[Long-term infection of a cell culture from newborn mouse brain with the FNV strain of yellow fever virus (author's transl)].

A cell culture from brains of one day old mice was infected with a high multiplicity of the French neurotropic strain of yellow fever virus (FNV); the infected cell culture produced and released infectious FNV for more than 180 days post-inoculation with titres between 10(0.6) and 10(6.4) PFU/ml. The cell sheet exhibited some rare plaques of round cells with a slow centrifugal extension; the destruction of the cell sheet was not complete before 200 days post-inoculation.


Long-term tissue culture of epithelial-like cells from human skin (NCTC strain 2544). II. Viscosity changes after enzyme treatment.

Human skin epithelial-like cells (NCTC strain 2544) were grown in NCTC 135 medium. Neuraminidase and hyaluronidase were added to the growth medium. Cells were incubated 96 h at 36 degrees C. Growth rate and viscosity of cell suspensions were measured after forming single cells mechanically (mopping). With addition of neuraminidase and hyaluronidase, respectively, the growth rate remains unchanged. With neuraminidase a distinct raise in viscosity was achieved, whereas with hyaluronidase only a small effect was seen. The characteristic structure viscosity is maintained in all forms of the viscosity curves at different shear-rates.


Insidious strut fractures in a DeBakey-Surgitool aortic valve prosthesis.

Recent reports of cage wear occurring in DeBakey-Surgitool aortic valve prostheses prompted us to examine with image intensification all our patients who have had this type of prosthesis implanted. One patient, who was asymptomatic, was discovered to have a prosthesis with two fractured struts. This patient's prosthetic valve was replaced successfully with a stented porcine heterograft prosthesis. Including the valve removed from this patient, 8 DeBakey-Surgitool aortic valves with structural defects have been reported to the manufacturer. In the absence of a catastrophic event, patients with valves having fractured or worn struts may be totally asymptomatic, and routine periodic roentgenographic examination may be the only way of detecting strut wear or fracture.


Comparative haemodynamic effects of clonidine and guanfacine.

Dose-response relationships were established for the acute effects on arterial pressure and heart rate of the antihypertensive agents, clonidine and guanfacine, administered intravenously or intramuscularly to anaesthetized rats. The intramuscular route appeared to be preferable to the intravenous, for the direct pressor potency of each drug was thereby greatly reduced in relation to the hypotensive efficacy. The potency of clonidine was 10-20 times that of guanfacine, but the same maximal fall in blood pressure was obtained with either agent administered by either route. Both agents caused a marked, dose-related suppression of plasma renin activity. When either clonidine or guanfacine was administered twice daily for 3 weeks and then discontinued, a phase of blood pressure overshoot with tachycardia commenced within 24 hr of the last injection. These withdrawal effects were more evident in guanfacine-treated rats than in clonidine-treated rats.


[Interrelationships between carnitine metabolism and fatty acid assimilation in Pseudomonas putida (author's transl)].

The carnitine metabolism and some relations to the fatty acid metabolism were studied in Pseudomonas putida by means of control of growth, analysis of metabolites, and determination of enzyme activites. The strain grew on gamma-butyrobetaine, D,L- and L-carnitine, glycinebetaine, choline, D,L-norcarnitine, D,L-gamma-amino-beta-hydroxybutyrate, and D,L-beta-hydroxybuty-rate. Although the strain used straight-chain fatty acids of 2-16 C-atoms, it was only able to grow on O-acyl-L-carnitines of 10 or more C-atoms in the acyl-group. Addition of carnitine stimulated the growth on long-chain fatty acis. The formation of trimethylamine increased, if L-carnitine or gamma-butyrobetaine were the only carbon sources, and decreased, if these trimethylammonium compounds were carbon as well as nitrgen sources. L-Carnitine induced the carnitine dehydrogenase as well as the beta-hydroxybutyrate dehydrogenase, gamma-Butyrobetaine as carbon and nitrogen source induced the carnitine dehydrogenase, too. In the crude extract the specific activiteis of beta-hydroxybutyrate dehydrogenase were 0.7 or 1.6 mumoles.min-1.mg-1 after growth on L-carnitine and D,L-beta-hydroxybutyrate, respectively. The synthesis of both enzymes was repressed by glycinebetaine, glucose and long-chain fatty acis. Dependent on the nitrogen source L-carnitine was catabolized via two different pathways.


[Diagnosis and outcome of cerebral distress in newborn infants who presented signs of fetal hypoxia. Prospective study].

The prospective study covered 60 full-term newborns, who presented exclusively signs of acute fetal distress. It had two major aims: --the analysis of the clinical and EEG symptomatologies, allowing the assessment of the cerebral damage in the neonatal period; --the evaluation as to whether the post-asphyxia cerebral damage may remain undiagnosed in the neonatal period, sequellae revealing it secondarily. Clinical and EEG supervision was undertaken during the first week; it was continued till 3 years of age in 45 of the 56 survivors. During the first week of life, 50 infants had at least once, an abnormal neurologic manifestation. The signs for a poor outcome are "unexpected" fetal distress, Apgar score below 2 at 1 min., seizures occurring or persisting after 48 hours, severe clinical and/or EEG changes occurring more than once. Prognosis is considered as favorable if EEG or clinical examination are consistently normal, or if EEG and clinical examination are normalized at 6 days of life.


Serologic and cross-immunity studies with contagious ecthyma and goat pox virus isolates from the western United States.

Contagious ecthyma and goat pox viruses were isolated from goats affected with papulopustular epidermal lesions. Results of in vitro serum neutralization and in vivo cross-immunity studies indicate that these contagious ecthyma and goat pox isolates from the western United States are antigenically dissimilar and that exposure or vaccination with one isolate could not be used as a method of inducing immunity to the other. Exposure to each isolate conferred immunity to re-exposure with the same agent. The serum neutralization test indicates that the severity and persistance of lesions to goat pox infection influences the nature of the antibody response to an initial exposure.


Bovine respiratory syncytial virus infection of bovine embryonic lung cultures: enhancement of infectivity with diethylaminoethyl-dextran and virus-infected cells.

The effects of incorporating diethylaminoethyl-dextran (DEAE-D) in the inoculum with bovine respiratory syncytial virus (BRSV) on the infectivity of BRSV was evaluated. A concentration of 40 microgram DEAE-D/ml provided maximal enhancement of infection as determined by the time of onset of cytopathic effect (CPE), the percentage of cells infected by the inoculum, and the amount of virus produced. When DEAE-D was used in the inoculum, the CPE appeared a day earlier, the percentage of cells infected by the inoculum, as determined by the fluorescent antibody test, was increased 11 times, and the viral titer was increased 2 times as compared to results obtained without DEAE-D. Bovine respiratory syncytial virus-infected cultures contained much cell-associated virus which could be liberated by sonication to increase the titer of virus stocks. The use of BRSV-infected cells rather than supernates from BRSV-infected cells increased the rate at which a cytopathic effect developed, although it did not substantially increase the titer of virus which was harvested. The use of DEAE-D in the inoculum and the passage of BRSV-infected cells instead of viral suspensions was found to be the quickest and most effective method of consistently obtaining BRSV with a titer of about 10(5.5) TCID50/ml.


Influence of head position on the prognosis of experimental subarachnoid hemorrhage.

Autogenous blood was injected repeatedly into the intracranial subarachnoid space of cats, the heads of which were placed in one of four positions (prone, supine, left side down, and right side down). Epidural pressures, mean aortic blood pressures, and pulse rates were measured, and their responses to the repeated injections were analyzed. The distribution of the injected blood was different among the four groups. The cats in the sulpine position had the greatest amounts of blood in the posterior fossa and tolerated the injections least well. The position of the head at the time of a subarachnoid hemorrhage may influence the prognosis; positions that favor accumulations of blood around the brain stem carry the greatest risk.


A twin analysis of dietary intake: evidence for a need to control for possible environmental differences in MZ and DZ twins.

In the NHLI Twin Study MZ twins are shown to "get together" substantially more often than DZ twins. With this result as an indicator of differences in shared environment, the assumption of equal shared environmental variation for MZ and DZ twins is assessed using nutritional data calculated from a food frequency questionnaire. Six nutrients show significant genetic variance for the total sample. However, when stratified on the basis of how frequently twins see each other, none of the nutrients shows significant genetic variance for both strata. A similar pattern is seen for several individual items from the questionnaire. In addition, four of the nutrients show significant correlation between the absolute difference in the nutrient intake of MZ twin pairs and how often they "get together." These data appear to show that unequal environmental effects may lead to falsely high estimates of genetic variance for nutrient intake.


Positive and negative geotaxis: sex-linked traits in Drosophila pseudoobscura.

Using a Hirsch classification maze, selection was made for positive and negative geotactic behaviors in three different strains of Drosophila pseudoobscura. Hybridization studies were then carried out with flies from the diverged strains. The geotactic scores of the parents and F1 flies indicate that both negative and positive geotactic behaviors in these strains are strongly influenced by genes in the X chromosome. Additional hybridization studies using flies from strains with similar phenotypes suggest that the diverged strains contain similar alleles and the number of loci in the X chromosomes responsible for these types of behavior is limited. The loci may be highly organized in the X chromosome.


The formation of lipid-linked sugars as intermediates in glycoprotein synthesis in rabbit mammary gland.

1. The incorporation of d-[1-(14)C]mannose, d-[2-(3)H]mannose and N-acetyl-d-[1-(14)C]-glucosamine into glycoproteins and lipid-linked intermediates of mammary explants obtained from lactating rabbits was studied. The amount of radioactivity incorporated into lipid-linked intermediates was very low compared with the incorporation into protein. Most of the radioactivity incorporated into the chloroform/methanol-soluble fraction was present as neutral lipid. Radioactivity from d-[2-(3)H]mannose was incorporated mainly into the fatty acid moiety, whereas radioactivity from d-[1-(14)C]mannose and N-acetyl-d-[1-(14)C]glucosamine was present in the glycerol moiety of triacylglycerol. 2. The labelled lipid-linked intermediate that was soluble in chloroform/methanol/water (10:10:3, by vol.) was partially characterized and was found to exhibit properties characteristic of an oligosaccharide linked to lipid via a pyrophosphate bridge. It migrated largely as a single zone of radioactivity on t.l.c. and was eluted from a column of DEAE-cellulose acetate as a single peak by 50mm-ammonium acetate. 3. The oligosaccharide moiety was released from the lipid by mild acid hydrolysis. The size of the oligosaccharide was estimated by paper chromatography to be 10 or 11 monosaccharide units. 4. d-[1-(14)C]Mannose was incorporated largely into glycopeptides with molecular weights in the range 40000-80000, as determined by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. Label from N-acetyl-d-[1-(14)C]glucosamine was incorporated into a glycopeptide with an electrophoretic mobility identical with that of rabbit casein (mol.wt. 32000) as well as into glycopeptides of higher molecular weight. 5. Approx. 50% of the total radioactivity in the protein labelled from N-acetyl-d-[1-(14)C]glucosamine was present as galactosamine, a component of the carbohydrate portion of rabbit casein. No labelled galactosamine was present in the lipid-linked oligosaccharide labelled from N-acetyl-d-[1-(14)C]glucosamine. It thus appears that the lipid-linked oligosaccharide is not involved in the glycosylation of casein.


