Showing papers by "University of Maryland, Baltimore published in 1974"
TL;DR: The spectrum of illness and the immunologic response produced by cholera in volunteers were studied and Titers of vibriocidal antibody rose after diarrhea, peaked the second week after challenge, and rapidly fell during the next four weeks.
Abstract: The spectrum of illness and the immunologic response produced by cholera in volunteers were studied. The strains of Vibrio cholerae used were classical Inaba 569B and classical Ogawa 395. An oral dose of 108 organisms in buffered saline was required to induce the diarrhea of cholera. When given with live organisms, NaHCO3 lowered the infecting dose from 108 to 104 organisms. Clinical manifestations of infection varied from culturally positive formed stools to "rice water" diarrhea. Severe diarrhea did not have an explosive onset but rather progressively increased in volume during a 24-hr period. In 45% of cases the stool was positive for V. cholerae before the onset of diarrhea. Titers of vibriocidal antibody rose after diarrhea, peaked the second week after challenge, and rapidly fell during the next four weeks.
317 citations
TL;DR: A critical review of the ecology of chigger-borne rickettsiosis (scrub typhus) is presented, based upon a synthesis of both published and unpublished information, and considers that chiggers in the L. deliense -group constitute the major vectors of this disease, and it is considered that they also serve as the primary reservoir of the infection in nature.
Abstract: A critical review of the ecology of chigger-borne rickettsiosis (scrub typhus) is presented, based upon a synthesis of both published and unpublished information. All the epidemiological characteristics of chigger-borne typhus are attributable to the habits and other features of the vector chiggers. This rickettsiosis is found in a remarkably broad range of habitats, presumably in all areas where members of the Leptotrombidium deliense -group of chiggers and wild rats of the genus Rattus coexist, ranging from semideserts to alpine reaches in the mountains, and from sandy beaches to dense but disturbed forest. The habitats are characterized by the presence of changing ecological conditions, wrought by man or nature, and expressed by transitional types of vegetation, even if these are in circumscribed foci as along jungle streams. The intimate association between the rats, chiggers and secondary vegetation (which together with Rickettsia tsutsugamushi , the etiological agent, constitute the “zoonotic tetrad”) is an ancient one. We postulate that as Rattus and associated chiggers of the subgenus Leptotrombidium penetrated new areas and habitats, they diversified, and as the chiggers adapted to other hosts in the new regions, such mammals became secondarily involved in the ecology of the rickettsiosis. Chiggers in the L. deliense -group constitute the major vectors of this disease, and we consider that they also serve as the primary reservoir of the infection in nature, perpetuating the cycle by transovarian transmission of the rickettsiae from the naturally infected female mite to the next generation. While chiggers can acquire rickettsiae from a rodent host by feeding, laboratory data suggest that only rarely can this result in infection in another mammal, whether by a chigger that has become infected while feeding and then reattaching to a second host (which is unusual in itself) or by transovarially infected progeny. However, while such an event may be difficult to demonstrate in the laboratory, the same low percentage of success in the field would be significant in the natural cycle because of the vast numbers of chiggers involved, and because of the amplification that would ensue by transovarian transmissionof acquired infection over a period of generations. Small mammals (“theraphions”) like rats, voles, and tree-shrews which are primarily ground-dwelling are important in the ecologyof the rickettsiosis by serving as major hosts of the vector chiggers. Arboreal rodents and commensal rats play little role in the infection, apparently because they seldom come in contact with ground infested with the L. deliense -group. Rickettsia tsutsugamushi differs significantly from other members of the genus, and the similarities between them apparently represent convergence towards existence as intracellular parasites with cycles in both mammals and arthropods. The so-called serotypes of the agent, in contrast, are quite divergent. The widespread range of certain serotypes, and the fact that they may be transmitted by several species of chiggers suggest that infection acquired from theraphions may be significant in the ecology of the rickettsiosis. By using chiggers of the L. deliense -complex and wild rats as indicators of the presence of this infection, “oasis chigger-borne rickettsiosis” has been demonstrated among relict faunae in “ecological islands.” Such faunal data indicate that the infection may be present in areas where it has not yet been demonstrated, as in northern Iran and some southern republics of the U.S.S.R., parts of Tibet, Sinkiang, etc.
