Does the anatomical location of a muscle affect the influence of undernutrition on muscle fibre number?

Nutritional restriction during muscle fibre number development invariably has a more detrimental effect on the biceps brachii than on the soleus. The difference may be due to the relative proportions of fibre types in the muscles or the anatomical location of the muscles. To distinguish between the effects of location and fibre type the biceps (fast, cranial and proximal), soleus (slow, caudal and distal), and extensor digitorum longus (EDL) (fast, caudal and distal) were examined from control and undernourished guinea pig neonates. A 40% reduction in maternal intake resulted in a reduction in neonate body and muscle weights (P < 0.005), biceps (P < 0.05) and EDL fibre numbers (P < 0.005), but did not affect soleus fibre number. At birth the ratio of fast fibres to slow was 7.5 for the biceps, 7.0 for the EDL, and 1.5 for the soleus. The effect of undernutrition on muscle fibre number therefore seems to be a function of the fibre types in that muscle.


A teaching model to illustrate the variation in size and shape of the maxillary sinus.

A technique to produce teaching models of the maxillary sinus is described. Dental impression material is injected into the maxillary sinus of a cadaver and subsequently dissected out. Using an impression and mould technique in a series of steps, a stone model of the maxillary sinus is produced. The shape, size and configuration of the model can be seen and the dimensions measured. A radiopaque impression material can be used so that the radiographic outline of the maxillary sinus on standard radiographic projections can be shown. Models of both dentate and edentulous patients can be used to show anatomical variation and the relationship to teeth and are useful in teaching both gross and radiographic anatomy. Since 10 out of 11 specimens had 3 walls leading to the apex from a 4-sided base, it would appear that the classical description of a 4-sided pyramidal shape to the maxillary sinus is relatively uncommon.


Site-directed mutagenesis of amino acid residues involved in the glutathione binding of human glutathione S-transferase P1-1.

The four residues of human glutathione S-transferase P1-1 whose counterparts were indicated by X-ray crystallography to reside in the GSH-binding site of pig glutathione S-transferase P1-1 were individually replaced with threonine or alanine by site-directed mutagenesis to obtain mutants R13T, K44T, Q51A, and Q64A. The kinetic parameters, susceptibilities to an inhibitor, S-hexyl-GSH, and affinities for GSH-Sepharose of the latter were compared with those of the wild-type enzyme, and pKa of the thiol group of GSH bound in R13T was shown to be equivalent to that in the wild type. From the results, Lys44, Gln51, and Gln64 were deduced to contribute to the binding of GSH. On the other hand, Arg13 seems to be essential for the enzymatic activity as mainly involved in the construction of a proper structure of the active site.


Major ATPases on clofibrate-induced rat liver peroxisomes are not associated with 70 kDa peroxisomal membrane protein (PMP70).

We previously reported that novel Mg(2+)-ATPases were induced in rat liver peroxisomes by clofibrate administration and that these activities consisted of at least two types of enzymes, N-ethylmaleimide (NEM)-sensitive and -resistant. Here we present evidence that neither of these major peroxisomal ATPases is associated with the 70-kDa peroxisomal membrane protein (PMP70), because: (i) proteinase K treatment of peroxisomes resulted in inactivation of only NEM-sensitive ATPase, whereas disappeared PMP70 completely; (ii) NEM-sensitive ATPase activity was barely immunoprecipitated with anti-PMP70 IgG; (iii) the solubilized ATPases behaved differently from PMP70 on native PAGE; and finally (iv), the major peroxisomal ATPases were separated from PMP70 on gel filtration chromatography.


Chain length distribution of the products formed in solanesyl diphosphate synthase reaction.

Factors that affect the termination of isoprenoid chain elongation catalyzed by prenyltransferase were investigated. The chain-length distribution of reaction products of solanesyl diphosphate synthase [EC 2.5.1.11] homogeneously purified from Micrococcus luteus changed dramatically according to the concentration of the complex formed between isopentenyl diphosphate and Mg2+ (IPP-Mg) in the reaction mixture. However, the concentration of the complex between farnesyl diphosphate and Mg2+ (FPP-Mg), the priming substrate for this synthase, did not affect the product distribution, provided that the concentration of IPP-Mg was maintained at a certain level. Thus, the level of IPP-Mg is decisive in affecting the chain length distribution of the products of the prenyltransferase reaction, and the Mg(2+)-dependent variability of product specificity so far observed can now be understood in terms of the effect of IPP-Mg concentration.


Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase by 2,5-di(tert-butyl)-1,4-benzohydroquinone.

We characterized the interaction of 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) with the sarcoplasmic reticulum (SR) Ca(2+)-ATPase from rabbit fast-twitch skeletal and canine cardiac muscles by examining the effect of this agent on the ATPase reaction. tBuBHQ at less than 10 microM inhibited ATP hydrolysis by both isoforms of Ca(2+)-ATPase by up to 80 and 90%, respectively. The half maximal inhibition of these enzymes was observed at about 1.5 microM tBuBHQ. Thus, this agent potently inhibits the fast-twitch skeletal and slow-twitch skeletal/cardiac isoforms of SR Ca(2+)-ATPase. tBuBHQ at 5-10 microM inhibited the rate of decomposition of the phosphoenzyme intermediate (EP), measured as a ratio between ATPase activity and the EP level in the steady state, by 35-40%. It also inhibited formation of EP by decreasing the rate of Ca2+ binding to the Ca(2+)-deficient, nonphosphorylated enzyme to about 1/8 of the control value. These results indicate that tBuBHQ has at least two sites of action in the reaction sequence for the SR Ca(2+)-ATPase.


Preferential activation of phospholipase A2 by low concentrations of phosphatidic acid with long-chain fatty acids in rabbit platelets.

The role of phosphatidic acid (PA) in the signal transduction system of platelets was studied using 1-stearoyl 2-arachidonoyl PA (PASA). When PASA was added to rabbit platelets, aggregation occurred. BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase, as well as p-bromophenacyl bromide and mepacrine, inhibitors of phospholipase A2, inhibited the aggregation induced by low concentrations of PASA, but not that induced by high concentrations. PASA also stimulated, in a dose-dependent manner, arachidonic acid liberation, lysophosphatidylcholine and diacylglycerol formation, and mobilization of intracellular Ca2+; all of which were dependent on the presence of Ca2+ in the outer medium. The arachidonic acid liberation was inhibited by p-bromophenacyl bromide or mepacrine, while diacylglycerol formation by low concentrations of PASA was inhibited by BW755C. With platelet membrane fractions or with the platelets made permeable to Ca2+ by pretreatment with ionomycin, PASA caused arachidonic acid liberation in the presence of Ca2+. Furthermore, PASA enhanced the activity of phospholipase A2 partially purified from platelet cytosol acting on 1-palmitoyl-2-[14C]arachidonoyl-glycerophosphoethanolamine. These results provide evidence that PASA preferentially potentiates the activation of phospholipase A2 in cooperation with Ca2+, suggesting that PA acts as a positive feedback regulator to potentiate the activation of phospholipase A2 and contributes to the amplification of platelet activation.


Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells.

Mitoxantrone, a new anthraquinone, showed inhibitory an effect on protein kinase C (PKC) activity. Its IC50 value was 4.4 micrograms/ml (8.5 microM), which is much lower than those of the well-known anthracyclines daunorubicin and doxorubicin, the IC50 values of which are more than 100 micrograms/ml (> 170 microM). Kinetic studies demonstrated that mitoxantrone inhibited PKC in a competitive manner with respect to histone H1, and its Ki value was 6.3 microM (Ki values of daunorubicin and doxorubicin were 0.89 and 0.15 mM, respectively), and in a non-competitive manner with respect to phosphatidylserine and ATP. Inhibition of phosphorylation by mitoxantrone was observed with various substrates including S6 peptide, myelin basic protein and its peptide substrate derived from the amino-terminal region. Their IC50 values were 0.49 microgram/ml (0.95 microM), 1.8 micrograms/ml (3.5 microM), and 0.82 microgram/ml (1.6 microM), respectively. Mitoxantrone did not markedly inhibit the activity of cyclic AMP-dependent protein kinase, casein kinase I or casein kinase II, at concentrations of less than 10 micrograms/ml. On the other hand, brief exposure (5 min) of HL60 cells to mitoxantrone caused the inhibition of cell growth with an IC50 value of 52 ng/ml (0.1 microM). In HL60 cells, most of the PKC activity (about 90%) was detected in the cytosolic fraction. When HL60 cells exposed to 10 micrograms/ml mitoxantrone for 5 min were observed with fluorescence microscopy, the fluorescence elicited from mitoxantrone was detected in the extranuclear area. These results indicated that mitoxantrone is a potent inhibitor of PKC, and this inhibition may be one of the mechanisms of antitumor activity of mitoxantrone.


Purification and characterization of two casein kinases from ejaculated bovine spermatozoa.

Two protein kinases active on casein and phosvitin were partially purified from the soluble fraction of ejaculated bovine spermatozoa. They were operationally termed casein kinase A and B based on the order of their elution from a phosphocellulose column. CK-A showed an approximate molecular mass of 38 kDa, and it phosphorylated serine residues of casein and phosvitin utilizing ATP as a phosphate donor (Km 19 microM). Enzyme activity was maximal in the presence of 10 mM MgCl2, whereas it decreased in the presence of spermine, polylysine, quercetin, and NaCl (20-250 mM). CK-B seemed to have a monomeric structure of about 41 kDa; it underwent autophosphorylation and cross-reacted with polyclonal antibodies raised against recombinant alpha, but not beta, subunit of human type 2 casein kinase. It phosphorylated both serine and threonine residues of casein and phosvitin, utilizing ATP (Km 12 microM) but not GTP as a phosphate donor. Threonine was more affected in the phosphorylated phosvitin than in the partially dephosphorylated substrate. CK-B was active toward the synthetic peptide Ser-(Glu)5 and calmodulin (in the latter case, in the presence of polylysine), and it was activated by spermine, polylysine, MgCl2 (30 mM), and NaCl (20-400 mM). The activity of the enzymes was not affected by cAMP, or the heat-stable inhibitor of the cAMP-dependent protein kinase, or calcium.


Calcium-induced fragmentation of skeletal muscle nebulin filaments.

