Showing papers in "Annals of the New York Academy of Sciences in 1970"

Impedance Cardiography as a Noninvasive Method of Monitoring Cardiac Function and Other Parameters of the Cardiovascular System

Abstract: Classical physiology texts describe the basic function of the heart as a blood pump. Ironically, after centuries of research since William Harvey's disclosure of the nature of the circulatory system,I the pumping action of the heart remains an elusive parameter to measure without resorting to inconvenient, expensive, and somewhat traumatic procedures requiring sterile surgery to insert catheters into or near the heart. At the same time, relatively simple, noninvasive methods are available to record other parameters related to myocardial function such as electrical activity, pulse rate, and blood pressure. Obviously, a great need exists for a similarly simple noninvasive method of obtaining information concerning the mechanical activity of the heart. About 300 years elapsed following Harvey's classic experiment before Atzler and Lehmann attempted to utilize small transthoracic electrical impedance changes observed during the cardiac cycle to study myocardial function by a capacitance systern.2 Nyoboer and c o ~ o r k e r s ~ . ~ and others5 later modified and improved on this work. Geddes and Baker have published an excellent review of the use of electrical impedance measurements in the detection of a variety of physiological events? A previous report' presents our first results with the present impedance system to measure cardiac output by a somewhat dzerent approach. Smith and colleagues,8 Harley and associates? and Judy and co-workers1° have reported varying degrees of success in measuring cardiac output with this approach. Siege1 and Fabian\" have reported on the application of this system to the quantification of myocardial contractility. We have also reported on the time relations between left ventricular ejection and the negative value of dZ/dt.I* The purpose of this communication is to present the system described as the impedance cardiograph that has evolved after several years of research in this laboratory and some of its applications to measurements of parameters related to the cardiovascular system. The four-band electrode configuration is shown in FIGURE 1. Conductive strip electrodes, approximately 6 mrn wide, are placed, two around the neck and two around the abdomen. The outer two electrodes are spaced at least 3 cm away from the inner electrodes in order to obtain accurate readings and to avoid nonlinearities in the electrical parameters involved. Of the inner two electrodes, one is placed around the b a x of the neck and the second at the level of the xiphisternal joint. The outer two electrodes are positioned as shown. The electrodes are numbered 1, 2, 3, and 4 from the neck down and are connected to the impedance cardiograph by the appropriate, numbered clips on the patient-connecting cable of the instrument. A disposable tape-on electrode has been fabricated by the 3M Company, St. Paul, Minn. The electrode is constructed from one mil aluminum deposited on a polyester film and bonded to an adhesive backing, and usually does not require

Quenching of singlet oxygen

Abstract: Dye-sensitizcd photooxygenation of olefins, dienes and heterocyclic compounds proceeds via singlet oxygen, formed by energy transfer from triplet sensitizer t o oxygen.'%2 The dyes that sensitize photooxygenations are also sensitizers for photodynamic action, a term which refers to the detrimental effects on organisms of these dyes in the presence of light and oxygen3 Chlorophyll is among the most effective sensitizers for dye-sensitized photooxygenations of organic substrates. Photosynthetic organisms, however, are apparently protected from the lethal effects of their own chlorophyll by carotenoids. Mutants lacking carotenoids, and normal plants in which carotenoid syntehsis has been inhibited, are easily killed by light and oxygen; such organisms are also unusually sensitive t o the effects of sensitizing dye^.^-^ The mechanism of carotenoid protective action has been debated for some time. Tt is known that /3-~arotene '~~ and lycopene\" quench triplet sensitizers a t a diffusion controlled rate; however, since oxygen also quenches triplet sensitizers a t a comparable rate (to give singlet oxygen)',2, quenching of triplet chlorophyll by carotenes cannot be responsible ror the protective effect unless the local concentration of carotenes greatly exceeds that of oxygen. We speculated that if singlet oxygen was the reactive intermediate in the photodynamic effect, carotenoids might act by removing singlet oxygen, either by quenching in some manner or by reaction. This mechanism can easily be distinguished kinetically from sensitizer quenching.1° Scheme 1 shows mechanisms in which either triplet sensitizer or singlet oxygen are quenched.

