Reduced in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells. The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3-28 months) to the polyclonal mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age-related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age-related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age. Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28-month-old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1-year-old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.


Functional development of the interacting cells in the immune response. III. Role of the neonatal spleen. Neonatal splenectomy and congenital absence of the spleen were shown to be associated with lack of primary IgM antibody synthesis, deficient bone marrow-thymus cell synergism. altered mitogen responsiveness and depressed homing patterns of thymocytes to the spleen. Using congenitally asplenic animals, altered B-T cell cooperation was manifest at the T cell but not B cell level. This correlated with the ability of thymus cells from either congenitally asplenic or neonatally splenectomized (NSx) animals to respond to the B cell mitogen lipopolysaccharide although there were no detectable Ig=ells present. To determine the role played by the spleen in the development of T cell function, NSx animals were given either irradiated or normal spleen grafts. Both irradiated and unirradiated grafts restored normal B-T cooperation and normal mitogenic responses of thymus cells. However, neither type of spleen graft was successful in restoring normal homing patterns to the spleen. It is concluded that the splenic microenvironment influences T cell maturation very early in life and that only some of the effects attributable to the absence of the spleen can be reversed by the reintroduction of this tissue as a graft.


Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis. Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid.


[Immunologic development disorders and disease incidence]. Interference with any organ system during development leads to permanent damage. Severe disease or starvation during the first four months of extrauterine life lead to a persistent deficiency of cell mediated immunity, which changes the life expectancy and later disease patterns in population groups. Severe intercurrent disease, starvation or trauma later in life lower cell mediated immunity only temporarily.


[Physiologic and clinical manifestations of brain-dominance (author's transl)]. The effects of brain-dominance in psychology, electrophysiology and the axial muscles are described. 1. Left-sided vascular hemispheric brain-distrubances, with or without aphasia, reduce, compared with arteriosclerotics, without focal signs, verbal, action-and total IQ, those on the right side only the action and total IQ. When comparing right- and left-sided frontal, frontoparietal and frontotemporal vascular disturbances - with or without a aphasia-, the left-sided frontotemporal lesions had a lower action- and verbal IQ, even if there were no signs of aphasia. In children aged between 12 and 40 months we found no correlation between the degree of motor dominance and mental development. Among children with delayed speech development--and therefore also in children with subnormal development--the number of lefthander was significantly higher than with the other children. 2. One can show electromyographically that, when a muscle is voluntarily contracted, there is simultaneous contraction of the same muscle on the other side. This contralateral motorspread happens more often from the stimulation of the dominant side to the subordinated side than vice versa. Ipsilateral somato-sensory cortical response is more common when stimulating the dominant than the subordinated ulnar nerve and develops ontogenetically parellel with right- or left-handedness. 3. Stabilographic registration can show a right-sided prevalence of swing of the vertical axis of the body, which probably is related to a lower irritability of the vestibular apparatus on galvanic stimulation. With the eyes open, the right-sided deviation of the bodyaxis increases which can be explained by greater functional strength of the right visuomoto system, which itself can be shown by the higher frequency of right-sided optocinetic nystagmus.


Co-operation across histocompatibility differences. The role of inhibitory T cells in preventing successful T-B interaction. The efficiency of interaction of helper T cells with memory B cells of varying histocompatibility types has been studied in an in vitro microculture system. Such studies show that I-A region matching does not necessarily determine that efficient co-operation will take place. Failure to co-operate under circumstances where T and B cells match in I-A can be attributed to radiosensitive suppressor T cells. The nature of the gene differences which provoke the activity of such suppressor cells have also been examined, and it would seem that even single S.D. differences in the MHC are sufficient to generate 'suppressor' T-cell activity.


The generation of memory cells. I. The role of C3 in the generation of B memory cells. Adult thymectomized, repopulated mice were chronically depleted of circulating C3 by treatment with cobra venom factor after primary immunization with dinitrophenylated haemocyanin (DNP-KLH). This treatment totally abrogated the development of B-cell memory in such mice, as assayed by a co-operative lymphocyte transfer. The failure of memory development appeared to involve impaired precursor proliferation following priming. It was further shown that the localization of DNP-KLH in splenic lymphoid follicles is both antibody and C3-dependent; thymus-deprived mice make sufficient antibody to DNP-KLH to effect follicular localization of the antigen. On the basis of these and earlier observations we suggest that the development of B-memory cells involves the formation of antigen-antibody-C3 complexes on dendritic cells in lymphoid follicles. C3 may serve to stabilize the antigen bridge between dendritic cells and virgin precursors. In complete contrast, C3 depletion had little effect on the functional expression of primed B cells, thus suggesting that only the early stages of B-cell triggering are C3 dependent.


Complications and immunological studies of measles virus infection in antithymocyte-treated hamsters. A study was done to investigate possible late central nervous system (CNS) complications of latent measles infection in hamsters. Signs of CNS disease, consisting of myoclonus and paralysis, occurred in some weanling hamsters inoculated intraperitoneally at 3 or 9 days of age with antithymocyte serum (ATS) and measles virus, but no late complications in adult life attributable to measles virus were seen. A single series of ATS injections plus an injection of measles virus resulted in sustained antibody formation postulated due to establishment of a latent viral infection, whereas similar treatment with normal rabbit serum plus virus caused no or minimal antibody response. The majority of hamsters receiving ATS as newborns and ATS plus virus as weanlings also did not produce antibody. This differential effect of ATS may be due to combined elimination of suppressor and helper cells in the latter ATS-treated group and of suppressor cells only in the former ATS-treated group. Cellular immunity could not be evaluated since lymphocytes from inoculated and uninoculated hamsters released equal and variable amounts of 51Cr for both infected and noninfected labeled, allogeneic hamster target cells.


Immunology of the infant rat experimental model of Haemophilus influenzae type b meningitis. The age-related acquisition of serum anticapsular and bactericidal antibodies to Haemophilus influenzae type b observed in rats was similar to that of humans. The antigenic source for this "natural" immunity was not identified since neither pharyngeal infection with H. influenzae b nor enteric colonization by cross-reacting bacteria was detected. Infant rats surviving H. influenzae b bacteremia failed to respond immunologically to the capsular polysaccharide. However, surviving rats demonstrated no impairment of immune responsiveness to this antigen after subsequent immunization with live bacteria in adulthood. In passive protection experiments, antibodies directed against the type b capsular polysaccharide represented the major protective specificity. However, a small protective effect of antibodies to noncapsular antigens also appeared to have been demonstrated.


Study of colour blindness in school children. Of the 1553 male and 519 female students in schools of Patiala, between the age group of 10 and 15 years, 3.85% males and 0.38% females were found colour-blind. The students were tested by Ishihara Charts, Edridge Green Lantern and then assayed by Pickford Nicolson Anomaloscope and the results were presented in detail. In addition, the affected students were also tested for their acuity of vision and were found normal.


Activation of the alternative complement pathway by Haemophilus influenzae type B. The results of the following study demonstrate that Haemophilus influenzae type B (HITB) is able to activate the alternative complement pathway. They also demonstrate that the activation of the alternative pathway by HITB is not mediated by the capsule.


Pathogenesis of latent herpes simplex virus infection of the trigeminal ganglion in guinea pigs: effects of age, passive immunization, and hydrocortisone. Latent herpes simplex virus (HSV) infection of the trigeminal ganglion, after corneal inoculation of virus, was investigated in guinea pigs. The effects of several factors on the establishment of ganglionic latency were investigated. Latently infected guinea pigs were clinically normal, and virus was isolated from the trigeminal ganglia by co-cultivation. It was found that newborn guinea pigs were significantly more susceptible than adult animals to the development of latent HSV infection of the trigeminal ganglion. The susceptibility of newborn guinea pigs was very much decreased, however, if they received passive immunization with immune serum or if they were born of actively immunized mothers. On the other hand, the susceptibility of adult animals, usually somewhat resistant to the development of latent HSV ganglionic infection, was markedly increased by the parenteral administration of hydrocortisone.


Effect of thermal trauma on numbers and function of T and B cells from mouse spleen. Swiss-Webster female mice were given a moderately severe burn, and studies were carried out on the number and function of T and B cells from the spleens of burned and normal mice. The results showed a significant decrease (p less than 0.05) in the number of T and B cells for 2-3 days after burning with a rapid return to normal and a subsequent rise above normal at 14 and 21 days postburn (p less than 0.05). In the test for function, burned mice had a significant decrease in spontaneous mitotic activity of both T and B cells during the 21-day postburn period. When spleen lymphocytes were incubated with purified mitogens, both T and B cells showed a significantly diminished mitotic response in most of the burned animals.


Morphine analgesia and its modification by drugs altering serotonin (5-HT) and dopamine levels in the brain. Morphine analgesia in mice was significantly potentiated by pretreatment with 5-hydroxytryptophan (5-HTP), especially with higher dose of morphine. Morphine analgesia was antagonised by reserpine. With l-dopa it was antogonised when the dose of morphine was minimal but with increased dosage of morphine, there was no significant effect.


