Operating room scheduling by computer.

The surgical operating room schedule has been produced automatically for more than 2 years in our large teaching hospital. In order to apply computer technology to the complex surgical scheduling problem a special programming approach was devised. We discuss this approach under the headings of Expand, Sort, Order and Assign. Consistent, reliable schedules, unaffected by weekends and holidays, are produced by a clerk trained to use a computer terminal. Our program is adapttable to other institutions once the scheduling parameters and operating priorities are delineated.


Age, chronic obstructive pulmonary disease, and Innovar induced ventilatory depression during regional anesthesia.

The effect of Innovar on ventilatory response to CO2 was studied in 35 patients undergoing peripheral surgery with regional anesthesia. The dosage schedule (per 70 kg body weight) was 2 ml intramuscularly, prior to the block, and 1 ml intravenously, after the block. The decrease in mean CO2 response slope (15 percent decrease from control 30 minutes after the first dose) was not statistically significant. Control slope varied inversely with age (r = 0.41, p less than 0.05), and (in 22 patients) directly with the FEV1/FVC ratio (r = 0.54, p less than 0.02) and with the combined variables (FEV1/FVC)/age (r = 0.58, p less than 0.01). Depression of CO2 response slope following Innovar did not vary with age or FEV1. We conclude that, in otherwise normal patients, these doses of innovar cause only minor depression of ventilatory response to CO2. However, in those patients who already have a depressed response (the elderly and those with a decreased FEV1/FVC ratio), this additional depression occasionally may be clinically important.


The care of patients with phantom limb pain in a pain clinic.

Patients referred to the Pain Clinic at the University of Virginia Medical Center with genuine phantom pain rather than stump pain have been treated by a variety of technics. Simple revision of drug therapy has proved helpful in some instances, as has repeated injection of trigger areas or neuromata, though surgical excision has proved necessary in some patients. Mechanical stimulation by stump tapping, prosthetic application, or electrical transcutaneous stimulation also may be useful. Sympathetic nerve block is occasionally very rewarding. Most patients need some form of psychological therapy. Rarely is cordotomy or higher central nervous system surgery required. There is no single best mode of therapy for phantom limb pain, nor can patients be guaranteed a permanent cure.


Intermittent exposure to 40 percent oxygen prolongs rat survival in 100 percent oxygen.

Prior intermittent exposure to 40 percent O2 protected rats against fatal O2 toxicity. Protection was not absolute, however, for the death of most rats in 100 percent O2 was not prevented but delayed considerably. Furthermore, those rats which did survive exposure to 100 percent O2 for long periods by virtue of prior-adaptation to increased O2 concentrations had pathologic changes in the lungs typical of chronic O2 toxicity. The very early demise of some rats indicated that 1 of 12 animals is hypersenstiive to high concentrations of inspired O2.


Experimentally induced anaplasmosis in neonatal isohemolytic anemia-recovered calves.

Anaplasma marginale infections were induced in 3 calves previously affected with neonatal immunohemolytic anemia (NIA). Similar infections were induced in 6 splenectomized and 7 intact calves. The response to infection by 3 calves (NIA recovered) closely resembled infections seen in splenectomized calves, being markedly more severe than similar infections in intact calves. Spleens from 3 (NIA recovered) calves after splenectomy were about one-tenth normal size. Marked recrudescing anaplasmal infections were not detected after splenectomy of the calves (NIA recovered), whereas marked recrudescing infections were observed after splenectomy of 2 intact calves having recovered from the primary infections.


Isolation of Dermatophilus congolensis and certain mycotic agents from animal tissues: a laboratory summary.

One hundred fifty-nine specimens from animal sources were examined for mycotic agents. Isolations were made from 57.9%. Dermatophytes were isolated from 13.2%, Dermatophilus congolensis from 10.7%, yeasts from 14.5%, and other fungi from 19.5% of the submissions.


Effect of systemic corticosteroids on antibody-forming cells in the eye and draining lymph nodes.

After the intracorneal injection of rabbit eyes with bovine gamma globulin, a systemically administered corticosteroid resulted in the following changes: (1) a reduction in the number of antibody-forming cells in the homolateral uveal tract and cornea; (2) a reduction in the ocular inflammatory response; and (3) a reduction in the number of antibody-forming cells in the draining lymph nodes, if high doses of corticosteroid were given.


[Zonal centrifuge purification of human rabies vaccine obtained on bovine foetal kidney cells (author's transl)].

A human rabies vaccine is prepared on bovine foetal kidney cells in absence of serum. This vaccine is concentrated and purified by zonal centrifugation. An immunogenic vaccine is obtained from the purified viral particles. Preliminary results are reported.


[Malignant cutaneous hemangioendothelioma. Clinicopathological and ultrastructural aspects (author's transl)].

Malignant cutaneous angio-endothelioma are tumors which develop from vascular endothelium. This is a study of one case along with the data compiled from 118 previously published cases. Clinically, this rare tumor is chiefly seen before the age of twenty of after sixty. Its appearance is polymorphic and often misleading. The clinical course of this disease in adults is always fatal, however, in children 20 p. 100 of the cases are reported curable. The histological picture shows a polymorphic pattern associated with vascular channels anastomosing in a plexiform network with large lacunae surrounded by papillary vegetations and plaques of fusiform, sarcomatoid cells as well as areas of angioblastic secretory cells. The ultrastructural study confirms that the tumor originates from endothelial cells which have lost their capacity to cover the capillary walls.


Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colon.

A total of 154 strains from 22 species of Bifidobacterium, Peptostreptococcus, Lactobacillus, Ruminococcus, Coprococcus, Eubacterium, and Fusobacterium, which are present in high concentrations in the human colon, were surveyed for their ability to ferment 21 different complex carbohydrates. Plant polysaccharides, including amylose, amylopectin, pectin, polygalacturonate, xylan, laminarin, guar gum, locust bean gum, gum ghatti, gum arabic, and gum tragacanth, were fermented by some strains from Bifidobacterium, Peptostreptococcus, Ruminococcus, and Eubacterium species. Porcine gastric mucin, which was fermented by some strains of Ruminococcus torques and Bifidobacterium bifidum, was the only mucin utilized by any of the strains tested.


Role of estrogen in controlling the genital microflora of female rats.

Plate counts of viable bacteria recovered by lavage from rat vaginae demonstrated that the number of bacteria associated with the vaginal epithelium varied cyclically and that this pattern was abolished by ovariectomy. After ovariectomy, vaginal bacterial counts remained relatively stable at low levels. The estrogen 17beta-estradiol (1,3,5(10)-estratriene-3,17beta-diol cypionate) administered to ovariectomized rats caused a significant increase in vaginal bacterial counts on day 3 post-treatment. A similar effect was seen in non-ovariectomized rats, but a larger dose of estrogen antagonist may have been present in non-ovariectomized animals. Progesterone (4-pregnene-3,20-dione) given with estradiol diminished the effect of the estrogen on vaginal bacterial counts, but did not abolish it. Progesterone administered without estradiol had no detectable effect on vaginal bacterial counts. These findings suggested that the cyclic variation in bacterial content of rat vaginae could be explained primarily as the effect of the secretory pattern of ovarian estrogen.


[Influence of clay on microorganisms conservation. I. Ultrastructural study of the biodegradation of Beauveria bassiana (Bals). Vuill. (entomopathogenous hyphomycete) in soil (author's transl)].

Blastospores of B. bassiana enclosed in fine mesh bags were submitted to soil microflora. Clay minerals coating fungal spores protected from by decreasing bacterial activity. The role of amoeba in biodegradation of fungi is also considered.


Alkaline phosphatase activity of rumen bacteria.

Of the 54 strains of rumen bacteria examined for alkaline phosphatase (APase) production, 9 of 33 gram-negative strains and none of 21 gram-positive strains produced the enzyme. The APase of the cells of the three strains of Bacteroides ruminicola that produced significant amounts of the enzyme was located in the periplasmic area of the cell envelope, whereas the enzyme was located in the strains of Selenomonas ruminantium and Succinivibrio dextrinosolvens was associated with the outer membrane. The localization of APase production in the cells of natural populations of rumen bacteria from hay-fed sheep was accomplished by reaction product deposition, and both the proportion of APase-producing bacteria and the location of the enzyme in the cell envelope of the producing cells could be determined. We suggest that this procedure is useful in detecting shifts in the bacterial population and the release of cell-bound APase that accompany feedlot bloat and other sequelae of dietary manipulation in ruminants.


Salmonellae in health foods.

Various health food products of different brands were purchased from stores in the metropolitan Atlanta area. These foods were examined for the presence of salmonellae by fluorescent-antibody and cultural methods. Included in the study were tablets of alfalfa, parsley, kelp, wheat bran, enzyme, bone meal, and vitamins. Beef liver powder and tablets and granola cereal were also studied. Salmonella minnesota, Salmonella anatum, and Salmonella derby were isolated from two of three lots of beef liver powder from one manufacturer. All other products were negative.


[Effect of various processes on the protein quality of food based on corn and soybeans].

The present study deals with the effect of various processing methods on the protein values of Maisoy, a blend of 30% whole soybean and 70% corn. The processes evaluated were: a) lime cooking using calcium hydroxide; b) toasting, and c) extrusion cooking, using an equipment known as the Brady Crop Cooker. The same blend of soybean/corn was processed by the same three methods. In addition, a sample of Maisoy--blend produced in Bolivia with the extrusion equipment previously indicated--was also evaluated. The evaluation of all products was carried out using the protein efficiency ratio method (PER). The capacity of two of the blends, with and without amino acid supplementation, of causing changes of deoxiribonucleic acid, ribonucleic acid, and protein in the content of muscle and liver was also measured. Lime cooking as well as extrusion cooking yielded a food with a protein efficiency ratio which varied from 2.30 to 2.60. Both processes destroyed the antiphysiological factors of soybean.


Pectinolytic ability of some mycorrhizal and saprophytic hymenomycetes.

Ectomycorrhizal fungi of the genus Boletus were able to use a restricted number of hexoses and disaccharides as single carbon sources. In the presence of a small amount of "start" glucose, induced growth occurred on a few additional carbohydrates. Even in the presence of "start" glucose, the ectomycorrhizal fungi could not utilize pectin, whereas certain litter-decomposing fungi grew rapidly using this compound as a carbon source. Only the litter-decomposers were able to use galacturonic acid, the monomer of pectic acid, as a carbon source. Possible mechanisms for the penetration and growth of ectomycorrhizal fungi into the middle lamellae of the root parenchyma are discussed.