On Eigenvalues and Colorings of Graphs, II

Abstract: A. J. Hoffman, I . B . M . , Nev York* and Leonard Howes, The City University of N. Y. 1. I n t r o d u c t i o n . I n t h e l a s t s e c t i o n of a p rev ious paper w i t h t h e same t i t l e [l], s e v e r a l theorems r e l a t i n g t h e e igenva lues of t h e adjacency ma t r ix of a graph G t o t h e c o l o r i n g number and r e l a t e d f u n c t i o n s of G w e r e s t a t e d without proof . The purpose of t h e pres e n t paper is t o supply t h e p roof s of t hose theorems, and some ostens i b l y s t r o n g e r r e s u l t s ob ta ined l a t e r . To e x p l a i n o u r r e s u l t s , some d e f i n i t i o n s a r e r equ i r ed . I f G is a graph, A(G)-the adjacency ma t r ix of G is a matr ix w i t h r o w s and columns corresponding t o t h e v e r t i c e s o f G , and A(G) = A = ( a i j ) = 1 if i and j a r e ad jacen t v e r t i c e s , 0 o the rwise . (A l l graphs a r e f i n i t e , und i r ec t ed , w i t h a t most one edge j o i n i n g a p a i r of v e r t i c e s , and no edge j o i n i n g a ve r t ex t o i t s e l f . ) I f G i s a graph, G t h e complementary graph o f G is def ined by t h e equa t ion J I = A(G) + A(;) . A c l i q u e is a graph G such t h a t A(G) = J I , -

Kinetics of indocyanine green removal from the blood

Abstract: Studies of kinetics of dye removal from the blood have greatly advanced our understanding of hepatic physiology. The dyes used mainly to investigate hepatic circulation and function are sulfobromophthalein, rose bengal and indocyanine green (ICG). This paper will be concerned with kinetics of hepatic removal of ICG. This dye appears to be bound primarily to alpha 1-lipoproteins in serum.' It does not exhibit extrahepatic removal or enterohepatic c i r c u l a t i ~ n , ~ ~ ~ is not chemically altered during its transit through the liver 2 9 4 and is nontoxic in the doses e m p l ~ y e d . ~ Accurate and continous recording of ICG blood levels is possible using dichromatic ear den~itometry.~ Different doses of ICG have been used to test liver function in man, ranging from 0.25-5 mg/kg body weight. Studies of clearance of 0.25-0.5 mg of ICG are relatively insensitive in detecting mild liver disease, whereas removal of 5.0 mg/kg of this dye furnishes a highly sensitive index to hepatic function in these instance^.^ Liver blood flow is rate limiting with low dye concentrations, and the amount of ICG removed from the circulation per unit of time is primarily a measure of liver blood flow. The ability of hepatocytes to take up dye becomes rate limiting at very high dye concentrations, and ICG clearance under these circumstances represents a sensitive measure of liver cell function. Clinically, it is not possible to use a sufficiently large dose of dye to measure capacity of hepatocytes to remove ICG independent of blood flow. Nevertheless, it should be possible to calculate maximal removal capacity from several submaximal values if hepatic uptake of dyes obeys Michaelis-Menten kinetics.

The relationship of plasma volume, portal hypertension, ascites, and renal sodium retention in cirrhosis: the overflow theory of ascites formation

