Imbalances of IgG subclasses and gene defects in patients with primary hypogammaglobulinemia. The chance mating of persons with structural or regulator gene abnormalities might be expected to result in individuals who lack the capacity to synthesize specific types of heavy chains and manifest as hypogammaglobulinemia. Disproportionate levels of IgG subclasses would then be expected since the heavy chains are synthesized at separate although closely linked loci. Several instances of such alterations in subclass concentrations have been found. One family has been encountered with probable structural gene abnormalities in the autosomal Gm loci. In addition to their genetic implications, IgG-subclass imbalances are of importance because of the variable distribution of biologic properties of immunoglobulins among the IgG subclasses, and because of the observation that certain antibody populations may be markedly restricted or limited to a single IgG subclass.


Heterogeneity of human circulating anticoagulants against antihemophilic factor (factor VIII). The heterogeneity of human circulating anticoagulants against antihemophilic factor (AHF, factor VIII) observed in seven patients, both with and without classic hemophilia, was investigated by neutralization of their activity with antiserums directed to whole IgG and to lambda and kappa light chains. All seven anticoagulants were immunoglobulins. Six appeared to contain both kinds of light chains, although the dual light chain composition of two of these could be demonstrated only at high concentration of antiserum. In one circulating anticoagulant, light chain specificity could not be demonstrated with small amounts of antiserum, and with larger amounts, only lambda light chain specificity was revealed. Whether or not this circulating anticoagulant really contained a single light chain type could not be ascertained with our technique. The evidence presented suggested that circulating anticoagulant antibodies against AHF are polyclonal in nature.


[Influence of sound and enzyme treatment on antigenic properties of human erythrocytes. II. Enzyme treatment]. Erythrocytes of group 0 cde/cde successively treated with bromelin and beta-glucuronidase (DFE) react not only with antibodies (anti-DFE) contained in the IgM-fraction of each human serum but also with Rh-specific antibodies of the IgG-fraction of anti-Rh-sera. This indicates, that the enzyme treatment makes accessible two different possibly crossreacting structures. Since anti-DFE is contained in the IgM-fraction of all human-sera, the antigenic determinant reacting with anti-DFE is considered a polyagglutinogen not identical with the well known polyagglutination-phenomena (T, Tn and Cad) as it is shown by comparative investigations with anti-T and anti-Tn as well as anti-Cad active seed extracts.


Cataloging audiovisual materials: a new dimension. A new more comprehensive system for cataloging audiovisual materials is described. Existing audiovisual cataloging systems contain mostly descriptive information, publishers' or producers' summaries, and order information. This paper discusses the addition of measurable learning objectives to this standard information, thereby enabling the potential user to determine what can be learned from a particular audiovisual unit. The project included media in nursing only. A committee of faculty and students from the University of Alabama in Birmingham School of Nursing reviewed the materials. The system was field-tested at nursing schools throughout Alabama; the schools offered four different types of programs. The system and its sample product, the AVLOC catalog, were also evaluated by medical librarians, media specialists, and other nursing instructors throughout the United States.


Training and supervision of library shelvers. This paper describes a program prepared at the University of Southern California Norris Medical Library, which utilizes audiovisual methods for shelver training and detailed work assignment sheets in conjunction with shelver supervision. The slide/script training series serves both as a time-saving device for the shelver supervisor and as an effective and interesting instructional device. The work assignment sheets, with the aid of a shelving calculation chart, enable the supervisor to give realistic assignments without having to give instructions orally.


Tumour imaging radiopharmaceuticals.

Tumour imaging radiopharmaceuticals. 32P, 131I-labeleed human serum albumin, 75Se-seleno-methionine, 107Hg-chlormerodrin, 67Ga-citrate and labelled bleomycin compounds, among others are discussed with particular respect to their observed clinical characteristics and suggested mechanisms of uptake. It is shown that there are striking similarities in the kinds of tumours demonstrable by these agents and that all of them may be taken up into inflammatory exudates. It is suggested that, while differences in the metabolism of each agent clearly exist, their mechanism of tumour uptake may be predominantly non-specific. It is concluded that radionuclide tumour imaging is of potential value mainly from the point of view of ease of whole body scanning for follow-up purposes and whereas other diagnostic methods may be more accurate in specific areas, ease of whole body screening is rarely a feature of these techniques. Methods for studying human cancer are necessarily restricted and the tumour imaging technique provides a unique, dynamic means of tumour observation. From the clinical point of view, the questions of why some tumours image well and others do not, what is the effect of treatment on uptake and how specific is the technique, are of most importance. In order to improve tumour imanging, more emphasis must be given to improving the lesion: background radioactivity ratio of the agents rather than attempting to improve detection equipment.


The effect of dicynene on blood loss during and after transurethral resection of the prostate. The effect of Dicynene on blood loss during and after transurethral resection for benign enlargement of the prostate was studied in 76 patients. Median loss of blood at operation was 17 ml in those given Dicynene compared with 72 ml in the placebo group (p equals less than 0.001). Median postoperative blood loss was 38 ml in the Dicynene group, and 103 ml in the placebo group (p equals 0.05). Clinical evidence of deep vein thrombosis was found in neither group. Dicynene helps to reduce blood loss in transurethral resection.


Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. An autoradiographic study in Macaca fascicularis. By tracing radioactively labeled proteins transported by axonal flow, projections from area 4 to the ipsi- and contralateral neostriatum and claustrum were demonstrated in 7 monkeys. A reversed topographic organization was found on both sides for the corticoneostriatal and corticoclaustral projections. The most extensive terminal field could be observed in the putamen. In contrast, very few area 4 efferents seemed to terminate in the caudate nucleus. This suggests differential functions for the two striatal components in sensorimotor mechanisms. These unexpected results give further evidence for the superior sensitivity of the autoradiographic technique, although the limitations of the new method in delineating the injection field were noted.


Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study. In previous studies it has been shown that nerve growth factor (NGF) is taken up with a high selectivity by adrenergic nerve terminals and is transported retrogradely to the perikaryon11,22. It was the aim of the present experiments to investigate whether the sensory neurons exhibit the same high degree of selectivity for retrograde transport throughout the whole life cycle, although it is known that their dramatic response to NGF is confined to a short period of ontogenetic development. Unilateral injection of [125I]NGF into the forepaw of adult rats was followed by a preferential accumulation of radioactivity in the sensory ganglia (C6-C7) of the injected side. However, this preferential accumulation was not detectable earlier than 6 h after injection and reached a maximum (ratio between injected and non-injected side, 5:1) after 11-16 h. Transection of the plexus brachialis abolished and local administration of colchicine prior to that of [125I]NGF greatly reduced the preferential accumulation of radioactivity in the ganglia of the injected side. The rate of retrograde transport of NGF in sensory neurons was calculated to be 13 mm/h which is about 5 times faster than that in adrenergic neurons. The selectivity of this retrograde transport was demonstrated by the fact that injection of 125I-labeled bovine serum albumin and cytochrome c did not result in a preferential accumulation of radioactivity in the sensory ganglia of the injected side. Light microscopic autoradiography revealed heavily labeled cells in the sensory ganglia (C6-C7) of the injected side after administration of [125I]NGF into the forepaw. Only cells belonging to the large cell type were labeled. Prolonged (7 mug/g/day over 5 days) injection of NGF into the forepaw of 10-day-old rats did not result in a hypertropic response of the sensory neurons as far as can be judged from morphometric studies at the light microscopic level.


Distribution along the axon and into various subcellular fractions of molecules labeled with (3H)leucine and rapidly transported in the garfish olfactory nerve. The distribution of molecules labeled with [3H]leucine by fast axoplasmic transport in vivo has been studied in the garfish olfactory nerve after incorporation of the amino acid by the olfactory mucosa. Owing to the size of the nerve, it has been possible to follow the fate of the labeled molecules in 10 different subcellular fractions of 6 consecutive nerve segments. Each segment represents a different part of the profile developed by the transported radioactive molecules. In order to determine the influence of the perikaryon (rate of protein synthesis and rate of protein release into the axon) transport was studied under 3 different conditions: (1) intact nerves (simply labeled with [3H]leucine); (2) nerves cut from the cell bodies 6 h after application of [3H]leucine; and (3) nerves pulse-chase labeled for 1 h. Several conclusions can be drawn. (1) The bulk of the rapidly transported molecules are membranous axonal proteins, as determined by enzyme markers. Most are found in subcellular fractions representing 17% of the total axonal protein. They are synthesized very rapidly in the cell bodies (less than 1 h after isotope deposition) and exhibit the highest specific activities measured. These high specific activities were found in the same axonal membrane fractions in both plateau and crest, suggesting that the membrane precursors are transported as particles rather than as subunits. (2) The majority of these proteins are released into the axon immediately after synthesis; however, at least 30% of the labeled axonal membranous proteins are not released with the fast wave itself but progressively over a long period of time. (3) The majority of the moving material, particularly in membranous fractions, is left behind the fast wave and is deposited in the axon. When the front base of the fast wve has covered 70% of the total nerve length, only 19% of the labeled material of the main axonal membranous fraction appears still to be moving. (4) Proteins with high specific activities are found near the cell bodies and may be the result of early axonal transport of amino acids, diffusing later into the surrounding cells and being incorporated into proteins. Some free amino acids are also transported along the axon.


Effect of inhibiting protein synthesis on axonal transport of membrane glycoproteins in an identified neuron of Aplysia. Intrasonic injection of L-[3H]fucose into R2, the cholinergic giant neuron in the abdominal ganglion of the marine molluse, Aplysia californica, labeled 5 major glycoprotein membrane components, 3 of which were preferentially exported into the axon.  Brief exposure to anisomycin, a potent inhibitor of protein synthesis in Aplysia, almost completely blocked the appearance of [3H]glycoprotein in the axon; but fucosylation of proteins in the cell body was only partially inhibited.  Polyacrylamide gel electrophoresis showed that the 5 normal components were present in the cell body of inhibited neurons.  Thus, synthesis and insertion of glycoproteins into membranes do not guarantee export from the cell body: presumably completion of transportable organelles requires continuous synthesis of new proteins.  Longer exposure before injection resulted in reduced amounts of four of the glycoproteins, but one component continued to be formed.  Anisomycin can be used to resolve export of glycoproteins out of the cell body from subsequent movement along the axon.  When we exposed R2 to anisomycin after injection, [3H]glycoproteins, which had already entered the axon, were translocated along the axon normally; they were distributed in waves, the most distal moving at 50-60 mm/day.