222 citations
TL;DR: In this article, the authors evaluated human immunity acquired after cholera or provided by choline vaccines and found that immunity, either naturally acquired or vaccine-induced, appeared to be directed against the vibrio rather than against the toxin.
Abstract: Human immunity acquired after cholera or provided by cholera vaccines was evaluated. Previous diarrhea caused by infection with Vibrio cholerae induced complete protection against diarrhea after a second challenge with the homologous organism four to 12 months later; vibrios were recovered from only one of 21 patients challenged with the homologous organism. Four of six other men challenged again after the same interval with a heterologous serotype developed mild diarrhea. A whole-cell Inaba vaccine, given either parenterally or orally, produced significant protection against excretion of the organisms and lowered the incidence and severity of diarrhea; the vaccine was more effective when administered parenterally. A partially purified toxoid vaccine also provided some protection. An individual's immunity either to infection or to diarrhea was not correlated with his serum titer of vibriocidal antibody or his serum titer of antitoxin. Immunity, either naturally acquired or vaccine-induced, appeared to be directed against the vibrio rather than against the toxin. At present, cholera vaccines are less effective than previous infection in prevention of subsequent illness.
162 citations
TL;DR: Administration of vinblastine in two doses intraperitoneally to rats induced a prominent formation of autophagic vacuoles in rat liver parenchymal cells, and therefore, offers an excellent model for future studies on autophagy.
139 citations
TL;DR: Data suggesting that hyperthermia in conjunction with standard megavoltage radiation may present an alternative for circumventing the oxygen problem is suggested.
Abstract: THE American Cancer Society estimates that 250,000 people in the United States will die from cancer in 1974 and it has been speculated that 100,000 of them will die because of failure to control the primary tumour site1. In the report of a 1972 conference on particle accelerators in radiation therapy Bagshaw said: “… perhaps the most critical factor in determining success or failure in the sterilisation of a localised neoplasm with standard megavoltage radiation is the state of oxygenation of the cells being irradiated …”2. Cells which are poorly oxygenated when irradiated are more resistant to conventional X radiation than those which are well oxygenated. Many tumours are hypoxic and thus may be more resistant to radiation than the well oxygenated surrounding normal tissue. Considerable time and effort have been expended during the past decade in attempts to circumvent this problem. Efforts are currently focused on the use of heavy particles. We now have data suggesting that hyperthermia in conjunction with standard megavoltage radiation may present an alternative for circumventing the oxygen problem.
124 citations
TL;DR: It is indicated that extracellular acidosis protects Ehrlich ascites tumor cells and rat kidney cortex cells against injury from anoxia and production of protons by anoxic cells may be a protective feedback mechanism.
Abstract: The present study indicates that extracellular acidosis protects Ehrlich ascites tumor cells and rat kidney cortex cells against injury from anoxia. Parameters measured included cell potassium, adenosine 5'-triphosphate, and uptake of vital dyes. Cells survived longer at a p H of 5.6 to 6.5 than at a p H of 7.4; p H 7.9 was most detrimental. These findings indicate that production of protons by anoxic cells may be a protective feedback mechanism.
111 citations
TL;DR: The effects of acute lethal injury on the cell is summarized and a hypothesis of progression through the stages and the reversibility is discussed.
Abstract: Summary In this paper we have summarized the effects of acute lethal injury on the cell. Such injuries are defined as injuries that result in cell death within a relatively short period of time usually minutes or hours. Following death; the cell undergoes necrosis. Ultrastructural and biochemical methods are needed to study pathophysiology. The cell passes through a series of stages numbered 1 through 7. Stages 1 through 4 are reversible while 5 through 7 are irreversible. Injuries resulting in acute cell death and necrosis include direct damage to the cell membrane, for example by antibody and complement or non-penetrating mercurials or interference with mitochondrial energy supply as in ischemia. More complex injuries such as chemical toxicity in vivo probably act through these means. A hypothesis of progression through the stages and the reversibility is discussed.
108 citations
TL;DR: Two tyrosinase isoenzymes (EC1.1 and EC1.2) have been highly purified from Vibrio tyrosInaticus and represent the first characterization of tyros in bacteria from eubacteria.
93 citations
TL;DR: This result agrees with the conclusion of Kant and Steck that the dehydrogenase specific sites are located on the cytoplasmic surface of the membrane and suggests that the interaction between this enzyme and the membrane may have a physiological function.
