Temperature-dependent host range mutation in vesicular stomatitis virus affecting polypeptide L. We established previously that the temperature-dependent host range mutant, td CE 3, of vesicular stomatitis virus (VSV) New Jersey possesses temperature-sensitive RNA transcriptase activity. In this paper, we describe dissociation and reconstitution experiments designed to determine which VSV polypeptide is affected by the td CE 3 mutation. Wild-type VSV New Jersey (ts+), the temperature-dependent host range mutant (td CE 3), and the revertant of this mutant (td CE/R1) were used. Transcribing nucleoprotein preparations, isolated from purified virus particles, were treated in the presence of digitonin with either 0.9 M LiCl to produce supernatants containing virtually only the L polypeptide or 2.0 M LiCl to produce ribonucleoprotein pellets containing only the polypeptides N and NS. Supernatant and pellet fractions synthesized either no or only trace amounts of RNA in vitro. Reconstitution of the supernatants with the pellets in all combinations at 31 degrees C restored much of the transcriptase activity of the transcribing nucleoprotein preparations. RNA synthesis occurred at 39 degrees C when the three pellets were reconstituted with wild-type and revertant supernatants. However, supernatant of the mutant td CE 3 reconstituted with any of the three pellets resulted in little or no detectable transcriptase activity at 39 degrees C. This implies that the polypeptide affected by the td CE 3 mutation is the L polypeptide.


Specificity of initiation of transcription of simian virus 40 DNA I by Escherichia coli RNA polymerase: identification and localization of five sites for initiation with [gamma-32P]ATP. Simian virus 40 (SV40) DNA I was transcribed with Escherichia coli RNA polymerase in the presence of gamma-32P-labeled ribonucleoside triphosphates in order to investigate the specificity of initiation of in vitro transcription. ATP and GTP served as predominant initiating nucleotides, the former being incorporated about twice as much as the latter. Cleavage of [gamma-32P]ATP-labeled SV40 complementary RNA (cRNA) with T1 RNase followed by homochromatographic analysis of the resultant 5' initiation fragments revealed the presence of four specific initiation fragments 6 to 9 nucleotides in length, designated AI, AII, AIIIa, and AIIIb. By means of hybridization of [gamma-32P]ATP-labeled SV40 cRNA to DNA from specific adenovirus 2-SV40 hybrids and specific restriction endonuclease fragments of SV40 DNA before chromatographic analysis, it was possible to identify and determine approximate localizations of five [gamma-32P]ATP initiation sites on the SV40 genome: one in Hin-G close to the Hin-G-B junction, giving rise to the AII fragment, two in the overalpping fragment Hin-A-Hae-A,giving rise to AI and AIII fragments, and two in the fragment Hin-A-Hae-E, also giving rise to AI and AIII fragments. All five sites either fall within or lie near regions of the genome that are cleaved by S1 nuclease and subject to partial alkaline denaturation. These five sites lie on the minus strand of SV40 DNA and initiate RNAs that are copied in a leftward direction. Cleavage of [gamma-32P]GTP-labeled cRNA with pancreatic RNase liberated three major 5' initiation fragments of short length, GI, GII, and GIII, suggesting the presence of three principal GTP initiation sites.


Changes in synthesis of DNA-binding proteins during the onset of transformation in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus. Synthesis of cytoplasmic DNA-binding proteins was investigated after a shift from the nonpermissive to the permissive temperature in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus [ts339(RSV)]. Cells were labeled for several generations in [3H]leucine and were pulse-labeled with [35S]methionine for 1 h at the nonpermissive temperature (39 degrees C) and at the permissive temperature (33 degrees C, 5 h after shift from 39 degrees C). Proteins binding to sequential columns of double-stranded and single-stranded DNA-cellulose were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and the 35S/3H ratios were obtained for each column fraction and for individual polypeptides. The protein fractions binding to single-stranded, but not double-stranded, DNA and eluting at high salt concentrations (greater than 0.60 M NaCl) showed elevated 35S/3H ratios. This indicated increased synthesis of these proteins within 5 h after the onset of transformation. The majority of the polypeptides in these fractions showed increased synthesis as a consequence of transformation. One prominent polypeptide among them constituted 0.1% of the cytosol protein and had a molecular weight of 93,000. We conclude that the synthesis of proteins binding tightly to single-stranded DNA is increased early after the onset of transformation.


Spatial relationships of the proteins of vesicular stomatitis virus: induction of reversible oligomers by cleavable protein cross-linkers and oxidation. To delineate the proximity and spatial arrangement of the major structural proteins of intact vesicular stomatitis (VS) virions, protein complexes formed by oxidation or by bivalent cross-linkers were analyzed by two-dimensional electrophoresis on polyacrylamide slab gels. H2O2 oxidation of VS virions produced an N-polypeptide dimer (molecular weight, approximately equal to 110,000) on a first dimension gel that could be reduced to N monomers (molecular weight, approximately equal to 50,000). Proteins extracted from unreduced and unoxidized VS virions contained dimeric and trimeric forms of M-protein complexes as well as a heterodimer of M and N protein. Qualitatively similar VS viral protein complexes were generated by exposing VS virions to the reversible protein cross-linkers methyl-4-mercaptobutyrimidate (MMB), tartryl diazide (TDA), and dithiobis(succinimidyl proprionate) (DTBSP); cross-linked complexes on first-dimension gels were cleaved by reduction with 2-mercaptoethanol (MMB or DTBSP cross-linked) or by periodate oxidation (TDA cross-linked). In addition to covalently linked homodiamers of M and N proteins and a protein M-N heterodimer, the protein cross-linkers also generated homo-oligomers of G protein and a G-M heterodimer. These data suggest that the glycoprotein spike of VS virus is composed of more than one G protein. The existence of N-M and G-M heterodimers is consistent with the hypothesis that the matrix (M) protein may serve as a bridge between the G and N proteins in assembly of the VS virion.


Inclusion body disease of falcons (Herpesvirus infection) in an American kestrel. Postmortem examination of a captive-bred American kestrel (Falco sparverius) showed numerous white necrotic foci 1-2 mm in diameter throughout the liver and spleen. The results of light and spleen. The results of light and electron microscopic studies and experimental transmission to a captive American kestrel and a barred owl (Strix varia) suggests a herpesvirus similar to those dsecribed for owls and other falcons in the U.S. This is the first report of a naturally occurring case of inclusion body disease of falcons in the American kestrel.


Demeclocycline. Treatment for syndrome of inappropriate antidiuretic hormone secretion. The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of inappropriate antidiuretic hormone secretion. In all patients, demeclocycline hydrochloride (1,200 mg/day) induced production of hypotonic urine and corrected hyponatremia despite large fluid intakes. Comparison of the response to a standard water load before and during treatment showed a notable improvement in the response to water ingestion. Even though demeclocycline moderately impairs renal function, it appears to be the treatment of choice in the chronic form of the syndrome.


Modern day menstrual folklore. Some clinical implications. Clinicians are often unaware of the folk medical beliefs of their patients or consider them to be harmless and unimportant. Such beliefs are instrumental in shaping patient behavior, however, and may contribute to negative health practices. The information presented here demonstrates that attitudes toward a single bodily function, menstruation, may adversely affect women's body image, perception of disease causation, diet, willingness to take medication, contraceptive use, and the ability to plan pregnancies. The data are part of a pilot study in which patients in a clinic serving a multiethnic low-income population were questioned about their knowledge and beliefs concerning the female reproductive cycle. It is concluded that health personnel should strive to learn what women know and believe about their bodies and how they function, to improve health care provision.


Lung carcinoma in young adults.

Lung carcinoma in young adults. Twenty-four patients less than 40 years of age were diagnosed at Walter Red Army Medical Center between 1971 and 1976 as having lung cancer. The youngest patient was 19 years old. Only one was a nonsmoker. Most patients were symptomatic at the time of examination. The chest roentgenogram showed an infiltrate or consolidation in 9, a mass lesion in 13, and a pleural effusion in 1. Thirty-eight percent had adenocarcinoma, 21% had squamous cell carcinoma, and 21% large cell carcinoma. Nineteen patients had stage II or III disease at the time of initial examination, and only six had resectable tumors. Survival rates were poor.


Age-dependent response of mice to a mouse hepatitis virus, MHV-S. To a mouse hepatitis virus strain MHV-S, 4 week-old ICR mice were shown to be fully resistant irrespective of route and dose of inoculation, and fatal infection was produced only with cortisone treatment. Two-week-old mice also showed high resistance to MHV-S except for after intracerebral inoculation, and 60% of infected mice died. Mice aged 1 week or less, however, died after intracerebral, intraperitoneal, subcutaneous and intranasal inoculation, while some of them survived after peroral inoculation. Between mice aged 4 weeks and those aged 1 week or less, there was a significant difference in viral growth in the liver after intranasal inoculation, whereas almost the same degree of viral multiplication was seen in the brain of both age groups. Such age-dependent difference in susceptibility to a low-virulent mouse hepatitis virus especially after nasal inoculation is discussed in relation to natural infection in mouse breeding colonies.


Action of 5-hydroxytryptamine on isolated spinal cord of bullfrogs. Slow depolarizations of dorsal root nerve terminals and motoneurons, which were produced by 5-hydroxytryptamine (5-HT) applied directly to isolated bullfrog spinal cords, were recorded by the sucrose-gap method. These depolarizations were eliminated in the Ca-deficient Ringer's solution containing Mg, suggesting that these 5-HT depolarizations were not caused by a direct action of 5-HT on dorsal root nerve terminals or motoneurons but rather by actions of transmitters released from interneurons. Indeed, mephenesin, which is a selective blocker of polysynaptic transmission in the spinal cord, inhibited more markedly the 5-HT depolarization than the L-glutamate or GABA depolarization. The transmitter directly responsible for the generation of the 5-HT depolarization of dorsal root nerve terminals was not considered to be GABA as the 5-HT depolarization was not antagonized by picrotoxin. It would thus appear that 5-HT stimulates interneurons in the amphibian spinal cord and unknown transmitters released from these interneurons depolarize the dorsal root nerve terminals.


