Elementary components of synaptic transmission.

The analysis of chemical transmission at synapses, in particular at the neuromuscular junction, has proceeded from the cellular to the molecular level. Gradual refinements in electric recording technique have brought to light new features, first the quantal delivery of the transmitter substance, in multimolecular packets, from the nerve endings, and more recently the statistical elements of the postsynaptic potential change which arise from the molecular bombardment by acetylcholine and the transient opening of individual ion channels in the end-plate membrane.


Mucolipidosis IV.

Five new cases of Mucolipidosis IV are related and the seven cases in the literature reviewed. Neurological signs of the disorder and the value of skin and conjuncitival biopsies for its diagnosis are emphasized. Arguments in favour of a recessive autosomic inheritance are brought forth. The disease does not affect exclusively Jewish people. In two cases absence of oligosacchariduria was demonstrated.


Cranial computed tomography (CCT) findings in children treated with ACTH and dexamethasone: first results.

8 children with different petit mal epilepsies were systematically treated with ACTH and dexamethasone. CCT examinations were performed before, during and after treatment. In all children severe cerebral changes. enlargement of ventricles and subarachnoid space developed during the initial phase of treatment with Depot-ACTH. Similar changes, but to a less severe degree, could be demonstrated during the phase of dexamethasone therapy thereafter. In all patients cerebral changes disappeared after hormonal treatment had ended. At this point many children had a developmental spurt, developmental relapses could not be observed. It is suggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures. These results bear certain consequences as to the therapy of cerebral edema.


Krabbe's disease with unusual clinical and morphological features.

A progressive encephalopathy appeared in two sibs aged 7 and 5 months. The children died at 23 respectively 29 months of age. Autopsy of the second child disclosed a severe demyelination involving the whole brain. Only few globoid cells were identified. Ultrastructural and biochemical investigations confirmed the diagnosis of Krabbe's disease.


Chronological study of ultrastructural changes in the peripheral nerves in Marek's disease.

A chronological study was made of the ultrastructural changes in peripheral nerves following inoculation of 1-day-old chicks with a neurogenic strain of Marek Disease virus. No virus particles were found in nerves. Cellular infiltration of nerves was detected as early as 5 days after inoculation and by 3 weeks some nerves contained proliferative lesions which possessed many of the ultrastructural features characteristic of normal, reactive lymphoid tissue. About 4 weeks after inoculation, coinciding with the onset of neurological signs, areas of widespread demyelination appeared within these lesions; lymphocytes and macrophages penetrated and destroyed the myelin sheath, but spared Schwann cells and most axons. Later oedematous, sparsely infiltrated B type lesions were observed, some of which contained demyelinated nerve fibres undergoing repair; these were therefore a stage in the regression of the proliferative lesions. Our observations do not favour the hypothesis that cellular infiltration of nerves in Marek's disease is the direct result of auto-sensitization to normal myelin. They are consistent with the hypothesis that demyelination is a secondary feature and that the primary lesions are preferential sites for immune demyelination.


[Early bronchiolar-alveolar cell cicatricial carcinoma; a case report with 2 illustrations].

Only the solitary type of bronchiolo-alveolar cell carcinoma has a chance of being healed if surgery is performed in time. This type of tumor is often found as a cicatricial carcinoma in the periphery of the lung. Small tumors do not exhibit any clinical symptoms, they are either detected by mere chance or during radiological check-up or routine medical check-up of healthy persons. In the present case a small posttuberculous scar in the lung had been known to exist for ten years. Only a repeated routine medical check-up including X-ray examination and subsequent tomographic X-ray gave an indication for the performance of thoracotomy. While surgery was being performed the malignancy and the tumor type where cytologically determined and verified by histological examination of the excised tumor.


[Enophthalmic orbital metastasis].

Some orbital metastases (16 cases in the literature and 2 personal cases) involve a histologically typical enophtalmos with profuse fibrous stroma. They arise after squirrhous carcinoma of the breast or plastic linitis of the stomach.


Microassay of cyclic nucleotides in vessel wall. IV. Cyclic GMP phosphodiesterase activity.

Following our microassay for cyclic AMP phosphodiesterase (1978, Microvascular Res. 15:229), a new microassay for cyclic GMP phosphodiesterase (c-GMPPDE) activity was devised, combining the quantitative histochemical method of O.H. Lowry and J.V. Passonneau (1971, A Flexible System of Enzymatic Analysis, Academic Press, New York) with the thin-layer chromatography method of W.A. Scott and B. Solomon (1973, Biochem. Biophys. Res. Comm., 53, 1024). Using this method, c-GMPPDE activity can be accurately measured in a 250 microgram dry weight sample of tissue from the aortic wall. The optimal amount of sample and incubation time were studied, and two Km values were obtained. Low Km is 4.00 x 10(-6) and high Km is 1.25 x 10(-5). The activity of this enzyme was measured in the intima and media of the aorta of three rabbits, three cows and three pigs. The cyclic GMPPDE activities in tissue from cows, pigs and rabbits were 26.61 +/- 2.19, 20.40 +/- 1.35, 43.08 +/- 4.11 pmole/mg dry weight/min in the intima; 52.56 +/- 2.73, 16.07 +/- 3.30 and 66.51 +/- 4.60 pmole/mg dry weight/min in the media. With regard to the relationship between levels of cAMP and cGMP, the activities of cGMPPDE were 10-20 times higher than those of cAMPPDE. These assay systems should provide accurate tools for researching biological, physiological and pathological states of arterial tissues, particularly in the case of atherosclerosis.


Cystic partially differentiated nephroblastoma: an entity in the spectrum of infantile renal neoplasia.

Clinicopathologic features of 17 cases of "cystic partially differentiated nephroblastoma" (CPDN) including three seen in personal experience have been reviewed. CPDN has previously been designated by various terms such as "benign multilocular cystic nephroma," "polycystic nephroblastoma," and "cystic nephroma." The term CPDN is preferred because it aptly denotes the characteristic gross and microscopic features and the probable histogenesis of the lesion. CPDN occurs before 2 years of age. Clinically, abdominal mass is the most common presenting feature. CPDN is often diagnosed as Wilms' tumor on clinical and radiologic grounds. Grossly, the lesion is almost totally or predominantly multicystic. Microscopically, the cysts are usually lined by flattened to cuboidal epithelium. The septa contain a mixture of blastemal cells and poorly differentiated and well-differentiated epithelial and mesenchymal elements. It is this feature which distinguishes CPDN from multilocular cyst of the kidney. Although there is a suggestion that there might be two subtypes of CPDN-one with predominantly well-differentiated elements and the other with predominantly poorly differentiated elements-no definite conclusions can be drawn regarding the existence of such subtypes on the basis of available data. Arguments could be advanced in favor of both the neoplastic and dysgenetic nature of CPDN. However, the view that CPDN is a neoplastic lesion is favored. On the basis of available data, CPDN appears to take a benign course, and simple nephrectomy seems to be the treatment of choice. However, in view of the possibility of recurrence as shown by rare cases of congenital mesoblastic nephroma (another usually benign lesion in the spectrum of infantile renal necoplasia), regular follow-up is recommended.


Separate activation sites for cholecystokinin and bombesin on pancreatic acini: an electrophysiological study employing a competitive antagonist for the action of CCK.

The effects of dibutyryl cyclic guanosine 3':5' monophosphate (dbcGMP) on the electrical responses of in vitro mouse pancreatic acinar cells to caerulein, bombesin and acetylcholine, applied by microionophoresis, were investigated using intracellular microelectrode recordings. Exposure to dbcGMP (10(-3) mol . 1-1) quickly abolished the depolarization response to caerulein ionophoresis, while the bombesin-nonapeptide and acetylcholine-induced depolarizations were retained. Exposing acinar cells to 2 x 10(-4) mol . 1-1 dbcGMP reduced their sensitivity such that a 10-fold increase in the applied caerulein ionophoresis current was required to restore the responses to the same magnitude as those obtained in a dbcGMP-free environment. The response to topical applications of pentagastrin and CCK-33 were also abolished by dbcGMP. The results provide direct evidence that functional ACh, bombesin and CCK receptors are all present within the same acinar cell unit. The dbcGMP-induced inhibition of responses evoked by CCK-like peptides is immediate, specific and easily reversible. DbcGMP acts as a competitive antagonist of the CCK receptor on pancreatic acinar cells.


[Persistent non polio enterovirus infections associated with glomerulonephritis. 9 cases (author's transl)].

All patients are excreting the virus in urines and in 4 cases in stools. The virus has also been isolated from the blood. These cases focused on the possible role of enteroviruses as causal agents for the glomerulonephritis.


The nucleotide sequence at the 5' end of foot and mouth disease virus RNA.

