Structure and function of RNA replicase of bacteriophage Qbeta. (1) The RNA replicase induced by bacteriophage Qbeta consists of four non-identical subunits designated as alpha (mol. wt. 74000), beta (mol. wt. 64000), gamma (mol. wt. 47000) and delta (mol. wt. 33000), only one (subunit beta) of which is specified by the phage genome. (2) Subunit alpha (30 S ribosomal protein "S1" as well as translational interference factor "i") is required only for (+) strand-directed RNA synthesis in the presence of the host factor. (3) Qbeta replicase lacking subunit alpha (R-alpha) is capable of replicating templates other than (+) strand, such as (--), "6S" RNA, poly(C) etc., in the absence of the host factor. (4) Subunit beta is suggested to be the nucleotide-polymerizing enzyme, but is unable to initiate RNA synthesis by itself. (5) Subunits gamma and delta are identical to the protein synthesis elongation factors, EF-Tu and EF-Ts, respectively, and are required only for initiation of RNA synthesis, but not for elongation. (6) A model of Qbeta replicase is presented in order to discuss observed template-enzyme interactions.


Morphogenesis in Myxococcus xanthus and Myxococcus virescens Myxobacterales. 1. Myxococcus xanthus B and M. virescens V2 were compared with a view to establishing the control of their morphogenetic cycles. Both organisms are typical myxococci and on solid media with low concentrations of nutrient they form fruiting bodies, within which vegetative cells convert to myxospores. Ultrathin sections of vegetative M. virescens resembled those of M. xanthus and contained prominent heavily stained bodies, presumed to be polyphosphate granules. Shadowed preparations showed fimbriae associated with M. xanthus but not with M. virescens. 2. M. xanthus B converted to myxospores in liquid medium in response to certain alcohols. M. virescens V2 produced phase-refractile spheres, which were not viable and had an unusual ultrastructure. 3. The distributions of fruiting bodies on solid media containing 0.02% Casitone were recorded for the two species and were compared with a Poisson distribution. Cells responded to differences in cell density in a manner suggestive of a response to a chemotactic attractant. Cells growing vegetatively and also cells forming fruiting bodies produced 3',5'-cyclic adenosine monophosphate (cAMP) as measured by the incorporation of exogeneous [3H] adenosine into cAMP. 4. The significance of these findings for theories of fruiting body formation are discussed.


Superoxide dismutase from Mycobacterium species, strain Takeo. Superoxide dismutase from Mycobacterium species, strain Takeo, has been purified to homogeneity as judged by disc gel electrophoresis and ultracentrifugation. The enzyme was found to have a molecular weight of approximately 61 500 by sedimentation equilibrium and to contain manganese by atomic absorption and electron spin resonance spectra. The amino acid composition was also determined. The enzyme was considerably stable to the treatment with sodium dodecyl sulfate; unless incubating at 80 degrees C for 2 min, it was not completely dissociated into the subunits. The molecular weight of the subunit was found to be approximately 21 000. Antibodies against the superoxide dismutase were produced by immunization of rabbits with the enzyme, and the gamma-globulin fraction was purified. Superoxide dismutase preparations obtained from various species of mycobacteria and nocardia cross-reacted to different degrees with these antibodies on the Ouchterlony double diffusion plates. Comparative immunological studies indicated that strain Takeo might be most closely related to Myobacterium smegmatis among species of mycobacteria and nocardia tested. The antibodies against superoxide dismutase may be used as a valuable tool for the classification of mycobacteria.


Types of reaction in the regional lymph nodes in non-metastatic and minute-metastatic carcinoma of the uterine cervix. The authors studied tissue reactions in the regional lymph nodes of 68 patients with an invasive cancer of the uterine cervix at stage I and II of neoplastic disease. Two basic types of the lymph nodes reactions have been distinguished. In the first type of changes a reactive hyperplasia of sinusoidal histiocytosis predominated, as well as distinct activation of lymphocyte production within the follicles and numerous aggregates of plasmacytoid cells within the medullary cords. The second type of reaction was characterised by fibroplastic reaction causing constriction and block of capsular lymphatic and blood vessels, the pseudotransformation into hemolymph node and hematoxyphilic atrophy of lymphoreticular tissue. The authors' observations indicate that in case with the predominance of the second type reaction within regional lymph nodes arise favourable conditions for the production of distant metastases.


Antithymocyte globulin in renal transplant recipients. Report of a prospective randomized controlled trial. Horse antihuman thymocyte globulin (HAHTG) combined with prednisone and azathioprine (lmuran) was used as immunosuppressive therapy in a randomized controlled sutdy in 50 renal allograft recipients. Side effects of HAHTG administration given intravenously were mostly mild. In the treated group, four patients out of 26 died of infectious complications, whereas in the control group, three patients out of 24 died of infectious complications (chi2 = .01,P greater than .05). The graft survival at 18 months was ten of 24 in the control group and ten of 26 in the treated group (chi2 = 1.26, P greater than .05). Cumulative graft survival was 58.3% in the control group and 38.1% in the treated group at 18 months. However, if we consider the people who died with a functioning graft not as graft failure but as if they left the study, then the cumulative graft survival is 64.5% in the control group and 65.9% in the treated group. Thus, the mortality from infective causes and graft survival were not significantly different between the two groups. Hence, we draw the conclusion that use of HAHTG did not exert a beneficial effect on the ultimate outcome.


Relation between common antigen and membrane antigens associated with Marek's disease herpesvirus and turkey herpesvirus infections. The appearance of two kinds of membrane antigen (MA) in Marek's disease herpesvirus (MDHV) or herpesvirus of turkey (HVT) infected cells was examined using antiserum to the common antigen (common-Ag). No early-appearing MA(EMA) was detected in these cultures until 16 hours post-inoculation, after which a number of cells in these cultures had late-appearing membrane antigen (LMA) as detected by immunofluorescence (IF). Fluids from cultures infected with these viruses were examined for the presence of the common-Ag by agar-gel precipitation (AGP) test. No common-Ag was detected until 16 hours, but after 24 hours, it was detected by AGP test. These results suggest that the common-Ag is related to LMA but not to EMA.


[Cholestatic liver lesions of alcoholic etiology (a morphologic study)]. Results of histological, histochemical and electron-microscopy studies of puncture-biopsy specimens of the liver of 25 patients with alcoholic hepatitis are discussed. It is shown that acute alcoholic hepatitis develops, develops, as a rule against the background of steatosis and hepatocirrhosis as a result of the previous chronic consumption of alcohol. Lesions of the liver in this disease are of cholestatic character, which was due to the impairment of the metabolism of lipids, cholesterol and biliary acids under the effect of ethanol. The microscopic picture of alcoholic hepatitis is characterized by the presence of Mallory hyalin, intracellular congestion of the bile and predominance of neutrophilic leukocytes in the cell infiltrate. The characteristics make it possible to differentiate alcoholic hepatitis from viral one.


Progressive combined amyloid-elastic stain. A progressive staining technique is described that will permit demonstration of elastic structures and amyloid deposits in the same section. It is satisfactory for animal as well as human tissues, and for both pericollagen and perirecticulin types of amyloidosis.


[Estrus synchronization in cattle by means of chlormadinone acetate ("Bovisynchron" Jenapharm) in the tropics. II. First results of the estrus synchronization of cattle with "Bovisynchron" at the Republic of Mali]. The first experiments are reported on oestrus synchronization in cattle in the Republic of Mali. The animals recieved Bovisynchron twice a day orally over a period of 15 days. The synchronization effect was marked; insemination was performed on the 5th and 6th day p.s. The intensity of the oestrus and especially the results of pregnancy are in close relationship to the breeding conditions and the general status of the animals. The oestrus synchronization is considered a favourable biotechnical method for regulating the reproduction provided that the animals are kept stationary or temporarily stationary.


Transposition of great arteries. Early results of Mustard's operation in paediatric patients. Between May 1969 and June 1975, 43 patients with d-transposition of the great arteries, ranging in age from 2 months to 13 years (mean 19 months), underwent surgical correction. In the first 3 patients Mustard's original method was followed. Later a modified procedure was performed using a Teflon patch. Forty-two of the 43 patients had previously had 50 various palliative procedures, of which 30 were balloon atrial septostomy only. Five patients died in hospital (up to 5 weeks after operation). Of the 32 patients with simple repair of transposition of the great arteries (including 3 with ligation of a persistent ductus arteriosus), 3 died. One patient died as a result of complete AV block, one as a result of renal damage associated with unrelieved coarctation of the aorta, and one of cerebral infarction and peritonitis which probably were initiated preoperatively. Six patients who had additional surgery for pulmonary stenosis survived, including 3 patients who had closure of ventricur septal defect, including 2 who had debanding of the pulmonary artery, 2 died in a low cardiac output state. One infant operated on for subpulmonary stenosis developed permanent complete AV block and was successfully treated with a pacemaker. All the patients with combined operations had some problems postoperatively. The survivors improved greatly, but 2 patients died suddenly one, and one and a half years after the operation respectively.


Bipolar catheter electrograms for study of retrograde atrial activation pattern in patients without pre-excitation syndromes. The sequence of retrograde atrial activation of premature ventricular beats was studied in 12 patients without pre-excitation syndrome. Forward and retrograde AV nodal conduction times were within normal limits. The septal low right atrial (LRA2) deflection was inscribed 25 to 55 ms (ave: 37.9 ms) before the low left atrial (LLA2) electrogram and 35 to 75 ms (ave: 53.7 ms) ahead of the high right atrial (HRA2) deflection. LLA2 preceded HRA2 in 8 patients, more or less coincided with HRA2 in 3 cases, and was inscribed 10 ms ahead in 1 patient. In all cases a decrease in the coupling (St1-St2) interval resulted in a proportional increase of the septal LRA1-LRA2, LLA1-LLA2, and HRA1-HRA2 intervals. Atrial echoes occurring in 3 cases had a sequence of arrival of excitation at the recording sites which was similar to the ones shown by the same patients during ventricular pacing. This is in keeping with the existence of an upper common pathway located above the area where functional longitudinal dissociation occurred. Thus, it is concluded that impulses emerging from the AV node in a retrograde direction reach the septal low right atrium before they activate the explored low left atrial sites, regardless as to whether they arise in the ventricles or in the atria.