Twenty-four hour rhythms in serum and brain indoleamine concentrations: tryptophan-5-hydroxylase and monoamine oxidase activity in the rat. The relationship between the 24 h rhythm in 5-hydroxy-tryptamine (5HT) levels in rat brain, the availability of precursors of 5HT and the concentration of its major metabolite, 5-hydroxyindole acetic acid (5HIAA) has been investigated. Serum total and "free" tryptophan (TRY) levels and brain TRY levels all show a 24 h rhythm with highest concentrations in the middle of the dark phase i.e. 12 h displaced from that of the 5HT rhythm. No 24 h variation in either tryptophan-5-hydroxylase or monoamine oxidase activity was detected, nor did brain 5-hydroxytryptophan (5HTP) levels vary with clock hour. Changes in 5HIAA concentration paralleled those of 5Ht. The uptake of 14C-5HTP, 14C-TRY and 14C-5HT into homogenates of the septal region of rat brain did not display a circadian rhythm, although there was evidence that uptake of 14C-TRY in an isolated synaptosomal preparation from the same region was greater during the light phase, indicating the possibility that uptake of the precursor into the nerve ending may be, in part, responsible for the 24 h rhythm in brain 5HT. It is concluded that brain 5HT levels are independent of the serum or brain TRY concentrations measured. Since changes in 5HT with clock hour are paralleled by changes in 5HIAA, it also seems unlikely that the increase in brain 5HT during the light phase is caused by a decreased release of 5HT from nerve endings.


The effect of 60Co gamma-radiation and hydroxyurea on the in vivo chain growth of DNA in crypt cells of the small intestine of the mouse. DNA chain growth has been studied in small intestinal crypt cells of the mouse in vivo using a sensitive method. The method is designed primarily to study radiation-induced DNA-breaks and their repair; but since there are breaks in DNA at the replicating fork, it is also possible to study DNA chain growth after a 3H-thymidine pulse. We found that DNA chain growth is not depressed by 200 rad of 60Co gamma radiation. This finding supports the hypothesis that irradiation interfers mainly with the initiation of new replicons in mammalian cells affecting DNA chain growth only at higher doses. Hydroxyurea at sufficient dosage, however, depresses or even stops DNA chain growth in mouse crypt cells in vivo.


Ribonucleic acid synthesis in regenerating liver of irradiated adrenalectomized rats. The effect of whole-body irradiation on RNA synthesis in regenerating and non-growing livers was studied in intact and adrenalectomized rats. The animals were divided into four sub-groups: (1) control; (2) irradiation only; (3) partially-hepatectomized; and (4) irradiated partially-hepatectomized. Newly-synthesized RNA was determined by 30 or 40 min uptake of (6-14C) orotic acid. Both nuclear and polyribosomal RNA synthesis in regenerating livers of adrenalectomized rats were depressed below their control levels, regardless of whether irradiation was 2 hours before or 2 hours after partial hepatectomy. Specific radioactivity values of regenerating livers of adrenal intact and adrenalectomized rats were elevated above those of the non-growing livers from irradiated and unirradiated rats.


Effects of topically-applied olive oil on the response of hamster skin to single or multiple doses of 230kV X-rays. The effects of topically-applied olive oil on the response of hamster skin to single or multiple doses of X-rays has been studied. The olive oil was applied either 15 min or 1 hour before the radiation exposures. The treatment did not alter the temporal pattern of development and recovery from the radiation injury. For single exposers, olive oil did not alter the 1- to 30-day average skin response. However, when it was administered at each treatment when three radiation fractions were given over a 4-day interval (3 fractions/4 days), a significant increase in the amount of dose recovered was found compared with control irradiated animals. For controls, the average amount of dose recovered per fractionation interval, (Dn-D1)/(n-1), was about 505 rad. For animals treated with olive oil 15 min before irradiation, it was about 720 rad; and for those treated 1 hour before irradiation, it was 782 rad. The data indicate a definite radioprotective effect of topical administration of olive oil, but at present the mechanism is not known.


Comparison of three mammalian cell-lines with respect to their sensitivities to hyperthermia, gamma-rays and U.V.-radiation. Three types of cultured mammalian cells, from a rat ureter carcinoma (RUC-2), from a mouse mammary carcinoma (M8013), and from a Chinese hamster lung cell-line (CH-V79), have been compared with respect to various treatments. Using cloning assay, the sensitivity of these cell-lines was measured for ionizing radiation, U.V.-light and for temperatures of 41 degrees, 42 degrees, 43 degrees, 44 degrees and 45 degrees C. RUC-2 cells are the least sensitive to these treatments, except for 45 degrees C. M8013 is sensitive to gamma-rays and U.V.-irradiation. CH-V79 is sensitive to gamma-radiation and hyperthermia. Since sensitivity to one type of treatment does not correlate with similar susceptibility to the others, it is concluded that different mechanisms may be involved in inactivation by these treatments.


Intraspinal sacral root stimulation for controlled micturition. The intraspinal extradural segments of the sacral nerves were stimulated in an effort to obtain the combination of maximal detrusor contraction and minimal outflow resistance essential for effective micturition. Each root was stimulated unilaterally and bilaterally. In addition, each was separated into its motor and sensory components and these components were then individually stimulated. It was found that the most effective result was obtained with stimulation of root S2. As in the experimental animal, sacral roots in the human have a long intraspinal course that makes them accessible for implantation of electrodes. It is hoped that ongoing experiments will lead to the development of a chronically implantable sacral root electrode--thus providing a tool for efficient emptying of the denervated bladder.


Effect of thymic hormone on the response of different  lymphoid cell populations to T mitogens. The  effect of the thymus humoral factor (THF) on the response of different lymphoid cell populations to T mitogens  was studied. Lower THF concentrations were required to increase the response to concanavalin A (Con A) than to increase that to phytohemagglutinin (PHA), suggesting that T cell types at various stages of maturation are activated at different THF concentrations. Lower THF concentrations were required to enhance the mitogenic response of thymus cells than to enhance the mitogenic response of spleen cells, and this may be because of the higher incidence of target cells for THF activity in the thymus cell population. Spleen cells of adult thymectomized mice exhibited a higher sensitivity for THF than cells of intact control mice. Lymph node cells showed no increase in motogenic response after THF treatment. Similarly, THF did not affect the mitogenic response of spleen cells from nude mice. These results confirm our hypothesis that the targets for THF activity are the younger cells within the T cell lineage.


Relationships among some R plasmids found in Haemophilus influenzae. Tetracycline resistance in a strain of Haemophilus influenzae isolated in the United Kingdom was found to be determined by an apparently non-selftransmissible plasmid of 31 X 10(6) daltons (31 MDal), designated pUB701. Deoxyribonucleic acid hybridization studies indicated that pUB701 shares about 70% base sequence homology with the 30-MDal ampicillin resistance R plasmid RSF007 isolated in the United States from H. influenzae, and 64% sequence homology with the 38-MDal tetracycline and chloramphenicol resistance R plasmid pRI234, isolated in the Netherlands. Heteroduplex studies between RSF007 and pUB701 confirmed the fact that these plasmids were largely homologous, except that pUB701 contained the tetracycline resistance transposon TnD, whereas RSF007 contained the ampicillin resistance transposon TnA. A strain of H. parainfluenzae resistant to both chloramphenicol and tetracycline carried two species of plasmid deoxyribonucleic acid of 2.7 and 0.75 MDal. We were unable to prove that either resistance was plasmid-borne in this strain. Hybridization studies with a [3H]thymine-labeled tetracycline resistance enteric plasmid suggested that the tetracycline transposon was integrated into the chromosome of H. parainfluenzae UB2832. We conclude either that the strains we studied received R factors of the same incompatibility group  bearing different resistance genes, or that different resistance genes were translocated to a commom resident plasmid of H. influenzae.


Phosphorylation of the 18,000-dalton light chain of myosin during a single tetanus of frog muscle. Changes in the 32P content of proteins due to muscle contraction were investigated, using muscles dissected from liver frogs injected with [32P]orthophosphate. The only significant change found was in the radioactivity of the 18,000-dalton light chain of myosin; during a single tetanus, an increase of 85 to 90% occurred as compared to the resting muscle. This increase corresponded to about 0.4 mol of 32P per mol of light chain. The same increase in radioactivity of this light chain was also found upon caffeine-induced contracture of the intact muscle. It is postulated that the increased Ca2+ concentration in the sarcoplasm resulting from electrical stimulus or caffeine treatment activates the myosin light chain kinase which phosphorylates the 18,000-dalton light chain.


Nexus of frog ventricle.

Nexus of frog ventricle. Here were demonstrate in Rana pipiens ventricle a nexus with very unusual morphology. This tissue has been reported previously to lack nexuses. The nexus appears in thin sections of ventricle, fixed in aldehyde and OsO4 or permanganate as a series of punctate membrane appositions regularly alternating with regions of membrane separation. The junctional width at membrane appositions, as determined by microdensitometry and optical measurements, is 15-17 nm, and the width of the electron-translucent region between the junctional membranes is 1.8 nm. These values correspond closely to similar measurements of the more typical nexues in frog liver. Along the nexus the mean distance between punctate appositions is 74.5 nm. Freeze-cleave replicas of the nexuses between myocardial cells show particles 10.4 nm in diameter arranged in arrays of up to nine linked circles or partial circles on the PF-face and similar arrays of pits of shallow grooves on the EF-face. The mean diameter of the circles on both membrane fracture faces is 76.7 nm comparsion of the thin-sectioned and freeze-cleaved nexuses demonstrates an excellent correspondence between the spacing of membrane appositions along the junction and the diameters of the freeze-cleaved circles of particles and pits or grooves.


Improvement of the efficiency of ion-exchange cellulose columns and their application. Packing procedures and operating conditions for microparticulate ion-exchange cellulose columns were investigated. The efficiencies of ion-exchange cellulose and mixed-bed ion-exchange cellulose columns were compared. The mixed-bed columns contained ion-exchange cellulose and diatomite, and those with a 5:1 volume ratio of ion-exchange cellulose (average particle size 7 micronm) and diatomite were found to be superior in almost every respect. Medical, pharmaceutical, biochemical and environmental applications of this type of column are shown.


