Peroneal nerve conduction velocity after chronic electrical stimulation. The effects of electric stimulation on nerve conduction velocity of the peroneal nerve via surgically implanted electrodes was evaluated in a group of nine hemiplegic patients. After a mean duration of 25 months nerve conduction velocity averaged 47.3 meters/sec in the uninvolved and 46.1 meters/sec in the stimulated (paretic) extremity. In a control group of ten hemiplegic subjects who did not receive stimulation, nerve conduction velocity averaged 43.1 meters/sec in the hemiplegic leg, and 41.3 meters/sec in the uninvolved leg. These differences were not statistically significant. Maximum dorsiflexion strength was increased in all patients following chronic stimulation.


Problem oriented medical records: their impact on staff communication, attitudes and decision making. A comparative, two-stage between hospital study involving university rehabilitation centers was undertaken to evaluate the impact of the problem oriented medical record (POMR) on staff communication, attitude change and decision making. Staff characteristics varied from one center to another. The semantic differential component of the project did not reveal any change due to the POMR in the staff perception of the medical record, the health care team or the various health professions. However, team function with respect to the management of specific patients improved in the centers which implemented the POMR during the time period of the project.


Levodopa-induced myoclonus.

Levodopa-induced myoclonus. Twelve parkinsonian patients on long-term levodopa therapy developed intermittent, myoclonic body jerks. The movements consisted of single unilateral or bilateral abrupt jerks of the extremities and occurred most frequently during sleep. Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide. Levodopa-induced myoclonus may be related to intermittent increases of activity of serotonin in the brain and results from levodopa-induced dysregulation of serotonin activity.


[Intraosseous injections and the osseous pressure in patients with rheumatoid shoulder pain]. Intraosseous injection of physiological saline or local anaesthetic (prilocain) results in a marked relief of rest pain in rheumatoid shoulder. 28 shoulders were treated in tis way and the intraosseous pressure of the proximal end of the humerus was measured with simple central venous pressure equipment. The intraosseous pressure tends to decrease after injections.


Coronary artery reperfusion: effects of occlusion duration on reactive hyperemia responses. In 24 unanesthetized dogs, we monitored reactive hyperemia responses in the coronary vascular bed after different durations of coronary occlusion and during coronary artery reperfusion. After two hours of occlusion, no significant changes in functional capacity occurred, evidenced by unchanged peak reactive hyperemia, reactive hyperemia flow and repayment of flow debt responses. With occlusions of six hours or more, these responses were impaired upon reperfusion, and remained diminished for up to five days. In those animals reperfused after two and six hours of coronary occlusion, myocardial infarcts were significantly smaller than those seen in animals reperfused after 24 to 72 hours of occlusion (4%, 14%, 20% and 21%, respectively). Thus, the effectiveness of any reperfusion procedure depends on its early institution when the coronary vascular bed has minimal change in functional capacity and the size of the infarct can still be reduced.


Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. A study of the immunoglobulin (Ig) synthesis by peripheral blood cells of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and controls was carried out. Synthesis was markedly elevated in patients with active SLE, whereas patients with the active SLE or RA showed normal values. Treatment of 3 patients with active SLE resulted in a reduction of Ig synthesis that correlated well with the disappearance of disease activity. There results indicate that the abnormal immune process in active SLE, characterized by intense B-lymphocyte stimulation, is associated with the appearance of more highly differentiated B cells in the blood.


Cell-mediated immunity in rheumatic diseases. II. Mitogen responses in RA, SLE, and other illnesses: correlation with T- and B-lymphocyte populations. Lymphocyte responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were tested in normal patients and in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma (PSS), other connective tissue disease, and other illnesses. The relationship of lymphocyte response to diagnosis, therapy, and T- and B-lymphocyte populations was analyzed. Additional studies included the determination of proliferative responses of various combinations of purified T and B lymphocytes cultured with plant mitogens. Lymphocytes from patients with RA and SLE incorporated significantly less thymidine in the presence of plant mitogens as compared to normal and comparably ill subjects. Treatment had no effect on mitogen response. Responses to all three mitogens correlated closely in patients with RA, SLE, or PSS; no correlation was noted between the response to mitogen of lymphocytes in culture and the number of T cells cultured.


Review of variations in origin of left circumflex coronary artery. During the performance of 200 routine coronary angiograms, 5 patients with anatomical variants of the origin of the left circumflex coronary artery were found. The origin and course of the left circumflex coronary artery is described in each case. The practical importance of these variant vessels in patients being considered for coronary artery surgery is emphasized.


[The clinical problem of hereditary hemorrhagic diseases developing prolonged bleeding time]. Thirty-two patients with hereditary hemorrhagic diseases and a platelet functional abnormality were set apart from our group of patients with hereditary hemorrhagic diseases, and their symptoms, signs and hematological examinations were collected; the initial events and the age of the patients when they were obsserved, the main hemorrhagic manifestations during their clinical course, the clinical severity of the disorders, the survival of the patients and the laboratory test for hemostasis useful to make the diagnosis, were evaluated. In reference to bleeding time, thirty patients had abnormal bleeding time, but the other two had normal bleeding time.


[Kartagener's syndrome in childhood. Report of 2 cases]. Two cases of children with the syndrome (triad) of Kartagener are described. One of them presented two of the triad's components; the other one, probably complete, as a part of a partial revision of clinical charts, corresponding to children with "situs inversus", from 1970 to December 1973, at the Children's Hospital of Mexico. The literature is reviewed, concerning this unfrequently seen entity, finding a great majority of reports in children, less than 14 years old, a positive family history and serious respiratory disease complications on those affected. It is important to understand the early diagnosis and treatment of these patients, mainly if they have upper respiratory disease, to avoid future onset of bronchiectasis. The genetical aspects, as well as variable clinical affections are mentioned.


The interaction of alpha-1-antitrypsin with chymotrypsin, trypsin and elastase. The mode of inhibition by alpha-1-antitrypsin of chymotrypsin, trypsin and pancreatic elastase was examined by a kinetic method. All three enzymes were completely bound to alpha-1-antitrypsin; therefore, the dissociation constant of the enzyme-inhibitor complex was too low to measure with these methods. The dissociation constants for the three enzyme-inhibitor complexes were estimated to be less than 5 - 10 minus 9 M. However, alpha-1-antitrypsin could be specifically displaced from Sepharose-bound elastase with an irreversible inhibitor of that enzyme. Additional experiments showed that dioxane, 20% (v/v), blocked 100% of the inhibition of elastase, 16% of the inhibition of trypsin, and 0% of the inhibition of chymotrypsin. The effect was reversed by diluting the dioxane to 1% (v/v). These findings indicated that alpha-1-antitrypsin was tightly bound to the three enzymes studied but did not allow discrimination as to the nature of the inhibition. However, the competitive mode of inhibition was suggested by the displacement of alpha-1-antitrypsin from elastase by an irreversible inhibitor of the enzyme that bound covalently at the enzyme-active site. The variable susceptibility of the enzyme to blockage of the inhibition by low concentrations of p-dioxane suggested that hydrophobic bonds may be important in the interaction with alpha-1-antitrypsin.


Antinuclear antibodies in psychiatric illness: their relationship to diagnosis and drug treatment. Antinuclear antibodies occurred more often and in higher titres in psychiatric patients than in controls. Anti-DNA antibodies were not found. We suggest that antinuclear antibodies may be drug-induced and that lithium carbonate may have a particular tendency to produce this reaction.


Natamycin in genital candidosis in men.

Natamycin in genital candidosis in men. In a trial of natamycin, an antifungal antibiotic in a vanishing cream base, assessment was possible in 66 men with genital or anal candidosis. The overall cure rate was 82 percent, In 43 patients with culturally proven candidosis it was 98 percent. but in 23 patients treated solely on clinical impression it was only 52 percent. Symptoms were rapidly relieved in those who responded and there were no side-effects. In our hands, natamycin 2 per cent cream has proved to be a valuable preparation in the treatment of candidal balanitis.


Regulation of 5-hydroxytryptamine metabolism in mouse brain by adrenal glucocorticoids. The effects of glucocorticoid hormone on the metabolism of brain 5-hydroxytryptamine (5-HT) were studied in mice. A single injection of hydrocortisone acetate (HCA; 20 mg/kg, i.p.) accelerated the accumulation of 5-HT in whole brain after inhibition of monoamine oxidase activity by paragyline. The hormone did not appear to change brain tryptophan hydroxylase or 5-hydroxytryptophan decarboxylase activity. However, tryptophan levels in brain were elevated by 50% within 1 h after treatment with HCA. The effect of HCA on brain tryptophan levels was localized mainly in the nerve endings. In vitro synaptosomal preparations, HCA at 10(-5)-10(-7)M or corticosterone at 10(-5) M was found to stimulate the uptake of L-[3H]-tryptophan by the synaptosomes while androgenic and progesterone-like steroids were ineffective. These results demonstrate that glucocorticoids may directly act on nerve terminals in the regulation of 5-HT synthesis through an action on the uptake of tryptophan.


The effects of morphine and halothane anaesthesia on urine norepinephrine during and after coronary artery surgery. Urine concentrations and excretion rates of norepinephrine were measured in 28 patients anaesthetized with halothane or morphine before, during and for two hours after aortocoronary artery grafting procedures. All patients were paralyzed with d-tubocurarine, intubated and respiration was controlled. Urine was obtained for 90 minutes before induction, during induction, before, during and after bypass and postoperatively. In patients anaesthetized with halothane, urinary norepinephrine concentrations and excretion rates were not significantly different from preoperative values until the postoperative period. Patients anaesthetized with morphine did not have urine norepinephrine concentrations different from preoperative values until bypass, when they became significantly increased. All subsequent urine norepinephrine concentrations and excretion rates were significantly elevated when compared to preoperative values. These findings do not indicate a mechanism but they do demonstrate that morphine anaesthesia is associated with increased urinary and probably also increased plasma levels of norepinephrine during and after cardiopulmonary bypass in patients undergoing coronary artery operations.


Studies on the integrative activity of the vestibular nuclei complex. Central mechanisms currently used in clinical vestibular tests are far more complex than generally thought. The first synaptic station, the vestibular nuclei, represents a sensory-motor centre integrating vestibular impulses with proprioceptive afferents from muscles and joints. This convergence can be found on cells with long axons projecting to the oculo-motor system, to the spinal cord and to the thalamus as well as on cells without long projecting axons. There are also vestibulo-motor cells transmitting pure vestibular information.