Hepatitis-B surface antigen and antibody in Bantu patients with primary hepatocellular cancer. Hepatitis-B surface antigen (HBsAg) was found in the serum of 58 of 158 (36-4%) southern African Bantu patients with primary hepatocellular cancer by counter immunoelectrophoresis and in 94 (59-5%) by radioimmunoassay (RIA). The prevalence of this antigen in the general Bantu population using these methods was 7% and 9% respectively. Antibody against HBsAg was detected in 11-6% of the patients by passive haemagglutination (PH) and 13-4% by RIA, and in 33-4% (by PH) of a control population. Antibody sub-types were predominantly "adw" (69-2%) with a lesser frequency of "ayw" (23%), while 7-8% were indeterminate. The corresponding figures in the controls were 80-4, 8-4 and 11-2%. HBsAg was more common in younger patients. No relationship could be demonstrated between hepatitis-B antigenaemia and the presence of alpha-foetoprotein in high concentration, although there were far fewer patients in the alpha-foetoprotein-negative group.


Blood lead and erythrocyte delta-aminolevulinic acid dehydratase levels in Manchester taxi drivers. Among 40 Manchester taxi drivers the mean blood lead was 1.10 mumol/1 (22.8 mug per 100 ml). The mean erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity among 34 of them was 30.1 units. No significant association was found between the blood lead levels and erythrocyte ALAD activity in these 34 men. No significant association was found between either blood lead elvels or erythrocyte ALAD activity and duration of service or weekly mileage as a taxi driver or with drinking or smoking habits, or age. The mean blood lead of those with homes in the north east quadrant of the city was higher than of those living elsewhere but the difference was not statistically significant. Although there was no correlation between blood lead levels and the source of domestic water, the mean blood lead of those with lead domestic plumbing was appreciably higher than the level of those with copper plumbing. There was no indication that, by virtue of their occupation, the taxi drivers were liable to greater lead absorption than their fellow-citizens.


Probability analysis of the interaction of antibodies with multideterminant antigens in radioimmunoassay: application to the amino terminus of the beta chain of hemoglobin S. A simple theory, based on probability, is developed for the analysis of the interaction of multideterminant antigens with multispecific antisera in radioimmunoassays. The theory is completely general except for the assumptions that the determinants be unique and bind antibodies independently of one another. The analysis shows that the shape of the curve of bound/free as a function of the antigen concentration is very sensitive to the multiplicity of determinants. The predictive ability of the theory is illustrated for the case of antibodies to subregions of the N-terminal third of the beta chain of sickle hemoglobin, studied using antisera fractionated on affinity chromatographic columns of synthetic peptides. The implications for obtaining quantitative binding data by radioimmunoassay for natural antigens, which almost universally have more than one antigenic determinant on the same molecule, are discussed.


Characteristics of the macrophage uptake of proteinase-alpha-macroglobulin complexes. Complexes formed between labelled proteolytic enzymes (trypsin, subtilopeptidase A) and the alpha-macroglobulins of plasma are rapidly and selectively taken up by rabbit alveolar macrophages. The uptake occurs over a narrow zone of pH. Kinetics of the uptake is affected by temperature; in particular, incubation of macrophages at 37 degrees C before the addition of the labelled complex reduces the capacity to take up complexes. EDTA prevents the association of labelled complexes with macrophages, and can dissociate previously bound label. The effect of EDTA is reversed by the addition of calcium or magnesium or both. Iodoacetamide does not prevent the uptake of complexes but causes them to remain available for dissociation from the cells by EDTA. Incubation of complexes with macrophages at 37 degrees C with no iodoacetamide results in the appearance of trichloroacetic acid soluble products of the enzyme in the supernatant fluid. These observations indicate that the selective uptake of proteinase-alpha-macroglubin complexes by rabbit alveolar macrophages can be resolved into three phases: (1) membrane binding which depends upon divalent cations and is pH sensitive, (2) endocytosis inhibitable by iodoacetamide and (3) temperature-dependent hydrolysis of the contained labelled enzyme.


Demonstration of 8 S-cytoplasmic oestrogen receptor in rat mullerian duct. 1. High affinity macromolecular binding of the non-steroidal synthetic oestrogen [3H]diethylstilboestrol and of [3H] oestradiol-17beta in cytosol of Müllerian duct and uterus, and in blood plasma of perinatal rats, was investigated by sucrose density gradient sedimentation. 2. While [3H] oestradiol was bound to both the characteristic 8 S uterine cytoplasmic receptor and a 4 S component of uterine cytosol and plasma of 11-day-old rats, [3H] diethylstilboestrol was bound almost exclusively by the 8 S cytoplasmic receptor. 3. The greatly reduced binding of [3H] diethylstilboestrol to the 4 S plasma plasmic receptor in the Müllerian duct (precursor of the uterus) of 20-day-old foetuses.


A comparative evaluation of methods for isolation of RNA-directed DNA polymerase from cells in a reconstituted system. We have compared the relative merits of several procedures for the isolation of RNA-directed DNA polymerase (EC 2.7.7.7.) from cells using a reconsituted model system consisting of a mixture of woolly monkey (simian) sarcoma virus and a cultured human lymphoblastoid cell line, NC-37. When the cell-virus mixture was gently disrupted and fractionated by differential centrifugation, most of the added polymerase was recovered associated with a particulate fraction obtained from the post-mitochondrial supernatant. Purification of the polymerase was best achieved starting from this fraction. The particulate fraction itself can be purified by gel filtration through a Sepharose 2 B column. This procedure did not significantly alter the composition of viral and cellular DNA polymerases. Whereas as little as 7.5 - 10(5) viral particles were sufficient for the detection of RNA-directed DNA polymerase activity, a minimum of about 10(11) particles were necessary for the isolation and unequivocal characterization of the enzyme from the cell-virus mixture by subcellular fractionation and chromatographic separation from cellular DNA polymerases. Purified RNA-directed DNA polymerase had the same primer-template characteristics, sedimentation properties, and immunological cross reactivity as the enzyme purified from density gradient-banded virions of simian sarcoma virus. Methods involving total extraction of the cell-virus mixture either by repeated freezing and thawing followed by detergent treatment or by Dounce homogenization and treatment with high salt and detergent failed to provide RNA-directed DNA polymerase free of cellular DNA polymerases. Because of this, low levels of cellular RNA-directed DNA polymerase may be missed when these approaches are used.


Properties of human neutral bronchial mucins after modification of the peptide or the carbohydrate moieties. Trypsin and pronase treatment of purified human neutral bronchial mucins released small fragments from the C-terminal end of these molecules and resulted in slight increases in their sedimentation coefficient presumably reflecting conformational changes. The antigenic determinant of neutral bronchial mucins which appears to be located on this C-terminal fragment is destroyed by pronase or by treatments such as periodate oxidation or galactose oxidase-bromine oxidation which modify the carbohydrate moieties. Thus, both amino acid and carbohydrate residues are involved in the structure of the antigenic determinant.


[Change in lipid-protein interactions in the membranes of bacteria exposed to gramicidin S]. Effect of cyclopeptide antibiotic gramicidin S on some enzymes and physical state of isolated Micrococcus lysodeikticus membranes is studied. Malate and lactate dehydrogenases were monotonously inhibited under the increase of gramicidin S concentration, while the activity of NADH-dehydrogenase firstly decreased and then reversed to the initial level under further increase of gramicidin S concentration. The oxygen uptake under oxidation of NADH and malate with membranes almost completely inhibited by the antibiotic, while the activity of ascorbate-TMPD-oxidase activity slightly inhibited by the same concentration of gramicidin. The addition of Triton X-100 completely eliminated the inhibitory effect of gramicidin on malate dehydrogenase. The introduction into the membrane of spine probes (2,2,6,6-tetramethyl-4-palmitoylamidopiperidine-1-oxile and 2(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxyazolidinyloxile) revealed that gramicidin caused the condensation of membrane lipid component. It is suggested that ionic interaction of gramicidin S with membrane phospholipids brings to "a freezing" of lipids which is a direct cause of impairing the activity of membrane respiration enzymes and the change of their position in the lipid matrix, thus inhibiting energy-producing processes in cell.


[An immunochemical study of D-glyceraldehyde-3-phosphatedehydrogenase]. Immunochemical study of D-glyceraldehyde-3-phosphate dehydrogenase from rat skeletal muscle was done using antibodies, raised in rabbit. One molecule of the enzyme binds three antibody molecules at the equivalence point and eight molecules at full saturation of the antibody binding sites. Modification of SH-groups of the dehydrogenase with pCMB, as well as ADP-induced inactivation of the enzyme do not cause any alterations in the quantitative precipitation curve. This suggests that antigenic determinants and the active site are situated in different loci on the enzyme molecule. A quantitative relationship between the dehydrogenase concentration and the percentage decrease of its catalytic activity in the presence of antibody excess are established, and a mechanism of apparent inhibition in the insoluble immune complex is proposed.


Suppression of shear-induced hemolysis by three plasma proteins. Hemolysis was induced in erythrocyte suspensions by shearing between rotating metal disks 10 cm in diameter at 325 rev/min; stresses did not exceed 100 dynes/cm2. The role of proteins (gamma-globulin, G; albumin, A; fibrinogen, F) in the environment was tested in two ways. First, disks were precoated by exposure to protein solutions of physiologic concentration and then used to hemolyze the suspensions. Tests carried to 10(4) sec showed protective effects, relative to shearing with virgin disks, with a ranking G greater than A greater than F. Second, proteins were dissolved in the suspension media and hemolysis compared to the case without protein. Large suppression of hemolysis was found during storage (G approximately A greater than F) but only G offered significant protection against shear.


Mechanisms of immunodepression induced by viruses: possible role of infected macrophages. Some oncogenic and non-oncogenic viruses induce an immunodepression in their host by decreasing either humoral responses, cellular responses, or both. The mechanism of this immunodepression is still largely unknown, but it is generally agreed that there is a defect in the proliferative potential of lumphocytes in the infected host. Most of the viruses known to induce immunodepression appear to infect host macrophages. Failure of infected macrophages to provide a "proliferation signal" to lymphocytes, and/or destruction of lymphocytes in the lymphoid organs by toxic factors released by infected macrophages could be important mechanisms of immunodepression by viruses.