Sexual behavior of captive orangutans.

Opposite-sex pairs of orangutans were tested for sexual behavior during the intermenstrual period of the female. The male orangutan was the primary initiator of sexual interactions and initiated copulation forcefully on a daily basis, irrespective of female resistance. However, although single copulations occurred daily, copulations beyond the first occurred most frequently during midcycle. Other evidence of cyclicity in behavior was the midcycle decrease in female avoidance of the male and increased grooming, proceptivity, and masturbation by the female. Comparative analysis suggests that differences in sexual cyclicity among the great ape species are related to interspecies differences in sexual assertiveness of males and females. Sexual activity in the cycle is relatively brief when the female controls mating, more prolonged when the male is in control. This finding in man's closest taxonomic affiliates suggests that similar social factors may also influence the distribution of sexual interactions in the human cycle.


[Experiments with cultures of mammalian cells aboard the biosatellite "Cosmos-782"].

A considerable contribution to the investigation on biological importance of weightlessness was made by the experiments with animals in the artificial Earth satelites (AES) of "Cosmos" type. Cell cultures can serve as an ideal model to get a direct cell response to the effect of external factors. For the experiment in the AES "Cosmos-782", two thoroughly examined cell strains (L and 237) were chosen, which differed in a number of parameters (for example, duration of their mitotic cycles). Density of cell seeding and temperature of their cultivation in the laboratory experiment were calculated in such a way that the whole cycle of the culture development should take place under the conditions of weightlessness: the beginning of lag-phase--before launching and the stationary phase--after landing. The weightlessness was not shown to result in any genetical shifts revealed at chromosomal level. When cultivated after the flight, the cells do not change their mitotic cycle parameters, mitotic course and structural organization. The data obtained in the experiments with AES "Cosmos-368" and "Cosmos-782" (increase of mitotic index, some forms of mitotic pathology during the first terms of cultivation after the flight and enlargement of cellular nuclei) demonstrate the changes in the cell population which have formed under the conditions of weightlessness. Similar changes are observed while the cells propagate in the laboratory conditions. Indirect data on an earlier cell culture aging during the flight do not exclued the possibility that under weightlessness the rate of cell propagation could differ from that under gravitation.


[Analysis of the biorhythm frequency of bordered enterocytes during normal and inverted feeding regimens].

The study was performed during the period close to equinox in 236 male mice C57 Bl strain, sacrificed at equal intervals during 5 days. In paraffin sections, 5--6 mcm thick, stained after Dominici-Kedrovsky, with additional application of PAS-reaction and alcian blue, the cell height and width in the small intestine border enterocyte zone were determined. Calculation of autocorrelative function with the following determination of spectral density, infradian, circadian and ultradian biorhythmical components were estimated, as well as their changes under the influence of feeding regime inversion. At evening feeding, the greatest width of the brush border coinsides the beginning and the end of the digestion period. The width of the dark apical zone, where mitochondria are concentrated, synchronously changes at the end of digestion with the brush border, and then- with the cell basal zone. At morning feeding, by the degree of circadian phase change, the most liable are the indices reflecting organoid status, which are closely involved in absorbtion processes. Ultradian rhythm produces, on the background of circadian changes, additional raisis and abatements. Spectral composition, under inadequate feeding, is demonstrated to become more complex, mainly at the expense of ultradian rhythms, that speaks of their importance for the processes of adaptive rhythmical rearrangement.


Translation of endogenous message in embryonic chick erythroid cell polysomes in a cell-free protein-synthesizing system.

Polysomes from 5.5-day and 6.5-day embryonic chick erythroid cells contain messenger RNA (mRNA) which can be translated into products in a cell-free protein-synthesizing system. The products of the cell-free system coelectrophoresed with carrier globin chains from the cells from which the polysomal pellet was isolated. Wheat germ S30 fraction increases by 1.5--2.0 fold [3H] leucine incorporation into trichloroacetic acid-precipitable material directed by the endogenous mRNA on chick erythroid cell polysomes. The wheat germ probably provides a specific factor or factors absent in a shortage in the incubation medium.


Interaction of lipoprotein lipase with heparin-Sepharose. Evaluation of conditions for affinity binding.

Lipoprotein lipases from a variety of sources have been shown previously to bind to heparin and some related polysaccharides. For the present studies lipoprotein lipase purified from bovine milk was used. 1. In batch experiments binding of the enzyme activity to heparin-Sepharose occurred relatively slowly, so that 30min was required for the system to come to near-equilibrium. In contrast, release of the enzyme activity from heparin-Sepharose by addition of salt to the liquid phase occurred rapidly. 2. Some binding was observed also with unsubstituted Sepharose, but this binding had a low capacity compared with that observed with heparin-Sepharose. High salt concentrations, heparin or deoxycholate decreased the binding to unsubstituted Sepharose. These factors also increase the solubility of the enzyme, which is low. 3. Addition of heparin to the liquid phase caused a concentration-dependent release of enzyme activity from the gel. These results suggested that the binding of the enzyme to heparin-Sepharose was mainly through interaction with heparin. 4. The enzyme activity was also quantitatively displaced to the liquid phase at increased concentrations of salt. Among the positive ions tested the following order of effectiveness was noted: Cs(+) approximately K(+)>Na(+)>Li(+); and among the negative the following: SCN(-)>I(-)> NO(3) (-)>Br(-) approximately Cl(-). The differences were quite large. Thus addition of 0.16m-KSCN (in addition to the 0.32m-NaCl originally present) displaced one-half of the enzyme activity to the supernatant, whereas 0.8m-LiCl only displaced one-quarter. 5. The distribution of heparin in the gel also profoundly influenced the binding. Two series of gels were studied. One series was made by mixing heparin-Sepharose with unsubstituted Sepharose. Results obtained with these gels were those expected from a series of decreasing volumes of heparin-Sepharose. In contrast, a series of heparin-Sepharoses made with different degrees of substitution gave quite different results. With these gels the amount of enzyme activity bound per amount of heparin increased markedly, whereas the salt concentration needed to displace the enzyme activity from the gel decreased markedly with decreased concentration of heparin in the gel. 6. On stepwise elution of small columns of heparin-Sepharose the enzyme activity was eluted over a remarkably wide range of salt concentrations. When enzyme eluted at one salt concentration was re-applied, it gave the same elution profile as enzyme previously eluted at other salt concentrations or the entire enzyme preparation. These and other results suggested that, whereas the enzyme preparation was rather homogeneous in its binding to heparin, the heparin preparation was polydisperse in binding of lipoprotein lipase.


Sperm immobilizing antibodies in the serum and cervicovaginal secretions of infertile and normal women.

A search was made for sperm immobilizing antibodies in the sera and in the cervicovaginal secretions of 39 women in whom apparent cervical mucus hostility was the only explanation for infertility. Anti-sperm antibodies were found in 25.6 per cent of sera and 20.5 per cent of cervicovaginal secretions. No such antibodies were detected in controls.


Thrombocytopathia as a cause of menorrhagia. Two case reports.

Thrombocytopathia is a condition in which the platelets have a qualitative rather than a quantitative defect. Two patients with thrombocytopathia who presented with menorrhagia are described.


The problem of uveitis in Bendel State of Nigeria: experience in Benin City.

A review of 1987 patients with uveitis seen over an 11-year period in Bendel State of Nigeria has been undertaken; 56% of cases had a posterior/mid-peripheral uveitis, 15.1% a panuveitis, 21.5% an anterior uveitis. Acute anterior uveitis with classical symptoms was rarely seen. Its comparative rarity is presumably due to the absence of HL-A27 in Africans and altered immunological states from malaria and parasitic infections. Identified aetiological factors in anterior uveitis were leprosy (1 patient), tuberculosis (1 patient), herpes zoster (16 patients), and onchocerciasis (3 patients). The great majority of cases of posterior uveitis were of presumed toxoplasmic origin. Further studies are needed to demonstrate its mode of transmission in a population in which toxoplasmosis is endemic. Forest onchocerciasis is not a major cause of uveitis in southern Nigeria in the same way as savanna onchocerciasis is in northern Nigeria. Syphilis seems to play no part in the causation of uveitis in southern Nigeria. Better diagnostic facilities are required to determine the role of sarcoidosis and other possible causative factors. Uveitis is a major cause of blindness in Nigeria.


HLA-B27 frequency in Greek patients with acute anterior uveitis.

The histocompatibility antigen HLA-B27 was identified in 12 out of 33 patients with acute non-granulomatous anterior uveitis. This is a frequency of 36.36%, compared with 4.72% in controls. Seven patients had in addition evidence of systemic disease, including ankylosing spondylitis, sacroiliitis, Reiter's disease, Still's disease, and rheumatoid arthritis. Five of these were HLA-B27 positive, which suggests that the uveitis in many of these cases has a similar aetiology to the uveitis in those with rheumatic disease. It appears that the more severe cases of acute anterior uveitis are related more frequently to the presence of HLA-B27.


Protein which interacts with a stimulatory factor of RNA polymerase II of Ehrlich ascites tumor cells.

When partially purified Ehrlich ascites tumor RNA polymerase II was further purified on a column of phosphocellulose, stimulation of its catalysis of RNA synthesis by stimulatory factor S-II was greatly decreased. This decrease in sensitivity to the stimulatory factor was reversible: the enzyme eluted from phosphocellulose became sensitive to the factor when mixed with a protein fraction eluted from the phosphocellulose at high salt concentration. Evidence was obtained that this protein, named helper protein, binds, to the enzyme eluted from phosphocellulose, causing it to recover sensitivity to stimulatory factor S-II.


Amino acid dependent and independent insulin stimulation of cartilage metabolism.

