Anaerobic culture in podiatric practice. Although few podiatric infections are anaerobic, it is important to isolate, identify, and test all of the various types of bacteria for sensitivity. Dr. Lantor did not write this synopsis to analyze the procedures mentioned, but to outline some of the signs and symptoms associated with anaerobic growths and to make foot surgeons aware of the need for anaerobic culture techniques.


Immunocytochemical methods in the study of lymphoma and related conditions. The diagnosis and classification of malignant lymphomas is based upon traditional histological criteria evolved over the years by successive generations of pathologists. Immunoperoxidase methods applied to formalin paraffin sections have permitted a direct correlation of these established morphologic criteria with newer immunological concepts of the form and function of the B lymphocyte and its derivatives. Study of material from 500 cases of Hodgkin's disease, non-Hodgkin lymphomas, and myeloma has revealed that many of these conditions may find a common origin in the lymphocyte, and that some malignant cells, previously identified as malignant histiocytes or reticulum cells are rather related to or derived from the transformed lymphocyte or immunoblast. The corresponding tumors are thus more logically designated immunoblastic sarcoma. The study also reveals a claser developmental relationship between multiple myeloma and immunoblastic sarcoma than previously suspected, and suggests that all of the B cell lymphomas occur as part of a continuous spectrum of disease, rather than as separate entities as implied by current histological classifications. The study of immunoglobulin in formalin paraffin sections is illustrative of the great potential of this method in the diagnosis and study of neoplasia in general.


Subcellular localization of gonadotropins and testosterone in the developing fetal rat testis. Gonadotropins and testosterone were immunocytochemically localized in the fetal rat testes 16-18 days of gestation with the unlabeled antibody-peroxidase anti-peroxidase complex technique. Maximum staining for gonadotropins with antiserum to the beta chain of human chorionic gonadotropin (anti-hCGbeta) occurred at 16 days gestation in the seminferous tubule and 17 days gestation in interstitial (Leydig) cells. Anti hCGbeta sites were on the plasma membranes at the luminal aspects of Sertoli cells at 16 days gestation. In addition, intracellular hCGbeta sites were evident including the nucleus, nucleolus, ribosomes, some vesicles, lysosomes and centrioles. The stain for hCGbeta disappeared rapidly and by 17 days was limited to patches in the cytoplasm and nuclei. In the fetal testes, staining for anti-testosterone binding sites was most intense at 18 days of gestation either in lipid droplets or on nuclei of Leydig and Sertoli cells. Very little testosterone stain was observed before 18 days of gestation. These findings agree with physiologic data that suggest that gonadotropins bind to receptors and stimulate testicular development and the capacity for testosterone production.


Immunocytochemical evidence for vasopressin receptors. An electron microscopic study was made of mouse pituitaries immunocytochemically stained with anti-lysine vasopressin (LVP) as the primary antiserum in the unlabeled antibody peroxidase-anti-peroxidase procedure. Vasopressin (VP) was identified in the neurosecretory granules of the neural lobe which stained with peroxidase anti-peroxidase molecules. Electron density was induced in secretory granules of the pars intermedia (PI), both in the melanocyte stimulated hormone and ACTH cell types, probably indicating VP molecules attached to binding (receptor) sites. Omission of anti-LVP abolished staining both in the neural lobe and the PL Anti-LVP absorbed with antigen, by admixing with LVP, abolished staining in the neural lobe but not in the PI; according to optical density measurements the PI showed a +/- 22% staining increase over controls. Staining intensity in the PI probably reflects occupancy of binding (receptor) sites for VP. Exposure of PI granules to LVP before the usual staining sequence resulted in +/- 48% increased staining. In water-deprived mice with high endogenous VP titers, staining was +/- 33% and +/- 40% more intense than in normal mice. Solid phase absorbed and eluted antibodies to LVP provided additional proof that staining in both neural lobe and PI could be attributed to anti-LVP. Results indicate that binding or receptor sites for VP are located on secretory granules in the PL Possible physiological significance is discussed.


Steric hindrance as a factor in the reaction of labeled antibody with cell surface antigenic determinants. The binding of rabbit anti-human IgG labeled with 125I, shellfish glycogen or ferritin to human IgG attached to the surface of rabbit RBC with chromic chloride was studied. Maximum binding was noted with 125I labeled antibody. Slightly but consistently less binding was found with shellfish glycogen labeled antibody. The binding of ferritin labeled antibody was strikingly reduced--usually one-third or less of that found with 125I labeled antibody alone. This suggests that under the conditions of these experiments, the attachment of large labels to antibody molecules results in reduced antibody binding to surface antigen. Steric hindrance is probably at least in part responsible for this reduced binding.


High resolution dual laser flow cytometry. Flow cytometers based on optical sensing utilize external light sources and fluorescent dyes to measure one or more specific components or properties of individual cells or subcellular particles in liquid suspension. To provide for independent excitation of two dyes used in double staining experiments we have constructed a high resolution flow cytometer that uses two laser beams to provide two wavelengths of excitation. These beams are separated spatially so that cells flow through them sequentially, with a time separation of about 20 musec. Since the dyes are excited sequentially their emission occurs at different times and their emission spectra may overlap without causing any difficulty in analysis. We have developed new light collection optics that permit up to four measurements to be made on each cell. This approach greatly increases the number of dye combinations that can be used in flow cytometry, thus removing a significant limitation of single illumination instruments.


Immunoperoxidase localization of vitamin D dependent calcium binding protein. Calcium binding protein (CaBP) was localized by the indirect peroxidase-labeled antibody method in chick duodenum 72 hr after administering 32.5 nmol of cholecalciferol to vitamin D-deficient chicks. CaBP was observed in cytoplasm and nuclei of absorptive cells but was absent from goblet cells. Our results are consistent with the suggested functional role for CaBP in the prevention of intracellular accumulation of calcium by preventing mitochondrial accumulation of calcium, enhancing removal of calcium from absorptive cells, and/or preventing the "leaking" of calcium into cells through the lateral borders. They are not consistent with an extracellular functional role for CaBP.


Use of horseradish peroxidase to block nonspecific enzyme uptake in immunoperoxidase microscopy. Intrinsic tissue peroxidase activity can be more or less successfully destroyed by methanol-H2O2 treatment. It has been found, however, in our laboratory that horseradish peroxidase (HRP) coupled to antibody will bind to some tissue components on a nonspecific basis and remain to take part in the histochemical stain. This contributes considerably to the background. This difficulty can be largely overcome if the tissues are pretreated with a solution of horseradish peroxidase which binds with nonspecific tissue sites. The adsorbed enzyme, along with the intrinsic peroxidase, can then be successfully inactivated by methanol-H2O2 treatment. By this method of blocking, there is considerable reduction in background staining.


Isolation and cultivation of bovine ephemeral fever virus in chickens and chicken embryos. Unadapted bovine ephemeral fever (BEF) virus was isolated from cattle blood after intravenous inoculation into chicken embryos. Infected embryos died or hatched as abnormal chickens. The chick embryo was slightly less sensitive to unadapted BEF virus than were Vero cell cultures, but the use of embryos avoids the several blind passages that are required to isolate BEF virus in unweaned mice. Chick embryos were considerably less efficient than Vero cell culture or unweaned mice in detecting Vero cell-adapted and mouse-adapted BEF virus respectively. Viraemia was demonstrated in chicken embryos at 1-4 days and in one-day-old chickens at 1-3 days after intravenous inoculation of BEF virus. BEF virus was demonstrated by isolation and by immunofluoresence in heart, brain, lung and liver of chicken embryos at 1-5 days and in lung and liver of one-day-old chickens at 1-2 days, after intravenous inoculation. The isolated viruses were confirmed as BEF virus by neutralization with immune mouse ascitic fluid. BEF neutralizing antibodies were produced in 4-week-old and adult chickens after intravenous inoculation with BEF virus.


High and low level tetracycline resistance in Shigella sonnei. The results presented in this paper confirm the existence of two types of tetracycline resistance in Shigella sonnei. One group of strains had a high level of resistance to tetracycline and oxytetracyline, with a variable level of minocycline resistance. The second group had a lower level of tetracycline resistance and were sensitive to minocycline. After conjugation with E. coli K12 the selected E. coli transconjugants had the same levels of resistance as the parent Sh. sonnei strain, with one exception. Sh. sonnei 87 was resistant to a high level of tetracycline, but was able to transfer only low level resistance. It is suggested that Sh. sonnei 87 carriers two plasmids: pSU1, a conjugative plasmid conferring a low level of tetracycline resistance, and pSU2, a non-conjugative plasmid which confers a high level of resistance to tetracycline.


A study of acute respiratory disease in the community of Port Chalmers. I. Illnesses within a group of selected families and the relative incidence of respiratory pathogens in the whole community. A study of respiratory diseases in the semi-isolated community of Port Chamlers, New Zealand, began in April 1973. The intensive surveillance of a selected group fo 26 families involved the weekly reporting of illness, the collection of specimens for virus, Group A streptococci and Mycoplasma pneumoniae isolation and the collection of sera at 6-month intervals. A total of 956 illnesses were reported during 32 months. The median number of illnesses per year were: infants 4.4, children 2.5, female adults 2.4 and male adults 2.0. Of all these illnesses, 57% were upper respiratory, 31% were lower respiratory and 9% were enteric. The severity of these illnesses was not greater than would be expected in open communities. Surveillance by pathogen isolation only of the whole community through the patients in the general practice was carried out concurrently. A total of 640 nasopharyngeal swab specimens were collected from which 161 viruses, 47 Group A streptococci and 2 M. pneumoniae were isolated. The overall isolation rate was 33%. The similarities between the epidemiological patterns of respiratory disease in the open community and the isolated community are discussed.


Properties of the cell surface Fc-receptor induced by herpes simplex virus. Detection of peroxidase-antiperoxidase soluble complexes (PAP) bound to the surface of herpes simplex virus-infected cells has been used to demonstrate virus-induced Fc receptors and to study their distribution. The PAP method is more sensitive than hemadsorption with immunoglobulin-coated sheep red blood cells, and can be used to study localization by light and electron microscopy. Our results indicate that capping takes place after the receptor is engaged by antigen-antibody complexes and that at least a portion of the bound ligand is internalized.


