[Encephalitis and humoral immunity].

[Encephalitis and humoral immunity]. Fourteen children with viral infection of the central nervous system have been examined with respect to their function of humoral immunity. Serum concentrations of immune globulins have been measured and antibody titers determined. Iso- and hetero agglutinins as well as antibodies against diphtheria, pertussis, and tetanus if the children were vaccinated have been measured. Anti viral antibodies were tested if children reported the respective infection in their history. Selective antibody deficiency have been found in three children all of whom had normal serum IgG and two elevated IgM levels. These three children showed complications in the course of infection. Nine children had elevated serum IgM and titers of IgM-antibodies were also in or above the high normal range.


[Herpes simplex (author's transl)].

[Herpes simplex (author's transl)]. About 1-2% recurrent herpes simplex infections are seen in adults. In childhood, secondary herpetic infections are very rare. In contrast, primary infections by herpes simplex virus are of great importance: herpes disseminatus neonatorum (type 2), gingivostomatitis herpetica (type 1), eczema herpeticum (type 1; in some cases, also type 2) and keratoconjunctivitis herpetica (type 1). The clinical and therapeutic data are discussed.


[Indirect hemagglutination test for detection of antibodies to cytomegalovirus in blood collected on blotting paper (author's transl)]. Indirect hemagglutination test for detection of antibodies to cytomegalovirus is highly sensitive and reproducible, if employed in well-defined conditions. Standardization of the various factors involved is necessary as well as their reciprocal equilibrium : sheep erythrocytes, antigen, dilution of tanin, buffers quality. The hemagglutination test can be performed on small volumes such as blood collection on blotting paper (PKU). Antibody titers were compared in the serum and the blood so collected in 104 subjects : the results were very similar and no "false negative" were found in any case. This way of collecting blood and hemagglutination are technical improvements in epidemiologic studies of cytomegalovirus infection. It can be hoped they will be adapted to other group herpes infections.


Polygraphic studies of normal infants during the first six months of life. I. Heart rate and variability as a function of state. This study examined spontaneous heart rate (HR) and variability as a function of age and sleep state in eight normal full term infants from birth to 6 months of age. Heart rates recorded during sleep were lower and less regular at 1 week (quiet sleep (QS) mean rate= 128, interquartile range = 6.4 beats/min; rapid eye movement (REM) = 134.5, 11.6) than at 1 month (QS = 138.6, 3.4; REM 139.6, 4.2). Rate  decreased sharply from 1 to 3 months (QS = 118; REM 123.8) and decreased only slightly therafter (6-month QS = 113.5; REM 118.9). Variability decreased rapidly in REM from 2 to 4 months (from 11.4 to 9.1) and less quickly from 4 to 6 months (from 9.1 to 8.2), while QS variability decreased at 1 month (from 6.4 to 5.7) and became stable from that point (6.0 at 6 months). Waking heart rate and variability were both relatively low at 1 week (163, 11.2 beats/min) and increased from that age to 1 month (167.4, 14.3). Rate decreased rapidly in waking at 3 months (152 beats/min) and more slowly therafter (152 beats/min at 4 months, 149 beats/min at 6 months), whereas variability remained elevated until after 3 months, becoming stable at a lower level during later infancy (3 months = 14.8,6 months 11.7). Lowest values of rate and variability were found in QS and the highest values were found in waking at all ages, except at 1 week. Heart rates during REM closely approximated those in QS, whereas variability values more closely resembled those of waking.


Antibody to Varicella-Zoster virus in parturient women and their offspring during the first year of life. A nursery outbreak of varicella is reported. Serum from 200 parturient women and 131 of their offspring were studied for antibody to varicella-zoster (V-Z) virus to analyze their immunity to varicella. Antibody titers were measured by the sensitive fluorescent antibody to membrane antigen (FAMA) technique. It was found that approximately 5% to 16% of women of child-bearing age in New York City are susceptible to varicella. Women from Puerto Rico or other subtropical and tropical areas are more likely to be susceptible (16%) than others (5%). Infants born to mothers with detectable V-Z FAMA titers almost always had detectable V-Z antibody at birth. In serial serum specimens obtained from 67 initially seropositive babies during the first year of life, it was found that by 6 months of age most infants were no longer passively protected against varicella. These observations may explain why varicella is not uncommonly observed in young babies.


Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. 1. Mainpulation of inspiratory and expiratory-inspiratory neurons. The property of the neuronal membrane to be permeable to metabolic modifiers of two regulatory enzymes has been utilized to manipulate the spike activity of inspiratory (I) and expiratory-inspiratory (EI) neurons of the bulbar respiratory centre. The neurons have been classified according to their response to lung distention or collapse (alpha- or beta-type) and to hyperventilation (tonic firing denoted by "+", cessation of activity by "-"). Using extracellular microelectrodes for single unit recording, the medulla oblongata was superfused with a metabolite-containing CSF. The various neuronal sub-types exhibited a differential activating or inhibitory response to one or several metabolic effectors. For example Ialpha+ units were activated by 5 mM glucose-6-phosphatase (G-6-P) and 3.5 mM 3-phosphoglycerate (3-PGA), which both inhibited Ibeta+ neurons, while 5 mM AMP inhibited Ialpha+ much more strongly than Ibeta+ cells. The spike density of Ialpha- and Ibeta- neurons was increased in the presence of 2.5 mM fructose-6-phosphate and 3.5--5 mM AMP, but became reduced by G-6-P. In contrast, 3 mM fructose-1,6-diphosphate and 5 mM 3-PGA activated the Ialpha- but inhibited the Ibeta- neurons. The EIbeta units were characteristically activated by 10 mM citrate, which inhibited all I-type neurons. Activations of the Ialpha and Ibeta neurons led to an accelerated respiratory rate and a higher tidal volume, while the opposite was true for EIbeta neurons. Intravenous injection of metabolites could not duplicate the striking effects under local applications.


Metabolic control of respiratory neuronal activity and the accompanying changey-expiratory neurons. Expiratory-related neurons have been classified according to their phase relation within the respiratory cycle, their response to lung distension and collapse (alpha- and beta-type), and to hyperventilation (tonic firing denoted by "+", cessation of activity by "-"). The dorsal surface of the medulla oblongata was superfused with a metabolite-containing CSF solution and the activity of expiratory (E) and inspiratory-expiratory (IE) neurons was extracellulary recorded. The neuronal sub-types established by their functional behaviour could equally be distinguished by their differential response to one or several metabolites. In contrast to inspiratory (I) neurons, Ealpha- Ebeta-, Ebeta- and IEbeta- neurons are inhibited by 3.5 mM AMP, but are activated by 10 mM citrate (with the exception of Ebeta+ units). Furthermore I cells are activated by ATP, while Ealpha and Ebeta units become inhibited. Vagotomy in some instances affected the response of some IEbeta units. An increase in spike density of IEbeta+ and Ealpha- cells is paralleled by a reduction of both the respiratory rate and the tidal volume, while a lower spike density in IEbeta+, IEbeta- and Ealpha- units is accompanied by increases in respiratory rate and tidal volume. In the case of Ebeta+ and Ebeta- cells lower activity is associated with an increased tidal volume. No metabolite-induced changes could be obtained with cardiovascular or unspecific reticular neurons.


Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. III. Phase shifts in respiratory neurons induced by inflation and collapse of the lung, hyperventilation, or metabolic modifiers. Phase shifts between inspiratory-related and expiratory-related discharge patterns can be reversibly induced in respiratory neurons following volume changes of the lung, hypocapnic apnea as a result of hyperventilation, or superfusion with certain metabolic modifiers. Phase-spanning expiratory-inspiratory or inspiratory-expiratory discharges are frequently induced in those neurons which are activated either by pulmonary stretch receptors or collapse afferents. The same is true for regulatory effectors which activate key steps of the neuronal metabolism such as ADP, 3-phosphoglycerate, L-glutamine, fructose-6-phosphate and fructose-1,6-diphosphate. In contrast, inhibitory vagal inputs or superfusion with citrate, an inhibitory metabolic modifier, revert preexisting expiratory-inspiratory discharges into a phase-coupled inspiratory pattern. It is postulated that the respiratory neuronal networks represents a time-optimal control system which strives to adjust to a new equilibrium value in a minimum of time, following a given mechanical or chemical perturbation. Following the hypothesis advanced by Cohen (1974) that the phase-spanning units modulate the activity of the in-phase neurons, it is suggested that the additional recruitment of expiratory-inspiratory and inspiratory-expiratory units provides a measure of the quality of time-optimal control and hence a performance index of the system.


Junctional and extrajunctional acetylcholine receptors in normal and denervated frog muscle fibres. Noise analysis experiments with different agonists. Ionic channel properties of acetylcholine receptors located in, in the vicinity of, or far away from a frog neuromuscular junction were investigated by noise analysis of drug induced current fluctuations. For drugs applied to the junction, in certain cases two Lorentzian curves were necessary to describe the data. It is postulated that the reason for this observation is that a contribution from perijunctional receptors was being observed. The conductance of a single channel in the junction was independent of the nature of the agonist and had an average value of 17.9 pS (temperature range 8-25 degrees C, solution buffered with Tris). After denervation for 21 days the conductance gamma was 7.5 pS at extrajunctional locations. In the close neighbourhood of the junction (peri-junctional receptors) values were found between 4 and 19 pS. The mean value of the open channel life-time tau in the endplate exposed to acetylcholine was 2.4 ms at 8-11 degrees C. This value was 0.90 ms with carbachol, 0.50 ms with succinylcholine, 0.28 ms with decamethonium and 0.45 ms with nicotine. The receptors outside the endplate exhibited tau-values which at a given temperature were 2-3 times larger than those at the endplate. Raising the temperature to 23 degrees C reduced all tau-values by factors of 2-3. It is concluded that at least two types of ACh-receptors with different properties exist in the muscle membrane, possibly produced by ACh-receptive units in different states of aggregation.


