[Antialdosterones and enzymes of the adrenal gland].

With subcellular fractions of animal adrenals, the authors have looked for the effect of antialdosterones on different aspects of adrenal metabolism (steroidogenesis, some enzymes of intermediary metabolism, mitochondrial respiration). Antialdosterones act on mitochondrial respiration by inducing an uncoupling effect. Nature of this uncoupling cannot yet by precised. Antialdosterones inhibit steroidogenesis with concentrations corresponding to blood concentrations observed during treatment with these compounds. This inhibition could explain the annulation of hyperaldosteronism secondary to sodium loss and kaliemic replenishment. This enhance the interest of antialdosterones over other diuretics.


[Arterial and renal parenchymal histological data in the areas on polar and truncal arteries in arterial hypertension of adult patients].

The Cardiac Clinic reports its experience of 16 cases having unilateral curative renal surgery for hypertension in the adult, and has found a particularly high incidence (8 per cent of all cases). A study has been made of the lesions in the malformed and dysplastic renal arteries on the one hand, and of the correspondingly ischaemic and atrophic renal parenchyma on the other. Attention is drawn to the cases of unilateral renal atrophy (50 per cent of cases), the commonest involving gross lymphoplasia of congenital arterial origin. The other cases are of stenotic dysplasias, and special points to notice are the spread of the dysplasia towards the parenchyma, the presence of multiple aneurysms which militate towards nephrectomy, and the relative frequency of dysplasia of the intima (2 cases out of 8).


Dynamic changes of optokinetic after-nystagmus (OKAN) caused by brief visual fixation periods in monkey and in man.

Optokinetic nystagmus (OKN) continues after the cessation of visual stimulation in complete darkness as primary optokinetic after-nystagmus (OKAN I). After variable periods of time, it is followed by secondary OKAN (OKAN II). Short periods of visual fixation during OKAN I in monkey and in man inhibit OKAN I, but enhance OKAN II. The enhanced OKAN II starts earlier, lasts longer, and often reaches higher slow-phase velocities than in control experiments. Therefore, OKAN II depends not on the ocurrence or strength of OKAN I, but mainly on parameters of the preceding optokinetic stimulus. Results suggest that OKAN I duration is partially determined by the development of OKAN II.


Treatment of childhood epilepsy with dipropylacetic acid (DPA).

Dipropylacetate (DPA) was used in the treatment of different types of epilepsy in 112 children aged 1--20 years, with a mean age of 9.2 years, for a period of 19.8 months, ranging from 1 to 49 months. Of this group, 64 children were therapy-resistant to other antiepileptic medications prior to the introduction of DPA; 31 were treated for the first time with an antiepileptic drug, which was DPA; 44 were treated with DPA alone; and 68 had one or more additional antiepileptic medication. The following results were found while DPA was administered in a relatively high dosage with a mean of 48 mg/kg body weight/day and ranging from 7 to 125 mg/kg/day. 1. Statistically, the results are significantly better in primary generalized epilepsy than in partial or in secondary generalized epilepsy. 2. Ninety-two percent of 51 patients who had absences were treated successfully. The same applies to 87% of 30 patients with primary generalized grand mal with spike wave, to all four patients who had impulsive petit mal, and to 47% of the 15 patients who had centrencephalic myoclonic-astatic petit mal. 3. Positive effect of DPA in partial epilepsy and secondary generalized epilepsy was seen only if the EEG pattern was 'centrencephalic' besides focal changes. During therapy with DPA, five patients with pure focal EEG showed an increase in seizure frequency, which demonstrated complete therapeutic failure. 4. Centrencephalic seizure activity (irregular spike wave, 3/s spike wave, and more than 3.5/s spike wave) were treated successfully (P less than 0.001). Focal changes or focal sharp wave with tendency to spread or generalization were treated unsucessfully.


The cost of school dental care: a preliminary economic analysis.

The cost of school dental care provided by the South Australian School Dental Service is compared with the cost of funding similar care through an hypothetical alternative based on fee-for-service. The results of both cost-benefit and cost-effective analysis suggest that the school dental programme is an economically acceptable method of delivering school dental care.


Cost of health care services in the treatment of cancer.

In the provision of cancer therapy, usage of expensive cancer facilities and deployment of cancer services to the full, the aims and performance of a comprehensive cancer centre have been discussed. Increasing utilization of cancer chemotherapy and its cost have been contrasted with that of radiotherapy. With the current expansion in oncology there is a limit to what the cancer centre can make available within the specific tumour clinic role and for general cancer treatment purposes at other hospitals. It is timely to attempt rationalization of the cancer arrangements peripheral to the centre.


Substrate specificity and properties of uridine diphosphate glucuronyltransferase purified to apparent homogeneity from phenobarbital-treated rat liver.

1. The purification to homogeneity of stable highly active preparations of UDP-glucuronyltransferase from liver of phenobarbital-treated rats is briefly described. 2. A single polypeptide was visible after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, of mol.wt.57000. 3. Antiserum raised against the pure enzyme produces a single sharp precipitin line after Ouchterlony double-diffusion analysis. 4. The pure UDP-glucuronyltransferase isolated from livers of untreated and phenobarbital-pretreated rats appears to be the same enzyme. 5. The Km (UDP-glucuronic acid) of the pure enzyme is 5.4 mM. 6. The activity of the pure enzyme towards 2-aminophenol can still be activated 2-3-fold by diethylnitrosamine. 7. UDP-glucose and UDP-galacturonic acid are not substrates for the purified enzyme. 8. The final preparation catalysed the glucuronidation of 4-nitrophenol, 1-naphthol, 2-aminophenol, morphine and 2-aminobenzoate. 9. Activities towards 4-nitrophenol, 1-naphthol and 2-aminophenol were all copurified. The proposed heterogeneity of UDP-glucuronyltransferase is discussed.


Immunochemical characterization of casein from rabbit mammary gland.

1. Excellent precipitating antibodies to rabbit recombined casein polypeptides were obtained in a sheep after 8 weeks of immunization with rabbit recombined polypeptides coupled to Sepharose-albumin. 2. The antiserum was assessed for specificity by several immunochemical techniques and was monospecific when tested against acid-precipitated casein, recombined casein and extracts of lactating rabbit mammary tissue. 3. A specific anti-casein immunoglobulin fraction was prepared by immunoadsorption of the antiserum by using Sepharose-recombined casein as immunoadsorbent. 4. The specific anti-casein immunoglobulin was used to prepare a Sepharose-anti-casein immunoadsorbent for the isolation of casein from extracts of rabbit mammary tissue.


Superoxide dismutase and catalase in the protection of the proton-donating systems of nitrogen fixation in the blue-green alga Anabaena cylindrica.

1. Superoxide dismutase activity was present in the heterocysts and vegetative cells of Anabaena cylindrica, but was always lower in the heterocysts. 2. No qualitative differences were found in the superoxide dismutase from the two cellular types. 3. Catalase activity was also present in both cellular types. 4. Most of the NADP reductase activity, as assayed with menadione or ferredoxin as electron acceptor, was localized within the heterocysts. 5. Studies on H2 consumption showed that most of the hydrogenase activity was associated with the heterocysts. 6. The results are discussed in terms of the postulate that superoxide dismutase and catalase are involved in the protection of the proton-donating systems participating in N2 fixation and H2 metabolism of heterocysts.


Functional heterogeneity of UDP-glucuronosyltransferase as indicated by its differential development and inducibility by glucocorticoids. Demonstration of two groups within the enzyme's activity towards twelve substrates.

1. UDP-glucuronosyltransferase activity towards 12 substrates has been assessed in rat liver during the perinatal period. 2. Between days 16 and 20 of gestation, enzyme activities towards the substrates 2-aminophenol, 2-aminobenzoate, 4-nitrophenol, 1-naphthol, 4-methylumbelliferone and 5-hydroxytryptamine (the 'late foetal' group) surge to reach adult values, while activities towards bilirubin, testosterone, beta-oestradiol, morphine, phenolphthalein, and chloramphenicol (the 'neonatal' group) remain negligible or at less than 10% of adult values. 3. By the second postnatal day, enzyme activities towards the neonatal group have attained, or approached adult values. 4. Dexamethasone precociously stimulates in 17-day foetal liver in utero transferase activities in the late foetal, but not the neonatal group. A similar inductive pattern is found for 15-day foetal liver in organ culture. 5. It is suggested that foetal glucocorticoids, whose synthesis markedly increases between days 16 and 20 of gestation, are responsibile for triggering the simultaneous surge of all the hepatic UDP-glucuronosyltransferase activities in the late foetal group. The neonatal group of activities apparently require a different or additional stimulus for their appearance. 6. The relationship of these two groups of transferase activities to other similar groups observed during induction by xenobiotics and enzyme purification is discussed.


Metabolism and the triggering of germination of Bacillus megaterium. Concentrations of amino acids, organic acids, adenine nucleotides and nicotinamide nucleotides during germination.