Endogenous C-type viruses: double agents in natural life processes. C-type RNA viruses have been described in about 20 different vertebrate species. Their presence in man is suggested by electron microscopic, biochemical and serologic studies, although a definite re;icating human virus has not yet been isolated. These viruses are inherited through the germ cell and their production is regulated by genetic information carried in the host cell (i.e. endogenous virus). Two classes of endogenous C-type viruses have been recognized in certain animals particularly the mouse: ecotropic and xenotropic. They may have their counterparts in man. Ecotropic viruses spread through the host and can be easily transmitted to cells of the same species; they can produce malignancy. Xenotropic viruses cannot infect cells from their host species but are infectious for cells from heterologous species. The interaction between xenotropic and ecotropic viruses could lead to the transfer among species of genetic information relating to normal life processes and malignancy. These C-type viruses may play a role in evolution, normal development and differentiation as well as autoimmune disease and cancer.


[Change in the fractional composition of thrombocytic proteins during experimental acute radiation sickness]. Thrombocytic proteins of healthy and irradiated rats were divided into 13 fractions by anode electrophoresis in the polyacrylamide gel. In rats with acute radiation sickness there was a reduction in the content of thrombocytic proteins with an electrophoretic mobility corresponding to the prealbumin, albumin, gamma-globulin and fibrinogen; an increase in the protein content with the mobility corresponding to the alpha- and beta-globulins was seen.


[Detection of neoplastic cells in the bloodstream]. A study was made of the efficacy of trypan blue, acridine orange, tetracycline and oxytetracycline for detection of tumour cells injected into the blood stream of rats. The cells were identified in the mesenteric microvessels by intravital microscopy. Fluorescence of fluorochromized cells was observed in the blue-violet (lambda max = 400 nm) and ultra-violet (lambda max = 365 nm) irradiation of the fluorescent lamp and in the laser irradiation (lambda = 337 nm). The cells stained with acridine orange had a higher fluorescence intensity and a more distinct structure than those labelled with tetracyclines. Identification of cells with trypan blue was more difficult. The fluorescent method of determination is rather simple and permits to indentify tumour cells directly in the blood stream.


[Results of a 4-year of alpha-fetoprotein in Vietnam (1969--1973)]. ALPHA-Fetoprotein (alpha-FP) was revealed by the method of double diffusion in gel in 66% of hepatocellular carcinoma cases, but the frequency of findings both in hepatoma and in other diseases increased when electroimmunodiffusion (a more sensitive method) was used. Results of quantitative determination of alpha-FP in the patients after ligation of the hepatic artery pointed to reduction of its content in the blood serum, this confirming the value of its determination for prognosis.


[Immunofluorescent study of antibodies to streptococcus group A polysaccharides in connective tissue sections]. Purified antibodies against a specific determinant of group A streptococcal polysaccharide were obtained. These antibodies were investigated by the immunofluorescent method on tissue sections of the heart and heart valves. No cross-reactions between group A streptococcal polysaccharide and mammalian connective tissue were revealed.


[Antigen-specific lysis in vitro of lymph node cells of intact mice injected with RNA from viable lymph node cells of immunized animals]. Supernatant fluid obtained after centrifugation of the suspension of viable lymph node cells of immunized animals proved to induce in vivo in the lymph node cells of intact mice sensitivity to lysis with a specific antigen in vitro. This property was possessed after chromatography of the supernatant fluid on Sephadex G-200 by the 3rd fraction (MW about 30000 dalton). DNA-ase, trypsin or deproteinization failed to influence whereas RNA-ase inactivated this fraction in respect to the inducing properties.


Physical facilities of medical school libraries in the United States, 1966-1975: a statistical review. This paper, based on information received from a questionnaire to which 107 of the present 114 medical school libraries in the U.S. responded, shows the vast growth and expansion of such libraries. The 86 libraries which have been built, expanded, under construction of planned during 1966-1975 represent the greatest expansion in the history of medical school libraries. This "decade of revolution" can be attributed to the evergrowing resources, primary users, and services discussed in this paper. The survey results can also be useful to those institutions planning or remodelling such library facilities in the near future.


Selecting for health sciences library collections when budgets falter. The economic plight of the 1970s often limits the librarian, who should be the final selector, to insufficient funds for acquiring essential publications. The librarian, in addition to making every effort to acquire the best possible collection, must provide access from other libraries, within and outside one's parent institution, to materials not acquired; for this purpose, an effective document delivery network has proved more significant than formal plans for shared acquisitions. Too much is published, but the choices become more manageable with selection criteria that include limiting subject scope and keeping within the English language. In regard to journals, new titles should be added only reluctantly; cancellation lists compiled with the help of selective lists, the librarians' judgment, and users' responses; and newsletters and state journals pruned to a mimimum. As to books, selective lists should be consulted; congress proceedings generally ignored; and reprinted collections, multiple copies, and gifts considered with care. Book reviews are more useful selection aids now that lack of funds causes delays in purchasing than when new titles were acquired promptly with less discrimination. Audiovisual media, although widely pushed, do not replace printed materials, are not of central importance to many faculties, are expensive, and thus comprise a bandwagon which the impoverished library cannot afford to board without extra funding. The less money there is, the more need for a librarian's selection skills.


TALON--the first five years.

TALON--the first five years. The South Central Regional Medical Library Program, Region IX in the national network of medical libraries, was one of the last to be organized and funded. The particular makeup of this organization has permitted a good deal of flexibility in the identification and implementation of various types of network services and activities. The following is a brief account of some of these network functions during the first five years relating the successes and failures in network strategies and describing the further evolution of programs and refinement of a regional plan which will advance network services.


A computer-generated catalog of audiovisuals. A computer-generated catalog of nonprint media is described. Examples are given of four access points to the data base: (1) main entry, (2) title, (3) MeSH terms, and (4) broad subject categories. The data input procedure is summarized. The AV catalog as the basis for a union list is evaluated, and finally, the catalog in relation to certain local problems is discussed.


[Effects of the electric current on the fundamental processes of stimulation in the heart]. On the basis of experimental studies on isolated preparations from different regions of the heart and on perfused hearts of animals, it was possible to distinguish at least four basic actions of an electric current: 1. the release of excitations, 2. with continuous current, an electro-tonic influence on the pacemaker activity in the sense of a cathodic advancement, or an anodic inhibition 3. with alternating current, stimulation of the vegetative nerves of the heart, 4. a direct, reversible damage of the membrane by the current. Depending on the conditions of the action of the current (nature of current, current density, period of action, moment of start of action, etc.) the basic actions can lead to difference influencing of the heart functioning. Excitation, occurrence of fibrillation and defibrillation are due to stimulation. Heart stoppage may be the expression of vagus stimulation or a direct damage to the membrane. The occurrence of these effects is discussed for each case.


Inhibition and stimulation of rapid axonal transport in vitro by sulfhydryl blockers. The effects of sulfhydryl blocking agents have been studied on the rapid axonal transport in vitro of [3H]leucine-labelled proteins in the frog sciatic nerve. The transport was inhibited in the presence of low concentrations of N-ethylmaleimide (NEM) (greater than or equal to 10(-5) M), p-chloromercuribenzene sulfonic acid (PCMBS) (greater than 10(-5) M) or ions of heavy metals, Cd2+ (greater than or equal to 5 X 10(-5) M), Hg2+ (greater than or equal to 5 X 10(-6) M) and Cu2+(greater than or equal to 10(-4) M). Both the amount and the rate of transported radioactivity were reduced. Transport inhibiting concentrations of these agents also inhibited the binding of colchicine in rat brain or frog nerve supernatants. The amount of transported proteins was increased at an unchanged transport rate by a very low concentration of NEM (10(-6) M), PCMBS (10(-6) M) and Cd2+ (10(-6)M), which did not affect the binding of colchicine. The present results suggest that stimulation of axonal transport can be achieved through an interaction with sulfhydryl groups.


The significance of retrograde axonal transport for the accumulation of systemically administered nerve growth factor (NGF) in the rat superior cervical ganglion. The present study has shown that after intravenous injection of [125I]NGF the time-course of appearance of radioactivity in all organs studied with the exception of sympathetic and sensory ganglia, roughly paralleled that of the blood. The highest levels were reached immediately after injection, after which the radioactivity decayed rapidly within the firsh hour. By contrast, in the superior cervical ganglion there was a small but significant increase within the first hour. After this the radioactivity remained constant for about 4 h and then increased dramatically (7-fold) when the radioactivity in other tissues had declined to very low levels. Measuring the proportion  of radioactivity in the plasma which represents immunologically active NGF, we found that within 30 min after injection all the radioactivity represented unchanged [125I]NGF. After this time the proportion of immunologically active NGF decreased gradually and reached a final level of about 10-15%. Evidence that the radioactivity accumulated in the superior cervical ganglion by retrograde axonal transport represents unchanged [125I]NGF was provided by gel electrophoresis. The results are interpreted as follows: the initial small increase in the sympathetic ganglia may result either from [125I]NGF taken up by short collateral fibres within the ganglion or from a direct accumulation of blood-borne [125I]NGF by the cell bodies of the adrenergic neurones. The dramatic increase occurring after 4 h is caused by the moiety of [125I]NGF reaching the cell body by retrograde axonal transport. This interpretation is supported by autoradiographic studies which showed that 1 h after [125I]NGF injection there was only very sparse  labelling of the ganglion, whereas 24 h later virtually all the cell bodies were heavily labelled. Moreover, it could be shown that the lag period between intravenous injection and subsequent accumulation of [125I]NGF in the adrenergic cell bodies was considerably shorter after transection of the postganglionic fibres distal to the cell body [the transected fibres were allowed to regenerate for 7 days] resulting in a reduction of the distance between the site of uptake and accumulation.


[Development of C cells of the thyroid gland of the rat under an antithyroidian treatment inducing gamma tumors]. In the normal ageing rat is observed a progressive hyperplasia of the C cells. In the rat treated by an antithyroideal drug, the hyperplasia is much more important than in normal. It already appears during the treatment and grows up after its stop. This observation means that the C cells hyperplasia, which reaches later to gamma tumors production, is not due to the TSH oversecreted under the antithyroideal drug influence.


