The defense mechanism of splitting: developmental origins, effects on staff, recommendations for nursing care.

Splitting as a predominant defense mechanism is used by a large number of people. It is characterized by projection of good and bad qualities onto people in the environment and malformed ego functioning. Nurses need to understand the developmental origins, formation of ego deficits and defense mechanism of splitting so that they can care for these people. Effective nursing care is dependent on leadership which anticipates splitting, maintains a cohesive staff group and intervenes appropriately. Limit setting provides the most effective treatment modality as it supplies the missing internal function of the deficient ego. With this use of limit setting staff will prevent splitting and foster socially acceptable behavior. This will have a dual effect of beginning ego reconstruction and increasing self-esteem for the patient and treatment success for the staff.


Adenosine 3'5'-monophosphate phosphodiesterase of buffalo spermatozoa.

The cyclic AMP-phosphodiesterase (EC 3.1.4.17) of buffalo spermatozoa is distributed in the head, mid-piece and tail fractions and has multiple forms, 70% of which is in the bound form. The bound enzyme was not solubilized by Triton X-100, lubrol or hyamine 2389. Kinetic measurements of the soluble enzyme showed two apparent Km values for low and high cAMP concentrations, i.e. 4.5 and 100 micro M with Vmax values of 0.25 and 2.0 nmol cAMP hydrolysed min-1 mg protein-1. The bound enzyme had an apparent Km of 66.6 microM with a Vmax of 0.75 nmol cAMP hydrolysed min-1 mg protein-1. The pH for optimum enzyme activity was 7.5 and Mg2+ was essential for the activity of the soluble and bound enzymes. Methylxanthines, ATP, ADP and ppi inhibited the soluble and bound enzymes, ATP being the most potent inhibitor.


Suppression of the hypothalamic-pituitary-adrenal axis after subcutaneous cortisone acetate administration in rats.

Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone.


Relation of steroids to liver oncogenesis.

Experience with pathological material from 150 women with liver tumors is reviewed. The features of liver cell adenoma and focal nodular hyperplasia are sufficiently different that the vast majority of the benign tumors can be easily subclassified. Although most occurred in women ingesting steroids, the wide usage of oral contraceptives makes it difficult to prove a causative role. Nineteen of the tumors were malignant and, to date, 12 of those patients have died of their disease. Since hepatomas are much more common than benign liver tumors, one must be even more circumspect in indicting steroids in their causation. In this group of women none had cirrhosis, whereas in the general population cirrhosis is a very common precedent lesion. Further investigation of estrogens and primary liver carcinoma would be timely.


Role of oral contraceptive agents in the pathogenesis of liver tumors.

Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors.


Survey of primary liver tumors and oral contraceptive use.

The American College of Surgeons' survey data on 378 female and 165 male cases of primary liver tumors reported by 477 hospitals in the United States during 1970--1975 are presented. In males, 91.5% of the tumors were malignant, confirming the rarity of benign liver tumors in males. Among females, 43.9% were malignant and 56.1% were benign. Of the 212 benign tumors, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A positive history of oral contraceptive use was found in nearly half of all tumors, 65% of benign tumors, 74% of hepatic cell adenomas, and 74% of focal nodular hyperplasias. High frequencies of benign tumors were observed in the age group 20--30 yr. More than 80% of the tumors in this age group were found in oral contraceptive users. Symptomatology was more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between use of oral contraceptives and hepatic cell adenomas and focal nodular hyperplasias.


Role of hepatitis B virus in primary liver cancer.

There is an excess prevalence of markers of active infection with hepatitis B virus in patients with primary liver cancer in many parts of the world. Early age of infection with hepatitis B virus is likely to be an important factor, resulting in persistent infection that may progress to chronic liver damage. Results of recent experimental studies are consistent with integration of hepatitis B viral DNA with host cell DNA molecules. It is likely that primary liver cancer is the cumulative result of several cofactors including infection with hepatitis B virus; genetic, immunologic, hormonal, and nutritional factors; and environmental factors including mycotoxins and chemical carcinogens.


Precancerous changes in the human liver.

Knowledge of the cellular changes that lead to hepatic neoplasia in humans is limited. Cirrhosis is a common antecedent or accompaniment of liver cell carcinoma and it seems that both its etiology and its time of duration are relevant risk factors. Many cellular changes have been observed in patients and among populations considered to be at risk. Of these, liver cell dysplasia is the most striking, and studies of its prevalence, natural history, and association with particular forms of cirrhosis suggest that it is a precancerous change. Bile duct carcinoma may follow infestation with liver flukes and duct epithelial hyperplasia is present before the development of cancer. Angiosarcoma from several causes is commonly preceded by a peculiar fibrosis, vascular changes, and Kupffer cell hyperplasia.


Pathology of primary liver cancer.

After a brief survey of the factors that play a role in the etiopathogenesis of human hepatocellular carcinomas, a detailed description is given of the macroscopic and microscopic features of human liver cancers as well as their association with cirrhosis. The ultrastructural features of liver cancers of various degrees of differentiation are described. The mode of spread, metastasis formation of primary liver cancers, and most frequent causes of death of liver cancer patients are reviewed.


Biochemical strategy of hepatomas.

An insight into the ordered pattern of enzymatic and biochemical imbalance of cancer cells was made possible, at least in part, by the molecular correlation concept, the concept of key enzymes, and the use of biological model systems. With these approaches the pattern of gene expression in neoplasia can be studied in terms of the activities of key enzymes and their linking with neoplastic transformation and progression. An ordered pattern of biochemical imbalance was recognized in carbohydrate, pentose phosphate, purine, pyrimidine, DNA, and polyamine metabolism and in other biochemical areas. Current work is directed to clarifying the enzymology and metabolic pattern of thymidine metabolism and CTP biosynthesis since these areas are of particular importance in selective chemotherapy and rescue. The activities of key enzymes in thymidine metabolism have been correlated with the growth rates in a spectrum of hepatomas. Increases in the activities of four key enzymes in CTP biosynthesis appear to be specific to neoplasia because no similar pattern was observed in the normal adult resting or regenerating liver or in the fetal and developing liver. The overall pattern discovered in transplantable rat hepatomas applies to other rodent tumors. It is of particular importance that the pattern of biochemical imbalance is also applicable to human hepatocellular carcinomas. With the recognition of the ordered pattern of reprogramming of gene expression in hepatomas, the path is open for the development of sensitive assays for biochemical diagnosis of liver tumors and for a rational design of selective chemotherapy and rescue.


Limitations of current treatment methods for primary carcinoma of the liver.

Because the liver is the largest organ in the human body and is situated deep in a body cavity, large amounts of the parenchymal tissue can be replaced by malignant tissue before any symptoms are noticed. When clinical symptoms are present, the cancer has usually reached an advanced stage, severely limiting the useful application of current treatment methods for cure or prolonged palliation. At present, surgical resection may be expected to produce long-term survivors in 25% of patients resectable for cure. Improved tests for earlier diagnosis and increased awareness on the part of the physican and the patient are needed to permit diagnosis of this cancer in patients with stage I disease, which can be controlled for long periods of time.


Ultrastructure of hepatocellular tumors.

The lesions that appear during hepatocarcinogenesis can be separated into morphologically distinct entities, which have been arranged into sequences believed to represent stages in carcinogenesis. Similarly, the primary and transplantable hepato-cellular carcinomas (HCC) can be arranged into a sequence of stages believed to represent the progression toward the ultimate cancer cell. Separation of morphological entities has been most successful in rat liver. Ultrastructural studies differentiate between lesions derived from hepatocytes and those originating in other cellular components of the liver. They show that there is variability and divergence in the structure of cellular organelles in the early stages of carcinogenesis, that there is simplification of cellular structure and of organelles during the progression of HCC, and that qualitative changes specific for cancer cells do not exist. Toxic changes associated with the process of carcinogenesis are loss of stacks; wrapping of cisternae around mitochondria; dilation, denudation, and vesiculation of cisternae; increase of autophagy; depletion of glycogen, and enlargement of nuclei and nucleoli. Early changes are storage of glycogen and hyperplasia of smooth endoplasmic reticulum. Subsequent alterations are increased variability in the size, shape, and structure of mitochondria and in the structure of endoplasmic reticulum, including the appearance of fingerprints. A transient stage recognizable by storage of lipid may represent a degenerative process. Ultrastructural characteristics of basophilic cells such as abundance of free ribosomes and absence of glycogen and of smooth endoplasmic reticulum suggest that they may be a stage in the formation of HCC. Progression of HCC is associated with a decrease in the number and size of mitochondria, reduction of mitochondrial cristae, decrease in the number and complexity of microbodies, reduction of the tubulovesicular form of smooth reticulum, accumulation of free ribosomes, and increase of the granular component and condensation of the fibrillar component of nucleoli. Various types of nuclear inclusions reflect the increased mitotic rate of the neoplastic tissue. Changes of the cellular surface are believed to be associated with the ability of the cells to invade and metastasize. Future investigations will require the use of single doses of potent carcinogens, application of morphometric methods at the ultrastructural level, and acceptance of primates as models for human hepatocarcinogenesis.


Histology and ultrastructural aspects of virus-induced primary liver cancer and transplantable hepatomas of viral origin in chickens.