Acute leukemia in children: experience in Saskatchewan in 1966-72. In 1966-72 in Saskatchewan there was a significant improvement in survival of patients up to 16 years old with acute leukemia treated intensively.  The rate of complications was low.  Attention to the emotional needs of the patients and parents and formation of parent mutual-support groups improved the acceptibility of intensive therapy.


Radionuclide immunoglobulin lymphangiography: a case report. Iodine-131-labeled immunospecific gamma globulin derived from immunization of rabbits with F antigen, a tumor associated antogen in Hodgkin's disease, has been utilized for intralymphatic infusion in a patient with known recurrent Hodgkin's disease inthe inguinofemoral and pelvic regions.  Rectilinear scanning successfully delineatedthe tumor masses, and external monitoring showed retention of activity in the tumor sitesover an 8-day period.


Modification of radiation injury to normal tissues by chemotherapeutic agents. The effects of several cancer chemotherapeutic agents on radiation damage to normal intestine, esophagus, and lung tissue were evaluated in LAF 1 mice using quantitative endpoints. In all tissues tested, actinomycin D increased injury and BCNU did not. In the intestine, adriamycin enhanced radiation damage more than any other agent. Bleomycin increased damage in the esophagus but not in the lung or intestine. Cyclophosphamide increased injury only in the lung, where vincristine caused minimal injury, and hydroxyurea, none. Only prednisolone caused significant radioprotection when given at the time of irradiation or at the time of expected death from pulmonary injury.


Combined chemotherapy in childhood rhabdomyosarcoma. Twenty-two children with rhabdomyosarcoma were treated with combination chemotherapy using vincristine, actinomycin D, and cyclophosphamide for varying time periods. Chemotherapy, usually combined with radiation therapy, was given to early stage patients after they had had a com plete or partial tumor resection. Three of nine patients who had widespread metastatic (stage III) disease at initiation of therapy had complete tumor regression and four of  nine had partial tumor regression. However, the median durations of response and survival were brief (3 and 8 months respectively). Five patients with localized resectable (stage I) disease have survived without evidence of tumor recurrence from 33 to 69 months after their initial diagnosis. Of eight patients with incompletely  resected regional (stage IIB) disease, one has survived without disease recurrence for 36 months, thought the median survival time of the remaining seven patients was 14 months. In stage IIB patients the duration of response was proportional to the duration of chemotherapy which suggests that chemotherapy should be given for at least 18-24 months.


Combination chemotherapy with bleomycin (NSC-125066), vincristine (NSC-67574), and methotrexate (NSC-740) plus split-course radiotherapy in the treatment of non-oat-cell bronchogenic carcinoma. Twenty-seven unselected patients with limited disease non-oat-cell bronchogenic carcinoma were treated with a chemotherapy- radiotherapy protocol which consisted of bleomycin, vincristine, and methotrexate followed by split-course radiation. There were 15 objective responders with a median survival time in excess of 70+ weeks in contrast to a median survival time of 26 weeks for nonresponders (P less than 0.01). Objective benefit was limited to the epidermoid carcinoma group since none of the adenocarcinoma group achieved a greater than 50% reduction in maximum tumor diameter. The median survival time for the entire groups was 42 weeks in contrast to a recent split-course radiotherapy historical control group whose median survival time was 38 weeks. Toxic effects were predominantly gastrointestinal.


Kinetics of both leukemic and normal cell population reduction following 5-azacytidine. The cytotoxic effect of 5-azacytidine (AzaCR) on normal hematopoietic colony-forming units (NCFU) and L1210 leukemic colony-forming units (LCFU) in the femoral marrow of BALB/c x DBA/2 F1 mice was studied using the spleen colony assay. Dose-survival curves for LCFU and NCFU were biphasic. Repopulation of LCFU was rapid at a low dose of AzaCR (0.1 mg/mouse) but was delayed for greater than 6 days at higher doses (0.25 mg/mouse and above). Of the agents tested in this system, only AzaCR exhibited these properties. Survival of mice with L1210 leukemia following AzaCR administration was prolonged beyond that predicted by the degree of LCFU reduction alone, and reflected the delay in LCFU repopulation. In contrast, repopulation of NCFU in normal mice was not delayed at a high dose of AzaCR (0.5 mg/mouse). AzaCR produced a nine-fold greater reduction of NCFU in leukemic mice than in normal mice, measured 5 days after AzaCR injection. While divided doses of AzaCR produced LCFU cytotoxicity equivalent to a single dose, 24-hr infusions of high doses were inferior to single infections.


Binding of bleomycin to DNA in bleomycin-sensitive and -resistant rat ascites hepatoma cells. The 14C activity of [14C]bleomycin bound to DNA in bleomycin-sensitive rat ascites hepatoma cells (AH-66) was 8.7 times higher than in resistant cells (AH-66F) when the cells were incubated with [14C]bleomycin. The difference in permeability to bleomycin was not significant; uptake of [14C]bleomycin by the sensitive cells was only 1.2 times larger than that by the resistant cells, and the radioactivity incorporated into the nuclei of sensitive cells was only 1.3-fold greater. The bleomycin-inactivating enzyme level in the resistant cells was 3.5 times higher than in the sensitive cells, indicating that the antibiotic incorporated into the resistent cells was reduced in DNA-binding activity to a large extent. The level of protein-free thiol compound in the sensitive cells was 1.8-fold higher than in the resistant cells, suggesting a possible enhancement of bleomycin action by intracellular thiol compound as is found in vitro. These factors probably affect the DNA strand scission and the sensitivity of cells to this antibiotic. Binding of [14C]bleomycin to DNA in vitro was studied in the presence and the absence of dithiothreitol. A large portion of the radioactivity bound in the presence of dithiothreitol was unstable to acid, but the acid-resistant binding was also enhanced by this thiol compound.


Clinical trial of bleomycin (NSC-125066) in the treatment of metastatic renal carcinoma. This study had the limited aim of ascertaining the efficacy of bleomycin in controlling m etastatic renal carcinoma. Fifteen patients received bleomycin intramuscularly and five patients received the drug via continuous infusion. Only two patients had responses, both mixed. We concluded that the therapeutic value of bleomycin in the treatment of advanced renal carcinoma is negligible.


Viral expression, oncogenicity, and antigenicity of a mouse salivary gland tumor and two cell lines derived from it. An in vitro cell line (SGT) derived from a mouse submaxillary gland adenocarcinoma (TGS) containing A and B viral particles maintained its oncogenicity only for newborn isogeneic hosts (C3H/He mice) immunosuppressed with antithymocyte serum. Inoculation into adult isogeneic animals did not cause tumor but provided partial protection against a challenge with TGS cells. The loss of oncogenicity for nonimmunosuppressed isogeneic hosts was accompanied by the acqusition of oncogenicity for adult, nonimmunosuppressed, xenogeneic hosts (golden hamsters) given subcutaneous inoculations of SGT cells on the back. From the tumor grown in the hamster, which is histologically similar to the original tumor of the mouse, an in vitro cell line (HWS) was derived. The comparative analysis of the 2 cell lines, SGT and HWS, led to the following conclusions: (a) the karyological pattern of the 2 cell lines in virtually the same; (b) the cell surface antigenic pattern is similar for the 2 cell lines, as determined by colony inhibition test and cytotoxicty test; (c) the cells of the HWS line behave serologically as a mouse-hamster hybrid, also as determined by colony inhibition and cytotoxicity tests; (d) both cell lines have only intracytoplasmic viral particles of the A type; and (e) agglutination with the plant lectins concanavalin A and wheat germ agglutinin occurs at lower concentrations of agglutinin for HWS cells than for SGT cells.


Variable effects of a lipotrope-deficient, high-fat diet on chemical carcinogenesis in rats. Earlier studies demonstrated enhanced chemical carcinogenesis in the liver, colon, and probably esophagus of male rats that were fed a lipotrope-deficient, high-fat diet. In further experiments, designed to examine the range of the dietary effect on chemical carcinogenesis, rats were fed either the marginally lipotrope-deficient, high-fat diet or an adequate control diet, and treated wit- N-2-fluorenylacet-amide, 3,3 diphenyl-3-diemthylcarbamoyl-1-propyne, N-methyl-N-nitroso-N'-nitroguanidine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, aflatoxin G1, or ethionine. N-2-Fluorenylacetamide indiced hepatocarcinomas more rapidly and in higher incidence in deficient rats than in control rats. 3,3-Diphenyl-3-dimethylcarbamoyl-1-propyne induced a higher incidence of hepatocarcinomas but not gastric tumors in deficient rats. Aflatoxin B1, included as a positive control, was significantly more hepatocarcinogenic in deficient rats. Gastric tumor induction by N-methyl-N-nitroso-N'-nitroguanidine and induction of tumors of the urinary bladder by N-[4-(5-nitro-2-furyl)-2thiazylyl]formamide were not influenced by diet. Aflatoxin G1 and ethionine were toxic to deficient rats, and carcinogenic doses could not be administered.


Cellular phosphorylation of 1-beta-D-arabinofuranosylcytosine 5-azacytidine with intact fibrosarcoma and leukemic cells. The phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C) by A(T1)C1-3 hamster  fibrosarcoma cells and L5178Y murine leukemic cells was studied, using intact cells. The cellular phosphorylation of both these nucleoside analogs appears to follow Michaelis-Menton kinetics. The apparent Km value for ara-C in the fibrosarcoma and leukemic cells was about 40 muM, whereas the apparent Km values for 5-aza-C in these cells were about 1.3 and 0.41 mM, respectively. Deoxycytidine and cytidine were found to be potent competitive inhibitors of the phosphorylation of ara-C and 5-aza-C, respectively, ara-C and 5-aza-C were found to be weak competitive inhibitors of the phosphorylation of deoxycytidine and cytidine, respectively. A clone isolated from the fibrosarcoma cells that was partially resistant to the cytotoxic effects of ara-C exhibited a higher Km value for both ara-C and deoxycytidine than the wild-type fibrosarcoma cells.