Abstract: Renal sodium retention, ascites, and portal hypertension coexist in cirrhosis. It is generally held that renal sodium retention results from ascites formation. According to this belief, ascites is initiated by portal hypertension through leakage of excessive lymph from a congested liver, causing effective plasma volume to contract and renal sodium retention to follow as a consequence of this contraction. We would like to propose an alternate theory: that ascites formation in cirrhosis is a consequence of plasma volume expansion, and that renal sodium retention helps to promote this expansion. In this overflow theory of ascites formation portal hypertension is considered to expand mechanically the splanchnic bed, creating the condition for ascites to form as plasma volume expands further with the development of renal sodium retention. Such a theory reopens the question of what is the ultimate stimulus for renal sodium retention in cirrhosis with ascites. We first questioned the traditional reason given for renal sodium retention in cirrhosis when we confirmed the findings of many investigators that total plasma volume is elevated in the presence of ascites.1 We presented evidence that this elevation was not an artifact due to leakage of radioactively tagged albumin into ascites or the thoracic duct lymph space during the period of equilibration of this material in the plasma. Portal hypertension appeared to be the cause of the plasma volume expansion because the plasma volume correlated well with wedged hepatic vein pressure and fell following relief of portal hypertension by means of a portacaval anastomosis. Subsequently, we showed that portal pressure does not fall during the spontaneous loss of ascites and the appearance of sodium in the urine, and total plasma volume remains constant, suggesting that nonportal, or effective plasma volume does not contract when ascites is forming. 2 Recently, we have made two additional observations which are the subject of this communication: ( 1 ) The rate of ascites formation does not increase tollowing paracentesis nor does the plasma volume fall, both of which should occur if the traditional concept of ascites formation is correct. (2) Ascites could be made to reform in a patient with cirrhosis by administering a sodium-retaining hormone. This observation indicates that it is possible for ascites to form as a consequence of plasma-volume expansion in cirrhosis.

Mitochondrial responses to carbon monoxide toxicity

Abstract: CO not only bonds hematin iron in blood hemoglobin but also ligands hematin iron atoms of cytochrome a/sub 3/. Nonuniform distribution of CO means that rapidly metabolizing tissue are more susceptible to CO toxicity. Mitochondria are protected by branching and cushioning mechanism so CO toxicity response is not linear as in COHb formation. O/sub 2/ flux in respiratory change is not altered by CO. In these in vitro experiments, as little as 100 ppM CO transiently disrupted cytochrome system in transition from anoxia to nonmoxia, slowing the oxidaton of the chain. Pigeon mitochondria were extremely sensitive to CO when in metabolically-active (uncoupled) state. Increased binding of CO to cytochrome a/sub 3/ during anoxia was observed.

Neoplasia and downs syndrome

Abstract: When a child with Down’s syndrome (DS) and leukemia was admitted to the ward during my internship in 1947, experienced practitioners recalled other such cases but saw nothing special in this “double jeopardy.” An etiologic relationship was first suggested in 1954 by Bernard and coworkers,l who described three cases in France. Two years later, a greater appreciation of the frequency with which the two diseases occurred together came from reports of four children so affected in North Carolina and another four in Minne~o ta .~ These numbers seemed more than one would expect by chance in these locales. Krivit and Good,4 the Minnesota investigators, then hit upon the idea of sending questionnaires to 300 hospitals with pediatric services concerning children seen at each with DS and leukemia, under four years of age, within a specified calendar interval. There were only 125 responses, and although the study fell far short of complete ascertainment, three times more children with both diseases were observed than were expected by chance in the entire nation during the interval. Subsequently, the risk leukemia in children with DS was found to be many times greater than that for the general population.5--”

Dye‐sensitized photooxidation of proteins*

Abstract: In 1900, Raab' reported that living cells could be killed by illumination in the presence of certain dyes; a short time later it was found that molecular oxygen was required for this process.z Such dye-sensitized photooxidation processes are usually termed \" photodynamic \" reactions by biologist^.^ Although the killing of cells by photodynamic treatment is a rather complicated process, in the final analysis it must result from the photooxidation of critical component molecules of the cell, such as proteins and nucleic acids. The present paper is concerned with the protein aspects of this problem. The first report of photodynamic effects on proteins was in 1903 when von Tappeiner and his students showed that enzymes such as diastase, invertase and pepsin were inactivated by illumination in the presence of e o s h 4 Since that time a great deal of work has been done on the photodynamic degradation of proteins, especially enzymes. To date, over sixty crystalline proteins have been studied in this regard.3 Since this conference is devoted to singlet oxygen, it should be pointed out that not all cases of the dye-sensitized photooxidation of proteins can be interpreted in terms of a singlet-oxygen mechanism. Singlet oxygen may be involved in the inactivations sensitized by many types of dyes, such as the thiazines and the fluoresceins. However, in other cases, as with flavine and anthraquinone sensitizers, singlet oxygen appears to play only a minor role. Even with those dyes in which singlet oxygen is presumed to be involved, the evidence is only circumstantial, since studies of the effects of singlet oxygen on amino acids and proteins have not yet been reported in the literature. Since space is very limited, only the more recent references on each topic will be listed. These may be consulted for a more extensive entry into the literature on the sensitized photooxidation of proteins.

