Biosynthesis of the basal lamina as a result of interaction between thyroid and mesenchymal cells in culture. Porcine thyroid cells were cultured alone or in mixed cultures with mesenchymal cells. The formation of a basal lamina in vitro was investigated ultrastructurally. Follicular reassociation of thyroid cells occurred in both types of culture; however, it was followed by formation of the basal lamina only when mesenchymal cells were present. The present findings suggest an epithelial origin of the basal lamina resulting from an interaction with mesenchymal cells.


Cine-densitometric measurement of coronary arterial stenoses. Computer-aided operator-interactive densitometry has been developed and applied to determine the percent stenosis for obstructive lesions in the coronary arterial tree. Phantom experiments performed to assess system linearity, accuracy of densitometric measurements, nonuniformity in image amplified response, and the interference of structure noise in measuring precision have been described. Three observers assessed the reproducibility of the method by repeating analyses on 20 stenoses in man recorded on 35-mm cine angiograms. Calculation of the intra- and interobserver errors found that their values significantly decrease with increasing percent stenosis. The reproducibility of the technique was also tested on stenoses that were exposed at multiple angles. The results agreed with those found for the intra- and interoperator errors. Limitations of the densitometric approach and desirability of further automation of the measurements are also discussed.


Evaluation of segmental left ventricular wall motion by equilibrium gated radionuclide ventriculography. The ability of equilibrium gated radionuclide ventriculography to detect segmental left ventricular (LV) wall motion abnormalities was determined in 26 patients undergoing cardiac catheterization. Multiple gated studies obtained in 30 degrees right anterior oblique and 45 degrees left anterior oblique projections, played back in a movie format, were compared to the corresponding LV ventriculograms. The LV wall in the two projections was divided into eight segments. Each segment was graded as normal, hypokinetic, akinetic, dyskinetic, or indeterminate. Thirteen percent of the segments in the gated images were indeterminate; 24 out of 27 of these were proximal or distal inferior wall segments. There was exact agreement in 86% of the remaining segments. The sensitivity of the radionuclide technique for detecting normal versus any abnormal wall motion was 71%, with a specificity of 99%. Equilibrium gated ventriculography is an excellent noninvasive technique for evaluating segmental LV wall motion. It is least reliable in assessing the proximal inferior wall and interventricular septum.


Pulmonary atresia and suprasternal echocardiography. A 54-year-old housewife with pulmonary atresia and ventricular septal defect developed increasing cyanosis, dyspnea, weakness, and myocardial ischemia. Initial cardiac catheterizations with angiography, including subtraction techniques, did not definitely indicate main pulmonary artery or right or left pulmonary arteries that would make her amenable to currently available surgical correction. Single-crystal suprasternal notch echocardiography indicated the presence of a small but definite right pulmonary artery. She subsequently underwent first-stage surgical correction after angiography and selective catheterization of aortopulmonary shunt vessels, which also revealed the presence of small proximal pulmonary arteries.


Foreign body retrieval from the heart by two catheter technique. Foreign bodies that lodge accidentally in the heart or great vessels can be retrieved successfully without thoracotomy. This report describes retrieval of a 15-centimeter-long central venous catheter lodged in the right side of the heart. Two catheters were introduced to effect retrieval, one from the arm and the other from the leg. To our knowledge this approach has not been described previously.


Survival with total occlusion of the left main coronary artery. Significance of the collateral circulation. Four patients with total occlusion of the left main coronary artery are described. Angina pectoris was severe (NYHA class 3--4) and had lasted 20 months to seven years. Three patients had experienced a myocardial infarction. All displayed large collaterals arising from a nearly normal right coronary artery and feeding both the left anterior descending and the left circumflex arteries. The left ventricular ejection fractions ranged from 20% to 65%, and all patients had varying degrees of left ventricular asynergy. Coronary artery bypass surgery resulted in a marked improvement in three patients; one patient who underwent an aneurysmectomy died two months after the operation. The data show that total occlusion of the left main coronary artery is compatible with survival if adequate collateral supply develops from the right coronary artery. In this rare angiographic subset collateral circulation is clearly functionally significant.


Chronic oral vasodilator therapy to control heart failure in postinfarction ventricular septal defect. This report describes a 70-year-old woman with biventricular failure following an anteroseptal infarction complicated by interventricular septal rupture. Treatment with nitroprusside followed by oral hydralazine eliminated the failure and reduced the shunt from 2.75 to 1 to 1.7 to 1. She is asymptomatic post-discharge. Chronic medical therapy including oral vasodilators may be an acceptable alternative to surgery in a small minority of patients with this complication of myocardial infarction.


Congestive cardiomyopathy with segmental wall motion abnormalities and a non-uniform pattern of fibrosis. A case of congestive cardiomyopathy in a 46-year-old smoker with single-vessel right coronary artery disease is presented. Segmental contraction abnormalities were present in the anterior wall. Pathologic analysis showed diffuse fibrosis consistent with a cardiomyopathy in areas of abnormal contraction and normal muscle in areas of normal contractility. Segmental wall motion abnormalities have been reported but none with microscopic studies of areas of both abnormal and normal contractility.


Echocardiographic findings in cardiogenic shock due to right ventricular myocardial infarction. The echocardiographic findings in a patient with cardiogenic shock secondary to acute right ventricular myocardial infarction based on typical clinical, electrocardiographic, and hemodynamic features are described. The echocardiogram demonstrated a large RV/LV minor axis ratio caused by a volume overload of the right ventricle and an underfilled left ventricle. The interventricular septum showed abnormal movement, presumably due to right ventricular overload or severe disease of the left anterior descending coronary artery. Diminished septal systolic thickening, as seen in our patient, may be explained by extension of the infarct from the right ventricle to the adjacent part of the septum. Predominant right ventricular involvement can be a cause for a correctable hypotension in patients with acute myocardial infarction and should therefore be recognized early. The echocardiographic picture demonstrated in our patient, when considered in conjunction with the clinical status, can be useful for early diagnosis.


Ejection fraction derived by M-mode echocardiography: a table and comments. Left ventricular ejection fraction is frequently quantitated by M-mode echocardiography despite limitations, including 1) the ability to measure an accurate left ventricular short axis, 2) the mathematic and geometric assumptions used to derive the volumes from which the ejection fraction is calculated, and 3) the lack of applicability to asynergic ventricles. Nevertheless, using a cubed function or correction formula, ejection fraction can be calculated for symmetrically contracting, normally sized, and enlarged left ventricles. A table and accompanying comments are presented.


Characterization of Op3, a lysis-defective mutant of bacteriophage f2. We have isolated a conditional lethal mutant of bacteriophage 12 which makes plaques only on E. coli strains carrying a UGA suppressor. It grows normally in nonsuppressing hosts but does not lyse such strains. The mutation complements with amber mutations in each of the three known phage cistrons. These observations lead us to postulate the existence of a fourth gene in the RNA phage.


Binding of mammalian ribosomes to MS2 phage RNA reveals an overlapping gene encoding a lysis function. The main binding site for mammalian ribosomes on the single-stranded RNA of bacteriophage MS2 is located nine tenths of the way through the coat protein gene. Translation initiated at an AUG triplet in the +1 frame yields a 75 amino acid polypeptide which terminates within the synthetase gene at a UAA codon, also in the +1 frame. Partial amino acid sequence analysis of the product synthesized in relatively large amounts by mammalian ribosomes confirms this assignment of the overlapping cistron. The same protein is made in an E. coli cell-free system, but only in very small amounts. Analysis of the translation products directed by RNA from op3, a UGA nonsense mutant of phage f2, identifies the overlapping cistron as a lysis gene. In this paper we show that the op3 mutation is a C yield U transition occurring in the second codon of the synthetase cistron, which explains the lowered production of phage replicase (as well as lack of lysis) upon op3 infection of nonpermissive cells. We discuss the properties of the overlapping gene in relation to its lysis function, recognition of the lysis initiator region by E. coli versus eucaryotic ribosomes and op3 as a ribosome binding site mutant for the f2 synthetase cistron.


Identification of a cell surface glycoprotein involved in cell aggregation in D. discoideum. Analysis of the composition of cell surface-associated glycoproteins of D. discoideum by lactoper-oxidase-catalyzed radioiodination, followed by isolation by Con A-Sepharose chromatography, revealed that the developmentally regulated cell surface expression of a certain glycoprotein (gp150) parallels the onset of mutual cellular cohesiveness (Geltosky, Siu and Lerner, 1976). We have purified gp150 and raised specific antibodies to it. Through utilization of the specific antibody and a fluorescence-activated cell sorter, the expression of gp150 on the cell surface has been studied. Starting from a low level in noncohesive (vegetative) cells, there is a rapid accumulation of gp150 on the surfaces of aggregating cells. A peak level of expression is achieved by 10 hr and maintained at least until the steps of terminal differentiation. Most significantly, monovalent Fa'b derived from anti-gp150, when added to aggregation-competent cells, blocks the cells' ability to reaggregate. Fab's derived from antisera with different specificities were ineffective inhibitors of cell aggregation. These results suggest that gp150 serves an intimate role in cell adhesion.


Gap junctional communication in the preimplantation mouse embryo. In this study, we examined cell-to-cell communication via gap junctional channels between the cells of the early mouse embryo from the 2-cell stage to the preimplantation blastocyst stage. The extent of communication was examined by monitoring for the presence of ionic coupling, the transfer of injected fluorescein (molecular weight 330) and the transfer of injected horseradish peroxidase (molecular weight 40,000). In the 2-cell, 4-cell and precompaction 8-cell embryos, cytoplasmic bridges between sister blastomeres were responsible for ionic coupling and the transfer of injected fluorescein as well as the transfer of injected horseradish peroxidase. In contrast, no communication was observed between blastomeres from different sister pairs. Junction-mediated intercellular communication was unequivocably detected for the first time in the embryo at the early compaction stage (late 8-cell embryo). At that stage, ionic coupling was present and fluorescein injected into one cell spread to all eight cells of the embryo. Injected horseradish peroxidase was passed to only one other cell, however, again indicating the presence of cytoplasmic bridges between sister blastomeres. Junctional communication with respect to both ionic coupling and dye transfer was retained between all the cells throughout compaction. At the blastocyst stage, trophoblast cells of the blastocyst were linked by junctional channels to other trophoblast cells as well as to cells of the inner cell mass, as indicated by the spread of injected fluorescein. In addition, the extent of communication between the cells of the inner cell mass was examined in inner cell masses isolated by immunosurgery; both ionic coupling and the complete spread of injected fluorescein were observed.


