Thyroxine analogues. 23. Quantitative structure-activity correlation studies of in vivo and in vitro thyromimetic activities. Quantitative structure-activity correlation studies of thyroid hormone analogues have been utilized to examine (1) in vivo rat antigoiter activities; (2) in vitro binding affinities to intact rat hepatic nuclei, solubilized rat hepatic nuclear protein receptors, and the plasma protein thyroxine binding globulin; and (3) correlations between in vivo antigoiter activities and in vitro binding to nuclear receptors. These studies provide a more precise elucidation of the relative importance of the physiochemical factors which influence thyromimetic activities. In particular, they (1) provide the first systematic QSAR examination of drug-receptor interactions and of the dependence of in vivo activity on such interactions; (2) demonstrate the importance of the interactive effects of the 3' and 5' substituents and of the 4'-OH with each other as well as with nuclear receptors in influencing binding affinity; (3) support the hypothesis that binding to nuclear receptors is the first step in initiating the events which lead to subsequent hormonal expression; (4) show that the free energy of binding to nuclear receptors can be factored into the contributing physicochemical properties of the substituents; and (5) suggest factors that need to be considered in designing new analogues.


Synthesis, structure, and reactivity of adenosine cyclic 3',5'-phosphate benzyl triesters. A series of triesters of adenosine cyclic 3',5'-phosphate was synthesized by treatment of the free acid with various diazoalkanes (R=H, CH3, C6H5,0-NO2C6H4, p-NO2C6H4, p-CH3C6H4). The resulting diastereomeric mixtures were separated into their axial and equatorial components. Hydrolysis of the compounds was examined as well as photolysis of the photolabile o-nitrobenzyl ester. All compounds were then tested for their ability to activate the cAMP-dependent protein kinase and for their ability to serve as a substrate for the cAMP phosphodiesterase showing almost no effect on either enzyme. In a biological assay the benzyl triesters were able to penetrate into C 6 rat glioma cells and to induce the typical morphological alteration of the cell shape known for high cellular levels of cAMP. It was concluded that the benzyl triesters of cAMP are useful derivatives which can be efficiently and specifically converted to the parent nucleotide. Benzyl derivatives of biologically active phosphodiesters may provide a useful tool for study in biology and pharmacology.


Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine. In order to evaluate the influence of the cyano group on the antiviral activity of pyrimidine deoxyribonucleosides, a moderate yield, unified approach to the synthesis of both 5-cyanouridine and 5-cyano-2'-deoxyuridine was developed. Thus, treatment of the appropriate acetylated 5-bromouracil nucleoside with NaCN or KCN in Me2SO at 90-110 degrees C gave, after deblocking, 35-45% yields of the corresponding 5-cyanouracil nucleosides. 5-Cyanouridine was devoid of significant activity against vaccinia virus, herpes simplex-1, and vesicular stomatitis virus, but 5-cyano-2'-deoxyuridine, while lacking activity against herpes simplex, showed significant inhibition of vaccina virus; for instance, 5-cyano-2'-deoxyuridine inhibited vaccinia virus replication at concentrations 10-20 times that required for inhibition by the known antivirals, 5-iodo-2'-deoxyuridine and 1-(beta-D-arabinofuranosyl)adenine. Replacement of the 5-halogeno substituents of pyrimidine deoxyribonucleosides thus decreases, but does not abolish, antiviral activity.


Agonist effects of beta-phenethylamines on the noradrenergic cyclic adenosine 3',5'-monophosphate generating system in rat limbic forebrain. Stereoisomers of p-hydroxynorephedrine. Significant agonist activity for the specific noradrenergic cyclic adenosine 3',5'-monophosphate (cAMP) generating system in rat limbic forebrain requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, neither of the enantiomers of p-hydroxynorephedrine nor of p-hydroxynorpseudoephedrine mimics the agonist activity of (R)-norepinephrine. It has yet to be established whether or not one of the p-hydroxynorephedrines exhibits antagonist activity in this same system.


Cyclic nucleotide levels in mouse mammary epithelial cells during growth arrest and growth initiation in culture. Intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in high and low tumorigenic mouse mammary epithelial cells during growth arrest in 1% fetal bovine serum and during the first 60 minutes after serum stimulation of cell proliferation in arrested cultures. Stationary MCG-T14 cells, which are highly tumorigenic and grow to high densities in 1% serum, exhibited lower levels of cAMP, higher levels of cGMP, and a lower ratio of cAMP to cGMP than quiescent MCG-V14 cells, which have low tumorigenicity and achieve low cell densities in 1% serum. Within 5-10 minutes after cell growth was initiated in arrested cultures by the addition of serum, both cell lines responded with a fourfold to fivefold increase in cGMP and a concomitant 50% decrease in cAMP. MCG-T14 cells exhibited the highest intracellular levels of cGMP and the lowest cAMP to cGMP ratio within 10 minutes after serum addition.


Tissue-specific antibodies against human lung and breast carcinoma dehistonized chromatins. Tissue-specific antisera against human lung and breast carcinoma dehistonized chromatins were obtained. The specificity of these antisera was determined by complement fixation. In the presence of antiserum against human lung carcinoma, only chromatins from lung carcinoma fixed complement significantly, whereas chromatins isolated from human breast carcinoma, HeLa cells, normal lung tissue, breast tissue, or term placenta were negative (i.e., inactive). In a similar assay with the use of antiserum against dehistonized breast carcinoma chromatins, only breast carcinoma chromatins fixed complement. Immunohistochemical localization of the antigens by the horseradish peroxidase bridge method demonstrated their presence in the nuclei.


Herpesvirus saimiri-induced lymphoproliferative disease in howler monkeys. Four of 5 howler monkeys (Alouatta caraya) experimentally infected with Herpesvirus saimiri (HVS) developed a rapidly fatal malignant lymphoma accompanied by peripheral T-cell lymphocytosis. HVS was isolated from fresh and tissue cultured blood and tissue lymphocytes and from cell cultures derived from nonlymphoid organs. Humoral antibodies against HVS-induced antigens were detected in the sera of the animals. The in vitro response of the peripheral blood lymphocytes to mitogenic stimulants was depressed following HVS infection.


Immunopathogenicity and oncogenicity of murine leukemia virus. III. Quantitation of spontaneous virus expression. Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues. There was, however, a direct correlation between numbers of virions in epithelial tissues and levels of serum gp70.


Effect of immune manipulation on natural immune responses to murine mammary tumor antigens. The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered.


Lymphoproliferative diseases of fowl: JM-V leukemic lymphoblasts in cell culture. JM-V leukemic lymphoblasts were established in cell culture. The cultured cells (JM-VLC cells) were transplantable in young chicks and produced a disease indistinguishable from JM-V lymphoblastic leukemia as initiated by whole-blood inoculation. JM-VLC cells maintained a normal female karyotype through 13 passages in Rhode Island Red cockerels. With the use of JM-V antisera and antisera from birds with naturally occurring Marek's disease (MD), specific antigens were detected on the surfaces of living cells. Intracellular antigens were detected with anti-MD virus sera after cultivation for at least 1 day at 37 degrees C. In spite of the expression of MD antigens, the presence of herpesvirus particles associated with the cultured cells, and the occurrence of foci of multinucleated cells in kidney cultures from chicks inoculated with cellfree preparations of JM-VLC cells, the pathologic potential of the cultured cells was that of JM-V leukemia.


Isolation of T-lymphocytes from disaggregated tumors, with high purity and good percentage recovery. A combination of two cell separation methods was utilized for the isolation of thymus-derived lymphocytes (TL) from enzymatically disaggregated tumors. Passage through Sephadex G-10-glass bead columns to remove adherent cell types followed by exposure to IgG-coated sheep red blood cell monolayers for removal of Fc receptor-bearing inflammatory cells provided functional TL suspensions of high purity with good percentage recovery.


Evidence that B-lymphocytes carry the nuclear pocket abnormality associated with bovine leukemia virus infection. Peripheral blood lymphocytes from 3 cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool-adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin (B-cells) and the frequency of lymphocytic nuclear pockets in each sub-population were then determined. In each case the adherent population consisted predominantly of B-cells with an increased nuclear pocket frequency, whereas the nonadherent cells were 98.99% negative for surface immunoglobulin (non-B-cells) and contained essentially no nuclear pockets. These findings provided additional evidence that the B-subpopulation of cells was highly involved in bovine leukemia oncogenesis.


Partial characterization of a herpes-type virus (K9V) derived from Kaposi's sarcoma. A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts.


Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma and other neoplastic conditions. Sera from patients with nasopharyngeal carcinoma (NPC) or other malignant diseases and from apparently healthy controls were examined for Epstein-Barr virus (EBV) antibodies. A difference existed in the percentage of positive sera among the groups studied. High-titer antibody levels were observed in the NPC group, but no statistical difference was found among other groups of patients and controls. The data reaffirmed the association of EBV with NPC but did not support its etiologic role in the development of other human neoplasms.


Establishment of an Epstein-Barr virus-determined nuclear antigen-negative human B-cell line from acute lymphoblastic leukemia. A human B-cell line designated as BALL-1 was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). Neither Epstein-Barr virus (EBV) particles nor EBV-determined nuclear antigen (EBNA) was detectable. The morphologic and growth characteristics were clearly distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. BALL-1 cells probably originated from the donor's leukemia cells as judged from their cytogenetic, morphologic, and surface features. The BALL-1 line was the first EBNA-negative B-cell line established from ALL.


Plasma ACTH in rats following medical adrenalectomy. We have previously reported that surgically adrenalectomized nonstressed rats showed delayed secretion of the expected increase in plasma ACTH concentrations following adrenalectomy.(1) However, increased plasma ACTH concentrations were always detected when these animals were subjected to severe stress, and their responsiveness increased again seven days or more following surgical adrenalectomy. We are now reporting similar results which were obtained following prolonged systemic glucocorticoid administration (medical adrenalectomy) in similar groups of rats.