Foot and mouth disease virus RNA has been treated with RNase H in the presence of oligo (dG) specifically to digest the poly(C) tract which lies near the 5' end of the molecule (10). The short (S) fragment containing the 5' end of the RNA was separated from the remainder of the RNA (L fragment) by gel electrophoresis. RNA ligase mediated labelling of the 3' end of S fragment showed that the RNase H digestion gave rise to molecules that differed only in the number of cytidylic acid residues remaining at their 3' ends and did not leave the unique 3' end necessary for fast sequence analysis. As the 5' end of S fragment prepared form virus RNA is blocked by VPg, S fragment was prepared from virus specific messenger RNA which does not contain this protein. This RNA was labelled at the 5' end using polynucleotide kinase and the sequence of 70 nucleotides at the 5' end determined by partial enzyme digestion sequencing on polyacrylamide gels. Some of this sequence was confirmed from an analysis of the oligonucleotides derived by RNase T1 digestion of S fragment. The sequence obtained indicates that there is a stable hairpin loop at the 5' terminus of the RNA before an initiation codon 33 nucleotides from the 5' end. In addition, the RNase T1 analysis suggests that there are short repeated sequences in S fragment and that an eleven nucleotide inverted complementary repeat of a sequence near the 3' end of the RNA is present at the junction of S fragment and the poly(C) tract.


Characterization of the major altered leader sequence of late mRNA induced by SV40 deletion mutant d1-1811.

d1-1811 is a viable SV40 mutant with a 40 base pair deletion that includes the major wild-type capping site of late mRNA at map position 0.72. The late viral mRNAs induced by d1-1811 have now been further characterized by inversed S1-mapping analysis. The S1-resistant, 32P-labeled RNA fragments derived from the leader region were examined by fingerprinting and by analysis of RNase T2-generated 5'-terminal cap structures. The results show that most if not all of the mutant leader fragments analyzed have their 5' terminus to the left of the d1-1811 deletion site, i.e., closer to the origin of DNA replication. The major altered leader fragment is a continuous transcript from the DNA in the region 0.716 to 0.761 map unit and its 5' terminus has been precisely mapped at nucleotide L290. The observation that the cap structure of the major altered leader is only a minor cap species in wild-type late RNA suggests regulation in the use of different capping sites in SV40.


Rapid  mapping of transposon insertion and deletion mutations in the large Ti-plasmids of Agrobacterium tumefaciens.

A procedure is presented, that has allowed the rapid assignment of transposon Tn1 and Tn7 insertion sites in the large (130 Md) nopaline Ti-plasmid pTiC58, to specific restriction enzyme fragments. Total bacterial DNA is isolated from Agrobacterium tumefaciens strain C58 mutants that carry a transposon in their Ti-plasmid, and digested with an appropriate restriction endonuclease. The fragments are separated on an agarose gel, denatured and transferred to nitrocellulose filters. These are hybridized against purified wild type pTiC58, or against segments of PTiC58, cloned in E. coli using pBR322 as a vector plasmid. DNA sequences homologous to the probe are detected by autoradiography, thus generating a restriction enzyme pattern of the plasmid from a digest of total bacterial DNA. Mutant fragments can be readily identified by their different position compared to a wild type reference. This protocol eliminates the need to separate the large plasmid from chromosomal DNA for every mutant. In principle, it can be applied to the restriction enzyme analysis of insertion or deletion mutants in any plasmid that has no extensive homology with the chromosome.


The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts.

The relationship between pyrimidine dimers (measured as endonuclease-sensitive sites) and newly-synthesized DNA has been examined in several different ways, with the following results:- 1. After UV-irradiation of normal human fibroblasts the frequency of pyrimidine dimer sites in sections of DNA which have been synthesized immediately before the UV-irradiation is similar to that in the bulk DNA. 2. The frequency of pyrimidine dimer sites in the parental strands of replicating DNA in UV-irradiated normal human fibroblasts is similar to that in the bulk DNA. 3. In UV-irradiated XP variant cells the size of DNA synthesized in the presence of caffeine immediately after UV irradiation accurately corresponds with the average interdimer distance in the parental DNA. This suggests that in this experimental situation each pyrimidine dimer gives rise to a disocntinuity or a termination site in the daughter strand.


New genes and promoters suggested by the DNA sequence near the end of the coliphage T7 early operon.

We have employed the dideoxynucleotide chain-terminating method to determine the nucleotide sequence of T7 DNA between the physical map positions 18.9% and 19.8%. The most striking features of this sequence are two perfect 21-basepair repeats, each of which appears to contain a promoter for late transcription. In each case the promoter sequence incorporates a putative translational terminator on its left (5'-side of the "sense" strand), and overlaps a potential ribosome-binding site on its right. The region probably lies immediately distal to the early operon, and may contain two short, hitherto unreported protein-coding sequences.


RNA polymerase I from higher plants. Evidence for allosteric regulation and interaction with a nuclear phosphatase activity controlled NTP pool.

RNA polymerase I was isolated from parsley cells grown in suspension culture and from soybean hypocotyls. Kinetic studies of the enzyme revealed that RNA polymerase I is an allosteric regulated enzyme. The enzyme activity was influenced by nucleoside triphosphates (NTP) and divalent cations. NTP exceeding a 1:1 ratio of these two components acted as allosteric inhibitors, contrary to free divalent cations, which had promotive effects on the RNA polymerase I. Furthermore, isolated nuclei from parsley exhibited a powerful nucleoside triphosphatase (NTPase) activity. Contrary to RNA polymerase I, this enzyme was stimulated by NTP exceeding the 1:1 ratio of NTP and divalent cations. Free divalent cations had an inhibitory effect. Assuming that a causal connection of these two processes does exist, a possible role of this NTPase would be the control of NTP pools in relation to divalent cations and thus regulating RNA synthesis.


The binding of an avian myeloblastosis virus basic 12,000 dalton protein to nucleic acids.

The binding of a basic 12,000 dalton protein (p12) from avian myeloblastosis virus to viral RNA and heterologous DNA has been investigated. The binding stoichiometries and constants were determined by an extrinsic fluorescence assay. In both cases each bound p12 molecule occupies four nucleotides and the apparent binding constant is approximately 1 x 10(6) M-1. Binding is non-cooperative and there is no apparent difference in the interaction of p12 with viral RNA or heterologous single-strand DNA. The relative binding constant at various ionic strengths was assayed by the nitrocellulose filter procedure. Analysis of the data revealed that each bound p12 molecule forms three ion pairs with the nucleic acid.


Scintigraphic detection of gynaecological tumours by 99mTc-HSA blood pool imaging.

Three cases of scintigraphic visualization of gynaecological tumours by 99mTc-HSA blood pool imaging are presented, i.e. one case of fibrothecoma ("cold" area visualization) and two cases of fibromyoma ("hot" area visualization). It is suggested that this technique may be useful in the preoperative evaluation of gynaecological tumours and their vascularity.


A suggested classification of breast pain.

A system of classification based on the work of Preece et al. (1976) is described. The results of applying this classification over a 4 month period (representing 84 patients) are described.


An insulinoma presenting with reactive hypoglycaemia.

A 57-year-old woman presented with symptoms which were cured by the removal of an insulinoma. The case was atypical in that symptomatic hypoglycaemia occurred only after meals or glucose administration but never during fasting, and thus if plasma insulin activity had not been measured an incorrect diagnosis of reactive hypoglycaemia might have been made on the basis of symptoms and oral glucose-tolerance test. Reactive hypoglycaemia resulted from an increased rate of glucose assimilation and possibly also from a decreased rate of gluconeogenesis due to the immense insulin secretion provoked by glucose or food. The findings suggest that a diagnosis of hypoglycaemia should not be made until the possibility of an insulinoma has been excluded by measurement of plasma insulin activity during a period of hypoglycaemia.


The heterogeneity of nerve growth factor receptors.

Chick embryonic sensory ganglia cells have two specific nerve growth factor receptors, site I and site II receptors, whose binding affinities differ by two orders of magnitude. As judged by both steady state binding and kinetic data, the two receptors behave independently. The rate of dissociation of the labeled nerve growth factor from site I receptors is increased in the presence of unlabeled nerve growth factor even when its concentration is below that of the labeled growth factor used to equilibrate the cells, a phenomenon which cannot be explained by negative cooperativity. Site I receptors are present only on neurons while site II receptors are present on both neurons and nonneuronal cells. At the concentration of nerve growth factor which produces half maximal stimulation of neurite outgrowth 8% of site I and 0.1% of site II receptors are occupied. This occupancy of site II receptors falls to about 0.01% with bisdesarginine beta nerve growth factor, a derivative which is as biologically active as the unmodified factor but which binds with lower affinity to site II receptors. These data support the idea that interaction of nerve growth factor with site I receptors is responsible for the initiation of neurite outgrowth.


[Immobilization of nicotine amide adenine dinucleotide derivatives and their function as cofactors of bacterial formic dehydrogenase].

NAD+ was modified with respect to the C(6)-amino group of the adenine residue by iod acetic acid alkylation in N1-position and subsequent rearrangement into N6-position. By condensation of N6-carboxy methyl-NAD+ with 1,6-diamino hexane, N6-[(6-aminohexyl)-acetamide]-NAD+ was synthesized. This process was controlled spectrophotometrically and by analytical isotachophoresis. NAD+ derivatives were found to maintain high co-enzymic activity in the reaction of formic oxidation with formic dehydrogenase from gram-negative methylotrophic bacteria, str. 1. Kinetic parameters of the reaction involving the resultant components were determined. NAD+N6-derivatives were covalently bound with the water insoluble carrier--Sepharose 4B and water soluble carriers--acrolein and 4-vinyl pyridine copolymers and dextran. The rates of formic dehydrogenase reduction of the native and immobilized cofactors were compared.


Interaction of thyroid hormones with target tissues: effects of hepatic mRNA population.

Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA.


Regulation of pyruvate dehydrogenase by insulin action.