90 citations
TL;DR: The results indicate that rapid membrane permeability changes of EATC follow fixative action, consistent with known greater stabilizing effects of GA on model protein systems since cells were also rendered relatively stable to osmotic stress during fixation.
Abstract: Effects of fixation with glutaraldehyde (GA), glutaraldehyde-osmium tetroxide (GA-OsO4), and osmium tetroxide (OsO4) on ion and ATP content, cell volume, vital dye staining, and stability to mechanical and thermal stress were studied in Ehrlich ascites tumor cells (EATC). Among variables investigated were fixation time, fixative concentration, temperature, osmolality of the fixative agent and buffer, total osmolality of the fixative solution, osmolality of the postfixation buffer, and time of postfixation treatment in buffer (Sutherland, R. M., et al. 1967. J. Cell Physiol. 69:185.). Rapid loss of potassium, exchangeable magnesium, and ATP, and increase of vital dye uptake and electrical conductivity occurred with all fixatives studied. These changes were virtually immediate with GA-OsO4 or OsO4 but slower with GA (in the latter case they were dependent on fixative temperature and concentration) (Foot, N. C. 1950. In McClung's Handbook of Microscopical Technique. 3rd edition. 564.). Total fixative osmolality had a marked effect on cell volume with OsO4 but little or no effect with GA or GA-OsO4. Osmolality of the buffer had a marked effect on cell volume with OsO4, whereas with GA or GA-OsO4 it was only significant at very hypotonic buffer osmolalities. Concentration of GA had no effect on cell volume. Osmolality of the postfixation buffer had little effect on cell volume, and duration of fixation or postfixation treatment had no effect with all fixatives. Freezing and thawing or centrifugal stress (up to 100,000 g) had little or no effect on cell volume after all fixatives studied. Mechanical stress obtained by sonication showed that OsO4 alone produced poor stabilization and that GA fixation alone produced the greatest stabilization. The results indicate that rapid membrane permeability changes of EATC follow fixative action. The results are consistent with known greater stabilizing effects of GA on model protein systems since cells were also rendered relatively stable to osmotic stress during fixation, an effect not noted with OsO4. After fixation with GA and/or OsO4 cells were stable to osmotic, thermal, or mechanical stress; this is inconsistent with several earlier reports that GA-fixed cells retain their osmotic properties.
89 citations
TL;DR: The effects of internal cobalt, cadmium, and nickel are qualitatively similar to those of zinc: only calcium among the cations tested is without effect.
Abstract: We have studied the effects of internally applied divalent cations on the ionic currents of voltage-clamped squid giant axons. Internal concentrations of calcium up to 10 mM have little, if any, effect on the time-course, voltage dependence, or magnitude of the ionic currents. This is inconsistent with the notion that an increase in the internal calcium concentration produced by an inward calcium movement with the action potential triggers sodium inactivation or potassium activation. Low internal zinc concentrations (∼1 mM) selectively and reversibly slow the kinetics of the potassium current and reduce peak sodium current by about 40% with little effect on the voltage dependence of the ionic currents. Higher concentrations (∼10 mM) produce a considerable (ca. 90%) nonspecific reversible reduction of the ionic currents. Large hyperpolarizing conditioning pulses reduce the zinc effect. Internal zinc also reversibly depolarizes the axon by 20–30 mV. The effects of internal cobalt, cadmium, and nickel are qualitatively similar to those of zinc: only calcium among the cations tested is without effect.
TL;DR: The experiments to be described were designed to test the hypothesis that the macromolecules responsible for ion transport as well as parameters of the transport system such as magnitude and/or sensitivity to internal and external ions might also be a function of the field strength.
