[Lytic enzymes produced by Actinomyces levoris].

The composition of the enzyme complex produced by Actinomyces levoris which exhibits lytic action on the cell walls of Streptococcus lactis was studied by gel filtration on Sephadex G-25, ion exchange chromatography and isoelectric focusing. The complex was found to contain at least seven enzymes having different isoelectric points and substrate specificity. The enzymes were divided into three groups. (1) The enzyme with pI 10.2 seems to be a specific glucosidase; it possesses a high activity of the cell wall lysis and lacks a proteolytic activity. (2) The enzymes with pI 9.2 and 9.0 are, apparently, specific lytic proteases; they display both lytic and proteolytic activities. (3) The enzymes with pI 10.0, 9.5, 5.7 and 4.2 are, presumably, non-specific lytic proteases; they have a low lytic activity and a high proteolytic activity.


[Acylase activity of mycophilic fungi].

The acylase activity was studied with 65 cultures of mycophilic fungi belonging to 56 species and 33 genera. Among these: 9 species displayed the acylase activity toward ampicillin; 8 species, toward phenoxymethylpenicillin; 6 species, toward benzylpenicillin; and 21 species manifested the complex activity. Many of the active species belonged to the bionecrotrophic group of mycophilic fungi, the number of necrotrophic fungi was less, while that of biotrophs and saprotrophs was even lower.


[Intracellular oxygen and the radiosensitization of cells of the blue-green alaga, Anacystis nidulans].

The photosynthetic system of the blue-green alga Anacystis nidulans was inactivated by 30% at a dose of 100 krad of gamma irradiation in N2. If the cells were irradiated in N2+2% CO2 in the light, their radiation sensitivity was increased with an oxygen enhancement ratio of 2.0. Neither light nor CO2 taken separately affected radiosensitization of the cells which increased almost to the same extent as under aerobic conditions in the presence of both light and CO2. The intracellular oxygen of the photosynthetic origin caused apparently the same radiosensitization as oxygen derived from the extracellular sources.


[Multiplication of Bdellovibrio bacteriovorus in the cytoplasm of the bacterial host].

The bacterial parasite Bdellovibrio bacteriovorus was studied in the process of its interaction with the host bacterium Pseudomonas fluorescens. As has been shown by time-lapse microcinematography, along with the normal growth of B. bacteriovorus in the periplasmatic space of the host bacterium, occasionally (4--5%) the parasite is located in the cytoplasm where the complete stage of its intracellular growth takes place with the release of progeny.


Delta factor can displace sigma factor from Bacillus subtilis RNA polymerase holoenzyme and regulate its initiation activity.

A protein with a molecular weight of 21,000 daltons is found associated with a fraction of Bacillus subtilis RNA polymerase core. This protein (delta) does not react with antibody made against sigma factor and has a peptide map which is significantly different from sigma factor. At ratios of 2:1 to 4:1 (delta:holoenzyme) the delta displaces sigma factor completely from the core and associates in a 1:1 ratio with core to form delta-core. Under the same incubation conditions sigma factor at a ratio of 10:1 (sigma factor:delta-core) does not displace delta from the delta-core. The delta-core has much less activity as compared to holoenzyme on various DNA templates. However, sigma factor does stimulate the activity of delta-core enzyme under conditions of RNA synthesis. These observations and the results of others suggest that delta-core enzyme binds initially to specific DNA sites followed by delta release from the core-DNA complex and that the sigma factor binds to the core-DNA complex to initiate RNA synthesis. Thus both delta and sigma factors are required in a sequential fashion for specific transcription to occur in B subtilis.


Calculations for beam-flattening filters for high-energy x-ray machines.

A flattening filter is an important component in a medical accelerator to modify the photonbeam properties. To simplify the calculations of the flattening-filter profile, we have developed a computer program which sums primary and scatter and then makes iterations in the primary component to produce a desired total-dose profile. The program can account, to first order, for radial spectral changes by using an effective primary attenuation coefficient which varies with radius. Calculations made to model the Clinac-4 dose profiles using the measured variation of half-value layer with radius show good agreement with the measured data. It is shown that the variation of quality within the beam impairs the flatness that can be achieved over a range of depths. Since perfect flatness cannot be achieved for small and large fields with one flattening filter, one may choose a primary profile which is a compromise over a range of field sizes and depths. A compromise profile for a 4-MV beam is discussed.


The role of X-linked lethal and viable male-sterile mutations in male gametogenesis of Drosophila melanogaster: genetic analysis.

The possibility that viable male-sterile mutations occur in vital genes and the role played by lethal mutations and viable male-steriles in male gametogenesis were studied. Five sterile loci were identified among the 30 most proximal vital loci of the X-chromosome and two of them were shown to be allelic with lethal mutations. Fertility test on gynanders for nonautonomous lethal mutations proved that vital genes operate autonomously in male gonads, independently of their effect on somatic tissues. Fertility tests of ts lethals, shifted to the nonpermissive temperature after the TSP, showed that 40% of vital genes function in male gonads. It is further shown that about the same proportion of vital genes is operating in female gonads and that the two groups overlap by about 70%. The role of viable and lethal male gametogenesis is discussed in detail.


The effect of inversions on mitotic recombination in Drosophila melanogaster.

The effect of inversions on mitotic recombination outside the inversion was studied in inversion-heterozygotes. Seven euchromatic inversions of the X-chromosome, with breakpoints within the interval between two cell markers, were chosen. The size of the inverted region and the distance from the proximal breakpoint to the proximal cell marker varied. Mitotic recombination was X-ray induced in larvae and clones scored in the tergites of emerged adults. The frequency of recombinants between both cell markers and the frequency of recombinants proximal to the proximal cell marker was used to estimate the effect of interference in pairing caused by the inversions. Such an effect only occurs in small chromosome intervals. This indicates that homologous sequences are tightly paired in the interphase nuclei of somatic cells. This conclusion is derived from data based on X-ray induced mitotic recombination. The possibility of extending this conclusion to non-irradiated cells is discussed.


New regulatory mutations affecting the expression of the threonine operon in Escherichia coli K-12.

The promoter of the threonine operon was joined to the structural genes of the lac operon in Escherichia coli K 12. The synthesis of beta-galactosidase was thus repressed by threonine plus isoleucine in the fusion strains. To isolate mutations which affect the expression of the threonine operon, alterations in the level of expression of the lacZ gene were selected. A new type of regulatory mutation was discovered.


Sarcoplasmic calcium-binding proteins in protochordate and cyclostome muscle: characterization of a new protein from amphioxus.

A sarcoplasmic calcium-binding protein (SCP) has been purified from the muscle of the protochordate Amphioxus and shown to be more similar to invertebrate SCP's than to their counterpart found in vertebrates, i.e. parvalbumins. The Amphioxus protein has a pI of 4.9, is rich in tyrosine and tryptophan, has a molecular weight of 22,000 and binds strongly 2Ca2+ with a pK of 7.88. Magnesium competes with calcium for only one of the two metal-binding sites and induces positive cooperativity in Ca2+ binding. In cyclostome muscle (lamprey and hagfish), no protein with high affinity for Ca2+ or Mg2+ could be found, irrespective of molecular weight. Instead, a protein with moderate affinity for Ca2+ (less than or equal to 10(5) M(-1)) was detected: it has a molecular weight of 60,000 and might be quite ubiquitous, as the presence of a similar protein has been reported both in red and white muscle of vertebrates such as chicken and rabbit.


[Long term disodium-Cromoglycate treatment in children with bronchiale asthma who responded unsatisfactorily to hyposensitation (author's transl)].

The authors treated 53 asthmatic children for 1/2 to 2 years with Disodium-cromoglycate (Intal). The patients were selected of 412 children suffering of bronchial asthma. The patients were living at home and controled by the outpatient consultation of the hospital. The criteria of selection were: 1. Failure of hyposensitization-treatment, or symptomatic therapy. 2. Polysensibilisation. 3. Anaphylactic shock. 4. Lack of positive skin tests to allergen extracts ("endogenous asthma"). 40 patients got also specific hyposensitization during or before the Intal treatment. The Intal treatment ameliorated definitively the clinical course of illness in 45 patients: only 8 children continued to have serious attacks. The FEV 1.0 and the peak flow rates did not change during the therapy which shows an unaltered tonus of bronchial smooth muscles. Vital capacity rose a significantly and the residual volume decreased during the treatment. Exogenously asthmatic children showed the best response to Intal if it was combined with specific hyposensitisation.


Interindividual variation in the responses of cultured human lymphocytes to exposure from DNA damaging chemical agents: interindividual variation to carcinogen exposure.

Human population variability to standardized doses of N-acetoxy-2-acetylaminofluorene (NA-AAF) and 7, 12-dimethylbenz(a) anthracene (DMBA) was determined in cultured lymphocytes by measuring (a) differential stimulation of unscheduled DNA synthesis after 1 h induction of DNA damage by 10 micrometer NA-AAF, (b) the level of NA-AAF induced chromosome aberrations remaining after 8 h of DNA-repair synthesis, and (c) the level of [3H]DMBA bound to DNA after 18 h incubation of resting lymphocytes in 5 micrometer DMBA. All 3 parameters indicated individual variation to carcinogen exposure and were correlated to the population differences in age, sex, blood pressure and mortality rates. Males always had a greater potential to accumulate DNA-damage than did females regardless of the sampled population. DNA-damage potentials increased with increasing age, blood pressure or mortality rates. There was always proportionally greater DNA-damage potentials in the males than in females. The in vitro response of mature granulocytes to a 10 micrometer NA-AAF dose, as estimated by [3H] thymidine incorporation from unscheduled DNA synthesis, was much lower than lymphocyte response. Nevertheless, individual variations in granulocyte NA-AAF induced unscheduled DNA synthesis paralleled the inter-individual fluctuations observed in the lymphocyte responses to NA-AAF.


The use of a mutationally unstable X-chromosome in Drosophila melanogaster for mutagenicity testing.

Somatic eye-colour mutations in an unstable genetic system, caused by a transposable element in the white locus of the X-chromosome in Drosophila melanogaster, is suggested as an assay system for mutagenicity testing. The system is evaluated by comparison with a corresponding system in a stable X-chromosome. Its sensitivity is confirmed with X-ray and EMS treatment, and it is found to be confined to the specific segment of the X-chromosome where the transposable element is localized.