Antibody in cats to mammalian RNA tumor virus interspecies antigens. The studies were undertaken to determine whether the cat, a mammalian species that carries xenotropic endogenous C-type virus(es) and in addition undergoes horizontally transmitted oncogenic C-type RNA tumor virus infections, responds immunologically to the mammalian C-type virus interspecies antigens. Sera from normal cats and from cats with spontaneous or virus-induced neoplasms were examined for antibodies to interspecies antigen antigen by complement-fixation inhibition, by inhibition of the paired radioiodine-labeled antibody technique (PRILAT inhibition), and by two-step radioimmunoelectrophoresis. Using three separate complement-fixation inhibition systems designed to detect antibodies to interspecies antigen(s), 23 of 23 sera from tumor-bearing cats and 24 of 31 sera from normal cats were positive in both systems. The negative sera were from germ-free cats. Among the 49 positive sera, 47 yielded titers of 1:16 or greater by one or more complement-fixation inhibition tests. Of these 47 sera, 42 were positive by the paired radioiodine-labeled antibody technique inhibition test; the 5 paired radioiodine-labeled antibody technique-negative sera were from normal specific-pathogen-free cats. Direct reaction with the interspecies determinant on the p30  protein from Rauscher murine leukemia virus by immunoglobulin from cats immunized with feline leukemia virus was shown by two-step radioimmunoelectrophoresis. The feline antibody was also identified as an immunoglobulin by column chromatography and two-step radioimmunoelectrophoresis. These antibodies did not fix guinea pig complement during reaction with the interspecies antigen. That other mammals may produce similar noncomplement-fixing (guinea pig) antibodies to RNA tumor virus antigens is likely.


Inhibitory and anti-inhibitory factors of rat serum active on the G1-S transition of hepatocyte cell cycle. Rat hepatocytes are responsive to a serum factor inhibiting their progression through the cell cycle from the late G1 phase to the S phase. After fractionation of normal adult rat serum by two chromatographic steps on DEAE cellulose and sephadex gel filtration, the inhibitory activity was linked to proteins having a high electronegative charge and of apparent high molecular weight. Polyacrylamide gel electrophoretic analysis of active fraction showed that the alpha1 macroglobulin was its main component. Male and female baby rats were sensitive to the inhibitory factor from normal rats. Contrary to the normal adult rat serum the whole hepatectomized adult rat serum did not exhibit any ingibitory activity on the G1-S transition. However, two components having antagonist activities: an alpha1 globulin and a gamma globulin, were separated by chromatographic procedures from hepatectomized rat serum. (a) The alpha1 globulin showed an inhibitory activity. It had an apparent molecular weight lower than that found in normal rats. Its activity was sex related: only male baby rats were responsive. (b) The factor present in the gamma globulin fraction was found to be antagonistic to the alpha1 globulin factor. Its occurrence after hepatectomy explains the absence of inhibitory activity in the serum of hepatectomized rats.


Reversible ultrastructural changes of arcuate neurons after vinblastine injection into the median eminence of the rat. The ultrastructural effects of vinblastine on the arcuate neurons and median eminence were studied in the rat.  The animals were stereotaxically injected with solutions of 1 mM and 5 mM vinblastine into the median eminence and killed 3, 8 and 21 days after injection.  Eight days after injection of 1 mM vinblastine the neurons of the arcuate nucleus showed marked changes.  The Golgi complex was more distinct and considerable increases in the populations of dense bodies, granulated vesicles and coated vesicles were observed.  Changes in the axo-somatic synapses and degenerating fibers in the surrounding neuropil were also characteristic of the experimental animals.  The outer zone of the median eminence showed numerous degenerated nerve fibers and fibers engulfed by glial cell processes.  Eight days after injection of 5 mM vinblastine arcuate neurons and median eminence showed similar changes, but quantitative differences were noted.  A striking ultrastructural recovery of the arcuate neurons and axons in the outer zone of the median eminence was observed 21 days after injection of either 1 mM or 5 mM vinblastine.  The results are discussed in relation to axoplasmic transport and axonal degeneration.


Surface differentiation of hemopoietic cells demonstrated ultrastructurally with cationized ferritin. The ultrastructural cationized ferritin (CF) technique was employed as a probe of the surface binding characteristics of the various cell types present in normal human bone marrow. The number of CF particles per micron length of cell surface were counted and data subjected to statistical analysis. All cells of the bone marrow exhibited CF reactivity. The extent of labeling was cell specific and could be related to the stage of maturation of the cells in a given lineage. In the neutrophilic series, myeloblasts showed moderate labeling while promyelocytes and myelocytes revealed only minimal binding; CF binding increased sequentially in metamyelocytes, band and segmented neutrophils. Eosinophils and eosinophilic myelocytes showed similar membrane differnetiation patterns while basophils exhibited stronger CF labeling that other granulocytic cells. Lymphocytes were strongly reactive while monocytes and their precursors were moderately labeled with CF. Surface reactivity of developing nucleated erythrocytic cells was similar to that of the lymphocytes. Surface labeling from the proerythroblasts to early normoblasts stage was identical, CF binding increased in the late normoblasts stage and then decreased in the reticulocyte and mature erythrocyte stages. The extent of surface CF reactivity of the marrow cells was markedly different from that obtained with Thorotrast and colloidal iron. Thorotrast and colloidal iron stained the surface of all marrow cell intensely but failed to yield distinctive surface labeling patterns for the differing cell population in bone marrow.


Cobalt sulphide staining of optic fibres in the brain of the cricket, Gryllus campestris. Neuronal projections from one optic lobe to other parts of the brain were stained in the cricket Gryllus campestris using the cobalt sulphide technique and Timm's sulphide-silver method. The results are: Four tracts directly connect the medulla with the lobula and medulla of the contralateral optic lobe. Direct medullar projections end mainly in the non-glomerular neuropile of the protocerebrum, but also penetrate the calyx of the mushroom bodies, pons and central body in small numbers. A few somata which send fibres into the medulla lie in the pars intercerebralis, in the protocerebrum ventral to the opposite beta-lobe, the outer margin of the medulla of the contralateral optic lobe and between deuto- and tritocerebrum. The anatomical and physiological relevance of the stained connections is discussed.


Utilization of yolk platelets and lipid bodies during the myogenesis of Xenopus laevis (Daudin). The premyoblast and differentiating mononuclear myoblasts of the metameric striated muscles of Xenopus laevis were analysed for vitellolysis and lipid body utilization. In the course of myoblast differentiation the stainability of platelets stained with safranin and fast green shows essential variations. The platelets appear to lose their affinity for safranin and subsequently begin to stain with fast green. The yolk platelets were found to contain basic proteins, non-histone proteins, and phospholipids. The lipid bodies appear in the myoblast cytoplasm at the onset of vitellolysis and they disappear after yolk reserves have been utilized. After the deutoplasmatic material has been used the myoblast nuclei begin to divide and this leads to the formation of polykaryocytes.


An ultrastructural study of the microfilaments in rat brain by means of heavy meromyosin labeling. I. The perikaryon, the dendrites and the axon. Nervous tissue pieces from the caudate nucleus and the substantia nigra of the rat were incubated in cold glycerol solutions of decreasing concentrations and then transferred into standard phosphate buffer (pH 7.0) or into tris-K+-Mg++-Ca++ buffer (pH 7.9) containing HMM, prepared from rabbit skeletal muscle by tryptic digestion. As controls, pieces were immersed for an identical period in the same buffers (1) without HMM or (2) with HMM to which had been added 2.5 mM Na+ pyrophosphate or 5 mM ATP. In control neurons smooth-surfaced microfilaments, about 50 A in diameter, were observed. After reaction with HMM, the microfilaments were increased in number and density and in width to 180-200 A. A meshwork was formed. Arrowheads pointing in the same direction were spaced at regular intervals (300-350 A) among short segments of the surfaces of the microfilaments, depending upon the plane of section. More often, however, typical arrowheads were not observed, and the surfaces of the microfilaments were seen coated with polarized side-arms cross-bridging the spaces between adjacent elements at more or less regular intervals. When cross-sectioned, the microfilaments appeared as dense dots from which a material of lesser electron density radiated. Following incubation in HMM solutions containing Na+ pyrophosphate or ATP, no arrowhead structures were seen. Of particular interest was the structural relation of the actin-like filaments with occasional, tapered myosin-like filaments, and with the plasma membrane, which served as anchor points. Mitochondria and smooth ER membranes were observed to be attached to the actin-like filaments or enmeshed in the network. The microtubules, as well as most of the neurofilaments, were disrupted by the glycerination procedure at 4 degrees, and thus no precision about the structural relationship of the actin-like filaments with the latter elements could be added. The role of the actin-like filaments in the transport of material, by a mechanism of chemomechanical transduction, throughout the neuron from sites of synthesis to functional locations, and between several functional locations, is discussed.