When chicken breast muscle myofibrils were treated with a solution containing 0.1 mM CaCl2 and 30 micrograms of leupeptin/ml, nebulin filaments were fragmented into 200-, 180-, 40-, 33-, and 23-kDa subfragments. All the subfragments except the 180-kDa one were released from the myofibrils. The fragmentation of nebulin filaments seems to be induced by the binding of large amounts of calcium ions. Similar changes took place in nebulin filaments in post-mortem skeletal muscle. It has been proposed that nebulin co-exists with thin (actin) filaments and participates in stabilizing their organization [Wang, K. & Wright, J. (1988) J. Cell Biol. 107, 2199-2212]. Thus, the above result suggests that Ca-induced fragmentation of nebulin filaments destabilizes the organization of thin filaments and is a key factor in meat tenderization during post-rigor aging.


Purification and characterization of nebulin subfragments produced by 0.1 mM CaCl2.

Nebulin, which forms a long inextensible filament in sarcomeres, was fragmented into 200-, 180-, 40-, 33-, and 23-kDa subfragments on treatment with 0.1 mM CaCl2. The subfragments released from myofibrils were successfully purified by immunoaffinity column chromatography. The 200-, 40-, 33-, and 23-kDa subfragments were released from myofibrils and occupied 80% of the nebulin filaments. The remainder comprised the 180-kDa subfragment bound to the myofibrils. There is a possibility that an entire nebulin filament is constructed from the 200-, 180-, 40-, 33-, and 23-kDa subfragments. We have developed a new "fluorescence-method" to detect the binding of calcium ions to a protein using quin2, and clarified that nebulin is a calcium-binding protein, and that calcium ions bind to the 200-, 40-, and 23-kDa subfragments. Nebulin filaments are probably fragmented on the binding of large amounts of calcium ions to the 200-, 40-, and 23-kDa subfragments.


Site of attachment of mercuribenzoate in crystals of an actin:DNase I complex.

Crystals of a complex of chicken gizzard G-actin and DNase I were soaked in a solution of radioactive 4-hydroxymercuribenzoate (MB). The soaked crystals, which contained 0.93 mol of MB per mol of G-actin, were dissolved in "G-buffer" and digested with trypsin, and the resulting peptides were fractionated by thin-layer chromatography. The MB is exchangeable between peptides that contain cysteine residues, but the data obtained here suggested that MB attached to the cysteine residue at the 373rd position of the G-actin molecule.


Preparation and characterization of troponin C from bullfrog skeletal muscle.

Troponin C was isolated from the skeletal muscle of bullfrog (Rana catesbeiana), and its relative molecular mass was estimated to be 18,000 by SDS/polyacrylamide gel electrophoresis. In its amino acid composition, bullfrog troponin C was similar to that of the frog (Rana esculenta) but different from that of rabbit. Its ultraviolet spectrum was consistent with its amino acid composition. The ultraviolet difference spectrum of the Ca(2+)-loaded form vs. the metal-free form indicated that the single Tyr residue and some Phe residues in the bullfrog troponin C molecule were affected by the conformational change associated with Ca2+ binding. On electrophoresis in polyacrylamide gel in 14 mM Tris and 90 mM glycine, the metal-free and Mg(2+)-loaded forms migrated slower than the Ca(2+)-loaded form. The property is shared by rabbit troponin C but not parvalbumins or calmodulin. The ATPase activity of CDTA-treated myofibrils reconstituted with bullfrog troponin C showed the same Ca(2+)- and Sr(2+)-sensitivity as that of those reconstituted with rabbit troponin C. Bullfrog troponin C is, thus, physiologically the same as rabbit troponin C, in spite of several marked differences in their physicochemical properties.


The binding of adenine nucleotides to apo-electron-transferring flavoprotein.

Apoprotein of electron-transferring flavoprotein (ETF) reacts with FAD as follows: A*<-->A, A+FAD<-->holoETF. Two different forms of apoETF (A* and A) convert into each other and only one of them, A, can associate with FAD [Sato, K. et al. (1991) J. Biochem. 109, 734-740]. In the present study, the reactions between apoETF and ATP, ADP, AMP, riboflavin, or FMN were investigated. It was revealed that all three adenine nucleotides bind with apoETF with the same kinetic reaction scheme as FAD, and compete with FAD. These results suggest that the nucleotides bind to A with the same location as the ADP part of FAD in holoETF and that the ADP-binding site of apoETF is generated upon conversion from A* to A. Neither riboflavin nor FMN bound to apoETF regardless of the presence or absence of the nucleotides, indicating that the ADP part of the FAD molecule is essential to the incorporation of the isoalloxazine ring into ETF. The binding rate constant of FAD to A was 1/20 of that of ADP while the dissociation rate constant was 1/1,000. This indicates that the riboflavin part of FAD inhibits the binding of FAD by steric hindrance, while after the binding, it stabilizes the complex.


Further studies on aspartate aminotransferase of thermophilic methanogens by analysis of general properties, bound cofactors, and subunit structures.

Aspartate aminotransferase (AspAT) [EC 2.6.1.1] of thermophilic methanogen was further characterized with the enzyme from Methanobacterium thermoautotrophicum strain FTF-INRA as well as M. thermoformicicum strain SF-4. AspAT of strain FTF-INRA was similar in the amino donor specificity to the enzyme of M. thermoformicicum strain SF-4, in that it was active on L-cysteine and L-cysteine sulfinate in addition to L-glutamate and L-aspartate. The enzymes gave similar absorption spectra having maxima at around 326 and 415 nm with no pH-dependent shift but were found to contain 1 mol of tightly bound pyridoxal 5'-phosphate (PLP) per subunit. Reconstitution of each apoenzyme with added PLP resulted in partial recovery of the original enzymatic activity, suggesting a significant conformational change of the active site region upon removal of the cofactor. Polyacrylamide gel electrophoresis (PAGE) and gel filtration analyses revealed a tetrameric structure (180 kDa) of identical subunits with a molecular mass of 43 kDa for each of these enzymes. Electric current was found to affect the interaction or affinity of each subunit, promoting dissociation of the native enzyme into the monomeric form. Alkaline treatment was effective only for dissociation of the enzyme from strain SF-4. They were distinguishable by the more rapid reassociation of the monomer to the native aggregated form in the enzyme of strain FTF-INRA.


Isolation and characteristics of scallop sarcoplasmic reticulum with calcium transport activity.

Sarcoplasmic reticulum with calcium transport activity has been isolated from the cross-striated adductor muscle of the scallop, which lives in cold (< or = 20 degrees C) sea water, by using pH 7.0 buffer solution both to homogenize the tissue and to sediment the membrane fraction. The yield of the preparation was 60-100 mg protein from 100 g of the scallop muscle. Ca(2+)-activated ATPase protein of about 100 kDa accounted for 40-50% of the protein preparation. The maximum activities of ATP-dependent, oxalate-facilitated calcium accumulation and Ca(2+)-ATPase were observed at a pH of about 7.0 and temperature of 20-30 degrees C, and their values were about 2 mumol Ca2+/mg of protein/min and about 3 mumol ATP hydrolysis/mg of protein/min, respectively. At 0 degree C, 10-20% of these activities was maintained, while at 37 degrees C, the activities were irreversibly lost. The Ca(2+)-ATPase activity was half-maximally activated at about 0.3 microM [Ca2+]. The ATPase activity exhibited non-Michaelian behavior with respect to ATP, with two different Km values of approximately 10 microM and 0.1-0.3 mM. GTP, CTP, and ITP were also hydrolyzed by the preparation at a rate of 10-30% of that of ATP. The preparation was stored at -80 degrees C with retention of function for about a year.


Modification of pig liver dimeric dihydrodiol dehydrogenase with diethylpyrocarbonate and by rose bengal-sensitized photooxidation: evidence for an active-site histidine residue.

Dihydrodiol dehydrogenase from pig liver was inactivated by diethylpyrocarbonate (DEP) and by rose bengal-sensitized photooxidation. The DEP inactivation was reversed by hydroxylamine and the absorption spectrum of the inactivated enzyme indicated that both histidine and tyrosine residues were carbethoxylated. The rates of inactivation by DEP and by photooxidation were dependent on pH, showing the involvement of a group with a pKa of 6.4. The kinetics of inactivation and spectrophotometric quantification of the modified residues suggested that complete inactivation was caused by modification of one histidine residue per active site. The inactivation by the two modifications was partially prevented by either NADP(H) or the combination of NADP+ and substrate, and completely prevented in the presence of both NADP+ and a competitive inhibitor which binds to the enzyme-NADP+ binary complex. The DEP-modified enzyme caused the same blue shift and enhancement of NADPH fluorescence as did the native enzyme, suggesting that the modified histidine is not in the coenzyme-binding site of the enzyme. The results suggest the presence of essential histidine residues in the catalytic region of the active site of pig liver dihydrodiol dehydrogenase.


Inhibition of dimeric dihydrodiol dehydrogenase by 4-hydroxyphenylketone derivatives: aspects of inhibitor structure and binding specificity.

Dimeric dihydrodiol dehydrogenases from pig liver, monkey kidney, and rabbit lens were inhibited more potently by 4-hydroxyphenylketones such as 4-hydroxybenzaldehyde, 4-hydroxyphenylglyoxal, and 4-hydroxyacetophenone than by isoascorbate and ascorbate, known inhibitors of the enzymes. No significant inhibition was observed with 2- or 3-hydroxyphenylketones, phenylketones with a functional group other than a hydroxy group at the 4-position, and 4-hydroxyphenyl derivatives without a carbonyl group. The steady-state kinetic analyses of the inhibition of the pig liver enzyme indicated that the 4-hydroxyphenylketones, similarly to ascorbate and its epimer, bound to an enzyme-NADP+ binary complex as competitive inhibitors with respect to dihydrodiol substrate. The inhibition by the 4-hydroxyphenylketones was uncompetitive with respect to isoascorbate, and the addition of one of the 4-hydroxyphenylketones or isoascorbate with NADP+ afforded a great protective effect against inactivation of the enzyme by diethylpyrocarbonate or by heat treatment, which indicates that 4-hydroxyphenylketones and isoascorbate bind at the same site in or near the active center of the enzyme. The structural comparison of 4-hydroxybenzaldehyde and ascorbate suggests that the hydroxy group at C-5, carbonyl group at C-1 and lactone ring of ascorbate are important for the binding to the enzyme.


Purification and characterization of monomeric isocitrate dehydrogenase with NADP(+)-specificity from Vibrio parahaemolyticus Y-4.

NADP(+)-dependent isocitrate dehydrogenase [IDH: EC 1.1.1.42] was purified to electrophoretic homogeneity from Vibrio parahaemolyticus Y-4, and shown to be a monomeric protein of molecular weight 80,000 with a pI of 5.0. The amino acid composition and partial sequence at the N-terminus resembled those reported for other bacterial monomeric IDHs. Immunotitration with antisera to the monomeric and dimeric enzymes (antisera to IDH-II and -I of Vibrio ABE-1) showed an immunochemical distinction between the monomeric and dimeric IDHs, but there is similarity within the IDHs of each group. The circular dichroism spectra of the native and heat-denatured enzyme are also similar to those of monomeric IDH (IDH-II of Vibrio ABE-1). These monomeric IDHs are proteins comprising 17-22% helix and 25-35% beta-pleated sheet in the native state.


