Mouse mammary tumor virus polypeptide precursors in intracytoplasmic A particles. Intracytoplasmic A particles were analyzed by immunodiffusion and sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) before and after enzymatic cleavage with trypsin. A common antigen in A particles was detected by antisera prepared against purified intracytoplasmic A particles, purified mouse mammary tumor virus (MMTV), and a purified MMTV core polypeptide (p28). Despite this correlation, no SDS--polyacrylamide band migrating at p28 was observed in purified intracytoplasmic A particles. However, after incubation with trypsin, A particles subjected to SDS--PAGE produced only two polypeptide bands. They were observed at p28 and p15-10. Ouchterlony analysis of the trypsin-cleaved A particles revealed no alteration in the antigenicity of the particles. These results suggested that some structural components of intracytoplasmic A particles are polypeptide precursors of MMTV core proteins.


Estrogen receptor assay in human breast cancer. A Workshop on Receptor Assay in Breast Cancer Tissue at the Fourth International Congress on Hormonal Steroids was held in Mexico City, September 2-7, 1974. This report reviews the various methods of steroid receptor assay in breast cancer discussed at this Workshop.


Low oncogenic potential of avian endogenous RNA tumor virus infection or expression. Of chickens either spontaneously producing or exogenously infected in ovo with Rous-associated virus, type O (RAV-O), an endogenous virus of the chicken, only 1 died with lymphoid leukosis (LL), the most common neoplasm associated with the leukosis-sarcoma virus group. Because the chickens were not kept in strict isolation, it could not be assumed that the one LL was induced by RAV-O. In contrast, RAV-1-infected chickens from the same lines had a high incidence of LL and other neoplasms. Over 800 chickens of several inbred lines were maintained in plastic isolators free of exogenous avian leukosis-sarcoma virus infection for from 500 to nearly 1,000 days of age. No LL was observed, even though some lines are known to produce RAV-O spontaneously or to express inherited gs antigen. Three neoplasms of unknown etiology were observed, but none generally associated with leukosis virus infection. We concluded that avian endogenous virus expression had little, if any, oncogenic potential, and that exogenous avian leukosis viruses were responsible for most naturally occurring neoplasms.


Ecotropic leukemia viruses in congenic C57BL mice: natural dissemination by milk-borne infection. The incidence of infectious murine leukemia virus (MuLV) in congenic-resistant C57BL mice was studied. No constant relationship between the incidence of MuLV and the H-2 complex was apparent. Two lines, B10 and B10.A, were examined in detail because the incidence of MuLV in B10 was low and the virus appeared relatively late in life, whereas B10.A animals had a relatively high incidence of infection by MuLV early in life. Further studies of B10.A mice revealed an almost universal concordance between the virologic status of the mother and her offspring. This was particularly evident when (B10 times B10.A)F1 animals were compared with (B10.A times B10)F1 mice: Although genetically identical, the incidence of MuLV in the latter was high, whereas in the former it was low. Transmission of MuLV by milk was proved by foster-nursing experiments; when the infants of MuLV-positive B10.A mothers were suckled on MuLV-negative B10.A mothers, they were free of MuLV. Milk-borne infection may account for the natural dissemination of MuLV among some inbred lines of mice.


C-type viruses in chimpanzee (Pan sp.) placentas. C-type virus particles were observed by electron microscopy in placentas from 7 of 9 chimpanzees (Pan sp.). These viruses were morphologically similar to those observed in placentas of other primates.


Mitochondrial and herpesvirus-specific deoxypyrimidine kinases. To characterize and compare the thymidine (TdR) and deoxycytidine (CdR) kinase isozymes of uninfected and herpesvirus-infected cells: (i) the subcellular distribution of the isozymes has been studied; (ii) a specific assay for CdR kinase has been devised; (iii) the TdR kinase isozymes have been partially purified; and (iv) the purified enzymes have been analyzed by disc polyacrylamide gel electrophoresis, isoelectric focusing, and glycerol gradient centrifugation and by substrate competition and dCTP inhibition studies. The results indicate that there are interesting individual differences with respect to nucleoside acceptor specificity between the cytosol and mitochondrial pyrimidine deoxyribonucleoside kinases of uninfected cells and between the enzymes induced by different herpesviruses. In the cytosol of uninfected mouse, chicken, and owl monkey kidney cells, two different proteins, TdR kinase F and CdR kinase 2, catalyze the phosphorylations of TdR and CdR, respectively. TdR kinase F does not phosphorylate CdR, nor does CdR kinase 2 phosphorylate TdR. A second TdR kinase isozyme present in HeLa(BU25) mitochondria (TdR kinase B) also lacks CdR phosphorylating activity. In contrast, a genetically distinctive deoxypyrimidine kinase (TdR kinase A) of mouse, human, and chick mitochondria catalyzes the phosphorylation of both TdR and CdT. Three herpesviruses, marmoset herpesvirus and herpes simplex virus types 1 and 2, induce in the cytosol fraction of LM(TK-) mouse cells isozymes which share common properties with mitochondrial TdR kinase A, including the ability to catalyze the phosphorylation of both TdR and CdR. However, the herpesvirus-induced deoxypyrimidine kinases differ from mitochondrial TdR kinase A with respect to sedimentation coefficient, sensitivity to dCTP inhibition, and antigenic determinants. The herpesvirus-specific and the mitochondrial deoxypyrimidine kinases exhibit a preference for TdR over CdR as nucleoside acceptor. Pseudorabies virus and herpesvirus of turkeys induce cytosol TdR kinases resembling the other herpesvirus-induced TdR kinases in several properties, but like cellular TdR kinase F, the pseudorabies virus and herpesvirus of turkeys TdR kinases lack detectable CdR phosphorylating activities. Finally, a marmoset herpesvirus nutant resistant to bromodeoxyuridine, equine herpesvirus type 1, and Herpesvirus aotus induces neither TdR nor CdR phosphorylating enzymes during productive infections.


DNA synthesis and DNA polymerase activity of herpes simplex virus type 1 temperature-sensitive mutants. Fifteen temperature-sensitive mutants of herpes simplex virus type 1 were studied with regard to the relationship between their ability to synthesize viral DNA and to induce viral DNA polymerase (DP) activity at permissive (34 C) and nonpermissive (39 C) temperatures. At 34 C, all mutants synthesized viral DNA, while at 39 C four mutants demonstrated a DNA+ phenotype, three were DNA+/-, and eight were DNA-. DNA+ mutants induced levels of DP activity similar to thhose of the wild-type virus at both temperatures, and DNA+/- mutants induced reduced levels of DP activity at 39 C but not at 34 C. Among the DNA- mutants three were DP+, two were DP+/-, and three showed reduced DP activity at 34 C with no DP activity at 39 C. DNA-, DP- mutants induced the synthesis of a temperature-sensitive DP as determined by in vivo studies.


Properties of feline leukemia virus. III. Analysis of the RNA. The kinetics of virus labeling was used to study the maturation of viral RNA in the Rickard strain of feline leukemia virus. Viral RNA labeled over differing intervals was characterized by gel electrophoresis and velocity sedimentation in sucrose gradients made up in aqueous buffer and 99% dimethyl sulfoxide. Labeled virus was found within 30 min after adding radioactive uridine to the cells and production of labeled virus reached a maximum at 4 to 5 h after pulse labeling. Native RNA from feline leukemia virus resolved into three size classes when analyzed by electrophoresis on 2.0% polyacrylamide-0.5% agarose gels: a 6.2 x 10(6) to 7.1 x 10(6) mol wt (50 to 60S) class, an 8.7 x 10(4) mol wt (approximately 8S) class, and a 2.5 x 10(4) mol wt (4 to 5S) class. From two experiments during which RNA degradation appeared minimal, these made up to 57 to 76%, 2 to 5%, and 6 to 12%, respectively, of the total RNA. The 8S RNA in feline leukemia virus has not previously been reported. The 50 to 60S RNA from virus harvested after 4 h of labeling electrophoretically migrated faster and sedimented more slowly in sucrose gradients than did the same RNA species harvested after 20 h of labeling. This argues for an intravirion modification of the high-molecular-weight RNA. The large subunits of denatured viral RNA from both 4- and 20-h labeled-viral RNA electrophoretically migrated with an estimated molecular weight of 3.2 x 10(6) but sedimented with 28S ribosomal RNA (1.8 X 10(6) mol wt) when analyzed by velocity sedimentation through 99% dimethyl sulfoxide.


Site on the RNA of an avian sarcoma virus at which primer is bound. In vitro transcription of the avian tumor virus RNA by RNA-directed DNA polymerase is initiated on the unique cellular 4S RNA. Previous studies have shown that on the average there is one such RNA primer hydrogen bonded to each viral 35S RNA. The present study confirms that finding and demonstrates that, at least for the majority of 35S RNA molecules, the primer is bound at a site close to the 5'-terminus.


Escherichia coli capsule bacteriophages. IV. Primary structure of the bacteriophage 29 receptor, the E. coli serotype 29 capsular polysaccharide. Using periodate oxidation, methylation analysis, characterization of oligosaccharides by Smith degradation or partial acid hydrolysis, as well as proton magnetic resonance, the primary structure of the Escherichia coli serotype 29 capsular polysaccharide (the receptor of E. coli K phage 29) was reinvestigated. The polymer was found to consist of hexasaccharide repeating units of the following structure: (see article).