Identical twins with differing forms of ventricular pre-excitation.

Identical 10-year-old twins, both with electrocardiograms showing a short PR interval and a normal QRS complex but with dramatically different electrophysiological characteristics, are described. One twin experienced episodes of rapid palpitation and on one occasion was resuscitated from ventricular fibrillation. An intracardiac electrophysiological study confirmed the presence of an atrioventricular nodal bypass tract and in addition revealed the presence of an accessory atrioventricular pathway, thus demonstrating that the patient had both the Lown-Ganong-Levine and Wolff-Parkinson-White syndromes. Re-entry tachycardia and atrial fibrillation, with a very rapid ventricular rate, were precipitated. After treatment with amiodarone, the patient became asymptomatic and a repeat study showed that the features of the atrioventricular nodal bypass tract were no longer present and though re-entry tachycardias using the accessory atrioventricular pathway could still be induced, their rates were slower than before treatment. The other twin, in spite of an identical surface electrocardiogram, was asmymptomatic. An electrophysiological study showed the features of an atrioventricular nodal bypass tract but there was no evidence of additional atrioventricular accessory connections and a tachycardia could not be induced.


Failure of suckling to transfer immunity to a syngeneic rat sarcoma.

Young born to and suckled by mothers rendered immune to a syngeneic sarcoma showed no acquired resistance to challenge with tumour. Whilst other workers had found that allograft immunity could be transferred by milk, we conclude (1) that lymphocytes present in the milk cannot transfer immunity to tumour-specific antigens when absorbed by suckling, and (2) that transfer of maternal immunoglobulins either pre- or postnatally also does not protect against s.c. inoculated tumour.


Mitoses in normal and psoriatic epidermis.

The morning count of mitoses in uninvolved epidermis of psoriatics is not significantly different from normal skin. The afternoon count is higher than the morning in both, and significantly higher in uninvolved than in normal epidermis. These results may be interpreted as favouring the existence of a non-cycling G2 population in human epidermis. This G2 population could be released into mitosis by the factors involved in diurnal variation, and might be larger and more labile in psoriatics than in normals. The pathogenesis and aetiology of psoriasis may be related to such a G2 population.


Maternal plasma and amniotic fluid prolactin levels in normal and hypertensive pregnancy.

Prolactin levels in the plasma and amniotic fluid of 121 normal pregnant women, 78 women with pre-eclampsia and 30 women with essential hypertension complicating pregnancy were determined by radioimmunoassay. Mean prolactin levels in plasma, but not in amniotic fluid, were significantly lower than controls in the group with pre-eclampsia (P less than 0.01) and in the group with essential hypertension (P less than 0.05). These findings suggest altered production and/or clearance of prolactin from the maternal compartment in these patients and may explain their increased response to pressor agents.


Infra-red transillumination stereophotography of the iris in Fuchs's heterochromic cyclitis.

The structural pattern of the iris in 13 patients with Fuchs's heterochromic cyclitis (FHC) was studied by infra-red transillumination stereophotography. All eyes with FHC showed atrophic changes of the iris. Extensive iris atrophy appeared as light, even translucence of the iris, associated in some cases with occasional dense small patches or pigment clumps. Moderate punctate, patchy or radiate, or extensive atrophy of the sphincter muscle was seen in all eyes with FHC. Radial contraction folds of Schwalbe, structural folds of Schwalbe, and circular contraction folds on the posterior surface of the iris were visualised in few eyes with FHC, whereas they were seen in most contralateral eyes. The results suggest that infra-red transillumination sterophotography can be used as a diagnostic method in FHC.


Retinal dystrophies associated with peripheral retinal vasculopathy.

A pair of identical twins with cone-rod dystrophy and 1 patient with dominant retinitis pigmentosa are reported who had a peculiar vascular retinopathy characterised by perivenous accumulation of fluorescein in the temporal periphery. Other retinal dystrophies associated with leaking retinal vessels are discussed.


Calcium digestibility in cows as influenced by the excess of alkaline ions over stable acid ions in their diets.

1. Statistical analyses were carried out on results obtained under strictly-controlled conditions in metabolism stalls with forty-one different rations fed to 127 adult non-pregnant dry cows, and with fourteen other different rations fed to thirty-five adult non-pregnant lactating cows that had calved 2-6 months earlier and whose daily milk production ranged from 11 to 20 kg. 2. Correlations between calcium digestibility and values for the sum of the alkaline ions sodium and potassium minus the sum of the stable acid ions chloride, sulphate and phosphate were calculated for all fifty-five experimental diets. 3. The results showed that the excess of the anions over the cations, in rations maintaining a positive Ca balance but not in rations allowing a negative Ca balance, increases the absorption of Ca from the intestine. Phosphorus, not alone but with chloride and sulphate, is the most important component of this effect.


A model for the estimation of volatile fatty acid production in the rumen in non-steady-state conditions.

A method of estimating volatile fatty acid (VFA) production in the rumen in non-steady-state conditions was proposed. Laboratory models indicated that good estimates of total production over a complete feeding cycle could be obtained even when a wide range of production rates and volume changes occurred during the experiment. But estimates of instantaneous production rates might have contained large errors unless some attempt was made to match the infusion rate of labelled VFA to the rate at which VFA was produced in the rumen.


On supplementing the selenium intake of New Zealanders. 2. Prolonged metabolic experiments with daily supplements of selenomethionine, selenite and fish.

1. The daily intake of selenium by three subjects was supplemented with 100 microgram Se as selenomethionine (Semet-Se) or sodium selenite (selenite-Se)/d for 10-11 weeks, or with 65 microgram Se as in mackerel (Scomber japonicus) (fish-Se)/d for 4 weeks. 2. Urinary and faecal excretion of Se was measured and also Se concentration in whole blood, plasma and erythrocytes. Measurements on blood were made at intervals after supplementation had ceased. 3. Selenite-Se was not as well absorbed (0.46 of the intake) during the first 4 weeks as Semet-Se (0.75 of the intake) and fish Se (0.66 of the intake). 4. Blood Se increased steadily with Semet-Se, from 0.08 to 0.18 microgram Se/ml, but more slowly with selenite-Se, reaching a plateau in 7-8 weeks at 0.11 microgram Se/ml. Plasma Se increased more rapidly with Semet-Se than with selenite-Se, so that initially with Semet-Se plasma Se was greater than erythrocyte Se. 5. Daily urinary excretion increased with all forms of supplement, with initially a greater proportion of absorbed selenite-Se being excreted than Semet-Se or fish-Se. A close relationship was found between plasma Se and 24 h urinary excretion. The findings suggested that there was a rapid initial excretion of presumably unbound Se then a slower excretion of residual unbound, loosely bound or bound Se. 6. Total retentions of 3.5 mg selenite-Se and 4.5 mg Semet-Se were large when compared with an estimate of body content of 6 mg Se, derived in another paper (Stewart, Griffiths, Thomson & Robinson, 1978). Retention of Semet-Se and fish-Se appeared to be reflected in blood Se, whereas for selenite-Se, blood Se reflected retention for only a short period after which Se appeared to be retained without altering the blood Se. This suggested that Semet-Se and selenite-Se were metabolized differently. 7.  A double blind-dosing trail with 100 microgram Semet-Se was carried out for 12 weeks on twenty-four patients with muscular complaints in Tapanui, a low-Se-soil area. Blood Se increased in the experimental group (from 0.067 to 0.143 microgrm Se/ml); clinical findings were not conclusive and will be presented elsewhere. 8. Bood Se was measured in New Zealand residents before travelling to Europe or to North America. On return their blood Se was increased, and depending upon the period of time spent outside New Zealand some values reached concentrations found in visitors and new settlers to New Zealand. 9. The results from these studies and the earlier studies of single and multiple dosing have been used to look at the various criteria in use for assessing Se status of subjects. It is suggested that plasma Se be used in preference to 24 h urinary excretion, and in addition to whole blood Se and glutathione peroxidase (EC 1.11.1.9) activity.


Action of phospholipases A2 on phosphatidylcholine bilayers. Effects of the phase transition, bilayer curvature and structural defects.

We examined the action of porcine pancreatic and bee-venom phospholipase A2 towards bilayers of phosphatidylcholine as a function of several physical characteristics of the lipid-water interface. 1. Unsonicated liposomes of dimyristoyl phosphatidylcholine are degraded by both phospholipases in the temperature region of the phase transition only (cf. Op den Kamp et al. (1974) Biochim. Biophys. Acta 345, 253--256 and Op den Kamp et al. (1975) Biochim. Biophys. Acta 406, 169--177). With sonicates the temperature range in which hydrolysis occurs is much wider. This discrepancy between liposomes and sonicates cannot be ascribed entirely to differences in available substrate surface. 2. Below the phase-transition temperature the phospholipases degrade dimyristoyl phosphatidylcholine single-bilayer vesicles with a strongly curved surface much more effectively than larger single-bilayer vesicles with a relatively low degree of curvature. 3. Vesicles composed of egg phosphatidylcholine can be degraded by pancreatic phospholipase A2 at 37 degrees C, provided that the substrate bilayer is strongly curved. The bee-venom enzyme shows a similar, but less pronounced, preference for small substrate vesicles. 4. In a limited temperature region just above the transition temperature of the substrate the action of both phospholipases initially proceeds with a gradually increasing velocity. This stimulation is presumably due to an increase of the transition temperature, effectuated by the products of the phospholipase action. 5. Structural defects in the substrate bilayer, introduced by sonication below the phase-transition temperature (cf. Lawaczeck et al. (1976) Biochim. Biophys. Acta 443, 313--330) facilitate the action of both phospholipases. The results lead to the general conclusion that structural irregularities in the packing of the substrate molecules facilitate the action of phospholipases A2 on phosphatidylcholine bilayers. Within the phase transition and with bilayers containing structural defects these irregularities represent boundaries between separate lipid domains. The stimulatory effect of strong bilayer curvature can be ascribed to an overall perturbation of the lipid packing as well as to a change in the phase-transition temperature.