A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia. The diffusional water permeabilities of collecting ducts in the presence and absence of antidiuretic hormone have been measured in isolated papillae from normal, hypokalaemic and hypercalcaemic rats. In a similar in vitro situation the effect of antidiuretic hormone on the papillary content of cyclic AMP has been measured. The diffusional water permeability of collecting ducts in the absence of antidiuretic hormone did not differ significantly in papillae taken from the different groups of rats. The diffusional water permeability in the presence of ADH was 7.4 +/- 0.2 (S.E.M.) mum s-1 in collecting ducts taken from normal rats. In collecting ducts taken from hypokalaemic or hypercalcaemic rats the corresponding values were 5.9 +/- 0.3 and 5.8 +/- 0.5 mum s-1 respectively. This significant decrease (P less than 0.01) in the response to antidiuretic hormone would shift the point at which distal tubule fluid first attains isotonicity with the interstitium. If this shifts from cortex to medulla a greater amount of water enters the interstitium of the medulla and produces an impairment of maximal urinary concentrating ability and this defect could explain most of the observed results in hypokalaemic and hypercalcaemic. Cyclic AMP content of the tissue after the addition of ADH was reduced in papillae taken from hypokalaemic rats. This reduced activation of adenyl cyclase could be the mechanism responsible for the impaired response in water permeability but it is also possible that there is interference, with the chain of reactions mediating permeability changes, at a separate site.


The effect of lithium on the permeability response induced in the collecting duct by antidiuretic hormone. The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.


Persistance of intramuscular deposits of vitamin D3 in slaughter pigs. In pigs given injections of 1.5 mill IU vitamin D3 in oil intramuscularly 9, 5 or 3 weeks before slaughter residues in the depots were very high (table 1). Certain cuts of pork from pigs treated in this way should therefore be regarded as unacceptably polluted. Furthermore the practise of using oily vitamin D preparations for injection in veterinary medicine appears to be unjustified in modern husbandry.


[Meningo-radiculitis following tick bite]. The authors report nine cases of acute inflammatory polyradiculoneuritis developing one to eleven weeks after a tick bite, regressive, painful and asymmetrical, with an albumino-cellular reaction in the CSF. They stress the very particular physiognomy of this type of meningo-radiculitis, its seasonal occurrence and the uncertain nature of its pathogenesis.


[Gastrointestinal amyloidosis].

[Gastrointestinal amyloidosis]. A series of 29 cases of amyloidosis of the alimentary tract is reported. Five cases (17%) were primary amyloidosis; 14 cases (48%) were amyloidosis secondary to other diseases (such as chronic inflammatory and neoplastic diseases); 10 cases (35%) were amyloidosis of the heredo-familial type connected with Familial Mediterranean Fever. In 23 patients (79%) the diagnosis was established by biopsies, and in 6 more cases on autopsy. Gastrointestinal involvement was found in all age groups. Gastro-enterologic complications observed in the present series include: diarrhea, malabsorption, ileus and gastrointestinal bleeding. In addition other conditions such as jaundice (3 cases), esophagitis and acute hemorrhagic pancreatitis were observed. In 22 patients proteinuria was observed and in 13 patients the nephrotic syndrome. Among 17 patients, in 11 the clinical picture before death was that of terminal renal failure. The survival after diagnosis among 14 patients reached 4 years in 9 cases, and 19 years in one case. The diagnostic value of the rectal biopsy is emphasized.


[Adrenal insufficiencies caused by isolated corticotropic deficiency. 2 cases]. Isolated adrenocorticotropin deficiencies are rare. Two cases are reported, one, with hypoglycaemia, the other with weakness and hypotension, with a review of the published cases during the past twenty years. The adrenal defect impairs severely the glucocorticoid secretion while aldosteron is normal. Tetracosactid stimulates adrenal secretion. ACTH activity measurable in serum is very low and not affected by metyrapone. Other pituitary secretions are normal. The hypothalamic or pituitary level of the defect will be situated when CRH test available.


[Low thyrotrope hormone: a new entity].

[Low thyrotrope hormone: a new entity]. The combination of the TRH stimulation of TSH release with the plasma iodide (PII) increase test, which gives a physiological measure of TSH basal activity, allows characterization of a syndrome we have called a low pituitary TSH reserve. These patients were euthyroid, had a normal PII increase test but a mild or no response to TRH. It was chiefly found in acromegaly and diabetes mellitus, after prolonged high levels of thyroid hormones or hypophysectomy. It appears to be a transient state between normal and abnormal thyrotropin function. So the absence of TSH increase after TRH injection can be of diagnostic value only when other tests of thyrotropin function are performed.


[Bronchiolo-alveolar cancer].

[Bronchiolo-alveolar cancer]. The bronchiolo-alveolar adenocarcinoma, less frequent than other types of bronchopulmonary cancers, occurs more frequently during pulmonary fibrosis. Besides a mucous bronchorrhea of little meaning, the clinical manifestations belong to the advanced stages. The X-ray, unreliable and variable, shows a variety of pictures from mono or multinodular ones to pseudopneumonic infiltrates. Usually no information could be derived from bronchoscopy. Positive cytological examination of sputum are unfrequent. Early surgery brings longer remissions than in other types of bronchopulmonary cancer. Diagnosis can only be made from the histology of the exeresis sample. The tumour cells, cuboidal or columnar, are arranged in mono or pluri-stratified layers in the inter-alveolar septa, which progressively become fibrous. This cancer has an original histogenesis: it would originate from the neoplastic metaplasia of type II pneumocytes or of respiratory bronchiole cells, invading the pulmonary alveoli by sliding or by contiguity. Far from the initial foyer, the spreading seems mostly done through airways.


Modification of 6-aminopenicillanic acid derivatives. In order to prepare intermediate for further transformation of penicillins), and to obtain new derivatives with enlarged spectrum of biological activity some semi-synthetic phenoxyalkanepenicillins were subjected to the esterification, amidation and hydroxyamidation reactions. Hydroxyamidation i.e. synthesis of corresponding penicilline-hydroxamic acids was a complex reaction depending on the structure of hydroxylamine used. The two-directional reaction course, with beta-lactam bond splitting, was specific for unsubstituted hydroxylamine only. A number of new penicilline hydroxamic acids and N-methoxypenicilline amides, with intact and cleaved beta-lactam ring were synthesized.


Coherent anti-Stokes Raman scattering (CARS) spectra, with resonance enhancement, of cytochrome c and vitamin B12 in dilute aqueous solution. Coherent anti-Stokes Raman scattering (CARS) spectra have been obtained for ferrocytochrome c and cyano cobalamin in aqueous solution at millimolar concentrations, using a pair of tunable dye lasers pumped by a pulsed nitrogen laser. Resonance enhancement was obtained by tuning the omega1 laser to the visible absorption bands of the samples. The spectral features correspond to those observed in the conventional resonance Raman spectra. It appears that CARS spectroscopy, with its advantageous fluorescence rejection, can be usefully applied to biological samples by exploiting resonance enhancement. While the background scattering from water is 10 times higher than that of benzene and other aromatic solvents, it is actually at the low end of the scale for most liquids. The anomalously low background of aromatic liquids is thought to result from competition by the unusually efficient stimulated Raman scattering which they display. Off-resonance spectra for both cobalamin and cytochrome c contain negative peaks, i.e., absorption bands in the background. These are interpreted as inverse Raman processes induced by the omega1 photons in the presence of the continuum provided by the background scattering. While both CARS and the inverse Raman effect are subject to resonance enhancement, the wavelength dependence of CARS is evidently steeper.


Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process. We have previously demonstrated with radioimmunoassay techniques that physiologic concentrations of thyroid hormone stimulate an increase in growth hormone production in GH1 cells in culture. In this study, with radiolabel techniques and selective immunoprecipitation, we demonstrate that L-triiodothyronine stimulates growth hormonw production solely by inducing an increase in the de novo synthesis of the polypeptide hormone. L-Triiodothyronine stimulated synthetic rates of growth hormone by 1.5-fold in 1.25 hr, 2-fold in 2.5 hr, to a maximal of 3- to 4-fold after 8.5 hr of incubation. The time interval between significant L-triiodothyronine binding to putative nuclear receptors and a detectable increase in growth hormone synthesis was 45-60 min. Studies on the effect of actinomycin D, 3'-deoxyadenosine, and cycloheximide support the thesis that L-triiodothyronine induces the accumulation of an RNA species which is rate limiting for growth hormone synthesis and lends further support for a primary action of thyroid hormone at the nuclear level.


Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes. Nitrofurans, a class of antibacterial drugs in extensive use, interferes with gene expression in a highly specific manner. While in the low dose range (0.5-25 mug/ml), 5-nitro-2-furfurylidene-1-aminohydantoin has no effect on transcription, it inhibits specifically the expression of one class of genes in translation. The specific inhibition concerns the inducible genes. The inhibition of messenger RNA expression occurs at the initiation step. The action of nitrofurans, thus, indicates heterogeneity in the population of mRNA molecules and in the translational machinery and suggests the possibility of selective translational control.


Novel structure at 5'-ends of nascent DNA chains. Because of their association with protein short nascent DNA chains in Escherichia coli can be separated from other cellular DNA by chromatography on hydroxylapatite. Protein-free DNA chains of less than 500 nucleotides in length are resistant to degradation from the 5'-end by alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] and spleen phosphodiesterase (oligonucleate 3'-nucleotidohydrolase; EC 3.1.4.18). In contrast, DNA chains containing more than 500 nucleotides are degradable. From these results we conclude that short nascent DNA chains are structurally modified at their 5'-ends. The nature of this structure and its possible functions are discussed.


ATP-PPi exchange activity of progesterone receptor. Progesterone receptor preparations from avian oviduct catalyze a pyrophosphate (PPi)-exchange reaction between ATP and 32P-labeled PPi. The reaction requires ATP exclusively and is Mn++-dependent. This enzyme activity is detectable in receptor preparations that have been purified extensively by chromatography on ATP-Sepharose and DEAE-Sephadex columns. Polyacrylamide gel electrophoresis of purified preparations reveals a comigration of [3H]progesterone-receptor complex and the enzyme activity. The PPi-exchange reaction is inhibited by both o-phenanthroline and rifamycin AF/013, which also block the nuclear binding of progesterone receptor. These findings indicate that progesterone receptor may be an enzyme or a subunit of an enzyme that is active in nucleotide metabolism.


Differential synthesis of blocked and unblocked 5'-termini in reovirus mRNA: effect of pyrophosphate and pyrophosphatase. Viral mRNA synthesized in vitro by reovirusassociated enzymes contained 5'-terminal ppG, GpppG, or m7GpppGm. Selective synthesis of one type of 5'-end was obtained by adjusting the composition of the transcription reaction mixture based on a series of reactions proposed for formation of blocked, methylated 5'-terminal sequences of mRNA (capformation). The presence of inorganic pyrophosphate increased the proportion of ppG 5'-ends, while addition of pyrophosphatase yielded mRNA with 5'-terminal GpppG, which in the presence of a methyl donor was converted to m7GpppGm.