Adenovirus transcription. II. RNA sequences complementary to simian virus 40 and adenovirus 2DNA in AD2+ND1- and AD2+ND3-infected cells. The genomes of the two nondefective adenovirus 2/simian virus 40 (Ad2/SV 40) hybrid viruses, nondefective Ad2/SV 40 hybrid virus 1 (Ad2+ND1) and nondefective hybrid virus 3 (Ad2+ND3), WERE FORMED BY A DELETION OF ABOUT 5% OF Ad2 DNA and insertion of part of the SV40 genome. We have compared the cytoplasmic RNA synthesized during both the early and late stages of lytic infection of human cells by these hybrid viruses to that expressed in Ad2-infected and SV40-infected cells. Separated strands of the six fragments of 32P-labeled Ad2 DNA produced by cleavage with the restriction endonuclease EcoRI (isolated from Escherichia coli) and the four fragments of 32P-labeled SV40 DNA produced by cleavage with both a restriction nuclease isolated from Haemophilus parainfluenzae, Hpa1, and EcoRI were prepared by electrophoresis of denatured DNA in agarose gels. The fraction of each fragment strand expressed as cytoplasmic RNA was determined by annealing fragmented 32P-labeled strands to an excess of cellular RNA extracted from infected cells. The segment of Ad2 DNA deleted from both hybrid virus genomes is transcribed into cytoplasmic mRNA during the early phase of Ad2 infection. Hence, we suggest that Ad2 codes for at least one "early" gene product which is nonessential for virus growth in cell culture. In both early Ad2+ND1 and Ad2+ND3-infected cells, 1,000 bases of Ad2 DNA adjacent to the integrated SV40 sequences are expressed as cytoplasmic RNA but are not similarly expressed in early Ad2-infected cells. The 3' termini of this early hybrid virus RNA maps in the vicinity of 0.18 on the conventional SV40 map and probably terminates at the same position as early lytic SV40 cytoplasmic RNA. Therefore, the base sequence in this region of SV40 DNA specifies the 3' termini of early messenger RNA present in both hybrid virus and SV40-infected cells.


Plaque assay of avian sarcoma viruses using casein. The caseinolytic activity of several strains of Rous sarcoma virus (RSV), conditional and nonconditional mutants of RSV, and nontransforming avian leukosis viruses was investigated. Only those viruses capable of transforming chick fibroblasts in vitro induced lysis of casein incorporated into an agar overlay. Lysis produced distinct clear areas in the turbid casein-agar gel which allowed a quantitative "plaque" assay of cell transformation. Casein plaque formation could not be separated from morphological conversion in cultures infected by wild-type RSV strains. In plates infected by mutants temperature sensitive for transformation, the caseinolytic activity appeared to be affected by temperature to a lesser extent than morphological conversion.


Denaturation map of polyoma DNA.

Denaturation map of polyoma DNA. A denaturation map of polyoma DNA cleaved by Eco R1 to form linear molecules was established by electron microscopy. Partial denaturation, under the same conditions, of fragments obtained by Haemophilus influenzae restriction enzymes allowed us to align the denaturation map with the already established physical map of polyoma DNA (Griffin et al., 1974).


Polyadenylic acid sequences in rhinovirus RNA species from infected human diploid cells. Polyadenylic acid sequences were shown to be present in rhinovirus virion RNA. Virus-specified RNA from human embryo lung cells infected with rhinovirus also contained polyadenylic acid but did not contain any polyuridylic acid sequences.


Base sequence differences between the RNA components of Harvey sarcoma virus. The 50 to 70S RNA of the Harvey sarcoma-Moloney leukemia virus (MLV) complex consists of 30 to 40S RNA subunits of two different size classes and contains sequences homologous to Moloney mouse leukemia virus and to information contained in a C-type rat virus, termed NRK virus. We have isolated by preparative gel electrophoresis the large (component 1) and the small (component 2) 30 to 40S RNA species from the Harvey sarcoma-MLV complex. Harvey RNA component 1 was completely complementary to DNA transcribed from MLV RNA and showed no homology to DNA transcribed from NRK virus when annealed under conditions of DNA excess. Harvey RNA component 2 was about 65% complementary to MLV DNA and about 33% complementary to NRK virus DNA. Approximately 60 to 80% of the MLV-specific sequences in RNA component 2 is either a distinct molecular species or is part of a hydrid molecular including NRK virus- and MLV-specific sequences. The rest of the MLV sequences in component 2 could be accounted for by degraded component 1 co-purifying with component 2. The possible role of these sequences in the ability of the virus to transform cells is discussed.


Mapping simian virus 40 mutants by construction of partial heterozygotes. Simian virus 40 temperature-sensitive mutants ts A28, A30, B1, B11, and D101 are associated with the region of the genome defined by the restriction endonuclease fragments Hind-I, H, F, G, and E, respectively.


Mucinous adenocarcinoma of the renal pelvis: discussion of possible pathogenesis. A case of mucinous adenocarcinoma of the renal pelvis is reported. The role of infectious agents and the embryologic formation in relation to the malignancy are discussed. Diagnosis of this rare malignancy rests on a high degree of suspicion, coupled with radiologic and cytologic procedures.


Acute granulomatous hepatitis. Occurrence in cytomegalovirus mononucleosis. Two previously healthy adults with acute granulomatous hepatitis attributable to cytomegalovirus (CMV) monucleosis had prolonged fever, heterophil-negative lymphocytosis with numerous atypical forms, minor alterations in hepatic function, and evidence on biopsy, of a nonspecific acute hepatitis with granulomata. Infection with CMV was corroborated by a rising titer of complement-fixing antibody in case 1 and by a high titer of antibody that later fell in case 2. It is important to exclude CMV ivfection as an etiologic factor in cases of acute granulomatous hepatitis and fever of unknown origin.


Xeromammography in early detection of breast cancer. Sixty-four carcinomas were detected in 1,315 women examined by xeromammography in 1973. Seventeen carcinomas were occult and 14 were detected in women referred for clinically benign lesions. The remaining 33 carcinomas were diagnosed on the basis of both clinical and roentgenographic examination. There were three false-negatives. Two of these lesions were obscured by very dense fibrocystic disease. The third lesion was called benign due to an error in interpretation. There were eight false-positives; four of these demonstrated intraductal hyperplasia and asymmetry, which may be a precursor to frank malignant change. Xeromammography is suggested as a highly accurate means of detecting occult mammary carcinomas and clarifying the nature of clinically suspected lesions.


Complement requirement of neutralizing antibodies in different classes of immunoglobulin appearing in rabbits and guinea pigs after primary and booster immunizations with herpes simplex virus. Rabbits and guinea pigs were immunized with herpes simplex virus and bled periodically. The sera were fractionated into slow IgG, fast IgG and IgM by DEAE-cellulose column chromatography, and complement-requiring (CRN) and nonrequiring neutralizing (N) antibody activities were estimated. In early sera of rabbits, the two IgG and IgM fractions possessed about equal CRN activities, although some animals showed a slightly lower activity in fast IgG. In guinea pigs, the early CRN activity resided mainly in slow IgS (7 S gamma2). The early IgG antibody of guinea pigs differed from that of rabbits in that it resembled IgM in resistances to heating at 70 C and to 2-merceptoethanol. The level of CRN IgM antibody in rabbits declined following a peak reached in 2 to 3 weeks, whereas such a decline was never observed in guinea pigs. N IgG antibody was developed a few weeks after the first immunization in rabbits and much retarded in guinea pigs. In both species, booster immunization quickly evoked N antibody in the two IgG fractions and also CRN IgM antibody, but in the case of rabbits the IgM antibody disappeared soon. It is concluded that IgG plays an important role in humoral immunity from the initial stage of the immunization course.


Influence of dialysate calcium concentration and vitamin D on serum parathyroid hormone during repetitive dialysis. An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration.  The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used.  Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments.  Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate.  No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis.  Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml.  Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients.  After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients.  These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis.  Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary.


Renal phosphate reabsorption in the rat: effect of inhibitors. The maximum rate of inorganic phosphorus (P1) reabsorption (Tmp1) was measured during phosphate infusion in chronically parathyroidectomized rats. In either initially hydropenic rats or others which underwent moderate preliminary saline loading, Tmp1 tended to rise during early phosphate infusion and then decline, so that steady-state Tmp1 values were similar to the P1 reabsorption rates at the animals' own evelated endogenous plasma P1 concentrations. These results indicate that the "self-depression" of Tmp1 during phosphate infusion is not dependent upon the progressive stimulation of endogenous parathyroid hormone secretion. Parathyroid hormone and dibutyryl cyclic adenosine monophosphate (AMP) decreased Tmp1 substantially, whereas acetazolamide inhibited P1 reabsorption at lower filtered P1 loads but did not diminish Tmp1.


[The requirements of vitamin D (cholecalciferol) and of 25-hydrocalciferol (25HCC) in premature children during their early life (author's transl)]. The necessary daily amount of vitamin D3 in premature infants was calculated by Hövels and his group as being 25 mcg (1000 I.U.). This was in agreement with our own investigations. Without vitamin D3, however, the incidence of rikkets in premature and small-for-dates newborns occurred usually at the beginning of the second month of life. Clinical signs of rickets are still absent at this time, while an increased activity of the serum alkaline phosphatase signals the beginning of the illness. Three groups of prematurely born infants received up to 50 days daily oral doses of 12.5 mcg vitamin D3 (=500 I.U.), 25 mcg vitamin D3 (=1000 I.U.) or 9 mcg 25-hydroxycholecalciferol (25-HCC), respectively, while one untreated group served as control. No differences were noted between the four groups in the serum values of calcium and phosphorus. The activity of the alkaline phosphatase tended to be higher in the untreated and the 500 I.U. groups. The differences were prouved by the chi2-test to be significant (see table 2 and 3). It appeared that 9 mcg of 25-HCC prevented the rise in alkaline phosphatase slightly better than 25 mcg of vitamin D3 (1000 I.U.). On a mcg base 25-HCC seems three times as effective as cholecalciferol. One could speculate about a delayed hydroxylation of cholecalciferol (vitamin D3) to 25-HCC.


