T cell-mediated cytotoxicity for L 929 fibroblasts infected with Banzi virus (flavivirus). During infection with Banzi virus, splenic thymus-derived cells of C3H/RV mice developed immunologically specific cytotoxicity for Banzi virus-infected, C3H-derived L 929 fibroblasts. Cytotoxic activity was detected by six days after viral inoculation, was maximal by eight days, and decreased to background levels by 16 days. There was no consistently significant difference in Banzi virus-specific cytotoxicity of spleen cells from C3H/RV and C3H/He mice, which are genetically resistant and susceptible, respectively, to the lethal flaviviral encephalitis. Therefore, the ability of the host to develop killer cells did not, in itself, lead to protection from lethal infection. These experiments are, to our knowledge, the first demonstration of cell-mediated cytotoxicity to a flavivirus.


Improved identification of antitrypsin phenotypes through isoelectric focusing with dithioerythritol. Isoelectric focusing has replaced acid starch-gel electrophoresis for the routine determination of antitrypsin phenotypes in recent years. We observed increased sharpness of antitrypsin bands and decreased background stain following the addition of DTE to serum before isoelectric ofcusing in polyacrylamide gels. DTE and DTT were the only sulfhydryl reducing agents which produced this effect. Electrophoretic mobility of antitrypsin bands was increased very slightly. Decreased background stain resulted from the precipitation of albumin. Precipitation (coagulation) of albumin was complete in serum after 60 min incubation at 37 degrees C at concentrations of 30 mM DTE or DTT. Optimal pH for denaturation was 7.6 to 8.8. Ionic concentrations reduced the strength of the coagulum at 2.5M sodium chloride but had little effect at lower concentrations. Marked temperature effects were noted. As a result of these studies, we recommend examination of native and reduced (30 mM DTE) serum on isoelectric focusing in polyacrylamide gel for all samples submitted for routine antitrypsin phenotype determinations. It also seems possible that the nontoxic DTE (DTT) precipitation of albumin could prove useful for studies of serum proteins other than alpha 1-antitrypsin.


Clonal distribution of HLA-restricted antigen-reactive T cells in man. The [3H]thymidine suicide technique was used to test the hypothesis that the response of immune human T cells from HLA-D/DR heterozygous donors to the soluble protein antigen purified protein derivative (PPD) is clonally expressed and consists of the concurrent proliferation of at least two separable subpopulations of lymphocytes. The results showed that each of the two subpopulations react to one or the other of the HLA-D/DR antigens presented together with PPD by allogeneic monocytes. In addition, using in vitro priming techniques of in vivo sensitized lymphocytes from heterozygous donors, it was possible to generate specific memory cells capable of recognizing the priming soluble protein antigen together with the HLA-D/DR determinant present in the initial sensitizing culture.


Cold reactive antilymphocyte antibodies in neurological diseases. Cold reactive (15 degrees C) antilymphocyte antibodies were detected in the sera of 33% of patients with multiple sclerosis, 50% with Guillain-Barré syndrome, 42% with myasthenia gravis, and 38% with polymyositis. We did not detect such antibodies against autologous cells in multiple sclerosis. In multiple sclerosis there was no correlation between the presence of antilymphocytic antibodies and disease activity or duration. In patients with multiple sclerosis, myasthenia gravis, and polymyositis there was no correlation between the presence of cold reactive antilymphocyte antibodies and abnormalities of T or B cell levels.


Communicating hydrocephalus as a cause of aqueductal stenosis. Eleven cases of presumed aqueductal stenosis with onset of symptoms after the first decade were reviewed. Ten patients had complete occlusion and one a high-grade stenosis. In 10, the dilated lateral ventricles caused a marked inferior displacement of the third ventricle. Postshunting diagnostic studies on six of these patients revealed ascent of the third ventricle, and in three of these the aqueduct was shown to be patent. It appears that in some cases of advanced communicating hydrocephalus the descending third ventricle kinks or pinches shut the aqueduct, adding an obstructive component which accelerates the clinical picture. The mechanism and clinical features of this process are discussed.


Excitability changes in peripheral nerve fibers after repetitive electrical stimulation. Implications in pain modulation. The Melzack-Wall gate control theory has been invoked to explain the peripheral analgesia resulting from repetitive electrical stimulation of peripheral nerve. This model emphasizes presynaptic inhibitory interactions among afferent fiber terminals in the spinal cord. An alternative explanation, that of velocity change in peripheral nerve fiber conduction, has been suggested by compound action potential studies from our laboratory. The present study was designed to extend this work, and to investigate the single fiber changes subsequent to brief (5- to 20-minute) periods of repetitive, high frequency (180 to 200/sec) electrical stimulation through an implantable peripheral nerve cuff device of the type used clinically for pain relief. Most fibers, regardless of their diameter (estimated from conduction velocity), show one or more of the following characteristics: a transient slowing of conduction velocity, an increase in electrical threshold and/or a decrease in response probability following a period of repetitive electrical stimulation. This supports the hypothesis that there are changes in direct peripheral nerve fiber excitability occurring under conditions simulating clinical electroanalgesia.


The role of corticosterone in the loss in immune function in the zinc-deficient A/J mouse. Previous studies from this laboratory have shown that zinc deficiency causes rapid atrophy of the thymus with subsequent loss of T-cell helper function in the young adult A/J mouse. The purpose of this investigation was to determine if zinc deficiency constituted a chronic stress on the mouse leading to the elevation of glucocorticoid levels which is known to destroy thymic lymphocytes. The results of these experiments indicate that zinc-deficient mice indeed have increased levels of plasma corticosterone (115 mug/100 ml plasma) compared to mice fed zinc-adequate diets (40 mug/100 ml plasma). A significant reduction in T-cell helper function, which occurred 4 days after this rise in steroid concentration, suggests that corticosterone may contribute to the loss in immunity; however, about half of the total loss in T-cell helper function occurred prior to the increase in plasma corticosterone and was due to other factors associated with the lowered zinc levels.


Evaluation and control of a respiratory exposure to 3-(dimethylamino) propylamine. In 1974 a study was undertaken to assess the symptoms and pulmonary function of a group of 25 workers who were exposed to an epoxy resin system in the mold room of a ski manufacturing plant. The amine 3-dimethylamino propylamine (3-DMAPA) was the only volatilized substance. Assemblers, the sub-group with the highest breathing zone exposure to 3-DMAPA (0.9 ppm), had the highest prevalence of symptoms and a significant decrease in lung function over the workshift. Extensive improvements in local ventilation reduced the average breathing zone exposure to nearly one-seventh of the 1974 concentration. A 1977 cross-sectional study showed that at this level there was a marked reduction in symptoms and the expiratory function of assemblers no longer decreased over the workshift. Longitudianl comparison of the lung function of workers exposed more than two years showed evidence of a decrease from 1975 to 1977, but none from 1977 to 1978.


Factor XI deficiency resulting in severe postoperative hemorrhage after odontectomy. A case of factor XI deficiency has been presented. The patient required 91 units of fresh frozen plasma for hemostasis, which is more vigorous therapy than was to be expected from reviewing the current literature.


Antipyretic effect of acetaminophen suppositories in rats. An animal model used yeast-fevered rats to measure the relative antipyretic effects of different commercially available acetaminophen-containing suppositories. A laboratory-prepared acetaminophen-containing suppository and placebo suppositories also were investigated. Release from the suppositories was measured in vitro. All acetaminophen products containing 600 mg of drug elicited significant decreases in the rectal temperature of fever-induced rats.


The heat produced by frog muscle in a series of contractions with shortening. 1. Heat production has been measured in muscles undergoing rapid shortening 1 sec after the start of stimulation in a 2 sec tetanus. In a series of three such tetani where the periods of shortening were separated by 5 sec the shortening heats in the second and third tetani were 111 (+/- 4)% and 116 (+/- 6)% respectively of that in the first tetanus (mean +/- S.E. of mean, nine experiments). 2. When a similar series was carried out after an interval of 3 min the shortening heat in the first tetanus of the second series was 127 (+/- 3)% of that in the first tetanus of the first series (mean +/- S.E. of mean, three experiments). 3. The results are not in agreement with those of Dickinson & Woledge (1974). The discrepancy is explained by an artifact which, with certain arrangements of the apparatus, affects the measurements of shortening heat in a series of contractions. We have measured this artifact by two independent methods; the shortening heat values quoted above have been corrected accordingly. 4. The increase in the shortening heat in repeated contractions is not a specific consequence of previous shortening; an increase of the same magnitude is observed following isometric tetani. 5. During the time when the muscle is shortening, the total rate of heat production, which is initially high, falls to a steady value. This value is not significantly different in the three tetani of the series.


Adenosine receptors in frog sinus venosus: slow inhibitory potentials produced by adenine compounds and acetylcholine. 1. Membrane potential changes produced by adenosine and adenine nucleotides, acetylcholine, and vagus nerve stimulation were studied by intracellular recording in the sinus venosus of the frog, Rana pipiens. 2. Acetylcholine (ACh) released from the vagus nerve terminals evoked a slow hyperpolarization lasting several seconds in the cells of the sinus. Ionophoretic application of ACh from a micropipette produced a response which is similar in time course and amplitude to that evoked by vagus nerve stimulation. Bath application of ACh caused a steady hyperpolarization in quiescent preparations, or cessation of action potential generation in spontaneously active preparations. 3. Adenosine and adenine nucleotides produced hyperpolarizations when applied by addition to the bath or by ionophoresis from micropipettes. The hyperpolarization produced by ionophoresis of adenine compounds was somewhat slower than that produced by ACh. 4. Adenosine and the adenine nucleotides, 5'-AMP, 3'-AMP, 2'-AMP, and 5'-atp were virtually equipotent in their action. Adenosine was at least 1000-fold more potent than other purine and pyrimidine nucleosides or adenine. Both the ribose and adenine groups were important for agonist activity. 5. The concentrations of agonist required to produce half-maximal responses were estimated from dose--response curves as 3 x 10(-7) M for ACh and 2 x 10(-6) M for ATP. ACh is about 7 times more potent than ATP in producing a hyperpolarization. 6. Adenine compounds act directly upon the cardiac muscle fibres: bath or ionophoretically applied adenine compounds act even when transmitter release from nerve terminals is blocked with high (Mn2+) or when ACh receptors are blocked with atropine. 7. Adenine compounds act on the surface of the muscle fibre membrane. Analogues of adenosine which do not enter the cell are potent agonists of the receptor. An adenyl oligonucleotide too large to enter the cell was 2.6 times more potent per mole than adenosine in producing a hyperpolarization. Drugs such as dipyridamole and 6-(2-hydroxy 5-nitrobenzyl) thioguanosine, which are potent blockers of adenosine transport, potentiate the response of the sinus cells to adenosine. 8. Aminophylline and theophylline are competitive antagonists of adenosine action. The apparent Ki for aminophylline inhibition was 5 microM. 9. The response produced by adenine compounds is partly caused by an increase in the permeability of the membrane to K+. The maximum response to both ACh and adenine nucleotides approached the estimated level of EK or ECl. Replacing extracellular chloride with impermeant isethionate had no effect on responses to ACh or adenine nucleotides. The hyperpolarization was not produced by an activation of an ouabain-sensitive pump since 20 microM-ouabain had little effect on the response to adenosine. 10. The response to vagus nerve stimulation is completely blocked by 50 nM-atropine...