LDH isozymes of human T and B lymphocytes. Peripheral lymphocytes were obtained from five normal healthy adults. T and B lymphocytes were separated by rosette formation. LDH (L-lactate: NAD-+ oxidoreductase, EC 1.1.1.27) isozymes were studied on both populations after agar gel electrophoresis. The mean B lymphocyte pattern was: LDH-1, 7.2%; LDH-2, 25.0%; LDH-3, 39.2%; LDH-4, 21.9%; LDH-5, 6.6%. The mean T lymphocyte pattern was: LDH-1, 25.8%; LDH-2, 35.1%; LDH-3, 28.3%; LDH-4, 9.4%, LDH-5, 1.3%. This makes the T lymphocytes look more aerobic than the B lymphocytes. Daudicells had the following pattern: LDH-1, 8.4%; LDH-2, 19.1%; LDH-3, 26.6%, LDH-4, 24.9%; LDH-5, 20.9%.


The two human trypsinogens. Inhibition spectra of the two human trypsins derived from their purified zymogens. The two human anionic trypsinogens 1 and 2 were purified from human pancreatic juice by gel filtration on Sephadex G-100 and by chromatography on DEAE-cellulose. After activation of their respective zymogens by porcine enterokinase, human trypsins 1 and 2 were studied for their reaction with a wide variety of proteinase inhibitors. Kunitz pancreatic trypsin inhibitor and human pancreatic secretory trypsin inhibitor completely inhibited both human trypsins at a stoichiometric inhibitor-to-enzyme ratio of one to one. In contrast, bovine pancreatic secretory trypsin inhibitor (Kazal's inhibitor) failed to inhibit either human trypsin. The inhibition of both human trypsins by porcine pancreatic secretory trypsin inhibitor was demonstrated. The reactions of the trypsins with chicken ovomucoid, Ascaris lumbricoides (type suis), human sperm and blood plasma trypsin inhibitors were studied. The most striking difference between the two human trypsins was the reaction with soybean trypsin inhibitor (Kunitz). Trypsin 2 was completely inhibited in a one-to-one molar ratio while trypsin 1 was poorly inhibited. The presence of a prekallikrein in human pancreatic juice is discussed.


Studies on bacteriophage M13 DNA. 1. A cleavage map of the M13 genome. A physical map of the bacteriophage M13 genome has been constructed on the basis of specific cleavage of M13 replicative form DNA by bacterial restriction endonucleases. The 13 fragments produced by the enzyme from Haemophilus aphirophilus (endonuclease R.Hap II) as well as the 10 fragments produced by the enzyme from Haemophilus aegyptius (endonuclease R.Hae III) have been ordered by analysis of partial digest products and by analysis of overlapping sets of fragments. In addition, the single site in M13 replicative form DNA cleaved by the restriction enzyme from Haemophilus influenzae Rd (endonuclease R.Hin dII) has been located more precisely. With this unique site as a reference point, the H. aphirophilus cleavage sites and the H. aegyptius cleavage sites have been localized on the map.


[Pregnancy in teenagers (author's transl)]. In this study pregnancy, delivery and the newborn infant of 151 juvenile primiparas and 1034 adolescent primiparas were analyzed and were compared with a group of 3563 primiparas 21, 23 and 25 years of age. Regarding the obstetric history and the intrapartum period there was no increase incidence of complications among the young patients, however we found among the older women an increase in the incidence of operative deliveries. In the postpartum period it was noted that the young primiparas had a higher incidence of postpartum bleeding caused by atonia of the uterus and also an increased incidence of placental complications with a high rate of manual placental extraction and curettages. A positive correlation was found between premature birth and perinatal mortality and the younger the age of the mother. The newborn of the young mothers was also lighter and shorter at birth and had a higher incidence of malformations. This study has shown, that juvenile expectant mothers are a risk group for obstetricians and pediatricians.


Thymus lymphocytes. Efflux and restoration phases after peripheral exposure of mice to phytohaemagglutinin. Juvenile Swiss mice experienced significant diminutions in thymic content of both small, non-proliferating and larger, proliferating lymphocytes within 12 hours after intraperitoneal injection of phytohaemagglutinin. These alterations, which may predate alterations in lymphocyte traffic and morphology elsewhere, were interpreted as being the consequence of a massive thymus lymphocyte emigration, not of in situ cytolysis, and were effaced by intrathymic lymphocyte restoration toward control numbers by 24 hours.


Cell-mediated immune responses in Staphylococcus aureus infections in mice. Delayed hypersensitivity to staphylococcal antigens was shown in mice repeatedly infected with Staphylococcus aureus. It was characterized by footpad swelling at 48 hours with a mononuclear cell infiltrate and could be transferred to non-infected recipients by T lymphocytes from infected animals, but not by serum. Recipients of immune T cells produced very severe necrotic lesions when challenged with staphylococci. This was in contrast to the protection against necrosis in recipients afforded by serum from infected donors. When both serum and cells were transferred into the same mouse the humoral effects overshadowed or perhaps inhibited those mediated by cells with resultant protection against staphylococcal dermonecrosis.


Anti-DNA Investigated the DNA bentonite flocculation technique. The DNA bentonite flocculation test was used to investigate the presence of antibody to DNA. In most sera a prozone-like phenomenon was found, caused by a non-specific inhibition of serum. Anti-DNA was found with extreme frequency in patients with SLE, chronic liver disease, acute hepatitis, infectious mononucleosis, and blood donors over the age of 60, but was found rarely or not at all in patients with some other disease or blood donors under 60 years of age.


Cell-mediated cytotoxicity to moloney sarcoma in syngeneic and allogeneic rats. Cell-mediated cytotoxicity in the primary immune response to Moloney sarcoma tumor (MST) in allogeneic and syngeneic rats was found to be predominantly T-cell-dependent. A minor non-T-cell cytotoxic activity may also have been detected. CMC was presumably directed against tumor and viral related antigens in the syngeneic host and primarily against alloantigens in the allogeneic host. CMC was more virgorous in the syngeneic host. This may be due to differences in quantities or immunogenicities of the various antigens involved. Two peaks of T-cells in effector populations were observed during a 20-day post-inoculation period. The first peak corresponded to peak T-cell-mediated cytotoxicity on day 8 and the second peak occurred on days 13 or 14 when CMC was minimal or undetectable.


Cellular basis for the immune response to methylcholanthrene-induced tumors in mice. Heterogeneity of effector cells. Immune resistance to methylcholanthrene-induced tumors has two phases, an early specific and a late non-specific phase. Both phases were found to be T-cell-dependent in vivo. Thus, adult thymectomized, irradiated, bone-marrow-protected mice bearing H-1 tumor isografts showed impaired resistance to challenge with homologous (H-1) and heterologous (H-3) tumor cells. In each case resistance was restored by injection of thymus cells. In vitro analysis of the cellular basis of resistance revealed that different mechanisms were involved in the two phases. The cytotoxic effect of immune spleen cells taken during the early specific phase was inhibited by pretreatment with anti-O serum and complement and by removal of macrophages. Neither procedure, however, interfered with the cytotoxic potential of immune spleen cells taken during the late non-specific phage of immunity. Passage of immune spleen cells through rabbit-IgG anti-mouse immunoglobulin-coated columns (which yielded a T-cell-enriched, B-cell-depleted population) resulted in abrogration of cytotoxicity whether the cells were obtained during the early or the late phase of resistance. The inability of late-phase spleen cells to kill was explicable in terms of B-cell removal since T-cells and macrophages had been shown to be ineffective at that time. In contrast, the failure of column-treated cells from the early phase to kill was found to be due to removal of adherent cells rather than B-cells since cytotoxicity (1) was abrogated by passage through control columns coated with rabbit-IgG anti-sheep red blood cell antibody which did not retain B-cells and (2) could be restored by addition of immune macrophages (from anti-O serum-treated spleens). Taken together, these results indicate that the cellular basis of immune resistance to methylcholanthrene-induced tumors is heterogeneous. The early specific phase seems to be mediated by an interaction between T-cells and macrophages; the late none-specific phase, although T-cell dependent in its induction, depends on a different effector mechanism, possibly involving a cell or its products of the B lineage.


Induction of specific changes in the surface membrane of myeloid leukemic cells by steroid hormones. Normal mature macrophages and granulocytes have surface membrane receptors for specific immunoglobulin and immunoglobulin complement, which can be detected by rosette formation with erythrocytes coated with antibody (EA) or with antibody and complement (EAC). There are three types of myeloid leukemia cells, IR-+D-+, IR-+D-minus and IR-minus D-minus. IR-+D-+ cells were induced to form receptors for EAC but not- for EA by the steroid hormones prednisolone, dexamethasone and estradiol. Induction required protein synthesis and was not inhibited by cordycepin or vinblastine. Optimum induction required the continued presence of the hormones. IR-+D-+ cells were also induced by these hormones to migrate in agar, attach to the surface of a Petri dish and form macrophages. IR-+D-minus cells showed a lower inducibility by these hormones and no formation of macrophages. There was no induction of any of these changes with IR-minusD-minus cells. The steroid hormones progesterone, testosterone and cortisone did not induce these changes in any of the leukemic cells and inhibited induction by prednisolone, dexamethasone and estradiol. The results indicate that specific surface membrane changes in myeloid leukemic cells can be induced by certain steroid hormones.


Photoreactivation of bacteriophage phi chi 174. U.V.-irradiated single-stranded DNA-bacteriophage phi chi 174 shows a photoreactivable sector of 0-17. That this sector is relatively small compared with those for the double-stranded DNA-phages T2 and T6 (about 0-5) does not necessarily seem to be due to the pyrimidine dimers in single-stranded DNA being intrinsically a poorer substrate for the photoreactivating enzyme. This follows from the observation that intracellularly irradiated single-stranded phi chi 174 DNA also shows a photoreactivable sector of 0-4 to 0-5. The same value is obtained for intracellularly irradiated double-stranded phi chi 174 DNA. Photoreactivation of intracellularly irradiated single-stranded phi chi 174 DNA is not constant with U.V. dose for the lower dose ranged. Possible explanations for this are discussed.