Abstract: The potential difference across the membranes of most excitable cells is of the order of 50 to 100 mV inside negative. Although this potential difference may seem rather small in absolute magnitude, it occurs across an interface of such extreme thinness that the resultant electric field ( 1 00,000 V/cm) approaches the dielectric breakdown point of many lipid materials. Since many of the constituents of the membrane are either charged particles or polar molecules, their orientation in the membrane might be affected by the presence of such large potential gradients, and it seems reasonable to suppose that the macromolecules responsible for ion transport as well as parameters of the transport system such as magnitude and/or sensitivity to internal and external ions might also be a function of the field strength. The experiments to be described were designed to test this hypothesis by altering the potential gradient across the membrane in two ways: (1 ) by passing hyperpolarizing electrical currents across the membrane and (2) by changing [ K ] i or [ K ] o , procedures that are known to change the membrane potential since the membrane is highly permeable to this ion. Brief reports of the effects of hyperpolarizations on sodium efflux from cephalopod axons have appeared p r e v i o ~ s l y . ~ * ' ~ In addition to the general orienting effect that an electrical field might be expected to have on any polar macromolecule, membrane potential might have a specific effect on Na : K transport in squid axons because of the electrogenic character of the pump (one cycle of pump operation moves more positive charges outward than inward). Because pumping extrudes a net charge from the cell, changing the potential gradient must change the amount of work that the pump does per cycle and thus might be expected to change either therate of pumping (i.e., magnitudes of the Na or K fluxes) or their sensitivity to external ions.
01 Jan 1974
TL;DR: In only two of 30 infants who had repeated neurological examinations and who were at least 4 years old at the time of the last examinations could the neurologic abnormality be attributed solely to hypoglycemia which had been adequately treated.
Abstract: A follow-up study was done on the physical growth, neurological and EEG abnormalities and intellectual development of 39 treated hypoglycemic children and 41 matched controls up to 5 to 7 years of age.
Although there were no significant differences in mean height and mean weight at 5 to 7 years of age, mean head circumferences remained smaller in the hypoglycemic groups when compared to that of the controls.
No significant EEG differences were found between the groups but a significant difference in neurologic abnormalities was seen. However, in only two of 30 infants who had repeated neurological examinations and who were at least 4 years old at the time of the last examinations could the neurologic abnormality be attributed solely to hypoglycemia which had been adequately treated. These abnormalities were occasional nonfebrile seizures. In a third infant moderate neurologic abnormalities could be traced to unrecognized and inadequately treated symptomatic hypoglycemia, in a fourth to microcephaly and hypoglycemia, and in one infant spastic quadriplegia was associated with cerebral hemorrhage and hypoglycemia.
Although there were no differences in the mean yearly IQ scores between the groups, a significantly (p < .05) larger number of hypoglycemic children had IQ scores below 86 (13 of 25) than did the controls (six of 27) at 5 to 7 years of age.
TL;DR: The reaction appears to be generally applicable for selective 3-(O-carboxymethyl)oxime formation in steroids possessing multi-carbonyl groups, thus facilitating the coupling of steroidal haptens to protein at the C-3 position of the steroid molecule for enhanced immunospecificity.
TL;DR: The chamber method of culturing chick embryo cells was developed, and the technique used to plaque Rickettsia was modified, which permitted the detection of morphologic changes induced by antibiotics and the determination of minimal inhibitory concentrations and rates of killing of rickettsiae.
Abstract: chamber method of culturing chick embryo cells was developed, and the technique used to plaque Rickettsia was modified. These methods permitted the detection of morphologic changes induced by antibiotics and the determination of minimal inhibitory concentrations and rates of killing of rickettsiae. With Rickettsia prowazeki the minimal inhibitory concentrations were 1.0, 0.1, 0.06, and 0.008 [tg/ml for chloramphenicol, doxycycline, erythromycin, and rifampin, respectively. The in vitro actions of doxycycline and minocycline were indistinguishable from that of tetracycline. Doxycycline, rifampin, and erythromycin killed rickettsiae at clinically attainable concentrations, but the rates of action were too slow for eradication of the organisms from the human host under conditions usually associated with the treatment of typhus fever.
TL;DR: Mutants defective in synthesis of the three phage T4 internal proteins, IPI, IPII, and IPIII, were isolated by an immunological screening procedure and results are discussed in terms of an assembly-core model for T4 head formation.
TL;DR: Transmission electron microscopy of plastic-embedded tissue specimens which had been previously dehydrated by the critical point drying method demonstrated that little damage occurred from this procedure.