An ultrastructural study of the microfilaments in rat brain by means of E-PTA staining and heavy meromyosin labeling. II. The synapses. To identify structures involved in the translocation of the synaptic vesicles towards the presynaptic membrane, an ultrastructural study has been undertaken by means of (1) the E-PTA stain and (2) the HMM-labeling procedure. Using serial sections of E-PTA stained nervous tissue, especially those made in transversal and tangential planes, the geometric order of the presynaptic grid and of its constituents has been described in detail. It consisted of dense projections having the shape of small truncated pyramids cut parallel to their hexagonal bases which rested on the electron-lucent presynaptic membrane. The dense projections were arranged at the points of equilateral triangles. Around each dense projection, six asymmetric hexagonal holes were seen to be arrayed in an hexagonal pattern, forming thus the presynaptic sieve. From the spiny tops of the dense projections, which appeared as specialized structures of the dense material coating the inner surface of the plasma membrane at the level of the synaptic cleft, fine filaments, 40--60 A in diameter, radiated and formed a three-dimensional meshwork pervading the presynaptic bag. The dense cytoplasmic coating delineating the plasma membrane served as anchor points for these microfilaments. Upon incubation with rabbit skeletal muscle HMM the microfilaments underwent specific structural changes, consisting of: (1) a striking increase in diameter; (2) the association of periodic and polarized substructures with their surfaces. The synaptic vesicles and mitochondria were seen to be attached to the numerous HMM-decorated filaments or enmeshed in the network formed by these filaments. The actin-like filaments were anchored to the plasma membrane at many points and to the presynaptic dense projections. Following incubation in the buffer alone or in buffer HMM solutions containing Na+ pyrophosphate or ATP, no arrowheaded structures were observed. Thus, a network consisting of actin-like filaments was demonstrated in the presynaptic bag. Of particular interest was the structural relation of the actin-like filaments with the occasional, tapered myosin-like filaments. The role of the presynaptic actin-like network in the transport of synaptic vesicles towards the presynaptic membrane by a mechanism of chemomechanical transduction is discussed. In the postsynaptic dendrite or dendritic spine, a filamentous network was observed to be attached to the subsynaptic web by means of the E-PTA stain and of the HMM-labeling procedure. The occurrence of an actin-like meshwork in the postsynaptic region is suggested to produce changes in the macromolecular configuration of the postsynaptic membrane by a "mechanoenzyme" system similar to that described in the mitochondrial membrane.


Golgi studies of the first optic ganglion of the ant, Cataglyphis bicolor. The neurons of the first optic ganglion (the lamina) in the desert ant, Cataglyphis bicolor, have been studied with the light microscope after Golgi silver impregnation. The different types of retinal and laminal fibres and their configuration are compared with the results obtained in the bee. The first synaptic region in the visual system of the ant lies proximally to the fenestrated layer below the basement membrane and the layer containing the monopolar cell bodies. The synaptic region can be separated into three morphologically different zones: (1) The most distal layer where the short visual fibres end at two different levels. The short visual fibres and some laminal fibres (monopolar cell fibres) also show lateral elements in this region. (2) The second layer appears almost free of branches of retinal and laminal fibres. (3) The most proximal layer, which has a characteristically dense horizontal structure resulting from the lateral elements of long visual, centrifugal, monopolar and tangential fibres. Nine cell axons arising from each ommatidium leave the retina. Six of these are short visual fibres and end at two different levels in the lamina. Three different types of short visual fibres can be distinguished by their different terminal depths and lateral branching pattern. The remaining three fibres, the long visual fibres, terminate in the medulla. They can be distinguished from each other by their lateral elements in the lamina neuropile. The five morphologically different laminal fibre types (axons of the monopolar cells in the lamina) have different shapes and different arborizations at different levels. Tangential, centrifugal and incerta sedis-fibres, which originate either from cell bodies in the cell body layer at the periphery of the outer chiasma or more centrally, terminate in the synaptic region of the lamina. Consideration is given to the clearly demarkated arrangement and length of the branching pattern of retinal and laminal fibres at different levels of the synaptic region of the lamina. In addition, a hypothetical connectivity pattern is discussed.


Regulation of neurosecretory activity in the freshwater pulmonate Lymnaea stagnalis (L.) with particular reference to the role of the eyes: a quantitative electron microscopical study. The process of neurosecretion in the Caudo-Dorsal Cells (CDC) of the freshwater snail Lymnaea stagnalis, which produce an ovulation hormone, shows a diurnal rhythmicity. Synthesis, transport and release of the neurosecretory material (NSM) is high during the evening and the early night and low during the rest of the day, while storage of NSM mainly occurs during the daytime. In the present study the role of the eyes in the regulation of the CDC-rhythm was investigated. During a 24-hr period, at time intervals of 6 hrs, cerebral ganglia, which contain CDC, of blinded and control snails (5 per group) were fixed and the CDC were studied with quantitative electron microscopical methods. The CDC of the controls showed a distinct diurnal thythmicity. Blinding, on the other hand, clearly affected this rhythmicity. The results indicate that after blinding the circadian CDC-rhythms of individual snails are no longer synchronous with each other ("interanimal desynchronization"). It is suggested that the rhythm of CDC neurosecretory activity is synchronized by the natural light/dark cycle via the eyes. The information from the eyes probably reaches the CDC via a nervous pathway. True snyapses and three types of synapse-like structures were found on the CDC. Their role in the regulation of CDC-activity is discussed. The effect of blinding is specific for the CDC; blinding does not influence the diurnal rhythmicity of another type of cerebral neurosecretory cells, the Light Green Cells (LGC). The CDC within a cluster act synchronously. This synchrony does not depend upon the presence of the eyes. Some structures which may be involved in establishing this synchrony, such as subsurface cisterns, desmosome-like structures and "specific release sites", are described.


[Progressive multifocal encephalitis (PML)]. In four cases of progressive multifocal leucoencephalitis the basic disease was always a malignant lymphogranuloma. Changes in the brain were multifocal, however the frontoparietal area of the white matter was affected most frequently and foci in this part were oldest. In these foci demyelination with atypical astrogliosis predominated, and there was a very small number of scavenger cells. At the periphery of foci always proliferation and enlargement of homogenous oligodendroglia nuclei were found sometimes with inclusions which in immunoassay sometimes had a common antigen with papovirus SV 40 and on electronoptic examination always contained many virions of the papovirus. No direct relationship was found between the duration of the neoplastic process, its type and changes in the CNS.


[Placenta and hypotrophy of the fetus].

[Placenta and hypotrophy of the fetus]. The authors analyzed 50 cases of foetal hypotrophy using morphological methods. In the introduction of their paper they reviewed findings reported in the literature on placental causes and briefly also data on the sequelae of foetal hypotrophy for the foetus. Bioptic examination of the placenta can help to differentiate between foetal hypotrophy and immaturity. In foetal hypotrophy of placental origin it is important to differentiate between a primarily hypoplastic placenta (associated sometimes with congenital malformations of the foetus) and secondary insufficient placentas due to impaired uteroplacental circulation or other causes. In some instances both basic disorders may combine.


[Leiomyoblastoma of the digestive tract]. Five cases of leiomyoblastoma of the stomach and one located in the small intestine have been reported. Two of the gastric tumours metastasized. The characteristic feature of leiomyoblastoma is vacuolation of the cytoplasm of polygonal tumour cells, with regularly demonstrable transitions into smooth muscle cells. The size of the neoplasm and the presence of mitoses do not represent sufficiently reliable features permitting to recognize the biological behaviour of the tumour. Cellular and nuclear pleomorphism seemed to be a much more reliable index of malignancy in the two cases of ourselves.


[Electron microscopy demonstration of the myoblastic origin of various tumours]. In the histogenetic classification of spindle-cell tumours, in particular malignant ones, it is an advantage to use electronoptic examination. It proves useful in particular in the diagnosis of tumours of myoblastic origin. Inadequate formol fixation of bioptic material in this group does not matter too much and does not alter diagnostic structures which was proved by four illustrative observations (an angioleiomyoma of the subcutaneous layer, congenital generalised fibromatosis with a muscular component, rhabdomyocellular sarcoma of the urinary bladder, alveolar rhabdomyosarcoma).


[Staining of Mycobacteria using non-traditional methods]. Nine modifications of the Gram method were tested with respect to their ability to stain mycobacteria. The results obtained were rather variable. Moreover it appeared that not all the methods would reliably visualize mycobacteria within histological sections. In particular, the mycobacteria occurring in a case of fibrocaseous tuberculosis appeared to be less stainable by the Gram method. If the Ziehl-Neelsen and the Gram method were combined to stain a single section, only some mycobacteria appeared to take the blue Gram stain.


[The paracommissural regions (brain neurohemal formations) of diplopods. Preliminary note]. The paracommissural plates of Diplopods are neurohemal "organs" anatomically not individualized in bodies separate from the brain. They lie near the transverse commissure (tritocerebral commissure s.l.). They are composed of at least two distinct types of axon terminals, glial cells, tracheae and a neural lamella facing a blood sinus. The axons of paracommissural plates of originate in neurosecretory cells lying in the ganglions of the transverse commissure. The release of granules partly occurs by exocytosis.


[Uptake and transport of exogenous peroxidase in the masticatory muscles of cats. Localization of ganglionic neurons]. Retrograde axonal transport of Horseradish peroxydase (HRP) has been used to trace the cells of origin of proprioceptive fibers in jaw-closing and jaw-opening muscles. After injection of HRP in young cats' masticatory muscles (masseteric, temporal, pterygoid, mylohyoid and digastric) labelled neurons were found in the ipsilateral semi-lunar ganglion and trigeminal mesencephalic nucleus. It is concluded that sensory endings are present in jaw-opening as in jaw-closing muscles; possibly the afferent fibers from muscle endings of the opener muscles have their somata in the mesencephalic nucleus, afferent fibers from tendinous receptors in the semi-lunar ganglion.


[In vivo study of the hypocalcemic, hypophosphoremic, hyperlipemic, and immunogenic activities of the oligopeptide fragment common to ACTH, alpha and beta MSH, and beta lipotropin]. The intravenous injection that was given to rabbits which consisted of 0,5 mg of a common heptapeptide to ACTH4-10, BETA MSH11-17 hormones, and to beta lipotropic47-53 hormone (beta LPH47-53) was followed at the end of an hour by an augmentation of 70% of total lipids, and at the end of two hours by a lowering of calcemia (around 27%) and of phosphoremia (20%). The injection of a tetrapeptide corresponding to only ACTH7-10 bound to a nitrobenzylhydralamin and in presence of a Freund adjuvants has provoked the formation of corresponding antibodies.


[The cellular reticular structures induced by Baculovirus in the lepidoptera Galleria mellonella]. Induction of filamentous nuclear structures by Baculoviruses are observed in the hemocytes of Galleria mellonella larvae. Modalities of detection of these virus-induced structures by means of sheep or rabbit globulines labelled with fluorescein isothiocyanate are described.


[Uptake and transport of exogenous peroxidase in the masticatory muscles of the cat. Localization of motor neurons]. In the present work, a topographical localization of masticatory muscle motoneurons was undertaken. Horseradish peroxydase injected in each muscle can be transported in the retrograde direction to the corresponding motoneurons cell bodies. Jaw-closing muscle motoneurons were identified in the dorsal part of the motor trigeminal nucleus whereas jaw-opening muscle motoneurons were observed in the ventro-medial region.