Phosphodiesterase inhibitors: their comparative effectiveness in vitro in various organs. The inhibitor constants of several inhibitors for cyclic AMP- and cyclic GMP-phosphodiesterase from various organs are compared. The inhibitors were classical theophyline, papaverine, and some of newly developed inhibitors: an imidazolidinone compound, RO20-1724, and two phthalazinol compounds, EG 467 and EG 626. Among the inhibitors tested, papaverine and EG 626 were found to be the most potent. Both compounds were extremely inhibitory to platelet and arterial phosphodiesterases. EG 626 was much more inhibitory to cyclic AMP phosphodiesterase than to cyclic GMP phosphodiesterase in platelet- and brain-extract and RO20-1724 was inhibitory to cyclic AMP- but not cyclic GMP-phosphodiesterase in brain-extract. When the skin adenyl cyclase was activated by AMP, the addition of theophylline blocked this activation, but EG 626 or EG 467 further potentiated the activation. These in vitro studies may serve as basic screening tests for the effectiveness of the specific phosphodiesterase inhibitors.


Breast carcinoma, thyroid carcinoma, and T3 thyrotoxicosis in a male cretin. A male patient with clinical and radiographic evidence of cretinism was found to have T3 thyrotoxicosis. The cause was thought to be a well-differentiated follicular carcinoma of the thyroid. Although the disease was not documented, the patient probably had long-standing hypothyroidism. Untreated primary thyroid failure accompanied by high serum thyroid stimulating hormone (TSH) may be carcinogenic to the thyroid. The association of thyroid abnormalities and male breast carcinoma is discussed.


The cellular lesions of Farber's disease and their experimental reproduction in tissue culture. In a case of Farber's disease, lysosomal inclusions were shown to contain lamellar, rectilinear, or curvilinear material. In tissue culture, when fibroblasts from the patient were overloaded with ceramides containing nonhydroxylated fatty acids a lysosomal accumulation of small curvilinear structures identical with those observed at autopsy were seen. These inclusions persisted for several weeks after the cells were replaced in a normal culture medium. Normal fibroblasts overloaded in the same experimental conditions showed identical, although less numerous, lysosomal inclusions, which disappeared rapidly in a ceramide-free culture medium. No inclusions were found after overloading normal or pathologic fibroblasts with ceramides containing hydroxylated fatty acids.


Arginine-rich cationic proteins of human eosinophil granules: comparison of the constituents of eosinophilic and neutrophilic leukocytes. Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition.


Metabolism of kinins and angiotensins in the isolated glomerulus and brush border of rat kidney. In order to localize the activities of kallikrein, kininase, angiotensin I converting enzyme, and angiotensinase in the kidney, rat kidneys were homogenized and glomeruli and brush border were isolated. The yield and purity of glomeruli preparations were high. The similarity of the structure of the isolated glomeruli in situ was established by scanning and transmission electron microscopy and freeze-fracture. The morphology of isolated brush border of proximal tubules was compared to brush border in situ. Isolated brush border, devoid of core material, retained its converting enzyme, kininase, and angiotensinase activity confirming our previous findings that these enzymes are bound to plasma membrane. Isolated glomeruli contained little or no kallikrein. In addition, compared to renal brush border, renal glomeruli contained a relatively low concentration of kininase, angiotensin I converting enzyme, and angiotensinase. The results of these experiments support the idea that the brush border of the proximal tubule is the major site of inactivation of kinins and angiotensins and that renal kallikrein enters the tubular filtrate distal to the glomeruli and proximal tubule.


Induction of brain tumors in hamsters with BK virus, a human papovavirus. The oncogenicity of BK virus for the central nervous system was studied in newborn hamsters. The virus was weakly oncogenic after intracerebral inoculation. Two of 45 hamsters treated with antithymocyte serum developed tumors whereas no untreated hamsters developed tumors. Both tumors were choroid plexus papillomas by histologic and electron microscopic examination. Cells cultured from one tumor had growth characteristics of transformed cells and had intranuclear T antigen; but infectious virus could not be rescued. Cultured tumor cells were weakly oncogenic for hamsters, but theoncogenicity of these cells was enhanced when the recipient animals were treated with antithymocyte serum. The possible role of host immune response as a basis for the weak oncogenicity of BK virus is discussed.


Prospects for the clinical use of exogenous interferon. Sufficient quantities of human leukocyte interferon have become available for small-scale clinical studies during the past years. The present status of the interferon treatment of respiratory infections, herpes keratitis, hepatitis B, osteogenic sarcoma, and some other tumours is surveyed. The pharmaco-kinetic and toxicological data obtained are summarized. The first clinical experiments with human fibroblast interferon have also been started. The prospects for mass production of human interferons for clinical use are discussed briefly.


Distribution of exogenous cyclic adenosine 3', 5'-monophosphate in rabbits and cats. The appearance and disapperance of total radioactivity in plasma and cerebrospinal fluid (CSF) were studied after a single intravenous injection of tritium-labelled cyclic adenosine 3', 5'-monophosphate (cAMP) into rabbits and cats. The radioactivity was rapidly cleared both from plasma and relatively stable when compared to plasma cAMP level. Exogenous cAMP in plasma does not seen to distribute into CSF by a simple diffusion.


Tumors of the major salivary glands.

Tumors of the major salivary glands. Tumors of the major salivary glands are reviewed according to classification, location, surgical procedure and end results. Our data of the incidence of benign and malignant tumors show that the most commonly involved area is the parotid gland and the most frequent is of the mixed variety. In the parotid region 80 percent are benign and 20 percent are malignant; whereas, in the submandibular gland, the malignant and benign tumors are equally distributed. The need for an extensive surgical attack and inclusion of contiguous structure is dictated by the nature of the malignant disease. The role of postoperative irradiation is discussed as is the indication for neck dissection. Management of the facial nerve, relative to malignant tumors of the parotid gland, is considered in detail.


Detection of poliovirus antigens and antibodies: microindirect haemagglutination and haemagglutination inhibition tests for poliovirus types I, II, and III. Microtitre indirect haemagglutination (IHA) and IHA-inhibition (IHAI) procedures were adapted to determine the reactivities of type I, II, and III poliovirus antibodies and antigens. Glutaraldehyde-fixed sheep erythrocytes were sensitized for these tests with concentrated, partially purified preparations of type I, II, and III poliovirus. Antibody titres by IHA were generally 10 to 100 times greater than serum microneutralization (SN) titres. The SN and IHA reactivities of three kinds of sera were compared. Of these sera, virus type specific antibodies, in monospecific guinea pig sera one week after immunization and in sera from hyperimmunized horses, could be readily differentiated and measured; antibodies in human diagnostic specimens, however, showed some intertypic cross reactivity. Monovalent one-week immune guinea pig sera reacted specifically in the IHAI test to differentiate viruses, and could be used for virus typing and differentiating strains of poliovirus type III.


Control of the Production of orthophosphate repressible extracellular enzymes in Neurospora crassa. The abilities of purine- and pyrimidine-requiring mutants to produce six orthophosphate repressible extracellular enzymes, alkaline phosphatase, 5'-nucleotidase, acid phosphatase, two nucleases and ribonuclease N1 were examined by culturing these mutants in low and high phosphate media containing nucleotide or nucleoside. All the purine requiring mutants produced significantly reduced amounts of alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alkaline nuclease and acid nuclease ranging 0.5-4.2, 5.0-17.4, 25.0-100, 20.3-67.5 and 6.2-48.5%, respectively. Production of ribonuclease N1 was found to be rather stimulated (150-564%) in these mutants. Essentially the same results were obtained for pyrimidine requiring mutants. Among those mutants ad-2 and ad-9 showed relatively high enzyme producing activity. Especially the production of ribonuclease N1 in ad-2 and ad-9 ranged to 4.9- and 5.6-fold that in the wild type. Though nuc-1 mutant (A1) has no ability to produce all these six repressible enzymes, double mutants A1ad-2 and A1ad-9 produced a significant amount of ribonuclease N1 in low and high phosphate media and acid phosphatase in low phosphate media.


Genetics of carbon catabolite repression in Saccharomycess cerevisiae: genes involved in the derepression process. A recessive mutant cat1-1, wild type CAT1, was isolated in Saccharomyces cerevisiae. It did not grow on glycerol nor ferment maltose even with fully constitutive, glucose resistant maltase synthesis. It prevented derepression of isocitrate lyase, fructose-1,6-diphosphatase and maltase in a constitutive but glucose sensitive maltase mutant. Derepression of malate dehydrogenase was retarded and slowed down. Sucrose fermentation and invertase synthesis was not affected. Respiration was normal. From this mutant, two reverse mutants were isolated. One was recessive, acted as a suppressor of cat1-1 and was called cat2-1, wild type CAT2; the other was dominant and allelic to CAT1 and designated CAT1-2d and cat2-1 caused an earlier derepression of enzymes studied but did not affect the repressed nor the fully derepressed enzyme levels. CAT1-2d and cat2-1 did not show any additive effects. It is proposed that carbon catabolite repression acts in two ways. The direct way represses synthesis of sensitive enzymes, during growth on repressing carbon sources whereas the other way regulates the derepression process. After alleviation of carbon catabolite repression, gene CAT1 becomes active and prevents the activity of CAT2 which functions as a repressor of sensitive enzyme synthesis. The CAT2 gene product has to be eliminated before derepression can actually occur. The time required for this causes a delay in derepression after the depletion of a repressible carbon source. cat1-1 cannot block CAT2 activity and therefore, derepression is blocked. cat2-1 is inactive and derepression can start after carbon catabolite repression has ceased. CAT1-2d permanently active as a repressor of CAT2 and eliminates the delay in derepression.