Guinea pig homologues of TL and QA-2 antigens. The H-2, thymus-leukemia (TL), and Qa-2 antigens of mice are encoded by closely linked genes on murine chromosome 17, and have structural similiarity in that each antigen is borne on a approximately 44,000 dalton molecule associated with beta2 microglobulin (beta2mu). The extensive homology of major histocompatibility complex (MHC) products that exists for the mouse and guinea pig suggested that a similar homology might exist for products of genetic regions closely linked to the MHC. By taking advantage of the selective association of beta2mu with H-2, Qa-2, and TL antigens, and by using the technique of sequential immunoprecipitation, we demonstrated two previously undescribed guinea pig molecules reactive with anti-guinea pig beta2mu. The first molecule was composed of a 36,000 dalton glycoprotein associated with beta2mu and was found on guinea pig thymocytes, but not lymphocytes. The second molecule was composed of a 40,000 dalton glycoprotein associated with beta2mu, and was found on both guinea pig thymocytes and lymphocytes. By structure, chemical composition, association with beta2mu, and tissue distribution, the first molecule is an attractive candidate for the guinea pig homologue of TL antigen, whereas the second fits the criteria for the guinea pig homologue of Qa-2 antigen.


Possible role of macrophage glycolipids as receptors for migration inhibitory factor (MIF). Guinea pig peritoneal exudate cells incubated with water soluble glycolipids obtained from macrophages show an enhanced response to migration inhibitory factor. Incorporation of these glycolipids into liposomes greatly facilitates their interaction with indicator cells. Enhancement of peritoneal exudate cell responsiveness to migration inhibitory factor was specific for glycolipids from guinea pig macrophages. Glycolipids extracted from guinea pig brain and polymorphonuclear leukocytes as well as several bovine and porcine glycolipids had no effect. Specificity of enhancement was not due merely to a preferential association of macrophage glycolipids with indicator cells. The possible role of macrophage glycolipids as receptors for MIF is discussed.


Distinct subpopulations of IgG memory B cells respond to different molecular forms of the same hapten. Spleen cells from mice primed with the thymus-dependent antigen trinitrophenyl keyhold limpet hemocyanin several months earlier can be cultured in vitro to give vigorous IgG antihapten PFC responses to thymus-dependent (TD) and thymus-independent (TI) forms of the same hapten. Here we show that the IgG memory precursors that respond to these two forms of the hapten constitute functionally distinct subpopulations. We have designated these subpopulations as B1gamma and B2gamma to represent secondary precursor cells responding to TI and TD antigens, respectively. Three types of evidence for these subpopulations are presented: 1) In vitro secondary IgG responses to TD and TI forms of the TNP hapten are additive when both forms are added to the same culture. 2) The precursor frequencies for the TD and TI antigens are additive, but addition is not observed between two TD or two TI antigens. 3) Each population can be selectively eliminated by BUdR and light treatment without affecting the other population. The ontogenetic relationships between these subpopulations are discussed in relation to all presently proposed subpopulations B1mu, B2mu, B1gamma, and B2gamma.


Vectorcardiographic identification of myocardial scar: a discriminative study with automatically processed vectorcardiographic information. A multivariate discriminative procedure for the vectorcardiographic identification of ischemic myocardial scarring was performed utilizing data from 1,162 vectorcardiograms (VCGs) obtained in clinically normal subjects and 90 VCGs obtained from patients proved at autopsy to have ischemic myocardial scars. The VCGs from patients with myocardial scars were divided into two groups, a design group of 50 cases and an evaluation group of 40 cases. The best vectorcardiographic variables to discriminate the clinically normal group from the design group with scars were identified by stepwise linear discrimination. Sixteen vectorcardiographic variables were then used for discriminative analysis. This analysis correctly identified myocardial scars in 45 of the 50 VCGs in the design group (sensitivity 90%); among the 1,162 VCGs from clinically normal subjects, 32 were misidentified as myocardial scar (specificity 97.2). The sensitivity of these defining criteria was then tested in the 40 cases of myocardial scar in the evaluation group and found to be reproducible; 34 of the 40 cases of this group (85.0%) were correctly identified as having a myocardial scar. The multivariate discriminative criteria developed in this study had greater sensitivity and specificity than standard methods usually employed in electrocardiography and vectorcardiography. The criteria defined need to be evaluated in a large series that includes instances of cardiac pathology of nonischemic nature.


Radioimmunoassay and automated enzyme immunoassay for the determination of thyroxine. The EMIT homogeneous enzyme immunoassay for the determination of thyroxine (T4) was adapted to an automatic analyser (Type Kem-O-Mat) and compared with a conventional radioimmunoassay. Sera from 92 patients whose thyrometabolic status was being examined, and control sera with 3 different T4 concentrations were analysed by both methods. Day-to-day analyses of the control sera gave variation coefficients between 6 and 10% for both methods. The mean value for T4 in the patients sera was 111 nmol/l (8.6 microgram/dl) determined by the enzyme immunoassay and 109 nmol/l (8.5 microgram/dl) determined by the radioimmunoassay; the correlation coefficient was r = 0.9.


Entry of Trypanosoma (Schizotrypanum) dionisii to macrophages in vitro and its subsequent fate therein. Observations by phase contrast, fluorescence and electron microscopy showed that epimastigotes of Trypanosoma (Schizotrypanum) dionisii (grown in vitro) were phagocytosed posterior end first by mouse peritoneal macrophages in vitro. Many were subsequently digested as a result of phagosome-lysosome fusion but others survived by apparently inhibiting this fusion and/or escaping from the phagosome into the host cell's cytoplasm. These survivors replicated as amastigotes. Long trypomastigotes, separated from populations grown in vitro by passage down a column of glass beads (with or without prior exposure to guinea-pig serum), were phagocytosed by either pole and all were subsequently digested.


Mobilization of the Proteus mirabilis chromosome by R plasmid R772. The P-1 incompatibility group plasmid R772 can mobilize the chromosome of Proteus mirabilis strain PM5006. The decreasing gradient of recombinant recovery frequencies found for markers which were increasingly distal to 0 min with plasmid D donors was not found with R772. Instead, it produced recombinants for all markers at frequencies of about 5 X 10(-5) per donor. This is about 10-fold lower than the plasmid transfer frequency. Recombinants were stable and recombination was only detected over short segments of the chromosome which corresponded to about 10 min on the D plasmid map of the chromosome. All recombinants had inherited R772 and expressed all properties of the plasmid. Attempts to isolate variant plasmids with increased frequencies of recombinant formation were unsuccessful.


Serological characteristics of pili determined by the plasmids R711b and F0lac. The plasmids R711b (at present IncX) and F0lac (IncFV) both determine pili morphologically like those of F (IncFI), and confer sensitivity to the F-specific filamentous bacteriophages, but not to the F-specific isometric RNA phages. Detailed serological studies show that the two pilus types are unrelated, and that neither is related to any of the previously defined F pilus serotypes. Adsorption of the isometric RNA phage MS2 to R711b pili occurs in the presence but not in the absence of formalin, which presumably prevents elution of reversibly adsorbed virions. No adsorption occurs with F0lac pili. MS2 multiplication, as measured by titre increase tests in liquid medium, is found with neither plasmid. The two plasmids are not incompatible. These observations indicate that R744b and F0lac are different both from one another and from the plasmids belonging to the incompatibility groups IncFI--IV.


Basic amino acid inhibition of cell division and macromolecular synthesis in Saccharomyces cerevisiae. Growth of Saccharomyces cerevisiae on poor nitrogen sources such as allantoin or proline was totally inhibited by addition of a non-degradable basic amino acid to the medium. Cells treated with lysine contained greatly reduced quantities of histidine and arginine. Conversely, lysine and histidine were severely reduced in arginase-deficient cells treated with arginine. When all three basic amino acids were present in the culture medium, growth was normal suggesting that synthesis of all three basic amino acids was decreased by an excess of any one of them. Inhibition of growth was accompanied by a fivefold increase in the observed ratio of budded to unbudded cells. These morphological changes suggested that DNA synthesis was inhibited. Consistent with this suggestion, addition of a basic amino acid to the culture medium substantially reduced the ability of the cells to incorporate [14C]uracil into alkali-resistant, trichloroacetic acid-precipitable material. RNA and protein synthesis, although decreased, were less sensitive to the effects of such additions.


Preliminary seroepidemiological studies on the human syncytial virus. The seroepidemiology of the human syncytial virus was investigated by means of an indirect immunofluorescence test on 241 sera from Kenya, Tunisia, Singapore and Britain. These included sera from patients with nasopharyngeal carcinoma, other tumours of the oro-nasopharynx, tumours of other parts of the body, and from normal donors. In this study, the virus was found to infect only Kenyan Africans and all but one of these seropositive subjects had tumours, particularly of the oro-nasopharyngeal spaces. The significance of these findings is discussed.


Immunoperoxidase detection of baculovirus antigens in insect cells. The sequence of events in the infection of TN-368-10 and TN-368-13 cells by Autographa californica nuclear polyhedrosis virus (AcMNPV) was investigated by using the indirect immunoperoxidase technique. Antisera raised against enveloped nucleocapsids detected homologous antigens at 6 to 8 h post infection which was about 2 h before the appearance of both intracellular and extracellular infectious virus. Similar tests using polyhedrin antiserum showed that polyhedrin is first synthesized at 12 h post infection, 2 to 4 h after the appearance of infectious nonoccluded virus. The immunoperoxidase technique was also applied to four other invertebrate cell lines after inoculation with AcMNPV. The most significant result was that 90% of AcMNPV-inoculated Bombyx mori 5 cells produced enveloped nucleocapsid antigens and infectious virus but only 1% or less of the cells produced polyhedrin. This disparity emphasizes the need for assays for NPV infection that are independent of polyhedron production.


A model for the adsorption of phage P22 to Salmonella typhimurium. A new model for the adsorption of bacteriophage P22 to its host Salmonella typhimurium is proposed. The main feature of this model is that only three of the six tail proteins found on the mature phage function during adsorption. This model explains why there is a difference in the specific endoglycosidase activity of the tail protein of mature virions as opposed to unattached tail protein. It also accounts for the cubic relationship between p.f.u. and tail protein concentration in in vitro assembly experiments.