Effect of X-irradiation on 3-H-glucosamine uptake by human embryo fibroblasts. The incorporation of 3-H-glucosamine into unirradiated and X-irradiated (905 rad) cultures of human embryo fibroblasts was studied by light microscopic, autoradiographic and biochemical methods in pulse-chase experiments. The precursor was 3-H-glucosamine. In unirradiated cells the grains appeared in various subcellular regions in a particular order: at first over the Golgi complex, then over the whole cytoplasm and finally at least some of the labelled macromolecules emerged from the cell. The radioactivity emerging from the cell appeared to be protein bound. Due to the effect of irradiation, the uptake of 3-H-glucosamine by the interphase cells was considerably decreased. The amount of radioactivity per cell indicated both the inhibition of cytoplasmic segregation and migration of labelled macromolecules from the cell. In the mitotic figures appearing after the release from radiation-induced mitotic block (approximately 30 hours after irradiation), the grain counts were still considerably lower than the controls. The functional and structural radiation injury of the Golgi-complex was suggested by the less well-defined sequence of localization of radioactive macromolecules than in control cells.


Lymphocyte depletion in peripheral blood of acutely gamma-irradiated rats. Groups of albino rats were exposed to 200, 800, 2000 and 5000 R of 60-Co gamma-radiation. Peripheral blood samples were taken from the tail at 1, 2, 4, 8 and 24 hours after irradiation. Calculation of the lymphocyte count per unit blood volume was made for each sample. Control rats were also mock-irradiated and sampled in the same manner. The time response of the lymphocyte count indicated that within the first hour, there was a drastic prompt drop. From one to eight hours after irradiation, the counts declined continuously, and from eight to twenty-four hours less rapidly. The depletion rates for the one to eight hour period were calculated and found to be statistically different for all groups, except between 2000 and 5000 R.


Chromosomes and cellular radiosensitivity. IV. A new radiotaxon represented by the ferns. Survival curves were constructed and D0 values determined after X-irradiation of single-celled germinating spores of 14 species of ferns, which had a wide variation in interphase chromosome and nuclear volumes and in DNA content per chromosome and per nucleus. A good fit to a line of slope equal to -1 is given on a log-log plot relating D0 to interphase chromosome volume. In a previous publication (Sparrow, Underbrink and Sparrow 1967), ferns fell into radiotaxon VIII, but the new data suggest that they should be assigned to a new group (VIIa) falling midway between radiotaxa VII and VIII. The calculated energy absorption per chromosome at D0 for VIIa is also intermediate between those for VII and VIII. If the value of this parameter is set at 1 for radiotaxon V, that for VIIa is approximately 32 times greater and the radiotaxa V, VI, VII and VIIa form a series 1 : 4 : 14 : 32. The new results indicate that radiotaxon VIII may have to be abandoned unless some other radiobiologically unexplored group (e.g. algae) fills the gap.


Prophage inductive efficiency of alkylating agents and radiations. The prophage inducing efficiency in E. coli K-12 (lambda) of a number of agents--alkylating agents and radiations--has been compared at a high survival of bacteria. The inducing effectiveness (per alkylation in DNA) and efficiency (compared with mutation frequency in E. coli Sd-4) was found to decrease in the order 2-hydroxyethylating agents (2-hydroxyethyl methanesulphonate and ethylene oxide) greater than isopropyl methanesulphonate approximately equal to methyl methanesulphonate greater than ethylating agents (diethyl sulphate, ethyl methanesulphonate). The low inducing activity of the ethylating agents could not be explained with respect to their reactivity towards targets of differing nucleophilicity, nor could the effectiveness in mutagenicity or the ability to break the chromosomes in the presence of metal ions be invoked. The high inducing efficiency of hydroxyalkylating agents may be related to their ability to break DNA strands.


Effect of whole-body irradiation on transcription in the rat thymus. Studies were carried out to elucidate the mechanism underlying the impairment in RNA synthesis in the rat thymus after whole-body exposure to X-rays (1000 rad). The ability of thymus nuclei to catalyse RNA polymerization in vitro was adversely affected in irradiated rats. Further experiments showed that whole-body irradiation caused a considerable decrease in both the activity of RNA polymerase and the template efficiency of chromatin but not in that of DNA isolated from chromatin. These radiation-induced changes in transcription seem to arise partly from the direct effect of radiation on the thymus itself and partly from the abscopal mechanism(s).


Chain reactions and radiosensitization: model enzyme studies. The influence of persulphate ions on the radiosensitivity of dilute aqueous solutions of ribonuclease and lysozyme has been studied under a variety of conditions. Rate-constants for reactions of the sulphate radical, SO4, with a variety of solutes and transient product spectra of some of these reactions are reported. The presence of persulphate ions in general enhances the radiation sensitivity; in nitrous-oxide-saturated persulphate solution, a chain reaction has been demonstrated.


Methylase activities from Haemophilus influenzae that protect Haemophilus parainfluenzae transforming deoxyribonucleic acid from inactivation by Haemophilus influenzae endonuclease R. Specific methylases that have the properties of deoxyribonucleic acid (DNA) modification enzymes have been isolated from Haemophilus influenzae strain Rd. Two activities ((Methylase IIa and methylase III) were found to protect transforming DNA of H. parainfluenzae from the action of H. influenzae restriction enzymes. To determine the specificty of the protection, a procedure based on biological activity was developed for the separation and purification of the restriction endonucleases from H. influenzae strain Rd. Two endonuclease R activities presumably corresponding to Hind II and Hind III (P. H. Roy and H. O. Smith, 1973; H. O. Smith and K. W. Wilcox, 1970) were characterized by differences in their chromatographic properties, ability to attack T7 DNA, and inactivation of the transforming activity of different markers of H. parainfluenzae DNA. One endonuclease R enzyme (Hind II) attacked T7 DNA and was found to inactivate the dalacin resistance marker (smaller than 0.01% activity remaining) with only a slight effect on the streptomycin resistance marker (83% activity remaining). Methylase IIa treatment protected 40% of the dalacin resistance marker of H. parainfluenzae DNA from inactivation by Hind II. The other restriction activity (Hind III) was inert towards T7 DNA and inactivated the streptomycin resistance marker of H. parainfluenzae DNA (smaller than 0.01% activity remaining) without any effect on the dalacin resistance marker. The methylation of H. parainfluenzae DNA accomplished by methylase III protected 60% of the transforming activity of the streptomycin resistance marker of H. parainfluenzae DNA from the action of Hind III.


Phosphorylation and dephosphorylation of frog rod outer segment membranes as part of the visual process. The light-activated phosphorylation of rod outer segment membranes may be an intermediary process controlling photoreceptor responses. We have measured phosphorylation of the opsin moiety of rhodopsin in isolated frog retinas and in rod outer segment suspensions and have demonstrated a phosphorylation-dephosphorylation sequence in the suspensions. The results indicate that these reactions take place in vivo and may be physiologically relevant. Extraction of a protein kinase activity from rod outer segment membranes renders the membranes incapable of phosphorylation, but the light-activated reaction can be reconstituted by mixing the soluble extract and the "depleted" membranes. Illumination of the extract is without effect. Thus the light activation mechanism resides in the membranes. Regeneration of rhodopsin from opsin and 11-cis retinal does not influence the phosphorylation. Once activated, the reaction may use either rhodopsin or opsin as the substrate. Furthermore, 11-cis retinal regenerates rhodopsin from phosphorylated opsin without releasing bound phosphate. The isolated rod outer segment which contains regenerated rhodopsin thus differs from one that is dark adapted in that phosphate can remain bound and the phosphorylation reaction remains activated. Dark adaptation in vivo must include at least two membrane associated reactions beyond regeneration of rhodopsin's spectral properties: dephosphorylation, and the inactivation of the phosphorylation process.


Ultrastructural characteristics of the non-immune rosette-forming cell. Non-immune rosette formation, where a non-sensitized lymphocyte is surrounded by three or more sheep red blood cells, is an in vitro technique which is thought to be specific in the identification of thymus-dependent (T) lymphocytes. Using the electron microscope and tissue culture techniques, we have studied the ultrastructure of the rosette-forming lymphocyte which has been stimulated by various cellular mitogens. Non-sensitized but stimulated lymphocytes, which form rosettes, have a morphology similar to that of previously identified T cells, adding further credence to the concept that non-sensitized rosette-forming cells represent a population of T cells. Changes in the binding pattern of the sheep red cell membrane to the lymphocyte have been identified which may represent an early phase of cell 'activation'. This marker of activation offers a potential method of studying membrane responses in attempts to localize cellular defects involving the T lymphocyte. In addition, preliminary studies using fluorescein-labelled sheep red blood cell fragments suggest specific attachment of labelled membrane to the T lymphocyte, allowing rapid identification of T cells in smears or tissue preparations.


Human bone marrow lymphocytes.  I. Distribution of lymphocyte subpopulations in the bone marrow of normal individuals. This study was undertaken to determine the proportions and in vitro immune capacities of lymphocyte populations in the bone marrows of normal humans. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates by linear sucrose gradient centrifugations. Simultaneous peripheral blood and bone marrow specimens from each individual were assayed for lymphocyte surface markers and mitogen responsiveness. Maximal possible contamination of bone marrow aspirates by peripheral blood was determined by performing aspirates on individuals who had received 51chromium-labeled autologous erythrocytes. Rhymus-derived (T) lymphocytes, as determined by the sheep red blood cell (E) rosette assay, comprised 8.6-(plus or minus 1.6)% of the total bone marrow lymphocyte pool. Bone marrow-derived (B) lymphocytes, as determined by the presence of a complement receptor, made up 15.4-(plus or minus 1.9)% of the lymphocyte pool whereas 74.6 (plus or minus 2.4)% of mononuclear cells lacked easily detectable surface markers. These findings could not be explained by contamination with peripheral blood lymphocytes since contamination was corrected for in the calculations. Lymphocyte-enriched suspensions of bone marrow cells responded to stimulation with phytohemagglutinin, concanalin A, and particularly pokeweed mitogen. In vitro incubations of bone marrow and peripheral blood lymphocytes with tritiated thymidine followed by determinations of E and erythrocyte antibody complement (EAC) rosettes were performed. Simultaneous rosetteradioautographs demonstrated that the proliferative potential of bone marrow B lymphocytes was greater than peripheral blood B lymphocytes (P less than 0.01). On the other hand, the proliferative potential of bone marrow T lymphocytes was the same as that of peripheral blood T lymphocytes. These findings demonstrate that in addition to containing B lymphocytes the normal bone marrow contains a small fraction of T lymphocytes similar to the mature T lymphocyte pool found in the peripheral blood. These T cells most probably enter the bone marrow parenchyma as part of the normal recirculating lymphocyte pool.