Intracellular distribution of alpha-fetoprotein and albumin messenger RNAs in developing mouse liver. Intracellular distribution of active mRNAs for alpha-fetoprotein (alphaFP) and albumin in fetal and adult mouse liver was studied. Livers were fractionated into nucleus and cytoplasm. The latter was further fractionated by sucrose density-gradient centrifugation into four subfractions, the top fraction containing soluble components, the 1.0 M sucrose layer containing primarily 80S ribosomes, the 1.5 M sucrose layer containing light polysomes and the pellets containing heavy polysomes. RNA was extracted from each fraction and its ability to direct the synthesis of alphaFP and albumin was determined in a mouse sarcoma 180 cell-free system. Distribution of alphaFP and albumin mRNAs in fetal mouse liver was similar; 2% in the nucleus, 98% in the cytoplasm, of which more than 90% was found in the polysome fractions. The results suggest that alphaFP and albumin mRNAs, once formed, are quickly and efficiently utilized for protein synthesis. The major proportion of albumin mRNA in adult mouse liver was also found to be associated with polysomes. However, the amount of translatable alphaFP mRNA was low in all subcellular fractions examined, suggesting that transcription or processing of alphaFP mRNA is defective in adult mouse liver.


Arrangement of morphological subunits in bacterial spinae. The filament, that is helically arranged to form the bacterial spina, is composed of morphological subunits (oligomers) about 5.6 nm in width and 11 nm in length. The oligomers are asymmetrical in that the inner surface is grooved. Image analysis of negative-stained spinae ribbons indicates that the oligomers are paired, possibly beaded structures, the arrangement of which is easily distorted during preparation. In intact spinae, the oligomer orientation may be normal to the filament axis, but in collapsed freeze-etched spinae, the oligomers are inclined at a constant angle of about 72 degrees to the filament axis.


[A RNA extract from oncogenic and non oncogenic strains of Agrobacterium tumefaciens is an indispensable element for the induction of tumors in Datura stramomium]. An RNA bound to the reverse transcriptase of Agrobacterium tumefaciens has been isolated and shown to be oncogenic for stem tissues of Datura stramonium grown under axenic conditions. The tumorous nature of the cellular change induced by the infectious rna was demonstrated by serial grafts of tumors on Datura stems and by cultivation of tumorous tissue in vitro on a medium without supplemental auxins and cytokinins. Active cellular proliferation within tissues of Datura stems was a prerequisite for expression of the oncogenic potential of the RNA. Further, infectious RNA was isolated from avirulent and attenuated strains of Agrobacterium tumefaciens including attenuated derivatives of strain AC58 which have been "heat-cured" of the plasmid associated with virulence. It is proposed that the infectious RNA is an essential but not the sole component of the tumor-inducing mechanism of the crown-gall bacterium.


Characterization of Streptococcus bovis bacteriophages. About 25 Streptococcus bovis bacteriophages were isolated from abattoir wastes, bovine rumen fluid, and lysogenic strains of S. bovis. Eight phages were selected and characterized by morphology, stability, rate of adsorption, single-step growth curve, serum neutralization, and antigenic relationship. Two distinct morphological phage types were found, one of which has not been previously reported for group D streptococci.


Characterization of a temperature-sensitive mutant of Saccharomyces cerevisiae that undergoes uncontrolled protein synthesis. A mutant of Saccharomyces cerevisiae, DW137, isolated after treatment of a wild-type strain with ICR-170. The mutant was respiration-deficient and showed abnormal cell division when grown at 30 degrees C. In addition, the mutant was temperature-sensitive and underwent lysis when grown at 37 degrees C. Random spore analysis, induced reversion profiles, and complementation analysis indicated that the abnormal phenotypes were under the control of a single recessive mutation caused by a base-pair substitution in a nuclear gene. Macromolecular analysis of the mutant at permissive and restrictive temperatures showed that at restrictive temperatures the mutant cannot synthesize DNA. Surprisingly, at restrictive temperatures, protein synthesis in the mutant continued at a rate greater than that observed at permissive temperatures. Cell death and lysis of the mutant could be prevented by treatment of cultures with cycloheximide, an inhibitor of protein synthesis. The data suggest that the abnormally high rate of protein synthesis and the inability to synthesize DNA are jointly responsible for death of the cells, and most probably play and integrating role in the incipient cell lysis.


The problem of caring for the dying in a general hospital; the palliative care unit as a possible solution. The general hospital as a setting for terminal care has disturbing deficiencies: particularly, the medical, emotional and spiritual needs of the patients and their families are generally neglected. Consideration of the options for improving the situation led to the opening of the palliative care unit (PCU) at the Royal Victoria Hospital, Montreal, which is staffed by an interdisciplinary team with a positive and creative attitude to death and bereavement. The palliative care service comprises three areas of care -- the PCU itself, a domiciliary service and a consultative service -- as well as research, teaching and administrative functions.


Use of the Brompton mixture in treating the chronic pain of malignant disease. Physical, psychological, financial, interpersonal and spiritual factors all modify the appreciation of chronic pain. The Brompton mixture is a highly effective, flexible, safe and convenient means of controlling the chronic pain of malignant disease. The mixture is a solution containing morphine; the dose of narcotic can be varied with the need for analgesia. It is given regularly, usually every 4 hours, with a phenothiazine, the main aims of therapy being prevention of pain rather than treatment, an unclouded sensorium and a normal affect.


The Brompton mixture: effects on pain in cancer patients. Terminally ill cancer patients were given the Brompton mixture and a phenothiazine in an attempt to control their pain. The mixture was administered to patients in three hospital environments: a palliative care unit (PCU), general wards and private rooms. Pain was measured in 92 patients with the McGill-Melzack Pain Questionnaire. The Brompton mixture controlled pain in 90% of patients in the PCU and in 75% to 80% of patients in the wards or private rooms. The differences in pain scores between the PCU patients and the other groups were significant. The mixture produced substantial decreases in the three major dimensions of pain: sensory, affective and evaluative. Comparison of these results with data obtained in an outpatient pain clinic showed that the Brompton mixture was strikingly more effective than the traditional methods of managing cancer pain.


Presence of blood group H antigen on a carcinoembryonic antigen, and its enzymatic modification into blood group A and B specificities. A carcinoembryonic antigen (CEA-M) was purified from a hepatic metastasis obtained from a blood group O patient with cancer of the rectum. Using 125I-labeled carcinoembryonic antigen (CEA) and blood group antisera, H specificity has been found on the CEA-M. As the addition of anti-H to anti-CEA does not modify the extent of binding of labeled CEA-M to its antibodies (86%), the H and CEA determinants are carried by the same molecule. The affinity chromatography of CEA-M on an immunosorbent "anti-H-Sepharose" demonstrated that a proportion of CEA-M molecules might bear both H and CEA antigenic determinants. In addition, glycosyltransferases were used to modify the blood group H specificity into blood group A or B specificities.


Temporary interruption of regional blood flow combined with local hyperthermia for cancer chemotherapy. A striking chemotherapeutically curative effect on tumor was obtained by means of temporary interruption of regional blood flow combined with local hyperthermia. By analyzing various basic conditions required for this system using Ehrlich tumor implanted in the hind limbs of mice, the following were found to be essentially indispensable to obtain satisfactory chemotherapeutic effects: (a) a time interval of 1 to 3 min after systemic i.v. administration of drug to the mice, (b) use of a tourniquet on the tumor-bearing mouse limb to stop blood flow, and (c) warming at 37-41 degrees (d) for a period of at least 30 to 60 min. Among the chemotherapeutic drugs tested in the present study, Carbazilquinone (NSC 134679) was the most effective because it revealed the strongest antitumor effect despite its relative innocuousness to nontumorous adjacent normal tissues. Applying the present method, a large syngeneic mouse sarcoma transplanted to the limb 7 days before the experiment also completely regressed in 6 of 9 mice.


Differential mechanisms of increased alpha 1-fetoprotein production in rats following carbon tetrachloride injury and partial hepatectomy. Possible differences in the mechanisms of increased alpha1-fetoprotein (AFP) production following carbon tetrachloride (CCl4) intoxication and partial hepatectomy were studied with 5-week-old rats at the time of sacrifice. The maximum level of serum AFP reached in 4 days after a single dose of CCl4 was much higher than that after partial hepatectomy, although the incorporation of [3H]thymidine into liver DNA increased nearly to the same extent by either of these treatments. In the remnant after partial hepatectomy, the DNA synthesis that was further accelerated by treatment with a lower dose of thioacetamide was not associated with any further increases of serum AFP levels. However, CCl4 given to partially hepatectomized rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats were depressed by Mitomycin C given in vivo, whereas the increases in partially hepatectomized rats were not. Treatment with 8-azaguanine inhibited both increase of serum AFP levels, although the inhibition was much less or was insignificant in partially hepatectomized rats. These results suggest that existence of different underlying mechanisms of the increased AFP production for the two experimental conditions.


Reversibility and irreversibility of liver tumors in mice induced by the alpha isomer of 1,2,3,4,5,6-hexachlorocyclohexane. The characteristics of liver tumors in mice induced by the alpha isomer of 1,2,3,4,5,6-hexachlorocyclohexane (alpha-BHC), were studied with emphasis on their reversibility of irreversibility. Male 8-week-old DDY mice were fed basal diet supplemented with 500 ppm of alpha-BHC for 16, 20, 24, and 36 weeks and then were fed basal diet without alpha-BHC for 4, 8, 12, 16, 24, or 36 weeks. At various intervals, 13 to 20 mice were killed for light and electron microscopic observations. The incidences of liver tumors in mice induced by alpha-BHC increased progressively on continuous administration of alpha-BHC, but when its administration was discontinued some tumors disappeared. Histologically, after alpha-BHC administration for 24 weeks, most tumors were nodular hyperplasias, and there were only a few well-differentiated hepatocellular carcinomas. However, 60 or 72 weeks after the beginning of the experiment, most of the liver tumors were hepatocellular carcinomas and there were only a few nodular hyperplasias. At a later stage, 60 or 72 weeks, the liver parenchymal tissue in nontumorous areas was essentially normal, but small foci were occasionally seen in nontumorous areas that were composed of remaining hyperplastic nodular cells, phagocytic cells, Kupffer cells, and leukocytes. These findings suggest that the reversible tumors were usually nodular hyperplasias whereas the irreversible tumors were hepatocellular carcinomas. After alpha-BHC administration was stopped, many mesenchymal cells infiltrated the nodular hyperplastic lesions, and degenerated liver cells were found. These observations indicate that mesenchymal cell elements may be important in reversing the growth of liver tumors induced by alpha-BHC.