Synthesis of type I collagen by human smooth muscle cells in vitro. Human vascular smooth muscle cells, derived from explants of medial smooth muscle of a fetal aorta, were grown in vitro and examined with phase and electron microscopy for characteristic morphologic features of smooth muscle cells and for the biosynthesis of connective tissue proteins. Their patterns of growth and ultrastructure were similar to those described for other species of cultured arterial smooth muscle cells. Most cells contained varying amounts of myofilaments interpersed with dense bodies, rough and smooth endoplasmic reticulum, mitochondria, various sized vesicles, lysosomes, and lipid droplets. Extracellularly, small amounts of electron-dense material and microfilaments were observed adjacent to or between the cells. The over-all morphology suggested that the smooth muscle cells were actively engaged in protein synthesis. Although we could not identify banded collagen fibrils in 10- to 14-day-old cultures by electron microscopy, the cells synthesized and secreted a collagen characterized as type I collagen. A hydroxyproline-containing protein composed of two alpha-1 and one alpha-2 chains was extracted from the cell layer. The triple helical precursor of type I collagen, procollagen, was secreted into the medium.


Peroxisome depletion in rat liver during pneumococcal sepsis. Biochemical and morphometric analysis reveal that the peroxisomal content of rat liver cells is markedly reduced during pneumococcal sepsis. It is suggested that during some bacterial infections, hepatic synthesis of acute-phase serum proteins occurs at the expense of peroxisomal protein synthesis and results in reduction of the peroxisomal protein pool and number of peroxisomes.


Cellular membranes and membrane-bound enzymes in vitamin E deficiency. A histochemical, cytochemical, biochemical, and morphologic study of the liver of the Pekin duckling. The objective of this investigation was to find out whether vitamin E deficiency, apart from influencing the lipid component of cellular membranes, also influences the protein component. For that purpose a number of membrane-bound enzymes in the liver of the Pekin duckling were histochemically, cytochemically, and biochemically examined. Furthermore, cells, cellular membranes, and protein particles in membranes were morphometrically investigated. Histochemically five membrane-bound enzymes appeared to be stimulated in vitamin E deficiency: 5'-nucleotidase, glucose-6-phosphatase, isocitrate dehydrogenase (NADP), tetrazolium reductase (NADH), and tetrazolium reductase (NADPH). 5'-Nucleotidase and glucose-6-phosphatase were also investigated cytochemically and biochemically. The cytochemical localization of these enzymes was identical in control and vitamin E-deficient ducklings. Biochemically, a stimulation of these two enzymes also could be demonstrated. The increase per milligram of DNA appeared to be largest whereas the increase per milligram of protein, per milligram of phospholipid, and per milligram of RNA was only half of the increase per milligram of DNA. This can be explained by the 30 per cent increase of the cell volume in vitamin E deficiency leading to an increase of protein, phospholipid, and RNA per cell. The thickness of membranes and the diameter of protein particles in membranes were measured in liver parenchymal cells. In vitamin E deficiency the thickness of the outer mitochondrial membrane and the diameter of protein particles in this membrane were smaller whereas the thickness of the endoplasmic reticular membrane was larger. The increase of the activities of mitochondrial and microsomal enzymes and the decrease of the thickness of the outer mitochondrial membrane and of its protein particles are interpreted to be the result of the influence of free radicals on membranes with electron transport functions. The increase of 5'-nucleotidase activity in the plasma membrane is likely to have a different cause; it may be related to the transport of nucleotides across this membrane.


Encephalitis in suckling rats induced with rat cytomegalovirus. Encephalitis has been induced in suckling rats by intracerebral inoculation of rat cytomegalovirus. This agent has been carried through five animal passages without changes in virulence. Principal sites of viral attack were the meninges and ependyma with limited parenchymal invasion from these sites. Characteristic features of cytomegalovirus disease observed included cytomegaly, formation of nuclear and cytoplasmic inclusions, and polykaryocytosis. Fundamental tinctorial and optical differences were noted between nuclear and cytoplasmic inclusions, the latter being characterized by their phloxinophilia which contrasts with the hematoxylinophilia of nuclear inclusions. Differential interference microscopy improved visualization and photography of cytoplasmic inclusions. Hydrocephalus developed in a few of the animals and was studied in late phases of the disease.


Physiology of the natural polyamines putrescine, spermidine and spermine. The biochemistry and biological function of the naturally occurring polyamines, putrescine, spermidine, and spermine, have been reviewed with special reference to animal organisms. These compounds are universally distributed in all living material. Their biosynthesis from ornithine and methionine is accurately controlled and may fluctuate according to the metabolic needs of the cell. Polyamines strongly and specifically interact with nucleic acids in vitro. It appears that under physiological conditions a substantial portion of cellular polyamines is noncovalently bound to nucleic acids and nucleic acid-containing structures such as ribosomes. Polyamines are able to stimulate protein and ribonucleic acid synthesis in vitro. In several systems characterized by rapid growth polyamines and ribonucleic acid accumulate in parrallel. Evidence that polyamines may have an essential role in protein and/or nucleic acid synthesis is substantiated by recent observations on polyamine-deficient bacterial mutants, although no specific function has been established with certainty as yet. Some clinical applications of polyamine research related to cancer are also discussed briefly.


Loss of epinephrine stimulated synthesis of cyclic adenosine 3':5' monophosphate during maturation of rabbit and human reticulocytes. The adenylate cyclase activity of rabbit reticulocytes is localized in the stroma. Rabbit reticulocytes are four times more active than mature erythrocytes in transforming in situ formed [14C] adenosine triphosphate into [14C] cyclic adenosine 3':5'-monophosphate. Similarly, anaemic human red blood cells show higher activity in effecting this transformation. The adenylate cyclase activity is stimulated by epinephrine, 40% in rabbit reticulocytes, and 70-80% in anaemic human RBC but not in erythrocytes. Both the reticulocytes and erythrocytes can bind [14C] epinephrine, but the reticulocytes bind a relatively large amount. A glycogen phosphorylase that can be activated by cyclic adenosine 3':5'-monophosphate is detected only in reticulocytes. Both reticulocytes and erythrocytes contain a phosphodiesterase which can hydrolyse cyclic 3':5'-adenosine monophosphate and which is activated by imidazole and inhibited by methyl xanthines.


[A electromyographic study of the vestibular reflexes. A clinical experimental study on human beings (author's transl)]. It is reported about myography on testpersons with normal vestibular function as well as on patients after operativ dissection of the VIII. nerve, neuropathia nerv. vest. and M. Menière. On the base of these findings it is supposed that myography proofes to be a useful help in the judgement of the specific influence of the vestibular organs on the motoric system. The myographic changes of the muscular activity after caloric stimulation give exact information about the entire vestibular system and especially about the vestibular-spinal-pathways. The best way of testing the vestibular activity is performed on musculars with symmetric, simultaneous and reziproke intented innervation, f.i. on the sternocleidomastoidei muscels in slight deflected position of the head. Most significant for the vestibular influence are an increase of the base-activity and the appearance of groups of potentials which are related to the vestibular stimulus in time and intensity.


Neurologic implications of glomus tumors in the head and neck. Seventy-six patients with glomus tumors were evaluated. The incidenc- of cranial nerve paralysis in 37 percent and the incidence of intracranial extension is 14.6 percent. Jugular foramen syndrome is associated with 50 percent, and hypoglossal nerve involvement with 75 percent incidence of posterior fossa extension. Horner's syndrome is associated with 50 percent of middle cranial fossa invasion. The incidence of CNS tumor involvement with cranial nerve paralysis (not including VIIth nerve) is 52 percent.


Role of cytidine triphosphate and cytidine diphosphate in promoting inositol entry into microsomal phosphatidylinositol. The Mn2+ activated incorporation of myo-inositol-3H into subfractions of phosphatidylinositol in rat liver microsomes was studied in the presence and absence of cytidine triphosphate or cytidine diphosphate choline using phosphate buffer. The distribution of labeled inositol among molecular species of microsomal phosphatidylinositol was also investigated in vivo. In other experiments, the release of radioactivity from microsomes labeled with inositol-3H in the phospholipid was measured after the addition of Mn2+, unlabeled inositol, and cytidine nucleotide. Similar chase experiments were conducted with microsomes containing phosphatidylcholine-14C or phosphatidylethanolamine-14C. The addition of cytidine triphosphate or cytidine diphosphate choline stimulated the rate of inositol-3H entry into microsomal phosphatidylinositol by 3.5 to 4-fold and the monoenoic plus dienoic, trienoic, tetraenoic, and polyenoic species contained 6-7, 6, 78-81, and 7-9%, of radioactivity, respectively. These latter patterns were very similar to those observed among the corresponding molecular species when the Mn2+ stimulated entry of free inositol into phospholipid was studied in the absence of added cytidine nucleotide. In chase experiments, the release of radioactivity from phospholipid in the presence of cytidine trephosphate or cytidine diphosphate choline was greatly enhanced by the addition of free inositol when microsomes containing phosphatidylinositol-3H, but not phosphatidylcholine-14C or phosphatidylethanolamine-14C, were employed. Therefore, under the present conditions, cytidine triphosphate and cytidine diphosphate choline appear to stimulate the entry of inositol into phosphatidylinositol by enhancing the Mn2+ activated exchange reaction in rat liver microsomes. The results suggest further that phosphatidylinositol is the preferred substrate when this reaction is stimulated by cytidine nucleotide.


Japanese encephalitis in an Australian soldier returned from Vietnam. An imported case of Japanese encephalitis is reported and discussed. Recent literature on the clinical aspects of the disease is reviewed. Although the disease is unlikely to become a problem in Australia, it will remain a serious hazard to nonimmune personnel moving into an endemic area.