Increased affinity of guinea pig thymocytes and thymus-dependent lymphocytes for papain-treated rabbit erythrocytes compared to untreated erythrocytes. The affinity of guinea pig thymocytes and peripheral T lymphocytes for rabbit erythrocytes was found to be enhanced following treatment of the erythrocytes with papain. By increasing the numbers of rosette-forming cells and giving stronger, more stable rosettes, this procedure increases the usefulness of the reaction as a T cell marker in guinea pigs.


Growth properties and alloantigenic expression of murine lymphoblastoid cell lines. Murine lymphoblastoid cell lines were evaluated for their expression of Thy-1 and thymus leukemia (TL) differentiation alloantigens.  Two culture conditions were shown to affect this expression.  Cells grown in fetal bovine serum (FBS)-enriched medium expressed up to 15 times the amount of TL as cells grown in horse serum (HS)-enriched medium.  Thy-1 expression was less affected by the type of serum used for culture.  The phase of growth when the cells were harvested, was demonstrated to affect the expression of Thy-1.  The expression of Thy-1.2 for one cell line examined, L-251A, during logarithmic growth was threefold greater than cells collected during either lag or stationary growth.  When culture conditions were standardized a ranking of the amount of Thy-1 and TL expressed by several cell lines was made.  All cell lines, except one, L-1210, expressed Thy-1.  There was a 450-fold difference in the expression of Thy-1 between the cell lines evaluated.  Seven cell lines expressed TL-1,2,3 with a ninefold difference in the amount of expression.  The L-251A cell line was cultured in a 14 liter fermentor for a 26 day period.  During this time TL and Thy-1 expression did not vary significantly, demonstrating that lymphoblastoid cell lines can be cultured on a continuous basis and will continue to express their surface alloantigens.


On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets. Spleen cells cultured with syngeneic trinitrophenyl (TNP)-modified stimulator cells display a cytotoxic effect against syngeneic TNP-modified targets, but not against modified targets from unrelated H-2 haplotypes.  Targets that share the K and I region of the H-2 complex with the stimulator (or effector) cell are lysed to the same extent as the specific targets, while targets that share the I region only are not.  When only the D region is shared, a weak cytotoxic effect is observed.  Therefore, the stimulator (or effector) and target cell must share the K or D but not the I region of the H-2 complex in order for optimal cytotoxicity to occur.  Spleen cells sensitized to irradiated TNP-modified H-2-allogeneic cells are cytotoxic to these specific cells.  Coculture of F1 hybrid cells with irradiated TNP-modified parental cells result in a cytotoxic effect against only those specific parental cells and not TNP-modified cells from the other parent.  The cytotoxic effect of the F1 effector cells in the cell-mediated lympholysis test is blocked by the addition of unlabeled TNP-modified targets that are H-2 syngeneic with the sensitizing parental strain, but not H-2 syngeneic with the other parental strain.  These data demonstrate that the specificity of the effector cell in this syngeneic cytotoxicity system is directed against altered self H-2-controlled-gene products, rather than a requirement for sharing of histocompatibility genes between effector and target cell in order for lysis to occur.  The role of H-2 antigens in determining the sensitivity of a target cell to T-cell-mediated lysis is discussed.


The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. Helper cell induction to nonparticle antigens in vitro requires the cooperation of T cells and macrophages, but does not occur if the macrophages are allogenic.  The reasons for this were investigated.  Malfunction of allogenic macrophages was excluded by cultures with their syngenic T cells; suppressor cell induction was excluded by admixture experiments.  Thus, T cells and macrophages only cooperated if they were genetically similar.  The genetic locus (loci) involved was mapped.  Using congenic lines differing only at the H-2 complex, the genetic control of T-macrophage interaction was localized in the H-2 region.  Mice with intra H-2 recombinants were used to map the T-macrophage interaction locus in the I-A region of the H-2 complex (formerly known as poly-D, L-ala-poly-L-lys.  Recombinants were also used to exclude the presence of another T-macrophage locus either the K, I-B, or I-C, SS-Slp, or D regions of the H-2 complex.  Genetic restrictions for T-macrophage interaction in helper cell induction was shown in mice of the H-2-k, d, b, q, s genotypes as well as in H-2 recombinants.  The possible mechanisms and significance of this genetic restriction are discussed.


Suppression of in vitro antibody synthesis by immunoglobulin-binding factor. Alloantigen-activated mouse T cells secrete a factor which binds to the Fc fragment of IgG and blocks complement (C) activation by IgG (immunoglobulin-binding factor, IBF).  IBF was found to suppress the direct plaque-forming cell (PFC) response of mouse spleen cell cultures to sheep erythrocytes and to dinitrophenylated aminoethyldextran (T-independent antigen).  Purification of IBF by affinity chromatography on IgG-coated Sepharose columns led to an increase of the suppressive capacity with IgG, IgM, or Fab2 from IgG) the factor responsible for inhibiting the PFC response could not be dissociated from that responsible for the inhibitory activity of IBF on C-dependent hemolysis.  No effect was seen when cultures were pretreated for 6 h, or when IBF was added at 72 h.  These data are compatible with the view that IBF is a soluable mediator of suppressor T cells which may interfere with terminal differentiation of antibody-forming cell precursors.


Feedback induction of suppressor T-cell activity. Adoptively transferred carrier immune T cells interact with nonimmune T cells in recipients in a fashion which generates specific immunosuppression although both the immune and normal cells function quite well as helper cells when not admixed.


Transplantation behavior of A.TH and A.TL T-cell lymphomas in congenic resistant and hybrid strains. Seven spontaneously arising T-cell lymphomas originating in A.TH or A.TL mice, which are congenic for the immune response gene (I) chromosomal segment were described.  When transplanted into partner strains which were incompatible at the I region, the tumors were rapidly rejected.  Rejection was proposed to be due to the presence of antigens controlled by I-region genes.


IgM-induced tumor cell cytotoxicity mediated by normal thymocytes. In summary, we have found that IgM, from mice which have undergone regression of primary MSV tumors, will induce cytotoxicity against the appropriate target cells by normal splenocytes and normal thymocytes.  The thymocyte-induced cytotoxicity i


Cell migration into the "established" lateral motor column in Rana pipiens larvae. Neuronal turnover has been demonstrated during the period of differentiation and maturationof motor neurons in the developing lateral motor columns of Rana pipiens larvae. As determined by thymidine-3H labeling, cells continued to migrate into the lateral motor column (LMC)while there was a concurrent reduction in LMC cell numbers. Notably, cells in the lumbosacral LMC ceased to be labeled following thymidine-3H injection at an earlier time than forthe brachial LMC. This is consistent with a caudo-cephalic direction of development amongthe two pairs of motor columns in the spinal cord. Since neuronal turnover occurs followingthe initial formation of the LMC and continues after the maximum number of cells has beenattained, it is proposed that neuronal turnover may be a mechansim that allows for neuralreadjustment and refinement during spinal cord development.


Prolactin-thyroxine antagonism and the metamorphosis of visual pigments in Rana catesbeiana tadpoles. The relationship between prolactin-thyroxin antagonism and the metamorphosis of visual pigments in larval amphibians has been investigated using bullfrog (Rana catesbeiana) tadpoles. Althought prolactin-thyroxine antagonism is demonstrable by morphological criteria, ovineprolactin does not appear to anatagonize thyroxine-induced rhodopsin synthesis. The hypothesisis offered that prolactin-thyroxine antagonism is the result of differential gene activities which are opposite in their physiological effects.


The effect of prolactin and thyroxine on tail resorption in R. pipiens: in vivo and in vitro. Thyroxine induces tail resorption in anurans both in vivo and in vitro. This event is accompanied by an increase in the activity of the hydrolytic enzymes acid phosphtase and B-N-acetylglucosaminidase. Prolactin treatment promotes tail growth and directly antagonizes the action of thyroxine on tail tissues. This is evident at the gross morphological level as well as at the biochemical level where prolactin inhibits the increase in activity on the hydrolytic enzymes that occurs during thyroid hormone induced resorption.


The formation of virus polyribosomes in L cells infected with vaccinia virus. The fate of early virus messenger RNA in the cytoplasm of vaccinia-infected L cells has been studied during the first hour after infection. The RNA is made in the virus core structure from which it is rapidly released. It accumulates in the polyribsome fraction, where at least 75% is bound to ribosomes through an EDTA-sensitive link. Three distinct structures have been identified as possible intermediates in virus polyribosome formation. The first is a ribonucleoprotein complex (RNP) in which virus RNA is associated with cellular proteins. A complex having apparently similar properties, is formed when virus RNA is added to a cytoplasmic extract in vitro. The other two structures may consist of an RNP moiety associated with the small ribosomal subunit, or with a single ribosome. At least part of the RNA isolated as RNP appears to be a precursor of the virus messenger found in polyribosomes.


Isotope cisternography and ventriculography in congenital anomalies of the central nervous system. The author discusses the value of isotope cisternography and ventriculography in the diagnosis of a variety of congenital anomalies of the central nervous system (CNS) associated with either hydrocephalus or a disturbance in cerebrospinal fluid (CSF) flow and absorption. In sincipital encephaloceles the techniques demonstrate CSF communication with the anomalous sac and the frequently associated hydrocephalus with occipital lesions. In porencephaly and cerebral agenesis, the isotope demonstrates ventricular reflux and remains in the cystic dilatation indicating abnormal CSF absorption; isotope ventriculography also reveals a delayed CSF absorption and the possible sites of CSF obstruction in Arnold-Chiari malformations and Dandy-Walker syndrome. In addition to their differential diagnostic value isotope studies can be a helpful guide in the choice of the proper surgical treatment of some CNS anomalies.