The differences in atrioventricular conduction of premature beats in young and adult goats. Atrioventricular (AV) conduction was studied in anesthetized, open-chest, 1-35-day-old goats. Atrial, bundle of His, and ventricular bipolar electrograms were recorded, and the functional refractory periods of the AV conduction system and the ventricles were determined. Supraventricular premature excitation invaded the ventricles during their vulnerable period. This AV conduction property is different from that of the adult goat heart; thus, the existence of a lateral accessory bypass tract was investigated. Electrocardiographic leads I, aVF, and V10 revealed no delta waves indicative of ventricular preexcitation. Bundle of His electrograms showed that: (1) bundle of His excitation always preceded the onset of ventricular depolarization, (2) no shortening occurred in the bundle of His to ventricular activation time following early atrial premature beats, and (3) the functional refractory period of the AV node was less than that of the ventricle. The ventricular epicardial excitation sequence indicated no involvement of a lateral bypass tract in the AV conduction of basic or premature beats. Interruption of the bundle of His caused complete AV block. Therefore, no functional lateral accessory bypass tracts are present in the young goat heart, and the AV node and the ventricular specialized conduction system of the young goat are capable of conducting premature atrial excitation to the ventricles within plus or minus 10 msec of the expiration of the ventricular functional refractory period.


Concealed ventricular extrasystoles due to interference and due to exit block. Two cases of sinus rhythm with ventricular extrasystoles are reported in which extrasystoles arising from the same focus obey the rule of "comcealed bigeminy" and the "rule of bigeminy". In a comparatively rapid sinus rhythm, shortening of the sinus cycle favors the appearance of extrasystoles, and the extrasystoles obey the fule of "concealed bigeminy"; namely, sinus impulses intervene between extrasystoles in even numbers. The sinus impulses here include those both conducted and not conducted to the ventricles. Conversely, in a comparatively slow sinus rhythm, interectopic sinus impulses appear in odd numbers only, and the extrasystoles obey the "rule of bigeminy"; namely, lengthening of the sinus cycle favors the appearance of extrasystoles. From these observations, a new mechanism governing both of the rules is suggested as follows. Ectopic impulses arise following all the interctopic sinus beats, but they become concealed extrasystoles of two types. One of them is the "concealed extrasystole due to interference at the external end of the ventricular-ectopic (V-E) junction."The other is the "concealed extrasystole due to exit block within the V-E junction" because of refractoriness following stimulation. They alternate with each other. In the of "concealed begeminy", the last concealed extrasystole intervening between manifest extrasystoles is due to exit block, whereas in the "rule of bigeminy", it is due to interference.


Prolonged left ventricular ejection time in the post-premature beat. A sensitive sign of idiopathic hypertrophic subaortic stenosis. Failure of the pulse pressure to increase in the post-premature beat is considered characteristic of idiopathic hypertrophic subaortic stenosis (IHSS). The sensitivity and specificity of this response were compared to the change in left ventricular ejection time (LVET) in 12 patients with IHSS, in ten control patients with valvular aortic stenosis (AS) and in five normal subjects. The post-PVC pulse pressure increased in all normals and in nine of the ten patients with AS. In IHSS this response was inconsistent. A positive Brockenbrough sign was seen in only 33%. On the other hand, LVET increased greater than 20 msec in eleven of twelve patients with IHSS, whereas all normal subjects and all patients with AS showed either decreases in LVET or increases smaller than 20 msec. Prolongation of the LVET during the post-PVC beat greater than 20 msec appears, therefore, to be a more sensitive sign of IHSS than the corresponding change in pulse pressure.


Agarose gel electrophoresis of plasma lipoproteins using the Durrum cell. 1. A low cost method for lipoprotein electrophoresis in agarose gel is described. The basic procedure, described by Noble, has been modified for use with a Durrum cell which is commonly used for paper electrophoreis. 2. Up to 28 samples can be analyzed per Durrum cell in 4 hours. 3. A staining technique, which involves filtration of a suspension of Sudan Black B, allows for rapid staining and provides satisfactory reproducibility from run to run. 4. In a small number of patients a double pre-beta band is seen, and is different from sinking pre-beta and floating beta lipoproteins.


Application of differential light scattering to the latex agglutination assay for rheumatoid factor. When a suspension of particle is irradiated with a collimated beam of monochromatic polarized light of a wavelength close to the particle size and the intensity of the scattered light is measured as a function of angle, the scatter intensity is characterized by a series of relative maxima and minima. The nature of the signal depends on several significant variables that are characteristic of the particles. We have constructed a differential light scatter photometer and have applied the technique to analysis of rheumatoid factor by using latex particles coated with fraction II gamma-globulin. The results suggest that such a photometer may have potential applications in antigen-antibody assays based on the use of sensitized particles.


The analgesic properties of delta-9-tetrahydrocannabinol and codeine. The administration of single oral doses of delta-9-tetrahydrocannabinol (THC) to patients with cancer pain demonstrated a mild analgesic effect. At a dose of 20 mg, however, THC induced side effects that would prohibit its therapeutic use including somnolence, dizziness, ataxia, and blurred vision. Alarming adverse reactions were also observed at this dose. THC, 10 mg, was well tolerated and, despite its sedative effect, may analgesic potential.


Effects of tricyclic antidepressants on drug metabolism. The effects of chronic treatment with amitriptyline and nortriptyline on the elimination from plasma of warfarin, dicumarol, phenytoin, and tolbutamide were examined in man. No alteration of plasma half-life of warfarin, phenytoin, or tolbutamide was observed following dosage with the tricyclic antidepressants used. There was no consistent effect on the metabolism of dicumarol following treatment with amitriptyline or nortriptyline although the bioavailability of dicumarol appeared to be increased. In some subjects, this increased bioavailability was associated with significant prolongation of the plasma half-life of dicumarol due to its dose-dependent kinetics.


The value of combined 5-fluorouracil and x-ray therapy in the palliation of locally recurrent and inoperable rectal carcinoma. The difficulties of treating patients with pelvic recurrence from rectal cancer by further suegery, chemotherapy or by radiotherapy are summarised. Fifty-fibe patients with this form of recurrence are presented to whom 5-fluouracil was administered to improve the effectiveness of radiotherapy. A safe and effective regime is described which produced complete relief of pain in 66 percent of the patients who presented with this symptom with a further 16 percent obtaining partial relief. Total resolution of tumour masses and complete relief from mucoid rectal discharge were achieved less often, although the majority of patients derived benefit from treatment. An important finding of this study has been that in this particular group of patients a short, low-dose course of combined therapy was as effective, both in the relief of symptoms and the prolongation of survival, as more prolonged high-dose treatment.


Mobilization of leucocytes and subsequent release of histamine and lysosomal enzymes into the peritoneal and pleural cavities of rats by actinomycin D (dactinomycin). 1. The effects of intraperitoneal injections of actinomycin D on the temporal characteristics of the accumulation of the inflammatory exudate and cells into the peritoneal and pleural cavities were studied in male Sprague Dawley rats. 2. A measurable quantity of the exudate appeared in both cavities within 24 h and reached maxima in the peritoneal and pleural cavities on the fourth and third days, respectively. Thereafter, the accumulated volume of liquid decreased progressively in the peritoneal cavity but stayed more or less at about the same level in the pleural cavity until the sixth day. 3. The pooled peritoneal and pleural exudates contained neutrophils, macrophages, mast cell and eosinophils. The leucocyte infiltration occurred in two phases, the maximum cell numbers being found on the third and fifth days. A precipitous fall in the number of leucocytes occurred on the fourth day. Neutrophils and macrophages accounted for 85-95% of the total number of leucocytes. 4. The supernatant of the inflammatory exudate after centrifugation at 3,000 g contained histamine and the soluble lysosomal enzyme proteins, acid phosphatase and beta-glucuronidase until the sixth day following the initial dose of actinomycin D. 5. It is suggested that the release of lysosomal enzymes in the exudate, subsequent to leucocyte mobilization and the release of histamine from the mast cells, are probably involved in the genesis of inflammatory conditions induced by actinomycin D.


Reversible interstitial pneumonitis associated with low dose bleomycin. A patient with nodular histiocytic lymphoma was treated with bleomycin; she later developed interstitial pneumonitis documented by lung biopsy. The dose of bleomycin producing this complication was lower than previously reported, and the pulmonary toxicity was apparently completely reversible.


A reliable method of quantifying G-band position in chromosomes. The locations of chromosomal bands in the muntajac (Muntiacus muntjak, Zimmerman) are shown to be constant, that is the bands occupy the same relative position regardless of the state of contraction of the chormosome. Each band can thus be assigned a precise location. Different banding techniques produce bands at identical locations and thus precisely similar patterns, with one notable exception in which certain bands disappear. It it proposed that this more exact procedure be used to identify chromosomal bands, especially in cases of chromosomal rearrangement. It may be of particular use in computer analyses of karyotypes.


The B-chromosome system of Tettigidea lateralis (Say). II. New karyomorphs, patterns of pycnosity and giemsa-banding. Additional samples from a discrete population of the pygmy grasshopper Tettigidea lateralis, at the periphery of the species range, have shown that the frequency of the B-chromosomes has remained stable over a two year period (30-35%), and that there is not significant difference for this metric in the two sexes. The intensity of the preferential movement of the B with the X at male first meiotic division has also remained constant in time and homogenous in different individuals. Hence it is possible that this distortional effect plays a role in the equilibrium frequency of the B in the population. The B's may possess special adaptive properties under ecologically marginal conditions, since in a number of more 'central' demes they occur at much lowere frequencies (7-9%). -Unique morphological and/or behavioral variants of the standard B were encountered in addition to distinct cases of spontaneous fragmentation of A elements. The meiotic behavior and chromatic expression of these centric fragments provide evidence on the possible origin and evolution of supernumeraries. A modified. Giemsa staining technique has been used to identify regions of centromeric (C-) hererochromatin in mitotic and meiotic chromosomes. The C-banding pattern of the X and the allocyclically similar B is compared. It suggested that the B may have originated from the X by deletion of centromeric heterochromatin. This may have affected the centromere "strength" of the nascent B leading to its preferential movement with the X at anaphase I.