Alteration of the intracellular energetic and ionic conditions by mengovirus infection of Ehrlich ascites tumor cells and its influence on protein synthesis in the midphase of infection. Mengovirus infection of Ehrlich ascites tumor cells caused a change of the intracellular ATP concentration. It increased by 35% within the first 3 h postinfection and then declined to zero within the next 5 h. The decrease in the ATP concentration was due, at least in part, to leakage of ATP into the medium, where it could be demonstrated by the luciferin-luciferase assay. Gross leakage of ATP was observed at 4.5 h postinfection, concomitant with the production of the first intracellular, infectious virus particles. A similar concentration decrease was detected for Mg(2+), the polyamines, and K(+), whereas an increase in the Na(+) concentration was observed. The intracellular Mg(2+) concentration varied synchronously with the ATP level, rising by 16% during the first 3 h postinfection and then progressively falling to lower values in the late period of the infectious cycle. After an initial slight enhancement, the putrescine, spermidine, and spermine concentrations declined at about 1.5 h postinfection. Wherease the intracellular K(+) concentration increased by 17% during the first hour postinfection, the Na(+) concentration diminished by the same value within the same time period, leaving the internal ionic strength unchanged early in infection. Three hours after the beginning of virus infection, there was a rapid decline of K(+) and enhancement of Na(+) within the cell. These alterations of the intracellular energetic and ionic conditions seem to be, at least in part, responsible for the cessation of virus-specific protein synthesis in mengovirus-infected Ehrlich ascites tumor cells commencing 3 to 3.5 h postinfection.


Analysis of precursors to the envelope glycoproteins of avian RNA tumor viruses in chicken and quail cells. Immune precipitation with monospecific antiserum was employed to study the intracellular synthesis of viral glycoproteins gp85 and gp37. Labeled gp85 and gp37 were detected from lysates of cells transformed with Rous sacroma virus, strain B77, after long-term labeling with radioactive glucosamine or phenylalanine. Immune precipitates prepared from lysates of cells pulse-labeled for a short time resulted in a glycoprotein of 92,000 molecular weight (gp92). This precursor was stable in B77-transformed Japanese quail cells for several hours, whereas in chicken cells it could be chased within a few hours into virion glycoproteins gp85 and gp37. Similarly, the precursor for the structural viral proteins, pr76, persisted in quail cells much longer than in chicken cells. During very short pulses or in the presence of a glucosamine block (25 mM glucosamine), the antiserum against the viral envelope glycoproteins detected a precursor of higher electrophoretic mobility of approximately 70,000 molecular weight, "p70." Fucose label entered gp92 and gp85 as well as "p70." Proteolytic treatment of virion-bound gp85 in vitro generated two discrete glycoproteins of 62,000 and 45,000 molecular weight, but did not result in an increase in the amount of gp37.


Donation of N- or B-tropic phenotype to NB-tropic murine leukemia virus during mixed infections. The IC isolate of Moloney murine leukemia virus (MuLV), which is NB-tropic, was grown in cells producing conditionally defective or defective virus particles derived from N- or B-tropic MuLV. The infectious MuLV that was then released was found to be sensitive to Fv-1 restriction but produced NB-tropic progeny upon passage. These results indicate that this NB-tropic MuLV can acquire sensitivity to Fv-1 restriction by phenotypic mixing with N- or B-tropic MuLV. It is thus suggested that NB-tropic MuLV is insensitive to Fv-1 restriction simply because it lacks the determinants of tropism.


Formation of reticuloendotheliosis virus pseudotypes of Rous sarcoma virus. Superinfection of chicken embryo fibroblasts transformed by the defective Bryan strain of Rous sarcoma virus (BH-RSV) with two different reticuloendotheliosis viruses (REVs), REV strain T (REV-T) or spleen necrosis virus (SNV), resulted in the production of infectious sarcoma virus pseudotypes. These pseudotypes were neutralized by antiserum prepared against SNV and were unable to infect chicken cells preinfected with either REV-T or SNV. These results suggest that defective BH-RSV is able to use the glycoprotein from REV to form infectious pseudotypes. On the other hand, neither REV-T nor SNV was able to supply a functional reverse transcriptase to the polymerase-negative mutant BH-RSValpha, nor was REV-T or SNV able to complement the defect in the internal protein gene of the temperature-sensitive avian sarcoma virus mutant NY45.


Multiple free viral DNA copies in polyoma virus-transformed mouse cells surviving productive infection. Mouse 3T6 cells were infected with polyoma virus at high multiplicity, and survivors were isolated. Clones from single cells were then established and were found to be resistant to a second infection. However, in some clones viral functions could at least be partially expressed during reinfection, as judged from a stimulation of nuclear tumor antigen expression. One such clone was studied in detail. These cells were transformed and produced low amounts of virus (less than 1 PFU per cell per generation). The persistent infection did not seem to be a carrier-state phenomenon, since infectious-center assays showed that most cells produced virus. The resistance of the cells to reinfection can be explained by interference from viral DNA present in the cells, averaging about 1,500 "free" copies per cell. This DNA had the normal physical characteristics of polyoma DNA. However, it had a slightly larger size than authentic polyoma DNA. Mapping with restriction endonucleases showed that the addition to the DNA was about 5% of the wild-type genome and was located close to the origin of DNA replication. This DNA was infectious, although it had a 10-fold lower infectivity than wild-type polyoma DNA. Both virus and DNA from the polyoma-resistant cells had a small-plaque morphology, as opposed to the large-plaque morphology of the virus used for the initial selection of cells.


Simian virus 40 gene A regulates the association between a highly phosphorylated protein and chromatin and ribosomes in simian virus 40-transformed cells. The species of proteins associated with chromatin and ribosomes of simian virus 40 (SV40)-transformed and untransformed monkey, mouse, and rat cells have been compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after phosphorylation of these proteins either in vivo or in vitro. In vitro phosphorylation was carried out by protein kinase associated with these organelles and [gamma-(32) P]ATP as the phosphoryl donor. The reaction products contained both phosphoserine and phosphothreonine in approximately equal amounts. The electrophoretic analysis of the phosphorylated proteins revealed that the highly phosphorylated protein with a molecular weight of approximately 90,000 (90K protein) was associated with chromatin and ribosomes from transformed cells but not from untransformed cells. The 90K protein could be extracted from chromatin and ribosomes with 0.5 to 1.0 M NaCl or KCl. The 90K protein was still associated with the runoff ribosomes prepared by the puromycin reaction of the post-mitochondrial supernatant in the protein-synthesizing system. In vitro phosphorylation of chromatin and ribosomes from SV40 tsA-transformed mouse and rat cells indicated that the amounts of 90K protein associated with these organelles decreased greatly when the cells were cultivated at the restrictive temperature. A similar temperature-dependent decrease in the amount of (32)P-labeled 90K protein was observed in nonhistone chromosomal and ribosome-associated protein fractions prepared from SV40 tsA-transformed cells labeled with [(3)H]leucine and [(32)P]orthophosphate in vivo. In vitro phosphorylated 90K protein in nonhistone chromosomal and ribosome-associated proteins extracted with high salt was not immunoprecipitated with anti-SV40 T sera.


Characterization of simian virus 40 tsA58 transcriptional intermediates at restrictive temperatures: relationship between DNA replication and transcription. When nuclei from simian virus 40 (SV40)-infected cells are lysed with Sarkosyl and the chromatin is pelleted, the supernatant fluid contains a nucleoprotein complex capable of synthesizing viral RNA (Laub and Aloni, Virology 75:346-354, 1976; Gariglio and Mousset, FEBS Lett. 56:149-155, 1975). The level of activity of the RNA polymerase in the complex increased during infection in parallel with the amount of viral DNA that had been synthesized. If cells infected at 33 degrees C with the SV40 mutant tsA 58 were shifted to the nonpermissive temperature of 40 degrees C at any time between 18 and 48 h postinfection, no viral DNA replication was detected after 45 min and no new rounds of synthesis were initiated after 20 to 30 min. However, after this shift, polymerase activity associated with the nucleo-protein complex did continue to increase for 5 h, at which time it reached a plateau. There was an increase of RNA synthesized from both the early (E) and late (L) SV40 DNA strands, and there was a threefold increase in the ratio of early-to-late RNA species after the shift. In comparable experiments with cells infected with wild-type virions, no increase in polymerase activity occurred because of the temperature change alone. At 33 degrees C, the relative amount of RNA transcribed from the wild-type E-strand was less than tsA 58 at 33 degrees C and did not increase after a shift to 40 degrees C. The tsA 58 transcriptional complexes extracted from cells grown at 33 degrees C sedimented heterogeneously in sucrose gradients, with a peak near 26S. There were no detectable alterations in the sedimentation properties of the complexes when tsA 58-infected cells were shifted to 40 degrees C for 2 h. We conclude that continued synthesis of viral DNA is not an obligatory prerequisite for maintenance of late viral transcription nor is the sedimentation of the transcriptional complex at 26S related to actively replicating DNA molecules serving as templates for transcription. Further, an increase in late transcription can occur under conditions where reinitiation of viral DNA synthesis is prevented. The increase in the synthesis of early and late RNA at the restrictive temperature without concurrent DNA synthesis is discussed in relationship to the function of the A gene product.