In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase. Physiologic and molecular aspects of this regulation are reviewed, and the results of recent studies are described. Insulin deficiency in the rat (diabetes or starvation) is shown to inhibit the conversion of inactive (phospho-) complex into active (dephospho-) complex by the phosphatase by an effect on the substrate for the phosphatase (phosphorylated complex). This change is stable and persists during isolation, incubation, and extraction of mitochondria or purification of phosphorylated complex. The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P. The ratios of decarboxylase tetramer (alpha 2, beta 2) : dihydrolipoyl acetyltransferase monomer : dihydrolipoly dehydrogenase monomer were 1:1:0.5. Inactivation of the complex was accomplished by incorporation of a single phosphate into one alpha subunit of the decarboxylase tetramer. Two further phosphates are then incorporated and these additional phosphorylations inhibit reactivation of the complex by the phosphate. It is suggested that multisite phosphorylations may inhibit reactivation of the complex by the phosphatase in diabetes and in starvation.


Identification and partial characterization of some components of hormone-stimulated adenylate cyclase.

Adenylate cyclase can be resolved into at least two protein components, neither of which by itself catalyzes the formation of cyclic AMP with Mg-ATP as substrate. Mixture of the two reconstitutes Mg-ATP-dependent, fluoride- and Gpp(NH)p-stimulable activity. One, a heat-labile, N-ethylmaleimide-sensitive protein of molecular weight 190,000 can catalyze cyclic AMP formation with Mn-ATP as substrate, and is therefore proposed to be the catalytic moiety of the adenylate cyclase complex. The other protein (or proteins) is more resistant to heating or N-ethylmaleimide, and is proposed to confer upon the catalyst the ability to ultilize Mg-ATP as substrate. It is also required for the regulation of that activity by guanine nucleotides, hormones, and probably fluoride ion. The catalytic protein is found in a phenotypically adenylate cyclase-deficient (AC-) variant of S49 lymphoma cells. The thermostable regulatory protein can be resolved from the catalyst by heat treatment or N-ethylmaleimide treatment of plasma membranes of wild-type S49 cells, rat or rabbit liver, or avian erythrocytes, and is also found in a phenotypically adenylate cyclase-deficient hepatoma cell line. Mixture of AC- S49 membranes, which contain the beta-adrenergic receptor, with a crude detergent-solubilized preparation of the regulatory protein reconstitutes hormone-stimulable adenylate cyclase activity. Binding of the regulatory protein to the membranes is a time- and temperature-dependent process that requires an activating ligand of the adenylate cyclase system [fluoride, Gpp(NH)p].


Processing of common precursor forms of adrenocorticotropin and endorphins in cultures of mouse pituitary cells and in mouse pituitary.

The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) in mouse pituitary cells (AtT-20) have been investigated. Three forms of the precursor have been resolved by sodium dodecyl sulfate (NaDodSO4) polyacrylamide gel electrophoresis with apparent molecular weights of 29,000, 32,000 and 34,000 (29K, 32K, and 34K ACTH-endorphin). The three precursor forms have a very similar peptide backbone, but their carbohydrate content differs. In particular, a tryptic glycopeptide has been observed in 32K ACTH-endorphin which is not present in 29K ACTH-endorphin and has been identified as a tryptic peptide containing the alpha(22--39) sequence of ACTH. Pulse chase and continuous-labeling studies with radioactive amino acids and sugars suggest that the 29K form is converted to the 32K and 34K forms of the precursor by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate.


Self-administration of delta 9-tetrahydrocannabinol by rats.

The present study examines the dose-response pattern of delta 9-tetrahydrocannabinol self-injection in naive rats at 80% reduced body weight and 100% body weight, both conditions with a fixed-time 1 min (FT-1) food delivery schedule. The results indicated that food deprived animals tested on a FT-1 min schedule self-injected low doses of delta 9-THC at a higher rate than those animals at 100% body weight and on a FT-1 min schedule. Animals at 80% reduced body weight without a schedule did not differ from rats self-injecting delta 9-THC at free feeding situation. These findings suggest that rats without previous history of drug dependence self-administer low doses of delta 9-THC and that the interaction between the food deprivation state and the environmental contingencies introduced by a FT-1 min schedule is a critical variable in the acquisition period.


Effect of autoanalgesia on CNS enkephalin receptors.

Fear conditioning to foot shock (15 sec/day, 12 days) elicited autoanalgesia in 10 male (Sprague-Dawley) rats, while 17 non-shock control rats exhibited no analgesia as measured by the tail-flick assay. The binding of 3H-leu-enkephalin to synaptosomal preparations isolated from fear conditioned (experimental) and control animals was analyzed. At leu-enkephalin concentrations of 10(-9) M or less, both synaptosomal preparations demonstrated high affinity binding with dissociation constants on the order of 10(-10). Binding of leu-enkephalin could not be displaced by a hundred-fold excess of naloxone at leu-enkephalin concentrations less than 10(-9) M. However, the ability of naloxone to compete with leu-enkephalin for binding sites progressively increased at concentrations greater than 10(-9) M leu-enkephalin. At these ligand concentrations, the competition of naloxone for leu-enkephalin binding sites was more dramatic in the control than in the experimental animals. These data support the existence of two classes of receptors for leu-enkephalin, one of which is not blocked by opiate antagonists. Furthermore, changes in binding capacity associated with autoanalgesia produced by conditioned fear are consistent with the hypothesis of endogenous release of opiate-like peptides in response to stress.


Disease of the vertebral basilar system.

Patients with acute bilateral, crossed, or multisystem neuroanatomic symptoms associated with cranial nerve palsies may have vertebral basilar system disease. Surgically correctable lesions are usually not found in these patients, and medical therapy with short-term anticoagulation or antiplatelet agglutination may be prescribed in those patients with transient ischemic attacks or progressing stroke.


[Observations on the behaviour of anti-HAV antibodies (author's transl)].

The behaviour of anti-HAV antibodies was studied in the following conditions: a) a sample group of 2645 subjects from a healthy population; b) a group of 32 subjects with previous HB-Ag negative viral hepatitis; c) 12 cases of acute virus A hepatitis; d) a group of 18 anti-HAV positive women at the end of their pregnancies the antibodies were thus also studied in the funicular blood and in the newborn babies. The results showed: a) high reactivity (78%) of the healthy population to anti-HAV's; b) the possibility of an a posteriori diagnosis of virus A hepatitis in the presence of serology, negative for B type hepatitis, and positive for the anti-HAV's but with a titre higher than 1:200; c) the possibility of a serological diagnosis of acute virus A hepatitis in the presence of serology, negative for B type hepatitis and positive for the anti-HAV's with high and progressively increasing titre; d) the possibility of anti-HAV antibodies passing from mother to foetus, and the rapid elimination of the antibodies by the newborn baby within a month of his birth.


[Protective effect in the serum of rabbits inoculated with BHK-21 cells infected with foot-and-mouth disease virus].

The present investigation was developed to determine the presence of protecting effects in the serum of rabbits inoculated with BHK 21 cells infected with foot-and-mouth disease virus, subtype C2. The rabbits received 252 mg. of antigens harvested 60, 65, 75, 90, 120 and 210 minutes post infection. These antigens were inactivated with two procedure: formaldehyde 0.015% and beta-propiolactone 0.2% and were inyected with incomplete Freund's adjuvant; the last inoculations were given with live antigen without adjuvant. The immunization period lasted approximately for six months. A seroprotection test in suckling mice was performed with each antiserum. The antisera corresponding to 75, 120 and 210 minutes post infection had protector effect. But antisera obtained with BHK cells at 75 minutes showed highly significant protective effect, as compared with the other two sera.


[Subtypes of foot-and-mouth disease virus type A. Genetic markers of clones obtained from 4 strains isolated in Argentina between 1961 and 1970].

The results obtained studying the genetic markers g, t and rtc of different clones of subtypes of foot-and-mouth disease virus type A are presented in this paper. The subtypes were isolated during outbreaks of foot and mouth disease in Argentine. No significative differences among the subtypes were observed with the t marker. For the other markers, the results seem to indicate a gradual change related with the serological variation. Because of their sensibility to guanidine hidrochloride, it is possible to conclude that the studied clones do not belong to the so called European strains.


Salmefamol and salbutamol. An experimental comparative study of their action on tracheal and bronchial smooth muscles.

An experimental comparative study has been undertaken to evaluate the action of salmefamol and salbutamol, two sympathomimetic drugs specific for the beta-receptors, on tracheal and bronchial smooth muscles. Salmefamol showed a more intense, longer-lasting beta-adrenergic activity than salbutamol did.


[On the pathogenesis of isocyanate-induced asthma].

3 asthmatic patients, occupationally exposed to vapors of toluylene diisocyanate (TDI), responded with a moderate to strong elevation of airway resistance up to the 26th h after inhalation challenge by 0.006--0.02 ppm TDI. No changes in chest radiographs and in DLCO were found. In none of the patients' sera, isocyanate-specific antibodies could be detected by RAST and Ouchterlony test. Change of job resulted in one case in an immediate interruption of the asthmatic symptoms, whereas in 2 patients recovery was slow over a period of 3 to 8 months and not complete. Our investigations suggest a toxic effect of isocyanates, which depends on their concentrations, and an important pharmacological reaction; but, up to now, there were no signs of allergic mechanisms.