Neuroepithelial (colloid) cysts of the septum pellucidum. The authors present two cases of neuroepithelial (colloid) cysts found above the diencephalic roof, occupying the space between the two fornices and the two leaves of the septum pellucidum, and describe the clinical history, neurological, and neuroradiological findings. Both lesions were removed through a right transventricular-transseptal approach. No other report of such a lesion in this location could be found in the review of literature. The pathogenesis of these cysts, both above and below the diencephalic roof, is discussed in light of the developmental anatomy of the area under consideration. In view of their origin from the neuroepithelium in the diencephalic roof, whether by a process of invagination into the third ventricle or by evagination into the velum interpositum, the so-called colloid cysts are more appropriately termed neuroepithelial cysts.


Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring. Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation.  The control animals received only olive oil.  Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney.  This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet.  A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed.  In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue.  Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed.  Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses.


Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom. 1. The effect of Centruroides sculpturatus scorpion venom on single frog myelinated nerve fibres was studied. Sodium currents through the nodal membrane were measured under voltage-clamp conditions before and after exposure to venom in Ringer solution 1-5 mug/ml. for 1-3 min. 2. Centruroides venom brings about repetitive firing and increased membrane potential noise. Spontaneous firing was also observed. Eventually the nodal membrane becomes inexcitable following venom treatment. 3. Under voltage clamp with a step depolarization of the membrane potential, activation and inactivation of sodium currents turns on, reaches a peak within about 25 msec, and then declines over several hundred milliseconds. As the amplitude and duration of the depolarizing pulse are increased, the size of the venom-induced current that follows also increases. 4. The venom-induced current turns on exponentially with a time constant near the value of the time constant for recovery from inactivation, tau-h, at the resting membrane potential. A depolarizing pulse inactivates this new current component, while a hyperpolarizing pulse leads to a larger venom-induced current immediately after the hyperpolarization. Its time course and membrane potential dependence indicate that the venom-induced current is modulated by the sodium inactivation process. 5. The membrane potential dependence of sodium activation in some channels is shifted by 40-50 mV in the hyperpolarizing direction. Depolarization increases the proportion of channels with shifted activation gating by first-older kinetics. Following a depolarizing pulse the activation parameter, m-3, remains elevated for hundreds of milliseconds, allowing channels to reopen as recovery from inactivation occurs. 6. A kinetic model with normal inactivation gating and shifted activation gating in some channels accounts for the observed voltage-clamp currents and for the repetitive firing evoked by Centruroides venom. In the model normal channels are converted to channels with shifted activation gating by a voltage dependent reaction. 7. The results suggest limits to possible coupling between sodium channel activation and inactivation. Transitions of the inactivation parameter, h, can occur normally in channels with a shifted membrane potential dependence for activation.


Studies on convulsants in the isolated frog spinal cord. I. Antagonism of amino acid responses. 1. The isolated frog spinal cord was used to study the effects of picrotoxin, bicuculline, and strychnine on the responses of primary afferents to amino acids. Recording was by sucrose gap technique. 2. A series of neutral amino acids was found to depolarize primary afferents. Optimal activity was obtained by an amino acid whose carboxyl and amino groups were separated by a three-carbon chain length (i.e. GABA). Amino acids with shorter (i.e. beta-alanine, glycine) or longer (i.e. delta-aminovaleric acid, epsilon-aminocaproic acid) distances between the charged groups were less potent. Imidazoleacetic acid was the most potent depolarizing agent tested. 3. Picrotoxin and bicuculline antagonized the primary afferent depolarizations of a number of amino acids tested with equal specificity. Depolarizing responses to standard (10- minus 3 M) concentrations of beta-alanine and taurine were completely blocked by these convulsants, while depolarizations to 10- minus 3 gamma-aminobutyric acid (GABA) were only partially antagonized. Glycine responses were unaffected by these agentsk; Strychnine completely blocked beta-alanine and taurine depolarizations and incompletely antagonized several other neutral amino acids. GABA, glutamate, and glycine depolarizations were not affected. 5. These results suggest that there are at least three distinct populations of neutral amino acid receptors on primary afferent terminals: a GABA-like receptor, a taurine/beta-alanine receptor, and a glycine-like receptor. The strychnine resistance of the glycine responses indictaes that the primary afferent receptors for glycine differ from those on the somata of spinal neurones.


The interaction of lithium ions with the sodium-potassium pump in frog skeletal muscle. 1. The effects of external Li on Na and K efflux as well as those on K influx were studied in high Na muscles from Rana pipiens. 2. In the absence of external Ba, substitution of K-free Li for K-free Mg resulted in an increase of both Na and K efflux. The additional of ouabain produced an inhibition of Na efflux and at the same time a marked increase in the efflux of K. 3. K permeability was greatly reduced by adding 2 mM-Ba to the incubation solutions. Under these conditions, Li gave rise to a ouabain sensitive Na efflux which was 57% of that in the absence of Ba. On the other hand, the efflux of K was only slightly increased and was not affected further by ouabain. 4. The activation curves of Na efflux against the stimulating cation concentration in Na-free Mg-Ba Ringer followed a more or less hyperbolic function for both K and Li. While half-maximal activation was attained at higher concentrations of Li than of K, the maximal efflux in Li was smaller than in K. 5. The extra Na efflux produced by K was increased when Li was added to the media. This increment was not a simple additive effect and was independent of the Li concentration. In addition, at some concentrations Li increased the ouabain-sensitive K influx, whereas at others it reduced it. 6. Reversible changes in membrane permeability to monovalent cations were accomplished by incubating the muscles in the presence of Nystatin, 50 mug/ml. When internal K was reduced to values around 1-2 mumole/g (using Li as a replacement), thus minimizing the possibility of K leaking out of the cells, both Ko and Lio were able to promote a ouabain-sensitive extra efflux of Na. 7. The residual Na efflux in (K+Na)-free solutions was not affected by the removal of Ca from the media in either Mg or Li solutions, both in the absence and the presence of Ba. On the other hand, the values for the residual efflux were higher in Mg (0-00228 min-1) than in Li (0.00135 min-1). 8. These results fully support the notion that Li ions have a K-like activating action on the Na pump in muscles. In addition, they suggest that some other kind of interaction may exist between Li and the Na-K pump.


Induction of L-forms of Haemophilus influenzae in vitro. The induction of L-forms of Haemophilus influenzae by penicillin, amoxycillin and glycine has been studies in vitro on a nutrient-agar medium. The minimal inducing concentrations of the antibiotics were generally the same as their minimal inhibitory concentrations, but the addition of a sub-inducing concentration of glycine lowered the minimal inducing concentration of penicillin. Preliminary observations have shown that L-forms are induced by penicillin or amoxycillin on a medium in which mucoid sputum forms the sole source of nutrients, and that they remain viable for at least 48 h in the absence of added osmotic stabiliser. The minimal inducing concentration on "sputum agar" is within the range of concentrations measured in sputum from patients receiving amoxycillin therapy. The implications of these observations in relation to bactericidal therapy of haemophilus infections of the respiratory tract are discussed.


Aldosterone-induced moulting in amphibian skin and its effect on electrical capacitance. The resistance and capacitance of the isolated amphibian skin have been determined from measurements of the response of the voltage across the skin to small steps to current. Previous work indicates that the electrical impedance of frog skin, when the skin is bathed with Ringer's solution on both sides, is largely determined by the properties of the functional outward-facing membrane of the skin, the outer membrane of the stratum granulosum (P.G. Smith, 1971, Acta Physiol. Scand. 81:355). This membrane can be represented by a resistance and capacitance in parallel. Aldosterone, which induces conversion of the s. granulosum into a cornified cell layer and transformation of the cell layer below into a new s. granulosum, also causes a transient rise in resistance and a short-lived decrease in capacitance to about one-half its initial value. It is suggested that these electrical changes are caused by the transitory presence of two functional outward-facing membranes in series. The method of determining resistance and capacitance from the voltage response is discussed in the Appendix.


Influx and efflux of sodium at the outer surface of frog skin. The unidirectional Na influx j12, and Na efflux, j12, at the epithelial surface of the frog skin were determined under various experimental conditions. The j21 was taken as the difference between j12 and the simultaneously measured shortcircuit current (SCC). Errors in j12 determination originating from various transport rates within the skin were kept to a minimum using a normalization procedure. Under control conditions, j12 (1.20 muEquiv/cm-2. hr) was found to be only slightly larger than the SCC (1.10 MUEquiv/cm-2. hr). After inhibition of the transepithelial Na transport by amiloride, ouabain, low temperature and low Na concentration, the reduction of j12 and SCC was almost identical, indicating that the entrance of Na into the epithelium is rate limiting for the transepithelial transport. Compared to the control, j21 remained unchanged after amiloride and ouabain, but was insignificantly reduced at low temperature and significantly reduced at low Na concentration. These data are consistent with the assumption that the Na efflux follows mainly an extracellular pathway.


Pulmonary emphysema and liver disease.  Occurrence in an alpha-antitrypsin-deficient adult. An elderly woman manifested both pulmonary and hepatic disease secondary to alpha 1-antitrypsin deficiency.  The liver biopsy specimen showed the characteristic findings of this condition, most importantly, the presence of PAS-positive, diastase-resistant intracytoplasmic inclusions.


Effects of tonicity on the resting tension in bullfrog ventricle. A study of the effects of hyper -and hypotonic media on resting tension were examined in ventricular muscle of the bullfrog was undertaken because only few studies on resting tension from the viewpoint of E-C coupling in the heart muscle are available. Thin strips obtained from the bullfrog ventricle were perfused in the sucrose-gapped chamber, which allowed the effective stimulation and the simultaneous measurement of the contractile tension and the intracellular membrane potential. Hypertonic solutions up to 3.0 T, prepared by adding NaCl or sucrose, induced a triphasic response,  namely an initial rapid decline, a secondary slow development of contracture and a final transient off-contraction. Both the second and the final responses were strongly sensitive to the calcium concentration of the bathing medium and were completely abolished by depleting external calcium ions. The initial decreasing phase was not sensitive to external calcium but was progressively augmented by increasing the initial muscle length, whereas the dehydration process, estimated by measuring the muscle weight, was unaffected by muscle stretch. The changes in the membrane potential were not essential for these responses. It was concluded that the initial tension decline results from the passive process due to volume change while the sustained contracture as well as the transient off-contraction are produced by some active process involved in E-C coupling. Hypotonic solutions induced a monophasic contracture which is insensitive both to the external calcium concentration and muscle stretch. The possible mechanism for the genesis of the response was discussed.