The macroscopic, light microscopic and electron microscopic features and biological properties of MC-29 virus-induced hepatocellular carcinomas in chickens are described. The tumors developed in noncirrhotic livers within a very short time and formed metastases. Virus production was also evidenced in the tumors. There were also indications of virus production in the transplantable tumors. The tumors grew equally well after sc, ip, or im inoculation. In about 25% of the tumor-bearing animals, tumorous nodules developed in the liver. It could not be established whether they were metastases or primary liver cancers induced by viruses released from the transplantable tumors.


Transformation-defective mutants of Rous sarcoma virus with longer sizes of genome RNA and their highly frequent occurrences.

Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77 and Rous-associated virus-7. td viruses spontaneously segregated in uncloned TYPR-C also contained genomic RNA of a size similar to tdTYPR-C RNA. On the other hand, two td mutants isolated from another stock of PR-C (LAPR-C) had the class b RNA. Fingerprint analysis confirmed that tdTYPR-C and tdLAPR-C were derived by deletion from clone 2 of TYPR-C and LAPR-C, respectively, and also showed that clone 2 of TYPR-C had sequences in its genome RNA different from those of LAPR-C, although it gave a fingerprinting pattern similar to the latter. These results strongly suggest that differences between the nucleotide sequences in TYPR-C and LAPR-C RNA may result in different extents of deletion.


Translation of encephalomyocarditis virus RNA in reticulocyte lysates: kinetic analysis of the formation of virion proteins and a protein required for processing.

In cell-free extracts derived from rabbit reticulocytes, encephalomyocarditis RNA can be translated completely, and the products can be processed extensively to give encephalomyocarditis virion proteins and several nonvirion proteins, including a genome-coded protein required for processing. The latter is probably a protease. Translation is very efficient. Under typical conditions, each EMC RNA is translated approximately eight times during a 3-h period. Kinetic analyses (time-course experiments, pulse-chase experiments, and pulse-stop experiments) have been used to determine the time of appearance of major products, and these times have been correlated with map positions. The gene for the putative protease is located near the middle of the genome downstream from the virion protein genes. Ribosomes can travel the length of encephalomycarditis RNA within 30 min, but there is a delay in their progress along the RNA at some point soon after they traverse the region coding for virion protein precursors. This delay results in the accumulation of precursors for a period of about 10 min before the putative protease is made and virion proteins (epsilon, alpha, and gamma) are released by proteolysis.


Biochemical behavior of MC-29 virus-induced transplantable chicken hepatoma.

Studies were performed to test the applicability of the molecular correlation concept developed in chemically induced transplantable rat hepatomas to virally induced transplantable hepatoma in chicken. In a comparison of the activities of carbohydrate, purine, and pyrimidine key enzymes in rat and chicken hepatomas, similar patterns were observed in rodent and avian tumors. These results show that the enzymatic imbalance elucidated in chemically induced rat hepatomas is applicable to the virus-induced hepatoma in chicken, independent of the nature of the carcinogenic agent and the species.


Comparative study of tumor-specific transplantation antigens of MC-29 chicken hepatoma and Rous sarcoma virus-induced sarcomas in mice.

Immunization of CBAT6T6 mice with MC-29 hepatoma antigen did not change the take of Rous sarcoma virus, Schmidt-Ruppin strain [RSV(SR)] mouse tumors after sc transplantation. Immunization with MC-29 hepatoma antigen only slightly increased the average survival time of the mice and significantly decreased tumor growth only at the minimal lethal dose level. Immunization of mice with MC-29 hepatoma antigen and immunization with chicken Rous sarcoma gave similar results; both elicited much less transplantation resistance than immunization with irradiated RSV(SR) mouse tumor cells. The data indicate that there are common tumor-specific transplantation antigens of MC-29 hepatoma and Rouse sarcoma, but further in vitro experiments are needed to prove this.


Capsid protein precursor is one of two initiated products of translation of poliovirus RNA in vitro.

Previous studies in our laboratory have demonstrated that cell-free systems translating the Mahoney strain of poliovirus type I RNA utilize two unique initiation sites. In this study, defective-interfering particles of poliovirus, which contain deletions in the region encoding the capsid proteins, are shown to initiate translation of proteins in vitro at these same two sites. Both the standard virus and the defective-interfering virus RNA direct the synthesis of two polypeptides labeled with n-formyl-methionine (fmet) at their amino termini. The size of the smaller fmet polypeptide synthesized in vitro by the defective virus appears identical in size to that of the standard virus. However, the larger-molecular-weight fmet polypeptide is reduced in size from 115,000 to 69,000 daltons. This correlates exactly with the reduced size of the precursor to the capsid proteins synthesized by the defective virus in vivo and with the size of the deletion in the defective virus RNA (1,200 bases). This provides genetic evidence that the 115,000-dalton fmet polypeptide synthesized into vitro by the standard virus is NCVP1a, the precursor to the coat proteins. Although the identity of the small (5,000 to 10,000 daltons) fmet polypeptide is not clear, several lines of evidence enable us to exclude the possibility that it is VP4, the smallest viral capsid protein.


Chromatin alterations and gene function disorder in MC-29 virus-derived hepatoma.

The disorder of gene expression in hepatomas was studied by following certain metabolic alterations (enzyme stimulation, nucleic acid labeling) after glucocorticoid treatment and analyzing the site of action of glucocorticoids. Compared to normal liver, the MC-29 virus-derived transplantable hepatoma (VTH) responded abnormally to glucocorticoids, which failed to stimulate the activity of certain enzymes (glucose-6-phosphatase, aryl hydrocarbon hydroxylase) or to inhibit DNA synthesis. Since the binding capacity of the cytosol steroid receptor was the same in liver and VTH but the interaction between the steroid receptor and DNA was reduced in VTH, it was concluded that structural alterations of chromatin nonhistones--including processed steroid receptor--may be responsible for the lack of physiological responses to steroids in VTH. Furthermore, the increased proportion or repetitive sequences in VTH DNA may be a feature of the disorder of gene regulation in malignant cells.


Hepatocyte suspensions and cultures as tools in experimental carcinogenesis.

Isolation of preneoplastic cell populations would greatly facilitate analysis of the development of liver carcinogenesis. Suspensions of intact single cells can be prepared in an almost quantitative yield by two-step perfusion of the isolated liver. In the first step the liver is perfused with a Ca2+-free buffer (or with EGTA) in order to irreversibly cleave the desmosomes; in the second step perfusion with Ca2+-activated collagenase dissolves the collagenous extracellular matrix. The resulting single-cell suspension will be a mixture of intact normal and preneoplastic hepatocytes, other liver cell types (mostly Kupffer and endothelial cells), damaged cells, and subcellular debris. Intact hepatocytes can be purified--e.g., by differential centrifugation--but separation of preneoplastic from normal cells has not yet been achieved. Density gradient separation or selection in culture on the basis of the unique properties of preneoplastic hepatocytes (e.g., drug resistance) may prove useful. The use of hepatocyte cultures and liver-derived epithelial cell lines as test systems and models for chemical carcinogenesis in vitro is briefly reviewed.


Protein synthesized early after infection is linked to the termini of adenovirus type 2 DNA synthesized in vivo and in vitro.

The human adenovirus DNA genome contains a protein (CBP, or covalently bound protein) linked to each 5' terminus. To assess whether CBP is synthesized early, infected cells were incubated with hydroxyurea from 1 to 18 h postinfection, the hydroxyurea was removed, cycloheximide was added, and viral DNA was labeled with [3H]thymidine from 18 to 23 h postinfection. Removal of hydroxyurea at 18 h postinfection permits the synthesis of viral DNA, whereas cycloheximide maintains the block in late viral protein synthesis. Three lines of evidence are presented to show that viral 3H-labeled DNA prepared by this procedure was linked to CBP: (I) the DNA sedimented more rapidly than protein-free DNA (i.e., protinase treated) in neutral sucrose gradients containing guanidine  hydrochloride; (ii) the DNA banded at a lower density than protein-free DNA in CsCl gradients containing guanidine hydrochloride; and (iii) neither the 3H-labeled DNA nor the end fragments produced by EcoRI digestion entered a 1.4% agarose gel during electrophoresis. These experiments are strong evidence that CBP is not a product of a late viral gene and is therefore the product of either an early viral gene or a cell gene. Experiments were performed to test whether CBP is attached to viral DNA synthesized in vitro by a soluble complex that synthesizes exclusively viral DNA as completed viral genomes in vitro. In vitro-labeled DNA was analyzed by velocity sedimentation, equilibrium sedimentation, and agarose gel electrophoresis as described above. Our results indicate that the majority of in vitro-synthesized DNA molecules were attached to CBP. These results, which indicate that CBP is synthesized early after infection and is attached to viral DNA labeled in vitro by a soluble replication complex, are consistent with the idea that CBP may play a role in viral DNA replication.


Polyoma viruses with mutations at endonuclease HindII site 1: alterations at the COOH terminus of VP1.

Four mutants of polyoma virus lacking endonuclease HindII site 1 were isolated and characterized with respect to the VP1 coding sequence. Three of these mutants had deletions that removed 0.2 to 0.3% of the genome. All three deletion mutants encoded VP1 proteins that were smaller than wild type and that lacked one or more tryptic peptides normally found in the wild-type VP1 protein. Our results suggest the HindII site 1 is at, or very near, the carboxy terminal end of the coding sequence for VP1. A model for the peptide organization in that region is presented.


Subcellular Localization of simian virus 40 large tumor antigen.