Efficacy, safety and hypothalamic-pituitary-adrenal axis function in patients with asthma treated with cloprednol.

Cloprednol was tested in 25 patients with chronic reversible bronchial obstruction, with respect to changes in hypothalamic-pituitary-adrenal (HPA) axis function and its efficacy on their clinical asthma. Patients were treated by a single morning dose for a 6-month period. The HPA axis function as estimated by fasting plasma cortisol levels did not show any significant changes, but adrenal response, assessed by ACTH stimulation test, was found slightly less at 6 months than at 3 months and at baseline. Pulmonary function tests--FEV1 and Raw--showed some improvement during the trial period. The score of respiratory complaints and symptoms, as well as the subjective status of the patients, showed a trend towards improvement. No significant side effects were observed.


[Association of acquired polyagglutinabilities of types T and B. An observation].

Although T and acquired B polyagglutinabilities are not exceptional, simultaneous occurence of the two types is a rarer phenomenon. Ten days after an open heart surgery operation, the patient, age 55, had an infectious syndrom : two strains, Clostridium perfringens and Peptococcus variabilis were isolated. Simultaneously, her red cells were found to be polyagglutinable. The association of T and acquired B polyagglutinabilities could be demonstrated by serological studies of the patient's red cells, and by in vitro transformation of normal red cells using culture supernatants obtained from the two isolated strains.


Hodgkin's disease and infectious mononucleosis.

Sequential sero-positive infectious mononucleosis is described in 3 sibs, 2 of whom subsequently developed Hodgkin's disease. EB virus antibodies were present in the serum of both cases.


Angiotensin converting enzyme. III. Changes in serum level as an indicator of disease activity in untreated sarcoidosis.

The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma.


Angiotensin converting enzyme. IV. Changes in serum activity and in lysozyme concentrations as indicators of the course of untreated sarcoidosis.

The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity.


Determination of quartz on membrane filters by X-ray diffraction.

An X-ray diffraction method is described for the quantitative determination of quartz in dust samples. The analysis was done directly on a collecting cellulose ester membrane filter of the type used in an air sampler. Quantitation was achieved by the measurement of the quartz line intensities with a digital integrator and by the comparison of these values with those measured from calibration standards prepared on similar filters with water suspensions. The overall precision of the procedure was 8%. When the method was applied to foundry dusts, the accuracy of the quartz analysis was fou,d to be within 10% at the 1- to 10-mg level of total loading. The detection limit for quartz was below 0.1 mg.


[Coronary atherosclerosis and serum lipoproteins].

VLDL triglycerides were increased both in obese patients and obese controls. In lean CHD patients the VLDL triglycerides were higher than in lean controls but lower than in obese CHD patients. CHD patients had lower HDL cholesterol than controls. The lowest HDL cholesterol was observed when VLDL triglycerides were high in both CHD patients and controls. However, the differences in HDL cholesterol between CHD patients and controls with low VLDL triglycerides were more marked. It appears that factors other than VLDL triglycerides may also contribute to the low HDL cholesterol observed in CHD patients. Serum cholesterol and triglycerides did not reflect the more subtle changes occurring in the lipoprotein lipids of CHD patients.


[Treatment of smokers by the chirotesist Hermano. 5 year catamnesis].

A study of a random sample of 532 cigarette smokers was made among the persons treated by the chirothesist Hermano in Seon (Switzerland), who had cured smokers of their nicotine addiction. They were examined immediately befroe the treatment ritual, then 4 months, 1 year and 5 years after the treatment. The patients of the healer were chosen from all the strata of the population. They were heavy smokers with an average of 31 cigarettes smoking rate per day for males and 24 cigarettes per day for females. Four months after the treatment, 40% of the treated persons, 12 months after the treatment 32.5% and 5 years after it 20% of the treated persons were completely freed of recidivism. Another 3.7% did smoke but only sporadically up to 5 years. Two thirds of the patients mentioned a suggestive effect which they consciously registered or which they remembered in the sense that their urge to smoke had diminished partly or disappeared completely thanks to the treatment. The analysis of the dynamics of recidivism showed that apart from its complete absence the cases of partial success in the sense of a moderation of the smoking, or as to a transitional stoppage were only a few. The methodical control of the follow-up study showed that the recidivists showed a lesser readiness to answer during the catamnestic examinations and it is therefore necessary for all the follow-up studies as well as for the comparative therapeutical research to take into consideration the degree of completeness of the catamnestic examination.


[Histological study of the bone marrow in 96 cases of Waldenstrom's macroglobulinemia. An evaluation with clinical, haematological and biological data (author's transl)].

Bone marrow biopsy in Waldenstrom's macroglobulinemia shows three types of lesions: lympho-plasmocytic and reticular infiltration, which is the most common, reticular infiltration, and aplastic marrow, more seldom. In all cases the reticulinic network is increased and thickened. These lesions are diffuse or nodular. Diffuse infiltration is more severe and has a median duration of 62 months instead of 82 months in nodular infiltration.


[Lymphomas of the spleen and bone marrow lymphoid nodules (author's transl)].

Many nodular primitive non-Hodgkin's lymphomas of the spleen have a favourable course after splenectomy or chemotherapy. Several observations of this type have been reported in the literature, in which the concept of malignancy is discussed, authors referring to a presarcomatous state or to an idiopathic splenomegaly. The evaluation of the extension of those sarcomas, however, very often show hepatic lesions, and always an increase in the lymphoid marrow nodules. The significance of these nodules is discussed here, with reference to 14 personal observations. These nodules may not always reflect a real extension of the sarcoma to the marrow. From a practical point of view, the presence of lymphoid marrow nodules, when associated with an isolated splenomegaly, is a strong argument to suspect a sarcoma of the spleen, and indicates a splenectomy.


[Non secretary plasma cell leukemia with intracytoplasmic kappa light chains (author's transl)].

A 53 years old female patient with plasma cell leukemia (more than 90% plasma cells in the peripheral blood, and an absolute plasma cell count reaching 147,000/mm3) is described. Electrophoresis and immunoelectrophoresis of serum and concentrated urine did not reveal any paraprotein. No surface immunoglobin has been detected on plasma cell cytoplasmic membranes. The presence of intracytoplasmic kappa light chains has been demonstrated by immunofluorescence and electron microscopy using the immunoperoxydase technique.


[Adult medulloblastomas. Clinical, anatomical and therapeutical study on seventeen cases (author's transl)].

Medulloblastoma is classically a childhood tumor, but one third of the cases occurs in adulthood. 17 adult cases are reported here (12 men, 5 women). The average age was 26 years 6 m (from 16 to 47 years). Pre-surgical clinical course is shorter before 30 years (7 months) than after (up to 24 months). Initial symptoms were intracranial hypertension with signs of lateralisation in 2:3 of the cases (cranial nerve and pontocerebellar syndroms). Vertebral angiography, scintigraphy, tomodensitometry helped to the diagnosis. Morphologically, two variants of tumors were found: soft and infiltrative classical medulloblastoma (12 cases) and desmoplastic medulloblastoma which was firmer and better limited (5 cases). The treatment consisted of a surgical removal, as complete as possible, then of an entire neuraxis radiation. Three operated patients died before 6 weeks. Among the 14 other cases, six patients are still alive three years, four other, five years and one, 22 years after the operation. This histological type was of no influence on the post-operative course. Remote metastasis were noted in cauda equina (3 cases), in spinal cord (1 case), in bones and lymphatic nodes (3 cases).


[Circulating immune complexes in rheumatoid arthritis. Results of a personal research (author's transl)].

Using the technic of Pillot and Grangeot (précipitation by PEG 6,000 at 2.5%, followed radial immuno-diffusion), the authors have detected circulating immune complexes (CIC) 38 times in a group of 55 RA. The presence of CIC is significantly more frequent in sero-positive RA, but without correlation between the concentration of CIC and the positivity rate of Waaler-Rose reaction. There is no correlation between the evolutive state of RA and the presence or the concentration of CIC. The sedimentation rate is, in mean, significantly higher in RA with CIC; but, among these, there is no correlation between sedimentation rate and the concentration of CIC. In the group studied, the CIC are present in all cases of RA with vasculitis or visceral symptoms.


[Effects of an antiinflammatory drug (diclofenac) in primary chronic glomerulo-nephritis (author's transl)].

Chronic Glomerulo-Nephritis (GN) are among nephrologic diseases, frequent and severe. In most of them immunological process are involved. Non steroïdal antiinflammatory drugs are able to reduce proteinuria, mainly in Membrano-Proliferative GN and IgA Mesengial GN. A protracted administration is necessary for proteinuria reappeared when treatment is interrupted. With long term administration renal prognosis is improved and severe renal insufficiency delayed. Among active antiinflammatory drugs (indometacine, ketoprofen, diclofenac, flurbiprofen, etc.) diclofenac is one of the best tolerated.


[Pituitary investigations in idiopathic haemochromatosis (author's transl)].

Twelve patients with idiopathic hemochromatosis have been studied. Hypogonadotropic hypogonadism with normal prolactin appears to be a most constant finding. Other hypophysal functions are preserved. A rapid exploration of such patients with LHRH-TRH and insulin tolerance test is proposed.


[Value of radiological examination in patients with pheochromocytoma. Results in four cases (author's transl)].