A considerable amount of evidence suggests that metabolism of germinants or metabolism stimulated by them is involved in triggering bacterial-spore germination. On the assumption that such a metabolic trigger might lead to relatively small biochemical changes in the first few minutes of germination, sensitive analytical techniques were used to detect any changes in spore components during the L-alanine-triggered germination of Bacillus megaterium KM spores. These experiments showed that no changes in spore free amino acids or ATP occurred until 2-3 min after L-alanine addition. Spores contained almost no oxo acids (pyruvate, alpha-oxoglutarate, oxaloacetate), malate or reduced NAD. These compounds were again not detectable until 2-3 min after addition of germinants. It is suggested, therefore, that metabolism associated with these intermediates is not involved in the triggering of germination of this organism.


Metabolism and the triggering of germination of Bacillus megaterium. Use of L-[3H]alanine and tritiated water to detect metabolism.

L-[2,3-3H]Alanine was used to probe for metabolism of alanine during triggering of germination of spores of Bacillus megaterium KM. No detectable incorporation of label into any compound, including water, was found, indicating that any metabolism involving the alanine germinant must be at a very low rate and also that alanine racemase is absent from spores of this strain. Spores were germinated in 3H2O to find if any of the many metabolic reactions causing irreversible incorporation of 3H into reaction products took place during triggering of germination. No incorporation was detected until 2-3 min after addition of germinants. It is therefore concluded that a wide variety of metabolic routes, including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway and amino acid metabolism are either not involved in the reactions causing the triggering of germination or operate at an extremely low rate during this process.


Demonstration of functional heterogeneity of hepatic uridine diphosphate glucuronosyltransferase activities after administration of 3-methylcholanthrene and phenobarbital to rats.

After the administration of 3-methylcholanthrene to adult male rats, activities of hepatic UDP-glucuronosyltransferase towards six from a group of 12 substrates were stimulated by 250-350%. Activities towards the remaining six substrates were unaffected. Conversely, after phenobarbital administration, activities formerly stimulated by 3-methylcholanthrene remained unchanged, and the other six activities were stimulated by 160-280%. The relationship of these two groups of transferase activities to other evidence suggesting the same heterogeneity of the enzyme is discussed.


Comparison of atenolol with propranolol in the treatment of angina pectoris with special reference to once daily administration of atenolol.

Fourteen patients with angina pectoris completed a double blind trial of atenolol 25 mg, 50 mg, and 100 mg twice daily and propranolol 80 mg thrice daily. In comparison with placebo, all active treatments significantly reduced anginal attacks, consumption of glyceryl trinitrate, resting and exercise heart rate, resting and exercise systolic blood pressure, and significantly prolonged exercise time. There was no significant difference between the effects of propranolol and atenolol. Nine patients completed a further trial comparing atenolol given once or twice daily. Both regimens were effective and there was no significant difference between the reductions in anginal attacks, glyceryl trinitrate consumption, systolic blood pressure, or heart rate. Twenty-four-hour ambulatory electrocardiograms showed that atenolol consistently reduced heart rate throughout the 24-hour period whether given once or twice daily. Atenolol is a potent antianginal agent which, in most patients, is likely to be effective once daily.


Anaesthesia for studies of the cerebral circulation: a comparison of phencyclidine and althesin in the baboon.

The effects of phencyclidine on cerebral blood flow, cerebral metabolic rate for oxygen and carbon dioxide reactivity were compared with those of Althesin in six baboons. Under similar and stable levels (Stage 1) of electroencephalographic activity cerebral blood flow and the cerebral metabolic rate for oxygen were significantly less during the infusion of Althesin when compared with the values obtained during the infusion of phencyclidine. Reactivity to carbon dioxide was present and similar during the infusion of either drug.


E.E.G. monitoring for the control of anaesthesia produced by the infusion of althesin in primates.

The continuous infusion of Althesin under electroencephalographic (e.e.g.) control provided a constant level of light anaesthesia for periods of 1--5.5 h during experimental brain hypoxia in spontaneously breathing baboons and Rhesus monkeys. Polygraphic records (respiration, heart rate, arterial pressure, cerebral venous sinus pressure, end-tidal gas concentrations) and also estimation of blood-gas tensions, pH, and concentrations of pyruvate and lactate demonstrated a steady physiological state. Various methods of e.e.g. monitoring were tested to establish an optimal assessment of depth of anaesthesia as a guide to the control of the rate of infusion of Althesin. A purpose-built modification of the Cerebral Function Monitor was found to give unequivocal recognition of changing depths of anaesthesia.


Immunity to Brucella in mice vaccinated with a fraction (F8) or a killed vaccine (H38) with or without adjuvant. Level and duration of immunity in relation to dose of vaccine, recall injection and age of mice.

Immunity to Brucella in the mouse, assessed by bacterial spleen counts 15 days after intraperitoneal inoculation of a standard challenge of B. abortus 544, has been studied with two vaccines, one experimental, composed of a fraction of the bacterial cell-wall (F8) extracted from B. abortus 99, the other of killed whole bacteria, B. melitensis 53 H38, taken as reference (H38). The level of primary immunity depended on the dose of vaccine, the presence of oil adjuvant and the age of the mouse. The presence of adjuvant enabled the immunization to F8 to continue beyond the first month, to reach its maximum around the fourth month, and to remain stable for at least 7 months. A booster injection 3 or 6 months after the primary vaccination reinforced existing immunity but did not increase it beyond a certain level. The effect of the recall injection was clearly demonstrated with low doses which gave a lower level of primary immunity.


Endometrial ossification associated with secondary infertility.

A patient with secondary infertility and endometrial ossification after a spontaneous is described. The aetiology and pathogenesis of endometrial ossification are discussed.


Von Hippel's disease in association with von Recklinghausen's neurofibromatosis.

Ten members of a large family who showed manifestations of either von Hippel-Lindau disease or von Recklinghausen's neurofibromatosis were examined. Three of 10 members were found to have retinal angiomas which had not been present on fundus examination 3 years previously. These angiomas were associated with ocular and systemic signs of neurofibromatosis. These cases show overlapping manifestations of different phakomatoses and provide support for the concept of a common aetiology for these diseases.


The procuticle of Drosophila: heterogeneity of urea-soluble proteins.

Proteins, soluble in 7 M urea, 4 M guanidine hydrochloride, or 2% sodium dodecyl sulfate, have been extracted from untanned larval cuticles of Drosophila melanogaster. A major protein fraction, apparent molecular weight 8000 - 10 000, is resolved into eight different components (five major, three minor) by gradient gel electrophoresis under nondenaturing conditions. Proteins extracted in 7 M urea have been resolved by diethylaminoethylcellulose chromatography into five fractions, three of which are greatly enriched for electrophoretically homogeneous proteins. The five fractions have different amino acid compositions. Electrophoretic variants involving four of the five major proteins have been obtained. Preliminary genetic analysis indicates that at least three of the five proteins are specified by separate structural genes.


Structure of iturine A, a peptidolipid antibiotic from Bacillus subtilis.

A mixture of iturines extracted from Bacillus subtilis gave, on column chromatography, iturine A, iturine B, and iturine C. Iturine A has the entire antifungal activity. It is a mixture of two homologous peptidolipids C48,H74N12O14 and C49H76N12O14 (mp 177 degrees C, [alpha]D-1.7 degrees in methanol (c 0.05 g/mL); mol wt 1042 and 1056). The lipid moiety is a mixture of 3-amino-12-methyltridecanoic acid and 3-amino-12-methyltetradecanoic acid. The peptide moiety contains 7 mol of amino acids: D-Asn2, L-Asn, L-Gln, L-Pro, L-Ser, and D-Tyr. A cyclic structure for iturine A with the serine residue linked to the fatty amino acids through a peptide bond has been domonstrated. By mild HCl hydrolysis, lipid-soluble and water-soluble peptides were obtained. They were analyzed by chemical methods and by mass spectrometry. Permethylated and perdeuteriomethylated derivatives of iturine A were also subjected to mass spectrometric analysis. Both chemical analysis and mass spectrometry led to the cyclic structure I for iturine A.


Retention of the oxygens at C-2 and C-3 of D-ribulose 1,5-bisphosphate in the reaction catalyzed by ribulose-1,5-bisphosphate carboxylase.

Ribulose-1,5-bisphosphate carboxylase catalyzes the conversion of D ribulose 1,5-bisphosphate and CO2 to 3-phospho-D-glycerate, with retention of the oxygen atoms at both C-2 and C-3 of the substrate. This observation is consistent with mechanistic pathways involving an enediol intermediate and eliminates suggested mechanisms that involve covalent intermediates between the enzyme and ribulose 1,5-bisphosphate in which the substrate oxygen at C-2 or C-3 is compulsorily lost.


Mapping of transcribed regions of Euglena gracilis chloroplast DNA.

RNA transcription from defined regions of the Euglena gracilis chloroplast genome has been characterized by hybridization of total cell RNA to 3H-labeled chloroplast DNA restriction endonuclease fragments. Chloroplast DNA was digested into five fragments of 53, 35, 25, 10, and 6.9 kilobase pairs (kbp) with Pst1. The 53-kbp DNA was also subfractionated by BamHI digestion. The extent of transcription of the Pst1 fragments was found to be 30, 17, 15, 2.2, and 2.3 kb of RNA, respectively. The total amount of RNA transcription of 67 kb represents 26% to the double-strand information content of the genome. Transcribed regions are dispersed throughout the DNA. The RNA transcripts are present in two major abundance classes in the cell. High abundance transcripts of approximately 10(6) copies/cell were mapped in the rRNA gene region of the 53-kbp fragment and in the 35-kbp fragment. Low abundance transcripts of approximately 1000--4000 copies/cell were mapped in all five Pst fragments.


