order of magnitude greater than that observed in the freshly isolated cells. However, the freshly isolated cells could be restored to a sensitivity similar to cultured cells by the addition of InsP(4) at a concentration two orders of magnitude lower than that of Ins(2,4,5)P(3). We discuss the implications of this with respect to the actions of InsP(4), including the possibility that disruption of the cellular structure during the isolation of the cells exposes an extreme manifestation of a possible physiological role for InsP(4) in controlling calcium-store integrity.

Acetylcholine↗