Autoantibodies to B lymphocytes in a patient with hypoimmunoglobulinemia. Characterization and pathogenic role. In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm(3) with 0.5-1.5% bone marrow-derived (B) cells and 98-99% thymus-derived (T) cells. Anti-lymphocyte antibodies were detected by immunofluorescence and by microlymphocytotoxicity with increased reactivity at +4 degrees C. They belonged to the IgM class and were polyclonal. Studies performed with various normal lymphocyte subpopulations, several lymphoblastoid cell lines and lymphocytes from immunodeficiency patients showed that these antibodies reacted with B cells. The corresponding antigen(s) is distinct from membrane-bound immunoglobulins, is not an alloantigen, and is probably unrelated to the la-like molecules. Pokeweed mitogen stimulated B cells appear to lose this antigen. Cells from various lymphoproliferative disorders were tested. T-derived and "non T-non-B" leukemic cells did not react with the antibody. Malignant cells from B-derived lymphomas and prolymphocytic leukemias were reactive. The incidence of positivity of the leukemic cells among patients with common B chronic lymphocytic leukemia was surprisingly low (one-third of the patients). The autoantibody nature of the anti-B-cell antibodies and their pathogenic role in the genesis of the patient's hypoimmunoglobulinemia was demonstrated by the effect of removal of antibodies by massive plasmaphereses which were followed by a dramatic and transitory increase of B-cell figures. Whereas most primary immunodeficiency syndromes appear to result from an arrest in the differentiation capabilities of immunologically competent cells, autoantibodies to circulating B lymphocytes may be incriminated in the pathogenesis of some cases of hypogammaglobulinemia.


Classical conditioning of hippocampal theta patterns in the rat. Electrical stimulation (88 HZ) of the lateral hypothalamus elicited a sustained theta response at hippocampal recording sites of rats immobilized with succinylcholine. By pairing this unconditioned stimulus with a 10-sec presentation of a light, conditioned theta responses were demonstrated in as few as 40 trials. Spectral analysis of hippocampal bioelectric patterns during acquisition, extinction, and reconditioning indicated that the earliest change as a result of conditioning is a loss of power in EEG frequency below 8 HZ, followed by the development of a peak at 8 HZ with further conditioning. Extinction was associated with an increase in power in the frequencies below 8 HZ. When the conditioned rats were tested in the absence of the neuromuscular blocking agent, the conditioned stimulus elicited a theta response that was associated with slow motor activity on 70% of the trials.


Lymphocyte reactivity in the aged.

Lymphocyte reactivity in the aged. Lymphocyte reactivity in cultures toward the nonspecific T and B cell mitogens, phytohemagglutinin (PHA) and pokeweed (PWM), was studied in 46 subjects in three groups: a) young healthy persons, b) elderly healthy persons, and c) hospitalized elderly patients with atherosclerotic cardiovascular disease. No statistically significant differences in the lymphocyte reactivity of young and old healthy persons toward PHA could be observed with different incubation times, mitogen concentrations, or serum sources. A significantly decreased lymphocyte response was found in elderly hospitalized patients compared to young and elderly healthy subjects. In contrast, no differences in the lymphocyte reactivity toward PWM could be found among the three groups, including a comparison between elderly healthy and elderly hospitalized persons. The results suggest that the B lymphocyte-dependent response to a B lymphocyte stimulator is more stable than is the T cell response in aged subjects.


Are visual anomalies related to reading ability? Although reading ability is known to be related to a large number of factors, when a child having a reading problem is brought to an optometrist he (or she) has the responsibility of determining whether or not a visual anomaly may be a major or contributing cause of the reading problem. A review of the literature indicates that myopia is consistently associated with good reading performance; and that hypermetropia, astigmatism, lateral phorias, poor fusional vergences, strabismus and color vision anomalies tend to be associated with poorer than average reading performance. Well-designed and well-controlled studies are needed, particularly concerning the effect on reading ability of the correction of visual anomalies. Until such studies have been done, any child who has a reading problem deserves a thorough optometric or ophthalmologic examination and the correction of any visual anomalies found.


The role of macrophages in the generation of T helper cells. V. Evidence for differential activation of short-lived T1 and long-lived T2 lymphocytes by the macrophage factors GRF and NMF. The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived 'T1' cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages. The present results may explain some of the discrepancies reported in the literature concerning the genetic requirements and specificity of T cell activation.


Failure of B lymphocytes in human blood to regenerate surface immunoglobulin after its removal by antibody. In culture, human blood B cells regenerated surface IgM and IgD after their removal by a brief treatment with pronase. In contrast, surface Ig was poorly reexpressed after interaction with specific antibody. Both classes of surface Ig were suppressed after treatment with antibody specific for only one. B lymphocytes from spleen and tonsils regenerated surface Ig after treatment with either pronase or anti-Ig. We suggest that the particular sensitivity of circulating B cells to anti-Ig-surface Ig interaction may be reflection of their state of maturation.


Studies of tolerance to DNA in NZB/NZW F1 mice. Administration of sDNA-poly-D-lysine (DNA-PDL) to newborn NZB/NZW F1 mice (B/W) was previously shown to prolonge survival and to decrease nephritis and DNA antibodies. In this study, B/W mice treated from birth with DNA-PDL were found to be tolerant to immunization with sDNA on PDL or mBSA carriers in  adjuvants. Tolerance to sDNA was present and was hapten-specific carrier-dependent. IgG and IgM anti-nDNA circulating antibodies were suppressed. Continuous tolerization was necessary to maintain tolerance. Tolerance to sDNA could be transferred by spleen cells, by tolerized thymus cells, and by tolerized bone marrow cells, suggesting that both T and B cells participated in this phenomenon.


Lymphocytes binding polyriboadenylic acid and synthesizing antibodies to nucleic acids in autoimmune and normal mice. Splenic lymphocytes from both normal and autoimmune mice bind significant quantities of polyriboadenylic acid (poly rA) when incubated with radiolabeled poly rA for 40 min at 37 degrees C. This poly rA binding is specifically inhibited by an excess of nonradioactive poly rA and by anti-mouse immunoglobulin. Poly rA binding is decreased by exposing spleen cells to Pronase and is restored by subsequent culture for 18 to 72 hr. Poly rA-binding activity is associated more with bone marrow-derived than with thymus-derived lymphocytes. These results suggest the presence of autoantigen-binding lymphocytes in normal as well as autoimmune mice. Furthermore, spleen cells from normal and autoimmune mice cultured for 72 hr synthesize and secrete antibodies to poly rA and DNA. These antibodies can be recovered from the culture supernatants by a solid immunoadsorbent technique and antibody immunoprecipitation. The synthesis of antibodies to nucleic acids by normal spleen cells suggests that autoreactive lymphocytes may be released from normal immunoregulatory control during in vitro culture conditions.


Association of a low molecular weight helper factor(s) with thymocyte proliferative activity. Human mixed leukocyte supernatants contain thymocyte proliferative activity (TPA) and a low m.w. helper factor, designated HP-1, which is capable of partially restoring the antibody response of T-cell-deficient adherent murine spleen cells to the thymic-dependent antigen, SRC. TPA and HP-1 appear to have a comparable m.w. (14,000 to 14,500 daltons) by Sephadex gel filtration column chromatography. Furthermore, HP-1 and TPA exhibit similar patterns of heterogeneity on DEAE-cellulose chromatography, elute together on CM-cellulose chromatography, and manifest identical patterns of migration on polyacrylamide gel electrophoresis. These data suggest that the TPA and HP-1 activities reside in either the same molecule(s) or in different molecules with identical charge/mass ratios. Furthermore, the results support the hypothesis that the helper activity of HP-1 is derived from its capacity to activate T and/or pre-T cells.


Measurement of DNA-binding immunoglobulins in systemic lupus erythematosus. A radioimmunoadsorbant assay for quantitating DNA antibody in the IgM, IgG, and IgA classes is described. The method was standardized allowing expression of results in absolute terms. Effects of rheumatoid factor on the results were investigated. The new assay was found to correlate well with the Farr assay for DNA antibody. Serum levels of DNA antibody in all three immunoglobulin classes reflected the degree of clinical activity of SLE.


Spaced food but not electrical brain stimulation induces polydipsia and air licking. An attempt was made to induce polydipsia in rats whose lever pressing was reinforced with food pellets or electrical brain stimulation. Nine food-deprived, water-sated rats drank water excessively during sessions in which food pellets were delivered. When brain stimulation was substituted for food, drinking immediately ceased. Delivering brain stimulation according to a variety of schedules, pairing brain stimulation with food reinforcement, and substituting an air stream for water, each failed to produce polydipsic licking. These results show that polydipsia is not induced by all reinforcers.


Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG. Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.


Lectin-driven maturation of cytotoxic effector cells: the nature of effector memory. In an attempt to define further the activation of effector T-cell function with concanavalin A (Con A), we examined the ability of Con A to generate effector memory in mouse lymph node cells in vitro. In the course of these studies, it became necessary to define parameters by which memory could be defined. These parameters include length of time of exposure to signal required to generate full cytotoxic function; time of onset and kinetics of blast cell formation; requirement for DNA synthesis; sensitivity to the drug 5'-bromodeoxyuridine; and kinetics of the cytotoxic response to alloantigen. By these criteria, mouse lymph node cells exposed 12 days previously to Con A behave qualitatively differently from unprimed mouse lymphocytes. We found that the time of onset and kinetics of DNA synthesis could not be used to distinguish primary and secondary cytotoxic responses. We propose that the parameters defined in these stidues  can be applied generally in determining whether a given cytotoxic response involves primed (memory) or unprimed cells.


Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. The complement regulatory enzyme, C3b inactivator (C3bINA), has been purified from human serum by affinity chromatography on an anti-C3bINA Sepharose column. Subsequent chromatography on DEAE-cellulose and removal of IgG with anti-IgG Sepharose resulted in a product which was found to be homogeneous by polyacrylamide gel electrophoresis at pH 8.9 and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The molecule is composed of two disulfide bonded polypeptide chains with mol wt of 50,000 and 38,000 daltons. Human CobINA was found to be a glycoprotein containing at least 10.7% carbohydrate and to have a normal serum concentration of 34 +/- 7 mug/ml (mean +/- 1 SD). Highly purified C3bINA cleaved neither free C3b nor free C4b if trace amounts of contaminating beta1H were removed from these proteins with anti-beta1H Sepharose. However, in the presence of highly purified beta1H and C3bINA, both C3bIna, both C3b and C4b were cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their structure. The action of C3bINA and beta1H on C3b produced two fragments of the alpha1-chain which did not dissociate without reduction of the molecule. These fragments have mol wt of 67,000 and 40,000 daltons. The action of C3bINA and beta1H on C4b resulted in cleavage of the alpha'-chain giving rise to the 150,000-dalton C4c and the 49,000-dalton C4d fragments which dissociated without reduction. To produce from C3b the immunochemically defined C3c and C3d, fragments, the action of an additional serum enzyme appears to be required, the effect of which can be mimicked by trypsin.


Novel idiotypic and antigen-binding characteristics in two anti-dinitrophenyl monoclonal antibodies. Monoclonal anti-dinitrophenyl antibodies generated in the splenic focus system from B cells of adult BALB/c mice were studied for the presence or absence of murine anti-T15 (M anti-T15) reactivity and for their ability to bind phosphorylcholine (PC). Two foci of the 680 clones analyzed bound PC, and one of these antibodies reacted with M anti-T15 and anti-Fab on a 1:1 weight basis. The discovery of a clonotype reactive with M anti-15 but not with rabbit anti-T15 (R anti-T15) serum, the converse of the R anti-T15+, M anti-T15- clonotype identified in the PC-specific repertoire, points to the novel idiotypic relationships which may be found among homogeneous antibodies binding diverse antigens. The R anti-T15-, M anti-T15+ clonotype may represent a distinct set of hypervariable region sequences inserted into the T15 framework or may be a somatic variant of the T15 germ-line sequence. In addition, the maximum frequency with which this clonotype occurs within the B-cell pool is estimated.


Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice. We used immunofluorescence to examine the developmental relationship of Ia and IgD on B cells. Pre-B cells in fetal liver did not express Ia. Only very few surface IgM-positive (sIgM+) B cells in fetal spleen were found to be Ia+ and were weakly stained for Ia. After birth there was a linear increase in the proportion of sIgM+ spleen cells which expressed Ia, reaching 95% by 9 days. Adult bone marrow also contains a sizeable proportion of sIgM+ Ia- cells. Unstimulated cells from fetal or newborn liver and spleen expressed Ia at the same rate in culture. Anti-Ia antisera suppressed the LPS-induced differentiation of IgM and IgG plasma cells in cultures of neonatal lymphocytes. Ia was also detected on IgM and IgG plasma cells in vitro suggesting that lipopolysaccharide (LPS)-stimulated B cells by may express Ia antigens, induced by LPS, or appearing as part of normal differentiation. IgD did not appear on sIgM+ cells until 3 days of age and then rose slowly to reach adult levels later than Ia antigens.


Induction of a ragweed-specific allergic state in Ir-gene-restricted nonresponder mice. Mice of the inbred strains, C57BL/6 and C57BL/10 (H-2b), are genetically incapable of developing IgE antibody responses to ragweed pollen extract (RE) or its dinitrophenylated derivative, DNP-RE. This nonresponsiveness has previously been thought to reflect the absence of a relevant H-2-linked Ir genes controlling responses of inbred mice to these antigens. However, pretreatment of H-2b mice with either low doses of ionizing X irradiation or cyclophosphamide abrogates the nonresponder status of such animals, apparently by removal of a suppressive mechanism normally inhibiting development of IgE responses to these antigens. The implications of these findings for mechanisms of genetic control of IgE antibody synthesis and the Ir-gene concept are discussed.


The generation of killer cells to trinitrophenyl-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens. Negatively selected mouse and rat lymphocyte populations, specifically deprived of alloreactivity to a particular major histocompatibility complex (MHC) haplotype, are nevertheless fully capable of responding to trinitrophenyl (TNP)-modified allogeneic stimulator cells and developing cytotoxic T-lymphocyte activity to TNP-altered allogeneic target cells. As for syngeneic systems, lytic expression of those responder killer cells also requires MHC identity between the target and stimulator cell populations. Such a finding argues strongly against two variations of the dual recognition hypothesis: like-like interactions and adaptive differentiation. Instead, these data favor either the altered self model or a third variation of the dual receptor model, where one of the relevent receptors is specific for the modifying antigen and the second is a low affinity receptor unable to be triggered in the absence of a modifying antigen.


Generation of cytotoxic effector cells by immunocompetent thymus cell subpopulations. Immunocompetent mouse thymus cell subsets (TH-2) cultured with allogeneic TH-2 cells, required a peripheral lymphoid cell in order to generate specifically cytotoxic T cells (CTL) in vitro. The helper cell is identified as a B cell, and can be supplied either in the mixture of target or responding peripheral cells, or in optimal ratios of 10:1 to 20:1 as nonproliferating cells syngeneic to the responder, when both responder and target are TH-2. Allogeneic helper cells are much less effective. Kinetic studies indicate that helper cell activity involves initial interaction with stimulator cell and is then required throughout the period of generation of cytotoxic lymphocytes. Addition of critical levels of certain IgG preparations, particularly IgG2A appears to support generation of CTL in TH-2/TH-2 cultures but is considerably less effective than intact B cells. Cytotoxicity generated under these conditions has the same genetic requirements for I-region histoincompatibility between stimulator and responder, and for K or D identity of stimulator and target cell, as has been reported for peripheral cell CTL.


Antibody-specific immunoregulation.

Antibody-specific immunoregulation. In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.


Immunostimulators induce granulocyte/macrophage colony-stimulating activity and block proliferation in a monocyte tumor cell line. Monocyte tumor cell line PU5-1.8 does not normally produce colony-stimulating activity (CSA) required by granulocyte and macrophage progenitors to proliferate and mature in agar. However, CSA is induced in the culture line by as little as 10 ng/ml endotoxic lipopolysaccharide (LPS), with maximum CSA production and release to the medium between 2 and 3 days of incubation. Derived lipid A, but not alkali-treated LPS, is also active. Induction requires RNA and protein synthesis, but is not blocked by mitomycin C or Colcemid. Other inducers of CSA include Mycobacterium Bacillus Calmette-Guérin, tuberculin protein preparation purified protein derivative, zymosan, and phorbol myristate. All inducing agents are specific inhibitors of the monocyte tumor cell proliferation in vitro. Latex beads, another macrophage-activating agent, are rapidly phagocytosed by PU5-1.8 cells, but neither inhibit growth nor induce CSA.


Delayed facial palsy after head injury.

Delayed facial palsy after head injury. Where facial palsy follows head injury  after many days, the mechanism is not clear, and there has been no detailed study on this condition. In this prospective study, an attempt is made to estimate this complication of head injury, and to study its pathogenesis, natural history, prognosis, and sequelae which differ markedly from Bell's palsy. It has a much worse prognosis and so surgical decompression should be considered early in this condition.


HLA antigens in multiple sclerosis.

HLA antigens in multiple sclerosis. The frequency of the MLC activating HLA-Dw2 determinant was found significantly increased to 68% among 37 patients with long-standing multiple sclerosis, compared to 30.2% among healthy controls. A similar (or stronger) degree of association was found with an "Ia-like" B cell specificity, SOW, while the association with HLA-B7 was less apparent. No correlation between HLA-Dw2 and signs of local synthesis of oligoclonal IgG or measles or rubella virus antibodies in the CNS was observed.


Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter. Electrical stimulation of the periventricular gray matter is an effective means of relieving several types of pain without destruction of neural tissue. The effects are long lasting, often bilateral, and with judicious use do not appear subject to adaptation. However, sustained uninterrupted stimulation for several hours does lead to a reversible decrease in effectiveness. Side effects from stimulation are minimal and cause little or no untoward emotional changes. The results are discussed in terms of activation of an endogenous pain inhibitory mechanism that involves naturally occurring opiate-like factors such as the enkephalins and endorphins.


New synthesis of 1,4,2-dioxazoles and their pharmacological properties. A series of 3-substituted 5-methoxycarbonyl-5-methoxycarbonylmethyl-1,4,2-dioxazoles was prepared by addition of hydroxamic acids to acetylene esters. Eleven of these previously unknown compounds were submitted to general pharmacological screening, and several displayed modest CNS depressant activity.


Quantitative determination of fenclorac in serum. A spectrophotometric method for the analysis of fenclorac and its metabolite, 3-chloro-4-cyclohexylbenzeneglycolic acid, in human serum was developed. The parent compound represented at least 90% of the total species present in blood; the metabolite was present to the extent of about 10%, primarily in the elimination phase. The basic procedure consists of extraction of both compounds from serum, further extraction to remove interfering substances, alkaline conversion of fenclorac to the alpha-hydroxy acid metabolite, oxidation of this metabolite to the corresponding benzaldehyde derivative, and spectrophotometric measurement of the absorbance of the aldehyde at 252 nm. A comparison of serum concentrations obtained by this method with concentrations calculated from 14C-data following oral administration of 1-14C-fenclorac to eight normal adult volunteers indicated a 90% correlation between methodologies over a range of 1.4-25.5 microgram of fenclorac/ml of serum.