Sequence of a rabbit anti-Micrococcus lysodeikticus antibody light chain.

The complete sequence of rabbit antibody light-chain L 120 has been elucidated. The antibody was raised against Micrococcus lysodeikticus bacteria and is specific for the external part of the cell wall. All protein used in this work was obtained from a single 50-mL bleeding. The variable region of L 120 is compared to 13 other sequences of chains of different specificities. The constant region of this b4 k chain is identical to that of two other constant regions published earlier. The general structure of the rabbit light chain is compatible with the three-dimensional folding proposed for human myeloma chains.


Particle aggregation in photosynthetic membranes of the blue-green alga Anacystis nidulans.

Freeze-fracture electron microscopy demonstrates that in photosynthetic membranes of the blue-green alga Anacystis nidulans quenched from a temperature below growth temperature, areas devoid of membrane particles occur. We suggest that this phenomenon is related to phase transitions in the photosynthetic membrane.


Ribulose-1,5-biphosphate carboxylase-deficient plastome mutants of Oenothera.

In spite of only slightly subnormal pigment contents, two plastome mutants of Oenothera (Valpha, Isigma) were practically incapable of photosynthetic CO2 fixation and another one exhibited considerably reduced photosynthesis (IVbeta). While other photosynthetic enzymes were present as far as investigated, ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) activity was very low or missing altogether. As shown by gel electrophoresis, mutant IVbeta contained some, though little, fraction I protein. In the other two mutants fraction I protein could not be detected. Also, neither the small nor the large subunit of ribulose-1,5-biphosphate carboxylase could be found in these mutants. In immunodiffusion experiments with a monospecific antiserum against rye ribulose-1,5-bisphosphate carboxylase, only extracts from wild-type Oenothera produced visible precipitation lines. Still, the presence of very low levels of immunochemically reactive antigen was indicated for all three mutants. The highest level was observed in mutant IVbeta. The behaviour of the mutant extracts suggested that the antigens of mutant and wild type leaves reacting with the antiserum were not identical. All mutants appeared to have a coupled electron transport system as shown by ATP measurements, light scattering and 515 nm absorption changes. Linear electron transport was possible in the mutants. Still, the photoresponse of cytochrome f and fluorescence measurements suggested altered electron transport properties in the mutants. These are interpreted to be secondary lesions of the photosynthetic apparatus caused by primary deficiency in ribulose-1,5-bisphosphate carboxylase activity. From the absence in two mutants (Valpha, Isigna) of the small subunit of ribulose-1,5-bisphosphate carboxylase, which is known to be coded for by nuclear DNA and to be synthesized on cytoplasmic ribosomes, it appears that the genetic system of the plastids is capable of interfering with the genome-controlled synthesis of plastid components.


Vesicle production of heated and stressed erythrocytes.

Human erythrocytes develop vesicles by budding when heated to temperatures close to the thermal transition for spectrin. Regularly spaced strings of vesicles also develop if cells heated to 51--54 degrees C are pulled into unstable shapes by flow of liquid between cover slips. These strings of vesicles develop when cells which had attached to the glass are restrained in the flow by a long membrane-bound tether which maintains a connection with the attachment site on the glass. Breakup into regularly spaced vesicles suggests the breakup of a liquid-like cylinder by growth of Rayleigh instabilities. The ratio of length:diameter of the fragments of cylinder on which each disturbance grew ranged from 2.2 to 5.4 to 1 with a peak of 3.2, as measured from scanning electron micrographs. The upper limit of the range is slightly less than the ratio for the disturbance most likely to grow if surface tension and viscosity alone controlled the vesicle formation. Similar vesicle formation when the form-maintaining structures were weakened has been reported in other systems.


Bilayer-gel membranes. Formation and some properties.

We developed a new procedure which induces multifunctional reagents to crosslink at one interface between a black bilayer and the adjacent water phase. This procedure yields "bilayer-gel" membranes, i.e. membranes consisting of a bilayer and a polymer layer. The bilayer-gel membrane may tentatively be considered to be a new membrane system, because the formation of the polymer layer changes some bilayer properties. We studied bilayer-gel membranes composed of a bilayer of oxidized cholesterol and of a polymer layer of poly-L-lysine crosslinked by glutardialdehyde. Compared to unmodified bilayers, this membrane system has an electrical conductance of the same magnitude, the same electrical capacity and similar shapes of current-voltage dependences. However, this system is asymmetrical and differs in ion selectivity and increased stability from an unmodified bilayer.


The influence of branched-chain and omega-alicyclic fatty acids on the transition temperature of bacillus subtilis lipids.

The influence of branched-chain and omega-alicyclic fatty acids on the transition temperature of Bacillus subtilis lipids was studied by measuring the fluorescence depolarisation of the probe 1,6-diphenyl-1,3,5-hexatriene incorporated into lipid bilayers. Only anteiso-C15 and C17 fatty acid-enriched lipids showed no transition in the observed temperature range. Compared to the transition of normal lipids iso-fatty acid-enriched lipids have a slightly higher transition temperature. The incorporation of omega-alicyclic fatty acids with increasing size of the alicycle leads to a decrease in the transition temperature. A possible role of omega-cyclohexane fatty acids in Bacillus acidocaldarius is proposed.


Clustered and interspersed repetitive DNA sequences in four amphibian species with different genome size.

We have compared the amount of clustered and interspersed repetitive sequences in the genome of four Amphibia with different DNA contents per haploid nucleus: two Anura (Xenopus laevis, 3 pg and Bufo bufo, 7 pg) and two Urodela (Triturus cristatus, 23 pg and Necturus maculosus, 52 pg). High molecular weight DNA of the four species was denatured and reassociated to the same Cot in order to obtain duplex sequences with a similar reiteration frequency. Single-stranded DNA was digested off with the Aspergillus S1 nuclease. DNA was then fractionated according to the molecular weight through an agarose A-50 column. We found that the amount of long repetitive sequences is roughly proportional to the genome size in the four species, while the number of short (about 300 base pairs) repetitive sequences is increased many-fold in the species with the larger DNA content, both in Anura and in Urodela.


Turnover of rat liver malic enzyme during induction by protein deprivation.

The half-lives of hepatic malic enzyme and total liver soluble proteins were determined in protein-sufficient and protein-deficient rats after injection of tracer doses of radioactively labeled leucine. The results obtained in these experiments have demonstrated that the increased levels of malic enzyme obtained under conditions of severe protein restriction are due to elevated rates of synthesis of the enzyme protein, with no apparent change in the rate of its degradation.


Mouse fetal hemoglobin.

Using isoelectric focusing, a fetal hemoglobin was found in the peripheral blood of C57BL/6 fetal mouse during the 14 to 20 days gestational period. In acid-urea polyacrylamide gel the pattern of this fetal hemoglobin was different from that of the adult hemoglobin. The mouse fetal hemoglobin was differentiated from the mouse adult hemoglobin by immunodiffusion reaction. It suggests that there is a transient fetal hemoglobin in the C57BL/6 mouse during gestational age.


Changes in conformation and immunological activity of ovalbumin during its modification with different acid anhydrides.

In order to probe the cause and nature of conformational changes induced by the chemical modification of amino groups in proteins, five acylated derivatives of ovalbumin namely 21% acetylated, 32% succinylated, 90% butyrated 92% succinylated, and 95% acetylated ovalbumins were prepared and their molecular and immunological properties were systematically investigated. As evidenced by the ultraviolet difference spectral, solvent perturbation, gel filtration, and viscosity data, acylation of the amino groups produced a definite conformational change in native ovalbumin whose extent was higher for higher degrees of chemical modification. The solvent pertubation data showed an exposure of 0.5 tryptophan and 3 tyrosine residues in native ovalbumin; the exposure increased to 1 tryptophan and about 5 tyrosine residues in the maximally modified proteins (i.e. 90% butyrated, 92% succinylated, and 95% acetylated ovalbumins). The Stokes radius (2.7 nm) and intrinsic viscosity (3.9 ml/g) of ovalbumin increased, respectively, to about 3.4 nm and 7.7 ml/g upon acylation of its 18 lysine residues; the intrinsic viscosity of 95% acetylated ovalbumin was 7.2 ml/g. The reduced viscosity of ovalbumin (4.2 ml/g) which remained unaltered on raising the pH to pH 11.2, increased to 7.9 ml/g on succinylation of 18 lysine residues. On raising the ionic strength from 0.15 to 1.0, the value decreased from 7.9 to 6.2 ml/g. These observations taken together with the fact that the intrinsic viscosities of 92% succinylated and 90% butyrated ovalbumins are identical, argue against the presently prevalent proposal that electrostatic effects alone are responsible for the disruption of native protein conformation during chemical modification. The immunological activity of ovalbumin towards rabbit anti-ovalbumin expectedly decreased with acylation of its amino groups but the three maximally modified ovalbumins retained 40% immunological activity. This taken along with the spectral and viscosity data showed substantial native structure (format) in the three maximally acylated derivatives. The rabbit antiserum against 95% acetylated ovalbumin did not cross-react with acetylated lysozyme and reacted poorly with the native and 92% succinylated ovalbumins suggesting that the antigenic make-up of the three maximally modified ovalbumins is different.