In vitro translation of Harvey murine sarcoma virus RNA. The viral RNA of the Harvey strain of murine sarcoma virus (Ha-SV), which does not encode for any known viral structural polypeptides, has been translated in a nuclease-digested, cell-free system. The major protein product of the in vitro translation reaction has a molecular weight of 21,000 and is initiated faithfully with [35S]formylmethionine from formyl-[35S]methionyl-tRNAFMET. This polypeptide is clearly distinct from the RNA of the Moloney strain of type C helper virus used to pseudotype the Ha-SV. The intensity of the 21,000-dalton polypeptide on gels correlates well to the concentration of Ha-SV RNA in different viral RNA preparations. These experiments indicate that a polypeptide marker for Ha-SV is now available for the first time. The possibility that this protein is the product of the rat portion of the Ha-SV genome is discussed.


Regulation of herpesvirus macromolecular synthesis. VI. Synthesis and modification of viral polypeptides in enucleated cells. Cells were enucleated with cytochalasin B after infection with herpes simplex virus 1. When protein synthesis was blocked by cycloheximide from the time of infection, mRNA for viral alpha-infected cell polypeptides (ICP) 4, 0, and 27 accumulated in the cytoplasm and was expressed after the removal of both drug and nucleus. A host protein, ICP 22, whose synthesis is stimulated in intact cells, was not made, and viral protein ICP4, which is normally modified to a form that migrates more slowly in polyacrylamide gels, was not modified in the absence of the nucleus. After enucleation at 2 h postinfection, a number of viral beta and gamma proteins continued to be made, starting at 20 to 25% of the normal rates and declining with a half-time of about 2 h. The synthesis of ICP 4 declined more rapidly, suggesting that it is switched off in the cytoplasm.


Replication of herpesvirus DNA. III. Rate of DNA elongation. The rate of pseudorabies virus DNA elongation was measured by three different techniques: density shift experiments, radioautography examined by light microscopy, and radioautography examined by electron microscopy. The rate of the fork movement at 37 degrees C was estimated to be approximately 1 micron/min.


Cell-free synthesis of herpes simplex virus proteins. Polyribosomes isolated from herpes simplex virus type I (HSV-1)-infected cells have been used to program a eucaryotic cell-free translation system. At least 10 HSV-specific polypeptides, with apparent molecular weights of 25,000 to 160,000, are synthesized by wild-type HSV-infected polyribosomes. Polyribosomes prepared from thymidine kinase-negative mutants of HSV direct the synthesis of three putative nonsense termination polypeptides. HSV-specific polypeptides synthesized in vitro are precipitated with antiserum to HSV-infected cell proteins.


Episomal viral DNA in a Herpesvirus saimiri-transformed lymphoid cell line. The lymphoid cell line #1670 has been derived from the infiltrated spleen of a tumor-bearing marmoset monkey infected with Herpesvirus saimiri. The cells contain both types of H. saimiri DNA, unique light (L-) DNA (36% cytosine plus guanine) and repetitive heavy (H-) DNA (71% cytosine plus guanine), without producing infectious virus. Viral DNA was found to persist in these cells as nonintegrated circular DNA molecules. Closed circular superhelical viral DNA molecules were isolated by three subsequent centrifugation steps: (i) isopycnic centrifugation in CsCl, (ii) sedimentation through glycerol gradients, and (iii) equilibrium centrifugation in CsCl-ethidium bromide. The isolated circles had a molecular weight of 131.5 +/- 3.6 x 10(6). This is significantly higher than the molecular weight of linear DNA molecules isolated from purified H. saimiri virions (about 100 x 10(6)). Partial denaturation mapping of circular molecules from #1670 lymphoid cells showed uniform arrangement of H- and L-DNA sequences in all circles. All denatured molecules contained two L-DNA regions (molecular weights of 54.0 +/- 1.8 x 10(6) and 31.5 +/- 1.3 x 10(6)) and two H-DNA regions (molecular weight of 25.6 +/- 1.9 x 10(6) and 20.0 +/- 0.8 x 10(6)) of constant length. Maps of both L-regions suggested that the sequences of the shorter L-DNA region were a subset of those of the longer region. The sequences of both L-regions had the same orientation. Circular molecules from H. saimiri-transformed lymphoid cell line #1670 appeared to represent defective genomes, containing only 75% of the genetic information present in L-DNA of H. saimiri virions.


Presence of Epstein-Barr virus receptors, but absence of virus penetration, in cells of an Epstein-Barr virus genome-negative human lymphoblastoid T line (Molt 4). This paper reports a unique type of interaction of Epstein-Barr virus (EBV) with an EBV receptor-positive, genome-negative human lymphoid T cell line (Molt 4), which can be summarized as follows. Although Molt 4 cells express receptors for EBV, they appear to block the penetration of this virus. These observations are derived from combined studies with immunofluorescence and electron microscopy. It is possible that T cell lines bearing receptors for EBV may express such a control on virus penetration.


Electrophoretic analysis of the molecular weight of murine mammary tumor virus RNA. Molecular weight determinations of native and subunit RNAs of murine mammary tumor virus (MuMTV), a type B oncornavirus, were performed by polyacrylamide gel electrophoresis and compared with molecular weights of well-characterized avian cellular RNAs and tobacco mosaic virus RNA. From extrapolations of semilog plots of the molecular weights of the standard RNAs versus relative electrophoretic mobilities and Ferguson plots, the subunit and native RNAs of MuMTV were found to possess molecular weights of 2.93 X 10(6) and 6.45 X 10(6), respectively. These data support the assumption that two subunit molecules comprise the native RNA of MuMTV.


Properties of the polyoma viruses induced from BHK-21 cells transformed by A gene mutants. Polyoma viruses induced to replicate at 31 degrees C in BHK-21 cells transformed by polyoma A gene mutants retain the thermosensitive growth characteristics and genome structure of the original mutants used for transformation.


Characterization of visna virus envelope neuraminic acid. Visna virus particles inhibit influenza virus hemagglutination in an assay for neuraminic acid-containing viruses. Pretreatment of visna virus with neuraminidase abolished hemagglutination inhibition activity but did not significantly affect attachment, infectivity, or virus-induced cell fusion in sheep choroid plexus cell monolayers.


Mucinous adenocarcinoma of the prostate. The third case of mucous-forming adenocarcinoma of the prostate with metastases to the bone is reported. The primary tumor was unresponsive to definitive radiotherapy and subsequent metastases to the lung, liver and bone failed to respond to hormonal manipulation and chemotherapy.


Androgen binding in human testis.

Androgen binding in human testis. Cytosol preparations of human testis contain macromolecules that bind tritiated dihydrotestosterone. Studies of steroid competition, heat sensitivity and dissociation rate constants indicate a similarity to serum testosterone-estradiol-binding globulin. The amount of binding of tritiated dihydrotestosterone is greater than could be explained by contamination of testis by serum.


Pancreatic carcinoma. Survival following detection by ultrasonic scanning. The survival of 28 patients with pancreatic cancer was studied following initial detection of this malignant neoplasm by ultrasonic scanning. By ultrasound examination, 24 patients had an abnormality, and 21 had a demonstrable mass. Twenty-seven patients are now deceased, and the overall survival ranged from eight days to 24 months (mean, 6.1 months). The results of this study indicate that diagnosis by ultrasonic scanning had no effect on the survival of patients with pancreatic carcinoma.


Tangier disease (alpha-lipoprotein deficiency). A patient with asymptomatic hypocholesterolemia, mild hyperbilirubinemia, and splenomegaly was found, on lipoprotein analysis, to have Tangier disease (alpha-lipoprotein deficiency). He represents the first patient with the disease in the northeastern Unit States. Although free of clinical evidence of atherosclerosis at age 38 years, the patient has widespread tissue cholesterol ester deposition and a stron family history of atherosclerosis. Tangier disease may be much underdiagnosed; it should be suspected in every patient with hypocholesterolemia.


Human reovirus-like agent infection. Occurrence in adult contacts of pediatric patients with gastroenteritis. Sixty-four adult family contacts of 61 young patients with gastroenteritis were included in a study for evidence of concurrent infection with the human reovirus-like agent (HRVLA) of infantile diarrhea. Evidence of infection was detected in 26 (41%) of the adult contacts. The HRVLA infection occurred significantly more often among adult contacts of pediatric patients infected with HRVLA (55%) than among contacts of young patients not infected with the agent (17%). Mild cases of gastroenteritis developed in only three of the contacts infected with HRVLA.


Indications for liver and brain scans. Screening tests for patients with oat cell carcinoma of the lung. From 1973 to 1975, scans of the liver and brain as routine screening procedures were performed on patients with oat cell carcinoma of the lung at the Memorial Sloan-Kettering Cancer Center. Normal test results were observed in 20 of 21 and 32 patients who showed no clinical evidence of involvement of the liver and brain. Only one scan in 21 and one in 35 yielded new information concerning possible organ involvement. We concluded that scans of the liver and brain are not useful methods of screening the patient with no clinical evidence of oat cell carcinoma.


Peripheral nerve conduction velocities in chain-saw operators. The motor, sensory and mixed nerve conduction velocities of median and posterior tibial nerves were measured in seventeen forest workers engaged in chain-saw operation for 2 to 16 yr (mean 12 yr). The conduction velocities were significantly diminished in the distal part of the upper limb. The sensory nerve conduction velocities (SCV) of the median nerve at the part of the palm were slow in 12 workers; longer residual latency, in 6; and the mixed nerve conduction velocities slowed at the part of the forearm, in 6. From the relationships of the nerve conduction velocities to white finger attacks and electromyograms, it was assumed that vibration directly affected the distal part of the sensory and motor nerve fibers in the upper limbs, and that the diminished SCV in the palm was one of the most sensitive indices of vibration effects.