Karyotype and chromosomal banding pattern in Heteropeza pygmaea. The chromosomes of somatic and germ line cells of female embryos produced by paedogenesis were studied. The haploid set in somatic cells consists of one long submetacentric chromosome, one large acrocentric, one medium metacentric and two small acrocentrics. The length vs arm index karyogram makes it possible to distinguish all but the two pairs of small acrocentric chromosomes. --Atempts were made to develope a method for banding pattern visualization. The best result was obtained using trypsin which induced banding in the chromosomes of the somatic cells and occasionally also the germ line cells. The resulting banding patterns were frequently not identical in members of a chromosome pair. There was also a variation between metaphases within an embryo as well as from different embryos. Some tentative explanations for these results are discussed.


Molecular basis of chromosome banding. I. The effect of mouse DNA fractions on two fluorescent dyes in vitro. The effects of mouse satellite, main band and total DNA on the fluorescence intensity of quinacrine and of the bibenzimidazole derivative Hoechst 33258 were tested in solution. No significant differences were noticed between the double-stranded DNAs in spite of the 5% difference in AT-content between satellite and main band DNA. Single-stranded DNAs enhanced the fluorescence intensity of Hoechst 33258 far less than double-stranded DNAs. Having been denaturated and then reassociated the DNA fractions were intermediate in their enhancing effects on the fluorescence intensity of Hoechst 33258, the differences presumably being due to different degrees of reassociation. The effect of denatured and subsequently reassociated satellite DNA on the fluorescence intensity of quinacrine was similar to that of the native DNAs. Main band and total DNA quenched the fluorescence intensity of quinacrine more after denaturation-reassociation than it did when native. In the discussion the results are related to known cytological data.


Molecular basis of chromosome banding. II. The effect of silver and mercury ions on the fluorescence intensity of acranil-DNA complexes. Silver and mercury ions are known to react with the bases of nucleic acids in solution. At low cation/base ratios Ag+ has an affinity for GC pairs in DNA, whereas Hg++ is preferentially bound to AT-rich nucleic acids. We have used fluorometry to measure the effect of these cations on the fluorescence intensity of preformed complexes of acranil and DNA in solution. The results are: 1) Ag+ enhances the fluorescence intensity presumably by affecting the dye intercalated in the vicinity of GC-pairs. 2) The addition of Hg++ leads to a quenching of the fluorescence intensity of the complex at low ion/base ratios, suggesting an effect on the dye molecules bound to AT pairs. At high GC-content of the nucleic acid, slight enhancement of the fluorescence intensity occurs with Hg++. 3) With both metals there is a correlation between base content of DNA and effect on the intensity of fluorescence indicating base specificity of the dye-polymer interaction.


C banding in polytene chromosomes of Simulium ornatipes and S. melatum (Diptera: Simuliidae). Polytene and mitotic chromosomes of Simulium ornatipes and S. melatum were subjected to C banding procedures. In both species polytene chromosomes consistently show C banding of centromere regions, telomeres, nucleolar organiser and, unexpectedly, numerous interstitial sites. The interstitial C banding sites correspond to morphologically single polytene bands. Their response is graded and independent of band size. Interstitial C bands in S. ornatipes are scattered throughout the complement, whereas in S. melatum they are clustered. Supernumerary heterochromatic segments in S. ornatipes also exhibit strong C banding and inverted segments can differ from standard in C banding pattern. -- Mitotic chromosomes of both species show a single centric C band with indications of two weak interstitial bands in S. ornatipes, suggesting that many C band regions, detectable in polytene chromosomes, are not resolved by present techniques in mitotic chromosomes. -- Contrary to current opinion that C banding is diagnostic for constitutive heterochromatin, the interstitial C band sites of polytene chromosomes are regarded as euchromatic. Conversely, the heterochromatic pericentric regions of S. ornatipes are not C banded. -- It appears that polytene chromosomes offer a promising system for the elucidation of C banding mechanisms.


On the independence of the CNV and the P300 components of the human averaged evoked potential. We report an experiment designed to assess the interactions between the CNV and the P300 components of human event-related potential. Eight subjects were each presented with series of experimental trials on all of which either a 1200 c/sec or an 800 c/sec tone was presented. There were three independent variables: (a) The presence or absence of a warning flash 1000 msec prior to the tone. (b) The task assigned to the subject--that is subjects were either to make a discriminative response to the tone or, on half the series, to predict prior to the tiral which of the two tones would be presented. (c) The predictability of the tone frequency. On half the series high and low tones alternated from trial to trial. On the other series, tones were chosen randomly on each trial. The data show that the amplitude of the P300 component is not affected by the presence or absence of a warning stimulus. Furthermore, the distributions of P300 and the CNV over the scalp are quite different. These conclusions are supported by a principal component and a discriminant analysis of the data. We conclude that the CNV and the P300 reflect the activity of functionally distinct cortical mechanisms.


Sleep physiology at high altitude.

Sleep physiology at high altitude. All night sleep EEG, EKG, and respiration were recorded from six young men during 2 nights at sea level and 4 nonconsecutive nights at high altitude (14.110 ft., 4301 m). Sleep at high altitude was chraacterized initially by a significant decrease in Stages 3 and 4, a significant increase in the number of arousals, and a trend towards more time spent awake. In terms of actual time spent sleep, however, a relatively good night's sleep was obtained, which suggests that the objective sleep disturbance was not commensurate with the marked subjective complaints of sleeplessness. Periodic respiration during sleep was frequent at high altitude, was quickly terminated by oxygen administration, was not clearly related to the increased number of arousals, and usually was not seen during REM periods. Heart rate was increased during sleep at high altitude. All measures tended to return towards sea level means during 12 days at altitude. We suggest that the marked increase in the number of arousals may account for the disparity between the subjective reports and objective measures of sleep disturbance at high altitude. Although the objective sleep disruption is probably related in some fashion to hypoxemia, it is unclear whether hypoxemia itself or the alkalosis commonly present shortly after arrival at altitude is the major factor.


[Electrophysiologic semiology of daytime sleep in 7 to 9-year-old children]. The afternoon sleep of 12 children aged 7-9 was studied; its electrophysiological indices and sequential organization were described and compared to those of afternoon sleep of adults and to those of night sleep of adults and children. The EEG indices which differentiate sleep patterns of children from adults' were the following: abundance of slow rhythms from onset of sleep; absence of low voltage fast activity at sleep onset and during REM sleep; early appearance of a large amount of transitory potentials in the form of sharp rolandic waves and sharp occipital waves. Moreover, either focal or generalized paroxysmal discharges occasionally occurred. Even when it covers a complete sleep cycle, the afternoon sleep of children appears shorter than both that of adults and the first cycle of night sleep in children of the same age. The organization of sleep components does not allow identification of the classical stages defined in adults nor to  describe homogeneous stages which are specific to children. The very atypical character of REM sleep also makes it difficult to differentiate unequivocally the classical slow and paradoxical sleeps. The significance of rolandic and occipital sharp transients is discussed; the role of maturation and the influence of the time of occurrence within the circadian rhythm are considered, in order to explain the phenomenological and temporal characteristics of day sleep in children.


Long term follow-up of EEG changes following therapeutic surgery in epilepsy. Four cases, given in some detail, illustrate the effort to compare scalp EEGs taken before surgery for intractable seizures with those recorded some years postoperatively, and to relate these, together with the computer analyses of seizure activity recorded in depth, with the pathology found in the removed tissue and, importantly, with the postoperative clinical state of the patient. These four cases illustrate the following results: (1) Confirmation by histology and ultrastructure studies of abnormal neuronal tissue at the site pinpointed by computer analysis of EEGs as the driving focus for the electrical seizure discharge. (2) Correlation of clinical and behavioral improvement with normalization of the EEG, objectively quantified by computer analysis. Examples are given of excellent recovery (3 cases) and one of, at present, partial recovery.


Electrical phenomena associated with movements of the eyelid. A series of observations were made on a normal subject, a subject with a non-metallic prosthesis and one with unilateral facial paralysis in order to demonstrate the role of the eyelid in the production of the electrical potential seen during blinking. The findings support the hypothesis that moving the eyelid over the positively charged cornea of an intact ocular globe alters the electrical field around the globe and is therefore responsible for the recorded potentials. The data are consistent with previous findings that the polarity of the potential due to eyelid movement is opposite that due to vertical ocular rotation in the same direction. The potential occurs in the absence of ocular rotation.


"Alpha-pattern coma" in high voltage electrical injury. Two cases are reported in which reversible deep coma subsequent to high voltage electrical injury occurred in association with  alpha frequencies in the EEG. The EEG pattern differs from the alpha rhythm of the normal awake patient by its diffuse distribution and unresponsiveness to a variety of stimulation. The term "alpha-pattern coma" is introduced to designate the occurrence of this pattern in comatose patients. The EEG in the cases described initially demonstrated activity in the alpha frequency which occurred in a generalized distribution and was unresponsive to stimulation. During the early stages of recovery an increased incidence of theta and delta activity was observed. The recovery records contained a low voltage alpha rhythm and responded to photic stimulation. The literature on this subject is reviewed and the possible modes of pathogenesis are discussed. The authors conclude that such examples of alpha-pattern coma are the result of diffuse cerebral damage and might be detected more frequently in comatose patients who survive if these patients are studied earlier in their clinical course with EEGs.