Gap junctional communication in the post-implantation mouse embryo. We studied the extent of cell-to-cell communication via junctional channels in in vitro-implanted mouse blastocysts by monitoring ionic coupling and the spread of two injected low molecular weight dyes, fluorescein and Lucifer yellow. In the early attached embryos, both trophoblasts and cells of the inner cell mass (ICM) were ionically coupled to one another. Dye injections in either trophoblasts or ICM cells resulted in spread to the entire embryo. As older and more developed embryos were examined, the spread of injected dye was progressively more limited. In the most developed embryos examined, dye injected into a cell in the ICM region resulted in spread throughout the ICM but not into the surrounding trophoblast cells, while dye injected into a trophoblast cell did not spread to any other cell in the embryo. Simultaneous monitoring of ionic coupling and dye injections in embryos of intermediate stages in this transition revealed that the trophoblast and ICM cells were ionically coupled, even across the apparent boundary where no dye was observed to pass. In the latest stage embryos examined in which no injected dye was observed to move out of the ICM, ionic coupling was still observed between the cells of the ICM and the trophoblasts. Furthermore, in the more developed embryos, dye injected into the ICM region frequently was not transferred to all the cells of the ICM, thus suggesting a further compartmentalization of due spread within the ICM. Our observations that ionic coupling is more extensive than the detectable spread of injected dyes may perhaps reflect a reduced number of junctional channels. With fewer channels less dye would pass between cells, so that, together with continuous quenching, the transfer of injected dye would not be detectable. This partial segregation of cell-to-cell communication as indicated by the limited dye spread may parallel specific differentiation processes, in particular that of giant trophoblast, embryonic ectoderm and extraembryonic endoderm differentiation.


Mutants of Chinese hamster ovary (CHO) cells with altered colcemid-binding affinity. Clones of CHO cells stably resistant to colcemid have been isolated in the presence of the nonionic detergent Tween 80 after mutagen treatment. Successive single-step selections for increasing resistance were performed resulting in lines after three selection steps about 10 fold more resistant to colcemid than the parental cells. Three observations indicate that these colcemid-resistant (CMR) mutants are different from the colchicine-resistant permeability mutants isolated previously. First, their relative resistance to colcemid was not diminished in the presence of detergent which promoted increased drug permeability. Second, the CMR clones displayed limited cross-resistances only to tubulin-binding compounds. Third, the binding affinity of labeled colcemid by cytoplasmic extracts from CMR clones was reduced, and the reduction was greater in the more resistant clones. No reduction in binding of labeled colcemid was observed in the membrane-altered colchicine-resistant mutants. All these observations are consistent with the CMR clones being tubulin-altered mutants. In further support of this conclusion, we observed that tubulin purified from a CMR mutant still possessed reduced colcemid-binding affinity compared with that from parental cells.


Identification with cellular microtubules of one of the co-assemlbing microtubule-associated proteins. In this paper we describe a procedure for detecting proteins associated with cytoplasmic microtubules in vivo. Detergent-extracted cytoskeletons of NIL8 hamster cells are prepared under conditions which preserve the microtubules. The cytoskeletons are then extracted in the presence of calcium, which depolymerizes the microtubules and quantitatively extracted cytoskeletons are prepared from cells that have been incubated with colchicine. The cytoskeletons from these cells contain no microtubules or tubulin. Electrophoretic analysis of the calcium extracts of the colchicine-treated and untreated cells reveals several radioactively labeled polypeptides. There is, however, no apparent quantitative or qualitative difference between the two extracts other than the tubulin polypeptides. Each of the extracts is mixed with an excess of unlabeled calf brain microtubule protein and carried through cycles of temperature-dependent microtubule assembly. Distinct species from each extract co-assemble at a constant ratio, but only one polypeptide is uniquely derived from cells containing intact microtubules. The molecular weight of this polypeptide is similar to that proposed for the tau species detected in brain microtubule preparations.


Evidence for the formation of nucleosome-like histone complexes on single-stranded DNA. Using histones reconstituted with RNA and DNA celluloses, we have shown elsewhere that histones elute identically with salt from single- and double-stranded DNA, but differently from RNA (Palter and Alberts, 1979). In this paper we characterize further the suspected specific binding interactions between histones and single-stranded DNA. Nuclease digestion of complexes of histone reconstituted with single-stranded DNA generates only a small yield of discrete (approximately 9S) particles. We can, however, efficiently obtain such 9S "nucleosome-like" complexes when nuclease treatment is avoided and histones are reconstituted directly with short single-stranded DNA pieces. Strikingly, these 9S subunits contain an equimolar composition of the four nucleosomal histones. When these subunits are visualized in the electron microscope, they appear as globular particles which are morphologically indistinguishable from normal mononucleosomes. Based on their sedimentation properties, histone-to-DNA ratio, histone composition and particle diameter, we conclude that they represent an octamer of the four histones (containing two molecules of each histone) associated with single-stranded DNA. These data, viewed in the context of other information concerning chromatin, suggest that nucleosome cores may become transiently bound to single strands of DNA as DNA and RNA polymerases pass.


Selective and accurate initiation of transcription at the Ad2 major late promotor in a soluble system dependent on purified RNA polymerase II and DNA. Transcription of Ad2 DNA templates in the presence of crude cellular extracts supplemented with exogenous (purified) RNA polymerase II is selectively and accurately initiated at the major late viral promoter at map position 16.45. Specific initiation has been demonstrated by a combination of hybridization, nuclease S1 mapping, size and partial sequence (fingerprint) analyses of the transcripts generated with various templates. With intact Ad2 DNA, transcription is terminated  ell before the end of the 28 kb transcription unit is reached. With truncated templates (which contain intact promoter regions and several hundred base pair segments of the transcribed region) the expected run-off products are observed, along with a low level of prematurely terminated transcripts. The 560 nucleotide run-off product of the Sma l-f template (coordinates 11.6-18.2) was shown to contain all the large RNAase T1 oligonuc eotides that are characteristic of the corresponding in vivo transcript from this region; in addition, the 5 terminal undecanucleotide appears to be both capped and methylated. We have investigated various parameters (salt, metal ion and template concentrations) that affect the level of specific transcription in the crude system and have found that, under optimal conditions, specific transcription of Ad2 DNA continues for several hours. In addition, specific transcription initiation at the late promoter is observed with extracts derived from either virus-infected or uninfected KB cells and with class II RNA polymerases isolated from either human calf, murine or amphibian cells. RNA polymerase II from wheat germ does not function in this system.


The nucleotide sequence of the initiation and termination sites for ribosomal RNA transcription in X. laevis. In this study, we have located the sites of transcription initiation and termination on a cloned fragment of ribosomal DNA from X. laevis, and have sequenced the surrounding nucleotides. As reported previously (Reeder, Sollner-Webb and Wahn, 1977), about 25% of the 40S rRNA precursor molecules isolated from oocytes have polyphosphate 5' termini and are therefore presumed to represent primary transcripts. These ends hybridize specifically to the 221 bp DNA fragment and removed the overhanging DNA region with S1 nuclease. In the other, we hybridized 40S RNA to a 221 bp fragment of ribosomal DNA. The nucleotides encoding the 5' end of the 40S RNA were located more precisely by two methods. In one, we hybridized 40S RNA to the 221 bp DNA fragment and removed the overhanging DNA region with S1 nuclease. In the other, we hybridized 40S RNA to a smaller DNA fragment and extended the recessed 3' terminus of the DNA using reverse transcriptase. The resultant DNA fragments were sized on sequencing gels. Both determinations map the 5' end of 40S RNA at the same site in the rDNA, about 2250 bp upstream from the Eco RI site in the 18S rRNA coding sequence. At this site we find a DNA sequence beginning AGGGGAAGAC.... which agrees with partial sequence data from the 5' end of polyphosphorylated and bulk 40S rRNA. Features of this region of the ribosomal DNA will be discussed in this paper. A 227 nucleotide region surrounding the initiation site was also sequenced from an independently derived clone and found to differ in only one nucleotide. In addition, a sequence is found about 1100 nucleotides upstream from the 5' end of the gene that has 90% homology to the sequence from nucleotides minus 125 to +4 in the initiation region. At the termination region, X. laevis ribosomal DNA has a single recognition site for the restriction enzyme Hind III in each repeating unit. Using the S1 nuclease technique, the 3' termini of both the 40S precursor and mature 28S rRNA are seen to map within this recognition sequence. The sequence surrounding the Hind III site has striking homology to termination sites recognized by other RNA polymerase classes. Sequences with similar features are also found upstream from the initiation site.


Expression of the mitochondrial genome in Xenopus laevis: a map of transcripts. The twelve most abundant transcripts in X. laevis mitochondria were characterized, and their coding regions were mapped on the mitochondrial DNA (mtDNA) by R loop mapping in the electron microscope and by RNA gel transfer hybridization. The transcripts map in nonoverlapping positions with one exception, and they account for about 80% of the coding capacity of mtDNA. Ten of the twelve RNA molecules contain poly(A): the two poly(A)-lacking transcripts are the rRNAs. Analysis withe single-strand-specific nucleases clearly demonstrated the absence of intervening sequences from the coding regions for seven RNAs. For two RNAs, uninterrupted coding sequences are strongly suggested and one RNA could not be analyzed. Eight transcripts of low abundance and high molecular weight were characterized, and their coding regions were mapped approximately. They overlap the coding regions of the abundant mitochondrial RNAs and could be precursors of these RNAs. Most of the RNA molecules characterized were shown to be transcribed from the heavy strand of mtDNA. No abundant discrete light-strand transcript was found.