Covering and packing in graphs, i.

Abstract: T h e r e i s cons iderable i n t e r e s t i n two r e l a t e d types of graph theore t ic problems. m i n i m u m number of g r a p h s with a c e r t a i n p r o p e r t y whose union is a given graph , The cor responding packing p r o b l e m , on the o ther hand , s e e k s the m a x i m u m number of subgraphs of a given g r a p h which have the opposite proper ty . subgraphs a r e r e g a r d e d as s e t s of l ines . s tudy of t h e s e two types A cover ing problem involves finding the

The comparative ultrastructure of the algal chloroplast

Abstract: In preparing this paper, I had two big decisions to make. First, whose classification of the algae should I use, and second, which terminology should I use to describe chloroplast ultrastructure? I decided to use Christensen’s classification of the algae because overall it correlates fairly well with chloroplast ultrastructure. Since Christensen’s classification of the algae has not yet been mentioned in this conference, I will summarize it briefly. Christensen separates the algae into four divisions: the Cyanophyta, comprising one class, the Cyanophyceae; the Rhodophyta, comprising one class, the Rhodophyceae; the Chromophyta, comprising nine classes, the Cryptophyceae, Dinophyceae, Raphidophyceae (the Chloromonads) , Chrysophyceae, Haptophyceae, Craspedophyceae (the collared flagellates, which I will not mention again since none are known to have chloroplasts), the Bacillariophyceae, Xanthophyceae, and Phaeophyceae; and the Chlorophyta, into which he puts four classes. These are the Euglenophyceae, the Chlorophyceae, and two groups of algae that he removed from the green algae because of ‘differences in flagellation, the Prasinophyceae and Loxophyceae. The differences between these two classes are not clear-cut, and in this paper I will follow Peterfi and Manton * and lump the Loxophyceae with the Prasinophyceae. The question of which terminology of chloroplast ultrastructure to use is a more difficult one. For all other cell organelles, electron microscopists have now more or less agreed on a standard terminology. Who, for example, would still call the endoplasmic reticulum alpha cytomembranes? However, if you want to describe only the membranes of a chloroplast, you have a dozen odd terms to choose from-discs, thylakoids, frets, partitions, lamellae, lamellations, stacks, grana, bands-despite the fact that the membranes of all chloroplasts are built on a basic structural plan. The basic unit of the chloroplast is a flattened membrane-limited sac which Menke has named a thylakoid. Others, myself included, have called these sacs discs. In the interest of a uniform terminology, I propose that we abandon the word disc and use thylakoid henceforth. I propose to use the wbrd granum specifically to refer to a stack of appressed thylakoids, many of which are short and round and of approximately equal diameter, whereas others, which are interspersed with these, extend across the stroma to form part of a neighboring granum or even of the same granum. This leaves the problem of what to call the groups of two or three appressed or loosely associated thylakoids which extend across the chloroplasts of most algae. Stacks is probably the most descriptive word, but it is not a very euphonious one, and it implies a pile of some height rather than an extended flat layer.

Studies of Epstein-Barr virus.

Abstract: This paper constitutes an up-to-date summary of some of the EB virus research activities conducted in the Roswell Park Memorial Institute Viral Oncology Section. The investigators associated with the studies reported here include Drs. Julius Horoszewicz, Virginia Dunkel, Yorio Hinuma, Robert Zeigel, Mitsuru Konn, Junji Yamaguchi, Luis Avila, and John Gentile and James Blakeslee and Mrs. Susan Leong. The primary emphasis of the program has been directed at elucidating the role in human disease of the herpes-type virus (EB virus) found in numerous cultures of human hematopoietic cell lines and Burkitt lymphoma cell lines.