Effect of alcohol and task on hemispheric asymmetry of visually evoked potentials in man. The study examined the effect of a dose of alcohol producing a mean blood alcohol content of 90 mg% on components of the scalp-recorded visually evoked potential (VEP) both with and without a visual discrimination task to control the level of attention, and the interaction of amplitudinal hemispheric asymmetry of the VEP with alcohol treatment and the discrimination task. Ingestion of ethyl alcohol producing a mean blood alcohol content of 90 mg% affected VEPs recorded from the central scalp by attenuating the overall amplitude of the later VEP components (60-200 msec) and by significantly reducing hemispheric asymmetry in the amplitude of these VEP components. Alcohol attenuates VEP components P90-N120 and N120-P180, and the task of counting flashes and attending to discriminate double flashes increased amplitude of VEP components N60-P90 and P90-N120 in control and placebo conditions. Several studies have reported that the VEP recorded from the right hemisphere of human beings is larger than the VEP recorded from the homologous location in the left hemisphere. Evoked potentials recorded under control and placebo conditions in this study also demonstrated a hemispheric asymmetry with right larger than left for component P90-N120. We also found a reliable alcohol by hemispheric asymmetry interaction. Alcohol selectively depressed the amplitude of the right hemisphere VEP (P90-N120) component to a significantly greater extent than the left hemisphere VEP was affected.


The characteristics of EEG activity and the subjective estimation of time during dreams of different structure. During dreams evoked by stimuli of a certain duration, the EEF was studied in healthy subjects and in patients with implanted electrodes (EEG, ESCoG (electrosubcorticogram), unit activity). Estimation of the temporal structure of the dream was made from the verbal account of the subject. In the case of an unformed dream the duration of the dream was shown to be adequately estimated, the EEF and ESCoG patterns to be rather variable, and correlation between the bioelectric activities of different structures to be nearly absent. Apparently, in these cases, only some of the structures participate in the formation of dreams, which accounts for their unstructure, with no disorder of temporal and spatial relationships, is accompanied by certain orderly rhythms, similar EEG and ESCoG patterns, and a high correlation between bioelectric processes occurring in the structures under study. Dreams with a complex structure, with simultaneous action in different aspects and with major overestimation of their duration, are accompanied by polymorphous EEG and ESCoG patterns. Almost no correlation is observed between bioelectric processes in different structures. Apparently these dreams are associated with independent activities in different structures and, in the verbal account, the subject tends to place the events in a certain temporal order which creates the effect of considerable acceleration of the time flow.


Hypothalamic temperature during the sleep cycle at different ambient temperatures. Hypothalamic temperature during complete and incomplete sleep cycles (slow wave sleep followed by fast wave sleep and slow wave sleep followed by arousal, respectively) has been studied in freely moving cats at 20 degrees C and 0 degrees C ambient temperatures. The results show that sleep and thermoregulatory processes interact and, at 0 degrees C ambient temperature, become mutally exclusive. The occurrence of fast wave sleep is related to an opptimum range of hypothalamic temperatures which is specific in each enviromental conditions.


The Mongolian gerbil (Meriones unguiculatus) as a model for the study of the epilepsies: EEG records of seizures. EEG recordings have been made from freely moving, seizure sensitive gerbils during seizures of varying severity. The localization of seizure activity in various brain areas and the generalization of this activity could be correlated with the observed motor manifestations. Paroxysmal observed motor manifestations. Paroxysmal bursting has also been recorded in the parietal cortex of a xeizure sensitive animal in which no concomitant peripheral motor activity was evident. These observations strengthen the suggestion that selectively bred epileptic strains of Meriones unguiculatus may be a suitable animal model for the study of the epilepsies.


EEG in brain abscess: its value in localization compared to other diagnostic tests. The EEG records of 13 cases of brain abscess were reviewed for their value in localization. Of the 11 cases of supratentorial abscesses localization was achieved in 10, and correct lateralization in the remaining 1 case. Two other cases were cerebellar abscesses; 1 of them showed a false cerebral localization; the other showed no focal abnormalities. The most consistent EEG localizing sign was focal arrhythmic delta waves. These were as slow as 0.5 c/sec in 6 of the 13 cases. Epileptiform discharges in the pre-operative EEG were seen in 4 of the 13 cases. Asymmetry of beta activity correctly lateralized the abscess in 7 of the 11 supratentorial abscesses. Generalized abnormalities when present correlated with depression of consciousness rather than with the duration of illness or the presence of raised intracranial pressure. Indium brain scans were done in 6 supratentorial abscesses and provided correct or approximate localization in 5. Carotid angiograms were also done in 7 cases and localized the abscess in 6. Our findings show that the EEG is comparable to brain scans and contrast radiological studies in localizing supratentorial abscesses. We feel that the combination of EEGs and brain scanslization in suspected brain abscess.


A quantitative comparison of traditional reading of the EEG and interpretation of computer-extracted features in patients with supratentorial brain lesions. The EEGs of adult patients with suspected supratentorial brain lesions were recorded on paper and on magnetic tape, using a small computer. The spectra of 16 channels were computed on a 40 sec sample. For each channel, a ratio of the type (delta + theta)/(alpha + beta) was computed and displayed on the computer terminal, a measure of the asymmetry in slow wave activity between homologous areas of the head was also displayed. This display is called a canonogram. It is believed to be a meaningful representation of the important characteristics of the EEG in the presence of supratentorial lesions. In order to assess the clinical value of the canonogram, the presumed localization of the lesion obtained from the interpretation of the traditional EEG and from that of the canonogram were compared to the known location of the lesion is a group of 87 subjects. The comparison was made quantitative by the use of a structured report encoding the traditional interpretation and that of the canonogram as well as the reference data (unequivocal surgical, radiological and clinical localizing evidence). The results varied among the anatomical regions: whereas in the frontal and occipital regions the EEG was slightly more accurate than the canonogram, both methods were similar in the temporal areas and the canonogram seemed more accurate in the centro-parietal regions. An attempt was made to interpret these differences. Furthermore, three readers read the cononograms and gave very consistent interpretations. These results show the reliability and value of this simple computer display for the particular type of EEG studied.


The vibration stimulus. Effects of viscous-elastic resistance of skin on the amplitude of vibrations. Accurate measurements of the vibration amplitude were Fig. 7. Reproducibility of double determinations of the vibratory perception threshold (log V2) in normal persons and uraemic patients. PH=pulp, big toe; MM=medial malleolus. Axes show read values in volts transformed into a log V2 scale. Full and strippled lines indicate mean and 95% confidence limits of expected variation (ref. Table II). Made possible by a piezo-electric transducer (accelerometer). With constant voltage to the vibrator slight compression of the tactor against the skin produced an increase in amplitude, similar to that seen with compression against a rubber diaphragm. Further compression had a variable effect on the vibration amplitude, depending on the nature of the underlying tissue (bone, soft tissue). An exact calibration of the vibration stimulus strength therefore appears impossible, and a comparison of the acuity of vibratory perception is invalidated by the different viscous-elastic protion amplitude and the square of the voltage, as seen for vibrations in air, was also demonstrable between independent measurements of the vibratory perception threshold (VPT) in the two terms. The intra- and interindividual variations in terms of the amplitude and the square of the voltage were of the same order. On a logarithmic scale the reproducibility of VPT was independent of the threshold stimulus strength.


Differences in sleep in patients with Parkinson's disease. Twenty-three Parkinson patients were recorded during 2 or 3 consecutive nights. Their treatment, if any, was withdrawn for at least 15 days before the first recording session. Some qualitative abnormalities were noticed during each night in 13 of these patients. They consisted in: 1. Repetitive blinking at the beginning of the night when the lights were turned off, persistence of the electromyographic activity of the chin muscles during paradoxical sleep, occurrence of rapid eye movements and blepharospasms during slow wave sleep before the onset of paradoxical sleep episodes, and alpha rhythm during paradoxical sleep. 2. The study of these signs showed that association between blinking and persistence of the activity of the chin muscles during paradoxical sleep is never encountered. 3. The patients with chin muscle activity during paradoxical sleep had a 50% decrease in paradoxical sleep as compared with the group of patients with repetitive blinking. 4. The possibility that lesions of the locus coeruleus are responsible for this decrease in paradoxical sleep is discussed.


Motor unit activity and preprogramming of movement in man. The activity of single motor units (MUs) is studied during voluntary dynamic movements in man. It is shown that as soon as a MU is set into activity, i.e., at the beginning of the myoelectric burst which precedes the start of the limb movement, there exists a consistent relationship between the peak velocity (for a given inertia) had the interval between the first two consecutive discharges of this MU. Thus, it is likely that when the amplitude of the movement is voluntarily limited, the peak velocity of the movement is preprogrammed.


Changes in frequency and amplitude of delta activity during sleep. Modified period analysis was applied to all-night sleep recordings from 14 young adult males. The modifications involved addition of measures of integrated amplitude and of time in frequency band to the zero crossings and zero counts of the first derivative. The analysis was directed toward changes in the characteristics of delta activity (0--3 c/sec) across the night. Delta shifted toward lower frequencies and decreased in amplitude as sleep progressed. These trends were apparent in mean values for successive periods of slow-wave sleep (SSWPs). For epochs of record classified as stage 4 EEG, these trends were seen both within and across SSWPs. The physiological significance of these changes is unknown. We suggest that they may reflect the kinetics of the metabolic processes underlying sleep. Whatever their theoretical significance, the present results provide new, normative features of the sleep EEG which are not evident in sleep stage classification. The trends we observed appear sufficiently reliable to merit empirical investigation as a function of age, clinical state, or the administration of drugs in addition to further studies aimed at determining their biological significance.


The frontal CNV: its dissimilarity to CNVs recorded from other sites. Two new techniques were used to study the distribution of the CNV recorded from the scalp of humans. One technique was for the suppression of eye movements and the elimination of them fron the average data. The other technique was for the recognition of differences in the form of CNVs recorded from different sites. The latter technique utilized an average vertex CNV as a template pattern against which CNVs from the vertex, left and right frontal, central and parietal sites were matched. The results showed that the frontal CNV was different in form from the vertex, central and parietal Cnvs and that the vertex, central and parietal CnvS were similar in form. An analysis of the amplitudes of CNVs showed that the frontal CNVs were significantly smaller than the CNVs from all other sites, that the vertex CNV was significantly larger than the parietal or central CNVs and that the central CNV was significantly larger than the parietal CNV. There were no differences in amplitude between hemispheres within Condition A responding with the right hand) or Condition B (responding with the left hand) or between Conditions A and B. The results are discussed with respect to their possible theoretical implications.