Relationships between the chemical structure and pharmacological activities of D(-)S-and L(+)R-tropinoylcholines at cholinergic sites. D(-)S-and L(+)R-tropinoylcholines were synthesized and their antagonisms to acetylcholine (ACh) were studied at muscarinic receptors (guinea-pig longitudinal ileal muscle), acetylcholinesterase (AChE) and pseudocholinesterase (ChE). Tropinoylcholines were reversible competitive antagonists at muscarinic receptors. D(-)S-tropinoylcholine exhibited a higher affinity as an antagonist at muscarinic receptors than the L(+)R-isomer. ONE MOLECULE OF THE ANTAGONIST COMPETES WITH ONE MOLECULE OF THE AGONIST AT EACH MUSCARINIC RECEPTOR SITE. Tropinoylcholines were competitive inhibitors of AChE. L(+)R-tropinoylcholine exhibited a lower K1 and a higher affinity for AChE. Therefore, muscarinic receptors were stereospecific for the D-configuration, whereas AChE was stereospecific forthe L-configuration of tropinoylcholine. Tropinoylcholines were week agonist at nicotinic receptors (frog rectus abdominis); they were substrates of ChE at low concentrations, but they inhibited ChE partially at high concentrations. L(+)R-tropinoylcholine had a lower apparent Km and a higher affinity than its isomer. Therefore, the esteratic site of ChE is possible stereospecific for the L-configuration of tropinoylcholine. Both tropinoylcholines were mixed inhibitors (competitive and noncompetitive) of ACh hydrolysis by ChE. The results imply that the tropinoylcholines interact at a second site as well as the esteratic site.


Current-voltage curve of sodium channels and concentration dependence of sodium permeability in frog skin. 1. The inward facing membranes of in vitro frog skin epithelium were depolarized with solutions of high K concentration. The electrical properties of the epithelium are then expected to be governed by the outward facing, Na-selective membrane.2. In this state, the transepithelial voltage (V) was clamped to zero and step-changes of Na activity in the outer solution ((Na)(o)) were performed with a fast-flow chamber at constant ionic strength, while the short-circuit current was recorded.3. At pre-selected times after a step-change of (Na)(o) the current response (I) to a fast voltage staircase was recorded. This procedure was repeated after blocking the Na channels with amiloride to obtain the current-voltage curve of transmembrane and paracellular shunt pathways. The current-voltage curve of the Na channels was computed by subtracting the shunt current from the total current.4. The instantaneous I(Na)-V curve thus obtained at a given (Na)(o) could easily be fitted with the constant field equation in the range between -50 and zero mV. This fit yielded approximate estimates of P(Na), the Na- permeability of the Na-selective membrane (at this (Na)(o)) and the cellular Na activity, (Na)(c). As residual properties of the serosal membrane were ignored the computed values are expected to underestimate the true ones.5. At constant (Na)(c), the steady-state value of 1/P(Na) increases linearly with (Na)(o). Error analysis and the effect of drugs show that the dependence is not due to the residual properties of the inward facing membranes but reflects the true behaviour of P(Na).6. The steady-state P(Na) at a given (Na)(o) is smaller than the transient P(Na) observed right after a stepwise increase of (Na)(o) to this value. The time constant of P(Na)-relaxation is in the order of seconds.7. In conclusion, Na transport through open Na-selective channels of the outward facing membrane of the stratum granulosum cells can be described as an electrodiffusion process which as such does not saturate with increasing (Na)(o). However, when added to the outer border of the membrane Na causes a decrease of P(Na) within several seconds. It is considered that binding of Na results in closure of Na channels.


Chemical energetics in repeated contractions of frog sartorius muscles at 0 degrees C. 1. Recovery oxygen consumption (DeltaO(2)) was measured in aerobic, unpoisoned frog sartorius muscles at 0 degrees C following a series of repeated tetani.2. For a series of tetani having nearly identical tension-time integrals, DeltaO(2) was dependent on the interval between tetani and reached a maximal value for intervals equal to or greater than 200 sec.3. For a series of tetani at short (5 sec) intervals, DeltaO(2) was not distinguishable from DeltaO(2) following a single long tetanus having a tension-time integral similar to that of the sum of the series.4. A model is proposed to account for these observations in terms of the initial chemical reactions (Delta approximately P) including a saturable non-steady state reaction which utilizes about 1 mumole Delta approximately P/g and which is superimposed on an energy utilization proportional to the tension-time integral. Measurements of DeltaO(2) and Delta approximately P as functions of tetanic duration and interval between tetani are consistent with such a model.5. These experiments show that, in addition to parameters usually considered, the previous contractile history of a muscle plays a significant role in determining the chemical energy cost of an isometric contraction.


Relaxation experiments using bath-applied suberyldicholine. 1. The effect of step changes in membrane potential on the end-plate conductance change produced by bath-applied suberyldicholine was studied in voltage-clamped frog muscle fibres. 2. The suberyldicholine-induced conductance increased exponentially from its previous equilibrium level to a new equilibrium level following a step hyperpolarization. 3. For low suberyldicholine concentrations the time constant of this relaxation was independent of the concentration. 4. For low suberyldicholine concentrations the voltage dependence of equilibrium conductance and relaxation time constants was identical. 5. Bungarotoxin pretreatment did not affect the responses beyond a simple reduction in their amplitude. 6. The conductance evoked by high suberyldicholine concentrations was less voltage-sensitive than that evoked by low concentrations. 7. A new model for explaining noise and relaxation data is proposed. This postulates rate-limiting binding steps followed by a voltage-dependent isomerization.


Voltage jump analysis of procaine action at frog end-plate. 1. In the absence of procaine the end-plate conductance evoked by suberyldicholine increases exponentially to a new level following a step hyperpolarization. In the presence of procaine the suberyldicholine-evoked conductance first rapidly decreases and then slowly increases following a hyperpolarizing step. The fast relaxation has a time constant of approximately 1 msec, and the slow relaxation a time constant of 10-150 msec.2. The existence and sign of these two relaxations is predicted by a sequential model in which procaine enters and blocks open but not closed end-plate channels. The concentration dependence of the fast and slow relaxation time constants agrees well with the predictions of this model, and allows the apparent dissociation constant for binding of procaine within the open channel to be estimated at about 20 muM at -80 mV membrane potential.3. This apparent binding constant is voltage sensitive. It decreases e-fold for 50 mV hyperpolarization, suggesting that the procaine binding site is electrically half way through the channel.4. Procaine concentrations comparable to the dissociation constant for binding to open channels strongly depress the equilibrium current evoked by low suberyldicholine concentrations. This finding is not in accord with the sequential model.5. A cyclic model in which procaine binds to both closed and open channels explains well the equilibrium observations. The affinity of procaine for closed channels is similar to its affinity for open channels, and is also increased by hyperpolarization. This model also fits well the kinetic observations, if it is assumed that blocked channels open and close much more slowly than unblocked channels.6. The concentration dependence of the relaxation amplitudes disagrees with the predictions of the sequential model, but agrees well with the predictions of the cyclic model.7. No other model appears to explain the various observations as economically as the cyclic channel blocking model. If the model is correct the ;gate' controlling the end-plate channel must be in the inner half of the membrane.


A non-T, non-B human leukemia cell line (NALM-1): establishment of the cell line and presence of leukemia-associated antigens. A permanent hematopoietic cell line, designated NALM-1, was established from the peripheral blood of a patient who was in blastic crisis of Ph1-positive chronic myleocytic leukemia. By means of a panel of specific xenoantisera, the NALM-1 cells were found to express a specific antigen of acute lymphoblastic leukemia and blast leukemia-associated antigen. The cells exhibited no cell-surface receptors for sheep erythrocytes, IgG, or complement; neither cell-surface immunoglobulins nor cytoplasmic immunoglobulin were observed. Furthermore, normal T-cell or B-cell antigens, detectable by the antisera used in this study, were not found in the NALM-1 line.


Haemophilus influenzae pneumonia in adults. Thirty cases of Haemophilus influenzae pneumonia with clinical and laboratory features have previously been recorded in adults. During the past three years, we have examined 18 patients in whom this diagnosis was established by transtracheal aspirate or blood culture. Our study suggests that H influenzae, both typable and nontypable strains, is a more frequent cause of pneumonia in adults than previously appreciated. We found no clinical values that distinguished H influenzae pneumonia from other bacterial pneumonias. A properly performed Gram's stain of a transtracheal aspirate specimen is classical in its appearance and facilitates instritution of appropriate initial treatment. The emergence of both typable and nontypable organisms resistant to ampicillin makes it important that organisms be isolated from reliable samples for sensitivity testing. With appropriate therapy, the prognosis for patients with H influenzae pneumonia appears to be good.


Professional productivity and quality assurance phases II-V. This study attempts to demonstrate that an emergency/ambulatory nurse practitioner (NP) performs her role in emergency medicine with reliability and thoroughness; that she can effectively work as part of a nurse practitioner-physician team (NP/MD), provided her capabilities are fully used and that her role is complementary to the physician's. The team effort results in a reciprocal effect as demonstrated by professional performance patterns (PPP) and a subliminal triage effect should develop between NP and the physician. A "weighted" professional productivity formula is presented that has interesting potential. Time flow data is presented along with other demographic data. The problem oriented medical record format, as adapted for emergency medicine, again demonstrated effective auditability.


Relief of acute musculoskeletal pain using transcutaneous electrical neurostimulation. In the emergency department of Dover Air Force Base Hospital, a primary care facility for active duty, retired, and dependent patients, transcutaneous electrical neurostimulation was employed for six months as initial treatment for musculoskeletal pain in 34 patients with acute symptoms. Pain relief ranging from 0 to 100% was achieved in a variety of acute pain states. Only one patient did not obtain pain relief. Although some patients did not receive permanent relief from pain, a significant number of patients did benefit from this new modality.