[Calcinosis of the cardiac coronary arteries]. In patients who had died due to various diseases and also in practically healthy individuals aged from 10 to 79 years calcinosis of the coronary arteries was studied morphometrically and histologically. The incidence and the extend of calcinosis implicating the coronary arteries increased with growing age and were more pronounced in males than in females. In analysis of observations uncovered, irrespective of the cause responsible for death, a direct relationship between the area of calcinosis and that of atherosclerosis in grosso modo (correlation factor of 0.46) was noted; the diseased in consequence of diverse affections demonstrated considerable variations in the development of arterial calcinosis. More often than not calcinosis of the coronary arteries was definable in atherosclerotic plaques carrying an important fibrotic component, in cases of necrosis and in those marked by a low lipids content and poor vasculalarization of an altered wall of the coronary artery. Calcinosis of the coronary arteries occurred more often than did their stenosis on 50% or more of the lumen. There has been established a direct relation between the frequency of the coronary artery stenosis and the area of calcinosis. The latter usually appears as a sign of disseminated atherosclerosis rather than as that of a progressive atherosclerotic process.


[Effect of trypsin-like enzyme inhibitor on certain metabolic processes in the acute period of experimental myocardial ischemia]. The effect of trasylol upon the activeness of proteolysis in the cytoplasm and mitochondrial-lysosomal fractions of the heart muscle was studied in the acute experimental period of myocardial ischaemia (5 days) along with a determination of the spectrum of the iso-enzymes of the lactate- and malate- dehydrogenases. For the evaluation of oxidation processes in vitro the iections. Trasylol was found to limit the proteolysis in the cytostructures of the myocardium cell, to increase the activity of the transaminases, as well as to help the normalization of thespectrum of the NAD-dependent iso-enzymes. At the same time, under the effect of the employed drug, the myocardial consumption of the radioactive carbon from the acetate Na-2C-14 increases.


[Intraoperative hemodynamics in patients with pre-infarct stenocardia and acute myocardial infarct]. Intraoperative haemodynamics was studied in 31 patients with pre-infarction angina pectoris and in 3 patients with acute myocardial infarction. Twelve of them (3 with myocardial infarction) were subjected to a graphic examination of 12 haemodynamic parameters. Aorto-coronary bypass procedures using autovenous grafts were demonstrated to improve the contractile function of the left-ventricular myocardium in this group of patients, as manifested in a decrease of the binite diastolic pressure, increase of the cardiac index and stroke volume in the aorta. Tracing the intraoperative haemodynamics helps in determining the immediate postoperative prognosis and in choosing the optimum regimens of drug therapy. The determination of the volume blood flow in the bypass with the help of a flowmeter is a compulsory procedure, since it permits an objective assessment of the adequacy of the conducted revascularization of the myocardium.


[Comparative research at the "mesoptometer" and "nyktomat" (author's transl)]. This paper deals with the results of comparative reserach into twilight vision as found by tests at the "Mesoptometer" and "Nyktomat". The research population consisted of 168 persons. Their reactions at the test instruments during various functional tests are demonstrated by means of diagrams. While there is good correspondence between the two test instruments in the range of contrast essential for attesting night driving ability, differences can be shown to exist in the critical range of marginal values.


[Action of different components of the kallikrein kinin-system on sperm motility in vitro (author's transl)]. In vitro experiments with human semen showed a significant increase of quantitative and qualitative sperm motility after addition of kallikrein at concentrations of 1 KU/ml. Stimulation of sperm motility was further increased and extended by addition of human serum as a source of kininogen. Kinins added directly also showed enhancement of sperm motility. In contrast, carboxypeptidase B, a kininase, significantly reduced sperm motility. The physiological and therapeutical aspects of these results are discussed.


Hereditary alpha1--antitrypsin deficiency associated with congenital extrahepatic bile duct hypoplasia. A child, two months of age, suffering from cholestasis and biliary cirrhosis, was found to be homozygous for alpha1-antitrypsin deficiency Pi type ZZ associated with high degree extrahepatic bile duct obstruction. The clinical, protein-chemical, genetic, histological and immuno-histochemical findings in the patient are reported and the relationships between these two anomalies interpreted. An interaction between the very rare defects rather than random association is suggested.


Narrowing the gap between medical and mental health evaluation. Some of the problems facing evaluators of medical care have been dealt with by individuals examining mental health programs. Mental health research has focused more on outcome studies that include a multidimensional approach in evaluation. Techniques have been devised in that field that make the evaluative process patient specific and goal oriented. Borrowing some of these methods to make medical care evaluation include a problem-oriented outcome, which incorporates patient satisfaction, compliance with medical therapy, and relief of symptoms, could lead to more accurate data on the health delivery system.


Approaches to the management of fulminant hepatic failure. This discussion has concerned the management of fulminant hepatic failure with stage III or IV encephalopathy occurring in a patient with previously normal liver function. Basic medical management must include special attention to the metabolic, neurologic, hemorrhagic, and infectious complications common to this syndrome as well as aggressive supportive care. Because the mortality rate remains high in spite of these measures, a variety of other approaches to therapy continue to be evaluated. These include corticosteroid administration, exchange transfusion, plasmapheresis, and the development of extracorporeal hepatic support systems.


A diurnal rhythm in melanocyte-stimulating hormone content of the rat pituitary gland and its independence from the pineal gland. Resting pituitary melanocyte-stimulating hormone (MSH) content was studied in adult rats kept under a controlled 14 h light-10 h dark regimen. A diurnal rhythm was found in pituitary MSH levels, showing peak values at 4.00-6.00 p.m., and low values during darkness and the beginning of the light period. The normally occurring fall in pituitary MSH content between 6.00 p.m. and midnight was also found in rats exposed to a prolonged photoperiod. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy, as well as pinealectomy, did not block the rhythm in pituitary MSH, and had no effect on pituitary MSH content. In addition, melatonin administered i.v. did not affect pituitary MSH levels, either when MSH activity was tested on the Anolis skin in vitro, or when the in vivo assay with hypophysectomized frogs (Rana pipiens) was used. It was concluded that the diurnal rhythm in pituitary MSH content is not directly related to the light-dark cycle and is not controlled by pineal melatonin or any otherpineal factor.


[Thymolytic activity of chlorimipramine]. Chloroimipramine in vitro on human lymphocytes stimulated by phytohaemoagglutinin at concentrations from 1 to 10 g/ml leads to mitotic block. Treatment of normal or suprarenalectomized rats with high doses of the drug administered orally leads to a reduction in the weight of the thymus. The hypothesis that chloroimipramine possibly plays a part in immunitary processes is put forward.


Maternal and fetal outcome associated with hemoglobin E trait and hemoglobin E disease. A study of 20 patients with hemoglobin E trait abnormality and 8 patients with hemoglobin E disease in pregnancy is presented. The hematologic abnormality in HbE hemoglobinopathy is mild though hemoglobin values are significantly lower than in HbA patients. Fetal wastage is no  increased and the salvage rate is high (live births over 95 per cent). The mean birthweight of the baby in HbE patients is significantly lower than in HbA patients, but the incidence of prematurity is not significantly increased in HbE patients. Blood loss at delivery is not markedly affected by hemoglobin type. The incidences of postpartum hemorrhage, preeclampsia, and malaria are not significantly increased in HbE patients; the reason for the significant increase in incidence of abruptio placentae in HbE is not known. No maternal deaths or congenital fetal abnormalities were recorded. It is concluded that the course of pregnancy in HbE trait abnormality and HbE disease is relatively benign.


Mycotic keratitis by Fusarium. A review and report of two cases. World literature on the subject reports 112 cases of keratomycosis by Fusarium, including the two cases described in this paper and some personal communications. In most of these cases (60--70%) there is a history of trauma inflicted by vegetable matter or by foreign bodies introduced into the eye (metal, sand, stone, etc.). The different species of Fusarium isolated are F. episphaeria, F. dimerum, F. moniliforme, F. nivale, F. oxysporum, and F. solani. The treatment recommended in a 5-percent suspension or unguent of pimaricin (natamycin).


Common gastroenterological problems. II.--Sliding hiatus hernia. A sliding hiatus hernia is a common radiological finding and is not always relevant to the patient's symptoms. The possibility of an alternative explantation for the complaint of retrosternal pain or dyspepsia should always be considered, and when anaemia is present the site of occult blood loss is often lower in the gastrointestinal tract. The majority of patient's with symptomatic gastro-oesophageal reflux can be controlled with medical measures. Surgical intervention in cases of uncomplicated hiatus hernia should be recommended only after careful preoperative assessment and even then a satisfactory result cannot be absolutely guaranteed.


Acute pancreatitis.

Acute pancreatitis. A general survey of acute pancreatitis has been given, with the emphasis on diagnosis and management. Attention is drawn to the difficulties that sometimes arise in the accurate diagnosis of the acute upper abdominal illness and in the assessment of complications arising during the treatment of acute pancreatitis. The importance of the routine use of 'Trasylol' (aprotinin) during the acute attack is emphasized. The indications for operation are discussed in relation to achieving accurate early diagnosis, the management of certain complications and the prevention of further attacks. The mortality rate of acute pancreatitis has dropped considerably with improvement in the diagnostic rate and the routine use of intensive conservative treatment, but the prognosis of septic complications is still grave and will be improved only by the universal recognition that pancreatic suppuration is no ordinary septic process and that the timing of surgical drainage is critical.


Effect of hamycin on plasma cholesterol of rat. Hamycin, a polyene antibiotic, when administered orally with food or by a cannula or administered intraperitoneally produced a dose-dependent hypocholesterolemic effect on normal albino rats. A 50% decrease occurred in serum cholesterol level at 25-50 mg/kg oral dose of hamycin. No further decrease occurred in serum cholesterol level with increase in the oral dosage. Decrease in the serum cholesterol occurring with 0.5-1.0 mg/kg, ip dose of the antibiotic was similar to that observed with oral hamycin and suggest that the effect was possibly mediated through mechanisms other than those involving prevention of absorption of cholesterol through the gastrointestinal tract.