The inhibitory effect of cysteine on the mutagenic activities of several carcinogens.

The Salmonella/microsome mutagenesis assay was used to determine the effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic actions of several carcinogens: N-methyl-N'-nitro-N-nitrosoguanidine. N-acetoxy-2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, 4-nitroquinoline-1-oxide, methyl methanesulfonate, 5-nitro-2-furaldehyde semicarbazone, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, aflatoxin B1 and the nitrosation products of methylurea and methylguanidine. Cysteine, at non-toxic concentrations, significantly decreased the frequency of reversion to histidine prototrophy when it was added to treatment mixtures. The extent of the inhibition of mutagenic action by cysteine depended on the carcinogen studied as well as the doses of cysteine and carcinogen employed. Cysteine (2.5--10 mM) completely inhibited the mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine and methylguanidine nitrosation products while only partially preventing the mutagenic effects of the other carcinogens assayed. Inhibition of 5-nitro-2-furaldehyde semicarbazone-induced mutagenesis occurred only with higher cysteine concentrations (20--200 mM).


Mutagenic effects of vinyl chloride on Drosophila melanogaster with and without pretreatment with sodium phenobarbiturate.

Treatment of Drosophila males with 1--20% vinyl chloride in air gave an increased frequency of complete and mosaic recessive lethals. Pretreatment with phenobarbiturate for 24 h caused an increase in the mutagenic effect of vinyl chloride. This indicates that the mixed-function oxygenase system can be induced in Drosophila in the same way as in mammals.


Psychosocial and biomedical aspects of deaths associated with heroin and other narcotics.

Our findings point to sizable intercity differences in the United States among certain psychosocial and biomedical aspects of deaths associated with narcotics. Secondly, narcotic-involved deaths are not purely accidental, but many are motivated by suicidal goals and a smaller percentage by homicidal intentions. And finally, in addition to the errors that have been surmised to occur in estimates of psychoactive drug deaths from heroin and other narcotics owing to inadequate reporting or other shortcomings in data collection, there are biomedical errors due to variations in the quality control of toxicological laboratories.


Mutator genes--pacemakers of evolution.

Initially a genetic oddity, male recombination in Drosophilaelanogaster is now being viewed as a means of detecting mutator activity and chromosome breakage in hybridising populations and is causing us to reconsider the source and rate at which genetic variability may be generated in nature.


Functional specialisation in the visual cortex of the rhesus monkey.

Anatomical and functional studies of the visual cortex of the rhesus monkey have shown that it is made up of a multiplicity of distinct areas. These seem to be functionally specialised to analyse different features of the visual environment.


Distribution and tissue specificity of 4-aminobutyrate-2-oxoglutarate aminotransferase.

A rapid and specific method for assaying 4-aminobutyrate-2-oxoglutarate aminotransferase was developed. The method was based on the selectivity of ion exchange resin and the speed of vacuum filtration. With this new method, the aminotransferase activity in various tissues has been determined as follows: brain, 10.2; spinal cord, 11.8; liver, 5.7; kidney, 4.6; heart, 0.5; lung, 0.4 nmol glutamate formed/min/mg. No activity could be detected in muscle preparations. When the aminotransferases were tested with the antibody against the purified 4-aminobutyrate aminotransferase from brain, no difference could be detected among brain, spinal cord, and kidney preparations as judged from the results of immunodiffusion, inhibition of enzyme activity by antibody, and microcomplement fixation. It is concluded that 4-aminobutyrate aminotransferases from various tissues of the mouse are probably identical or closely related.


Ultrastructural localization of cations in the rat pars distalis under various experimental conditions.

Modifications of the pyroantimonate technique were used to localize intracellular sites of bound cations in the pars distalis of normal and hypothyroid rats and in rats with increased levels of plasma calcium. In the normal animal, cations were localized within most intracellular organelles and sometimes on the membranes involved in exocytosis. The amount of bound cations within pituitary intracellular organelles was considerably augmented in rats injected intravenously with calcium chloride. However, in the thyroidectomy cells of hypothyroid rats, the amount of cation precipitate appeared to be selectively increased in the dilated rough endoplasmic reticulum (RER). The calcium chelator, EGTA, and X-ray microprobe analysis revealed the presence of calcium in cation deposits.


Genetic markers in cycloid psychosis.

Frequencies of HLA antigens, blood groups, serum groups and red cell enzyme types in patients with cycloid psychosis were compared with those in patients with bipolar psychosis and in normal controls. Patients with cycloid psychosis showed (1) an increased frequency of the Rh-negative type compared to controls, (2) an increased frequency of the K(+) phenotype compared to both bipolar patients and controls, and (3) an increased frequency of the serum group Gc2--1.


Extracranial vertebral aneurysm with neurofibromatosis.

With neurofibromatosis neuromas of the cranial and cervical nerves are common findings and meningiomas and ependymonas appear more often than in the average population. Vascular manifestations of the disease are also commonly known in the renal and gastrointestinal vessels but rarely in the large cerebral arteries. The case of a 50 year old man with neurofibromatosis and a vertebral aneurysm is reported. The plain X-ray of the cervical spine and the Pantopaque myelogram were compatible with a cervical neuroma and the patient was operated but a large aneurysm of the vertebral artery was found. The operation was discontinued and vertebral angiography was performed revealing a large saccular aneurysm which war excised. This aneurysm is most probably a manifestation of vascular disease with neurofibromatosis.


Gamma hydroxybutyrate in the monkey. I. Electroencephalographic, behavioral, and pharmacokinetic studies.

Gamma hydroxybutyrate (GHB) was administered to adult and prepubescent rhesus monkeys intravenously in varying dosages while an electroencephalogram (EEG) was recorded from scalp electrodes and the body core temperature was monitored. Blood and cerebrospinal fluid samples were assayed for gamma hydroxybutyrate. GHB produced a trancelike stupor in all the monkeys, associated with marked EEG changes and hypothermia. There was a striking age specificity in that prepubescent rhesus monkeys responded to a lower threshold dosage, had a higher incidence of myoclonic jerking, and showed characteristic EEG changes not seen in the adult animals. The EEG-behavioral changes paralleled the hypothermia. There was good correlation between the serum levels of GHB and the EEG-behavioral effects. These studies suggest that the GHB-treated monkey may have utility as a petit mal seizure model.


Gamma hydroxybutyrate in the monkey. II. Effect of chronic oral anticonvulsant drugs.

Gamma hydroxybutyrate (GHB) was administered intravenously to monkeys that had been pretreated orally for 2 weeks with various anticonvulsant drugs or with L-DOPA at different dosage levels. Continuous electroencephalographic (EEG) monitoring was performed during and after GHB administration. Bloood was assayed for GHB and for the anticonvulsant drug the animal was receiving. The EEG and behavioral changes produced by GHB were improved by ethosuximide and phenobarbital, made worse by phenytoin, and unchanged by L-DOPA.


Why do HMOs seem to provide more health maintenance services?

Greater use of preventive services by enrollees of HMOs than of other health plans is often assumed to reflect differences in philosophy about "health maintenance." But organizational forms are less important than extent of insurance coverage in influencing use of preventive services. Policy options for improved health status will have to challenge ideologies of prevention and financing.


Effects of reserpine on the incidence of 9,10-dimethyl-1,2-benzanthracene-induced tumors in pinealectomised and thymectomised rats.

After reserpine treatment the incidence of dimethyl-benzathrance-induced tumors was found to be significantly higher in pinealectomised rats than in intact or thymectomised ones. A very high rate of DMBA-leukemia was observed in immune deficient pinealectomised rats after reserpine administration. It is therefore suggested that the neuro-endocrine disturbances, due to removal of the pineal gland in the new-born animals, are latent and become evident after reserpine administration, as reflected in an increased tumor incidence.


The visual deprivation syndrome.

The variety of experimental manipulations shown to induce amblyopia in young cats and monkeys is described. A brief monocular eye closure of only one week or an artificial strabismus of only two weeks produces profound long-lasting changes in the electrophysiology and anatomy of the visual system. A poor quality of visual experience, an image imbalance between the two eyes, or any spatial or temporal incompatibility can produce these symptoms of amblyopia.


Application of basic research data to clinical amblyopia.

The rhesus monkey has evolved as a useful model for the study of amblyopia caused by neonatal lid closure and experimental strabismus and anisometropia. In view of the behavioral and anatomic similarities of the visual system in humans and rhesus monkeys, there is reason to believe that the neurophysiologic and anatomic anomalies identified in animals as part of the "visual deprivation syndrome" occur in humans as well. Animal research has led to better understanding of the basic mechanisms responsible for the development of amblyopia and the manner in which form vision deprivation and abnormal binocular interaction contribute to the various forms of unilateral and bilateral amblyopia. The period of susceptibility to abnormal visual stimulation in humans needs to be better defined, and the clinician must take precautions to avoid uncontrolled occlusion or prolonged unilateral cycloplegia in infants. Even though the factors leading to amblyopia in patients with unilateral or bilateral congenital cataracts are now better understood, the visual results are still disappointing. It is possible that the residual aniseikonia after contact lens correction may be amblyopiogenic in these patients.


Comparison of vertical and horizontal optokinetic nystagmus in the squirrel monkey.

Horizontal and vertical optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) of squirrel monkeys were compared with those of rabbits, cats and humans that were previously described. Squirrel monkeys showed similar findings to cats, in which vertical optokinetic nystagmus (VOKN) is not as well elicited as horizontal optokinetic nystagmus (HOKN) and down-pursuit OKN is poorer than up-pursuit OKN. As to the reasons that bring about different responses of OKN and OKAN (and vestibular nystagmus) in different planes, we speculated two possibilities: compensatory activation of horizontal eye movement for narrowed visual field accompanied by frontally positioned eyes, and the gravity that restricts and modifies posture and locomotion. Directional difference of VOKN may be caused by a physiological mechanism that makes visual fixation not susceptible to downward movement of the ground surface during forward locomotion.


[HLA and erythrocyte genetic markers in a family with hereditary angioneurotic edema (author's transl)].

The study deals with a family of 22 members spreading over four generations; 14 members suffer from hereditary angio-neurotic edema; all of them have been typed for 30 antigens of the A and B loci in the HLA System and for ABO and Rhesus erythrocyte markers. There is no connection between the disease and any of the markers considered. As for the HLA system, there should be at least 7 chromosomic recombinants to account for the relationship with one of the haplotypes involved.