In vitro replication of simian virus 40 DNA in a nucleoprotein complex. A simian virus 40 (SV40) nucleoprotein complex, extracted from nuclei isolated from a monkey cell line infected with SV40, continued DNA replication in the presence of a nuclear extract, cytosol, ATP, and ATP-regenerating system, and the four deoxyribonucleoside triphosphates. The DNA products of replication were also found as nucleoprotein complexes. Forty percent of the replicating viral DNA, labeled in vivo, was converted into covalently closed, superhelical DNA during incubation in vitro. Although the remaining labeled DNA was not converted into mature viral DNA, it was elongated to its full genome length. Failure to terminate replication successfully was not caused by endonuclease activity, since covalently closed DNA, labeled in vivo, was not damaged during incubation in vitro. When [alpha-32P]dATP was present during the incubation, the label appeared first in replicating DNA and later in mature DNA; no unusual products were labeled in vitro. The covalently closed SV40 DNA made in vitro had the same superhelical density as viral DNA made in vivo. These data demonstrate that viral nucleoprotein complexes ("minichromosomes") are able to continue DNA replication outside of the nucleus.


Catabolite modulator factor: a possible mediator of catabolite repression in bacteria. Water soluble extracts of Escherichia coli cells have been found to exert an extremely strong repressive effect upon the expression of catabolite sensitive operons. The compound responsible for this activity has been partially purified and proves to be of low molecular weight and heat stable. The effect of this compound, hereafter designated as catabolite modulator factor, is only partially antagonized by adenosine 3':5'-cyclic monophosphate. The possible role of catabolite modulator factor in the physiological regulation of catabolite repression is discussed.


V irus and lectin agglutination of erythrocytes: spin label study of membrane lipid-protein interactions. Techniques of spin-label electron spin resonance have been used to prove changes in the structure of the lipid phase of erythrocyte membrane after agglutination by viruses and lectins. When chicken erythrocytes are agglutinated by Sendai and influenza viruses and by the lectins concanavalin A and wheat germ agglutinin, the membrane lipid phase becomes more fluid, as detected by three different lipophilic spin-laveled probes. Colchicine, vinblastine, and tetracaine inhibit the fluidization of chicken erythrocyte membrane by Sendai virus, whereas cytochalasin B has no effect. The effect of colchicine was time dependent, the initial inhibition decreasing with longer preincubation times. Extensive treatment of erythrocytes with proteases or neuraminidase, while not altering the bilayer structure, abolishes the effect of Sendai virus on the erythrocyte membrane, suggesting that a change in the interaction of the receptor protein with the lipid phase occurs upon virus attachment. Glutaraldehyde fixation increased the structural rigidity of the chicken erythrocyte membrane and inhibited the effect of viral agglutination. No change in bilayer structure was observed upon agglutination of human erythrocytes or the isolated plasma membranes of either human or chicken erythrocytes. This result is consistent with the drug sensitivity of the effects of agglutination upon chicken erythrocytes, since human erythrocytes and isolated membranes lack microtubule-like structures.


An approach to the targeted attachment of peptides and proteins to solid supports. A novel approach to affinity columns is described that is based on the high avidity of biotinylated molecules for avidin attached to solid supports. Biocytin amide [Nepsilon-(+)-biotinyllysine amide] was coupled to the COOH-terminal carboxyl group of corticotropin(1-24) [ACTH(1-24)] to form [biocytin25]ACTH(1-25) amide. The ability of this peptide to stimulate steroidogenesis of bovine adrenocortical cells was within experimental error identical to that of ACTH(1-24). The peptide also binds to avidin and avidin-Sepharose, forming stable complexes. Thus, with biotin as the anchor, the adrenocorticotropically active segment of the ACTH molecule was attached to a solid support in a targeted manner. The general applicability of this principle for the attachment of peptides and proteins to solid supports is discussed.


Partial purification and characterization of the mRNA for rat preproinsulin. Electrophoretically homogeneous messenger RNA for rat preproinsulin has been prepared from an islet cell tumor by the use of oligo(dT(-cellulose chromatography and sucrose density gradient centrifugation. The molecular weight of the mRNA is about 210,000, as determined by polyacrylamide gel electrophoresis in formamide, and its sedimentation coefficient is 9.3 S in sucrose gradients containing 0.2 M NaCl. These results indicate that the synthesis of preproinsulin is directed by a monocistronic mRNA 600 nucleotides in length and requires approximately 55% of the molecule's coding capacity.


On the specificity of synapse formation. Clonal neuroblastome X glioma hybrid cells form synapses with striated muscle cells from different muscles and from different organisms, such as chick, mouse, and rat. Under appropriate conditions 65-80% of the muscle cells exhibited synaptic responses. The results indicate that most striated muscle cells have the same specificity for synapse formation and suggest that synaptogenesis is not dependent on interactions between complementary molecules on neuron and muscle cells that code for different synaptic connections.


Reversion from transformed to normal phenotype by inhibition of protein synthesis in rat kidney cells infected with a temperature-sensitive mutant of Rous sarcoma virus. By the use of a rat kidney cell line infected with a temperature-sensitive Rous sarcoma virus, we have shown that, at permissive temperatures where the cells are transformed, concanavalin A induces a clustering of its cell membrane receptors into patches, and the intracellular smooth muscle myosin-like protein is in a disordered state. By contrast, with infected cells grown at nonpermissive temperatures, the addition of concanavalin A does not alter the uniform distribution of its receptors, and the smooth muscle myosin-like protein is arranged in an ordered filamentous structure. These results are consistent with the hypothesis that the myosin protein is part of an intracellular aggregating-disaggregating complex. In the normal cell it is in its aggregated state and inhibits the lateral mobility of the concanavalin A receptors in the membrane; in the transformed cell the complex is relatively disaggregated and permits the concanavalin A receptors to be mobile. The addition of protein synthesis inhibitors to infected cells grown at the permissive temperature causes the cell to change from the transformed phenotype to the normal. Removal of the reversible inhibitors causes the cells to revert to the transformed phenotype. These results show that (i) protein synthesis, presumably of an unstable product of the transforming gene of the temperature-sensitive virus, is required to maintain the transformed state in these infected cells at the permissive temperature; and (ii) protein synthesis is not required for the intracellular myosin-containing complex to revert from its disordered transformed state to its ordered normal state. This suggests that the product of the transforming gene directly or indirectly causes the disaggregation of the myosin-containing complex in the process of transformation.


Rous-sarcoma-virus-transformed fibroblasts having low levels of plasminogen activator. Several clones of transformed chick embryo fibroblasts infected with wild-type B77-C or Prague-C strain of Rous sarcoma virus have been isolated from soft agar suspension. These clones were screened for plasminogen activator activity by overlaying monolayer cultures with medium containing agar, casein, and chicken plasminogen. Twenty-three percent of all of the isolated clones showed little caseinolytic activity, 42% had intermediate activity, and 35% had high activity. Although the clones with low plasminogen activator activity had no more than twice the activity shown by uninfected fibroblasts, they did not differ significantly from clones possessing high levels of plasminogen activator in their morphology, 2-deoxyglucose transport, or efficiency of colony formation in soft-agar.


Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus. Complementary DNA (cDNA) synthesized by Moloney murine sarcoma virus (M-MSV) was separated into two parts, the first, termed MSV-specific cDNA, composed of nucleotide sequences found only in M-MSV viral RNA, and the second, termed MSV-MuLV common cDNA, composed of nucleotide sequences that were found in both M-MSV and murine leukemia virus (MuLV) VIRAL RNAs. RNA complementary to the MSV-specific cDNA was not found in several other MSV isolates, nor in ecotropic MuLV, mouse mammary tumor virus, or several murine xenotropic oncoviruses. Cellular DNA of several species was examined for the presence of nucleotide sequences complementary to MSV-specific cDNA. Cells transformed by M-MSV did contain MSV-specific cDNA in their DNA. Normal mouse cell DNA apparently contained the majority of MSV-specific nucleotide sequences. Cellular DNA of related species contained proportionally less MSV-specific cDNA. Hybrids of MSV-spedivic cDNA and cellular DNA of related species melted at lower temperatures than hybrids of MSV-specific cDNA and mouse cellular DNA. RNA from normal mouse adult or embryonic cells did not contain detectable nucleotide sequences complementary to MSV-specific cDNA. Transformation of cells with M-msv resulted in transcription of RNA hybridizing with MSV-specific cDNA. Methylcholanthrene-induced mouse sarcomas and cell lines derived from them did not contain RNA complementary to MSV-specific cDNA. Mouse cell lines transformed with avian sarcoma virus or Kirsten MSV-specific cDNA. RNA homologous to MSV-specific nucleotide sequences is measurably present only in cells transformed by M-MSV and not in cells transformed by other biological or chemical agents that also cause sarcomas.


Cellular cholesterol ester accumulation induced by free cholesterol-rich lipid dispersions. The influence of lipoprotein composition on free cholesterol (RC) esterification and accumulation of esterified cholesterol (EC) was studied in cells of Fu5AH rat hepatoma exposed to culture media supplemented with (FC/P) ranging from 0.6 to 2.8. In the presence of normal human serum, FC-lecithin dispersions witb a FC/P greater than one stimulated both the esterification of FC and the accumulation of cellular EC. Conversely, dispersions with FC/P values of approximately one had no effect on either FC esterification or the accumulation of EC when compared to cells grown in the absence of lipid dispersions. No stimulation of cellular response was obtained when FC-rich dispersions were added to cells in the absence of serum; however, stimulation was observed when cells were exposed to isolated human serum lipoproteins (very low density, low density, and high density). With each lipoprotein, FC-lecithin dispersions with FC/P values less than one inhibited cholesteryl ester accumulation, FC-rich dispersions stimulated, and dispersions with FC/P values of approximately one had an effect equivalent to that of isolated lipproteins alone. These studies extablish that cellular FC esterification and EC content are not influenced solely by the FC concentration of medium, but rather respond to the ratio of FC to phospholipidl These studies also suggest that serum lipoproteins participate in the transfer of FC carried by FC-rich lecithin dispersions to cells.