Intracellular distribution of (14C)bleomycin and the cytokinetic effects of bleomycin in the mouse tumor. The differential effects (BLM) on cycling and noncycling cells were investigated with a mouse ascites tumor in vivo. An i.p. injection of 37.0 or 111.1 mug BLM per g caused a decrease in tumor cell number but an increase in percentage of tumor cells in mitosis. There are no significant differences between the percentage labeled mitoses at various times after pulse labeling by tritiated thymidine of BLM-treated tumor cells and by that of an untreated control, except that the height of the second peak was significantly lower in the treated cells. Hence BLM may be cell cycle nonspecific, and the BLM-induced decrease in cell number, i.p., may stimulate some nondividing cells to reenter the division cycle. However, the fact that percentage of cells in mitosis versus time after the administration of BLM showed two peaks indicates the possibility that another cause of the increase in mitotic figures might be a relative increase of cycling cells due to higher sensitivity of noncycling cells to the agent. Autoradiographic studies on the intracellular distribution of [14C]BLM revealed the following. (a) There were few necrotic cells in mitosis that incorporated much [14C]BLM into the cytoplasm at each time point and the mitotic figures gradually increased with time after i.p. injection of the isotope, while necrotic cells other than in mitosis, most of which were heavily labeled, increased in number with time. These findings seem to be related to the possibility that cycling cells may be less sensitive to BLM. The mode of intracellular distribution of [14C]BLM in mitotic cells changed with time and appeared to reflect the drug susceptibility depending on the cell cycle phase when labeled.


The significance of DNA damage in the cell cycle sensitivity of Chinese hamster ovary cells to bleomycin. Chinese hamster ovary cells have been treated with bleomycin at various stages in the cell cycle. Mitotic cells, which exhibit least survival, show the greatest amount of DNA strand breakage and a marked inhibition of DNA replication in the subsequent S phase. Strand-rejoining experiments suggest that this is primarily due to differences in the amount of damage produced in the DNA but does not exclude the possibility that cells at the various cell stages also differ in their ability to repair this damage. DNA breakage also occurs in cells incubated in bleomycin at 4 degrees.


Inhibition of mammalian and oncornavirus nucleic acid polymerase activities by alkoxybenzophenanthridine alkaloids. The alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) have been reported to possess antileukemic activity in mice. These compounds were tested for inhibition of reverse transcriptase activity of an RNA tumor virus and DNA polymerase, RNA polymerase, and polyadenylic acid polymerase activities of NIH-Swiss mouse embryos. Reverse transcriptase and DNA polymerase activities were strongly inhibited by these antileukemic alkaloids, whereas RNA polymerase and polyadenylic acid polymerase activities were only moderately affected. Viral and cellular DNA polymerase activities were potently diminished by the alkaloids when poly[d(A-T)], poly(dA)-oligo(dT), and poly(rA)-oligo(dT) template primers were used in the reaction mixture; however, no inhibition of enzyme activity was obtained with poly(rC)-oligo(dG) as template primer. These results suggest that alkoxybenzophenanthridine alkaloids inhibit DNA polymerase activity by interaction with A:T base pairs of the template primer.


In vivo and in vitro "markers" of human cervical intraepithelial neoplasia. The human uterine cervix offers a unique opportunity to study the early lesions of squamous cell carcinoma, i.e., carcinoma in situ and dysplasia [combined as cervical intraepithelial neoplasia (CIN)]. In vivo, the patients with CIN have the epidemiological common denominators or "markers" of early onset of coitus, multiple sexual partners, 1st delivery before age 20, and antibodies to herpes simplex virus type 2 more frequently than do controls. The lesions themselves have specific epithelial and vascular changes observable with the colposcope in addition to the usual histological markers from biopsy specimens. The chromosomes and DNA content of cells in these lesions are abnormal. In vitro, the cells from CIN have characteristics somewhat between normal and invasive carcinoma. They lack contact inhibition and may be transferred for several generations, in contrast to normal cervical epithelial cells. The fibroblasts from areas adjacent to DIN are different from normal fibroblasts. The mitotic mechanism in cells cultured from CIN has a significantly prolonged prophase and telophase when compared to similar normal cells. The surface of CIN cells, unlike normal cells, has numerous microvilli when examined by scanning electron microscopy and has characteristic differences from normal cells with numerous elongated, irregular microvilli. With the transmission electron microscope, an increase in microvilli and a decrease in desmosomes and tonofibrils are seen in CIN cells. Some of these markers are being used clinically to manage patients with CIN. Other markers are the basis for further investigation of human carcinogenesis.


Functional markers and growth behavior of preneoplastic hepatocytes. Functional markers and growth behavior of abnormal hepatocytes at several stages of liver carcinogenesis were studied. Early lesions, i.e., hyperplastic foci and areas, did not accumulate iron in siderotic livers, had persistent glycogen stores, were not more agglutinable by concanavalin A, and were associated with alpha-fetoprotein secretion, but were not independent secretors of high amounts. The cells in the early lesions had an increased mitotic index, but cells from livers with early lesions did not have an increased survival in cell culture or the ability to grow in soft agar. The more developed lesions, hyperplastic nodules, also did not store iron, had persistent glycogen, did not display increased concanavalin A agglutinability, and were not independent secretors of high levels of alpha-fetoprotein. Similarly, nodule cells were proliferative but did not display an increase in survival in cell culture. In addition, both iso- and autotransplantation of nodules into mammary fat pads resulted in persistence but not growth of nodule cells. On the other hand, hepatocellular carcinomas regularly grew upon transplantation. Thus, early lesions and hyperplastic nodules were proliferative lesions did not possess autonomous growth capability comparable to that of hepatocellular carcinomas.


Precancerous changes in the stomach.

Precancerous changes in the stomach. Intestinal metaplasia is often associated with human gastric carcinoma. Intestinalization seems to be a typical example of abnormal differentiation and is possibly a precancerous state. For investigation of intestinal metaplasia, a method for visualizing disaccharidases using Tes-Tape was developed; this method was applied to many specimens of stomach surgically removed for the treatment of gastric carcinoma. More than 130 specimens of human stomach were investigated. Intestinalization was classified into types I and II intestinal metaplasia. In type I intestinal metaplasia, sucrase, maltase, trehalase, alkaline phosphatase, goblet cells, and Paneth cells were present; while the type II intestinal metaplasia, sucrase and maltase were present but alkaline phosphatase and trehalase were absent. In type II, goblet cells were present but not Paneth cells. The histochemical technique for sucrase was newly devised. Some of the villi with goblet cells in the area of intestinalization in the stomach were not stained by sucrase activity, although most of the villi were stained. The presence of a third type of metaplasia was suggested. Purified sucrases obtained from the intestine and one case of type I intestinal metaplasia showed blood group reactivity due to the oligosaccharide side chain. However, purified sucrases obtained from two cases of type II intestinal metaplasia were negative in blood group reactivity. A close relation between distribution of alpha-fetoprotein and carcinoembryonic antigen in gastric carcinoma and that in surrounding intestinal metaplasia is discussed.


Synthesis and the lethality of bleomycin in bacteria. The bleomycins are antitumor agents composed of various cationic amides of a common inactive bleomycinic acid. At 1 mug/ml at 37 degrees, the naturally occurring spermidine derivative of bleomycin (A5) was far more lethal to Escherichia coli than were several other bleomycins tested. An exponential loss of viability was produced for 2 hr in various strains of E. coli growing in a synthetic medium. In the stringent E. coli, strain 15 TAU (thymine-arginine-uracil) rel A+ (arginine), withholding thymine did not affect the rate of killing. However, uracil starvation completely blocked killing by the antibiotic. Arginine deprival partially inhibited bleomycin killing in the stringent cell but had little effect on the lethality of the antibiotic in a relaxed isogenic strain actively synthesizing RNA. Similar results were obtained with another isogenic pair, stringent CP78 and relaxed CP79. Thus, the lethality of the antitumor agent, bleomycin, which is reported to produce breaks in bacterial and animal cell DNA in vivo and in vitro appeared totally dependent on RNA synthesis in E. coli. Nevertheless, chloramphenicol, which blocks protein synthesis and relaxes RNA synthesis in the stringent strains, also significantly inhibited the lethal action of the antibiotic, reducing the exponential rate of killing.


Preferential localization and rate of loss of labeled alloantibody from rat tumors and skin transplants carrying the corresponding alloantigen. 125I-Labeled rat histocompatibility antibody was prepared from sera of Buffalo rats immunized with a transplantable fibrosarcoma induced by methylcholanthrene in a Fischer 344 rat. After i.v. injection this antibody was shown to localize with high specificity in transplants of a second Fischer 344 tumor or Fischer 344 skin grafts onto immunosuppressed Buffalo rats. These represent conditions such that only tumor or skin grafts carry the corresponding antigen. In skin transplants localization at 24 hr corresponded to 80% and in tumor to 30% of the injected dose in tissue equal to 1% of the rat weight. However, rapid loss of the 125I label from the target tissues indicated that degradation of antibody fixed to target cells was rapid and that the half-time of the intact antibody was less than 2 days.


Human cell-mediated cytotoxicity estimated by lymphocyte titration. Human lymphocyte immunity to tumor-derived target cells was estimated by titrating lymphocyte concentration to achieve a 50% reduction of target cell survival. This lymphocyte titration assay gave estimates of cytotoxicity that were different from those obtained with the conventional cell-mediated cytotoxicity assays but were more proportional to lymphocyte activity. Estimates of cytotoxicity obtained using the lymphocyte titration assay were reproducible upon repeated testin over the course of several months and were relatively unaffected by two- to fourfold variations in target cell concentration. Target cell-specific cytotoxicity was reproducible but often did not appear to be tumor specific.