The synthesis of phosphatidylcholine by adult rat lung alveolar type II epithelial cells in primary culture.

1. The formation of phosphatidylcholine from radioactive precursors was studied in adult rat lung alveolar type II epithelial cells in primary culture. 2. The incorporation of [Me-14C]choline into total lipids and phosphatidylcholine was stimulated by addition of palmitate, whereas the incorporation of [U-14C]glucose into phosphatidylcholine and disaturated phosphatidylcholine was stimulated by addition of choline. Addition of glucose decreased the absolute rate of incorporation of [1(3)-3H]glycerol into total lipids, phosphatidylcholine and disaturated phosphatidylcholine, decreased the percentage [1(3)-3H]glycerol recovered in phosphatidylcholine, but increased the percentage phosphatidylcholine label in the disaturated species. 3. At saturating substrate concentrations, the percentages of phosphatidylcholine radioactivity found in disaturated phosphatidylcholine after incubation with [1-(14)C]acetate (in the presence of glucose) [1-(14)C]palmitate (in the presence of glucose), [Me-14C]choline (in the presence of glucose and palmitate) and [U-14C]glucose (in the presence of choline and palmitate) were 78, 75, 74 and 90%, respectively. 4. Fatty acids stimulated the incorporation of [U-14C]glucose into the glycerol moiety of phosphatidylcholine. The degree of unsaturation of the added fatty acids was reflected in the distribution of [U-14C]glucose label among the different molecular species of phosphatidylcholine. It is suggested that the glucose concentration in the blood as related to the amount of available fatty acids and their degree of unsaturation may be factors governing the synthesis of surfactant lipids.


Differentiation of the contribution of the two subunits of lutropin to its in vivo activity.

Porcine and ovine lutropins were acetimidated at amino groups to various degrees and the effects of the modification on the induction of ovarian ornithine decarboxylase activity were examined. A drastic (84%) loss of biological activity was observed upon modification of two amino groups in porcine lutropin. The results with ovine lutropin derivatives were quite similar. Circular dichroism measurements showed no conformational changes and dissociation into subunits was not observed in the derivatives. Accordingly, the loss of biological activity was not a by-product of conformational changes. It was concluded that lutropin carries a single binding site which is constructed by surface residues or regions located on both the alpha- and beta-subunits of the hormone.


Chemical analysis of stalk components of Dictostelium discoideum.

Structural components of the stalks of mature fruiting bodies of Dictyostelium discoideum have been isolated and characterized after solubilizing non-structural components with urea and sodium dodecyl sulfate. The urea/sodium dodecyl sulfate-insoluble stalks are composed of about 52% cellulose, 15% protein and 3% of a non-cellulosic heteropolymer in a covalently bound matrix. Non-covalently bound fatty acid containing material was also found. The composition and structural interrelationships of these components are essentially identical to that of the urea/sodium dodecyl sulfate-insoluble surface sheath which is produced earlier in development before culmination. These results suggest that the same components are involved in making structural elements which differ substantially in their functional role in the developmental sequence as well as in their spatial and temporal localization and morphological appearance.


Postnatal maldevelopment of the retina.

The effect of certain factors on the early postnatal development of the retina was studied by electron microscopy. Although the retina of developing rats injected with sodium iodate on the 1st and 7th postnatal days showed no retardation of development of photoreceptor outer segment, it began to degenerate about 3 weeks after birth. The retina of developing rats exposed to strong light from the 1st to 5th postnatal day revealed slight developmental retardation of the photoreceptor outer segment and the photoreceptor outer segment began to degenerate about 3 weeks after birth. The vitamin A deficient developing rat it began to degenerate nearly 3 weeks after birth. In spite of induction of developmental retardation of the photoreceptor outer segment of the retina, development of the photoreceptor outer segment was not completely inhibited by moderately acting factors. However, 3 weeks after birth, the photoreceptor outer segments began to degenerate. Therefore, some factors during the early postnatal period can cause the late appearance of degeneration of the retina. The characteristics of retinal degeneration are the same as those found in the retinas of adult rats which are affected by each factor. These degenerations later recover morphologically.


Developmentally regulated slime mold lectins and specific cell cohesion.

Evidence has been presented that cell surface lectins and complementary receptors appear on the surface of slime molds cells of 2 species, D. discoideum and P. pallidum, as they differentiate from a noncohesive to a cohesive form.  Cohesion of P. pallidum cells measured to a quantitative assay can be blocked by reagents that would be expected to interfere with complementary interaction of cell surface lectin and receptor: namely, specific sugars, specific glycoproteins, and specific univalent antibody fragments. Although none of these experiments are definitive, the weight of the evidence suggests that at least some aspect of specific cellular cohesion is mediated by the interaction of cell surface lectins and complementary receptors.


Effect of corticosteroid therapy on the phagocytosis of antibody-coated platelets by human leukocytes.

Patients with idiopathic thrombocytopenic purpura (ITP), a disorder in which antibody coated platelets are cleared from the circulation by phagocytic cells, are often treated with glucocorticoids. The effect of corticosteroids on the recognition and ingestion of sensitized platelets by phagocytes can be quantified in these patients and compared to changes in platelet levels. Six patients with ITP were treated with 96 mg daily of methylprednisolone for 5 days. This treatment raised their platelet count and simultaneously decreased the ability of their granulocytes to phagocytize antibody-coated platelets and C3-coated paraffin oil droplets. Corticosteroid treatment did not affect the binding of antibody to platelets or the quantity of antibody in the patients' serum. The ingestion defect was present in isolated, washed leukocytes and persisted for 3-5 days after the corticosteroids were discontinued. Granulocytes and purified monocytes obtained from patients with other medical disorders receiving corticosteroids also ingested paraffin oil droplets and opsonized platelets at a slower rate. These studies provide direct evidence that corticosteroids induce a generalized phagocytic defect and that this may be the mechanism by which corticosteroids raise the platelet count in patients with ITP.


Analysis of 2,4-D and 2,4,5-T in lingonberries, wild mushrooms, birch and aspen foliage.

A method was developed for residue analysis of 2,4-D and 2,4,5-T in lingonberries, wild mushrooms, birch and aspen foliage. The method involves the extraction of the residues with diethyl ether followed by alkali hydrolysis, purification by column chromatography, methylation of the free acids and their determination by gas chromatography. The limit of detection is 0.05 ppm for 2,4-D and 0.02 ppm for 2,4,5-T for a 20 g sample with a recovery of 75% +/- 11%. Results of some analyses are also reported.


The influence of alachlor, trifluralin, and diazinon on the development of endogenous mycorrhizae in soybeans.

Preplant incorporated treatments of 2 and 4 kg/ha of trifluralin and diazinon had no significant effect on growth, P accumulation or root colonization by mycorrhizal fungi in soybeans planted in an Andover clay loam. At 4 kg/ha, alachlor and trifluralin inhibited root development of 25 day-old plants. The 4 kg/ha alachlor treatment reduced shoot weight of 25 day old plants significantly and suppressed mycorrhizal development of 25 to 60 day old plants. At currently used commercial rates neither alachlor, trifluralin, nor diazinon affected mycorrhizal development under the conditions of the experiment.


Perinatal post-mortem radiography--experience with 2500 cases.

A review of 2500 routine post-mortem radiographic examinations of perinates is presented. It is concluded that the procedure is of value in the detection of abnormalities which may have contributed to the death of the perinate and which may have escaped detection at autopsy. The use of contrast agents may assist in the evaluation of congenital abnormalities, especially of the cardiovascular system. Post-mortem radiographic examination may be especially helpful in the evaluation of perinates for whom permission for autopsy is denied. Post-mortem radiography may assist in the gathering of statistical data and may provide useful material for teaching and research.


Psychiatric problems in the first year after mastectomy.

The psychiatric morbidity associated with mastectomy was assessed in 75 women by following them up from the time they presented with suspected breast cancer to one year after the operation. Fifty women with benign breast disease served as controls. Throughout the follow-up period the incidence of psychiatric problems was higher among the women who had undergone mastectomy. One year after surgery 19 (25%) of these women compared with only 5 (10%) of the controls needed treatment for anxiety or depression or both, and 16 (33%) compared with 3 (8%) respectively had moderate or severe sexual difficulties. Altogether 29 patients in the mastectomy group (39%) and six of the controls (12%) had serious anxiety, depression, or sexual difficulties. Of the eight women in the mastectomy group who sought help for their problems, only two felt that the help given had been appropriate. The inability to recognise and treat these emotional disturbances is a common and serious problem. Monitoring by specially trained nurses and social workers might help to identify them earlier and even reduce them.


Facilitatory and inhibitory effects of electrochemical stimulation of the amygdala on the release of luteinizing hormone.

The effect of amygdaloid stimulation on the release of luteinizing hormone (LH) was studied in unanesthetized, unrestrained rats. Electrochemical stimulation (anodic D.C.) was applied at 11.30 h through stainless steel electrodes chronically implanted into different amygdaloid nuclei; medial (Men.), cortical (Con.), central (Cn.), or basolateral (Bln.). A plastic cannula inserted into the jugular vein was used for obtaining blood samples at different times of the experimental procedure. In rats on the day of proestrus, stimulation (100 micronA/30 sec) in the Bln. resulted in blockade of spontaneous ovulation and of the preovulatory LH release and that in the Cn. produced a delay in the hormone discharge. On the contrary, stimulation in the Men. was effective in advancing the time of the normal LH surge, while no change of the normal pattern occurred from the Con. Stimulation (100 micronA/60 sec) of ovariectomized estrogen primed rats applied in the Men. or the Con. induced LH release, while that in the Bln. or the Cn. had no effect. The release of LH by Men. stimulation and the blocking effect of Bln. showed a close relationship with the amount of current delivered. Lower thresholds were required for inhibition than for activation. The release of LH induced by stimulation in the Men. of ovariectomized estrogen primed rats occurred at the same time of the day whether the stimulus was applied at 8.30 h, 11.30 h or 14.00 h, indicating a modulatory effect of the amygdala. No changes in serum LH concentration were observed after stimulation of the Men. of castrated estrogen primed male rats or in the Bln. of ovariectomized non-primed rats. The present results indicate that the amygdala exerts a dual effect on the release of LH, the Bln. being inhibitory and the Men. and Con. facilitatory.


Effects of phenytoin on acetylcholinesterase activity and cell protein in cultured chick embryonic skeletal muscle.