The distribution of simian virus 40 large tumor antigen in subcellular fractions from simian virus 40-transformed hamster (H-50) and mouse (VLM) cells and from simian virus 40-infected monkey cells was determined. Solubilized [(35)S]-methionine- or (32)P(i)-labeled surface membrane and nuclear fractions were prepared, immunoprecipitated with hamster anti-T serum, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor antigen with an apparent molecular weight of approximately 96,000 was detected in both subcellular fractions. Minor components of approximately 68,000 and approximately 56,000 with anti-T reactivity which labeled with [(35)S]methionine were also detected in both fractions from H-50 cells, as were components of approximately 140,000 and approximately 56,000 from VLM cells. The 56,000 component appeared to be greatly reduced in (32)P(i)-labeled surface membrane fractions. Normal cells or cells transformed with a heterologous agent, such as polyoma virus or a chemical carcinogen, lacked immunoprecipitable tumor antigen. Cell fractionation was monitored by [(3)H]thymidine labeling, NADH-diaphorase activity, and Na(+)-K(+)-dependent ATPase activity. These analyses revealed only trace contamination of surface membranes by nuclei, extremely low levels of nuclear rupture during homogenization, and an approximate 10-fold enrichment of surface membrane. Reconstruction experiments demonstrated that soluble tumor antigen failed to associate or copurify with surface membranes during fractionation procedures. These results indicate the presence of a protein in the plasma membrane of cells transformed or infected by simian virus 40 that is immunologically indistinguishable from nuclear tumor antigen.


Structural analysis of the intracellular RNAs of murine mammary tumor virus.

We have characterized murine mammary tumor virus (MuMTV)-specific RNA in several types of cells in which viral DNA is transcribed into RNA: cultured GR mouse mammary tumor cells, S49 lymphoma cells from BALB/c mice, lactating mammary glands from C57BL/6 mice, and mink lung cells infected in vitro with MuMTV. In all cell types studied, there are three distinct species of intracellular viral RNA, with sedimentation coefficients of 35S, 24S, and 13S (or molecular weights of 3.1 X 10(6), 1.5 X 10(6), and 0.37 X 10(6), as determined by rate-zonal sedimentation in sucrose gradients and by electrophoresis in agarose gels under denaturing conditions. These three viral RNA species appear to be present regardless of viral RNA concentration, responsiveness to glucocorticoid hormones, production of extracellular virus, and use of either endogenous or acquired MuMTV proviral DNA as template. The three viral RNAs display characteristics of mRNAs in that they are polyadenylated, associated with polyribosomes, and released from polyribosomes by treatment with EDTA; hence all three species presumably direct the synthesis of virus-coded proteins. The two larger species of viral RNA are probably responsible for synthesis of the structural proteins of the virion, but the function of the 13S RNA is not known. Both of the subgenomic RNAs contain sequences found at the 3' terminus of 35S (or genomic) RNA. However, only the 24S RNA (not the 13S RNA) contains sequences which are located at the 5' terminus of 35S RNA and are apparently transposed during RNA synthesis of maturation, as described for subgenomic mRNA's of other retroviruses.


Simian virus 40 gene A regulation of cellular DNA synthesis. I. In permissive cells.

The kinetics of host cellular DNA stimulation by simian virus 40 (SV40) tsA58 infection was studied by flow microfluorometry and autoradiography in two types of productively infected monkey kidney cells (AGMK, secondary passage, and the TC-7 cell line). Prior to infection, the cell populations were maintained predominantly in G0-G1 hase of the cell cycle by low (0.25%) serum concentration. Infection of TC-7 or AGMK cells by wild-type SV40, viable deletion mutant dl890, or by SV40 tsA58 at 33 degrees C induced cells through S phase after which they were blocked with a 4N DNA content in the G2 phase. The infection of TC-7 cells by tsA58 at 41 degrees C, which was a nonpermissive temperature for viral DNA replication, induced a round of cell DNA synthesis in approximately 30% of the cell population. These cells proceeded through S phase but then re-entered the G1 resting state. In contrast, infection of AGMK cells by tsA58 at 41 degrees C induced DNA synthesis in approximately 50% of the cells, but this population remained blocked in the G2 phase. These results indicate that the mitogenic effect of the A gene product upon cellular DNA is more heat resistant than its regulating activity on viral DNA synthesis and that the extent of induction of cell DNA synthesis by the A gene product may be influenced by the host cell.


Late replicative intermediates are accumulated during simian virus 40 DNA replication in vivo and in vitro.

Simian virus 40 (SV40) replicating chromosomes were extracted from nuclei of infected cells. The chromosomes in the extract were resolved on neutral sucrose gradients, and the extent of replication of the DNA in the chromosome peaks was determined. The extract, in combination with cytosol factors and the appropriate  precursors, supports the continued replication of viral DNA. The products of the incubation were mature form I DNA and molecules (after deproteinization) with sedimentation coefficients, in neutral sucrose, of 22S and 29S. The results of our analysis of this system indicate the following. (i) The 22S molecule, which has been described by previous workers, is a relaxed, replicating molecule and is an artifact of the in vitro system. (ii) When the in vitro synthesis is performed at optimal ionic strength (150 mM potassium acetate), the artifactual 22S molecule does not appear. (iii) Late replicative intermediates do accumulate in vivo and in vitro. The major late form accumulated is 91% completed. (iv) The replicating chromosomes can be resolved into two distinct peaks on neutral sucrose gradients. The molecules in these peaks differ in extent of replication. (v) The nuclear extraction procedure preferentially extracts early replicating chromosomes. The relevance of these data to the problem of SV40 and cellular chromosome replication and termination is described.


Evolutionary relationships of the primate papovaviruses: base sequence homology among the genomes of simian virus 40, stump-tailed macaque virus, and SA12 virus.

Physical maps of the genomes of the two newly discovered primate papovaviruses, SA12 and stump-tailed macaque virus (STMV), were generated by restriction endonuclease analysis. The base sequence homologies among the genomes of SA12, stump-tailed macaque virus, and simian virus 40 (SV40) were studied by heteroduplex analysis. Heteroduplexes between SA12 and SV40 DNAs and stump-tailed macaque virus and SV40 DNAs were constructed and mounted for electron microscopy in various amounts of formamide to achieve a range of effective temperatures. At each effective temperature, the regions of duplex DNA in the heteroduplexes were measured and localized on the SV40 physical and functional maps. By analyzing the data from this study and rom our previous study (N. Newell, C. J. Lai, G. Khoury, and T. J. Kelly Jr., J. Virol. 25:193-201, 1978) on the base sequence homology between the genomes of BK virus and SV40, some general conclusions have been drawn concerning the evolutionary relationships among the genomes of the primate papovaviruses. The extent of homology among the viral genomes does not reflect the phylogenetic relationships of their hosts. At comparable effective temperatures Tm - 33 degrees C), the heteroduplexes between the DNAs of BK virus and SV40 contained the largest amount of duplex (about 90%). The heteroduplexes made between SA12 and SV40 DNAs were slightly less homologous, containing about 80% duplex. The heteroduplexes made between SV40 and stump-tailed macaque virus DNAs were only 20% duplex under the same conditions. When the various heteroduplexes were mounted for microscopy at effective temperatures greater than Tm - 33 degrees C, the fraction of the duplex DNA decreased in each case, indicating the existence of considerable base mismatching in the homologous regions. When specific coding or noncoding regions of the viral genomes were compared, the data indicated that the extent of sequence divergence differed markedly from one region to another. In all the heteroduplexes studied, there were two regions, located near the junctions between early and late regions on the SV40 map, which were essentially nonhomologous. All of the heteroduplexes studied showed significantly greater homology in the late region than in early region. Within the late region, the sequences coding for the major capsid polypeptide, VP1, were the most highly conserved.


Detection of virus-specific RNA in simian sarcoma-leukemia virus-infected cells in in situ hybridization to viral complementary DNA.

An in situ molecular hybridization system which will detect retrovirus RNA in the cytoplasm of individual virus-infected cells has been developed. The technique was applied to cells infected with simian sarcoma-leukemia virus, where the virus-specific RNA was detected by hybridization to simian sarcoma-leukemia virus 3H-labeled complementary DNA. The system is useful for detecting viral RNA-containing cells in the presence of an excess of virus-negative cells and for determining which type of cell in a heterogenous population is  expressing viral RNA.


Clinical features of acute coxsackie B viral myocarditis.

Clinical features of 11 patients of acute Coxsackie B viral myocarditis diagnosed by neutralizing antibody titers were reported. All patients had a flu-like symptom and 8 patients had fever. Initial cardiac manifestations were congestive heart failure in 9 patients, and syncopal attack in 4 patients. Electrocardiographic abnormalities frequently observed were non-specific ST-T changes, low voltage, and intraventricular conduction, disturbances including 4 patients of complete A-V block due to trifascicular block. Ten patients had a rise of serum enzymes. It seemed that in severe patients the serum enzymes rose markedly. From the analysis of laboratory and histological findings. Coxsackie B viral myocarditis were often complicated by hepatitis.


Clostridium perfringens exotoxins. VI. Reactivity of perfringolysin O with thiol and disulfide compounds.

The reactivity of perfringolysin O with thiol and disulfide compounds was studied. The activation potency of thiols was roughly proportional to the reaction rate constants of 5,5'-dithiobis-(2-nitrobenzoic acid) with thiols, which should be inversely proportional to their oxidation-reduction potentials. 1,2-Dimercaptoethane, which had the highest rate constant, most potently activated the toxin among the thiols tested and 4,4'-dipyridyl disulfide, which is known to be one of the most potent thiol-disulfide exchanging reagents, strongly inhibited toxin activity. Toxin activity was also inhibited by other thiol inhibitors.


