Central action of narcotic analgesics. Part III. The role of endogenous noradrenaline in hyperactivity induced by morphine or fentanyl in mice.

Hyperactivity produced in mice with morphine or fentanyl, and methylamphetamine was antagonized by naloxone. The depression of locomotor activity induced by codeine was practically unchanged by the opiate antagonist. L-DOPA did not restore the stimulatory action of morphine and fentanyl in reserpinized mice. The hyperactivity produced by morphine and fentanyl was abolished in mice treated with alpha-methyl-p-tyrosine, but this was restored by L-DOPA administration. Agents inhibiting the central noradrenaline receptors, phentolamine, phenoxybenzamine, and aceperone, prevented or even reversed the locomotor stimulatory action of morphine and fentanyl. Pimozide did not affect the increase of locomotor activity produced by morphine, but depressed that induced by fentanyl. Haloperidol, used in a dose which did not affect the locomotor activity of mice, completely blocked or even reversed the stimulatory action of morphine and fentanyl, and potentiated the depression of locomotor activity produced by pentazocine and codeine. Diethyldithiocarbamate significantly depressed, but did not inhibit completely the stimulatory action of morphine and fetanyl. The stimulatory action of methylamphetamine was also significantly depressed. It seems that the stimulatory effect of morphine and fentanyl depends on the release of endogenous noradrenaline.


[Daily variations in the secretion of several hormones in obesity].

The 24-hour variations in the corticotropine, cortizol, thyrotropin, thyroxin, renin, aldosterone, and somatotropin secretion were studied in patients with obesity with the excess of body weight of 51--133% (84.7 + 7.8%) and in healthy persons of normal weight. Obesity proved to be accompanied by marked disturbances of the 24-hour variations of corticotropine, cortizol, thyrotropin, thyroxin, renin, and aldosterone. Unequally marked shifts in 24-hour variations in the secretion of various hormones indicated different changes in the corresponding structures of the hypothalamus during the obesity development. Changes in 24-hour variations in corticotropine and cortizol secretion were in the same direction in alimentary-constitutional and hypothalamic obesity.


[Lipid-cellular (lipoid-cellular) tumors of the ovaries].

In accordance with in International Histological Classification of the ovaries lipidocellular (lipoidocellular) tumours are referred to a separate group. Analysis of literature data and the author's observations demonstrated that neoplasms differing by histogenesis of newgrowth formation were placed in this group. Evidence in favour of revision of this point of the classification is presented, and suitable recommendations are given.


Evaluation of plasma neurotoxin concentration in uraemic polyneuropathic patients.

Purification of b4-2 sub-peak obtained on DEAE Sephadex A25 chromatography gave us the possibility of quantifying the plasma concentration of the neurotoxin present in uraemic patients with active polyneuropathy. From the purified neurotoxin isolated by kieselguhr and cellulose chromatography we calibrated analytic columns for b4-2 analysis. Plasma concentration, measured in 6 uraemic neuropathic patients, is between 13 and 19 mg/litre. In 52 uraemic patients without neuropathy, the plasma concentration is between 3 and 9 mg/litre. In 20 healthy subjects the plasma concentration is less than 1 mg/litre. The weekly neurotoxin removal in uraemic patients without neuropathy, treated  by a five hours RP6 session 3 times a week, is of the same order of magnitude as the weekly urinary excretion in healthy subjects. Preliminary results of a tentative identification of this purified product indicate that it is not a polypeptide but an acid-polyol with carbohydrate structure.


Human polyoma virus (HPV)--a significant pathogen in renal transplantation.

Routine cytological screening of Papanicolaou-stained smears of the urinary sediment from 57 renal allografts in 51 patients has resulted in the detection of seven cases of Human Polyoma Virus (HPV) BK infection--14% of the total number. Infection was confirmed by virus isolation and electron microscopy (EM). The cytological, histological and ultra-structural data are described and related to the clinical progress of the patient. Four out of the seven cases are discussed in more detail as histological material was available; in three of these, there was evidence of stenosis of the transplant ureter with virus infected cells in the ureteric epithelium and in one case also in the renal tubules. Administration of high dose steroids may provoke active infection with HPV in ureteric epithelium damaged by ischaemia and inflammation. The similarity between the clinical features of an HPV infection and a rejection episode make it imperative to confirm the diagnosis quickly and accurately. Cytological examination of the urinary deposit by light microscopy is a simple, inexpensive procedure which provides positive diagnosis of the typical virus inclusions within an hour of receiving the urine specimen in the laboratory. This can be confirmed by removing single cells from the original cytological slide preparation and processing them for EM using a technique described by Coleman et al [1].


[Indirect lymphography of the thyroid gland. 2].

Indirect lymphography of the thyroid gland was performed in 144 patients. A conclusion was drawn that the use of superfluid oil contrast preparations of lipidol, miodyl type etc. in indirect lymphography of the thyroid gland will permit to obtain the exhaustive information on the state of the endocrine organ and regional lymph nodes. Lymphography with the aid of oil contrast preparation iodolipol diluted with ether and heated to the body temperature is less informative; water-soluble contrast agents were less effective. All the test contrast agents proved to be ineffective for detection of changes in the lymph nodes. Use of iodolipol for lymphography of the thyroid gland without preliminary mixture with ether is not recommended.


Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)]adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simplex virus (HSV), whereas the more active inhibitor of the deaminase, 2'-deoxycoformycin, does not. At 10 micron EHNA, which does not affect viability, growth, or DNA synthesis of uninfected HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 60%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 micron) does not inhibit HSV replication whereas in combination with 10 micron EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% whereas protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in two different ways, depending on whether it is used alone or in the presence of cordycepin.


Exposure of DNA bases induced by the interaction of DNA and calf thymus DNA helix-destabilizing protein.

The reaction of chloroacetaldehyde with adenine bases in DNA to give a fluorescent product was used to study the availability to intermolecular reaction of positions 1 and 6 of adenine in DNA complexes with calf thymus DNA helix-destabilizing protein. No inhibition of this reaction was observed when heat-denatured DNA was complexed with the protein at a protein/DNA weight ratio of 10:1, compared to free DNA. On the contrary, the same reaction was inhibited markedly for denatured DNA in the presence of calf thymus histone HI at protein/DNA weight ratio of 2:1. Furthermore, the exchange rate for hydrogens of amino and imide groups of DNA bases in DNA strands with deuterium in the solvent was totally unaffected upon complexing of DNA with the DNA helix-destabilizing protein as examined by stopped-flow ultraviolet spectroscopy. These results indicate that the DNA helix-destabilizing protein forms a complex with single-stranded DNA, leaving DNA bases uncovered by the protein. The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein. The possibility of "unstacking" of DNA bases induced by the protein is discussed.


Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein.

The gene order of the ml Moloney sarcoma virus (mlMSV) specific pP60gag (P60) was determined by direct chemical analysis of the polyprotein. P60 was cleaved with cyanogen bromide (CNBr) into eight partial and complete fragments ranging in mass from 10,000 daltons to 58,000 daltons. Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30. The polarity of p15 and p12 in a CNBr fragment of P60 was determined by carboxypeptidase A digestion; likewise the CNBr fragments of p30 were ordered by aminopeptidase digestion. The linear arrangement of P60 CNBr fragments gave the gene order of NH2-p15-p12-p30-COOH. The m3 isolate of MSV expresses a P70 gag polyprotein. Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30. However, the presence of peptides unique to the 10,500-dalton COOH-terminal fragment of m1MSV p30 and not present in the p30 of either m3MSV or Moloney leukemia virus suggested that the gag gene deletion in the m1 isolate begins in the p30 reading frame.


Sequence of a RNA templated by the 3'-OH RNA terminus of defective interfering particles of vesicular stomatitis virus.

We have sequenced the endogenous RNA polymerase product produced by disrupted purified virions of vesicular stomatitis virus defective interfering particles by using the newer one-dimensional rapid gel sequencing techniques and confirming this with a modified two-dimensional gel vectoring technique. The sequence of this 46-nucleotide RNA is: 5'(pp)pACGAAGACCACAAAACCA-GAUAAAAAAUAAAAACCACAAGAGGG(U)COH3'. We infer that this sequence is identical to the sequence at the 5' end of infectious vesicular stomatitis virus RNA and is complementary to the sequence of the 3'-OH terminus of this defective interfering particle genome RNA.


Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia.

When isolated rat pars intermedia cells were incubated for 10 min with radioactive amino acids, one major labeled protein with a molecular weight of 30,000 +/- 1500 was extracted. This protein was shown to contain in its sequence the antigenic determinants for corticotropin and beta-melanotropin by immunoprecipitation. When the radioactivity incorporated into this large molecular weight protein during the first 10 min was chased by a further incubation in presence of an excess of unlabeled amino acid, the initial protein was degraded into several smaller peptides including beta-endorphin and beta-lipotropin. Another 18,000-dalton peptide was also observed and was tentatively identified as a large molecular form of corticotropin. From the kinetics of the maturation of the initial precursor, it is concluded that the initial cleavage of the 30,000-dalton peptide gives rise to beta-lipotropin and the 18,000-dalton form of corticotropin. beta-Lipotropin is subsequently cleaved to form beta-endorphin.


Polyoma virus giant RNAs contain tandem repeats of the nucleotide sequence of the entire viral genome.