Two early dynamometers. An historical account of the earliest measurements to study human muscular strength. An account of two of the earliest dynamometers is presented, together with results of the first experiments attained with them. The Graham--Desaguliers dynamometer was developed in London in 1763 to measure human muscular force, in such a way that synergistic muscles could not impart a false mechanical advantage to the test. The Regnier dynamometer was invented in Paris in 1798 to measure the traction properties of artillery-horses, but was desinged as an all-purpose instrument to measure specific human muscle groups as well. Dynamometers were developed to record human strength along a continuum, to remove the need for a dead-weight or biological standard, and to measure many different groups of muscles, not just those of lifting or pushing. The foundations of modern clinical dynamometry are described.


The use of A23187 to demonstrate the role of intracellular calcium in causing ultrastructural damage in mammalian muscle. Electron micrographs show that treatment of mouse diaphragm with the divalent cation ionophore A23187 causes major ultrastructural damage in the muscle. During the first 30 min of exposure to A23187, the mitochondria swell markedly but after 40 min they undergo further ultrastructural changes and a rapid dissolution of the myofilaments is also seen at this time. In place only remnants of the filaments remain. It is suggested that the ionophore causes the release of Ca2+ from the sarcoplasmic reticulum which, initially, is taken up by the mitochondria, causing then to swell; after 40 min the mitochondria release the accumulated Ca2+. It is argued that the rise in [ca2+]i stimulates neutral proteases in the myoplasm and that the sequence of events following ionophore treatment may act as a model for the involvement of Ca2+ in various myopathies. We have shown previously (29) that treatment of the cutaneous pectoris muscle of the frog with the divalent cation ionophore A23187 has three major effects: (i) The membrane potential (Em) is depolarized, an action that is found only when the Ca2+ -concentration of the bathing saline is very low. (ii) It causes an increase in resting tension and the development of contraction. This effect is found at both normal (1.8 mM) and low values of [Ca2+]o and is, therefore, independent of Ca2+ entry and of changes in Em. The ionophore is believed to act primarily by releasing Ca2+ from intracellular stores. (iii) It causes major ultrastructural damage to the muscle filaments. The evidence suggests that A23187 acts at the sarcoplasmic reticulum of frog muscle, causing the release of stored Ca2+ , and the consequent rise in [Ca2+]i stimulates a Ca2+ -activated protease which is responsible for the myofilament degradation. A calcium-activated factor has been isolated from rabbit skeletal muscle; this enzyme operates at neutral pH, hydrolyses denatured casein, and specifically removes the Z-lines and alpha-actinin from skeletal muscle (24). A Ca2+ -activated protease with a pH optimum of 7.5 has also been purified from porcine skeletal muscle; it removes Z-discs, degrades troponin and tropomyosin and partly degrades M lines, and it has been suggested that it may have a physiological role in the disassembly of intact myofibrils during the metabolic turnover of myofibrillar proteins (6, 7). This protases is not localized in membrane-bounded sub-cellular particles, but is believed to be in direct contact with the cytoplasm (26). These findings are of particular interest in thelight of recent suggestions that the cellular necrosis observed in various muscle diseases is a consequence of an increased net influx of calcium into cells which causes, in turn, calcium overloading of the muscle mitochondria (34, 35). We have, therefore, extended our previous studies with frog muscle by the examination of the action of A23187 on the mammalian skeletal muscle of mouse diaphragm...


Dynamic renal transplant imaging with Tc-99m DTPA (Sn) supplemented by a transplant perfusion index in the management of renal transplants. We have performed 955 studies on 152 patients with 167 renal transplants. Images were recorded following bolus injection of 12-15 mCi Tc-99m DTPA (Sn). The data were stored on a computer and analyzed by generation of region-of-interest curves from (a) the iliac artery distal to the transplant, (b) the kidney, and (c) a background area. A perfusion index was adopted: formula see text. In 276 studies the patient clearly had acute tubular necrosis (ATN), rejection, or a normal kidney on retrospective analysis. The normal perfusion index has a value below 150, and it increases with falling perfusion, such as is seen in rejection and in renal-artery stenosis. The use of this index in addition to sequential images and changes in the region-of-interest curves usually allows separation of rejection from ATN and, particularly, rejection from normals. When serial studies are performed, the separation of rejecting from nonrejecting transplants is excellent, although renal-artery stenosis may cause similar changes in perfusion.


Enzymological properties of pantothenate synthetase from Escherichia coli B. Following a previous report on physicochemical properties, the enzymological properties of a homogeneously purified preparation of pantothenate synthetase were described. The optimum pH was 10.0 and optimum temperature 30 degrees C. The lyophilized enzyme was very stable on standing at -20 degrees C. K+ or NH4+ and Mg2+ were required as activators; other cations examined were inhibitive to various extents and the enzyme required ATP as the energy supplier. Some omega-amino acids exerted strong inhibition, and the enzyme was inhibited by some chelating agents but was not affected by SH compounds and SH inhibitors. Apparent Km for pantoate was 6.3 x 10(-5)M, for beta-alanine 1.5 x 10(-4)M, and for ATP 1.0 x 10(-4)M. According to the method of Cleland, the enzyme reaction proceeds by a Bi Uni Uni Bi Ping Pong mechanism and a scheme showing the order of binding of substrates and releasing of products is presented.


Adhesion to normal human uroepithelial cells of Escherichia coli from children with various forms of urinary tract infection. The ability to adhere to normal human uroepithelial cells was compared for Escherichia coli strains isolated from the urine of girls with acute pyelonephritis, acute cystitis, or asymptomatic bacteriuria, and from the stools of school children without bacteriuria. Strains from those with acute pyelonephritis had high adhesive ability, whereas strains from those with acute cystitis had intermediate and strains from girls with asymptomatic bacteriuria or from normal feces had low adhesive ability. Strains of serogroup O4K12 had good adherence regardless of origin. E. coli of the eight O groups commonly found in patients with acute pyelonephritis adhered more than did strains of other O groups. Spontaneously agglutinating strains had less adhesive ability than did the O-typable ones.


Selected Hand Test personality variables related to accidents in female drivers. The Hand Test was administered to 170 females ranging in age from 17 to 72 years to determine if specific personality tendencies measured by the Hand Test would be significantly related to incidence of automotive accidents. Results indicated that the personality characteristic associated with DIR was significantly correlated with accidents, but that relationships differed somewhat with age.


Toward an objective evaluation procedure of the Kinetic Family Drawings (KFD). The feasibility of employing a quantitative scoring procedure for evaluating the Kinetic Family Drawings (KFD) was examined. A quantitative scoring procedure was developed from the clinical hypotheses Burns and Kaufman (1970, 1972) to score 21 measurable KFD styles, actions, and characteristics. The scoring procedure was employed to evaluate 116 KFDs obtained from four groups of boys to determine the effectiveness of the procedure to differentiate among two levels of emotional adjustment and the two levels of age. The results indicated that four of seven sets of extracted component scores significantly differed between the emotionally well-adjusted and the emotionally disturbed groups. One set of component scores significantly differed between the younger and the older groups, while two sets of component scores did not differ among any of the four groups. The KFD total score was found to differ significantly only between the young emotionally disturbed and the young emotionally well-adjusted groups. It was concluded that a quantitative scoring procedure for the KFD is feasible.


More on the reliability of the kinesthetic aftereffects measure and need for stimulation. Recently, some have argued for a renewed interest in the kinesthetic aftereffects procedure (KAE) as a personality measure even though it may show low test-retest reliability. These arguments indicate that first-session KAE is valid but later-session KAE is not, due to the supposed appearance (in later sessions) of unwanted functional similarity between different aspects of the KAE procedure. Functional similarity leads to reduced reliability and validity of the retest. Data from two new studies do not support this functional similarity hypothesis, but these data do support the KAE by showing test-retest reliability. Also, the data show some new but tentative experimental evidence for the construct validity of second-session KAE as a measure of need for stimulation. These data do support the KAE as a personality measure but, when contrasted to arguments that only first-session KAE is valid, the data indicate that this is unresolved.


Preservation of solubilized and emulsified systems I: Correlation of mathematically predicted preservative availability with antimicrobial activity. Mathematical models were investigated for the distribution and antimicrobial activity of chlorocresol in solubilized and emulsified systems stabilized with a nonionic surfactant. The concentration of free preservative in the solubilized systems was described adequately by an equation widely used to describe the binding of small molecules to macromolecules. For the emulsions, this equation was combined with an expression for the partitioning of the preservative between the oil and water phases. It was confirmed that short-term antimicrobial activity can be related to the free (unbound) preservative concentration in the aqueous phase and that preservative solubilized within the surfactant micelles or partitioned into the oil phase does not contribute to short-term preservation.


Denture esthetics is more than tooth selection. The selection of the proper mold and shade of denture teeth is but one part of denture esthetics. Compensating for lost alveolar bone, correctly positioning anterior teeth for lip support, and reestablishing the correct vertical dimension of occlusion, in combination with proper tooth selection, creates good denture esthetics. Proper contour and normal physiologic movement of the muscles enhances an esthetic denture, whereas improper support can severely detract from it. Even though denture construction requires a step-by-step progression, these steps cannot be isolated but rather must be integrated to produce an optimal result.


The role of saliva in retention of maxillary complete dentures. In this study maxillary denture retention was influenced by the salivary volume between the denture base and the mucous membrane. An optimum intervening salivary volume, at which the greatest retention was developed, was also observed. It was observed from determination of electric resistance of palatal mucous membrane that inward and outward flow of intervening saliva was greater in the denture with poor retention than in the one with good retention. Moreover, when the salivary volume between the denture base and mucous membrane was optimum the salivary flow under the denture was minimum.


Visualization of stress and strain related to removable partial denture abutments. The following conclusions are based on the conditions set forth in this investigation and apply to forces acting through a vertical direction of application only: 1. The unilateral removable partial denture produced no more stress than the bilateral removable partial denture. 2. The fully active Dalbo removable partial denture resulted in the greatest stressbreaking action. 3. The rigid Dalbo removable partial denture resulted in the least ridge displacement. 4. The rigid Dalbo removable partial denture resulted in the greatest stress concentrations in the distal abutment. 5. None of the attachments tested resulted in a distribution of the stresses along the edentulous ridge. 6. The use of two abutments (double abutments) resulted in greater stress concentrations in the distal abutment than the use of single abutments. 7. Forces in the single abutment were resisted along the long axis of the root. 8. Forces in the double abutments were resisted along the long axis of the distal abutment.


Combined endodontic and restorative treatment considerations. Endodontic treatment for pulpal pathology should result in an asymptomatic tooth with a sealed canal. Restorative treatment for the pulpless tooth should provide protection against fracture and the needed resistance against masticatory stress to allow the tooth to resume normal function.