Mechanism of human keratinocyte migration on fibronectin: unique roles of RGD site and integrins.

The migration of human keratinocytes over the wound bed plays an important role in the re-epithelialization of cutaneous wounds. Fibronectin, a large glycoprotein matrix component that is abundant within cutaneous wound beds, promotes keratinocyte migration. However, the mechanisms by which keratinocytes migrate over fibronectin are unknown. In this study, we sought to identify specific sites within the fibronectin molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. The data show that the domain within the fibronectin molecule that induces human keratinocyte migration is the 120 kD cell-binding domain close to the carboxyl terminus. The 40 kD heparin-binding domain near the carboxyl terminus and the 45 kD gelatin-binding domain near the amino terminus did not promote keratinocyte migration. In addition, keratinocyte migration on both fibronectin and the 120 kD cell-binding domain was completely inhibited by the presence of GRGDSP peptide, suggesting that keratinocyte migration on fibronectin is mediated by recognizing the RGD sequence located within the cell-binding domain of fibronectin. Furthermore, keratinocytes were able to migrate directly on immobilized RGD substratum. Cell migration on fibronectin is mediated by the alpha 5 beta 1 integrin since antibodies blocking the alpha 5 and the beta 1 subunits completely inhibited keratinocyte migration on fibronectin. In addition, we demonstrate that human keratinocytes express alpha 5 beta 1 integrin in culture by flow cytometry.


WGA-binding, mucin glycoproteins protect the apical cell surface of mouse uterine epithelial cells.

Expression of apical cell surface proteins and glycoproteins was examined in polarized primary cultures of mouse uterine epithelial cells (UEC). Lectin-gold cytochemistry revealed that wheat germ agglutinin (WGA) bound specifically to the components of the apical glycocalyx as well as intracellular vesicles. Double labeling with the pH sensitive dye 3-(2,4-dinitroanilino)-3'amino-N-methyldipropylamine (DAMP) demonstrated the acidic nature of the WGA-staining intracellular vesicles. The enzymatic and chemical sensitivities of the WGA binding sites on the apical cell surface were monitored both by WGA-gold staining as well as by 125I-WGA binding assays. In thin sections, a large fraction of these sites were removed by pronase; however, application of a wide variety of proteases, glycosidases, or chemical treatments to the apical surface of intact UEC failed to reduce WGA binding. In no case did treatments designed to remove sialic acids reduce 125I-WGA binding more than 12%. In contrast, endo-beta-galactosidase as well as a combination of beta-galactosidase with beta-hexosaminidase succeeded in removing 28% and 77% of these sites, respectively. These studies suggested that the majority of the apically disposed WGA binding sites involved N-acetylglucosamine residues rather than sialic acids and included lactosaminoglycans. Many of the proteins detected at the apical cell surface by lactoperoxidase-catalyzed radioiodination were WGA-binding glycoproteins. A major class of these glycoproteins displayed Mr > 200 kDa by SDS-PAGE and was heavily labeled metabolically by 3H-glucosamine or by vectorial labeling at the apical cell surface with galactosyl transferase and UDP-3H-galactose. Analyses of the 3H-labeled oligosaccharides labeled by either procedure indicated that a large fraction of the apically disposed WGA-binding oligosaccharides consisted of neutral, O-linked mucin-type structures with median MW of approximately 1,500. Oligosaccharides in this fraction were partially (15%) sensitive to endo-beta-galactosidase digestion and bound to Datura stramonium agglutinin (68%), demonstrating the presence of lactosaminoglycan sequences. UEC were an extremely effective barrier to attachment or invasion by either a highly invasive melanoma cell line, B16-BL6, or implantation-competent mouse blastocysts. In contrast, neither uterine stromal cells nor a non-polarizing UEC cell line, RL95, prevented B16-BL6 attachment.(ABSTRACT TRUNCATED AT 400 WORDS)


Switching from differentiation to growth in hepatocytes: control by extracellular matrix.

Studies were carried out to analyze how different extracellular matrix (ECM) molecules regulate hepatocyte growth and differentiation. Freshly isolated rat hepatocytes were cultured on non-adhesive plastic dishes that were pre-coated with defined densities of either laminin, fibronectin, type I collagen, or type IV collagen. Sparse cell plating densities were used to minimize cell-cell contact formation and all studies were carried out in chemically defined medium that contained a saturating amount of soluble growth factors. Dishes coated with a low ECM density (1 ng/cm2) supported hepatocyte attachment, but did not promote cell spreading or growth. Computerized image analysis confirmed that over 80% of cells remained free of contact with other cells under these conditions. Yet, these round cells maintained high levels of albumin gene expression as well as elevated secretion rates for multiple liver-specific proteins (albumin, transferrin, and fibrinogen), regardless of the type of ECM molecule used for cell attachment. When ECM coating densities were raised from 1 to 1,000 ng/cm2, cell spreading, expression of histone mRNA, DNA synthesis, and cell proliferation all increased in parallel. Activation of growth by high ECM densities was also accompanied by a concomitant down-regulation of differentiated functions and again, dishes coated with all four types of ECM molecules produced similar effects. Thus, the ability to switch hepatocytes from differentiation to growth (i.e., between different genetic programs) is not limited to a single ECM molecule, a distinct three dimensional ECM geometry, or due to alteration of cell-cell interactions. Rather, the regulatory signals conveyed by immobilized ECM molecules depend on the density at which they are presented and thus, on their ability to either prohibit or support cell spreading.


Initial characterization of heat-induced excess nuclear proteins in HeLa cells.

Exposure of mammalian cells to hyperthermia is known to cause protein aggregation in the nucleus. The presence of such aggregates has been detected as the relative increase in the protein mass that is associated with nuclei isolated from heated cells. We have characterized these excess nuclear proteins from the nuclei of heated HeLa cells by two-dimensional gel electrophoresis. The abundance of cytoskeletal elements which co-purify with the nuclei did not increase with exposure to hyperthermia, indicating that these proteins are not part of the excess nuclear proteins. In contrast, several specific polypeptides become newly bound or increase in abundance in nuclei isolated from heated cells. Members of the hsp 70 family were identified as a major component of the excess nuclear proteins. Among the other excess nuclear proteins we identified ten that had apparent molecular weights of 130, 95, 75, 58, 53, 48, 46, 37, 28, and 26 kilodaltons. Since hsp 70 is mainly cytoplasmic in non-heated cells, its association with nuclei in heated cells indicates that one mechanism accounting for the heat-induced excess nuclear proteins is the movement of cytoplasmic proteins to the nucleus. We also obtained evidence that increased binding of nuclear proteins is another mechanism for this effect. No overall increase or decrease in the phosphorylation of nuclear proteins was found to be associated with such altered binding or movement from the cytoplasm to the nucleus.


Mechanism of zinc uptake by microvilli isolated from human term placenta.

The mechanism of zinc (Zn) uptake by microvillous membrane vesicles prepared from human term placenta has been studied. The uptake was complex, with two processes being identified. In the first process, uptake was rapid, reaching equilibrium within 2 min, and was temperature dependent, with a Q10 of 1.5. Equilibrium Zn levels were sensitive to osmotic pressure, with Zn binding at infinite osmolarity being 69% iso-osmotic value. The uptake was saturable, with a Vmax of 58 +/- 2 nmol/mg protein/min and an apparent Kt of 128 +/- 13 microM. Uptake was inhibited by increasing extravesicular K+ concentration, dropping from 0.91 +/- 0.03 nmol/mg/min at 0 extravesicular K+ to 0.47 +/- 0.03 at an extravesicular K+ concentration of 150 mM ([Zn] = 1.0 microM). In the presence of both valinomycin, an electrogenic ionophore, and nigericin, an electroneutral exchanger, an outwardly directed K+ gradient stimulated Zn uptake. Similarly, preloading vesicles with Zn and imposing an inward gradient resulted in a temperature dependent efflux of Zn. The data suggest that there is a K+ dependent Zn transporter in vesicle membranes, and we suggest that the evidence is biased in favour of a Zn/K+ exchanger rather than Zn being dependent on the membrane potential.


Inhibition by 1,25 dihydroxyvitamin D3 of c-myc down-regulation and DNA fragmentation in cytosine arabinoside-induced erythroid differentiation of K562 cells.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on DNA fragmentation, altered expression of the heat shock protein (hsp) 70 gene, and protooncogenes c-myc and c-myb was studied during chemical induction of erythroid differentiation in K562 cells. Preincubation of K562 cells with 1,25(OH)2D3 did not alter the concentration of hemoglobin in cells which did differentiate, but led to a reduction in the accumulation of low molecular weight DNA generated by Ara-C administration. The extent of this reduction was similar to the degree of inhibition of hemoglobin formation in the culture as the whole. Preincubation with 1,25(OH)2D3 had no effect on the increase of hsp 70 gene expression induced by a 48-hr treatment with Ara-C, but prevented the Ara-C-induced down-regulation of the protooncogene c-myc. The protooncogene c-myb was down-regulated after 15 min of treatment with Ara-C, and exposure to 1,25(OH)2D3 prior to Ara-C caused a further down-regulation of its expression. The data suggest that the events associated with erythroid differentiation may be separable into at least two groups; one of these may have an influence on the kinetics of the cell cycle traverse, and the other may be related to the expression of the erythroid phenotype.


Stimulation of endothelial cell proliferation by vanadate is specific for microvascular endothelial cells.

Micromolar concentrations of sodium orthovanadate stimulated the proliferation of bovine capillary endothelial cells, but not bovine aortic endothelial cells. Vanadate was equally potent at inducing protein tyrosine phosphorylation and changes in morphology in both types of cells. However, vanadate treatment lead to an inhibition of protein tyrosine kinase activity in the aortic endothelial cells, but not the capillary endothelial cells. In capillary endothelial cells, the effect of vanadate was additive with basic FGF (bFGF) at low concentrations of bFGF. There was no interaction between bFGF and vanadate in aortic endothelial cells. TGF-beta, which inhibits the induction of endothelial cell proliferation by bFGF, appeared to shift the dose response curve to vanadate in capillary endothelial cells, increasing the proliferative effect of vanadate at low vanadate concentrations, but decreasing the proliferative effect at higher vanadate concentrations.


Induced thermotolerance to apoptosis in a human T lymphocyte cell line.