The bulk of late virus-specific RNA synthesized in polyoma virus-infected mouse cells is larger than a single strand of poloma DNA. The arrangement of viral nucleotide sequences in these giant polyoma RNAs was studied by electron microscopy of hybrids between purified high molecular weight viral RNA and the HindII-1 fragment of polyoma DNA, which contains 91% of the viral genome. Hybrid molecules containing a short single-stranded gap (corresponding to the 9% of viral sequences not present in HindII-1), flanked by double-stranded regions, were photographed and measured. The majority of hybrid molecules contained no single-stranded loops or branches, showing that all viral sequences are transcribed contiguously and that no nonviral sequences are present in the RNA. Hybrid molecules, containing RNA up to 3.5 times the genome length, had a repeating structure of single-stranded gaps 8% of genome length interspersed with double-stranded regions 89% of genome length, showing that giant polyoma RNAs contain tandem repeats of the nucleotide sequence of the entire viral DNA. A small proportion of hybrid molecules contained single-stranded branches or deletion loops in characteristic positions, indicating that RNA "splicing" may occur on high molecular weight nuclear polyoma RNA.


Gonadal luteinizing hormone receptors and adenylate cyclase: transfer of functional ovarian luteinizing hormone receptors to adrenal fasciculata cells.

Luteinized rat ovaries contain a high concentration of particulate luteinizing hormone (lutropin, LH) receptors and a small quantity of lipid-associated receptors that float in the 360,000 X g supernatant fraction of ovarian homogenates. During fractionation of Lubrol-solubilized LH receptors and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] from the ovary and testis, LH receptors and adenylate cyclase were coincident on gel filtration, but could be resolved during ion-exchange chromatography of soluble ovarian preparations and were completely separated by lectin-affinity chromatography on Sepharose-concanavalin A. For further analysis of receptor-adenylate cyclase coupling, the lipid-rich fraction of ovarian luteal cells was used to transfer gonadal LH receptors to isolated adrenal fasciculata cells. The lipid vesicles obtained from ovarian homogenates by flotation at 360,000 X g contained 5--10% of the ovarian LH receptors and were devoid of adenylate cyclase activity. During incubation of lipid-associated receptors with dispersed rat fasciculata cells at 16 degrees C, progressive incorporation of LH binding sites into the adrenal cells was observed. When adrenal cells bearing heterotopic LH receptors were incubated with 1 nM human choriogonadotropin, cyclic AMP production was consistently stimulated, with an accompanying increase in corticosterone production. These results indicate that LH receptors exist as separate entities from adenylate cyclase in the gonadal cell membrane and can become functionally coupled to adenylate cyclase to evoke cyclic AMP production and steroidogenesis in the host adrenal cells to which they are transferred.


Enzymatic conversion of 5'-phosphate-terminated RNA to 5'-di- and triphosphate-terminated RNA.

We have isolated from vaccinia virus cores an enzyme, 5'-phosphate-polyribonucleotide kinase, that in the presence of ATP and Mg2+ catalyzes the conversion of 5'-phosphate and 5'-diphosphate termini of RNA to the 5'-triphosphate species. With the exception of dATP, other nucleoside triphosphates were inactive as phosphate donors; activity with dATP was 10% of that observed with ATP. The purified enzyme did not phosphorylate 5'-hydroxyl- or 5'-monophosphate-terminated polydeoxyribonucleotides, although a variety of 5'- monophosphate-terminated RNA chains were active as phosphate acceptors. By using a coupled system of 5'-phosphate-polyribonucleotide kinase and guanylyltransferase in the presence of ATP, GTP, Mg2+, and S-adenosylmethionine, capping of 5'-P-, 5'-PP-, and 5'-PPP-RNA was demonstrated; in the absence of 5'-phosphate-polyribonucleotide kinase only 5'-PPP-RNA was capped by guanylyltransferase.


Interferoids: in vitro and in vivo conversion of native interferons to lower molecular weight forms.

Mouse interferons appear as two distinct molecular forms, one migrating at 38,000 daltons in sodium dodecyl sulfate/polyacrylamide gels and one migrating at 22,000 daltons; these interferons comprise about 80% and 20% of total activities, respectively. When such interferon preparations are briefly exposed to acidic periodate buffer, the larger interferon species is apparently converted to the smaller form since the activity at 38,000 daltons is completely eliminated while the activity at 22,000 daltons increases significantly; upon further oxidative cleavage, antiviral activity becomes detectable migrating at 15,000 daltons. Because no native mouse interferon has been reported as such small molecules, this antiviral activity is designated mouse "interferoid" to distinguish it from the native, naturally occurring interferon forms. Prolonged acidperiodate treatment fails to quantitatively convert the 22,000-dalton interferon to the 15,000-dalton interferoid since both are inactivated. When L cells are induced to make interferon in the presence of glycosylation inhibitors, either D-glucosamine or 2-deoxy-D-glucose, they produce approximately normal levels of antiviral activity. However, when such preparations are analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, little activity (<10%) migrates as either the 38,000-dalton or 22,000-dalton native interferons. The interferons and interferoid are antigenically and hydrophobically indistinguishable. These data suggest that induced mouse cells normally synthesize the interferoid as a precursor polypeptide that is either partially or extensively modified by carbohydrate additions to produce, respectively, the 22,000- and 38,000-dalton mouse interferons. Because interferoid is apparently fully biologically active without these moieties, chemical synthesis of such unmodified polypeptides or active fragments from them appears feasible.


A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA.

Protein synthesis initiation factors prepared from rabbit reticulocyte and mouse ascites ribosomes were tested for the ability to crosslink to the 5' cap of mRNA. Crosslinking of one polypeptide of apparent molecular weight 24,000 was inhibited by the cap analogs, m7GMP and m7GDP, indicating a specific interaction with the cap. Although specific crosslinking of the 24,000 molecular weight polypeptide was found with eukaryotic initiation factor 3 and to a lesser extent with initiation factor 4B, both of these factors contained less than stoichiometric amounts of this polypeptide. The crosslinking method provides a highly sensitive and specific assay for cap-binding proteins and should facilitate their purification for functional studies.


O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.

Virion RNA of poliovirus type 1 has been analyzed for the linkage between genome-protein VPg and the polyribonucleotide chain. Hydrolysis of the linkage with acid or alkali and enzymatic degradation lead to the conclusion that the bond is neither a phosphodiester such as nucleotidyl-(P-O)-serine (or threonine) nor a phosphoramidate such as nucleotidyl-(P-N)-amino acid. VPg-RNA can be iodinated by the Bolton and Hunter reagent [iodinated 3-(4-hydroxyphenyl)propionic acid N-hydroxysuccinimide ester] but not by the chloramine-T or lactoperoxidase procedures, an observation suggesting that VPg does not contain accessible tyrosine. However, VPg can be labeled with [3H]tyrosine in vivo. Hydrolysis of VPg-[32P]pUp with 5.6 M HCl at 110 degrees yielded 32P-labeled O4-(3'-phospho-5'-uridylyl)tyrosine that could be cleaved with micrococcal nuclease to O4-[32P]phosphotyrosine and uridine 3'-[32P]phosphate. These data establish that VPg is linked to the poliovirus genome by a bond between the O4 of tyrosine and the 5'-P atom of the terminal uridylic acid residue. The 5' end of polio genome RNA can now be described as VPg(Tyr-O)-pU-U-A-A-A-A-C-A-G.


DNA supercoiling by Xenopus laevis oocyte extracts: requirement for a nuclear factor.

A purified system is described for the introduction of negative supercoils into simian virus 40 DNA. The system consists of histones H2A, H2B, H3, and H4, DNA-relaxing enzyme, and a purified factor from Xenopus laevis stage 6 oocyte nuclei. The nuclei are prepared en masse by the technique of F. Scalenghe, M. Buscaglia, C. Steinheil, and M. Crippa [(1978) Chromosoma 60, 299-308]. The supercoiled simian virus 40 DNA prepared by this method is indistinguishable from simian virus 40 supercoiled DNA prepared from infected monkey cells.


Electron spin resonance studies on interaction of complement proteins with erythrocyte membranes.

Sheep erythrocytes have been spin labeled with 5-, 12-, and 16-nitroxystearic acid in order to investigate complement-induced changes in the physical state of the lipid bilayer. Formation of osmotic lesions in the membrane causes an increase in the fluidity of the membrane which overcomes the decrease in membrane fluidity caused by the interaction of the complement proteins. A decrease in membrane fluidity is observed only when complement-lysed membranes are resealed or when complement proteins react with isosmolar ghosts that do not undergo osmotic lysis. The decrease in bulk fluidity of the membrane is first observed when C8 binds to the membranes bearing C5b67 and is enhanced upon the subsequent binding of C9. The decrease in membrane fluidity shown by the electron spin resonance spectra of spin-labeled fatty acids suggests that certain of the complement proteins penetrate the membrane and interact with hydrophobic regions of the lipid bilayer.


Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: fibronectin and procollagen.

Antibodies to fibronectin and to distinct types of procollagens and collagens were used in immunofluorescent staining to localize these proteins in cell cultures. Normal human skin or lung fibroblasts produced a fibrillar pericellular matrix in which fibronectin and procollagen (types I and III) showed extensive codistribution. Fibronectin and procollagen were synthesized by the same cells as judged by double-stain immunofluorescence. Pericellular procollagen was specifically digested with collagenase without an effect on the fibrillar distribution of matrix fibronectin. Brief treatment with trypsin removed both matrix proteins. The human tumor cell lines HT-1080 (fibrosarcoma) and RD (rhabdomyosarcoma) produced little or no matrix fibronectin or procollagen. At sites of cell contact, simian virus 40-transformed lung fibroblasts (VA13) produced small amounts of pericellular fibrillar matrix fibronectin that codistributed with procollagen type I. Intracellular fibronectin and procollagen were visualized in all of these human sarcoma cell lines. When chicken embryo fibroblasts infected with a T class mutant (NY68) of Rous sarcoma virus temperature-sensitive for transformation were maintained at the nonpermissive temperature (41 degrees ) the cells had normal phenotype and a fibrillar matrix containing fibronectin and procollagen was present. At the permissive temperature (35 degrees ), the cells showed transformed phenotype and the matrix was lost. The failure to produce a pericellular fibronectin/collagen matrix may account for several phenotypic characteristics of transformed cultured fibroblasts.