Cultured pectoral muscle from 11-day-old chick embryos was treated for 48 h with phenytoin (diphenylhydantoin, DPH) in concentrations ranging from 15 to 270 microgram/ml on days 7-9 in vitro. Acetylcholinesterase (AChE, EC 3.1.1.7), creatine phosphokinase (CPK, EC 2.7.3.2), and lactic dehydrogenase (LDH, EC 1.1.1.27) activities, [3H]leucine incorporation into protein, and total protein of the cultures decreased in a dose-related manner with DPH concentrations of 30 microgram/ml and greater. Total AChE activity and AChE activity released into the medium were specifically decreased with 15 microgram DPH per millilitre. In cultures treated chronically with 15 microgram DPH per millilitre on days 5-13 in vitro, total AChE activity and AChE activity released into the medium were 66.0 +/- 13.2 and 64.7 +/- 11.8% of untreated controls, respectively, but cellular AChE activity, cell protein, and [3H]leucine incorporation into protein were unaffected. The results indicate that DPH specifically decreases the total net synthesis of AChE activity by a direct action on cultured chick embryo muscle.


The effects of temperature on growth of four high Arctic soil fungi in a three-phase system.

The effect of temperature on the growth of Chrysosporium pannorum, Cylindrocarpon sp., Penicillium janthinellum, and Phoma herbarum, isolated from tundra soils, was studied. The growth in two systems, glucose-mineral agar plates and sand, moistened with glucose-mineral broth, was compared. All isolates showed an exponential increase in mass (measured as protein increase) in sand and a linear rate of extension on agar. Radial increase on agar was shown not to be a good index of growth in sand. Trends in growth rates in the sand cultures indicated that all four fungi can grow at low temperatures. The growth rate for Penicillium janthinellum at 15 degrees C was higher than at 20 degrees C, and Cylindrocarpon sp. and Phoma herbarum had higher growth rates at 2.5 degrees C than at 5 degrees C. These data suggest that there may be some adaptation by these fungi to growth in Arctic regions.


Torulopsis pampelonensis sp. nov. A new species of yeast isolated from beech forest soil.

A new yeast species, Torulopsis pampelonensis is described. Six strains were recovered from a gleyic Andosol under a beech forest and two other strains from the surface of fallen leaves of Fagus silvatica L. Although it showed some morphological and physiological similarities with Torulopsis tannotolerans Jacob and Torulopsis navarrensis Ramírez and Moriyón, it differed from all Torulopsis species presently known.


Relationship between iron-limited growth and energy limitation during phased cultivation of Candida utilis.

The yeast Candida utilis was continuously synchronized by the phasing technique (6 h doubling time) with either iron or nitrogen as the limiting nutrient. Iron limitations resulted in decreased molar growth yields with respect to the carbon substrates and ammonia and in increased specific rates of oxygen uptake. Relatively low energy-charge values were maintained by the iron-limited culture. All these taken together seemed to indicate that the growth of the yeast under iron limitation was also limited by metabolically available energy. Consideralbe amounts of ethyl acetate were produced by the yeast under phased cultivation when the growth was limited by iron but not by nitrogen. In vitro studies using cell-free extracts showed that the substrates for ethyl acetate synthesis were acetyl coenzyme A (acetyl CoA) and ethanol. Under iron-limited growth acetyl CoA seemed to be diverted to ethyl acetate formation rather than being oxidized through the tricarboxylic acid (TCA) cycle. The possibility of energy limitation under iron-limited growth being brought about by the reduced capacity of the yeast to oxidize acetyl CoA through the TCA cycle is considered.


RNA and protein synthetic patterns during germination of Polysphondylium pallidum microcysts.

During microcyst germination in the cellular slime mould Polysphondylium pallidum, an immediate rapid increase in the rate of protein synthesis ([3H]leucine incorporation) is observed within 15 min after the initiation of germination. The data, corrected for amino acid pool changes, reveal that the rate of protein synthesis reaches its peak at 1 1/2 h, after which it decreases. A low level of RNA synthesis ([3H]uridine incorporation) is observed after 1 h and this rate increases markedly after 2 h. Analysis of the RNA species shows a low level of synthesis of all ribosomal RNA's which begins between 1 and 2 h and increases after 2 h. The synthesis of a heterogeneously distributed, poly(A)-containing fraction of RNA (presumptive mRNA) is initiated some time after 2 h and the synthesis of a small molecular weight species in the 4-5S region is observed after 3 h. Thus, it seems that Polysphondylium microcysts show sequentially initiated synthesis of RNA during germination.


Ultrastructural observations on the histogenesis of alveolar rhabdomyosarcoma.

Ultrastructural examination of an alveolar rhabdomyosarcoma revealed that the bulk of the tumor was composed of small polygonal cells containing polyribosomes, short strands of rough endoplasmic reticulum, and variable amounts of glycogen; the cells were joined by small desmosome-like structures. Similar cells, as well as a variety of larger forms which appeared to be derived from the small cells, were observed along the septa; the larger forms developed a copious cytoplasm and occasionally produced myofilaments. Some of these cells were separated from the septa by basement membranes. Giant cells were also present in the alveolar spaces; these formed neither basement membranes nor myofilaments. The septa themselves were composed largely of collagen and fibroblasts. It is suggested that the commonly proposed correspondence of alveolar rhabdomyosarcoma to the myotube stage of muscle differentiation is incorrect; if anything, the overall pattern of the tumor is epithelial-like, and may correspond to the organization of mesenchymal cells at the stage of somite differentiation. The resemblance of the masses of small tumor cells to the cells of Ewing's sarcoma is discussed.


Tumor and lymphoid cell lines from a patient with carcinoma of the colon for a cytotoxicity model.

Three tumor cell lines (COLO 201, COLO 205, and COLO 206) have been established from ascites fluid obtained from a male patient with adenocarcinoma of the colon. In addition to the tumor lines, two lymphoid lines (COLO 197 and COLO 200) have been established from the same patient, with one line from the original biopsy and one from peripheral blood. Characterization of the tumor cell lines revealed four cell types that differ from most colon cell lines reported by others. Chromosome markers were identical in COLO 201 and COLO 205. A long-arm isochromosome 5 observed in COLO 201 and COLO 205 was absent in COLO 206. Statistical analysis of autosomal polysomy revealed that these cell lines were stable and indicated that there may be a cytogenetic basis for the three predominant types of cell morphology. The lymphoid cell line derived from the peripheral blood had a normal male karyotype. The lymphoid cell line derived from a biopsy specimen had a mode of 46 and a deleted chromosome 7 marker. Both lymphoid cell lines had B-cell characteristics. These autochthonous cell lines have been used for immunological studies in cytotoxicity assays and immunoglobulin characterization.


Ultrastructure of the theca interna of ovarian follicles in sheep.

The theca interna of non-atretic ovarian follicles from 2.0 mm in diameter up to the stage shortly following ovulation was studied by light and electron microscopy. In follicles less than 3.0 mm in diameter, the theca interna consisted of about 8-12 layers of flattened cells, together with many capillaries and small bundles of collagen. Two main forms of cellular differentiation were seen. These were towards either fibroblast-like cells or presumed steroidogenic cells whose cytoplasm contained large amounts of predominantly smooth tubular endoplasmic reticulum, to which some ribosomes were attached. The majority of cells were of relatively undifferentiated or intermediate structure. In larger follicles up to the early stages of oestrus the theca interna cells became larger and less flattened, and cells rich in tubular endoplasmic reticulum became proportionately more numerous. By 18 h after the onset of oestrus the theca interna was oedematous, and many cells possessed pseudopodia. Many cells also contained numerous lipid droplets, but there were no signs of thecal cell degeneration or death. Shortly after ovulation the basal lamina of the membrana granulosa was incomplete, and it became more difficult to distinguish between theca and granulosa layers. Structural heterogeneity, with two major cell types and cells of intermediate structure, was present at all stages. It was concluded that: (1) the theca interna of 2.0-2.9 mm follicles contained many cells whose structure was compatible with a steroidogenic capacity; (2) changes in the differentiated thecal cells up to the early stages of oestrus were quantitative rather than qualitative, and suggestive of an increased steroidogenic capacity; (3) the accumulation of lipid in many cells of the theca interna by 18 h after the onset of oestrus probably reflected a reduction in steroidogenic activity; and (4) there was no evidence of any structural specialization to facilitate the transport of steroids from the theca interna to the membrana granulosa.


The sub-structure of nucleosomes.

A model for the sub-structure of the core particle of the nucleosome in chromatin, based on results from neutron and x-ray scattering and other physico-chemical observations, is presented. Two disc-shaped heterotypic tetramers of histones, opposed face-to-face, form the core protein. Each tetramer is enclasped by an annulus of DNA and the two annuli are joined by a linker piece. The mode of self assembly of core particles in solution is derived as are the changes in conformation of the core particle which occur on transcription and chromosome replication.


The phosphorylation of thymidine and the synthesis of histones in ammonia-treated eggs and egg fragments of the sea urchin.

Unfertilized sea urchin eggs may be preloaded with workable amounts of 3H-thymidine. After fertilizing the eggs or treating the eggs with ammonia, the preloaded thymidine is incorporated into DNA in amounts that are proportional to the number of chromosomes that are replicated. The phosphorylation of the internal thymidine is turned on by fertilization and ammonia treatment, but 3H-TTP does not accumulate because it is immediately used for nuclear DNA synthesis. Accumulation of 3H-TTP occurs only in ammonia-treated enucleate fragments in which no nuclear DNA synthesis can occur. Along with the phosphorylation of thymidine, the synthesis of histones occurs in ammonia-treated enucleate egg fragments.


Hyperthermic treatment (43 degrees C) rapidly impedes attachment of fibroblasts to culture substrates.

Hyperthermic (43 degrees C) exposure of Chinese hamster fibroblasts for more than 30 min, either in suspension or as a monolayer, significantly inhibits their ability to attach to the culture substrate. This finding as well as the effect of hyperthermia on membrane proteins and on surface topology are rapidly expressed and differ from the inhibition of colony formation which is a later effect of hyperthermia on reproductive ability.


A possible effect of vitamin D metabolities on cell adhesion.

The effect has been studied of the metabolites of vitamin D on the adhesion of 3T6 fibroblast cells and of pig aortic endothelial cells in culture. 1,25-dihydroxycholecalciferol (x10(-7)M) caused a decrease within 2 h in the adhesive qualities of the cells causing them to float free in the medium; the largest effect was seen with the endothelial cells. All the metabolites of vitamin D tested produced an effect including 25-hydroxyvitamin D which appeared to also have a major toxic effect on the endothelial cells.


A new type of primary granule in guinea pig heterophil granulocytes.

Guinea pig heterophil granulocytes were found to have three types of granules which are formed sequentially during the development of the cells in the bone marrow and differ in shape and electron density: nucleated, azurophil and specific granules. Early promyelocytes proved to synthesize nucleated granules of medium electron density prior to the formation of azurophil granules which are highly electron dense, by late promyelocytes. Since the formation of nucleated granules and azurophil granules is restricted to promyelocytes, both can be considered to be primary granules. The moderately dense specific granules (secondary granules) appear later during granulopoiesis and are firstly present in the myelocyte.