The effects of insulin on embryonic chicken cartilage in organ culture and the dependence of these effects on essential amino acids have been studied. In the presence of all essential amino acids, insulin: (1) increases 2-deoxy-D-glucose and alpha-aminoisobutyric acid uptake; (2) increases [5(-3H] uridine flux into uridine metabolites and the intracellular UTP pool; (3) expands the size of the intracellular UTP pool; (4) does not change the specific activity of the UTP pool; and (5) stimulates RNA, proteoglycan, and total protein synthesis. In lysine (or other essential amino acid)-deficient medium, the effects of insulin are different. While insulin stimulates incorporation of [5(-3)H] uridine into RNA, it does so by increasing the specific activity of the UTP pool without increasing RNA synthesis. Insulin stimulates 2-deoxy-D-glucose and alpha-aminoisobutyric acid uptake but no longer stimulates proteoglycan, total protein, or RNA synthesis or expands the size of the UTP pool. These data indicate that there are amino acid dependent and independent effects of insulin on cartilage. Transport processes are amino acid independent, while synthetic processes are amino acid dependent.


The lipid composition of muscle cells during development.

Developmental changes in the phospholipid, cholesterol, and fatty acid composition of chicken pectoralis muscle cells were analyzed during development in vivo and in tissue culture. The phospholipid composition of muscle cells showed only minor changes during in vivo or in vitro development but there were significant alterations in fatty acid composition. During in vivo development between the 12th and 22nd days the concentration of palmitate and arachidonate decreased with increase in linoleate. In cultured muscle cells the fatty acid composition changes with surprising plasticity depending on the fatty acid supply. Compensatory changes were observed in the chain length and unsaturation of several fatty acids, aimed presumably at maintaining the physical properties of the lipid phase relatively constant.


Localisation and characterization of the fatty acid synthesizing system in cells of Glycine max (soubean) suspension cultures.

In course of a study of fatty acid synthetase in higher plants, non-green cell suspension cultures of Glycine max (soybean) served as model tissues. For the first time, a fatty acid synthesizing system was characterized in cell cultures of higher plants and was found to be solely located in proplastids of the cells. Optimum activity of the fatty acid synthesizing system in proplastids was observed between pH 8.0 and 8.2; with [1-14C]acetate as substrate, cofactors required were CoA, ATP, Mn2+, Mg2+, HCO3-, NADH and NADPH. The system was more sensitive towards NADH than NADHP. [1-14C]Acetate,[2-14C]-malonate and [3-14C]pyruvate served as precursors for fatty acids, indicating the presence of pyruvate dehydrogenase activity in proplastids. In disrupted proplastids, [2-14C]malonylCoA was a better precursor than [1-14C]acetylCoA. After incubation of proplastids with [2-14C]malonate, a small shift, from palmitic acid to higher homologs, of label incorporated was observed, as compared to incorporation of label from [1-14C]acetate and [3-14C]pyruvate. Under the conditions of the experiment, only small amounts of polyunsaturated fatty acids, the main fatty acid components of this organelle, were synthesized. In respect to fatty acid synthesis, the non-green cell suspension culture resembles photosynthetic leaf tissue.


Glyceride synthesis by four kinds of microbial lipase.

Apart from their usual mechanism of action, lipases from Aspergillus niger and Rhizopus delemar also catalyzed the synthesis of glycerides from oleic acid and glycerol. Lipases from Geotrichum candidum and Penicillium cyclopium were inactivated by oleic acid, but were stable in the presence of casein, albumin or buffer of appropriate pH. Lipases from Aspergillus niger and Rhizopus delemar synthesized glycerides from, not only fatty acid, but dibasic acids and aromatic acids, making ester bonds only at position 1 and 3 of glycerol. In contrast, lipases from Geotricum candidum and Penicillium cyclopium synthesized glycerides only from long chain fatty acids, and made ester bonds at all three available positions  of the glycerol molecule.


The chromophore topography and binding environment of perididin.chlorophyll a.protein complexes from marine dinoflagellate algae.

1. The peridinin.chlorophyll a.protein complex from Amphidinium carterae (Plymouth 450) shows spectroscopic characteristic (absorption, CD, fluorescence polarization, lifetime and energy transfer) essentially identical with peridinin.chlorophyll a.protein complexes from Glenodinium sp., Gonyaulax polyedra and Amphidinium rhyncocephaleum. 2. The apoprotein of peridinin.chlorophyll a.protein complexes is globular, with an isotropic rotational relaxation time (e.g. 33 ns for the A. caterae peridinin.chlorophyll a.protein), as deduced from the dynamic depolarization data. 3. The chromophores (4 peridinins and 1 chlorophyll a for peridinin.chlorophyll a.protein complexes from Glenodinium sp., G. polyedra and A. rhyncocephaleum and 9 and 2, respectively, for peridinin.chlorophyll a.protein of A. carterae) are accommodated in a hydrophobic crevice and not exposed to the solvent. The surface of the protein is highly hydrophilic. 4. No evidence for chlorophyll-chlorophyll interactions in the A. carterae peridinin.chlorophyll a.protein was obtained. This implies that binding crevices for two chlorophylls and half of peridinins (four to five) are located at some distance from each other. 5. The peridinin.chlorophyll a.protein complexes function as the photosynthetic antenna pigment. In addition, peridinins effectively protect chlorophyll a from photodecomposition.


Electrochemical evaluation of lactate dehydrogenase immobilized in polyacrylamide gels.

Lactate dehydrogenase (EC 1.1.1.27) has been immobilized in polyacrylamide gels over a platinum grid matrix. The immobilized enzyme is used to oxidize L-lactate in the presence of nicotinamide adenine dinucleotide (NAD+) and ferricyanide. The NADH produced is then chemically oxidized back to NAD+ by ferricyanide. The coupled reduction of ferricyanide ions to ferrocyanide ions results in a measurable electrochemical potential. This measurable zero-current potential is found to be Nernstian in nature and directly proportional to the logarithm values of L-lactate concentration over the range of 2 X 10(-5) to 5 X 10(-2)M. The results indicate that immobilized lactate dehydrogenase can be incorporated into a system to detect L-lactate acid in aqueous solutions.


Practical identifiability of growth and substrate consumption models.

The estimation of parameters in several dynamic models, which describe growth and substrate consumption, has been carried out using a modified Gauss-Newton-type method. The four models considered are Monod, Contois, linear specific growth rate, and an enzyme kinetic model. The initial values of the differential equations are included in the parameter vector which will be estimated. The efficiency of the method and the confidence limits of the parameters were studied using simulated measurement noise. The experimental results describe Trichoderma viride growing on glucose as the main carbon source.


[Prolongation of sleep following creation of a generator of pathologically enhanced excitation in the orbital cortex].

Acute experiments on cats showed that injection of tetanus toxin into the orbital cortex (which destroys various types of inhibition) resulted in the formation of a local generator of pathologically enhanced excitation in this cortex area. Chronic experiments showed that cats with such a generator in the orbital cortex developed pathological changes of sleep, expressed in reduction of the duration of wakefulness and development of the slow-wave and paradoxical sleep phases being, retained. The results of this investigation confirm the view on the participation of the orbitofrontal cortex in sleep induction. They are in favour of the general conception on the role of the determinant structure in the nervous system activity and the theory of the generator mechanisms of the neuropathological syndromes characterized by the hyperactivity of the system.


[Mechanism of action of heparin on lymphoid cells in vitro].

Heparin ability to interfere significantly with the passage of antibodies from the antibody-forming cells was shown in vitro on CBA/C mice, using a 2 percent erythrocyte suspension as an antigen. A partial restoration of the plaque formation ability was observed in vitro by the supplement of substances possessing the features of "Triton" X-100 detergents, deoxycholate to the suspension of spleen plaque forming cells treated with heparin. Hence, it was concluded that heparin was capable of interacting with the outer membrane of immunocompetent cells inhibiting the passage of synthesized antibodies to the milieu.


[Quantitative histoenzymatic analysis of the adenohypophysis and adrenal cortex during the early stages of involution].

A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.


[Macroscopic anatomy of the human fetal thymus in the 2d half of uterine life].

The dissection under an operative microscope of 46 foetuses from a homogeneous series measuring 80 to 390 mm C-R (crown-rump) is the subject of a gross anatomic study of the thymus. The authors point out the size, the lobulation and connections with the vascular pedicles of the neck: the thyropericardeal sheet.


[Scanning and transmission electron microscope study of the amniotic epithelium in the rat at the end of gestation].

The pattern of the amniotic epithelium during the eight last days of pregnancy is described with the aid of scanning and transmission microscopy. A flattening of the cells appears near the term. Their area becomes progressively greater increasing their contact surface with the amniotic fluid. Simultaneaously, their microvilli become more numerous. During the 20th, the 21st and the 22nd days of pregnancy, we observed cytoplasmic processes emanating from the base of the cell interrupting the basal membrane and entering the underlying connective substance. No evidence of cell degeneration was seen.


Abuse and neglect as a cause of mental retardation: a study of 140 children admitted to subnormality hospitals in Wiltshire.

The survey of 140 children under 16 in two subnormality hospitals showed that 3 per cent of the children had definitely been rendered mentally handicapped as a consequence of violent abuse, and that a possible maximum total of 11 per cent might have been thus rendered mentally handicapped. In 24 per cent of the children, neglect was considered to be a contributory factor in reducing intellectual potential. Impairment of intellect from abuse and neglect, especially in those with 'vulnerable' brains due to pre-existing abnormality, may be much commoner in children than is generally realized.


Advances in the management of non-seminomatous germinal tumours of the testis.

Experience in the management of 146 consecutive patients with non-seminomatous tumours of the testis has led to a plan of management based on retroperitoneal lymph node dissection as the primary treatment modality, with use of adjuvant therapy dependent on pathological findings. Chemotherapy has proved to be the most important adjuvant with postoperative radiation therapy reserved only for patients with extensive retroperitoneal metastatic disease. 3-year crude survival for patients with all stages of disease was 78% and in those in whom the disease was confined to below the diaphragm the survival rate was 85%.


Neonatal and "perinatal" mortality rates by birth weight.

Neonatal and "perinatal" mortality rates by birth weight were compared for Sheffield and for England and Wales. The fall in neonatal mortality rate for Sheffield infants weighing 2500 g or less was partly due to the excessive fall in numbers in the 1000 g or less group: this effect was also present in England and Wales but was less pronounced. Perinatal mortality rates may be lowered either by reducing (a) the number of stillbirths, (b) the number of preterm live births, or (c) by salvaging a greater percentage of the latter. For liveborn births it is suggested that the second approach would be better than the third. So far there is no evidence that superintensive care for those weighing 1000 g or less reduces their mortality rate.