The intervening sequence in the 26S rRNA coding region of T. thermophila is transcribed within the largest stable precursor for rRNA. We studied the transcription of the intervening sequence in the 26S rRNA coding region of the extrachromosomal rDNA molecules in the macronucleus of T. thermophila by hybridization of purified nuclear rRNA precursors or cytoplasmic 26S rRNA to purified native rDNA or specific rDNA restriction fragments. Examination of R loop hybrids in the electron microscope and analyses of S1-protected rDNA fragments in alkaline agarose gels showed that mature 26S rRNA, nuclear pre-26S rRNA and a fraction of the pre-rRNA molecules containing both the sequences for 17S and 26S rRNA all lack the region corresponding to the intervening sequence. The rest of the pre-rRNA molecules, however, hybridize in a colinear fashion to the whole coding region, and thus must contain the intervening sequence. We can conclude from these results that the intervening sequence is transcribed within the primary transcription product of the rDNA, and that the post-transcriptional removal of the intervening RNA sequence is a very early processing event in the organism.


Isolation and characterization of a cloned rat insulin gene. The two nonallelic genes, insulin I and II of the rat, are separated by at least 7 kb of DNA. There is no obvious similarity in the sequence organization surrounding each gene, although the coding regions of the genes themselves share extensive homology. In three strains of rat, the insulin II gene lies predominantly on a 4.0 kb Eco RI restriction fragment, whereas the insulin I gene is located on a 9.4 kb Eco RI fragment in the Hooded strain, on a 7.2 kb Eco RI fragment in the Osborne-Mendel strain, and on both a 9.4 and a 7.2 kb Eco RI fragment in Sprague-Dawley rats. The 9.4 kb Eco RI fragment from Hooded rat DNA was isolated using the lambda cloning system, and the nucleotide sequence of this isolated rat insulin I gene and adjacent regions was determined. A translation in one frame of the sequence of the cloned gene confirms the protein sequence determined for rat pre-proinsulin I. The coding region of this gene lacks intervening sequences, although a presumptive intervening sequence of 119 bp is located in the 5 untranslated region preceding the prehormone sequence. The junctions around the 119 bp segment are identical to those which flank intervening sequences of other eucaryotic genes, AGGT. The site of polyadenylation was determined by direct sequence comparison with rat insulin cDNA clones, and a potential 5 "capping" site is proposed. A DNA sequence preceding this 5 "capping" site in the rat insulin I gene, TATAAAGC, is homologous to corresponding regions in other eucaryotic genes that have been proposed as putative promoter sites for the initiation of transcription.


The structure and evolution of the two nonallelic rat preproinsulin genes. In the rat, there are two nonallelic genes for preproinsulin. The insulin end products are very similar and are equally expressed. We have isolated clones carrying these genes and their flanking sequences, and characterized them by DNA sequencing and electron microscopic analysis. We have established the primary structure of the preproinsulin mRNAs and the signal peptides of these two proteins. One of the genes contains two introns: a 499 bp intron interrupting the region encoding the connecting peptide and a 119 bp intron interrupting the segment encoding the 5 noncoding region of the mRNA. The introns are transcribed and present in a preproinsulin mRNA precursor. The other gene possesses the smaller, but not the larger, of the two introns. Calculations based on the divergence of the two preproinsulin nucleotide and amino acid sequences indicate that these genes are the products of a recent duplication. Thus one of the genes gained or lost an intron since that time.


Effects of Staphylococcus aureus lysozyme on human fibroblasts. The purified lysozyme excreted by Staphylococcus aureus strains promotes elongation and spreading on plastic surfaces and stimulates DNA synthesis of human fibroblasts (WI38). This enzyme also raises twofold the saturation density level of cultures of these cells. It is suggested that the primitive and main effect of lysozyme on fibroblasts is the triggering of morphogenesis.


Cellular senescence and the analysis of generation time distributions. Generation time analysis by time lapse cinematography is an important method for investigating cellular senescence in culture, but its interpretation is complicated by several types of bias and artifact, including small sample size, cut-off bias, changes in global growth rate, and phase of the population growth cycle. When these factors are considered, interpretation of the data base used by previous investigators changes considerably, and does not reveal any differences in growth behavior between middle and late passage WI-38 cells. Nor does it support the transition probability theory either of cell cycle transit or of culture senescence.


Cellular uptake of ribonucleic acids entrapped into liposomes. Ribonucleic acids were entrapped into phospholipid vesicles (liposomes). After incubation of the liposomes containing RNA (L- RNA), the RNA was introduced into the cells. The kinetics of L- RNA uptake by the cells in culture were studied. The uptake of L- RNA is linear over a broad vesicle concentration range depending on temperature, and at 37 degrees C uptake levels reach a plateau after 3 hours. Inhibitors of cellular energy metabolism have little effect on the uptake, and thus fusion, as the main mechanism of uptake, is proposed.


[Morphology of the heart conduction system]. Using his own experience and literary research, the author gives an outline of the morphology of the conduction systems of normal children's and adult hearts, including its blood supply.


[Lipofuscinosis of the liver].

[Lipofuscinosis of the liver]. Liver tissue biopsy performed in a man of 44 and another man of 52, who had for long periods of time been using phenacetin-containing analgesics, revealed accumulations of lipofuscin in hepatocytes, in sinoendothelia and in Kupffer's cells. Apart from more frequent destruction of hepatocytes, there were no microscopic or ultrastructural changes suggesting any major liver tissue damage.


[Papovavirus papillomatosis in beagles]. Canine papillomatosis was diagnosed in 5 out of 12 dogs of the beagle race, aged three to four months, two weeks after arrival from a breeding station. The histological as well as electronmicroscopical findings were typical of the disease.


Absolute stereochemistry of the trans-dihydrodiols formed from benzo[a]anthracene by liver microsomes. Through application of the exciton chirality method, absolute stereochemistry has been assigned to the (+)-and (-)-enantiomers of four of the five metabolically possible trans-dihydrodiols of the polycyclic hydrocarbon benzo[a]anthracene (BA). The (+)- and (-)-enantiomers of each of these dihydrodiols can be separated as their diastereomeric bis-esters with (-)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid by high pressure liquid chromatography (HPLC). BA 3,4-, 5,6-, 8,9- and 10,11-dihydrodiol are formed in 38%, 36%, 78% and 66% enantiometric purity, respectively, by liver microsomes from phenobarbital-treated rats, whereas the liver microsomes from 3-methylcholanthrene(MC)-treated rats form BA 5,6-, 8,9- and 10,11-dihydrodiols with higher optical purity (62%, 96% and 96%, respectively). BA 3,4-dihydrodiol is formed from (+/-)-BA 3,4-oxide by microsomal epoxide hydrase in very high enantiometric purity (78%). The major enantiomer of the BA dihydrodiols formed by liver enzymes has R,R absolute stereochemistry in each case. In parallel with previous studies on the metabolism of benzo[a]pyrene, the more tumorigenic (-)-enantiomer is the predominant isomer of BA 3,4-dihydrodiol formed by liver microsomes from BA.


In vivo binding of N-2-acetylaminofluorene and its N-hydroxy derivative to the DNA of fractionated rat liver chromatin. The in vivo binding of radioactive N-2-acetylaminofluorene (AAF) and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to the DNA of rat liver chromatin was examined. The chromatin was fractionated into putative transcriptionally active and inactive fractions by hydrodynamic shearing and subsequent glycerol gradient centrifugation, DNAase II digestion followed by MgCl2 aggregation of transcriptionally inactive chromatin, or mild digestion with micrococcal nuclease. Carcinogens were administered for various times prior to sacrifice. Irrespective of the duration of exposure, no preferential binding of either carcinogen to DNA was detected in any of the fractions prepared by hydrodynamic shearing of DNAase II digestion. When micrococcal nuclease was utilized, a 2-fold increase in carcinogen bound to the DNA of that chromatin fraction containing the smallest molecular weight fragments was detected. These small molecular weight fragments produced by micrococcal nuclease have been postulated to be derived from in vivo transcriptional units. Additionally, when DNAase II was used to probe chromatin from rat livers which had been exposed to a carcinogenic regimen of AAF, no preferential binding of radioactive N-OH-AAF to the DNA of any chromatin fraction was detected.


Metabolic activation of 3-amino-5H-pyrido[4,3-b]indole, a highly mutagenic principle in tryptophan pyrolysate, by rat liver enzymes. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagenic principle in tryptophan pyrolysates, binds to DNA after metabolic activation by rat liver enzymes. The enzymes for activation of Trp-P-2 were found in both microsomes and the cytosol. The reaction required NADPH and ATP, metabolic and was inhibited by 7,8-benzoflavone. Considerable binding was observed with only microsomes as enzyme source, but further addition of cytosol enhanced the binding, enhancement depending on the amount of cytosol added. Inducers for microsomal mixed-function oxidases induced activating enzyme(s) for Trp-P-2, 3-methylcholanthrene being most effective, followed by polychlorinated biphenyls and then phenobarbital.


The nephrotoxicity of p-aminophenol. II. The effect of metabolic inhibitors and inducers. Inducers and inhibitors of the microsomal mixed function oxidase system have no consistent effect upon the nephrotoxicity of p-aminophenol, or on binding of the compound in vivo to cell protein. p-[ring-3H]Aminophenol was bound in vitro to kidney microsomal protein and to a lesser extent to liver. The binding was enhanced by preincubation of the p-aminophenol in air and inhibited by ascorbate, GSH, N2 and NADPH. These findings indicate that in contrast to paracetamol hepatoxicity which is dependent upon the mixed function oxidase system, that nephrotoxicity of p-aminophenol is dependent upon oxidation to a toxic metabolite by some other pathway. A similar metabolite may be responsible for the nephrotoxic action of phenacetin.