[Sensitivity of bacteria to antibiotics. Evaluation of a rapid automatic method (author's transl)].

A rapid automated sensitivity testing system is evaluated in this report. The results have been compared with the standard disk diffusion method (ICS). Three hundred strains recently isolated from clinical cases : Enterobacteriaceae, Staphylococcus aureus, Streptococci D, Pseudomonas aeruginosa, have been tested. The general agreement between the two techniques was 89 p. cent.


[Morphobiological characteristics of infusoria of the genus Chilodonella (Ciliata: Chlamydodontidae)].

8 species of fishes from fishfarms of central and north--western regions of the USSR were examined. Chilodonella cyprini Moroff, 1902 and Ch. hexastichus Kiernik, 1909 were found. The reproductive process of infusoria was investigated. The data on the susceptibility of hosts of different species and age are given. The variability of Chilodonella depending on localisation and water temperature is shown.


Hyperalimentation catheter passing into the spinal canal causing temporary paraplegia.

A patient with a hyperalimentation catheter in the spinal canal is presented. This resulted in an extradural fluid mass and partial paraplegia that eventually cleared.


Vesicoureteral reflux in the primate: III. Effect of urinary tract infection on maturation of the ureterovesical junction.

Recurrent bladder infections in the monkey appeared to cause a delay in maturation of the ureterovesical junction. This was not significant since it did not ultimately prevent maturation. Bacteriuria was prolonged when reflux was present.


Organochlorine insecticide residues in bovine milk and manufactured milk products in Illinois, 1971-76.

Monitoring activities were initiated in 1971 to survey the occurence and levels of organochlorine insecticide residues in bovine milk and manufactured milk products in Illinois. Dieldrin residues were the most prevalent, and were found in 96 percent of the samples. Dieldrin also accounted for the highest average residue concentration (0.09 ppm). Only 0.3% of the samples contained illegal insecticide residues. Levels of DDT and lindane were generally declining, but those for dieldrin and heptachlor epoxide tended to remain constant.


p,p'-DDE, polychlorinated biphenyls, and endrin in oldsquaws in North America, 1969-73.

Organochlorinated compounds were monitored in oldsquaws (Clangula hyemalis) and their food from Lake Michigan between October and May, 1969-72; in adult oldsquaws, eggs, young, and food from northwest Hudson Bay in 1971; and in oldquaws from five wintering areas other than Lake Michigan in 1971-73. Analyses were conducted on 300 carcasses, 14 wings, 29 gullet samples, and 11 clutches. Average residues in carcasses from Lake Michigan ranged from 4 to 107 ppm PCBs, 2 to 42 ppm DDE, and less than 0.1 to 0.7 ppm endrin. Differences in DDE levels occurred between several sex and age classes during December on Lake Michigan; these differences were not apparent in the spring. Increases in DDE and PCB residues for oldsquaws occurred on Lake Michigan between December and May. DDE residues in the wing and carcass were significantly correlated. Residues were relatively low in oldsquaw foods from Lake Michigan; concentration factors between the food and the ducks varied between 1X and 22X, depending on the date and compound. Organochlorinated residues were lower in Arctic than in Lake Michigan food samples. DDE in paired male and female oldsquaws was highly correlated, as was DDE in females and clutches. Eggshell thickness had declined 4.5% compared with eggs collected before 1947. Residues were higher in oldsquaws wintering on the Great Lakes and lowest in oldsquaws from coastal areas.


Residues of polychlorinated biphenyls, DDT, and DDT metabolites in Pennsylvania streams, community water supplies, and reservoirs, 1974--76.

Pennsylvania streams, community water supplies, and open water reservoirs were analyzed for PCB mixtures, DDT, and DDT metabolites. Streams were sampled in 1974 and again in 1975. Only 4 of 19 stream locations were contaminated. Maximum concentrations in community supplies of Aroclor 1242 (2 locations), Aroclor 1254 (3 locations), and sigmaDDT (2 locations) were 350, 260, and 620 ng/kg, respectively. Of the 110 community water supplies sampled in 1975 and 1976, only 7 contained residues. Maximum concentrations in community supplies of Aroclor 1242 (4 locations) and sigmaDDT (2 locations) were 460 ng/kg and 75 ng/kg, respectively. The seventh contained 0.7 ng/kg of dieldrin. None of the three open water reservoirs contained detectable residues of the compounds of interest. Essentially no correlation was found between PCB and DDT analogs in streams and those in fish from streams which had been samples at similar locations in a related study in 1976.


[Anorexia: a redoubtable complication of the surgical treatment for obesity after jejuno ileal by-pass (author's transl)].

Three cases of severe anorexia are reported. It results in a strong protein malabsorption with hepatic steatosis and in a syndrome of mental depression which needed the re-establishment of the intestinal-continuity. Although a mild post-operative anorexia is regular and contributes to the weight loss, massive anorexia must be considered as a new and redoubtable unpredictible complication of the surgical treatment for obesity, which may hinder the intestinal adaptation and increase the protein malabsorption.


[Acute renal failure in the course of occupational lead intoxication. Chelation therapy responsability (author's transl)].

In a patient with occupational plumbism and a normal kidney function, EDTA therapy (1 g/24 h) resulted in a massive lead excretion (15 000 microgram/24 h) together with acute renal failure. A direct nephrotoxic effect of EDTA was excluded: after renal function returned to normal, EDTA could be subsequently readministered at progressively increasing doses (250 mg to 1 g/24 h) without any renal dysfunction. These findings strongly suggest a close relationship between the burden of lead mobilized by EDTA and the acute renal failure. This case can be classified as acute lead nephropathy of which only a few instances have been reported in the literature. The interest of monitoring lead excretion during chelation therapy is particularly emphasized.


[Treatment of diabetic ketoacidosis and hyperosmolality with low dose insulin infusion (author's transl)].

Fifteen patients were treated with low-dose (5 u/hour) insulin infusion, including 10 cases of ketoacidosis, 3 cases of hyperglycemia without acidosis in severely affected diabetics, and 2 cases with hyperosmolality. The treatment was successful in all cases. Insulin was infused at a constant rate, during 12 hours as a mean value. Blood glucose fell regularly and no hypoglycemia occured. Serum potassium varied within narrow limits, and no accident related to hypokalemia was observed. The correction of ketoacidosis was delayed, as compared to that of hyperglycemia. The two elderly patients with hyperosmolality recovered quickly and completely. The method of low-dose insulin infusion seems thus effective and easily applicable, at least in an intensive care unit. Our experience prompted us to increase (10 u/h) rather than to decrease the insulin infusion rate, with the aim to obtain a faster correction of ketoacidosis.


[Evaluation of diagnostic methods. Application to the diagnosis of benign or malignant colonic tumours (author's transl)].

The evaluation of diagnostic methods has become a necessity in clinical practice in order to select those techniques with the best possible cost-effectiveness ratio. Using simple informational indices such as sensitivity or specificity, it is possible to analyse the literature devoted to diagnostic methods in a given disease. This method is here applied to the problem of the detection of colonic tumours, benign or malignant, and gives an estimation of the informational value of occult blood examinations, rectosigmoidoscopy, simple barium enema, double contrast barium enema and colonoscopy.


[Diagnosis of hyperprolactinaemias: respective value of response to THR and to bromocriptine (author's transl)].

Seventy tests of stimulation with hypothalamic thyreotrophic hormone liberation factor, and 35 bromocriptine inhibition tests were carried out on a routine basis in patients with latent or frank hyperprolactinaemia. Pathological hyperprolactinaemia does not have a single clinical pattern: frank, it takes the form either of an exteriorised pituitary adenoma (14 cases), or of an amenorrhoea-galactorrhoea syndrome with or without micro-adenoma (12 cases); latent, it takes the form either of isolated amenorrhoea (17 cases) or of dysovulatory sterility (16 cases). Amongst the dynamic tests available, it is worthwhile to make a choice, and in the case of frank hyperprolactinaemia, the authors propose use of the bromocriptine inhibition test in the first instance. The TRH test is reserved for verification of the results of neurosurgery. As far as latent hyperprolactinaemia is concerned, it may be identify only by the TRH test, with the resultant possibility of specific treatment.


[Von Recklinghausen's disease: functional pulmonary changes. 2 case reports].

We report two cases of patients with Von Recklinghausen disease. They exhibited typical cutaneous and diffuse intrapulmonary lesions accompanied by effort dyspnea. Multiple radiological abnormalities were noticed and the pictures showed nodular and interstitial lesions as well as emphysematous areas. Pulmonary function tests revealed more or less marked hypoxemia without hypercapnia, and decreased maximal expiratory flows due, at least in part, to a loss of elastic recoil.


Characterization of a mouse DNA clone containing an immunoglobulin variable region gene.

A 4.8 kilobase mouse embryo DNA fragment was inserted into a phage lambda genome and was subsequently characterized by electron microscopy, restriction enzyme mapping and partial DNA sequencing. This fragment contains a 400 base sequence which is homologous to that of an immunoglobulin light lambda chain mRNA which spans 3.3 to 3.7 kilobases from one end of the fragment. Restriction enzyme mapping as well as partial nucleotide sequencing of the 3' terminal of the homology region confirm the previous conclusion [Tonegawa, Brack, Hozumi and Schuller, Proc. Natl. Acad. Sci. USA. 74, 3518-3522 (1977)] that the cloned DNA fragment contains a Vlambda gene sequence which is separate from any Clambda sequence.


The properties of gene Dm 225, a representative of dispersed repetitive genes in Drosophila melanogaster.

The properties of Dm 225 DNA, a fragment of D.melanogaster genome 2.9 kb in length excised by EcoRI endonuclease and cloned in the lambda gt phage or pMB9 plasmid, are described. The DNA hybridizes to a significant portion (0.8%) of total polysomal poly(A)(+)RNA (mRNA). The size of the hybridizing mRNA is about 2.3 kb (19S); it is present in the fraction of heavy polysomes. Dm 225 DNA fragments obtained with the aid of Hae III endonuclease have been mapped. mRNA hybridizes with all the fragments. In one of the end fragments, the 3'-end of mRNA has been localized and thus the direction of transcription determined. About 250 copies of the gene Dm 225 are present in the haploid genome of D.melanogaster, and all of them have the same size upon restriction with EcoRI endonuclease. On the other hand, the sequences of the genome adjacent to Dm 225 DNA are different and may vary from one cell line to another as evidenced by experiments in which the D.melanogaster DNA was restricted by Hind III endonuclease. In combination with in situ hybridization data /1,2/ the results obtained in this paper demonstrate that the structural gene present in Dm 225 DNA is a representative of a multiple gene family dispersed throughout the whole genome of D.melanogaster.Images


The cleavage site of the restriction endonuclease Ava II.