A brief exposure to elevated temperatures elicits, in all organisms, a transient state of increased heat resistance known as thermotolerance. The mechanism for this thermotolerant state is unknown primarily because it is not clear how mild hyperthermia leads to cell death. The realization that cell death can occur through an active process of self destruction, known as apoptosis, led us to consider whether thermotolerance provides protection against this mode of cell death. Apoptosis is a common and essential form of cell death that occurs under both physiological and pathological conditions. This mode of cell death requires the active participation of the dying cell and in this way differs mechanistically from the alternative mode of cell death, necrosis. Here we show that mild hyperthermia induces apoptosis in a human leukemic T cell line. This is evidenced by chromatin condensation, nuclear fragmentation and the cleavage of DNA into oligonucleosome size units. DNA fragmentation is a biochemical hallmark of apoptosis and requires the activation of an endogenous endonuclease. The extent of DNA fragmentation was proportional to the severity of heat stress for cells heated at 43 degrees C from 30 to 90 minutes. A brief conditioning heat treatment induced a resistance to apoptosis. This was evident as a resistance to DNA fragmentation and a reduction in the number of apoptotic cells after a heat challenge. Resistance to DNA fragmentation developed during a recovery period at 37 degrees C and was correlated with enhanced heat shock protein (hsp) synthesis. This heat-induced resistance to apoptosis suggests that thermotolerant cells have gained the capacity to prevent the onset of this pathway of self-destruction. An examination of this process in heated cells should provide new insights into the molecular basis of cellular thermotolerance.


Fibroblast growth factor upregulates PGG/H synthase in rabbit microvascular endothelial cells by a glucocorticoid independent mechanism.

The present study was undertaken to determine the effects of acidic fibroblast growth factor (aFGF) on eicosanoid synthesis in microvessel endothelial cells derived from rabbit left ventricular muscle (RCME cells). We observed that aFGF increased AA conversion to PGE2 in a time- and dose-dependent manner, and the stimulatory effect was abolished by actinomycin D and cycloheximide. Acidic FGF increased the recovery of PGG/H synthase activity following aspirin treatment, suggesting an action on de novo PGG/H synthase synthesis. Acidic FGF increased the incorporation of [35S] methionine into a 70 kD immunoreactive PGG/H synthase band. PGG/H synthase synthesis following aspirin treatment was also increased by transforming growth factor beta, while epidermal growth factor basic FGF and platelet derived growth factor were without effect. In addition, the actions of aFGF on de novo PGG/H synthase were compared in several endothelial preparations. Acidic FGF treatment of aspirin treated endothelial cells from rabbit lung microvessels and small pulmonary artery and from human lung microvessels all showed an increase in PGG/H synthase recovery. In contrast, similar treatment of human umbilical vein endothelial cells was without effect. Pretreatment of RCME cells with dexamethasone (1 microM) did not alter the aFGF induction of PGG/H synthase activity. We conclude that aFGF stimulates PGE2 production by a mechanism that includes the de novo synthesis of PGG/H synthase. This mechanism appears to be distinct from previously described glucocorticoid sensitive translational controls of PG synthase synthesis by epidermal growth factor in smooth muscle and mesangial cells.


1,25-Dihydroxy-vitamin-D3 enhances antiproliferative effect and transcription of TGF-beta1 on human keratinocytes in culture.

Both TGF-beta and 1,25-dihydroxy-vitamin-D3 (1,25(OH)2D3) have been reported to decrease the proliferation of normal human keratinocytes. The effect and expression of TGF-beta in keratinocytes treated with 1,25(OH)2D3 was investigated. Human keratinocytes were grown in the presence of various concentrations of TGF-beta and/or 1,25(OH)2D3 prior to enumeration. TGF-beta, alone, has a half maximal dose of inhibition (ED50) of approximately 750 pg/ml after seven days in culture in Keratinocyte Growth Medium (KGM; Clonetics) supplemented with 1.5 mM calcium. When 1,25(OH)2D3 (10(-7)M) was also added to cultures with various concentrations of TGF-beta, the ED50 shifted an average of 2-fold less. The presence of TGF-beta (10 pg/ml) augmented the potency of 1,25(OH)2D3 by at least 10-fold. In keratinocyte cultures, the antiproliferative effect of the two compounds together is synergistic. In keratinocytes grown for 1 week in the presence of 1,25(OH)2D3 at 10(-6)M, the TGF-beta 1 message increased approximately 5-fold. An increase is detected within 2 hours of exposure to 1,25(OH)2D3. There was only a 50% increase in the levels of TGF-beta 2 and no detection of TGF-beta 3. When keratinocyte cultures were treated with 1,25(OH)2D3 and neutralizing antibodies to TGF-beta, the induced-antiproliferative activity was blocked by more than 50%. The keratinocytes produced more active than latent TGF-beta after growth with high doses of 1,25(OH)2D3.


Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB.

We have examined the ability of transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor-BB (PDGF-BB) to regulate the expression of various integrins in cultured rabbit vascular smooth muscle cells (SMC). We found that expression of the alpha v beta 3 integrin complex was induced by both growth factors, although TGF-beta 1 appeared to be the more potent inducer. mRNA level of the beta 3 integrin subunit was undetectable in quiescent cells and enhanced by both growth factors, while the alpha v integrin subunit mRNA level did not change with growth factor addition. Therefore, appearance of the alpha v beta 3 integrin protein complex after growth factor stimulation was due to increased expression of the beta 3 integrin subunit mRNA. The TGF-beta 1 induced increase in beta 3 integrin mRNA was delayed, but did not require prior protein synthesis, since cycloheximide was unable to block the increase in beta 3 mRNA level. By contrast, PDGF-BB induced a more rapid increase in beta 3 integrin mRNA level that peaked by 6 h after growth factor addition and no detectable beta 3 integrin mRNA remained after 24 h. Interestingly, the PDGF-BB induced elevation of beta 3 integrin, although more rapid, was completely inhibited by cycloheximide. Expression of the alpha 5 integrin subunit in response to growth factors was very similar to beta 3. However, in contrast to beta 3 and alpha 5, neither TGF-beta 1 nor PDGF-BB were able to alter the expression of the beta 1 integrin subunit in vascular SMC. However, in TGF-beta 1 treated cells, there was a large increase in expression of a 190 kDa polypeptide that was associated with the beta 1 integrin subunit. This 190 kDa polypeptide was not detected in PDGF treated SMC or in TGF-beta 1 treated fibroblasts. The alpha 1 integrin subunit has a MW of approximately 190 kDa and is capable of complexing with beta 1. Analysis of the alpha 1 integrin subunit mRNA level indicated that it was indeed induced by TGF-beta 1, but not by PDGF-BB, suggesting that the 190 kDa polypeptide may be the alpha 1 integrin subunit. These results indicate that TGF-beta 1 and PDGF-BB are potent but distinct activators of integrin expression in vascular SMC.


Quick and accurate method to convert BCECF fluorescence to pHi: calibration in three different types of cell preparations.

A rapid, easy, and accurate method for converting the fluorescence of BCECF to pH, as an alternative to the nigericin method, is described. The ratio of the fluorescence intensities for BCECF can be converted to pH between 4 and 9 by a formula similar to the one used to calculate [Ca2+]i from the fluorescence of fura2. The formula is inverted because H+ binding to BCECF causes a decrease in fluorescence, whereas Ca2+ binding to fura2 causes an increase in fluorescence. The ratio of the fluorescence intensities is a sigmoidal function of the [H+] between pH 4 and 9 with an essentially linear mid region from pH 6 to 8. This calibration procedure in cells is similar to the popular method for fura2 where ionomycin, Ca2+, and an alkaline EGTA solution are added in succession to change the intracellular pCa from 4 to 9. For BCECF in cells, a protonophore, FCCP or CCCP, is added and the cells are titrated with acid to an intracellular pH of 4 and then back to pH 9 with base by observing the gradual change in fluorescence as it asymptotically reaches its limiting minimum and maximum values. This method does not require changing the medium to one with high KCl to depolarize the membrane potential nor does the proton concentration need to be equilibrated across the plasma membrane. The technique can be used to calibrate BCECF in sheets of cells, as well as suspensions of cells over a wide range of pH sensitivities.


[Safety of cholecystectomy by laparotomy in elective situation and in emergency].

Cholecystectomy is the only effective treatment of gallbladder stones. A retrospective study was carried out on results of 658 cholecystectomies by laparotomy without choledochotomy performed between January 1987 and December 1989, to determine morbidity and mortality of elective and emergency surgery and by age. Operations for tumors of the gallbladder and choledolithiasis were not included in the analysis. During this period, cholecystectomy was performed electively in 387 cases and under emergency conditions in 261 patients. Mortality and post-operative morbidity were 0% and 14.7% respectively after elective surgery, increasing to 1.1% (Fisher = 0.0617) and 25.2 (p = 0.0004) respectively after emergency operations. This large increase in postoperative morbidity in urgent cases was due to an increase in systemic and not local complications, as a result of the higher proportion of emergency operations with advancing age. Since elective cholecystectomy is safe it can be proposed to patients with symptoms, including the elderly. It is difficult at present to compare results of cholecystectomy by laparotomy with those of laparoscopy since the average age of in the latter category is markedly lower and the number of acute cases still low. The principal advantage of celioscopy could be a long term reduction in systemic complications in emergency operations.


[Prognostic factors of femoropopliteal shunts. Retrospective study of a series of 52 shunts].

Between January 1986 and January 1991, 52 femoropopliteal shunts were carried out in 51 patients for lesions defined by the Ad Hoc Committee as grade III in 36 cases, grade II in 10 and grade I in 6. The shunt graft used was the internal saphenous vein in situ in 34 cases, inversed in 13 cases, and a PTFE prosthesis in 5 cases. The postoperative course included 12 complications and one death. At the end of the study, 10 shunts had thrombosed and 4 patients had required a major amputation. Actuarial analysis at 5 year follow up showed primary permeability of 56% and secondary permeability of 60%. Statistical analysis of secondary permeability as a function of the distal bed, an associated diabetes or the in situ or inversed venous shunt, failed to demonstrate any significant difference. These femoropopliteal venous shunts in critical ischemias reduced the incidence of major amputations, the proportion of limbs saved being higher than that for shunt permeability from the 6th postoperative month. Poor results were recorded for femoropopliteal shunts using prostheses.


[Peritonitis after spontaneous rupture of a pyonephrosis into the peritoneal cavity. Apropos of a case].

Peritonitis by fistulization of a pyonephrosis is an extremely rare complication usually diagnosed perioperatively. Treatment is by immediate or deferred nephrectomy after ensuring the functional condition of the contralateral kidney.