Functional consequences of tryptophan modification in human fibrinogen.

When human fibrinogen was modified with H2O2, inter- and intra-molecular cross-links of fibrinogen were formed, accompanied with oxidation of tryptophan, methionine and tyrosine residues. These cross-links may be closely associated with oxidation of tryptophan residues. The polymerization activity of fibrinogen with thrombin was decreased markedly by this modification. Modification of tryptophan residues in fibrinogen was also performed with 2-hydroxy-5-nitrobenzyl bromide. Modification of two out of a total 78 tryptophan residues in the molecule with the reagent led to the intensification (1.7 times) of the polymerization activity with thrombin and further modification of the next two residues led to complete loss of the polymerization activity. The first two tryptophan residues to be modified are in Fragment D, and the next two occur in Fragment E.


Surface differences and similarities in two homologous proteins. Cytochrome b5 and cytochrome b2 core.

From previous work (Guiard, B., Groudinsky, O. and Lederer, F. (1974) Proc. Natl. Acad. Sci. U.S. 71, 2539-2543) it is now clear that the overall secondary and tertiary structure of cytochrome b2 core is very similar to that of cytochrome b5. We present here a direct comparison of circular dichroism  spectra and low-temperature absorption spectra which bring further evidence about this structural similarity. Cytochrome b2 core reacts only sluggishly with cytochrome b5 reductase, showing a lack of correspondence with the reductase binding area in cytochrome b5. On the other hand, literature data indicate similar electron transfer rates between cytochrome c on one hand, cytochrome b5 and cytochrome b2 core on the other hand. A structural inspection of cytochrome b2 core suggests that the mouth of the heme crevice in the latter is the most likely region for interaction with cytochrome c, with perhaps ionic bonds slightly different from those proposed by Salemme (Salemme, F.R. (1976) J. Mol. Biol. 102, 563--568) for the cytochrome c-cytochrome b5 interaction. In view of this partial surface similarity, the lack of immunological cross-reactivity between the two hemoprotein cores is attributed to their close similarity with the cytochrome b5 of the antibody-producing rabbit.


Serum inhibitors of desialylated glycoprotein binding to hepatocyte membranes.

Identification of the material present in human serum which is responsible for inhibition of binding of desialylated glycoproteins to rat hepatocyte membranes was accomplished by means of affinity chromatography using Sephadex to which the galactose-specific lectin, Ricinus Communis Agglutinin (RCAI) was covalently bound. RCAI-Sephadex was capable of extraction of virtually all of the inhibitory activity from cirrhotic serum. The RCA I-bound inhibitory activity could be eluted with 0.05 M D-galactose. The D-galactose eluate when subjected to radioimmunoelectrophoresis against a number of specific antibodies to human serum glycoproteins produced arcs corresponding to alpha 1-acid glycoprotein, alpha2-macroglobulin, IgG, IgA, and IgM. In another experiment putative terminal galactosyl groups of desialylated glycoproteins in the D-galactose eluate from cirrhotic serum exposed to RCAI-Sephadex were labelled with tritiated borohydride after treatment with galactose oxidase. Subsequent gel electrophoresis showed peaks of radioactivity throughout the area of the gel corresponding to protein molecular weights of the 19 S, 7 S, and 4 S classes. It thus appears that a heterogeneous population of desialylated serum glycoproteins accounts for the inhibition of binding of desialylated glycoprotein to the hepatocyte membrane and that these desialylated glycoproteins are present in small amounts in normal human serum and in greatly increased quantities in serum from patients with cirrhosis.


Synthesis of actin by cultured guinea pig megakaryocytes. Complex formation with fibrin.

Guinea pig megakaryocytes were isolated from femoral marrow and cultured in the presence of radioactive amino acids. Radioactivity was incorporated into several proteins including a 42 000 dalton polypeptide identified as actin by DNAase agarose affinity chromatography. Quantitative immunoelectrophoresis of megakaryocyte extract revealed that 3.0% of the total solubilized cellular protein was fibrinogen. Immunoabsorption studies using anti guinea pig fibrinogen beads failed to reveal the presence of newly synthesized radioactive fibrinogen in the cellular extract, however, radioactive actin was detected in the eluates obtained from the immune beads. When guinea pig fibrinogen was clotted with thrombin in the presence of radioactive megakaryocyte extract, a complex formed between a high molecular weight species of fibrin and actin. No actin fibrinogen complex was detected. The results suggest that actin synthesized by megakaryocytes complexes with fibrin formed from a relatively large pool of non-radioactive intracellular fibrinogen.


[Redox processes during sensitization and allergic reaction to microbial antigens].

The effect of sensitization and delayed allergic response (DAR) to brucellosis antigen on the processes of glycolysis and dehydrogenase activity of Krebs' cycle was studied. The increasing sensitivity to Brucella was accompanied by inhibition of the dehydrogenase activity and increasing glycolysis. The changes were more pronounced in sensitization to living brucella. In DAR not only the dehydrogenase activity but also the processes of glycolysis were inhibited. Reduction of the aerobic fractions and excess of isoenzyme spectrum lactate dehydrogenase was observed both in sensitization and in DAR. Correction of biochemical shifts produced decreasing sensitization and inhibiting DAR symptoms.


[Transplacental penetration of 7,12-dimethylbenz(a)anthracene and its distribution in the organs of rat fetuses].

Rats were given 7,12-dimethylbenz(a)anthracene (DMBA) intravenously in a dose of 15 mg/kg on the 21st day of pregnancy; its content in the liver, placenta, and the fetus was determined by the fluorescent-spectral method. The maximal concentration was reached in 10--15 min in the liver and placenta of the pregnant rats (45 and 6.3 microgram/kg, respectively) in comparison with a slower (in one hour) elevation in the fetal tissues (2.4 microgram/kg). It took about 5 hours for all the tissues to be cleared of the carcinogen. One hour after the administration DMBA was unevenly distributed in various fetal organs--the maximal content in the liver, and the minimal--in the "carcass" in comparison with the content in other organs (the kidneys, lungs, brain, intestine). The results obtained failed to correlate with the data on the predominant origination of the tumours in the kidneys and the nervous system of rats in transplacental DMBA action.


Orbitocranial asymmetry.

Eleven cases are chosen to illustrate the differential diagnosis of deforming lesions of the bony orbit and its vicinity, which cause unilateral proptosis or other cranio-facial disfigurement. Three distinct varieties of orbito-cranial neurofibromatosis are distinguished, and they are contrasted with other deforming lesions of childhood--unilateral craniosynostosis, chronic juvenile subdural hygroma of the temporal fossa and congenital facial hemihypertrophy. Adult lesions are represented by intrinisic tumours of the orbit and paranasal sinuses, and by the commonest two processes deforming the sphenoid bone, meningioma and osseous fibrous dysplasia.


The clinical and economic effects of early return to work after elective inguinal hernia repair.

Since 1 January 1976 male patients of four consultant surgeons undergoing elective repair of a unilateral inguinal hernia have been included in a trial to see if 'early' return to work or normal activity is associated with an increased recurrence rate and also to investigate any economic consequences. To date 295 patients have been entered into the trial and the first 150 have been reviewed at 1 year. There was a complete follow-up at 1 year. There was 1 recurrence (0.7 per cent) at 1 year, and this had occurred by the time the patient came to the clinic to be included in the trial. Patients supervised by their general practitioner were off work for 78.5 days, while those advised to return to work early were off work for 52.1 days. This difference of 25.4 days is significant at the 0.1 per cent level. Loss of earnings while off work was reported by 36.7 per cent of patients, and the average sum lost was 19.86 per week. Thus, patients lost 72.06 on average. If patients went back to work at 52 days instead of at 78 days, the benefit to the economy would be of the order of 7 m., and this 'early' return to work is not associated with an increase in the recurrence rate at 1 year.


A new method for the rapid measurement of body composition in critically ill surgical patients.

A rapid, non-invasive method for the measurement of absolute amounts of fat, protein, minerals and water in the body has been developed which is applicable to very ill patients. The patient is weighed and skinfold thickness is measured with calipers. The body contents of potassium, nitrogen, sodium, chlorine, calcium and phosphorus are measured in a whole-body radiation counter after irradiation with fast neutrons. From these values absolute amounts of body fat, protein, minerals and water are calculated. The procedure, which takes about 40 min, is carried out with the patient lying supine on a couch. The errors in the absolute measurement of the components expressed as percentages of body weight are: for fat, 4.5 per cent; for protein, 1.6 per cent; for minerals, 0.8 per cent; and for water, 4.9 per cent. The radiation dose is equivalent to that of a chest radiograph (50 mrem). We have used this technique (a) to determine the tissue composition of the weight lost in 16 patients after excision of the rectum; (b) to establish that the weight gained by 16 patients receiving intravenous nutrition was mainly water; and (c) to show that in 10 patients who received a simple solution of amino acids for 2 weeks after rectal excision body protein was preserved as efficiently as in 10 similar patients who received a full course of intravenous nutrition. This is the first time body weights of living persons have been broken down into terms of fat, protein, minerals and water, and the method should help to solve a number of metabolic and nutritional problems in clinical surgery.