Carcinoma arising in the cyst of the liver--report of three cases--. A generally recognized concept dictates that surgical intervention for non-parasitic cysts of the liver is mostly palliative such as aspiration of the content, suture and closure, internal or external drainage, marsupialization, and unroofing of the cyst, while total excision of the entire cyst, which sometimes necessitates hepatic resection, is not usually recommended.3, 6, 9 The results of these lesser procedures have been acceptable, favoring those conservative procedures. This paper presents three cases with carcinoma arising in the cysts of the liver. Review of the present cases with five comparable cases appearing in the literature revealed that young female population and left lobe of the liver are frequently involved. Hence the general trend for palliative procedures should be reassessed. Possible malignancy should be considered when a patient belongs to this category, the cystic content is not clear, or the cystic wall presents irregular texture with nodules. The carcinomatous changes would have been of higher incidence than reported if the entire cysts had been more carefully examined.


[Daily periods of aldosterone, sodium, and potassium excretion in the urine of newborns, infants, and children: influence of long-term steroid treatment and of the blockage of adrenergic beta-receptors (author's transl)]. Aldosterone, sodium, and potassium excretion in the urine of six newborns (5, 6, and 9 days), seven infants (2, 3, 4, and 6 months) and eight children (4, 5, 6, 12, and 15 years) was determined at 3-hour intervals during a 24-hour period via gas chromatography and/or flame photometry. The circadian rhythmn of aldosterone excretion could already be ascertained in the 5-day-old newborns. All babies and children examined showed a distinct increase in aldosterone excretion between 3 and 6 am or 6 and 9 am. On the overage, 41% of the total daily amount was excreted between 3 and 9 am. Excretion of sodium and potassium was very low for the newborns and infants. Only in small children and in school children did sodium excretion and the molecular relationship Na/k in urine have a statistically significant negative correlation with the excretion of aldosterone. After long-term prednisone therapy, the maximum amount of aldosterone was excreted in the afternoon. The findings after treatment with propranolol and administration of dexamethasone over a three-day period were similar.


[Studies on the antimicrobial effect of vitamin D (author's transl)]. In in vitro studies vitamin D3 proved inhibitory on strains of Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae. Escherichia coli, and Candida albicans. In the presence of 5x10(4)-9x10(4) IU/ml vitamin D3 the organisms were killed or reacted with a marked growth inhibition.


Viral infections of the captive Kenya baboon (Papio cynocephalus): a five-year epidemiologic study of an outdoor colony. Rectal swabs, throat swabs, fecal samples, tissues, and sera were collected from 334 adult and infant Kenya baboons (Papio cynocephalus) in captivity at this institution over a 5-year period. A total of 4,893 specimens were collected, resulting in the isolation of 582 viral isolates (11.9%). The month of November yielded the lowest isolation rate, while the month of January produced the highest rate. The most commonly isolated viruses in adults and infants were SV6 and SV23, followed by N125, SV15, and SV17 in that order in adults, and SA7, N125, SV15, V340, and SV17 in that order in infants. Nine serotypes, namely enteroviruses SV19, SV42, SA5, A13, and N203, as well as adenoviruses SV15, SV20, SV31, and SV37, were isolated only from adults. Two adenovirus serotypes, SA7 and V340, were recovered predominantly from infants.


Naturally occurring mouse hepatitis virus infection in the nude mouse. A group of athymic nude mice developed an unusual chronic wasting disease within 1-3 months after their arrival into the laboratory. Affected nude mice had severe, acute-to-chronic, active hepatitis with multinucleated giant hepatocytes and fibrosis. Vascular and central nervous system lesions were frequently present, giant cell peritonitis, ascites, and multinucleated giant cells in the intestinal epithelial villi were less frequently observed. Mouse hepatitis virus was isolated from the livers of three mice with lesions. The virus, when inoculated into nude mice, produced lesions similar to those observed in the natural outbreak.


Experimental cytomegalovirus infection and the developing mouse inner ear: in vivo and in vitro studies. Mouse cytomegalovirus causes perilabyrinthitis in the cochlea following intracranial inoculation of the newborn mouse. In spite of infection of cranial nerve ganglion cells and Schwann cells the organ of Corti achieves normal adult morphology including efferent nerve endings. No involvement of neuroaxons is seen. In comparison human cytomegalovirus infection causes endolabyrinthitis without involving periotic connective tissues or nerves even in the presence of meningoencephalitis. The lack of epithelial infection and susceptibility of periotic connective tissues to mouse cytomegalovirus was confirmed by infection of fetal mouse otocysts in organ culture. The mouse model of cytomegalovirus ear infection shows greater similarities to other herpesvirus infections of the ear such as varicella-zoster than to human cytomegalovirus and thus remains extremely useful for the study of herpetic neuronal and ear infection.


Survival of patients with carcinoma of breast without lymph node metastases in relation to the tumor types. Carcinoma of breast radical mastectomy specimens were examined. The tumors were classified in accordance with their morphologic appearance. The tumors were also graded on the basis of their cytological makeup and assigned a cytologic malignancy score (CMS). While the classification of tumors was based on the overall pattern of the tumor, the CMS was arrived at by examining the least differentiated portion of the tumor. The following conclusions were suggested by the study: Patients with tumors with high CMS have a poor prognosis, even in the absence of axillary lymph node metastases. It appears reasonable to suggest that patients without overt metastases, but with high CMS, should be considered for treatment with all therapeutic measures available. Such an aggressive approach to patients with low CMS does not appear to be justified.


The histomorphologic spectrum of endocervical (Müllerian) adenocarcinoma--a potential prognostic indicator. A review of all patients with endocervical adenocarcinoma seen at the Universtiy of Kentucky Medical Center from 1962 through 1972 yielded 15 patients with tissue-verifiable primary endocervical adenocarcinoma that had no associated sarcomatous or squamoid features. These patients varied from 17 to 73 years old with a mean age of 47 years. A malignant clear cell pattern was present in 8 patients and in 3 of these individuals that prominent morphologic feature was associated with hobnail cells. Five patients with clear cell carcinomatous changes in the endocervix were born prior to the use of diethylstilbestrol (DES) and 2 of the remaining 3 patients were exposed to DES during the first trimester of pregnancy. Other morphologic types of endocervical adenocarcinoma included mucinous adenocarcinoma in 9 patients (60%) and basaloid adenocarcinoma in one patient (7%). Cellular atypia of endocervical glands, which in some areas was consistent with adenocarcinoma in situ was found in 9 of the 15 patients with invasive endocervical cancers. Both vessel invasion by tumor cells and tumor necrosis were associated with a poor prognosis.


[Krukenberg's tumor of the ovary].

[Krukenberg's tumor of the ovary]. A 42-year-old woman, 7 months after a gastric resection for carcinoma, again underwent surgery because in the area of the left adnexa she developed a tumor, the size of two fists. Laparotomy revealed a typical Krukenberg tumour in the left ovary only. The histological finding: carcinoma gelatinosum.


Spontaneous mutations in ageing human cells: studies using a Herpesvirus probe. Several fundamental theories of ageing postulate that spontaneous mutations increase in somatic cells as they age. This has not until recently been directly tested in mammalian cells, because of the problem of estimating mutation rate in declining cell populations. One possible approach is to infect cells with lytic virus and measure the mutation frequency in virus made by the cellular machinery. Three temperature-sensitive mutants of Herpesvirus were used to infect human fibroblasts in vitro. The reversion frequency was examined in virus harvested from young and old cells. It was found that with tsE there was a hundredfold increase in reversion rate in old compared to young cells, with tsD the rates were roughly similar and with tsG a fortyfold decrease in old cells. These differences are not due to differential rates of virus production. It is proposed that errors in specific functions in old cells influence the spontaneous mutation rate of the three viral mutants in opposite directions. It is pointed out that certain unknown factors limit the usefulness of viral probes in ageing research and cast doubt on previous work of this type.


Somatic cell hybrids derived from terminally differentiated rhesus cells and established mouse cell lines. The mechanisms of normal cell differentiation in vivo may be related to some features of cellular aging in vitro in that both are considered to be under genetic control. Diploid rhesus choroidal melanocytes and purified peripheral lymphocytes were fused by means of inactivated Sendai virus with three long-term murine cell lines which lacked either hypoxanthine-guanine phosphoribosyl transferase or thymidine kinase. Cell hybrids were selected by their growth in medium containing hypoxanthine, aminopterin, thymidine, and glycine. G-banded chromosomes were analyzed and elements from both the rhesus and the established mouse cell lines were identified in all metaphases. Hybrids derived from choroid X mouse cells contained more than one chromosome set from the mouse, but those between lymphocytes and established cell lines had only one. However, in every combination continuously replicating hybrids were produced; most of them have undergone more than 40 subculture passages. Our results demonstrate not only that DNA synthesis can be re-initiated in postreplicative cells, but also that DNA continues to replicate in a manner consistent with the life span of the long-term cell line parent.


[Acupuncture for pains of the face and the head is there any reasonable application? (author's transl)]. The physiological bases of the treatment with Acupuncture as well as its practical application in pain therapy were discussed at the meeting of the ORL-Society of Munich on the 4th December, 1976.


[The clinical entity of primary tracheal cylindroma (author's transl)]. On the grounds of 5 own observations of primary tracheal cylindroma and under consideration of the cases mentioned in literature on this subject, the repeatingly occurring and, therefore, probably typical characteristics of this kind of tumour were described. In the course of the disease, three phases may quite easily be differentiated, and the special features of the main symptoms (dyspnoea, cough, expectoration, hoarseness) as well as apparently specific, however inconstant changes in the blood picture were set forth.


Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion. This study was undertaken to assess the role of alpha-adrenergic receptors in the somatostatin-mediated inhibition of pancreatic glucagon secretion. In dogs, somatostatin inhibited the pancreatico-duodenal vein output of glucagon. During an infusion of the alpha-adrenergic blocking agent phentolamine, somatostatin did not significantly inhibit the output of glucagon. Thus, alpha-adrenergic mechanisms appear to influence the ability of somatostatin to decrease pancreatic glucagon secretion.