The authors report 4 cases of pheochromocytoma and analyse the interest of the different x ray examinations. The authors show the interest of angiography, particularly selective angiography, for small tumors, ectopic and multiple abdominal localisations, and metastases. The benign or malignant nature of the tumor, in the absence of metastases, is difficult to assess by x ray examinations alone.


[Quantitative study of the medullar fibrosis in 84 cases of idiopathic myeloid splenomegaly (author's transl)].

84 bone marrow biopsies were analysed by quantification methods with Classimat. The initial diagnosis was: idiopathic myelofibrosis with splenomegaly. A previous study divided the patients among three categories, according to the classification in three progressive stages of the bone marrow disease. The quantitative lecture was done after reticulin coloration, "in blind", and on several biopsies from the same patient. The results show good correlation with classical histologic methods. The quantitative measure of fibrosis is already important as soon as the first stages of the disease. Correlations with prognosis are more difficult to define.


[Treatment of headaches in general practice. A therapeutic study (author's transl)].

A therapeutic study was conducted by practitioners working in a group practice, to evaluate the activity of tiapride in treating headaches, over a period of 1 year. The results were satisfactory in 60.6% of cases, especially in patients with headaches of psychogenic or digestive origin. The dosage was 150 to 200 mg orally, and the product was well tolerated apart from somnolence which was noted in about 1 case out of 4.


[Sideroblastic anemia in a multiple myeloma treated by melphalan (author's transl)].

A case of sideroblastic anemia arised in multiple myeloma is related. Eighteen cases of literature are studied. This evolution usually appears in old and remitted myeloma. The pathogeny of the sideroblastic anemia is unknown, and possibly related to leukemia complicating multiple myeloma.


[Porcelain gallbladder and cancer (author's transl)].

The porcelain gallbladder is a rare entity. It reaches especially the old woman. Most of the porcelain gallbladders have a great clinical latence. A cancer of the gallbladder exists in eleven per cent of the cases: this justifies a systematic cholecystectomy of the calcified gallbladders, even if they are asymptomatic. Another digestive cancer exists in nine per cent of the cases. Three personal observations of porcelain gallbladder which are associated with a cancer are described: they confirm the facts of the literature.


Preliminary report on an unidentified virus from infantile myocarditis.

A preliminary report on an unidentified virus from two cases of infantile myocarditis is presented. The virus isolated from two separate occasions showed characteristics of an enterovirus. The significance of this virus in its association with infantile myocarditis requires further investigation.


[Acute tuberculous meningitis in children. A report on 4 cases (author's transl)].

Four children were treated for acute tuberculous meningitis. One child died and 2 others were left with severe neurological sequellae. The diagnostic and clinical signs of tuberculous meningitis are reviewed. Treatment includes the administration of an association of INH-rifampicine and ethambutol orally, or INH-ethambutol-ethionamide intravenously when oral administration is impossible. Intrathecal injections of rifamycine SV can be given for acute forms. Corticoids have only one indication: intracranial hypertension with cerebral edema, which requires surgical decompression if no improvement is obtained. The fact that cases of tuberculous meningitis are still notified, is a justification for early BCG vaccination and regular control of the tuberculin allergic reaction.


[Duodenal ulcer and pyloric micro-gastrinoma. A report of one case (author's transl)].

We report a case of micro-gastrinoma associated with a duodenal ulcer. This ulcer was severe and a gastrectomy (Finsterer) was performed. Pathologic examination showed a "carcinoid islet cell-tumor" with argyrophil granules in the cells' cytoplasme and ultrastructural studies confirmed neurosecretory granules with dense central core. Using the immunofluorescence and immunoperoxydase technic with several anti sera against polypeptide hormones we were able to show it was a pure gastrinoma. We presume this association is a new entity in gastrin-cells pathology.


[Extensive scabies in a baby (author's transl)].

The authors are reporting a new case of widespread scabies in a baby. They take this opportunity to emphasize on the atypical erythematous and excoriated papular rash which sometimes may be vesicular and hyper-keratotic. This widespread eruption may mimic generalised dermatitis, pustular psoriasis and even histiocytosis X. They also underline importancy of longlasting ointment with fluorinated steroid being responsible for this widespread eruption.


[Functional renal failure (FRF) in cirrhosis (author's transl)].

Frequent complication of advanced cirrhosis, spontaneous or in response to different causes, FRF is chiefly characterized by hyponatraemia, progressive azotaemia, hyperkalaemia and severe oliguria. Its functional nature is proved but its mechanism remains doubtful: it may be due to decreased "effective" plasma volume or renal arteriolar constriction. Its treatment is disappointing and in spite of new technics, gives only transitory improvements.


[Review on the properties of glial cells of the central nervous system (author's transl)].

During the past 15 years, increasing studies have been devoted to glial cells, i.e. oligodendrocytes, astrocytes and microglial cells of the central nervous system. Although most of their functions remain mysterious, the concept of intracellular interactions between neurons and neuroglia becomes more and more substantiated. This review describes some aspects of phylogeny of glia, recent technical approaches to the study of these cells, their major morphological and biochemical characteristics, their maturation as well as their pathology.


Silica and silicates in femoral lymph nodes of barefooted people in Ethiopia with special reference to elephantiasis of the lower legs.

Electron microscopy of femoral lymph nodes of barefooted Ethiopians show the presence of numerous particles of colloid-size and electron-density in the lysosomes of the macrophages in the gland. On diffraction analysis, the particles are found to be amorphous. Elemental microanalysis of the X-ray spectrum indicate the predominance of Si, Al and Fe. In elephantiasics some particles contain silicon alone, presumably silica. The distribution of the Al/Si ratios of the particles in subjects with elephantiasis of the lower legs show a difference from that of non-elephantiasics which is statistically "highly significant" at p less than 0.001. The importance of this as a possible aetiological factor in the disease is discussed. The hypothesis that the disease is discussed. The hypothesis that the disease is a silicosis of the peripheral lymphatics of the lower limbs is supported by the present study.


Inhibition of lactate dehydrogenase activity from Dirofilaria immitis by suramin.

Lactate dehydrogenase from adult D. immitis was partially purified and characterized. The molecular weight of the enzyme was determined to be 130 000. The specific activity of the lactate dehydrogenase was 4.1 U/mg in the direction of NADH-oxidation and 0.38 U/mg protein in the direction of NAD-reduction. The Michaelis constants were determined to be 0.028 mM and 0.9 mM for NADH and NAD, respectively. Suramin was found to be a potent inhibitor of the lactate dehydrogenase activity. The inhibition constant was calculated to be 0.006 mM. The type of inhibition by suramin was competitive with respect to the cofactors. The Km-values for pyruvate and lactate were determined to be 0.3 mM and 11mM, respectively.


Study of cell surface antigens induced by herpes simplex virus. Note II. Some properties of the antigens.

Surface antigens induced by herpes simplex virus infection in HeLa cells remain unaltered after treatment of the cells with 2% formalin for 10 min or with 0.08% trypsin for 15 min at 37 degrees C. A longer trypsin treatment (for 1 hour) will cause gradual alterations in the virus-induced antigens. Hence, these antigens are proteins deeply implanted within the cellular membrane. Their mobility--optimal at 37 degrees C--allows aggregation of the antigens in the form of caps or patches by polyvalent ligands such as IgG.


Transplacental cancerization by Rous sarcoma virus.

Experimental data obtained in the mouse are presented, pointing to the possibility of transplacental transmission of the genetic information contained in the genome of Rous sarcoma virus(RSV), by either intact RSV virions or nucleic acids extracted from infectant suspensions of tumors induced by the Carr(Ziber) on Bryan RSV strains.


Enterovirus diseases with neurological determinations in adults. Clinical and virological study.

Enteroviruses--4 polio, 30 Coxsackie and 20 echovirus strains--were isolated from 54 patients with neurologic disease. In 29 cases (53.7%) viruses were isolated from the CSF, blood clot and nerve tissue homogenates. The correlation of the complex clinical data and the localisation of the lesions in the CNS demonstrate the involvement of cranial nerves, of the long bulbar motor pyramidal and extra-pyramidal tracts, of the reticular formation, a.o. These aspects are in accordance with the localisation of the lesions especially in the brain stem and in the hypothalamus, in most of our patients. The extent and complexity of the lesions suggest a predominatly vascular dissemination.


Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids.

Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain.


Regulation of Neurospora crassa nucleosidases by some environmental factors.

Enzymic cleavage of N-glycosidic bonds of AMP, GMP, and inosine by the cell-free extracts of Neurospora crassa has been studied. The enzymic activities with these substrates appear to be discrete from one another. The levels of these enzymes in the cell vary with age, and are dependent upon the inoculum size, aeration rate, and phosphate level in the medium. Glucose (or ribose) controls the phosphate-mediated repression of all the three nucleosidases of this fungus.


[Eye and lymph drainage].