The actions of tubocurarine at the frog neuromuscular junction. 1. The action of tubocurarine on voltage-clamped frog muscle end-plates has been re-examined by means (a) equilibrium dose-ratio measurements, (b) current fluctuation measurements and (c) voltage-jump relaxation measurements. 2. The equilibrium measurements can be interpreted as implying that tubocurarine has (a) a competitive blocking action, with a dissociation constant of 0.34 microM, which is not dependent on membrane potential, and (b) an additional voltage-dependent blocking action. 3. In the presence of tubocurarine two kinetic components can be seen. The faster one is similar to, but rather faster than, the normal ion channel closing rate. The other is much slower (1--3 sec), and, in relaxation experiments it is in the opposite direction to the fast relaxation. 4. A number of alternative explanations for the results are discussed. The mechanism that fits them best appears to be a combination of competitive block (or block of shut channels), with a strongly voltage-dependent block of open ion channels by tubocurarine. Estimates of the rate constants for channel blocking (and their voltage dependence) are derived. From these estimates the dissociation constant for the binding of tubocurarine to open channels appears to be roughly 0.12 microM at --70 mV and 0.02 microM at --12 mV. 5. Several potential sources of error in the experiments, and in their interpretation, are discussed. The most serious of these are problems associated with diffusion in the small volume of the synaptic cleft, viz. (a) changes in cleft concentration consequent on changes in binding, and (b) ionophoretic flux of antagonist and agonist into the synaptic cleft.


A voltage-dependent gate in series with the inwardly rectifying potassium channel in frog striated muscle. 1. The degree of tubular potassium depletion and the decrease of potassium conductance due to hyperpolarizing pulses in striated muscular fibres have been examined with the three micro-electrode voltage-clamp technique. 2. The conductance of the fibre membrane has been measured in different extracellular K+ concentrations from 1 to 10 mM. 3. Comparison of the two sets of measurements shows that changes in tubular K+ concentration are not sufficient to account for the conductance decrease associated with hyperpolarization. 4. The presence of a voltage-dependent gate in series with the inwardly rectifying channel for K+ ions, suggested by Almers (1972a, b), is thus confirmed.


Intersarcomere dynamics during fixed-end tetanic contractions of frog muscle fibres. 1. The stability of sarcomere lengths along single twitch fibres from frog muscles was examined during fixed-end tetani, using a spot follower apparatus to monitor the length of a central segment. 2. Internal movement, with most of the fibre lengthening and small regions at the ends shortening as the contraction proceeded, was always seen at fibre lengths beyond those corresponding to a sarcomere length of 2.3 micrometer. 3. The rate of lengthening of the central region was fastest during the slow phase of tension rise (creep) but continued at a slower rate throughout the tetanus. These observations are in accord with the idea that progressive development of sarcomere non-uniformity is responsible for the creep phase. 4. Observations at various muscle lengths of the rate of decay of tension and the duration of the slow phase of relaxation suggest that movement during relaxation is due to sarcomere length non-uniformities and variations of decay rate with sarcomere length. 5. The rate of tension fall after stimulation ceases in an isometric sarcomere, and the factors which determine that rate, are discussed in view of evidence from fixed-end and length-clamped tetani, and recently reported experiments using aequorin.


The effect on tension of non-uniform distribution of length changes applied to frog muscle fibres. 1. The stability of sarcomere lengths along single frog twitch fibres was examined, during lengthening and shortening, using a spot follower appparatus to monitor or control the length of a central segment. 2. During active shortening from sarcomere lengths beyond 2.2 micrometer the end sarcomeres shortened dramatically, while much of the fibre did not shorten at all. It is proposed that this is the cause of the tension failing to recover, after the shortening ceased, to the value of isometric tension at the shorter length. 3. During active lenghtening from sarcomere lengths beyond 2.2 micrometer, non-uniformity of stretch was seen, with the middle stretching more than the ends. Some maintained extra tension after stretch above that appropriate to the longer length was found, as were consistent changes in internal movement, and in the shape of the tension record during relaxation. 4. Measurements of stiffness during and after a lengthening suggest that no increased activation is involved. Observation of internal movement during the raised tension after a lengthening contradicts theories involving 'locked on' bridges. 5. From these and other observations, an explanation for the extra tension in terms of non-uniformity of sarcomeres is proposed. The explanation is in accord with that previously suggested for the creep phase of tension rise seen at these lengths.


Factors affecting the movement of amino acids and small peptides across the vascularly perfused Anuran small intestine. 1. In the vascularly perfused frog small intestine, the characteristics of the washout into the vascular bed of L-leucine and glycine have been investigated following loading either as free amino acids or as the dipeptide glycyl-L-leucine. In both cases, the washout of the two amino acids was biexponential and could be ascribed a fast rate constant K1 and a slow rate constant K2. The K1 for glycine was always smaller than that for L-leucine. 2. The K1 and K2 for L-leucine had a Q10 of 1.71 and 2.66 respectively, while steady-state transfer of the amino acid exhibited a Q10 of 2.45. 3. Vascular perfusion rate affected the K1 but not the K2 for L-leucine. 4. Na+ replacement in the lumen did not affect K1 and K2 for either amino acid from the mixture or the peptide, but did reduce the pool size of both when taken up as free amino acids. Peptide uptake, as measured by pool size, was not affected by luminal Na+ replacement. 5. If Na+ in the lumen was replaced with Li+, all substitutions of Na in the vascular bed inhibited the exit of L-leucine. 6. These results are discussed in relation to a model proposing that sodium pumping across the basolateral membranes of the epithelial cells to keep the intercellular spaces patent is an important factor in the movement of amino acids from the enterocytes to the blood stream.


[A critical study of the relations between superficial or profound electrical potentials and regeneration in vertebrates (author's transl)]. It has been claimed that the action of the central and peripheral nervous systems on the regeneration process could be mediated through an electrical field which can be detected at the superficial limit of the animal tested. In this paper, it is demonstrated that superficial d. c. potentials detected on the skin of an amphibian are strickly correlated to the well-known skin ionic active transport mechanism and are quite independent of deep innervation. Moreover, reinforcing the deep electrical field through an amputated limb of a mammal (Wistar rat) doex not initiate regeneration, as has been claimed. We demonstrate that the insertion of d.c. generator does not significantly increase tritiated thymidine incorporation into the DNA of amputated animals as compared to control ones. Furthermore, wound healing proceeds in the same way in both groups. It is concluded that an electric field regeneration relationship remains to be demonstrated.


Requirement of HLA compatibility between T- and B-cells in mitogen-induced in vitro immunoglobulin production. The necessity for human leukocyte antigen (HLA) compatibility in T- and B-cells in the differentiation of B-cells into immunoglobulin-producing cells (Ig cells) was studied in cultured human lymphocytes stimulated with pokeweed mitogen. We found that, despite the histocompatibility antigen difference, allogeneic T-cells from healthy donors could help B-cells to differentiate into immunoglobulin-producing cells to almost the same degree as autologous T-cells. However, T-cells from an apparently healthy subject whose sister had died of severe combined immunodeficiency did not collaborate with HLA-incompatible allogeneic B-cells in vitro, although her T-cells collaborated with autologous B-cells as well as B-cells from a brother with identical HLA-A, -B and -D. This indicates that the mechanism which in normal cases overcomes HLA antigen incompatibility was defective in this case. It further indicates that one of the mechanisms necessary in B- and T-cell interaction requires HLA compatibility.


Maturation in B lymphocytic leukaemia.

Maturation in B lymphocytic leukaemia. Surface markers were studied serially in two cases presenting as acute B cell lymphocytic leukaemia. The leukaemic lymphocytes in both cases had the mouse erythrocyte receptor (MER) and surface immunoglobulin (SIg) with lambda light chain. Changes interpreted as an increase in immunological differentiation were observed in both, during the course of the disease and its treatment. These changes were loss of MER, increase in density of SIg, and the acquisition of SIgA. Selection of therapy to influence differentiation may ultimately afford better control of the lymphocytic leukaemias.


Five year study of postpartum hemorrhage: Queens of Angels Hospital, 1973--1977. Postpartum hemorrhage accounts for about one quarter of the deaths in the obstetric hemorrhage group. Blood loss is the most important underlying cause of morbidity. To save blood, the obstetrician must partice "preventive medicine" by being cognizant of any situation during pregnancy, labor and delivery which may result in increased blood loss.The methods and principles by which these situations can be prevented or treated are discussed.


[Reproduction study of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101) in rabbits. Administration of M73101 during the period of major organogenesis (author's transl)]. M73101 and aspirin were evaluated for the effects on prenatal development of progeny in JW-NIBS strain rabbits. Pregnant females were given orally M73101 (0, 50, 120 and 300mg/kg/day) or aspirin (200mg/kg/day) on days 6 to 18 of gestation. They were sacrificed on days 29 of pregnancy and their fetuses were examined for abnormalities. The results were summarized as follows: 1. During the dosing period, females received 300mg/kg of M73101 showed pronounced body weight depression and decrease in food and water intake. But after the dosing period, these influences were not seen. Females received aspirin did not show such phenomena. 2. There were no adverse effects on number of implants, litter size, fetal mortality or fetal weight, and no malformed fetuses attributable to the drugs were seen in each group.