The carbon monoxide body stores

Abstract: The localization of carbon monoxide in the tissues of man and animals remains a basic problem for study. It is clear that most of the body CO stores are found in blood chemically bound to hemoglobin; a number of investigat0rs ,2 ,~J~J~J* however, have obtained evidence that 10-15% of the total body CO is located in extravascular tissues in normal man. (Values as high as 25% have been obtained in dogs8). It is likely that most of the extravascular CO is chemically bound to hemoproteins such as myoglobin, cytochromes a3 and P450, catalase, peroxidases, and others. Less than 1 % of the body CO stores appears to be physically dissolved in body fluids, since the partial pressure of CO in tissues is very small, even when blood carboxyhemoglobin (COHB) concentrations are elevated, and in addition, CO is relatively insoluble in water. In this paper, I will discuss some of the physiological variables that influence partition of CO between blood and extravascular tissues. In addition, I will review recent experimental data that pertain to the processes that influence the total body CO stores.

Myocardial and systemic responses to carboxyhemoglobin

Abstract: John Haldane, in a series of courageous experiments performed on himself in 1895,' concluded that the symptoms of carbon monoxide intoxication closely resembled the effects produced by exposure to decreased concentrations of oxygen. Although he did not observe serious symptoms at rest until his hemoglobin was at least one-third saturated with carbon monoxide, exertion produced mild dyspnea and palpitations when as little as 14% carboxyhemoglobin (COHB) was present. Haggard2 in 1921 and Chiodi and coworkers3 in 1941 observed increases in cardiac output and pulse rate with COHB concentrations between 16 and 20%. The latter investigators did not measure changes in minute ventilation contrasting to the hyperventilation observed by both Haldanel and Haggard2 in their studies. Recently, Chevalier and associates* observed that the oxygen debt incurred during exercise-a measure of overall circulatory integrity-increased significantly when the COHB concentration was raised to 5 % . We have studied the physiologic effects of relatively small amounts of COHB by measuring the acute cardiorespiratory changes following the inhalation of carbon monoxide in human subjects and in dogs.5 This paper reviews certain theoretic aspects of systemic and myocardial oxygen exchange and summarizes our findings. THEORETIC ONSIDERATIONS

Photosensitized oxygenation as a function of the triplet energy of sensitizers

Abstract: Evidence has accumulated over the past years that singlet oxygen, presumably in its lAg state, is the responsible intermediate in certain photooxygenation reactions of the two thoroughly studied classes of organic substrates: (1 ) substrates that contain the structural element of cis-l,3-dienes such as cyclic 1,3-dienes, aromatics such as anthracene, and several heterocyclic compounds such as furans, and (2) olefins containing allylic hydrogen atoms. Class 1 substrates give rise to cyclic peroxides in 1,4-cycloaddition reactions analogous to the adducts produced in Diels-Alder reactions, whereas Class 2 compounds form allylic hydroperoxides in which the original double bond has shifted into the allylic position, Le., the hydroperoxide formation occurs analogous to the " ene " r e a ~ t i 0 n . I ~

The physics, chemistry, and biology, of singlet molecular oxygen*

Abstract: The physics, chemistry, and biology of singlet molecular oxygen are topics of the liveliest current research interest. Yet just six years ago, singlet oxygen was considered to be a molecular species of passing astrophysical interest, and rather limited as a research subject. Recent discoveries concerning the easy generation of singlet molecular oxygen in large amounts, its ready detection by a variety of methods, and its unusual chemical reactivities, have made this subject one of the most rapidly developing research fields. There is possibly no better example of the interplay of various disciplines, from the most abstruse theory (antisymmetrized molecular orbitals) and abstruse measurements (high resolution spectroscopy of gases) to the most practical applications (mechanism of smog production). Singlet molecular oxygen, even though it is an excited species, is proving to be an almost ubiquitous intermediate in systems that were once considered to be the exclusive domain of normal (triplet) oxygen. In this paper we shall attempt to give a panoramic view of singlet molecular oxygen: what it is, what its properties are, how it can be made and detected, and various mechanisms by which it seems to be involved in physical, chemical, and biological processes. Spectroscopic observations on singlet molecular oxygen were made as early as the 1930's. Childs and Mecke (1931) made' absolute intensity measurements on light absorption to the 'C: state of oxygen, deducing a value of 7.1 seconds for the intrinsic mean lifetime of this excited state; Ellis and Kneser (1933) reported2p3 the spectrum for absorption to the 'A, state of oxygen. High resolution studies later (1947-48) supplied the physical data now known for singlet and triplet oxygen given in TABLE 1. It was not until 1965 that absolute absorption measurements were made4 (Badger et al.) for the absorption to the 'Ag state, giving the astonishingly long intrinsic mean lifetime of 2,700 seconds (45 min). (The lifetimes given are for the limiting condition of zero pressure and are much shortened by environmental perturbation effects.) The physical data on the three lowest electronic states of molecular oxygen reveal very small structural changes upon excitation, as shown by the near constancy of the internuclear distances. The potential curves for molecular oxygen (FIGURE 1) reflect this by the near coincidence of the potential minima for the three lowest states. The potential curves reveal also the high stability of O2 toward dissociation, the D i value (corresponding to the heat of dissociation) being 5.080 eV (117.2 kcal/mole). Another feature revealed by the potential curves of FIGURE 1 is that the