Lack of correlation between tumorigenicity and level of plasminogen activator in fibroblasts transformed by Rous sarcoma virus.

We have previously isolated, from agar suspension culture, clones of chicken embryo fibroblasts transformed by B77 and Prague strains of Rous sarcoma virus (RSV) that varied in the expression of plasminogen activator activity [Wolf, B. A. & Goldberg, A. (1976) Proc. Natl. Acad. Sci. USA 73, 3613-3617]. All of the clones exhibited an altered cellular morphology, an increased rate of sugar transport, and a high efficiency of colony formation in agar suspension regardless of the level of plasminogen activator. Because B77 and Prague strains of RSV replicate as well as cause sarcomas in chickens, the tumorigenicity of the transformed cells could not be evaluated with clones of these cells. In order to determine the oncogenicity of clones with various levels of plasminogen activator, it was necessary to isolate cells transformed by the replication-defective Bryan strain of RSV, which release noninfectious virus. All of the agar suspension clones of transformed cells, derived by infection of chicken embryo cells with replication-defective Bryan RSV, fell within the continuum observed for B77- and Prague-transformed clones with respect to altered morphology, increased rate of sugar transport, efficiency of colony formation in agar suspension, and variations in plasminogen activator activity. All of the clones, regardless of the level of plasminogen activator, produced tumors when as few as 5 x 10(2) cells were injected into the wing web of 1-day-old chicks. The latency period for tumor formation after injection of cells was similar regardless of the level of plasminogen activator of the injected cell. Primary explants of tumors resulting from inoculation of clones having low, intermediate, or high activator activity displayed a spectrum of activator activity.


Coordinate control of corticotropin, beta-lipotropin, and beta-endorphin release in mouse pituitary cell cultures.

Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D(16v) line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 muM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10(-6) M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (beta-lipotropic hormone-size material) and 3500 (beta-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts.


Expression of simian virus 40 early genes in transformed rat cells is correlated with maintenance of the transformed phenotype.

Early viral polypeptides synthesized in simian virus 40 rat transformants were identified by immunoprecipitation using anti-T (tumor) antigen immune serum. Four polypeptide classes could be identified, which were not detectable in extracts of nontransformed cells and were not precipitated from transformed cell extracts by nonimmune serum. Their apparent M(r) were 92,000, 63,000, 56,000, and 19,000. A similar pattern was observed in extracts from lytically infected cells, but the relative rate of radioactive labeling of the M(r) 63,000 and 56,000 species was in this case significantly lower than in transformed cells. In tsA30 transformants of type A, which maintain the transformed phenotype at high temperature, only minor quantitative variations of this pattern were observed when the cultures were shifted from 33 degrees to 40.5 degrees . In contrast, the rate of labeling of the four virus-specific polypeptides was decreased by 90% or more at high temperature in the temperature-sensitive N transformants. In all cases, a coordinated variation of the radioactivity associated with the different polypeptide classes was observed. These results suggest that the synthesis or processing, or both, of the viral early proteins may be controlled by different mechanisms in various types of simian virus 40 transformants and, furthermore, that it may be under the positive control of a virus-coded protein in transformed cells of type N.


Reversion of transformed glycolysis to normal by inhibition of protein synthesis in rat kidney cells infected with temperature-sensitive mutant of Rous sarcoma virus.

Normal rat kidney cells infected with a temperature-sensitive mutant (LA23) of Rous sarcoma virus exhibit the transformed phenotype when grown at 33 degrees and the normal phenotype at 39 degrees. We have previously shown [Ash, J.F., Vogt, P.K. & Singer, S.J. (1976) Proc. Natl. Acad. Sci. USA 73, 3603-3607] that the addition of protein synthesis inhibitors to LA23-infected cells grown at 33 degrees causes them to revert, over a period of 12 hr, to the normal phenotype with respect to morphological and cytoskeletal characteristics. We now show that reversion of the metabolic characteristics of the transformed phenotype to those of the normal also occurs under these conditions. LA23-infected cells show an increased rate of aerobic glycolysis at 33 degrees compared to that at 39 degrees. They also show a different sensitivity of that rate to dinitrophenol and oligomycin at 33 degrees compared to 39 degrees. Such cells grown at 33 degrees in the presence of cycloheximide or abrin rapidly recover the aerobic glycolysis characteristics of the normal phenotype. These results support the thesis that transformation by the src gene of the Rous sarcoma virus is a pleiotypic and reversible process, such as is involved in a pleiotypic enzymic modification reaction and its reversal.


Receptor-mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibits growth of human fibroblasts.

The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The r-[25-HC oleate]LDL suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis. This suppression did not occur when lysosomal hydrolysis of r-[25-HC oleate]LDL was inhibited by chloroquine. When fibroblasts were incubated with r-[25-HC oleate]LDL in the absence of a source of cholesterol, the cells developed an abnormal morphology, their growth was inhibited, and the cells died. The toxic effects of r-[25-HC oleate]LDL were prevented when the growth medium was supplemented with cholesterol in ethanol or with mevalonate, the product of the reductase reaction. These data suggest that the toxicity of r-[25-HC oleate]LDL was due to its suppression of reductase, which in turn caused cellular cholesterol deficiency. The r-[25-HC oleate]LDL did not suppress reductase activity nor did it alter the growth or morphology of mutant fibroblasts lacking LDL receptors, which were obtained from a patient with homozygous familial hypercholesterolemia. These experiments demonstrate the feasibility of using reconstituted LDL to selectively deliver hydrophobic compounds other than typical cholesteryl esters to cells possessing LDL receptors.


Translocation of a hydrocarbon fluorescent probe between Epstein-Barr virus and lymphoid cells: an assay for early events in viral infection.

Translocation of the hydrocarbon fluorescent probe diphenylhexatriene (DPH) between membranes was studied by fluorescence polarization (P) analysis. First, using a model system, the high P value (0.324) of DPH-labeled cholesterol/phosphatidylcholine liposomes and the low P value (0.157) of DPH-labeled phosphatidylcholine liposomes allowed detection of DPH translocation between interacting liposomes. This was monitored by the change in P in either direction. Early events during cell-virus interactions were similarly studied by monitoring DPH translocation. The P value of DPH-labeled Epstein-Barr Virus (EBV) was significantly higher (0.350-0.392) than the P value of DPH-labeled lymphoid cells (0.238-0.289). Hence, DPH translocation could be detected by changes in P following incubation of DPH-labeled EBV and nonlabeled cells. A marked decrease in P was observed after incubation of DPH-labeled EBV with either nonlabeled lymphoblastoid Raji cells or fresh human B lymphocytes. However, only a slight decrease in P was obtained when DPH-labeled EBV was incubated with either nonlabeled fresh human T lymphocytes or fresh T or B rabbit lymphocytes. Moreover, incubation of fresh human B lymphocytes with the purified C3 component of complement (a putative inhibitor for the EBV receptor) prior to the addition of DPH-labeled EBV abolished the observed decrease in the P value. Most of these experiments were carried out with both the P3HR-1 and the B95-8 strains of EBV. DPH translocation, as determined by fluorescence polarization analysis, is, therefore, measuring some early event during interaction of this enveloped virus and mammalian cells. The potential applicability of this technique to other viruses is illustrated by an experiment with Semliki Forest virus.


Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells.

In vitro stimulation of spleen cells from mice immune to Sendai virus results in the generation of effector cells that lyse unmodified allogeneic target cells in addition to syngeneic cells modified by virus. These cells are immunologically specific because their lysis may be blocked by cold targets syngeneic to either the stimulator or the responder. These results support our proposal that the development of alloreactivity can be explained by the crossreactivity between modified self major histocompatibility complex antigens and alloantigens. We propose that exposure to autologous major histocompatibility complex antigens modified by foreign antigens in our environment results in the expansion of the pool of T cells that will respond to alloantigens sharing crossreactive determinants.


Epstein-Barr virus and human chromosomes: close association of the resident viral genome and the expression of the virus-determined nuclear antigen (EBNA) with the presence of chromosome 14 in human-mouse hybrid cells.

Fourteen hybrid clones derived from the fused cultures of human lymphoblastoid FV5 cells and 5-bromodeoxyuridine-resistant mouse fibroblastic MCB2 cells grown in hypoxanthine/aminopterin/thymidine selective medium were examined for the presence of Epstein-Barr virus (EBV) DNA, the expression of the virus-determined nuclear antigen (EBNA), and the presence of human chromosomes, in the course of serial passage in vitro. Among the hybrid clones tested, 3 were positive for EBV DNA and EBNA, whereas the remaining 11 were totally negative. The chromosome investigations showed that human chromosome 14 was consistently involved in all three EBV genome-positive and EBNA-positive hybrid clones, but not in any negative clones. In 10 subclones isolated from 1 of the 3 positive clones, all of which contained only chromosome 14 of the human chromosomes, a concordant segregation of EBNA, EBA DNA, and chromosome 14 was evident. These findings suggest that the resident EBV genome is closely associated with chromosome 14 and the presence of this particular chromosome alone is sufficient for the maintenance and the expression of EBV genetic information in human lymphoblastoid cells.


Corticotropin, lipotropin, and beta-endorphin production by a human nonpituitary tumor in culture: evidence for a common precursor.