[Reproduction study of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101) in rats (II). Administration of M73101 during the period of major organogenesis (author's transl)]. Pregnant female rats were given orally M73101 (0,100,250 and 600 mg/kg) or aspirin (225 mg/kg) on gestational days 7 to 17. About two-thirds of treated females in each group were sacrificed at day 21 of pregnancy and their fetuses were examined for abnormalities. The remaining females were allowed to deliver spontaneously in order to observe postnatal development of their offspring. The results were summarized as follows: 1. No significant effects of M73101 on number of the corpora lutea, litter size, fetal mortality, fetal weight or sex ratio were observed, but aspirin exhibited the intrauterine deaths and growth retardation in fetuses. 2. No external, internal or skeletal malformations attributable to M73101 were seen in fetuses, although aspirin caused malformations of various organ systems. 3. No apparent effects of M73101 on F1 generation were observed on postnatal development including emotionality, learning ability and reproductive performance. There were no adverse influences of M73101 on postnatal development of F2 generation. Aspirin, however, showed adverse effects on postnatal survival, growth, emotionality and mating performance of F1 generation.


Simultaneous surgical treatment of tetralogy of Fallot and coronary artery aneurysm due to mucocutaneous lymph node syndrome in a 4-year-old child. The simultaneous correction of tetralogy of Fallot and an aneurysm of the coronary artery due to mucocutaneous lymph node syndrome (MCLS) in a 4-year-old boy was successfully performed. Of the four aneurysms found on the coronary angiogram at the age of six months, the smaller three regressed spontaneously leaving slight dilatation and thickening of the arterial wall during the 4-year follow-up period. However, the largest one in the right coronary artery, which remained almost the same size, showed marked stagnation of blood in the aneurysm with the possibility of thrombosis and resultant myocardial infarction. At operation, there was a large aneurysm in the right coronary artery, 9 mm in width and 18 mm in length. The wall of the aneurysm was very thick and tightly adherent to the myocardium. The aneurysm was resected and an aorto-coronary bypass graft was fashioned from a saphenous vein taken from the patient's mother, since an autogenous vein was not available. A ventricular septal defect was closed and pulmonary stenosis was relieved without any difficulty. Postoperative cardiac catheterization and coronary angiography four weeks after the operation revealed satisfactory correction of the tetralogy of Fallot and a patent aorto-coronary vein graft. Several problems regarding surgical treatment of coronary artery aneurysm due to MCLS are discussed.


Cryoactivation of inactive renin in human plasma. The mechanism of the increase in renin activity in human plasma which had been kept -5 degrees C for 4 days (cryoactivation) was investigated. From the results of clinical studies, it is likely that the controling mechanism of inactive renin has something in common with that of active renin. The experimental data showed that the increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, p less than 0.001, n = 10). Soybean trypsin inhibitor, aprotinin and di-isopropylfluorophosphate (DFP) inhibited cryoactivation, indicating that the cryoactivation is due to the action of a trypsin-like serine enzyme. Trypsin which had no effect on plasma renin activity in the presence of the same amount of soybean trypsin inhibitor at 37 degrees C, activated the renin activity during cold incubation, suggesting that the dissociation of the trypsin-inhibitor complex may have taken place at a low temperature. Endogenous trypsin inhibitor is also likely to lose its affinity to endogenous trypsin-like enzyme at a low temperature.


An analysis of the effect of adrenaline on electrogenic Na+ pump of visceral nerve fibers in bullfrogs. The effect of adrenaline (Ad) on the electrogenic Na+ pump of bullfrog visceral nerve fibers was studied, by testing the effect of this drug on the K-activated hyperpolarization (KAH) of these nerve fibers. KAHs were recorded by adding K (0.2--5 mM) to an extracellular K-free solution with which preparations were previously perfused and the actual KAH amplitude (net KAH) was estimated by taking into account the amplitude of membrane depolarization induced by K in the presence of ouabain (0.001 mM). The dose-response relation between K concentrations and net KAHs follows Michaelis-Menten kinetics; the log dose-response relation showed a sigmoid curve and the Lineweaver-Burk Plot of dose-response relation showed a straight line when nH=1.3. The net KAH was augmeted by Ad (0.03--1 mM); facilitative effects of three kinds of catecholamine on the net KAH were Ad greater than noradrenaline greater than isopreterenol. The log dose-response curve was shifted to the left in parallel in the presence of Ad; the Lineweeather-Burk plot showed a straight line when nH=1.3 and this line met the control line at the ordinate point where K concentration is infinitive, while the apparent dissociation constant (Km) decreased to 0.82 from 1.3 mM (control) in the presence of 0.3 mM Ad. Net KAH was augmented by the removal of extracellular Cl or by the action of TEA; the membrane resistance was expected to increase under these experimental conditions. The dose-response relation obtained under these conditions showed an increase of maximum response without changes in Km value. It was concluded on the basis of the present results that the increase in net KAH by Ad was due to an increase in the electrogenic Na+ pump current. The mechanism underlying such an Ad action was discussed, and it was suggested that the rate of the electrogenic Na+ pump was increased by the action of Ad.


Impedance changes during the electrical and mechanical activities of a bullfrog heart. Electrical impedance of a bullfrog ventricle was recorded epicardially by the V-I method and the bridge method together with an electrocardiogram (ECG) and a contraction curve, in terms of shortening. Impedance change during one cardiac cycle of a contracting ventricle corresponded completely to the contraction curve in its time course: impedance decreased during systole and attained minimum at the peak of contraction, and the durations of both curves were almost identical. The ratio of impedance just before T-wave to that just after R-wave ([ZT]/[ZR]) of an in situ heart was increased when the ventricle contracted isovolumetrically by means of mineral oil: the ratio was far less than 1.0 in control ventricle, while it was more than 1.0 in oil-filled one (2/3 cases). Upon isometric condition or treatment of cadmium the motion restricted ventricle caused an increase in the impedance ratio ([ZT]/[ZR]) to higher than 1.0, as in the case of oil-filled ventricle. The epicardial recording of ventricular impedance seems to consist of two components: contraction(shortening-dependent impedance change, which reflects the membrane activity. Vigorous contraction will probably mask the latter and reveal only the former.


Phenothiazine-induced ventricular tachycardia following acute overdose. The chronic use of phenothiazine is known to result in ventricular arrhythmias in certain patients. The occurrence of cardiac abnormalities following acute phenothiazine overdose is less well documented. Phenothiazine-induced ventricular tachycardia, when it occurs in the overdose situation, may be refractory to conventional antiarrhythmic drugs. We present a case in which the usual therapy was unsuccessful. Only after a transvenous pacemaker was inserted was the patient's condition reversed.


[Use of electrical muscle stimulation for the prevention of neuormuscular disorders during 45 days' antiorthostatic hypokinesia]. Healthy test subjects exposed to a 45-day head-down tilting (- 6.5 degrees) showed a decline of the tone and strength of certain muscle groups, a decrease of leg circumference, a deterioration of the walking pattern, and a reduction of exercise tolerance (provocative tests with bicycle ergometry pedaling at a moderate and maximum rate). Electrostimulation of muscles applied by the Tonus-2 equipment for 30 min twice a day, 6 days a week helped to reduce the level of hypokinesia-induced disorders.


[Effect of vestibular stimuli on visual tracking with a limited tracking sector]. The paper presents the results of studying visual tracking of the targets which moved with a constant amplitude of angular displacement. The tracking was carried out during an interaction of vestibular and optic sensors. The tracking stability was related to the coincidence of the direction of vestibular and optic stimuli.


Simultaneous measurement of serum 25-hydroxycholecalciferol and 25-hydroxyergocalciferol. A method for the selective measurement of serum 25-hydroxycholecalciferol and 25-hydroxyergocalciferol has been developed. The two hydroxysecosteroids were measured in a control group and in a group of ambulatory patients treated chronically with anticonvulsant drugs. In both groups the serum levels of 25-hydroxycholecalciferol and 25-hydroxyergocalciferol followed a log normal distribution. No significant difference could be elicited between the control and the treated groups for either hydroxysecosteroid. Furthermore the data shows how important is the dietary source of vitamin D in our environment.


Histiocytosis X of the ear and temporal bone: review of 22 cases. Histiocytosis X encompasses three syndromes characterized by the idiopathic proliferation of histiocytes: eosinophilic granuloma, Hand-Schuller-Christian syndrome, and Letterer-Siwe disease. At the Mayo Clinic between 1926 and 1978, 22 patients with histiocytosis X had involvement of the ear or temporal bone. These patients comprised 15% of all patients with histiocytosis X seen during that period. The ages at onset of the disease ranged from 2 months to 49 years. The most frequent otologic symptom was aural discharge (15 patients), followed in frequency by swelling in the temporal region (11 patients), vertigo (6 patients), and deafness (5 patients). Clinical findings included otitis media (13 patients), otitis externa with or without granulation tissue (10 patients), and osteolytic lesions of the temporal bone (9 patients). A high index of suspicion is required to recognize the otologic manifestations of histiocytosis X for two reasons: the systemic manifestations of the disease are often so dramatic that the ear findings are overlooked, and the otologic findings of histiocytosis X can mimic more common diseases, including simple otitis externa, aural polyps, acute mastoiditis, chronic otitis media, and metastatic lesions.