Assessment of the pulmonary vascular bed by echocardiographic right ventricular systolic time intervals.

Echocardiography was used to measure right ventricular systolic time intervals (RVSTI) in 85 normal children (group I) and in 229 patients undergoing cardiac catheterization (group II). Corrected right ventricular pre-ejection period (RPEPC) and right ventricular ejection time (RVETc) (based on regression analysis of group I) and RPEP/RVET were each correlated with pulmonary artery (PA) diastolic and mean pressures and pulmonary vascular resistance (PVR). The best correlation (0.83) was between a second degree polynomial of the RPEP/RVET and PA diastolic pressure. The RPEP/RVET allowed prediction of PA diastolic pressure within 10 mm Hg in 85% of the patients. The utility of RPEP/RVET was confirmed in sequential data of 22 patients, in whom alteration in RPEP/RVET accurately reflected the changing PA diastolic pressure. The RPEP/RVET could not be used to assess PA pressure in six patients with congestive cardiomyopathy nor in 18 patients with complete right bundle branch block (CRBBB).


Long-term clinical course and symptomatic status of patients after operation for hypertrophic subaortic stenosis.

Long-term results of operation for IHSS were reviewed in 124 patients operated upon between 1960 and 1975. Most patients improved symptomatically and manifested marked reduction in LV outflow gradient at rest postoperatively. However, ten (8%) patients died of causes related to operation, 14 (12%) had persistent or recurrent severe functional limitation, and 11 (9%) died up to 13 years postoperatively due to hypertrophic cardiomyopathy. Overall annual mortality rate was 3.5% and was 1.8% for late deaths alone. Of 11 late postoperative deaths, six were sudden and five were due to chronic heart failure. Atrial fibrillation was significantly more common in patients who died late postoperatively than in survivors. Nine of the 11 late deaths had associated medical problems that may have contributed to their outcome. In conclusion, long-lasting clinical improvement occurred in most patients who survived operation for IHSS. However, 12% of patients deteriorated clinically over the 5.2 year average follow-up, and there is continued, small annual mortality.


The interference of endogenous antibodies to bovine lactalbumin in the radioimmunoassay of human lactalbumin in serum.

Using a radioimmunoassay for the milk protein lactalbumin in human serum, we have found that falsely high results can be caused by cross-reacting human antibodies to bovine lactalbumin. A reliable method of circumventing this problem is described. When such interference had been eliminated, circulating lactalbumin was not detected in normal men or post-menopausal women, but could still be found in a proportion of non-pregnant, non-lactating pre-menopausal women.


Special problems in the radioimmunoassay of plasma aldosterone without prior extraction and purification.

A new method for the radioimmunoassay of plasma aldosterone is described. The assay is performed directly on plasma without extracting or purifying the aldosterone. The method fulfilled the usual requirements for the demonstration of accuracy. Extensive data on the properties of the antisera are given.


Antibody dependent cellular cytotoxicity of lymphocytes in patients with renal diseases of immunopathological origin.

Antibody dependent cytotoxicity (ADCC) of lymphocytes from twenty-two patients with histologically proven chronic glomerulonephritis and eight patients with SLE nephropathy was studied in a xenogeneic assay on chicken red blood cells and in an allogeneic test system using Rh(+) human erythrocyte targets. ADCC activity of the lymphocytes of patients with chronic glomerulonephritis did not differ from that of normals, while all patients with SLE nephropathy showed significantly lower cytotoxicity than healthy controls. The possible role ADCC in the pathogenesis of renal diseases of immunopathological origin is discussed.


Post-exposure phenomen in murine lymphoma L5178Y-S cell populations grown in media containing tritiated compounds.

Murine leukaemic lymphoblasts L5178Y-S were exposed to: (a) 104 muCi of 3HOH for time intervals from 25 to 600 h, (b) 10 muCi of L-[4,5(n)-3H] lysine for 25 to 600 h, and (c) 0.05 muCi of [methyl-3H]thymidine for 4 to 600 h. Extended post-exposure observations of growth disturbances and viability changes indicate marked differences between heritable lesions induced by the three tritiated compounds. After exposures to tritiated lysine and tritiated water, the damage was predominantly of non-lethal character while in the populations previously exposed to tritiated thymidine most of the cells eliminated during the post-exposure growth were lethally damaged. In all cases examined growth retardation was observed followed by growth at the normal rate. An exception concerned a cell culture exposed for 600 h to tritiated thymidine for which the slowed-down growth was observed for ca seventy cell generations.


Susceptibility of L5178Y-R and L5178Y-S cells to HTO, 3H-lysine and 3H-thymidine exposure.

Two strains of murine leukaemic lymphoblasts: L5178Y-R and L5178Y-S differing in the X-ray sensitivity by a factor of ca. 2 and showing X-ray-UV-light cross-sensitivity were exposed to: (a) 104 muCi/ml of HTO for time intervals from 25 to 600 h, (b) 10 muCi/ml of L-[4,5(n)-3H]lysine for 25 to 600 h, and (c) 0.05 muCi/ml of [methyl-3H] thymidine for 4 to 600 h. After completion of the exposure, survival was determined by cloning or by backward extrapolation of growth curves. In the case of HTO and 3H-thymidine exposure time the survival relationship passed through broad minima (75--200 and 50--400 h for (a) and (c), respectively). After longer exposures, higher survivals were observed reaching values close to 1 in the extreme cases. The results of shorter exposures indicate that L5178Y-R and L5178Y-S cells considerably differ in their susceptibilities to the tritiated compounds and that this difference increases with the shift of 3H localization towards DNA.


Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage.

Synchronized suspension cultures of Chinese hamster ovary cells (CHO) were labeled with various doses of 3H-thymidine or 125I-iododeoxyuridine to evaluate the cytocidal effects of intranuclear radionuclide decay. Damage produced by radionuclide decay outside the cell nucleus was studied on cells exposed to 125I labeled, monovalent concanavalin A. After labeling, the cells were resynchronized in G1-phase and incubated for 36 h at 4 degrees C to permit dose accumulation. Cell lethality was evaluated by the standard colony assay. Based on radionuclide incorporation data, cellular dimensions, and subcellular radionuclide distributions, the cumulative dose to whole cells, cell nuclei, and cellular cytoplasm was calculated from the known decay properties of 3H and 125I. As expected, DNA associated 125I (LD50: 60 decays/cell; 45 rad) was much more toxic to CHO cells than 3H (LD50: 1350 decays/cell; 380 rad) 380 rad) or external X-irradiation (LD50: 330 rad). In contrast, membrane associated 125I was surprisingly non-toxic (LD50: 19 600 decays/cell). At 19 600 decays/cell the dose to the cell membrane was approximately 52 krad and the overlap dose into the cytoplasm was about 2470 rad. Even at these high dose levels, membrane damage or cytoplasmic damage apparently did not contribute significantly to radiation induced cell death. With 19 600 decays on the plasma membrane the CHO nuclei received an overlap dose of about 410 rad. As can be seen from the LD50 data for 3H and X-rays, a nuclear dose of 410 rad should be sufficient to account for 50% cell death. These findings indicate that, although intranuclear decay by electron capture is extremely destructive, identical decay events in the plasma membrane cause only minimal cell damage. This parallels our earlier studies on 67Ga labeled leukemia cells which showed that electron capture decay in the cytoplasm is also highly ineffective in killing mammalian cells. It therefore appears that radiation-induced cell lethality in dividing mammalian cells results primarily from nuclear damage. Cytoplasmic or membrane contributions to radiation-induced cell death, if any, must be minimal. By implication, these findings refute the enzyme release hypothesis and similar theories designed to explain mitotic death in terms of cytoplasmic or membrane damage rather than nuclear damage.


Molecular suicide studies of 125I and 3H disintegration in the DNA of Chinese hamster cells.

The shape of the survival curve for cells inactivated by tritium decay in DNA is modified by the presence of halogenated pyrimidines in the DNA in a manner analogous to their effect on X-ray induced reproductive death. The large shoulder found for tritium suicide is removed completely by coincorporation of 10(-6) M IUdR. The oxygen enhancement ratio for 125I and tritium disintegrations in unsynchronized Chinese hamster cells was determined for cells permitted to accumulate damage from these events at 4 degrees C. The oxygen enhancement ratio for 125I induced damage is 1.4. This is much smaller than the OER found for tritium decay which is similar or more than that found for X-ray exposure under the same conditions. These results suggest that the nature of the lesions produced by 125I decay in DNA are analogous to those produced by high LET radiation while those lesions produced by tritium are similar to lesions produced by roentgen rays. In synchronous V79 cells the effects of 125I induced damage in different regions of the mammalian cell DNA was examined taking advantage of the fact that DNA replication in hamster nuclei follows a time-dependent three dimensional pattern. The experiments indicate that 125I decays accumulated in the G2-period of the cell cycle have different efficiences for the induction of reproductive death depending on the region of the DNA which is labeled. The efficiency for the induction of reproductive death appears to be a maximum in DNA that replicates in V79 cells near the end of the DNA replication cycle. Electron capture events are dramatically efficient in the production of lethal chromosome aberrations. In CHO cells synchronized in the G1-stage of the cell cycle stored in the frozen state the efficiency for the induction of dicentric and ring chromosomes is 0.03. The dose response curve for the induction of these aberrations is linear in contrast to the curvilinear response found for roentgen ray exposure under the same conditions. Data on this kind suggest that there may exist "critical" regions within mammalian cell nuclei where chromatin fibers from two different chromosomes are in close proximity to each other and both are damaged non-repairably by a single electron capture event.


Cell survival and cytogenetic responses to 125I-UdR in cultured mammalian cells.

The relative toxicity of DNA precursors labeled with iodine-125, iodine-131, or hydrogen-3 was studied in exponentially growing Chinese hamster cells. Per decay, iodine-125 was found to be approximately 12 times as lethal as iodine-131 and 16 times as lethal as hydrogen-3. Chromosomal aberrations induced in these cells by the three radionuclides occurred with the same relative efficacy as their lethal effects.


Chromosome damage in Chinese hamster cells produced by 125I-UdR at the site of its incorporation.