Serious infections caused by diphtheroids.

Abstract: Corynebacteria are gram-positive, nonmotile, catalase-positive, pleomorphic bacilli that are part of the normal human skin, mucus membrane, and intestinal flora.l.2 With the exception of Corynebacterium diphtheriae, these organisms (i.e., diphtheroids) have traditionally been considered to be nonpathogenic for man. These ubiquitous organisms frequently contaminate clinical cultures. For example, in our experience and that of others: as many as 1-3% of all blood cultures contain diphtheroids. However, diphtheroids are capable of producing serious disease in man. The purpose of this report is to describe 52 cases of serious infection caused by diphtheroid organisms collected from our experience and from reports in the literature. Recognition of diphtheroids as a cause of infection may be difficult, not only because they are common contaminants of clinical cultures but also because they may be confused with certain strains of streptococci" and with Listeria monocytogenes. Indeed, some of the early reports of disease caused by diphtheroids were subsequently shown to have been caused by L. mono~ytogenes.~ Another problem with recognition of diphtheroid infections is the fact that these organisms may require prolonged incubation for primary isolation. In the cases to be reported, a median of five days of incubation was required for primary isolation, but as long as two weeks of incubation was necessary for some strains. Further difficulties arise from fastidious growth requirements of some strains. For example, at least 16 of the 52 patients to be reported had infecting organisms that required anaerobic or microaerophilic conditions. In addition, several diphtheroid organisms have been isolated only with hypertonic media.6 The clinical data on the 52 patients are shown in TABLES 1 and 2. TABLE 3 summarizes the diseases caused by diphtheroids in the 52 patients. Thirty-one of the 52 patients, or 60%, had bacterial endocarditis, as evidenced by sustained bacteremia and a clinical course suggestive of endocarditis. The other 2 1 patients had a variety of infections including meningitis, osteomyelitis, and bacteremia. It is of interest that anaerobic or microaerophilic diphtheroids were the causative microorganisms in the majority of patients (12/21) with infections other than endocarditis. By contrast, only four of the 31 diphtheroid strains that produced endocarditis were noted to be anaerobic or microaerophilic. The predisposing conditions in the 3 1 patients with diphtheroid endocarditis are listed in TABLE 4. There was a striking association of diphtheroid endocraditis with cardiac surgery and with valvular prostheses. Ten of the 31 patients developed bacterial endocarditis within two months after undergoing cardiac surgery