Pathology of diarrhea due to mouse hepatitis virus in the infant mouse.

Two-day-old mice were inoculated orally with a mouse hepatitis virus which had been isolated from a suckling mouse with fatal diarrhea, and a systemic infection was shown to be established, though enterotropism of the isolate was evident. Significant viral growth and syncytium forming lesions were first detectable in the intestines at day 2 postinoculation, followed by the development of focal necrotic hepatitis. The virus titer in both liver and intestine attained maximum levels at days 4 to 5. Death occurred at day 5 or later, and 60 to 100% mice died during the first 2 weeks of life. Before death, some mice showed neurologic signs with high titered viruses recovered from the brain. The necrotizing lesions were also demonstrated in the lung and lymphoid organs.


Continuous lines of RSV-transformed embryo cells and peritoneal macrophages of Japanese quails.

Four continuous lines of RSV-transformed quail cells were established; QERC-31F and QERC-31N cells derived from quail embryo cells and PERP and PERY cells from adult quail peritoneal macrophages. Marked morphological difference was noted between QERC-31F and QERC-31N; the former showed fusiform shape and the latter nodular shape. Both PERP and PERY showed macrophage-like morphology with phagocytic capacity. All four cell lines contained gs antigen and gp 85. Production of transforming virus was found in QERC-31N, PERP and PERY. In spite of failure in production of transforming virus, EQRC-31F was demonstrated to produce C-type particles by electron microscopy and to contain tumor-specific surface antigen by in vivo immunization and in vitro microcytotoxicity tests.


Histopathological factors predictive for prognosis of lung cancer.

This study was done on 110 lung cancer patients who had received surgical resection consisted of two groups; one group of 43 who survived more than 5 years without recurrence and the other group of 67 who died within one year following surgery. Prognostic significance of the histopathological features at the primary tumor site as well as the regional lymph nodes were compared between the two groups. Blood vessel invasion by the tumor and lymph node metastasis appeared to be equally significant prognostic factors. Patients having the both factors had little chance for survival. Abundant lymphoid cell infiltration around the tumor was associated with longer survival. Lymphoid cell infiltration at the site of blood vessel invasion also was associated with better prognosis. Follicular hyperplasia and paracortical hyperplasia in the regional lymph nodes were favorable prognostic indicators, whereas sinus histocytosis was poorly significant prognostic indicator.


Assessment of host immune status during progressive growth and after excision of DNA virus (simian virus 40) tumors in hamsters: comparison of tumor-specific and tumor-unrelated parameters of immune responsiveness.

The kinetics of cell-mediated immunity to simian virus 40 (SV40) tumor-specific transplantation antigen (TSTA) were compared to the kinetics of tumor-unrelated parameters of immune responsiveness in the assessment of the immune statuses of inbred MHA/SsLAK hamsters during the course of progressive syngeneic SV40 tumor growth and after tumor excision. With the use of the tumor cell neutralization test in vivo and the macrophage migration inhibition assay in vitro, specific cellular immunity to SV40 TSTA was detected by 4 days after tumor cell inoculation, when the tumor was small. This tumor-specific immune response was no longer detected at 7 days after tumor cell inoculation, when the tumor had reached a mean diameter of 12.5 mm, but it returned by 14 days after surgical excision of the tumor. The patterns of host responsiveness to mitogens in spleen cells derived from tumor-bearing animals or from tumor-excised animals generally showed little or no correlation with the kinetics of tumor-specific cellular immunity. The kinetics of the humoral immune response to murine erythrocytes, as determined by hemagglutination assays, correlated much more closely with the kinetics of tumor-specific immunity than did the responses to mitogens. IgG antibody (T-dependent) responses were more affected by progressive tumor growth than were IgM antibody (T-independent) responses. The data suggest that results of tests with the use of tumor-unrelated parameters of immune responsiveness for the assessment of the immune status of cancer patients should be interpreted with caution.


Association of tumor induction by ultraviolet light-inactivated adenovirus 2-simian virus 40 recombinants with a specific segment of simian virus 40 DNA.

The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.


Pleiotropic phenotype of cultured murine cells resistant to maytansine, vincristine, colchicine, and adriamycin.

A noncloned subline of 3T3FL cells was developed that was resistant to the toxicity of the ansamycin alkaloid maytansine. Culture of 3T3FL cells with serially increasing concentrations of maytansine resulted in a cell line resistant to maytansine at concentrations 118-fold higher than concentrations cytotoxic for parental cells. Resistant cells (3T3r) exhibited cross-resistance to colchicine, vincristine, adriamycin, and, to a lesser extent, cytochalasin B. Studies of binding and uptake of tritiated colchicine suggested that drug resistance of 3T3r cells might reflect decreased uptake of drug without decreased binding to surface receptors. Murine sarcoma virus transformed 3T3r cells less efficiently than 3T3FL cells.


Immunocytochemical distribution of mouse mammary tumor virus antigens in BALB/cfC3H mammary epithelium.

The distribution of mouse mammary tumor virus (MuMTV) antigens was studied in normal, preneoplastic, and neoplastic mammary epithelia from female BALB/cfC3H mice with the use of a polyvalent anti-MuMTV serum and indirect immunoperoxidase techniques. The MuMTV antigens were on the apical surface or in focal cytoplasmic aggregates or diffused throughout the infected cells. As much as 70% of all cells in adenocarcinomas and as much as 100% of all cells in preneoplastic hyperplastic alveolar nodules contained MMTV antigens. Comparable percentages of cells from mammary glands of multiparous mice were MuMTV-positive. Some mammary tissues of nullparous and primiparous mice did not contain detectable MuMTV antigen. The MuMTV antigen-containing cells in lactating mammary glands tended to be in discrete lobuloalveolar clusters surrounded by antigen-negative alveoli. The percentage of MuMTV-positive cells in a given gland was proportional to the amount of virus found in the animal's milk.


Reduced prevalence of the Lucké renal adenocarcinoma in populations of Rana pipiens in Minnesota.

Northern leopard frogs (Rana pipiens) afflicted with the Lucké renal adenocarcinoma virtually disappeared from Minnesota in the autumn of 1977. Frogs from four sites in Minnesota counties (Polk, Otter Tail, Kandiyohi, and Scott) with a previously high prevalence of Lucké renal tumor were studied. In the past decade, prevalence averaged 4.2% in 29 collections (total, 1,870 frogs). No tumors were detected in 685 frogs autopsied in the autumn of 1977 by the method of previous studies. Frog collections, each comprised of 20 or more individuals, were compared for the presence or absence of tumor-bearing frogs. Significantly fewer collections contained tumor-bearing frogs in the autumn of 1977 than did collections of previous years.


H-2-dependent regulation of the high level of expression of ecotropic murine leukemia virus.

Adult B10.Y mice, which are congenic with C57BL/10ScSn ((B10) mice for the H-2 region, expressed a high titer of infectious ecotropic virus in the spleen. F1 hybrids between B10.Y and B10 mice were negative or had very low levels of virus expression. In (B10.Y x B10)F2 segregant mice, the high virus phenotype segregated with the H-2pa haplotype of B10.Y, whereas the virus-negative phenotype was associated with the H-2b haplotype of B10. Molecular hybridization experiments with a selected ecotropic AKR murine leukemia virus cyclic DNA probe indicated that both partner strains possessed ecotropic virus sequences and that the number of sequences present was the same in B10.Y mice as in B10 mice. This finding excluded the possibility that the H-2-related effect might be due to the presence of additional viral structural genes within or close to the H-2 region of B10.Y mice. The level of expression of this endogenous ecotropic virus was therefore affected by regulatory genes of the H-2 region.


[Hormone receptors and hormone action (author's transl)].

All hormones act only on their target tissues. The ability of a tissue to react to a hormone is due to the presence of a receptor in or at the cell. There are two classes of hormone receptors: those bound to the membrane and those present in the cytosol. Peptide hormones generally act through membrane receptors. The interaction of a hormone with its receptors leads to an activation of the adenylate cyclase and the production of cyclo-AMP, the second messenger. In cases where several hormones act on the same tissue (example: adipose tissue) they must interact with their specific receptors, but presumably with the same adenylate cyclase. This interaction is discussed. The receptors for steroid hormones are not membrane-bound, but present in the cytosol. They are specific proteins which bind the hormone rather tightly. This results in a change in protein conformation, sometimes accompanied by a dimerization; the modified receptor is then transferred to the cell nucleus where it stimulates transcription. The control mechanisms of transcription are discussed; the most probable mode of action is removal of a repressor or repressor-like component from chromatin which results in deinhibition of transcription. mRNA is then produced and translated into protein. Post-transcriptional controls have been postulated, but never unequivocally demonstrated.


[Structure and function of biological membranes (author's transl)].

Biological membranes are essentially asymmetric two-dimensional solutions of proteins in a bimolecular lipid layer. The overall structure and many physical properties of biological membranes can be explained by the fact that membrane proteins and membrane lipids contain hydrophilic as well as hydrophobic domains. Most biological properties of the membrane are determined by the membrane proteins which can catalyze directional processes. With the membrane protein cytochrome oxidase it will be demonstrated how the three-dimensional arrangement of membrane proteins can be studied by chemical, fluorometric, and electron optical methods. However, it is in most cases still impossible to explain the function of a membrane on the basis of its molecular architecture.