[Composition and content of cytochromes in Rhodopseudomonas palustris in relation to growth conditions]. Differential spectra, CO spectra and spectra of hemochromes were studied in the cells of Rhodopseudomonas palustris grown in aerobic conditions in the light and in the darkness; the terminal oxidase was cytochrome a. This cytochrome was not detected in the cells cultivated in anaerobic conditions in the light. The content of cytochromes b was higher in the cells grown in aerobic conditions in the darkness; the content of cytochromes c was higher in the cells cultivated in anaerobic conditions in the light.


[Function of cytochrome c in a mutant of Candida mycoderma yeasts lacking in cytochromes b and a+a3]. The mutant of Candida mycoderma was studied, which lacked cytochromes b and a+a3. The mutant contained only cytochrome c which functioned with cytochrome c peroxidase in the absence of any cytochrome c oxidases.


[NAD-dependent N-methylglutamate dehydrogenase--new enzyme metabolizing methylamine in methylotrophs]. The properties of N-methylglutamate dehydrogenase, a new enzyme of methylamine metabolism in a facultative methylotroph Pseudomonas methylica, strain 2, were investigated. The enzyme was strictly dependent on the NAD presence and was not connected with particles in cell-free preparations. The enzyme appeared to be incucible and its activity increased after the growth of the cells in a medium containing methylamine.


In vitro repair of UV-or x-irradiated bacteriophage T4 DNA by extract from blue-green alga Anacystis nidulans. The cell-free extract from blue-green alga Anacystis nidulans contains enzymatic activities which repair in vitro transforming DNA of bacteriophage T4 damaged by UV light or X-rays. The repair effect of the extract was observed with double-stranded irradiated DNA but not with denatured irradiated DNA. The level of restoration of the transforming activity depends on the protein concentration in the reaction mixture and on the dose of irradiation. A fraction of DNA lesions induced by X-rays is repaired by a NAD-dependent polynucleotide ligase present in the extract. The repair of UV-induced lesions is the most efficient in the presence of magnesium ions, NAD, ATP and the four deoxynucleoside triphosphates. The results indicate that the repair of UV-irradiated DNA is performed with the participation of DNA polymerase and polynucleotide ligase which function in the cell-free extract of the algae on the background of a low deoxyribonuclease activity.


[Translation of hormone receptor interactions into biological function. A hypothesis (author's transl)]. Published data revealing discrepancies between the kinetics of hormone binding and adenylate cyclase activation are critically analyzed. This analysis gave rise to the hypothesis concerning the translation of hormone receptor interactions into biological function, i.e.: adenylate cyclase activation. Because the lifetime of the hormone receptor complex is too long, other steps in signal transfer are considered for the control of adenylate cyclase activity.


Sinusitis of the maxillary antrum.

Sinusitis of the maxillary antrum. Twenty-four adults with clinical evidence of sinusitis were studied by 65 needle punctures of the maxillary antrum. Fourteen of 15 sinuses with normal transillumination and 19 of 26 that were dull had normal aspirates, whereas 24 of 24 that were opaque had abnormal aspirates (P less than 0.001). Marked mucosal thickening as determined radiologically (Water's view) was associated with abnormal aspirates whereas lesser mucosal thickening was not (P less than 0.001). In acute sinusitis, there was a strong correlation between high aspirate leukocyte counts (greater than 1000 per cubic millimeter) and infection as manifested by bacterial titers of greater than 10(5) per milliliter or the isolation of virus fungus (P greater than 0.001). Anterior-nasal-swab cultures correlated poorly with direct aspirate culters. Organisms frequently recovered from the sinus included Haemophilus influenzae, Strepto coccus pneumoniae, and anaerobic bacteria. Rhinovirus was recovered twice. Antibiotics were usedful in patients with acute sinusitis if the organism was sensitive in vitro (P less than 0.001).


How specific are nuclear "receptors" for thyroid hormones? The presence of "high-affinity-saturable" binding sites for thyroid hormones of similar characteristics not only in isolated nuclei but in all the major extranuclear cellular components, as well as the failure of cytosol to promote nuclear binding, invalidates the analogy with steroid hormone receptors and necessitates a more critical assessment of the physiological relevance of current approaches to binding of thyroid hormone in vitro nuclear preparations.


Is the evolution of insulin Darwinian or due to selectively neutral mutation? A model for the evolution of insulin mainly in terms of adaptive processes is discussed. The model depends critically on the relationship of sequence changes to the three-dimensional structure and the role of various parts of this structure in the conversion of the proinsulin molecule to the active form, the storage of insulin, its transport to the site of action and its interaction with a receptor.


Dopamine- and apomorphine-sensitive adenylate cyclase in homogenates of rabbit retina. Dopamine (0.5-100 muM) as well as apomorphine (1-100 muM) were found to be potent stimulators of adenylate cyclase in homogenates of rabbit retina. When compared with the dopamine-effect at 10 muM, half-stimulation was also obtained in response to noradrenaline or adrenaline, whereas isoprenaline or phenylephrine were ineffective. Furthermore, the dopamine-induced production of cyclic AMP wab blocked by chloropromazine and haloperidol. These data would suggest the occurrence of a specific "dopamine receptor" in the retina of the rabbit.


Glucose-6-phosphatase (EC 3.1.3.9) and esterase (EC 3.1.1.1) activities of microsomes prepared from perfused rat livers after partial outflow block or phalloidin poisoning. Microsomes were prepared from perfused rat livers after different perfusion procedures. The yield of microsomal protein and the kinetic data (Km, Vmax) of glucose-6-phosphatase (3.1.3.9) and esterase (3.1.1.1) activities were analysed in each preparation. No marked differences were detected between conventionally prepared liver microsomes and those from livers perfused 1 hr with an erythrocytes-free medium under the conditions of open outflow. If the outflow pressure was increased artificially, the yield of microsomal protein decreased. The Vmax of both enzymes was markedly increased, whereas the Km values remained unchanged. The same microsomal alterations occurred when perfused rat livers were poisoned with phalloidin in vitro under the condition of open outflow. Our findings indicate that microsomal alterations in livers from poisoned animals might be due to microcirculatory disturbances, and not primary effects of the toxin on the endoplasmatic reticulum.


Adenylate cyclase and phosphodiesterase in the rat gastric mucosa after starvation, feeding and pentagastrin. The effects of starvation, feeding and pentagastrin on gastric mucosal adenylate cyclase (AC) and phosphodiesterase (PDE) activity were studied in the rat. 1. Starvation for 24 hrs and 48 hrs reduced both NaF stimulated and basal AC activities. 2. Feeding of starved rats slowly raised the AC activity up to 430% within 4 hrs after feeding. This effect was more pronounced under basal conditions than with NaF stimulation. 3. A single i.p. injection of pentagastrin (125 mug/kg) caused a stimulation of basal AC lasting 45 min, which was followed by a subsequent decrease in the basal and NaF stimulated enzyme activity. 4. PDE activity was not influenced by starvation and feeding but underwent a transient inhibition by pentagastrin. Accordingly gastric mucosal cAMP levels after starvation, feeding and pentagastrin are regulated by changes in AC and not in PDE activity. The rise in AC activity after feeding appears to be related to functions other than H+ and pepsin secretion.


Comparative effects of adenosine and adenine and guanine nucleotides on drug biotransformation in rats. The effect of various nucleotides and adenosine on the hepatic biotransformation of hexobarbital sodium (HB) and p-chloro-N-methylaniline (PCMA) was determined in male rats. Intraperitoneal administration of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), alone and in combination with theophylline, and the cyclic adenosine 3',5'-monophosphate (cAMP)-theophylline combination prolonged HB sleeping time by more than 70%. cAMP or dibutyryl cyclic guanosine 3',5'-monophosphate (DBcGMP), alone or in combination with theophylline, failed to significantly alter the duration of HB-induced hypnosis. Plasma levels of HB upon awakening suggested that the increase in sleeping time was apparently not due to an altered sensitivity of the brain to the barbiturate. The effect appears to be related to an impairment of HB metabolism since only those compounds that inhibited HB oxidation when added to liver slices prolonged hypnosis. In addition, 5'-AMP, adenosine, and cyclic guanosine 3',5'-monophosphate (cGMP) failed to alter HB biotransformation by liver slices. A similar pattern of impairment of metabolism by liver slices was observed when PCMA was used as the substrate. The inhibitory effect of DBcAMP was not altered by concurrent addition of either cGMP or DBcGMP. No impairment in the rate of microsomal PCMA biotransformation resulted from addition of adenosine or any of the nucleotides used in this study.


Pre- and post-junctional receptor-mediated cholinergic interactions with adrenergic transmission in guinea-pig vas deferens. Isolated, superfused, field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline, was used to study the interaction between exogenous and endogenous acetylcholine and adrenergic neuroeffector function. Exogenous acetylcholine was found to exert a dual muscarinic effect on the preparation, consisting of depression of the secretion of tracer noradrenaline from the sympathetic nerves, as well as enhancement of the nerve stimulation-induced contraction of the preparation. The results indicate that endogenous acetylcholine may play an analogous role, since eserine enhanced the nerve stimulation-induced contraction, without markedly affecting the secretion of labelled noradrenaline (the effect was abolished by atropine), while higher concentrations of atropine depressed the contraction and actually enhanced the secretion of labelled noradrenaline. The findings support the concept that guinea-pig vas deferens has a dual, cholinergic as well as adrenergic, innervation, and that the cholinergic nerves exert a dual modulatory effect on sympathetic neuro-effector function in this tissue: Firstly they appear to restrict the secretion of sympathetic neurotransmitter (via pre-junctional muscarinic receptors, on the adrenergic nerve terminals), and secondly they seem to enhance the excitability of the smooth muscle to sympathetic neurotransmitter (via post-junctional muscarinic receptors, on the smooth muscle cells).