Interaction of 9-hydroxyellipticine with two forms of partially purified rabbit lung cytochrome P-450. Inhibition of lung microsomal benzo[a]pyrene hydroxylase. 9-Hydroxyellipticine (9-OHE), a potent inhibitor of rat liver monooxygenase activities, binds to the various forms of partially purified lung cytochromes P-450 from untreated and 3-methylcholanthrene (3-MC)-treated rabbits. The spectral data (lambda max: 428 nm (ox.), 447 nm (red.), Ks: 10 microM and 5 muM for cytochrome I and cytochrome II from 3-MC-treated rabbits respectively) resemble those obtained with cytochrome P-450 purified from liver of Aroclor 1254-pretreated rats (lambda max: 428 nm (ox.), 445 nm (red.), Ks: 8 microM). 9-OHE has been shown to inhibit the benzo[a]pyrene hydroxylase activity of rat and rabbit lung microsomes. The inhibitory effect was higher towards the 3-MC-induced lung microsomes than with the control microsomes. However, the lung microsomes, as well as the liver microsomes of rabbits were less sensitive to inhibition by 9-OHE than the corresponding microsomes from rats. These results suggest that rabbit and rat cytochromes P-450 have subtle structural differences.


Influence of cellular environment on toxicity of nitroheterocycles. The preferential sensitivity of hypoxic cells to nitroheteroxycles is thought to result from the actions of toxic intermediates of drug reduction produced under hypoxic conditions. However, a lack of oxygen also alters the biochemical state of the cell and may indirectly enhance the sensitivity, of hypoxic cells to these drugs. This hypothesis was tested by 'conditioning' mouse L-929 cells in oxygen-free buffer, then exposing the cells to nitrofurazone under both aerobic and anaerobic conditions. After conditioning, the rate of cell inactivation by nitrofurazone was equal in air or nitrogen-equilibrated buffer. Pretreatment of cells in 1 muM rotenone or 0.5 mM 2,4-dinitrophenol for one hour under aerobic conditions increased the sensitivity of the cells to nitrofurazone under aerobic conditions. Similar rates of cell killing were obtained when mouse L-cells were heated in buffer for 30 min at 43 degrees before incubation with nitrofurazone in either air or nitrogen. Also, incubation of cells with nitrofurazone in the presence of 0.1% glucose, or at a cell density less than 10(5) cells/ml significantly enhanced cell killing, especially under aerobic conditions. Thus, the intracellular state of the cell, manipulated by altering the cellular environment, influenced the cellular sensitivity to nitrofurazone. Similar results were not, however, obtained with the nitroimidazoles, dimetronidazole and misonidazole; pretreatment for 2 h in buffer under anaerobic conditions did not increase the sensitivity of L cells to subsequent drug treatment in air-equilibrated buffer.


Isolation and structure determination of enzymatically formed styrene oxide glutathione conjugates. When styrene oxide was incubated with glutathione in the presence of rat liver cytosolic fraction, two conjugates were formed. Structural investigation by mass spectrometry (MS), proton magnetic resonance (PMR) analysis and chemical fragmentation showed the presence of two positional isomers, namely S-(1-phenyl-2-hydroxyethyl)glutathione and S-(2-phenyl-2-hydroxyethyl)glutathione in a ratio of approx. 60 : 40.


Identification of some products from the reaction of trans-4-aminostilbene metabolites and nucleic acids in vivo. Esters of N-hydroxy-N-acetylaminostilbene react with guanosine, adenosine and cytidine in vitro and yield a number of different reaction products, some of which have been recently identified. We have now demonstrated that Urd-N3,alpha-beta,OH-AABB, Guo-N1,alpha-beta,OH-AABB, AdoN1,alpha-N6,beta-AABB and a Guo-O6 derivative are also formed in vivo, when the precarcinogen trans-4-dimethylaminostilbene is orally administered to female Wistar rats. However, these reaction products constitute only a small fraction of the adducts formed with liver rRNA. N-Acetylaminobibenzyl-alpha,beta-threo-diol is released from liver RNA upon hydrolysis. Comparison of the adduct pattern resulting from the reaction of N-acetoxy-N-acetylaminostilbene with yeast RNA in vitro and that obtained from in vivo rat liver RNA reveals not only quantitative but also qualitative differences. This indicates that reactive metabolites other than hydroxamic acidesters may contribute to the in vivo binding.


The tissue disposition and urinary excretion of cadmium, zinc, copper and iron, following repeated parenteral administration of cadmium to rats. The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The kidney weight relative to body weight showed a dose-related increase in weight of 25--65%. Excretion of cadmium in the urine increased directly with dosage and the increase was most significant when kidney damage had probably occurred. Administration of cadmium also resulted in dose-related increases in the urinary excretion of zinc, copper and iron. The cadmium concentration of blood increased with dosage of cadmium, and the plasma concentrations of zinc and copper were also raised but plasma iron concentration was diminished.


A difference between two strains of rats in their liver non-haem iron content and in their response to the porphyrogenic effect of hexachlorobenzene. Female Agus rats developed hepatic porphyria at a much faster rate than female Porton-Wistar rats when fed a diet containing 0.01% of hexachlorobenzene (HCB). They also showed a greater inhibition of liver uroporphyrinogen decarboxylase [EC 4.1.1.37] activity and a marked stimulation of 5-aminolaevulinate synthetase [EC 2.3.1.37]. The difference between the two strains could not be correlated with differences in the liver concentrations of HCB. However, control Agus rats were found to possess significantly higher levels of total non-haem iron in their livers than the Porton animals. This was particularly apparent after 24 h of starvation and is further evidence for the involvement of iron in the pathogenesis of HCB-induced porphyria. The posterior lobes of the livers from the Agus rats given HCB became porphyric more slowly than the remainder with less severe inhibition of uroporphyrinogen decarboxylase. In contrast to their increased susceptibility to HCB, the Agus rats were less susceptible to another prophyrogenic agent, 3,5-diethoxycarbonyl-1,4-dihydrocollidine.


Role of dimethylnitrosamine-demethylase in the metabolic activation of dimethylinitrosamine. In vivo administration to rats of the mixed-function oxidase modifiers 3-methylcholanthrene (MC), pregnenolone-16 alpha-carbonitrile (PCN) or beta-naphthoflavnoe (beta-f) inhibits the hepatic microsome-catalyzed in vitro binding of dimethylnitrosamine (DMN) to DNA. This parallels their effect on DMN-demethylase I, regarded to be the sole activating step in DMN carcinogenesis and fails to account for the previously observed anomaly that MC and PCN inhibit, while beta-NF enhances, the hepatocarcinogenic activity of DMN. The in vitro binding of DMN is clearly dependent on microsomes and NADPH, and is strongly enhanced by soluble cytoplasmic proteins; the presence of the latter has no effect. however, on the relative response to pretreatment by the modifiers. In mice beta-NF enhances and PCN inhibits DMN-demethylase I; beta-NF has no effect on either the cytochrome P-450 level or on the LD50, while PCN strongly increases the cytochrome P-450 level but without influencing the LD50. Neither of the two modifiers has any effect in mice on the host-mediated mutagenicity of DMN in a dose-response study, except for the highest dose of DMN (200 mg/kg) where PCN pretreatment significantly enhanced mutagenicity. To account for the anomalous observations, other potential pathways of DMN metabolism have been explored. Whole rat liver nuclei or isolated nuclear membrane fractions contain no DMN-demethylase or diethylnitrosamine-deethylase activity. In a microsomal mixed-function amine-oxidase assay system neither purified enzyme preparations nor whole microsomes catalyze NADPH oxidation in the presence of DMN as substrate. In addition, the purified enzyme does not catalyze formaldehyde production in the DMN-demethylase assay system. Benzylamine, a typical inhibitor of mitochondrial monoamine oxidase (MAO), is a potent inhibitor of DMN-demethylase activity, but microsomes are devoid of MAO activity. Furthermore, purified MAO has no DMN-demethylase activity. The differential effect of modifiers on the carcinogenicity of DMN probably involves pathways other than DMN metabolism.


Toxic action of 2'-chloro-2,4-dinitro-5',6-di(trifluoromethyl) diphenylamine in the rat. 2'-Chloro-2,4-dinitro-5',6-di(trifluoromethyl)diphenylamine (CDTD) is a potent uncoupler of oxidative phosphorylation in isolated rat liver or brain mitochondria. The concentration of CDTD causing 50% uncoupling in vitro is dependent on the mitochdonrial protein concentration and is 2 nM at 0.9 mg protein/ml for rat liver mitochondria. Oxidative phosphorylation can be restored to CDTD uncoupled liver mitochondria by the addition of a 10 000-fold molar excess of bovine serum albumin to DCTD. Rats given a lethal dose (7.0 mumol/kg) of CDTD intrapertioneally show signs of toxicity typical of uncoupling agents. Mitochondria isolated from the livers of these rats show almost complete inhibition of ATP synthesis and mitochondria obtained from the livers of rats at various times after a single oral dose show maximal inhibition of ATP synthesis 4 h after dosing with complete recovery by about 24 h. A single oral administration of 58 mumol/kg or above, but not intraperitoneal injection, of CDTD into rats produced an increase in the water content of the brain and spinal cord. The additional fluid has been shown to contain Na+ ions. The increase in cerebral fluid is dose related, no effect being seen at 23 mumol/kg. This extra fluid is thought to be responsible for the hind limb weakness observed in these rats. These observations suggest that there are two facets to CDTD toxicity: early deaths (within 2 h), which appear to be due to uncoupling of oxidative phosphorylation, and delayed deaths, 2--3 days after dosing which are probably related to an increase in fluid in the brain and spinal cord.


Comparison of the interaction of tricyclic antidepressants with human polymorphonuclear leukocytes as monitored by the generation of chemiluminescence. The interation of imipramine with human polymorphonuclear leukocytes (PMNs) results in a chemiluminescence (CL) response which has been attributed to the electronic excitation of the imipramine molecule resulting from a reaction of the drug with reactive oxygen species. In order to determine what portion of the tricyclic molecule is involved in this reaction, the interaction of other tricyclics with PMNs was monitored by chemiluminescence. It was observed that tricyclic antidepressants having a carbon atom at position 5 of the ring moiety (amitriptyline, for example) did not yield CL with either resting or zymosan-activated PMNs. In fact this group of compounds inhibited the zymosan-induced CL response. However, CL was observed, with both resting and metabolically-activated PMNs, from several tricyclics having a heterocyclic nitrogen at position 5. These included imipramine, desipramine, opipramol and iprindole. Chlorimipramine, which has a chlorine atom at position 3 of the ring system, failed to yield CL with resting or stimulated cells. Similarly, imipramine N-oxide failed to yield CL with resting cells, but enhanced CL was observed with zymosan-activated PMNs. On the basis of these observations it appears that some aspect of the ring moiety, other than just a heterocyclic nitrogen, facilitates a reaction between these molecules and reactive oxygen which culminates in the generation of CL.