POLYAMINE CHANGES DURING DEVELOPMENT OF Drosophila Melanogaster

Abstract: The significance of polyamines in biological processes has been recognized since the initial discovery of the requirement by Hemophilus parainfluenzae for either putrescine, spermidine or spermine as an essential growth factor.l3 Since this initial observation, the polyamines have been reported to be growth factors for various microorganisms,g plants,2 cultured mammalian cells,13 and insects.F+ In addition the polyamines have been implicated as prominent polycations, closely associated with nucleate biosynthesis in rapid growth systems including microorganisms,” regenerating rat The relatively rapid development and well-characterized biological parameters of Drosuphila melanogaster have facilitated this first report concerning polyamine levels throughout the life cycle of a multicellular organism. Larval, pupal, and adult stages of D . melanogaster have been previously demonstrated to contain spermidine and putrescine,x and the preferential association of spermidine with the cell nuclei of isolated larval salivary glands has been demonstrated by radioautographic procedures.* Also, the incorporation of labeled uridine into RNA of salivary gland nuclei is enhanced by exogenous spermidine, when added to organ-cultured salivary glands.8 The method of Seiler and Wiechmann,21 which relies on the conversion of spermidine and spermine to highly fluorescent I-dimethylaminonaphthalene-5sulfonamide (dansyl) derivatives, was employed for quantitative assays. However, the solvent system was modified to allow the simultaneous direct quantitation of dansyl putrescine, which could not be sufficiently resolved from dansyl ammonia by the original method. l.c and the chick

Bacteremia with and without meningitis due to yersinia enterocolitica, edwards1ella tarda, comamonas terrigena, and pseudomonas maltophilia

Abstract: This report describes four cases of bacteremia (two associated with meningitis) in which four unusual gram-negative organisms were identified as etiologic agents: Yersinia enterocolitica, indol-positive (meningitis and panophthalmitis), Edwardsiella tarda (meningitis) , Comamonas (Pseudomonas) terrigena (acute bacterial endocarditis), and Pseudomonas maltophilia (pneumonia). The isolation of E. tardal and of Y . enterocolitica2 from these cases are the first known instances in which meningitis was caused by these organisms. In addition, the latter case is the only culture-proven human Y . enterocolitica infection in the United States in 21 years (1947-1968). The finding of C . (P.) terrigena is, to my knowledge, the only reported involvement of this organism as an agent of bacteremia. P. maltophilia has previously been recovered from blood cultures. All of the organisms described would have been misdiagnosed, had not certain specific methods and procedures been used. Except for the E. tarda meningitis, where there was a history of SLE and steroid therapy, the other three patients had no previous history of antibiotic treatment or underlying debilitating disease. All four became ill outside the hospital. The E. tarda infection proved fatal, while the other three recovered on antibiotic therapy; the patient with Y . enterocolitica meningitis suffered complete loss of vision in one eye. The report includes brief case histories and literature reviews of each organism described. Biochemical and physiologic characterizations and diagnostic criteria useful in identification, as well as antibiotic susceptibility data, are presented.

On the physical basis of cell morphogenesis

Abstract: Morphogenetic mechanisms are so diverse that it is useful to classify them in terms of the processes that change size and shape of objects in general. Two broadcategories of effective processes are: (1) the addition or loss of discrete elements of volume, and (2) the deformation or expansion of preexisting volume. The first process is evident in the self-assembly of viruses from their parts, the deposition of cellulose on secondary walls, and assembly phenomena in general (e.g., slime mold aggregation). It is characteristic of this mode of morphogenesis that the preexisting structure need not be altered or stretched during growth. The process is akin to the addition of bricks to a wall. The other type of process, expansion (contraction) of preexisting surface and volume, is involved whenever, as an obligatory feature of morphogenesis, preexisting points in the growing object move relative to one another. The analogy here would be the inflation of a balloon. As is well known, marks placed on the growth zone of growing plant parts do move with respect to one another, This mode of morphogenesis appears to be typical for membranebounded structures.

Carbon monoxide bonding in hemeproteins

Abstract: Although carbon monoxide is a neutral diatomic molecule, it will serve as a ligand to metals to form metal carbonyls. However, CO is highly selective not only as to the metal, but also in regard to the oxidation and spin states of the metal. Metal-CO binding in biological systems depends not only upon the presence of a suitable metal in the right state but also upon the availability of a binding site either by displacement of another ligand by CO or by addition of CO to an unoccupied site, the case now accepted for deoxyhemoglobin and deoxymyoglobin. Bonding between metal and CO ligand in metal carbonyls has been described as “synergistic” in the sense that, at least formally, two types of bonding which mutually reinforce each other can be evoked.’ The neutral CO molecule can serve as a sigma-donor, e.g., donating an electron pair through carbon for sharing with the metal. However, the CO ligand can also serve as a pi-electron acceptor from filled metal orbitals of appropriate symmetry. The greater the pi-character of the metal-carbon bond, the smaller the pi-character associated with the intraligand or C-0 bond. In valence bond formalism species I and I1 represent contributing species. The synergistic aspect of the bonding emerges from the fact that a stronger metal pi-donor to ligand pi-acceptor interaction will enhance the ligand sigma-donor to metal sigma-acceptor interaction, and vice versa. In other words,