Effects of 6-hydroxydopamine Treatment at birth on the submaxillary gland of the rat. Six and 18 months after neonatal administration of 6-hydroxy-dopamine or surgical sympathetic denervation the submaxillary gland of the rat showed a marked depletion of noradrenaline stores. Six months afer removal of the superior cervical ganglion the gland's endogenous noradrenaline was lowered to 0.032 +/- 0.004 mug/g while after neonatal 6-hydroxydopamine the values were 0.228 +/- 0.023 mug/g (controls 2.145 +/- 0.382 mug/g). Eighteen months after either type of sympathetic denervation the neurotransmitter was still depleted. In rats treated with 6-hydroxydopamine the sailagogue effect of injected noradrenaline was potentiated 2.7-fold while the potentiation of the effect of noradrenaline was 3.6 times after surgical denervation. The magnitude of the supersensitivity developed to isoprenaline did not differ between both types of denervation. No supersensitivity to the cholinomimetic agent, methacholine, was observed. Cocaine administration or removal of the superior cervical ganglion slightly increased the supersensivity to noradrenaline in rats treated with 6-hydroxydopamine. Eighteen months after surgical or chemical denervation, the activity of choline-acetyl-transferase in the submaxillary gland was increased by about 50%. Of the respiratory enzymes studied, sussinic dehydrogenase, fumarase and cytochrome oxidase, the activity of only the latter was markedly reduced by a chronic sympathetic denervation. From the results obtained it is concluded that neonatal treatment with 6-hydroxy-dopamine causes a permanent and almost complete sympathectomy of the submaxillary gland of the rat.


The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle. In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP.


On the role of alpha-methyldopamine in the antihypertensive effect of alpha-methyldopa. In renal hypertensive rats the cerebral concentration of alpha-methyldopa, alpha-methyldopamine, alpha-methylnoradrenaline, dopamine and noradrenaline as well as the blood-pressure were determined simultaneously. The antihypertensive effect followed a time course identical to that of the increase in the cerebral concentration of alpha-methyldopamine and of the decrease in the concentration of dopamine, whereas lowering of blood pressure on the one hand, and changes in the levels of alpha-methylnoradrenaline and noradrenaline, on the other, were not related to each other. Dose-response relationships showed the same correlations and lack of correlations, respectively. These results suggest that non-betat-hydroxylated catecholamines play a major role in mediating the antihypertensive effect of alpha-methyldopa or, alternatively, that only the newly biosynthesized alpha-methyl-noradrenaline is effective in lowering blood pressure.


Polypeptides isolated from ribosome-like structures occluded in avian myeloblastosis virus (AMV). The protein composititon of ribosome-like particles isolated from AMV was determined by acrylamide gel electrophoresis and by immunological methods. It was established that the protein spectrum of ribosome-like particles differed significantly form the total protein spectrum of AMV. The most characteristic protein components of ribosome-like particles had a molecular weight in the range of 70 000--110 000. Apart from these proteins, the viral ribosomal particles contained  a small amount of proteins with a molecular weight of 14 000--35 000 that could not be removed even by extensive purification. Immunological studies of the proteins of ribosome-like particles revealed the presence of antigenic determinants of ribosomal proteins. Furthermore, throughout the purification procedure the material contained components that reacted with antibodies against gs antigens.


Mammalian tropism of B77(RBI) virus. Expression of virus genome in the hamster sarcoma cell clones. In contrast to the B77 virus, its B77(RBI) rat variant continuously produced by the rat RBI sarcoma cells in vivo and in vitro, efficiently induced progressively growing tumors in hamsters and transformed hamster embryo cells in vitro. Both, induced tumors and transformed cell cultures showed production of infectious virus and presence of the avian gs-antigen. Clonal analysis of the established hamster sarcoma cell line RBHtc brought evidence that despite the quantitative differences in the virus production and gs-antigen content among various clonal populations, full expression of the B77(RBI) virus genome does occur in each cell of the virus-induced hamster sarcoma. The permissive relationship of the B77(RBI) virus with rat and hamster cells as well as changed antigenic composititon implies that a genetic change of the virus occured, which is reflected in its increased mammalian tropism and its genetically stable firus-productive interaction with mammalian cells. The possible explanations of these phenomena are discussed.


The experience with clinical application of hydron pouches in tumor chemotherapy. Hydron pouches were applied in three cases of embryonal hepatomas in infants. Cyclophosphamide (one case) and methotrexate (two cases) were used for filling of pouches in order to accomplish local chemotherapeutical effect directly on the tumor. Histopathological examination showed good compatibility of pouches to the liver tissue. No therapeutical effect was observed in a set of experiments due to a small size of pouches as compared to big masses of tumor. Some suggestions for further development of this method are presented.


In vitro cellular responsiveness in multiple sclerosis patients to a viral isolate from multiple sclerosis brain tissue and to other antigens. The Clausen modification of the leukocyte migration test was used to test patients with multiple sclerosis, normal subjects, and patients with other neurologic diseases for cell-mediated immunity to 6/94 virus (a parainfluenza virus previously isolated from the brain tissue of a multiple sclerosis patient), c-RNA virus isolated from a tumor, and the nonviral antigens Candida and purified protein derivative. Leukocytes of multiple sclerosis patient showed significantly less mean inhibition of migration by the 6/94 virus (but not by the c-RNA virus, purified protein derivative, and Candida) than did the cells of normal controls and patients with other neurologic diseases. The relationship of these findings to previous observations in this area and to the pathogenesis of multiple sclerosis is discussed.


Mononeuropathy due to vincristine toxicity. Vincristine sulfate is a known neurotoxin. Peripheral neuropathy is the most common toxic manifestation and is usually of the symmetrical, mixed, sensory-motor type. With this report we alert other physicians to another feature of vincristine neurotoxicity, namely, mononeuropathy.


Some perspectives on the role of biostatistics and epidemiology in the prevention and control of mental disorders. The paper reviews progress made in the past 30 years in the development of statistical and epidemiological methods in the mental health field. Applications have included determinations of need for psychiatric care and supporting personnel; interpretation of morbidity indices, and cross-national comparisons of diagnoses of mental disorders. Much remains to be done. Progress would include better measurement of incidence, duration, and prevalence of mental disorders; more precise estimates of service needs; more effective programs to prevent or reduce disability. Particularly needed are field-research units under long-term funding with the task of assessing effectiveness of mental health programs at the catchment-area level.


Neurological complications of haemophilia. Peripheral nerve lesions are well recognised complications of the haemophilias but impairment of autonomic function has not previously been reported. Two patients of the severe older haemophiliac population in the area were found to have impotence in association with signs of peripheral nerve damage. The basis proposed for this is autonomic nerve injury associated with intramuscular haemorrhage.


Response of pituitary-adrenal axis on partal stress. The circulating level of ACTH (by radioimmunoassay) and cortisol (by competitive protein binding) were determined at 1- to 2-hour intervals during spontaneous labor (N=8) and induced labor (N=28) and after delivery. There were no differences in ACTH levels between primiparous and multiparous women. The primiparous women displayed a higher level of cortisol throughout labor than the multiparous women, but not after delivery. After spontaneous onset of labor, ACTH levels were always lower than after elective induction of labor, while there were no differences in the levels of cortisol. The hypertensive complications of pregnancy did not affect the secretion of ACTH. In normal pregnancy the rise of cortisol during labor and after delivery was significant, but it was not significant in the group of patients with hypertensive complications.


Invasive vulvar Paget's disease.

Invasive vulvar Paget's disease. Seven cases of invasive vulvar Paget's disease are presented. These are compared with 10 cases of intraepithelial vulvar Paget's disease. On the basis of both clinical and histopathologic observations, the concept of intraepithelial vulvar Paget's disease is supported, and this entity is distinguished from the invasive form. Therapy for the latter is discussed.


Dermatitis from neutral red therapy of herpes genitalis. A case of contact dermatitis from neutral red dye applied for treatment of herpes genitalis is presented. A review of the literature revealed 5 other patients with a similar reaction. We suggest that neutral red dye treatment for herpes should be used with caution in patients with an allergic history.


Growth and skeletal maturation in asthmatic children: effect of corticosteroid treatment. The effects of corticosteroid treatment on growth and skeletal maturation were evaluated in 189 children with severe asthma who were referred for care at a residential treatment center.  Height age on admission was significantly retarded in 8-10% of patients who had received little corticosteroid treatment previously and in 35% of patients who had taken steroids daily for more than 2 years.  Children who had been treated with steroids intermittently or on alternate days were comparable to those who had taken steroids rarely.  During an average residential period of 17 months, patients whose daily steroid treatment was discontinued had a relative gain in height age of 5 months; children who were started on daily steroids had a 5-month delay in growth.  Evaluation of skeletal maturation at the time of admission revealed that skeletal age was more retarded than height age in the boys and less retarded than the height age in the girls.  During the period of residence, the changes in bone age paralleled the changes in height age.


1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance. This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, "pseudodeficiency" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure.  It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3.  The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity.  In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy.  In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR.  These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.


Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents. Levodopa, 0.5 gm/1.73 sq m, and propranolol, 0.75 mg/kg, were administered orally to 23 children with short stature and 10 children suffering from various disorders. Glucose and insulin tolerance tests and arginine infusions were also utilized in some of these subjects to determine growth hormone (GH) response. Seventeen subjects with short stature had a GH peak greater than 5 ng/ml to the combined levodopa-propranolol provocative test (DPPT). The mean GH peak concentration obtained in this group was 19.6 +/- 1.8 (SEM) ng/ml, and in 94.1% of these children the peak was obtained at either 30, 60, or 90 minutes following the administration of the two drugs. Six subjects with short stature who failed to respond to the DPPT had abnormal responses to at least two other stimulatory tests and were classified as GH-deficient. Two subjects among the ten suffering from various disorders failed to respond to the DPPT. The first was a case of chromophobe adenoma of the pituitary gland with primary amenorrhea and luteinizing hormone deficiency, and the second a case of Hand-Schüller-Christian disease. The DPPT appears to be a reliable, safe, and easy-to-perform test to determine GH reserve.


Reduction of Clostridium perfringens by feed additive antibiotics in the ceca of chickens infected with Eimeria tenella. Two experiments were performed ot investigate the effect of feed additive antibiotics on Clostridium perfringens and Enterobacteriaceae in the ceca of chickens infected with Eimeria tenella. In the first experiment, chickens were continuously fed rations containing thiopeptin, 2 mg./kg.; bacitracin, 20 mg./kg.; penicillin, 12 mg./kg.; or chlortetracycline, 22 mg./kg. One day after antibiotic feed was given, each bird received an oral inoculation of 30,000 E. tenella oocysts. The growth of C. perfringens was stimulated by the infection in unmedicated chickens. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline suppressed the number of C. perfringens recovered 5 and 7 days after infection. Enterobacteriaceae were increased by the infection, but dietary antibiotics did not reduce the increase. In the second experiment, chickens were given feed containing amprolium plus ethopabate, 125 plus 8 mg./kg., and a combination of the coccidiostat and one of 4 antibiotics: thiopeptin, bacitracin, penicillin, or chlortetracycline. Birds were each given an oral inoculation of 30,000 coccidiostat-resistant E. tenella oocysts. Infection resulted in an increase of C. perfringens in the unmedicated control and the coccidiostat-treated groups. Dietary thiopeptin, bacitracin, penicillin, or chlortetracycline reduced the number of C. perfringens found 5 and 7 days after infection. Counts of Enterobacteriaceae were increased by the infection, but dietary antibiotics did not suppress the increased counts. In both experiments, dietary administration of antibiotics did not reduce gross cecal lesions.


Assignment of gene(s) for cell transformation to human chromosome 7 carrying the simian virus 40 genome. Somatic cell hybrid clones between either C57BL/6 or Balb/c mouse peritoneal macrophages and two different simian virus 40 (SV40)-transformed human cell lines deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase) were obtained in hypoxanthine-aminopterin-thymidine selective medium. All the hybrid cell clones contained the human chromosome 7, which carries the SV40 genome, and were SV40 tumor (T)-antigen positive. No hybrid cell clones studied displayed the density-dependent inhibition of cell growth characteristic of normal cells; all clones had a high saturation density and gave origin to cell colonies when plated in soft agar. Since the expression of the transformed phenotype was always associated with the presence of the human chromosome 7, which carries the SV40 genome, it is concluded that this chromosome contains gene(s) [Tr gene(s)] coding for "transforming factor(s)."


Augmentation of lymphocyte cytotoxicity by antibody to herpesvirus saimiri associated antigens. Sera from owl monkeys infected with Herpesvirus saimiri (HVS) mediated antibody-dependent lymphocyte cytotoxicity (ADLC) against virus-infected owl monkey kidney cells. Peripheral blood lymphocytes from rhesus monkeys served as effector cells in this cytotoxic assay. ADLC titers increased along with membrane immunofluorescence (MF) titers but among some sera, the ADLC titers were much higher than expected from the MF titers, suggesting that multiple serum factors were involved in mediating ADLC in this system. Absorption of both low and high titered sera with HVS-infected owl monkey kidney cells removed all ADLC activity. Preliminary results from serial serum samples from two infected monkeys that developed leukemia and/or lymphoma demonstrated that ADLC but not MF titers increased to high titers with progression of disease and followed essentially a different kinetic pattern than that noted by MF. The possible significance of these findings in relation to malignant disease induced by this virus is discussed.


A structural change of the plasma membrane induced by oncogenic viruses: quantitative studies with the freeze-fracture technique. In BHK21 hamster cells a significant increase in density of intramembranous particles occurs in freeze-fractured plasma membranes after transformation by hamster sarcoma and polyoma viruses. A similar change has been observed in chick embryo cells infected and transformed by a mutant of Rous sarcoma virus thermosensitive for transformation, at both permissive and nonpermissive temperatures. There is also an increase in particle density in chick cells infected with the Rous-associated avian leukosis virus type 1. The newly appeared particles may represent the insertion of new proteins in hydrophobic regions of plasma membrane, in response to the action of oncogenic viruses.


Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 5: Effects of lubricants and flow conditions. The effect of talc, magnesium stearate, stearic acid, and Acrawax C, which are commonly used as lubricants, on the dry-binding efficiency of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone, and mannitol were investigated. The effect of Aerosil which is sometimes utilized as a flow conditioner for directly compressible powder blends was also studied. The type and concentration of lubricant or flow conditioner appeared to influence the binding efficiency of the binders investigated to various degrees. The results showed that the bonding characteristics of all the binders tested except mannitol were reduced by the addition of the lubricants and the flow conditioner.


The development of mitochondrial oxidative enzymes in rat heart muscle. Three different developmental patterns have been found in the heart muscle mitochondria: (a) Activity of inner membrane enzymes, succinate-cytochrome c reductase and rotenone-sensitive NADH-cytochrome c reductase, was found to increase rapidly after birth till the 25th day; no further increase was found till the 60th day. Both brances of the respiratory chain, i.e. NADH-dependent and flavoprotein-linked were found to develop in parallel. (b) Activity of retoenone insensitive-NADH cytochrome c reductase, an outer membrane enzyme, did not show any change during developement. (c) Activity of monoamine oxidase, another outer membrane enzyme, was found to increase after the 10th day of postnatal life and the increase in activity continued till the 60th day.


Activity of the inner and outer membrane oxidative enzymes in brown adipose tissue mitochondria. 1. The specific activity of cytochrome-oxidase, succinate-cytochrome c reductase and su-cinate-oxidase of brown adipose tissue mitochondria of 17-day-old rats was found to be twice as high in brwon adipose tissue mitochondria as in the liver. The specific activity of rotenone-sensitive NADH-cytochrome c reductase and NADH-oxidase was found to be six times higher in brown adipose tissue mitochondria than in the liver. 2. Brown adipose tissue mitochondria have extremely low activity of outer membrane enzymes. When compared with liver the specific activity of rotenone-insensitive NADH-cytochrome c reductase was found to be seven times lower, the specific activity of monoamineoxidase up to 30 times lower according to the substrate used. 3. The optimum conditions for the determination of both NADH-cytochrome c reductases in brown adipose tissue mitochondria were more specified on the base of the following findings: (a) the outer membrane rotenone-insensitive NADH-cytochrome c reductase is strongly inactivated by freezing-thawing, (b) freezing-thawing, alone is insufficient to release completely maximal activity of rotenone-sensitive NADH-cytochrone c reductase, freezing-thawing activite can be further potentiated by e.g. trypsin treatment. 4. The activities of the outer membranes of brown-adipose tissue mitochondria are discussed with regards to the structural integrity of the outer membrane, the activities of the inner membrane enzymes are discussed with regards to the functional specifity of the tissue.


REM sleep and the analytic process: a psychophysiologic bridge. Recent research on the physiology of REM sleep has supported the hypothesis that it serves processes of psychologic adaptation. This study examines the relationship between physiologic parameters of REM sleep and evidence in analytic material of the need for adaptation. Significant correlations were found between defensive strain before sleep and REM latency, and between change in defensive strain from evening to morning and total REM time.


Clinical measurement in psychoanalysis: an approach. Measurement of the complex phenomena in psychoanalysis is approached by defining interrelated elements in the analytic situation and specifying the range of their variation in scales which can be both generalized and made specific for an individual patient. Using this approach in transcripts of psychoanalytic sessions, we rate painful emotion, impairment of defensive maneuvers, and activation of threatening conflictual fantasies. This preliminary study involved rating of tape-recorded sessions by psychoanalytically oriented judges. Quantitative estimates appeared to relate in many ways to qualitative fluctuations in the patient's state. Such an approach may be helpful in developing more effective clinical theory about emotions, defensive processes, and transference fantasies.


Some effects of ACTH 4-10 on performance during a serial reaction task. Eighteen subjects worked continuously for half an hour in a self-paced reaction task. Half of the subjects were injected with ACTH 4-10 (30 mg/s.c.) and the other half with a placebo. The subjects injected with ACTH 4-10 showed a larger improvement in reaction time during the experimental session than the placebo group. However, this effect disappeared in a short retest, which was given half an hour after the experimental session. These results suggest that ACTH 4-10 has no effect on skill acquisition, but counteracts the build-up of reactive inhibition during the experimental session; that is, the peptide suppresses the decrease in motivation, which usually occurs during continuous performance tasks. This notion is confirmed by an analysis of the frequency distributions of the reaction times. Treatment effects were only found for the long reaction times. Long reaction times tend to occur with increasing frequency as a function of time-on-task and are an indication for the level of motivation of the subject. It was concluded that ACTH 4-10 counteracts the usual decay in performance as a function of time-on-task due to increasing boredom and mental fatigue.