Cell volume growth after cell cycle block with chemotherapeutic agents. The effects of various chemotherapeutic agents on the volume of Chinese hamster V79 fibroblasts and murine lymphoma L5178Y cells were studied by electronic volume spectroscopy. Cells arrested in the division cycle by a chemotherapeutic block continued to grow in volume resulting in abnormally large cells unable to reduce their volume by cell division. This was observed in cells treated with colcemid, vinblastine, excess thymidine, hydroxyurea, ARA-C, 5-fluorouracil, actinomycin-D and bleomycin, but not with puromycin or cycloheximide. Increase in cell volume of blocked cells was correlated with a decrease in cell survival as measured by clonogenic ability. The results suggest the possibility of volume spectroscopy for a rapid in vitro test to determine tumor sensitivity to chemotherapeutic agents and the in vivo monitoring of response to chemotherapy. Mechanisms for increased cell kill by a second agent acting selectively on enlarged cells are considered.


Ultrastructural localisation of proteoglycans in the odontoblast-predentin region of rat incisor. The localization of proteoglycans in the predentin of the rat incisor was investigated by ultrastructural histochemistry. Ruthenium red stained the cell coat of the odontoblasts as well as intracellular vesicles. There was also a staining of the extracellular matrix, but not of collagen fibers in the predentin. Treatment with the enzyme hyaluronidase prior to staining with ruthenium red abolished the staining of the vesicles and the extracellular matrix but not that of the cell coat. Bismuth nitrate and phosphotungstic acid gave similar staining of odontoblast vesicles and extracellular matrix. It is likely that the stained structures contain proteoglycans. The importance of these proteoglycans and their ultrastructural localization are discussed in relation to intracellular transport and the calcification process.


A critical evaluation of the relationship between the presynaptic network, synaptic vesicles and dense projections in central synapses. Synapses of the oculomotor nucleus of Echidna have been examined ultrastructurally with the aim of integrating data obtained from osmicated and nonosmicated PTA stained material. Particular emphasis has been laid on the relationship between the synaptic vesicles of the osmicated material and the presynaptic network and vesicular grid of the PTA material. This relationship has been explored qualitatively by examining osmicated material of varying qualities of fixation. Such material contains dense projections in addition to synaptic vesicles, and various vesicular network appearances. A variety of measurement techniques have shown that the PTA network is characterised by reticular strands, spaces, and regular hexagonal units smaller than vesicles, these observations prompting the formulation of a "vesicle-network coincidence" model of the presynaptic terminal. This model has been tested by tracing the profiles of vesicles within the PTA network and comparing their size and shape frequency distributions with those of osmicated synaptic vesicles. The distributions have been found to be essentially similar, suggesting that vesicles can be located within the network, and that the hexagonal network units are formed only in the presence of an underlying vesicular matrix. Additionally, the following points have emerged: 1) the dense projections in the two types of material appear to be quivalent; 2) a loose correlation exists between dense projections and vesicles in osmicated terminals, increase in the area of the dense projections being associated with a decrease in the area of the vesicles; 3) network and dense projection units are similar. In view of the similarity between network and dense projection units, the demonstrated vesicular basis of the network raises the question of whether dense projections are entirely independent structures, or whether they depend in part for their existence on the nearby presence of synaptic vesicles.


Immunocytochemistry of pituitary corticotroph cells in terrestrial turtle (Testudo mauritanica). The immunocytochemical and histochemical characters of the corticotroph cells of the Turtle adenohypophysis have been studied. These cells are localised in the rostral part of the gland and are revealed by Is anti ACTH (1-24) and (17-39). They are also colored with lead hematoxyline and PAS-Orange G. The corticotroph nature of these cells is confirmed by the study of their modifications after treatment with amphenone and ACTH. The Is anti ACTH also reveal most of the cells of the pars intermedia; while the Is anti beta-MSH reveals only these cells and some scatter cells of the pars distalis.


[Study of prostaglandin synthesis during anaphylactic shock in guinea pigs]. In guinea pigs actively sensitized with ovalbumin and shocked, we have measured blood histamine and histaminase, pulmonary content in cycli AMP and prostaglandins (PG) E1, E2 and F2alpha. In pulmonary efferent blood, both PGE and PGF are increased. In lung tissue, only PGF2alpha, which are bronchoconstructive mediators, are increased. Th increased level in PG seems to have two origins: first a specific increase, then an increased synthesis secondary to histamine release.


Cryptogenic pulmonary eosinophilia.

Cryptogenic pulmonary eosinophilia. The clinical and immunological features of fifteen cases of cryptogenic pulmonary eosinophilia are reported. There were ten women (mean age 35.4 years) and five men (mean age 42 years). Eight gave a previous history of asthma and seven had none. Thirteen of the fifteen patients had negative skin test to common allergens. Many features of a systemic illness were present in the asthmatic and non-asthmatic groups including anaemia, weight loss, fever and a grossly raised ESR. An absolute polymorphonuclear leucocytosis was frequent as well as the obligatory increase in blood eosinophils used as one of our criteria for inclusion. Hepatomegaly (three cases), splenomegaly (four cases) and hilar node enlargement (one case) were seen in the group without asthma. Evidence of renal involvement or necrotizing vasculitis was notably absent and the response to small doses of corticosteroids was dramatic. Immunologically the striking feature was a disproportionate increase in blood eosinophils compared with only minor elevations in the total serum IgE levels. This stands in contrast to patients with bronchopulmonary aspergillosis and helminth infestation. Studies of cytophilic antibodies using histamine liberation after challenge with antibodies to immunoglobulin sub-classes in six patients showed a marked increase in IgG2 and lesser increases of IgE and IgG3. No evidence of antibodies specific to A. fumigatus was found. The amount of cytophilic antibody was also in contrast to that found in bronchopulmonary aspergillosis.


alpha1-Fetoprotein measurement in blood spotted on paper: discriminating test for hereditary tyrosinemia in neonatal mass screening. We describe an electroimmunodiffusion technique for measuring alpha1-fetoprotein in blood spotted on chromatography paper. The system is being used as a complementary test in a neonatal mass-screening program for detection of inborn metabolic diseases in the Province of Quebec. In a series of 102 cases of neonatal hypertyrosinemia, the test has proven to be highly discriminative for hereditary tyrosinemia. It has permitted early detection of eight cases of this disease, including two that would have been missed by the previously used screening procedure, tyrosine measurement only. The test not only virtually eliminates the risk of misdiagnosis or missed diagnosis, but also permits earlier diagnosis of hereditary tyrosinemia and considerably reduces the follow-up work required for newborns with transitory tyrosinemia. The AFP test is simple, fast, practical, and inexpensive. Combined with tyrosine determination, it constitutes an optimal device for mass screening of hereditary tyrosinemia.


Androgens.

Androgens. Testosterone is synthesised mainly if not entirely by the leydig cells and secreted episodically with a slight circadian variation. Only the free, nonprotein-bound fraction of the testosterone in the circulation is biologically active. This free testosterone passes into the target cells and is taken up by specific receptors in the muscle. In some other target tissues, testosterone is first reduced to 5alpha-dihydrotestosterone which is then taken up by specific receptors in the cytoplasm and transferred to the nucleus. Anti-androgens appear to act principally by inhibiting this uptake.


Clinics in endocrinology and metabolism. Investigative procedures. In patients with hypogonadism, the exact cause of the deficient androgenisation is not always clinically apparent. The data presented demonstrate that by means of hormone measurements, basally or after stimulation tests, the exact level of the lesion can usually be determined. This allows a decision with regard to appropriate therapy to be made on the basis of an accurate diagnosis. In many instances basal measurements of pituitary and gonadal hormones are all that is required to decide the level of the lesion. Care in interpreting basal levels is required, however, in view of methodological limitations and of known physiological variations with age, time of day and hour-to-hour fluctuations. If the basal hormone levels are borderline, or if the 'reserve function' of part or all of the hypothalamic-pituitary-gonadal axis needs to be assessed, than the appropriate stimulation test should be performed. The indication for these stimulation procedures and results obtained in different conditions are described and problems of interpretation discussed.


Testicular tumours.

Testicular tumours. With modern methods of diagnosis, staging and treatment, seminoma is a highly curable tumour. The worse results for the treatment of teratomas are likely to improve particularly as methods for detection of the tumour improve and as types of treatment are increasingly combined in a way which takes account of the biology of the tumour and the strength and limitation of each treatment modality. Stage I and II teratoma should receive irradiation after orchidectomy although when bulky retroperitoneal disease is present irradiation alone is rarely capable of securing local tumour control. In these cases chemotherapy may achieve nodal regression preparatory to irradiation. Excision of residual masses after irradiation should be considered in teratoma. Chemotherapy is the treatment of choice for disseminated teratoma but maintaining tumour control poses problems. Whole lung irradiation following chemotherapy is being assessed in selected patients.


Description of the banding patterns of human chromosomes by acriding orange reverse banding (RFA) and comparison with the Paris banding diagram. A reference diagram is presented which is comparable to the Paris banding diagram but which was based primarily on chromosomes studied by acridine orange reverse banding. Comparison with the Paris Conference (1971) banding diagram was made. Bands were combined in 13 instances and subdivided in 10 cases. The number of bands was found to depend primarily upon the length and quality of the chromosomes. No major differences between the present diagram and the Paris banding diagram were observed. Moreover, the results with acriding orange reverse banding were comparable to those previously reported with Giemsa R banding. In addition, sequential Q banding and R banding were carried out in the same cells. No significant differences in resolution of bands were observed when these two techniques were compared.


Alpha-fetoprotein and the prenatal diagnosis of central nervous system disorders. A review. The use of amniotic fluid alpha-fetoprotein measurements in the early prenatal diagnosis of central nervous system disorders is reviewed. The method is sensitive and specific and has had a pronounced effect on the counselling of mothers who have already had a child with spina bifida or anencephaly. Measurement of other amniotic fluid components, such as fetal macrophages, beta-trace protein, alpha2-macroglobulin or fibrinogen-degradation products, is less reliable and these should not be used in making primary diagnoses. The assay of alpha-fetoprotein in maternal serum shows signs of being a useful preliminary screening process, and may identify pregnancies where amniocentesis and confirmatory amniotic fluid determinations should be offered.


[Hyperthyroidism with hypercalcaemia (author's transl)]. Anorexia, constipation, vomiting and somnolence in a 39-year-old woman were at first misinterpreted as being of psychological and autonomic nervous system origin. Further clinical and biochemical tests revealed hyperthyroidism associated with hypercalcaemia and hypercalciuria. Thyrostatic treatment for 12 days caused regression of the hypercalcaemia and, after subtotal resection, serum calcium levels and urinary calcium excretion returned to normal for good. The hypercalcaemia syndrome must therefore be assumed to have been the direct result of the hyperthyroidism.