Predatory behavior in the cat elicited by lower brain stem and hypothalamic stimulation: a comparison.

The predatory attack of a cat against a rat elicited by lateral hypothalamic, ventral midbrain and ventromedial periaqueductal gray stimulation has been compared. Regardless of the region stimulated, the attack behaviors were found to be identical with respect to response topography, preference for the rat as an attack object, the distance at which the cats would approach and attack a rat and the success in finding and attacking the rat when the cats were blindfolded. However, the minimum current required to elicit the predatory attack by periaqueductal gray stimulation was 3-4 times less than that required to elicit the same behavior by ventral midbrain and lateral hypothalamic stimulation. The difficulty in reconciling these results with the preeminent role assigned to the hypothalamus in the organization of predatory aggressive behavior was considered.


Chromosomes and DNA of Microtus. II. Confirmation of deletion of constitutive heterochromatin in M. agrestis cells in vitro.

The distribution of constitutive heterochromatin has been examined by C-banding in two somatic cell lines, grown in vitro, from a female Microtus agrestis. One line retains one intact X chromosome together with the short arm of the other X chromosome, while the other cell line retains only the short arm of one X chromosome. Thus, each cell line has lost substantial amounts of heterochromatin from the sex chromosomes, but this material has been deleted from the cells, and not translocated to other chromosomes. Nonetheless, both cell lines continue to propagate well in vitro.


The evolution of mature teratoma from malignant testicular tumors.

During the period of 1969--1976, twelve cases of malignant germ cell tumor of the testis were seen in which the diagnosis was associated with the subsequent development of one or more metastases composed histologically of fully mature teratoma. These patients had a variety of primary germ cell tumors in the testis and were treated with radiation therapy and/or chemotherapy in addition to surgery, prior to the development of mature teratomas in different anatomic sites. The development of mature teratoma in this clinical setting seems to be a favorable prognostic sign, inasmuch as only one of the 12 patients has died with known persistent cancer. Since the incidence of this phenomenon seems to be increasing, the mechanism is probably related, directly or indirectly, to therapy.


Urinary glycosaminoglycan patterns in angiosarcoma of the liver.

Glycosaminoglycans extracted from 24-hour urine specimens from patients with hepatic angiosarcoma and from normal/controls were separated as cetylpyridinium complexes into "hyaluronic acid," "chondroitin sulfate," and "heparin" fractions, then further separated and characterized by anion-exchange chromatography and hyaluronidase susceptibility. The chromatographic pattern of the urinary chondroitin sulfate fraction in patients with angiosarcoma of the liver differed from those of controls in that there was a relative increase in the total amount of uronic acid in a hyaluronidase-resistant fraction and a decrease in a fraction susceptible to hyaluronidase digestion. These changes appeared to become more pronounced with advancing disease. Chromatographic patterns and determinations of hyaluronidase susceptibility indicated that the resistant fraction was heparan sulfate and that the susceptible fraction was chondroitin-4-sulfate and/or chondroitin-6-sulfate.


Structure-function correlations in the reaction of bis(thiosemicarbazonato) copper(II) complexes with Ehrlich ascites tumor cells.

Examination of a series of substituted bis(thiosemicarbazonato) copper(II) complexes shows that their reaction with Ehrlich ascites tumor cells can be understood in terms of the relative reactivity of the complexes with sulfhydryl groups. In general, the order of reactivity of the complexes correlates directly with their respective degrees of cytotoxicity and ability to inhibit DNA synthesis and cellular respiration. The parent complex, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II), leads to widespread cellular effects with the suppression of DNA synthesis particularly sensitive to the complex. The apparent reversible inhibition of DNA synthesis and thymidine uptake hy 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) copper(II) and its lack of cytotoxicity are explained in terms of the chemical properties of this complex.


Ultrastructural study of the persistence of colchicine-induced cytological changes in Harding-Passey melanoma.

Electron microscopic observations were undertaken on Harding-Passey melanoma in control tumors, colchicine-treated tumors, and tumors that were passed through five transplantations in mice subsequent to colchicine treatment. The untreated Harding-Passey melanoma tumor was composed of pleomorphic cells the cytoplasm of which contained tubulovesicular mitochondria and numerous free and membrane-attached ribosomes. Type A virus particles were observed in both mitotic and interphase cells. Colchicine-treated tumors exhibited several typical colchicine mitotic cells arrested in metaphase. A most significant feature of the colchicine administration was the appearance of microfilaments in both interphase and mitotic cells, a feature not observed in cells of the untreated tumor. Electron microscopy of colchicine-treated tumors carried through five transplantations at biweekly intervals revealed the presence of microfilaments in tissues fixed at each of the transplantations. It therefore appears that the cytological effects of colchicine resulting in the appearance of filaments in melanocytes of the Harding-Passey melanoma are more enduring than they were initially presumed to be.


Tumor induction with the N'-acetyl derivative of 4-hydroxymethyl-phenylhydrazine, a metabolite of agaritine of Agaricus bisporus.

N'-Acetyl-4-(hydroxymethyl)phenylhydrazine was administered as a 0.0625% solution in drinking water continuously for the life span of Swiss mice, from 6 weeks of age. Compared to that in untreated controls, in treated animals the lung tumor incidence rose from 15 to 34% in females and 22 to 48% in males, whereas the incidence of blood vessel tumors increased from 8 to 32% in females and from 5 to 30% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and angiomas and angiosarcomas of the blood vessels. The commonly eaten mushroom Agaricus bisporus contains beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, which under certain conditions yields 4-hydroxymethylphenylhydrazine and L-glutamic acid. Since 4-hydroxymethylphenylhydrazine is relatively unstable, its acetyl derivative was synthesized for this study. The possible environmental significance of the findings is discussed.


Acute toxicity of maytansine in F344 rats.

The toxicity of maytansine given by sc administration was studied in 5-week-old mald F344 rats. The LD50 (14-day) was 0.48 mg/kg. A dose response to drug administration was indicated by body weight changes and diarrhea. A single, acutely toxic dose of maytansine was shown to possess marked activity against dividing cells which was regarded as an important factor in the pathogenesis of acute lesions in tissues with a normal high rate of cell division. Histologically, mitotic figues were observed in many tissues from 6 to 24 hours after drug administration. Subsequently, necrotizing lesions led to atrophic changes in gastrointestinal tract mucosa, thymus, spleen, bone marrow, and testis. Maytansine also induced hemorrhagic lesions in parenchymatous organs and brain and perivascular monomuclear infiltration in the meninges, and chromatolysis and vacuolation of dorsal root ganglion cells, accompanied by clinical signs of ataxia. Ulcerative skin lesions were observed at the sc site of drug administration.


Structural features and quantitative age-dependent changes in the intervascular barrier of the guinea-pig haemochorial placenta.

The haemomonochorial placenta of the guinea-pig undergoes several quantitative changes between the 49th and 64th days of gestation, all of which are in such a direction as to increase the efficiency of transplacental transport. The fetal vessels become larger, the maternal vessels increase in surface area by proliferation of microvilli, and the effective mean distance between the two vessel sets decreases. The magnitude of these changes suggests that the efficiency of transport of hydrophilic solutes across the maternal-fetal interface could double, although changes in the number of permeation sites per unit area may modify this relationship. The presence of open intercellular spaces and fenestrations in the fetal endothelium suggests that this layer may not be a major permeability barrier in the guinea-pig, but may create an unstirred layer of extracellular fluid between endothelium and syncytiotrophoblast.


Extrinsic allergic alveolitis from bird exposure. Studies on the immediate hypersensitivity reaction.

Six patients with extrinsic allergic alveolitis had weak immediate and strong late reactions of intracutaneous injection of bird serum. Biopsy of the late reaction revealed vasculitis and immunoglobulin and complement deposition in one. The antibody responsible for the immediate hypersensitivity could be transferred in serum. It was short lasting (4 hr) and resistant to heat and 2-mercaptoethanol. No evidence of an immediate reaction in the lungs could be detected following inhalation challenge as judged by examination of spirometry, flow volume loops and single breath nitrogen washout curves.


Immediate and late onset asthma from occupational exposure to soybean dust.

Most patients sensitive to soybean experience gastrointentinal symptoms, urticaria, angioedema, and asthma after ingestion. However, we report here a previously non-allergic patient who developed immediate and late onset asthma after breathing soybean flour used in the manufacture of food supplements. She exhibited positive immediate and late skin test sensitivity as well as a positive bronchial challenge to a soybean flour extract. In contrast to another patient with an anaphylactic response after soybean ingestion, the radioallergosorbent test (RAST) to soybean antigen was negative in our patient.


RAST in the diagnosis of hypersensitivity to horse allergens. A comparison with clinical history and in vivo tests.

Case history, skin tests and RAST were compared in a group (n = 40) of children with a history suggesting allergy to horses and in a group (n = 43) in whom there was no suspicion of hypersensitivity to horses. There was an agreement of 91% between case history and prick test. The same magnitude of agreement was found between case history and RAST (89%), and the agreement between RAST and prick test was 90%. The results of this investigation are clearly in contrast to earlier earlier reports, in that there was a very good correlation between prick test, RAST and case history. The results suggest that: (a) a proper evaluation of the skin test is of critical importance for the degree of correlation with other diagnostic tests; and (b) RAST is as reliable as carefully performed and evaluated skin tests.


Human dander in house dust allergy.

The possible role of human dander in house dust allergy was investigated. Naturally shed human mite-free skin squames were collected from bedding and used to prepare a human dander extract. When the extract was coupled to cyanogen bromide-activated paper discs, and used in the RAST assay, IgE titres to the skin extract were observed in the sera from several patients with house dust allergy. The sera with IgE to the skin extract also had high IgE titres to either house dust, D. pteronyssinus or cat fur. RAST inhibition studies revealed cross-reaction between the human skin extract and both a D. pteronyssinus extract and a cat fur extract.


Determination of tricyclic antidepressant, clomipramine (Anafranil), in plasma by a specific radioimmunoassay procedure.