Prevalence of serum lipid abnormalities in chronic hemodialysis. Fasting levels of serum triglyceride, cholesterol, high-density lipoprotein (HDL), apoprotein A-I, HDL cholesterol, and HDL triglyceride were measured in 94 uremic males receiving maintenance hemodialysis and 6 uremic males receiving chronic peritoneal dialysis. These patients had higher serum triglyceride levels (p less than 0.001) and lower cholesterol levels (p less than 0.001) than normal controls. The dialysis patients treated with androgen or propranolol and those who were hypothyroid or diabetic had significantly higher triglyceride levels than the other dialysis subjects. The dialysis patients who had no additional secondary causes of hypertriglyceridemia had abnormalities in HDL; in comparison to normals and triglyceride-matched controls, these patients had elevated HDL triglyceride levels and low HDL cholesterol levels, despite similar HDL apoprotein A-I levels. The HDL cholesterol levels appeared to be lower in those patients than could be accounted for by their degree of hypertriglyceridemia.


Purification of herpesvirus nucleocapsids by fluorocarbon extraction. Purified nucleocapsids were prepared from herpes simplex virus type-1 and herpes simplex virus type-2 infected cells, using a fluorocarbon extraction technique with Freon 113. Fifty to 85% of the total nucleocapsid population remained 'nucleated' or full in terms of the nucleic acid core making them useful as a source of DNA. CsCl banded DNA represented 30--40% of the theoretical yield of the total nucleocapsid population.


Studies on the neutralization of herpes simplex virus. VIII. Significance of viral sensitization for inactivation by complement. Early and late IgG of rabbits immunized with herpes virus showed, respectively, 8-fold and 2-fold enhancement of neutralization endpoint in the presence of complement (C). Kinetic curve experiments employing an appropriate amount of virus revealed that both neutralization and sensitization followed first-order reaction, and each IgG possessed a certain range of concentration where neutralization was negligible while sensitization was marked. Dose responses of neutralization and sensitization velocities demonstrated that the C enhancement of late IgG was about 7-fold and that of early IgG more than 20-fold. These facts suggested that the IgGs contained two different entities of complement-requiring (CRN) and non-requiring neutralizing (N) antibodies at different proportions, only the former being responsible for sensitization. The different CRN: N ratios obtained by the endpoint and kinetic methods may mean either that the two antibodies differ in avidity for the virus or that the number of critical sites per virion for CRN antibody is greater than that for N antibody. In this interpretation, sensitization by CRN antibody as well as neutralization by N antibody is thought to result from attachment of a single antibody molecule to the viral critical site. Alternative explanations, ascribing the mechanism of neutralization to steric hindrance of critical sites or to multiple hit of those sites by antibody, were denied by analyses of the present data.


Consumer evaluation of natural therapists and general practitioners. In recent years orthodox medicine has been extensively criticized while alternative therapies have increasingly attracted the interest of patients. A consumer evaluation of alternative therapists and general practitioners is reported and implications are discussed. The study determined also that a significant number of the natural therapy patients felt their therapist provided a primary health care service. The characteristics of this group and reasons for their affiliation are considered.


The mental health visitor and psychiatric after-care. The results of a project, originating in South Australia, designed to assist the discharge of psychiatric patients are described. The project introduced a new category of mental health worker, the mental health visitor. These mature-age "subprofessionals" attached to social work departments after a brief, specific, in-service training, have worked closely with Mental Health Services psychiatrists, psychologists and social workers in various situations. They have established good relationships with social workers in other agencies and with general practitioners and their activities have included initial assessment, liaison and after-care. The demand for them appears to be increasing.


Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge. The prophylactic intranasal medication with a new antiviral compound, 1-phenyl-3-(4 phenyl-2-thiazolyl) guanidine (CL 88,277) was evaluated in humans against rhinovirus 44 challenge. One ml containing 250 mg of CL 88,277 was administered to 10 seronegative volunteers three times a day plus one dose prior to the rhinovirus challenge (32 TCID 50) and for six consecutive post-challenge days. Ten other subjects received 56% polyethylene glycol (PEG-400), the solvent of CL 88,277 at the same time. Five subjects in each of the CL 88,277-treated and placebo-treated groups developed illness. There were no differences between the two groups in the occurrence of the severe illness and of the moderate and severe illnesses. Each sign and symptom occurred almost equally in the two groups and there was no difference in their scores between the two groups. The challenge virus was isolated from both groups but the total number of the virus isolates was less and the time span of virus excretion was shorter for the drug-treated group. The post-challenge serum antibody titers were markedly lower in the drug-treated group. Prophylactic intranasal CL 88,277 medication did not affect the course of illness induced by rhinovirus 44 challenge. It appears, however, that the virus replication in the nose was reduced and as a result the serum antibody response was diminished. PEG-400 caused a transient irritation of the nasal mucosa in all recipients.


[Ultrastructure of cytoplasmic deposits and enzyme studies in human primary liver cancer]. Authors examined of the fine structure and electronhistochemical properties of deposits observed in two cases of primary liver carcinoma. It was established, that these deposits are formed by filaments consisting of fine granules of 70 A in diameter. On the basis of morphological picture and results of the investigation by enzymatic-dogestion technique it is believed, that deposits are the product of the rough-surfaced endoplasmic reticulum and their occurrence indicate the impairment of it's function. Deposits--as revealed by the enzymatic-digestion technique--consists of complex material, the protein component of which contain large quantities of basical amino acids.


[Advances in the treatment of malignant tumors in childhood: Wilm's tumor as an example (author's transl)]. The advances in the treatment of the Wilm's tumor have been made both surgically and in the conservative field. Extirpation through a lateral incision has given way to the broad transabdominal exposure. Inoperable tumors are very rare. Cytostatics like actinomycin D and vincristine are already applied intraoperatively. The choice of cytostatic and the duration of cytostatic therapy is adjusted to the intraoperative staging. The Society for Pediatric Oncology has worked out a modified plan of treatment in accordance with the growth of the tumor, in addition irradiation is applied according to the tumor staging. The results are stated as between 60 and 70%, the histology of the tumor and the age of the child, in addition to the growth of the tumor, being especially important.


[Treatment of primary hyperlipoproteinemias of type IIB and IV with butylbiguanide and clofibrate (author's transl)]. 21 patients with primary hyperlipoproteinemias of type IIb and IV were treated for 8 weeks with placebo, 8 weeks with 0.3 g butylbiguanide and 1.5 g clofibrate/day and then for 8 weeks with 1.5 g clofibrate/day. In 12 patients a second placebo phase of 8 weeks followed. After 8 weeks of combined treatment with butylbiguanide and clofibrate the serum triglycerides decreased from 725 mg to 269 mg/100 ml. During the following period of clofibrate treatment the serum triglycerides increased after 4 and 8 weeks to 326 mg and 306 mg/100 ml respectively. The combined treatment with 0.3 g butylbiguanide and 1.5 g clofibrate/day is more effective in lowering elevated serum triglycerides and cholesterol than 1.5 g clofibrate alone.


Accentuated vascular and endocrine response to SQ 20881 in hypertension. We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.


Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brainstem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered.


Recommendations for a national policy on poliomyelitis vaccination. Declining numbers of adequately vaccinated persons, new data about the comparative safety and effectiveness of live, attenuated and killed poliomyelitis-virus vaccines, increased consumer awareness of adverse reactions and pressure from manufacturers seeking protection from liability were factors leading the Institute of Medicine to re-examine poliomyelitis vaccination programs. The relative merits of live and killed virus vaccines as immunizing agents were reviewed within the context of the 60 to 70 per cent level of poliomyelitis vaccination now reached in the United States. Until about 90 per cent of persons are adequately immunized, the continued use of live-virus vaccines for infants is recommended, with provision that certain categories of persons receive killed-virus vaccine. Vaccination with attenuated live virus of children 11 to 12 years old is suggested to reduce vaccine-associated disease when they become parents of vaccinated infants. Recommendations are made on education, research, liability and informed consent as they pertain to prevention of polyomyelitis.


Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex.


Endogenous opioid peptides: multiple agonists and receptors. Opioid peptides were assayed by inhibition of 3H-naloxone and 3H-leu-enkephalin binding in brain homogenates and by depression of contractions of the guinea pig ileum and mouse vas deferens. We conclude that the opioid peptidergic system has agonists of different characteristics which interact with more than one type of receptor.


Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressor response to hypothalamic stimulation. The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused and electrically stimulated with a push-pull cannula. Superfusion of the hypothalamus with (+/-)-, (-)-propranolol, sotalol, practolol or metoprolol caused a concentration-dependent inhibiton of the pressor response to hypothalamic stimulation. (+/-)-Propranolol and a procaine concentration equi-anaesthetic to the concentration of (+/-)- and (-)-propranolol were ineffective. Lower concentrations of propranolol and metoprolol were needed to inhibit the pressor response than of sotalol or practolol. Superfusion with practolol and tolazoline impaired the pressor response to a greater extent than did superfusion with each of the drugs alone. Hypothalamic superfusion with isoproterenol elicited a concentration-dependent enhancement of the rise of blood pressure during electrical stimulation of the hypothalamus. It is concluded that beta-adrenorecptors are present in the posterior hypothalamus and that they are involved in the pressor response elicited by electrical stimulation of the hypothalamus. Propranolol and metoprolol seemed to possess a higher affinity to the beta-receptors of the hypothalamus than sotalol or practolol.