Changes in behavioural characteristics of elderly populations of local authority homes and long-stay hospital wards, 1976-7.

Behavioural characteristics of the elderly populations of seven local authority residential homes and three long-stay hospital wards were assessed in 1976 and 1977 with the Crichton Royal behavioural rating scale. In 1977 the levels of behavioural problems had increased in the residential homes, but declined in the hospital wards. Differences between the homes had decreased as the overall level of problems increased. The findings suggested that the additional burden of caring for increasing numbers of severely disabled elderly people was affecting the balance of institutional care, and a radical reappraisal of present patterns of care may be necessary to meet their future needs.


In-vitro activity of antimicrobial agents against Neisseria gonorrhoeae in Brussels.

The minimum inhibitory concentrations (MICs) of 18 antimicrobial agents against 104 strains of Neisseria gonorrhoeae isolated in the Brussels area between January and October 1976 have been measured. The MICs for penicillin G, ampicillin, amoxycillin, carbenicillin, and cephalexin showed a bimodal distribution. The second modus strains of cephalexin (MIC = 6.25 microgram/ml) were relatively resistant to penicillin G (MIC greater than or equal to 0.08 microgram/ml). About 51% of all strains were relatively resistant to penicillin G, 40.5% to ampicillin (MIC greater than or equal to 0.16 microgram/ml), 46% to amoxycillin, and 47.5% to carbenicillin. For cephalexin and cephaloridine, 25% and 8.5% respectively of all strains were relatively resistant (MIC greater than 3.12 microgram/ml). For cefazolin all MICs fell into a range of 0.097--3.12 microgram/ml. Resistance to tetracycline, doxycycline, minocycline, erythromycin, and spiramycin (MIC greater than or equal to 1 microgram/ml) was found in 9.5%, 7%, 6%, 36.5%, and 71% respectively of all isolates. No strains were resistant to rifampicin. For chloramphenicol and thiamphenicol the MICs ranged from 0.39 to 12.5 microgram/ml and from 0.195 to 3.12 microgram/ml respectively. The results for sulphamethoxazole, trimethoprim, and the combination of sulphamethoxazole and trimethoprim in a 20:1 ratio are given and discussed. The fractional inhibitory concentration (FIC) indices have also been calculated. No beta-lactamase-producing strains were found, and a contingency coefficient C has been determined for all the pairs of antibiotics investigated.


In-vitro antimicrobial susceptibility of Neisseria gonorrhoeae in New Zealand.

Four hundred and forty-two isolates of Neisseria gonorrhoeae were tested by an agar dilution method for their susceptibility to penicillin, ampicillin, tetracycline, cephaloridine, and spectinomycin. Of these isolates, 295 were tested for their susceptibility to sulphamethoxazole and to trimethoprim by the same method, using Oxoid diagnostic sensitivity test agar plus 7.5% laked horse blood instead of Proteose No. 3 agar plus 1% IsoVitaleX and 1% haemoglobin. One hundred (22.6%) of the isolates were found to be relatively resistant to penicillin (minimum inhibitory concentration (MIC) less than 0.1 iu/ml), but only 1.1% had a MIC of 1 iu/ml or higher. Ampicillin was slightly more active than penicillin in that all isolates were inhibited by 0.5 microgram/ml or less. For 3.7% of isolates the MIC of tetracycline was 2 microgram/ml or higher. All isolates were sensitive to spectinomycin. By calculating the Spearman rank correlation coefficient (rs), a high correlation (rs greater than 0.5) was found between susceptibility to penicillin and susceptibility to ampicillin, tetracycline, and cephaloridine. Low correlation (rs less than 0.2) was found between susceptibility to penicillin and susceptibility to spectinomycin, sulphamethoxazole, and trimethoprim.


The neuroanatomy of amnesia. A critique of the hippocampal memory hypothesis.

The discovery that medial temporal lobe lesions produce amnesia in humans if the lesion extends sufficiently far posteriorly to include the hippocampus forms the keystone of the hippocampal memory hypothesis. Strong supporting evidence comes from the occurrence of mammillary body disease in Korsakoff's psychosis. Disease of the posterior cerebral artery confirmed the observations on the medial temporal lobectomies by showing that pathology in the ventromedial quadrant of the temporal lobe produces amnesia. The occasional piece of contradictory evidence was sufficiently ambiguous to be dismissed or re-interpreted. Although the contradictory evidence that emerged from animal research created severe difficulties, opinion had crystallized on the matter to the degree that the data were unable to force rejection of the hippocampal memory hypothesis. This necessarily led to the conclusion that the animal model is a poor one: either the human hippocampus is unique with respect to memory or the tests which are used in animals do not tap the same mnemonic processes that are impaired by the human lesions. Both these arguments are nearly impossible to refute. The brain of every species is different and there is no way in which monkeys and humans can be tested under identical conditions. There has never been much enthusiasm for the suggestion that the human hippocampus is so different from other animals that this uniqueness could account for the apparent differences between the behavioural effects of human and animal hippocampal lesions. However, many experimenters have devised clever tests of the possibility that the problem is in the animal behavioural measures. Given sufficient circularity of reasoning, the project must necessarily eventually be successful. The argument is that if the usual tests of learning and memory that are used with animals are not disrupted by hippocampal lesions, then these are not tests of the kinds of learning and memory defects displayed by human amnestics. One has only to search for tasks that are disrupted by hippocampal lesions in animals, and these then must tap the same memory processes that are disrupted by the human lesions. The possibility has rarely been seriously considered that it might be damage to some structure in the ventromedial quadrant of the temporal lobe other than the hippocampus that is responsible for the amnesia. The amygdala and entorhinal area have been ruled out by both the human and animal data. However, the temporal stem is a likely possibility. Its position makes it vulnerable to the surgical approach which was used in human medial temporal lobectomies, and its damage in animals produces deficits in learning and retention. When medial temporal lesions were made in monkeys in the same way that they were made in humans, inadvertent damage to the temporal stem occurred along with the intended amygdaloid and hippocampal injury. Symptoms characteristic of damage to the temporal cortex resulted from these lesions and they were probably caused by the damage to the stem...


Electroencephalographic studies myoclonus.

Electroencephalographic studies were carried out in 30 patients with various kinds of myoclonus. It was confirmed that the technique of jerk-locked averaging with a backward averaging program was useful for detecting cortical spikes in association with the spontaneously occurring myoclonus, which are not recognized on the convential polygraph, and for evaluating the temporal and topographical relationship between the spike and the myoclonus. By this technique, cortical spikes were shown to precede the myoclonus of a contralateral upper extremity muscle by 7 to 15 ms ith progressive myoclonic epilepsy showed a high amplitude somatosensory evoked potential (SEP) in response to electrical stimulation of the median nerve. The N33 component of this high amplitude SEP was found to be similar to the myoclonus-related cortical spike in their wave form, time relationship and topographical distribution, suggesting an involvement of similar physiological mechanisms in the genesis of both phenomena. Myoclonus in these patients is compatible with "pyramidal" or "cortical loop reflex" type.


Familial myoclonic epilepsy with ataxia and neuropathy with additional features of Friedreich's ataxia and peroneal muscular atrophy.

A family is described in which a mother and three of her five children showed myoclonic epilepsy. The mother and one son were also ataxic; one other son had additional features of Friedreich's ataxia, and a daughter had peroneal muscular atrophy as well as myoclonic epilepsy and ataxia. Although some of these disorders have been associated in previously reported families, the occurrence of all three disorders in members of one family seems to be unique. It is concluded that this family shows the manifestations of one, probably dominant, gene. The differences in age of onset and manifestations may be explained by the action of one or more subsidiary genes.


The intrinsic connections of the cortex of area 4 of the monkey.

The intrinsic connections of area 4 of the monkey have been investigated with axonal degeneration methods after the placement of microelectrode lesions within the cortex. The fibre degeneration is restricted to within a few millimetres of the damage and is asymmetrically distributed in the form of an ellipse with its long axis anteroposteriorly. The same pattern is found in all topographic subdivisions of the motor cortex. There are two distinct zones of degeneration, dense fine terminal degeneration for 200 to 300 micrometer all around the lesion, and a moderate degree of fibre terminal degeneration for a further 2 to 3 mm. The intrinsic connections are disposed predominantly in a horizontal or oblique direction and within the laminae of origin, but there are fibres passing between adjoining laminae and between layers III and V and VI. Two horizontal plexuses of degenerating fibres are present, at the boundary layers II and III and at the level of the Betz cells, and these fibres arise within the cortex. The afferent and efferent fibres of the cortex are arranged strictly perpendicular to the surface. The extent and pattern of the intrinsic connections of area 4 are very similar to those of area 17 of the visual cortex.


An electron microscopic study of the termination of intracortical axons upon Betz cells in area 4 of the monkey.

After small lesions within the cortex of area 4 of the monkey degenerating axon terminals have been seen with the electron microscopy to contact the cell bodies, proximal parts of the apical dendrites and initial segments of Betz cells 0.5 to 2.5 mm from the damage. The degenerating axon terminals make symmetrical synapses which are presumed to be inhibitory in function. The degenerating terminals are probably from the axons of the basket cells described in Golgi-impregnated material, and which correspond to the large stellate cell recognized in electron microscopic studies.