We have determined that the type II restriction enzyme Ava II, isolated from Anabaena variabilis, recognizes and cuts the sequence (formula: see article). The eight Ava II sites of pBR322 have been mapped, as well as a unique site for Ava I.


Mechanism of suppression in Drosophila. VII. Correlation between disappearance of an isoacceptor of tyrosine tRNA and activation of the vermilion locus.

The possibility that tyrosine tRNA modifies the catalytic activity of tryptophan oxygenase that is produced by the vermilion mutant (v) in Drosophila melanogaster is reconsidered. Dietary conditions can modify the ratio of the two major isoacceptors of tyrosine tRNA: one condition allows 85--90% to exist as the second isoacceptor, and another condition allows less than 5% to exist in this form. The function lacking in the vermilion mutant is partially restored when the second isoacceptor of tRNATyr is reduced to low levels (less than 40%), but the function is greatly reduced when this isoacceptor is present as 50% or more of the total. These data support the hypothesis that tRNATyr may be associated with and regulate tryptophan oxygenase. The corresponding isoacceptor of tRNATyr found in a suppressor mutant, su(s)2, should not have any effect on the function of the vermilion gene, and, indeed, it did not. The tRNAs for tyrosine, aspartic acid, and histidine all have one isoacceptor that contains nucleoside Q and all undergo parallel changes in flies raised on the various diets. It appears that these dietary changes affect the ability to synthesize or modify Q or to remove or insert it into tRNA.


Replication of poly dA and poly rA by a drosophila DNA polymerase.

The activity of a 7.3S-8.3S Drosophila DNA polymerase was characterized in detail using poly dA.p(dT)[unk] and poly rA.p(dT)[unk]. With poly dA.p(dT)[unk], Mg(2+) ion was the preferred divalent cation, and enzyme activity was inhibited by K(+) ion and by spermidine. With poly rA.p(dT)[unk], Mn(2+) ion was the preferred divalent cation and enzyme activity was stimulated by K(+) ion and by spermidine. The dependence of enzyme activity on the concentration of primer-template and on the ratio of primer to template was the same in both reactions. The two enzyme activities were identically inhibited by N-ethylmaleimide. Poly dA was replicated extensively and poly rA was replicated partially. The activation energy for poly dA replication was twice that for poly rA replication. Enzyme activity with poly dA.p(dT)[unk] was more stable to thermal inactivation than was enzyme activity with poly rA.p(dT)[unk]. These studies suggest that the same enzyme responds to both the deoxy- and the ribohomopolymer template but that the mechanisms of replication may be different.


Meeting exceptional nutritional needs. 1. Total parenteral nutrition.

The provision of adequate nutrition to hospitalized patients with exceptional caloric requirements has been a problem until the recent advent of intravenous hyperalimentation. With total parenteral nutrition (TPN), the nutritional needs of any patient can be met by infusion. TPN solution is hypertonic, and administration requires central venous cannulation. The subclavian vein is usually chosen as route of access to the superior vena cava. Strict aseptic technique must be used in inserting the catheter and making up and administering the solution. TPN is not without risk. Infection is always a possibility, as are metabolic alterations, such as electrolyte imbalance, fluid overload, osmotic dehydration, and essential fatty acid deficiency.


Oral methionine loading as a cause of acute serum folate deficiency: its relevance to parenteral nutrition.

Oral methionine supplements (8.0 g daily for 4 days) were given to five normal volunteers who continued to eat their usual diet. This treatment resulted in a significant fall in serum folate concentration. Three days after the end of treatment concentrations had not completely returned to control values. The fall in concentration was prevented by giving oral folic acid supplements. It is suggested that folic acid supplements should be given to patients who are receiving intravenous infusions of amino acid mixtures.


Streptoccocus faecalis endocarditis: an emerging problem?

The clinical features of 16 patients with Streptococcus faecalis endocarditis are reviewed and the currently favoured antimicrobial regimens for such infections are detailed.


The problems of massive small bowel resection and difficulties encountered in management.

Massive small bowel resection is imperative in the management of several pathological conditions and is accompanied by high operative mortality. In those that survive, serious nutritional disturbances are inevitable. Intestinal adaptation is said to occur but cannot be relied upon. Long-term parenteral nutrition is problematical and often unsuccessful. Many surgical procedures have been adopted in an effort to improve prognosis and have been found wanting. Controlled experimental studies in the use of reversed segments and a limited number of reported clinical cases using the method after massive resection suggest that this technique may improve the function of the residual intestine to such an extent that other supportive measures are unnecessary.


Maternal vitamin E alters passively acquired immunity of chicks.

Passively transferred antibody levels were significantly increased in plasma of two- and seven-day-old chicks when the dams were fed 150 and 450 p.p.m. vitamin E prior to immunization with Brucella abortus. However, if the hens were fed 90, 300 and 900 p.p.m. vitamin E before immunization, the chicks evidenced no increase in antibody titers relative to controls. This nonlinear antibody response by the reticulo-endothelial system to vitamin E confirms in Gallus domesticus similar results reported for other species.


Response of broiler chickens to low level intake of polychorinated biphenyl isomers.

Commercial-type broiler starter and finisher feeds containing 0, .1, 1.0, 5.0, 10.0, or 20.0 ppm of polychlorinated biphenyl isomers (PCBs) as Aroclor 1254 (Monsanto) were fed to male broiler chicks (Arbor Acres 70 X Cobb) from hatching to 8 weeks of age. Feed intake and body weights were recorded on a weekly basis. The birds were killed at 8 weeks of age and samples of leg and breast muscle and adipose tissue were removed from each bird for PCBs analysis by gas chromatography (Pesticide Anal. Manual, FDA, '74). Linear log-log dose response curves with confidence limits were fitted to all data. There was a progressive, significant reduction in growth in response to increasing levels of PCBs fed. PCBs toxicity symptoms were seen at 10 and 20 ppm levels. All tissues showed significant, progressive accumulations of PCBs in response to increased dose.


[Substrate specificity of lipase from Pseudomonas fluorescens].

Substrate specificity of lipase isolated from the culture liquid filtrate of Pseudomonas fluorescens BKM-B-1151 was investigated with respect to vegetable oils and animal fats (olive, sunflower, cotton, mustard and soybean oils; beef and hog fats and their glycerides and fatty acid esters). The preparation showed a high specificity to the quantitative composition of the reaction mixture (substrate: enzyme ratio), chemical structure of the substrate, and the emulgator type (gelatine, gum arabic and Triton X-100). The lipase preparation hydrolyzed oils and water-insoluble fatty acid esters. The latter indicated an involvement of lipase.


[Gonadotropin from the bovine pineal body. Evidence of its similarity with the luteinizing hormone of the pituitary gland].

Gonadotropin affiliated by biological and immunochemical properties to the luteinizing hormone of the hypophysis was revealed in the purified extracts from the bovine pineal glands. Biological properties of gonadotropin from the pineal glands were assessed by the reactions specific of the luteinizing hormone. Immunochemical properties of gonadotropin were studied by means of gel-precipitation in agar gel, immunoelectrophoresis and radioimmunochemical analysis. It was found that the specific content of gonadotropin in the epiphysis was 80 times lower than the specific content of the luteinizing hormone in the hypophysis, but exceeded the LH concentration in the blood serum 555 times and in the cerebrospinal fluid 6.8 times. Immunoreactive LH was absent in the extracts of the brain cortex, the liver and the ovaries. A theoretical interpretation of a possible physiological role of the LH-like gonadotropin in the endocrine regulation of the reproductive function of the organism is given in this work.


[Isolation of the islands of Langerhans and their transplantation under experimental conditions].

Isolated islets of Langerhans were obtained from sexually immature rats by means of collagenase. Interperitoneal isotransplantation of the islets to rats with alloxan diabetes caused an improvement of their condition, normoglycemia, and elevation of the immunoreactive insulin level, and prolonged survival of these rats, in the presence of coarse morphological changes in the endocrine part of the pancreas of the recipient (in 2--4 weeks). It is suggested that the insular cells of the islets of Langerhans isolated from the immature rats were viable.


[Enzymatic profile of the exudate leukocytes in diabetes mellitus].

The activity of enzymes regulating the processes providing functional activity of leukocytes was studied in the exudate leukocytes of healthy rabbits and animals with alloxan diabetes. Rabbits with diabetes displayed a reduction of hexokinase, phosphoglucomutase, glucose-6-phosphate dehydrogenase and adenylate kinase activity. The activity of UDPH-pyrophosphorylase, UDPH-glycogentranspherase, 6-phosphogluconate dehydrogenase and glutathion reductase showed no significant changes in the exudate leukocytes in diabetes. A reduction of hexokinase and glucose-6-phosphate dehydrogenase limiting glycolysis and the pentose-phosphate cycle, respectively, providing energy for leukocytes and important in protein metabolism of these cells, is of great significance in the reduction of functional activity of leukocytes in the inflammatory focus in diabetes.


Organization of immunoglobulin heavy chain genes and allelic deletion model.

We have assessed the number of times the gene sequence encoding constant regions of mouse immunoglobulin heavy chains gamma1, gamma2a, and gamma3 are represented in the mouse genome by hybridization kinetic analysis. All three genes are present at one copy each per haploid genome in normal tissues and myelomas producing IgM or IgG3. IgG1-producing myelomas, however, contain 1 copy each of the gamma1 and gamma2a genes and 0.5 copy of the gamma3 gene per haploid genome. IgG2b-producing myelomas contain 1 copy of the gamma2a gene and 0.5 copy each of the gamma1 and gamma3 genes per haploid genome. IgG2a-producing myelomas contain 1 copy of the gamma2a gene and 0.5 copy each of the gamma1 and gamma3 genes per haploid genome. In myelomas producing IgA, all three gamma genes are represented 0.5 times per haploid genome. In order to account for the results we propose an allelic deletion model: (i) The specific deletion of heavy chain constant region genes accompanies the recombination of a variable region gene to a constant region gene. (ii) The portion of the chromosome that resides between two joining sequences is excised out of the chromosome. (iii) The recombination occurs on one of the alleles. Based on this model we also propose that heavy chain genes are arranged on one chromosome in the following order; variable region genes, unknown spacer sequence, mu, gamma3, gamma1, gamma2b, gamma2a, and alpha.