Comparative studies on the '5'-cap' and in vitro translational activity of cytoplasmic and nuclear poly A(+) RNA1. The translational activities of cytoplasmic poly A(+)RNA of normal rat liver and Novikoff hepatoma cells in the wheat germ cell free system were found to be approximately 15-20 times greater than tose of the corresponding nuclear poly A(+) RNA. The translationsl activities were 85 and 62 pmoles 3H-leucine incorporated/micron g cytoglasmic poly A(+) RNA for the liver and tumor respectively and 3-4 pmoles 3H-leucine incoporated/micron g nuclear poly A(+)RNA. Inasmuch as intergity of the '5'-cap' of mRNA is essential for its translational activity, quantitative comparisons were made of its content in these RNA fractions. Of the total 32P incorporated into the tumor cytoplasmic poly A(+) RNA, 0.41% was in the '5'-cap'; in nuclear poly A(+) RNA, the '5'-cap' contained 0.11%. After periodate oxidation and labeling with KB3H4, m7 guanosine, the 5'-terminal nucleoside in both liver and Novikoff hepatoma nuclear poly A(+) RNA contained approximately 20% as much isotope as in the cytoplasmic poly A(+) RNA. These results suggest the lower translational activity of nuclear poly A(+) RNA is partly related to its lower content of the '5'-cap'. Molecular selection of poly A(+) RNA for transport out of the nucleus or further cytoplasmic processing may account for the higher percentage of the '5-cap' and the greater translational activity of the cytoplasmic poly A(+) RNA. During these studies, it was also found that the m7 guanosine of the '5'-cap' was not removed during translation of the mRNA in the wheat germ system; this result suggests that the '5'-cap' may associate with allosteric binding sites of initiation factor(s).


Integration of genomes on infectious viruses. The article contains a review relating to the integration of genomes of infectious viruses in Eukaryotic cells. Data are presented that were obtained in the study of tissue cultures chronically infected with viruses, in the study of pathologic and ecologic processes. Based on the evidence accumulated, some theoretical and applied aspects of the problem are discussed.


[The significance of dietary fat in arteriosclerosis. An outmoded theory? (author's transl)]. The high cholesterol content of an atheroma, the frequent occurrence of myocardial infarction with high serum cholesterol, the extensive arteriosclerotic changes in diseases with high serum cholesterol (nephrosis, myxedema) and the occurrence of cholesterol deposits in the aorta in some animals fed with cholesterol are the principal arguments for the lipid theory of arteriosclerosis. But since many observations contradict this theory and the composition of the atheroma is the same as for many granulation tissues which are interpreted as a healing process, it is postulated that atheroma tissue is also to be interpreted as part of a reparative process. Such a hypothesis could explain all the well-known arteriosclerotic changes. Longterm studies in man for testing the serum cholesterol-lowering action of the "unsaturated" vegetable oils include serious errors of method and permit no confirmed conclusions.


[Significance of diabetes mellitus in the activation of the varicella zoster virus (author's transl)]. Eruptive herpes zoster infection (VZV) and its primary and secondary diseases are reported in 28 patients aged between 25 and 85 years. In 2 cases, malignant primary diseases were found. In 16 patients, a disorder of glucose utilization was diagnosed, 8 of them accompanied by a disorder of fat metabolism and 5 by a hyperuricemia. In one case a severe encephalomyelitis was observed. In 2 patients the activation of the VZV infection was related to the cytostatic or immunosuppressive therapy of a generalized Hodgkin's disease and a multiple sclerosis. Once a liver abscess as a sequel to amebic dysentery was diagnosed and once a megaloplastic anemia with symptoms of a funicular myelopathy following a vitamin B12 deficiency syndrome. In VZV infection the search for basal metabolic disorders is of particular importance.


[Vaccinations of animals and human health (author's transl)]. Vaccination of animals may have both positive and negative effects on human health. The negative consequences largely occur with live vaccines. The protection provided by vaccination to animals is taken advantage of for human health in the most diverse ways, both directly and indirectly. Typical examples are vaccination of dogs and cats against against rabies and inoculation against diseases of cattle, horses and dogs in which reoviruses of serotypes 1, 2 and 3 are involved. An important contribution to the protection of human health is also provided by vaccination with inactivated pathogens against leptospirosis and salmonellosis, against stomatitis vesicularis and American equine encephalitis and in developing countries against brucellosis.


Alkaline sucrose sedimentation studies of MMS-induced DNA single-strand breakage and rejoining in the wild type and in UV-sensitive mutants of Saccharomyces cerevisiae. MMS-induced DNA single-strand breakage and rejoining was studied in the RAD strain and in rad6 and rad21 mutants, both very sensitive to this treatment as compared with the wild type. Alkaline sucrose gradient centrifugation showed that MMS treatment reduced the molecular weight of DNA in the RAD strain and in rad6 and rad21 mutants to the same extent. Four hours of post-incubation in synthetic growth medium after treatment with a dose of 0.4% MMS which reduces cell survival of RAD, rad21 and rad6 to 50, 20 and less than 0.01%, respectively, resulted in a significant increase in the molecular weight of DNA in the wild type, but in only slight increase in mutant strains. When the strains were exposed to a lower dose of MMS (0.04%) which led to 100% survival of RAD and 50 and 20% survival of rad21 and rad6, respectively, wild-type DNA sedimented to the position of control DNA, while in both mutants the increase in molecular weight of DNA was less pronounced.


Caffeine toxicity in drosophila strains having different MMS sensitivities. Larvae of Drosophila melanogaster were fed with caffeine, and the induced lethality was recorded using two different methods. With a wild-type strain a whole dose-response curve was obtained. The two sexes were equally sensitive. Four genetically different strains, showing different MMS sensitivities, were tested with two caffeine doses. The strains differed significantly in their caffeine sensitivity, but there existed no correlation between MMS and caffeine sensitivity.


Asbestos and glass fibres in bacterial mutation tests. Asbestos fibres are carcinogenic in man and experimental animals but fine glass fibres are known, at present, only to be carcinogenic in experimental animals. Asbestos and glass fibres have been studied in mutation tests using auxotrophic strains of Escherichia coli and Salmonella typhimurium. The mutagenic activities of the positive control mutagens ultraviolet light, potassium chromate, ethyl methanesulphonate and benzo(a)pyrene were detected in the experiments. However, no mutagenic activity was found to be associted with any of the asbestos and glass fibres tested over a wide range of concentrations. The implications of these findings for the mode of action of asbestos and glass fibres as carcinogens are discussed.


Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease. We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.


Plasma high-density lipoprotein concentrations in chronic-hemodialysis and renal-transplant patients. Since epidemiologic studies show that the risk of clinically evident atherosclerosis correlates negatively with concentrations of high-density lipoprotein, we sought to determine whether patients on chronic hemodialysis or recipients of renal transplants had alterations in this lipoprotein similar to those described in other disorders associated with accelerated forms of atherosclerosis. High-density-lipoprotein cholesterol concentrations in both groups of renal patients were significantly lower than control values (P less than 0.01), and their ratios of low-density-lipoprotein to high-density-lipoprotein cholesterol were significantly higher (P less than 0.01) than those observed in both randomly selected controls and in controls matched for plasma lipid levels (control, 2.4 +/- 1.2, dialysis, 3.7 +/- 2.1, and transplant, 5.4 +/- 2.3 mg per 100 ml [mean +/- S.D.]) if, as experimental evidence suggests, high-density lipoprotein retards the development of atherosclerosis, and low-density lipoprotein has opposite effects, the higher ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol found in chronic-dialysis and renal-transplant patients may be related to their premature morbidity and mortality from cardiovascular causes.


Adherence of human peripheral blood lymphycytes to measles-infected cells. Enhancement by prostaglandin E1. We studied the effect of prostaglandins in vitro on an immune reaction mediated by T cells; adherence of lymphocytes to measles-virus-infected human epithelial cells. Normal human lymphocytes adhered to a mean +/- S.D. 20.1 +/- 5.2 per cent of these HEp-2 cells. The percentage positive cells increased to 50.3 +/- 5.7 when lymphocytes were incubated with 10(-6) M prostaglandin E1 (P less than 0.01 vs. untreated lymphocytes); 10(-8) M and 10(-10) M were as effective. Prostaglandin F2alpha had no effect on lymphocyte adherence. Prostaglandin E1 increased lymphocyte cyclic AMP five to 10 times whereas prostagladin F2alpha did not affect cellular levels of this nucleotide. Dibutyryl cyclic AMP (10(-8) M) increased lymphocyte adherence: positive human epithelial cells increased from 16.0 +/- 2.4 to 38.7 +/- 1.1 per cent (P less than 0.01). Prostagladin E1 also increased adherence of lymphocytes from patients with systemic lupus erythematosus from 21.8 +/- 5.8 to 52.5 +/- 9.2 per cent (P less than 0.01). These results indicate that prostagladin E1 and cyclic AMP may serve to stimulate T-cell function and cell-mediated immunity.


The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.


Defective interfering particles with covalently linked [+/-]RNA induce interferon. Defective interfering (DI) particles of vesicular stomatitis virus which contain covalently linked complementary [+]message and [-]anti-message RNA as a single-stranded ribonucleoprotein complex within the particle, are extremely efficient inducers of interferon. A single particle can induce a quantum yield of interferon. A single molecule of double-stranded RNA presumed to form, at least in part, on entry into the cell is thought to induce interferon synthesis. Conventional [-]RNA DI particles with the same polypeptide composition as [+/-]RNA DI particles fail to induce interferon.