Analysis of the geometry of finishing lines for full crown restorations. The geometry exhibiting the least marginal discrepancy in this investigation was the shoulder of the slightly oversize casting (Fig. 4). This was significantly better (p = .05) than the oversize bevel, the control shoulder, or the control bevel.


Analysis of stress on a fixed partial denture with a blade-vent implant abutment. Using a two-dimensional finite element method, a study was made that compared the behavior of a model mandibular posterior fixed partial denture constructed on the second premolar abutment and a blade-vent implant imbedded at the site of the second molar with the behavior of a fixed partial denture constructed on the second premolar and second molar abutments. The following were the results: 1. Deflections of the implant fixed partial denture were less than those of the natural tooth fixed partial denture in vertical and inclined loads. 2. Stress concentration was markedly found in the pontic and the mesial and distal parts of the premolar retainer in both restorations and the implant neck in the implant fixed partial denture. 3. In the implant fixed partial denture, stresses induced in the surrounding bone became higher around the posterior abutment and became lower around the premolar retainer than the stresses produced with the natural tooth fixed partial denture. 4. Therefore it was suggested that, to relieve stress to the surrounding bone around the implant abutment, occlusal forces loaded to the implant fixed partial denture have to be more concentrated on the premolar abutment than do forces loaded to the natural tooth fixed partial denture.


Laboratory procedures for fitting removable partial denture frameworks. A technique has been described for fitting a removable partial denture framework to the master cast prior to adapting it in the mouth. Emphasis should be placed on maintaining the original contour of the framework throughout the procedure. The amount of metal removed should be only that necessary to seat the casting on the master cast without abrading the stone. When finishing the tooth-contacting surfaces on the casting, very light pressure should be used to burnish the rough surfaces, not reduce them. If these steps are accomplished carefully in the laboratory, the dentist should be able to fit the framework in the mouth in a minimum of time (Fig. 7).


The psychological training of Abraham Flexner, the reformer of medical education. The great reformer of American medical education was Abraham Flexner. His basic emphasis was to insist that medical education should be solidly based on science. Not a physician, Flexner's specialized training was in psychology. This paper traces the major influence on Flexner's thinking (primarily the works of Hall, Stumpf, and Lotze) and relates these influences to his emphasis on the importance of basic science.


Analysis of the antigenic composition of Trypanosoma brucei brucei bloodstream and culture forms by the quantitative direct fluorescent antibody methods. The quantitative direct fluorescent antibody (QDFA) methods were employed for the antigenic analysis of bloodstream forms and culture procyclics of 2 variants, TRUM (Trypanosome Research University of of Massachusetts) 106 and TRUM 107, of Trypanosoma brucei brucei. Intact and trypsinized trypanosomes were studied. It was demonstrated that: (A) The specific variant antigens are localized in the surface coat of bloodstream trypomastigotes. (B) In addition to the common antigens shared by bloodstream forms and culture procyclics, there are also certain antigens unique to these latter stages. (C) Still another group of antigens, not found in the culture procyclics, appears to be shared by the bloodstream forms, irrespective of their variant-specific antigens. These antigens may be present in part in the coat or on the cell membrane and in part within the cytoplasm. (D) Irrespective of the bloodstream-form variant from which they are derived, the procyclics are antigenically the same. The QDFA results are analyzed statistically and discussed in the light of the available literature.


[The treatment of the tumors by hyperthermia (author's transl)]. This paper is a review of the biological effects of hyperthermia and of their mechanisms. A great interest has been stimulated for the treatment of the tumors by hyperthermia alone or associated to chemo and radiotherapy. The clinical application needs an accurate control of the temperature which raises difficult technical problems.


Identification of the spermatogenic stages in living seminiferous tubules of man. Parts of human seminiferous tubules containing late spermatids with condensed nuclei (Stage II) absorbed more transmitted light than did parts at other stages. Spermatogenic stages I, III, IV and VI were identifiable by phase-contrast microscopy.


Effects of RMI 12,936, a synthetic antiprogestational steroid, on the oestrous cycle and ovulation in the rat. RMI 12,936 inhibited the vaginal cycle and ovulation in the rat. This effect was not mimicked by oestrogen and was partly reversed by progesterone. Ovulation was restored by injection of hCG and the inhibition was associated with reduced cyclic and tonic LH secretion while hypophysial LH levels were generally unaffected. Hypophysial sensitivity to LH-RH was reduced compared with that when ovulation was blocked with sodium pentobarbitone. It is concluded that RMI 12,936 blocks ovulation by causing a reduction in hypophysial sensitivity to LH-RH and that this is probably an antiprogestational effect.


Studies on antitumor agents, 2. Syntheses and antitumor activities of 1-(tetrahydro-2-furanyl)-5-fluorouracil and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil. Convenient and efficient methods were developed for preparing 1-(tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU, 3) [trade name, Futraful (Ftorafur) or FT-207], which is used clinically as an antitumor agent, and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU, 4). For the syntheses, 2,4-bis(trimethylsily)-5-fluorouracil (Me3Si-FU, 1) and 2-acetoxytetrahydrofuran (Thf-OAc, 2) were condensed in the presence of Friedel-Crafts catalysts, such as SnCl4 and BF3-Et2O in dichloromethane, or in the presence of NaI in acetonitrile to give Thf-Fu or Thf2-FU depending on the reaction conditions and workup procedure. A trace of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU, 5) was formed in these reactions. Thf2-FU was easily hydrolyzed to Thf-FU. 2-Methoxytetrahydrofuran can be used instead of Thf-OAc for preparation of Thf-FU under similar conditions. The optimal ratios of Me3Si-FU, Thf-OAc, and SnCl4 or NaI for preparation of Thf-FU and Thf2-FU were determined. In all cases, 2-2.5 equiv of Thf-OAc with respect to Me3Si-FU gave the best results. The yields of Thf-FU and more especially of Thf2-FU were greatly dependent on the relative amount of SnCl4, and 0.01-0.1 equiv of the catalyst with respect to Me3Si-FU gave the best results. Thf2-FU was found to be effective against murine solid tumors and it was less toxic than Thf-FU when given orally. The antitumor activity of 3-Thf-FU is also reported.


1-[4-(4-Chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate, a new potent antifungal agent. The preparation and antifungal properties of 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate 1 are described. It is particularly effective against in vivo Candida albicans infections (mice), maintaining good activity down to 0.25% formulation strength and showing unusually low reinfection rates after treatment is ended.


Pain in childbirth.

Pain in childbirth. Sheila Kitzinger describes pain and its control throughout the various stages of childbirth. She stresses the value of antenatal preparation as well as the need for a supportive environment during the labour stages. All concerned--the porspective parents, doctors, midwives and any other personnel in a maternity unit should be educated to be able to provide such an environment.


Ca2+ transport by chondrocyte mitochondria of the epiphyseal growth plate. In a study of the Ca2+ kinetics of mitochondria of chick epiphyseal chondrocytes, the rate of Ca2+ uptake was linear up to a medium Ca2+ concentration of 30 mum. The half maximal transport rate occurred at 34 mum Ca2+. The Ca2+ uptake rate, expressed as a function of time, was 35 nmoles/mg protein/min; the presence of Mg2+ had little effect on Ca2+ accumulation. While these kinetic parameters did not differ significantly from mitochondria of cells of nonmineralizing tissues, the respiratory characteristics of the chondrocyte organelles exhibited functional differences. Thus, up to 350 nmoles Ca2+/mg protein, chondrocyte mitochondria performed coupled oxidative phosphorylation. Calcium uptake was energy supported, while Ca2+ binding was low. Addition of respiratory inhibitors and uncouplers to these mitochondria resulted in a rapid loss of more than 80% of the total Ca2+. The Ca/Pi ratio of the extrudate was very similar to the ratio of the ions in cartilage septum fluid. In the most mineralized zones of the epiphyseal plate, there was little change in the state 4 respiratory rate, but nonspecific Ca2+ binding was elevated and a high percentage of the total Ca2+ was in a nonextrudable form. The results indicate that in cells preparing for mineralization, much of the total mitochondrial Ca2+ is in a form that can be transported to the calcification front. In cells close to the calcification front, nonextrudable Ca2+ may form calcium phosphate granules described by other investigators.


High resolution scanning electron microscopy in biology: artefacts caused by the nature and mode of application of the coating material. Results of high resolution secondary electron observations of the haemocyanin molecule from the marine whelk Buccinum undatum are given. The choice of metal used for surface coating of the sample (gold, gold--palladium or carbon/gold--palldium) and the mode of application of this metal (thermal vacuum evaporation or diode sputtering) were both found to be of utmost importance when working at high magnifications in the scanning electron microscope. Sputter coating with gold gives poor results because of a granular and cracked appearance of the surface film. The haemocyanin molecules were difficult to recognize in these preparations. Best results were obtained by a thermal vacuum evaporation of gold--palladium. It is suggested that the inferior results seen after sputter coating may be due to the high temperatures wihch the specimen experiences during the sputtering, even when cooling of the specimen stage is carried out. Other specimens (diatom valves and latex spheres) were also studied at high magnification giving the same results as the haemocyanin molecules.


A method for the removal of epoxy resins from tissue in preparation for scanning electron microscopy. A method for unmounting entire resin-embedded samples for SEM observation is described. This technique is particularly useful when correlation of TEM and SEM images is desired for material that is no longer available for conventional SEM preparative procedures. Sample embedded in a variety of epoxy-type resins were trimmed of excess resin and placed in a concentrated solution of sodium methoxide. After complete dissolution of the resin, the tissue was washed in a graded series of sodium methoxide in methanol--benzene, transferred to acetone, critical point dried, mounted on stubs, and coated with gold-palladium. Upon viewing in the SEM, the tissue sample showed remarkable preservation of detail at relatively high magnifications.