Acetylcholine and cAMP in adrenal medulla:indirect effect. Catecholamine release and cAMP accumulation were studied in bovine adrenal medulla slices in vitro. Acetylcholine (10(-4) M) and salbutamol (10(-6) M) caused increased release of catecholamines and accumulation of cAMP. Incubation in Ca2+ -free medium abolished the release of catecholamines and the increase of cAMP caused by acetylcholine but not that caused by salbutamol. In a membrane fraction of adrenal medulla acetylcholine (10(-4) M) had no effect on adenylate cyclase activity but salbutamol (10(-6) M) caused substantial activation of adenylate cyclase. It is suggested that acetylcholine has no direct effect on adenylate cyclase or cAMP in adrenal medulla and the accumulation of cAMP observed in slices incubated with acetylcholine is due to the effect of catecholamines, released by acetylcholine, on the medullary cells.


Aphasia in multiple sclerosis.

Aphasia in multiple sclerosis. In a 17-year-old woman, motor aphasia developed during her second bout of multiple sclerosis, characterized by absent spontaneous speech, paraphasias in naming and repetition, and marked orofacial apraxia, with relative preservation of written language and intact auditory comprehension. A mild right hemiparesis was associated. Bilateral cerebral lesions were demonstrated on a computerized tomographic brain scan. The aphasia remitted over 1 month.


Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome. A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems.


Facts and reflections on thalamocortical reverberation of impulses. Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge ("slow after-activity"), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous "spindles" evoked by stimulation. This conclusion is supported by the following facts: Spontaneous "spindles" and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone.


Encephalopathy associated with lamellar residual bodies in astrocytes (Towfighi, Grover and Gonatas 1975):a new observation. A 7-year-old male patient presented a few episodes of convulsions during the first year of life. The psychomotor development has been normal during that period of time after which a steadily progressive deterioration occurred. Increasingly severe pyramidal signs, optic atrophy, quadriparesis and progressive evolution towards a decorticate state were noted. Skin and neuromuscular biopsies were not contributory. A brain biopsy showed the presence of lamellar inclusions in astrocytes and, to a lesser extent, in neurons. Such features have only been reported once in two siblings by Towfighi et al. (1975). The nosological situation of this disease is discussed.


Synaptic processes in pericruciate cortical neurons evoked by pyramidal tract stimulation in cats. In cats anesthetized with chloralose and pentobarbital and immobilized with D-tubocurarine activity of 423 pericruciate cortical neurons was recorded (342 extra- and 81 intracellularly); 78 neurons had spontaneous activity. Stimulation of the pyramidal tract evoked antidromic action potentials in the pyramidal neurons with a latent period of 0.5-16.0 msec. Recurrent and lateral PSPs also developed both in pyramidal and in unidentified neurons in all layers of the cortex; IPSPs were recorded in 46.7% of neurons, EPSPs in 21.0%, mixed responses in 26.0%, and no visible changes were found in 6.3%. The latent period of the IPSPs was 1.5-14.0 msec, ther amplitude 1.3-17.0 mV, their rise time from 4 to 18 msec, and their duration 18-120 msec (sometimes up to 250-500 msec). In 30% of cases in which IPSPs appeared, their course was divided into two phases: fast (duration 10-20 msec) and slow. EPSPs developed after a latent period of 2.6-29.0 msec; their amplitude was 1.0-7.8 mV and their duration from 10.0 to 50.0 msec. In 51.2% of spontaneously active neurons the antidromic volley inhibited their activity in the course of 200-400 msec, in 19.5% it stimulated their activity, in 7.4% it had a mixed effect, and in 21.9% no visible change took place in their activity. The role and participation of axon collaterals of pyramidal neurons and of the interneuronal system in the formation of these processes are discussed.


The Brenner tumor: a clinicopathologic review. The Brenner tumor of the ovary has been the topic of voluminous clinical and pathologic literature since its original description by Macnaughton-Jones in 1898. One of the major problems confronting most investigators of this uncommon neoplasm has been the question of histogenesis. There is general agreement that the tumor is derived from surface (coelomic) epithelium, as are the serous and mucinous cystadenomas. Most Brenner tumors are asymptomatic except for some which have features suggestive of estrogen production. The major pathologic variants are the proliferating and the malignant Brenner tumors; a poor prognosis is associated with the latter neoplasm. Approximately 30% of all benign Brenner tumors have a second histologic type of tumor in the ipsilateral or contralateral ovary, a serous or mucinous cystadenoma in most cases. Brenner tumors have also been reported in the broad ligament and in the testis on rare occasions.


Thecomas and granulosa-theca cell tumors of the ovary: an analysis of 51 tumors,. A retrospective study of 51 thecomas and granulosa-theca cell tumors of the ovary seen at Confederate Memorial Medical Center in Shreveport, Louisiana, is presented. Endometrial tissue was available for study in 38 of the 51 patients. The relation of these tumors to endometrial morphology suggests an excessive estrogenic stimulation in most cases. The microscopic pattern and degree of pleomorphism was of no value in predicting which tumors would behave in a malignant fashion. The incidence of endometrial malignancy associated with these tumors was only 7.8%, which was less than was anticipated. The addition of irradiation and/or chemotherapy is, in our opinion, difficult to evaluate since many of the women with these tumors die of unrelated causes before a recurrence is evident.


Human chorionic gonadotropin and its subunits in hydatidiform mole and choriocarcinoma. Serum human chorionic gonadotropin (hCG) was measured by a radioreceptorassay (RRA) and radioimmunoassay (RIA) and serum hCG-beta and hCG-alpha by RIA in 10 patients with intact mole, 3 patients with choriocarcinoma, and 4 patients with hydatidiform mole during treatment. hCG levels by RRA were higher in 5 of 10 molar pregnancies and ranged from 20,900 to 100,000 ng/ml and from 30,000 to 100,000 ng/ml by RIA. hCG levels by RRA and RIA paralleled one another closely during treatment of hydatidiform mole. hCG-alpha was higher than hCG by RRA and RIA and hCG-beta in molar pregnancies, in the uterine venous blood draining a uterine choriocarcinoma, and during chemotherapy of choriocarcinoma. In 2 of 3 choriocarcinoma patients who eventually developed cerebral metastases, hCG-alpha increased while hCG and hCG-beta were declining or negative. hCG-beta was usually lower than hCG or hCG-alpha in all the cases studied. These results demonstrate the production of free alpha and beta subunits in trophoblastic disease. Further, due to the biospecificity, simplicity, and rapidity, the RRA of hCG is a sueful diagnostic aid during treatment of trophoblastic neoplasia until the levels fall to within the sensitivity range of the assay. Finally, the RIA of hCG, hCG-beta, and hCG-alpha, which requires several days, should be performed until they become negative or fall within normal range.


[Comparative study of the multiple molecular forms of NAD-dependent glutamate dehydrogenase in the liver and femoral muscle at different stages of swine embryogenesis[]. The multiplicity of NAD-dependent glutamate dehydrogenase (GDH) was studied in the liver and femoral muscle of 30, 60 and 108 days old pig embryos by the method of discelectrophoresis in polyacrilamide gel. The GDH was shown to be presented in the tissues under study by 3--4 multiple molecular forms. Specific ratios of the multiple GDH forms were established in the tissues under study at different stages of embryogenesis.


Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. The radicular pain of sciatica was ascribed by Mixter and Barr to compression of the spinal root by a herniated intervertebral disc. It was assumed that root compression produced prolonged firing in the injured sensory fibers and led to pain perceived in the peripheral distribution of those fibers. This concept has been challenged on the basis that acute peripheral nerve compression neuropathies are usually painless. Furthermore, animal experiments have rarely shown more than several seconds of repetitive firing in acutely compressed nerves or nerve roots. It has been suggested that "radicular pain" is actually pain referred to the extremity through activation of deep spinal and paraspinal nociceptors. Our experiments on cat lumbar dorsal roots and rabbit sural nerves have confirmed that acute compression of the root or nerve does not produce more than several seconds of repetitive firing. However, long periods of repetitive firing (5-25 min) follow minimal acute compression of the normal dorsal root ganglion. Chronic injury of dorsal roots or sural nerve produces a marked increase in mechanical sensitivity; several minutes of repetitive firing may follow acute compression of such chronically injured sites. Such prolonged responses could be evoked repeatedly in a population of both rapidly and slowly conducting fibers. Since mechanical compression of either the dorsal root ganglion or of chronically injured roots can induce prolonged repetitive firing in sensory axons, we conclude that radicular pain is due to activity in the fibers appropriate to the area of perceived pain.


A new technique for recording of intradental sensory nerve activity in man. A technique was developed to record intradental sensory nerve activity in man. The method involves permanent fixation of electrodes in dentin thus enabling continuous recordings to be made. Acute as well as long term influences on excitability of sensory nerve endings in the tooth can thus be studied. A coincidence between recorded spike activity and pain sensation was observed.


[Copper and nervous system. An experimental study (author's transl)]. Sodium azide is known to produce alterations in mammalian copper proteins, thus rendering them unable to bind exogenous metal, which remains in the "labile pool" condition. Continuous administration of sodium azide at LD50 for 30 days causes copper accumulation in several tissues and even in the nervous system, with characteristic changes in neurones and glial cells, very much resembling the alterations observed in Wilson's disease. Dietary copper administration, on the contrary, though raising the level of tissue-bound metal, does not produce cellular damage. These findings allow us to suppose that sodium azide may alterate the coppper chelating proteins in the tissues, especially in the nervous system, thus causing the storage of cell-toxic "labile pool" metal. The pathogenesis of Wilson's disease and the problem of "pathoclisis" in the nervous system are debated.


Familial abdominal chemodectomas with associated cutaneous angiolipomas. The occurrence of cutaneous angiolipomas and intra-abdominal retroperitoneal chemodectomas in two brothers is described. Both died from malignant dissemination of the chemodectomas. It is possible but speculative that two other brothers suffered from the same syndrome.


Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. I. Subcellular localization and properties. The de novo cytidine-5'-diphosphocholine (CDP-choline) pathway enzymes: choline kinase (CK); phosphorylcholine cytidyltransferase (CyT), and phosphorylcholine glyceride transferase (PCGT), and the phosphatidylcholine-lysophosphatidylcholine (PC-lysolPC) cycle pathway enzymes: lysophospholipase (LPL), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acyl-CoA LAT) were studied in the rabbit lung subcellular fractions. The purity of the fractions was examined by the marker enzymes and electron microscopy. The lamellar bodies had the highest concentration of phospholipids (10.0 mumol/mg protein, 80% of which was phosphatidylcholine (PC), about 10-fold higher than that of mitochondria (0.8) and microsomes (1.0) (50% of which was PC in both fractions). The lamellar bodies contained no enzymic activities of either the CDP-choline pathway or the PC-lysoPC cycle pathway. The enzymic activities of CK, CyT, LPL, and LAT were found mainly in the soluble fraction (about 40% for CK and CyT, and 70% for LPL and LAT); PCGT and acyl-CoA LAT were microsomal enzymes. Some general properties of PC-lysoPC cycle enzymes were also studied. The activities of LPL, LAT, and acyl-CoA LAT were not stimulated by the divalent metal ion Ca+. Their activities were inhibited by 10(-3) M diisopropyl phosphorofluoridate (DFP). The role of the PC-lysoPC cycle pathway enzymes in remodeling the lung PC is discussed.


Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. II. Marked differences in the effect of gestational age on activity compared to the CDP-choline pathway. Lysophosphatidylcholine (lysoPC), a breakdown product of phosphatidylcholine (PC), might be important in pulmonary PC synthesis through fatty acid exchange reactions. This study defines the levels of three of the enzymes of the PC-lysoPC cycle pathway (lysophospholipase (LPL) (EC. 3.1.1.5), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acryl-CoA LAT) (EC. 2.3.1.23)) in developing fetal rabbit lung and compared them with the enzymes of the CPD-choline synthetic pathway (choline kinase (CK) (EC. 2.7.1.32), phosphorylcholine cytidyl transferase (CyT) (EC. 2.7.7.15), and phosphorylcholine glyceride transferase (PCGT) (EC. 2.7.8.2). Lung homogenates of fetal rabbits of known gestation, newborn, and adult rabbits were used for the enzyme, protein, and phospholipid analyses. Total lung phospholipid, PC, and protein increased with gestational age. Thirty days' gestation, newborn, and maternal lung activities of CK, CyT, and PCGT had decreased to only 50% of their activities at 22-26 days' gestation. In contrast, LPL and LAT activities increased 4-5-fold from 22-26 days to 30 days' gestation, and increased further in the newborn lung, finally to a level matching maternal lung (about 8-10-fold higher than the 22-26 days' gestation activities). The microsomal acyl-CoA LAT also showed a similar increasing activity with gestational age. In fetal lung, enzymic activities for the apparent major PC synthetic pathway decreased. In contrast, the marked increases in LPL, LAT, and acyl-CoA LAT activities with increasing gestational age and at birth suggests importance of the PC lysoPC cycle pathway in regulating synthesis and turnover with maturation.


Antibody persistence after primary immunization with trivalent oral poliovirus vaccine. Five years after primary infant immunization with trivalent oral poliovirus vaccine, employing either a three-dose primary series as recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) or a four-dose series as recommended by the Committee on Infectious Diseases of the American Academy of Pediatrics. 115 children were serologically tested for persistence of neutralizing antibodies by the microneutralization test. Of the 57 individuals immunized according to the ACIP recommendation, antibody persistence was demonstrated in 92% for type 1 poliovirus, 98% for type 2, and 84% for type 3. Of those 58 individuals originally receiving a four-dose primary infant immunization series, the persistence of antibody was 98% to type 1, 98% to type 2, and 87% to type 3. Twenty-one of 24 negative sera showed neutralizing ability when tested by a more sensitive plaque reduction test. Thus, individuals completing either immunization schedule demonstrated satisfactory persistence of neutralizing antibody to all three poliovirus types over a five-year period.


REM and dreaming.

REM and dreaming. 4 subjects were awakened after long REM periods and 12 other subjects after short REM and after NREMs. The mean numbers of words, dream episodes, and spontaneous remarks about being interrupted in the middle of a dream were significantly different in the reports of the three groups. It is suggested that the present view of the relationship between REM and dreaming is not conclusive.


Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Microperfusion experiments were performed in rats to assess the effect of luminal application of theophylline and the more lipophilic 3-isobutyl-1-methylxanthine (IBMX) on feedback regulation of glomerular filtration rate. Elevation of loop of Henle flow from 0 to 40 nl/min caused a 20.3 +/- 4.5% reduction of stop flow pressure (SFP) and a 32.2 +/- 3.7% reduction of early proximal flow rate (EPFR) when the perfusate was a 140 mM NaCl solution. When theophylline was added in a concentration of 5mM SFP fell by only 5.3 +/- 1.8% and EPFR by 7.9 +/- 33%, changes which were significantly smaller than in the control perfusions (P less than 0.01). An identical change of loop of Henle flow in the presence of IBMX in concentration of 1 and 5 mM was associated with a 4.5 +/- 3.9% decrease and a 12.1 +/- 2.7% increase of EPFR. In orthograde perfusion experiments full inhibition of the feedback response was noted at an IBMX concentration of about 1 mM while during retrograde perfusion a concentration of 0.4 mM was sufficient to produce the same effect. This indicates that methylxanthines diffuse out of the loop of Henle to a considerable extent. Methylxanthines reduced absolute and fractional water absorption along the loop of Henle to some extent while Cl absorption rates and early distal Cl concentrations were not significantly altered. Cyclic AMP applied from the luminal side in a concentration of 10 mM did not affect the feedback response of EPFR to flow elevation from 0 to 40 nl/min. Luminal application of dibutyryl cyclic AMP at 10 mM induced a small, but significant reduction of the feedback response when tested by paired t-test (P less than 0.05). Our results show that luminal application of methylxanthines strongly interfere with feedback regulation of glomerular filtration rate. It is unclear at present whether this effect is related to inhibition of cyclic nucleotide phosphodiesterase and a rise in tissue cyclic AMP levels or to interference with a mechanism involving the local action of adenosine or 5'-AMP.


Aspartate and other inhibitors of excitatory synaptic transmission in crayfish muscle. Synaptic currents were measured in voltage clamped crayfish muscle fibers which were triggered either by stimulation of the motor axon (EPSC), or by L-gutamate (gEPSC) applied by microiontophoresis or superfusion. Among a number of analogues of glutamate, L-glutamic-acid-gamma-methyl ester, L-glutamic-acid-dimethyl ester and L-aspartate, were reasonably specific antagonists at the motor synapses, although at relatively high concentrations. Aslo, 2-amino-4-phosphono-butyric acid and morphine were effective antagonists; the action of morphine, however, seemed to be unspecific. Aspartate was further shown to decrease the size of the quantum EPSC, without affecting the probability of release of transmitter or the potential change recorded from the presynaptic nerve terminal. The results also indicate that aspartate, after longer incubations, is released as a false transmitter. The dose-response curve to short glutamate pulse is shifted by aspartate to higher glutamate concentrations, without affecting the steep slope of the dose-response curve or the saturation level. This effect can be interpreted as competitive inhibition by aspartate, with an equilibrium concentration of aspartate at the receptor of 0.3--1.5 mmol/l. In longer glutamate applications the receptor desensitizes rapidly. Aspartate reduces this desensitization in addition to its competitive inhibitory effect. Suppression of desensitization can be more effective than inhibition in long glutamate applications; in this case aspartate apparently potentiates the effects of glutamate.


Acrylamide poisoning.

Acrylamide poisoning. A small epidemic of acrylamide poisoning amongst workers in the construction industry is described. The clinical features of this condition are reviewed and two cases are described in which residual neurological problems persisted for over 1 year. The literature on acrylamide poisoning is reviewed and it is recommended that this substance should only be handled in the open air or in well ventilated areas. Its use in confined spaces such as tunnels appears to be unduly hazardous.


Gynaecomastia associated with gonadotrophin-secreting carcinoma of the lung. A 67-year-old man developed dermatomyositis. Investigation revealed an oat cell carcinoma of the lung. When he developed unilateral gynaecomastia this tumour was found to secrete gonadotrophins. The gynaecomastia disappeared after treatment with an anti-oestrogen--tamoxifen. This use of tamoxifen has not previously been described. Partial tumour regression was obtained with several cytotoxic drug regimes. His dermatomyositis responded to this treatment and remains in remission.


[Effect of thermal load and ACTH administration on the ATPase activity of homogenates and microsomal fractions of the tissues of growing rats]. A study was made of the age dynamics of the ATP-ase activity in the homogenates and the microsomal fractions of the liver, kidneys, brain and muscles of albino rats. It was shown that in young animals the change of the ATP-ase activity in the tissues (the index of energy metabolism) in response to the ACTH administal life the shifts in the ATP-ase activity of different tissues after the thermal stress and administration of ACTH proved to vary in character.


[Effect of insulin on the reactivity of the myocardium to hydrocortisone]. Experiments were conducted on rats. A study was made (with the aid of histological and histochemical methods) of the effect of administration of hydrocortisone, insulin, and also of the combined administration of these hormones on the myocardial structure and metabolism. Hydrocortisone administration for 30 days proved to derange the metabolism and to cause dystrophic changes in the myocardium. In combined administration of hydrocortisone and insulin these dystrophic changes were much less pronounced.


Rehabilitation program following polycentric total knee arthroplasty. A rehabilitation program which has been used successfully in improving the postoperative range of motion of patient undergoing total knee arthroplasty is outlined. The specific objectives are strong quadriceps setting, straight leg raising, flexion of the knee to at least 90 degrees, and extension of the knee to 0 degrees. The program emphasizes the importance of early institution of exercises and early ambulation.