[On the physiology and pharmacology of endorphins (author's transl)].

Endorphins are peptides with opiate-like action synthesized in various tissue, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gyl-Phe-Met-OH) is likely to be a fragment of the peptides alpha- and beta-endorphin, both showing opioid-like actions, as well as of beta-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. beta-liportropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulator or even of neurotransmitters. The pharmacological actions of endorphins resemble those of "classical opiates", both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet.


Catecholamine secreting tumor of the glomus jugulare.

A case of endocrinologically active glomus jugulare is presented. The localization within the tumor of the catecholamine hyperproduction was demonstrated by selective venous sampling from the vena jugularis externa draining the tumor. The norepinephrine/epinephrine ratio was high and of the same order in blood, urine and cerebrospinal fluid. Bioassay showed high levels of intratumoral norepinephrine and epinephrine. The ways of treatment and their influence on the catecholamines are briefly discussed. In every phaeochromocytoma-like syndrome both the existence of catecholamine hyperproduction and the anatomical site of this hypersecretion have to be precisely documented in order to define the correct treatment to be applied.


Effects of experimental marijuana and tobacco smoke inhalation on alveolar macrophages. A comparative stereologic study.

Male rats were exposed for 30 consecutive days to whole smoke from either marijuana or tobacco cigarettes. At the end of this period, anesthetized animals from the two smoke-exposed groups together with their age-matched, nonexposed controls underwent bronchopulmonary lavage, and the free lung cells obtained were fixed and collected for light and electron microscopy. Measurements made on 1-micrometer. sections indicated slight, but statistically nonsignificant, shifts in the frequency distributions of alveolar macrophage profile diameters after both exposure regimens. Stereologic techniques were used to study the subcellular morphology of alveolar macrophages from the three groups of animals. Statistically significant changes were found in cells from tobacco-exposed animals in the volume densities of mitochondria, lipid inclusions, lysosomes, remaining cytoplasm, and the surface to volume ratio of the cell. In contrast, only two parameters in the cells from marijuana-exposed animals were found to have changed significantly, with a 3-fold increase in the volume density of lipid inclusions and a slight reduction in the volume density of the remaining cytoplasm. Possible reasons for the differences in the response of the cells in the two smoke-exposed groups are discussed.


Lithium antagonism of ethanol-induced depletion of cerebellar guanosine-3',5'-cyclic monophosphate and stimulation of striatal dopamine release.

Long-term lithium treatment antagonized the behavioral intoxication, depletion of cerebellar guanosine-3,5'-cyclic monophosphate and stimulation of striatal dopamine release induced by a single dose of ethanol. Blood ethanol concentrations were significantly reduced after lithium treatment in a dose-dependent manner.


Pathogenesis of Hobbs' heat-sensitive spore forming Clostridium perfringens type A strain.

Food poisoning in man due to heat-sensitive strains of Cl. perfringens type A appeared to be mediated through enterotoxin synthesized in vivo during sporulation. A minimum of 2.0 X 10(5) vegetative cells suspended in sporulation medium was sufficient to elicit gut-loop response in rabbits. The functional disturbance in the gut as well as the structural changes were progressive and proportional to the size of the inoculum up to a dose limit of 2.0 X 10(7) vegetative cells and beyond this the changes remained steady.


Induction of pre-early nuclear antigen(s) in HEL cells infected with human cytomegalovirus.

Human cytomegalovirus (HCMV)-specific nuclear antigen could be detected within 1 hr after infection in human embryo lung cells by the anticomplement immunofluorescence (ACIF) test. This antigen has been named the pre-early nuclear antigen (PENA) in this paper. Serum absorption tests suggested that PENA is immunologically different from the early antigen and the major nuclear inclusion antigens detected by the indirect immunofluorescence test before and after viral DNA replication, respectively. PENA-forming ability of the virus corresponded to its plaque forming ability. PENA formation was not affected by phosphonoacetate but was inhibited by the addition of inhibitors of RNA and protein syntheses or by UV-irradiation of infecting virus, suggesting that the formation of PENA depends on the expression of infecting virus gene functions. Virus-specific proteins were isolated by indirect immunoprecipitation from HCMV-infected cells exposed to 35S-methionine. SDS-polyacrylamide gel electrophoresis of the immunoprecipitate showed that at least two species of virus-specific polypeptides with molecular weights o.f 70,000 and 30,000 were synthesized de novo within 3 hr after infection.


[Comparative study of the analysis of lipoproteins with different electrophoretic methods (author's transl)].

In 100 unselected sera the lipids were analysed with different methods. A commonly used method of the lipoprotein-electrophoresis, which evaluates the pherogram after staining with lipid-strains, was compared with the quantitative lipoproteinelectrophoresis according to Wieland and Seidel. The analyses were supplemented through the enzymatic estimation of total cholesterol and triglycerides. Only in 55 cases the results were identical. The improved diagnosis of lipoproteins is due to the complete and reproducible demonstration of HDL (high density lipoproteins) bands, which are found with the staining methods only in half of the cases. On the contrary the relative proportion of the VLDL (very low density lipoproteins) is increased three-fold with the staining methods.


[Defective organification of iodine in an infant demonstrated with 123J and gamma camera (author's transl)].

A defective organification of iodine is demonstrated in a two year old male infant. The availability and a relatively simple radiation detector and storage system (gamma camera and 1600 word memory) gives a reasonable low radiation dose, allows correction for extrathyroid neck activity and obviates problems of collimation.


Do adenine derivatives have a special role in biological regulation?

The hypothesis is raised "that adenine by way of its many derivatives plays an important role in regulating a wide variety of biological functions". Evidence is cited for such a role in cell-to-cell communication, intracellular regulation and interorganism communication. It is predicted that many more key biological functions will be found to be modulated by adenine derivatives and that adenine compounds which have not yet been studied in great depth will become recognized as biological regulators. The hypothesis also predicts that some disease states may be caused by perturbations of the adenine derivative-receptor system.


[Electron microscopic study of normal Bacillus anthracoides spores and after exposure to a chloroactive disinfectant].

The fine structure of Bacillus anthracoides spores is similar in general to that of other, taxonomically related species of spore forming bacteria. However, the former is characterized by a well-developed multilayered exosporium and the heterogeneous structure of an envelope. The lethal effect of a chloroactive disinfectant (2/3 of calcium hypochlorite basic salt) is caused by changes in the structural organization of spores, which interferes with the normal permeability barrier and metabolic processes.


[Investigations concerning the hypothalamic-hypophysial regulation of aldosterone secretion (author's transl)].

In 17 patients with retrospectively healthy adrenals we performed a LHRH-test, a TRF-test and an ACTH-test in the short modification. Additionally we determined plasma aldosterone and renine levels. Concerning the LHRH-tests and the TRF-tests we did not find any differences on the aldosterone values. Concerning the ACTH-tests in the short modification we found an increase of the aldosterone values which resembled that of the cortisol levels (increase of cortisol 104.7%, increase of aldosterone 93.3%). The renin values remained unchanged. Therefore the plasma aldosterone levels are modified in accordance with the cortisol levels by hypophysial influences.


Normal and pseudorabies virus infected primary nerve cell cultures in scanning electron microscopy.

Primary cell cultures from the central nervous system of the embryonic rat were inoculated with pseudorabies virus. Their morphological changes were studied by phase contrast microscopy and by scanning as well as by transmission electron microscopy. Uninfected cultures display two distinct cell layers in scanning electron microscopy: a flat continuous monolayer supports a heterogeneous population of individual, presumably neural cells, which emit processes of different number and size. The latter cells form contacts by a dense network of fibres. Infectious virus is propagated in these nerve cell cultures with similar effectivity as in other cultures. The infectoin leads to fusion and death of the cells. By the time the cytopathic effect is visible, nearly all cells, including those of neuronal and those of nonneuronal appearance, are studded with ample amounts of virus-sized particles. The particles represent viruses as demonstrated by transmission electron microscopy or by treatment with a hyperimmune serum directed against pseudorabies virus structural components. Hyperimmune serum leads to clustering of the particles at the cell surface. The amount of virus particles per surface unit was about 10 times higher on neural cells as compared to primary rabbit kidney cells. The concentration of infectious particles in the supernatant, however was approximately the same. The system described appears to be useful for the study of acute virus effects on neural tissue under strictly controlled conditions.


Canine viral enteritis. Recent developments.

Two apparently novel viral gastroenteritides of dogs were recognized in 1978: one caused by a parvo-like virus (CPV) and one by a corona-like virus (CCV). A rotavirus has also been tentatively associated with neonatal pup enteritis. Canine viral enteritis is characterized by a sudden onset of vomiting and diarrhea, rapid spread and high morbidity. Treatment is only supportive but must be initiated promptly. Infected animals should be isolated immediately; the extremely contagious nature of these diseases makes them difficult to contain. Feces from infected dogs appear to be the primary means of transmission. Sodium hypochlorite solutions (eg, Clorox) are recommended for disinfection. The development of effective vaccines is an immediate and pressing problem.


[Scanning microscopic study of the action of perchloric acid on emptying of the pulporadicular cavity].

Following a rapid review of techniques of mechanical and chemical emptying of the pulporadicular cavity, the use of perchloric acid and hypochlorite of sodium and oxygenated water is described by means of scan microscope histological slides.


[New results on hyperglobulinemic purpura of Waldenström in childhood (author's transl)].