The cell-growth inhibitory effect of interferon. Studies of a resistant cell-subline. Studies performed in the CSV subline of mouse L-cells suggest that activated endogenous and/or exogenous viral infection might be the factor that modifies the cell surface and, in consequence, the sensitivity of the cell to the cell-growth inhibitory action of interferon. In contrast with the parental L-cells, the CSV subline obtained by prolonged passage of L-cells in the presence of interferon shows an altered electron microscopic morphology, absence of C type particles and a decreased agglutinability with Concanavalin A. It is resistant to the cell-growth inhibitory effect of interferon but retains the sensitivity toward its antiviral effect. However, the sensitivity of the CSV subline toward the cell-growth inhibitory effect of interferon increased significantly after treatment with 5-iododexyuridine, infection with the Harvey strain of mouse sarcoma virus and/or prolonged passages in vitro. In this respect, the CSV subline resembles the primary mouse embryonic cells. Since sensitivity of CSV cells increased also after treatment with cyclic 3'-5' adenosine monophosphate and/or prostaglandin E2, it is possible that the cell-growth inhibitory effect of interferon is mediated through the "second messenger" system.


Physical, chemical and serological properties of C-type virus associated with transplantable rat Thurzo-Svee leukemia. Cells of rat Thurzo-Svee leukemia produce C-type virus. Viral particles are shown to contain high-molecular weight RNA and RNA-dependent DNA polymerase the virus possesses mammalian gs-3 antigen and rat species-specific gs-1 antigen and thus appears to be of rat origin.


Skeletal changes and growth in experimental uremia. Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure.


Coxsackie A9 focal encephalitis associated with acute infantile hemiplegia and porencephaly. The factors underlying acute infantile hemiplegia are seldom identified. Coxsackie A9 focal encephalitis was documented for the first time in a 3-month-old infant with fever, hemiconvulsions, and hemiplegia followed by a static motor deficit and epilepsy. It has been suggested that the acute infantile hemiplegia associated with encephalitis results from an arteritis or venous sinus thrombosis with subsequent cerebral infarction. However, this was not observed in our patient. Rather, a series of brain scans, computerized tomograms, and a cerebral angiogram clearly documented the evolution of a focal necrotizing encephaloclastic process resulting in a porencephalic cyst. Serial cerebrospinal fluid viral cultures were necessary to isolate the etiologic agent (tcoxsackie A9). The infant did not have a neutralizing antibody response to the infecting viral agent despite an apparently intact immune system, which possibly may be explained by the developed of immune tolerance or an insufficient amount of infecting viral antigen. This emphasizes that serologic studies alone may not be adequate to document an acute central nervous system viral infection. This patient also typifies the poor prognosis in infants presenting with acute hemiplegia, fever, and convulsions in the absence of cerebrovascular occlusion.


[A case of recurrent hemoperitoneum caused by hepatocarcinoma]. A case of recurring haemoperitoneum caused by liver cancer is presented. This neoplasia, rare itself in Italy, may have a variety of clinical pictures. Recurring haemoperitoneum is quite exceptional and mistaken diagnosis and aetiopathogenetic interpretation are the likely results. The symptomatology is illustrated and the problem of diagnosis is discussed.


[Contribution of laparoscopy-biopsy to the diagnosis of primary liver neoplasms]. After a review of the literature, personal observations of primary benign and malignant tumours of the liver, studied using laparoscopic biopsy are presented and the importance of this examination in the early diagnosis of primary hepatic tumours is stressed. This examination, particularly when associated with biopsy, is very useful since it reduces diagnosis time with little or no risk to the patient with a high percentage of positive results.


Endometrial cancer associated with feminizing ovarian tumor and polycystic ovarian disease. Feminizing ovarian tumors and polycystic ovarian disease may cause endometrial cancer by abnormal, unopposed endogenous estrogenic stimulation. We reviewed the clinical course of 72 endometrial cancer patients with a concomitant feminizing ovarian tumor or polycystic ovarian disease and compared tumor characteristics and treatment results with those exhibited by 523 patients treated for endometrial cancer alone. With functioning ovarian tumor and with polycystic ovaries, the cancer tended to be more often low-grade, low-stage, and superficial than did endometrial cancer alone. The high 5-year and 10-year survival rates observed in our functioning ovarian tumor-polycystic ovary patients support the conclusion that endometrial carcinoma with a coexistent endogenous estrogenic stimulus has a more favorable prognosis (P less than 0.01) than endometrial carcinoma alone.


Inhibition of glycolytic enzymes of rat liver and hepatomas by free fatty acids. The action of free fatty acids on glycolytic enzymes was compared in normal and neoplastic tissues. Preincubation of tissue supernatant fractions with octanoate or laurate caused an inhibition of the activities of hexokinase and phosphofructokinase. An inhibition was also observed of lactate production with either glucose or glucose 6-phosphate as substrate. A similar degree of inhibition was observed for actions on normal liver and kidney, on the 7800 and 3924-A hepatomas and on the MK-3 renal cortical tumor. The possible relationship between the inhibition of glycolytic enzymes by fatty acids and anti-tumor activity previously observed with these compounds was noted.


The effect of crocetin on skin papillomas and Rous sarcoma. A carotenoid compound, crocetin, was used in two different types of tests involving animal tumors. These tests showed that crocetin both decreased the numbers of tumors as well as delaying onset.


Scanning electron microscopic studies of herpes simplex virus transformed cells. The surface morphology of herpes simplex virus transformed cells was examined by scanning electron microscopy in exponentially growing and density inhibited rat embryo fibroblast cultures. The cell surface of oncogenically-transformed cells became more villated and many microvilli showed branching. C-type virus particles budding from the cell surface were commonly observed. Virus induced cytopathic effects observed by scanning electron microscopy, included rounding up and detachment of degenerating cells from the substrate.


A status report: human prostatic carcinoma, with emphasis on potential for viral etiology. Several parameters of the biology of cancer of the prostate have been reviewed with a continuing assessment of the possible etiologic role of virus. These aspects include epidemiology, clinical studies, morphology, pathology, enzymology, immunology, endocrinology, model animal studies, in vitro systems, and viral investigations. From available literature it is concluded that, to date, the association with several urogenital tissues of herpes-type viruses has been best documented. It is suggested that a fundamental barrier to more sophisticated virologic and biologic studies is the lack of long term cell cultures of normal and pathologic prostate epithelium from males of all ages.


[Somatic hybridization and oncogenesis: induction of tumors in mice by administration of mixtures of cells of the homologous organs and their hybrids]. The 2 months old C57BL/6J mice were injected with the mixtures of kidney and spleen cells from mice of the same strain or of the same cells following the hybridization induced by Sendai virus. The tumours of liver, kidney and lymphoid system appeared in 25% of recipients within 12--14 months. The result obtained is predicted by the general theory of oncogenesis proposed early by L. B. Mekler.


Blindness following blowout orbital fractures. Blindness following blowout fractures is an unfortunate complication. The ophthalmologist must be aware of the events and sites of injury to the optic nerve which lead to visual problems. Preventive measures include immediate recognition of the signs of impending optic nerve compression and execution of treatment without delay. The importance of monitoring vision cannot be overstressed. Judicious surgery involves a post-injury delay in cases that are improving daily. The avoidance of additional surgical trauma with implant insertion during that period may help prevent postoperative blowout blindness.


Incidence of recurrent herpes labialis and upper respiratory infection: a prospective study of the influence of biologic, social and psychologic predictors. In a 3-year prospective study of recurrent herpes labialis (RHL) in a population of 149 student nurses, 40 to 50 per cent of the variance in incidence could be explained by a small group of variables. Measures of previous experience with RHL accounted for the largest fraction of the explained variance, followed by upper respiratory infection (URI) rate, socioeconomic status, and mood trait, in order of declining influence. Timing of RHL episodes was not related to phase of the menstrual cycle.


The role of cutaneous mechanoreceptors in thermal sensation and pain. The functional behavior of slowly adapting cutaneous mechanoreceptors under combined thermal-mechanical stimulation was investigated by single-unit recordings from the lumbar dorsal roots of the cat. Increased sensitivity to bimodal stimulation was observed in 24 of the 28 units studied, employing stimulus-response functional behavior as the basis for judgment. Low-threshold receptors generally did not exhibit increased spontaneous firing as accompaniment to heightened sensitivity, while such enhanced basal activity was usually observed in moderate-threshold units in addition to increased reactivity. Information theory calculations performed on these stimulus-response data revealed that 15 of the 24 "heat-sensitive" receptors were additionally characterized by an enhanced ability to transmit neural information under bimodal  stimulation. These results were interpreted as supporting pattern theories of pain as opposed to the concept of receptor specificity. No contradiction was observed, however, between the present results and those of other investigators. The present conclusions derive from new criteria for thermal reactivity based upon innovative stimulus conditions.


Long-term alloxan diabetes in the rat. Study of mesangial cell morphology by serial biopsies. Experimental diabetes in the rat was induced by alloxan (40 mg/kg body weight) and resulted in permanent hyperglycaemia (mean glycaemia: 403.0 mg/100 ml). The animals were left untreated for more than 16 months. The mesangial cell of the renal glomerulus was studied by serial biopsies performed each month under light anaesthesia in the diabetic animals and in normal controls of the same age. Large dense bodies appeared in the cytoplasm after 3 months in the diabetics and after 10 months in the controls. With time, a larger number of mesangial cells contained these dense bodies. At the end stage they seem to be mainly lipidic. When NO3Ag is given in the drinking water the dense bodies accumulate particles of silver, suggesting that they contain fragments of the basement membrane. While the acid phosphatase reaction was negative in biopsy specimens from diabetic animals, it remains possible that the large dense bodies belong to the lysosomial system. This point, as well as the pathologic significance of the dense bodies is currently investigated.