A continuous line (DMS-79) of human pulmonary small cell carcinoma cells was shown to secrete immunoreactive adrenocorticotropin (ACTH), lipotropin, and beta-endorphin concomitantly into the culture medium. Gel filtration of the culture medium demonstrated at least five components: high molecular weight material(s) that had ACTH, lipotropin, and beta-endorphin immunoreactivities and materials similar to ACTH, beta-lipotropin, gamma-lipotropin, and beta-endorphin in their immunoreactivities and apparent molecular weights. The same components were observed when gel filtration was carried out in 6 M guanidine-HCl, and the high molecular weight material(s) appeared to consist of more than one component, with molecular weights in the range of 15,000-40,000. Immune affinity chromatography of the high molecular weight component(s) from gel filtration with a specific anti-(1-24)ACTH serum demonstrated that the ACTH, lipotropin, and beta-endorphin immunoreactivities were possessed by the same molecule(s), suggesting that ACTH, lipotropins, and beta-endorphin were derived from a common, high molecular weight precursor.


Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites.

The neuroendocrine bag cells in the abdominal ganglion of Aplysia generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. We find that synchrony, afterdischarge, and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. We have distinguished two independent types of refractoriness. The first (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The second form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the first afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the first afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. We have shown that both serotonin and dopamine stimulate the formation of cyclic AMP in the bag cell clusters and in the pleurovisceral connectives and that the occurrence of an afterdischarge is associated with a specific increase in total cyclic AMP in bag cell bodies. Moreover, afterdischarges can be generated in unstimulated preparations by extracellular application of the cyclic AMP analogues, 8-benzylthio-cyclic AMP or 8-methylthio-cyclic AMP. Our data suggest that serotonin and/or dopamine may control bag cell activity and that activation of adenylate cyclase is linked to bag cell afterdischarge.


L-aspartate: evidence for a role in cone photoreceptor synaptic transmission in the carp retina.

A number of putative neurotransmitter substances and their antagonists were applied to the carp retina while intracellular recordings from L-type cone horizontal cells were made. Of all the substances tested, L-aspartate was found to be the most potent agent in depolarizing these horizontal cells in dark-adapted, partially light-adapted, and Co2+-treated retinas. Furthermore, DL-alpha-aminoadipate, an L-aspartate antagonist, blocked the effects of both the endogenous photoreceptor transmitter and exogenously applied L-aspartate on the horizontal cells. The results suggest that L-aspartate and the natural transmitter interact with the same population of postsynaptic receptors in the horizontal cell membrane.


Induction of neurite outgrowth by a conditioned-medium factor bound to the culture substratum.

Heart-cell conditioned medium (HCM) induces rapid neurite outgrowth from isolated neurons in culture. The following evidence indicates that this action of HCM is due to a trypsin-sensitive factor which attaches to the polyornithinecoated culture substratum: (i) Pretreatment of the culture substratum with HCM allows rapid neurite outgrowth to occur even in unconditioned media. The active factor remains bound to the substratum during the period of neurite outgrowth. (ii) The substratum-bound activity is destroyed by trypsin treatment, but is insensitive to collagenase, RNase, and DNase. (iii) The factor that binds to the substratum is essential for neurite outgrowth, because HCM is no longer active when the material that binds to the polyornithine substratum has been removed by passage of the HCM over a series of culture dishes. However, this "depleted" HCM is still able to support the growth of nonneuronal cells. (iv) Most significantly, when neurons are cultured in whole HCM, the extent of neurite outgrowth is proportional to the amount of substratum-bound activity and not to the amount in solution, indicating that the substratum-bound form of the factor is more active. Previous observations [Collins, F. (1978) Dev. Biol. 65, 50-57] suggest that HCM promotes neurite outgrowth by increasing the adhesion between nerve cell surface extensions and the polyornithine-coated culture substratum. It is possible, therefore, that the factor in HCM that binds to the substratum possesses sites to which nerve cell surface components adhere.


Cyclic GMP injected into retinal rod outer segments increases latency and amplitude of response to illumination.

We have injected cyclic GMP intracellularly by iontophoresis through the recording electrode into single rod outer segments of the isolated superfused retina of the toad. Bufo marinus. The two most marked effects of the injection are: (i) the latency of the hyperpolarizing membrane-potential change caused by illumination is increased from 5 to 50 times normal, the increase in latency being inversely proportional to the light stimulus intensity; and (ii) the amplitude of the hyperpolarizing receptor potential is increased. These effects are reversible. Our findings are consistent with the hypothesis that cyclic GMP is a link in the molecular chain of events that controls the inward flow of sodium ions in light and darkness. The increased latency we observe after injection of cyclic GMP may be caused by a time delay necessary for light-activated phosphodiesterase to hydrolyze the excess cyclic GMP. By this reasoning the excess cyclic GMP perpetuates the dark current long after illumination. Excitation may be controlled by cyclic GMP if, as our experiments suggest, its hydrolysis initiates the hyperpolarizing receptor potential.


Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation.

This review article is designed to further enlighten the physical therapist about pathways transmitting nociceptive information and about systems capable of inhibiting this transmission. At present, little information exists to explain how transcutaneous electrical nerve stimulation effects changes in pain perception. Contemporary knowledge regarding proposed modes of action for this modality is presented in light of current neurophysiological information. In explaining the action of transcutaneous electrical nerve stimulation, alternatives to the gate-control theory of pain are suggested as being quite possible. Questions regarding future investigations are proposed.


Introduction to the use of transcutaneous electrical nerve stimulation devices.

Transcutaneous electrical nerve stimulation is an ancient but newly discovered modality. Initially intended for use in chronic pain syndromes, transcutaneous electrical nerve stimulation may be even more useful in managing acute pain. Although procedures for the use of this device are relatively simple, additional knowledge about selecting and adjusting the device as well as clinical experience will largely determine the degree of success obtained with this modality. Adjusting transcutaneous electrical nerve stimulation units can alter the stimulus efficiency. No one wave-form is the most effective, but characteristics of effective wave-forms are known. In addition, the patient must be knowledgeable and cooperative when transcutaneous electrical nerve stimulation is applied.


Peripheral neural excitability. Implications for transcutaneous electrical nerve stimulation.

Basic neurophysiological principles necessary for understanding the effectiveness of transcutaneous electrical nerve stimulation are presented. Peripheral and central neural mechanisms are reviewed, and the effects of individual pulse characteristics on neural excitability are analyzed. Representative commercial stimulators are compared, and wave-forms for different load conditions are illustrated. Discussion includes important considerations for clinical effectiveness and for patient acceptance and safety.


[Neurogenic claudication and claudication by arteritis of the lower limbs].

Intermittent claudication of neurogenic origin can be traced to three basic causes: --either a chronic circulatory deficiency in the arteries leading to the spinal cord, whether these arteries be the site of an atheroma of the ostia, an inflammation or a loco-regional compression. In such cases, the claudication is painless which differentiates it from the arteritis claudication of the lower limbs. --or to a compression of the roots of the cauda equina and to a lesser degree of the spinal cord, through a narrow rachidian canal that is hereditary or acquired, and relative or absolute. --or finally to a sheathing peripheral neuropathy of the lower limbs. The two latter causes are accompanied by pain, and make it necessary to widen the classical notion of the intermittent claudication (Dejerine's non painful intermittent claudication of the spinal cord).


[Kaposi's disease and venous insufficiency].

This case involves a 28-year-old man suffering from severe circulatory failure with blue and cold limbs resulting from childhood polio and showing circumscribed plaques of angio-dermatitis (Favre and Chaix) with a tumor-like appearance resembling Kaposi's angiosarcomatosis. These facts described by Mali in circulatory ailments, especially following phlebitis, should be known to phlebologists. They differ from Kaposi-like disease by the much rarer arterio-venous fistula (described by Bluefarb and Stewart). It is possible that there are mixed forms and that the cases attributed to simple circulatory failure may be due to the minimal linkage of arterio-venous fistulas that can be detected only by arterio-selection.


[Cholangiocarcinoma in a patient with hepatosplenic atrophy subsequent to thorotrast administration (author's transl)].

A case of cholangiocarcinoma observed in a woman of 38 following carotidographic examination with Thorotrast is described: the presence of radioactivity was also demonstrated by gamma spectrometry. The high mean dose absorbed by the liver (estimated at about 3,000 rad) together with the high relative biological effectiveness of the alpha contribution and the time lapse justify the hypothesis that the neoplasia was caused by irradiation.


Stress simulation: ACTH and zinc effect on trace metals in liver and spleen.

Effect of ACTH and zinc acetate subcutaneous injection on the trace metals in liver and spleen was investigated in male Wistar rats. Iron, copper, zinc and manganese in liver, and iron, copper and zinc in spleen were analyzed by AAS method. The iron, copper and zinc levels in liver, and iron levels in spleen showed a significant decrease at 1-1 h 30 min after administration of 30 UI of ACTH but values returned to normality or showed slightly higher levels at 4 h 30 min-7 h 45 min. Zinc acetate injection only elicited an increase in liver and spleen zinc levels. Results are discussed in relation with results given in previous papers.


Pathobiology of cortical neurons in metabolic and unclassified amentias.