Interactions of phospholipid vesicles with murine lymphocytes. I. Vesicle-cell adsorption and fusion as alternate pathways of uptake. The interactions of mouse thymocytes with unilamellar phospholipid vesicles comprised of dimyristoyl lecithin (DML), dipalmitoyl (DPL), dioleoyl lecithin (DOL), and egg yolk lecithin (EYL) were examined in vitro. In cells treated with [3H]DML or [3H]DPL vesicles, electron croscope (EM) autoradiographic analysis showed most of the radioactive lipids to be confined to the cell surface. Transmission EM studies showed the presence of intact vesicles (DPL) and collapsed or ruptured vesicle fragments (DML) adsorbed to the surfaces of treated cells. In cells treated with DPL vesicles containing a water-soluble dye (6-carboxyfluorescein; 6-CF), most of the fluorescent vesicles were localized at the periphery of the treated cells. Furthermore, substantial fractions of the cell-associated DPL and DML could be released by a mild trypsinization without damaging the cells. These results suggest that the uptake of DML and DPL is primarily due to vesicle-cell adsorption. Such an adsorption process appears to be enhanced at or below the thermotropic-phase transition temperature of the vesicle lipid. Under certain conditions these adherent vesicles also formed patches or caps on the cell surface. In cells treated with DOL or EYL vesicles, transmission EM and EM autoradiography showed relatively little exogenous vesicle lipid located at the cell surface. Thymocytes incubated (37 degrees C) with [14C] EYL vesicles containing a trapped marker, [3H]inulin, incorporated both isotopes at identical rates. In separate experiments it was found that this marker was located inside the treated cells. Thymocytes treated with DOL vesicles containing 6-CF exhibited a uniform and diffuse distribution of dye in the internal volume of the cells. Little cell-associated EYL or DOL could be released by trypsinization. Evidence against endocytosis of intact vesicles as a major pathway of vesicle uptake is also presented. These observations, coupled with the demonstration of vesicle-cell lipid exchange as a minor component of vesicle uptake suggest that incorporation of EYL and DOL vesicles by thymocytes is primarily by vesicle-cell fusion.


Interactions of phospholipid vesicles with murine lymphocytes. II. Correlation between altered surface properties and enhanced proliferative response. The effect of unilamellar lipid vesicles composed of dioleoyl lecithin (DOL), egg yolk lecithin (EYL), 1:1 EYL:cholesterol (Chol), dipalmitoyl lecithin (DPL), and dimyristoyl lecithin (DML) on the mitogenic response in mouse lymphocytes was tested. Cortisone-resistant thymocytes were briefly treated with lipid vesicles and subsequently stimulated with concanavalin A (con A). All of the lipid vesicles induced an enhanced mitogenic response on day 3 as tested by [3H]TdR incorporation and by counting total cells. The order of enchanced [3H]TdR incorporation (less than or equal to 5.3 times the control) was DML greater than DPL greater than 1:1 EYL:Chol greater than EYL congruent to DOL greater than untreated control cells. These increases were paralleled by increased numbers of total cells. The response of spleen cells to a B-cell mitogen, bacterial lipopolysaccharide, was similarly enhanced by vesicle pretreatments in the same order. Vesicle treatments alone were not mitogenic Pretreatment of cells with lipid vesicles modified lectin binding: DML and DPL increased the binding of [125I]con A by three to four times the control, whereas 1:1 EYL:Chol, EYL, or DOL had little or no effect. The binding of [125I]phytohemagglutinin-P (PHA-P) to vesicle-treated cells was indistinguishable from untreated cells. The lectin (con A; PHA-P)-induced agglutination of vesicle-treated cells was also modified by different lipid vesicles in the same order as the mitogenic response. Based on the results presented in the accompanying report [6], we find that the cell surface adsorption properties of the applied lipid vesicles correlate with their ability to enhance the mitogenic response, and that they modify agglutinability and lectin binding. These results are further discussed in terms of the possible alteration of membrane properties and subsequent cellular activity.


Effects of in vivo priming on in vitro induction of cytotoxicity. I. Non-specific augmentation by in vivo presensitization with allogeneic or xenogeneic cells. In vivo presensitization of donor mice of responding cells with third party cellular antigens augmented in vitro generation of cytotoxic T lymphocytes in allogeneic and xenogeneic combinations. In vitro induction of detectable cytotoxicity in presensitized responding cells required the incubation period needed for in vitro primary response. However, such cytotoxic T lymphocytes were generated after in vitro stimulation with monolayers of methylcholanthrene-induced tumor cells, UV-irradiated or heated spleen cells which had proved to be effective in secondary but not in primary response. Presensitized responding cells exposed to 600R-irradiation did not augment in vitro induction of cytotoxicity in normal responding cells. The augmenting effect of presensitized responding cells may be attributable to radiosensitive T cells which are in a transitional state in differentiation from typical unprimed cells to typical primed cells.


Partial purification, physicochemical characterization and biological function of a rosette-decreasing factor (RDF) extracted from guinea pig thymus. A factor that decreases rosette formation between guinea pig T-cells and rabbit red blood cells (RRBC) was extracted from the thymus of the guinea pig. The active factor could be extracted from the spleen as well as the thymus, but not from the liver or kidney. The active factor of the thymic extract was found in the precipitates produced by 80% saturated ammonium sulfate and it was separated from the water-soluble fraction of the precipitates. The molecular weight of the partially purified substance was estimated to range between 10,000 and 30,000 by filtration through a diaflow membrane. From the studies on physicochemical characterization, it might be a heat-resistant basic peptide probably bound to a ribonucleotide moiety. This factor reduced rosette formation between RRBC and guinea pig T-cells, but did not reduce erythrocyte-antibody-complement rosette formation. This factor also inhibited mitogen (concanavalin A, phytohemagglutinin-P)- induced DNA synthesis of guinea pig lymphocytes and antigen-induced DNA synthesis of sensitized guinea pig lymphocytes.


Impact of computerized tomography on neuroradiological investigations in South Australia. Although there has been a reduction in cerebral angiographic (33%), pneumoencephalographic (70%) and radionuclide brain scanning (28%) investigations since the introduction of computerized tomography in South Australia, there has been a significant increase (56%) in the total number of neuroradiological investigations performed. At the same time, the number of patients who underwent neuroradiological investigations has risen by 75%. This is equivalent to approximately one person in every 290 per year.


Ontogeny of the cells synthesizing IgE reaginic antibodies. IgE and IgD antibodies to ovalbumin were analyzed in animals immunized by three different techniques. The results showed that IgE and IgD immune responses could be induced more or less independently by different immunization schedules. Moreover, the triggering of the IgD membrane receptors of the IgE-B lymphoid cells which seems necessary to obtain a primary reaginic immune response, does not necessarily seem to induce an IgD immune response at the same time. We conclude IgE and IgD circulating antibodies are synthesized by two different B lymphoid cell lines.


Surface glycoproteins of resting and activated human T lymphocytes. This review summarizes some recent studies on the surface glycoproteins of human thymocytes and T lymphocytes. Purified cells were surface labeled by the galactose oxidase-NaB3H4 or periodate-NaB3H4 techniques. The radioactive membrane glycoproteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. Thymocytes and T lymphocytes show characteristic surface glycoprotein profiles which are easily distinguishable from those of the other main groups of human leukocytes. We observed specific changes in the surface glycoprotein patterns which correlate with the degree of maturation and functional activation of T cells. Surface molecules carrying T cell specific antigens were identified by immune-precipitation from lysates of surface labeled thymocytes and T lymphocytes using rabbit anti-human T cell antibodies. Finally we describe a leukocyte membrane glycoprotein which is a precursor of serum alpha 1 acid glycoprotein (orosomucoid).


Survival and DNA repair in ultraviolet-irradiated haploid and diploid cultured frog cells. Survival and repair of DNA following ultraviolet (254-nm) radiation have been investigated in ICR 2A, a cultured cell line from haploid embryos of the grassfrog, Rana pipiens. Survival curves from cells recovering in the dark gave mean lethal dose value (Do) in the range 1.5--1.7 Jm-2 for both haploid and diploid cell stocks. The only significant difference observed between haploids and diploids was in the extent of the shoulder at low fluence (Dq), the value for exponentially multiplying diploid cells (3.0 Jm-2) being higher than that found for haploids (1.2 Jm-2). Irradiation of cultures reversibly blocked in the G1 phase of the cell cycle gave survival-curve coefficients indistinguishable between haploids and diploids. Post-irradiation exposure to visible light restored colony-forming capacity and removed chromatographically estimated pyrimidine dimers from DNA at the same rates. After fluences killing 90% of the cells, complete restoration of survival was obtained after 60-min exposure to 500 foot-candles, indicating that in this range lethality is entirely photoreversible and therefore attributable to pyrimidine dimers in DNA. Dimer removal required illumination following ultraviolet exposure, intact cells and physiological temperature, implying that the photoreversal involved DNA photolyase activity. Excision-repair capacity was slight, since no loss of dimers could be detected chromatographically during up to 48 h incubation in the dark and since autoradiographically detected "unscheduled DNA synthesis" was limited to a 2-fold increase saturated at 10 Jm-2. These properties make ICR 2A frog cells useful to explore how DNA-repair pathways influence mutant yield.


Abnormal lymphocyte capping in a patient with severe combined immunodeficiency disease. Despite the presence of normal numbers and distribution of T and B lymphocutes and normal levels of serum immunoglobulins, a five-month-old infant failed to show any evidence of T-cell or B-cell immunity. In trying to identify a specific membrane abnormality as a potential cause of the immunologic dysfunction, we examined the lateral mobility of the cell-surface receptor for concanavalin A. In contrast to normal cells, in which the receptor is distributed uniformly over the cell surface, the patient's lymphocytes showed an unusually high accumulation of concanavalin A receptors in surface caps. This capping abnormality appeared in both T and B lymphocytes and was exaggerated by colchicine, an inhibitor of microtubule assembly. These findings support the theory that plasma-membrane-cytoskeleton interactions have a role in the expression of specific immunity; the findings also identify new areas that should be considered in trying to understand the primary immunodeficiency diseases.


The factor VIII abnormality in severe von Willebrand's disease. We attempted to characterize the small amounts of factor VIII-related antigen detectable in the severe recessive form of von Willebrand's disease with newly developed radioimmunoprecipitin techniques and radiocrossed immunoelectrophoresis. Previous studies have failed to demonstrate factor VIII-related antigen in most patients tested even with the highly sensitive immunoradiometric assays. Using the newer techniques, we found antigen in the plasma of six of eight patients with severe von Willebrand's disease from different kindreds. Qualitative abnormalities of the trace quantities of factor VIII-related antigen were demonstrated in five of the patients, with absence or relative decrease of the larger, less anodal forms. In addition, five distinct patterns were observed, each suggesting a different molecular abnormality. Heterozygous parents had normal to moderately decreased factor VIII-related antigen, with normal crossed immunoelectrophoretic patterns. This study suggests that severe von Willebrand's disease is a heterogeneous syndrome with various underlying molecular defects.