C-type virus particle formation in erythroblastic islands in spleens of C3Hf mice injected with erythropoietin. Previous studies suggested a possible association between C-type virus particle formation and erythropoiesis. In this experiment, normal C3Hf mice were injected with erythropoietin in order to increase the rate of erythropoiesis. Sections of spleen from these animals revealed extensive areas of erythroblasts. C-type particles, budding from erythroblasts, were often observed in such areas of spleen from every mouse injected with erythropoietin. In contrast, in sections of spleen from control mice, zones of erythropoiesis were limited, and only a few scattered C-type virus particles were observed in some of the animals examined.


Replication of murine leukemia virus in bone marrow-derived lymphocytes. Murine lymphoid cells were infected in vitro with WN 1802 B, a naturally occurring murine leukemia virus isolated from the spleen of an 18-month-old BALB/c mouse. Normal spleen and bone marrow cells were more susceptible to infection than were cells prepared from thymus and lymph node. Spleen cells from athymic nu/nu mice also could be readily infected with virus. Permissive cells did not ingest iron readily infected with virus. Permissive cells did not ingest iron filings and did not adhere to plastic. Exogenous replication of murine leukemia virus was enhanced in spleen and lymph node cells treated with lipopolysaccharide, a bone marrow-derived lymphocyte mitogen. Conversely, cells treated with the thymus-derived lymphocyte cell mitogens, phytohemagglutinin and concanavalin A, were less capable of supporting murine leukemia virus replication. These studies suggest that the natural host for WN 1802 B is the bone marrow-derived lymphocyte.


Opiate receptor: autoradiographic localization in rat brain. Opiate receptor sites in rat brain can be labeled in vivo by [3H]diprenorphine, a potent opiate antagoinst. Using techniques to minimize diffusion in fresh, frozen, unfixed brain, we have localized [3H]diprenorphine by autoradiography to visualize the distribution of opiate receptors. Silver grains indicative of the binding of labeled [3H]diprenorphine are discretely localized in numerous areas of the brain with very high densities in the locus coeruleus, the substantia gelatinosa of the spinal cord, and in clusters within the caudate-putamen, amygdala, and parts of the periventricular gray matter.


Neurobiological Considerations of the mode of action of lithium carbonate in the treatment of affective disorders? The effects of lithium on membrane function and cellular processes are considered in relation to lithium's physiochemical properties. Several cellular regulatory functions, including cyclic AMP formation and metabolism and biogenic amine neurotransmitter metabolism, are examined as possible mechanisms whereby lithium might exert its mood stabilizing actions. The necessity for understanding lithium's interactions with "receptors" - the molecular sites affected by lithium - in considering its pre-and post-synapatic effects in stressed.


Role of cyclic nucleotides in cell growth and differentiation. A simple model is depicted below that suggests some unifying principals in the action of cyclic nucleotides in the GO-to-G+ interconversion, differentiation, and transformation (see article). The letters with G+ subscripts (AG+ through EG+) represent cell states at different increasing levels of "determination" (see sect. vE). Cells in each of these states are continuously reproducing themselves through cell division (i.e., they are in G+). As an alternative to cell reporduction, cells at each level may move toward or enter GO, which is conceived of not only as a quiescent state but also as a state in which differentiated properties are more fully expressed. This state is designated by letters with GO subscripts (AGO through EGO). Entrance into this more expressed state will usually be reversible (nerve cells and red blood cells are two exceptions). Sometimes movement toward GO and full expression may require a number of cell divisions. Ultimately, however, there usually will be a slowing or cessation of cell division. The transformed state, according to this model, is one in which cells have lost the ability to enter the "expressed" CO state. However, they do remain differentiated in the sense that they have maintained their level of determination and can be induced to enter into the expressed state, as for example in the case of DBcAMP treatment of transformed fibroblasts. In most cases, cAMP appears to stimulate cells to proceed toward XGO (where X = A,B,C,D, or E) and toward fuller expression of their differentiated functions. It is not the sole mediator of this transition. In cell types where cAMP plays this role, transformation may arise through a defect in the ability to raise cAMP levels in response to growth-regulatory signals or in a defect in the cell's ability to respond to cAMP. In other cell types, cAMP may not be involved in the CO-to-C+ transition or may act in the opposite direction (see sect. II). It remains to be seen whether these situations are ture exceptions or whether different loci of regulation are involved. For example it is possible that in certain cases where cAMP has been shown to stimulate growth that it is stimulating growth toward a more expressed state. Other actions of cAMP relating to cell-cycle traverse have been discussed (sect. III). Investigations of the action of cGMP are still at a preliminary stage of development. There is evidence consistent with the idea that cGMP mediates conversion toward the G+ state in some cell types (see sect. II) under certain conditions. However, further studies are required to establish this as a fact. There has been little or no reported evidence relating to a role for cGMP in expression of differentiated properties, nor has there been any significant evidence as yet for other cell-cycle roles of cGMP. It should be apparent that the areas of biology covered in this review are only beginning to evolve biochemically...


Aspects of smooth muscle function in molluscan catch muscle. 1) Catch in Mytilus ABRM may be a specialization of a mechanism common to all muscles that gives rise to stretch resistance in the resting state. Catch appears to be due to actin myosin interaction. Since this interaction is regulated by nerves, it provides a convenient model for studying resting stretch resistance. 2) Studies of the structure of Mytilus ABRM revela two types of intercellular connections: a) direct connections between muscle fibers [these nexal (gap) junctions interconnect the muscle cells electrically]; b) muscle fiber-collagen-muscle fiber connections [these provide mechanical connections between muscle cells via collagen fibers]. The structure of Mytilus ABRM supports speculation that smooth muscle filaments are organized into contractile units. 3) A rise in cAMP levels occurs in response to the relaxing transmitter, serotonin. It is not certain whether the cAMP system directly controls the ability of the contractile proteins to interact or whether it regulates intracellular levels of Ca2+. 4) Calcium ions in activation are derived from two sources: an internal source, probably the sarcoplasmic reticulum, and an external source, across the muscle membrane. 5) The nature of catch remains in question, although most evidence favors the linkage hypothesis.


The effect of ACTH and diazepam on the uptake of tritiated uridine into brain, muscles and liver of infant rats. In 2-day-old rats, ACTH increases the uptake of 3H-uridine in the brain; no such effects were observed in the msucle and liver tissue. Diazepam does not affect the uptake of 3H-uridine into the brain tissue, but decreases the uptake into the muscle tissue. In the brain tissue of infant rats, ACTH does not change the distribution of radioactivity of intraperitoneally administered 3H-uridine among U, Urd, UMP, UDP and UTP. Diazepam increases the amount of radioactivity, found at the U spot. In the muscle, both ACTH and Diazepam increases the amount of radioactivities found in the Urd spot. A significant correlation between the radioactivity of UMP+UDP+UTP and the specific activity of RNA was proved only in the brain. The ratio: specific activity of brain RNA/radioactivity of UMP+UDP+UTP was thus used as a tentative indicator of the biosynthesis of brain RNA. Neither ACTH nor diazepam altered this ratio in infant rats.


Interaction of histones with human serum proteins. The authors describe the interactions of whole calf thymus histone and its fractions with the human serum proteins. Immunoelectrophoretic analysis revealed two types of interactions: 1) a decrease in the electrophoretic mobility of a whole, immunochemically uniform fraction, and 2) a decrease in the electrophoretic mobility of only some molecules of such a fraction. In this association, the arginine-rich histone fraction (F3) was found to be the most active. The findings are important for interpreting the results of biological treatments.


An operation for syndactyly, and its results. We describe our method of operation for syndactyly repair and our results in 62 patients (74 hands, 143 commissures), all treated more than two years ago. The operation was performed on patients aged from 17 months to two years (except those with acrosyndactyly). Postoperative web formation was not seen in any of these patients.


Small-cell carcinoma of the lung. Cytological, roentgenologic, and clinical findings in a consecutive series diagnosed by fine-needle aspiration biopsy. Small-cell anaplastic carcinoma was diagnosed cytologically in 54 of 2,726 consecutive transthoracic fine-needle aspiration biopsies. Histological material was available in 31 cases (28 anaplastic small-cell carcinomas, 1 carcinoid tumor, 1 adenocarcinoma, and 1 reticulum-cell sarcoma). Fine-needle aspiration cytology is reliable enough to permit a definite diagnosis of small-cell carcinoma, especially when combined with the roentgenograms and clinical findings.


Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man. The accuracy of the scintigraphic diagnosis of acute myocardial infarction with 99mTc-pyrophosphate, 99mTc-tetracycline and 99mTc-glucoheptonate was assessed in 63 patients, 43 of whom had clinical evidence of acute myocardial infarction. In 15, studies with both 99mTc-tetracycline and 99mTc-pyrophosphate were performed. Accuracy was greatest with 99mTc-pyrophosphate (17/17 true positives, 8/10 true negatives) contrasted with 99mTc-tetracycline (12/25 true positives, 6/11 true negatives) and 99mTc-glucoheptonate (3/13 true positives, 2/2 true negatives). 99mTc-pyrophosphate was the most sensitive tracer for the detection of acute myocardial infarction. The diagnostic accuracy with 99mTc-glucoheptonate was poor.


AG 60.99: A promising contrast agent for computed tomography of the liver and spleen. AG 60.99, an emulsion of poppy-seed oil, is proposed as a promising organ-specific agent for computed tomography (CT) of the liver and spleen. This agent not only opacifies the hepatic parenchyma enough to enhance visualization of the bile ducts but also demonstrates the vascular anatomy with smaller doses than those required for conventional studies.


Angiographic features of malignant fibrous histiocytomas. The angiographic findings in 2 cases of metastatic fibrous histiocytoma are discussed. A lesion in the brain was completely avascular and displaced the surrounding vessels, whereas the renal lesions were hypovascular, usually well demarcated, sometimes exhibited beak formation, and demonstrated fine, corkscrew-like tumor vessels with delayed emptying but no tumor blush or early draining veins.


Adhesive arachnoiditis following lumbar radiculography with water-soluble contrast agents. A clinical report with special reference to metrizamide. The frequency of adhesive arachnoiditis following lumbar radiculography with methiodal sodium (95 patients), methylglucamine iocarmate (20 examinations in 18 patients), and metrizamide (77 examinations in 73 patients) was found to be 29% in patients who were not operated on between methiodal studies and 48% in those who were operated on. With both methylglucamine iocarmate and metrizamide the frequency was very low. No changes indicating adhesive arachnoiditis were seen with these media in patients who were not operated on between radiographic examinations.