Abstract: This study utilized scanning and transmission electron microscopy of renal tissue to provide new information on the gross and microscopic structure of the kidney. The luminal surface of the proximal convoluted tubule was characterized not only by the border of microvilli, but also by crater-like depressions, and circumferential folds. In tissue processed for scanning electron microscopy the proximal tubular cells separated along their lateral surfaces clearly exposing the topography of the lateral cell projections of cytoplasm which have been generally unavailable for viewing because of their interdigitation with adjacent cells. The various segments of the nephron were identified on the basis of position in the kidney, general morphology, and the distribution and form of apical microvilli, cilia, or flaps. The external surface of the papillary tip had several parallel furrows into which the collecting ducts opened. Large plaquelike depressions lined the papillary surface. The opposed surface of the renal pelvis had small plaque-like depressions separated by narrow ridges. Transmission electron microscopy of plastic-embedded tissue specimens which had been previously dehydrated by the critical point drying method demonstrated that little damage occurred from this procedure.
TL;DR: This study indicates that the pre-ejection period (PEP) is a unique noninvasive measurement of biological end organ responsiveness with thyroid dysfunction; a short PEP is characteristic of uncomplicated thyrotoxicosis and serial changes in PEP may be a useful index of therapeutic response.
Abstract: Systolic time intervals (STI) were determined from simultaneous records of the electrocardiogram, carotid pulse and phonocardiogram in 17 consecutive patients with thyrotoxicosis and sinus rhythm. None of the patients had clinical evidence of congestive heart failure. Intervals measured included electromechanical systole (Q-S 2 ), heart sound interval (S 1 -S 2 ) and left ventricular ejection time (LVET). From these, the pre-ejection period (PEP), isovolumetric contraction time (ICT) and Q-S 1 intervals were derived. Deviations (ΔSTI) of observed values from expected values (Weissler equations) for the same heart rate were obtained by subtraction. The mean deviation of the thyrotoxic patients ± sem from the normal population were ΔQ- S 2 * = –37.8 ± 4.2; ΔLVET = –4.0 ± 4.1; ΔPEP * = –33.8 ± 1.8. The shortening of PEP was due largely to a shortened ICT (ΔICT * = –27.2 ± 1.1). In eight patients studied serially during treatment the short PEP returned to the normal range concurrently with serum T 4 measurements. This study indicates that the PEP is a unique noninvasive measurement of biological end organ responsiveness with thyroid dysfunction; a short PEP is characteristic of uncomplicated thyrotoxicosis and serial changes in PEP may be a useful index of therapeutic response. * P
TL;DR: Examination of the endothelial surface of arterial segments distal to the occluding clip revealed the presence of numerous “crater-like” defects as well as outpouchings or “balloons” which are suggested to cause interference with blood flow and the for mation of platelet thrombi by their protrusion into the lumen.
Abstract: The scanning electron microscope (SEM) has been employed to study the effects of ischemia on the luminal surface of the common carotid artery. Fifteen adult rabbits were lightly anesthetized and the common carotid arteries surgically exposed. The right carotid artery was occluded with a single Heifetz clip for five minutes (five animals), 15 minutes (five animals), and 30 minutes (five animals). Following removal of the clip, the animals were immediately perfused with glutaraldehyde and the arteries excised and prepared for critical point drying. Four additional rabbits were perfused following the same method with no surgical procedures performed in the neck. Normal aortas were also examined. The nature and frequency of endothelial cell alterations were determined by analysis of ten randomly selected SEM fields. Examination of the endothelial surface of arterial segments distal to the occluding clip revealed the presence of numerous "crater-like" defects as well as outpouchings or "balloons." The numbers ...
TL;DR: This finding implies that lysine racemase in this strain, while detectable in cell extracts, is not physiologically functional in intact cells at a rate that would permit growth of mutants blocked in the l-lysine pathway, suggesting a mechanism in bacteria for maintaining regulatory patterns in pathways that may have lost their capacity to support growth.