Neuronal plasticity in the limbic system during classical conditioning of the rabbit nictitating membrane response. II: Septum and mammillary bodies.

Neuronal unit activity was recorded from several limbic system structures during classical conditioning of the rabbit nictiating membrane response to a tone CS. Air puff to cornea was used as a UCS. The present and past investigations of hippocampal activity using this paradigm show a neuronal plasticity which develops early in training, increases rapidly and shifts forward in time as behavioral conditioning develops. Recordings from the lateral septal region demonstrate the same within-trial pattern of unit discharge seen in hippocampus, indicating a projection of hippocampal plasticity over precommissural fornix pathways. Medial septal neurons, on the other hand, respond in an excitatory manner to the onsets of tone and air puff stimulation. While unit discharges seen in hippocampus and lateral septum occur only during the paired (learning) paradigm, medial septal activity is identical under both paired and unpaired (control) conditions. The latter fact lends support for a sensory interpretation of medial septal responses, and is consistent with anatomical evidence of a major septohippocampal projection originating from this region. In contrast to results for lateral septum, recordings from medial and lateral mammillary nuclei indicate only small, diffuse excitation that exhibits no consistent changes over training, and is not related to activity seen in hippocampal or septal regions. The apparent lack of correspondence between learning dependent unit measures obtained from pre- and postcommissural fornix structures is entirely consistent with current modified descriptions of limbic system anatomy.


The production of toxic metabolites by Chaetomium spp. isolated from solis of permanent pasture.

One hundred and two isolates of Chaetomium spp. have been identified from 2563 soil samples collected from permanent pasture at Nappan, Nova Scotia. Chaetomium umbonatum was the Chaetomium species most commonly isolated. Fifty-six of the Chaetomium isolates were grown in the laboratory and the cultures examined for the production of toxic metabolites. The culture filtrates of 12, and extracts of mycelium of 18, of these isolates inhibited bacterial growth. Chetomin was detected in nine mycelium extracts and isolated from four of the mycelium extracts. Chaetoglobosins were isolated from three mycelium extracts.


Regional and subcellular distribution of gold in brain of gold thioglucose obese mouse.

By employing neutron activation analysis, endogenous content of gold was estimated quantitatively in discrete brain areas and in subcellular fractions of the hypothalamus of gold thioglucose (GTG) induced obese mice. The highest concentration of gold was obtained in the ventromedial hypothalamus (VMH) reaching approximately 100 ng/mg wet tissue. Significantly higher concentrations were observed in other hypothalamic subareas followed by certain limbic areas and the thalamus, while in the cerebral and the cerebellar cortex the gold concentration was very low. Subcellularly, the hypothalamic gold was principally recovered in the supernatant fraction particularly after a hyposmotic shock treatment of the crude mitochondrial fraction. Contrary to GTG, treatment with gold thiomalate (GTM) did not induce obesity in the mouse, although considerable amount of gold was observed in the VMH, a finding suggesting the existence in the VMH of at least a two step mechanisms for inducing GTG obesity. To identify the satiety neuron transmitter, an analysis of certain enzyme activities involved in the synthesis of known transmitters, such as acetylcholine or gamma-aminobutyric acid (GABA), was made in the GTG-obese mice. There were no significant changes in any of the areas functionally related to the VMH.


Serum thyroxin levels during hyperthermia evoked in the monkey by intrahypothalamic injection of PGE1, 5-HT or pyrogen.

Serotonin (5-HT), prostaglandin E1 (PGE1) or a bacterial pyrogen (E. coli or S. typhosa) was microinjected in a volume of 1.0--1.5 microliter into the hypothalamus of the unanesthetized monkey to evoke a long-term hyperthermia. Samples of venous blood collected every 15 min, before, during and after each fever were analyzed by radioimmunoassay for plasma thyroxin levels. There was no statistically significant correlation between plasma thyroxin values and a given phase of the hyperthermic episode induced by the microinjections of 5--HT, PGE1 or bacteria. The possibility that an enhanced release of the thyroid hormone serves to sustain a long-term elevation in temperature evoked by a centrally acting pyrogenic substance is not supported.


Psychiatric presentation of epilepsia cursiva.

Coarse brain disease can first present as a behavioural or psychiatric disorder. Partial seizures with complex symptomatology (psychomotor or temporal lobe epilepsy) may offer particular difficulties in differential diagnosis from the "functional psychoses". The authors report a case of "running epilepsy" (epilepsia cursiva), that first presented as a behavioural problem, and review the literature on this rare form of psychomotor epilepsy.


The clinical significance of carcinoembryonic antigen in the plasma and tumors of patients with gynecologic malignancies.

Carcinoembryonic antigen is elevated in the plasma of approximately 30% of patients with endometrial adenocarcinoma, 50% of patients with ovarian carcinoma, and 60% of patients with cervical carcinoma. The incidence of elevated plasma CEA is directly related to stage of disease, and in ovarian cancer to cell type. Immunodiffusion and immunoelectrophoretic studies have indicated that CEA from ovarian and cervical cancers is similar to colonic cancer CEA. Tumor staining for CEA by the immunoperoxidase method (indicating a CEA concentration of greater than or equal to 3.0 microgram/g tissue) is positive in about one-half of the patients with elevated plasma CEA levels. However, there is no definite relationship between tumor and plasma antigen levels. Carcinoembryonic antigen levels charcteristically return to normal within 8 weeks following complete surgical removal of tumor. In contrast, antigenemia often persists up to 4 months following curative radiation therapy. A progressive rise in plasma CEA has preceded clinical diagnosis of recurrence in about half of the patients studied. Serial plasma CEA determinations in patients whose plasma or tumors initially contain elevated amounts of antigen provides information concerning the biologic behavior of malignancy which may be of clinical significance to the patient.


Studies on an oncofetal antigen, POA.

This paper describes the purification and partial characteristics of a putative oncofetal antigen, POA, which appears to be associated with the pancreas. POA is a glycoprotein of molecular weight between 800,000 and 900,000 daltons. It is found in fetal pancreas and pancreas cancer tissue, but not in normal adult pancreas. It is clearly different from carcinoembryonic antigen, other known tumor associated antigens, acute phase reactants and normal serum proteins. A quantitative rocket immunoelectrophoresis assay was developed for POA. Its specificity was monitored routinely by double immunodiffusion against known fetal and adult standards. The assay was performed on sera from over 700 patients. The results demonstrate that POA is found in the sera of most individuals. However, by far the highest absolute levels and the highest frequency of elevated levels was found in sera of patients with carcinoma of the pancreas. Elevated levels of POA were also found in the serum of a proportion of patients with carcinomas of the lung, stomach, colon, biliary tract, and breast and in a few other individuals with benign conditions. The spectrum of patients who have elevated levels of POA in their serum is quite different from that found with CEA or other known tumor markers.


Evaluation of intensification and maintenance programs in the treatment of acute lymphoblastic leukemia.

This cooperative prospective study was designed to answer the following questions in cases with acute lymphoblastic leukemia induced to achieve complete remission with the combination of vincristine and prednisone (if by day 29 the bone marrow was not M1, daunorubicin was added to the former regimen) and who received preventive CNS therapy with 2400 rad of cobalt-60 to craniocervical region and simultaneously intrathecal methotrexate and dexamethasone: 1) Is a short intensification with cytosine-arabinoside and cyclophosphamide immediately after complete remission useful? 2) Does the use of weekly doses of 6-mercaptopurine and methotrexate have the same maintenance effect as daily 6-mercaptopurine and twice weekly methotrexate? and 3) Do further 3 month-doses of intrathecal methotrexate and dexamethasone help to decrease still more the incidence of meningeal leukemia? From October 1972 to December 1975, 473 previously untreated patients entered this study and 465 (390 children and 75 adults) are evaluated in this paper. Of them, 373 (80%) achieved complete remission (children 84% and adults 61%). Out of 109 "high risk" children (one or more of the following characteristics at diagnosis: marked organomegaly, mediastinal widening, leukocytosis above 50000/mm3 and CNS involvement) 83 (76%) and out of 281 "standard risk" children (all the others) 244 (87%) achieved complete remission. The median duration of complete remission according to different prognostic factors was as follows: "high risk" children 10 months, adults 24 months and "standard risk" children 25 months. Duration of complete remission of the "standard risk" children in relation to with or without intensification, daily or weekly maintenance and additional intrathecal therapy or none, showed no significant difference; however, those who received intensification, daily maintenance and further intrathecal therapy behaved slightly better. Median survival for all the cases of this study was as follows: adults 10 months, "high risk" children 12 months and "standard risk" children 26 months. At 36 months, 13% of "high risk" children, 25% of adults and 39% of "standard risk" children are still alive. We conclude that the variables studied in this protocol did not show significant extension of complete remission, however the sum of them seems to offer some advantage. Moreover, what appears clear is the importance of prognostic factors which must be taken into account in future studies.


The significance of intracytoplasmic proteins in Reed-Sternberg cells.