[T and B lymphocytes before, during, and after cytostatic therapy of acute lymphoblastic leukemia (ALL) in children (author's transl)]. In 56 children with acute lymphoblastic leukemia (ALL) T and B lymphocytes and immunoglobulins (IgG, IgM, and IgA) were studied before, during, and after therapy. At the time of diagnosis T lymphocytes were normal, the number of B lymphocytes was increased, and immunoglobulins usually were normal. Only two of 30 children had abnormally low immunoglobulin levels. Under therapy a progressive lymphopenia was observed. B cells were depressed most extensively. IgG and IgA levels showed a nadir during early treatment, i.e. after remission induction for IgG and 4-8 months after diagnosis for IgA. IgM was markedly elevated after meningosis prophylaxis. After cessation of therapy lymphocytes increased with an intense rebound of B cells. The recovery was not fully completed after one year free of therapy.


Use of autologous fascia lata as a pericardial substitute following open-heart surgery. Thirteen patients requiring repeat open-heart surgery had autologous free fascia lata grafts implanted to effect complete pericardial closure. In four patients, the graft was used to augment the pericardial space because of myocardial failure and enlargement. In the remainder, fascia lata was used because shrinkage, scarring, or absence of the pericardium from prior operation prevented primary closure. No hemodynamic problems related to implantations of the grafts were seen. The harvesting of the grafts produced no functional deficits, and complications at the donor site were insignificant. Complete pericardial closure with fascia lata protects underlying myocardial structures (i.e., saphenous vein grafts) in the event that further reoperation for bleeding or infection is required. In addition, it provides for compartmentalization of the mediastinum, allowing accurate assessment of the site of postoperative bleeding.


Autologous blood transfusion during cardiac surgery. A re-evaluation of three methods. The use of autologous blood transfusion to decrease blood bank requirements and improve coagulation parameters during cardiac surgery is still controversial. This study was undertaken to re-evaluate three methods of autologous blood transfusion. Before bypass, 13 to 15 percent of the patient's estimated blood volume was removed and stored with either CPD or heparin at room temperature and returned via a peripheral vein after bypass. All patients had significant abnormalities in their PTT, PT, and platelet counts after bypass. Heparinized autologous blood removed from the vena cava cannula was the only technique which significantly improved the PTT and platelet count. Total blood bank requirements were significantly less for the autologous blood groups than for controls. There was a saving of 18 percent in banked blood requirements. Fresh frozen plasma and platelets were not found to be routinely needed during cardiac surgery.


Evaluation of saphenous vein bypass surgery with multistage treadmill test and ventricular function studies. The study includes 50 patients with severe, stable angina who have undergone the saphenous vein bypass operation. Patients were evaluated preoperatively and postoperatively with regard to exercise tolerance, incidence of stress-induced agina, ST-segment changes of ischemia, and ventricular function as indicated by stroke work index (LVSWI) and ejection fraction. Comparisons were made between patients with complete revascularization (CR) and patients with postoperative residual ischemia (RI). Results revealed that exercise duration improved significantly in both the CR and RI groups. In the CR group, angina and ischemic ST changes were completely eliminated. In the RI group, there was a 25 percent incidence of stress angina and a 50 percent incidence of ischemic ST-segment changes. In neither group was the ejection fraction significantly different from preoperative values. LVSWI decreased significantly in both groups postoperatively.


Pericardial constriction as a late complication of coronary bypass surgery. A 55-year-old man had progressive dyspnea, recurrent atrial arrhythmias, and severe right heart failure following coronary bypass surgery. His condition improved only slightly with the usual decongestive therapy. When transferred for further studies 5 months after the operation, he had typical clinical and hemodynamic findings of constrictive pericarditis. Review of chest films following the bypass operation revealed a large pericardial effusion or hematoma, the incomplete resolution of which probably caused the pericardial constriction confirmed at thoracotomy. The man was treated by pericardiectomy. A recent report on the incidence of overt tamponade soon after bypass surgery suggests that a significant volume of pericardial fluid accumulates in the early postoperative course in many instances and that late constriction may not be a rare complication. In treating patients who have circulatory congestion after such operations, it is important that the physician consider constrictive pericarditis and not assume that the clinical findings are the consquence of myocardial failure.


[Cardiovascular reactions in orthostatic tests and human resistence to vestibular stimuli]. The paper discusses the relationship between the vestibular stability of man and his cardiovascular regulation that develops during the recumbent-to-upright change of the body position. It describes specific parameters typical of the intermediate processes of the cardiovascular system that are prognostically important for the evaluation of the vestibular stability. The paper gives equations of multiple regression helping to predict the level of vestibular resistance with respect to the pattern of intermediate processes of the cardiovascular system during orthostatic tests.


Ischemic cardiomyopathy: medical versus surgical treatment. The natural history of patients with ischemic heart disease and depressed left ventricular function is dismal, and medical therapy has failed to alter its course. To assess the results of aorta-coronary bypass grafting in patients with coronary artery disease and decreased left ventricular ejection fraction (LVEF less than or equal to 0.3), we compared 70 medically treated patients to 46 patients having aorta-coronary bypass grafting. The duration of follow-up was 6 to 72 months (mean 19 months). All patients had angina pectoris. Congestive heart failure was present in 56 percent (39/70) of the medical and 43 percent (20/46) of the surgical group. The medical group had a mean LVEF of 0.20 and a mean left ventricular end-diastolic pressure (LVEDP) of 29 mm. Hg. The surgical group had a mean LVEF of 0.21 and a mean LVEDP of 24 mm. Hg. Three vessel disease was found in 60 percent (42/70) of the medical group and 83 percent (38/46) of the surgical group. The operative mortality rate in the surgical group was 4 percent (2/46). There were four late deaths. The 2 year actuarial survival rate for medical and surgical groups was 47 percent and 83 percent, respectively. Significant improvement in angina pectoris and/or congestive heart failure was found in 16 percent (11/70) of medically treated patients and 95 percent (38/40) of the surgically treated patients. Aorta-coronary bypass grafting can be performed in patients with poor left ventricular function with a low operative mortality rate, relief of angina pectoris, and improvement in symptoms of congestive heart failure.


[Simultaneous occurrence of pure red cell aplasia and malignant lymphoma (author's transl)]. A case report will be given about a patient, in whom a pure red cell aplasia preceded an IgM paraprotein-aemia and the clinical manifestations of a malignant B-cell lymphoma. The discussion deals with the question of a fortituous occurrence of two different diseases or of a common pathogenetic mechanism by which the PRCA could be considered as a paraneoplastic manifestation of an immunoproliferative disease.


Impaired humoral immunity in treated Hodgkin's disease. To define the contribution of aggressive lymphoma treatment to the risk of post-splenectomy septicemia, we investigated the humoral immunity of 44 patients with Hodgkin's disease. Specific antibody against Haemophilus influenzae Type b was significantly reduced (mean, 147 ng per milliliter, P less than 0.01) in patients receiving combined treatment (radiotherapy and chemotherapy), whereas single treatment reduced titers marginally (chemotherapy) or not at all (radiotherapy). Untreated patients had normal values (396 ng per milliliter), and splenectomy was without effect. In some patients who received combined treatment, titers were reduced to levels seen in infants. IgM levels were likewise normal in untreated patients. Chemotherapy, however, significantly reduced IgM levels (P less than 0.025), an effect potentiated by prior splenectomy. IgG, IgA, alternate-pathway activity, C3, C4 and CH50 were all normal or elevated. Aggressive treatment with chemotherapy and radiation impairs humoral defense against encapsulated micro-organisms, and thus magnifies the risk of post-splenectomy septicemia in patients with Hodgkin's disease.


Dynamics of folded proteins.

Dynamics of folded proteins. The dynamics of a folded globular protein (bovine pancreatic trypsin inhibitor) have been studied by solving the equations of motion for the atoms with an empirical potential energy function. The results provide the magnitude, correlations and decay of fluctuations about the average structure. These suggest that the protein interior is fluid-like in that the local atom motions have a diffusional character.


Radiological manifestations of infratentorial retrocerebellar cysts. The clinical and roentgenographic findings in ten patients with infratentorial retrocerebellar cysts are presented. An approach to the neuroradiological evaluation of retrocerebellar cysts and their differential diagnosis are discussed.


Shifting of the blood T:B lymphocyte ratio in myasthenia gravis patients after thymectomy. The immunologic role of thymus in human adults is still unclear, in a high percentage of patients with myasthenia gravis, improvement of the disease follows thymectomy. The biologic basis of this phenomenon is also unknown. We found that patients thymectomized for more than 9 months have a low percentage of T cells (mean 34 percent). The mean T cell percentage in control myasthenia gravis patients is 52 percent. Patients thymectomized for more than 18 and 24 months exhibit values of T cell percentage not lower than those of patients thymectomized for more than 9 months. Our results may be interpreted according to a humoral action of the thymus in regulating the percentage of T lymphocytes.


Cerebellar hemorrhage: unusual ventriculographic findings. A case of a cerebellar (vermian) hematoma that communicated with the fourth ventricle as seen on air study is presented. Although vertebral angiography appears to be the first diagnostic procedure of choice, the angiographic study may not be definitive diagnostically because it may be difficult to distinguish fourth ventricular enlargement from a cystic hematoma cavity in communication with the fourth ventricle. An air study may then be required to differentiate between such diagnostic possibilities.


A computerized prenatal record.