[Tumors of the pineal region. Part I: neurologic and neuroradiologic symptoms in 23 patients]. After a short anatomical review about the neighbourhood of the lamina quadrigemina 23 patients with different processes in the pineal region were investigated with regard to their neurological symptoms and radiological findings. Symptoms of the eyes in conjunction with signs of elevated intracranial pressure in most of the cases show the way to the diagnosis which will be completed by ventriculography, angiography, and recently by computer tomography with regard to the expansion of the process; any prediction about the kind of tumour is possible only in a little percentage.


Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results. Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.


Application of metrizamide in the radiographic evaluation of the neurologically diseased patient. Metrizamide (Amipaque) is a new water-soluble contrast agent for use in the intrathecal space. Extensive animal and clinical studies have demonstrated its low toxicity. The advantages to the use of metrizamide include the fact that it is miscible with cerebrospinal fluid and can fill narrow spaces, is sufficiently radiopaque to outline delicate structures within the central nervous system, is completely resorbed from the subarachnoid space, and, to date, has not been implicated in the formation of adhesive arachnoiditis. Application of metrizamide to the evaluation of neurologically diseased patients has included myelography, intracranial cisternography, and ventriculography, as well as various techniques in conjunction with computerized tomography. These various uses of metrizamide are discussed together with some indications and advantages. Metrizamide has now replaced Pantopaque and gas as the most commonly used intrathecal contrast agent at the University of Texas Health Science Center at Dallas.


Familial amentia, unusual ventricular calcifications, and increased cerebrospinal fluid protein. A sibship originally reported by Friedman and Roy as showing severe mental retardation, strabismus, hyperactive tendon reflexes, lalling speech, and foot deformities was restudied. Three major additional findings were noted. The cerebrospinal fluid protein concentration was increased two to three times above normal in four siblings who were available for study. Radiographs of cranial structures in three siblings showed identical pathologic intracranial calcifications which correspond in distribution to the choroid plexus. The choroid plexus was not demonstrable in one patient when radiolabeled 99m-Tc-pertechnetate was injected without perchlorate. Neuropathologic findings in one sibling included small subcortical heterotopias and atrophy of the choroid plexus with encasement by glial fibrils. These findings denote a new heredofamilial neurologic syndrome associated with mental retardation and a disorder of choroid plexus.


Pregnancy-specific beta-1-glycoprotein levels in normal and toxemic pregnancy. Maternal plasma levels of pregnancy-specific beta-1-glycoprotein (PSBG) in 166 normal and 169 toxemic pregnancies were measured by radioimmunoassay in the third trimester. Individual PSBG levels were studied in 16 women during weeks 7 through 39 of normal pregnancy. The levels were found to increase as pregnancy progressed. During the third trimester neither normal nor toxemic pregnancies showed any circadian rhythm in PSBG levels. In toxemic pregnancies low PSBG values were seen mainly in cases with intrauterine growth retardation (IUGR). Plasma PSBG concentrations at weeks 39-40 in toxemic patients correlated positively with placental weight. No such correlation was found in normal or toxemic pregnancies at 37-38 weeks or in either group between PSBG level and infant birth weight, birth length, or Apgar score. In toxemic pregnancies with low PSBG values during the last trimester, birth weights were somewhat lower than in those with normal levels. Thus, low levels of maternal plasma PSBG may reflect IUGR, but will be of little value for assessment of fetal condition at birth.


Implications of Ewald's second law for evaluation of vestibular function. The significance of Ewald's second law in the evaluation of the vestibulo-ocular reflex (VOR) was investigated using the transfer characteristics of the vestibular and VOR systems in normal rabbits and rabbits in which one horizontal semicircular canal had been blocked. The transfer characteristics of the vestibular system were derived from the experimental results reported by Goldberg and Fernández in 1971. A comparison was made of the properties of the bilateral and monolateral VOR systems with the predictions of a piecewise linear model of the vestibular system. The data received quantitatively collaborate the prediction of Ewald's second law as it applies to the VOR responses.


[Glomerulonephritis: critical evaluation of immunological tests performed routinely (author's transl)]. The clinical value of the immunological tests performed routinely has been evaluated in 91 patients with various histological types of glomerulonephritis. An antigen possibly involved in the pathogeny of renal disease was found in 24% cases. However, in most instances no direct link between the presence of this given antigen and the disease could be observed. Therefore systematic investigations for antigens should be restricted to dosages of antistreptolysin and antinuclear antibodies and to determination of Hbs antigen. Immune complexes, which were observed in many cases, were of no discriminant value for the clinician. Dosages of the complement fractions and the determination of cryoglobulins can be helpful for diagnostic, follow-up and treatment. Our results justify a restricted selection of the routine immunological tests used in patients with glomerulonephritis. More specific investigations remain useful when they are clinically oriented.


Covalent structure of subunits of bacterial luciferase: NH2-terminal sequence demonstrates subunit homology. The heterodimeric subunit structure of bacterial luciferase was demonstrated more than 10 years ago. The enzymes from both Beneckea harveyi and Photobacterium fischeri have since been studied in detail; they each consist of two nonidentical subunits, designated alpha and beta. Both are required for bioluminescence activity, with the active center apparently confined to the alpha subunit. Amino acid sequence analysis of the NH2 termini of the alpha and beta subunits of the B. harveyi and P. fischeri luciferases not only confirms the earlier observation that the alpha subunits are homologous but also demonstrates that the NH2-terminal sequences of the beta subunits of the luciferases from the two genera are homologous. Furthermore, within each luciferase, the NH2-terminal sequences of the alpha and beta subunits are similar, suggesting the possibility that the genes coding, for alpha and beta may have arisen by gene duplication, presumably prior to divergence of the lines leading to present-day luminous bacteria.


Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. In previous studies we demonstrated that the tumor-promoting agent 12-O-tetradecanoyl phorbol 13-acetate (TPA) and related macrocyclic diterpenes are potent inhibitors of the binding of epidermal growth factor (EGF) to its cell surface receptors in HeLa cells. The present study explores the specificity and mechanism of this effect. We have found that the same effect is observed in various cell types derived from mice, rats, or humans. In HeLa cells TPA inhibits the initial binding of EGF and also accelerates the loss of previously bound EGF from cells. The released EGF is recovered largely intact in the medium, indicating that TPA does not induce increased proteolysis or increased cellular internalization and degradation of EGF. The TPA effect on EGF receptors is mediated by a highly temperature-dependent process because TPA inhibition of EGF binding, and TPA-induced release of prebound EGF, are much greater at 37 degrees C or 22 degrees C than at 4 degrees C. A curious feature is that when cells are grown in TPA for one or more days they escape or become refractory to TPA inhibition of EGF binding. Taken together, these results suggest that TPA inhibits EGF binding not by binding directly to the "active site" of the EGF receptor but by indirectly altering the conformation or inducing the clustering of EGF receptors. These and other membrane effects of this tumor promoter suggest that it is a valuable probe for elucidating complex aspects of membrane structure and function.


Evidence for a large internal pressure in biological membranes. We have developed a method (hygroscopic desorption) for measuring the binding of small molecules to membranes. With this method, we have found that the binding of the amphipathic compounds chlorpromazine, 2,4-dinitrophenol, and 1-decanol to various cell membranes is remarkably low, with partition coefficients, Kp, no larger than about 0.1. On the other hand, with phospholipid vesicles of large or small diameters, Kp values for these compounds were much larger. The results suggest that there exists in membranes a large internal pressure that excludes the amphipaths from the membranes and that does not exist in phospholipid vesicles.


Tumor-enhancing suppressor activator T cells in spleens and thymuses of tumor immune mice. Cells from the spleens and thymuses of BALB/c mice whose Moloney sarcoma virus (MSV)-induced, primary sarcomas have regressed 2-3 months earlier ("MSV regressors") or are in the process of regressing can, when adoptively transferred to syngeneic mice given MSV at the age of 20 days, prevent the natural regression of the MSV sarcomas in the recipient mice. The cells responsible for this tumor-enhancing effect express the Thy 1 marker. They are not demonstrable in the thymuses of normal untreated mice or in mice that have either been immunized against or are bearing methylcholanthrene-induced sarcomas. The tumor-enhancing cells are not destroyed after administration of 400 rads (1 rad = 1.00 x 10(-2) J/kg) of whole body radiation. However, the effect of the irradiated cells is seen only in the presence of a nonirradiated T-cell population, represented in the thymuses of normal control mice, with which we postulate that they interact. Studies on a transplantable, chemically induced, murine leukemia virus antigen-negative sarcoma, MCA-1460, further support the concept that relatively radioresistant thymus cells from immune mice can enhance tumor outgrowth by interacting with radiosensitive T cells that are present in nonimmune mice.


Platelet receptors for human Factor VIII/von Willebrand protein: functional correlation of receptor occupancy and ristocetin-induced platelet aggregation. Previous studies of von Willebrand disease indicate that a deficiency of blood clotting Factor VIII/von Willebrand factor (FVIII/vWF) activity is responsible for the failure of platelets to participate fully in the initial stages of hemostasis. We have recently identified specific FVIII/vWF binding sites on platelets, suggesting that the interaction of these sites with FVIII/vWF may be functionally important in the development of platelet clumps. We have now studied how different ristocetin concentrations, various known platelet aggregation inhibitors, and the exposure of platelets to proteases affect the ability of platelets to bind FVIII/vWF and to form aggregates. Our results demonstrate a highly significant linear correlation between the degree of FVIII/vWF receptor binding and the extent of ristocetin-induced platelet aggregation. Because neither FVIII/vWF binding nor platelet aggregation occurs after platelets are exposed to low concentrations of proteases, the FVIII/vWF receptors must be in the platelet membrane. We conclude that the interaction between FVIII/vWF protein and its receptors on the platelet membrane is an important mechanism by which platelet aggregation occurs during primary phase hemostasis.