A radioimmunoassay is reported for the tricyclic antidepressant drug, clomipramine (Anafranil, Geigy). Antisera generated in rabbits to clomipramine conjugated to bovine serum albumin at positions 10 and 11 were specific, cross reacting less than 5% with the pharmacologically active metabolite, desmethylclomipramine. Specificity was confirmed by the good agreement in titres observed when the samples were assayed with and without a pre-assay thin-layer chromatographic purification. Intra- and inter-assay variations were less than 8 and 13%, respectively, with a sensitivity of 175 ng/liter. Results obtained agreed well with those reported by other groups  using double radioisotope derivative assays. The method has a high throughput rate, one technician can assay 200 samples in duplicate in a working week; and it is sufficiently precise, sensitive, and specific for use in routine minitoring of the drug in plasma and for checking patient compliance with dosage regimen.


Trisomy 4p: five new observations and overview.

Five new cases of trisomy of the short arm of chromosome No. 4 are presented. In two brothers the abnormality arose from segregation of the 4p chromosome present in the mother who is a carrier of a centric fission of one No. 4 chromosome. In the other three patients, the chromosome imbalance originated from segregation of a balanced maternal 3p/4q or 4/22 translocation. The available data, derived from the 4p trisomics reported so far, are adequate to establish trisomy of the short arm of chromosome No. 4 as a definite clinical entity. The most outstanding findings include growth retardation of prenatal onset, severe mental deficiency, microcephaly and a peculiar constellation of facial dysmorphisms. The dermatoglyphic patterns and the radiological findings may help towards a correct interpretation of the syndrome.


Diurnal variation of prednisolone binding to serum corticosteroid-binding globulin in man.

Serum corticosteroid-binding globulin (CBG, transcortin) binding capacity for prednisolone and for cortisol, and levels of the circulating cortisol were evaluated in healthy adult subjects and in patients under long-term treatment with prednisone. Blood samples were drawn at 4-hr intervals throughout at least 24 hr; the prednisone administration was discontinued 24 hr before starting examination. Circadian fluctuations in the CBG-binding capacity for prednisolone occurred in healthy subjects: maximum binding was at 12 midnight and minimum binding at 8 a.m. The diurnal pattern of prednisolone-binding capacity was characterized by phase shifts of approximately 12 hr and 8 hr compared with those of serum cortisol and cortisol-binding capacity, respectively. There were no diurnal variations of prednisolone- and cortisol-binding capacity in the prednisone-treated patients. Moreover, the levels of both capacities, expressed as micrograms bound steroid/100 ml, were significantly reduced with respect to normal control subjects. Cyclic variations in serum CBG-binding capacity may represent an additional factor accounting for temporal differences in the action of synthetic corticoids which are bound by the transport protein. Synthetic derivatives when chronically administered may interfere not only with the adrenal secretion but also with the serum transport of glucocorticoids.


The frequency of Candida infections in pregnancy and their treatment with clotrimazole.

In an open study, 243 pregnant women were investigated for Candida infection of the vagina. Clinical diagnosis, confirmed by culture, showed that 163 (56%) were infected at some time during pregnancy. Infected patients were treated for 6 days with clotrimazole, I vaginal tablet per day plus cream applied externally. Treatment was considered as well accepted by all, and as successful in 84% of cases in the first trimester, 87% in the second, and 78% in the third trimester. There was no evidence of a relationship between Candida infection of the mother and the incidence of abortion or other disease of the newborn. It is suggested that early treatment of Candida infections of the vagina during pregnancy can greatly reduce the incidence of fungal infections in the newborn. In this series, only 3 of the 200 live births had a post-partum fungal infection: all were delivered by Caesarian section and the infection was not recorded until the third month in hospital.


Dissociation of increased 5-hydroxyindoleacetic acid levels and physical dependence: the effects of naloxone.

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.


An improved radioimmunoassay for serum gentamicin levels using 125I-labelled gentamicin.

1. A radioimmunoassay is described for the measurement of gentamicin in serum or plasma. 2. The assay technique uses a tracer labelled with iodine-125 rather than tritium, and has advantages over previously reported radioimmunoassay methods (Longmore et al., 1976; Lewis, Nelson & Elder, 1972) with regard to rapidity, precision and simplicity of preparation of labelled gentamicin. 3. The iodination technique is simple and gives tracer in high yield, at high specific activity, and with complete immunological identity to unlabelled gentamicin. 4. There is a significant correlation between results obtained by this technique and by a microbial assay method but the radioimmunoassay is more rapid, specific and accurate.


Pulsatile release of luteinizing hormone and the secretion of ovarian steroids in sheep during anestrus.

The peripheral concentration of LH and the secretion rates of estradiol-17beta and androstenedione were measured every 10 min for 4 h during anestrus in six ewes with utero-ovarian autotransplants. The basal concentration of LH was 0.45 +/- 0.06 ng//ml (NIH LH S14; mean +/- SEM), with pulses of LH (6.0 +/- 0.3 ng/ml; N = 5) occurring with an average frequency of one per 5 h. The basal secretion rate of estradiol-17beta was 0.5--1.3 ng/min. Each pulse of LH was followed by a rise in the secretion of estradiol-17beta. Maximum secretion of estradiol-17beta was 5.18 +/- 0.72 ng/min and was reached 25 min after LH discharge. Basal secretion of androstenedione was higher than estradiol-17beta at about 1.5 to 3.4 ng/min, and increased to a maximum 26.8 +/- 6.6 ng/min 25 min after LH discharge. Steroid secretion was not maintained at maximum rates and had returned to basal levels 2 h after LH discharge. The data show that the ovary of the anestrous sheep is capable of secreting steroids following pulses of endogenous LH. These results strongly suggest that as in the luteal phase of the cycle, the quantity of estradiol and androstenedione secreted by the ovary is related to the frequency of episodic pulses of LH.


Enhanced endogenous insulin secretion after treatment with monocomponent insulin.

Eight maturity-onset diabetic patients who had no infections, liver diseases or other endocrine diseases which might affect carbohydrate metabolism were treated with monocomponent lente insulin, which is known to have little antigenicity, until blood sugar was controlled. The diurnal values of the blood sugar (BS) and immunoreactive insulin (IRI) were obtained before treatment and on the third day after the withdrawal of insulin treatment. One patient was dropped from the study because of insulin antibody formation. The total integrated IRI area in the diurnal profile was increased from 98.9 +/- 23.7 to 186.1 +/- 37.7 muU.h/ml (p less than 0.05), while the total blood sugar area was decreased from 7,500 +/- 1,200 to 5,510 +/- 1,214 mg-h% (p less than 0.05). Oral Glucose Tolerance Test on the fourth day after the withdrawal of insulin treatment showed increased IRI response compared to pretreatment. It is concluded that endogenous insulin secretion could be increased in the diabetic patient by the metabolic control with exogenous insulin injections.


The diurnal rhythm of plasma aldosterone and plasma renin activity in patients with congestive heart failure.

Study on a diurnal rhythm of plasma aldosterone (PA) and plasma renin activity (PRA) was performed in 8 patients with congestive heart failure. All patients had been digitalized and received diuretics under mild sodium restriction. An obvious diurnal rhythm of PA similar to the normal subjects, with the lowest value in the evening and the highest value in the morning, was observed in 7 of 8 cases, while a diurnal rhythm of PRA was obscure except in one case. The PA generally did not run parallel with PRA. Although the reason of the absence of PRA diurnal rhythm in congestive heart failure was not clear, it was considered that reninangiotensin system did not play a significant role for the development of PA diurnal rhythm in congestive heart failure. The determined PA values were entirely within normal range except in 2 cases, although they were administered the potent diuretics chronically. A high PA value was observed only in early morning in one case, while all determined PA values were extremely high in another case with severe congestive heart failure involved in cardiac liver cirrhosis. The PRA values were relatively low in 2 cases, normal in 5 and high in one.


Effects of apomorphine combined with chlorpromazine and pimozide on the estrous cycle in rats.

Chlorpromazine (CPZ) a neuroleptic which has both antiadrenergic and antidopaminergic activity when administered in doses of 5 to 25 mg/kg s.c. inhibited ovulation and induced pseudopregnancy. Pimozide which possesses only an antidopaminergic action induced only pseudopregnancy (in doses between 0.05-10 mg/kg s.c.). Apomorphine (APO), a dopaminergic agonist, prevented the pseudopregnant effect of both neuroleptics, especially of CPZ, but failed to counteract the ovulation-blocking action of CPZ. APO itself had an antiovulatory action, but only in large doses (above 5 mg/kg s.c.), and only in a few animals. Our data plead for the importance of dopaminergic mechanisms in the inhibition of prolactin secretion (by means of PIF) and for the stimulatory role of adrenergic transmission in the ovulation process (by means of LRF). These results fail to support the proposed stimulatory role of dopamine on the LRF secretion. On the contrary, they do not exclude the possibility of its inhibitory action.


Derivation of hybrids between a thymoma line and spleen cells activated in a mixed leukocyte reaction.

We have established 16 independent hybrid lines derived from a fusion between an AKR thymoma and mixed leukocyte reaction-stimulated C57BL/6 spleen cells. The hybrids express both parental H-2 alleles and show hybrid glucose-6-phosphate isomerase activity. Two of the lines showed Fc receptor activity not expressed in the parental thymoma. The AKR Thy-1.1 allele was expressed in all hybrid lines, but no Thy-1.2 could be detected. No killing activity was retained in the hybrid cells, probably because Sendai virus-mediated fusion of killer cells resulted in the lysis of the thymoma fusion partner.


Apomorphine-induced locomotion and gnawing: evidence that the experimental design greatly influences gnawing while locomotion remains unchanged.

In a recent study we have shown that it was possible to recognize and record two independent behavioural patterns elicited by apomorphine (s.c.): one behaviour characterized by increased locomotion, sniffing and repetitive head and limb movements and another, characterized by compulsive gnawing. In the present study we have further characterized the gnawing and the locomotion patterns, their dependence on the experimental design and on the test environment. We found that the apomorphine-induced gnawing was easily modified by factors such as the design of the test-box and the habituation of the animal to the test-box. Locomotion, on the other hand was essentially independent of such factors and seemed more compulsive than the so-called "compulsive gnawing".


Baclofen-induced modification of conditioned discriminative avoidance behaviour and contraversive turning in the rat.