Antigens of a human breast carcinoma cell line (BT 20). I. Synthesis of serum proteins, membrane-associated antigens, and oncofetal-associated antigens. The synthesis of various products by a human mammary cell line (BT 20) was studied by incorporation of 14C-labeled amino acids, choline, glucosamine, or galactosamine into nondialyzable materials. These products had molecular weights ranging from less than 12,300 daltons to more than 200,000 daltons. They were analyzed by immunoelectrophoresis and double diffusion in agar. Among the synthesized products, the following proteins were identified: beta2-glycoprotein I, alpha2HS-glycoprotein, alpha2-lipoprotein, actin, beta2-microglobulin, carcinoembryonic antigen, three oncofetal-associated antigens, and various erythrocyte membrane-associated antigens (namely, glycophorin). Synthesis of milk proteins was not detectable. Only the protein moiety of the glycophorin molecule seemed to be synthesized. The beta2-microglobulin was synthesized in an unbound state as well as bound to a glycoprotein whose relationship with the transplantation or tumor antigens must be determined. The three oncofetal-associated antigens were also synthesized in vitro by human fetal tissues and neoplastic and dysplastic human mammary tissues.


A reevaluation of B-lymphocyte levels in peripheral blood from cancer patients. B-lymphocytes were quantitated in mononuclear cell suspensions derived from the peripheral blood of patients with various nonlymphoreticular cancers. The method used was anti-IgM and anti-IgD membrane immunofluorescence. The mean percentage of circulating B-lymphocytes in 78 cancer patients tested was 5.3 +/- 4.6 with a range of 0--18%. Those values were compared with a mean of 9.4 +/- 4.0 and a range of 3--20% for 46 apparently normal individuals. The difference was highly significant (P less than or equal to 0.001). The mean percentage of B-cells in cell suspensions from 43 patients that were tested prior to treatment was 5.8 +/- 4.8 with a range of 0--18%. Very low values were observed both in the presence and absence of therapy, and a correlation with stage of disease could not be established. The low values were associated with decreased T-cell numbers and significantly increased monocyte levels. The fact that those values were significantly lower than have been reported previously for cancer patients was discussed as was the identity of the cells that previously had been counted as B-lymphocytes.


Pathogenesis of Marek's disease: early appearance of Marek's disease tumor-associated surface antigen in infected chickens. Marek's disease tumor-associated surface antigen (MATSA) appeared in different lymphoid tissues of P-line chickens soon after they were infected with BC-1 strain of Marek's disease virus. MATSA-bearing cells first appeared in spleens by 5 days post infection (PI) and were observed through a 21-day experimental period at mean levels varying from 3.8 to 21.9% of the total cells examined. Lower percentages of MATSA-bearing cells were observed in the thymus, in the bursa of Fabricius, among peripheral blood lymphocytes, and among bone marrow cells beginning 7 days PI. The antigen was not detected on normal lymphocytes from chickens or chicken embryos, nor was it detected on cultured chicken embryo fibroblasts infected or transformed by avian RNA tumor viruses.


Development of teratomas from embryos transplanted into outbred and inbred adult hamsters. Six- to 8 1/2-day inbred MHA/SsLak and outbred Syrian golden hamster embryos and 14-day fetal lungs, testes, and portions of small intestine were transplanted into cheek pouches or under kidney capsules of adult recipients. Embryonic grafts gave rise to benign teratomas, irrespective of the age of the embryo, transplantation site, and the strain or stock of recipient. Fetal lung and testis grew little in extrauterine sites, whereas fetal intestine formed large mucus-filled cysts lined with proliferating and apparently functionally active epithelium.


Primary splenic tuberculosis in transplant candidates. Caseous granulomatous lesions, consistent with tuberculosis, were found in the spleen in two of our renal transplant candidates. There was no clinical evidence of tuberculosis in either patient. Only one patient had a positive tuberculin skin test whose chest film showed hilar calcifications suggestive of healed granulomatous disease. Because of this incidental finding in the spleen, both patients were placed on antituberculous therapy. There has been no evidence of active tuberculosis in either patient despite the use of usual doses of immunosuppressive drugs.


Post-laryngectomy tracheostome stenosis--etiology and treatment. The etiology of post-laryngectomy tracheostome stenosis is reviewed. This condition is not common if preventive measures are used at the time of surgery and during the postoperative period. However stenosis will occasionally occur. We have not been satisfied with standard revision techniques but have had success with radical excision of the stenosed area followed by reconstruction with superiorly based bilateral pedicle flaps.


Surgical repair of complete subglottic stenosis. Two cases of complete subglottic stenosis, with absence of any subglottic airway, are presented. Both patients were treated via an anterior tracheo-crico-thyrotomy with excision of scar tissue. In both patients the newly created lumen was stented with Silastic covered with a buccal graft. One of these patients also had a hyoid bone autograft inserted between the cut edges of the cricoid ring. Both patients were successfully decannulated. The literature is reviewed in order to trace the history of the development of the procedures used.


The uses and limitations of auricular composite grafts. Composite autografts of skin and cartilage from the auricule are useful in the reconstruction of defects in many areas of the head and neck. However, their use has certain limitations if minimal loss of the graft is to be achieved. A variety of examples are presented by the authors and the limitations are summarized.


Longterm treatment with brompheniramine and phenylpropanolamine in recurrent otitis media--a double-blind study. A double-blind study has been performed in 44 children with recurrent episodes of otitis media and/or secretory otitis media using a combined preparation of brompheniraminemaleate and phenylpropanolaminehydrocloride (Lunerin mite). No significant prophylactic effect was found on symptoms of respiratory tract infections or middle ear diseases during the trial period of nine months. The result suggests that further critical studies should be performed with such preparations which for the time being are used abundantly for the prevention of middle ear infections or effusions.


Dextran sulfates as a contaminant of DNA extracted from concentrated viruses and as an inhibitor of DNA polymerases. Dextran sulfate is commonly used with polyethylene glycol to concentrate viruses before extraction of their DNA. However, dextran slulfate then easily contaminated such DNA and acted as a potent inhibitor of DNA polymerases from Bacillus subtilis (III), phage PBS2, and phage T4. Dextran sulfate only weakly inhibited Micrococcus luteus and Escherichia coli DNA polymerase I preparations.


Interaction between bacteriophage Sf6 and Shigella flexner. The Shigella flexneri phage Sf6 has an isometric head with hexagonal symmetry 53nm in diameter. The noncontractile tails in 16 nm long and terminates with a base plate containing six spikes. Sf6 is typical of the C phages in the morphological classification of Bradley. Phage Sf6 processes alpha-1,3-endorhamnosidase activity as demonstrated by methylation and reducing end group sugar analyses of the products obtained on interaction with the O-polysaccharide chain of S.flexneri strains which have the O-group 3,4 antigen. The major end product was an octasaccharide with the following structure: Rha III-GlcNAc-Rha I-Rha II-Rha III-GlcNAc-Rha I-Rha II. Acetylation of 0-2 of rhamnose III of the O-polysaccharide chain, either brought about by Sf6 lysogenization or found in wild-type S. flexneri (3b) strains, prevented enzymatic hydrolysis. O-deacetylation of the polysaccharide chain again made it susceptible to the S6f endorhamnosidase.


Cryptococcosis in columbiformes at the San Diego Zoo. Two cases of cryptococcosis in columbiformes exhibited at the San Diego Zoo are described. The organism isolated from the first case had morphological, chemical and temperature growth characteristics of C. neoformans. The culture from case 2 died before it could be examined biochemically or by mouse inoculation.


Furosemide compared with hydrochlorothiazide. Long-term treatment of hypertension. In a double-blind crossover study, the effectiveness of furosemide, 40 mg twice daily, was compared with hydrochlorothiazide, 50 mg twice daily, in hypertensive patients. Both hydrochlorothiazide and furosemide significantly reduced blood pressure (BP) during three months of therapy. However, the fall in BP was consistently greater with hydrochlorothiazide than with furosemide, although the difference was significant only with respect to systolic BP. The somewhat greater antihypertensive effectiveness of hydrochlorothiazide may be related to its longer action permitting a more continuous diuretic effect and, hence, maintenance of reduced extracellular fluid volume throughout the 24-hour period.


Rapid recovery from massive diazepam overdose. Two patients were hospitalized in moderately deep coma after ingestion of large doses of diazepam (500 and 2,000 mg) with suicidal intent. Neither patient experienced important complications; both recovered fully and were discharged within 48 hours. Concentrations of diazepam and its three pharmacologically active metabolites (desmethyldiazepam, temazepam, and oxazepam) were determined in multiple samples drawn during and after hospitalization. High concentrations of all four compounds were present in early samples, then declined slowly during the next one to two weeks. Rapid clinical recovery after diazepam overdose is not attributable to rapid elimination of active compounds from the body, but more likely to adaptation or tolerance to their depressant effects.


False-positive cryptococcal antigen test and cervical prevertebral abscess. A false-positive latex agglutination test for cryptococcal antigen occurred in a patient with a cervical prevertebral abscess and vertebral osteomyelitis caused by Klebsiella pneumoniae. Using a commercial latex agglutination test kit, a cryptococcal antigen titer of 1:32 was found in the CSF, but no cryptococcal antigen was found when the CSF was retested at a reference laboratory. The false-positive test resulted in unnecessary therapy with amphotericin B and delay in appropriate diagnostic studies and therapy.


A preliminary study in the detection of cardiac disorders via phase-invariant signature algorithm of ECG. The present paper presents a simple and unambiguous computer-assisted method for the detection of cardiac disorders by processing the electrocardiogram. A new technique "Phase Invariant Signature Algorithm (PISA)", has been described, which is useful in the detection of cardiac abnormalities by investigating certain statistical properties of the measured waveform of ECG in a "phase-locked" fashion. This method of detection of abnormalities in the heart was used in the changes in the hypoxic action potential and in the ECG due to ionic changes and ischemia in the heart of cats and dogs. The signature of the normal ECG or action potential was straight-line. Any change in the waveform of ECG or action potential was detected as spikes in the signature. This method of detection of cardiac abnormalities does not require a priori reference to any standard ECG. The results indicate that this new method is capable of detecting cardiac disorders at an early stage and hence a higher sensitivity than the presently available type of ECG analysis. This method is in the developmental stage and further studies are being carried out.


Liver transplantation.

Liver transplantation. From March 1963 through June 1976, 111 patients received orthotopic liver homografts. Forty-two of the recipients had congenital biliary atresia. Other common diagnoses were chronic aggressive hepatitis, Laennec's cirrhosis, and primary hepatic malignancy. There were also other assorted, less common diagnoses. Thirty-one of the 111 patients (28%) lived at least one year and 15 are still alive with follow-ups of 2 1/2 to 8 1/2 years. Seven of the patients lived for more than five years, and 6 of these 7 are still alive. In 1975 and 1976, clinical-pathologic correlations on all these patients were carried out with Professor K.A. Porter of London. The most common causes for failure were technical misadventures, including biliary tract problems, vascular thromboses, and the use of ischemically damaged livers. Rejection was less of a problem than had been realized. In view of these findings, improvements in intraoperative and postoperative management were made with particular reference to biliary tract drainage and to the use of microvascular techniques. Treatment of a new series of 30 patients was begun in July 1976, and completed in December 1977. After 6 to 22 months, 15 of the 30 most recently treated patients are alive, all living outside the hospital. Thus, the outlook after transplantation appears to have greatly improved, and a one-year survival rate of 50% is projected.