A computerized prenatal record. An entirely computerized ambulatory medical record system is operational in a large health maintenance organization. A unique subsystem was designed for use in prenatal care, in which the provider's completion of a single encounter form at the time of visit meets all the information requirements of care delivery, administration, and quality assurance. Instead of using a conventional paper chart, computer-generated summaries and flow charts are automatically provided for scheduled visits and for use as a hospital preadmission record, significantly reducing the provider effort expended on record keeping. On-line inquiry function is also available using terminals at the ambulatory center and the hospital. The computer data base has been used for quality assurance studies in prenatal care. The system is well accepted by providers, is reliable, and is cost effective.


Osteosarcoma during pregnancy.

Osteosarcoma during pregnancy. Four white women who developed osteosarcoma during pregnancy were referred for treatment, 2 prior to delivery and development of metastases, and 2 after delivery and development of metastases. After amputation, these patients received combination chemotherapy with either vincristine-cyclophosphamide or adriamycin-cyclophosphamide followed by high-dose methotrexate with leucovorin rescue. Two patients survived, 1 tumor-free and 1 with bony and soft tissue metastases. Management of pregnant patients with osteosarcoma should include the use of adjuvant systemic chemotherapy to prevent detectable metastases. This treatment should follow amputation or resection and early termination of pregnancy.


Pregnancy in cirrhotic and noncirrhotic portal hypertension. The course of pregnancy in 1 patient with chronic active hepatitis (CAH) and cirrhosis, and another with extrahepatic portal vein obstruction (EHPVO) is described. The management of pregnancy in these diseases associated with portal hypertension is discussed and risks of pregnancy are compared. The patient with CAH presented with anovulatory cycles, and ovulation occurred following immunosuppressive therapy. Both women experienced massive upper gastrointestinal bleeding from esophageal varices. Bleeding was difficult to control and required variceal ligation in 1. Both patients manifested features suggesting cerebral edema indicating the need for caution with fluid and electrolyte therapy. Recovery of the woman with CAH after termination of pregnancy was slow. Review of literature demonstrated that variceal bleeding occurred in 43% of women with EHPVO compared to 23% of those with CAH and cirrhosis. Additional complications including hepatocellular failure (24%) occurred in patients with CAH but not in EHPVO. The management of pregnancy in portal hypertension and advice for contraception or sterilization are discussed.


[Structure of the morphogenetic movements of gastrulation in Anura. I. Destabilization of ooplasmic segregation and cleavage under the action of clinostatic rotation]. The yolk segregation in the developing Rana temporaria egg was studied both in vivo and under the effect of clinostate rotation, i. e. slow rotation around the horizontal axis imitating the state of weightlessness. From the moment of fertilization and during the whole period of cleavage the yolk was shown to subdivide succesively in distinct phases which differ by the characteristic value of yolk granules. During the normal development, in spite of the marked variability of form and mutual position of phases, the main elements of their animal-vegetative order are preserved. Under the effect of clinostate rotation the process of normal segregation becomes destabilized and variations in the egg structure are expressed by the beginning of gastrulation in the diversity of variants of distribution of the cellular material competent to different morphogenetic movements.


[Structure of the morphogenetic movements of gastrulation in Anura. II. The elementary morphogenetic processes]. The clinostate rotation causes a wide range of gastrulation abnormalities in the Anura. A special investigation has shown that all gastrulation variants may be represented as various spatial-temporal compositions of the same morphogenetic processes isolated by means of formal experimental procedure. These processes are structurally stable rearrangements of tissue morphology and are spread in the tissue as a wave embracing more and more cells. The change of one local morphology for another may proceed either in the form of "shock wave", a moving distinct border between the cells already switched and not yet switched to the new automorphous movement, or in the form of "deployment" when the transition from one local morphology to another is continuously deployed in space.


[Electron microscopic study of rapid morphogenetic processes in embryonic tissue explants of amphibia]. Submicroscopic rearrangements are described. They serve as the bases of rapid (up to 20 min) changes in the form of the common frog neurula explants: formation of filamentous layer under "naked" surface, appearance of lobopodia on "naked" surface, their "flow", cell polarization and submersion. In all these processes an active part appears to be played by microtubules and microfilaments the bundles of which are always oriented along the long axes of active cells or the directions of passive mechanical tensions. In the cells which are not yet polarized the microtubules form under the surface adjacent to the already polarized cell. This may be considered as one of the chains of cooperative cell polarization.


[Study of the cytostatic action of the cytoplasm of oocytes and mature ova of the common frog and sturgeon (Acipenser stellatus)]. The presence of the cytostatic factor found by Masui and Markert (1971) in the cytoplasm of oocytes and eggs of Rana pipiens was verified in the cytoplasm and mature inactivated eggs of the common frog Rana temporaria and sevryuga Acipenser stellatus. The cytoplasm was injected to the embryos of the same species at different phases of the first cleavage division in the animal region of one of the two blastomeres. The injection of cytoplasm did not cause the arrest of cleavage divisions. Many embryos proceeded to gastrulation. The cytoplasm of maturing oocyte and mature egg in the common frog and sevryuga, unlike in R. pipiens, has no cytostatic effect.


Autoantibodies in cancer patients.

Autoantibodies in cancer patients. The prevalence of antinuclear antibodies was increased in patients with adenocarcinoma of the corpus uteri, chronic lesions of the cervix uteri, malignant melanoma, non-malignant pigmented skin lesions and basal cell carcinoma. The prevalence of smooth muscle antibodies was increased in patients with squamous carcinoma of the cervix and malignant melanoma. The prevalence of antibodies to gastric parietal cells and thyroid epithelial cells was not increased in any group of patients.


The causes of interstitial pneumonitis in immunocompromised children: an aggressive systematic approach to diagnosis. A systematic, aggressive approach to the immunocompromised child with interstitial pneumonitis has been used in 24 consecutive patients. Parent and physician awareness of early symptoms and signs had been emphasized. When laboratory data confirmed clinical suspicion, open lung biopsy was done and lung tissue was studied by impression smears, sections, and culture techniques. The etiologic agent was established by stained impression smears within three hours of receipt of tissue in 21 of 24 patients. Eighteen of 24 patients survived. Patients had a poor prognosis if they required ventilatory assistance (five of seven died) or had respiratory symptoms for three days or more prior to biopsy (four of 13 died). Children with solid tumors who had absolute lymphocyte counts less than 500/cu mm, had received chemotherapy and radiotherapy to the chest, and had developed Pneumocystis carinii pneumonitis had a poor outcome (all three died).


[Effect of cortisone on calcium metabolism. Attempt at correction by 5,6 trans 25-hydroxycholecalciferol, 25-hydroxycholecalciferol and vitamin D2]. 14 patients receiving small doses of predisolone and 7 high doses were divided at random into three groups. Each group received for four weeks, 100 microgram of vitamin D2 or 25 hydroxyvitamin D3 or 5,6 trans-25 hydroxyvitamin D3. The 25 hydroxy and 5,6 trans-25 hydroxyvitamine D3 were able to increase intestinal calcium absorption. 25 Hydroxyvitamin D3 had an osteolytic action, increasing urine calcium and hydroxyproline and, once, in a patient slight hypercalcemia was observed. By constrast, 5,6 trans-25 hydroxyvitamin D3 decreased PTH and caused a significant decrease in urine hydroxyproline.


Rheumatologic conditions of the wrist.

Rheumatologic conditions of the wrist. With the exception of the arthritis associated with rubella, acute wrist conditions have no pathognomonic physical findings. The primary physician can diagnose and treat the majority of wrist problems presented. Referral to a rheumatologist is necessary only when confronted with an anxious patient or an individual having persistent wrist pain and swelling of obscure etiology. This article focuses on rheumatologic problems of the wrist that are most likely to come to the attention of the primary physician.


Pitfalls in transhepatic portography.

Pitfalls in transhepatic portography. Difficulties commonly encountered in transhepatic catheterization of the portal vein and interpretation of portograms are discussed. A long-sleeved trocar is recommended. Curved guide wires and deflector assemblies may assist in superselective catheterization of the tributaries of the portal vein. The judicious use of embolic material (small volumes, slowly injected) should guarantee the success and safety of this technique. Transhepatic obliteration of the gastroesophageal veins is a relatively simple and usually successful form of palliative treatment for actively bleeding and stable gastroesophageal varices. Thoroughness of the embolization procedure and of interruption of blood flow in the gastroesophageal veins is necessary to prevent early recurrence of bleeding.


Angiography of massive hemorrhage secondary to pancreatic diseases. Twenty patients with massive abdominal hemorrhage related to chronic pancreatitis, pancreatic neoplasms and arteriovenous malformations were studied angiographically. Abdominal hemorrhage drained most frequently into the gastrointestinal tract, but also flowed through cutaneous drain sites and fistulas, intraperitoneally, into pseudocysts and once into a large pancreatic tumor. The most common angiographic observation in pancreatitis was pseudoaneurysm formation. Both patients with arteriovenous malformation had dilated, racemose feeding arteries and early dense filling of the draining veins. Three patients had pancreatic carcinoma and documented bleeding from gastroesophageal varices related to portal or splenic vein occlusion by the tumor. Five patients were treated by vasopressin infusion, balloon tamponade, or therapeutic embolization.


[Neurological and clinical features of posterior fossa tumors in children (author's transl)]. Reevaluation of clinical records and radiological examinations in 132 cases of posterior fossa tumors under 16 years of age. The diagnostic contribution of neuroradiological investigations is discussed with special reference to air ventriculography; 9 cases are reported in detail.