[Effects of alpha-methyl-dopa on new born kitten sleep. Behavioral evolution during the first month post-birth (author's transl)]. The paradoxical sleep (PS)-suppressing effect of alpha-methyl-Dopa was studied in kittens at birth. The new burn animal received daily injections of alpha-methyl-Dopa during the 2 first weeks of life. States of sleep were studied during the treatment (days 1 to 14) and after administration of the drug way halted (days 15 and 16). Daily injections of alpha-methyl-Dopa induce an average PS-deprivation of 72%. This deprievation is compensated for by a significant increase in quiet sleep (QS)-rate which is found to be up to 3.5 times that of kittens not receiving alpha-methyl-Dopa. A progressive return of PS-ratio to normal, without PS rebound, is observed after drug administration ceases. Alpha-methyl-Dopa produces a sedative effect on the kitten which remains relatively hypotonic during the treatment. Behavioural studies carried out over the first month after birth show no significant delay in the ponderal growth nor in the acquisition of stereotyped behaviour patterns. However motor coordination is delayed 2 weeks in these kittens.


Effects of a new butyrophenone derivate (Buronil) on nocturnal sleep in normal man. Nocturnal sleep was studied in eight young normal volunteers (3 female and 5 male students) with polygraphic technique during 2 periods of 10 night each. After 2 adaptation and 2 baseline nights with placebo, they were given methylperone (Buronil) 10 or 50 mg per night during three nights and then again placebo for three withdrawal nights. The study was made double blind. The scoring of the records was done according to the manual by Rechtschaffen and Kales (1968). No changes of sleep stages were seen during the drug periods. The lower dose gave an increase of sleep latency but a decrease of number of awakenings during the night. An increase of REM-periods was shown after 50 mg and also a decrease of REM-latency and REM-density. The only significant change during withdrawal periods was a decrease of REM-sleep after methylperone 50 mg, so there was no "barbiturate type" of withdrawal. The change was also different from that of chloropromazine, which has no clear rebound effect.


Ultrastructural changes in the placenta of the ewe following foetal infusion of cortisol. The placental changes which followed continuous infusion of cortisol into the sheep foetus in the later stages of gestation were, like the hormonal changes, broadly similar to those of spontaneous parturition. There was, however, a premature separation of foetal and maternal tissues in certain areas of the placental cotyledons, and this separation appeared to protect the foetal epithelium from the degenerative changes which normally take place in the short space of time between the birth of the lamb and the delivery of the foetal membranes. The results suggest that an experimental model in which premature labour is induced by the administration of cortisol to the foetus is probably incomplete, and that additional factors almost certainly contribute to the cascade phenomenon of spontaneous parturition.


Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects. In sleep studies of (a) patients with the "fibrositis syndrome" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpha-rhythms in the non-rapid-eye-movement (NREM) sleep EEG.  This phenomenon has been termed alpha-delta sleep.  In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of muscoloskeletal and mood symptoms comparable to the symptoms seen chronically in the patients.  It is suggested that the external arousing stimulus, which induced alpha-delta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism.  Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms.  It is proposed that the "fibrositis" symptom complex be considered a "non-restorative sleep syndrome".  Evidence froms presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms.


A biochemical hypothesis to explain the mechanism of luteal regression. It seems likely that luteal regression may involve a direct biochemical action of prostaglandin F2alpha (PGF2alpha) on the luteal cell since there are now several reports that PGF2alpha can directly inhibit steroidogenesis in vitro. However, the mechanism of such an action of PGF2alpha remains obscure. This article initially reviews the central role of adenosine 3,I5I-mono-phosphate (c-AMP) in initiating and maintaining the structural and functional changes occurring on luteinisation. A mechanism is suggested, supported by results obtained using granulosa cells in tissue culture, in which PGF2alpha initiates functional luteolysis by inhibiting further synthesis of c-AMP. This mechanism is then used in conjunction with further in vitro observations to provide a possible explanation for the inability of PGF2alpha to regress newly formed corpora lutea. Finally, the possible mechanisms of structural regression are discussed.


Secretion rate of prostaglandin F during induced labor in goats. Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.


Compartive behavioral effects of dibutyryl cyclic AMP and prostaglandin E1 in mice. Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to stuey the interaction of PGE1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE1 (0.01-5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. decreases in SLMA were produced by PGE1 (79%), DBcAMP (41%) and DBcAMP-PGE1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE1 or DBcAMP+PGE1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed.


Structural requirements for the binding of prostaglandins. The binding of prostaglandins and analogs to the lipocyte PGE receptor was shown to exhibit a high degree of structural specificity. Small changes, particulary at the 9-keto or 15-hydroxyl position, were found to drastically diminish interaction with the receptor. Studies of a rather substantial number of compounds revealed a close relationshio between affinity for the lipocyte PGE receptor and the ability to stimulate cyclic AMP synthesis in the isolated mouse ovary. In general, activities in these two parameters follow the biological potencies generally recognized for the compounds.


RNA synthesis by isolated Yoshida ascites hepatoma A.H. 130 cells mitochondria. Mitochondria isolated from Yoshida ascites hepatoma A.H. 130 cells are able to incorporate 3H-UTP into RNA. The reaction has been extensively characterized and appear to be supported by a typical DNA-dependent RNA polymerase, and no special differences with the system of normal rat liver mitochondria have been found.


On the diuretic action produced dibutyryl cyclic AMP in dogs. Experiments were undertaken on order to elucidate the mechanism  of diuresis induced by dibutyryl cyclic AMP in dogs. Intravenous injections of dibutyryl cyclic AMP produced an increase in urine flow in dogs hydrated with saline. It was also noted that dibutyryl cyclic AMP produced an increase in myocardial contraction, renal blood flow and glomerular filtration rate; In addition, unilateral injection of dibutyryl cyclic AMP into the left renal artery produced diuresis bilaterally. Based on the above findings it was suggested that the diuretic action induced by dibutyryl cyclic AMP is associated with its hemodynamic effect.


Technique of lymphography in the rat.

Technique of lymphography in the rat. Most the lymphatic system in the rat was directly observed in our experiment by radiological means. The lymphatics of the limbs were firstly revealed by subcutaneous injection of Patent Blue V. Lipiodol was used as radio-opaque compound injected by a micro-technique fully described by the authors.


Vinblastine-induced ultrastructural changes in perisinusoidal cells of the rat liver. Vinblastine, given intravenously to rats, leads to disappearance of microtubules, formation of paracrystalline inclusions and accumulation of fat droplets in the cytoplasm of the perisinusoidal cells of the liver suggesting that microtubules of the perisinusoidal cells play a role in lipid metabolism.


Comparison of the effects of vitamin D3, dihydrotachysterol, and parathormone on calcium kinetics in the rat. Rats were treated with 100 I.U. (= 2.5 mcg) Vit. D3/day during 14 days and submitted to a radio-Calcium assay of Calcium kinetics. The results were compared with those obtained in weight-matched pair-fed controls, and with those obtained in former experiments applying dihydrotachysterol and parathormone. Vit. D3, which is transformed to a hormone, increased the fast exchange compartment, the exchange rate between the compartments, the endogenous fecal Calcium excretion rate, and the bone uptake and release rates. These findings indicate that the Vit. D-hormone is more similar in its action to the other hormone, parathormone, than to its close chemical relative dihydrotachysterol.


Heterodox practitioners and the availability of specialist advice. The characteristics of the principal categories of more professional heterodox practice are examined. It is concluded that rheumatic diseases are one of the likeliest fields for conflcit between orthodox and fringe medicine. The distribution of manpower engaged in alternative systems of health care is compared with that of orthodox medical services. The limited data on  utilization of unorthodox remedies are reviewed. Far from conflict ensuing, it is argued that dialogue must develop in order to submit procedures like manipulation to satisfactory clinical trial.


[Mixed tumors and cylindromas].

[Mixed tumors and cylindromas]. The lacrimals glands may be the focus of the pleomorphic tumours with the same property as the major and minor salivary glands. Their localisation causes different clinical and therapeutic consequences. The cylindromes or Adenoid Cystic Carcinoma are to be put on a parallel with the pleomorphic tumours, though the issue of the clinical evolution is very different for each of them.


Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of dietary manipulation. To study the metabolism of the abnormal plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency we performed five dietary experiments designed to perturb their distribution and composition. Four patients with the disease were given successive diets that differed in triglyceride, carbohydrate, or cholestrol content, and after each dietary period the lipoproteins were analyzed by combinations of preparative and analytical ultracentrifugation, gel filtration, chromatography, and disc gel electrophorsis. Lowering the intake of long chain, dietary triglyceride descreased the concentrations of the large very low density lipoproteins, the large and intermediate low density lipoproteins, and the small high density lipoproteins by as much ad 79 %, but either increased or did not change the concentrations of the small very low and low density lipoproteins. Re-adding long chain triglycerdine to the diet generally reversed these effects, but increasing the dietary cholesterol without lowering the dietary triglyceride only decreased the concentration of plasma cholesteryl ester. We conclude that the concentrations of the large very low and low sensity lipoproteins, the intermediate-sized low density lipoproteins, and the small high density lipoproteins are related to the absorption and subsequent transport of long chain dietary fatty acids. Since these lipoproteins are rich in unesterified cholesterol and lecithin, two polar lipids that form a substantial part of the surfaces of chylomicrons, components of chylomicron surfaces may accumulate in the patient's plasma following enzymic removal of chylomicron triglyceride and contribute to several of the abnormal lipoproteins.


Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of incubation with lecithin: cholesterol acyltransferase in vitro. To study the effect of lecithin: cholesterol acyltransferase (LCAT) on the plasma lipoproteins of patients with familial LCAT deficiency, whole plasma or the lipoprotein fraction of d smaller than 1.006 g/ml (VLDL) was incubated in the presence of LCAT and subsequently examined by chemical, physical, and immunological techniques. The following occured upon incubating either hyperlipemic or nonlipemic plasma: The concentrations of polar lipids decreased, particulary in the large molecular weight lipoprotein subfraction of d 1.019-1.063 g/ml (LDL2) and in the lipoprotein fraction of 1.06301.25 g/ml (HDL). The concentration of cholesteryl ester (CE) increased, particularly in the VLDL and in the lipoprotein fractions of d 1.006-1.019 g/ml (LDL1) and LDL2. The concentration of arginine-rich apolipoprotein decreased in the HDL and increased in the VLDL and LDL1. The concentrations of the C-apoliproteins appeared to change in the opposite direction. The concentration of apolipoprotein B in the LDL increased concomitantly with an increase in the concentration and flotation rsate of the small LDL2. The concentration apolipoprotein A-I in the HDL increased; and a major component in the HDL fraction became identical in apperance to normal HDL. Upon incubating a patient's isolated VLDL in the presence of LCAT, lipoproteins with properties similar to normal LDL2 were formed. These experiments show that the LCAT reaction can alter the apolipoprotein content and physical properties as well as the lipid content of the patient's lipoproteins.


[Encapsulating peri-hepatitis. Apropos of 4 cases]. The authors report 4 cases of encapsulating peri-hepatitis, including an angiographic study. Selective arteriography of the coeliac trunk showed extremely sinuous intra-hepatic arteries in 3 of these cases, and obstruction of the portal vein, in one case. Catheterisation of the hepatic veins showed a pressure gradient between the obstructed hepatic vein and the free supra-hepatic pressure, showing a post-sinusoidal block. In 2 of the 4 cases, ascites was chylous. Lymphography carried out via lymphatics in the foot was negative in 3 cases where it was carried out. One case showed, on two successive laparoscopies, that micro-nodular cirrhosis was present before the development of encapsulating peri-hepatitis.


[Cytogenetic study of 30 couples having had several spontaneous abortions]. In 30 couples consulting after two or more failed pregnancies, the authors detected two women with reciprocal translocation in the heterozygous condition: t (5 ; 6) (q 35 ; q 21) in one case. t (5 ; 10) (q 15 ; q 25) in the other case. In both cases, there was, later, birth of a normal boy of karyotype 46, XY. It thus appears obvious that the balanced structural changes which occur in the fertility of these couples, reduces the latter.


[Radiologic study of gastric transit after ingestion of natural soda water]. Is a barium meal modified when soda water is used as a drink? In a series of 60 patients, the authors studied radiologically, a barium meal after taking ordinary tap water and after taking soda water. They observed after taking soda water, an increase in volume of the air pocket at the upper end of the stomach with, in 69% of cases, return to normal within 10 minutes. Gastric emptying occurred more rapidly with soda water in 40% of cases, and identically in 30% of cases.


[Pathology of peripheral nerves (elementary lesions, their development and different types of neuropathies) (1st part)]. The ultrastructural features of the normal components of the endoneurium are described. The sequence of events of axonal (wallerian) and segmental demyelination are enumerated. The process of ageing in the peripheral nervous system is analysed.


[Arrector muscle in patients with scleroderma. Histological and histo-enzymological study]. In a previous paper, we have found, at post-mortem examination of three cases of scleroderma, the oesophageal smooth muscle alterations already predicted by physiologists and reported by Treacy. These lesions mostly consist of a loss of the staining properties of the differenciated cytoplasm of the muscle cell, preceding any appearance of interstitial fibrosis. We have already reported these muscle lesions at all other levels of the digestive tract (stomach, small and large bowels), and also in the bladder muscle. In the present study, we have attempted to precise these notions in biopsies and have studied the arrector pili muscles in normal skin of 13 sclerodermic patients by means of histochemical (Regaud, Mallory, etc. ...) and enzyme stains. In all cases, we have been able to identify morphological alterations of the muscle fiber, mostly consisting in an irregular pattern of enzyme properties, especially when diaphorases, dehydrogenases and ATP ases were concerned. This work seems to confirm that the primary site of the sclerodermal lesions is situated in the smooth muscle fiber.


[Ultrastructural study of the arrector muscle in the patient with scleroderma. Preliminary analysis apropos of 3 cases]. An electron microscope study of the arrector pili muscle, using biopsies obtained from clinically and histologically healthy skin in 3 cases of scleroderma, showed the primary origin of the muscle disorders. They showed a certain number of changes, both of the differentiated cytoplasm and of the common cytoplasm.


[Psychosomatic study of duodenal ulcers in young adults in the military]. The authors report the relationship between psychological disturbances and duodenal ulcer, and discuss the conclusions of three studies carried out in military personnel. The group of young adults during war time, permitted them to analyse the role of psychological trauma in the onset and relapse of this disease. In young soldiers during peace time, there was significant affective immaturity. Finally, a study of young adults before call up, permitted comparison with military personnel. Rather than a study of specific characteristics, it appears that one should consider their dynamic organisation in order to understand the onset of symptoms.


[Pathology of the peripheral nerve. (Teasing, the various degrees of denervation, onion bulbs) (2nd part)]. Anatomical data for the interpretation of teased fibres are described. The different degrees of degeneration in a peripheral neuropathy are enumerated and criteria to identify them are given. The onion bulb formation process is analysed and some morphologically different types are proposed.


[Muscular disorders of the patient with scleroderma. Clinical study]. In scleroderma, the scapular striated muscles may be affected showing rapid fatigability, and sometimes, muscle wasting with EMG changes. The smooth muscle changes, well known in the esophagus, where they lead to loss of peristalsis, may also be marked in other parts of the digestive tract. They lead to various symptoms, such as cramps, vomiting and diarrhea.


[Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis]. The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of "metacritical aggravation" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct.


[Bone metastases of colonic and rectal neoplasms. Apropos of 11 cases]. The authors report 11 personal cases and discuss the characteristics of bony metastases in carcinoma of the colon and rectum. The frequency of these metastases is fairly low (1.3% of all cases of bony metastases) as tumours of the large intestine do not tend to migrate to the bones. Sometimes bony metastases are the presenting symptom but, usually the metastases occur within 5 years of the diagnosis of the primary tumour. The clinical picture shows no special characteristics. Radiologically, these bony metastases may be either single or multiple. Their distribution recalls that of other metastases in the bones with a few differences, however. The special frequence of pelvic involvement, distal localisations (hands or feet) are not exceptional. Metastases usually give rise to osteolysis. The mixed appearances are, however, not rare, and usually give a pseudo-sarcomatous appearance, with invasion of the soft parts and very marked periosteal reaction. Sometimes, bony condensation may be noted. The treatment of rectal and colonic cancer with bony metastases, is disappointing as the disease is always fatal within a relatively short period, usually less than one year after the diagnosis of the bone involvement. The histological appearances of the bony lesions depend on differenciation of the tumour and the characteristics of the neighbouring bony abnormalities which, in our experience, usually include both osteolysis and osteogenesis.


[Abnormalities of lumbar transverse processes]. The transverse processes of the lumbar vertebrae sometimes present rare abnormalities, or major abnormalities, which may be contrasted with congenital lesions concerning their volume, shape and direction. After a rapid review of the general and clinical characteristics, radiological analysis of the 59 cases collected in the literature and 6 personal cases, permits a provisional classification of the three varieties of lesion encountered. Apart from the rareness of cases known up to now, the interest of this study is to attract attention to the etiology which is still unknown, whether congenital or traumatic, and consequently, to the possible medico-legal consequences. Once again, as in other fields, the authors attract attention to the undoubted advantages of routine XRay of the lumbar spine and of the sacral area, one of which may be to discover the true etiology of the abnormalities encountered.


[Various clinical aspects of cutaneous leishmaniasis, a disease too often unrecognized in the Paris area. Diagnostic and therapeutic problems]. Muco-cutaneous leishmaniasis is now more frequently observed in France owing to population movements. One should learn to recognise the disease, the various aspects of which are presented here (7 cases). They recall the necessity of associating direct search for leishmania in the serous exsudate from the lesions or on histological sections, routine culture of swabs on agar jelly en riched with blood and on heart-brain blood medium. The immunoglobulin estimation sometimes revealed significant increase in their levels, but the sero-immunologic reactions by the indirect immuno-fluorescent method, were all negative. The best treatment is N-methylglucamine antimoniate by intradermal injection under the lesions or, in some cases, the parenteral route. On the other hand, metronidazole does not seem to be efficacious in skin leishmaniasis in this part of the world.


[Suppurative trichophytosis of animal origin. Apropos of 38 recent cases]. This study of 38 cases observed over a period of 7 years emphasizes the constancy of rural contamination, whether professional or not. An enquiry carried out among veterinary surgeons in this region, showed the increasing frequency of the animal infection particularly in young oxen, hence the increased risk of kerions. The author recalls the clinical description of kerion of the scalp in children and sycosis barbae in adults, in which one may also encounter folliculitis of the limbs. The parasite isolated, included various strains of Trichophyton, e.g., Trichophyton Trimentagrophytes, Tr. verrucosum and, more rarely, Tr. magnini. On the other hand, bacteriological examination was usually negative, there were only two cases of secondary staphylococcal infection. The authors emphasize their concept of the disease which is probably an immune process. Finally, rather than the usual treatment, they emphasize the possibilities of social re-insertion; the disease should be recognised as an occupational disease.


[Anti-nuclear antibodies in collagen diseases]. The authors sought serum antinuclear antibodies by the indirect immunofluorescent method in 3,260 patients, and found these antibodies in 293 of them. 90 patients had a level equal or greater than 1/50. Among the latter, 54 had some form of collagen disease. The following facts are emphasized: -- antinuclear antibodies are always present in lupus erythematosus. Their levels fall under the influence of treatment when nephritis occurs; -- their frequency is greater (13 cases out of 16) during scleroderma, with often a hazy appearance; -- they are lower during rheumatoid arthritis (23% of cases had a significant level), and their presence is not a sign of worse prognosis; -- they were absent in other forms of collagen diseases.