The case of a 13 year old girl with benign purpura hypergammaglobulinemica Waldenström. Besides the characteristic clinical symptoms and the respective laboratory results new findings we demonstrated, which might shed some light into the pathogenesis of this disease. The transformation rate of lymphocytes was decreased particularly after stimulation with ConA. The T-lymphocytes which are reduced in their function are unable to sufficiently control the activity of mesenchymal cells which results in an increased production of glycosaminoglycans. The demonstration of glycosaminoglycan-inclusion-bodies in the mononuclear bone marrow cells of the patient could be explained by the above mentioned mechanism. Upon therapy with D-penicillamine the clinical state improved along with a reduction of the sedimentation rate, the serum protein and the serum gamma-globulin.


[Covalent bond between RNA and protein in encephalomyocarditis virus].

Deproteinized encephalomyocarditis [32P]RNA, after digestion with a mixture of RNases A, T1 and T2, yields mononucleotides and a labelled compound, which is positively charged at pH 3.5. This product can be digested with pronase and has a close electrophoretic mobility to a protein with a molecular weight of 7000-8000. Covalently bound nucleotide-peptides were isolated from this compound after treatment with RNases and pronase. It was shown that the 5'-terminal uridylic acid is covalently linked with peptides. The phosphodiester bond between uridylic acid and peptides is discussed.


Evidence for the release of endogenous substance P from intestinal nerves.

The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5 x 10(-9) M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5 x 10(-8) M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5 x 10(-8) M. Furthermore, substance P in concentrations up to 7.5 x 10(-8) M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5 x 10(-9) M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses.


[Structure and correlation of "fast" and "slow" background impulse activity of visual cortex neurons].

Background and optically modified impulse activity of neurons in visual cortex of unanaesthetized rabbits was analyzed. By means of joint interval histograms it was shown that neurons can be distinguished by the ratio of burts (intervals to 15-40 ms) and extraburst activity and by the shape of transition from one from of activity to another. The extraburst activity comprises 63% of impulses and its ratio to bursts of 2 or 3 and more impulses was 27:3:1. Burts impulse distribution showed a relative stability of timing pattern within bursts and small number of burst impulses (2.4 on the average). Bursts of 3 and more impulses (3.6 on the average) are not rhythmical and 79% of them contained long intervals (18.6 +/- 2.4 ms) before the shortest one (7.9 +/- 0.9 ms). Optical stimulation resulted in bursts containing core impulses, shorter intervals and beginning with the shortest interval in most neurons. This may testify to the increase of the EPSP steepness and amplitude. 20% of cortical neurons showed background bursts containing more impulses and shorter intervals in comparison with evoked bursts.


[Polysynaptic effects in neurons of the cervical portion of the cat spinal cord induced by activation of long propriospinal pathways].

Effects evoked in cervical moto- and interneurons by stimulation of lateral (LF) and ventral (VF) funicles at low thoracic level were studied in anaesthetized cats; degeneration of descending supraspinal fibres was provided by preliminary cord sections. LF and (or) VF stimulation evoked PSPs (usually mixed) in 57 of 90 studied motoneurons. Monosynaptic EPSPs were "primary" actions in 9 motoneurons while poly(di)-synaptic EPSPs or IPSPs--in the rest. Intensity of excitatory synaptic action on motoneurons of proximal muscles was substantially higher than on "distal" ones. LF and VF stimulation excited interneurons localized in the ventral quadrant and had no action on interneurons situated more dorsally. The effects studied are suggested to be mainly a result of activation of long proporiospinal fibres ascending via LF and VF to the cervical enlargement; certain part of reactions is supposed to be transmitted via collaterals of descending propriospinal fibres to the cervical neurons.


[Display of a monosynaptic excitatory connection in the structure of a crosscorrelation histogram].

Reflection of the monosynaptic excitatory connection in the cross correlation histogram structure was investigated using mathematical model of neuron interactions. The peculiar features of crosscorrelation histogram primary peak waveform and situation permitting distinguishing the monosynaptic excitatory connection from the monosynaptic excitatory shared input were described. Variation of primary peak magnitude with the model parameters describing mechanisms of the action potential generation and synaptic excitation transmission was shown. The autocorrelation histogram structure is shown to be reflected in the crosscorrelation histogram structure on both sides of the primary peak and to take part in the forming of secondary peaks and troughs.


EBV-specific humoral antibodies in nasopharyngeal carcinoma patients in Cuba.

Sera of 24 patients with nasopharyngeal carcinoma (NPC) and of 60 healthy donors were studied for presence of IgG and IgA antibodies against different antigens induced by Epstein--Barr virus (EBV). The results obtained demonstrate that NPC in Cuba, as in other countries, is accompanied by elevated antibody titers against EBV-specific IgG antibodies, whose levels strongly differ from those of healthy persons. Patients with NPC in Cuba had higher titers of antibody against VCA of EBV in comparison with patients of Caucasian origin in those countries where NPC, the same as in cuba, is rarely found. Cuban NPC patients had high levels of antibody against EA, often higher than in NPC patients in endemic zones of this disease.


[Downward migration of the optic system after transsphenoidal approach of a giant eosinophilic adenoma (author's transl)].

Headache and visual impairment resulting from downward migration of the optic system in an acromegalic patient, occurred after one year postoperatively. A 25-year-old woman with eosinophilic adenoma was operated on via transsphenoidal approach and irradiated (5,000 rads) following the operation. After the operation, bitemporal hemianopia was thoroughly improved and serum HGH level was also markedly decreased after radiation therapy. One year later, headache and visual impairment recurred. Pneumoencephalogram revealed that the infundibular and optic recessus of the third ventricle were elongated and descended into the sella turcica. The second operation was performed by subfrontal approach and the optic system was found to be migrated into the sella, which we assumed to be the cause for the recurrence of the headache and visual field defect. In order to prevent this type of complication, it would be recommended to fill up the dead space in the sella with bone or cartilage fragments in addition to muscle pieces, as was suggested by Guiot et al.


[Hemorrhagic lesion of the sciatic nerve caused by chronic infection and iatrogenic factors].

The author reports a 50-year-old woman with haemorrhagic lesion to the sciatic nerve during a chronic infectious process and treatment with chemotherapeutic agents. The nerve was damaged by pressure exerted by extravasated blood or haemorrhage from vasa nervorum.


Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation.

Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20--100), 100(20--120), and 120 (50--200) muA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synpatic components of the thalamic evoked potential was 50--60% (P less than 0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.


Cell-mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis.

Cell-mediated immunity to poliovirus was demonstrated in 21 of 33 patients suffering from amyotrophic lateral sclerosis (ALS), whereas no response to poliovirus was found in patients suffering from other neurologic disorders or in healthy controls. Three of the severe bulbar cases produced a migration inhibition factor (MIF) in the presence of poliovirus, although skin tests to common antigens were negative. An increased incidence (46 percent) of HLA-A3 was found in patients with amytrophic lateral sclerosis. Nine of the 13 patients with HLA-A3 antigen also had a positive index of MIF to poliovirus. These findings suggest a strong linkage between HLA-A3 and poliovirus in the pathogenesis of amyotrophic lateral sclerosis.


Role of adrenergic structures in functional control over the cerebral circulation.

An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with alpha and beta adreno-blockers showed that the constrictor response of the cerebral vessels is due to excitation of alpha-adrenergic structures and the dilator response to excitation of beta-adrenergic structures. A possible mechanism of these changes is postulated.


Lactic acidemia, mitochondrial myopathy, and basal ganglia calcification.

A 27-year-old man had limb weakness, short stature, neurosensory hearing loss, seizures, mild peripheral neuropathy, neurogenic bladder, elevated cerebrospinal fluid (CSF) protein content, primary lactic acidemia, and basal ganglia calcification. Muscle biopsy revealed numerous ragged-red fibers. On electronmicroscopy there were mitochondrial alterations, including many intramitochondrial inclusions. The mother of the patient had Vogt-Koyanagi-Harada syndrome, a combination of rare disorders in the same family that has not been previously described.


Ephaptic transmission in chronically damaged peripheral nerves.

Several weeks after damage of the sciatic nerve in adult rats, a stable electrical (ephaptic) interaction forms between pairs of injured sensory and motor axons. Fiber-fiber interaction occurs when the nerve ends in a neuroma, after end-to-end nerve suture and after nerve crush injury. Unlike the transient "artificial synapse" created acutely on section of a nerve, this form of crosstalk is long-lasting. Its existence lends support to the hypothesis that ephaptic interaction is an important factor in neurologic pathophysiology.


Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.


Ethylene oxide neurotoxicity: report of four cases and review of the literature.

Four workers were exposed to ethylene oxide gas. Acute encephalopathy occurred in one, and peripheral neuropathy in three, two of whom were symptomatic. Nerve conduction velocity studies were abnormal in three, including the asymptomatic patient. Decreasing the amount of exposure resulted in relief of symptoms. The abnormal nerve conduction studies did not change in two patients who continued to work at a lower level of exposure, whereas the conduction abnormalities improved in the patient who was removed from exposure.


H reflex analysis of segmental reflex excitability in flexor and extensor muscles.