Up to now lymphatics in the eye could not be pointed out. An ocular lymph drainage is denied. Földi succeeded in producing experimentally the syndrome of "lymphostatic encephalopathy and ophthalmopathy" by operative blockade of the cervical lymphatics in animals. In the first part of the present paper a historical view considering the subject "Eye and lymphatic system" is given. In the second part it is entered into the particulars of own experimental studies. As to our own investigations, rabbits have been injected 99mTc-sulfur-colloid, 99mTc-microcolloid, 99mTc-Albumin and 198Au-colloid into the retrobulbar space, anterior chamber, vitreous body and subconjuctival space of one eye. Measurements of the activity's distribution have been made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after section with a sodium iodine crystal well counter (Clinimat-200, Picker). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. After injection in the retrobulbar space a significant concentration of the activity could be observed for the most part in the equilateral Lymphonodulus cervicalis profundus. By the cervical lymph blockade the removal of lymphoctopic substances from the retrobulbar space was largely inhibited. After injection in the anterior chamber a significant concentration could be observed for the most part in the equilateral Lymphonodulus cervicalis superficialis. After intravitreal injection a drainage to the bilateral deep cervical lymph nodes could be observed. After injection into the subconjunctival space a significant accumulation of activity could be registered in the equilateral Lymphonoduli mandibulares and cervicales superficiales. The data substantiate a segmental lymph drainage from the eye: vitreous body and retrobulbar space for the most part into the Lymphonoduli cervicales profundi, anterior chamber and subconjunctival space for the most part into the Lymphonoduli cervicales superficiales been studied. In albino-rabbits indiaink has been injected into the vitreous body and afterwards its drainage has been controlled histologically (frozen sections). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. The lymph node dissection causes a massive deceleration of the India-ink's outflow; the perivascular connective tissue shows a clear edematous relaxation. The histological evidence suggests that 1. the vitreous body 2. the interstice between the glia cells of the papilla 3. the pial tissue between the neurone bundles of the optic nerve 4. the perivascular space around the central vessels of the retina 5. the subarachnoid sheath of the optic nerve may be interpreted as prelymphatic pathway.


The shark rectal gland: a model for the active transport of chloride.

The rectal gland of the spiny dogfish, Squalus acanthias, provides an easily studied model of active chloride transport powered indirectly by Na-K-ATPase. Co-transport of sodium with chloride can be demonstrated in membrane vesicles isolated from basolateral membranes of the gland. Chloride secretion is under the hormonal control of vasoactive intestinal peptide, and possibly other agents, via adenyl cyclase and cyclic AMP. A similar mechanism is probably responsible for the active transport of chloride across other biological membranes.


Insulin response to an oral glucose load in relation to Lp(a)/pre-beta 1-lipoprotein levels in non-diabetic patients with peripheral vascular disease and in controls.

An oral glucose tolerance test (OGTT) was performed in 21 patients with previously known or recently detected peripheral vascular disease as well as in 16 age-matched controls. The angiographic results and the results in a physiological investigation were used to classify patients with high and low stenosis and normal controls, respectively. No significant differences in mean levels of insulin and blood glucose were found between patients with high and low stenosis, respectively, or between normal controls and (a) the whole group of patients with high stenosis, (b) only those with high stenosis who had not undergone arterial surgery. However, individuals with high amounts of Lp(a) lipoprotein were found to have significantly lower insulin mean levels during the OGTT and an even lower mean fasting level as compared to individuals without detectable Lp(a) lipoprotein. In the group of individuals with high amounts of Lp(a) lipoprotein, the glucose mean levels were also significantly lower, during a part of the OGTT. These findings are in agreement with previous results and suggest that inherited metabolic differences exist between individuals with high and zero or low levels of Lp(a) lipoprotein.


Histochemical characteristics of diphosphate nucleoside consumption in cat and rat nervous system.

Consumption of diphosphate nucleosides is investigated by histochemical methods in rat and cat nervous system. Results show NDP-ase is effectively in histological sections from animals previously perfused with glutaraldehyde or formaldehyde. Histochemical reaction is increased in presence of Ca++, Mg++, Mn++ or imidazole and inhibited by L-DOPA and Noradrenaline in incubation medium. A comparative study of TPP-ase and NDP-ase activities to dilucidate the identity of both enzymes is described.


[Electron-microscopic investigations on the localisation of the thiamine pyrophosphatase in the hippocampus of the Wistar rat (author's transl)].

This report describes the ultratopochemical localization of the thiamine pyrophosphatase in the pyramidal cells of the CA3 region of Wistar rat hippocampus. Attention was focussed on the occurrence of the enzyme out of the Golgi field. Thiamine pyrophosphatase was demonstrated in dendrites and - to a lesser extent - in axons. TTPase containing synapses were rather seldom and belonged to the axo-dendritic type. A hypothetic model concerning the transport and the distribution of the enzyme within the cell is presented.


Mucosaccharide histochemistry and histoenzymorphologic observations on the epidermis of Ariosoma balearicum de la Roche (Anguilliformes, Pisces).

The epidermis of Ariosoma balearicum consists of three layers - the basal layer, the middle layer and the outer layer. In between the basal cells are found clusters of small lymphocytes which show a moderat acid phosphatase activity. The middle layer and the outer layer are composed of three types of cells - the polygonal cells, the mucous cells and the club cells. The mucosubstances within the mucous cells exhibit the properties of neuraminic acid containing mucosaccharides with vicinal hydroxyl, sulfate esters and carboxyl groupings. The superficial cells of the outermost layer are capable of secreting sulphated and carboxylated mucosubstances to form an extracellular mucous coating which in fish epidermis seems to be necessary for the accumulation of electrolytes. The club cells are generally provided with one nucleus or double nuclei which appear displaced from the center and constitute the main histological component of the middle layer. The contents of these cells, in addition to a strong protein uptake visualized by the positive reactions exhibited in the coupled tetrazonium and mercuric bromophenol blue preparations, gave positive response to neutral mucosubstances which appear to be a glycoprotein involved in the slime secretions. Alkaline phosphatase and TPP-hydrolysing enzyme which could be detectable in the basal layer and the basement membrane were correlated with the probable role that they could play in the transportation of various chemicals and nutriments through the cell membranes.


[The mechanism of the tetrazolium reduction and the effect of phenazinmethosulfate (author's transl)].

Modern results of the literature form the basis for the presentation of a scheme which shows the reduction of tetrazolium salts and the action of phenazine methosulfate under histochemical conditions. The reduction of tetrazolium salts passes the radical state and it hapens principally on the niveau of the flavin proteins and the ubiquinone. The importance of the superoxide radical for the reduction of tetrazolium salts under aerobic conditions is emphasized.


Histochemical and ultrastructural study of adult human tendon.

The authors have studied the enzymhistochemical and ultrastructural pictures of tenocytes of adult human tendons. High succinate dehydrogenase, cytochrome oxidase, TPN-diaphorase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity were found, as indicated both oxidativ, anaerobic and pentose-phosphate shung activity. Phosphorylase and glutamate dehydrogenase activity was medial, lipase and alcaline phosphatase activity was slight. In tenocytes well developed rough endoplasmic reticulum and GOLGI apparatus, large amount of free ribosomes were found.


Endobronchial granular cell tumor. Cytology of a new case and review of the literature.

We report the 45th case of endobronchial granular cell tumor in the literature and describe in detail the cytologic findings in bronchial brushings and post-brush washings. Our findings differ from those of the only other cytologic report of such a lesion. We review the literature and summarize the clinical and pathologic findings of endobronchial granular cell tumors. Cytologically the differential diagnosis is between granular cells, respiratory epithelial cells and macrophages. We feel that our criteria make the distinction between them easy. However, most importantly, one must suspect the lesion; otherwise, these "benign cells" will be passed over by the screening cytotechnologist.


Regional ketamine-induced depression of neuromuscular transmission in man.

The intravenous injection of ketamine in the human arm with isolated circulation, using the same technique as for intravenous regional anesthesia, produces a dose-related depression of neuromuscular transmission, as evidenced by the evoked response to supramaximal stimulation of the ulnar nerve with a nerve stimulator. The dose range of ketamine was 200, 25, 10, 5, 1, 0.5 and 0.25 mg, in 20 ml of 5% dextrose in water. The exact mechanism of this effect is discussed. This depression may have clinical significance under certain circumstances.


Nuclear inclusions in the human adenohypophysis. A fine-structural study of nontumorous and adenomatous pituitaries.

Electron microscopy revealed the presence of nonviral nuclear inclusions in human nontumorous as well as adenomatous adenohypophysiocytes, regardless of cell type. Based on ultrastructural appearances, the inclusions have been classified as simple bodies, complex bodies and filamentous aggregates. Many transitional forms were noted between the simple and complex bodies, however, no relationship between the nuclear bodies and filamentous aggregates was found. It can be concluded that the three types of inclusions are normal nuclear constituents. Since no accumulation of these structures was observed in cells associated with enhanced secretion it appears that they are not related to hormonal hyperactivity in the human adenohypophysis.


T and B lymphocyte subpopulations and leukocyte terminal deoxynucleotidyl-transferase in energy-protein undernutrition.

Children with energy-protein undernutrition showed a reduction in the number of circulating T lymphocytes identified on the basis of their ability to form rosettes with sheep red blood cells. T cells with a receptor for IgM (Tmu) were decreased whereas T cells with a receptor for IgG (T gamma) were increased. Surface immunoglobulin bearing B cells were comparable in well nourished and malnourished subjects but the proportion of B alpha was increased in the latter. "Null" cells without the conventional markers of T or B cells were proportionately increased. Leukocyte terminal deoxynucleotidyl-transferase activity was elevated in the majority of undernourished children and correlated with the proportion of "null" cells. The significance of these observations is discussed and it is suggested that "null" cells represent immature undifferentiated T lymphocytes.


Influence of lithium on cyclic AMP accumulation in isolated rat fat cells.