Uracil incorporation into nascent DNA of thymine-requiring mutant of Bacillus subtilis 168.

A thymine-requiring mutant of Bacillus subtilis strain 168 accumulates short DNA chains after brief pulses with [(3)H]thymidine. Reversion of the thy mutation to thy(+) abolishes the accumulation of short DNA chains, suggesting that the accumulation is related to the thy mutation. The reason for this accumulation has been further investigated by analysis of a mutant with a defective uracil-DNA glycosidase activity (urg). The accumulation of short DNA chains in thy(-) cells is abolished by the deficiency of uracil-DNA glycosidase activity. In thy(+) cells, the deficiency of the glycosidase activity does not change the sedimentation profile of pulse-labeled DNA. DNA isolated from thy(-)urg(-) cells is fragmented by successive treatment with purified uracil-DNA glycosidase and alkali, indicating that uracil residues are present in this DNA. DNA isolated from thy(+)urg(-) cells is not fragmented by the same treatment. Significant radioactivity is detected in the dUMP region, when [(3)H]uridine-labeled DNA from thy(-)urg(-) cells is hydrolyzed and analyzed by thin-layer chromatography. Only a trace amount of radioactivity, which is not influenced by the deficiency of uracil-DNA glycosidase activity, is found in the dUMP region in DNA hydrolysates from thy(+) cells. These results suggest that, in thy(-) cells, uracil is incorporated into DNA and the accumulation of short DNA chains results from the excision-repair of this uracil whereas in thy(+) cells, uracil is seldom, if ever, incorporated into DNA.


Nitrogen electron nuclear double resonance and proton triple resonance experiments on the bacteriochlorophyll cation in solution.

Electron nuclear double resonance signals of the pyrrole nitrogens of bacteriochlorophyll alpha cation in a solution of CH2Cl2/CH3OH (6:1) have been observed. The nitrogens are inequivalent: the hyperfine coupling constants were determined to be 2.36 and 3.18 MHz (0.84 and 1.14 G, respectively). Triple electron nuclear double resonance experiments have yielded the signs and values of nine proton hyperfine coupling constants. The assignment based on these data agrees well with previous work (Borg, D.C., Forman, A. & Fajer, J. (1976) J. Amer. Chem. Soc. 98, 6889-6893); in addition, two methine protons have been identified. Spin densities calculated from the hyperfine couplings are compared to reported molecular orbital calculations.


Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion.

Previous studies have demonstrated that both the antibody and T-lymphocyte proliferative immune responses to poly(Glu53Lys36Phe11)n (GLphi) are under the control of two major histocompatibility-linked immune response (Ir) genes. One gene, termed Ir-GL phi-alpha, has been mapped to the I-C or I-E subregion of the major histocompatibility complex, while the other, termed Ir-GL phi-beta, has been mapped to the I-A subregion. In this paper we examine the effect of anti-I-region-associated (Ia) antisera on the T-lyphocyte proliferative response to GL phi. Antibodies directed against Ia antigens coded for by genes in either the I-A or I-C subregion were found to inhibit the proliferative response to GLphi. These results suggest that a function mediated by two Ir gene products can be blocked by anit-Ia antisera directed against either one, and thus, that both products are expressed on the cell surface.


Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization.

B leukemia cells from four different patients were hybridized with a mouse myeloma cell line with polyethylene glycol as a fusing agent. The original leukemia cells all expressed immunoglobulin on their surface, but failed to secrete it. Over 200 different human-mouse somatic cell hybrids were obtained; 57% of them secreted human immunoglobulin in large amounts. Human immunoglobulin secretion can be a stable property of these hybrid cells over months of continuous culture. In each case the human immunoglobulin secreted was restricted to the light chain type expressed by the parental B leukemia cell. In addition, these hybrid cells secreted the original mouse myeloma protein and a variety of mixed human-mouse immunoglobulin molecules.


Variable region genes for the immunoglobulin framework are assembled from small segments of DNA--a hypothesis.

Sequences of each of the four framework segments FR1, FR2, FR3, and FR4 of the variable regions (V-regions) of light and heavy chains of immunoglobulins were grouped into sets with identical sequences. Sets contained from 1 to 18 members. When each V-region was traced from one FR to the next, it was seen that members of the same set in FR1 could be associated with different sets in FR2, FR3, and FR4. This suggests that the framework for the light and heavy chain V-regions is assembled during embryonic development from sets of minigenes for each FR segment. FR4 from three sets of human V(k)I chains also contained members of V(k)II, V(k)III, and V(k)IV subgroups; one FR2 set contained eight rabbit V(k), one human V(k)IV, and four mouse V(k) and an FR4 set contained two human V(H)III and one mouse V(H)III, indicating substantial evolutionary preservation of these sequences and suggesting that the sets of minigenes are highly conserved in the germ line. The clone of Tonegawa et al. [Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O. & Gilbert, W. (1978) Proc. Natl. Acad. Sci. USA 75, 1485-1489] could be a hybrid FR1 and FR3 coming from minigenes of MOPC 315 (a V(lambda)II) whereas FR2 would come from MOPC 104E (a V(lambda)I). That FR4 is not joined to the rest of the V-region in 12-day-old mouse embryo DNA is also in accord with this hypothesis. Mouse sperm DNA should be examined to establish whether the hypothesized minigenes are separated by intervening sequences and whether the complementarity-determining (hypervariable) regions or segments of the V-region are separated from the framework in genomic DNA. Sperm DNA from rabbits or other species could be used to search for minigene segments whose sequences are identical in several species.


Helical Bacillus subtilis macrofibers: morphogenesis of a bacterial multicellular macroorganism.

Helical bacterial macroorganisms have been produced by the selection of appropriate Bacillus subtilis mutants and the establishment of specific growth conditions. Threadlike fibers ranging in length to approximately 1 cm are produced in fluid culture by the parallel association of many division-suppressed filaments in helical arrangement. A more open ball-like structure of complicated woven architecture may also be produced. Macrostructure morphology is regulated by genetic, physiological, and nutritional factors. The pitch angle of surface filaments in helical macrofibers varies as a function of macrofiber diameter, indicating a flexible response of individual cell surfaces to the forces responsible for helical morphology. Three classes of mutants have been obtained that are concerned with helix directionality: (i) mutants that form only left-handed helix macrofibers, (ii) mutants that form only right-handed helix macrofibers, and (iii) conditional mutants able to form either left- or right-handed helix macrofibers depending upon nutritional environment. Aggregate structures containing both left- and right-handed macrofibers have been obtained by coculturing appropriate mutants. In addition to providing information on the organization of the bacterial cell surface, this new system offers unique and unusual opportunities to study cell-cell interactions, primitive morphogenesis, and the properties of a multicellular bacterial form.


Electric shock titration: effects of meperidine, anileridine and alphaprodine.

The effects of meperidine, anileridine and a alphaprodine were studied in the squirrel monkey whose behavior was maintained under a 2.0-sec schedule of shock increment. Low doses of all three drugs had no effect, whereas higher doses decreased responding at the zero shock intensity. Slightly higher doses of meperidine and anileridine increased responding at the zero shock intensity and produced convulsions.


Alcohol self-administration in monkeys (Macaca radiata): the effects of prior alcohol exposure.

Responding by 4 monkeys was maintained under a fixed ratio 10 (FR 10) schedule for either food, intravenous sucrose or alcohol. The 20 hr sessions were divided so that food was available during hours 1, 6, 11, 16 and alcohol or sucrose during hours 2-5, 7-10, 12-15, and 17-20. All animals failed to maintain responding for isocaloric sucrose but continued to respond for food during those sessions. Responding under alcohol conditions was positively accelerated in 2 animals that were not previously exposed to alcohol, whereas prior exposure to alcohol produced maximal response rates during the first alcohol test session. The effects of alcohol in all monkeys were to suppress responding maintained by food and this suppression could not be produced with programmed infusions of isocaloric sucrose.


Electric shock delivery system for rhesus monkeys: its effect on escape responding.

The present experiment evaluated a simple chronic electric shock delivery system for rhesus monkeys restrained by a harness and arm arrangement used in experiments involving intravenous drug delivery. Electric shock was delivered via two small electrodes surgically implanted in the lumbar muscle. During experimental sessions, responding on a fixed-ratio 10 schedule terminated the delivery of a train of 100 electric shock pulses and produced a 3 min timeout. A maximum of 19 trials were possible during each daily session. Overall rate of responding increased as electric shock intensity was increased from 0 to 4 mA and the characteristics of responding were similar to previous studies using other systems and species. The results demonstrate that electric shock delivered by the present system is a negative reinforcer. In addition, the system is easy to implant, causes little tissue damage, relatively long-lasting and can be used in experimental situations which involve responding maintained by intravenous drug delivery in rhesus monkeys.


Cocaine as a discriminative stimulus for responding maintained by food in squirrel monkeys.

Squirrel monkeys were trained in a choice procedure to discriminate a dose of 100 micrograms/kg cocaine from saline. Following an injection of cocaine, responding on the right lever was reinforced with food, whereas following an injection of saline, responding on the left lever was reinforced with food. A high degree of stimulus control (100% correct) was established within 20 experimental sessions. The dose-response function of cocaine on lever choice was then determined. When intermediate doses (10, 25 and 50 micrograms/kg) were administered prior to test sessions, a dose-dependent generalization decrement was seen. One monkey was found to discriminate as low as 25 microgram/kg cocaine from saline.


Calibration and evaluation of a system of total body in vivo activation analysis using 14 MeV neutrons.

A system has been established for determining the total body contents of calcium, phosphorus, sodium, chlorine and nitrogen by neutron activation analysis using sealed-tube neutron generators and a shadow-shield whole-body counter. The system was calibrated using three anthropomorphic phantoms of different sizes, filled with various mixtures of the activatable elements in amounts similar to those in man. The reproducibility determined from replicate measurements, was on average +/- 2.9% (SD). The average uncertainty in absolute measurements was estimated to be +/- 4.2% (68% confidence interval).