Visualization of the neuron in its entirety through the use of the rapid Golgi method has permitted detection of several pathobiological features of neurons that are intimately associated with profound mental retardation in infants and children. In cases of unclassified mental retardation, dendrites and particularly dendritic spines exhibit severe developmental abnormalities. Dendritic spines, the postsynaptic components of axospinodendritic synapses, may be absent or abnormally long and thin in retardates. Evidence is presented that some cases of progressive neurobehavioral deterioration in infancy and early childhood may be due to progressive degeneration of dendritic spine systems (dendritic spine "dysgenesis"). Golgi and electron microscopic studies of neurons in human and feline ganglioside storage diseases indicate that ganglioside accumulation in cortical neurons initiates several complex alterations in neuronal geometry and morphology. Small and medium pyramidal cells form massive structural compartments (meganeurites) that frequently give rise to secondary neurites and other embryonic growth processes. Meganeurites may possess spines and spine-synapses. Other cells such as large pyramidal neurons may exhibit many somatic spines, whereas intrinsic cells of the cortex (and caudate) are unaffected morphologically by ganglioside accumulation. It is suggested that neuronal geometry distortion and aberrant synaptogenesis are important factors in the onset of neuronal dysfunction in ganglioside storage disorders. These studies also point to an important role of gangliosides in neurite formation in immature mammalian cortical neurons. Perisomatic processes and somatic spines are normal morphological components of the cell body of Purkinje cells through the 28th fetal week of human gestation. By 36 weeks the Purkinje cell somas exhibit a smooth surface contour. Prominent polydendritic processes, perisomatic protuberances, and somatic spines are detectable by Golgi methods applied to Purkinje cells in Menkes' disease and Down's syndrome long after these somatic components should normally disappear. Thus Purkinje cell soma membrane differentiation is a particularly sensitive process that can provide information on mechanisms of site-specific membrane regulation.


Gas exchange abnormalities produced by venous gas emboli.

Bubbles of either He, N2 or SF6 were infused intravenously into anesthetized dogs at a rate of 0.2 ml/kg/min. Alterations in pulmonary gas exchange were quantitated by the invert gas elimination method during control, steady state infusion and resolution phases. The hypoxemia produced was predominantly due to regions of low VA/Q rather than pure shunt, and the increase in physiological dead space was due to the addition of high VA/Q regions rather than 'pure' dead space. The VA/Q distribution returned to normal within 30 minutes of stopping the He or N2 bubbles, but remained abnormal for longer periods with SF6 bubbles. The net elimination of insoluble gases (such as He or N2) was only slightly impaired by bubble emboli, provided the cardiac output remained constant. Early pulmonary edema from bubble embolization was documented by increased wet weight/dry weight ratio, but the increased lung water was not apparent on histological examination. This form of pulmonary embolus is unique in that there is a constant fraction of the vasculature blocked although any given region with embolus is undergoing continuous resportion of the bubble. This produced a partial obstruction of the affected gas exchange units which manifests as regions of high VA/Q rather than pure dead space.


Characteristics of the washout dead space.

The dead space volume was reproducibly measured in normal and diseased lungs by analysis of an inert gas washout. This washout dead space was appreciably larger than that measured by the Fowler technique. In the patients, the washout dead space (VD(0)) formed 72% of the physiological dead space volume, while the Fowler (VD(F)) method accounted for only 50%. The VD(O) increased significantly with age in males, but not in females. VD(F) was not well related to age in this population. VD(O) and VD(F) did not relate to lung volume in these subjects. Although that portion of the dead space delivered in Phase I was significantly greater in males than in females, it was not responsible for the difference in dead space measured by the two techniques. This volume difference was found in that portion delivered late in the breath (Phase III). The nature of this volume is speculative, but may involve a parallel dead space that is measured in addition to the series dead space.


[The role of vestibular and proprioceptive afferent pathways in the reaction to pushing (author's transl)].

The reaction to pushing was studied in 6 normal subjects and 3 patients with bilateral peripheral vestibular lesions. The reaction to pushing was tested on the anterior tibial and soleus, by modifying the proprioceptive afferent impulses. The respective parts of the vestibular, proprioceptive, visual components, and of a sudden, start are analyzed; the afferent impulses obtain information from the initial posture and modulate the relative importance of these different factors at a supra-segmentary level.


[Opaque meato-cisternography in study of atypical or incomplete syndromes of cerebellopontile angle (value for diagnosis and early treatment of neurilemmoma of the 8)].

It is well-known today that there is a cisternal "no man's land" between the petrous bone and the cerebral trunk in which a tumour can develop insidiously. The clinical signs are very variable and often in contradiction with those described for larger tumours. Tomodensimetry is indicated, but it is not conclusive if the mass is limited to the internal auditory canal or if it extends into the angle for less than 15 mm. Opaque meato-cisternography alone, gives the following information: 1. When a pseudo-tumoural syndrome is present, the auditory canal and cisterna are well opacified. 2. If there is a tumour which extends for more than 20 mm into the cisterna, the oil has a rounded, interrupted contour, and other radiological examinations are useful in this case. 3. When the tumour extends for less than 20 mm into the angle a rounded continuous contour is seen, and Hirtz's axial incidence can be used to measure the tumour diameter. 4. Finally, when temporary opacification faults have been eliminated (after retilting), opaque meato-cisternography is the only examination able to demonstrate the early stages of a tumour, in the intra-canal stage. This early diagnostic procedure has enabled one of us to excise tumours of moderate of even very small volume, under the best surgical conditions, and with functional and vital results which we would not have obtained at a later date.


[Detection of tubercular infection after BCG vaccination].

The author has followed several groups of children over a period of many years and evidenced the general decrease of the level of tuberculin reactivity. The implications are discussed, of the B.C.G. vaccination on the tuberculous allergy and the possibility to differentiate post-vaccinal allergy with the aid of skin testing, using 2 and 10 PPD units. The importance is stressed, of the vaccinal scar as an indication of a good immune reactivity, and thus of protection against contamination with virulent tuberculous baccili. The time is foreseen, when systematic vaccination with B.C.G. will reduce to such a significant degree the number of cases of tuberculosis in children that differential diagnosis on the basis of tuberculin allergy will not be necessary.


[Experience gained in the Pecica region (Arad) regarding the organizational aspects of the integration of antitubercular chemotherapy in the basic health network].

The present paper reports on the author's experience concerning certain organizational aspects in the closely surveyed treatment of tuberculosis following integration of this activity in the general health network. Emphasis is layed on the role of the general practitioner and ancillary staff who must work under the guidance of a specialist in pneumophyhisiology. The importance of personal motivation in the general health services and the role of health education of the patients is underlined.


[Surgical treatment of bronchial adenomas].

The authors make an analysis of the experience acquired in the Clinic of Thoracic Surgery of Bucharest, based on interventions carried out in 42 cases of bronchial adenoma hospitalized between 1962 and 1976. The fact is stressed that in none of the 42 operated patients was the carcinoid syndrome encountered with any of its specific manifestations. Also on the basis of the experience obtained the bronchologic criteria for benignity of this type of tumour (absence of the infiltration in the mucosa, surrounding the tumour) is considered as non-significant because there are frequently areas of malignant transformation inside the tumour itself, or at its lower pole that cannot be explored by bronchoscopy. Surgical treatment of bronchial adenoma included a wide range of techniques, from simple lobectomies to bronchoanastomotic interventions, and resections of the trachea. The study of postoperative results showed a good prognosis and survivals of appreciable duration only when the intervention was carried out in the I-st and the II-nd stages of the disease. This also stresses the necessity for an early diagnosis and rapid surgery in these bronchial adenomatous tumours (most of which are of the carcinoid type).


[Risk factors and high-risk groups in the prevention of tuberculosis].

Starting from the premise that in the methodology of tuberculosis control priority should be given to the higher risk groups, the authors tried to identify such groups and list them in the order of their priority within the district of a dispensary serving a population of about 400,000 inhabitants. On comparing the results of the detection of risk factors among the population in general with that per endangered groups it was found that the former presented a decrease (from 1.09 to 0.44 per thousand) and the latter an increase (from 0.91 to 1.5 per thousand). The 126 747 examinations for risk factors revealed a succesive increase in the detection indices as follows: 0.76 per thousand among students, 1.36 per thousand in silicogen risk enterprises, 2.07 per thousand among the workers on building sites, 2.22 per thousand among diabetics, 2.76 per thousand among contacts, 2.85 per thousand among hyperergic subjects, 3.89 per thousand among former patients no longer on the files, 4.17 per thousand among alcoholics and patients under psychical treatment, 6.01 per thousand among patients with minimal lesions and 6.82 thousand among those with sequelae.


[Current incidence and clinical significance of non-culturable bacilli or those culturable with difficulty].

An analysis of 246 patients with positive smear present bacilli and negative cultures revealed that in only 9% of the cases no organized previous treatment had been applied, although almost half of these had benefited from short courses with streptomycin associated with penicillin before an exact diagnosis of tuberculosis had been made. Since the remaining 91% had had 1--2 months of chemotherapy, which frequently included rifampicin, the authors stress that microscopically detectable germs are frequently incapable to develop on culture media. These are frequently non-viable bacteria and in such conditions no subsequent modifications of the currently applied therapy scheme should be attempted. The authors show that only 26,2% of the germs from 519 positive cultures have developed after 21 days from the seeding. At 30 days the overall proportion increased to 71,2% while at 45 days 22,7% more positive cultures appeared and an additional 6,1% cultures became positive at 60 days. Tubercle bacilli become increasingly demanding and slower growing. If at 21 days only one colony was evident in 6% of the cases, while an infinite number of colonies were present in 58% of the cultures at 60 days a single colony was found in 42% of the cases, in contrast with only 9% cases with an infinite number of colonies (P less than 0,001). The delay in the growth of bacilli was parallel with the duration of chemotherapy. The results are compared with data from the literature.


[Cerebral hemodynamic disorders in patients with chronic decompensated respiratory insufficiency. Physiopathogenetic considerations].