Localization of spontaneously hyperactive B cells of NZB mice to a specific B cell subset. NZB mice produce numerous autoantibodies and have a subpopulation of B cells characterized by marked spontaneous hypersecretion of IgM. The latter trait is determined by autosomal genes, in F1 hybrids of NZB and normal strains. We tested the hypothesis that the hypersecreting B cells of NZB mice are contained within a specific subpopulation by examining (CBA/N X NZB)F1 hybrids. CBA/N mice have an X-linked recessive defect that results in the absence of a functionally distinct B cell subpopulation and impaired antibody responses. The hyperactivity of B cells, characteristic of the NZB parent, was transmitted to the F1 female, but was not expressed by the F1 male, which manifested the CBA/N B cell hyporesponsiveness. By contrast, the NZB xenotropic virus was expressed equally by both male and female F1 mice. We conclude that the NZB B cell abnormality resides within the B cell subpopulation affected by the CBA/N mutation.


Monoclonal antibody directed to a B-cell antigen present in rats, mice, and humans. Spleen cells from a LEW.AVN rat immunized with cells from an MNR rat were fused with mouse myeloma cells to produce hybrid cell lines. One of these hybridomas produced a monoclonal antibody that was cytotoxic for bone marrow-derived (B) but not thymus-derived (T) cells. The antigen defined by this antibody is determined by a gene linked to the major histocompatibility complex (MHC). The antigen is also present on B cells of most mouse strains and is determined by an MHC-linked gene in this species as well. In both rats and mice, the gene determining the antigen maps within the immune response region of the MHC. All human B-cell lines, but not T-cell lines, and B but not T cells of all human donors tested so far are also positive for this antigen. Among human-mouse somatic cell lines that have lost various human chromosomes, this B-cell antigen is present on all lines that are positive for HLA antigen but is absent from all lines that have lost HLA.


"Hybrid" synapses formed by foreign innervation of parasympathetic neurons: a model for selectivity during competitive reinnervation. Selectivity of synapse formation after nerve regeneration was tested in the parasympathetic cardiac ganglion of frogs (Rana pipiens). First, we tested the ability of somatic motor axons to establish synaptic connections with denervated ganglion cells by implanting the hypoglossus nerve into the vagotomized heart. After several weeks, stimulation of the implanted hypoglossus mediated a parasympathetic-like inhibition of the heart rate, and synaptic responses produced by hypoglossal stimulation were recorded intracellularly in ganglion cells. Light and electron microscopy indicated that implanted hypoglossal nerve terminals contacted parasympathetic ganglion cells only on their axons and not on the cell body (where most vagal synapses are found in control animals). Second, we tested whether regenerating vagal preganglionic axons would complete with foreign (hypoglossal) terminals for innervation of cardiac ganglion cells. We allowed the vagus nerve to regenerate in animals in which the implanted hypoglossus had established functional contacts with the cardiac ganglion. Vagal axons were able to reinnervate the heart and reestablish synaptic connections on the cell bodies of ganglion cells. Furthermore, functional transmission at the foriegn (hypoglossal) terminals disappeared concomitant with vagal reinnervation.


Transcatheter arterial occlusion in the management of rectosigmoidal bleeding. Transcatheter arterial occlusion was performed in five patients with recurrent rectosigmoidal bleeding. Four had malignant neoplasms, and the fifth, an arteriovenous malformation. The superior hemorrhoidal artery was embolized in two patients, the inferior mesenteric artery in two, and the left internal iliac artery in one patient. In four patients, immediate and complete control of rectal bleeding was achieved, and gradual control was accomplished in the fifth patient. Left lower quadrant pain and fever developed in three patients. The possibility of rectosigmoidal bleeding from the internal iliac artery is stressed.


The diagnostic and therapeutic role of angiography in lingual arterial bleeding. Selective external carotid angiography proved effective in the diagnosis of lingual arterial bleeding in seven patients. The cause of the hemorrhage was carcinoma of the tongue in six patients and stab wounds in one. Therapeutic Gelfoam embolization controlled hemorrhaging in four patients.


Spontaneous ventriculostomy and ventricular diverticulum. Four cases of ventricular diverticulum are presented, 2 with spontaneous ventriculostomy. In 2 patients, the cause was monoventricular hydrocephalus through congenital stenosis of the foramen of Monro, with paraventricular diverticula and spontaneous ventriculostomy. Both patients had a cystic space in the quadrigeminal and supracerebellar cistern. In one patient during pneumoencephalography, the ventricular diverticulum filled via the ventriculostomy. The other 2 patients had congenital stenosis of the Sylvian aqueduct with the formation of a large supratentoria cyst connecting with the posterior part of the third ventricule.


Cardiac imaging in nuclear medicine.

Cardiac imaging in nuclear medicine. With the rapid improvement in instrumentation and radiopharmaceuticals, cardiovascular nuclear medicine has undergone dramatic growth. Radiotracer techniques for the estimation of myocardial blood flow, metabolism and cardiac hemodynamics have been accepted into routine clinical practice. These techniques are also providing sensitive tools to help us elucidate cardiac physiology and pathophysiology. This review explores a number of recent developments in this rapidly changing field.


Myocardial positron tomography with manganese-52m. The biodistribution of radiomanganese (54Mn) was studied in mice, rats, and dogs. Disappearance of radioactivity from the blood was extremely rapid, with a half-time of approximately 0.8 minutes. This resulted in very favorable myocardium-to-blood ratios, even at early times after administration. The myocardial uptake in dogs was greater than 3% at three and 15 minutes, with myocardium-to-blood ratios of about 40:1 at 15 minutes. Positron tomograms obtained with 52mMn clearly demonstrated regional myocardial perfusion. There was good correlation (r = 0.89) of microsphere-to-radiomanganese distribution in the infarcted dog heart.


Proliferative haemorrhagic enteropathy.

Proliferative haemorrhagic enteropathy. This study indicates that viable Campylobacter sputorum subsp mucosalis are not present or are present in small numbers in the mucosa of pigs dying of proliferative haemorrhagic enteropathy. The changes present in the mucosa are similar to those seen in pigs recovering from adenomatosis and the evidence obtained indicates that the intracellular organisms observed in this condition are indeed mucosalis. The presence of large amounts of IgA in the altered tissue of both proliferative haemorrhagic enteropathy and porcine intestinal adenomatosis indicates that the failure to recover bacteria may be immunologically mediated but is not simply related to the presence or absence of antibody in the respective conditions.


[Tomodensitometry and spinal pathology]. The authors describe the possibilities and the limitations of the "scanner" in spinal pathology. Use of the third dimension and the certainty of absolute measurements, make this a very interesting method that can be applied to several areas of spinal pathology, especially traumatology and detection of primary and secondary tumors. It seems that this technique may be used in particular in the study of canal stenoses. There are future possibilities in view for segmentary densitometry, which gives better results than overall scintigraphy, especially in locating metastases. At present, studies are underway using contrast solution in order to study the possibilities of interpreting the content-container relationship.


[Antinuclear antibodies: immunological characteristics and clinical significance]. Fifty sera containing antinucleolar antibodies were o gathered in a routine laboratory during testing for antinuclear antibodies with indirect immun-fluorescence over a five-year period. The patients involved were suffering from sclerodermia (13 cases), rheumatoid arthritis (7 cases), polymyositis (3 cases), lupus (2 cases), various rhumatismal disease (59 cases) and non rhumatismal diseases in 16 cases, including 5 malignant diseases. In 80 per cent of the cases nucleolar fluorescence was combined with nuclear fluorescence of another type. The antibodies were almost always of the IgG category and belonged in 2/3 of cases to several immunoglobulin categories, most often IgG-IgA. Pretreatment of the liver cuttings with RNase always modifies the nucleolar fluorescence, most often making it negative, and pretreatment with DNase using a combination of enzymes 10 times higher also modifies it (more often decreasing it than making it negative), which indicates that the nucleolar antigen, probably an ARN with a low molecular weight, also depends upon the ADN.


[Changes in blood calcium, phosphorus and alkaline phosphatase levels in rheumatoid polyarthritis and other types of inflammatory rheumatism]. Albuminemia, calcemia, phosphoremia and alcaline phosphatasemia were measured in three groups of 52 subjects each : rheumatoid arthrits, inflammatory rheumatisms other than rheumatoid arthritis and lumbarthrosics serving as a reference group. Calcemia and albuminemia were significantly lower in patients suffering from rheumatoid arthritis, whose calcemia corrected in relation to albuminemia is, on the other hand, normal : the increase in corrected calcemia pointed out by Kennedy, was not noted. Corrected calcemia was also normal in ankylosing spondylitis, but it was significantly higher in polymyalgia rheumatica. Phosphoremia was shown to be normal but alkaline phosphatases were higher than normal in the three groups.


[Absence of circulating immune complexes and of serum anti-IgG antibodies during ankylosing spondylarthritis]. The sera of 161 subjects hospitalized in a rheumatology department were tested for anti-IgG antibodies using a "PEG radioimmunoprecipitation assay" (RIPEGA), for circulating immune complexes using the liaison test with Clq 125I, and dosage of complement and its metabolites. No significant difference was found between the group of 37 ankylosing spondylitis and the group of 44 control subjects. The results were identical, whatever the form of the disease, be it peripheral or central, and evolutive or non evolutive. On the contrary, the study of the rheumatoid arthritis (47 seropositive and 34 seronegative) provided results in conformity to previous works. The different physiopathogenic origin of these two chronic inflammatory rheumatisms is discussed by the authors.


Pneumocystis carinii pneumonia in children. Previous descriptions of Pneumocystis carinii pneumonia have emphasized a variety of radiographic patterns which most often apply to advanced disease. We reviewed the chest roentgenograms of children taken at or just after the onset of clinical symptoms. Subtle but definite abnormalities of pulmonary vessels, hila, parenchyma, and aeration were observed. Appreciation of these early changes is necessary to initiate prompt treatment. The role of lung biopsy and the histologic features of these patients are also discussed.


Postpartum examination: a reevaluation.

Postpartum examination: a reevaluation. Four hundred patients were polled to determine their attitudes and experiences regarding birth control measures, length of postpartum bleeding, and compliance with the advice to avoid sexual intercourse until the postpartum examination. As postpartum bleeding decreases and/or stops, there is a marked tendency for patients to resume full activity. Many patients resume coitus very early and participate frequently with apparent significant complication.