The effects of baclofen, a gamma-aminobutyric acid derivative, on conditioned avoidance behaviour and on the turning produced by unilateral 6-OHDA lesions of the s. nigra were investigated in rats. The small impairment of conditioned avoidance behaviour induced by baclofen (1-4 mg/kg i.p.) was potentiated by combination with benztropine, an anticholinergic agent. Moreover, baclofen reversed the suppression of avoidance responses and the inhibition of turning induced by physostigmine, suggesting an interaction of baclofen with cholinergic transmission processes at the nigrostriatal level. After alpha-methyltyrosine, baclofen like haloperidol, produced a marked increase in avoidance response failures suggesting an additional inhibitory effect of the compound on dopaminergic transmission. The pattern of results indicates that baclofen affects the feedback-loop regulation processes in the nigrostriatal area of the brain.


Enkephalin: radioimmunoassay and radioreceptor assay in morphine dependent rats.

A sensitive and specific radioimmunoassay for enkephalins is described which discriminates between leucineenkephalin and methionine-enkephalin. Total opioid peptide activity was assayed by the ability of brain extracts to compete for opiate receptor binding. In rats treated with morphine and/or naloxone, opiates were separated from opioid peptides by Dowex AG-50W column chromatography prior to radioreceptor assay. Chronic administration of morphine failed to alter immunoreactive enkephalin levels or total opioid activity in radioreceptor assays.


Piperoxane reduces the effects of clonidine on aggression in mice and on noradrenaline dependent hypermotility in rats.

Aggression in isolated male mice and hypermotility in rats produced by the noradrenaline releaser H 77/77 were studied after the s.c. administration of the alpha-adrenergic agonist clonidine and the alpha-antagonist piperoxane. Clonidine 0.005--0.5 mg/kg inhibited both behaviours while piperoxane showed a weak and short-lasting antiaggressive effect and no H 77/77 antagonism. Inactive doses of piperoxane reduced the inhibitory effects of clonidine. The results indicate that isolation-induced aggression in mice and H 77/77-induced hypermotility in rats are behavioural signs related to the availability of noradrenaline at the receptor.


Tolerance to cocaine-induced convulsions in the cat.

Two groups of female cats (6 each) were used: (1) a seizure group which received a minimum convulsive dose (MCD) of cocaine i.v., and (2) a subseizure group which received a subconvulsive dose of cocaine i.v., for 13 successive days. Determination of the MCD across 13 days in the seizure group and on Day 14 in the subseizure group revealed significant tolerance to cocaine-induced convulsions. However, reverse tolerance to cocaine-induced abnormal behavior developed as dystonic posture and speed of stereotyped movement increased during the 13-day treatment period in the subseizure group. These data are discussed in terms of local anesthetic and catecholaminergic effects of cocaine, as well as possible differential effects of various routes of administration.


The effect of superior temporal lesions on the recognition of species-specific calls in the squirrel monkey.

Eleven squirrel monkeys (Saimiri sciureus) were trained to discriminate species-specific calls from non-species-specific complex sounds in a go, no-go procedure with social contact as positive reinforcement. The task required that the animals not only responded to a particular call but that this response should be generalized to any squirrel monkey call, whether or not it had been presented previously in training. After having reached a performance level of 75% correct responses in three consecutive sessions, seven animals received bilateral lesions of the auditory cortex; the other four animals served as controls. It was found that small lesions within the superior temporal gyrus did not interfere with the discrimination task. Lesions destroying about three quarters of the auditory cortex led to loss of retention; during retraining the animals did not reach criterion, but performed significantly above chance. These animals were able, however, to master a simplified version of the task where one species-specific call had to be discriminated from one non-species-specific sound. Animals with almost total ablation of the auditory cortex were capable of mastering neither the generalized task nor the simplified version. From these results, together with those of the literature, it is concluded 1) that recognition of complex sounds is not possible after complete auditory cortex ablation, probably because of interference with gestalt-formation processing, and 2) that species-specific calls are processed in the auditory system in the same way as other complex sounds.


Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation.

L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G1) and larger (G2) DNA contents from the dominant S phase peak with intermediate DNA content.


Structure-activity relationships in reactivators of organophosphorus-inhibited acetylcholinesterase. XI - Bisquaternary compounds of beta-(4-pyridyl)acraldoxime.

Several bisquaternary salts of beta-(4-pyridyl)acraldoxime were prepared and tested for their reactivating potency on phosphorylated electric eel cholinesterase. The in vitro testing revealed that the new compounds have little to no effects.


The biochemistry of depression.

The author outlines the hypothesis of the role of amines in depression. Postulating that depression involves a derangement of amine metabolism in which a deficit of amine activity occurs in certain areas of the brain which in turn results in altered transmission, the theory proposes that certain antidepressant drugs effect an elevation of brain amines restoring normal transmission and relieving the depression.


Mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations by various mycotoxins.

Mutagenicity of various mycotoxins and the efficiency of mutagenic mycotoxins in producing DNA single-strand breaks and chromosome aberrations were examined using a mammalian cell line. It was found that aflatoxin-B1, mycophenolic acid, patulin, penicillic acid, and sterigmatocystin induced 8-azaguanine-resistant mutations. Aflatoxin-B1, mycophenolic acid, and sterigmatocystin had little effect on DNA single-strand at high concentrations. In the treatment with patulin and penicillic acid, severe breaks were found at higher concentration than at the concentration where the mutation was induced. Incidence of chromosome aberrations by the treatment with these mycotoxins correlated fairly well with their mutagenic activity. Chaetoglobosin-B, fusarenon-X, (--)luteoskyrin, and ochratoxin-A did not induce 8-azaguanine-resistant mutation.


PSRO: issues in health care policy.

Enactment of the law regarding Professional Standards Review Organizations (PSROs) represents a major shift in health care policy in the United States. PSRO is an experiment in developing a national quality assurance system. It raises issues of quality versus cost control, professional versus public accountability, and confidentiality. These issues must be examined critically by social workers.


Prostaglandins and steroidogenesis by isolated rabbit ovarian follicles.

Prostaglandins of the F and E series at concentrations from 1 to 100 microgram/ml had no effect on steroidogenesis by isolated rabbit follicles. Indomethacin and 7-oxa-13-prostynoic acid at doses lower than 100 microgram/ml failed to prevent the LH-induced increase in testosterone accumulation by follicles. At 1 mg/ml these inhibitors prevented the LH effects. Prostaglandin E2 and F2alpha had no effect on testosterone accumulation. However, prostaglandin E2 seemed to enhance the LH-induced accumulation of androstenedione and progesterone by the follicles. These data suggest that prostaglandins play a minor role in steroidogenesis by isolated rabbit ovarian follicles.


[Blood proteins during short-term fasting and during supply of essential amino acids].

A most significant decrease of prealbumin and retinol-binding protein was observed in the serum during an absolute alimentary abstinence for five days, whereas the immunoglobulins IgG, IgA and IgM were not influenced. The decrease in the concentration of prealbumin and retinol-binding protein was significantly diminished through a minimum diet of 15 g essential aminoacids and 60 g carbohydrates. Both proteins form a complex in a mole ratio of 1:1. Based on the four to five times higher prealbumin concentration, we recommend this parameter for the routine observation of protein metabolism during weight reduction.


[Value of the nitroblue tetrazolium test (NBT) in the clinical diagnosis of bacterial infections].

107 patients and 27 normal individuals underwent the NBT test, as described by PARK et al., in order to ascertain whether it helps to diagnose a bacterial infection. The patients studied consisted of a group with bacterial infections, and a further group suffering from a variety of internal organic diseases of non-bacterial genesis. At the same time, the absolute leucocyte count, the differential blood count, the erythrocyte sedimentation rate, and the leucocyte phosphatase were evaluated. In 84% of the patients with bacterial infections, the values of the NBT test, which are normally between 3 and 14%, were considerably higher, while the value in patients without bacterial infection was only 4% higher than the normal rate. Neither with the leucocyte count, the erythrocyte sedimentation rate, the deviation to the left, nor with the alkaline leucocyte phosphatase was such accuracy obtainable. It is, however, essential that the methodology is closely observed, as even slight changes during the processing can alter the result. The evaluation of the preparations by an experienced analyst is, of course, prerequisite.


[Advances in infusion technics].

Two interesting developments in the area of infusion technology are being presented. The first product concerns a rather simple, but precise, and manually ajustable flow control device for intra-venous fluid administration without the need of having an infusion pump. The second product concerns a continuous flush device for arterial and venous indwelling cannulae. The main area of clinical application of the latter product is the combination with intraarterial catheters which are used to monitor various arterial pressures. Adaptation of the device to intravenous catheters is also possible. The main benefit derived from the flushing device is a significant prolongation of catheter function and patency.


Cladosporium herbarum extract characterized by means of quantitative immunoelectrophoretic methods with special attention to immediate type allergy.

Freeze-dried extract of Cladosporium herbarum Link ex Fr. was obtained by growing, harvesting, extracting, centrifuging, dialysing and freeze-drying. Quantitative immunoelectrophoresis using rabbit antibodies revealed the extraction procedure to be reproducible and the extract to be composed of 57 antigens, none of which originated from the substrate used in the growth. The molecular weight distribution and the approximate molecular weight of some antigens of C. herbarum were obtained using gel filtration. The pI distribution and the approximate pIs of a few distinct antigens of C. herbarum were obtained by isoelectric focusing. Preliminary identification  of 4 allergens from C. herbarum was performed by means of CRIE (crossed radioimmunoelectrophoresis).


Occurrence of specific precipitins against bovine whey proteins in serum from children with gastrointestinal disorders.

Children with cow's milk intolerance, clinically non-confirmed cow's milk intolerance, coeliac disease, non-confirmed malabsorption, other gastrointestinal disorders and normal children were investigated for the presence of precipitins against 40 individual bovine whey proteins by means of the crossed immunoelectrophoresis with intermediate gel technique. In the various groups of children the amount and specificity of bovine whey precipitins were neither connected with the various gastrointestinal disorders nor with alternating diet and challenge with milk. Bovine whey-specific IgE could not be detected in any of the patients clinically suspected for cow's milk intolerance by cutaneous test, RAST or CRIE. The immunoglobulin level of the patients investigated did not differ significantly from the normal ranges. It is concluded that investigations of serum precipitins against bovine whey proteins do not give any significant information concerning cow's milk intolerance.