[Surgery called tumoral reduction: myth or reality?].

The cytoreductive surgery (CS) or surgical debulking of tumors is supported by the following experimental concept: the maximal but incomplete resection of huge tumoral masses (debulking) induces the passage of remaining cancerous cells in proliferative cycle. So, these remaining cells become sensitive to chemotherapy, or eventually to radiotherapy. In this way, the CS appears to be a neoadjuvant treatment to the chemotherapy, this last treatment being the powerful therapeutic. In this study, we have studied successively: the theoretical basis of the CS, the experimental positive and negative arguments of this concept, and then the positive and negative clinical applications. At least, it seems that CS is more a myth than a reality, and that we should only keep the classical concepts of curative surgery or palliative surgery.


Diagnostic model for local temporal thermal change at the skin of the breast during extended application of diagnostic ultrasound.

A biophysical model is derived to account for the temporal thermal change at the skin of the breast as a result of ultrasound stimulation at the suspect lesion for seven minutes, with responses recorded using an infrared camera. Twenty-two patients were studied. The observed temporal responses for malignant cases have a different pattern from those of the benign cases studied and a mathematical model is used to investigate the controlling parameters. A new method is used to estimate the coefficients of the resulting difference equation which allows more useful diagnostic parameters to be computed than the corresponding continuous bioheat equation. The model is used to fit the experimental data. The results suggest that this method might be a rapid and noninvasive aid for distinguishing between benign and malignant breast tumours.


Mathematical models of wound healing in embryonic and adult epidermis.

Epidermal wound healing occurs by quite different mechanisms in embryos and adults. In the latter case, it has long been known that cells crawl inwards via lamellipodia to close the defect. In the embryonic system, recent evidence suggests that healing may be caused by a quite different mechanism, namely the contraction of a cable of filamentous actin at the wound edge. The authors use mathematical modelling to investigate both systems. A mechanical model for the initial formation of the actin cable in embryonic epidermal wounds is presented, which incorporates the important phenomenon of stress-induced microfilament alignment. Also discussed is a reaction-diffusion model for the healing of adult wounds subject to autoregulation of cell division. In both cases, the results suggest possible biological mechanisms for key aspects of the healing process.


Optimal chemical control of populations developing drug resistance.

A system of differential equations for the control of the growth of certain populations by the use of chemical treatment is presented. Rather general growth rates and kill rates of drugs, as well as drug resistance, are considered. A class of optimal control problems with a performance criterion depending on a parameter is formulated and shown to admit the same basic optimal strategy. Applications to cycle nonspecific chemotherapy and control of the growth of bacterial populations in cellulose media in paper production plants are described.


Quantitative analysis of platelet function using stagnation point flow aggregometry. First clinical results.

The clinical consequences of atherosclerosis result from vascular occlusion. The central role of platelet-vessel wall interaction in the initiation and perpetuation of this process is well established. Individual analysis and quantification of two major platelet functions underlying atherosclerosis and thrombosis, i.e. adhesion (platelet-wall interaction) and aggregation (platelet-platelet interaction), would contribute significantly towards elucidation of the mechanisms involved and therefore towards optimization of prophylaxis and therapy. The Stagnation-Point-Flow-Adhesio-Aggregometer (SPAA), in which such an evaluation of platelet function is possible, was thus standardized and its clinical reproducibility and predictive power assessed. Using the SPAA, a morphometric separation of adhesion and aggregation is obtained via dark field micrographs of platelet microthrombi formed during stagnation point flow of platelet rich plasma (PRP). Quantification is achieved via biomathematical evaluation of simultaneously obtained growth curves, whereby the degree of adhesivity and aggregability is reflected in the respective growth rate constants Kpw (%) and Kpp (%). Experiments with the PRP of 36 healthy volunteers were performed and the results compared to those obtained for 32 patients exhibiting angiographically verified peripheral arterial disease (PAD). The control group exhibited values (Kpw) ranging from 0.40% to 1.10% (average Kpw: 0.71 +/- 0.21%). Differences in average Kpw value between the control subgroup over and that under 45 years of age were absent. A spontaneous platelet aggregation was not observed in the controls (Kpp = 0%). The overall intraindividual Kpw variation in 18 volunteers examined 3 times or more ranged from a minimum of 3% to a maximum of 20% of respective Kpw value. The patients were divided into two subgroups: diabetics and nondiabetics. The nondiabetic group demonstrated an average Kpw of 1.56%. In addition, a spontaneous aggregation was observed in 50% of all experiments (average Kpp = 1.42%). The diabetic group exhibited the highest average adhesion value (Kpw = 1.94%) occurrence of spontaneous aggregation in all experiments (Kpp = 2.10%). The consistency in adhesion values obtained among the controls as well as the minimal intraindividual variance observed, demonstrates the reproducibility of the method. The statistically significant increase (p < 0.001) in adhesivity of patients as compared to controls, as well as the common occurrence of spontaneous aggregation can therefore be considered a pathologic platelet response reflecting the severity of the disease. Results obtained verify the presence of circulating hyperreactive platelets in PAD patient and indicate the predictive power of the method. Thus the SPAA may be of considerable aid in improving thrombosis prophylaxis and therapy.


A monkey model for mucoid vasculopathy.

Mucoid vasculopathy is a new vascular entity observed by the Author in autopsy material in Kerala, a southwest coastal state of tropical India. This non-atherosclerotic, non-inflammatory connective tissue disorder affects mainly arteries, veins, vasa-nervosum and fascial tissues. Characteristically, there are large deposits of acid mucopolysaccharide (glycosaminoglycan) material in the intima and media of arteries, accompanied by hyperplastic changes in cellular elements of the vessel wall and dystrophic changes in internal elastic laminae. There is secondary mineralization of elastic laminae and of medial mucoid material in some cases. To ascertain the role of diet in the aetiology of mucoid vasculopathy, groups of bonnet monkeys were fed protein-deficient normal carbohydrate, or protein-deficient high-carbohydrate tapioca (cassava) starch based diets or control diets of normal protein and carbohydrate for 3 or 5 months periods. The diet of the poorer sections in Kerala is deficient in protein and tapioca is the main source of carbohydrate. A generalised mucopolysaccharidosis and vasculopathy similar to the human condition and associated with some cardiomyopathic changes could be induced in the monkeys by protein deficient diets. These were enhanced both by ingestion of a high carbohydrate and by a longer experimental period. In order to exclude the effect of toxic factors which might be present in tapioca starch, experiments were repeated with corn starch as the carbohydrate: identical cardiovascular lesions were induced. The animal experiments established pivotal role for protein-deficiency in inducing mucoid vasculopathy with enhancement of degenerative cardiovascular lesions by ingestion of higher levels of carbohydrate in a protein-deficient state. This experimental study establishes a good animal model for mucoid vasculopathy.


Reduced thrombogenicity of vascular prostheses by coating with ADP-ase.

In this pilot study ADP-ase coated polyurethane (PU) vascular prostheses and noncoated (control) PU vascular prostheses (all vascular prostheses: ID 1.5 mm, length 1.5 cm) were implanted into the carotid artery of the rabbit to test whether ADP-ase might function as an adequate anti-thrombogenic coating. The prostheses were evaluated after 1 hour (n = 4) and 3 weeks (n = 8). After 1 hour, there was extensive accumulation of thrombus on the inner surface of the control PU vascular prostheses, in contrast to the ADP-ase coated prostheses. At 3 weeks, all control PU vascular prostheses (n = 8) were occluded, whereas only 1 of the 8 ADP-ase coated PU vascular prostheses. The patient ADP-ase coated PU prostheses showed already extensive endothelial healing. These results indicate the potential of ADP-ase to function as an effective antithrombogenic coating of small-caliber and microvascular PU prostheses.


Medical writing: inadvertent humor and other anomalies.

Although most readers consider medical publications to be somber and somnifacient, a critical eye will discover a remarkable array of absurdities and assorted other oddities, totally unintended by the authors. These eccentricities can be attributed to failure of the author to engage the mind before activating the pen, a lapse of attention during preparation of the manuscript, or an effort to convey profundity and conceal vacuity by inflated and pompous language. The egregious examples from prestigious journals included here should alert medical authors that eternal vigilance to clear, orderly reasoning and lucid, orderly language is crucial during preparation of a manuscript. To acquire a pleasing and distinctive literary style, read extensively of the literary masters, approach writing with enthusiasm for its challenges and rewards, experiment with the choice and arrangement of words and phrases, and read critically every word, phrase, sentence, paragraph, and section of your manuscript as though you were your most critical adversary.


Failure of selective shunting to intercostal arteries to prevent spinal cord ischemia during experimental thoracoabdominal aortic occlusion.

Paraplegia from spinal cord ischemia during thoracoabdominal aneurysm repair remains an unpredictable and unpreventable complication. In an effort to prevent spinal cord ischemia during aortic cross-clamping, preoperative angiographic localization of the blood supply to the spinal cord was performed in dogs. Sixteen animals underwent 60 minutes of thoracoabdominal aortic cross-clamping either without (control, n = 8) or with (shunted, n = 8) a selective shunt. Shunting was performed from the aortic arch to that isolated aortic segment angiographically shown to supply the thoracolumbar anterior spinal artery. Spinal cord blood flow was measured with microspheres just prior to cross-clamping, at 5 and 60 minutes after cross-clamping and at 5 minutes after restoration of aortic blood flow. Functional neurologic outcome was evaluated in animals at 24 hours postoperatively. Shunting did not decrease spinal cord injury. Seven of the 8 animals in the control group and 7 of the 8 in the shunted group developed paraplegia or paraparesis. Thoracic, but not lumbar spinal cord blood flow, was significantly increased in shunted animals. Spinal cord blood supply in dogs may be more segmental than previously believed. Technical problems in angiographic localization, spinal artery spasm, loss of spinal cord autoregulation or poor collateral circulation from the distal thoracic to the lumbar cord may also account for these results. Although shunting to aortic segments supplying the anterior spinal artery during thoracoabdominal aortic clamping may be attractive in humans, no benefit could be shown in this experimental model.


Ankle and toe systolic pressures comparison of value and limitations in arterial occlusive disease.

Ankle and toe systolic pressures represent the most convenient and useful measurements in the assessment of limbs with arterial occlusive disease. Each is a sensitive index of the presence and severity of the arterial obstruction and they both correlate with angiographic findings and with the severity of the symptoms. The measurements can be used to follow individual patients, to study the natural history of the disease, to assess prognosis and plan management, and to evaluate long-term results of surgical and transcutaneous interventions. However, because of the limitations of the ankle pressures related to the rigidity of the arterial walls of the tibial vessels and the more distal site of the measurement in the toes, measurements of pressure in the toes should be included in the evaluation of arterial disease in all patients with diabetes, and in all limbs with severe ischemia.