In normal adults, H reflexes are commonly found only in the antigravity calf and flexor carpi radialis (FCR) muscles. However, these responses may be more widespread if agonist muscles contract. This study demonstrates that H reflexes may be found in the peroneal (P) and anterior tibialis (TA) muscles in the leg and the extensor digitorum communis (EDC) muscle in the arm on contraction of the antagonistic calf and flexor carpi radialis muscles, respectively. H reflexes were also elicited regularly in the EDC by passive extension of the wrist. The data indicate physiologic unity of comparably acting human antigravity muscles and their antagonists in both the upper and lower extremities, and imply an important functional role of group II afferent fibers in normal motor system activity.


[The role of fiberoptic bronchoscopy in the diagnosis of pulmonary cancer].

Cancer of the lung is becoming increasingly common. In the U.S., it has the highest mortality of the neoplastic diseases, well ahead of cancer of the colon and rectum. Surgical and/or complementary management is poorly effective because it comes too late. Early diagnosis and treatment are essential, therefore. Preclinical diagnosis may be possible radiographically in certain fortunate cases, but this is never an early diagnosis. The latter is only possible through active bronchial cytology (bronchial brushing, selective washing, PBS) during and after flexible fibrobronchoscopy, which can be carried out under local anaesthesia at the outpatient level and causes very little distress to the patient. Data from a personal series are cited in support of the view that cytodiagnosis should be routinely employed in subjects at high risk (heavy smokers, persons with chronic bronchitis, emphysema, etc.).


[Criteria of surgical treatment in 148 cases of recto-sigmoid cancer].

The clinical aspects of cancer of the rectum and sigmoid colon are discussed, and stress is laid on the importance of symptomatological, radiological and endoscopical examination, including biopsy. A description is given of the surgical criteria employed in 148 cases, with particular attention to the indications for anterior resection of the rectum and abdominoperineal amputation of the rectum according to Miles.


Genital Chlamydia trachomatis infections in patients with cervical atypia.

Of 177 gynecologic outpatients with cervical dysplasia studied, 29 (16%) were found to excrete Chlamydia trachomatis from their urogenital tract. Sera collected from 93 of these patients were significantly more often positive for and showed higher levels of antichlamydial micro-complement fixation (CF) and immunofluorescence (IF) antibodies than sera obtained from the controls. However, when the sera were tested for anti-herpesvirus type II (HSV-II) and cytomegalovirus (CMV) antibodies, no difference between the cases and the controls were encountered.


Premature menopause: a reversible entity?

Secondary hypergonadotropic, hypoestrogenic amenorrhea, or premature menopause, is usually considered an irreversible process. Four patients with this entity were observed to have evidence of ovulation. Three of these patients became pregnant while they were treated with estrogen replacement therapy (ERT) for their hypoestrogenic symptoms. Estrogen replacement may be effective in reversal of this process.


Cell-mediated immunity in patients with cervical cancer.

In 16 patients with cervical carcinoma (stages II and III) tumor-specific and general immune reactivity was investigated. Cancer patients' skin reactivity was different from that of controls insofar as there was a decreased response to streptokinase-streptodornase as well as to DNCB. Absence of DNCB sensitization was mainly in stage III patients. Cell-mediated immunity to autologous and/or allogeneic tumor-associated antigens (TAA) was demonstrated in vivo and in vitro. 3 of 8 patients had positive skin reactions to autologous TAA and 8 of 14 reacted to allogeneic TAA. In the lymphocyte migration inhibition test, 8 of 14 patients reacted to autologous tumor membrane preparations and 3 of 10 to allogeneic pooled preparations. In addition, there was some indication of cross-reaction with antigens from a human squamous cell carcinoma of the lung. There was no reaction in vitro to normal cervical tissue and no association between tumor-specific reactions and herpes simplex virus type II antibodies could be demonstrated. Patients with DNCB sensitization and in vivo as well as in vitro lymphocyte reactivity to TAA had a better prognosis than nonreacting patients, indicating the value of combined immunological tests.


Lymphocyte subpopulation in primary lung cancer.

To determine whether impaired cellular immune responsiveness in lung cancer patients is related to a reduction in the number of T lymphocytes, circulating levels of T-rosette-forming lymphocytes were measured in 48 cases with primary lung cancer and compared to levels in 94 age-matched healthy subjects. The results show that T lymphocytes levels are significantly reduced in lung cancer patients. A possible consequence of reduced numbers of circulating T lymphocytes would be a diminution in tumor-inhibiting (T-cell) influences and a corresponding relative enhancement of blocking (B-cell) influences, a circumstance which would favor tumor proliferation.


Infectious mononucleosis.

An up-to-date review of the clinical diagnostic and treatment of infectious mononucleosis, emphasizing on new etiological concepts (Epstein-Barr virus) and pathogenetic (T and B lymphocytes) interaction is presented.


Diagnosis and treatment of pertussis.

A review of the diagnostic methods of pertussis (clinical, radiological, laboratoryy: 42 case reports in a period of 2 1/2 years, being all hospitalized children with pertussis, aged from 23 days to 7 years. A review of the treatment with hyperimmune globulin, antibiotics, symptomatic treatment, and the results obtained, is presented.


Ultrastructure of cardiovascular lesions induced by hypervitaminosis D and its withdrawal.

Aortic, coronary and cardiac lesions were induced in swine by a hypervitaminosis D3 diet Lipid-free intimal plaques overlying focally calcified medial or internal elastica occured in the thoracic aorta, pulmonary trunk and coronary artery of swine fed a basal ration supplemented with 250,000 IU of vitamin D3/kg of diet for an induction period of 4 months. Cartilage formation with minimal calcification was initiated in the aortic valve during this period. When such animals were subsequently fed only the basal ration free of excessive vitamin D3 for 3 months, intimal plaques regressed in the aorta and pulmonary trunk but progressed in the coronary artery. The calcific deposits in the medial elastica and internal elastica of all three arteries decreased in size. Atherosclerotic intimal thickening occurred in the main coronary arteries. The most severe lesion occupied 75 p.100 of the lumen area. Multiple intimal plaques were noted in the left atrium and aortic and mitral valves. The thickened intima at these coronary and cardiac sites contained calcified elastica and collagen fibers.


Immunovirologic assessment of American patients with nasopharyngeal carcinoma and occult primary tumors.

The Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma, suggesting an etiologic relationship. We have under-taken studies (1) to quantitate the relationship between antibody titers to EBV-associated antigens and nasopharyngeal carcinoma in American patients since most of the patients in previous studies were of either Asian or African descent and (2) to determine the relationship between antibody titers and the clinical course of the disease. Sera from patients with primary or recurrent nasopharyngeal carcinoma and from patients in remission, from patients with various other head and neck tumors (including occult primary lesions and lymphomas), and from normal controls were titrated for IgG antibodies to viral capsid antigen (VCA) and early antigen and IgA antibodies to VCA, using indirect immunofluorescence procedures previously detailed. High titers of antibodies to EBV-induced early antigens and VCA in the IgG fraction and VCA in the IgA fraction were frequently found in the sera of patients with nasopharyngeal carcinoma. A significant reduction in these titers was observed with clinical remission of the disease in treated patients. Preliminary findings suggest that EBV serology may be useful in the evaluation and treatment of patients with nasopharyngeal carcinoma and also in patients with cervical metastases from clinically occult promary sites in order to identify those with occult nasopharyngeal carcinoma.


Plasma cyclic nucleotide determination in the investigation of hypocalcemia.

Changes in plasma adenosine 3'5' (cAMP) and guanosine (cGMP) monophosphate, measured by specific radioimmunoassay, after 150 USP/M2 of bovine parathyroid hormone (bPTH) iv administered were studied in children with pseudohypoparathyroidism, and idiopathic hypoparathyroidism, and in normal controls. Basal concentrations of plasma cAMP (17 nmole/1 +/- 1, 6 SEM) and cGMP (8,7 nmole/1 +/- 1, 3 SEM) were the same in all studied children. Plasma cAMP in normal and idiopathic hypoparathyroid children significantly (30-fold, P less than 0.001) and constantly rose with a peak value (537 nmole/1 +/- 210 SEM) observed 5--10 min after bPTH injection. By contrast, no significant change in plasma cAMP occurred in children with pseudohypoparathyroidism. The data confirmed further the unability of pseudohypoparathyroid children to increase cAMP after exogenous PTH, while the cGMP response did not appear to be significantly modified. It is suggested that an injection of 150 USP/m2 bPTH with plasma samples for cAMP assay taken before and 10 min after hormone administration represents a simplified assessment of Ellsworth-Howard's test.


[Vasoactive intestinal peptide (VIP) in the Verner-Morrison syndrome (author's transl)].

An early diagnosis of the Verner-Morrison syndrome will greatly enhance the chances of curative resection. There is a striking need for a simple diagnostic test. A number of suggestions have been made for the presumed hormone mediator of this syndrome. Numerous reports have led to a wide acceptance that vasoactive intestinal peptide (VIP) is the responsible mediator for the pharmacologic actions of this peptide are similar to the physiological characteristics noted in the watery diarrhea syndrome. A raised plasma VIP concentration, on the other hand, would suggest the presence of a tumour. These observations argue for the radioimmunoassay measurement of plasma VIP in a patient with the watery diarrhea syndrome.


Mobile gamma cameras and 99mTc-labelled phosphates in acute myocardial infarction.

99mTc-labelled phosphates (PyP, IDP and MDP) were compared for their usefulness for the diagnosis of myocardial infarction. The results indicated the superiority of 99mTc-labelled imidodiphosphonate over the other 99mTc-labelled phosphates. At the same time, two mobile gamma cameras were compared with respect to their instrumental characteristics and clinical versalitity and their advantages and disadvantages are reported.