The present paper reports on 12 patients (8 males, 4 females) suffering from chronic decompensated respiratory failure, who presented concomitant transient haemodynamic disturbances in the carotid and vertebrobasilary systems, manifested by hemisphere or brain stem symptoms. Owing to the adaptive capacity of these patients there exists a certain tolerance threshold to hypercapnic hypoxemia, but following accentuated or rapid aggravation of acid-base hypercapnic hypoxemia, the biological balance is abruptly perturbed leading to cerebral haemodynamic disturbances. The pathophysiological mechanism of production appears to be the accumulation of acid ions caused by pH acidification of the cerebrospinal fluid. Increase in the cerebral arterial output with decrease in the rate of circulation and vascular resistance take place especially in the vessels with atheromatous or hyaline lesions. Under conditions of severe acidosic hypercapnic hypoxemia this, nevertheless, insures a minimum of 10--20% oxygen required by the metabolism of the nerve cell, sufficient for maintaining the structure of the cell (vita minima). These vasculometabolic mechanisms explain why with improvement of haematosis, following remission of the decompensated disease and fall in acidotic hypercapnic hypoxemia values, the cerebral haemodynamic disturbances also show a more or less evident remission because the nerve cells having maintained their structure are able to take up their function again.


[Effectiveness of the routine treatment of workers employed in the region of the Tuberculosis center, Constanţa].

The present work demonstrates the high overall efficiency of the present regimes in the treatment of tuberculosis (97%), provided the rules and indications are strictly complied with. The duration of the medical sick leave influences the regularity with which the treatment is applied. Many of the younger patients frequently accept to resume work at an earlier date. Earlier work resumption under present conditions should be had in view since it obviates the major drawbacks in the treatment of tuberculosis--socio-occupational disadaptation of the patients.


[Experimental neuropathy due to acrilamide. Histological and ultrastructural studies (author's transl)].

The effects of acrylamide intoxication were studied both in peripheral (PNS) and central (CNS) nervous system of rats. The animals were sacrified at different time intervals from the beginning of the intoxication. Histological and ultrastructural studies of peripheral nerves and long tracts of the spinal cord revealed a severe axonopathy, characterized by swelling of axons, particularly in the paranodal regions due to accumulation of neurofilaments with almost complete disappearance of neurotubules. There was also aggregation of dense bodies, swollen mitochondria and multivescicolar bodies in subaxolemmal regions. Presynaptic endings in the anterior horns of the spinal cord and in the cuneate nuclei were swollen and filled with packed filaments. Fiber degeneration at different stages was seen both in PNS and in CNS. These changes are not specific for acrylamide intoxication, having been observed in other experimentally induced neuropathies (n-hexane, Mn-BK, CS2, ...), as well as in a variety of diseases both genetically determined and due to exposure to toxic substances (glue-sniffing, leather cement poisoning, antiblastic therapy, ...). Accumulation of filaments in peripheral and central axons is the pattern of fiber degeneration characterizing the dying-back neuropathies. These axonal changes are particularly marked in the pacinian bodies as well as in the distal segments of the fibres. These data support the hypothesis that a dying-back neuropathy might depend on the direct effect of the toxic substance on the most vulnerable segments of the fibres, rather than on the perikaryon of the nerve cell, as previously supposed.


[Thorotrastoses--viewed in retrospect (author's transl)].

Thorium dioxide (Thorotrast) was used as a contrast medium from 1930 to 1945. It gave excellent contrast and was well tolerated during the application, but due to its radioactivity and its long biological half life it caused various late complications as fibrosis and malignant tumors. The late side effects of the substance are reported on, and the most frequent complication--the induction of hepatomas--is illustrated by two cases.


[Recurrent infectious parotiditis in the child (author's transl)].

On the basis of 18 cases of recurrent parotiditis in the child, the authors offer the current review of this condition: clinical features, radiological features, bacteriological features, course. They emphasize the importance of precise technique during sialography, which must include straight and lateral films. The progress of this condition is characterised by recurrences. These may be avoided by prolonged and appropriate antibiotic therapy. The improvement which takes place at puberty is of etiopathogenic significance. Bucco-dental septis, constantly present, is one of the causes favourising infectious parotiditis in child.


Cerebrospinal fluid content of adenylate kinase, lactate and glutathione in patients with meningitis.

Adenylate kinase activity and lactate concentration were measured in the cerebrospinal fluid (CSF) of 5 patients with bacterial meningitis, of 4 patients with probable bacterial meningitis, and of 18 patients with serous meningitis. Furthermore, for comparison measurements were also performed in CSF of 27 patients with meningism. Concomitantly glutathione was measured in CSF in most of the patients. Significantly higher values of these 3 parameters were found in the CSF of patients with bacterial and probable bacterial meningitis compared with those having serous meningitis and meningism. Adenylate kinase activity and lactate concentration in patients with serous meningitis were significantly higher than in those with meningism. All patients with a clinical diagnosis of meningitis studied so far also displayed an adenylate kinase activity in their CSF. The determination of adenylate kinase, lactate and glutathione levels in CSF might be a useful aid for the diagnosis not only of meningitis but also for the discrimination between bacterial and serous meningitis.


Free plasma 11-hydroxycorticosteroids and the response to beta1-24-corticotrophin in regular haemodialysis patients.

The adrenocortical function of 59 patients on regular hemodialysis treatment was tested on 105 occasions by measuring the 30-min response of free plasma 11-hydroxycorticosteroids (11-OHCS) after intramuscular injection of 0.25 mg Synacthen (beta1-24-corticotrophin). The morning basal levels of 11-OHCS were within the normal range. The increase of 11-OHCS after injection of Synacthen was less than normal in 25% of the patients. In 9 patients with a low response an extended Synacthen test was performed. This caused a normal increase in plasma 11-OHCS but the response came later than in normal persons. After 0.25 mg Synacthen intramuscularly the 30-min response of 11-OHCS seemed to be lower on the first day than on the second day after dialysis. The present study supports the view that the pituitary-adrenocortical system is essentially intact in patients on regular hemodialysis treatment.


Molecular cloning of polyoma virus DNA in Escherichia coli: plasmid vector system.

A series of recombinant plasmids containing polyoma virus (PY) DNA were constructed, and their biological activity was evaluated in mice and in cultured mouse cells. While all of the recombinants studied contain the complete, potentially infectious viral DNA, in no case was the intact recombinant PY-plasmid DNA, or live Escherichia coli containing the recombinant plasmids, capable of inducing PY infection of mice, either by feeding or by parenteral injection.


Molecular cloning of polyoma virus DNA in Escherichia coli: lambda phage vector system.

The biological activity of recombinant phage and recombinant phage DNA containing monomeric or dimeric polyoma DNA inserts was examined in mice and cultured mouse cells. Recombinant preparations containing a single copy of viral DNA were invariably noninfectious; molecules containing a dimeric polyoma DNA insert were at least seven orders of magnitude less infectious than polyoma virions after parenteral inoculation. No infection was detected with any recombinant preparation after oral administration.


Neurophysiological basis of acupuncture analgesia.

This article presents a view about the neural mechanism of acupuncture analgesia and the clinical and experimental evidences on which this view is based. The analgesic effect of acupuncture is considered essentially a manifestation of the interaction of afferent impulses from the region of pain and those from the point of acupuncture. It begins with a general information leading to the development of this sensory interaction theory in interpretation of acupuncture analgesia. The nature of the acupuncture feeling, the receptors activated by acupuncture, the types of fibers involved in transmission of the afferent impulses produced by acupuncture and the processes of interaction taking place at different levels of the central nervous system are described with particular reference to the integrative action of extralemniscal system including the bulbar reticular formation and the intralaminar structures of thalamus. The possible rôle played by the putative synaptic neurotransmitters such as serotonin is only very briefly mentioned.


[Aetiological and evolutive Particulars of parinaud's syndrome. Report of 19 cases (author's transl)].

After a summary of general specifications of Parinaud's syndrome the authors made a critical study according to 19 personal observations. They point to the aetiological interest of evolutive development of this syndrome when undergoing treatment for tumour and during the vascular malformations when fluctuations are an interesting clinical presumptive evidence.


[Granulomatous tuberculoid gastritis (author's transl)].

The authors report seven cases of tuberculoid granulomatous gastritis. Tuberculosis was the cause in three cases. Bilharziasis was the cause in two cases. Sarcoidosis was identified in one patient. In only one case was the etiology undetermined. This seems rare. Some of these form should be compared with experimental tuberculoid granulomatous gastritis, obtained after sensitisation to foreign substances included in the gastric mucosa. The organisation of the epithelioid and giant cell granuloma corresponds to an immune defence reaction of the stomach, bringing into play immunoglobulins IgG and IgM to lead to the formation of antigen antibody complexes in these tissues.


[Antithrombin III in 86 patients with venous thrombosis (author's transl)].

Antithrombin III concentration was studied in 86 patients with recurrent or extensive venous thrombosis. Two of them were found to have an hereditary antithrombin III deficiency. 25 patients receiving heparin therapy had low antithrombin III concentration. After stopping heparin treatment antithrombin rose to a normal level. Pathological antithrombin III modifications are recalled (synthesis decrease in liver diseases, intra vascular consumption during active venous thrombosis). Antithrombin III decreased activity induced by heparin treatment is pointed out.


[Use of plastic isolators in the prevention of infection in high risk patients with hematologic diseases].

The authors report a microbiological study of the flora of high risk adults with blood diseases isolated in hermetically sealed plastic isolater. This type of isolation is very effective in the prevention of infections due to hospital germs as such contamination occurred only twice in 292 days isolation and was found in only 0.8% on samples. The efficacy of methods of body decontamination and the incidence of infective complications in our series is also reported.


[Long term course of insulin secretion in treated noninsulin dependent diabetics (author's transl)].

The long-term effects of sulfonamides were studied by means of hyperinsulinemia tests in 82 diabetics over a period of 12 months (24 months for 30 of them). Whereas for those obese diabetics whose only treatment was dieting--alone or combined with biguanides--hyperinsulinemia attenuates itself as do also variations in glycemia, although some asynchronism remains, in those diabetics treated with sulfonamides--alone or in combination with other treatments--the insulinemia curve is hardly modified.


[Acute poisoning. Apropos of 1200 cases].