Lithium inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclase in vitro. It was found that lithium inhibited both the norepinephrine- and the glucagon-induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. It is suggested that lithium affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action.


On the mechanism of relaxation of tracheal muscle by theophylline and other cyclic nucleotide phosphodiesterase inhibitors.

The mechamism of action of theophylline was studied by investigating the relationship between relaxant effect and inhibition of cyclic nucleotide phosphodiesterase (PDE) and by studying interactions with adenosine actions. Guinea pig tracheal smooth muscle cyclic AMP PDE had two apparent KmS': 0.4 and 70 microM for cyclic AMP. Theophylline and papaverine competetively inhibited the low Km form. Hydrolysis of 2.0 microM cyclic AMP and cyclic GMP was inhibited by several drugs. Some agents (e.g. ZK 62 711, ICI 63,197, Ro 20--1724, dipyridamol) were considerably more potent as inhibitors of cyclic AMP than of cyclic GMP hydrolysis, while other agents (M & B 22.948 and dilazep) selectively inhibited cyclic GMP breakdown, and some (theophylline, papaverine, IBMX and SQ 20,006) showed little selectivity. There was a weak but significant correlation between inhibition of cyclic AMP phosphodiesterase and relaxation of tracheal smooth muscle in vitro. There was also a correlation between the ratio of IC25 cyclic AMP/IC25 cyclic GMP and the smooth muscle relaxation, indicating that inhibition of cyclic AMP rather than cyclic GMP hydrolysis determined relaxation. However, there was a marked tachyphylaxis to the relaxant effect of the cyclic AMP selective PDE-inhibitors, while the nonselective methylxanthines did not show tachyphylaxis. The effect of theophylline was antagonized by low concentrations of adenosine, which by itself caused a weak tracheal contraction. The effect of PDI-inhibitors can be partly explained by decreased cyclic AMP breakdown but other mechanisms, such as antagonism of endogenous adenosine, may contribute to the observed relaxant action.


Tryptophylglycine dipeptide in ACTH/MSH cells of the human hypophysis: its identification and studies on its antinociceptive effects in mice.

The ACTH/MSH cells of the pars distalis and pars intermedia of the mammalian hypophysis contain peptides with amino-terminal tryptophan which exhibit a strong fluorescence after treatment with modified formaldehyde vapour methods and with glyoxylic acid in the tissue sections from freeze-dried specimens. By homogenization of the hypophyses in ethanolic glyoxylic acid and subsequent heating the peptides can be converted to highly fluorescent beta-carboline derivatives; these can then be extracted with glacial acetic acid, separated by silica gel thin-layer chromatography and identified in UV light. Amino-terminal tryptophyl peptide from adult human hypophysis extracted and treated in this way gave the structure L-tryptophylglycine after acid hydrolysis. This structure was subsequently confirmed by producing a fluorescent derivative from authentic L-tryptophylglycine using the same reaction conditions as for the tissue homogenate. This derivative moved in the same way in thin-layer chromatography as fluorecent amino-terminal tryptophyl peptide extracted from human hypophysis. Thereafter a study was made of the antinociceptive effects of authentic L-tryptophylglycine administered subcutaneously in mice both alone and together with morphine. L-tryptophylglycine had no antinociceptive effects alone and neither did it change morphine antinociception. Also it had no apparent effects on the behaviour of mice. Thus, ACTH/MSH cells contain a dipeptide whose physiological function differs from the effects of ACTH, MSH and endorphins.


Electron microscopic features of a brain tumor induced in hamster by BK virus, a human papova virus.

In order to locate the target cells for malignant transformation by BK virus (a human papova virus) in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17) bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters.


Differentiation of the musculature of the teleost Brachydanio rerio. II. Effects of immobilization on the shape and structure of somites.

The development of the shape and structure of somites in the teleost Brachydanio rerio was studied in embryos under normal conditions and in immobilized embryos. Three different immobilization methods were applied: enclosure in agar, a glass rod in the neural tube and anaesthesia in MS-222. When the performance of the lateral body movements is prevented, the shape development of the somites in embryos and young larvae becomes reversed. When the agar-immobilization is terminated, the larvae resume their normal movements. In about 10 days, the shape of the somites is again as in control larvae. We conclude, that the lateral body movements have both a shape-determining and a shape-stabilizing role during the early stages of somite morphogenesis. It is suggested that in normal embryos differences in shortening between lateral and medial muscle fibres, cause differences in longitudinal growth of the muscle fibres and that the oblique muscle fibre arrangement is a consequence of these differences in growth. In immobilized embryos and larvae, the longitudinal growth of the muscle fibres is decreased. Also the difference in the longitudinal growth rate between lateral and medial muscle fibres diminishes in all somites. We conclude that for the normal morphogenesis of the somites the performance of the specific function, that is to bring about lateral body movements, is required. We suggest, that the impact of the lateral body movements on the development of the structure of the somites is mediated through adaptive growth of the muscle fibres. The suggestion may also apply to the development of the pinnate structure of muscles of higher vertebrates.


The role of cyclic AMP and cyclic GMP in byssinosis.

The lungs of female guinea pigs, either untreated or previously sensitized with aqueous extracts of cotton dust (AECD) were perfused via the pulmonary artery with 0, 10-6, 10-5 or 10-4 g/mL of lyophilized AECD in Tyrodes solution. Pressure changes in the pulmonary artery were monitored during this period. After perfusion, the pulmonary parenchyma was excised, frozen, and later analyzed for c-AMP, c-GMP, histamine, and total protein. Levels of c-AMP and histamine decreased while levels of c-GMP and pulmonary arterial pressure increased with increasing doses of AECD. Correlation coefficients, between the parameters measured, indicate that the ratio of c-AMP to c-GMP (c-AMP/c-GMP) was a better indicator of histamine depletion or change in pulmonary arterial pressure than was the level of either c-AMP or c-GMP alone. Comparisons of the relative changes in c-AMP, c-GMP, c-AMP/c-GMP, histamine, and pulmonary arterial pressure between sensitized and nonsensitized guinea pigs support the hypothesis that the acute changes in pulmonary function that follow breathing of cotton dust are due to the effects of pharmacoactive compounds and not to antigen-antibody response.


Metastatic carcinoma presenting as fulminant hepatic failure.

An unusual cause of fulminant hepatic failure is described. The patient, who presented with symptoms of liver disease, proved to have a small primary oat cell carcinoma of the lung with massive hepatic metastases. The clinical evolution was rapid, with marked elevations of SGOT (this without a prior hypotensive episode) and hepatic coma. Examination of the liver showed two types of necrosis: 1. infarction secondary to multiple tumor emboli in portal vessels and 2. overrunning of hepatic cell plates by expanding masses of tumor cells (somewhat analogous to piecemeal necrosis).


Partial trisomy 20 confirmed by gene dosage studies.

We describe a female infant with multiple congenital anomalies and mental retardation, pre- and postnatal growth failure, microcephaly, unusual facial appearance, and minor skeletal anomalies, all very suggestive of the partial trisomy 20(p) syndrome. Although she was born to karyotypically normal parents, she had an extra small metacentric chromosome. Analysis of metaphase and prometaphase chromosomes by GTG banding and Giemsa 11 staining showed that the extra chromosome was a number 20 with a deletion of the distal end of the long arm. Gene dose studies of adenosine deaminase (ADA) and inosine triphosphatase (ITP) supported the cytogenetic interpretation.


Small cell carcinoma of the lung and its histological origin. Report of a case.

A rare lung cancer consisting in part of small cell carcinoma of intermediate cell type and in part of well-differentiated papillotubular adenocarcinoma is described. Alcian blue-PAS staining was observed in the cytoplasm of the small cell carcinoma cells; the Grimelius argyrophil reaction was also positive in the cytoplasm of these cells. Electron microscopy revealed neurosecretory granules in the cytoplasm. At autopsy, a small cell carcinoma of intermediate cell type was found with both squamous features and gland formation. The cellularity and histological pattern of this tumor suggested the existence of a transitional pattern between small cell carcinoma of intermediate cell type, squamous cell carcinoma and adenocarcinoma. From the above findings, we think that small cell carcinoma including the intermediate cell type is derived from respiratory epithelial cells of endodermal origin with dedifferentiation of those cancer cells into neurosecretory cells.


Localization of myoglobin in normal and neoplastic human skeletal muscle cells using an immunoperoxidase method.

Using an immunoperoxidase method, myoglobin is localized in the cytoplasm of normal and neoplastic human skeletal muscle. The staining intensity is variable in individual cells. This can be explained by the variable concentration of myoglobin in the different fiber types of normal muscle or the different degree of differentiation in neoplastic muscle cells, respectively. A potential application of this method in tumor pathology is discussed in connection with myoglobin as a tissue-specific marker for skeletal muscle neoplasms.


Hormone producing pancreatic islet cell carcinoma: changing clinical presentation.

A patient with pancreatic islet cell carcinoma demonstrated spontaneous remission and recurrence of hyperinsulinism and disappearance of elevated plasma motilin levels. Despite evidence for gastrin production by the tumor initially, the Zollinger-Ellison syndrome was not diagnosed until three years after initial presentation. Diarrhea and steatorrhea could be attributed to hyperchlorhydria rather than to direct intestinal effects of elevated cirulating gastrin, gastric inhibitory peptide or motilin. Pancreatic islet cell carcinomas, considered as a type a APUD cell proliferation, frequently produce more than one hormone; the pattern of hormone secretion may differ with time and clinical manifestations may change accordingly.