Metaphase chromosomal aberrations were produced by 125I-labeled iododeoxyuridine (125I-UdR) incorporated into Chinese hamster Don cells at the end of the S-period of the cell cycle. Chromosome damage and the number of autoradiographic silver grains were recorded for whole cells, for chromosome pairs No. 4 and No. 5, and for the X and the Y chromosomes. The X and the Y chromosomes, which label late in S, were at least twice as heavily labeled as chromosome pairs No. 4 and No. 5--two readily recognizable autosomes of similar size. The incidence of chromosome damage was at least six times that which would have been expected from equivalent doses of X-rays and the incidence of damage was directly related to the number of silver grains over each chromosome. We estimate that it takes four to ten disintegrations to produce a visible chromosome aberration. The finding that chromosome damage is localized at the site of the 125I decay is most readily explained by the high flux of low energy Auger electrons occurring at the site of the decay of the incorporated 125I atom.


Anomalous effects of 125I after its incorporation into mammalian cell DNA.

During labeling of mammalian cells with 125I-iododeoxyuridine for studies on single-strand break induction and repair, care must be taken to keep the amount of 125I incorporated per cell to very low levels. Under some conditions enough 125I can be incorporated during the incubation period (generally about one generation time) to damage the repair systems of cells so extensively, even before they are frozen, that they cannot repair any of the breaks induced by the 125I during the time they are frozen to accumulate these breaks.


Effect of microdistribution of radionuclides on recommended limits in radiation protection, a model.

The heterogeneous distribution and accumulation of radionuclides in discrete areas of cellular and subcellular dimensions is called microdistribution. The biological effect of microdistributed radionuclides with low-range emissions is determined by the degree of irradiation of the radiosensitive microareas of the body. The critical microareas of the body are nuclei of such cells which (1) are radiosensitive, (2) are essential to maintaining life, (3) are irreplaceable, (4) have a long life span and/or renew themselves. In this sense, the stem cell nuclei are considered critical microareas of the body. Stem cells constitute only a small fraction of the total body's cellularity. In case of concentration of radionuclides in stem cell nuclei, such as from incorporated labeled DNA precursors, there is a total congruence of the radionuclide microdistribution with the radiosensitive microarea, and the biological effect is expected to be enhanced over that from a homogeneous distribution of the same amount of radionuclides. This situation is discussed for 3H, 14C and 125I incorporate into mice as tracers of DNA precursors. The average labeling intensity of the bone marrow cell nucleus was taken to represent the average labeling intensity of the stem cell nucleus. The dose to the stem cell nucleus, then, is derived from the number and energy of decays originating in the nuclear mass of 270 X 10(-12) g. The transmutation effect from isotopic decay in DNA is considered in order to arrive at dose equivalents. On the basis of known data on labeling efficiency of bone marrow and on stem cell proliferation kinetics in the mouse, the infinite accumulation of decays in and the total expected dose to the stem cell nucleus was calculated for intravenous injection or ingestion of 1 muCi 3H-TdR per g body weight. The distribution factor and an annual limit on intake for the mouse model was suggested. Corresponding data are presented for 14C-TdR and 125I-UdR. A special situation is given for the case of hot particles where there is a random relationship between microdistributed radionuclides and critical microareas of the body. In this instance, theory predicts a decreased biological effect in comparison to the situation where the same amount of radionuclides is homogeneously distributed. There is experimental evidence that supports the theoretical predictions particularly for the case of 236Pu dioxide in the human lung.


Comparison of tumor-associated surface antigens on cells from medulloblastomas and from other neoplasms of the human nervous system.

We used a new immunocytoadhesion method to test 15 different tumors of the human nervous system to see whether medulloblastomas share tumor-associated surface antigens (TSA) with other tumors. Antisera against medulloblastoma cells were raised in rabbits. One antiserum was adsorbed extensively with tonsil and adenoid cells and with cerebral tissues. Freshly isolated cells from 15 different tumors were first sensitized with the adsorbed antiserum and then rosetted with erythrocytes coated with purified antibody to rabbit immunoglobulin. We found that the antimedulloblastoma antiserum detected TSA on the immunizing medulloblastoma cells and on cells from 2 other medulloblastomas, but apparently not on cells from other tumors (astrocytomas, glioblastomas, neurinoma, meningiomas and craniopharyngioma). In addition, the antiserum probably detected the medulloblastoma TSA on some other tumors (oligodendroglioma, ependymoma  and malignant glioma of mixed type).


[Visceral kala-azar disease in a child (author's transl)].

Repeated blood cultures were negative in a six-year-old boy with high septic temperature. Rheumatoid arthritis, typhoid and brucellosis were excluded. There was no evidence of leukaemia (bone-marrow tests). There was hepatomegaly with increased transaminase activity. Cortisone treatment was begun for suspected collagen disease. Several liver needle biopsies at first revelaed increasingly severe necrotising changes, predominantly in the centres of the acini. There were no parasites demonstrable histologically. The spleen was increased in the isotope scan but, covered by the liver, not definitely palpable. Diagnosis of mediterranean Kala-Azar disease was then suspected (the parents reporting a camping holiday in Yugoslavia) and finally proven serologically. The previously treatment-resistant disease improved dramatically after administration of trivalent antimony (Fuadin).


[Autoimmune haemolytic anaemia, thrombocytopenia and thyroiditis: an immunopathological triad (author's transl)].

A 37-year-old woman developed acquired haemolytic anaemia and thrombocytopenic purpura. At the same time there were signs of hypothyroidism. Incomplete heat antibodies (direct Coombs test) were demonstrated as cause of the haemolytic changes, while high-titre thyroglobulin and microsomal thyroid antibodies as cause of the immunothyroiditis explained the hypothyroidism. Although serological demonstration of platelet antibodies did not succeed, the clinical and haematological findings suggested immunothrombocytopenia. Antibodies against smooth muscle produced no clinical symptoms. The activity of the incomplete heat autoantibodies was diminished as result of immunosuppressive treatment and haemolytic signs regressed. Platelet count rose and the haemorrhagic diathesis disappeared. Thyroid antibody titre rose at first but then markedly decreased. There was no demonstrable effect on the hypothyroidism so that it was necessary to administer thyroid hormones. This is the first published case of such immunopathological triad resulting from immunothyroiditis.


[Preliminary report on the neuropsychological study of women treated by beta-mimetic drugs in a gynecological clinic].

Twenty women hospitalized in a gynaecological clinic for threatening miscarriages were treated by beta-mimetic drugs and examined from a neuro-psychological viewpoint. Disorders in the quality of sleep, trembling fingers and modification in the tone of voice were noted, and associated in five cases, to a slight hypertonia, extra-pyramidal-like. Eleven women had difficulties in concentrating, and seventeen felt distressing changes of mood: mentism, pessimistic thoughts, feeling of being abandonned, and sometimes, beliefs of being persecuted, which in two patients required the administration of Haldol.


Steroidal control mechanism of cell proliferation in mouse uterine epithelium.

The percentage of labeled cells in the uterine luminal epithelium of cycling mice showed the different zonal distributions at each stage of estrous cycle after cumulative labeling with 3H-thymidine for 36 hr. It was estimated that the proliferating fraction in the epithelium at proestrus, estrus, metestrus, and diestrus was 100%, 100%, 40% and 5%, respectively. The percentage of labeled cells in the uterine luminal epithelium of cycling mice treated with progesterone remained below 10% level for at least 20 hr after injections of progesterone. Total labeling was attained in the uterine epithelium of castrated mice by the administration of estradiol-17beta. On the other hand, the cell proliferation in the uterine epithelium of castrated mice treated with estradiol and progesterone was markedly suppressed and the percentage of labeled cells remained approximately at 35%. The remaining cell population, however, still showed the mitotic potency when mice received estradiol. It is suggested from this study that the effect of progesterone is to suppress the epithelial cell proliferation and transfer cells into resting cell fraction which is still evoked to proliferate as the effect of estradiol and that a key factor controlling epithelial proliferation in mouse uterus during the estrous cycle is proliferating fraction rather than cell cycle time.


Changes of lactic dehydrogenase activity and combination of its subunits in rat anterior pituitary during puberty and in maturity, as well as during estrous cycle on the actue effect of estradiol and after castration.

LDH activity in the female rat anterior pituitary increases substantially at the opening of the vagina, after the gradual increase up to the 90st day no important change occurs. During the estrous cycle activity reaches its peak during the estrus, and lowest in ghe proestrus. Molecular organization of the enzyme shows a change only at the opening of the vagina, i. e. a sudden decrease of H/M ratio occurs, value of which does not change during the estrous cycle. Pituitary LDH activity and subunit ratio in males remains constant during life. LDH activity excess in mature female rat pituitary, being about the double as compared to males, develops at the age of about three months, the difference in H/M ratio however is manifest already during puberty. Anterior pituitary LDH activity and structure of the enzyme are affected by sexual hormones, primarily by estradiol, under physiological conditions, too. After ovariectomy LDH activity decreases gradually. The value before the opening of the vagina to be considered as basal level, develops in the 4th postoperative week. H/M  ratio decreases by 20 per cent one week after the operation and shows no change thereafter. Orchidectomy involves but a minor activity and H/M ratio decrease. Experimental findings on activity and subunit ratio are related presumably to prolactin cells and suggest that sexual hormone feedback effects in addition to polypeptide production pituitary metabolism.


Recovery of some functional properties of the detergent-extracted cholinergic receptor protein from Torpedo marmorata after reintegration into a membrane environment.

The change of affinity of the acetylcholine receptor for agonists and the influence of local anaesthetics has been studied in detail in receptor-rich membranes. These properties are changed after solubilisation by ionic detergents. A method for reproducibly reintegrating the receptor protein into a lipid environment is described. Reintegration of the receptor results in partial recovery of the binding and fluorescence properties of the membrane-bound receptor protein. In particular, the slow affinity change caused by agonists can be recovered but not the effect of local anaesthetics on this change. The fluorescence response to cholinergic ligands of the reintegrated receptor protein labelled with quinacrine does not appear identical to that found with the native receptor-rich membranes. It is suggested that the failure to recover the sensitivity to local anaesthetics is at the origin of the difficulties to regain functional reconstitution.


Studies on the conformation of the 3' terminus of 18-S rRNA.

We have studied the conformation of the 3' end of 18-S RNA from human, hamster and Xenopus laevis cells. The 3'-terminal oligonucleotide in a T1 ribonuclease digest of 18-S RNA from HeLa cells was identified, using a standard fingerprinting method. The sequence (G)-A-U-C-A-U-U-A, established by Eladari and Galibert for HeLa 18-S rRNA, was confirmed. An identical 3' terminus is present in hamster fibroblasts and Xenopus laevis cells. The ease of identification of this oligonucleotide has enabled us to quantify its molar yield relative to several other oligonucleotides, and hence to analyse the 3' terminus by several conformation probes. Its sensitivity to S1 nuclease, limited T1 ribonuclease digestion, bisulphite modification and carbodiimide modification was consistent with the terminal oligonucleotide being in a highly exposed conformation. The m6/2A-m6/2A-C-containing sequence of 18-S rRNA also appears to be in an exposed location on the basis of three of these probes.