Estrogen-progestogen therapy for gastrointestinal bleeding in hereditary hemorrhagic telangiectasia. Described is a patient with severe iron deficiency anemia and chronic gastrointestinal bleeding caused by hereditary hemorrhagic telangiectasia who was successfully treated with a combination of estrogen and progestogen.


Hepatic infections. Part II. The effect of acute and chronic hepatitis B antigenaemia on the reaction to antibodies to sheep red cells (microbial antigens) and human T-activated cells (exposed autologous tissue antigens). Using the agglutination of sheep red cells by human antibodies as an indicator of microbial antibody activity, a highly significant association was found between the response to the e antigen of the hepatitis B virus and the formation of strong antibody levels to microbial substances (chi 2(1) = 33). This kind of association was not found among chronic carriers of the hepatitis B virus who do not produce antibodies to the e antigen (chi 2(1) = 3,7). In the presence of e antigen activity, patients with acute virus B hepatitis almost always show significantly reduced levels of antibodies to microbial substances (chi 2(1) = 20). The findings indirectly reveal that e activity is associated with the inability of the liver to trap bacterial antigens. Circumstantial evidence further suggests that the e factor may bear antigens on its immunoglobulin-like structure very similar to microbial cell wall components. Accepting that human antibodies to the T (Thomsen-Friedenreich) antigen represent reactions to cryptantigenic membrane structure of autologous tissues, it was significant to record that increased anti-t activity is always demonstrated when virus B infections progress from the acute to the chronic carrier stage (chi 2(1) = 73). The most intense anti-T activity is commonly found in subjects who produce antibodies to the hepatitis B surface antigen (chi 2(1) = 138). In the presence of e antigen the amount of anti-T in circulation is always significantly depressed. Since this type of depression is not seen in patients with acute virus B hepatitis who lack the e antigen, we suspect that the reduced anti-T levels in e antigen-positive patients are linked with the in vivo exposure of T receptors by microbial neuraminidase.


[Results of the treatment of myeloma with a vincristine-melphalan combination]. The authors report the results obtained in a series of 20 multiple myelomas by an association Vincristin-Melphalan with a maximum therapeutic survival of 65 months. The median of survival is established at 27 months. The differences are a function of the initial values of the calcemia, the level of hemoglobin, the percentage of medullary plasmocytosis, but the essential factors appear to be the delay in the treatment, the stage of development established according to Salmon and Durie and particularly the presence or absence of a renal involvement. We have seen important fluctuations of certain immune parameters, particularly level of sheep rosettes and B cells detected by immunofluorescence.


Immunodiagnostic test for the early detection of carcinoma of the breast. A cytotoxic assay for the identification of circulating lymphocytes bearing surface ferritin was performed on 100 patients with malignant disease of the breast and in 50 healthy women. Forty-five patients were found to have a subpopulation of ferritin bearing lymphocytes, and all of them proved to have Stages I and II carcinoma of the breast. No such lymphocytes were identified in normal women, and in the remaining 55 patients, 33 had benign disease of the breast, 20 had Stage III carcinoma of the breast and two had Stages I and II carc-noma of the breast. It appears that this immunodiagnostic test may provide an additional tool for the early detection of carcinoma of the breast and may have a prognostic implication.


Arteriovenous malformations of the intestine. Arteriovenous malforamtions of the intestine are recognized as an uncommon cause of chronic gastrointestinal bleeding. In previous reports, the role of selective mesenteric angiography in the localization of the lesion has been emphasized; with confirmation by in vitro injection of radioopaque dye into the resected specimen. The histologic appearances of arteriovenous malformations are well recognized, although terminology is still confused. In this report, two distinct entities of small vessel malformation are described and the terms submucosal endothelial angiodysplasia and submucosal fibromuscular angiodysplasia are offered.


Thrombosis of the portal vein following distal splenorenal shunt. Portal vein thrombosis with a patent shunt is a distinct clinical entity which can follow selective distal splenorenal shunt and should be looked for in patients in whom ascites and abdominal pain develop postoperatively. Possible mechanisms include an increase in blood viscosity and a decrease in portal flow which may be aggravated by inadequate devascularization.


Immunosuppressive antilymphocyte serum. III. Different subpopulations of T lymphocytes are influenced at different doses of antilymphocyte serum. In these experiments, we have examined the effect of antilymphocyte serum (ALS) on T lymphocyte subpopulations in animals receiving nonimmunosuppressive, weakly immunosuppressive, and strongly immunosuppressive doses of different pools of ALS. Nonimmunosuppressive (inactive) sera were defined by their inability to prolong Fischer skin grafts on Lewis recipients. Weak immunosuppression was considered to have been achieved at doses of active ALS that induced prolonged survival of Fischer skin homografts but not the more strongly antigenic Wistar-Furth homografts. Similarly, strong immunosuppression was induced with doses of active ALS that resulted in prolonged survival of not only Fischer but also the Wistar-Furth grafts. Examination of Lewis rats treated under these conditions indicated that weakly immunosuppressive ALS created a shift in peripheral T lymphocyte subpopulations with an increase in the absolute numbers of one subpopulation (lymphocytes capable of forming rosettes with guinea pig red blood cells in fetal calf serum). This population shift induced by active ALS was dose dependent and occurred in spleen slightly before lymph nodes. Nonimmunosuppressive antisera failed to induce this change. Moreover, although these doses of ALS were capable of prolonging the survival of Fischer skin grafts and inducing the population change, there was no loss of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) in vitro. However, at doses of antiserum capable of prolonging the survival of Wistar-Furth skin grafts, the in vitro reactivity of T lymphocytes to these mitogens was more consistently suppressed. These data suggested that the degree of immunosuppression achieved with different pools or doses of ALS was attributable to variation in the susceptibility of different T lymphocyte subpopulations to suppression by ALS.


Cardiac arrhythmias in the anesthetized patient. Continuous monitoring of the electrocardiogram provides an opportunity for the veterinary surgeon to perform the surgical procedure in a safe and controlled manner. Arrhythmias can usually be eliminated by lowering the concentration of anesthetic and administering additional oxygen. Antiarrhythmic drugs are required when these measures do not control the problem and when surgery cannot be stopped. If a disturbance cannot be abolished or controlled with medication, the surgeon must weigh the potential gain of surgery against the potential risks of the arrhythmia.


Surgery of the trachea.

Surgery of the trachea. As our knowledge of the disease conditions affecting the airways increases, the opportunity and need to surgically invade these structures will increase accordingly. The importance of a carefully planned and excuted anesthetic protocol cannot be overemphasized; a well trained and experienced individual must monitor patients throughout the procedure and manipulate the anesthesia as required. With the use of current anesthetic equipment and techniques, the surgical correction of tracheal disorders can be accomplished safely.


Management of pyothorax.

Management of pyothorax. Pyothorax is a serious disease process which requires both medical and surgical intervention. Late recognition, management problems, and likely recurrence make successful treatment difficult and often frustrating. Aims of therapy should be to avoid undue stress to the patient, to relieve respiratory distress by thoracocentesis, to eliminate infectious agents with antimicrobials, to remove pleural exudate, and to provide supportive care. Close monitoring of the patient is necessary to prevent iatrogenic complications such as pneumothorax, hemothorax, hypothermia, or hypoproteinemia. Exploratory thoracotomy for removal of granulomatous material and fibroelastic pleural "peels" is occasionally necessary to resolve compressive cardiopulmonary lesions.


[Cancer of the stomach complicated by profuse hemorrhage]. Hemorrhagic gastric cancer is noted in 4-25% of observations, according to the author--in 23.5%, profuse hemorrhages as reported by the author make 3.4% of the total number of recorded gastric cancer cases and 14.4% among hemorrhagic gastric cancers. To detect the source of bleeding is very difficult. In 37% of observations profuse gastric hemorrhage is the first sign of stomach lesion. Female patients show the predominance of cancer of the stomach body and 1st grade blood losses, male patients--cancer of the proximal gastric portion and 3d grade blood losses. In relation to the anatomical type of growth a saucer--shape cancer is predominant. Gastric hemorrhage is not a reliable sign of inoperability, radical operations were performed in 31% of patients with the postoperative mortality in 15.7%. The death rate in non-operated patients was 36.8%.


[Effects of thymosin on human blood lymphocytes in vitro]. The activity of thymosin obtained from calf thymus was examined in the tests in vitro: the reaction of spontaneous rosette formation, blasttransformation reaction to PHA and the reaction of leucocyte migration inhibition. It was demonstrated that the activity which stimulates T-lymphocytes would appear only in cases where donor lymphocytes show depletion in terms of rosette formation and blasttransformation. In some patients thymosin was found to produce the in vitro activation of cell anti-tumor immunity.


[Studies on sensitization after repeated topic application of live attenuated influenza vaccine (Gripovax) (author's transl)]. A long term study with bivalent live influenza vaccine was carried out in 18 subjects with no previous history of egg protein hypersensitivity. Experimental conditions included a nine-fold vaccination schedule with collection of serum and nasal fluid. The parameters studied were determination of serium and local antibody formation as well as the demonstration of specific IgE antibodies in serum and nasal fluid. Our major interest was directed towards the question of potential sensitization after repeated doses of non-purified oral vaccine. The close medical follow-up of the subjects revealed no clinical signs of atopic reaction. There were no complaints regarding adverse reactions usually following local application of live influenza vaccines. Determination of total serum IgE rederately elevated levels before, during und after the trial; one vaccinated subject showed high concentrations prior to vaccination with no significant change during the experiment. That individual was ultimately classified atopic with a pronounced hypersensitivity to egg protein. Nevertheless this person tolerated nine doses of vaccine without side reactions and showed no significant increase in total or specific IgE antibodies. Concentrations of IgE in nasal secretion of non-atopic subjects are less than 2U/ml, whereas they are frequently higher in allergic patients and in the presence of nasal IgE levels greater than 4 U/ml one would expect a specific reaction to challenge allergens. In our vaccinees nasal IgE values were consistently within normal range, at no time exceeding 2.6 U/ml, even the atopic subject did not exhibit higher levels in nasal fluid. A correlation between systemic and local IgE antibodies revealed no pathognostic relations; in addition to this, specific IgE-serum-antibodies as measured in the RAST against ovalbumin allergen did not show any correlation to vaccination. These data present good evidence for the innocuity of the vaccine with regard to its repeated application in man.