Formation of adducts of parthenin and related sesquiterpene lactones with cysteine and glutathione. Parthenin, the major sesquiterpene lactone of Parthenium hysterophorus, a weed responsible for dermatitis in man is primarily restricted to leaf and stem trichomes. Parthenin forms a monoadduct with L-cysteine through the alpha-methylene group of the gamma-lactone and a biadduct with the endocyclic double bond on the cyclopentenone ring. Studies with other sesquiterpene lactones support the view that the types of adducts formed are correlated with the biological activity of the sesquiterpene lactones.


Metallothionein degradation: metal composition as a controlling factor. Degradation of the cadmium (Cd)-induced protein, metallothionein (MT) was studied in rat liver and kidney. The half-times (t1/2s) for degradation of the protein were found to vary according to the concentration of Cd in the tissues. In animals containing high Cd2+ concentrations, the t1/2 of degradation was significantly longer than in low Cd2+ animals. There were no significant differences in degradation times between liver and kidney. Purification of the MT by anion exchange chromatography revealed two species which had, in the liver at least, different degradation times. Since the metal content of the MTs did not vary throughout the time course of the experiment, it is proposed that the rate of degradation and hence the turnover of the protein is influenced by the ratio of Cd2+ to other bound cations (e.g. Zn2+ and Cu2+). Thus, the Cd/Zn ratio in the liver and the Cd/Cu ratio in the kidney determine the respective rates of degradation and hence turnover of the protein.


Purification of 1-monoacylglycerols containing alpha-branched-beta-hydroxylated fatty acids from lipids of Corynebacterium pseudotuberculosis. A complex mixture of monoacylglycerols, identified as (C30--C36) corynomycoloylglycerols was isolated from the diethyl ether/acetone-soluble lipids of Corynebacterium pseudotuberculosis.


Labelling of cardiolipin in vitro.

Labelling of cardiolipin in vitro. A method for labelling the polar head groups of cardiolipin is described. Labelling was carried out on sonicated cardiolipin/water suspensions. The free hydroxyl group of cardiolipin was oxidised with an excess of p-(diazonium) benzenesulfonic acid (DABS) and then reduced with NaB3H4. Isopropanol was oxidised in the presence of DABS to test the reactivity of the diazonium salts, and the reaction product was analysed by means of gas-chromatography. Labelled cardiolipin, identified by thin-layer chromatography (TLC), was chromatographically pure and identical to untreated cardiolipin. The hydrolysis of cardiolipin confirmed that the labelling was at the level of polar head groups.


Pseudo cord factors: derivatives of alpha-D-glucopyranuronosyl (1-1) alpha-D-glucopyranuronoside. We describe the synthesis of 6 pseudo cord factors (psi CF), analogs of the natural trehalose-6,6'-dimycolate, but based instead upon the dicarboxylic acid (TDA) that is obtained from trehalose by Pt-catalyzed oxidation. From TDA, several bis-amides ('mirror amide' psi CF) and a diester ('mirror' psi CF) of intermediate to high molecular weight were prepared. These superficially resemble cord facotr, have similar infared spectra and, like the natural product, several have impressive toxicity in mice and tumor-regression activity; but the latter property does not depend upon the former. A curious abrogation of biological activities results from introduction of a hexamethylene diamine 'spacer' between the carbohydrate core and the lipid substituents. The results suggest that (excepting the 'spacer' effect) the type of covalent linkage between the carbohydrate and lipid moieties may be relatively unimportant for expression of some of the biological activities of cord-factor-like glycolipids.


A new approach to the study of lipid-protein interactions in the structure of biological membranes. The lytic action of a number of N-acyl amino acids on lecithin liposomes was examined. The agents' affinity for lecithin liposome membrane was measured and the results obtained were treated to estimate the interactions of the amino acid residues with the lecithin polar head group at the surface of the liposome membrane. The data were considered in relation to the study of the surfactant effects on the erythrocyte volume. The ability of the suggested approach to obtain information on protein-lipid interactions inaccessible by other techniques is briefly commented on.


The solubilisation of some steroids by phosphatidylcholine and phosphatidylcholine-cholesterol vesicles. The solubility of the three steroid hormones, progesterone, testosterone, and estradiol-17 beta in water and phosphatidylcholine vesicles was measured after shaking and ultrasonication. All three steroids have low water solubility, which increases considerably at sonication for testosterone and estradiol-17 beta. The phosphatidylcholine vesicles have a very small solubilising capacity for the steroids; about 20 mumol/mol. This increases at sonication for estradiol-17 beta and decreases for testosterone. The capacity for progesterone is almost unaltered. The incorporation of cholesterol in the vesicles decreased the solubilisation capacity for testosterone and estradiol-17 beta but increased that for progesterone of shaked preparations. For the sonicated systems the cholesterol decreased the solubilising capacity for estradiol-17 beta but increased that for testosterone. The solubilisation experiments indicate that the steroid hormones are solubilised in the hydrocarbon part of the phosphatidylcholine bilayer and also 13CNMR results support this conclusion.


Variola minor in Bragança Paulista county, 1956. Observations on the clinical course of variola minor and on pregnancy in women with the disease. Occasional observations on the clinical course of 485 cases of variola minor composing an epidemic are reported. 17% of the cases showed a complication. Otitis was observed in one case. An erythematous rash limited to the upper chest, neck and head appeared, instead of the pock eruption, after the pre-eruptive phase, in a previously vaccinated case. Convulsions, drowsiness, stupor, delusions, dizziness or deafness were observed in 23 patients whose individual characteristics are also presented. One of these cases showed a definite neurologicl syndrome: encephalitis. Neurologic complications were mostly seen in patients with medium to severe variola minor. Neither abortion nor death were seen among 4 pregnant women who developed variola minor, even though one of them delivered, on term, a dead foetus, 4 months after developing variola minor.


Epidemiology of cutaneous leishmaniasis in Afghanistan. Part I: Zoonotic cutaneous leishmaniasis. From June to September 1977, a preliminary epidemiological investigation was carried out in some parts of northern Afghanistan (Aqcha, Mazar-e-Sharif and Paul-e-Khombri). The disease in these areas is of zoonotic type having Rhombomys opimus as reservoir and P. caucasicus and P. papatasi as vectors.


[Onchocerciasis in the Brazzaville region (Congo). Preliminary note]. The authors give the results of a global and rapid study, using a simple methodology, of a suburban onchocerciasis focus located in the vicinity of Brazzaville. It follows, from the entomological, parasitological and clinical data, that the transmission is high inside this focus and therefore, it seems necessary to take, all measures in order to eradicate the focus.


[Dynamic characteristics of hockey sticks and efficacy of shooting in ice hockey]. Previous studies have established that efficiency in shooting is influenced partly by the dynamic characteristics of the stick being used and partly by the morphology of the player. The purpose of the present study was therefore to verify the hypothesis stating that flexible sticks were superior to rigid ones in respect to the proficiency of shooting of pee-wee hockey players. This study has confirmed the superiority of the flexible stick over the rigid one in terms of speed and accuracy of shooting among pee-wee hockey players. Moreover morphological parameters and muscular strength were found to play a determining role in efficiency of shooting. In fact, it was suggested that the smaller and weaker the player the more advantageous is the use of a flexible stick. Through the use of strain gages fixed to the experimental hockey sticks, it was possible to determine that the speed of shooting is directly related to the acceleration imparted to the stick during the forward phase of the movement. It was also possible to demonstrate that for a given speed of the puck the more flexible stick required a smaller force than the rigid one.


Fatigue in ice skating: biomechanical considerations. This paper attempts to describe how the mechanical patterns in ice skating are affected by muscular fatigue. It reviews several investigations dealing with the effects of muscular fatigue on standing broad jump performance and running. It concludes that fatigue studies dealing with ice skating can be expected to show that the mechanical patterns in ice skating deteriorate as a result of muscular fatigue.


A longitudinal study of ice hockey in boys aged 8--12. A group of fifteen boys (experimental or competitive) were studied over a five year period of competitive ice hockey beginning at age 8. The subjects were members of a team which averaged 66 games per year, ranging from 50 at age 8 to 78 at age 12. In addition, they practiced twice a week with heavy stress on skating and individual puck handling skills. A second group of eleven boys (control or less competitive) were studied from age 10 to 12. The latter subjects played an average of 25 games per year and practiced once a week. All subjects were measured each year on skating and puck control skills, fitness-performance tests, grip strength, physical work capacity as well as height and weight. The results demonstrate learning curves for skating and puck control tests which, while typical in nature, show extremely high levels of achievement. Fitness-Performance, grip strength and physical work capacity levels of the competitive group are extremely high in comparison with data from other countries.


[Current means of controlling pediculosis outbreaks in the South of France]. The authors sum up the principal morphological, biological and ecological characteristics of the human lice. Moreover they recall the therapeutic and prophylactic measures which could be used against them, and they bring to mind their "in vitro and in vivo" research technics on comparative effectiveness of certain insecticides against head lice.


[Overview of dermatophytes in Mali].

[Overview of dermatophytes in Mali]. 517 isolations of dermatophytes collected in Mali are reported. The various species are described and the main findings are: --Trichophyton species are more common (85.5% isolated from scalp lesions and 77.5% from skin scrapings) than Microsporum species. --Trichophyton verrucosum and Microsporum canis have been found found for the first time in Mali. --Ill-defined clinical forms of scalp lesions caused by either T. schonleinii or T. soudanense occur in the subsaharian areas of the country.