[Embolisation of the finger arteries in the thoracic outlet syndrome]. Angiographic studies were undertaken in 18 patients with the signs of a thoracic outlet syndrome due to compression of the subclavian artery, associated with Raynaud's phenomenon. They demonstrated occlusion of the digital arteries in more than half the cases, on the side of the subclavian compression. In three patients with ischaemic pain in the fingers of only a few hours' or days' duration arteriography demonstrated fresh embolisation from the compressed subclavian artery.


Hyperthyroidism: diagnosis and treatment. The clinical diagnosis in cases of suspected hyperthyroidism is very valuable. Laboratory diagnosis rests largely on measurements of circulating thyroid hormones, with radio-iodine studies playing only a minor part. No one test is infallible and some understanding of basic physiological considerations is essential if serious errors are to be avoided. The choice of treatment plan is logically-based, but should take into account the quality of available services.


Sleep satiation in narcoleptic patients. Polygraphic sleep recording was performed in 20 narcoleptics with one or more of the auxiliary symptoms, 4 narcoleptics with only sleep attacks and 10 normals during one night and into the following day. Total sleep time in the narcoleptics did not differ significantly from that in the normals. Sleep of the narcoleptics with auxiliary symptoms was unstable with frequent awakening. The temporal organization of the REM--NREM sleep cycle was irregular in the narcoleptics with auxiliary symptoms, compared with those in the other two groups. Percentage of Stage 1 was significantly larger in the narcoleptics with auxiliary symptoms than in the other two groups and percentage of Stage 2 was smaller. Percentage of Stage 4 was smaller in the narcoleptics with auxiliary symptoms than in those with only sleep attacks. Percentages of Stages 3 and REM did not differentiate the three groups. Spindle density during Stage 2 did not differentiate the three groups. Sleep onset Stage REM was frequently observed exclusively in the narcoleptics with auxiliary symptoms. Excluding the instances showing sleep onset Stage REM, mean latency of initial episodes of REM sleep in the three groups was shorter after daytime sleep onset than after nighttime sleep onset. In the narcoleptics with auxiliary symptoms, no significant correlation was found between the percentage of Stage REM and clinical findings. the sleep attacks in narcoleptics are due to an ill-timed, strong tendency to fall asleep (including both REM and NREM sleep), and it is therefore suggested that they are manifestations of their disturbed circadian rhythm of sleep--wakefulness cycle.


Extinction of the Hoffmann reflex by antidromic conduction. We have shown that one cause of the extinction of the Hoffmann reflex by antidromic conduction in the alpha motor axons must be a relative refractoriness of the motoneuron pool. A hypothesized collision between the H-wave and the antidromic M-wave component is not disproved but it (and the incumbent assumptions about relative afferent and efferent conduction velocities) is shown to be unnecessary. A montonic variation of the M-wave with tonic soleus contraction (M-wave increasing with contraction) is observed but not explained.


Computer recognition of generalized spike-wave discharges. Twelve 12h daytime telemetered EEGs were read for generalized spike-wave (S-W) bursts by a computer and independently by three experienced electroencephalographers. The computer system was a hybrid of analog devices (tape-recorder, voltage summator, and high-pass filters) and a multipurpose laboratory digital device (PDP-12). The computer was programmed to identify only the location on the record and the duration of the generalized S-W paroxysms. From 1,462 discharges identified by both the readers and the computer, a consensus list of 609 was derived by selecting only those bursts identified by all three readers. The computer recognized 516 (85%) of those bursts on the consensus list; the computer's accuracy, as compared with the consensus, rose to 92% when portions of the EEG containing sleep were discounted. The computer also recognized as generalized S-W paroxysms 15 high-voltage transients, which none of the three readers selected. Ten of these, however, occurred during sleep. When the computer results were added to those of the three readers to permit a four-way inter-reader comparison, the computer was found to have had about as many isolated decisions as any of the three readers. In the number of bursts recognized, the computer tended to be about as conservative as the reader under whose guidance it was originally programmed. The computer's accuracy in measuring burst duration was not evaluated statistically.


Evidence for the presence of eye movement potentials during paradoxical sleep in cats. 1. Phasic activities related to eye movements in the dark in abducens nucleus (N.VI), lateral geniculate body (LGB), visual cortex, and lateral rectus muscle were analyzed in 18 cats with chronically implanted electrodes during waking and sleeping. 2. N.VI waves, both during waking and sleeping, were multiphasic, and two distinct wave forms were noticed on either side of the pons. The N.VI waves preceded each ocular movement by 10--20 msec. 3. Both during waking and paradoxical sleep (PS), N.VI waves always preceded those occurring in the LGB. During waking, eye movement potentials (EMPs) in LGB followed the onset of the N.VI wave with a long (greater than 60 msec) and variable latency, but followed the end of the same wave with a rather constant delay (about 20 msec). During PS, two distinct populations of latency were observed between onset of the pontine waves and that of LGB waves. The latency of one population was less than 35 msec, and of the other more than 66 msec. 4. Since the LGB waves following N.VI waves with a long latency were similar in a number of respects to EMPs during wakefulness (EMPw), they were judged to be EMPs (EMPps), and were distinguished from LGB PGO waves, which followed N.VI waves with a short latency. Cortical EMPps were observed as well, but occurred about 8--10 times less frequently than the PGO wave. 5. In the light of the present results, the mechanisms responsible for EMP and PGO wave activities are discussed.


Effects of ponto-mesencephalic lesions and electrical stimulation upon PGO waves and EMPs in unanesthetized cats. 1. Phasic waves similar to those observed in the visual system of the awake and sleeping cat ("EMP" and "PGO waves" respectively) were recorded in an area surrounding brachium conjunctivum of the mesencephalic reticular formation (MRF). 2. MRF waves during paradoxical sleep (PS) (MRF PGO wave) occurred 1--2 msec after the waves recorded in the abducens nucleus (N.VI PGO waves), while MRF waves in the alert cat (MRF EMPs) occurred 35--70 msec or more after EMPs in N.VI. 3. Both MRF EMPs in the dark and MRF PGO waves preceded EMPs and PGO waves recorded in the lateral geniculate body (LGB) by 20 msec. 4. There was a time lag of about 40 msec between right and left MRF PGO waves. 5. MRF stimulation elicited short latency responses (5--9 msec) in LGB during waking and sleeping states. During PS, the same stimuli further elicited PGO waves (latency greater than or equal to 40 msec) in the same structure. 6. Stimulation of LGB elicited short latency responses (5--9msec) in MRF. 7. Unilateral MRF lesions reduced by about 50% the number of LGB PGO waves without modifying other characteristics of the PGO wave activity. 8. Following unilateral MRF lesion, LGB EMPs were observed with each eye movement in the dark. However, LGB EMPs ipsilateral to the lesion were greatly reduced in amplitude and followed the EMPs in the opposite LGB by a time lag similar to that observed between bilateral LGB PGO waves. 9. Bilateral MRF lesions completely abolished PGO waves and EMPs observed with the animal in the dark. However, EMPs observed in the light remained unmodified. 10. From the present study it was concluded that LGB and visual cortex gross potential changes related to eye movements in the alert cat have both retinal and non-retinal components. Further, the significance of the MRF area in the mechanisms of EMP and PGO wave activities was discussed.


Cyclic EEG and motility patterns during sleep in restrained infant rats. When restrained in a quasi-fetal position, infant rats (2--3 weeks old) remain for an extended period in a sleep-like state as judged by polygraphic criteria. Moreover, they become very difficult to arouse by sensory stimuli, and show a level of spontaneous motility considerably higher than is normally found at this age during sleep. Phasic generalized body movements, which are often quite stereotyped, occur in trains at regular intervals, against a low background level of neck muscle tonus. The amplitude of the cortical EEG, especially in the delta band, is negatively correlated with the frequency of spontaneous motor burst activity. It is suggested that these REM-like "rapid body movements" in immature mammals may well represent a transitional stage between fetal behavior patterns and sleep motility in the adult organism.


[Sleep in the young adult studied through automatic analysis of recordings]. Our laboratory sleep polygraphic recordings are all automatically scored by a scoring system previously described. The automatic scoring reliability has already been estimated by a comparison with visual scoring. Nevertheless, it was interesting to investigate whether the picture of sleep given by this system, of a precisely defined group of subjects, was very different from that obtained by visual scoring for similar subjects in other laboratories. Therefore, we compared the results given by automatic analysis in a group of normal subjects aged 20--29 years with the results of Williams et al. (1974) for subjects of the same age. We thus mixed on purpose three sources of difference: the studied population, the laboratory and its habits, and the technique of scoring the records. This comparison showed a clear difference in the total time of sleep for men and women. This time, longer in our conditions, depended certainly on subjects and on recording conditions more than on automatic scoring. Sleep and stage latencies were not significantly different by the two scoring techniques. A difference appeared for waking latency, longer in our findings, but probably resulting from the definition of this parameter. The number of sleep cycles and their average duration were not different in the two techniques. Concerning sleep stages, stage 3 was slightly overestimated and stage 4 underestimated by automatic scoring compared with visual scoring, while there was no marked difference for the other stages. Finally, a larger number of stages are detected by the machine than by the human eye, which is probably due to the fact that the latter neglects some transitions from one stage to another when they are not important with regard to the context. Thus, apart from some differences resulting from the definition of parameters, there is a very large analogy between visual and automatic results of sleep scoring. The only effects of the latter are a slightly different assessment of the ratio of stages 3 and 4, in favour of stage 3, a larger estimate of the number of sleep stages, and a slight underestimation of REM sleep.