Prostaglandin mediated inflammatory changes induced by alpha-adrenoceptor stimulation in the sympathectomised rabbit eye.

Topical application of 50 microliter of 0.1% noradrenaline or 10% phenylepherine to either a surgically sympathectomised or a guanethidine treated rabbit eye induced a transient increase in intraocular pressure (IOP), between 90 and 150 min, followed by a fall to hypotensive levels. These changes were accompanied by the development of conjunctival and anterior uveal hyperemia and an aqueous flare. Fluorescein angiography and microscopic examination after intravenously injecting colloidal carbon showed that the major site of disruption of the blood-aqueous barrier occurs in the ciliary processes. Slightly elevated levels of protein and prostaglandin-like activity (PG) were detected in aqueous samples withdrawn 3 or 5 h after application of either adrenergic agent. Prior treatment with indomethacin or phentolamine prevented the ocular hypertensive phase as well as the inflammatory changes, suggesting that the inflammatory rebound is mediated by PG and that PG release under such circumstances is closely linked to alpha-adrenoceptor activation. By contrast, the rise in IOP occurring after each of several successive daily applications of an alpha-agonist to a normal rabbit eye was not accompanied by hyperemia or an aqueous flare and was not inhibited by indomethacin pretreatment.


Surgical approach to retromandibular parotid tumors.

Because of the anatomy of the deep lobe of the parotid and its restrictive boundaries, retromandibular tumors may be asymptomatic until reaching massive size. Removal by an intraoral approach may be not only disappointing but also disastrous, with disintegration of the tumor and generalized spillage in the wound. Our experience suggests that the best approach to any type of tumor in this region is through the upper lateral cervical tissues with consideration of a mandibular osteotomy if the tumor extends into the retropharynx or the nasopharynx. This review of 12 patients who required osteotomy describes a high success rate with minimal complications.


Locally recurrent carcinoma after breast reconstruction.

The incidence of locally recurrent carcinoma after mastectomy is low--between 6 and 20%. Recent case histories of 4 patients who were clinically free of breast carcinoma and who developed local recurrence after reconstruction are reviewed. Possible relationships of breast reconstruction to local recurrence are discussed. The development of capsule formation in the reconstructed breast may denote recurrent disease.


Nitroprusside and the duration of tubocurarine and pancuronium.

Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside.


Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 2. Theoretical study of experimental models.

A certain number of theoretical models of immunological relations that 2 foot-and-mouth disease viruses can support, were constructed so as to discuss in each case, the results of the factorial analysis of the data. This method provided a specific answer to each of the questions that were asked in the presence of a test of this kind. The results obtained with several immunological cross-tests comparable to that of the A Greece 69-A Allier viruses, illustrated most of the theoretical models.


[Feedstuffs contamination by Penicillium cyclopium Westling. Frequency of penicillic acid producing strains (author's transl)].

For the last six years, 246 samples of feedstuffs, suspected for animal disorder, have been subjected to mycological examination, Penicillium cyclopium was present with more than 10(3) and 10(5) propagules per gram respectively in 42% and 6% of samples. The feeds mainly concerned are, in decreasing order of P. cyclopium frequency and contamination level : barley, maïze mixed feeds (50%), the straw (41%), hays (21%) and milk replacers (10%) (table 1). The penicillic acid bioproduction by fifty strains freshly isolated from these feedstuffs is investigated on wet crushed corn (60% water). After incubation at 25 degrees C for a week, extraction by ethyl acetate and purification, quantification is done by fluorodensitometry on TLC plates after exposure to concentrated ammonia (fig. 1). Among the strains, 50% produces less than 5 ppm, 4% between 10-100 ppm, 20% (100-1 000), 20% (1 000-5 000) and 6% (5 000-10 000 ppm) (table 2). Maximal yield obtained was 8 240 mg/kg. Hypothesis of a log-normal distribution of toxigenic strength is not rejected (fig. 2). On the whole, frequency and toxic yields are higher for strains originating from cereals. One may think that only a quarter of the strains might be considered as actual potential penicillic acid producers in agricultural conditions.


[Serologic detection of rotavirus infection in swine from the region of Brittany (author's transl)].

Indirect immunofluorescence (micromethod) was used to detect antirotavirus antibodies. Sera (166) were collected on adult pigs at slaughterhouse in the following french departments: Finistere, Morbihan and Ille et Vilaine. Antibodies were detected in 83% of the samples.


Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 1. A Greece 1969 -- A Allier example.

A double immunological cross-test, carried out with the index K method, is subjected to a statistical analysis by a factorial experiment. The A Greece and A Allier viruses, which have been taken as an example of the calculations procedure, seem to be in 2 immunologically different subtypes.


The biology of affective disorders.

The clinical features, genetic data, psychopharmacological studies, hormonal abnormalities, and biochemical observations all serve to define major depressive illness as an inherited neurochemical disorder affecting the hypothalamus, and probably involving monoamine pathways. While the precise nature of the defect and its mode of transmission remain obscure, the rapid development of this field in less than two decades permits optimism that major depressive illness illness will be among the first "functional" psychiatric disorders to have its chemical pathology elucidated.


Modified procedure for the recovery of naturally accumulated poliovirus from oysters.

Methods were compared for their ability to recover poliovirus from oysters (Crassostrea gigas) which had been allowed to accumulate virus via normal filtration activities. Clarification procedures included glycine-NaCl and polyelectrolyte extraction methods followed by a variety of acid precipitation concentration methods. Polyelectrolyte flocculation followed by a beef extract-supplemented acid precipitation carried out at pH 3.5 yielded the most efficient recoveries. Direct assay of homogenates was found to be an unreliable method for determining the initial virus concentration in "naturally infected" oysters.


Viral heat resistance and infectious ribonucleic acid.

High-titer suspensions of poliovirus 1 and coxsackievirus B-2 were shown to contain a heat-resistant fraction when heated for 65 min at temperature ranging from 56 to 70 degrees C. The addition of ribonuclease to the heated suspensions eliminated plaque production in the cell cultures, indicating that the resistant fraction was infectious ribonucleic acid that had been liberated from ruptured viruses during the heating process.


Adsorption of enteroviruses to soil cores and their subsequent elution by artificial rainwater.

The adsorption and elution of a variety of human enteroviruses in a highly permeable, sandy soil was studied by using cores (43 by 125 mm) collected from an operating recharge basin on Long Island. Viruses studied included field and reference strains of polioviruses types 1 and 3 and reference strains of coxsackie virus B3 and echovirus types 1 and 6. Viruses suspended in treated sewage effluent were allowed to percolate through soil cores, and the filtrate was assayed for unadsorbed viruses. To determine the likelihood of desorption and mobilization, soil-bound viruses were subjected to a rinse with either treated sewage effluent or simulated rainwater which reflected the anion, cation, and pH characteristics of a typical northeastern United States rainfall. The results demonstrated that all polioviruses tested, including both reference and field strains, adsorbed extremely well to cores. Adsorption was somewhat reduced when clean, unconditioned soils were used. Soil-bound poliovirus strain LSc was not significantly mobilized by flooding columns with either a sewage effluent or rainwater rinse. One virus was mobilized by both types of rinses. The amount of viruses mobilized by rainwater rinses ranged from 24 to 66%. Variable adsorption-elution results were observed with other enteroviruses. Two guanidine-resistant mutants of poliovirus LSc demonstrated a soil adsorption-elution profile different from that of the parent strain. The data support the conclusion that soil adsorption-elution behavior is strain dependent and that poliovirus, particularly strain LSc, represents an inappropriate model.


Procedure for the recovery of airborne human enteric viruses during spray irrigation of treated wastewater.

Because of the relatively low number of indigenous enteric viruses recovered from secondary wastewater effluents, their presence in air (aerosols) as a result of wastewater spray irrigation requires extensive sampling. Methodology to allow the recovery of indigenous enteroviruses from aerosols generated at an operational wastewater irrigation site was tested under both laboratory and field conditions.


Structural changes associated with poliovirus inactivation in soil.

The loss of infectivity of poliovirus in moist and dried soils was a result of irreversible damage to the virus particles. The damage included (i) dissociation of viral genomes and capsids and (ii) degradation of viral ribonucleic acid (RNA) in the soil environment. Under drying conditions, capsid components could not be recovered from the soils. Further studies in sterile soils indicated that, under moist conditions, the viral RNA was probably damaged before dissociation from the capsid. However, in sterile, dried soil, RNA genomes were recovered largely intact from the soil. These results suggest that polioviruses are inactivated by different mechanisms in moist and drying soils.


In vivo effect of the Syndets Idet 5L and Swanic 6L ON ATPase activity in the teleost, Channa punctatus.

Channa punctatus were exposed to various sub-lethal concentrations of Idet 5L and Swanic 6L for 25 and 50 days. Brain and gill homogenates were analyzed for enzyme activity from treated and untreated fish. Enzyme inhibitions were highest in oligomycin-insensitive Mg++ ATPase, with pronounced effects (over 65% inhibition) after 50 days exposure of fish to 7.5 mg/L concentration of Swanic 6L. Fish exposed to lowest concentrations of syndets showed an insignificant activation of Na+-K+ and oligomycin-sensitive Mg++ ATPases in the gill.