Comparsions among VO2 max values for hockey players and runners. This study was designed to investigate the specificity of the VO2 max response of runners and hockey players for multistage tests done on the treadmill (RUN) or on the ice, skating a shuttle 20m course with (20m+) or without equipment (20m-) and a 140m oval course (140m-). Hockey players VO2 max in ml.kg-1.min-1 (n=10) were similar for the 4 tests (RUN: X +/- SD = 61.4 +/- 6.3; 140m-: 62.1 +/- 9.4; 20m-: 58.6 +/- 6.4; and 20m+: 59.9 +/- 7.4). VO2 max of runners (n = 10) were superior on the treadmill (68.6 +/- 4.5) as compared to the ice (140m-: 65.6 +/- 5.4). Hockey players as compared to runners, were 15% more efficient on the ice and 7.9% less efficient on the treadmill. The equipment increased the energy cost of skating by 4.8% and decreased the multistage test time by 20.3%. The low temperature arena as compared to the standard temperature laboratory, yielded lower heart rate response with multistage tests. Blood lactates (mg%) were similar for all tests done with hockey players (RUN: 128.3 +/- 19.3; 140m-: 126.8 +/- 14.7; 20m-: 133.0 +/- 17.5; and 20m+: 131.4 +/- 18.5), but lower on the ice (140m-: 87.7 +/- 15.9) as compared to the treadmill (127.2 +/- 26.4) for the runners. Maximal skating speed disclosed a relatively homogenous group of hockey players but their VO2 max scores were more widely distributed.


[Scanning electron microscopic observation of Schistosoma mansoni miracidia and cercariae]. The integumental surface of cercaria (Schistosoma mansoni was studied by scanning electron microscopy (SEM) at 400 to 20,000 magnifications. Cercariae studied by SEM showed clearly the surface topography. The spines have been seen by light microscopists and recognised as an adaptation for penetration of the host.


Respiratory and cardiovascular aspects of intermittent exercise with regard to ice hockey. The purpose of this review paper was to analyze the cardiorespiratory demands involved in playing ice hockey. Heart rate (HR) monitoring, by radiotelemetry during actual game performance, has indicated near-maximal cardiorespiratory efforts for the 2 1/2 to 3 minute on-ice shifts. Analyses of the temporal characteristics of the game, and thus the intermittent exercise (IE) schedules involved were also utilized to elucidate the cardiorespiratory demands of the sport. Compared to continuous exercise, at the same average power output, IE performance represents greater demand on both the central circulation and oxidative metabolism in the muscle cell. In IE, of time and intensity components typical of those found in ice hockey, laboratory data, compared to continuous exercise, showed a higher cardiac output, yet widened arterio-venous oxygen difference in the active muscles compensating for a lower muscle blood flow. Further, the literature suggested a reduced efficiency of the thermoregulatory system in IE, placing added demand on the cardiorespiratory system. The analysis suggests that training programs to increase aerobic power would be beneficial for ice hockey players.


Metabolic aspects of intermittent work with specific regard to ice hockey. The focus of this presentation was to examine the metabolic alterations that occur in muscle during ice hockey performance. An attempt was made to describe the significance of several factors that determine the nature and extent of energy producing processes during work and to relate these specifically to the ice hockey situation. The review concludes with an analysis of potential fatigue mechanisms that might occur with recommendations for their control.


[3 cases of tetradontidae poisoning observed in France]. The authors report 3 cases of food poisoning, one of them leading to a swift death, which they were able to observe on 1st January 1978 in the Drôme (France). They explain how burbot was the suspected food responsible for the auto-intoxication and how the X ray examination of the vertebrae of this fish allowed them to support the diagnosis of "tetrodonic" poisoning; the inquest did not allow to state precisely where the fish was caught. With regard to these French cases the authors point out that this type of pathology is made possible by the increasing importing of fish from tropical regions, in powder form or frozen products.


Thermoregulatory problems encountered in ice hockey. Despite the fact that ice hockey is played in lower than normal ambient air temperatures, its intense intermittent nature is such that the athlete encounters hyperthermal problems similar to those of most team athletes. This presentation discusses these problems and offers recommendations by which performance may be improved.


Characteristics of "old timer" hockey play. Many Canadian adults play Old Timer hockey to improve and/or maintain their cardiorespiratory fitness. This review examined the intensity and duration of play that characterizes adult noncontact hockey. The exercise intensity was assessed by continuously monitoring the heart rate response via telemetry. The duration of play was studied utilizing time-motion analysis, during the typical Old Timer game, the forwards spent 28 minutes on the ice when the heart rate was at least at 60% KM intensity. The forwards averaged 85% KM intensity during game activity. The mean heart rate response of the goaltenders was 143 beats per minute or 64% KM intensity.


[Tissue distribution of chloroquine in 18 cases of voluntary poisoning]. Chloroquine has been studied in some tissues of 18 subjects dead after fatal absorption of this drug. The assays have been made by U. V. Spectrophotometry, a simple, rapid and specific method. The found concentrations are highly heterogenous according to individuals and organs; generally, the higher levels are found in the liver, the spleen and the kidneys and the lower levels in the brain.


[2 new phlebotomi from French Guyana : Lutzomyia yuilli pajoti n. s. sp., and Lutzomyia claustrei n. sp]. The authors describe two new sandflies from Saül and Maripasoula (French Guyana). They give for each of them mensurations, drawings and differential diagnostic with related species or subspecies.


Glycogen depletion in a game-simulated hockey task. A game-simulated hockey task has been developed to closely approximate the actions in a hockey game including forward and backward skating, stops, starts, shooting and passing. As well, the test is similar to game conditions for number of shifts, activity time per shift, activity time per play and total active time on the ice. The purpose of this study was to measure the glycogen depletion during the task and to compare this with laboratory tasks and actual game conditions. The results demonstrate that the simulated tasks resembles on ice conditions during a game for heart rate and glycogen depletion. The preferential glycogen utilization by ST fibres but great depletion in FT fibres as well suggests that the task is strenuous enough to stimulate both FT and ST motor units.


Visual cues in ice hockey goaltending.

Visual cues in ice hockey goaltending. The effect of both the availability and the quality of visual cues preceding stick-puck contact was investigated for an ice hockey goaltending task. Thirty-four young (15.8 years) goaltenders observed filmed sequences of a hockey player approaching the net and directing a shot to one of the four corners. The film sequences were edited so that 2, 4 or 8 images were occluded prior to the impact of the stick with the puck, reflecting durations of 1/12, 1/6, 1/3 of a second, respectively. The subjects' performances for both the wrist and the slap shot were measured as well as the level of response confidence in both the horizontal and vertical planes. The results indicated that performance precision was aided by the increased availability of pre-shot visual cues. It was also evident that the wrist shot provided more cues for the goaltender than did the slap shot. Performances were found to be superior in the horizontal as compared to the vertical plane. In all dimensions, the subjects' perceptions of their success closely followed the actual performance patterns. It appeared that information that could facilitate anticipation in this goaltending task was both available and useable during the period that precedes the shot.


Speed of response characteristics of goalkeepers: a descriptive and developmental report. Photoelectric cells and accelerometers enabled the measurement of reaction, movement and total response times of the limbs of representative goalkeepers (N = 12) from five levels of organized hockey, under simple and choice test conditions. Speed of response characteristics fundamental to success at these levels of competition and the developmental improvement, which must occur annually to permit progress through the goalkeeping hierarchy, were suggested. The point at which the beginner's "reaction-type" pattern of goaltending must be augmented with "anticipation-type" behavior was explored. The concept that the ability to react and move is specific to the direction of the response was upheld at all levels of investigation. Standard deviation of the RT/MT/TRT's of each group reflected the degree of variability of performance that is tolerable at each level. This variability generally decreased with each ascending level within both testing conditions, with the exception of the CRT measures. Data collected over a two year period, for four subjects, revealed that the most evident longitudinal changes occurred in MT and that the youngest player experienced the greatest degree of overall improvement.


The basic stance of age-group ice hockey goalkeepers. Over 300 goalkeepers from the seven age-groups were sampled as part of a larger age-group normative survey. The photographic evidence delineates three basic goalkeeping stances in the younger age-groups. For a variety of reasons, one of the stances becomes dominant to all others and appears to be the one used by NHL, WHA and world international championship goal tenders.


Academic achievement and involvement in hockey: a post-hoc longitudinal study. Academic achievement, absenteeism, and athletic involvement (hockey) data were collected on 484 boys throughout British Columbia. School and minor hockey records were used to obtain longitudinal data for each boy from Grade 1 until high school graduation or school withdrawal. Results indicated that hockey players exhibit less school absenteeism than non hockey players, but are not different with respect to grade point averages. Hockey players, at the juvenile level or lower, tend to attain a slightly higher grade point average during the years they are playing hockey in comparison with their academic achievement during the years they are not playing hockey. Of the hockey players with lower than average I.Q.'s, those who exhibit poor achievement tend to drop out of hockey earlier than those who have average or above average grades.


Social determinants of violence in hockey: a review. Research on the social determinants of hockey violence is organized in this paper under three main headings: (1) the social organization of the hockey "system", (2) mass media portrayals of the professional game, and (3) the influence of players' reference others. It appears that these determinants all contribute to a social environment in which hockey performers perceive that the rewards of violence often outweigh the costs.


A comparison of selected hockey skating starts. The purpose of this study was to determine the effectiveness of three different methods of initiating forward movement (IFM). Six S's from four levels of Ice Hockey competition were instructed in the methods then were timed for 20 feet of forward skating from a standing start. Selected S's within each group were also analyzed biomechanically, via the cinema-computer process. Both statistical and biomechanical analysis showed a superiority of the rarely taught thrust and glide or "t" start over the two conventional techniques, the cross-over and normal standing start facing the direction of movement. Results indicate a need to include the thrust and glide in Ice Hockey instructional programs.


Institutionalized rule violation and control in organized minor league hockey. In minor league hockey, rule violation including the illegitimate use of force is institutionalized behaviour. Illegitimate tactics are among the minimal general criteria for the assessment and selection of players. No formal mechanism operates to socialize players to obey normative rules. The "official" control system is ineffective in preventing normative rule violation. However, it regulates the game according to constitutive rules preventing its disorganization, and creates the impression that players actually govern their conduct according to normative rules. An informal control system (combative and aggressive in orientation) legitimizes and regulates the amount and kinds of rule violation occurring, and highlights collective meanings of the occupation. A scheme is presented for reducing institutionalized rule violation. Team success (victory) and rule conformity are considered desirable and are rewarded. What value to assign these two "things" remains problematic. To avoid undermining motivation to win the contest, more value must be assigned team success than rule conformity. The question is how much more.