Radionuclide angiography in evaluation of chemodectomas of the jugular glomus. Clinical, radiographic, and radionuclide angiographic findings of three cases of jugular glomic tumor associated with hearing loss are discussed. In one case computed tomographic findings are discussed. It is concluded that radioisotopic techniques may be useful in diagnosis and follow-up of this tumor.


Observing the growth of Wilms' tumor.

Observing the growth of Wilms' tumor. Four children ranging in age from 2 1/2 months to 4 years had excretory urography initially for reasons other than evaluation of an abdominal mass. Three patients had repeat urography only after masses became apparent at intervals of 8.5 months, 9 months and 15 months after the initial urogram. The fourth patient was followed with interval excretory urography for urinary tract infection and a large renal mass was seen 13 months after the initial urogram. The results suggest that the present data on estimated rates of growth do not support the established theory of the rate of growth for Wilms' tumor.


Enzyme histochemistry of bone and cartilage cells. Initial studies indicated that bone and cartilage, when treated with a hypertonic glutaraldehyde fixative for a short period, retained significant enzyme activity for histochemistry and also maintained excellent fine structure. We used 6% glutaraldehyde in 0.1 M cacodylate buffer, pH = 7.2, 4 degrees C to fix small pieces of bone or cartilage for three hours while the tissues were being constantly agitated. These samples were demineralized in 10% ethylene diamine tetraacetic acid, buffered to pH = 7.2 with 0.1 M Tris HC1, at 4 degrees C. The demineralized tissue was frozen and cryostat sections 32 microns thick were taken for incubation at 37 degrees C in various media for histochemistry. For electron microscopic localization of enzymes a heavy metal capturing method had to be used. For light microscopy, the azo dye methods were frequently used, but these were not usable for electron microscopy. Alkaline phosphatase was found on the outer surface of osteoblast and hypertrophic cartilage cell membranes. The only intracellular enzyme activity was found on the mitochondrial membranes of the osteoclast and only when the pH of the media was lowered from the optimum 9.5 to 8.5. Alkaline phosphatase was not found along the osteocyte or young cartilage cell membranes...


Histochemical characteristics of vertebrate striated muscle: a review. (1) The histochemical staining pattern of succinic dehydrogenase (SDH) does not show unequivocal differentiation between the type I red and type II red fibres in mammalian striated muscles. (2) Since high biochemical activity of beta-hydroxybutyric dehydrogenase (beta-HOBDH) occurs in mitochondria of the type I red fibres, the histochemical localization of this enzyme may show a pattern of staining reciprocal to that seen for myofibrillar ATPase. (3) It remains to be confirmed that the type I red fibres, which are possibly slow-twitch physiologically, possess the highest concentration of myoglobin. The histochemical correlation of myoglobin and myofibrillar ATPase in serial sections should be studied. (4) In order to achieve a more realistic picture, various glycolytic and glycogenolytic enzymes should be incubated according to the gelatin film technique, or semipermeable membrane technique or collagen polypeptide technique. A histochemical correlation of phosphorylase, LDH, PFK, alpha-glycerophosphate dehydrogenase, and myofibrillar ATPase in adjacent muscle sections may throw light on the histochemical characteristics of the different fibre-types. (5) The specific histochemical demonstration of AMPase is achieved following preincubation of tissue sections. (6) ADPase has been demonstrated by the calcium precipitation technique only (GUTH and YELLIN, 1971). A number of studies claim, however, that ADPase is not demonstrable histochemically in muscle fibres. (7) The presence of magnesium ions is a prerequisite for the adequate histochemical demonstration of mitochondrial ATPase. The latter is inhibited almost completely by 40 mM Ca++ (when Mg++ is not added) at both neutral and alkaline pH values. (8) The histochemical activity of SR-AT-Pase seen as continuous reticula but without punctuate and sub-sarcolemmal staining possibly represents the extra ATPase of SR. (9) On the basis of myofibrillar ATPase reaction, an inherent heterogeneity, between the type II red and type II white may be recognized. In addition, the above fibre-types possess their respective sub-populations. (10) Following diK+ EDTA preincubation, some type II red fibres show selective lability. These are the mitochondria-rich fibres. Thus in the total absence of both punctuate and subsarcolemmal staining, the presence of mitochondrial ATPase activity under the histochemical conditions for myofibrillar ATPase is unlikely. (11) The reaction pattern of CK/ATPase (coupled reaction) at pH 6.9 is distinctly intermyofibrillar and unlike SDH-pattern. This reticular reaction is associated mainly with the SR and hence the importance of transphosphorylation in this organelle for the Ca++ uptake and muscle relaxation. (12) The CK/ATPase reaction at pH8.0 has shown important histoenzymatic characteristics. At this pH value the type I red fibres and slow-twitch soleus show myofibrillar reaction pattern. This identical histochemical behaviour suggests that type I red fibres are possibly slow-contracting...


Modification of the Warburg's flask for the study of electric current effect upon the activity of enzymatic systems. Modifications of the Warburg's flask were suggested for the study of the electric current effect upon enzymatic systems under directly stimulation "in vitro" and "in vivo" conditions. The proposed modifications made on the Warburg's flask were basically constituted by the insertion of two platinum and mercury electrodes in the principal reservoir. In order to demonstrate the efficiency and viability of the suggested modification, one experience concerning the effect of the electric current upon the cerebral glutamate decarboxylase activity was shown. The apoenzyme substrate system was activated 1.81 times by the electrical stimulation in absence of the coenzyme. In a similar way the complete system, that is, the apoenzyme-coenzyme-substrate was also stimulated. The physical phenomena seem to be of importance for the understanding of the physiology and biochemistry of the nervous tissue.


Inhibition of the glucose induced insulin release by somatostatin in the isolated perfused rat pancreas. Action of cyclic AMP, glucagon and glibenclamide. Insulin release in the perfused isolated rat pancreas was measured after stimulation with 16.5 mM glucose with and without somatostatin (cycle form, 100 ng/ml) in the medium. A complete blockage of the typical biphasic pattern of insulin release ocurred with somatostatin in the medium. Such blockage was abolished when cAMP (2.5 mM) and a 0.5 ml solution of glucagon (1 mg/ml) were continuously perfused for 20-minute periods and for 30-second periods correspondently. It did not take place when glibenclamide (HB-419) was perfused for a 20-minute period at a rate of 10 mug/ml. The results suggest that the adenylcyclase dependent mechanisms of glucose-induced insulin release are involved in the inhibition of the glucose-induced insulin secretion by somatostatin.


Relationship between losses in cytochrome oxidase activity and peroxidation of monosaturated phosphatidylcholines and phosphatidylethanolamines. Incubation of inner mitochondrial membranes from rat liver in the presence of inducers of peroxidation reactions, such as ascorbate or cysteine, produced a large loss in cytochrome oxidase activity parallel to the disappearance of phosphatidylcholine and phosphatidylethanolamine molecular species, which contained a saturated and an unsaturated fatty acid. The loss in enzyme activity was unrelated to alterations in other species of these phospholipids or other ones. These results may reflect the existence of specific associations within the membrane between cytochrome oxidase and monosaturated phosphatidylcholines and/or phosphatidylethanolamines.


Mitochondrial DNA of Yoshida ascites tumour cells. Physicochemical properties and biological function. Mitochondrial DNA from Yoshida A.H. 130 cells, has been characterized by determination of the buoyant density by CsCl equilibrium density gradient centrifugation and the thermal denaturation and renaturation behaviour. These studies have been carried out parallelly on nuclear DNA from the same cells in order to search for possible differences between both DNAs. Mitochondrial DNA of Yoshida cells presents an equilbrium in CsCl of 1.7154 g/cm3 and a sharp melting with a Tm of 92 degrees C. Nuclear DNA presents an equilibrium of 1.7030 g/cm3 and a Tm of 88 degrees C. The guanine plus cytosine content in both DNAs has been calculated from tumour results and compared with the content in normal rat liver cells M-DNA of tumour cells presents a higher guanine plus cytosine content than N-DNA, whereas in normal liver cells is higher in N-DNA. N-DNAs of both normal and tumour cells have the same guanine plus cytosine content, whereas M-DNA from tumour cells presents a significant increase (about 35%) with regard to this from normal liver cells.


The influence of prolonged ACTH treatment on rat adrenal steroidogenesis. A series of in vitro experiments using pregnenolone-14C-4 and progesterone-14C-4 as precursors were performed to determine the effects of prolonged ACTH administration on adrenal steroid biogenesis in the rat. Under ACTH administration there was a tendency for the isolated steroids to have larger quantities and specific activities from both precursors than under control conditions. In contrast to the rabbit, the rat did not produce any detectable amounts of 17 alpha-hydroxylated steroids under either control or prolonged ACTH treatment using the very sensitive double isotope derivative assay for quantitation.


Systemic stress in the production of cardiac thrombosis in hypercholesterolaemic rats. An experimental study to elucidate the effects of feeding a high fat diet, hypercholesterolaemia and superadded acute and chronic stress on the production of cardiac thrombosis was carried out in rats. The high fat diet contained 25 percent butter rat providing 45 percent calories from fat which produced significant increase of serum cholesterol and other lipids. Acute stress was induced by two injections of adrenaline on a single day which caused a marked transient alteration of haemodynamics. Chronic stress was of two types, physical and metabolic. The physical stress was induced by repeated exposure of the rats to electric shock or roller drum exercise, while metabolic stress was caused by repeated injection of ACTH. Rats of both acute and chronic stress groups showed variable degree of medial degeneration, hyaline and fibrinoid intimal deposits and calcification in coronary arteries. Cardiac thrombi were seen in 30 percent animals subjected to adrenaline shock. Among the chronic stress procedure 17 percent rats exposed to electric shock and only one rat of the ACTH group developed cardiac thrombosis but no thrombus was detected in those exposed to roller drum exercise. The myocardium showed patchy necrosis with or without calcification, Spontaneous mortality was maximum following acute adrenaline shock (25 %) while electric shock caused mortality in 17 percent animals. The other procedures did not lead to spontaneous mortality. This study highlights the significant role of high fat intake, hypercholesterolaemia and systemic stress in the pathogenesis of acute cardiac thrombosis and myocardial necrosis/infarction.