The team studied 1 200 cases of acute intoxications both accidental and self inflicted, self inflicted poisonings are much more frequent than accidental ones and in general occur more often amongst the young and by women; the median age is about thirty. Barbituric are often the means. There is a progressive increase in the use of tranquilizers and of thymo-analeptics as their use becomes greater. A mixture of poisons increases the dangers because this frequently results in more rapid loss of consciousness; also more than one poison increases the risk of shock and of thermo-regulation, respiratory problems necessitate intubation and artificial respiration which both increase the risk of assification. The characteristics of certain poisons are stressed and in particular the thymo-analeptics; also the supervision of the patients in an intensive care unit.


[Hodgkin's disease. T lymphocyte defect in patients in complete remission (author's transl)].

11 patients with Hodgkin's disease in remission, including 7 patients with an initial stage III-IV, off treatment for at least 6 months, were tested for blood T lymphocyte functions. All were completely re-evaluated at the end of treatment to assess complete remission. The number of peripheral blood lymphocytes was below 1,200/cu mm 5/11 patients. Absolute numbers of E-rosette-forming T lymphocytes were decreased in 8 patients, whereas active rosettes were normal in 4/6. A slightly increased percentage of EAC rosettes, a marker for B lymphocytes, was found in only 2 patients. In vitro lymphocyte reactivity to a sub-optimal dose of PHA was studied in 9 patients. A statistically significant defect of lymphocyte transformation was observed in the patient group T lymphocytes. A membrane change is suggested rather than a true depletion. The persistance of such abnormalities long after treatment may raise the question of a complementary immunostimulating treatment in these patients.


[Immunologic tests in the prognosis of solid malignant tumors].

Survival at 6, 12 and 24 months was studied in relation to the immunological findings before treatment and its variations after treatment in 600 patient and its variations after treatment in 600 patients with solid malignant tumours. Any change in any of these tests is a sign of poor prognosis proportional to the degree of this change. The most precise prognosis is given by an association of these tests. These two year survival rate for tumours without apparent spread was 87% if the tests were normal, 43% if one group of tests was disturbed and 11% if two groups of tests were abnormal. With local or regional spread, the survival was 52% in cases with normal tests, 12% if one group was disturbed, and 4% if both groups of tests were abnormal. With multiple metastases, the survival rates were respectively 24%, 4% and 0%. Thus the prognosis is less unfavourable for a tumour with general spread and normal immunological tests (24%) than for a localised tumour with a disturbance of two groups of immunological tests (11%). These immunological tests carried out before any treatment are thus very valuable in prognosis, independant of the apparent extension of the tumour. This indications are important in deciding on treatment.


[Minimal brain dysfunction. Our investigation of choreiform syndrome in children with MBD (author's transl)].

It is the purpose of this communication to study statistical correlations between the different symptomes of MBD ; speech defect, dyslexia, hyperactivity, poor muscular control, give a school handicap for about 10 per cent of children, excluding cerebral palsy, sensorial trouble, or intellectual defect. The choreiforme syndrome is a systematic investigation in a group of 60 children selected with two symptomes of MBD. Choreiform movements are found in 48 per cent of our MBD patients (40 per cent of patients with hyperactivity and 50 per cent of patients with serious dyslexia).


[Long term psychiatric treatment and surgical operations].

Frequently, long term psychiatric treatments are interrupted unfortunately. Although sometimes this interruption is necessary owing to the danger of an anaesthetic, particularly in the case of IMAO, this interruption should be only provisional or else a relapse will occur a few weeks later. It is always advisable to take the advice of a psychiatrist before interrupting the treatment.


[Salt-free diet and diuretics in the elderly (author's transl)].

A salt-free diet is usually useless or dangerous in the elderly subject. It has at present only rare indications, such as after acute pulmonary oedema or congestive heart failure during initial treatment. In all other cases, it may be replaced by a reasonable diet; sodium intake remains permitted, but naturally one should not fall in the opposite extreme. As in younger subjects, and provided one takes into consideration the subjacent renal condition, properly prescribed diuretics have transformed the situation in the treatment of heart failure as in essential hypertension. Naturally the patient still requires regular clinical supervision and laboratory tests which may in practice be limited to periodical estimation of blood urea and serum potassium, less regularly, blood sugar and uric acid.


Therapeutic abortion on psychiatric grounds. Part II. The continuing debate.

Over the past few decades, attitudes towards therapeutic abortion have gradually changed in many countries from denial and punishment to acceptance. The debate on this emotionally laden subject still continues. In this article, we review some of the recent literature covering therapeutic abortion on psychiatric grounds, including studies of women granted termination as well as those refused. Other related areas, such as the long-term effect on children born after the refusal of termination and the relevance of this to preventative psychiatry, are also considered.


[The effect of vincamine on vigilance disorders in the elderly (author's transl)].

The vigilance is, now, recognised as an active phenomenon submitted to definite structures, separate from those supervising sleep. A good cerebral function is required for vigilance maintenance and it is easily understood that cerebral alterations in aging result in vigilance decrease. The eminent repercussion of these disorders on the behavioral adaptation of the aged justified an awaking therapy. This original characteristic of vincamine, and specially of Pervincamine Forte Retard, is a fundamental discovery in cognitive functions maintenance of the aged people.


High-density lipoproteins in the prevention of atherosclerotic heart disease. Part I. Epidemiological and family studies.

It has recently been proposed that the concentration of the high-density lipoprotein (HDL) fraction in plasma bears a negative relationship to the incidence of atherosclerotic heart disease. The biological and environmental factors affecting plasma HDL levels and the evidence pertaining to the proposed 'negative risk potential' of this lipoprotein are reviewed. HDL concentrations are low at birth, but rise rapidly in early infancy to adult or above-normal adult levels. This trend is influenced by biological factors such as sex and ethnicity and by a host of environmental variables. Despite methodological inadequacies in some studies, the epidemiological evidence consistently reflects an inverse relationship between the level of HDL in the plasma and the risk of ischaemic heart disease. Investigations on families suffering from genetic dyslipoproteinaemias, characterized by reduced levels of low-density lipoprotein (LDL) relative to HDL, suggest that the LDL:HDL ratio is itself an important determinant of atherosclerotic heart disease. The practical application of this information is limited by the lack of reliable reference ranges in various population groups and the absence of quantitative data regarding the 'negative risk potential' of any given concentration of plasma HDL in the presence of other positive and negative risk factors.


[A study on the use of ginkor in proctology (author's transl)].

A total of 37 ambulatory patients with proctological conditions were treated with Ginkor as preparatory therapy before instrumental treatment (sclerosants or elastic ligatures). Greater importance was attached to its hemostatic activity; always objective though sometimes transitory, than to the improvement in various painful functional syndromes. Changes in hemorrhoidal morphology were not included in the assessment, as they demonstrate very little in the course of general treatment, except in bouts of acute inflammation and more particularly when oedema and thrombis occur. After treatment, the functional syndrome (heaviness, tenesmus) which was present in 29 patients was absent in 9 cases, reduced in 13, and unchanged in 7. Pruritus ani, which was present in 14 patients, was absent in 4 cases, reduced in 5, unchanged in 4, and impossible to evaluate in 1 case. Rectorrhagia disappeared in 12 out of 20 cases, was reduced in 4 cases, and persisted in 4 others. Overall, there were 12 very satisfactory results, 13 incomplete results, 3 moderate results, and 9 cases where no effect was noted.


High-density lipoproteins in the prevention of atherosclerotic heart disease. Part II. Biochemical role in the pathogenesis of atherosclerosis.

Evidence is presented that high-density lipoprotein (HDL) promotes the efflux of cholesterol from cells in vitro, and may thus play an important role in the transport of cholesterol from non-hepatic tissues to the liver for excretion. Hypothetical schemes are presented whereby this may be achieved in vivo. This putative function of HDL may be of particular importance in situations in which the capacity of cells to limit the uptake of cholesterol is exceeded, and may therefore constitute the basis for the proposed antiatherogenic action of plasma HDL. However, direct data on the transport function of HDL in intact organisms are meagre. Furthermore, a characteristic of mature atherosclerotic lesions is the extracellular, rather than the intracellular, deposition of cholesterol and other lipids, and the degree to which HDL may influence this process has not been demonstrated. Finally, in inherited disorders which markedly impair the putative HDL transport pathway, atherosclerotic heart disease is generally not an early or severe complication. Despite these caveats, the physiological significance of HDL deserves further attention in order to clarify the uncertainties enumerated above. The clinical application of plasma HDL assay is limited at present to excluding the clinically non-deleterious condition of hyperalpha (HDL)-lipoproteinaemia in patients suffering from familial hypercholesterolaemia.


Genetic and biochemical studies with the adenosine analogs toyocamycin and tubercidin: mutation at the adenosine kinase locus in Chinese hamster cells.

The pyrrolopyrimidine nucleosides toyocamycin and tubercidin show several unique features of growth inhibition in Chinese hamster ovary (CHO) cells. Stable mutants which are more than 600-fold resistant to these drugs are obtained in CHO cells at a strikingly high frequency of approximately 10(-3), in the absence of mutagenesis. The mutants resistant to toyocamycin (Toyr) and tubercidin (Tubr) exhibit similar cross-resistance patterns to the two selective drugs as well as to adenosine and 6-methyl mercaptopurine riboside, indicating that the same lesion is probably involved in all cases. The mutants examined were found to be deficient in the enzyme adenosine kinase (AK), indicating that the phosphorylation of these analogs is an essential first step in their toxic action. The above mutants (AK-) behaved recessively in cell hybrids, and segregation studies indicate that the AK locus is not linked to the X chromosome. The frequencies of similar Toyr mutants in other Chinese hamster lines, e.g., V79, CHW, M3-1, GM7, and CHO-K1, varied from similar to more than three logs less than that observed for CHO cells, indicating that various cell lines probably differ in the number of functional gene copies for this locus.