Analysis of dream contents by scaled and rated measurements. The study was undertaken in order to test a dream-rating scale and to propose some modifications, especially for use in laboratory situations where the effect of a given experimental factor is to be assessed on mental activity in sleep. Dreams collected from normal subjects under EEG monitoring were analysed in detail in order to establish definitions for each rating point of each dimension of the rating scale. The scoring of a second set of dreams by two judges using this scale resulted in an inter-rater agreement significantly above the level of chance agreement.


Distribution of lung metastases in the axial plane. A combined radiological-pathological study. The appearance of lung metastases and their distribution in the axial plane was studied on radiographs of formalin-vapour inflated fixed lungs. The results show that the vast majority of lung metastases are to be found at the periphery of the lung, irrespective of cavitation or of their shape or size. This distribution cannot be explained by hydro-dynamic factors, but may be related to the susceptibility of metastases in different parts of the lung. the metastases were also analysed as to their appearances, namely well-defined nodular, star-like, ill-defined edge and cavitating. No definite correlation with distribution was apparent but when extremely numerous, metastases were usually less than 1 cm in diameter with ill-defined margins. This could be due to their rapidity of growth.


Angiography in the diagnosis of retroperitoneal and mediastinal chemodectomas. Report of two cases. Two cases of angiographically demonstrated chemodectomas of uncommon locations and behavior are reported: one located retroperitoneally and one with multi-centric sites including both carotid bodies and the upper mediastinum, with late distant bone metastases. Based on this experience and that reported by others, the angiographic appearance of chemodectomas is described and the value of angiography in the diagnosis and therapy of chemodectomas is discussed.


[Differential diagnosis of microcalcifications, X-ray film analysis of 60 intraductal carcinoma, the triangle principle (author's transl)]. Roentgenological criteria of microcalcification in intraductal carcinoma were examined in 60 cases and verified by the "double-blind test". The triad polymorphy, dense colonization, triangle principle has proved to be of useful for the differential diagnosis.


Computed tomography of abdominal mass lesions in children. Initial experience. Use of a Delta scanner has resulted in delineation of neoplastic, obstructive and inflammatory renal diseases, hepatic tumors, and other abdominopelvic mass lesions. Of 47 patients examined, 32 had proved mass lesions. Computed tomography provided unique information about the complete delineation and nature of lesions and detected unrecognized lesions. Technical problems and solutions are discussed.


Correlation of computed tomography, gray scale ultrasonography, and radionuclide imaging of the liver in detecting space-occupying processes. The abilities of computed tomography (CT; scanning time=2.7 min), gray scale ultrasonography, and radionuclide imaging to detect and characterize space-occupying processes in the liver were compared. A numerical rating scale which emphasized detection abilities resulted in ultrasonography scoring 3.5 CT 3.2, and radionuclide imaging 2.9. CT resulted in no false positives and 6 false negatives, caused mainly by motion artifacts. The simplest technique, radionuclide imaging, also had the smallest number (2) of false negatives; it is therefore recommended as the screening procedure of choice. Sonography or CT should be done for those patients with a prior suspicious finding.


Improved myocardial infarct localization by combination of scintigraphy and ventricular wall motion evaluation. Localization of acute myocardial infarcts can be done directly by imaging 99mTc pyrophosphate in the infarcted myocardium, or indirectly by analysis of wall motion abnormalities. Combining these modalities improves the sensitivity and specificity of the study. Forth-nine consecutive abnormal studies were analyzed in which both wall motion and static images were obtained with a single injection of pyrophosphate. At least 50% of the acute infarcts were better localized (or additional information obtained) by combining the modalities.


A critical review of the efficacy of 99mTc pyrophosphate in detecting myocardial infarction in 103 patients. Patients imaged with 99mTc pyrophosphate for myocardial infarction between October 1975 and March 1976 were reviewed. There were 103 patients and 114 images obtained. The clinical criteria of either or electrocardiographic changes were used to validate a myocardial infarct. We experienced 92.4% true negatives, 68.7% true positives, 7.5% false positives and 31.3% false negatives. It technically compromised scans were exclude (those with blood-pool activity, overlying costal cartilage), the false-negative rate was 15.4%. These data show that the presence of a negative phosphate scan does not rule out the possibility of a recent small, less than 2.5-cm subendocardial myocardial infarction.


The efficacy of thallium 201, 99mTc phosphates, and 99mTc MAA in localizing small myocardial infarctions in the pig. An intercomparison was made of technetium phosphates, thallium 201, and technetium-labeled MAA to define areas of small myocardial infarction in pigs. Byinstilling 0.01 ml of mercury into the coronary arteries, 2-cm infarcts were created. Several of the infarcts were in the anterior left ventricular wall. None of the infarcts was imaged with 99mTc phosphates. Three of the seven thallium 201 images demonstrated only diffuse right ventricular activity. Three of the seven infarcts were imaged with technetium MAA; a perfusion defect was seen in the area of infarction. Technetium MAA is the most sensitive agent in defining areas of abnormal myocardial perfusion.


The radiological investigation of hepatic tumors in childhood. In hepatic tumors seen in children, treatment and prognosis differ from tumor to tumor and thus accurate determination of their extent and characteristics is important. Evaluation by gray scale ultrasonography, radionuclide imaging and angiography has produced definable characteristics for the various tumor types and often allows distinction from other intrahepatic processes. In addition, chemotherapeutic treatment of initially unresectable malignant hepatic tumors can be followed by nuclear imaging, ultrasound and angiography to determine therapeutic response.


Analogies and differences between reserpine PGO wave discharges and oculomotor phasic activity during paradoxical sleep in the cat. In the present study the analogies and differences between phasic PGO activity of parodoxical sleep and the reserpine induced PGO waves were investigated. The oculomotor phasic activities in chronic cats were studied. It appeared that the intrinsic organisation of latencies and the appearance of phasic waves in the four structures studied were common to both experimental situations. However the sequential patterns of discharges were different in PS and under reserpine treatment.


A structure-activity analysis of the preferred conformation of the benzyl substituent of tetrahydropapaveroline at the beta receptor. The effect of restricting the motion of the 3,4-dihydroxybenzyl substituent of tetrahydropapaveroline (THI) on its ability to stimulate the beta adenylate cyclase of the rat erythrocyte was investigated. A number of protoberberines and aporphines were tested as models of two classes of compounds where the benzyl substituent is rigidly but differently fixed. Unexpectedly, the beta agonist activity was associated with both structural types. This could be explained by the assumption that a phenylalanyl or tyrosyl residue of the receptor protein is free to rotate and bind with either position of the benzyl moiety as fixed in the protoberberine and aporphine structures.


Correlation of induced drug metabolism with titer of duck hepatitis virus in chickens. While chickens infected with duck hepatitis virus showed no signs of clinical illness, their levels of hepatic cytochrome P-450 in response to phenobarbital induction and their microsomal aryl hydrocarbon hydroxylase activities in response to 3-methylcholanthrene induction were each found to correlate with the titer of virus recovered from the livers. These clear correlations indicate that avian hepatic drug metabolism is significantly modified during viral infection.


Cyclic nucleotides and prostaglandins (PGs) produced by the rabbit oviduct: effects of estrogen treatment. Levels of cyclic AMP and cyclic GMP have been measured in oviducts of rabbits killed 68 hr after injection of human chorionic gonadotrophin (HCG) to induce ovulation. cAMP and cGMP levels were higher in the isthmus than in the ampulla. Estrogen treatment given at the same time as HCG increased cGMP levels. Levels of PGE and PGF in blood draining the oviduct were low and showed no effect of estrogen treatment at 68 hr after HCG.


The role of bursa-dependent responses in immunity to infectious laryngotracheitis. The effect of combined day-old surgical bursectomy and cyclophosphamide therapy on the response of young chicks to Brucella abortus antigen and cloacal vaccination against infectious laryngotracheitis virus (ILTV) was examined. The combined treatment effectively prevented the development of serum antibody to both B abortus and ILTV, yet when these chickens were challenged with virulent ILTV, they were found to be immune. It is suggested that immunity to ILTV may depend on the development of a cell mediated immune response.


Vagal control of diaphragm timing in cat while breathing at elevated lung volumes. This paper proposes and tests an hypothesis to account for the roles of the volume and rate components of vagal feedback in determining the steady-state pattern of breathing during continuous positive pressure breathing (PPB) and expiratory threshold loading (ETL) in Dial anesthetized cats. During PPB the duration of diaphragm activity (Tdi) is shortened; the duration of its expiratory pause (Tep) is lengthened with little or no change in cycle duration (Tt); with onset of inspiration, flow (dV/dt) is increased; as inspiration proceeds, flow decelerates (d2V/dt2). During ETL Tdi, Tep and Tt are all prolonged; dV/dt is decreased at onset of inspiration, with either no change or an acceleration in flow as inspiration proceeds. PPB and ETL cause similar increases in resting lung volume and Tep, and high negative correlations between Tdi and flow. These relationship suggest that the 'volume component' of vagal feedback is one important factor controlling Tep whereas the 'rate component' contributes to the restraint of Tdi.


[261 cases of bronchopulmonary cancer detected by radiophotography]. In Bucharest, district 6, of the 1 151 313 radiophotographies performed, 261 revealed bronchopulmonary cancers (22.6 per 10 000) of which 73% males and 27% females, the 50--70 years age group being the most affected (181 cases, i.e. 70%). The 85% deaths occurred within 2 years after detection. In 68% (177 cases) cancer was peripheral and in 32% centrohillar. The peripheral localization in 68% of the cases opens prospects for an early detection by dynamic follow up of the pulmonary radiophotography at shorter intervals, especially in the age group with a higher cancer risk (50--70 years), indicating in some cases immediate admission to a surgical department.