[Antithrombotic prophylaxis after surgical interventions on the major veins]. Eight-year experience in conducting antithrombotic prophylaxis, by methods elaborated by the authors, in 93 patients operated on for acute thrombosis in the system of venae cavae superior and inferior is generalized. On the basis of the results, the authors advanced the main principle of antithrombotic prophylaxis, the necessity for simultaneous correction of disorders of blood coagulation, fibrinolysis, and aggregation of formed elements of the blood. They showed that the efficacy of postoperative antithrombotic prophylaxis depends on the presence and character of hemodynamic disorders in the involved extremity. It is established that general fractional heparinization is not suitable for antithrombotic prophylaxis due to low efficacy and high rate of hemorrhagic complications. Continuous regional infusion of rheopolyglucin-heparin mixture with nicotinic acid and Trental ensures in most cases correction of the thrombotic condition of hemostasis and effective prevention of rethrombosis of the major veins with minimum hazard of hemorrhagic complications.


Phenylalanine metabolism in uremic and normal man. The metabolism of phenylalanine and tyrosine was evaluated in six normal men, five chronically uremic men, and three men undergoing maintenance hemodialysis. Phenylalanine, tyrosine, and 13 acidic metabolites of those amino acids were measured in plasma postabsorptively and in plasma and urine after a phenylalanine load of 100 mg/kg. In addition, five normal subjects and five dialysis patients ingested L-[14C]-phenylalanine (uniformly labeled) with the load. In uremic and dialysis patients, plasma phenylalanine rose higher and fell more gradually after the load, and tyrosine rose more slowly. The 24-hr urinary concentrations of phenylalanine and tyrosine were similar in the three groups. At 24 hr, cumulative expiration of 14CO2 was 20.2% in the dialysis patients and 28.4% in the normal subjects. Plasma phenylalanine levels and 14CO2 expiration varied with protein intake in normal subjects. In uremic and dialysis patients, plasma phenyllactic acid, p-hydroxyphenylacetic acid, and p-hydroxybenzoic acid were elevated, the last one markedly so. Moreover, plasma phenylpyruvic acid (PPA) and mandelic acid were detected only in dialysis patients. After the phenylalanine load, plasma conjugated phenylacetic acid rose in uremic patients, and PPA increased transiently in some dialysis patients. In urine of dialysis patients, concentrations of benzoic acid and conjugated o-hydroxyphenylacetic acid were decreased, and PPA was sometimes increased. The data suggest a mild impairment in the hydroxylation of phenylalanine which does not result in marked changes in plasma or in urinary metabolites after a phenylalanine load.


Response of plasma triglycerides to dietary change in patients on hemodialysis. The effect of reduction in dietary carbohydrate content of meal formula diets on plasma triglyceride concentrations was studied in 12 patients receiving chronic hemodialysis. Fasting plasma triglycerides decreased over a 10-day period in 11 of 12 patients in response to a decreased proportion of carbohydrate (from 50 to 35% of total daily calories) regardless of the type of fat used. Postprandial insulin responses were also significantly lower in the patients on the diets lower in carbohydrate. In addition, triglyceride kinetics were studied in three groups of patients. Patients with renal failure (dialyzed and undialyzed) had lower triglyceride production rates than those of control subjects, despite higher plasma triglyceride concentrations. Elevated (greater than 150 mg/100 ml) fasting plasma triglycerides are associated with lower triglyceride production rates in patients with chronic renal failure and may not be improved by conventional hemodialysis. A long-term study of the efficacy of reduction in dietary carbohydrate on plasma triglycerides is needed since routine hemodialysis does not appear to correct the lipid abnormality in patients with chronic renal failure.


Thoracic duct drainage and antilymphocyte globulin for renal transplantation in man. Thoracic duct drainage resulting in a lymphocyte depletion of more than 20 x 10(9) cells was performed during the three months prior to transplantation in 37 patients. Results obtained in this group of patients were compared to those in transplant recipients similarly treated, over the same period, but not subjected to thoracic duct drainage. Both groups received comparable doses of antilymphocyte globulins, azathioprine and corticosteroids. No clear-cut difference in transplantation outcome was found when recipients of kidneys from related living donors (whether HLA identical or HLA haploidentical) were considered. By contrast, an improved transplant survival and a decreased incidence of rejection crises were observed in recipients of kidneys from cadaver donors when a thoracic duct drainage was performed prior to transplantation. The immunosuppressive effect of thoracic duct drainage, probably enhanced by antilymphocyte globulin treatment, is therefore a valuable adjunct to more conventional methods of pretreating human cadaveric transplant recipients.


Importance of aliphatic amines in uremia. Five main aspects were addressed: 1)The demonstration that creatinine is an endogenous precursor of dimethylamine (DMA) in chronic renal failure. 2) The size of the body amine pool measured in transplant patients suggests sequestration in some intracellular compartment. This illustrates the possible error in directly relating serum concentrations to neurological toxicity. 3) Bacterial overgrowth and increased generation of duodenal DMA in the small intestine becomes apparent at a serum creatinine above 8 mg/dl. Two cases show that bacterial overgrowth preceded the increased duodenal DMA. 4)Clinical toxicity is demonstrated by i) correlation of abnormal neurobehavioral parameters with serum amine levels, and ii) by improvement with administration of nonabsorbable broad spectrum antibiotics. Results with adsorption agents are inconclusive. 5) Preliminary tests of behavior modification in a rat model by direct instillation of amines into the brain are positive for TMA but negative for DMA, but no DMA entry into brain cells is demonstrated in the latter. The generation of aliphatic amines represents only one part of a spectrum of alteration induced by proximal intestinal bacterial enzyme action that occurs in renal failure. It is possible that some bacterial activity is beneficial and that the net clinical result is a balance between the "good" and the "evil" bacterial effects.


The federal governments's role in management of end-stage renal disease. This presentation traces the history of the Federal government's support of research and development related to the therapeutic modalities dialysis and renal transplantation. A description is presented of the Federal government's role in introduction of these new treatment methods into medical practice and of the gradual assumption by the government of responsibility for funding of the cost of dialysis and transplantation in the United States. Current issues and problems related to the federally subsidized End-State Renal Disease Program are discussed. The concept of "technology assessment" is introduced followed by discussion of the vital role it must play in any future federal development and support of new medical treatment technologies which must be paid for with public moneys because of their high cost.


Selection of hemodialysis versus cadaveric transplantation. The records of 272 recipients of cadaver allografts and of 650 dialyzed patients (440 center dialysis and 210 home dialysis) were reviewed in an attempt to determine whether hemodialysis or transplantation is the best treatment for end-stage renal failure. Home dialysis patient survival is slightly better than that of cadaver kidney recipients and far better than center dialysis patient survival. When considering the quality of life assumed by the degree of social and professional rehabilitation, cadaver kidney transplantation appears the optimal choice. Finally, the life expectancy of a patient is higher if he embarks upon an integrated program where hemodialysis is a complementary adjunct to cadaver kidney transplantation.


Donor pretreatment in an unselected series of cadaver renal allografts. In a single center, an unselected non-exclusion series of 78 consecutive cadaver renal allografts in 76 recipients was studied. Since 1971, using kidneys obtained from donors pretreated with large doses of cyclophosphamide and methylprednisolone, excellent clinical results with 2-year graft-survival of 70% 5-year graft survival of 66% have been obtained. The improvement in results is believed to be aided by the reduction in allograft immunogenicity due to short-term donor pretreatment. In this series, poor tissue-matching grades are notable, heavily transfused patients are few, 33 patients were high risk, and 43 patients were presensitized. In spite of these negative selection factors, the results obtained in this pretreated series, with 18% of graft losses due to rejection, are superior to those obtained in patients who did not receive pretreated allografts during the same time period, with 34% of graft losses due to rejection, and 2-year and 5-year graft survivals of 57% and 53%, respectively.


[Experiences with the implantation of the 2-loop-medaillon-lens (author's transl)]. The experience with 100 primary implantations of the 2-loop-Medaillon-lens is reported. In 4% complications occured that decreased the visual outcome. The avoidance of complications is discussed. In the author's opinion implanting artificial lenses is a suitable method of visual rehabilitation - connected with little risk - of patients who are not suitable for correction with glasses or contact lenses. The indications and contraindications are discussed. The main indication is a onesided cataract.


[Surgical treatment of entropium senile (author's transl)]. The authors report on a modification of the entropion surgery of Celsus-Hotz which was successfully carried out in 87 patients with entropion senile from 1969 to 1976. After excision of an about 5 mm wide crescentshaped dermal tissue of the lower eyelid about 3 mm down the margin the muscle fibres of the M. orbicularis near the margin are resected. Before suturing the skin 3-6 stitches of Hotz are done to reduce the tarsus. The advantages of this technique are the safe therapeutical effect, the cosmetical effect and the easy correction of this operation in case of a failure.


[The Custodis procedure--technic and results (author's transl)]. Within the post 11 years 2,722 retinal detachments needed surgery. The mostly used procedure of Custodis consists in an implant, which covering the area of the hole is impressed into the sclera by mattress sutures. In 70% of our cases--due to Custodis--we succeeded in avoiding drainage of the subretinal fluid. Since 1966 the additional diathermy and/or lightcoagulation was mostly replaced by cryopexy. Summarizing the number of retinal detachments operated in the University clinic of Münster during 1955--1957 (Pau), 1958--1961 (Böke) as well as ours (1966--1977), 4,030 retinal surgeries (minus 10% encircling procedures) underwent within 18 years a Custodis procedure. The success rate of 85% indicates that Custodis' technic enables to optimal results.