Tissue culture, electron microscopic and enzyme histochemical investigations of extraadrenal paragangliomas. Light and electromicroscopical as well as histochemical investigations were performed on three cases of extraadrenal paragangliomas. They were localized in the carotid body, tympanicum and cauda equina region. Tissue of two cases was cultivated in vitro in nutrient medium TCM 199. The tumours were classified as paragangliomas of the paraganglionic type with typical cell clusters, of the adenomatous and angiomatous type. The enzyme histochemistry showed a very high dehydrogenase activity. Ultrastructurally numerous typical osmiophilic granules could be observed in the cytoplasm of the tumour cells. In tissue culture only a minimal cellular proliferative activity could be detected. The few proliferating cell colonies showed mostly characteristics of epithelial tissue and sometimes a similar behaviour to cells of a ganglioneuroblastoma. The minimal proliferative activity in vitro is in good agreement with the proliferative behaviour of the extraadrenal paragangliomas in vivo.


The alveolar lining film in experimental pulmonary collapse. Obstructive pulmonary collapse was produced by ligation of lobar bronchus in 41 healthy dogs. The atelectatic lung was examined electronmicroscopically by means of vapour fixation, ruthenium red procedure and tricomplex flocculation. The equilibration stability index of Pattle was determined and compared to the electromicroscopic findings. The experimentally produced obstructive pulmonary collapse was a mechanical phenomenon which secondarily caused qualitative changes in the production of the alveolar lining layer.


[Ultrastructure of the excretory system of the tick Ornithodoros papillipes (Argasidae)]. The ultafine structure of the Malpighian tubes in O. papillipes (Argasidae) was studied. It has been shown that the cells of different parts of the Malpighian tubes have their own peculiarities. The distal cells are characterized by the inclusions which can be interpreted as mucopolysaccharide ones. The main part of the tube was found to contain cells of two types. Most of the cells belonging to the first type have well developed microvilli and poorly developed basal invaginations. The cells of the second type, the number of which increases towards the proximal end of the tube, have small microvilli and narrow folds of the basal labyrinth entering deeply the cytoplasm. The cells of the second type are rich in mitochondria. The ultrastructure of the rectal sac has been studied. The cells of this organ have a polar structure: the apical surface is covered with microvilli, the plasmotic membrane forms deep folds at the base.


Rapid eye movement sleep, motoneurone inhibition, and apneic spells in preterm infants. Not principally different from the results obtained in more mature subjects, monosynaptic reflex excitability of spinal motoneurones in preterm infants decreases during active sleep. However, in preterm infants the electric reflex response is not abolished, and is not even continuously depressed during the entire active sleep period. Spinal motoneurone inhibition is demonstrable only during certain periods of active sleep, and it is during this state of decreased spinal motoneurone excitability when apneic spells predominantly occur.


Separation and characterization of cord serum lipoproteins. Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.


Lung phosphatidylcholine synthesis and cholinephosphotransferase activity in anencephalic rat fetuses with corticosteroid deficiency. Adrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of [14C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnoramlity was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6-12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21-22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes.


Prolonged sleep apnea and respiratory instability: a discriminative study. This report is based on a study of 53 infants, 28 of whom had clinically observed prolonged apnea (greater than or equal to 20 seconds) during sleep whereas the remaining did not. In addition to the clinical observations, each infant was studied in a sleep laboratory during a complete nap, and a continuous recording was made of respiratory activity and rapid eye movements. Measurements were made of all apneic pauses (greater than or equal to 2 seconds) observed in the laboratory and the two groups of infants were compared in terms of the frequency and average duration of apneic pauses, the longest apneic pause, the amount of periodic apnea, and the relative amount of apnea. The infants with prolonged sleep apnea had, during a single nap, more frequent and longer apneic pauses and more periodic apnea. This supports the hypothesis that respiratory instability during sleep and prolonged apnea have a common etiology. By employing a multiple linear regression model and including all laboratory apnea measures in a single analysis, a composite laboratory score was developed to differentiate members of the two groups. It would thus appear that the study of infants during a single nap could assist in the identification of infants at risk for prolonged sleep apnea and provide an indirect method for determining the influence of a number of variables on the occurrence of prolonged sleep apnea. Pediatrics, 59:962-970, 1977, SLEEP, APNEA, RESPIRATORY INSTABILITY.


A comparative study of the calcium accumulation by mitochondria and microsomes isolated from the smooth muscle of the guinea-pig taenia coli. The calcium uptake by mitochondria and microsomes isolated from the guinea-pig taenia coli was studied at physiological Ca2+ concentrations, buffered by Ca-EGTA mixtures. The Ca accumulation by the mitochondria was measured from the difference between the amount of Ca taken up in the presence and in the absence of a specific mitochondrial inhibitor. The Ca uptake by the microsomes was determined in a solution containing oxalate and a mitochondrial inhibitor. It was calculated from the difference in Ca uptake measured with and without ATP. By using this procedure, the necessity of extensive purification of the isolated fractions was avoided. The (Ca2+) for half-maximal transport in the mitochondria is 7 X 10(-6) M. At (Ca2+) lower than 2 X 10(-7) M, Ca is taken up in an energy-dependent way. In the microsomes the apparent Km for Ca is 7 X 10(-7) m. accumulation is still stimulated by ATP at a (Ca2+) as low as 4 X 10(-8) M. The results show that the rate of Ca uptake by the cell organelles corresponding to the microsomal vesicles is sufficiently fast to explain the speed of relaxation of the taenia coli. The results also suggest that these cell organelles are more important than the mitochondria in regulating the cytoplasmic Ca concentration.


Pharmacological evidence in vitro and in vivo for functional beta1 receptors in the cerebral circulation. Blood flow in the caudate nucleus was measured by the thermoclearance technique in non-anesthetized rabbits, accompanied by recording of electrocorticogram, systemic blood pressure, and Pao2 and Paco2 (mass spectrometry). Isoprenaline increased caudate nucleus blood flow and reduced systemic blood pressure. The beta2-receptor agonist, terbutaline, on the other hand, had only peripheral effects. The caudate nucleus flow response was selectively blocked by the beta1-receptor antagonist, practolol, whereas propranolol inhibited all effects of both agonists. Isoprenaline dilated isolated pieces of the tributary artery (middle cerebral) tested in cats, the effect being inhibited not only by propranolol but also by practolol. The results offer further evidence for the view that the beta-receptors in the cerebral vascular bed are of the beta1-type.


[Scanning of the myocardium with pyrophosphate-technetium 99m. 367 cases]. Pyrophosphate-99m Tc injected intravenously is almost invariably fixed in the infarcted zone in transmural infarctions less than 8 days old. Fixation occurs in only 2/3 of cases of rudimentary infarction. The degree of fixation is more or less proportional to the size of the peak of creatine phosphokinase. After the 8th day following infarction, fixation is slight or nil. It is inconstant in pre-infarction syndrome or simple angina. This examination complements clinical, electrocardiographic and enzyme findings, in particular in the case of difficult diagnosis.


[Scintigraphy using Technetium 99 m pyrophosphate in detection of bone metastasis of breast cancers. Analysis of 310 examinations]. Three hundred and ten bone scintigraphies were carried out in patients with a carcinoma of the breast. The results of these studies were compared not only with radiological findings but also the clinical and paraclinical course of the patients, the period of observation being between 8 and 44 months. Amongst the scintigrams in which no abnormality was detected, approximately 3.3% were obtained in patients with osteolytic metastases, the majority of these patients also having a rapidly growing primary tumourmamongst the patients with zones of hyperfixation and, at the same time, non-fixing metastases, 14/22 diedvery rapidly with diffuse bone metastases, this confirming the notion of poor prognosis in this "false negative" group. 11.3% of the abnormal results involved patients who showed no bone lesions more than 6 months after radio-isotopic examination "false positives". Of these, 12/18 were single lessions (41%). 14% of examinations carried out on a routine basis demonstrated metastases for which clinical and/or radiological confirmation was obtained only 2 to 9 months later.


Heterogeneity of 5' -termini of nucleolar 45S, 32S and 28S RNA in mouse hepatoma. The 5'-termini of nucleolar 45S, 32S and 28S RNA's were analyzed by means of thin layer chromatography and Dowex-1 colum chromatography. 45S RNA did not bear a triphosphate at the 5'-terminus, but various monophosphates are found. 5'-termini of 32S and 28S RNA's were also heterogeneous. These results indicate that 45S molecules as isolated with the conventional procedure may not contains the primary transcript of the ribosomal gene, but a collection of large precursors with different degrees of processing at the 5'-terminus. The processing of the primary transcript may thus involve some unknown trimming processes at the 5'-terminus before the first major cleavage takes place.


Specificity of DNA basic polypeptide interactions. II+ Influence of aromatic amino acid residues investigated with agarose bound lysine copolypeptides. Binding affinities towards DNA and base pair specificities of lysine copolymers, containing different amounts of Phe, Tyr or Trp residues, were estimated using a previously described chromatographic method. Incorporation of few aromatic residues into polylysine causes a decrease in the binding affinity, however, further raising the aromatic residue - lysine ratio results in a continous increase of affinity, which is most pronounced with the Tyr copolymers and not observed with polymers containing neutral aliphatic amino acid residues. AT-specificity increases concomitant with binding affinity in the case of the Tyr copolymers but not with the Phe copolymers. The interaction of DNA with the alternating Phe-Lys polymer is significantly stronger than with the random copolymer of equal residue composition. The molecular and conformational reasons determining specificity are discussed.