Audio-spinal influence in man studied by the H-reflex and its possible role on rhythmic movements synchronized to sound. An investigation was made of the time course of audio-spinal influences in man using the H-reflex technique and non-startling sounds. It was found that in all subjects the sound potentiated the H-reflex at a central latency of 80 msec, the peak facilitation (185%) being attained at 110--130 msec. The mean duration of this facilitation was 200 msec ranging from 120 to 460 msec. No inhibition was seen to follow the excitatory period. An habituation study showed a significant drop in peak facilitation after exposure to ten conditioning stimuli but a constant increase of the H-reflex above control level even after 60 presentations. The time course of this audiospinal facilitation was superposed over the EMG events during hopping to a simplified musical stimulus. In this situation, landing occurred some 50 msec prior to the ON beat or strong beat of the music. With this mode of synchronization, the timing of the ON and OFF beats of the musical stimulus would be suitable to potentiate the EMG events related respectively to the peak upwards acceleration determining the take-off and to the landing. It is inferred that during synchronized stereotyped movements to repetitive auditory stimuli, the motor events are timed to make best use of a potential audio-spinal facilitation.


A glass-insulated "Elgiloy" microelectrode for recording unit activity in chronic monkey experiments. A glass-coated microelectrode made of a stiff cobalt--nickel alloy is described. The thickness of the glass coating and the length of the uninsulated tip can be varied as desired. The electrode is stiff enough to insert through the relatively tough dura of the monkey in chronic experiments. Further, the recording site can be marked by electrolytic deposition of iron and the Prussian blue reaction.


Effects of sleep of restricted sleep. A cat case study. One male cat was adapted to different schedules of restricted sleep. The cat was allowed to go to sleep during a certain number of hours per day. During the rest of the 24 h period, wakefulness was enforced by means of a treadmill. The following schedules of restricted sleep were run: 12 h sleep--12 h treadmill (12S--12T), 8S--16T, 4S--20T. The cat was also adapted to a 36 h day: 12S--24T. The sleep was investigated after at least 2 weeks on each schedule and compared to ad lib. sleep (24S--0T). As available sleep time bacame shorter, the composition of the sleep changed. LSWS (in % of available sleep time) decreased, while DSWS % and REM sleep % increased. The length of the DSWS and REM sleep episodes increased with decreasing sleep time, as did sleep cycle length.


Evoked potential waveform differences produced by the perception of different meanings of an ambiguous phrase. To test the effects of perceived linguistic meaning on evoked potential (EP) waveform, an experiment was performed using the stimulus homophone "led" or "lead" in the single ambiguous phrase "it was /'led/". The phrase was presented aurally in sets of 60 repetitions, instructing the subject before each set as to the specific meaning of the stimulus word to be perceived. Averages of one hundred responses were obtained for each of the two meanings of the stimulus. Responses were recorded from scalp locations over Broca's and Wernicke's areas and homologous right hemisphere loci. Average waveforms evoked by the two meanings of the stimulus word were dissimilar for the left anterior locus and similar for the other three loci as indicated by correlations. The application of the Discrimination Index to these data disclosed that the EP waveform differences observed at the left anterior locus would not be attributed to random variability. Stepwise Discriminant Function Analysis on the same data revealed that responses from individual subjects could be classified according to experimental conditions at a greater-than-chance level. Discrimination was best for responses from left hemisphere loci. There was some commonality of discriminative EP components across subjects, specifically components late in the EP epoch. These data are interpreted as demonstrating an EP correlate of the processing of the contextual meaning of words.


Influence of color on the photoconvulsive response. Using the visual stimulator, the effect of color on the photoconvulsive response (PCR) was studied in 14 photosensitive patients. When stimuli of 15 c/sec flickers of white, red, yellow, green and blue light of 20 cd/m2 were given to the subjects, generalized PCRs were provoked only by the red-flicker. These PCRs were all inhibited by blue light of 1.9 cd/m2 when given either after the appearance of the PCRs or simultaneously with the red-flicker from the start. When blue light was given after the appearance of the PCRs the latency of appearance of the PCRs in response to the red-flicker showed an inverse relation to the disappearance latency of the PCR in response to the blue light. With blue light of 1 cd/m2, however, inhibition of the PCRs was seen in only 2 cases when it was given after the appearance of the PCR, and in only 1 case when the blue light was simultaneously given with the red-flicker from the start. These results clearly disclosed the following findings: (1) among various colored lights, an excitatory effect on generalized PCR was excitatory effect on generalized PCR was always seen only with red light at 15 c/sec and 20 cd/m2; (2) the PCRs provoked by the red-flicker were inhibited by blue light of 1.9 cd/m2, but not by blue light of 1 cd/m2.


Visual evoked potentials during the development of a spiking cobalt focus in rat neocortex. Averaged visual evoked potentials recorded from three electrode placements in visual cortex in response to single and paired light flashes were acquired from rats with epileptogenic cobalt implants or with stainless-steel control implants. Evoked potentials acquired after computer-detected epileptic spikes were also recorded from rats in the cobalt group. Epileptic spiking began between the 6th and 9th postoperative days and flashes then began to evoke epileptic spikes. Excitability cycles were assessed. On the day showing the maximum rate of spiking, excitability at the site of the cobalt was markedly reduced following flash-triggered or spontaneous epileptic spikes in almost all cases. By contrast, the electrode placement in contralateral homotopic cortex showed nearly normal excitability despite the presence of large amplitude epileptiform spikes and sharp waves projected from the site of the cobalt. The results are discussed with reference to other experimental findings.


Synchronization of the electrocorticogram by visceral and somatic bradykinin stimulation in anesthetized cats. The cortical response to visceral and somatic bradykinin stimulation was studied in cats under light to moderate pentobarbital anesthesia. Following the injection of bradykinin into arteries supplying visceral organs and somatic structures, a marked cortical synchronization was recorded. The bilateral, rhythmic discharge in the theta to alpha range was best seen on SI; occasionally the contralateral SI response was more prominent. The cortical synchronization and its distribution were the same for visceral and somatic stimulation. There was only minimal response desensitization to multiple injections of bradykinin in rapid succession. Following transection of the thoracolumbar spinal cord, synchronization failed to develop after hindlimb injections but continued to be seen after forelimb stimulation; similarly, partial denervation of a limb blocked the bradykinin response. No synchronization or desynchronization could be produced by epinephrine and nitroglycerine which caused phasic changes in systemic blood pressure equal to or greater than those seen with bradykinin. The results are discussed in terms of possible pathways and receptors. It is suggested that bradykinin acts primarily on free nerve endings common to visceral and deep somatic tissue with convergence of impulses occurring at spinal and higher levels. The preferential response of SI may reflect afferent activity generated by natural, painful stimulation of deep somatic and visceral organs. Normally, this component would be masked by the concomitant non-specific arousal response of the medial reticulo-thalamic system which was depressed by the anesthetic.


Driving of slow oscillations in the human somatosensory system. Potentials evoked by brief electrical pulses applied to the median nerve, were recorded from the frontal, central and vertex regions of human subjects. Averaging and spectral analysis showed that the responses contained time-locked components ranging in frequency from 0.75 to 4 c/sec and extending over periods as long as 3500 msec after the stimulus. There was no significant difference between evoked potentials induced by stimuli which were accompanied by a twitch in the muscles innervated by the median nerve and evoked potentials induced by stimuli which caused no muscular response. Stimulation by pulses separated by random intervals caused an increase in the amplitude of the late components over a broad frequency spectrum while periodic stimulation caused an increase in amplitude in much narrower ranges. When the frequency of stimulation was progressively increased from 0.25 to 5 pulses/sec it was found that the late oscillations could be "driven" at specific frequencies which caused an increase in the amplitudes of specific frequency components, harmonically related to each other and to the frequency of the stimulus. In a few instances in which a series of 125 individual evoked potentials was studied, it was found that the average computed from the last 50 potentials contained late components of considerably lower amplitudes than the average computed from the first 50 potentials. The administration of barbiturates caused a selective decrease in the amplitude of the late components and a redistribution of energy in the frequency spectrum. The essential characteristics of these late components: their wide distribution over the frontal, central and vertex regions, their occurrence over long periods after the stimulus, the decrease in their amplitude with repeated stimulation, indicating the possibility of "habituation", and their enhancement at specific frequencies of stimulation, suggest that they may be related to the activities of the nonspecific systems of the brain.


A simple sleep stage detector for the rat. A simple sleep stage detector for the rat is described, which uses as its sources of input the signal from a single hippocampal recording electrode and the signal generated by a motion indicator. The device is suitable for use in sleep studies and in experiments on REM sleep deprivation.


Termination of pregnancy by sheep anti-LHRH gamma globulin in rats. The effect of the administration of sheep anti-LHRH gamma-globulin (anti-LHRHG) on the maintenance of pregnancy was investigated in rats. Nidation was confirmed by laparotomy on day 7 or 8 of pregnancy. In one experiment, rats were then injected iv with 1 ml anti-LHRHG or normal sheep gamma-globulin (NSG) daily from days 7 to 11. The uteri were inspected again on day 14 of pregnancy, when it was found that complete resorption of the fetuses had occurred in the anti-LHRHG-treated rats, but that the fetuses were normal in the NSG-treated control rats. The effect of a single injection of 1 ml of anti-LHRHG on day 7, 8, 9, 10, 11, or 12 of pregnancy was also investigated. Administration on day 9 or 10 resulted in complete resorption of the fetuses by the time of the 2nd inspection on day 14, and treatment on day 8 or 11 was partially effective. However, treatment on day 7 or 12 exerted little effect on viability of the fetuses. None of the rats showed vaginal bleeding following treatment with anti-LHRHG. Termination of pregnancy by anti-LHRHG could be prevented by SC injection of 1 mug LHRH twice daily, or by 4 progesterone SC once daily, from days 9 through 12 of pregnancy. The ovaries of the rats treated with anti-LHRHG from days 7 to 11 were smaller than those of the NSG-treated control rats, and some of the corpora lutea underwent cystic degenerative changes. Lutein cells of the former were also smaller than those of the latter. Serum progesterone levels were reduced after a single injection of anti-LHRHG on day 9 or 10, but not on day 7 or 12 of pregnancy. There was excellent agreement between the reduction of serum progesterone and fetal resorption. Serum LH levels were low on days 7 through 12 in the anti-LHRHG-treated as well as the NSG-treated rats, and the possible suppressive effect of anti-LHRHG on LH could not be revealed because of insufficient sensitivity of the radioimmunoassay method. No significant difference was observed in serum prolactin levels between the groups of rats. The results clearly indicate that LHRH, by maintaining progesterone secretion, is indispensable on days 9 and 10 of pregnancy for the maintenance of pregnancy.