Effect of agar percentage, agar thickness, and medium constituents on antibiotics assay by disc diffusion method.

The factors affecting the sensitivity of nafcillin, vancomycin, oleandomycin, chloramphenicol, methacycline and novobiocin assay, using the paper disc diffusion method, were studied. Agar concentration and pour volume were found to influence the assay sensitivity of antibiotics. The type of assay medium was effective e.g. brain heart infusion agar was the best medium for nafcillin and methacycline; synthetic amino acid medium for oleandomycin; Muller Hinton agar for vancomycin and chloramphenicol; and G & R medium for novobiovicin. All additives, including inorganic ions, sugar, organic acids, complexing agents, surface active agents and blood, decreased the activities of the studied antibiotics. Higher activities of vancomycin, methacycline were observed at pH = 5, of nafcillin, chloramphenicol, and novobiocin at pH = 6, and of oleandomycin at pH = 7.


Relationship between the blood concentration of the drug and its cumulative effect: a pharmacokinetic analysis of the nephrotoxic action of gentamicin and streptomycin.

The general principle of dependence of cumulative effects on drug concentration in the blood is proposed. The registered response is regarded as a result of the dual effect of drug blood level and duration of action. The corresponding experimental design consists in maintaining the serum concentration values at several definite levels and determining the response values for each of them. The constant serum level of the drug could be achieved by means of continuous infusion calculated according to the pharmacokinetic model. This principle was proved in the acute experiments on cats which established a relationship between the nephrotoxic effect of gentamicin and streptomycin on the one hand and their concentration in the serum and duration of action on the other.


Urinary excretion of vanyl-mandelic acid correlated with ischemic heart disease.

The concentration of vanyl-mandelic acid is analysed in the urine collected within 24 hours from normal subjects, from those with painful ischemic cardiopathy, infarction and post-infarction sequelae. Statistically significant results have been obtained only in infarction patients. The study of the concentration of vanyl-mandelic acid by age decades points to the increase of average values throughout life.


Cardiovascular effects of amphepramone.

The i.v. administration of amphepramone in dogs induced a dose-related depressor reaction. This effect was due to a peripheral myotropic vasodilatation. When the drug was administered intracerebroventricularly it elicited a marked pressor response, due, to the release of catecholamines with its subsequent action on alpha-adrenergic receptors. Small doses of amphepramone administered in dogs, rats and rabbits, induced a sinus tachycardia. Larger doses brought about a sinus bradycardia, bradyarrhythmias, extrasystoles, ventricular bradycardia and ventricular fibrillation or asystolia. The respiratory movements as well as the EEG tracings were depressed by larger doses of amphepramone.


Blood and urinary catecholamine variations under the action of a high voltage electric field.

White Wistar male rats, weighing 150 +/- 20 g, adapted to the laboratory ambience during 12 days, were exposed to an electric field of 100 kV/m for 360 minutes in acute (once) or chronic experiment (12 days running). Urinary (nanogram h-1) and blood catecholamines (microgram/100 ml) showed a significant increase as compared to the controls, adapted to the ambience but not exposed to an electric field. The most accentuated increase was that of adrenaline in the acute experiment. In the chronic experiment the adrenaline response gradually failled.


The effect of a high-voltage electric fiedl on neurosecretion and on certain diencephalic protein fractions in the rat.

Exposure of Wistar male rats to an electric field of 100 lV/m for 120 minutes produced intense mobilization of the neurosecretory material in the supraoptic and paraventricular nuclei and significant changes in some protein fractions of the hypothalamus, pineal body and neurohypophysis. The significance and possible mechanisms of these effects are discussed.


The effect of prolonged dextran administration in guinea pigs.

Dextran 70 6% in 0.9% NaCl solution, injected intraperitoneally in guinea pigs, 10 ml/kg b.w./day, during a period of 27 days brought the lowering of the plasma proteins level, whie the total colloid osmostic pressure (due to Dectran and proteins) remained close to that of the control group. The concentration of typhus 0 antibodies and the number of precipitation lines assayed during immunodiffusion in gel were lower than in thd control group. The diminishing of the red blood cells number and of the amount of hemoglobin corresponds to the decreasing proportion of the erythroblastic series (in the bone marrow). Histological changes in the liver and in the kidney are minimal and could be explained by the effort made by these depurating organs to eliminate Dextran from the body.


The influence of partial resection of the small intestine on the pituitary gland.

Starting from the observations of other investigators according to whom massive resection of a portion of the small intestine brings about compensatory changes in the remaining intestine, the existence of a feed-back mechanism between the small intestine and the pituitary gland is postulated. The weight and histologic aspect of the pituitary gland were studied after resection of 50 cm jejunum in the white rat. The results showed increase in the weight of the pituitary and histologic signs of hyperactivity in the anterior lobe.


A comparison of some pharmacological actions of morphine and delta9-tetrahydrocannabinol in the mouse.

The effects of morphine and delta9-tetrahydrocannabinol(THC)on the tail-flick reflex, body temperature, and catecholamine synthesis were examined in the mouse in order to compare their effects in a single species and strain under uniform conditions. Naloxone antagonism of THC and cross-tolerance between morphine and THC were also studied. Both morphine and THC produced antinociception, hypothermia, and increased catecholamine synthesis at 30 min after s.c. injection. Morphine produced greater increases in dopamine synthesis and was a more potent antinociceptive agent, while THC produced greater increases in norepinephrine synthesis and was a more potent hypothermic agent. Naloxone pretreatment (1 mg/kg) partially antagonized the hypothermia and increase in catecholamine synthesis produced by THC. There was also cross-tolerance between morphine and THC, but it was asymmetric in that THC-tolerant animals were cross-tolerant to only the hypothermic action of morphine and morphine-tolerant animals cross-tolerant to only the antinociceptive action of THC.


Effects of d-amphetamine on the set point of the thermoregulatory system in rats.

Exposing a rat's tail to an ambient temperature lower than that sensed by the rest of the body causes an increase in body temperature. Pretreatment with d-amphetamine causes an even greater increase in body temperature. Morover, while control rats perceive any ambient temperature below 20 degrees C as 'cold', amphetamine-treated animals only perceive ambient temperatures below 20 degrees C as 'cold'. This effect of d-amphetamine was found not only when the body temperature of the rats was 20 degrees C, but also when the body was kept at ambient temperatures of 15 degrees--4 degrees C. Because this effect of d-amphetamine, i.e., shifting of the reference point among treated rats, was found in two other situations (behavioral thermoregulation and in studying the anorexic effects of d-amphetamine among rats kept at different ambient temperatures), the best explanation is that in addition to the effects of the drug upon some thermal sensory roles, it also causes a change in the value of the set point of the thermoregulatory system, and drug-treated rats perceive ambient temperatures of 10 degrees C as 'normal'.


Situational factors contributing to the placebos effect.

The influence of four variables (status of communicator of drug effects, attitude of dentist, attitude of dental technician, and message of drug effects) on the obtainment of placebo effects in an oral surgery clinic was investigated. Dependent variables were (1) rating of pain experienced from mandibular-block injection, (2) pre-post placebo state anxiety, and (3) pre-postplacebo fear of injection. Enthusiastic messages of drug effects produced statistically and clinically significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic. Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive, only the attitude factors obtained statistical significance. The status of the communicator accounted for very small portions of the variance.


Effects of learned safety and tolerance on alcohol consumption by the rat.

Evidence is presented that learned safety increases the rat's willingness to drink ethanol: induction of tolerance to ethanol following learned safety training produces a further increase. Rats with chronically implanted intragastric fistulae consumed substantially more (30%) alcohol when aversive post-ingestional effects were minimized by draining stomach contents during drinking than did rats allowed to retain stomach contents. Half the rats from each group were then made tolerant by prolonged forced alcohol intubation. Later testing showed an increase in alcohol consumption by rats receiving learned safety training or rendered tolerant, with the two factors being additive.


The effect of morphine on fear extinction in rats.

Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.


Behavioral supersensitivity to apomorphine following chronic narcotic treatment in the guinea pig.

Male albino guinea pigs were treated for 3 weeks with methadone, morphine, haloperidol, or saline. One week and 5 weeks following termination of treatment they were challenged with the directly acting dopaminergic agonist apomorphine. At the week 1 test the haloperidol and saline groups did not differ, but behavioral supersensitivity was apparent in significantly elevated mean stereotypy scores of the methadone and morphine groups relative to the saline group. The source of differences in mean scores was a higher peak score rather than increased duration of action. At the week 5 test the scores of the methadone group were even higher, the morphine group's scores were equivalent to the saline group's, and the haloperidol group's scores were significant depressed. This study indicates that a 3-week treatment period with methadone or morphine is sufficient to induce dopaminergic supersensitivity and suggests that there may be different time courses for the retention or expression of supersensitivity following these narcotics.


Sensitivity to apomorphine in the guinea pig as a function of age and body weight.

Male albino guinea pigs aged 4--10 weeks were challenged with 0.1, 0.2, and 0.4 mg/kg apomorphine. Mean stereotypy scores rose signfiicantly as a function of age. Stereotypy scores were better correlated with age than with body weight, suggesting that CNS maturation, rather than weight-related factors, were responsible. Although age and body weight were correlated, there was enough variability to make bvody weight an unreliable indicator of age.


Changes in morphine self-administration after tel-diencephalic lesions in rats.

Rats were trained to bar-press for intravenous infusions of morphine sulfate during 1-h daily test sessions. Rates of morphine self-administration were enhanced by lesions of the frontal cortex and hippocampus and transiently reduced by lesions of the medial forebrain bundle and medial thalamus. Dose-response studies indicated that sensitivity to morphine's rewarding property was decreased by frontal cortical and hippocampal lesions. Lesions of the posterior cortex, the tuberculum olfactorium, and the nucleus accumbens had no effect on self-administration behavior. The results are discussed in relation to previous findings with caudate and brainstem lesions. A neuroanatomical substrate for morphine reinforcement is suggested.


Acute and chronic effects of lithium chloride on physiological and psychological measures in normals.