[Coagulation and fibrinolytic system in the vascular risks diabetes mellitus and hyperlipoproteinemia (author's transl)]. 42 patients with minifest diabetes mellitus and 42 patients with primary hyperlipoproteinemia type II, IV or V (Fredickson) underwent analysis of cholesterol, triglycerides and agar-agarosegel-lipoprotein electrophoresis. Simultaneously clotting factors I--XIII, platelet count and aggregability, fibrinolytic activity and antithrombins were determined. The most accentuated disturbances were seen in hyperlipoproteinemia type II and in diabetes mellitus comprising increase of fibrinogen content, platelet reduction and enhanced platelet aggregability, hypofibrinolysis. Only minor differences of certain clotting factors could be detected comparing diabetes mellitus and hyperlipoproteinemia type II. Diabetes mellitus being complicated by micro- or macroangiopathia revealed additional significant alterations such as more pronounced increase of fibrinogen, further platelet reduction and aggregability. Increase of fibrinogen, platelt disturbances, hypofibrinolysis and alterations of antithrombin activity in connection with metabolic diseases may be regarded as additional risk to vascular complications.


[Neurophysiological bases of vestibular training]. Occupation-oriented vestibular selection is based on the two principles: selection of vestibular-resistant subjects, and increase of vestibular tolerance through training. The latter implies inherited ability of the central nervous system to attenuate vestibular reactions. The review surveys experimental data concerning attenuation (habituation) of vestibular reactions as a result of prolonged or reiterative excitation of labyrinthine receptors. The review discusses peculiar features of the development, stability and transfer of habituation. It gives data on disturbed habituation as a result of an exposure to stress-effects (hypokinesia, hypoxia, hypothermia) and certain drugs. The phenomenon of vestibular habituation is interpreted in terms of Sokolov's concept of the stimulus nervous model.


Surface antigens of the embryonic chick myoblast: expression on freshly trypsinized cells. Using an antiserum raised in rabbits against embryonic chick skeletal myoblasts (Anti-M-24), we have examined the trypsin and neuraminidase sensitivity and physiological expression of myoenic cell surface antigens. It was found that trypsin-released muscle cells more effectively inhibited, on a cell to cell basis, the cytotoxicity of Anti-M-24 for 24-h-old myoblast monolayers than did identical cells that had received a 3-4 h suspension culture recovery period from trypsinization. There was no such difference in absorptive capacities observed for any other embryonic chick tissue tested (e.g. brain, retina, liver, heart, and red blood cells) when freshly trypsinized cells were compared to ones which were given a 3-4 h culture period. If freshly trypsinized muscle cells were treated with high concentrations (30,000 international units (IU)/0.1 ml packed cells) of trypsin or with neuraminidase (30,000 IU/ml packed cells), there was a selective loss of myoblast-specific surface antigens. When single cells that had been in suspension culture for 3.5 h were reexposed to low concentrations (10,000 IU/0.1 ml packed cells) of trypsin, more antigenic sites were revealed on their surfaces as detected by an increased absorptive capacity in removing myoblast-binding antibodies from Anti-M-24. This increase in antigenic expression was time-dependent and inversely related to the length of culture time after trypsinization. Immunofluorescence studies revealed that tissue specific myoblast cell surface antigens are present on both muscle cells that were freshly dissociated and those that had been in suspension culture for 3-4 h. Furthermore, freshly trypsinized myoblasts possessed cell surface components that were highly antigenic; antiserum to such cells reacted extensively with both trypsinized and recovered muscle cells as detected by complement-dependent 51Cr release cytotoxicity assays and immunofluorescence. We conclude that embryonic chick myoblasts possess surface antigens that may be selectively removed by neuraminidase or high concentrations of trypsin. These antigens may be progressively masked, with increasing time of culture after protease-dissociation, by molecules that are sensitive to low concentrations of trypsin. Such masking of tissue-specific cell surface antigens could result in the display of molecular mosaics which may play a role in facilitating intercellular recognition and subsequent differentiation and histogenesis.


Energetics and molecular biology of active transport in bacterial membrane vesicles. Bacterial membrane vesicles retain the same sidedness as the membrane in the intact cell and catalyze active transport of many solutes by a respiration-dependent mechanism that does not involve the generation of utilization of ATP or other high-energy phosphate compounds. In E. coli vesicles, most of these transport systems are coupled to an electrochemical gradient of protons (deltamuH+, interior negative and alkaline) generated primarily by the oxidation of D-lactate or reduced phenazine methosulfate via a membrane-bound respiratory chain. Oxygen or, under appropriate conditions, fumarate or nitrate can function as terminal electron acceptors, and the site at which deltamuH+ is generated is located before cytochrome b1 in the respiratory chain. Certain (N-dansyl)aminoalkyl-beta-D-galactopyranosides (Dns-gal) and N(2-nitro-4-azidophenyl)aminoalkyl 1-thio-beta-D-galactopyranosides (APG) are competitive inhibitors of lactose transport but are not transported themselves. Various fluorescence techniques, direct binding assays, and photoinactivation studies demonstrate that the great bulk of the lac carrier protein (ca. 95%) does not bind ligand in the absence of energy-coupling. Upon generation of a deltamuH+ (interior negative and alkaline), binding of Dns-gal and APG-dependent photoinactivation are observed. The data indicate that energy is coupled to the initial step in the transport process, and suggest that the lac carrier protein may be negatively charged.


The molecular mechanism of dicarboxylic acid transport in Escherichia coli K 12. It is the purpose of this communication to review the properties of the dicarboxylic acid transport system in Escherichia coli K 12, in particular the role of various dicarboxylate transport proteins, and the disposition of these components in the cytoplasmic membrane. The dicarboxylate transport system is an active process and is responsible for the uptake of succinate, fumarate, and malate. Membrane vesicles prepared from the EDTA, lysozyme, and osmotic shock treatment take up the dicarboxylic acids in the presence of an electron donor. Genetic analysis of various transport mutants indicates that there is only one dicarboxylic acid transport system present in Escherichia coli K 12, and that at least 3 genes, designated cbt, dct A, and dct B, are involved in this transport system. The products corresponding to the 3 genes are: a periplasmic binding protein (PBP) specified by cbt, and 2 membrane integral proteins, SBP 1 and SBP 2, specified by dct B and dct A, respectively. Components SBP 1 and SBP 2 appear to be exposed on both the inner and outer surfaces of the membrane, and lie in close proximity to each other. The substrate recognition sites of SBP 2 and SBP 1 are exposed on the outer and inner surfaces of the membrane respectively. The data presently available suggest that dicarboxylic acids may be translocated across the membrane via a transport channel. A tentative working model on the mechanism of translocation of dicarboxylic acids across the cell envelope by the periplasmic binding protein, and the 2 membrane carrier proteins is presented.


Impairment of the hypothalamo-pituitary-ovarian axis of the athymic "nude" mouse. Pituitary and serum levels of LH and FSH and hypothalamic GnRH content were measured in acyclic, congenitally athymic (nu/nu) female mice. No significant differences were found between athymic and normal dioestrous mice of the same age (3 months). The serum LH level of the athymic mouse failed to increase 6 days after ovariectomy, but increased in response to injection of GnRH. The results suggest that the athymic nude mice suffer from impairment of hypothalamic control of the pituitary.


Lipofuscinogenesis in mice early treated with centrophenoxine. Previous studies in our and other laboratories indicated that there is a reduction in the neuronal lipofuscin in old rodents after several weeks of treatment with centrophenoxine. The present study investigates whether this chemical can prevent pigment formation if given early in life before the onset of pigmentogenesis. The study shows that the drug did not stop lipofuscin formation in 1 month old mice. But there was a consistent decrease in the pigment in the neurons of cerebral cortex and hippocampus of the treated animals compared to the age-matched controls. The degree of reduction was largely dependent on the duration of the treatment and a significant diminution was noted after treatment for five months or more.


[Nevus lipomatosus cutaneous superficialis]. Two cases of naevus lipomatosus superficialis (Hoffmann and Zurhelle) are described by the authors. The main clinical characteristics and histological peculiarities are reviewed. Both cases were disseminated and had typical localisation (pelvic area). The histological examination showed ectopic adipocytes in the dermis. The authors mare a reference to the different hypotheses on the pathogenesis of these lesions.


[Hereditary benign intra-epithelial dyskeratosis (Witkop--Von Sallman syndrome)]. A case of inherited intraepithelial benign dyskeratosis (Witkop-Von Sallmann syndrome) is presented by the authors. The diagnosis is based on clinical and histological peculiarities.


[Early or malignant ulcerative syphilis. Considerations apropos of 2 cases. Bibliographic analysis]. Two cases of early ulcerative syphilis observed in the city of La Plata, Argentina, in the last 13 years are presented. Cases n.o 1, classified as Queyrat type, was in a previously bad general condition, due both to excessive smoking and alcoholism and showed a classic blood serologic test, that was slightly reactive. Case n.o 2, Milian type, presented a previously excellent general condition. The classic blood serologic test and FTAabs. were strongly reactive. It showed only a significant depression of cell immunity, with regard to the bacterial cutaneous proofs (bacterial skin-tests) carried out "in vivo". In both cases the clinical aspect was similar, with ulcerative necrotic lesions and affectation of the general condition which coincided with the outbreak of those lesions. The response to treatment was good, with rapid improvement of the general condition while the improvement of the skin lesions was slower and occurred only within 3 weeks.


[Lichenoid pityriasis. Clinical study of 13 cases]. 13 patients with Pityriasis Lichenoides are studied clinical and histologically, showing a clinical polymorphism of the lesions, mainly in the papulous, vesiculous, and necrotic ones. The data about age, sex, evolution and response to the treatment in the present study are similar to those found by other authors. Constantly, we found, a variable degree of vasculitis. In almost all the cases there was a damage of the epithelium --exoserosis and exocytosis--, as well as presence in some cases, of red cells extravasated within the epidermis. In upper dermis we found in all biopsies, divers degrees of perivascular cell infiltration mainly composed of lymphocytes and histiocytes with predominance of the last ones, in five cases. In the majority of our cases, there was a strong relationship between the clinical and the histological aspects, but in some cases, mild lesions showed an acute microscopical picture. We are of the opinion that Pityriasis Lichenoides must be considered as a different entity from Parapsoriasis. In addition, we think that PL, is a clinical picture that manifests itself as a chronic or an acute form, and both types can be seen in the disease evolution. Finally, we could not find an evident influence and a positive response to the treatment in our patients with the classical therapeutics.