Experimental hypersensitivity pneumonitis: serum immunoglobulins G1, G2, M, A and E in Micropolysopra faeni sensitized and desensitized calves.

Weekly evaluation of serum antibody activity in IgA, IgM, IgG1 and IgG2 as well as serum IgE levels indicates highly significant reduction in IgE and elevation of IgA in calves experimentally desensitized with Micropolyspora faeni soluble antigen. Serum IgG2, IgG1 and IgM levels were also elevated. Results are discussed in the light of the possible significance of reagin-mediated reactions in initiation of hypersensitivity pneumonitis.


Diurnal changes in the rabbit's visual evoked potential.

Rabbits that have been exposed to the natural cycles of day and night exhibit marked diurnal changes in the shape of their Visual Evoked Potential in constant environmental conditions. The results of exposure to artificial 24 hr light-dark cycles strongly suggest that it is the regular alternation of daylight and darkness which acts as the synchronizing "Zeitgeber" for the V.E.P. rhythm which exists after exposure to the natural cycles of day and night. It would seem further that the V.E.P. changes reflect a square-wave like rhythm in the sensitivity of the visual system to photic stimuli, in which the sensitivity is much higher at night than in the day-time. The probable importance of the diurnal V.E.P. rhythm for the occurrence of daily fluctuations in behaviour is discussed.


Photoperiodic programming of diurnal changes in rabbit visual evoked potentials.

Rabbits which have been exposed for several weeks to the natural cycles of daylight and darkness, or to various fixed 24 hr light-dark alternations, exhibit in constant environmental conditions large diurnal changes in the shape of the Visual Evoked Potential. These changes run a square-wave like time course and seem to reflect a similar diurnal rhythm in the sensitivity of the visual system to photic stimuli. The relation between the durations of the two phases of the rhythm can, within wide limits, be changed by variations in length of the artificial or natural photoperiod. It further appears that after exposure to continuous illumination or darkness rabbits have either a free-running V.E.P. rhythm or no such rhythm at all. The probable importance of the diurnal changes in the visual system for the occurrence of seasonal fluctuations in behaviour is discussed.


Commonly asked clinical questions about methadone maintenance.

Clinical questions about methadone maintenance are posed and answered. The areas include eligibility, size of clinic, number of patients, optimal maintenance dose, special populations, side effects, services, schedules, and the involvement of others.


Circadian rhythms in the concentration of plasma thyroxine in vitamin A-deprived calves.

Over a period of approximately 11 months, a total of 57 24 hour experiments was performed on 5 calves. The animals were fed a vitamin A-free diet and showed the common signs of vitamin A deficiency. During each experiment blood samples were taken hourly and the plasma iodoprotein content of each sample was determined. Each set of 24 values was subjected to Fourier analysis in an attempt to elucidate 24 hour, sinusoidal rhythms in iodoprotein concentration. A rhythm was deemed to be present where the chance of random sampling producing the observed pattern of concentration was less than or equal to 0.05. 25 such rhythms were detected. As the probability of random sampling giving rise to 25 rhythms in 57 tests is extremely small, circadian rhythms are assumed to exist in vitamin A-deficient, as in normal, calves. Rhythms, the characteristics of which are described here, were observed under natural conditions of day and night, and with controlled light and darkness. It is suggested that the occurrence of the rhythms, in relation to the environmental patterns of light and darkness, is better related to other aspects of brain activity than to those concerned with vision.


Final results of Coffey's ureterosigmoidostomy in noncarcinomatous diseases.

The present report on 67 patients, in whom a ureterosigmoidostomy was performed on the ground of a benign indication, is to take a critical attitude towards ureterosigmoidostomy. In about 60 per cent of the cases satisfactory or good results can be achieved. Final comparisons with other methods of derivation cannot be made, since a sufficiently great number of late results is not yet available. In our opinion, it is doubtful if there will ever be an alternative. The operator's judgment and experience will always play an important role. Certainly the results can be improved by a lifelong close observation of the patients.


The influence of urethral position on urinary continence.

Bladder and urethral pressure responses to increasing intraabdominal pressure were studied in anesthetized cats. The results indicate that urethral responses are entirely passive and dependent on the intraabdominal position of the urethra. Urethral resistence to urine flow was not influenced by curare administration or complete sacral rhizotomy but was markedly decreased by phentolamine administration or the application of pressure directly to the bladder.


The strobilurins--new antifungal antibiotics from the basidiomycete Strobilurus tenacellus.

The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi. In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma. The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C16H18O3 for strobilurin A and C17H19C1O4 for strobilurin B.


Preparation of 6-epi-ampicillin and of 6-epi-alpha-hydroxybenzylpenicillin.

The preparation of 6-epi-ampicillin by hydrolysis of 6-epihetacillin is described. During this conversion, the formation of a diketopiperazine was also observed. The best yield was obtained at pH 7.0 and room temperature for 3 approximately 7 hours. The lowest yield of 6-epi-ampicillin and the highest formation of the diketopiperazine occurred in pyridine - acetic acid - water. Treatment of ampicillin (with D-aminophenylacetyl side chain) with nitrous acid gave alpha-hydroxybenzylpenicillin with about 66% of L- and 34% mandelyl side chain. Reaction 6-epi-ampicillin gave 6-epi-alpha-hydroxybenzylpenicillin with practically the same ratio of L- and D-isomers.


Purification and preliminary characterization of an aggregation-sensitive chemoattractant of Dictyostelium minutum.

Aggregative amoebae of Dictyostelium minutum are not attracted by cyclic AMP; they are sensitive to various attracting sources from which yeast extract was chosen to purify the chemoattractant. A small acrasin-like species-specific molecule which contains glycine and C5H5N5 has been purified 30,000-fold. Several characteristics of this chemotactic molecule, which is inactivated by an enzyme that is not species specific, are described.


Chemical structure of the active site of pig heart mitochondrial aspartate aminotransferase labeled with beta-chloro-l-alanine.

Formate-induced inactivation of pig heart mitochondrial aspartate aminotransferase by beta-chloro-L-alanine resulted in the modification of the epsilon-amino group of the lysyl residue which is involved in the formation of an aldimine bond with 4-formyl group of the coenzyme, pyridoxal 5'-phosphate. The tryptic peptide isolated from the labeled site of the enzyme was composed of 25 residues and exhibited positive circular dichroism at 325 and 254 nm where the pyridoxyl chromophore of the labeled site peptide absorbs, while the phosphopyridoxyl peptide isolated from the boro-hydride-reduced enzyme did not show any ellipticity in this spectral region. Its comparison with the analogous tryptic peptide from the labeled site of the cytosolic isoenzyme revealed a high degree of homology in their primary structures as well as in spectral properties. Structural analysis of the labeled site peptide and mechanistic consideration of the labeling process indicated that with both isoenzymes the phosphopyridoxyl group is covalently bound to the alpha amino group of the alanyl moiety derived from beta-chloro-L-alanine, the beta carbon of which is covalently linked to the epsilon-amino group of the lysyl residue.


Defective glycoproteins in the plasma membrane of an aggregation minus mutant of Dictyostelium discoideum uith abnormal cellular interactions.

Experiments involving the co-incubation of wild type (A3) cells of Dictyostelium discoideum and a spontaneous aggregation-minus mutant (HW 2) suggested that the mutant was defective in cellular interactions. The inhibition of A3 development by HW 2 cells and the differentiation of a small fraction of HW 2 cells which is allowed by A3 cells, both depend on cell contact. Therefore, we compared cell surface molecules in vegetative A3 and HW 2 cells by a variety of techniques to determine whether defects in HW 2 could be found prior to the inhibition of development in vegetative amoebae. Antigenic defects, or differences in binding of concanavalin A, or both, were localized to three plasma membrane macromolecules using glutaraldehyde-fixed sodium dodecyl sulfate gels of plasma membranes. Two periodic acid-Schiff-positive glycoproteins, and one glycolipid also differed in HW 2. Three glycoproteins had an increased sensitivity to pronase in isolated plasma membranes suggesting an alteration in their topography. Glycoprotein E, the major glycoprotein of vegetative plasma membranes is abnormal in topography, altered as a concanavalin A receptor, and is antigenically abnormal.


Purification of interferon from mouse Ehrlich ascites tumor cells.

Interferon production was induced in mouse Ehrlich ascites tumor cells by infection with Newcastle disease virus. The interferon produced was purified by precipitation with ammonium sulfate, chromatography on carboxymethyl-Sephadex, treatment with blue dextran and polyethylene glycol, gel filtration on Bio-Gel P-60 and Bio-Gel P-200, chromatography on phosphocellulose, isoelectric focusing, and chromatography on octyl-Sepharose. The specific activity of the product was 1.6 x 10(9) NIH mouse interferon reference standard units/mg of protein. Electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulfate indicated that the apparent molecular weight of the interferon-active material ranged from 25,000 to 35,000. As revealed by staining the gels with Coomassie brilliant blue, the interferon activity co-migrated with the major, broad protein band. Minor, stainable bands of proteins were free of interferon activity and their apparent molecular weight was smaller than 12,000.


Newly synthesized acetylcholine receptors are located in the Golgi apparatus.

Chick skeletal muscle cells in tissue culture were fixed and treated with saponin to allow [125I]alpha-bungarotoxin access into the cells while preserving ultrastructure. The kinetics of binding of iodinated alpha-bungarotoxin to intracellular acetylcholine (ACh) receptors and to surface A Ch receptors were comparable. About half of the intracellular ACh receptors are newly synthesized and in the pathway leading to incorporation into the plasma membrane. Correlated electron microscope autoradiographic and kinetic studies of this receptor population suggest that a substantial fraction of the newly synthesized ACh receptors are located in the Golgi apparatus, where they reside for approx. 2 h.


Sythesis of tropomyosin in cultures of differentiating muscle cells.

The accumulation of tropomyosin in cultures of differentiating muscle cells was quantitatively measured. Tropomyosin was isolated from cultured cells during and after myoblast fusion; both alpha- and beta-subunits were present in myotube cultures. During fusion small amounts of tropomyosin were detectable, but, as fusion approached a maximum, tropomyosin accumulation began to increase. The increased synthesis of tropomyosin after the initiation of muscle cell fusion is consistent with the increased synthesis of other proteins characteristic of muscle, including myosin.