Child abuse as an inhibiting factor for family planning.

The aim of this study is to determine the magnitude of the problem of using children as an economic asset to the family thus, in one way increasing the prevalence of child abuse in Egypt and also hindering the family planning program. Two focus-group interviews were conducted in urban & rural areas for 10 women with the same age range and socioeconomic background. All were non-users of any contraception. Subsequently an interview was conducted for all women who attended the Ob. & Gyn. Clinic at Ain Shams University Hospital in the period from June to August 1991, their ages ranged from 30-35 years and they never used contraception. Another group of women with the same characteristics were interviewed from a rural area at Fayoum Governorate. A questionnaire was filled for each interviewed woman. The total women interviewed in urban area is 340 while in the rural area they were 400 women. Sixty percent of urban women and 80% of rural women are illiterate, 70% of the urban & 100% of rural women are housewives. Their years of marriage ranged between 10-20 years and all of them have more than five children. A percentage of 73.5% of urban women and 85% of rural women stated that children are used as an economic asset to their families, they work in urban areas as assistants in motor repairs, hair-dressers, beggars, bakeries, shops, restaurants and factories while in rural areas they work as agricultural workers.


Experimental venous thrombosis: what animal model?

A new experimental venous thrombosis model is described and its role relative to other models is defined. Previous models are not satisfactory for all types of investigation. Opposite, present model based on the three classic thrombogenic factors is suitable for venous scintigraphy and evaluation of different forms of therapy for venous thrombosis of the limbs. So this model permits research on diagnosis and therapy of thromboembolic disease.


Epidemiologic study of premenstrual symptoms.

The frequency of selected premenstrual symptoms among 342 Egyptian women were analyzed in relation to demographic and reproductive characteristics. The frequency ranged from 36% for breast pain or tenderness to 66% for premenstrual stomach and back cramps, socioeconomic status, education, age at menarche, breast size, menstrual irregularity, and history of pregnancy are all associated with the premenstrual symptoms.


Raynaud's phenomenon: subjective influence of female sex hormones.

Recent studies with standardized laboratory measurements of skin blood flow suggest an influence of female sex hormones on vasospasm. Therefore we evaluated the influence of sex hormonal status on the subjective complaints of Raynaud's phenomenon and furthermore the combined presence of Raynaud's phenomenon and migraine. A detailed questionnaire was filled in by 130 primary Raynaud patients (31 males, 99 females), while 27 females, with regular menstrual cycles without the use of oral contraceptives, kept a diary with daily registration (during three months) of frequency, severity and duration of the vasospastic attacks. Complaints improved during pregnancy in 6 out of 23 females. No influence of the menopause or the use of oral contraceptives was found. An exacerbation in some phases of the menstrual cycle was present in 15 out of 80 females. The diaries, however, did not show such influence of menstrual cycle phase. Migraine was present in 21% of the Raynaud patients. In contrast to most reports in the literature and contrary to the results of laboratory research, this study shows that most females do not experience an important subjective influence of sex hormonal status on vasospastic attacks.


Dietary patterns and nutritional assessment of working children at Abou El-Dardar industrial area in Alexandria City.

The present study was undertaken in order to evaluate the nutritional status of young working children aged 8 to 18 years, working in workshops at Abou-El-Dardar industrial area in Alexandria Governorate. A total sample of 154 of young male workers were recruited from workshops. The nutritional status was assessed using anthropometric, dietary and biochemical criteria. The results of the study revealed that 45% of the working children were considered malnourished: 16% were wasted, 23% were stunted and 3% were both wasted and stunted and 3% were overweight. Analysis of nutrient intake revealed that the intakes were less than the recommended for energy, calcium, vitamin A, vitamin C and niacin, while the intake of protein, iron, thiamin and riboflavin were more than sufficient. About 77% of the young workers were found to have haemoglobin levels below the cut-off levels issued by WHO. A high prevalence of parasitic infection (food-borne) (72%) was found among young workers. The results also revealed that stunting, wasting and stunting together and overweight were more common in young workers who were both anaemic and had evidence of parasitic infection than those who were anaemic only or had parasitic infection only.


Cutaneous circulation in Raynaud's phenomenon during emotional stress. A morphological and functional study using capillaroscopy and laser-Doppler.

In order to assess the effects of emotional stress on the cutaneous microcirculation in patients suffering from Raynaud's phenomenon (RP) a group of 18 patients with this pathology and 16 healthy control subjects underwent an "arithmetical test". The microcirculatory response was examined using a laser Doppler apparatus. The results obtained showed a constantly reduced flow during mental stress in normal subjects; in the RP group it was possible to observe: a first subgroup with a reduced flow similar to that seen in normal subjects, and a second subgroup with a paradoxically increased flow. It is likely that the normal vasoconstrictor response is the expression of the functional impairment of the microcirculation alone (primary RP), whereas vasodilatation in response to mental stress is a sign, of the organic development of the disease right from an early stage.


Campylobacter jejuni in acute diarrhoea in infancy and its relation to faecal leucocytic count.

A prospective study was carried out to identify the relative risk of Campylobacter jejuni infection in 50 infants with acute diarrhoea, 24 infants with acute resistant diarrhoea and 25 healthy normal infants as a matching control group. Faecal samples were collected from the three groups and were cultured on both selective media for Campylobacter and other media for isolation of other organisms. Direct stool smears, stained with methylene blue, were examined for detection of faecal leucocyte in all samples. Campylobacter jejuni were isolated from 4 cases (8.0%) of the acute diarrhoeal group and 4 cases (16.6%) of acute resistant diarrhoeal group. The other bacterial pathogens isolated from our cases were Salmonella, Shigella, E. Coli, Proteus mirabilis, Vibrio Parahaemolytious Klebsiella, Streptococcus faecalis and Candida albicans. All cases from whom Campylobacter was isolated were bottle fed and their ages were below 6 months. Smears for faecal leucocytes were positive in 100% of Campylobacter isolated cases, 60% of Salmonella, 50% of Shigella, 14% of E. Coli and 100% were negative in all other cases. Thus it can be recommended that any case presenting with acute diarrhoea should be initially screened by faecal leucocytic counting, positive cases should be cultured for Campylobacter jejuni detection in addition to cultures for other organisms detection.


Delta virus infection in Egypt.

The present study was carried out on 124 serum samples of acute hepatitis B, 51 with chronic HBV infection, and 41 chronic HBsAg carriers. Sera were tested by ELISA for HBV markers and anti-delta (anti-HDV). Delta infection (anti-HDV) in acute HB was found to be 16.9% (21 out of 124), 23.5% in chronic HB cases (12 out of 51), and 21.9% among chronic HBsAg carriers (9 out of 41). Out of the twelve delta positive in chronic HB patients, ten (83%) were suffering from CAH (chronic active hepatitis) denoting a possible role of delta infection in deteriorating the course of the disease. A competitive inhibition of HBV replication by coexistent delta infection was demonstrated in the present study. This was reflected on anti-HBc IgM in the acute cases and on HBeAg in chronic HB cases. Anti-HBc IgM was 71.42% (15 out of 21) in delta positive acute HB patients versus 92.23% (95 out of 103) in delta negative acute HB patients. On the other hand, HBeAg percentage was 8.33% (1 out of 12) and 46.15% (18 out of 39) in delta and non-delta chronic HB patients respectively. The difference in both anti-HBc IgM and HBeAg as regards delta positive and negative patients was found to be statistically significant. Out of the twelve chronic HB cases with delta infection, four cases were negative for HBsAg (33.33%). This observation might be attributed to the clearance effect of hepatitis D virus (HDV) on HBsAg (Ischimura et al., 1988) or due to suppressing effect resulting in low undetectable HBsAg level in serum, (Sherlock, 1989). From the present study it may be concluded that delta infection is endemic in Egypt (its incidence ranged from 16.94% in acute HB to 23.53% in chronic HB infection), delta infection possibly also worsens the outcome of chronic HB patients. Delta infection may exert a competitive inhibitory effect on HBV replication.


Non-A, non-B viral hepatitis in Egypt.

A study was carried out on 200 patients of ages 20-40 years suffering from acute viral hepatitis. Sera were tested for markers of hepatitis B (HBsAg, and IgM anti-HBc) and hepatitis A (IgM-anti-HAV) by the ELISA technique. Sera negative for the markers of both viruses: Hepatitis A (HAV) and Hepatitis B (HBV) were subsequently tested for IGM Heterophil antibodies against Epstein-Barr virus (EBV) by the Monospot slide test to diagnose acute infectious mononucleosis and tested for anti-CMV (IgM) by ELISA technique for the diagnosis of acute Cytomegalovirus (CMV) infection. Non-A, non-B hepatitis (NANB) was diagnosed by exclusion. The results of the study showed that 133 (66.5%) patients had evidence of HBV infection, while only 9(4.5%) were diagnosed as HAV infection. EBV and CMV were the possible etiological agents of acute viral hepatitis in (3.5%) and 1%) respectively. Accordingly the Non-A, non-B hepatitis in this study amounts to (24.5%) of the acute viral hepatitis.


Evidence of a 1985-1987 outbreak of acute and chronic hepatitis in Egypt caused by a mutant hepatitis-B virus detected by spot-DNA hybridization test.

Sera from 65 acute and 113 chronic sporadic hepatitis were screened for serological markers of hepatitis-B virus (HBV) and hepatitis delta virus (HDV) and for HBV-DNA. The enzyme linked immune sorbent assay (ELISA) and dot-DNA hybridization tests were used. Two HBV-DNA probes and their labelling systems (biotin, radiolabelling with 32P and digoxigenin) were compared for sensitivity and specificity. The 65 acute sera had serological parameters of HBV infection in 38 (58%) when all these sera were HBsAg, IgM anti HBcAg positive plus HBeAg presence in 11/38 sera. Some of the acute sera had markers of acute HBV and HDV coinfection in 14 and superinfection in 13. Thus HBV with HDV represented 27 (41.5%) of the acute hepatitis in this study. Correlation of these serological markers with dot-DNA hybridization results showed that serum HBV-DNA was present in 36/38 (94.7%) of the acute HBV infection. In the case of acute HBV+HDV positive antigenemia 4/6 had serum HBV-DNA while 10/21 of acute HBV with anti-deltaV. IgM had serum HBV-DNA. There were four cases that gave HBV-DNA positivity in sera without combination of HBV markers suggesting infection with "mutant" HBV. In the chronic hepatitis sera there were markers of HBV past infection (IgG anti HBc in 63/113 and IgG anti HBs in 36/113). Yet, among these sera there was HBV-DNA positive signals (20/63 and 17/36) respectively. Analysis of some of these HBV markers also suggested infection with "mutant" HBV.