Polyamine metabolism in the central and peripheral nervous system

Abstract: The complexity of the nervous system tissue relative to other tissues of the organism is such that it is in some respects less suitable for biochemical study; however, because of its unique character, the study of the nervous system may provide some special insight into both the metabolism and function of the polyamines. The neuron is not only one of the most actively biosynthesizing cells in the animal body, but it also, along with its supporting cells, provides the means for communication, learning and memory. In 1924, Dudley and coworkers isolated spermine from bovine brain; this was the first indication that the polyamines were present in the nervous system.l Subsequently, Hamalainen determined the spermine content of some discrete areas of the humain brain.? With the development of improved analytical procedures, employing ion exchange chromatography, Rosenthal and Tabor established the presence of both spermidine and spermine in the rat brain.3 This was followed by a report by Kewitz, in 1959, of the occurrence of putrescine and spermidine in pig brain.4 Subsequently, it was reported that S-adenosylmethionine, a precursor of both spermidine and spermine was present in, and synthesized by, the rat brain.5 The first information on the distribution of the polyamines in discrete regions of the nervous system was the result of a study of the rabbit brain by Shimizu and associates in 1964.G These investigators also noted marked differences in the polyamine concentration in gray and white matter of human brain cortex. More recently, putrescine has also been isolated from the human brain.7 Although the polyamines and their metabolic precursors are present in relatively large amounts in the central nervous system (CNS), quantitatively the polyamines are the major amine constituents, there is no definite knowledge of their biological function. Our studies are directed toward clarification of polyamine metabolism and function in the nervous system.

Ethics in cooperative clinical trials.

Abstract: The ethical problems encountered in the design, development, and execution of cooperative clinical trials are, in general, similar to those encountered by the individual research worker. But these problems are at times more complex and their solutions more difficult, principally because of the variation in opinion among participating clinics. We shall try to give special attention to the ethical problems that are unique to cooperative trials, but shall often deal with those that are common to all clinical research. By contrast with many participants in this conference, our world of concern is with the treatment of sick patients, not with volunteers. The investigator in most cooperative studies is also the patient’s physician, and that presents very special ethical topics for discussion.

Physiological and biochemical effects on rats and mice exposed to small concentrations of carbon monoxide for long periods

Abstract: Pathogen-free mice and rats were exposed in chambers to 50 ppM CO for 5 days/wk (approx. 95 hr) for 3 months to 2 yr. Reproduction, growth, aging, various metabolic parameters, susceptibility to experimental infection, and mortality were not affected by CO. In general, no effect other than that attributed to chamber effect (e.g., initial heartbeat and ECG) was observed.

Factors influencing the inhibitory effect of carbon monoxide on cytochrome P-450-catalyzed mixed function oxidation reactions.

Abstract: Liver microsomal reactions under conditions of high rates of electron flux were more CO sensitive, and the Warburg partition coefficient for CO and O/sub 2/ with cytochrome P-450 was increased.

Physiological Significance of Polyphosphoinositides in Brain

Abstract: Our interest in the polyphosphoinositides of brain centers around the rapid turnover of their monoesterified phosphate groups (Brockerhoff & Ballou, 1962). Recentiy, enzymes that catalzye phosphorylation and dephosphorylation of the polyphosphoinositides have been studied. These are triphosphoinositide (TPI) phosphomonoesterase (Dawson & Thompson, 1964), phosphatidylinositol (PI) kinase (Colodzin & Kennedy, 1965: Kai et al., 1966b) and diphosphoinositide (DPI) kinase (Kai et al., 1968). Outside the nervous system, liver PI kinase was extensively studied by Michell & Hawthorne (1965) and Michell and co-workers ( 1967) ; kidney TPI phosphomonoesterase was investigated by Lee and colleagues (1968). The enzyme reactions are summarized below :