In the acute experiment six healthy volunteers were given orally two doses of lithium chloride, 16 and 32 mmol, and placebo sodium chloride 32 mmol in a double-blind standardized procedure, with a 1-week interval between treatments. Compared to sodium, lithium produced a decrease in subjective well-being, decrease of skin conductance fluctuations, and increase in plasma calcium concentrations. Dose-related effects were maximal at the first hour after ingestion, decreasing or disappearing at 3--5 h. Most effects did not correlate with plasma or erythrocyte lithium concentrations, but drug effects and feelings of nausea were highly correlated. Accordingly, most acute effects seemed due to peripheral drug effects. In the chronic experiment six healthy volunteers were given orally 16 mmol of lithium chloride or sodium chloride (placebo) twice a day for 1 week in a double-blind standardized procedure with a 2-week interval between treatment weeks. Compared to placebo, lithium produced feelings of subjective impairment, an increase in EEG slow waves and of auditory evoked response variability, a deficit in long-term memory, and an increase in plasma magnesium concentrations. Most lithium effects did not correlate with plasma or erythrocyte lithium concentrations.


Neuropharmacological and behavioral evaluation of prostaglandin E2 and 11-thiol-11-desoxy prostaglandin E2 in the mouse and rat.

Prostaglandin E2 (PGE2) and 11-thiol-11-desoxy Prostaglandin E2 (SHPGE2) were evaluated in a variety of behavioral and neuropharmacological procedures that are sensitive to neuroleptics. Clozapine (C), thioridazine (T), haloperidol (H), and fluphenazine (F) were also tested for comparison. All agents except T suppressed avoidance responses in trained rats at one or more doses without concurrently disrupting escape behavior. T, H, and F dose-responsively antagonized lesioned rat rotational behavior at nontoxic doses. T, H, and F induced catalepsy at doses considerably higher than those effective on rotational behavior. SHPGE2, PGE2, and C did not cause catalepsy and did not show statistically significant dose-response antagonism of rotational behavior at less than toxic doses. All agents tested blocked d-amphetamine-induced lethality and caused motor incoordination dose-responsively. SHPGE2, PGE2, C, and T caused statistically significant blockade of physostigmine-induced lethality. H and F were ineffective against physostigmine lethality. It was concluded that SHPGE2 and PGE2 demonstrated, qualitatively, a spectrum of neuroleptic like properties remarkably similar to C.


Analgesic effect of etorphine in rats with selective depletions of brain monoamines.

The analgesic effect of etorphine was compared with that of morphine in rats with electrolytic lesions of the nucleus medianus raphe or injected intraventricularly with 6-hydroxydopamine. The effect of both compounds was markedly reduced in animals with raphe lesions, but not significantly modified in those receiving 6-hydroxydopamine. Etorphine and morphine significantly increased the forebrain levels of 5-hydroxyindolacetic acid when administered subcutaneously at doses of 5mg/kg and 2 microgram/kg, respectively. Neither drug significantly affected the forebrain levels of monoamines. It is concluded that, as for morphine the integrity of the serotoninergic system in the brain is important for the full analgesic effect of etorphine.


Effects of 5-hydroxytryptophan, oxotermorine, and tetrahydroaminoacridine on apomorphine-induced stereotypy.

The stereotyped behavior induced by apomorphine in rats was inhibited by oxotremorine and tetrahydroaminoacridine (THA). 5-Hydroxytryptophan (5-HTP) did not change stereotypy scores. These data show influence of cholinergic mechanisms on such behavior. Possible clinical applications are discussed.


Experimental analysis of the 'happy hour": effects of purchase price on alcohol consumption.

An experimental analogue of a discount drink policy known as the "happy hour" was used to study the effects of purchase price on drinking behavior. Male volunteers with a prior history of either casual (N=20) or heavy (N=14) drinking were given free access to beverage alcohol during a 20-day period. Approximately half the subjects could purchase alcohol under a single-price condition (50 cents/drink), while a matched group was given a price reduction daily (25 cents/drink) during a three-hour period in the afternoon. The results demonstrated that the afternoon price reduction significantly increased alcohol consumption in both casual and heavy drinkers. Reinstatement of the standard purchase price effectively suppressed drinking in both groups. The findings are discussed in terms of the theoretical and research implications of environmental influences on drinking.


Methylphenidate and serum prolactin in man.

Methylphenidate induces psychostimulation and increases cardiovascular parameters, and its psychostimulant effects have been proposed to occur via  a dopaminergic mechanism. The effect of methylphenidate on serum prolactin was utilized as a method of evaluating methylphenidate's central dopamimergic effects.  Methylphenidate was not found to exhibit a consistent effect on serum prolactin. Thus, its effect on serum prolactin does not parallel its behavioral activating properties, suggesting that such activation may not involve dopamine. Possibly, norepinephrine or other noncatecholaminergic neurotransmitters are involved in methylphenidate-induced behavioral activation.


Chronopharmacological study of neuroleptics. II. Circadian susceptibility rhythm to chlorpromazine.

In order to study differences in the effect of the neuroleptics due to time of administration, rats were administered chlorpromazine (CPZ) in a variety of combinations of dose and time and the sedation period was measured. There was daily fluctuation in the sedative effect and the pattern of fluctuation differed according to dosage. A similar study under the condition of reversed light and dark gave a reversed curve of the daily fluctuation, showing that the rhythm of light and dark controls  the fluctuation externally. In an attempt to elucidate the mechanism of these phenomena, CPZ was administered at two different times, between which there was a significant difference in the sedation period, and time-course changes in plasma and brain concentration of the drug and its metabolites were measured. No difference was found. These results are interpreted as indicating that the phenomena could arise at the level of amine-receptor activity in the brain. In addidtion, daily fluctuation due to time of administration was noted in lethality.


A reappraisal of the interaction between tricyclic antidepressants and reserpine-like drugs.

The administration of trycyclic antidepressants followed by reserpine-like drugs elicits a pattern of stereotyped locomotor activity. Using desmethylimipramine (DMI) followed by tetrabenazine (TBZ), activity could be reliably elicited only in young rats, and only by using very high doses of TBZ. The latency of onset of activity was up to 5 h. Animals rendered active by DMI-TBZ failed to perform a well-established operant task. The activity syndrome was apparently unaffected by pre- or posttreatment with the dopamine antagonists spiroperidol or primozide, but partial antagonism was obtained with the noradrenaline antagonists phentolamine and phenoxybenzamine. The findings are discussed in relation to the mechanism of action of the effect and its relevance to the clinical action of tricyclic antidepressants.


Response-dependent effects of morphine on reinforcing lateral hypothalamic self-stimulation.

The effects of morphine (10mg/kg) on intracranial self-stimulation were studied in three separate test situations, each requiring rats to perform different types of responses. Self-stimulation was depressed in a test of rate of bar-pressing, to a lesser extent in a test of rate of wall-pressing in which a wider range of movements were reinforced, but not in a shuttle-box, with brain stimulation continuously available on one side of box. This resonse dependency suggests that the depressive effect of morphine on bar-pressing for lateral hypothalamic stimulation reflects a performance deficit rather than an effect on the reinforcing value of the stimulation.


Avoidance  conditioning and Hebb-Williams maze performance in rats treated prenatally with alcohol.

Throughout gestation pregnant Wistar rats consumed a nutritious liquid diet containing 35% ethanol-derived calories. Control mothers were fed lab chow. Subsequently, the offspring of the ethanol-fed mothers were found to be impaired on two-way avoidance conditioning when compared to control offspring, but did not differ from controls in their performance on the Hebb-Williams maze. Fostering and cross-fostering procedures indicated that the effect was due to prenatal influences arising from the drug treatment.


Stereotyped behavior and hyperthermia in dogs: correlation with the levels of amphetamine and p-hydroxyamphetamine in plasma and CSF.

A gas-chromatographic method for simultaneously measuring p-hydroxyamphetamine (pOA) against amphetamine (A) in plasma and CSF is presented. The time course of body temperature (Tb), stereotyped behavior (St), and A and pOA levels in plasma and CSF were studied after administration of 0.6 and 1.5 mg/kg p.o. of A to dogs. Stereotyped behavior reached maximal value 2.5 h after A, as did levels of A in CSF. The A levels in CSF decreased steadily in the following hours and simultaneously with the levels of A in plasma. St remained elevated and began to decrease after 6.5 h. The relationship between St and amounts of A was not linear but exponential. This suggest that both A and its metabolite contributed to this effect. In fact, a linear relationship was found between St and the amounts of pOA in CSF. Body temperature had a time course similar to A plasma levels, reaching peak value after 1.5 h and declining thereafter simultaneously with A. A linear relationship was found between Tb and the amounts of A in plasma. Thus Tb seems to be a peripheral A effect related to the presence of the drug in plasma.


Marked individual variability in heart rate "normalization" by ethanol.

In order to test Kissin's (1974) concept of "normalization" by ethanol (deviant prealcohol parameter values becoming less deviant after alcohol) in nonalcoholics, data on unselected mice and nonalcoholic humans were analyzed. These data were on heart rates (HR) of 1055 HS mice and 24 young adults, measured before and after receiving a dose of ethanol (mice: 1.4g/kg, i.p.;humans: 1.3g/kg, oral). Both mice and humans, on the average, show marked "normalization" inintially low HR usually increasing after alcohol, and initially high HR usually decreasing. The correlation between (1) deviation in  HR from the prealcohol mean and (2) change in HR after alcohol was -0.803 for mice and -0.538 for humans. There is very great individual variability, however, in the degree of this normalizing response, some individuals normalizing strongly and others not at all. Although first described in alcoholics, strong normalization by alcohol of several psychophysiological parameters is now known to occur in mice and seems likely to occur in some nonalcoholic humans. The possible relevance of these results to predisposition to alcoholism remains to be shown.


Antipunishment effects of diazepam: interaction with shock and food deprivation levels in pigs.

The effects of 1mg/kg diazepam on punished behaviour of pigs were investigated under various degrees, of food deprivation and/or shock level. Responses emitted during the punishment signal were affected more by the shock level than by the degree of food deprivation while nonpunished response rates were modified by neither factor. Diazepam treatment increased the number of responses emitted during the punishment signal but interacted with the shock intensity: drug effects were attenuated when the shock intensity was severe, in spite of an equivalent control baseline. Diazepam also increased the overall rate of nonpunished responding. The drug treatment had no reliable effect on flinch and escape thresholds measured in separate experiments. The effects of diazepam on punished responding do not appear to be related to eventual changes in food motivation or sensitivity to electric shock.


The three dose components of negative pion beam and their role in pion radiotherapy.