The relationship between aggression and performance outcome in ice hockey. This investigation determined if aggression is a means of obtaining success in amateur ice hockey. Two analyses were undertaken. The first examined the relationship between illegitimate tactics (as measured by penalty minutes accumulated) and team success, while the second compared the penalty minutes accumulated by successful individuals (i.e. all stars) with the penalty minutes accumulated by non-all stars. The sample was comprised of the 87 teams and their 1,667 players who participated in the Ontario University Athletic Association from 1971-72 to 1976-77. The relationship between team aggression and team success was analyzed with a Pearson Product Moment Correlation. A t test was used to compare the mean accumulated penalty minutes of all stars with those of non-all stars. The results failed to support the premise that aggression is a means to success for teams or for individuals.


Three hockey skills tests as predictors of hockey playing ability. The purpose of this study was to compare the test result times of 3 different hockey skills with the individual player ratings of coaches. By making these comparisons to the control rating, each test was evaluated as a predictor of hockey ability. The hockey players were all between the ages of 12 and 20 years of age and all 90 players were competitive team players. The three hockey skills tests were: the Illinois Agility Skate, the Finnish Skills Test, and the Hermiston Hockey Ability Test. Each player was allowed 3 trials and the best times were recorded in all cases. The preliminary results indicate that the Hermiston Hockey Ability Test was the best predictor (r = .7) with the results of the other two tests showing a coefficient of correlation of approximately 0.5. It was therefore concluded that in a competitive team of hockey, players' ability can best be assessed by using the Hermiston Hockey Ability Test. The two other tests were not as successful in their prediction of ability when compared to the criterion variable of coaches' ratings.


Nutrition and ice hockey performance.

Nutrition and ice hockey performance. Muscle glycogen is a major fuel for ice hockey. About 60% of the muscle glycogen in quadriceps muscle is utilized during a single game. When hockey games are played on successive days, studies reveal that muscle glycogen utilized during the second game is less than that of the first game. The diet of seven professional hockey players was studied for one week during the playing season to determine whether food selection could pose a problem for hockey performance. The data reveal that most players have a high protein intake, but that vegetables and fruit intakes were low. The problem of fuel supply for young hockey players is examined during tournament situations where up to three or more games may be played in a single day.


Determination of daunorubicin, doxorubicin and their fluorescent metabolites by high-pressure liquid chromatography: plasma levels in DBA2 mice. A rapid and nondestructive analytic method has been developed to separate and quantitate daunorubicin, doxorubicin, and their metabolites in biological fluids. This method combines the efficiency of high-pressure liquid chromatography and the sensitivity of fluorescence monitoring. The drug plasma levels achieved after IV administration of either daunorubicin or doxorubicin at 7 mg/kg into DBA2 mice were studied. The plasma disappearance curves are biphasic with a half-life of 1 min for the first elimination phase. In urine extracts, 13-hydroxy derivatives represent 80% of the fluorescence after injection of daunorubicin and only 4% after administration of doxorubicin.


Liquid chromatographic monitoring of daunorubicin and daunorubicinol in plasma from leukemic patients treated with daunorubicin or the daunorubicin-DNA complex. Fifteen patients with acute nonlymphocytic leukemia have been randomized for treatment with daunorubicin (1.0--1.5 mg/kg) either as the free drug (for 45 min or 4 h) or as the drug bound to a DNA carrier (for 5--6 h). The correlation between plasma kinetics of daunorubicin and its main metabolite daunorubicinol and the different administration schedules of daunorubicin has been studied by reversed-phase liquid chromatography. Plasma concentration kinetics of daunorubicin as well as the daunorubicin-DNA complex was biphasic in character. Maximum plasma level of daunorubicin was found during the infusion period. Its concentration decreased rapidly when the infusion stopped and was below the detection limit of the analytical method 2--4 h later. The data suggests a slower disposition of the duanorubicin-DNA complex compared with the free drug.


Comparative study in mice of the toxicity, pharmacology, and therapeutic activity of daunorubicin-DNA and doxorubicin-DNA complexes. We have compared the toxicologic, pharmacologic, and therapeutic properties of the DNA complexes of daunorubicin and doxorubicin, after intravenous (IV) administration into mice. The overall toxicity of doxorubicin is significantly reduced after IV injection as a DNA complex while daunorubicin-DNA is as toxic as free daunorubicin. On hemopoietic stem cells, daunorubicin-DNA was found to be more cytotoxic than daunorubicin, while the opposite was observed with doxorubicin and doxorubicin-DNA. Both complexes are more effective than the corresponding free drugs on the L1210 murine leukemia, when given IV at equitoxic doses. The tissue uptake in mice, after IV administration, is generally lower when the drugs are given bound to DNA. The stability of the two DNA complexes is very different in the bloodstream: daunorubicin-DNA behaves more like a prodrug of daunorubicin, while doxorubicin-DNA, remaining stable in the bloodstream, meets much more the requirements of an ideal drug-macromoleculare carrier entity.


Uptake of the daunorubicin-DNA complex in cultured fibroblasts. The uptake and fate of the daunorubicin-DNA complex have been studied in cultured rat embryo fibroblasts. 125I-DNA was digested by the cells and appeared as low molecular weight fragments in the incubation medium. Subcellular fractionation of fibroblasts, previously incubated with the complex, showed that daunorubicin was localized to nuclei and lysosomes. At a high incubation concentration (17.5 microM), the accumulation of the free drug exceeded that of the complex. However, at a lower concentration (1.75 microM), the accumulation of the complex was as high as that of the free drug. The results are consistent with an uptake of the complex into cultured rat embryo fibroblasts by endocytosis. However, it cannot be excluded that the complex partly dissociates in the incubation medium, and that daunorubicin and DNA thereafter enter the cells separately.


Biological activities of rubidazone.

Biological activities of rubidazone. Rubidazone (benzoylhydrazone daunorubicin) is a semisynthetic compound with a good experimental antitumor activity. Its main interest is its lower toxicity and cardiotoxicity. In human chemotherapy, it is considered a valuable drug.


Distribution and metabolism of rubidazone and daunorubicin in mice. A comparative investigation of the distribution and metabolism of rubidazone and daunorubicin was conducted in NMRI mice, after a single IV dose of either rubidazone (8.4 mg/kg) or daunorubicin (7 mg/kg). The anthracyclines were analyzed by high-pressure liquid chromatography and fluorometry. Daunorubicin was the main compound found after daunorubicin administration, except in kidney and urine, where daunorubicinol was the main metabolite with trace amounts of aglycone. In contrast, rubidazone undergoes extensive metabolism into daunorubicin, daunorubicinol, and aglycone. The total drug level is significantly lower after rubidazone administration in kidney, heart, gastrointestinal tract, spleen, and urine, and the biliary excretion of rubidazone is more important than that of daunorubicin. When compared with daunorubicin, significantly less daunorubicinol is produced after rubidazone administration.


In vitro and in vivo study of cross resistance between daunorubicin and daunorubicin-DNA complex in Ehrlich ascites tumor. The antitumor effect of daunorubicin and of two preparations of daunorubicin-DNA complexes were compared in equitoxic doses against the Ehrlich ascites tumor and in a subline of this tumor resistant to daunorubicin. The therapeutic efficacy of both complexes was significantly better than that of free daunorubicin in the sensitive tumor. The daunorubicin-resistant tumor was found to be cross resistant to both daunorubicin-DNA complexes. In vitro, the steady-state uptake of daunorubicin was considerably lower when the drug was added as a complex compared with addition as free drug. Experiments in which the uptake of daunorubicin and of DNA was determined simultaneously showed no significant uptake of DNA in either cell line. Together, these data indicate that even if daunorubicin is administered as a complex, the membrane transport in Ehrlich ascites tumor cells takes place solely as free drug.


Uptake of free and DNA-bound daunorubicin and doxorubicin into human leukemic cells. Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. The uptake of unbound daunorubicin was higher than that of doxorubicin. At drug concentrations of 1.75 microM and higher the uptake of the free drugs was greater than that of the bound forms, but at lower drug concentrations the uptake was about the same. This could at least partly be explained by a greater dissociation of the DNA-drug complexes at lower drug concentrations. The uptake into normal leukocytes was of the same order of magnitude as that into leukemic cells. There was a great interindividual variation in the accumulation of both free and DNA-bound drugs in the cells from leukemic patients. This variation might be of importance for the prediction of individual sensitivity to the different drugs.


DNA-binding parameters of daunorubicin and doxorubicin in the conditions used for studying the interaction of anthracycline-DNA complexes with cells in vitro. Affinity constants of daunorubicin and doxorubicin for DNA at 37 degrees C and in presence of 10% serum were determined by an optical method and calculated from Scatchard plots. Values from 0.10 to 0.12 and from 0.13 to 0.16 X 10(6) M-1 were obtained for daunorubicin and doxorubicin, respectively. According to these affinity constants, the amounts of free drugs were calculated for various concentrations of daunorubicin-DNA or doxorubicin-DNA and for various molar ratios. In a large range of concentrations there is rather stable concentration of both free drugs, and these concentrations are inversely proportional to the nucleotides/drug ratio. The amount of free drug present in the medium is low as long as the concentration of daunorubicin-DNA or doxorubicin-DNA is higher than 1 microgram/ml (expressed as drug concentration). At lower concentrations, however, the percentage of free drug increases very sharply.


Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report. Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.


Daunorubicin-DNA and doxorubicin-DNA. A review of experimental and clinical data. Experimental data on the pharmacokinetic, toxic and therapeutic properties of daunorubicin-DNA and doxorubicin-DNA complexes are reviewed and summarized as well as the available reports on clinical trials performed with these anthracycline-DNA complexes. These results are discussed in view of the further development of the drug-carrier concept of cancer chemotherapy.