In vitro culture of leukaemic cells from 81 patients with acute leukaemia. Bone marrow and/or blood cells from 81 patients with acute leukaemia, including 50 patients with acute myeloid leukaemia, were cultured in vitro using the agar culture method. The cells were cultured either in a single layer assay or with a normal source of colony stimulating factor (CSF) included in the culture. In almost all cases an abnormal growth pattern was seen, ranging between no growth and an excessive number of clusters. Immature granulocytic cells and macrophages were the dominating cell types in clusters and colonies from 14 out of 16 patients with acute myeloid leukaemia. In the patients with acute myeloid leukaemia the remission induction rate was found to be related to the cluster incidence. Thus, 75% of the patients with a cluster incidence between 0-100 obtained a complete remission (CR), while only 31% of the patients with a high cluster incidence (greater than 1000/2 x 10(5) cells) obtained a remission. Cluster formation in the unstimulated cultures of CSF-sensitive cells did not seem to be of prognostic value. The correlation between prognosis and in vitro growth in patients with acute myeloid leukaemia stresses the need of obtaining more insight in those factors other than drug sensitivity, which are of importance for the therapeutic response.


Nude mouse: a new experimental model for Pneumocystis carinii infection. Experimental infection with both human- and rat-derived Pneumocystis carinii has been produced in nude mice by intrapulmonary injection of lung homogenates that contained P. carinii and by environmental transmission. Most infected mice did not appear ill, and their lungs exhibited a mild and nonspecific inflammatory response. Thus, P. carinii can be transmitted from one animal species to another, and this result suggests that a defect in thymic-dependent lymphocytes is important in the development of the infection. Experimental work with P. carinii in the nude mouse should be performed in isolators because of the communicability of the organism.


Motion sickness: an evolutionary hypothesis. Since the occurrence of vomiting as a response to motion is both widespread and apparently disadvantageous, it presents a problem for evolutionary theory. An hypothesis is proposed suggesting that motion sickness is triggered by difficulties which arise in the programming of movements of the eyes or head when the relations between the spatial frameworks defined by the visual, vestibular, or proprioceptive inputs are repeatedly and unpredictably perturbed. Such perturbations may be produced by certain types of motion, or by disturbances in sensory input or motor control produced by ingested toxins. The last would be the important cause in nature, the main function of the emesis being to rid the individual of ingested neurotoxins. Its occurrence in response to motion would be an accidental by product of this system.


Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Relief of intractable pain was produced in six human patients by stimulation of electrodes permanently implanted in the periventricular and periaqueductal gray matter. The level of stimulation sufficient to induce pain relief seems not to alter the acute pain threshold. Indiscriminate repetitive stimulation produced tolerance to both stimulation-produced pain relief and the analgesic action of narcotic medication; this process could be reversed by abstinence from stimulation. Stimulation-produced relief of pain was reversed by naloxone in five out of six patients. These results suggest that satisfactory alleviation of persistent pain in humans may be obtained by electronic stimulation.


Return of myosin heads to thick filaments after muscle contraction. The heads of myosin molecules, which move to the vicinity of the thin filaments to react with actin during muscle contraction, return to the thick filaments after contraction. The return occurs in two stages; a rapid return of the majority of the myosin heads is followed by a slow return of the rest.


Preoperative diagnosis of rectal bleeding in an adult using a radioisotope scan. A 22-year-old man with burning pain in the lower abdomen and rectal bleeding had a sodium pertechnetate Tc 99m scan. The scan showed an area of uptake in the right lower quadrant which at operation was found to be a Meckel's diverticulum. The ability of ectopic gastric mucosa within a Meckel's diverticulum to concentrate sodium pertechnetate Tc 99 m allows for this noninvasive diagnosis of some types of rectal bleeding, especially when the cause has escaped detection by conventional endoscopic and barium contrast examinations.


Intracranial epidermoid tumor: discussion of four cases. Four cases of intracranial epidermoid tumor are presented. These are uncommon tumors with no specific signs or symptoms, and their diagnosis depends upon a high index of suspicion. Computerized axial tomography (CAT scan) was helpful in diagnosing one of the cases described and undoubtedly will be instrumental in identifying future cases. Epidermoid tumors are biologically benign. They are often amenable to resection, and therefore tissue diagnosis before starting any therapy is important.


Survival after distal splenorenal shunt. These data support the conclusions that the distal splenorenal shunt is attended by the highest post-shunt survival as yet reported for patients with non-alcoholic cirrhosis, portal hypertension and bleeding varices; the procedure is safe, and in this series, the mortality has been nil for 66 consecutive operations. An analysis of the causes of death suggests that continued alcohol abuse plays an important part in the late mortality among those in the post-shunt alcoholic cirrhosis group.


Left sided segmental portal hypertension following mesocaval interposition shunt. Following a mesocaval interposition shunt in three patients with cirrhosis of the liver, bleeding esophageal varices recurred in two and left sided portal hypertension partially persisted in one patient. Angiographic and pressure studies of the portal system demonstrated effective decompression of the greater splanchnic venous system but continued lesser splanchnic venous hypertension. Recurrent variceal hemorrhage ceased following splenectomy done as an emergency. In contrast to a standard portacaval shunt, it is suggested that after an interposition mesocaval shunt, altered jet streaming of mesenteric blood flow may divert gastrosplenic venous drainage away from the interposition shunt with persistence of lesser splanchnic venous hypertension. Recognition of this entity and of the need for splenectomy is advocated.


Bile acids, the "barrier," and reflux-related clinical disorders of the gastric mucosa. The present communication represents an effort to provide an overview of the available evidence (and speculation) which suggests that an interrelationship exists between bile acids, the so-called "gastric mucosal barrier," and certain clinical diseases of the gastric mucosa in which reflux of upper intestinal content appears to be a pathophysiologic common denominator.


The prevention and correction of hypocalcemia in the parathyroidectomized rat by portacaval shunt. Adult rats underwent end-to-side portacaval shunt either 30 days prior to or 12 days following parathyroidectomy. When portacaval shunt was performed initially, the serum calcium failed to decrease following subsequent parathyroidectomy and remained within normal levels up to 110 days. When parathyroidectomy first was done, the significant hypocalcemia was corrected subsequently by portacaval shunt and serum calcium remained close to the normal level up to 75 days. The effect of portacaval shunt depended on the calcium content of the food and was obtained only when rats were fed by a regular diet. Rats on a calcium-deficient diet were hypocalcemic, similar to the parathyroidectomized rats without the portacaval shunt. Prolonged calcium-deficient diet alone, without parathyroidectomy, did not by itself result in hypocalcemia either in the intact rat or in the portacaval shunted rat. The data indicate that portacaval shunt prevents and corrects hypocalcemia in the parathyroidectomized Lewis rat as long as sufficient calcium is available in the diet.


IgM participation in tumor rejection by immunized mice. IgG and IgM participation in tumor rejection was studied in DBA/2 mice immunized against L1210 leukemia and in Swiss mice immunized against Ehrlich adenocarcinoma. In both the systems, IgM globulins seem to be implicated and are present on the cell surface of macrophages, lymphocytes and cancer cells, while IgG globulins are present only on some lymphocytes. IgM are also present in the peritoneal washing fluids (obtained 24 h of the control group. In the former group, protein content is about three times higher than that in the control group, while the relative amount of heavy proteins (18 S) and light proteins (7 S) is quite similar. These observations are discussed, as is the possibility that some complement components as C3 may participate in the reaction.


[Changes in the level of alpha1-antitrypsin in bronchial asthma]. The alfa1-antitrypsin level was followed up in patients with bronchial asthma with different forms and severity of the disease. The latter was found to be elevated in all patient groups with an average of 335,38 mg% as compared with the controls 290.83 mg%, p less than 0,01. The elevated antitrypsin is explained with the allergic process and the secondary bacterial inflammatory reactions, triggering the formation of antienzyme substances, in order to inactivate the enzymes, playing a certain role in the pathogenesis of the first two processes--allergy and bacterial inflammation. In patients, both treated and not with cortisone, antitrypsin is elevated with no manifestation of significant difference for both patient groups. The cortisone preparations very likely do not supress the antienzyme systems in organism. As regards the pathogenetic role of alfa1-antitrypsin deficiency in asthma, the latter is admitted to play an insignificant role only in single cases.


Pneumocystis carinii pneumonia in children. From a retrospective study at the University of California, San Francisco, Medical Center, it is evident that pneumocystic carinii pneumonia is being seen more frequently as a secondary complication to the use of immunosuppressive drugs. This disease presents with nonspecific respiratory symptoms, therefore a high degree of suspicion and knowledge of the population at risk are necessary for an early diagnosis. Except for x-ray films of the chest, physical and laboratory studies are of minimal diagnostic value. In a patient with compromised immune defenses and respiratory distress, bilateral diffuse reticular infiltrates seen on a film of the chest are highly suggestive of pneumocystis carinii pneumonia. The diagnosis should be confirmed histologically because a variety of pathogens can cause these findings and each requires a specific treatment. At our institution, open thoracotomy is the method of choice for obtaining a lung biopsy specimen. Pentamidine isothionate is moderately effective against this usually fatal disease, but its effectiveness depends on beginning treatment early in the illness.


Treatment and prevention of primary ventricular fibrillation complicating acute myocardial infarction. Primary ventricular fibrillation especially occurs during the first hours after acute myocardial infarction and is often not preceded by premonitory ventricular premature beats. In hospital primary ventricular fibrillation can be prevented by an intravenous lidocaine regimen in a rather high dosage. By contrast the effectiveness of intramuscular lidocaine in preventing out-hospital primary ventricular fibrillation is unestablished. If recurrent attacks of primary ventricular fibrillation supervene, intervention with antiarrhythmic therapy and/or cardiac pacing is often unsuccessful. Repeated defibrillation should be carried out under these circumstances. If properly treated primary ventricular fibrillation is associated with a good short and long term prognosis.