Behavior of Biozzi high and low responder mice upon infection with Schistosoma mansoni.

Mice genetically selected for high (Ab/H) or low (Ab/L) humoral antibody responses were infected with Schistosoma mansoni in order to assess the role of antibodies in innate and acquired immunity to this parasite. AbH mice produced higher levels of humoral antibodies to schistosome antigens, but were more susceptible to infection than Ab/L mice. This was shown by the higher number of parasites recovered from Ab/H mice, by the larger size of the parasites themselves, by the number of schistosome eggs and their rate of deposition in the host liver. In addition, Ab/L mice could develop an acquired resistance to schistosome re-infection which was as good as, or possibly even better than the resistance developed by Ab/H mice. These findings suggest that humoral antibodies per se may not play a critical role in schistosome immunity, and at the same time call attention to the possible importance of macrophages in determining the results observed.


Induction of physical dependence on cyclazocine and pentazocine in the rat.

Rats were treated for 24, 48 or 72 h with slow release (SR) emulsions of morphine (75, 100 and 150 mg/kg), cyclazocine (75, 100 and 150 mg/kg) or pentazocine (100, 200 and 400 mg/kg). At these times the degree of physical dependence was assessed by examining the abstinence behavior (jumps + wet shakes), changes in body temperature and body weight induced by naloxone (5 mg/kg). The effects of SR treatments on brain levels of noradrenaline (NA), dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were also determined at these times. The results show that all three opiates induce physical dependence in the order of severity of morphine greater than cyclazocine greater than pentazocine. An elevation of 5-HT turnover also appears to be associated with the dependence produced by these opiates. These findings indicate that the increase in brain 5-HT metabolism is not a primary causative factor during opiate dependence, but occurs in response to some other process.


Enhancement of ethanol-induced sleep by whole oil of nutmeg.

In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1--4 g/kg), particularly deep sleep. Iproniazid (50-400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.


Mammalian spot test with moxnidazole, a 5-nitroimidazole.

Moxnidazole [3-(5-nitrol-1-methyl-2-imidazolyl)-methyleneamino-5-morpholinomethyl-2-oxazolidinone, HCl], known to be mutagenic in microbial tests and Drosophila, induced genetic alterations in somatic cells of mice. Ethyl methanesulfonate (EMS) served as positive control.


Destruction of the platelet aggregating activity of ristocetin A.

Hydrolysis of ristocetin A in 0.1 N HCl at 37 degrees C for 2 h resulted in the loss of its ability to induce platelet aggregation in platelet-rich plasma derived from guinea-pigs and humans. However its antibiotic activity against Staph. aureus was not lost.


The treatment of hyperprolactinemia with a new ergot derivative, lergotrile mesylate.

Lergotrile mesylate is an ergot alkaloid derivative modified to eliminate the vasoconstrictive properties of the parent compound while preserving the properties that inhibit pituitary secretion. Administration of the drug to women with amenorrhea-galactorrhea resulted in the lowering of serum prolactin concentrations. The duration of action was short, so that prolactin levels were near base line 6 to 8 hours after a 2.0-mg dose and morning prolactin concentrations were not persistently suppressed. Initial therapy was accompanied by the development of postural hypotension. Tolerance to this side effect of the drug developed after several days of treatment with gradually increasing doses. In one patient, long-term treatment resulted in reduction of breast secretions, resumption of menses, and conception.


[Posterior lobe of the rooster pituitary during prolonged conditioning of emotional stress].

Daily fights were chosen to kindle the situation of emotional stress in roosters. A marked decrease in contents of the neurosecretory substance and a large number of Herring's bodies in the hypophyseal lumen were observed within the 1st month. By the 60th day these signs of increased release of the neurohormones into the blood flow disappeared and the condition of hypophysis returned to the initial level. Simultaneously the intensity of the fights was reduced. The reason the normalization of hypophysis state consists, probably, in the adaptation of the roosters to the stressful situations.


Impairment by interferon of mitogen-induced DNA synthesis in chick lymphocytes.

Chick interferon preparations inhibit mitogen-induced DNA synthesis of chicken peripheral and spleen lymphocytes. Mock interferon preparations showed also some inhibition of mitogen-induced DNA synthesis. The degree of inhibition is concentration dependent but varies also with the relative time of addition of homologous interferon and mitogen. Addition of the interferon preparations 6 h before mitogen resulted in a stronger inhibition of DNA synthesis than if the interferon preparations and mitogen were added at the same time. The interferon preparations seem to affect the metabolism of lymphocytes in a mroe general way and not only the trigger mechanism of the mitogenic response since addition of interferon even 24 h after the mitogen inhibits the induced DNA synthesis.


Postabortion insertions of the pleated membrane.

The pleated or intrauterine membrane (IUM) was designed to fit a range of uterine sizes and shapes and to adjust to transient changes resulting from uterine motility. The retention and contraceptive abilities of postabortion IUM insertions are analyzed in this study of 154 IUM insertions made within 3 days of treatment for an incomplete or inevitable abortion. Results indicate low 1-year net cumulative event rates for pregnancy (1.7 per 100 users), expulsion (7.2 per 100 users), and removal for bleeding and/or pain (3.9 per 100 users). These rates were similar to those reported in  a study of interval insertions of the IUM; moreover, these results also compared favorably with corresponding rates of postabortion insertions reported in studies using other devices. Thus, the postabortion period is indicated as being an effective time for IUM insertion.


Effect of secretin on basal- and glucose-stimulated insulin secretion in man.

Plasma immunoreactive secretin and insulin concentrations were measured in fasting normal humans after intraduodenal infusions of hydrochloric acid, isotonic or hypertonic glucose. The effect of intraduodenal acidification or intravenous bolus injections of secretin on plasma insulin concentrations during infusions of glucose was also examined. The intraduodenal glucose load did not cause an increase in plasma secretin concentrations. Secretin concentrations rose after acid both in the fasting state and during infusions of glucose. A concomitant rise in insulin levels was however only observed during infusions of glucose. Intravenous injection of secretin in a dose which mimicked the response to intraduodenal acidification was without effect on the glucose-stimulated insulin release, while a 30 times higher dose caused a highly significant augmentation of the insulin release. The insulin response pattern to this high dose of secretin differed completely from that observed after intraduodenal infusion of acid. It is concluded and confirmed that the stimulating effect of secretin on insulin secretion is pharmacological and that secretin plays no significant role in the entero-insular axis.


Cell-mediated cytotoxicity in chronic active liver disease: a new test system.

An in vitro cytotoxicity system was developed for studying patients with chronic active liver disease using as the target cells 51Cr-labeled avian erythrocytes coated with cell membrane lipoprotein extracted from human liver and, as the aggressors, mononuclear cells from peripheral venous blood. Approximately 50% of 62 patients with chronic active liver disease showed cytotoxicity in this test system as did 5% of 100 apparently healthy controls. In addition, mild cytotoxicity was shown by 2 of 8 patients with the primary biliary cirrhotic syndrome and 2 of 17 persons with other liver diseases. No specific antibody was added to the test system and the cytotoxicity could be inhibited by free lipoprotein, antilipoprotein, and by aggregated Ig. Cytotoxicity also was abolished by the depletion from the mononuclear cells of cells phagocytic for iron filings. The effect of depletion of these phagocytic cells was not restored by the addition of 2-mercaptoethanol. These findings add further evidence that autoimmune responses to liver tissue occur in many patients with chronic active liver disease and, importantly, suggest also that these may occur in some apparently healthy people.


The production of chromosome aberrations in various mammalian cells by triethylenemelamine.

The cytogenetic effects of triethylenemelamine (TEM) were studied using five different mammalian tissues. Treatments of 0.1 and 0.2 mg/kg TEM on differentiating mouse spermatogonia and bone marrow cells showed no significant differences in the frequency of chromosomal aberrations produced in these two tissues. At higher doses, however, the sensitivites of the two tissues appear to be different. The frequency of aberrations varies with time after treatment, with the greatest amount occurring at the latter fixation times. Results of an experiment on primary spermatocytes indicated a correlation between the frequency of chromosome aberrations and DNA replication. Human peripheral leukocytes were utilized in an attempt to clarify the cell-stage specificity of TEM-induced chromosome aberrations. Cultures were treated with TEM prior to PHA stimulation (G0), as well as various time intervals after stimulation (late G,1 S, and G2). The most sensitive stages of the cell cycle to aberration induction were later G1 and S, with chromatid aberrations the predominant type. A very low yield of chromosome damage was observed with the G0 and G1 treated stages. The experiments described tend to support the view that TEM is most effective at inducing aberrations when an intervening round of DNA replication has occurred.


[A new method for assaying anti-inflammatory drugs. Quantitative analysis of pigment leakage into skin by Chromatoscanner CS-900 (author's transl)].

Although the pigment leakage method is one of the most conventional for determining vascular permeability, accuracy in macroscopic measurement of the diameter of the stained area with an arbitary scale leaves much to be desired. We developed a simple and beneficial method for quantitative assay using a densitometer (Chromatoscanner CS-900). Guinea pigs weighing 300 approximately 350 g were used. Formalin as a phlogistic, in a dose of 2.3 approximately 37 mg was injected intradermally in the shaved skin of the back, and 15 mg/kg of pontamine blue was then given into the femoral vein. One hour after the injection the animals were sacrificed and the skin of the back, which was stained by the leaked pigment, was stripped off and allowed to adhere to a wooden plate for 24 hours. Reflection and a zig-zag scanning technique were used to measure the volume of the leaked pigment. There was a liner relationship between the dose of formalin and the integrated values. A dose-dependent relationship was also obtained when histamine, serotonin, kallikrein and bradykinin were used as phlogistics. Representative anti-inflammatory drugs such as aspirin, hydrocortisone, oxyphenbutazone, benzydamine, diclofenac sodium, sodium salicylate and aminopyrine depressed the leakage due to formalin. Depression of leakage by aspirin in a dose of 400 mg/kg was the most remarkable. Pigment leakage elicited by histamine, serotonin, kallikrein and bradykinin was examined on the same individual animal. Aspirin more than the other agents depressed the leakages due to bradykinin and kallikrein. Hydrocortisone and oxyphenbutazone depressed the leakage due to bradykinin, serotonin and histamine, but enhanced that due to kallikrein. The results obtained were consistent with those of a previous study and as this method is simple and more reliable, it is applicable for assay of anti-inflammatory compounds.


[Contraception in children and adolescents].