Diagnostic aspects of the cytomegalovirus mononucleosis syndrome in previously healthy persons.

The mononucleosis-like syndrome due to cytomegalovirus (CMV) has many clinical features in common with classic Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). The hematologic and hepatic findings in both diseases are identical. Diagnosis of the CMV-IM syndrome usually can be made on the basis of indirect immunofluorescence for CMV macroglobulins (CMV-IgM). EBV virologic tests may also be necessary, as patients with primary EBV infections may have cross-reactions at low titer in the CMV-IgM test.


Accumulation of 125I in the oocytes, thyroids, and plasma of laying Japanese quail treated with cyclic AMP, theophylline, or prostaglandins E1 or E2.

Dibutyryl cyclic AMP, theophyline, or prostaglandins E1 or E2 were injected intraperitoneally into laying Japanese quail in an attempt to stimulate increased transference of iodide by the ovarian membranes. Theophyline induced increased 18-hr 125I accumulations (by 7 to 18% of the injected dose) of borderline significance in the growing oocytes of some test groups. Theophyline plus DBcAMP treatment lead to a slight increase in 125I accumulation in the thyroid. Other treatments had no apparent effect on 125I transference. The prostaglandins induced oviposition within minutes of injection, as has been reported for uterine application of prostaglandins by other investigators. Means for plasma 125I levels for treated quail were 1.7 to 12.5 times greater than control levels. Values for oocyte to plasma and thyroid to plasma 125I ratios, it appeared that DBcAMP, theophyline, and the prostaglandins inhibited rather than stimulated the accumulation of 125I by the ovary and thyroid of the quail.


Validation of an in vitro method for incorporating labelled cholesterol into human erythrocytes.

At least 85% of the cholesterol of human erythrocytes can be replaced by isotopically labelled cholesterol, by incubation of the cells with the plasma lipoprotein HDL3 into which labelled cholesterol has been incorporated from Celite. With erythrocytes containing 40% labelled cholesterol, the reactivity of the incorporated labelled cholesterol was the same as that of the remaining native cholesterol with regard to: oxidation by cholesterol oxidase for both intact erythrocytes and cell ghosts, extraction by cholesterol depleted plasma, and exchange for HDL3 cholesterol. Also, the reactivity of the cholesterol in the cells in which labelled cholesterol was incorporated was the same as in untreated erythrocytes.


[Clinical value of radionuclide imaging in the diagnosis of the adrenal cortex lesions].

Results of using radioisotopic visualization of the adrenal glands together with the hormonal profile determination ACTH, renin, aldosterone, cortisol) for the diagnosis of the adrenal gland affections are presented. Parameters of the scintigraphic appearance of the affected adrenal cortex were developed to distinguish six types of scintigraphic patterns of the adrenal gland, which were the most frequent. Clinical analysis of the results of the examination of patients indicated Conn's disease in 24 patients (it was verified during the operation), 12 had unilateral corticosteroma of the adrenal gland, 8 suffered from residual adrenal gland tissue, and 2 had metastases of malignant tumours of the adrenal glands. Accumulation of radiopharmaceutical preparations into the corpus luteum was revealed in one case.


[Participation of different parts of the tonsils and the hippocampus in the regulation of the pituitary-adrenal cortex system in rats].

In experiments on rats the effect of electric coagulation of the tonsil and hippocamp on the functional activity of the pituitary-adrenal axis was studied. The weight of the adenohypophysis after the coagulation of the medial or lateral tonsils proved to decrease; the ACTH content in the hypophysis and the cortocosteroid level in the peripheral blood plasma diminished, and the compensatory hypertrophy of the remaining adrenal gland was intensified in rats with destroyed medial tonsil. The dorsal hippocamp coagulation was accompanied by a decrease in the adenohypophysis ACTH content, and the ventral hippocamp destruction led to reduction of corticosteroid secretion into the adrenal vein; in both cases the reaction to the irritation was potentiated. It was concluded that different parts of the tonsil and hippocamp influenced the pituitary-adrenal function unequally.


[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes].

The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands.


Emotional disturbance following childbirth: clinical findings and urinary excretion of cyclic AMP (adenosine 3'5'cyclic monophosphate).

Emotional disturbance was assessed in a group of women in the first few days following childbirth and again 2 months and 1 year following childbirth; the clinical features are described. Variables such as social class, age and parity were not related to the level of emotional disturbance, but a history of marital problems, sexual difficulties, poor relationships with immediate family or disrupted family relationships in childhood were so related. Twenty-four hour urinary excretion of cyclic AMP (adenosine 3'5' cyclic monophosphate) was estimated in the same group of women on 2 occasions in the week following childbirth and again 2-3 months later in approximately one third of the original sample. Excretion of cyclic AMP in the few days following delivery was elevated compared with excretion 2-3 months later, and there was a significant rise in urinary excretion of cyclic AMP between the 1st and 2nd urine collections. Those women showing most emotional disturbance on the 3rd day after delivery and women indicating most mood change in the direction of becoming elated had the highest levels of cyclic AMP in the 2nd urine collection.


Influence of the DNA structure on the free radical induction due to proflavine and light treatment.

Induction of peroxide free radicals (detected by Electron Paramagnetic Resonance at 77 K) due to the photodynamic activity of proflavine was measured on bacteriophage phi X174 DNA either single-stranded (ss) as isolated from the virion, or double-stranded supercoiled (RFI) as isolated from the infected bacteria. Comparison was made with calf thymus DNA photosensitization. In order to use equivalent DNA-proflavine complexes, binding of the dye to the three DNA's was first determined under those conditions of high ionic strength favourable to the photodynamic reaction. Free radical induction was maximal for definite amounts of bound proflavine (which varied depending upon the DNA substrate) and at an ionic strength value of 0.5. The level of the maximal reaction increased in the following order: from phi Xss DNA to calf thymus DNA and finally to phi XRFI DNA. The conformation of the proflavine-DNA complex was thus a determinant for the efficiency of the photodynamic process. The ionic strength effect could not be explained by the evolution of the proflavine triplet state in irradiated proflavine-calf thymus DNA complexes.


Pharmacodynamics of stannous chelates administered with 99mTc-labeled chelates.

The pharmacodynamics of several tin compounds were studied in healthy rabbits, rabbits with myocardial infarcts, and isolated myocardial tissue. The results showed that tin chelates of pyrophosphate, HEDP, DTPA, and glucoheptonate are very unstable in vivo, giving rise to free stannous ions. These ions localize mainly in bone, with the rest being primarily excreted in the urine. They also concentrate more in infarcted than in normal myocardium; there they enter the mitochondria. The supernatant of homogenates contains bound and free fractions, demonstrating a subcellular distribution pattern similar to that of calcium ions. Tin chelates have different pharmacodynamics from the corresponding 99mTc chelates.


Enhancement of tissue structure visualization in breast specimen radiography.

A simple technique is described for producing enhanced radiographs of excised breast specimens with clinical mammographic equipment. Radiographs of specimens immersed in water are compared to radiographs of the same specimen in air. Using this fluid-balancing technique, visualization of tissue structure is enhanced, particularly when negative-mode Xerox or film is used.


A multihole catheter for maintaining longterm percutaneous antegrade biliary drainage.

The use of multihole catheters to achieve longterm antegrade biliary drainage in 43 patients with obstructive jaundice is described. Catheters were positioned with sideholes both above and below an obstruction and continued patency maintained. Better results were obtained using larger diameters and larger sideholes.


Pyrophosphate retention by previously irradiated renal tissue.

In 3 patients, each of whom had previously had part of one kidney included within the field during radiation therapy, whole-body bone imaging using 99mTc-pyrophosphate showed increased activity in the irradiated renal segment. Possible mechanisms of such renal uptake are discussed.


Comparison of radiopaque perfluorocarbon and Ethiodol in lymphography.

Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography.


Effect of prostaglandins on cyclic nucleotide levels in cultured keratinocytes.

Ginea pig ear epidermal cells (keratinocytes) were established in primary cultures using trypsin, and treated in their proliferative phase of growth with prostaglandins E1, D1, F1 alpha, E2, D2, or F2 alpha. This phase is induced by the addition of retinoic acid during cell plating. Intracellular content of cAMP and cGMP was measured by radioimmunoassay at various times after treatment. Maximum stimulation of cAMP levels was observed with PGD2, smaller increases with PGE2 and relatively transient rises with PGF2 alpha which were of low significance, but confirm earlier data. Similar results were observed with PGD1, PGE1, and PGF1 alpha with smaller increases. The effects of D and E PGs were biphasic. Significant increases in cGMP were immediately observed with PGD2 and PGE2. With PGF2 alpha, maximum cGMP levels were noted after some delay. All PGs tested showed some effect in elevating cyclic nucleotides in keratinocytes. The most striking result was the increase in cAMP on PGD2 treatment.


[Recurrences of the gastric carcinoma after surgery (author's transl)].

A series of 71 patients with recurrences of gastric carcinoma after operation is reviewed. The most frequent localization is the gastric bed (48 cases , 67.6%) while the local recurrences is less frequent (22 cases, 30.9%) and usually the esophago-cardial junction is affected. In one patient both the local recurrence and that of the gastric bed were present. The radiologic investigation was negative in about 60% of the patients because it is not useful for a correct examination of the gastric bed. In any case it must be considered essential for the study of the local recurrences and for the evaluation of the post operative anatomic patterns.