Abstract: The isolation of several mutant strains blocked in l-lysine degradation has permitted an assessment of the physiological significance of enzymatic reactions related to lysine metabolism in Pseudomonas putida. Additional studies with intact cells involved labeling of metabolic intermediates from radioactive l- or d-lysine, and patterns of enzyme induction in both wild-type and mutant strains. These studies lead to the conclusions that from l-lysine, the obligatory pathway is via delta-aminovaleramide, delta-aminovalerate, glutaric semialdehyde, and glutarate, and that no alternative pathways from l-lysine exist in our strain. A distinct pathway from d-lysine proceeds via Delta(1)-piperideine-2-carboxylate, l-pipecolate, and Delta(1)-piperideine-6-carboxylate (alpha-aminoadipic semialdehyde). The two pathways are independent in the sense that certain mutants, unable to grow on l-lysine, grow at wild-type rates of d-lysine, utilizing the same intermediates as the wild type, as inferred from labeling studies. This finding implies that lysine racemase in our strain, while detectable in cell extracts, is not physiologically functional in intact cells at a rate that would permit growth of mutants blocked in the l-lysine pathway. Pipecolate oxidase, a d-lysine-related enzyme, is induced by d-lysine and less efficiently by l-lysine. Aminooxyacetate virtually abolishes the inducing activity of l-lysine for this enzyme, suggesting that lysine racemase, although functionally inactive for growth purposes, may still have regulatory significance in permitting cross-induction of d-lysine-related enzymes by l-lysine, and vice versa. This finding suggests a mechanism in bacteria for maintaining regulatory patterns in pathways that may have lost their capacity to support growth. In addition, enzymatic studies are reported which implicate Delta(1)-piperideine-2-carboxylate reductase as an early step in the d-lysine pathway.
TL;DR: The horse appears to offer an ideal model for understanding the psychosocial, hemodynamic, and central nervous system mechanisms involved in these reactions to changes in the heart rate and rhythm of patients in coronary care units and a shock-trauma unit during social contact with other humans.
Abstract: The effects of human social contact on the electrocardiogram (EKG) and general behavior of 2 horses were explored. Petting elicited a slowing of heart rate, while a person entering and exiting elicited transient, but often marked heart rate increases. In both horses transient periods of T wave inversion occurred in the EKG during human contact. In one of the horses the frequency of dropped heart beats increased dramatically during successive trials of human petting. In this horse a total of 29 dropped heart beats were observed of which 23 occurred while a person was with the horse, although this contact occupied only 15 percent of the total observation period.
These findings parallel previous observations made with dogs. Similar observations of changes in the heart rate and rhythm of patients in coronary care units and a shock-trauma unit during social contact with other humans underscore the need to develop empirical analogues of these reactions. The horse appears to offer an ideal model for understanding the psychosocial, hemodynamic, and central nervous system mechanisms involved in these reactions.
TL;DR: It is suggested that immunisation against poliomyelitis and yellow fever is indicated in women contemplating travel to affected areas; for rubella and mumps vaccination and routine smallpox vaccination pregnancy is a contraindication, but vaccination should be mandatory for the pregnant woman travelling to smallpox-endemic area.
TL;DR: Three phenotypically distinct strains of Escherichia coli B were studied, suggesting that the sodium-activated glutamate transport system resides in the cytoplasmic membrane and that releasable binding protein(s) is not intimately involved in its function.
Abstract: Three phenotypically distinct strains of Escherichia coli B were studied: one in which the transport of glutamate was strongly stimulated by sodium, one in which the transport was relatively independent of sodium, and one which did not transport glutamate. Membrane vesicle preparations from the three strains followed the behavior of whole cells with respect to sodium-stimulated transport. Although glutamate-binding material could be released from cells by osmotic shock, its affinity for glutamate was not significantly influenced by sodium. Furthermore, the shocked cells retained sodium-stimulated transport. The accumulated results suggest that the sodium-activated glutamate transport system resides in the cytoplasmic membrane and that releasable binding protein(s) is not intimately involved in its function.
TL;DR: It is concluded that microtubules play little or no role in the maintenance of mature red cell shape; however, they play an important role inThe development of the flat discoid shape of avian erythrocytes during maturation.
TL;DR: BCNU, labelled with 14 C in the chloroethyl groups, decomposes in neutral aqueous solution to release half of its radioactivity as volatile products which are consistent with the existence of chloro methylcarbonium ions as reactive intermediates which would produce substituted nucleotides.
TL;DR: Two derivatives of CMP, 3-hydroxyethyl-CMP and 3,N4-ethano-C MP, have been identified in the acid hydrolysate of the polymer and may be related to the mechanism of action of this compound.
TL;DR: The physician must view unexpected death as the beginning of a family crisis, and realize that his role may extend far beyond the period immediately after death.