A new method has been developed for analyzing therapeutic negative pion beams into three LET (linear energy transfer) dose components inherent in such a beam. The technique utilizes thin silicon detectors to obtain pulse height spectra produced by the various particles in the beam traversing the detectors. It is shown that a low LET group is correlated with the incoming pions, muons and electrons; a medium LET group corresponds to protons, deuterons, tritons, and high energy alpha particles; and a high LET group is due to low energy alpha particles, 3He and recoil particles. Several beams used clinically have been studied.


Radionuclide emission computed tomography of the body of laboratory animals.

Selective studies in the monkey and baboon demonstrate the normal physiologic distribution of 99mTc radiopharmaceuticals using single-photon emission computed tomography. The cases demonstrated the ability of the Cleon Transverse Section Brain Imager TM to do emission computed tomography of various organs. This experience shows what can be expected when equipment for emission computed tomography of the body becomes available for patient studies.


Biosynthesis of 6-keto PGF1alpha by microsomal acetone-pentane powder preparations from hog aorta, ram seminal vesicles, and bovine corpora lutea: properties of same.

Acetone-pentane powders of microsomal rich acetone precipitated fractions, have been prepared from hog aortas, ram seminal vesicles, and bovine corpora lutea. These preparations are all active in converting C14 labelled PGH2 to prostacyclin. The reaction was followed by quantitation of the spontaneous hydrolytic product, 6-keto PGF1alpha. The heat stability, pH optima, reactions with inhibitors, and other properties of these types are discussed. The comparative behavior of the respective enzyme preparations shows that while qualitatively they behave in a similar manner, quantitatively, there are significant differences between them, particularly with respect to heat treatment, and response to inhibitors.


The serological reactions of Mycoplasma isolated from pneumonic sheep lungs in the Sudan.

Seven mycoplasma isolated from pneumonic sheep lungs were found to belong to two serologically unrelated groups. Isolates in one group reacted strongly with antisera to M arginini in the metabolic inhibition and growth inhibition tests. All isolates except one failed to react with antisera to M mycoides var capri or M mycoides var mycoides. The results of the present work support the previously reported division of the isolates into two groups on the basis of their biological properties.


A comparison of three serological tests in the diagnosis of caprine brucellosis.

The serum agglutination test (SAT), the Rose Bengal plate test (RBPT) and the milk ring test (MRT) were used in the diagnosis of caprine brucellosis. There was a close correlation between the SAT and RBPT when both tests were negative but the RBPT failed to detect 79.82 per cent of sera in excess of 50 iu. Also, owing to the relatively poor milking potential of the Nigerian goat and the false positive results with the MRT, it is concluded that the SAT offers a better serological diagnostic tool for caprine brucellosis in this locality.


Effect of thiol derivatives on mixed mucus and blood clots in vitro.

The disintegrating effect of three reducing thiol derivatives: [sodium mercaptoethane sulphonate (Mesna), N-acetyl-L-cysteine (NAC) and dithio-1,4-threitol (DTT)] was investigated in vitro upon blood clots formed in the absence or in the presence of tracheobronchial secretions and compared with the effect of iso-osmotic saline solution. The amounts of haemoglobin released from the clots after 30 min incubation and the initial rates of haemoglobin release were compared for the different products at different concentrations. All three reducing agents showed some ability to disintegrate mixed clots to an extent depending on their concentration. After 30 min incubation, statistical analysis showed a highly significant difference in favour of Mesna at the three concentrations used, i.e. 0.1, 1.0 and 10 mmol/1. The initial rate of haemoglobin release in presence of Mesna was at all concentrations significantly higher than that of NAC or DTT. The effects on normal blood clots were much less pronounced. The effectiveness of Mesna in splitting up mixed blood and mucus clots in the management of patients who had inhaled blood is discussed.


Changes in essential fatty acids in plasma  lipid fractions of polytraumatized patients with different parenteral nutrition.

We investigated changes in the fatty acid pattern of plasma lipids during the phase of total parenteral nutrition in two groups of polytraumatized patients. For parenteral nutrition we gave L-amino acid solutions in a dose of 0.24 g N day-1kg-1 body weight. In addition, we administered in the first group glucose and fructose, and in the second group glucose, fructose and fat emulsions in a total dose of 30 kcal day-1kg-1 body weight. In the latter group, the proportion of the fat emulsions was 30-40% of the calories administered. The most striking findings were the decrease of the essential fatty acids with regard to the phospholipid fraction from about 60% to 30% in the early post-traumatic phase. In the first group of patients we observed a further reduction of the essential fatty acids in the period of observation. This could be avoided by administering fat emulsions of the same type as we gave in the second group of patients. The functions of essential fatty acids in membranes and in the intermediary metabolism are discussed.


[Quantitative measurement of red cell antigens with Groupamatic].

Groupamatic 360 can be adapted to the quantitative measurement of erythrocyte agglutination reactions. Here the authors give the necessary conditions to obtain the best sensitivity and the best reproductibility. They have considered globular suspensions, incubation of the erythrocyte antiserums mixtures, centrifugation, agitation, photometric measurement. As concerns the quantitative technique, we used the average peripheral measurement obtained in the twleve cuvettes of the same selected disc sector. The calibration is fixed to 50 mV for a non agglutinated red cell suspension and to 950 mV for albumin in a saline solution. In these conditions, the best discrimination is obtained for agglutination with measures between 400 and 800 mV. The maximum sensitivity is reached with reactions corresponding to 600 mV, that is to say in our selected conditions with 50% of free red cells. The choice of the zone between 500 and 600 mV enables to detect variations from 1.5 to 2% in an antibody solution concentration. This zone is particularly favorable for quantitative work. Although a part of these operations in this preliminary work were manually effected, the automatic centrifugation, agitation, photometric measurement and results print out make possible a large number of measurements with very satisfactory reproductibility conditions. Besides, these experiments pointed out some factors of improvement which will be helpful for the new 360 G Groupmatic equipments.


Benign meningococcemia in childhood. A report of five cases with clinical and diagnostic remarks.

Five children aged 1/2--10 years with benign meningococcemia are reported. The clinical picture was quite uniform: good general condition, spikes of fever, skin eruptions as maculopapules--sometimes haemorrhagic, appearing in association with febrile periods, and arthralgia (big joints). The diagnosis involves either isolation of meningococci (MC) from blood, demonstration of MC with immunofluorescence in skin eruptions, or a significant elevation of MC antibody titre in connection with typical clinical signs and symptoms. Important differential diagnoses are Henoch-Schönlein syndrome, disseminated gonococcal infection, septicemia of other origins, subacute bacterial endocarditis, viral infections, hypersensitivity reactions and subsepsis allergica. By co-agglutination technique, the causative agent of meningococcemia in 4 of the 5 children was shown to be MC group B. These have some features in common with gonococci, whereby an incorrect diagnosis might be suggested as demonstrated in one of our patients. The question is raised whether MC group B is the main causative agent in benign meningococcemia.


Evaluation of spiramycin as a therapeutic agent for elimination of nasopharyngeal pathogens. Possible use of spiramycin for middle ear infections and for gonococcal and meningococcal nasopharyngeal carriage.

Varying doses of spiramycin were administered orally to healthy volunteers, and concentrations in serum and saliva were determined. The absorption of the drug was not significantly influenced by concomitant food intake. Saliva peak concentrations were 1.3--4.8 times higher than peak concentrations in serum. The elimination half life was 2--3 h in serum, and 4--8 h in saliva. Accumulation of the drug was seen in saliva but not in serum. The possible effect of spiramycin in eliminating bacteria from the nasopharynx was evaluated in vitro by comparing the spiramycin saliva concentrations with the MICs of bacteria known to establish themselves in the nasopharynx. At a concentration of 1.2 microgram/ml, spiramycin inhibited all investigated strains of group A streptococci, pneumococci and Branhamella catarrhalis, and at 2.4 microgram/ml all investigated gonococci. Concentrations of 19 and 38 microgram/ml, respectively, were required to inhibit all meningococci and Haemophilus influenzae. Following administration of 1.5 g spiramycin as a single daily dose for 3 days, the mean concentration in saliva reached or surpassed the MIC values of streptococci, pneumococci and Branhamella for 45 h, and of gonococci for 25 h. The possible use of spiramycin for prevention of relapses in acute otitis media and in treatment of serous otitis media is discussed, as well as the possible use of the drug in gonococcal and meningococcal nasopharyngeal carriage.


Isolation care of infection-prone burn patients.

An experimental and clinical study of spread of colonisation between burn patients, and their susceptibility to infection, was performed. Burn patients' polymorphonuclear neutrophil granulocytes (PMN) functioned poorly, particularly during the second week after injury which coincided with maximum growth of bacteria in the burn wound. Patients with large burns often dispersed S. aureus and Ps. aeruginosa but also beta-hemolytic Streptococcus to the air of their rooms. Airborne transfer of these bacteria was practically eliminated by nursing in single isolation rooms with plenum ventilation. In such rooms, cross-contamination was carried mainly via clothes. Patients with small burns sometimes were important sources of such contamination although they dispersed little bacteria to the air. A thorough change of barrier dress after close contact nursing delayed the first exogenous S. aureus colonisation until after the time of greatest impairment in PMN functions. A further reduction in cross-contamination would be possible with barrier garments impermeable to fluids and bacteria on points of contact, as shown in experiments with plastic apron as protective dress. Measurements of penetration through fabrics of particles suspended in air, commercially used, did not correlate to the performance of garments made from the fabrics in experimental nursing and clinical use. Bacteria were shown to penetrate fabrics through rubbing, particularly when wet where the microcolonies present on the cloth were separated into smaller units. An instrument was designed which measured such penetration, and was used to select fabrics for barrier garments. Tightly fitting barrier garments increased the disperal of bacteria from clothes worn underneath them. The wearing of barrier garments should therefore be restricted to close contact nursing. An open-roofed plastic patient isolator was designed and built. It did not appreciably reduce cross-contamination and gave psychological and practical problems. It seemed not to be a realistic alternative to better protective garments in isolation rooms.


Alcoholic liver disease, new aspects of an old problem.

In the therapy of alcoholic liver disease, two recent trends deserve consideration, one is the role of immunologic mechanisms and the other is the effect of nutrition. In various double blind studies no improved survival of corticosteroid treated patients with alcoholic hepatitis has been found. Intravenous hyperalimentation with amino acid solution combined with peroral feeding seemed, however, to have a beneficial effect in alcoholic hepatitis.