Morphologic and clinical aspects of estrogen receptors in carcinoma of the breast.

Morphological and cytologic features and preliminary survival data were correlated with the presence or absence of estrogen receptor protein in tissues from 123 primary and 26 metastatic carcinomas of the breast. The estrogen receptor positive tumors were somewhat smaller, 2.8 centimeters in diameter, than the estrogen receptor negative tumors, 3.2 centimeters, but the rate of axillary lymph node metastasis was similar. Fifty-eight per cent of the infiltrating ductal carcinomas, 64 per cent of 11 infiltrating lobular carcinomas and all eight less common cell types including: four mucinous; two papillary; one adenoid cystic, and one tubular carcinoma were estrogen receptor positive. Twenty-one of 33 aspiration smears performed were cytologically positive, the remaining 12 suspected of being carcinoma. Eleven of the 13 estrogen receptor negative tumors that were aspirated were positive possibly due to a lesser differentiation. Sixty per cent of the patients who nine to 40 months after operation are living without known recurrent disease had estrogen receptor positive tumors, but only 28 per cent of the 18 patients who have died of carcinoma of the breast or are living with known recurrent disease were in this category, suggesting that, in spite of a similar rate of axillary lymph node metastasis and without regard to the modality of treatment, estrogen receptor negative tumors tend to have a less favorable course.


High rates of enteric protozoal infections in selected homosexual men attending a venereal disease clinic.

Stool specimens from 89 high-risk, sexually active homosexual men were screened for enteric protozoal cysts. Patients whose specimens contained nonpathogenic cysts were investigated further by examination of fresh purged specimens. A total of 27 of the initial specimens (30%) contained protozoal cysts. Twenty-three patients (26%) harbored pathogens. There were 18 cases (20%) of amebiasis and 11 cases (12%) of giardiasis. Six men (7%) had concurrent amebiasis and giardiasis. The presence of infections correlated with a history of anilingus but not with place of birth, travel, or history of symptoms. The exceptionally high rate of prevalence of intestinal protozoal infection in this population suggests that enteric protozoal infections are important among sexually transmitted diseases.


Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma.


The control of lymphoid leukosis in a flock White Plymouth Rock chickens.

Lymphoid leukosis (LL) was successfully controlled in a commercial basic breeding line of White Plymouth Rock chickens. The control method has been developed for breeder flocks and consists of three elements: --In the flock under study, homogenates of embryos from all eggs collected during a number of 14-day periods are tested for the presence of LL viruses. --Only eggs from hens that have been shown not to shed virus in their eggs are used for the production of progeny. The offspring are reared in isolation during the first two months of life, at which time the age-related resistance against tumour formation by LL viruses appears to be sufficiently developed. --The chickens are subsequently inoculated intramuscularly with LL viruses of subgroups A and B transferred to a conventional chicken house. The vaccination raises a solid immunity to horizontal LL virus exposure and, due to the age-related resistance, tumour formation does not follow. No excretion of LL viruses could be detected in three generations of White Plymouth Rock chickens to which the three elements of the control procedure were applied. Clinical disease was not observed in any of the chickens under notice.


ELISA for the serology of FIP virus.

An enzyme linked immunosorbent assay (ELISA) for feline infectious peritonitis (FIP) virus serology is described. The assay is analogous to a previously developed indirect heterologous immunofluorescence test (IFT) in which transmissible gastroenteritis (TGE) viral antigen was used. Comparative testing of selected feline sera in both assays resulted in corresponding titers, which justifies the conclusion that the ELISA is a reliable test for the serology of FIP virus.


[Carcinogenic effect, on the liver, of an insecticide: aramite (author's transl)].

Aramite has been administered to male rats by oral route during 56 weeks at a daily dose of 400 mg/kg. There was a decrease of the body weight and several animals died. Liver hypertrophy was observed with neoplasic proliferation of parenchymatous cells and cholangiocarcinoma.


Where are they now? A follow-up study of suicide attempters from the Golden Gate Bridge.

The Golden Gate Bridge is currently the number one suicide location in the world. From the opening day, May 18, 1937 to April 1, 1978, there have been 625 officially reported suicide deaths and perhaps more than 200 others which have gone unseen and unreported. Proposals for the construction of a hardware antisuicide barrier have been challenged with the untested contention that "they'll just go someplace else." This research tests the contention by describing and evaluating the long-term mortality experience of the 515 persons who had attempted suicide from the Golden Gate Bridge but were restrained, from the opening day through the year 1971 plus a comparison group of 184 persons who made nonbridge suicide attempts during 1956--57 and were treated at the emergency room of a large metropolitan hospital and were also followed through the close of 1971. Results of the followup study are directed toward answering the important question: "Will a person who is prevented from suicide in one location inexorably tend to attempt and commit suicide elsewhere?"


Effect of cyclic AMP on transformation and proliferation of leishmania cells.

A correlation between cyclic AMP (adenosine 3' : 5'-monophosphate) concentration within Leishmania cells and proliferation and transformation is demonstrated. By addition of dibutyryl cyclic AMP and cyclic AMP-phosphodiesterase inhibitors to the culture medium the intracellular level of cyclic AMP was increased. In the presence of 1mM caffeine the level of cyclic AMP accumulated in L. tropica promastigotes from 90 pmoles up to 380 pmoles per 10(9) cells, whereas the proliferation rate decreased to 50%. In the case of L. donovani the transformation of amastigotes to promastigotes was inhibited by addition of dibutyryl cyclic AMP as well as caffeine and papaverine. Especially caffeine (2mM) and papaverine (0.1mM) reduced the transformation rate to less than 5% after 48 h, compared to 35% of the control.


Isolation of CEA-like material from urinary bladder carcinoma.

Carcinoembryonic antigen (CEA)-like material from urinary bladder carcinoma was purified and compared with the immunological and physico-chemical properties of CEA isolated from colon cancer. After immunoadsorbent purification, the final step in a purification procedure similar to that adopted for colon cancer CEA, two main molecular species were identified: 1) Material identical with colon cancer CEA with respect to molecular size, PCA solubility, ability to bind to Con A, and most important the ability to bind to specific monkey anti-CEA serum. 2) Material with the same chromatographic and immunological properties as NCA.


Adrenal cortical tumors in children.

A review of the literature reveals 230 cases of adrenal cortical tumors in children. We add an additional 7 cases. Signs, symptoms, laboratory studies, and treatment of this rare rate tumor are discussed.


Histopathology and epidemiology of breast cancer in the Padua area.

The histologic epidemiology of all breast cancer cases that had been diagnosed in the Padua area over an 11-year period was studied, and the absolute and relative distribution of breast cancer, location indices according to histologic types, 5-yr distribution and annual age-specific incidences of infiltrating and noninfiltrating cancers, as well as noncancerous disease were calculated. The results suggest that the Padua area should be considered a medium-high risk area along with England and Scandinavia.


Observations on outbreaks of respiratory disease in housed calves--(2) Pathological and microbiological findings.

Extensive pneumonic lesions were present in 42 out of 43 calves obtained for post mortem examination from 34 outbreaks of respiratory disease in Northern Ireland. Bronchiolitis and alveolitis with necrosis of bronchiolar mucosa which progressed to bronchiolitis obliterans and peribronchiolar fibrosis were prominent histopathological features in the lungs of calves obtained live. The majority of calves which died within the first two months of these outbreaks had severe exudative bronchopneumonia with marked vascular damage and necrosis of pulmonary parenchyma. Pasteurella spp, Mycoplasma spp and P13 virus were the organisms most frequently recovered from the pneumonic lungs.


[Serologic methods for the overall diagnosis of bovine herpes mamillitis].

Developed were methods of seroneutralization, agar gel precipitation, and complement-fixation test (CFT) for the complex diagnosis of herpes mamillitis of herpes mamillitis in cattle. An agreement was found between the results obtained with the use of each method. Highest sensitivity and specificity possessed the seroneutralization reaction with which a highest percent of positively reacting sera was revealed (18.6). However, the CFT method could preferably be applied in mass investigations as it is more quickly and readily used as a screening test. By means of the agar gel precipitation and CFT methods the antigenic relatedness between Bovid herpesvirus 2 and the remaining representatives of the herpes virus group, and chiefly Human herpes virus 1, could be demonstrated.


[Virus-neutralizing activity of colostral immunoglobulins in swine vaccinated with an inactivated vaccine against Aujeszky's disease virus].

Colostral globulins of sows immunized with an ethanol-saponin vaccine against Aujeszky's disease virus were fractionated through gel filtration by means of Sephadex-200. The virus-neutralizing activity of the globulin fractions identified through agar gel immunoelectrophoresis was evaluated by the virus-neutralizing test with cell cultures. The level of the antibodies found in class IgG substantially exceeded that of the IgA antibodies. It is believed that after muscular application of an ethanolsaponin vaccine against Aujeszky's disease the mammary gland of the vaccinated sows secretes virus-neutralizing antibodies mainly of the IgG class.


[Residues of the antifluke preparations, dovenix and acredist, in sheep milk and their effect on the biochemical blood indices of sheep].

The excretion of residual amounts of acedist and dovenix with the milk of sheep that had been treated with these preparations was established on the 24th, resp., up to the 27th day following treatment, though their presence in the milk was found to drop sharply after the third day. The treatment with acedist led to a dependable decrease (P less than 0.05) in the hemoglobin amount, the total protein, and the erythrocyte count, and a dependable increase (P less than 0.05) in the leukocyte count. The intensity of these changes subsided parallel to the decrease in the residual amounts of the preparation in the milk excreted. The treatment with dovenix did not result in any deviations of the indices refered to.