[Churg-Strauss allergic granulomatosis]. A 65 year old female patient with a 2 year history of bronchial asthma disseminated petechial, papulopustular and ulceronecrotic eruption and an isolated episode of intestinal bleeding. Chest X rays showed bilateral pulmonary infiltrates and laboratory examination revealed eosinophilia (17%) leucocytosis (22.900) and a severe renal insufficiency. Cutaneous biopsy revealed a necrotizing, leucocytoclastic vasculitis of the small blood vessels in the dermis as well as the hypodermis. The patient died 2 days after diagnosis and corticosteroid therapy had been started. Necropsy showed granulomatous and/or vasculitic lesions of the lungs, spleen, kidneys and skin. The clinical and laboratory aspects are discussed and the relevant literature is reviewed.


[Bone lesions in Kaposi's angiogenous reticulosis]. The bone lesions usually seen in Kaposi's sarcoma are described. Three patients with moderately severe skin lesions who showed bone lesions are reported. X-rays examination showed different types of pathologic aspects which are described. A thorough evaluation searching for bone lesions should be made in all cases of Kaposi's sarcoma, mainly those with extensive cutaneous lesions.


[Angiomas of the mouth].

[Angiomas of the mouth]. A patient with palatal hemangioma was subjected to study and the general characteristics of buccal hemangioma are analyzed. Their infrequent occurrence being remarkable. Maxillar angiomas have a reserved prognosis not only because of their histologic malignancy but also because of the threat of incoercible hemorrhage with the removal of dentures. Therefore radical surgical intervention or eventual radiotherapy is indicated.


[Ultrastructure of Darier's disease].

[Ultrastructure of Darier's disease]. Biopsies from four patients with Darier's disease were studied by electron microscopy. The desmosome-tonofilament complex does not seem to be primarily involved in the acantholytic process responsible for the epidermal cells separation with formation of suprabasal lacunae. Grains and corps ronds are consistent histopathological findings in Darier's disease: the ultrastructure of these cells is described.


The marathon: a history and review of the literature. An evaluation of the physiological, biochemical and psychological results obtained by various investigators on participants in competitive marathons is provided. The historical background of the studies on marathon runners suggests that much of the early information has been forgotten and has resulted in repetitive studies providing no additional insight into the physiological problems of these runners. However, the basic information obtained since the first scientific studies of participants in the 1899 marathon race has provided interesting and valuable information. The value of this older basic information to present and future investigators is emphasized. Suggestions for additional research based on results from both the earliest and the latest studies of marathon runners are made. Increasing participation in marathon races by individuals of both sexes, by individuals with various kinds of pathology as well as individuals of varying levels of physical competence suggests the value and need for research on these individuals before, during and after their involvement in such a strenuous and physiologically demanding physical task.


[Optimization of the local thermocoagulation process as applied to stereotaxic neurosurgery]. A mathematic model was set up to find the thermal response of tissues to thermocoagulation. This model was studied by means of an analogue computer so as to establish optimal operating parameters for high-resistance heating probes. The smallest size of the layer of incomplete necrosis was used as criteria for optimization. The results suggest that the best performance characteristics in thermal coagulation can be achieved by using controlled temperatures from 77 to 87 degrees C (applied intermittently or continually).


The stimulus-secretion coupling of glucose-induced insulin release XXVI. Are the secretory and fuel functions of glucose dissociable by iodoacetate? Iodoacetate inhibits glyceraldehyde-3-phosphate dehydrogenase activity in pancreatic islets and causes a time- and dose-related inhibition of glucose oxidation and lactate output by the islets. High concentrations of the drug (0.3 mM or more) fail to affect Ba2+-induced insulin secretion but inhibit glucose-stimulated proinsulin biosynthesis, 45Ca net uptake and insulin release. A mixture of fumarate, glutamate, and pyruvate, the oxidation of which is only partially reduced by iodoacetate, fails to protect the B-cell against the inhibitory effect of the drug. These findings are compatible with the view that glycolysis plays an essential role in the process of glucose-induced insulin release. At low concentrations of iodoacetate (up to 0.2 mM), the reduction in glucose metabolism coincides with a partial inhibition of proinsulin biosynthesis. However, the expected reduction in 45Ca net uptake and subsequent insulin release is masked by a concomitant facilitating action of iodoacetate, possibly due to interference with native ionophoretic processes. It is concluded that iodoacetate is not an adequate tool to dissociate, if they are dissociable, the fuel and secretory functions of glucose.


Elevated levels of pancreatic polypeptide in obese-hyperglycemic mice. The concentration and distribution of pancreatic polypeptide (PP) was studied in hyperglycemic obese (ob/ob) mice and homozygous (+/+) controls. By radioimmunoassay, the concentration of PP in the pancreas of ob/ob mice was greater both in the duodenal lobe (70.7%) and in the body and tail (66.3%) when compared to identical areas of control pancreases. Analysis of immunostained pancreatic tissue indicated that the number of PP cells per islet cross-section was significantly increased (58%) in the ob/ob tissue. The calculated total number of PP cells per average islet was elevated three times in the ob/ob islet. However, the proportion PP cell volume relative to the islet volume in ob/ob was one-half that of control islets. These results clearly demonstrate an elevation in both the number of PP cells per islet and the concentration of PP in the diabetic ob/ob murine pancreas.


Effect of phenoxyethanol on the permeability of Escherichia coli NCTC 5933 to inorganic ions. Concentrations of phenoxyethanol which retarded the growth rate of Escherichia coli NCTC 5933 in nutrient broth, stimulated the rates of respiration and total oxygen uptake of cell suspensions with glucose as carbon source, and were able to dissipate artificially induced membrane proton gradients. In cells with repressed oxidative phosphorylating activity, no stimulation of respiration was observed. These actions were characteristic of uncouples of oxidative phosphorylation. Similar concentrations of the drug caused additional increased permeability of the cytoplasmic membrane to K+ but not to Li+, Na+, Ca++, Mg++, NO-3, Cl-, So--4, or PO---4. Drug induced permeability of the membrane to protons and potassium ions were not found to be directly coupled.


Preferential uptake of thymidine by thymineless enterobacteria: its significance in DNA labelling. Minimum satisfactory concentrations of thymine and thymidine were determined for the growth of a high thymine-requirng (thy) mutant to Escherichia coli strain J5-3. Cultures were then grown in the presence of these concentrations of non-radioactive ('cold') pyrimidine together with 5 microCi/ml [methyl-3H)thymine, or [methyl-3H)thymidine (specific activities 5 Ci/m mole), and the uptake of radioactivity into ice cold trichloroacetic acid insoluble material determined. By far the most efficient labelling system was obtained if the label was supplied as radioactive thymidine and growth requirements satisfied by thymine alone. The addition of deoxyadenosine to the labelled thymidine/unlabelled thymine system dramatically reduced uptake of label. The addition of radioactive thymine with either thymine or thymidine to ensure satisfactory growth gave poor labelling. Using the [methyl-3H] thymidine/thymine system it was possible to increase the concentration of thymine from 8 to 64 microgram/ml with only a 25% reduction in label uptake after a 2 h period. The same system was also shown to be most efficient for labelling a thy derivative of another K12 strain, a thymine low-requiring (tir) K12 strain, a thy mutant of Klebsiella aerogenes 418 and a tir derivative of Salmonella typhimurium LT2.


In vivo formation of transmissible resistance factor by recombination between nontransmissible resistance factor and Col B factor. Germ-free swine were artificially contaminated with tetracycline (TC) sensitive strains of Escherichia coli and Klebsiella pneumoniae. One of these strains, E. coli 3306, was infected with a plasmid carrying kanamycin (KM) resistance, i.e., T-kan factor. Another strain, E. coli P-5, carried a conjugally transferable Col B factor. Among the nine strains used, only E. coli P-38 became TC-resistant after TC administration. Three types of TC-resistance E. coli P-38 strains were found; (a) one strain carried nontransferable TC resistance and could not produce colicin, (b) one strain carried TC resistance with a high transmission frequency which could not produce colicin, and (c) one strain carried TC resistance with a low transmission frequency that could produce colicin B. Genetic studies disclosed that the transmissible TC resistance factors, i.e., Rms105 (group b) and Rms104 (group c), were formed by recombination between Col B factor and nontransmissible TC-resistance (tet) determinant which appeared in E. coli P-38 mutants.


Proliferation of hemolysin-plaque-forming cells in nude mice and normal littermates subjected to antigenic competition. The increase of PFC per spleen and the development of hemolytic foci were examined to clarify the patterns of clonal expansion of B-lymphocytes in athymic nude mice (nu/nu) and normal littermates (nu/+) subjected to the procedure for antigenic competition between horse erythrocytes (HRBC) and sheep erythrocytes (SRBC). In normal littermates without pretreatment with HRBC, a small number of PFC and hemolytic foci of small size were detected 2-days after the challenge with SRBC. The number of PFC increased progressively from day 2 to day 4, and hemolytic foci increased in the number and size during the period. In nude mice, a small number of PVFC were detected on day 2 and the number increased only slightly from day 2 to day 4. No large hemolytic foci were detected during the period. In normal littermates subjected to the procedure for antigenic competition, the patterns of increase of PFC and development of hemolytic foci were similar to those in nude mice. In nude mice, the procedure for antigenic competition exerted almost no effect on the patterns.


Genetic control of granuloma response to oil-associated BCG cell wall vaccine in mice. Intravenous injection of mice with BCG cell wall vaccine induces granuloma in the lung. The granuloma induced as measured by lung weight showed marked strain differences; C3H/HeMs bred in this Institute (C3H), C3HeB/FeJ, P/J and A/He were low responders, whereas C57BL/6 and AKR/He were high responders. When C57BL/6 and C3H were compared, the responsiveness appeared to be inherent in each strain of mice providing strong evidence for genetic control in this phenomenon. Breeding experiments suggested that multiple loci, including a MHC-linked locus, were involved although the role of the MHC-linked loci was marginal.


Clinical patient management and the integrated health information system. Emerging progress in clinical applications of patient care computing is identified. The essential clinical skill is understanding what data are appropriate in any given patient care situation and extracting enough information to make the correct management decision. The value of the computer has less to do with the internal intellectual process of diagnosis than its contribution to the more manifest actions in support of clinical patient management. Techniques with which the computer is assisting in improving the clinical decisionmaking process are reviewed, and a mechanism to link them to active patient care settings is described. In addition, a trend toward the integration of various independent subsystems, so that expensive resources can be optimized for patient needs, is noted.