Lymphoid tissue of 42 patients with Hodgkin's disease was studied with immunohistological techniques on the light microscopic and ultrastructural level. The presence of IgG in some Reed-Sternberg (R-S) cells was confirmed, and in addition serial sections and a double staining technique revealed that these cells also contained both kappa and lambda light chains. Furthermore two serum proteins, human serum albumin and alpha-1-antitrypsin, were demonstrated in the same positive R-S cells. The ultrastructural localization of the immunoglobulin and of human serum albumin was not related to any protein synthesizing organelle or to structures related to endocytosis. It is suggested that the presence of immunoglobulin in R-S cells is the result of a disturbance of the cell wall integrity with subsequent nonspecific diffusion of immunoglobulin and other serum proteins into the cell. The presence of IgG therefore can not be taken as an argument for a B-cell origin of R-S cells. Possible mechanisms for the cell wall damage are discussed.


Cryopathic gangrene with an IgM lambda cryoprecipitating cold agglutinin.

Immunochemical and serologic studies of cold agglutinis in patients with chronic cold agglutinin disease (CCAD) have shown the almost exclusive occurrence of IgM kappa antibodies with specificity for the I antigen of red cells. An unusual subgroup of patients has been delineated in which the cryoprotein is IgM lambda, frequently lacks I specificity and often cryoprecipitates. Studies of such a protein from a patient with an unusual array of immunoproliferative disorders including Grave's disease with exophthalmos and Waldenstrom's macroglobulinemia indicate that the cryoprecipitating and cold agglutinating properties probably derive from the sam protein. The occurrence of this type of antibody should suggest the presence of a more aggressive lymphoproliferative disorder than simple CCAD.


Conservative management of operable breast cancer: ten years experience at the Foundation Curie.

514 patients were treated for a surgically operable (T1, T2, T3, N0, N1a, N1b) infiltrating breast carcinoma at the Foundation Curie, Paris, France, from 1960 to 1970 inclusive. Patients with tumors 3 cm or less and without axillary adenopathy had lumpectomy followed by radiotherapy. Patients with larger tumors and all patients with clinically significant lymph nodes (N1b) had exclusive radiotherapy (without lumpectomy). 120 had lumpectomy and 394 had exclusive radiotherapy. The five and ten years absolute survivals, free of disease (N.E.D.), for the lumpectomy are 85% and 75%, respectively. 12% had secondary surgery for local recurrence. The cosmetic results were satisfactory in 98%, with no severe radiation sequelae. The five and ten years, N.E.D., of the exclusive radiotherapy group are 68% and 43%. 55% had secondary surgery for persistent or recurrent disease. The cosmetic results were satisfactory in 85%. There were only three patients with severe radiation sequelae. The overall survival for 514 patients at five and ten years are 72% and 51%. Two-thirds of patients, alive at five years, had a preserved breast. Our conservative treatment resulted in survival at five and ten years comparable to those of radical surgery.


Primary management of operable breast cancer by minimal surgery and radiotherapy.

109 cases of breast cancer were treated by tumorectomy and radiotherapy or radiotherapy alone. Almost 30% with small tumors (T1, T2) were considered inoperable for medical reasons and 70% refused mastectomy. Over the past five years the number of patients refusing mastectomy has definitely increased. 59 cases of surgically resectable cancers (T1, T2, T3, N0, N1) had a minimum followup of two years (average 4 years +/- 3 months). Absolute and determinate survivals NED were 65% and 86%. There were four local recurrences (8%). Secondary mastectomy could be performed on three. Microscopic involvement of the surgical margin by cancer did not alter the local control rate. The cosmetic results were good in 98%. Gross removal of the tumor followed by radiotherapy may be offered as an alternative to mastectomy in patients with operable breast cancer.


Relation between time-dose and local control of operable breast cancer treated by tumorectomy and radiotherapy or by radical radiotherapy alone.

67 patients with tumors 3 cm or less and with negative axilla, who had lumpectomy and radiotherapy, and 122 patients with larger tumors or clinically positive axilla, who had radical radiotherapy without prior lumpectomy, were evaluated at five years to determine the optimum dose for local control. 7000 rad in seven to eight weeks controlled 85% of lumpectomy cases, whereas 8000 rad in 81/2 weeks were required to control two-thirds of cases treated by radical irradiation alone. Subclinical (N0, N1a) and clinical disease (N1b) in the axilla was controlled, in a very high percentage, when 6000 and 7000 rad were delivered, respectively. Dose response curves were obtained for clinical disease in the breast and axilla. No such response was elicited for subclinical disease. Undifferentiated cancers had higher recurrence rates than well differentiated tumors. Radiation fibrosis in lumpectomy cases was insignificant, whereas 10% of radically irradiated patients had fibrosis of the breast.


Management of operable breast cancer: the surgeon's view.

There is no ideal single operation for breast cancer. In planning the choice of surgery for breast cancer, one must be aware of its multicentric origin, and of the regional spread from the breast to the axillary and internal mammary lymph nodes. The scope of the surgical attack should be correlated with the clinical pathologic extent of disease in the individual patient with the aim of removing all disease present, while preserving appearance and function to the utmost. The main goal remains removal of all disease from the breast and its regional nodes. Three distinct operative procedures have been utilized--modified radical mastectomy--total mastectomy with axillary dissection, radical mastectomy, and extended radical mastectomy. In all instances, the appropriate operation is applied to the individual, with the concept of removing most efficiently all disease present in the breast and regional nodes. With this plan of therapy, a 10 year survival rate of 61% with a local recurrence rat of 7.7% has been attained in a group of 565 patients with 40% axillary node involvement. These data are crude and uncorrected for age, intercurrent disease and for those lost to follow-up. The best salvage has been attained in the so-called "minimal" breast cancers--95% well 10 years following modified radical mastectomy. The extended radical mastectomy has been superior to the radical mastectomy when axillary node disease is present. In the more complete operation, 54% 10 year survival has been attained in patients with axillary node metastases, compared with only 33% attained in those treated by the conventional radical mastectomy. Adjuvant radiation therapy is applied to the adjacent regional nodes, when indicated. Adjuvant multi-chemotherapy is in its infancy and still to be evaluated. It should be used as a supplement to adequate primary surgical treatment, and should not be used as a crutch for inadequate primary surgery.


Correlation of tubulin-binding and antitumor activities of podophyllotoxin analogs.

The tubulin-binding affinities of podophyllotoxin and 12 related compounds have been compared with the effectiveness of these drugs in three assays of antitumor activity: (1) The mastocytoma assay of inhibited tumor cell growth in vitro; (2) the 37 sarcoma assay of tumor remission in vivo; and (3) the Stentor regeneration inhibition assay which detects a requirement for microtubule polymerization. The results indicate that there is a positive Spearman rank correlation coefficient between the inhibition constant for the binding of colchicine to tubulin in the presence of these compounds and the effectiveness of the compounds in the three assays of tumor growth inhibition. It is suggested that tubulin-binding assays may be a useful step in the screening of podophyllotoxin-like compounds suspected of disrupting mitosis by binding to microtubule protein.


Confronting subsurface cisternae and desmosomes in HELA monolayer cultures.

Confronting subsurface cisternae (CSC) and desmosomes are abundant at sites of parallel apposition of plasma membranes in confluent epitheloid monolayers of HeLa cells. Both structures are absent in young and subconfluent cultures, where stable intercellular contacts do not occur. They first appear when the plane of intercellular contact approaches towards the vertical; they disappear when cells separate spontaneously at superconfluency or by treatment with EDTA. The structure of CSC, lacking ribosomes at their side facing the plasma membrane, might fit the production of glycoproteins involved in intercellular adhesion.


The formation of dihydrodiols by the chemical or enzymic oxidation of benz[a] anthracene and 7,12-dimethylbenz[a] anthracene.

When benz[a] anthracene was oxidised in a reaction mixture containing ascorbic acid, ferrous sulphate and EDTA, the non-K-region dihydrodiols, trans-1,2-dihydro-1,2-dihydroxybenz[a] anthracene and trans-3,4-dihydro-3,4-dihydroxybenz[a] anthracene together with small amounts of the 8,9- and 10,11-dihydrodiols were formed. When oxidised in a similar system, 7,12-dimethylbenz[a] anthracene yielded the K-region dihydrodiol, trans-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a] anthracene and the non-K-region dihydrodiols, trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz[a] anthracene, trans-8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz[a] anthracene, trans-10,11-dihydro-10,11-dihydroxy-7,12-dimethylbenz[a] anthracene and a trace of the 1,2-dihydrodiol. The structures and sterochemistry of the dihydrodiols were established by comparisons of their UV spectra and chromatographic characteristics using HPLC with those of authentic compounds or, when no authentic compounds were available, by UV, NMR and mass spectral analysis. An examination by HPLC of the dihydrodiols formed in the metabolism, by rat-liver microsomal fractions, of benz[a] anthracene and 7,12-dimethylbenz[a] anthracene was carried out. The metabolic dihydriols were identified by comparisons of their chromatographic and UV or fluorescence spectral characteristics with compounds of known structures. The principle metabolic dihydriols formed from both benz[a] anthracene and 7,12-dimethylbenz[a] anthracene were the trans-5,6- and trans-8,9-dihydrodiols. The 1,2- and 10,11-dihydrodiols were identified as minor products of the metabolism of benz [a] anthracene and the tentative identification of the trans-3,4-dihydriol as a metabolite was made from fluorescence and chromatographic data. The minor metabolic dihydriols formed from 7,12-dimethylbenz[a] anthracene were the trans-3,4-dihydrodiol and the trans-10,11-dihydriol but the trans-1,2-dihydrodiol was not detected in the present study.