Bordetella pertussis FHA antibodies in maternal/infants sera and colostrum.

The high incidence of pertussis in the first year of life confirms that susceptibility remains high for children in this age group despite > 90% pertussis vaccine compliance. In this respect, immunoresponse to Bordetella pertussis was investigated. Filamentous hemagglutinin (FHA) antibodies were studied due to their important protective role, in blocking the adherence of the bacteria to respiratory tract ciliated cells. The relative rate of detection and degree of positivity of IgG and IgA antibodies to Bordetella pertussis FHA were studied in maternal and infant sera and in colostrum samples of the respective mothers. The study comprised 143 mothers of child bearing age and 25 newborns. The highest percentages of serum IgG and IgA were present in the younger females group (15-25 yrs). Both IgG and IgA were detected in the same mother in 60% of them. The study showed that 96.9% of colostrum samples who were positive for IgA, were associated with IgA positivity in serum, also an increase in the degree of serum IgA positivity was associated with a higher rate of detection of IgA in colostrum. Maternal serum IgA could therefore be used as a marker for the future presence of IgA in colostrum. This work demonstrated that newborns show little passive immunity to pertussis, evidenced by the low placental transfer of IgG (35.7%) and the low rate of detection of IgA in the colostrum (41%). We concluded that, it would be advantageous to reimmunize pregnant women, without adequate serum antibody to Bordetella pertussis, with appropriate new vaccine which would offer a better passive immunity to their infants.


A genetic study of vitamin D deficiency rickets: 2-sex differences and ABO typing.

In a further attempt to study the role of genetics in vitamin D deficiency rickets, 400 rachitic infants randomly chosen and aged from 6 months to 2 years (14.3 +/- 3.5 months) were investigated for sex differences and ABO typing. A significant (P < 0.001) predominance of the male sex was found, sex ratio being 1.43. Blood group A was significantly (P < 0.001) associated with rachitic patients whether males or females. Alkaline phosphatase values were significantly (P < 0.01) higher in male infants 91% of them had levels above 30 K.A. units, while the corresponding percentage of girls was 72%. This indicates that the disease is more severe among males. The study gives added support for the belief that there is a genetic factor in nutritional rickets.


Comparative results of the immunogenicity of Edmonston-Zagreb and Schwartz measles vaccines administered to 60 Egyptian infants.

The present study was conducted on sixty 9-11 month infants attending a primary care clinic in a rural Giza governorate area. Patients were divided into two groups: the first group comprised 42 infants who were vaccinated with the Edmonston Zagreb measles vaccine strain, whereas the second group comprised 18 infants who were vaccinated with the Schwartz measles vaccine strain. Estimation of measles antibody titer by neutralization testing was determined by the microtiter technique prior to and 4 weeks post vaccination. The overall serconversion rate was 85%. Three infants failed vaccination. The Edmonston-Zagreb strain was superior to the Schwartz strain in inducing immunity to non immune infants. The nutritional status of the study group was abnormal in almost 1/2 (29/60) infants and borderline in 1/3 (20/60).


Prenatal care in primary health care centers of Al Hassa, Saudi Arabia.

The objective of this study was to determine the performance of Al Hassa primary health care (PHC) centers in the scope of prenatal care and to have a baseline data for future evaluation of achievement in that field. A retrospective study was done by collecting information on a pre-designed form from the available records in the PHC centers. The number of registered pregnant ladies for prenatal care in PHC centers was 10,594 which was equal to 58% of the estimated number of pregnant ladies in Al-Hassa, in 1409 H (the official calendar of Saudi Arabia corresponding to 1989). The immunization coverage by tetanus toxoid of the registered pregnant ladies was 66.7% for the first dose and 40.3% for the second dose. Forty six percent of the registered pregnancies was identified by PHC staff as high risk pregnancy. It was found that 64.4% of the high risk pregnancy was due to causes in the reproductive history, 25.4% due to associated medical conditions and 7.2% due to causes in the present pregnancy. A self criticism and future need to improve prenatal services are discussed.


Factors affecting birth weight in Kuwait. Part II: Pregnancy characteristics and health factors.

The aim of this was to determine the mean birth weight of Kuwaiti infants, the incidence of low birth weight and the impact of maternal age, smoking, health status, parents' consanguinity and pregnancy characteristics on infants' birth weight. The study was conducted in the major maternity hospital in Kuwait where the body weight of 1995 newborn infants was recorded shortly after birth. Data describing maternal age, duration of pregnancy, sex of the infant and maternal illness during pregnancy were recorded. Mothers were interviewed to collect data on duration between present and last pregnancy, birth order of the infant, parents' consanguinity and frequency of smoking. The results show that the mean birth weight was 3.5 Kg and the incidence of low birth weight was 3.4%. The results illustrate that young mothers were more liable to have small infants while old mothers were more liable to deliver a very heavy or low birth weight infant. The weight of the newborn infant was positively correlated with duration of pregnancy, duration between present and last pregnancy and birth order. The mean birth weight of male infants (3.51 Kg) was higher than females (3.47 Kg). Parents' consanguinity and maternal smoking had a slight effect on infants' birth weight. The results show that diabetic mothers delivered large babies. On the contrary, the incidence of low birth weight was highest (7.0%) among infants of hypertensive mothers.


Vaccination coverage before and after primary health care implementation and trend of target diseases in Al Hassa, Saudi Arabia.

There were two objectives of this study. The first was to determine the impact of vaccination coverage in the first year of life on the trend of the expanded program of immunization (EPI) target diseases in Al Hassa. The second was to determine the impact of primary health care (PHC) implementation in Al Hassa on vaccination coverage. A correlation matrex was computed for all the variables to determine the correlation between vaccination coverage by type of vaccine and reported cases of EPI target diseases. A negative correlation was noticed between Bacillus Calmette Guerin (BCG), Oral Polio Vaccine (OPV), Diphtheria, Pertussis and Tetanus (DPT) and measles vaccine and reported cases of corresponding diseases. This negative correlation was significant (P = 0.043) between measles vaccine and reported measles cases. The average vaccination coverage in the first year of life based on the total number of births significantly increased in 1988 and 1989 compared to the preceding four years (P < 0.01). It is concluded that with increased vaccination coverage in the first year of life against EPI target diseases, the number of reported corresponding diseases decreased, and that PHC implementation improved the vaccination coverage in Al Hassa.


Patient satisfaction with hospital services: determinants and level in a hospital in Kuwait.

The present study used a well-tested patient satisfaction measuring instrument to identify the determinants of the level of overall satisfaction with hospital services, and to examine the level of satisfaction with attributes of 7 specific dimensions of hospital services. Using multiple regression analysis, it was found that out of 12 patient characteristics, age was the most important determinant of overall satisfaction, followed by gender. Perceived health status, clinical department, and expectations about the quality of services before admission were also significant but less important determinants of overall satisfaction. Marital status, level of education, nationality, and previous hospitalization in the study hospital, in Kuwait, or in a western country hospital, all had no significant effect on overall satisfaction. Concerning the effect of satisfaction with specific dimensions of hospital services on overall satisfaction, it was found that satisfaction with physicians was the most important determinant of overall satisfaction, followed by satisfaction with housekeeping and with nurses. Satisfaction with hospital environment and facilities and with admission process were also significant but less important determinants of overall satisfaction, while satisfaction with food and radiology services did not affect overall satisfaction. The level of overall satisfaction as well as satisfaction with specific dimensions of hospital services were quite high. Physicians' care was the most favorably rated dimension, followed by admission process and housekeeping, while nursing care was the least favorably rated dimension. Among the attributes of physicians' and nurses' care, technical care and courtesy were the most favorably rated items; while communication, particularly imparting of information, was the least favorably rated aspect. Several attributes of the hospital environment and facilities and of the food services were found to be dissatisfying to patients.


Childhood aggression, adolescent delinquency, and drug use: a longitudinal study.

The interrelation of childhood aggression, early and late adolescent delinquency, and drug use was explored. Data were obtained for the subjects when they were 5-10 years old. Follow-up interviews were conducted when the subjects were between 13-18 years old and again when they were 15-20 years old. A LISREL analysis of the three waves of data indicated that childhood aggression is a precursor of adolescent drug use and delinquency, and that early adolescent drug use is correlated with contemporaneous delinquency as well as with later drug use and delinquency.


Effects of list organization and retrieval cues on children's delayed recall.

Developmental differences in recall were investigated as a function of mode of presentation (blocked vs. random), recall condition (cued vs. noncued), and time of recall (immediate vs. delayed). Ninety-six second graders and 96 fourth graders were the subjects, and the stimuli were 20 pictured items from five categories. Data on three dependent variables (item recall, category recall, and clustering score) were analyzed. Immediate recall was better than delayed recall, the fourth graders' overall performance was superior to that of the second graders, and the blocked presentation of items and the presence of retrieval cues at recall enhanced recall and organization in recall. Furthermore, an analysis of a three-way interaction on two dependent measures indicated that, in the noncued condition, immediate recall was better than delayed recall for children in both grades. However, in the cued condition, the fourth graders performed better during delayed recall than during immediate recall, whereas the second graders did better during immediate recall than during delayed recall.


A social-psychological perspective of dietary quality in later adulthood.

Nutrition has been implicated in the quality of life of older adults, beyond proving essential nutrients and calories. Recent concern about malnutrition has prompted a broader social-psychological approach to nutrition and aging research. The present investigation examined the relationship of self-actualization and social support to dietary intake. Data from 100 community-dwelling adults, ages 60-83 years, revealed significant and positive associations between the predictor variables and vitamin A, B vitamin complex, iron, and dietary fiber. Specifically, the personality trait of being internally motivated and the presence of support from family, friends and neighbors were found to positively influence dietary quality.


Vitamin B12 and folate status of a selected group of free-living older persons.

Vitamin B12 and folate status was determined in 50 male and 47 female free-living subjects (65-77 years) in winter and summer. The mean intake calculated from 3-day food records met the Canadian recommended intake (RNI) for both gender and season, however, probability analysis of dietary data revealed a number of subjects at risk of deficiency. Although the mean plasma levels were within the acceptable range for both vitamins, some 9 to 14% of individual subjects had folate plasma levels below normal. Fewer subjects had subnormal plasma vitamin B12 levels. Although mean values for dietary intake and plasma concentration of folate and vitamin B12 may indicate nutritional adequacy, a proportion of an older population may be at nutritional risk.