Coenzyme alterations in rats with experimental hypertension. The changes in the content of pyridine nucleotide coenzymes (NAD+ and NADH) in several models of experimentally induced hypertension, differing in mechanism (genetic spontaneous hypertension, renal one kidney Goldblatt hypertension, Adrenal-regeneration hypertension after INGLE-HIGGINS and Skelton, and NaC1 hypertension) were studied. An obvious difference between the changes in NAD+ and NADH in the various models of hypertension, was established: Thus in NaC1 hypertension a high level of the coenzymes in the kidneys and in the vessel wall was found, while the liver coenzyme content was in normal ranges. In ARH the coenzyme level was elevated not only in the kidneys and in the vessel wall, but in the liver as well. Treatment with hypotensive antilipolytic prostaglandin E1 decreased the coenzymes in ARH to normal values. Renal hypertension was characterized by a low content of oxidized NAD, an increased NADH, and a decreased NAD+/NADH ratio in the kidneys and the liver, while in the vessel wall the coenzyme level was moderately increased. The coenzyme changes in the kidneys of SHR were similar to those in renal hypertensive rats. However coenzyme level in the vessel wall of SHR was lower than in all the other forms of hypertension.


Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose. After healthy persons, aged between 20 and 35 years, had consumed either ethanol or ethanol and fructose, triglycerides, free glycerol, FFA, phospholipids and total cholesterol were determined. After a basic dosage of 0.5 g ethanol/kg body weight, each person received a maeintenance dosage of 0.1 g ethanol/kg body weight and hour. Control experiments were carried out on persons receiving only fructose and on fasting persons who consumed no ethanol. After 8 hrs, triglycerides rose in the ethanol group by 107 %, in the ethanol-fructose group by 63 %. FFA exhibited in both ethanol and ethanol-fructose groups an initial decrease, with a secondary increase in the ethanol group. The initial decrease was greater in the ethanol-fructose group. A significant rise in free glycerol by 419 % was observed 30 min after the intake of combined ethanol/fructose. Free glycerol rose under ethanol alone by 144%. The ohospholipids exhibited a slight rise in the ethanol group; no significant changes occured in the cholesterol. The blood ethanol level was lower under ethanol-fructose than under ethanol alone. The addition of fructose diminishes the ethanol-induced hypertriglyceridemia. Our investigations give further proof that, under short-term ethanol load, the fatty acids necessary for the increased triglyceride synthesis in the liver, originate predominantly from a peripheral lipolysis, and that changes in liver metabolism depending on the oxidation of ethanol are not of less importance for the development of the acute ethanol-induced hyperlipidemia.


Histochemical changes effected by aldosterone on compensatory renal growth in the rat. The activity of succinic dehydrogenase, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase was studied histochemically in the remaining kidney of male albino rats which had been subjected to unilateral nephrectomy and were subsequently treated with aldosterone. A marked increase in the activity of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase was noted on the initial postoperative days. The increase noted in succinic dehydrogenase activity is considered particularly important because in the control group succinic dehydrogenase activity remained unchanged throughout the experiment.


[Bursting pressure of colon in the rats and proteinase inhibition (author's transl)]. In the early postoperative period (third postoperative day) the colonic enterotomies show 45 per cent higher bursting pressure following administration of Aprotinin than the control group (p less than 0,02). On the fifth postoperative day no difference was noted between both groups. The interpretation of the results is difficult because specific parameters such as collagen content and collagenase activity were not determinated. The relationship between colonic anastomotic breakdown and collagenase and therefore the question of collagenase inhibition have to be discussed. It is suggested that activation of procollagenase is prevented because trypsin and kallikrein are inhibited by Aprotinin.


Pulmonary gas exchange in dogs ventilated with mixtures of oxygen with various inert gases. To study the influence of physical properties of the respired gas on alveolar gas exchange, alveolar-arterial partial pressure differences for O2 and CO2 were measured in anesthetized dogs that were artificially ventilated with gas mixtures of O2 in N2, He, Ar or SF6. In both hyposia and normoxia alveolar-arterial PO2 differences had the tendency to increase slightly in the sequence of the respired inert gases SF6 less than Ar less than N2 less than He, while arterial-alveolar PCO2 differences remained practically unchanged. Pulmonary diffusing capacity for CO(DCO), determined by the single breath technique, revealed no significant differences between the four gas mixtures used. The possible mechanisms underlying these results are discussed in connection with the physical properties of the respired gas mixtures.


Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor. The low molecular weight bronchial protease inhibitor isolated from purulent bronchial secretions of man was shown to be a potent inhibitor of the elastase from human granulocytes. At a molar ratio of 1:1, the inhibitor prevented elastase digestion of insoluble elastin and soluble elastin, and blocked the hydrolysis of t-BOC-L-alanine-p-nitrophenyl ester. The collagenolytic activity of granulocyte collagenase was not inhibited by the bronchial inhibitor. Antisera were raised in rabbits for the isolation of specific IgG fractions in order to localize and quantitate the inhibitor. 125I-labelled inhibitor was used to study enzyme interactions further by gel filtration. These studies demonstrated that the bronchial inhibitor formed firm complexes with granulocyte elastase but did not form complexes with granulocyte collagenase.


Influence of fat ingestion on lecithin:cholesterol acyl transfer rate in plasma of normal persons. Lecithin:cholesterol acyl transfer (LCAT) rate in plasma and lipid concentrations in total plasma and high density lipoproteins (HDL) were determined before and after oral fat loads in healthy human subjects. The changes of LCAT rate after fat loading were compared to the effect of chylomicrons or lipid emulsions added in vitro to fasting plasma. After the fat loads there was an increase of mean molar LCAT rate simultaneous with an increase of mean phospholipid (PL) and HDL-PL concentration but not simultaneous with the increase of mean triglyceride (TG) concentration. Individual changes of molar LCAT rate correlated positively with changes of PL, HDL-PL, and unesterified cholesterol (UC) concentration but not with changes of TG concentration in the separate plasma samples after the fat loads. If only the maximal changes in each subject in any sample at any time after the loads were taken into account, the maximal increase of molar LCAT rate correlated positively with the maximal increase of TG concentration. Molar LCAT rate was not influenced by addition of chylomicrons in vitro but increased after addition of a PL emulsion. It is suggested that LCAT rate is stimulated by an excess of PL in plasma and substrate lipoproteins. This excess of PL may be created in vivo temporarily during chylomicron catabolism. The stimulation of LCAT rate by fat ingestion emphasizes the importance of LCAT as a connecting link between triglyceride and cholesterol metabolism.


Studies on human serum high-density lipoproteins. VI. Studies on a cholesterol ester-releasing reaction in vitro. High-density lipoproteins (HDL) turn turbid during in vitro incubation, concomitant with the formation of a cholesterol ester-rich lipoprotein, designated HDL-sup. The increase in turbidity (A) formed in relation to incubation time (t) is an asymptotic function: A=Uo(1 - e-k1t), where Uo is the amount of HDL with the property of releasing HDL-sup and k1 the velocity constant of the reaction. The increase in turbidity and formation of HDL-sup was not related to cholesterol ester content of the incubated fraction nor to exogenous factors like bacterial growth. The in vitro incubation was accompanied by a cholesterol esterification with a mean production of 8 nmol cholesterol ester/mg HDL protein, but also by a more pronounced degradation of phosphatidyl choline, 148 nmol/mg HDL protein. These data indicate that the lipid changes are induced by a two-step lecithin:cholesterol acyltransfer (LCAT) reaction. This reaction caused in HDL lipids a consumption of surface material and an increase in 'lipid core', presumably leading to a weakening and disruption of the lipoprotein surface with a recombination of 'lipid core' material in the form of HDL-sup.


Relationship between lipid composition of very low density lipoprotein and electrophoretic mobility in agarose gel. Eleven patients with type IV hyperlipoproteinaemia were investigated. The lipid composition of three very low density lipoprotein (VLDL) subfractions (Sf 100-400, 60-100, and 20-60) obtained by density gradient ultracentrifugation were compared with their electrophoretic mobility in agarose gel. With decreasing Sf values there was cholesterol and phospholipid enrichment relative to triglyceride. All subjects had lipoprotein with beta mobility (LPbeta) in the Sf fraction of 20-60. LPbeta may represent normally occurring intermediary particles.


Effects of ethyl alcohol on the adenosine 3', 5'-monophosphate system of the human gastric mucosa. The effect of ethyl alcohol on the cyclic AMP system of the human gastric mucosa was studied in vitro. Corporic gastric mucosa was obtained from patients operated on for gastric or duodenal ulcers. Under the in vitro conditions used, ethanol at concentrations of 5% (v/v) or less stimulated the activity of adenylate cyclase and induced a dose-dependent rise of the gastric mucosal content of cyclic AMP. However, 10% ethanol increased the activity of adenylate cyclase but did not affect the gastric mucosal content of cyclic AMP. At the concentrations of 5 or 10%, ethanol inhibited the activity of cyclic AMP phosphodiesterase in a competitive manner. Reports in the literature indicate that oral ethanol stimulates the output of gastric acid at low but not at higher concentrations. The present results are consistent with the conception that the stimulatory effect of ethanol on the output of acid is mediated by an increase of the content of cyclic AMP in the gastric mucosa.


Unified mass-action theory for virus neutralization and radioimmunology. All ideas implicit in the papers since 1953 involved in applying mass-action thermodynamics to antibody-antigen reactions are unified by the use of: (a) the intermediary concept of extent of reaction; (b) the concept of intrinsic association constant; (c) a statistical analysis for probable complexes; and (d) identification of the complex or complexes that contribute to the bioassay. Several general theoretical examples are given that show the limitations of linear interpretations of equilibrium data. Two practical examples from the literature illustrate foot-and-mouth disease virus and influenza virus neutralization.


[Neuropsychiatric findings in a case of paramyoclonus multiplex]. In a subject affected with multiple paramyoclonus, showing asyncronous, bilateral, intermittent, spontaneous myoclonic jerks, a neuro-psychiatric investigation was performed. Several day-time poligraphic recordings were normal, while the night-time ones showed the lack of myoclonic jerks throughout the sleep. Metrazol activation pointed out a probable hyperexcitability of brain stem reticular formation. The psychiatric investigation, performed with a psychodynamic approach let realize the existence of a distortion of neuro-psychological functions due to an impaired elaboration of emotional information and psycho-structuring engrams. The Authors conclude for a posible convergence of biological and psychological factors causing the clinical symptoms.