Pneumocystis carinii pneumonia: epidemiology in Japan, and cyst concentration method. Pneumocystis carinii pneumonia has been markedly increasing recently in Japan. Most cases are seen after receiving anti-cancer and immunosuppressive therapy against their underlying diseases. No cases have been found in undernourished or premature infants. The authors proposed a new method which can concentrate the cysts efficiently from the human and animal lungs, and express the density of infection quantitatively at the same time. This method will especially be valuable to demonstrate the organism in light infection such as latent infection, after treatment, and so on.


[Lymphotoxin production by human lymphocytes. III. The action of adenovirus antigen]. In lymphocyte cultures (LC) from 5 immune donors blast transformation occurred as a result of the stimulting action of adenovirus antigen; the supernatants obtained from these cultures produced a cytotoxic effect on L cells, thus suggesting the presence of lymphotoxin (LT). No blast transformation and no LT production were detected in nonstimulated LC used for control, as well as in LC from 9 nonimmune donors. LT production was shown to depend on the time elapsed after recovery from acute adenovirus infection. LT production was found to be most intensive during the first 2 months after recovery.


[Further study of the problem of specific cellular receptors in delayed hypersensitivity]. The work presents the materials obtained as a result of the further study of specific T lymphocyte receptors with the use of so-called receptor antisera, i. e. antisera against the lymphoid cells of mice sensitized with one of the two antigens (Macobacterium tuberculosis or bovine gamma globulin); thus these differed from control antisera against the lymphoid cells of intact mice. These mouse antisera reacted with the lymphoid cells of guinea pigs in experiments of delayed-type hypersensitivity transfer. The cells of sensitized guinea pigs lost their ability to transfer hypersensitivity if, prior to their injection into the recipient guinea pigs, these cells were treated with the above-mentioned mouse antisera, i. e. antisera against the lymphoid cells of mice had a blocking effect on the lymphoid cells of guinea pigs. The blocking action of the antisera proved to be specific: antisera against the lymphoid cells of mice sensitized to bovine gamma gloublin blocked the cells of guinea pigs, also sensitized to bovine gamma globulins, but did not block the cells sensitized to Mycobacterium tuberculosis. The control antisera, taken in the same doses as the factor antisera, did not show a blocking effect on the specific activity of lymphoid cells.


Intermittent claudication--epidemiology and natural history. Epidemiological information on the prevalence, incidence and natural history of intermittent claudication and peripheral vascular disease is limited, partially by the limitation of techniques of their study. The available data from the literature are review and supplemented by results from an on-going survey the ankle blood pressure measurement with Doppler ultrasound.


Intermittent claudication--pathophysiological considerations. Intermittent claudication is a non-pathognomic symptom elicited by an inbalance between the metabolic demands of the exercising skeletal muscle and its blood supply. In normal conditions hyperemia to the working muscles will be impaired during the exercise by mechanical compression of the microvessels. The resulting anaerobic metabolism will cause further vasodilatation. Both phenomena (exercise and reactive hyperemia) contribute to a maximal increase in local blood flow as soon as the exercise is stopped. If the local circulation is impaired by occluding arterial disease (eventually complicated by aggravating factors) the tolerance to skeletal work is lowered and the circulatory reserves are entirely exhausted as demonstrated by the ischemic exercise-test. In the case of a major obstruction and poor collateralisation, a "steel phenomenon" may occur. The pharmacotherapeutic possibilities to cope with in this situation are briefly discussed.


[Intermittent claudication. Introduction to clinical diagnosis]. The history and the physical examination are still at the basis of the approach of the patient suffering from intermittent claudication. The history makes clear the specific symptom and its localization. The evolution of the disease, the social and professional handicap are defined. Other troubles and other localizations of the vascular disease are recognized and the nature of the risk factors etablished. The physical examination indicates the pattern and the distribution of the vascular lesions and orientates the pathogenic investigations. A rough assessment of the insufficiency of the cutaneous and muscular circulation is also possible.


Diagnostic work-up of patients with intermittent claudication. In this paper a number of techniques are described that provide information concerning the functional disturbances caused by anatomic lesions within the vascular system in patients with intermittent claudication. These techniques are part of a currently growing entity that is called the "Vascular Laboratory". Main characteristics of these techniques are that they are painless, atraumatic and without any danger to the patient. Therefore, they can both be used for diagnosis as well as for follow-up of the patients. Moreover, many of them are useful for detecting stenotic lesions at an early stage of evolution. In any patient with intermittent claudication, the walking distance, oscillography at rest and after exercise and systolic blood pressure determination should be performed. Segmental plethysmography is extremely sensitive mainly when performed together with systolic blood pressure determination. Venous occlusion plethysmography has been significantly improved in recent years and is capable of providing direct information concerning the circulation through the diseased limb. There seems to be tremendous improvement in the techniques using ultrasound allowing presently construction of an anatomic picture of the vessels (Ultrasonic arteriography).


Medical treatment in intermittent claudication. A variety of measures advocated in the treatment of intermittent claudication are critically reviewed. Daily leg exercises increase the walking ability but the mechanism of this effect remains controversial. To date, doubt persists whether drugs, either vasodilating or antithrombotic, are of any clinical value in this condition.


Noonan's syndrome and cyanotic congenital heart disease. A report of 4 cases and review of the literature. The clinical features of four adult patients with Noonan's syndrome and cyanotic congenital heart disease are presented. These findings, together with those of previously reported cases, illustrate the wide spectrum of cardiac anomalies that may be associated with the multiple somatic abnormalities of Noonan's syndrome.


The value of serum fibrinogen degradation products in the differential diagnosis between acute myocardial infarction and pulmonary embolism. Serum-FDP was measured in 148 patients with AMI or pulmonary embolism within 48 hours of the onset of symptoms or within 48 hours of the admission to hospital. Within 48 hours of the hospitalisation 14.6% of the patients with AMI Rand 81.8% of the patients pulmonary embolism showed a serum-FDP elevation to over 10 units/ml. The use of the analysis is limited by the time which elapses until the result is available, by the short duration of the serum-FDP elevation and by the lack of specificity of the examination.


The fate of patients with intraventricular conduction disturbances complicating acute myocardial infarction. The partial incidence and the early and late mortality were studied in 104 patients with acute myocardial infarction complicated by intraventricular conduction defects. Right bundle branch block and left anterior hemiblock had a greater incidence than the other conduction anomalies, while the hospital mortality was greater for the complete right bundle branch block combined with left anterior or posterior hemiblock, followed in order by complete left bundle branch block. Late morality was higher in cases with complete right bundle branch block combined with left posterior hemiblock and also in cases with focal block or left bundle branch block indicating a poor prognosis for these patients. For the rest sub-groups of patients late mortality was relatively low indicating the possibility of long survival after passing the acute phase. However, longer periods of observation are desirable for further estimation of their ultimate prognosis.


Potassium sparing effect of amiloride in patients receiving diuretics: a quantitative study. This study was undertaken in order to assess the K+ sparing ability of amiloride. Thirty patients with liver cirrhosis and ascites or congestive heart failure were divided into three groups and treated with amiloride (Group A), hydrochlorothiazide (Group B) and amiloride plus hydrochlorothiazide (Group C) for 15 days. In all groups there was an increased diuresis while only in group A and C there was a statistically significant rise of K+ serum levels and a slight increment of K+ urinary loss. Total body K+ evaluated by 42K increased in group A and C while decreased in group B. Our results seem to confirm that amiloride has a mild diuretic action with a powerful K+ sparing capacity; amiloride is also able to counterbalance and reverse hydrochlorthiazide induced K+ urinary loss.


Ultrastructure and function of interdigitating cells in the guinea pig thymus. Electron micrsocopic investigation of the thymus of normal guinea pigs of both sexes, approximately 3 months of age, have shown that the organ contains at least two types of non-lymphoid cells: epithelial reticulum cells and so-called interdigitating cells. The latter have been observed in the inner part of the cortex and are morphologically characterized by an irregularly shaped or kidney-shaped nucleus, many tubulovesicular cytoplasmic structures accumulated mostly within the cytocentre as well as by finger-like protrusions of the cytoplasm. These interdigitating cells are in close contant with neighbouring lymphocytes with partly destroyed pycnotic nucleus.


Light and electron microscopic studies on the medial forebrain bundle in the rat. I. Nerve terminals in the lateral hypothalamus of extrahypothalamic origin. Degenerated nerve terminals were demonstrated in the lateral hypothalamus of the rat following transection of the rostral and caudal fibres to the medial forebrain bundle (MFB) and a parasagittal cut along the lateral edge of the hypothalamus. In the light of these findings the termination of extrahypothalamic MFB pathways on intrinsic neurons is assumed.


Light and electron microscopic studies on the medial forebrain bundle in the rat. ii. nerve terminals from the medial hypothalamus. After the surgical interruption of connections between the medial and lateral hypothalamus of the rat axonal (transient) and nerve terminal degeneration was shown in the medial forebrain bundle (MFB) with light and electron microscopy. Following 1 mm long parasagittal cuts at various rostro-caudal levels the degeneration pattern within the MFB indicated a certain territoral arrangement of terminating fibres from the medial hypothalamus. After a parasagittal cut through the lateral retrochiasmatic area, degeneration was observed in the full length of the MFB. This suggests that a number of axons connect the medial and lateral hypothalamus through this area. With the aid of a parasagittal cut separating totally the medial and lateral hypothalamus, the degeneration of dendrites in the middle portion of the lateral hypothalamus was also revealed. These proved to derive from cells of the ventromedial nucleus.


A rapid factor VIII-related antigen electroimmunoassay. A micromethod using commercial antisera. A simple, rapid micromethod for determining Factor VIII-related antigen is outlined. The simplicity of the method, using commercial antisera, prepackaged buffer, plastic plates that readily accept the gel without precoating with agarose, and standard equipment makes the procedure adaptable to the routine laboratory. The results give a straight-line graph to the 0.50 units/ml range, and values as low as 0.03125 U/ml can be determined using log-log graph paper. A second range of standards gives values from 0.10 to 0.750 U/ml when plotted on semilog graph paper. A permanent record can be made after a first rapid visualization process, which permits reading the plates within 15 min of the two-and-a-half-hour electrophoresis time.