Time and dose influences on the behavioral effects of L-DOPA and 5-hydroxytryptophan after inhibition of extracerebral decarboxylase. The influence of time and dose factors on the locomotor activity and gross behavioral effects of l-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) were assessed a albino mice pretreated with the peripheral decarboxylase inhibitor, MK-486, L-DOPA caused stereotyped behaviors and a decrease in orienting responses and locomotor activity, followed at the highest dose by increased locomotor activity. 5-HTP caused a dose-dependent increase in orienting responses and locomotor activity followed after 90 min by a dose-dependent decrease in locomotor activity. Administration of MK-486 and L-DOPA followed in the same animal by 5-HTP resulted in a diminution of the effects seen after either drug alone. This apparent antagonism may result from competition between the two amino acids at sites of membrane transport in the brain.


The Syndrome of Enlarged Vestibule and Dysplasia of the Lateral Semicircular Canal in Congenital Deafness. A 5-year-old deaf-mute girl was shown on petrous bone tomography to have bilateral enlarged vestibules with assimilation of the lateral semicircular cannals, bilateral absence of the cochlea, aplasia of the left internal auditory canal with only the facial nerve compartment being present, and hypoplasia of the right internal auditory canal. The embryological basis of these inner ear abnormalities is discussed.


Intestinal adenomatosis in the pig: a possible relationship with a haemorrhagic enteropathy. An outbreak of a haemorrhagic enteropathy in a closed herd of pigs was followed by the appearance, in the same herd, of cases of intestinal adenomatosis. This paper now draws attention to similarties in the mucosal pathology which are present in the two conditions. The affected tissue showed substantial epithelial proliferation and retrospective electron microscopic studies of material from both these entities revealed the presence of bacteria of similar morphology within the cytoplasm of these epithelial cells.


[Symptomatic and evolutive characteristics of articular destruction noted in chondrocalcinosis]. Referring to 17 personal observations, the authors endeavour to clarify the main clinical and radiological traits of the destructive arthropathies occuring in patients suffering from diffuse, articular chondrocalcinosis. These arthropathies appear to be relatively frequent and older, obese women suffering from demineralization are more readily affected. The knees, coxo-femoral joints and the shoulders are principally concerned, and to a lesser extent the wrists, the trapezo-metacarpal joints and even the spine. The lesions can be polyarticular and symmetrical, be grouped in more or less random oligoarticular combinations or may occur in only a single joint space. Clinically, these destructive arthropathies give rise to severe pain and very marked functional impotence. The joints are swollen without any signs of inflammation. The joint movements are painful, stiff, and limited. Axial deviations are frequent. Radiologically, the lesions occur throughout the cartilage sheath, the inter-chondrial bone, and in the underlying epiphysary bone, in the form of massive geodes and massives loss of tissue substance. On the other hand, the process of reconstruction is very limited. In the patients studied, chondrocalcinosis was proved by the very characteristic pictures of calcic incrustations of the cartilage sheath and the fibro-cartilages, by the discovery of micro-crystals of calcium pyrophosphate in the articular fluid or, at biopsy, by the thickness of the synovial fluid. This chondrocalcinosis was primary in the cases. These destructive lesions were easily distinguishable from nervous or diabetic osteo-arthropathies, and from tumoral, infectious, rheumatic, or vascular changes. Thus, chondrocalcinosis is among the most common causes of osteo-articular destruction. It should be looked for systematically in all patients with lytic arthropathies of unknown etiology.


[Artificial language, allowing the computer storage of case report abstracts. Applications to the study of a year's examination of 5650 patients in a rheumatology institute]. An artificial language that makes it possible to put summarized results into a computer. Application of this method to the study of the results of one year consultations with 5650 patients in a institute of rheumatology. The authors present the results of one year's external consulta-with 5650 patients in the Rheumatology Institute of the Faculty of Medicine at Paris Cochin. These results were obtained by computer using an artificial language that made it possible to record and play back a spoken version of the summarized data from the patient's histories.


Factor XIII in a clinical material.

Factor XIII in a clinical material. In 339 patients with various diseases factor XIII (FSF) was determined with the specific amine incorporation method of Lorand et al (1969). Normal values were found in patients with renal (216 patients) or liver diseases (33 patients), in 39 patients with recurrent deep venous thrombosis and in 17 children with congenital cyanotic heart disease. Low levels were found in patients with various conditions, such as sepsis, multiple fractures and combustio complicated by an abnormal proteolytic activity (fibrinolysis and/or activation of the coagulation system with signs of disseminated coagulation). No correlation was found between the FSF and the fibrinogen values or the levels of fibrin/fibrinogen degradation products (FDP). Low FSF values were found in 4 patients with erosive gastritis, with gastrointestinal bleedings and a local fibrinolytic activity in the gastric juice. Although the FSF must be very low (smaller than 1%) if it is to cause bleedings, the low levels in these patients with many other coexisting disturbances in the coagulation system and/or an increased fibrinolytic activity most probably contribute to the increased bleeding tendency in such patients.


T-Lymphocyte deficiency following adult thymectomin man. 10 patients thymectomized about 20 years earlier were tested for delayed skin reactivity against mumps, streptokinase-streptodornase and PPD antigens. The T and B lymphocytes in peripheral blood were determined. 6 patients were surgically thymectomized and 2 of the received postoperative irradiation. 4 patients were treated with only high dose irradiation to the mediastinal compartment. None of the patients responded to all skin antigens, 1 was positive to two antigens and 3 to one antigen. The remaining patients were non-responders. The number of peripheral blood lymphocytes was slightly decreased in the patients. A significant decrease in the number of T-lymphocytes (p less than 0.005) was found in the whole patient group, and the depression was more pronounced in the surgically thymectomized patients (p less than 0.001). The number of B-lymphocytes was unaltered. It is concluded that the abnormalities in this patient group reflect a T-lymphocyte deficiency. The immunologic status of the patients before treatment is not known. However, in 3 patients with recently discovered untreated thymomas no abnormalities were found. Thus, adult thymectomy in man seem to lead to deficiency of cell mediated immunity, indicating an influence of the thymus in immunological functions during adult life.


[Immunological aspects of gastrointestinal neoplasms]. The mammalian immune system appears to play an essential role in preventing the development, and/or in controlling growth and spread, of malignant tumor cells. Antigenic properties of neoplastic cells and defense mechanism of the tumor host are briefly reviewed. The relative importance of immune reactions and other "non-specific" means of host defense with regard to tumor development and growth are discussed in the light of available experimental and clinical evidence. An attempt is made to incorporate these considerations into a hypothesis relating to the development of intestinal neoplasms.


[Malignant tumors of the anal canal and the anal margin]. 81 patients with tumors of the anal canal and anal margin treated at the Cantonal Hospital, Lausanne, during the period January 1942 to June 1974 have been studied. The morbid anatomy of transitional zone and cloacogenic carcinomas, subdivided into basaloid types, is related to the anatomy and histology of the normal anal canal. The average age of the patients was 66.5 years. The incidence of canal tumors was highest in women (71% of cases), but tumors of the anal margin were most frequent in men (75% of cases). The main symptom of anal canal growths in this series of advanced cases was blood on the feces; marginal tumours were associated with anal aching. Cloacogenic carcinomas of the basaloid type have the best prognosis; this is also related to the volume and invasion rate of the tumor, which are features difficult to assess. Melanomas have the worst prognosis; leiomyomas may grow like sarcomas despite their benign histological appearance. 18 patients had inguinal metastases, and only 2 of these are alive 2 1/2 and 3 1/2 years after excision of the rectum; the volume and histological type of the tumor were unrelated to the poor rate of survival. In the light of this experience, rectal amputation is the most effective prodecure for all canal tumors and for most tumors of the margin. Radiotherapy by itself is associated with an unacceptably high risk of actinic proctitis.


Improved myocardial performance following high 2-3 diphosphoglycerate red cell transfusions. Twenty-two matched coronary bypass surgery (CABS) patients were randomly divided into two groups; 11 patients in the control group received CPD-stored or fresh blood (mean age, 5.5 days) containing 70 percent of normal 2-3 diphosphoglycerate (2-3 DPG) and 11 patients received 2-3 DPG-enriched previously frozen, washed, concentrated red cells (2-3 DPG 150 percent of normal). Coming off cardiopulmonary bypass, when given a volume load, the high 2-3 DPG patients had a significant increase in cardiac index (2.95 L. per minute vs. 2.18 L. per minute, p smaller than 0.001) at similar filling pressures. At this time body oxygen consumption, in vivo P50, red cell 2-3 DPG, and arterial-venous oxygen content difference were all increased, but P minus vo2 was normal. Improved oxygen delivery occurred without decreasing mixed venous oxygen tension. The results suggest that, with volume loading, function in the heart with coronary artery disease is limited in part by available oxygen. By decreasing oxygen affinity for hemoglobin by altering red blood cells biochemically, myocardial performance can be improved safely.


[Patho-histological findings on pulmonary biopsy in patients after mitral commissurotomy and morphometric studies of the upper and lower pulmonary lobes (author's transl)]. Histological morphometric examination of the lungs of 22 patients with acquired mitral stenosis and 15 control persons is reported. The quotient obtained from wall thickness and lumen diameter of the pulmonary venules gives a reliable estimation of the haemodynamic changes found in the pulmonary vascular system in mitral stenosis patients. The typical changes in the pulmonary vascular system in these patients were observed particularly in the lower pulmonary lobe and to a lesser extent in the lingular of the upper lobe. Biopsy of the lower lobe is preferable in mitral stenosis operations because it results in a better clinical diagnosis.


[Electrode problems in pacemaker wearers (experiences with three electrode types) (author's transl)]. 3 types of electrodes (Medtronic 6903, EMT 588, MIP 2000) of 123 patients are examined by following criterial 1. rate of dislocation, 2. development of threshold, 3. time of application. We found: The Medtronic has the smallest rate of dislocation, the lowest range of threshold and is quickly placed in the right ventricle. The rate of dislocation of the EMT 588 is still just acceptable and it also has a sufficient low threshold, but in comparison to the other helical-wire electrodes the disadvantage of being rather difficult to place in the right ventricle. The MIP 2000 has not proved to be useful due to its large rate of dislocation.