Myocardial function in feline endotoxin shock: a correlation between myocardial contractility, electrophysiology, and ultrastructure. The nature of the myocardial depression observed in patients with septic shock, and in animals late in shock induced by endotoxin, is still under examination. These studies, in cats and kittens administered an LD80 dose of E coli endotoxin, were designed to examine the relationship between changes in myocardial contractility, in cellular electrophysiology and in ultrastructural morphology. There was no difference between tension developed in vitro by cardiac muscle removed from cats five hours after endotoxin administration and from cats not administered endotoxin. There was also no difference in their responses to calcium chloride or to anoxia. The action potential characteristics of ventricular muscle isolated from endotoxin treated cats were also not different from control, and ultrastructural damage was minimal and not extensive. Endotoxin (100 microgram/ml) had no effect on cardiac muscle in vitro, even after a one-hour contact time. It is concluded that the integrity of the myocardium is maintained even late in shock and that endotoxin has no direct effects on the heart.


The effects of mild normovolemic hemodilution on regional flow, oxygenation, and small vessel blood content in the rabbit heart subjected to acute coronary occlusion. The effect of mild hemodilution (hematocrit, 19%) on ischemic and nonischemic regions of myocardium during acute coronary occlusion was studied in 41 pentobarbital-anesthetized, open-chest New Zealand white rabbits. Blood flow in the control area determined with radioactive microspheres was unaffected by occlusion and increased 61.8% following hemodilution. The endo/epi ratio remained at about 1.0. Occlusion decreased flow in the affected region to 41% of the control myocardium, and endo/epi ratio decreased significantly to 0.76. Hemodilution raised flow in this area 84.3%. Occlusion increased small vessel blood content (a measure of open capillary density) in the ischemic region significantly. Hemodilution further significantly increased this volume in the occluded area, although the increase in the control region was not significant. Relative tissue pO2, measured polarographically, declined significantly following occlusion in the affected area. Isovolemic hemodilution did not affect relative O2 tension in either area. The data indicate that during mild hemodilution, the O2 supply-demand status of both the occluded and nonoccluded myocardial regions is maintained.


Failure of exogenous ATP and creatine phosphate to modify the course of E coli endotoxin shock in the cat. Exogenous adenosine triphosphate (ATP) (in combination with MgCl2) and also creatine phosphate (CrP), have been administered intravenously to endotoxin-shocked cats. Untreated shocked cats exhibited systemic hypotension during the first hour and again from four hours. Cardiac output fell progressively, and markedly elevated arterial lactate levels were evident within one hour of endotoxin administration. Treatment with ATP (10 mg/kg every 30 minutes) during shock led to rapid hemodynamic deterioration in all cats; most of the cats were dead before completion of dosing (at three hours). Long-lasting systemic hypotension and bradycardia were associated with this ATP administration and marked hypoglycemia developed in the survivors. Neither ATP (62 mg/kg) administered before endotoxin, nor CrP (500 mg/kg; administered either prior to endotoxin, or one hour afterwards) significantly modified the hemodynamic or metabolic changes associated with endotoxin shock in this species. Neither ATP nor CrP increased survival (assessed at five hours). Other workers have demonstrated improved survival from shock with ATP treatment. There may be species differences in the responsiveness to exogenous ATP or, alternatively, a difference in the role of high-energy phosphates in different types of shock.


Effects of vasodilators on mesenteric ischemia and hypoxia induced by hemorrhage. We compared the effectiveness of three pharmacologically and chemically dissimilar vasodilators (histamine, glucagon, and perhexiline) in reversing the hemodynamic and metabolic deficits of intestinal ischemia produced by hemorrhage. With intraarterial infusion into the superior mesenteric artery of anesthetized control dogs, all three agents increased mesenteric blood flow and oxygen consumption without altering systemic arterial blood pressure. Similarly, in the ischemic gut following moderate hemorrhage all three vasodilators increased mesenteric flow and oxygen consumption while reducing vascular resistance and not affecting systemic arterial blood pressure. On a molar basis glucagon was the most potent dilator drug. In severely hemorrhaged dogs whose intestinal blood flow had been reduced nearly 80%, glucagon restored oxygen uptake and vascular resistance to control levels. These findings demonstrate the efficacy of three different vasodilators in reversing the mesenteric ischemia and hypoxia produced by hemorrhage.


Recovery from endotoxin shock after extracorporeal perfusion without anticoagulation. The purpose of this study was to determine the effect of an extracorporeal nonanticoagulated perfusion system on survival from endotoxin shock in anesthetized closed-chest dogs. Dogs weighing approximately 18 kg were perfused four hours or used as nonperfused controls. In the perfused animals, blood was diverted from the distal aorta via plastic tubing at 1,000 ml/min into a reservoir and returned by means of a roller-type pump to the femoral veins. Whole blood clotting times increased from a control value of seven minutes to greater than 24 hours within 45 minutes of perfusion in the absence of exogenous anticoagulation. After blood became incoagulable, animals were infused with 3 mg/kg Escherichia coli endotoxin during a 30-minute period. Systemic pressures declined during the initial period but returned to base-line values; glucose remained at normal levels and all six dogs thus treated remained healthy survivors after seven days. On the other hand, animals infused with endotoxin without extracorporeal perfusion demonstrated hypotension, hypoglycemia, and diarrhea, and five of six dogs died within 36 hours.


Child health problems and programmes in two underdeveloped areas of the USA. There are areas in the USA where the health problems of children a similar to those of children in some developing countries. Traditional US health programmes have contributed to an improvement in the health status of many of these children but there remains much more to be done.


Renin response to hemorrhage in awake and anesthetized rats. Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.


Hypoxanthine in lethal canine endotoxin shock. Endotoxin shock was induced in Labrador retriever dogs by intravenous infusion of a lethal dose of Escherichia coli endotoxin (2 mg/kg body weight) over a three-hour period in order to study plasma hypoxanthine concentrations. The animals succumbed within 14 hours after start of the infusion. Terminally when aortic blood pressure dropped below 30 mm Hg and bradycardia had developed, the animals were resuscitated by external cardiac massage, artificial ventilation, and volume therapy. During shock no significant alteration of plasma hypoxanthine concentrations occurred. During the 12-minute period of resuscitation, however, hypoxanthine concentrations of both arterial and venous plasma increased rapidly compared to the initial values. The changes of the hypoxanthine concentration revealed an exponential pattern. The likely explanation for this phenomenon is is that during shock bypoxanthine was accumlated in the tissues due to tissue hypoxia and that the metabolite was washed out into the circulation during resuscitation.


Effect of traumatic injury on sensitivity to insulin. Disturbances in carbohydrate homeostasis are metabolic hallmarks in the host response to trauma. Since alterations in insulin responsiveness, especially insulin resistance, have been related to the metabolic sequelae of shock, the present study evaluated insulin responsiveness in traumatic shock. Injury (LD50) of fasted, male Holtzman rats (115 plus or minus 20 gm) by tumbling in the Noble-Collip drum resulted in hyperglycemia in spite of a concomitant hyperinsulinemia. The ability of insulin to lower plasma glucose was evaluated at either three hours or 24 hours post-trauma by means of glucose and insulin tolerance tests. The injured rats showed glucose intolerance and hyperinsulinemia three hours after injury but showed a normal glucose tolerance and hypoinsulinemia on the day after injury. Insulin was ineffective in lowering plasma glucose at both of these times. Noble-Collip tumbling trauma induced no systemic changes in insulin responsiveness in vitro at either time as evaluated by 1) epididymal fat pad glucose oxidation of U-D-14C-glucose to 14CO2 or 2) hemidiaphragm incorporation of U-D-14C-glucose into glycogen. The data suggest that insulin resistance is not due to a decreased capacity of various tissues to respond to insulin.


Effects of spontaneous respiration on canine left ventricular function. The purpose of this study was to determine the mechanism of the decrease in left ventricular stroke volume during spontaneous inspiration. We determined the transmural pressures of the left heart by measuring left atrial and diastolic left ventricular pressures relative to esophageal pressure. We estimated the directional changes in end-systolic and end-diastolic volumes of the left ventricle by determining the transit time of sound transmission between two ultrasonic crystals facing each other across the minor axis of the left ventricle. Left ventricular stroke volume decreased with spontaneous inspiratory effort as pleural pressure fell, regardless of whether lung volume increased or remained constant. The stroke volume was decreased during the fall in pleural pressure because of an increase in end-systolic volume with an essentially unchanged diastolic volume. Thus, the decrease in stroke volume was due to a decrease in ejection, rather than a decrease in filling of the left ventricle. We believe that left ventricular ejection was impeded by the fall in pressure around the heart relative to the pressure in the aorta. In spite of the essentially constant diastolic volume, diastolic left ventricular transmural pressure rose, suggesting that spontaneous inspiration decreases the diastolic compliance of the left ventricle. The change in diastolic compliance contributed to the decrease in stroke volume but was not the primary cause.


Relationship between changes in left ventricular bipolar electrograms and regional myocardial blood flow during acute coronary artery occlusion in the dog. The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrograms, in open-chest dogs following acute coronary artery occlusion. We found that the degree of regional myocardial ischemia was related quantitatively to the reduction in amplitude recorded with bipolar electrograms in the subepicardium and subendocardium, and to the increase in duration of subepicardial electrograms. Other characteristics measured in electrograms did not relate to the degree of ischemia. Despite a comparable reduction in regional myocardial blood flow, subepicardial conduction delay exceeded that recorded in the subendocardium, which often exhibited accelerated conduction.


Sympathetic modulation of hypercapnic cerebral vasodilation in dogs. We measured cerebral blood flow using both the radioactive microsphere technique and the cerebral venous outflow technique in dogs anesthetized with chloralase. The effect of sympathetic stimulation on cerebral blood flow was observed during both normocapnia and prolonged hypercapnia using both blood flow techniques. The increase in blood flow with hypercapnia was the same with both methods. During hypercapnia the venous outflow method showed a 38% decrease and microspheres an 18% decrease in cerebral blood flow with sympathetic stimulation. At normal CO2, stimulation caused a decrease in cerebral venous flow: no change was observed with the microsphere method. Analysis of the blood flow patterns to extracerebral tissues and evaluation of extracerebral arterial reference samples failed to prove the existence of axial streaming and subsequent skimming of microspheres within the cephalic circulation. It is concluded that direct electrical stimulation of the sympathetic innervation of the cerebral vessels is capable of reducing cerebral blood flow even during a profound hypercapnic vasodilation.