The control of SV40 transcription during a lytic infection: late RNA synthesis in the presence of inhibitors of DNA replication. The transition from early to late transcription of SV40 DNA in productively infected BSC-1 cells was analyzed using both inhibitors of DNA replication, and early (Group A) temperature sensitive (ts) mutants of SV40. Late virus specific cytoplasmic RNA sedimenting at 16S in neutral sucrose gradients and complementary to the plus (L) DNA strand of SV40 was detected in cultures infected in the presence of three inhibitors of DNA replication (Ara-C, FdU, and chloroquine), even though the inhibition of viral DNA replication appeared to be essentially complete. After infection with the early SV40 mutant tsA58, no DNA replication was detected at the restrictive temperature (41 degrees C) and no significant late RNA complementary to the plus (L) strand was found, in either the cytoplasm or nuclei of infected cells. These data support the concept that expression of late viral functions requires the initiation of viral DNA synthesis or a functional gene A protein, or both.


Nucleotide sequence of the restriction fragment Hind F-Eco RI2 of SV40 DNA. The nucleotide sequence of the SV40 genome region between the Hind K fragment and the Eco RI cleavage site has been determined by a combination of three different approaches : analysis of RNA products obtained by transcription with Escherichia coli DNA dependent RNA polymerase, partial degradations with snake venom exonuclease and base-specific chemical degradation of 5'-terminal labeled restriction fragments. This nucleotide sequence shows only one open reading frame and allows the deduction of a small segment of the amino acid sequence of VP1, the major structural protein.


Nucleotide sequence of the SV40 DNA restriction fragment Hind C-Hap 2. We here report the nucleotide sequence of the SV40 DNA fragment Hind C - Hap 2. The fragment was labeled at the 5'-ends by means of polynucleotide kinase and gamma-(32P) ATP and digested with a suitable restriction enzyme. The separated products were then partially degraded with the base-specific reagents dimethyl-sulphate or hydrazine followed by direct analysis on polyacrylamide gel. The Hind C - Hap 2 sequence is 126 base pairs long and one of the three possible reading frames for translation does not contain any termination codon. So, although no protein is known to be encoded by this region, the possibility cannot yet be completely ruled out. The sequence also contains several AT-rich blocks.


The sequence specificity of vertebrate DNA methylation. The relative quantity of 5-methyl cytosine in vertebrate nuclear DNA shows species and tissue variation. To determine whether this is due to the action of species or cell specific DNA methylases the sequence specificity of the 5-methyl cytosine distribution in the DNA of a range of cells has been partially characterised. The pattern of methylation was found to be remarkably constant and indicates stringent evolutionary conservation of the characteristics of vertebrate DNA methylation.


Histone Hl-DNA interaction. Influence of phosphorylation on the interaction of histone Hl with linear fragmented DNA. By measuring the fluorescence polarization of fluorescent histone H1 derivatives complexed with DNA, binding of the histone to DNA was studied as a function of ionic strength in the solution prior to and after the H1 phosphorylation on Ser-37 residue. Fluorescent labels were covalently linked either specifically to Tyr-72 residues or unspecifically to lysine residues in the H1 polypeptide chain. The values of the corresponding rotational relaxation times showed that at low ionic strength all the segments of the H1 molecule were immobilized on binding to DNA. The gradual increasing NaC1 concentration in the solution of H1-DNA complex was accompanied at first by additional retardation of the histone mobility in the complex, and then by progressive release of histone H1 from from the complex which was completed at 0.5-0.6 M NaC1 irrespective of phosphorylation. tat the same time the phosphorylation of histone H1 led to removal of the central and, presumably, N-terminal regions of H1 from DNA.


Nursing care of patients with viral hepatitis. The nurse's role in the care of clients with acute viral hepatitis is based upon a nursing assessment of the client and his family system, diagnosis and planning for the individual needs of the client, and anticipatory guidance related to the client's return to the family and community.


Covalent attachment of peptides to cytochrome C for automated sequence determination. Because small peptides are lost into the organic solvents used, it is virtually impossible to obtain the complete amino acid sequence of a small peptide using only an automated peptide sequencer of the spinning cup type. To overcome this problem we have extended peptides at the carboxy terminus by attachment to equine cytochrome c by a water soluble carbodiimide, relying on the acetylated N-terminus of the cytochrome to minimize its direct contribution to recovery of PTH-amino acids. The Model Peptide H-Leu-Trp-Met-Arg-phe-Ala-OH was used for most experiments. After reaction of 3H-peptide with cytochrome c, about one-third of the tritium counts migrated with cytochrome c during gel filtration. After attachment, the amino acid sequence of the hexapeptide was readily determined with a single cleavage Quadrol program in a Beckman 890B sequencer, whereas only the N-terminal residue was recovered without attachment. The repetitive yield after attachment was 95-96%, with 21-27+ overlap and an initial yield of 18-20%. Sequence data with other peptides illustrate applications and present limitations of our approach.


Purification of thioredoxin reductase from the Novikoff rat tumor. Thioredoxin reductase (E.C.1.6.4.5.) has been purified to about 95% homogeneity from the Novikoff ascites rat tumor. The enzyme contained two subunits of approximately 58,000 daltons, with one FAD per subunit. The amino acid analysis is reported. An immunoadsorbent was prepared and used for affinity chromatography in order to improve the yield of the enzyme.


[Characteristics of extracellular proteolytic enzymes of Actinomyces fradiae 0072]. The composition of extracellular proteinases from Actinomyces fradiae 0072 and their effect on proteins and synthetic substrates were studied. The enzyme preparation was found to have keratinolytic, caseinolytic, collagenolytic, collagenase, trypsin-like, carboxy- and aminopeptidase activities. Five low molecular weight proteinases capable to hydrolyse keratin, casein, azocollagen were obtained via fractionation of the enzyme preparation on DEAE-cellulose and Sephadex columns. Proteinases from Act. fradiae and aminopeptidase with a molecular weight of 31,000 were shown to be different enzymes. In hydrolysis of L-leucyl-2-naphthylamide the Michaelis constant and Vmax of the enzyme were found to be 3.02 X 10(-3) M and 0.35 X 10(2) micronM/ml-min, respectively.


On the bonding of FeO2 in hemoglobin and related dioxygen complexes. The celebrated Fe(II)0(2) versus Fe(III) (02-) debate over the formal representation of the Fe02 moiety in hemoglobin can be resolved by consideration of the utility of each formalism. In the context of rationalizing the gross structural and electronic features of end-bound dioxygen, particularly in light of a new closely related chromium complex, the M(III)-(02-) formulation is both chemically reasonable and most useful. In conjunction with a qualitative molecular orbital overlap picture, the differing magnetic states of enc-bound M02 complexes and other geometrical features can be rationalized or predicted.


[Change in the activity of lysosomal collagenase during autolysis of intramuscular connective tissue]. Changes in the total, free and bound activity of collagenase of the intramuscular connective tissue were studied during beef muscle maturation (2 degrees C). Lysosomes were isolated by differential centrifugation. The studies showed a relatively rapid release of collagenase from lysosomes and a comparatively high stability of the enzyme during slow autolysis of muscles.


Lipid-protein interaction in the phosphatidylcholine exchange protein. Incorporation of 2-acyl spin-labeled lecithin into the phosphatidylcholine protein from bovine liver results in an immobilization of the spin-label at the methyl and the carboxyl terminal end of the acyl chain. The nitroxide group on the protein-bound lecithin molecule is not accessible to ascorbate. This suggests that lecithin is buried in a pocket on the protein, which effectively shields the acyl chains from the medium.


[Cobalamin levels in rats with transplanted Zajdela ascites hepatoma]. The level of cobalamines in the kidney and liver of healthy rats and rats with implanted Zajdela ascites hepatoma (ZAH) was examined. The results were compared with the data obtained from the rats with sarcoma M-1. It was shown that different tumors had dissimilar effects upon the level of total cobalamines. However, the ratio of free cobalamines to protein-bound cobalamines (cobalamine-protein complexes) varied. The concentration of cobalamine-protein complexes increased in the liver, kidney and in the tumor. The experiments with ZAH demonstrated that ZAH cells contained appreciable amounts of cobalamines, whereas the supernatant contained only a minor quantity of cobalamines. Injections of 5'-deoxyadenosyl-B12 increased the level of cobalamines in ZAH cells and had a low effect on the level of cobalamines in the supernatant.


In vitro synthesis of messenger RNA by a defective interfering particle of vesicular stomatitis virus. A defective interfering particle derived from the heat-resistant strain of vesicular stomatitis virus was analyzed for the presence of virion-associated RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) activtiy. The RNA synthesizing capacity of the defective particles in vitro was similar to that of the wild-type virus. Characterization of the RNA produced in vitro indicated that the defective particles were able to synthesize vesicular stomatitis virus leader RNA and four virus mRNA species that sediment at 12-18 S. These RNA products were identical to the mRNAs synthesized in vitro by the wild-type virus in regard to size, polyadenylation, capping, and methylation. In contrast to the wild-type virus, the purified defective particles did not synthesize the large mRNA species sedimenting at 31 S in vitro. Possible mechanisms of homotypic and heterotypic interferences shown by this defective particle are discussed.


[Ketometabolite of vitamine A, its structure and enzymatic transformation]. The structure and enzymatic transformations of vitamin A keto-metabolite isolated from the rat liver were investigated. With the aid of physico-chemical methods, using isotopes 3/ and 18O, PMR and mass-spectrometry it was demonstrated that the metabolite was an ester of 4-keto-retinol with palmitic acid. The structure of 4-keto-retinal was confirmed by the chemical synthesis and by the enzymatic production of its derivatives. Under the influence of alcohol dehydrogenase 4-keto-retinol in the presence of NAD transformed into 4-keto-retinal which was oxidized into 4-keto-retinoic acid with the participation ofaldehyde oxidase. Similar oxidative enzymatic transformations occurred with the reduced form of the metabolite--4-hydroxyretinol. All the products were characterized in detail. Metabolism of 4-keto-retinyl-palmitate in vivo is realized via the same pathway as metabolism of retinyl-palmitate. The general pattern of oxidation of beta-ionone ring in position 4 of vitamin A and carotenoids is discussed.