Auditory evoked potentials during sleep in normal children from ten days to three years of age. Auditory evoked potentials (AEPs) to clicks of moderate intensity were studied in 130 normal sleeping children from 10 days to 3 years of age. Latencies of the principal response components were found to decrease with log age, i.e., change was most rapid during the first year of life. From 15 days of age to 3 years, mean latencies decreased as follows: P2 from 230 to 150, N2 from 535 to 320 and P3 from 785 to 625 msec. Variance was quite high, especially at younger ages. The fact that decreases in the latencies of the various components proceeded at different rates suggest that the components reflect quasi-independent neural substrates. The components of shortest latency displayed the weakest relationship to age. Findings with respect to latency for the subset of data obtained during stage 2 sleep were similar to those for the total population which contained responses recorded during several sleep stages. The amplitude of AEP components increased with age with the exception of N1P2 which decreased. Observations with regard to amplitude held both for the overall data recorded during several sleep stages and stage 2 data for components N0P1, N1P2 and N2P3. The amplitude trends for P1N1 and P2N2 were, however, not significant for the stage 2 subset. The maturation of the morphology of the AEP was characterized by a relative increase in the prominence of long latency components. The most striking change was the development of P3. High amplitude, V shaped P3 waves were also associated with stage 3-4 sleep. The changes which were delineated by this study for infancy and early childhood appear to be continuations of developmental trends reported for premature infants and neonates. AEPs are a reliable elicited measure which correlate well with maturation. They, therefore, can be a useful tool both in the study of central nervous system development and in the diagnosis of sensory and neurologic abnormalities.


Information processing during two types of EEG activity. A 15-year-old girl whose EEG contained frequent bursts of generalized sub-clinical spikewave activity was examined on a paced serial-choice response task with simultaneous EEG control. The task was carried out at three different speeds and three different information loads. Performance was compared during paroxysms of spike-wave activity and during normal EEG background activity. Four parameters of performance were compared, each parameter being somewhat differently affected by spike-wave activity. "Response ambiguity" was significantly increased in the presence of spike-wave activity, with a corresponding decrease in the amount of "information transmitted". The "absolute rate" at which information could be transmitted in relation to presentation rate was consequently reduced during spike-wave activity, the effect being most marked at the intermediate speed of presentation (1 signal/2 sec). However, when signals were presented very slowly (1/4 sec) the child's "relative information transmitted" during spike-wave activity approached that achieved under normal background conditions. Thus, accuracy of performance per se is not critically affected by spike-wave; rather it is the rate at which signals can be handled. Spike-wave may therefore be conceptualized as a form of "neural noise" whose effect is to reduce a subject's channel capacity.


The effect of stimulus orientation on the visual evoked potential in human subjects. The average evoked potential (AEP) produced by a stationary grating of high dark-bright contrast, recorded from the human occipital scalp, was less in amplitude when it was presented obliquely than when it was oriented horizontally or vertically, and in addition the amplitude was more variable for the oblique orientation. The Wiener-filtered average method was more sensitive to these inequalities than the conventional averaging. No orientational effect upon the AEP latency was observed. Results were discussed in relation to perceptual and neuronal responses.


Snoring.

Snoring. Eight heavy snorers underwent nocturnal polygraphic recordings. The principal results are the following: 1. Snoring is an inspiratory (or primarily inspiratory) noise linked to subobstruction of the upper airways. It appears with falling asleep (stage 1) and intensified progressively through the deepening of slow sleep; in REM sleep it becomes discontinuous and is comparable to stage 2 snowing in intensity. 2. In heavy snorers, obstructive apneas are always present and particularly abundant during light sleep (state 2) and REM sleep. 3. In heavy snorers during sleep the systemic arterial pressure reaches and remains at levels higher than those of wakefulness instead of diminishing normally. 4. Some degree of alveolar hypoventilation is associated with snoring when the apneas are especially abundant. These findings confirm the existence of significant polygraphic analogies between snoring and hypersomnia with periodic apneas and indicate that snoring may represent the first phase in the development of this syndrome. Moreover, the effects of snoring on alveolar ventilation and the systemic pressure during sleep suggest that heavy, constant snoring has physio-pathological implications for the cardio-circulatory apparatus.


Single unit activity in basal ganglia of monkeys during performance of a delayed response task. Single unit activity was recorded from the basal ganglia (caudate, putamen and globus pallidus) of monkeys during the performance of a delayed-response task. The task was divided into five epochs: stimulus onset, delay, pre-response, post-response and reqard. A high percentage of units recorded from the basal ganglia were found to show significant changes in activity during one or more epochs. Examination of the proportion of units excited or inhibited during a particular epoch indicated that brief increases or decreases in unit firing rates occurred "in phase" in both pallidum and caudate. Longer lasting firing rate changes, however, tended to occur in opposite directions in these two structures. This latter finding is interpreted as representing the consequence of persistent increases or decreases in activity of inhibitory interneurons in the caudate nucleus.


Pallidal and entopeduncular single unit activity in cats during drinking. It has been shown that pallidal units display changes in firing rate during food seeking and consummatory behavior. The purpose of the present work was to determine which properties of the ingested material or ingestive behavior were most potent in altering unit activity. Single unit activity was recorded in the globus pallidus and entopeduncular nucleus of awake restrained cats during introduction of fluid into the mouth. A very high proportion of pallidal and entopeduncular neurons showed changes in firing rate during fluid injection. Two patterns of response were observed. Typically, responses were phasic and time-locked to the occurrence of fluid presentation. Less frequently, a long lasting change in firing occurred which persisted throughout the period of fluid introduction. Additional observations indicated that both of these changes in firing rate seemed to be related to the sensory rather than the motor aspects of ingestion.


A simplified circuit for stimulus artifact suppression. This note describes a simple electronic method of eliminating time-locked stimulus artifacts from recordings of cerebral evoked potentials. The hardware required for a 16-channel battery-powered suppressor system costs less than $80. The complete circuit can be fabricated from readily available components on a single 6.5x4.5 in., 44-pin circuit board.


4-channel 24 hour cassette recorder for long-term EEG monitoring of ambulatory patients. A 4-channel cassette recorder capable of continuously recording the EEG for 24 h on a C-120 cassette is currently in use at the Montreal Neurological Institute. We have done a limited study on 20 patients with over 2000 h  of recording to evaluate the recording system, its limitations and its capabilities, and to develop methodology for its operations. The use of preamplifiers enables one to record the background EEG with a noise level of 3-5 muVpp on 4 channels continuously for 1 day. The electrodes can be hidden in the hair and the preamplifier under the collar, to allow the patient to carry on his normal activities at home and at work. Since the cassette and the batteries can be easily changed, the patient himself can prolong the recording for several days. The cassette can be played back as fast as 60 times on a Minograf EEG machine for compressed analysis or 20 times for more detailed write-out, to obtain a record equivalent to standard EEG recordings. The system was not designed to replace or compete with standard EEG recordings but when used on well defined clinical problems, or in specific research projects, it can enhance the diagnostic or research value of the EEG.


Oculomotor outflow and its relation to electrical activity of suprasylvian gyrus and pulvinar during paradoxical sleep in the cat. During paradoxical sleep, single unit activity was recorded from the posterior part of the middle suprasylvian cortex together with the electrical activity of the medial rectus eye muscles and that of the pulvinar nucleus. Experiments were performed on unrestrained cats, which slept in a dark cage. The intervals between the onsets of the successive phasic ocular EMG bursts were determined. There was a pronounced occurrence of intervals lasting 120-240 msec. The mean discharge rate of the suprasylvian cells during the 200 msec period after the onset of EMG bursts of brief duration was significantly higher than during the 200 msec period before the onset of such EMG bursts. The greatest increase in the mean discharge rate took place during the first 40 msec after the onset of the EMG bursts. A distinct theta activity was seen in the pulvinar during most of the recording time. Its frequency and amplitude varied in general relation to the occurrence and rate of the phasic ocular EMG bursts.


The clinical significance of occipital spikes as a sole response to intermittent photic stimulation. Forty-five patients who showed occipital spikes as a sole response to IPS have been studied over a 9 year period. Occipital spikes induced by IPS are non-specific, not constantly present and in themselves are not indicative of epilepsy. Occipital spikes alone are seen in a very small percentage of clinical photosensitive patients.


EEG findings in heroin addicts during induction and maintenance on methadone. This study investigated changes in the EEG of addicts initially on heroin as they progressed through the induction and maintenance phases of a methadone program. Spectral analysis of bipolar recordings revealed significant consistent differences only in the eyes-closed resting state. Patients under the influence of heroin showed large sharp peaks at 9-10 c/sec, particularly in the parieto-occipital recording. Methadone induction led either to marked reduction of this peak and widening of alpha band activity or to an increase in frequency of the alpha peak to 12 c/sec. After several months of methadone the alpha peak was still absent unless heroin abuse was present, a theta peak was present in three of four patients, and the alpha bandwidth remained broad. Changes in the theta band were more difficult to interpret.


The localization of equivalent dipoles of EEG sources by the application of electrical field theory. A technique is described for finding the position, magnitude and orientation of the equivalent electrical dipole of EEG activity given the pattern of potential differences recorded at the scalp. The technique is based on an iterative computer program implementing equations describing the electrical field of a dipole in a spherical conductor. The computer program was tested in vitro against data obtained from an inert spherical conductor (a bowl containing physiological saline, fitted with recording electrodes and a movable dipole) and an anisotropic conductor (a similarly equipped human skill including a simulated scalp). In both practical models, the computer program accurately located the dipole, the mean differences between observed and computed loci being of the order of 1 cm at widely different locations. This accuracy was maintained in the anisotropic model even though potentials transmitted through the skill were attenuated by 80%. In vivo, the program successfully located the equivalent generator of blink artefacts within the remaining eye of a one-eyed subject and, in a normal subject, localized the dipole of corresponding potentials to a midline inter-ocular position. In further investigation of normal subjects, the distribution of amplitudes at latencies within Wave V of the visual evoked response confirmed the loci of equivalent generators within posterior cerebral regions. The technique was also applied to the alpha rhythm indicating a posterior locus compatible with the view that alpha rhythm is generated chiefly by posterior cerebral cortex. Factors affecting the accuracy of the technique and the limitations of one-dipole models are discussed.