It is discussed how the adult type contraception fits the divergent needs of the youngsters. Oral contraceptives are suitable from the 16th year of life. Vaginal globuli and foams have also proved to be an effective means of contraception over that period of life. For anatomical reasons pessaries are not recommended, insertion of intrauterine devices is contraindicated because of their possible adverse effects. Experiences with university students taking d-Norgestrel as "morning-after-pill" have been favorable. The therapeutic abortion is regarded as an emergency measure to be employed only if anticonception failed. Adaequate education at the proper age and the importance of preventive measures are stressed.


[Effectiveness of the legal neoplasm prevention program in a cytological laboratory].

The test results of preventive gynecological examinations as assessed by a medium-sized cytological laboratory over a 5-year-period are reported. It is differentiated between the results found at first screening and at re-screening. Of the 34,121 women screened for the first time. 0.32% suffered from invasive cervical carcinoma or carcinoma of the corpus uteri and 0.41% from carcinoma in situ, whereas only 0.031% of the 192,089 re-screened women had invasive carcinoma and only 0.064% had carcinoma in situ. Thus the incidence of positive cases was 10 times higher with first check-ups as compared to annual follow-up screening. A retrospective inquiry with the participating physicians revealed among 116,020 cases 177 additional carcinomas ( = 0.15%), i.e. 122 breast cancers, 28 carcinomas of rectum or colon (5 primarily discovered by Haemoccult test) and 27 tumors of the skin, kidney or ovary. These results suggest the effectivity and neccessity of the Cancer Early Detection Program.


Ovarian response in the estrual cat receiving varying dosages of HCG.

Laparoscopy was utilized to determine the ovulatory response of the domestic cat to various dosages of human chorionic gonadotropin (HCG) administered intramuscularly at one or two time periods during estrus. A linear HCG dose-ovulatory response was observed in queens receiving 0--500 IU HCG as a single injection on day 1 or as injections given on days 1 and 2 of estrus. Animals treated with 500 IU HCG on day 1 or days 1 and 2 of estrus produced the maximum percent ovulation rates based on pre- and post-HCG ovarian morphology observation by laparoscopy (100.0, 95.9%, respectively). A single injection of 500 IU HCG produced a significant increase (p less than 0.05) in mean percent ovulation rate in comparison to the 0, 50 and 100 IU HCG single injections. Administration of 500 and 250 IU HCG for 2 days of estrus resulted in a greater percent ovulation rate than the 2-day injection of 50 IU (p less than 0.05). These results indicate that the proportion of mature follicles ovulating in an induced ovulator, such as the cat, is an increasing function of graded dosages of exogenous hormone.


Reliable detection of cystic fibrosis in skin-derived fibroblast cultures.

The specific induction of alkaline phosphatase with Tamm-Horsfall glycoprotein, isoproterenol, and theophylline in skin-derived fibroblast cultures from patients with cystic fibrosis permits one to reliably discriminate between cystic fibrosis patients on the one hand, and heterozygotes and normals on the other. It was found the fibroblast-like and intermediary types of amniotic fluid-derived cells behave essentially like skin-derived fibroblasts. These findings imply that if different amniotic fluid cell types can be reliably separated, prenatal diagnosis of cystic fibrosis should become feasable in the near future.


Centromere inactivation in a case of Turner variant with two dicentric iso-long arm Y chromosomes.

A 6-year-old girl of small stature and with some features of Turner's syndrome was found to have a karyotype with two-thirds of the cells possessing one, and one-third with two dicentric iso-long arm Y chromosomes. In metaphases with 46 chromosomes the majority of the abnormal Ys exhibited two primary constrictions. In cells with 47 chromosomes both isochromosomes prevalently had only one active centromere.


Growth of Chlamydia psittaci in macrophages.

Survival and growth of L-cell-cultivated Chlamydia psittaci occurred in mouse macrophages in vitro. Two major factors governing the intracellular fate of chlamydiae in macrophages are: (i) the multiplicity of infection (MOI), i.e., the elementary body (EB)-to-macrophage ratio, and (ii) the state of the EB. At a low MOI (1:1) survival and growth of live, untreated chlamydiae were optimal. The chlamydiae were internalized in macrophages within 30 to 40 min. EB proceeded to differentiate into reticulate bodies, which underwent multiplication and further matured into infectious EB in the professional phagocytic cells. In contrast, at a high MOI (100:1), survival of untreated chlamydiae was greatly reduced as a result of immediate damage to the macrophages. eb that were pretreated with heat (56 degrees C for 10 to 30 min) or coated with homologous antibody were rapidly destroyed in macrophage phagolysosomes. Fusion of ferritin-labeled lysosomes with heat-treated or opsonized EB-laden phagosomes occurred in 2 to 4 h, resulting in transfer of the ferritin marker into phagolysosomes.


Interaction of Chlamydia psittaci with mouse peritoneal macrophages.

L-cell-grown Chlamydia psittaci elementary bodies (EB) were rapidly phagocytized by mouse peritoneal macrophages in vitro. However, the intracellular fate of chlamydiae in macrophages appeared to be dependent on the multiplicity of infection (MOI), i.e., the EB-to-macrophage ratio, and the treatment of the EB. At an MOI of 1:1 or less, survival is maximal, and growth and multiplication of live, untreated chlamydiae did occur. In contrast, at a high MOI (100:1), survival of chlamydiae is reduced, as confirmed by release of 3H-labeled nucleic acid into the supernatant. At the high MOI, macrophage damage occurred that resulted in significant release of the lactic dehydrogenase, beginning 2 h postinfection. This immediated macrophage cytotoxicity as abolished by pretreatment of EB with heat (5 min at 56 degrees C) and was reduced about 50% by coating EB with homologous antibody. Pretreatment of the chlamydia with heat or opsonizing antibody provides increased uptake of EB by macrophages but may contribute to increased destruction of these obligate intracellular pathogens in professional phagocytic cells.


Do fatty acids exert a specific effect on human lymphocyte transformation in vitro?

Both saturated and unsaturated fatty acids (FA) bound to albumin inhibit phytohaemagglutinin (PHA) transformation of human lymphocytes cultured in fetal calf serum (FCS). With two unsaturated FA inhibition is maintained, however, when saturated and unsaturated FA are added simultaneously the inhibition is abolished. When lymphochtes are cultured in human AB serum, fatty acids neither inhibit nor stimulate PHA transformation. The reasons for the difference between FCS and human serum are discussed. These results argue against reports that unsaturated FA plays an immunoregulatory role in humans.


Effect of 2-bromo-alpha-ergocryptine (CB-154) on estrogen induced growth of the rat prostate.

Castrate male Sprague-Dawley rats were treated with either testosterone; testosterone and estradiol; testosterone, estradiol and 2-Bromo-alpha-Ergocryptine (CB-154), an inhibitor of prolactin secretion; or testosterone and CB-154. Estradiol potentiated testosterone-induced growth of the dorsal, lateral, and ventral prostate and this effect was not counteracted by CB-154. Estradiol only induced hypertrophy of the dorsal and ventral prostate, however, hyperplastic changes occurred in the lateral prostate.


Isolation of mycoplasmas from the genital tract of women with reproductive failure, sterility or vaginitis.

The presence of mycoplasma was investigated in 77 women with infertility, 34 women complaining of sterility, 92 women with vaginitis and 66 healthy control subjects. The group of infertile women was subdivided into those with one or two spontaneous abortions, those with three or more abortions and those with missed abortions. The isolation rate of mycoplasma from the vagina and cervix of the infertile women ranged from 18 to 36%. The endometrial isolation rate was 21% in women with missed abortions but lower in women of the other two subdivisions. Mycoplasmas were infrequently found in patients investigated for sterility. They were isolated at a higher rate in patients with vaginitis, especially in those with trichomonas-associated vaginitis. They were not found in healthy control subjects. In the endometria positive for mycoplasma no specific histological features for this infection were found.


Laboratory-acquired infections at the National Animal Disease Center 1960--1976.

Experience with exposure to, or infection with pathogenic agents at the National Animal Disease Center is summarized. A total of 60 laboratory-associated exposures to infectious disease agents were reported. Forty-nine exposures resulted from known accidents, but the other 11 were identified only after the development of clinical or serological manifestations of infection. Eighteen cases of laboratory-acquired infections were reviewed. Brucellosis, the most frequently reported laboratory-acquired infection, accounted for one-half of the cases summarized. Three cases of leptospirosis, two cases of Newcastle disease, two cases of ringworm, and a single infection with Mycobacterium bovis and with Salmonella arizonae were also encountered. The most frequently reported causes of exposure were: auto-inoculation or spray exposure associated with the use of the hypodermic syringe, cuts or lacerations, direct contact with infected animals, and mouth pipetting. Although the infecting event could not be identified in 11 infections, presumptive evidence suggests aerogenic transmission as a probable route of exposure in a number of such cases.


Metastatic phycomycosis in a horse.

Extensive subcutaneous phycomycosis of the lower hindlimb developed over a period of 8 months in a Thoroughbred filly. There was no response to treatments such as trichlorphon, sodium iodide, or etisazole. Extension of the limb lesion over the following 3 months was associated with an enlarged inguinal lymph node, which was removed. Characteristic phycomycotic lesions were observed in the node, and a fungus having the morphologic features of Hyphomyces destruens was isolated from both the limb and nodal lesions.


Spectrophotometric determination of pyrantel tartrate in swine feeds by method of standard additions: collaborative study.

The spectrophotometric method for pyrantel tartrate in swine feeds was collaboratively studied. Twenty-seven laboratories assayed feeds containing 0.0103, 0.0965, and 0.7902% pyrantel tartrate. Repeatability (sigmao) and reproducibility (sigmax) standard deviations were: sigmao = 0.00068%, sigmax = 0.00105% (10% of grand mean) for 0.0103% pyrantel tartrate level; sigmao - 0.0065%, sigmax = 0.0090% (10% of grand mean) for 0.0965% pyrantel tartrate level; and sigmao = 0.0415%, sigmax = 0.0743% (10% of grand mean) for 0.7902% pyrantel tartrate level. The mean theoretical recovery values for feeds containing 0.0103, 0.0965, and 0.7902% were 100, 97, and 96%, respectively. The method was adopted as official first action for feeds or concentrates containing 0.0106-0.8811% pyrantel tartrate.


Involvement of Rhizobium japonicum O antigen in soybean nodulation.

Non-nodulating mutant strains of Rhizobium japonicum lacked a surface antigen that was present on the wild type. This surface antigen is associated with the O antigen portion of the lipopolysaccharide. Paper chromatography of hydrolyzed lipopolysaccharide and O antigen revealed three major component differences between the non-nodulating strains and the wild type.