Sendai virus-induced hemolysis: reduction in heterogeneity of erythrocyte lipid bilayer fluidity. Hemolysis of human or chicken erythrocytes by Sendai virus causes a change in the structure of the erythrocyte membrane lipid bilayer that can be detected by spin label electron spin resonance. In the intact erythrocyte, the phosphatidylcholine derivative spin label exists in a more rigid environment than the corresponding phosphatidylethanolamine label. Virus-induced hemolysis tends to abolish this difference in fluidity, i.e., the region of the phosphatidylcholine spin label becomes more fluid and that of the phosphatidylethanolamine spin label becomes more rigid. Fatty acid derivative spin labels, which may detect some "average" environment, show no change in fluidity. The fluidity change is detected at several different positions in the fatty acyl chain of the phosphatidylcholine spin label. Sendai virions grown in Madin-Darby bovine kidney (MDBK) cells or grown in eggs and harvested early, which lack hemolytic activity, cause no significant change in bilayer structure. Hemolytic activity and the ability to alter erythrocyte bilayer fluidity can be activated in MDBK-grown Sendai virions by trypsin treatment in vitro and in early-harvest egg-grown Sendai virions by freezing and thawing. Erythrocyte ghosts prepared by osmotic hemolysis and resealed by treatment with Mg2+ or elevated ionic strength exhibit a difference in fluidity between phosphatidylcholine and phosphatidylethanolamine spin labels, although less than that observed in whole cells. Incubation of resealed ghosts with Sendai virus abolishes the difference in fluidity. Unsealed ghosts that have been extensively washed show no heterogeneity in membrane bilayer fluidity, and incubation with Sendai virus causes no further fluidity change. Virus-induced hemolysis as measured by hemoglobin release is more sensitive to inhibition by Ca2+ than is the associated fluidity change in the bilayer.


Pineal protein phosphorylation during serotonin N-acetyltransferase induction. The activity of soluble protein kinase (ATP:protein phosphotransferase,EC 2.7.1.37) and pattern of nuclear protein phosphorylation was monitored in cultured rat pineal glands during the induction of serotonin N-acetyltransferase (acetyl-CoA:serotonin N-acetyltransferase;EC 2.3.1.5)by l-isoproterenol. A nuclear protein appears to be phosphorylated during the early stages of enzyme induction but is not phosphorylated at later stages of induction. This correlates well with the need for RNA synthesis associated with the induction process. The nuclear protein was also phosphorylated when the pineal glands were treated with dibutyryl 3':5'-cyclic AMP. The soluble protein kinase activity appeared to decline during mid-to-late stages of enzyme induction, but there was no concomitant increase in the particulate protein kinase activity.


Primary structure of very low density apolipoprotein C-II of human plasma. Apolipoprotein C-II (apoC-II), a protein constituent of very low density lipoproteins of human plasma and the activator protein of lipoprotein lipase, has been isolated and its amino acid sequence has been studied. The protein has 78 amino acid residues and is lacking cysteine, cystine, and histidine. Chromatography on Bio-Gel P-30 in 25% formic acid of the cyanogen bromide digest of apoC-II yields three fragments designated as CNBr-I, -II, and -III. They contained 50, 19, and 9 residues, respectively. The alignment of the cyanogen bromide fragments has been established as CNBr-III-I-II by isolation and sequence of the tryptic peptides of the intact protein. The amino acid sequences of the tryptic and CNBr peptides were determined by conventional methods. With this information, it was possible to establish the complete amino acid sequence of apoC-II.


Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy. A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically.


Cell-free synthesis of two proteins unique to RNA of transforming virions of Rous sarcoma virus. We have utilized a reticulocyte lysate system to translate the 35S RNA of Rous sarcoma virus. Autoradiograms of the protein products separated on sodium dodecyl sulfate/polyacrylamide gels reveal a heterogeneous mixture of proteins of sizes ranging from 13,000 to 180,000 daltons. In comparing the translational products from 35S RNA of Prague B Rous sarcoma virus with those formed from the RNA of a transformation-defective deletion mutant derived from Prague B, we have found that two proteins, 25,000 and 18,000 daltons, are missing from the latter. Neither of these proteins is immunoprecipitated by monospecific antisera against the structural proteins of avian RNA tumor viruses. The combined atomic mass of 43,000 daltons corresponds to the amount of genetic coding capacity (40,000-50,000 daltons in terms of protein products) deleted from the RNA of the transformation-defective viruses. We propose that these proteins are coded for by the putative oncogene (onc) or sarc (src) gene and that one or both of them may be responsible for the oncogenic transformation caused by these viruses in infected cells.


Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution. Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. "Tumor progression" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral "xenogenization".


Biogenesis of poxviruses: analysis of the morphogenetic sequence using a conditional lethal mutant defective in envelope self-assembly. A conditional lethal, temperature-sensitive mutant of vaccinia, defective in assembly of the virus envelope and maturation, was characterized and shown to mimic exactly the aberrations produced by rifampicin. Analyses of the infection at restrictive and permissive temperatures were conducted with electron microscopy, isotopic pulse-chase experiments in which polypeptides were separated by polyacrylamide slab gels, and assays of core enzymatic activities. The data collected by several approaches reveal that assembly and maturation of vaccinia involves a tightly coupled sequence of interrelated events including the assembly of the envelope, post-translational cleavage of several virion polypeptides, and induction of the core enzymes.


Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system. Using specific antisera to methionine-enkephalin and leucine-enkephalin, we have visualized apparent enkephalin-containing neuronal fibers and terminals throughout the central nervous system of the rat. Immunoreactive enkephalin displays sharply defined localizations. Regions of highest immunofluorescent density include the laminae I and II of the spinal cord, the substantia gelatinosa of the caudal nucleus of nerve V, the vagal nuclei of the medulla, the periventricular and periaqueductal areas of the upper medulla and midbrain, dorsomedial thalamic regions, specific hypothalamic nuclei, the basal ganglia, particularly the globus pallidus and the central nucleus of the amygdala, and the lateral septum. In certain regions enkephalin immunofluorescence corresponds closely with the distribution of autoradiographic opiate receptor grains.


3':5'-cyclic AMP and hormonal control of puparium formation in the fleshfly Sarcophaga bullata. Injection of 3':5'-cyclic AMP (cAMP) into larvae of the fly Sarcophaga bullata 3-4 hr before the beginning of puparium formation (red-spiracle stage) greatly accelerates the onset of tanning without affecting initiation of puparium formation (anterior retraction). Accelerated tanning resembles real tanning in two important respects: the solubility of cuticular proteins becomes reduced and [U-14C]tyrosine is incorporated into the cuticle. Of a number of cAMP analogues tested, 3':5'- cyclic GMP, 2':3'-cyclic AMP, and 5'-AMP were inactive, dibutyryl-3':5'-cAMP had only slight activity, and cyclic IMP and deoxy-3':5'-cAMP showed some activity. Theophylline enhanced the effect of small doses of cAMP or of blood, diluted 1:8, active in the puparium tanning factor. Injection of dopa, dopamine, acetyldopamine, or epinephrine, but not of tyrosine, had an accelerating effect similar to that of cAMP. The tanning-inhibiting effect of DL-alpha-methyl-alpha-hydrazino-beta-(3,4-dihydroxyphenyl)propionic acid monohydrate is reversed by dopamine or epinephrine, but not by tyrosine, dopa, or cAMP. Evidence is presented to indicate that the responses to cAMP are not artifacts but reflect actual biochemical events during tanning.


Drinking behavior in water deprived rats after angiotensin receptor blockade. Angiotensin II is a peptide normally present in the bloodstream and central nervous system. Exogenous angiotensin induces drinking which is inhibited by saralasin, a specific receptor antagonist. Administration of saralasin does not reduce endogenously stimulated drinking. Angiotensin is dipsogenic after intravenous or intracerebroventricular infusion, raising the possibility of multiple access routes to the brain. Water deprived rats were given saralasin by both routes simultaneously to block the access of endogenous angiotensin to recentors reached from blood and ventricular cerebrospinal fluid (CSF). Water deprivation increased plasma (Na+), hematocrit, vasopressin content and renin activity but saralasin treatment did not reduce water intake after 30 or 60 min. Therefore, blood or CSF-bore angiotensin does not appear to be an absolute requirement for water deprivation drinking behavior.


Accuracy of computed tomography of the liver and biliary tract. Computed tomography (CT) is a highly accurate method of detecting and clarifying the nature of space-occupying lesions within the liver. Obstructive (surgical) jaundice can be differentiated from nonobstructive (medical) jaundice very accurately using CT scanning; when obstruction is present, its level and cause can often be diagnosed. CT is not a sensitive method of detecting hepatocellular disease. Sources of error in CT scan interpretation are analyzed.


Cardiac localization of 99mTc-(Sn)-pyrophosphate following irradiation of the chest. Of 70 consecutive cancer patients referred from radiotherapy for bone scans, 32% showed cardiac uptake of 99mTc-(Sn)-pyrophosphate; only 9% of a control group showed this uptake. Of those with prior left hemithorax irradiation, 60% showed cardiac uptake; only 12% of those with irradiation elsewhere showed this phenomenon (p less than .01). The patients who had no increased uptake tended to have shorter irradiation-to-scan time intervals (less than 10 months) than those who did show increased uptake (mean of 22 months).