[Sporadic recurrent hypertrophic polyneuropathy. Clinical-histological contributions on differential diagnosis]. The authors report about an own case of recurrent sporadic hypertrophic polyneuropathy and describe the clinical course and histologic picture with reference to the literature. The disease is characterized by recurrences of subacutely occurring polyradiculoneuropathy and sequent nearly complete remission. Clinical examination discloses preferentially symmetrically and distally occurring motor paresis while sensibility in most cases is less affected. The peripheral nerves may be enlarged after a few relapses and frequently painful to pressure during the bout. Excessive increase in CSF proteins is found only during the bout. Motor nerve conduction velocity is considerably reduced. Histological pictures typically present an onion bulb formation of the Schwann cells with marked proliferation of connective tissue. There frequently younger individuals are involved; the relation female to male is 3:1. Differentiation has to be made concerning hereditary and symptomatic forms of hypertrophic polyneuropathy. Etiological factors of the disease are discussed.


Bronchiolar adenomatosis. A case report. A case of bronchiolar adenomatosis (benign pulmonary adenomatosis) with unusually widespread pulmonary changes is presented. This disease is rare and occurs equally in both sexes. The tumourous growth is slow and can easily be mistaken for alveolar cell carcinoma, alveolar proteins, tuberculosis, sarcoidosis, or malignant pulmonary adenomatosis. The diagnosis can be made on a histological specimen from the affected lung. In spite of a benign histological picture, the disease may ultimately run an unfavourable course because of its malignant potentialities. A distinction between benign and malignant pulmonary adenomatosis may therefore only be made with certainty by a complete and careful postmortem examination.


High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. The concentration of gamma-aminobutyric acid (GABA) and the activity of glutamate decarboxylase (GAD) in rat and human pancreas were measured by sensitive assay methods. The GABA concentration in rat pancreas was 2.51 millimoles per kilogram (dry weight) and GAD activity was 2.58 mmoles per kilogram per hour. The GABA concentration and GAD activity in rat Langerhans' islets were 18.9 mmole kg-1 and 66.7 mmole kg-1 hour-1, whereas those in the exocrine acini were 1.97 mmole kg-1 and 4.67 mmole kg-1 hour-1, respectively. In an insulinoma region of human pancreas the GABA concentration was 25.5 mmole kg-1 and the GAD activity was 138.2 mmole kg-1 hour-1, but in the surrounding nontumor region these values were only 2.81 mmole kg-1 and 2.01 mmole kg-1 hour-1, respectively, similar to the values in normal rat pancreas.


Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness. The endogenous morphinomimetic brain peptides Met5-enkephalin and alpha-, beta-, and gamma-endorphins have been evaluated in rats after intracerebrospinal fluid injection. beta-Endorphin produces marked, prolonged muscular rigidity and immobility similar to a catatonic state, counteracted by the opiate antagonist naloxone; this effect occurs at molar doses 1/100 to 1/400 that at which the other peptides or morphine block the response to painful stimuli. All peptides evoked dose-related, naloxone-reversible, wet-dog shakes in rats that had not been exposed to drugs. beta-Endorphin produced hypothermia, whereas gamma-endorphin produced hyperthermia. Such potent and divergent responses to naturally occurring subtances suggest that alterations in their homeostatic regulation could have etiological significance in mental illness.


The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen? Microinjection of the C-fragment (also called beta-endorphin), which is amino acid sequence 61-91 of the endogenous pituitary hormone, beta-lipotropin (beta-LPH), in the periaqueductal gray of the rat resulted in profound sedation and catalepsy, while microinjection of smaller fragments-that is, methionine-enkephalin [sequence beta-LPH-(61-65)] and its related pentapeptide, leucine enkephalin, and alpha-endorphin [sequence beta-LPH-(61-76)] resulted in attenuated forms of this behavior. This indicates that the C-fragment is an important neuromodulator of the central nervous system. The similarity of this behavior to that seen after systemic administration to experimental animals of exogenous neuroleptics suggests that a disturbance in the bioavailability of this neuropeptide to receptor sites in brain-perhaps due to lack of enzymatic cleavage from the circulating parent hormone, beta-lipotropin--may be an etiological factor in those psychopathological states for which the exogenous neuroleptics exert an ameliorative influence.


The state of preservation of the cadaver of the Marquise of Tai found in the Han Tomb No. 1 in Mawangtui near Changsha as revealed by the fine structure of the muscle and other tissues. The cadaver in the Han Tomb No. 1 at Mawangtui near Changsha, Human Province, excavated during the Great Proletarian Cultural Revolution and the movement to criticize Lin Piao and Confucius, is the remains of the wife of Litsang, the Marquis of Tai, the Chancellor of the principality of Changsha in the early Western Han Dynasty. The cadaver, buried underground for more than 2,100 years, is very well-preserved. The results presented in this paper are a part of the multidisciplinary investigations of the state of preservation of the cadaver, which, together with the studies of the pathological changes and the cause of death, and the attempts at unveiling the secret of preservation, constituted the main objectives of the coordinated research activities for the Han cadaver. This paper describes the fine structure of the muscle and other tissues of the cadaver. By an extensive analysis of the electron micrographs of the psoas muscle, by fractionation of various fragments of the same, and by simulation experiments with fresh human muscle incubated with cathepsins, it is possible to show that the muscle fibril assumes the shape of a bamboo shoot and is made up of a stack of alternate layers of two "half A disks" (one wing of the A cylinder minus the H zone) to one Z disk, held together by remnants of the microfilaments and wrapped up in the sarcoplasmic reticulum. The H zone of the A band and the I filaments have preferentially autolyzed. The best preserved portions of the Han muscle still retain antigenicity to a certain extent. The best-preserved of all proteins is collagen, retaining much of the macromolecular, chemical and biochemical characteristics, whereas pancreatic enzymes, cytochrome C and other stable proteins could no longer be detected. The separation of degradative processes into endogenous autolysis and exogenous putrefaction, the synthesis of the factor of macromolecular stability and the factor of autolytic environment, and the disentanglement of the changes occurring soon after death and the long-term gradual changes, have been discussed in an attempt to understand how the corpse changed in the course of time and why it was so well-preserved. The well-preservedness of the cadaver of the Marquise of Tai once again testifies to the creative wisdom of the labouring class of our ancestors.


Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response. Human polymorphonuclear leukocytes treated with cytochalasin B release the lysosomal enzyme beta glucuronidase during contact with serum-activated zymosan particles. Histamine increases intracellular cyclic adenosine monophosphate and inhibits release of this enzyme. The H2 antihistamine metiamide blocks the histamine inhibition of lysosomal enzyme release and the increase in the intracellular adenoisine 3,5'-monophosphate of granulocytes. Chlorpheniramine, an H1 antihistamine, did not block the histamine inhibition of granulocyte lysosomal enzyme release.


Biosynthesis and function of gangliosides. Gangliosides are unique acidic glycolipids that are selectively concentrated in the plasma membrane of cells. Surface labeling studies have demonstrated that at least a portion of the oligosaccharde chain of gangliosides extends beyond the hydrophe) is imbedded in the membrane bilayer. It is becoming increasingly apparent that gangliosides participate in the internalization of environmental signals elicited by cholera toxin and glycoprotein hormones such as thyrotropic hormone and chorionic gonadotropin as well as other substances such as interferon and possibly serotonin. The mechanism by which cholera toxin binds to a specific ganglioside receptor on the celraction of trophic agents with gangliosides. We would predict that analyogous phenomena involving gangliosides will be discovered in brain. The biosynthesis of gangliosides proceeds by the ordered sequential addition of sugars to the lipid moiety. These reactions are catalyzed by a cluster of membrane-bound glycosyltransferases. Any alteration in the activity or specificity of one of these enzymes will result in a dramatic change in the ganglioside pattern of an afflicted cell or organ. The drastic consequences that accompany abnormalities of ganglioside synthesis have been documented in a heritable metabolic disorder in vivo and in tumorigenic transformation of cells in vitro. In this article, we have attempted to unify these observations and to provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena.


Electrotonic coupling: effective sign reversal by inhibitory neurons. Neurons in the buccal ganglia of Navanax inermis which control circumferential muscles of the pharynx showed typical electrotonic coupling when there was little synaptic activity in them. When there was much inhibitory activity, the effective sign of coupling was reversed; that is, hyperpolarization and depolarization of one cell caused depolarization and hyperpolarization of the others. A neural circuit explaining these results involes inhibitory neurons electronically coupled to and also inhibitory to the circumferential neurons that are themselves coupled. This circuit offers considerable flexibility for mediation of different activity patterns in this simple neuronal system.


[Lessons drawn from granulocyte transfusions in the treatment of infections complicating aplasia induced by anti-leukemic chemotherapy]. The authors report the results of leukocyte transfusions of white cells obtained by sedimentation from donors with chronic myeloid leukemia, and by a continuous output cell separator used in healthy donors. The percentage of therapeutic efficacy of these two techniques is respectively, 62 and 78%. Among the factors affecting transfusion efficacy, the dose of injected leukocytes, the immunological compatibility and the functional value of the injected cells, appear of major importance. A qualitative study of the polymorphs in chronic myeloid leukemia, assessed by reduction with tetrazolium nitro-blue (N.B.T.) after ingestion of latex particles, proved normal when studied in vivo in the recipient. The mode of action of transfused leukocytes is then discussed.


[Episodes of fever in the agranulocytic phase of the treatment of acute myeloblastic leukemia in adults]. This retrospective study of 44 attacks of fever during the agranulocytic stage of treatment of acute myeloblastic leukemia in adults, sought the cause of the fever, the efficacy of antibiotic associations and the efficacy of white cell transfusions. In 28 cases, the fever was associated with bacterial or mycotic infection, proved in 19 cases. Appropriate antibiotic therapy alone was able to cure the fever, whereas white cell transfusion did not seem of any use. In the 16 other cases, the fever appeared alone. Antibiotic associations were ineffective, whereas the fever was cured by white cell transfusions or cure of the agranulocytosis.