[Valvular replacement in florid endocarditis. Report on 5 cases]. This is an account of experience with valve replacement in patients with active endocarditis. In four patients the aortic valve was replaced, and in one, the mitral valve. Indication for surgery in all five cases was heart insufficiency. Two patients died, one of acute left heart failure five weeks postoperatively, and one of brain embolus in the presence of persisting acute endocarditis, four months postoperatively. Covered in the discussion are other indications for valve replacement in the presence of acute endocarditis, namely, serial emboli, fungus endocarditis, resistance to and toxic reactions of antibiotics, and mycotic sinus of valsava aneurysm. In conclusion, results obtained by other authors are reported.


[Thrombosis of the Björk-Shiley valve as an early fatal complication of the prothetic aortic valve replacement (author's transl)]. From a series of 28 patients subjected to aortic valve replacement with the Björk-Shiley tilting disc valve prosthesis 3 cases are reported in which massive thrombosis with valve dysfunction and fatal outcome occurred in the very early postoperative period. The autopsy findings and the examination of the blood coagulation state during the first 24 hours postoperatively disclosed in all 3 cases a hypercoagulability being responsible for the massive clot formation. The early recognition and establishment of the diagnosis of a hypercoagulability state and an immediate anticoagulant therapy with heparin are necessary for preventing such early fatal complications in patients with cardiac valve replacement.


[Preliminary experiences in use of the Sparks prosthesis for femoro-popliteal bypass and arterio-venous shunt in chronic hemodialysis (author's transl)]. The present paper summarizes our preliminary results using the Sparks-Mandril. The prothesis has been applied both as femoro-popliteal bypass graft and as arteriovenous shunt for hemodialysis in patients suffering from chronic renal failure. Indications, techniques and results of implantation both as femoro-popliteal bypass and as a.-v. shunt are outlined. It is concluded that in both cases the Sparks-Mandril has its well defined field of application.


[Mechanisms of transmitting excitation in the electromechanical connections system of frog phasic muscle fibers]. The effect of replacement of Na ions by isomorphic Li ions on the dynamic parameters of isometric contractions and the distribution of Na, K, and Li in the frog m. sartorius involved increase of the muscle maximum tension during first 10-15 min. A possible role of Na and Li ions in the muscle contraction is discussed with regard to the assumption of a mechanism of participation of Na ions in the transmission of excitation from the plasmic membrane to the sarcoplasmic reticulum membrane.


Removal of leukocytes from whole blood and erythrocyte suspensions by filtration through cotton wool. V. Results after transfusion of 1,820 units of filtered erythrocytes. 1,820 units of leukocyte- and platelet-poor erythrocyte suspensions were prepared by filtration through cotton wool. On the average more than 98% of the leukocytes and 90-95% of the platelets could be removed. The red cell recovery was 96%. 97% of the units given to polytransfused patients did not cause febrile reactions. Serological follow-up of future transplantation recipients indicated that the immunization may be avoided by using erythrocyte suspensions of fresh, filtered blood.


Platelet indirect radioactive Coombs test. Its utilization for PLA1 grouping. A platelet indirect radioactive Coombs test (PIRC) has been described. The technique for purification and labelling the antiglobulin has been precised. This test allowed the typing of platelets in the PLA system by using an absorbed serum from a mother of a thrombocytopenic child. Six other families of neonatal thrombocytopenias were tested. In three of them, the mothers were found PLA1 negative (PLA2, PLA2). Among a panel of 93 platelets, two (0.022) were found PLA1, negative. This PIRC test has many advantages compared to other tests such as platelet complement fixation, assay for blocking antibodies or antiglobulin consumption: it gives objective and quantitative results and is highly reproducible; anticomplementary serum may be tested.


Interstital nephritis in autoimmune hemolytic anemia. A case is reported of a 15-year-old boy with chronic autoimmune hemolytic anemia who developed renal insufficiency 3 years after splenectomy. An interstitial nephritis with striking lymphocytic infiltrates and sclerosed glomeruli could be demonstrated by percutaneous renal biopsy. Renal symptoms disappeared promptly after corticosteroid therapy. The renal lesions are thought to have arisen as part of the autoimmune disease.


Pneumocystis carinii infections in zoo animals. Pneumocystis carinii was found to be present in the lungs of twenty-three zoo animals in the Netherlands. The following species were represented: red kangaroo, common tree shrew, Senegal-Galago, Demidoff's-Galago, brown howler monkey, woolly monkey, long-haired spider monkey, white-eared marmoset, chimpanzee, three-toed sloth, palm squirrel, red panda, fennec fox, tree hyrax and large-toothed hyrax.


Effect of trasylol on packed cell volume and plasma kallikrein activation in acute Babesia argentina infection of splenectomised calves. Three groups of four splenectomised calves, three months old, were infected with Babesia argentina parasites. One group was inoculated intravenously with 2000 kallikrein inhibitor units (kiu)/kg body weight of the broad-spectrum proteinase inhibitor, Trasylol, three times a day for 5 days commencing on the 3rd day after infection (early treatment). The same dose of Trasylol was given to a second group for 3 days commencing 8 days after infection (late treatment). The third group was untreated. Parasite multiplication rates were similar in the three groups. In the early treated group levels of activated kallikrein in plasma were significantly lower than those in the other two groups. The early treatment group also showed significantly higher levels of plasma kallikrein inhibitor. No significant differences in total plasma kallikrein levels were seen among the three groups. Packed cell volumes in the treated groups remained significantly higher than those in the controls. The implications of these findings are discussed.


[Effect of primaricin on moulds and their aflatoxin formation in cheese]. The prior condition for the application of pimaricin is its heat stability (up to 80 degrees C) and the low penetration (around 2.6 mm), so that it is available for the effect on the cheese surface for a long period. With 13 different aflatoxin forming moulds, the inhibition on the mycel development and thereby on the aflatoxin formation was tested; the different strains were inhibited to various degrees. The effect on cheese was not definite, because the native cheese surface remained free of mould for 8 weeks after pimaricin treatment, whereas cheese slices dipped into pimaricin solution were covered with moulds very soon. The aflatoxin formation itself is only inhibited, if the growth of the moulds is inhibited. Therefore the cheeses have to be treated very early before strong growth of the moulds has started. The aflatoxin formation, however only starts at a certain growth period of the moulds, but at a not completed inhibition, a reduced aflatoxin formation has to be taken into consideration.


[Conduction disorders in aortic valve diseases]. Among 304 cases of aortic valvulopathies studied for surgical selection, the authors have found a high incidence of conduction disturbances (16% in aortic stenosis and 18,4% in aortic regurgitation). The conduction defects are mostly intraventricular among stenosis isolated or associated to regurgitation and mostly atrio-ventricular among pure aortic insufficiencies. The highest incidence (30%) being found in patients with bacterial endocarditis acute or healed. The incidence of conduction disturbances increases with age, with the presence of valvular calcifications, of left ventricular strain or failure, of coronary insufficiency and angina... practically with the duration and the severity of the valvular disease. Surgical risk is heavier and natural prognosis poorer in valvulopathies with conduction disturbances. But these disturbances never contraindicates surgery : it is sometimes necessary to insert a pacemaker with or without valvular replacement mostly in aortic stenosis with infrahisian conduction defects. During hemodynamic investigation of such cases one must be ready to stimulate the heart, particularly during right heart catheterization of patients with complete left bundle branch block.


Concealed retrograde conduction of an atrial echo in second degree A-V block of the Wenckebach type with modified ventricular acceleration. Whereas second degree A-V block showing the classical pattern of the Wenckebach phenomenon is easily diagnosed, variant forms of the Wenckebach phenomenon in second degree A-V block may pose difficulties to the interpretor. A case is presented, where modified acceleration of the ventricles--a crucial "pointer" to the Wenckebach A-V block -- is disturbed by concealed conduction of an atrial echo. Differences in the electrocardiographic manifestation between this and the classical type of second degree A-V block of the Wenckebach type are discussed.


[Demonstration of a major preexcitation syndrome during treatment of auricular flutter using intravenous injection of verapamil]. Electrophysiologic properties of various conduction pathways responsible for preexcitation syndrome are illdefined; they explain the incidence of arrhythmias : supraventricular tachycardia, atrial fibrillation and, in much rarer cases, flutter. The site of Verapamil activity is chiefly the atrioventricular junction, while its action on the refractory period of atrio-ventricular bypass is small and unforeseable. In a patient with type B. W.P.W. syndrome, complicated with atrial flutter Verapamil induced a preferential stimulation through the anomalous pathway. Right BBB which was obvious during the attack of atrial flutter, was hidden by the type B W.P.W. syndrome, the right branch being shunted by the anomalous pathway. The infrequency of atrial flutter in type B W.P.W. syndrome is emphasized.


[Arterial vascularization of the sino-auricular node of the heart in dogs]. In order to study the arterial blood supply of the sinus atrial node in the Dog, the authors have performed the post-mortem injection of the arterial branches going to this node. They observed 65 cases and they came to the following conclusions: in 31 cases (47.7%) the sinus atrial node is supplied by the artery of the sinus atrial node and by the anterior atrial artery, branch of the circumflex; in 20 cases (30.8%) besides the two arteries already mentioned there was also the anterior branch from the first portion of the right coronary artery; in 13 cases (20%) the sinus atrial node was exclusively supplied by the artery of the sinus atrial node and in one case (1.5%) it was supplied only by the first anterior atrial branch of the circumflex artery. Their findings are different from those of other authors and they attribute the failure in provoking experimental ischemia of the sinus atrial node in the Dog, to the rich blood supply of this node and to the different origins of the vessels supplying it.


From physical capacity to fitness to work in coronary patients. The authors studied the energetic expenditures of 15 coronary patients during work. The subjects with reduced physical capacity tolerated a high fraction of their VO2 SL during their work with activity peaks close to their maximal capacity.


Cardiac manifestations of digoxin intoxication. (Clinical correlations with serum levels). Clinical, electrocardiographic and laboratory data were found out in 52 patients with cardiac arrhythmias and conduction defects due to digoxin intoxication. Forty six nontoxic patients were also studied for comparison. Blood urea concentration was significantly higher in toxic patients as compared to nontoxic ones (P less than 0-01). Ventricular bigeminy and trigeminy (38.6%), multifocal ventricular premature beats (25%) and second or third degree A-V blocks (25%) were very much prevalent. Fairly good correlations have been observed between different cardiac arrhythmias and serum digoxin levels. Significantly higher mean serum digoxin levels were observed in patients with A-V block and multifocal ventricular premature beats as compared to patients with supraventricular arrhythmias.