Ultrastructure and microanalysis of "benign" and "malignant" breast calcifications. Differences in morphology between "benign" and "malignant" breast calcifications were observed in a pilot study utilizing scanning electron microscopy and x-ray analysis. Preliminary data suggest that there may also be chemical differences between calcifications and in the surrounding tissue.


Angiographic demonstration of growth of hepatocellular carcinoma in the hepatic vein and inferior vena cava. A total of 141 patients with hepatocellular carcinoma were examined by selective celiac and hepatic arteriography. In 7 the so-called "thread and streaks" sign or its equivalent was observed along the vertebral column at the level of the diaphragm where the hepatic veins enter the inferior vena cava. Extensive tumor growth in the hepatic vein and invading the vena cava was confirmed by autopsy in 3 and hepatic venography in 1.


Delination of lesions of the base of the skull by computed tomography. It is possible to delineate the extent of tumors related to the base of the skull by computed tomography in two planes. With current scanners, thin sections are possible and the artifacts produced by the bone are minimal. Bone and soft-tissue details can be visualized with clinically useful resolution. Precise evaluation of the extent of such lesions is important in determining surgical or radiotherapeutic approaches. Six illustrative cases are presented.


Rat osteogenic sarcoma cells:effects of some prostaglandins, their metabolites and analogues on cyclic AMP production. Cyclic AMP production by freshly isolated cells, from a 32P-induced transplantable rat osteogenic sarcoma, was stimulated by PGE1, PGE2 and to a less extent by PGF2alpha and PGA2. In the case of PGE2, the cyclic AMP content of cells was maximal within 5 min. The 13,14-dihydroderivatives of PGE1, PGE2 and PGF2alpha had approximately 40% of the activity of the parent prostaglandin whilst, in every case, the metabolites (15-keto and 13,14-dihydro-15-keto) had very little activity. Two prostaglandin endoperoxide analogues (U44069 and U46619) had only 10% of the activity of an equimolar dose of PGE2. The data presented in this paper demonstrates similarities between the responses of these cells and cells derived from bony tissue in terms of the ability of prostaglandins to stimulate bone resorption in tissue culture.


Relations between prostaglandin E2, F2alpha, and cyclic nucleotides levels in rat brain and induction of convulsions. Fully convulsant doses of pentamethylenetetrazole cause marked increase in rat brain cortical PGF2alpha, PGE2, cGMP and cAMP during seizures, whereas subconvulsant doses cause an increase of rat brain cortical PGF2alpha without affecting the other biochemical parameters considered. Rat cerebellar prostaglandins were not modified by the convulsant agent at either dosage.


[Care for single paraplegics by conscentious objectors (author's transl)]. A practical example shows that the rehabilitation of a single, dependent paraplegic cannot be terminated with the completion of the medical rehabilitation phase and the provision of an adequate job. The complete integration necessitates well organized care and assistance. In the described case this has been achieved by personal initiative, because for this problem complex there is a gap in the state rehabilitation system. Private care by conscentious objectors is described and put to discussion.


[Proton relaxation times of water in normal and transformed cells infected with temperature sensitive virus mutants (author's transl)]. Nuclear magnetic resonance spin-lattice relaxation times (T1) of tissue water protons are elevated in samples from tumors when compared to the corresponding normal tissues. In order to exclude differences between the normal and the tumorous tissue samples other than transformation as far as possible the T1values of cells infected by temperature sensitive transforming mutants of Rous sarcoma virus were measured. In this model genetic homogeneity of the host cells as well as identity of the viruses in the normal and transformed state is assured. In the transformed cells the protons relaxed more slowly than in the cells of normal phenotype which were kept at an only slightly higher incubation temperature.


The association of Wilms' tumor with second primary malignancies. Medulloblastoma occurs uncommonly in the neonatal period. Metastatic Wilm's tumor in a newborn is extremely rare. The coincidence of these two neoplasms in one infant, and an equally uncommon combination of Wilms' tumor and a cerebellar medulloephithelioma in another child prompted this report. The authors speculate on the mechanism of oncogenesis in these and other infants with neonatal malignancies.


Prevalence of hyperlipoproteinemia in men with gallstone disease. Lipoprotein disorders are associated with changes in the bile lipid composition, and gallstone disease has been reported to be common in hyperlipoproteinemic patients. To find out whether there is a significant correlation between hyperlipoproteinemia and gallstone disease, we compared the prealence of hyperlipoproteinemia in a consecutive series of male gallstone patients with that in an age-matched consecutive series of gallstone-free patients. The gallstone patients were hyperlipoproteinemic in 43.5% as compared with 22.5% in the control patients. This difference was statistically significant. Prebetahyperlipoproteinemia (type IV) was the most common lipoprotein disorder in gallstone patients as well as in control patients.


[Pancreatic island cell tumors and their syndromes. I. Insulinomas, organic hypertinsulinism]. Based on a retrospective investigation of 61 surgical and autopsy specimens, the histopathologic features and clinical manifestations of islet cell tumors are described. In 33 cases reviewed in the first part of this study there existed indications of primary hyperinsulinism (HI) which was generally verified through fast test, stimulation tests or by insulin determination. In 25 cases the HI was caused by benign B-cell adenomas and in 3 cases by metastasizing carcinomas. In another case, polymacronesia of the pancreas with all patterns from abnormally structured islets to true adenomas was found. This patient was free of symptoms after subtotal pancreatectomy. In 4 other cases neither adenomas nor evident islet changes were identified; subtotal pancreatectomy cured only one patient. The insulinomas were surgically removed in 16 cases locally and in 9 cases by partial pancreatectomy. In two patients the adenomas were detected only after a second operation, and a third suffered from HI despite removal of two adenomas. The majority of insulinomas were characterized by staining and immunohistological technique, and a few electronmicroscopically. Two types of differentiation could be distinguished. The symptomatology of the three carcinoma patients was complex. Two of these patients suffered from severe ulcer disease reminiscent of Zollinger-Ellison syndrome. The third patient fell ill with erythema and other symptoms known from the "glucagonoma syndrome". These malignant tumors could only be incompletely characterized by staining, immunohistology and electronmicroscopy.


[The problem of surgical therapy of malignant kidney tumors]. Critical examination of the results of surgical treatment and new surgical techniques have produced changes in the operative treatment of hypernephroid kidney cancer and nephroblastoma. The limits to operative treatment are, first, the local extension and infiltration of the tumor and, second, the grade and degree of metastases. Surgical removal of the hypernephroma seems to have a positive effect on metastasis regression only in the case of bone metastases. Nephrectomy is indicated only in cases with solitary metastases which can be removed at a second operation. The possibility of arterial embolization in renal hemorrhage in inoperable patients is demonstrated. Current aspects of the operative treatment of nephroblastoma are discussed.


[Herpes simplex encephalitis. A case report with support of the diagnosis by means of brain biopsy]. The pathogenesis, differential diagnosis and therapeutic problems of herpes simplex encephalitis are discussed. Early diagosis of herpes simplex as a leading, and possibly the sole, cause of acute necrotizing encephalitis is crucial to effective management. Decompressive craniotomy in the presence of fulminating cerebral swelling associated with acute onset of the disease is of value as an adjuvant to definitive therapy with antiviral agents.


[Daily excretion of antidiuretic hormone in bronchial carcinoma]. Daily arginine-vasopressin (AVP) excretion was determined by radioimmunoassay in 60 consecutive cases of untreated lung carcinoma. Control excretion was 61 +/- 34 (SD) in 41 healthy subjects and 50 +/- 38 ng/24 h in 10 patients with chronic lung diseases. Overall 20 out of the 60 cases of lung carcinoma presented with abnormally elevated urinary AVP; In the group with anaplastic oat-cell carcinoma, 15 of 23 had elevated urinary AVP with a mean of 370 +/- 331 (SD) ng/24 h if 2 cases with extremely high values of 11 100 and 55 300 ng/24 h respectively are excluded. None of the 9 patients with large-cell carcinoma had elevated urinary AVP, while only 3 of the 19 cases of epidermoid carcinoma and 2 of the 9 cases of adenocarcinoma had high urinary AVP, with means of 127 +/- 8 and 125 +/- 12 ng/24 h respectively. Plasma osmolality and sodium correlated inversely with AVP excretion. However, only 10 of 23 patients with increased urinary AVP had decreased plasma sodium, although one became hyponatremic 9 weeks later. In one patient AVP excretion normalized after radiotherapy. Plasma renin activity and urinary aldosterone were usually low when urinary AVP was high. Two cases with elevated plasma luteotrophic hormone and another with elevated plasma ACTH, all three presenting with oat-cell carcinoma, were found;


Feline oncornavirus-associated cell membrane antigen: expression in transformed nonproducer mink cells. The feline oncornavirus-associated cell membrane antigen (FOCMA) is a target for naturally occurring immunity that protects the cat against development of fibrosarcoma and leukemia. Feline sarcoma virus-transformed "nonproducer" mink cells express high levels of FOCMA, but not the major viral structural proteins. Transformation of the same cells by murine sarcoma virus, or infection with feline leukemia virus, which is nontransforming for epithelial or fibroblastic cells, did not induce FOCMA. Thus, FOCMA expression in mind lung cells is specifically associated with transformation by feline sarcoma virus.


Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Dexamethasone and prednisone in physiologic range increased angiotensin converting enzyme 7- to 16-fold in comparison to control in 3 days at maximal stimulation (4 nM steroid) in rabbit alveolar macrophages in culture. The increase was inhibited by actinomycin D (0.1 microng/ml) and 1 micronM cycloheximide, suggesting that de novo transcription and enzyme synthesis are responsible for the increased enzyme activity. This result is evidence for a regulatory mechanism for angiotensin converting enzyme, which is important in blood pressure control.