[Anatomo-clinical and experimental studies on pneumocystis carinii. Preliminary note]. The authors have been interested over the last year in the detection of pneumocystis carinii in patients with immune deficiencies, whether natural or artificial. After a brief historical and general introduction, they discuss their procedures, the pathological substances available, the staining techniques and the examination of autopsy specimens. They undertook experimental work on this micro-organism, e.g. the development of the germ in immuno-depressed rats and, from this material, numerous varied trials of culture and inoculation in new-born animals, chick embryos and cell cultures. Microphotographs illustrate this work which is still in progress.


[Bacterial infections and immunosuppression]. Organ transplantation and the modern treatment of leukemia have created a new situation favouring bacterial infection under immunosuppressive drugs. Exceptionally, due to pathogenic bacteria, these infections are usually due to various germs normally considered as inoffensive saprophytes, which may thus reveal immune deficiency in the patient. This immune failure, which is very pronounced in treated leukemic patients and following transplantation, is on the contrary often localised at a precise level during common infections. Knowledge of these levels is thus essential for the clinician who, in all infected patients, should assess the state of the skin, mucosal and tissue and humoral defences whether specific or non-specific in the light of modern immunological data. Infection in the immunodepressed subject requires urget treatment. Antibiotics are not the only form of treatment, one should supervise, maintain and restore adequate immune levels. Furthermore, antibiotics alone, although they reduce the frequency, do not finally improve the mortality rate from gram-negative septicemia acquired in hospital.


[Infectious complications observed during the use of antimitotic agents in hematology]. During acute lymphoblastic leukemia in children, bacterial infections occur during initial treatment, whereas virus infections are observed during remission. Mycoses and pneumocystis carinii infections are the commonest late complications. During agranulocytosis, any prolonged fever should be considered as due to infection and probably septicemia. The bacteria are usually of digestive origin. Antibiotic therapy is only very inconstantly efficacious, and the course follows closely the number of granular cells, thus justifying the use of white cell transfusions.


[Diabetes mellitus in pheochromocytoma]. The frequency of latent disorders of glucose regulation during pheochromocytoma, is evaluated at 75% of cases. Detailed analysis of 83 cases with a diabetic state, gave the following results: insulin dependent diabetes, 37 cases. Non-insulin dependent, 14 cases. Latent diabetes, 32 cases. The characteristics of the insulin-dependent diabetes were not always suggestive. Insulin dependency was, however, unusual above a certain age. We noted loss of weight in spite of good control of the diabetes, the absence of acidosis and ketosis contrasting with rapid loss of weight. In fact, it is above all the hypertension which should lead to diagnosis. Surgical operation, cures or improves considerably the diabetic state, thus proving the symptomatic nature of this diabetes.


[The nephrotoxicity of the methicillin-gentamycin combination. Apropos of 5 cases]. Interstitial nephritis with acute renal failure was observed in 5 cases out of 6 treated by the association of methicillin and gentamycin, wheras no case, was observed when each of these antibodies was used separately. The mechanisms which might explain the potentialisation of these two drugs are discussed.


[Immunoblasts. Morphology and significance in reactive and proliferative syndromes of lymphoid tissues]. The term immunoblast created by Dameshek, is useful in routine cytological and histopathological practice, for the diagnosis of lymphadenites and malignant blood diseases. This term designates a group of cells, the appearance of which is quite different from other cells of the lymphoid tissue. Their morphological characteristics are precise and they resemble transformed lymphocytes. These immunoblasts are derived from T and B lymphocytes. Using purely morphological methods the type B of certain immunoblasts may be suggested. Immunoblasts of the clear centers of follicles, immunoblasts undergoing plasma cell transformation, tumour cells constituting nodular immunoblastosarcomas, immunoblasts appearing in the tumor population of the myelomas and of Waldenström's macroglobulinaemia. The term immunoblast which evokes precise morphological criteria, should be maintained. This term cannot designate only B lymphocytes, but also transformed lymphocytes of type B or T.


[Senile common bile duct. Radiological study]. From this study carried out under sufficiently strict conditions to analyze normal common bile ducts of the third to the tenth decade, with radio-geometric measurement redusurement reducing errors as far as possible, it appears that: a) there is no difference in the frequency and the density of opacification of the bile duct in young or elderly subjects, b) that the radiological diameter of the normal bile duct becomes enlarged with time, according to the formula: (see article) which may be considered in routine clinical practice as a true increase in diameter of about 1 mm per decade. The limits of true diameter of the bile duct, in our experience, were +/- 3 mm at 30 years to +/- 7 mm after 80 years.


[Benign tumors of the pleura].

[Benign tumors of the pleura]. The authors report a case of benign tumour of the pleura in a 74 year old woman. This is a pediculated tumour of the right base posteriorly above the diaphragm, the pleural nature of which was recognised before surgery and which, microscopically, proved to be a localized, benign mesothelioma of fibroblastic type. Benigh tumours of the pleura are rare but raise two interesting problems: that of their precise origin which is debated, and their prognosis; the possibility of relapse should be borne in mind.


[Pulmonary metastasis from Vater's ampullomas]. The authors report two cases of carcinoma of the ampulla of Vater with numerous pulmonary metastases. This carcinoma is a malignant tumour with a very poor short-term prognosis. This tumour develops at the expense of the ampulla of Vater and may give rise to numerous pulmonary metastases and  carcinomato,s lymphangitis. Authors are not unanimous concerning the course and prognosis of these tumours. In fact, one may note two tendencies, one optimistic, which seems to us erroneous, the other pessimistic, which we share.


[Validity of bronchial flow measurement by Wright's air flowmeter. Comparison with maximal expiratory volume in a second]. The validity of measurement of bronchial air flow, using Wright's air flow meter, was studied comparing the maximum air flow thus obtained with the maximum expiratory volume in one second, used as unit of reference. During a first stage, the reproducibility of the test was determined this was excellent, 3.26% for the maximal flow rate and 2.48% for the maximum volume expired in one second. During a second stage were drawn up correlations between the two tests which were very narrow: O.971 in healthy sbjects, 0.919 in sick patients. The Wright flow meter is a strong, reliable and inexpensive instrument and will thus be very useful in the daily assessment of bronchiolar constriction at the bed side, and in the routine detection of obstructive syndromes.


[Idiopathic pulmonary hemosiderosis. Apropos of 1 case]. Idiopathic pulmonary hemosiderosis gives rise to anemia, due to repeated intra-alveolar hemorrhage, the reabsorption of which leads to hemosiderin deposits in the lung parenchyma. The authors report a case in a young woman aged 24 years whose illness started with anemia, then two months later, with hemoptysis and a broncho-pulmonary syndrome with a low grade fever. On the 6th month, there occurred a hazy infiltrate of both lung bases which was fleeting, mobile and recurrent. In the light of this triad of anemia, hemoptysis and infiltrates, the diagnosis of idiopathic pulmonary hemosiderosis was made and confirmed by three examinations:--Lung biopsy: siderophages were found in the sub-mucosa,--Radio-isotope examination, using Fe 59 which revealed iron deposits in the lung,--A surgical lung biopsy which showed a congestive area and a fibrous area. The congestive area was the site of recent hemorrhage, the alveolar limits were filled with siderophages. The fibrous area was the site of chronic repair of older hemorrhage. It was mutilating. The course was complicated by massive bleeding which led to acute recovering respiratory failure. The patient is at present stabilised by corticosteroids. Three hundred cases of idiopathic pulmonary hemosiderosis have been reported in the world literature. Although the main characteristic is intra-alveolar hemorrhage, its course has not yet been determined. It seems however, to be due to an immunologic process as shown by the relationship between this curious disease and Goodpasture's syndrome.


[Paraneoplastic hypercalcemia in primary bronchial cancer]. Paraneoplastic hypercalcemia is frequently observed in squamous cell carcinoma of the bronchus. Clinically, apart from the general symptoms which are always very marked, neurological signs are the most common. This hypercalcemia, accompanied by hypophosphatemia, is of sudden onset and immediately very high. Metabolic alkalosis, with hypokalemia and hypochloremia, differentiates it from true hyperparathyroidism. Symptomatic treatment is only transiently effective. However, the obvious effect of mitramycin may be useful before surgical operation, which alone produces a lasting normalisation of serum calcium. Inappropriate secretion of a parathormone substance by the tumour may be demonstrated by radio-immunoassay, and this explains a large number of cases of hypercalcemia but this does not exclude other possible factors in the etiology. Finally, hypercalcemia originally attributed to bony lysis, may be explained in some cases by a paraneoplastic process.


Gallium-67 tumor scanning.

Gallium-67 tumor scanning. Since its introduction in 1969, 67Ga has become the most widely employed tumor-scanning agent in nuclear medicine. While 67Ga is far from being the ideal tumor-scanning agent, it remains the best available isotope for this purpose. Gallium-67-citrate has been found to be of value in the staging and reevaluation of lymphomas as well as in detecting the extent and recurrence of lung tumors, breast tumors, malignant melanomas, testicular tumors, brain tumors, and malignant lesions involving the liver. In order to obtain maximum diagnostic value from gallium scanning, several technical factors have to be taken into consideration as well as an understanding of the nature of "false-positive" scans.


Hypoglycemia: the "undisease".

Hypoglycemia: the "undisease". Patients with a wise variety of medical problems have been labeled as having "hypoglycemia" during the past several years. Hypoglycemia, however, indicates only a diminished content of blood or plasma glucose. In individual cases the existence of hypoglycemia needs to be ascertained by objective laboratory measurements. Once confirmed, it is necessary to determine which of the many conditions capable of inducing hypoglycemia is present. Therapy must be directed against a specific diagnosis. It is not sufficient to decide by history without laboratory confirmation that a patient has hypoglycemia and then prescribe dietary modification.


Leiomyosarcoma of the broad ligament coincident with ductal carcinoma of the breast. Presented is a case of an isolated leiomyosarcoma of the broad ligament in a woman who had a synchronous ductal carcinoma of the breast. Carcinoma of the breast, thyroid, or colon is the most common second primary neoplasm in women with pelvic malignancy.


Spontaneous cytomegalovirus mononucleosis-like syndrome and aseptic meningitis. The spontaneous development of a cytomegalovirus infection in a healthy adult is described. This illness manifested with fever, headache, malaise, an absolute lymphocytosis with atypical lymphocytes, and liver function abnormalities, but without tonsillitis, pharyngitis, lymphadenopathy, or splenomegaly. Aseptic meningitis also was present. The pathogenesis of cytomegalovirus mononucelosis and its relationship to other related syndromes are discussed.