The mechanism of killing of mouse fibroblasts by the amino acid analogue 5-fluorotryptophan.

The mechanism of killing of A9 fibroblasts by 5-fluorotryptophan has been studied. L-tryptophan competitively relieves the growth inhibition caused by 5FT. After incubation with 5FT, 3H-5FT was incorporated into protein, replacing tryptophan residues. During the initial hours of incubation with 5FT, a specific inhibition was observed of the incorporation of L-tryptophan into protein; later this inhibition was followed by a general inhibition of protein synthesis and cell division. However, nuclear division continued after cell division had ceased. While 5FT was observed to be incorporated into protein after a 1 hour period in MEM + 0.40 mM 5FT in A9, no 3H-5FT was incorporated into protein in a mutant isolated by its resistance to killingy by 5FT. These results support the hypothesis that cell death occurs due to malfunctioning proteins which contain 5FT residues.


Expression of nervous system antigen-3 by lines of mouse fibroblasts and kidney cells and continued expression in hybrid cells.

In a survey of the expression on cultured mouse cells of the cell surface antigen known as nervous system antigen-3 (NS-3), it was found that RAG, a renal adenocarcinoma line, expressed that antigen. It was also observed that 3T3, a fibroblast line of unknown tissue origin, expressed NS-3. Cells of these two lines were hybridized with cells of two mouse L cell lines that did not express NS-3. Four hybrid clones were tested for both the 3T3 X L cell cross and the RAG X L cell cross, and all the hybrids were found to be NS-3 positive. All the hybrids had at least 40% as much activity as the NS-3 positive parent. Of the four parental mouse cell lines used, only 3T3 expressed Thy-1.2 antigen on the cell surface. In contrast to the continued expression of NS-3 on hybrid cells, Thy-1.2 antigen was not detectable on two clones of 3T3 X L cell hybrids that were tested.


The regulation by fibroblast growth factor of early transport changes in quiescent 3T3 cells.

This study involves the use of fibroblast growth factor (FGF) as a substitute for exogenous serum to examine the early transport changes which occur when quiescent 3T3 cells re-initiate active growth. FGF, in nanogram amounts, together with insulin and dexamethasone, can induce mitogenesis and mitosis in 3T3 cells GO-arrested by holding in growth medium containing 0.8% calf serum. In terms of quiescent cell transport activity enhancement, FGF is 300,000-fold more effective than fresh serum, on a protein basis. In addition, very short exposure of serum-depleted cells to FGF indicates that a distinct temporal or time sequence exists in the transport system activation process. For example, uptake of alpha-aminoisobutyric acid (AIB) and uridine are stimulated very rapidly, whereas hypoxanthine uptake does not respond until much later. Closer analysis shows that AIB uptake is maximally enhanced within zero to two minutes after FGF addition to cells. Finally, the stimulatory effect of FGF on transport system activities is specific in terms of the proliferative state of the cells to which it is added, and in terms of the uptake systems which respond to it.


Reversible inhibition of the hydrocortisone induction of glycerol phosphate dehydrogenase by cytochalasin B in rat glial C6 cells.

The hydrocortisone (HC) induction of glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) in rat glial C6 cells was inhibited reversibly and in a dose-dependent manner by cytochalasin B (CB). CB had no effect on basal level GPDH, total cellular RNA, DNA or protein content nor did it act as a general inhibitor of the rate of protein synthesis. CB did not appear to be acting via dissociation of microtubules since colcemid had no effect on the induction process. The addition of an alternate energy source (sodium pyruvate) did not relieve the CB inhibition of GPDH induction suggesting that CB is not exerting its effect by blocking glucose utilization. The inhibition by CB is not dependent on the temporal sequence of the induction process since it specifically inhibited GPDH induction at any time it was added. CB did not alter the rate of degradation of GPDH in these cells and direct measurements of the specific rate of synthesis of GPDH demonstrated that CB decreased the induced rate of GPDH synthesis by about 60%. The site of inhibition was more precisely defined  by experiments which demonstrated a 60% decrease in specific nuclear binding of 3H-HC even though total cellular uptake of 3H-HC was unaffected. This effect on nuclear binding of HC is sufficient to account for the decreased accumulation of GPDH activity in CB-treated cells.


Assessment of incompetence in canine aortic and pulmonary valve grafts and comparison of some methods of valve preservation.

A new method has been devised to assess the competence of the canine aortic valves, before implantation. This method would provide a better selection of aortic valves before their insertion and may reduce the incidence of postoperative incompetency. Comparison of canine pulmonary and aortic valve function, at various pressures, revealed that the pulmonary valves were regurgitant at higher pressures, in comparison to aortic valves. Formalin preserved valves were found to be significantly regurgitant.


Polyamine metabolism in enucleated mouse L-cells.

The distribution of polyamines between the nucleus and the cytoplasm, and the role of the nucleus in polyamine metabolism, have been studied using cells enucleated with cytochalasin B. Spermidine and spermine were found in the nuclear and the cytoplasmic fractions of L929 cells; their concentration was 3-fold higher in the former fraction. Ornithine decarboxylase activity was only found in the cytoplasm, and this activity could be stimulated in enucleated cells by the addition of fresh medium. These cells synthesized putrescine actively, but the putrescine made was not converted to spermidine, and accumulated to relatively high concentrations. Similarly, methionine did not act as a precursor to spermidine in enucleated cells, in contrast to whole cells, although it was incorporated into cell protein. Spermidine synthesis, unlike putrescine synthesis, appears to be completely dependent on a nuclear component.


On the mechanism of the Crabtree effect in mouse ascites tumor cells.

The addition of glucose to ELD and ELT/B1 mouse ascites tumor cell suspensions caused a 2.3-fold increase in the phosphorylation state ratio, (ATP)/(ADP) (Pi), because of a decrease in the intracellular Pi concentration. The addition of glucose to these cell suspensions has been reported by Chance and Hess ('59) to cause an increase in the study state reduction of cytochrome b and an increase in the steady state oxidation of cytochrome c. On a quantitative basis these two independent measurements suggest that a near equilibrium exists between the oxidation-reduction state of the mitochondrial electron carriers and the reactions of ATP synthesis (as expressed by the phosphorylation state ratio) both before and after glucose addition. We conclude that the mechanism of the inhibition of respiration by glycolysis (the Crabtree effect) is a decrease in the rate of electron transport caused by the mass action effect of the elevated phosphorylation state ratio.


Growth stimulating activity in bovine pituitary extract specific for a rat mammary carcinoma cell line.

We report the isolation of a bovine pituitary growth factor (MGF) for a rat mammary carcinoma cell line, 64-24, which was isolated from a highly hormone-dependent mammary tumor. The MGF has been partially purified by a series of Diaflo ultrafiltration membrane sievings, isoelectric focusing and Sephadex columns. The MGF has a molecular weight of approximately 1,000 to 2,000 daltons and has a U.V. absorption spectrum typical for a polypeptide. Its isoelectric point is approximately pH 3.8-4.0. The factor is heat stable. The growth stimulating activity of the MGF does not stimulate other rat cell lines (22-1, RMG or HTC lines) but is specific for the 64-24 mammary tumor cell line. The MGF is not among previously reported pituitary hormones or growth factors.


ATP, trehalose, glucose and ammonium ion localization in the two cell types of Dictyostelium discoideum.

Ultra-microfluorometric techniques were adapted to follow several compounds related to energy metabolism through the developmental cycle of Dictyostelium discoideum. Each compound (ATP, trehalose, glucose, and ammonium ion) was found to be present in stalk and/or spore cells. The accumulation of NH4+ was interpreted as an indication of protein degradation, a source of energy in this organism. During the early stages of differentiation NH4+ was localized only in prestalk cells. However, it accumulated in spore cells during culmination such that levels were comparable in the two cell types by the end of development. Trehalose, an energy source for germinating spores, was found in both cell types but was preferentially degraded in stalk cells late in development. Glucose, the degradation product of trehalose, was localized in prestalk cells and varied inversely with trehalose levels. ATP was not localized in a specific cell type during development. However, ATP declined in stalk cells at an earlier stage of development.


Continuous DNA replication in the nucleus of the dinoflagellate Prorocentrum micans (Ehrenberg).

The uptake of tritiated thymine into cells of a heterogeneous population of Prorocentrum micans was investigated using light-microscope and electron-microscope autoradiography. Specificity of thymine uptake into DNA was demonstrated by the specific removal of label from wax-embedded material using DNase and by the high degree of localization of nuclear label to chromosomes in the electron-microscope autoradiographs. All nuclei, including both dividing and non-dividing cells, showed a substantial uptake of label, indicating that nuclear DNA synthesis in Prorocentrum micans is a continuous process. The level of DNA synthesis does show considerable variation, however, with very high levels in some interphase nuclei. The continuous replication of nuclear DNA provides further evidence of dinoflagellate affinity to the prokaryotes, and indicates that Prorocentrum micans is a very primitive eukaryote cell.


Feulgen microdensitometry and analysis of S-phase cells in cervical tumour biopsies.

Tissue specimens from the cervical tumours of 70 patients undergoing radiotherapy were examined by Feulgen microdensitometry. Twenty-five of the 70 specimens were also subjected to in-vitro tritiated thymidine autoradiography to determine the proportion of DNA synthesising cells they contained. A spectrum of frequency distributions of nuclear DNA content was obtained from Feulgen microdensitometry, but by inspecting the data the basic DNA content of malignant cells could be established in most cases. Fifty-nine per cent of the tumours were 'diploid', 10% 'tetraploid', 13% 'diploid to tetraploid', and the remaining 18% 'aneuploid'. Grafical analysis of DNA frequencies from 48 'diploid' or 'tetraploid' tumours enabled the proportion of DNA synthesising (S) cells to be estimated by frequency distribution analysis. Estimates of the S component ranged from nil to 30%, were log normally distributed, and comparable to direct measurements of cells in S determined by autoradiography for 25 cases (range 1.2-28.7%). For all paired data the mean difference was 1.2 +/- 1.45% (confidence limits), suggesting that overall Feulgen microdensitometry analysis may be an equally valid technique in providing cellular kinetic information with human tumour material.