[Prospective study of echography versus phlebography in the detection of sural venous thrombosis].

Among all noninvasive techniques, high-resolution ultrasonography used alone has rarely been used for the diagnosis of thrombosis in the calf. Nineteen patients with suspected AVT were examined with ultrasonography and phlebography during 4 months. For each patient, a sonogram and a phlebogram were taken within less than 24 hours and interpreted independently. The sonographic exploration with a high-resolution (5 MHz) transducer covers all deep trunks and muscular veins (soleus or gastrocnemius muscles). The positivity criterion is the persistence of a hypoechogenic endoluminal image under moderate compression. According to the phlebographic data, 65% of the patients present with thrombosis. Ultrasonography has a sensitivity of 95% and a specificity of 99% for the study of the deep trunks. Ultrasonography screens more thromboses than phlebography (23 cases versus 17). On a whole, ultrasonography seems to be more sensitive than phlebography for the diagnosis of recent sural thrombosis.


[Arnold-Chiari malformation. Contribution of cerebral echography in the pretherapeutic evaluation].

From August 1988 to August 1989, we performed pre-operative sonographic examinations on eleven children who had Arnold-Chiari malformation (ACM). All children presented with myelomeningocele. ACM was the leading cause of hydrocephalus in infants and newborns. For eight children, hydrocephaly was particular by the discrepancy between the dilated atrium and the relatively small temporal horns. Two children have associated extra-neurologic malformations. Five patients were operated upon, with poor results in four. In our experience, ultrasonography was found very useful in patients presenting with myelomeningocele.


[Cerebral miliary tuberculosis. Apropos of 5 cases and review of the literature].

The authors report 5 cases of cerebral miliary tuberculosis studied by computerized tomography and review 5 cases of the literature. Computerized tomography can see very small tuberculomas, of several millimeters. Chest miliary tuberculosis is found in all their cases, and 3 of the 5 cases of the other authors. Because of the discretion of neurological signs and the association with chest miliary, we suggest to make a computed tomography of brain of all patients who have chest miliary tuberculosis despite the absence of neurological signs and we think that we will find out other cases of brain miliary tuberculosis.


[MRI of the spinal epidural fat in pathology].

The authors report about their experience with the merits of the normal systematization of epidural fat with MRI. On sagittal sections, this fat has a variable appearance, but its location along the spinal canal is constant. On axial sections, its morphology is suggestive of the level of section: cervical, upper or lower thoracic, lumbar. Some changes in this fat are precious data to explain local hypertrophy (scoliosis) or to locate an intra- or extradural process.


[Thoracic lymphoma and AIDS].

During the past 4 years, 122 patients with AIDS and 20 with thoracic lymphoma associated to AIDS were observed. There were 18 cases of non-Hodgkin's lymphoma, mostly at a high grade and a high b-cell stage (Burkitt's or Burkitt-like lymphoma) (16 cases). This prevalence reflects the general increase in the number of neoplasms secondary to immunosuppression, which goes along with the improvement of prevention and the control of opportunistic infections. Out of these 20 lymphomas in AIDS, 5 (25%) produced thoracic lesions; in 4 cases, the initial site of the disease was in a thoracic site. The frequency of such expressions is greater that reported in the literature. The radiological appearances are atypical relative to the classical signs of lymphoma in the general population, with predominantly nodular forms (60%) or peripheral, fast-growing masses that are likely to invade the thoracic wall. Isolate lymph node invasion is possible, as well as pleural effusion. Though not pathognomonic, this appearance is highly suggestive of lymphoma in AIDS (LDS) in HIV-positive patients. In all patients with pulmonary lymphoma, CT showed bilateral lesions in a greater number than plain radiography had shown, with morphological and CT appearances that allowed a correct approach of the diagnosis and an appropriate choice of the site of biopsy.


[What may be expected from endorectal echography and magnetic resonance imaging in the evaluation of local extension of cancer of the prostate?].

Thirty patients presenting with a clinical stage A or B cancer underwent TRUS and MRI with a body coil prior to radical prostatectomy. Imaging and pathology were correlated to assess the limits of TRUS and MRI in pre-operative staging of prostatic carcinoma. Results showed that TRUS and MRI had a sensitivity of 42 and 66% and a specificity of 89 and 94% respectively, for the diagnosis of macroscopic capsular effraction. Seminal vesicle invasion was diagnosed by TRUS with a sensitivity of 16% and a specificity of 81%. With MRI, the sensitivity and the specificity were 85 and 94% if only gross infiltration was considered. Sensitivity dropped to 45% if microscopic invasion was included. We conclude that: 1) postero-lateral venous plexus are more easily delineated by MRI, permitting a more accurate diagnosis of capsular penetration. 2) Seminal vesicle invasion cannot be diagnosed by TRUS as the echo-structure of the cancer and the caudal junction of the seminal vesicles and vas deferent are similar. 3) A normal caudal junction on TRUS or a normal bilateral hypersignal of the seminal vesicles on MRI are associated with seminal vesicle invasion in less than 5% of cases. 4) A normal caudal junction on TRUS eliminates false positive cases of MRI related to non tumoral hyposignals of the seminal vesicles.


[Renal lymphoma in a patient after kidney transplantation and cyclosporine therapy].

The effectiveness of renal transplantation has been considerably improved by the use of cyclosporine as an antirejection agent. However, because of those very same immunosuppressive properties, this substance may lead to several infectious or tumoral complications that raise complex therapeutic problems. This article reports about one case of immunoblastic lymphoma discovered in a patient who received renal transplantation and who had been treated with cyclosporine for two years.


[The role of the radiologist in the medicolegal procedure after an aviation accident].

The role of radiologic imaging studies in the forensic medical procedure following an airborne disaster is now well established. This report summarizes the experience and the results acquired with a recent air crash, and insists on three suggestions: the necessity of a prepared identification team consisting of specialist in forensic medicine, in forensic odontology and specialist in forensic radiology, and the usefulness of a suitable structure for the study and the storage of the dead bodies, the need for a compilation of radiological informations, notably dental X-Ray examinations for the flying personnel.


Review of the benefits of treating hypertension.

The main points covered in this review are as follows: 1. Hypertension is a major determinant of cardiovascular disease (CVD). As such it is a major cause of mortality, potential years of life lost, morbidity and long-term disability. 2. The incidence of CVD is directly related to BP. It is likely that this extends over the full range of BP although some writers believe that a J-curve of risk exists for CHD. 3. The relationship between long-term disability from CVD and BP requires further study. 4. Because of regression dilution bias, the gradient in risk of stroke and CHD with BP has been underestimated in the past. Recent research suggests that the risk of stroke increases at least tenfold and CHD sixfold over a range of usual DBP of 30 mmHg (equivalent to approximately 50 mmHg baseline DBP). 5. The population attributable risk (PAR) of CVD related to general elevation of BP in the population from a mean daily excess of sodium intake of 100 mmol/day is at least 30%. In typical industrialised countries the PAR for stroke and CHD from clinical hypertension is 36% and 22%, respectively. These estimates of PAR provide a guide to the maximum benefit that could result from either restriction of sodium intake in the whole population or ideal management of all persons with hypertension. In practice such targets are unlikely to be realised. 6. Recent analyses of clinical trials of treatment of hypertension suggest that the risk of stroke is reduced at all levels of initial BP to the extent predicted from observational studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Considerations regarding the cost and effectiveness of public and patient education programmes.

For nearly two decades, the National High Blood Pressure Education Programme has administered a programme of public, patient, and professional education in an effort to reduce uncontrolled hypertension, an important public health problem in the USA. A broad network has been established and many partners have joined forces to form the NHBPEP. During the tenure of the programme, awareness, treatment, and control rates for high BP have increased dramatically, and this has been associated with a nearly 57% reduction in age adjusted stroke mortality. In 1988, stroke cost this nation about $23.3 billion a year in direct and indirect costs. Much of this is attributed to uncontrolled hypertension. It seems likely that controlling hypertension saved nearly $1.5 billion in direct and indirect costs for stroke in one year alone. This is in addition to the other health care costs attributed to coronary heart disease that have been reduced as a result of treating high BP. A portion of this may be related to the NHBPEP.


[Acute toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in mice, rats and dogs.

Single oral, subcutaneous or intravenous administration to mice and rats and oral administration to dogs were performed to investigate the acute toxicity of FUT-187. 1) LD50 values in mice were 4,395 mg/kg for males and 3,626 mg/kg for females orally, 6,284 mg/kg for males and 5,492 mg/kg for females subcutaneously, and 39.4 mg/kg for males and 41.4 mg/kg for females intravenously. In rats, these values were 4,653 mg/kg for males and 3,761 mg/kg for females orally, 6,799 mg/kg for males and 3,343 mg/kg for the females subcutaneously and 21.8 mg/kg for males and 15.8 mg/kg for females intravenously. 2) Death occurred 2 hours after administration in a male dog of the 3,000 mg/kg group just after convulsion and nasal discharge were observed. 3) General symptoms in mice and rats included a creeping gait, convulsion, singultus, cyanosis, decreased locomotor activity, piloerection and salivation which were commonly observed by all routes. All dogs showed vomiting and decreased locomotor activity; the prone or lateral position, crouching, ataxic gait and salivation were also observed in many cases. 4) On autopsy, changes attributable to local irritation by FUT-187 were seen in all species except mice and rats dosed intravenously. For the gastro intestinal-tract (GIT), inflammation of the stomach, adhesions between the stomach and the liver and sclerosis, petechiae or ulcer were observed in mice and rats dosed orally. In the subcutaneous route, retention of the test compound and necrosis at the injection site were observed. Reddening and loss of mucosal smoothness were observed in the GIT of a dog which died; desquamation, congestion, hemorrhage and retention of tested compound in the digestive mucosa were observed on histopathology.


The evaluation of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) by oral administration in cynomolgus monkeys in a 13 week subacute toxicity study.

To assess the subacute toxicity of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) a 13 week subacute toxicity study by gavage was done in Cynomolgus monkeys at dosage levels of 0, 15, 45 and 135 mg/kg/day. Deaths were seen in the 135 mg/kg/day group; with associated debility. The animals that died had high plasma levels of FUT-187. Little weight gain was seen in the 135 mg/kg/day group. There were no clear treatment related effects on ophthalmoscopy or electrocardiography or on hematological, biochemical or urinalysis. There were no effects noted at necropsy or on histopathology and the causes of death for each of the 3 animals that died were suppurative glomerulonephritis, bone marrow depression and possible gavage injury respectively. The no-effect level for toxicology was considered to be 45 mg/kg/day.