[Intraluminal diverticulum of the duodenum in a child 11 years old (author's transl)].

The intra luminal diverticulum of the duodenum is normally detected when the patient is adult. A better knowledge of that pathology allows an early diagnosis. The observation of a child 11 years old is here related. The clinics, roentgenographic and signs are stated precisely according to the survey of the observations already publiced.


Lymph and pulmonary response to isobaric reduction in plasma oncotic pressure in baboons.

Plasma colloid osmotic pressure was reduced by 76% (from 19.6 +/- 0.6 to 4.7 +/- 1.5 mm Hg) in five baboons while pulmonary capillary hydrostatic pressure was maintained at a normal level. This resulted in fluid retention, weight gain, peripheral edema and ascites, but no pulmonary edema. Thoracic duct lymph flow increased 6-fold and pulmonary lymph flow 7-fold. Thoracic duct lymph had a lower colloid osmotic pressure (2.0 +/- 0.7 mm Hg) than plasma (4.7 +/- 1.5 mm Hg), whereas the colloid osmotic pressure of pulmonary lymph (4.7 +/- 0.7 mm Hg) was the same as that of plasma. The lymph-plasma ratio for albumin fell in thoracic duct lymph but remained unchanged in pulmonary lymph. The difference between plasma colloid osmotic pressure and pulmonary artery wedge pressure decreased from 15.3 +/- 1.9 to -0.7 +/- 2.9 mm Hg. Despite this increase in filtration force, the lungs were protected from edema formation by a decrease of 11 mm Hg in pulmonary interstitial colloid osmotic pressure and a 7-fold increase in lymph flow.


Influence of right ventricular hemodynamics on left ventricular diastolic pressure-volume relations in man.

To clarify the mechanism of displacement of the left ventricular diastolic pressure-volume function with alteration of loading conditions, the effects of nitroglycerin on pressure-volume relations in 13 patients were compared with those of amyl nitrite in 13 other patients during cardiac catheterization. After nitroglycerin, average systemic mean arterial pressure declined by 15.1 mm Hg (17%) and left ventricular end-diastolic pressure by 9.4 mm Hg (49%); right ventricular systolic and end-diastolic pressures fell 11.6 mm Hg (36%) and 5 mm Hg (41%), respectively. In all patients diastolic pressure-volume curves were significantly displaced downward and leftward. After amyl nitrite, average systemic mean arterial pressure fell 20.1 mm Hg (22%), but left ventricular end-diastolic pressure and right ventricular systolic and end-diastolic pressures were not significantly reduced. No significant displacement of diastolic pressure-volume curves occurred. Both the rate constant of the exponentially fit diastolic pressure-volume curve, and the rate of diastolic isovolumic relaxation (T) were unchanged after each drug. Thus downward displacement of diastolic pressure-volume functions after nitroglycerin appears to be dependent more upon reduction of right ventricular filling dynamics than coronary perfusion pressures. More favorable effects upon left ventricular function may be associated with reduction of both left ventricular filling pressures and systemic impedance (reflecting both "preload" and "afterload") than of systemic arterial pressures ("afterload") alone.


Clinical investigation of agents with prophylactic anti-allergic effects in bronchial asthma.

To determine the efficacy of ketotifen as an oral anti-asthmatic agent, experimental and therapeutic long-term trials were carried out. Four models were used in the expirmental therapeutic trials nad the antihistaminic agent clemastine and disodium cromoglycate were used as comparative substances. It was demonstrated that ketotifen provides protection against bronchopasm induced by allergens, histamine and exercise, but not against that induced by acetylcholine. In the therapeutic long-term trials, the efficacy and tolerance of ketotifen were compared with that of clemastine and disodium cromoglycate for a period of 6 months. In another study ketotifen was administered for 1 year. Ketotifen proved very effective in decreasing the frequency and duration of asthmatic attacks, concomitant medication could be reduced and the patients improved subjectively. From these trials it can be concluded that ketotifen is a safe and effective oral anti-anaphylactic agent for use in the long-term treatment of bronchial asthma.


Serum IgE levels in Chagas' disease.

Elevated levels of serum immunoglobulin E are found in many parasitic diseases caused by helminths. We have previously demonstrated that giardiasis was not associated with hyperimmunoglobulinaemia E. In order to determine the influence of Trypanosoma cruzi on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with Chagas' disease and those from matched healthy Brazilian controls. We suggest that protozoan parasitic infections do not increase serum IgE levels.


The effect of orally administered sodium cromoglycate on allergic reactions caused by food allergens.

In five patients who exhibited allergic reactions, four with asthma and one with angioneurotic oedema, to orally administered soybean flour, the protective effect of orally administered sodium cromoglycate has been investigated. Protection from reactions in soybean provocation tests has been achieved with doses ranging from 400 mg to 600 mg given four times daily.


Effects of orally administered sodium cromoglycate in asthma and urticaria due to foods.

Out of twenty patients with a history of asthma or urticaria attributed to food substances, ten reacted on oral challenge: seven with asthma, one with asthma and urticaria and two with urticaria alone. In five of the eight asthmatic reactors, the symptoms developed within a few sec and there was no associated rise in free venous plasma histamine. In those remaining, two with asthma, two with urticaria and one with both, the symptoms developed only after 20-30 min. A rise in free plasma histamine occurred only in the two subjects with urticaria alone. The third with urticaria and asthma did not have blood estimations performed. Sodium cromoglycate in a dosage of 800 mg a day for 1 week, or a single dose of 1.0 g by mouth, did not block any of the reactions. By inhalation it blocked the asthmatic reactions which developed within a few sec of challenge.


A comparative study of an aqueous grass pollen extract and glutaraldehyde-treated grass pollen-tyrosine adsorbate in the treatment of pollenosis.

Hyposensitization therapy gave a subjective improvement in 84% of grass pollen-sensitive patients receiving an eighteen dose course of aqueous pollen extract (SDV) and in 69% of patients receiving a three dose course of glutaraldehyde-treated pollentyrosine adsorbate (Pollinex). Systemic reactions to treatment were considerably more frequent with the aqueous course, but virtually absent with the short adsorbate course, which seems therefore more convenient for the patient. The SDV treatment induced a more pronounced IgG antibody response both in patients and in guinea-pigs receiving the clinical dosage schedule. The Pollinex treatment showed a tendency to enhance the IgE antibody response in new patients.


Effect of diluent temperature on creatine kinase values found for lyophilized controls and reference sera.

We report the effect of temperature of diluent on creatine kinase activity in several lyophilized controls. Creatine kinase activity was significantly greater when the lyophilized control was reconstituted with diluent at 4 degrees C as compared to 25 degrees C. This is an additional source of variation in creatine kinase controls.


An improved determination of total glycosaminoglycans in body fluids by formation of complexes with quinacrine: changes in amniotic fluid total glycosaminoglycans during normal pregnancies and in pregnancies at risk for mucopolysaccharidoses.

Acidic glycosaminoglycans form insoluble complexes with quinacrine and this has been exploited for their analysis in blood, urine and amniotic fluid. The method is specific for glycosaminoglycans including keratan sulphate and the samples do not have to be deproteinized. Values for normal urine, serum and amniotic fluid are presented. Urinary total glycosaminoglycans excreted by patients with mucopolysaccharidoses were also determined. The normal changes in amniotic fluid total glycosaminoglycans have been measured between 14 weeks' gestation and term, and values are given for amniotic fluid total glycosaminoglycans in several pregnancies at risk for mucopolysaccharidoses. It is suggested that this method is a potentially valuable analytical tool in the pre-natal diagnosis of mucopolysaccharidoses.


Trihexosylceramide alpha-galactosidase of human leucocytes.

Trihexosylceramide, isolated from human kidney and labelled in the terminal galactose position by oxidation with galactose oxidase and reduction with sodium boro[3H]hydride, was used to study some of the properties of human leucocyte alpha-galactosidase. The enzyme was inactive in the absence of detergent. Of all the detergents tested a crude sodium taurocholate preparation displayed the greatest activity. The optimal detergent concentration varied from 2 to 4 mg/ml depending on the protein concentration and indicating that the enzyme activity was dependent on the protein/detergent ratio. Because of its influence in regulating enzyme activity, it is essential that care must be taken to ensure that the protein/detergent ratio of all incubation mixtures is kept relatively constant whenever the diagnosis of Fabry's disease is attempted.


Demonstration of antibody for glutamic pyruvic transaminase (GPT) in chronic hepatic disorders.

The present paper describes the detection of an autoantibody for glutamic pyruvic transaminase (GPT) in sera of patients with chronic hepatic disorders. In 16 out of 500 patients, the existence of an antibody for pig GPT was demonstrated by the double antibody method, gel filtration and radioimmunoelectrophoresis. The antibody was demonstrated as an immunoglobulin G (IgG) with either polyclonal or monoclonal type (kappa or lambda). The binding portion of IgG with GPT was determined as the fragment Fab, but not Fc of IgG. Because the binding of 125I-pig GPT with the patient's antibody was displaced by human GPT, this antibody may have the characteristic of cross reacting with both pig and human GPT. Although the mechanism of production of the antibody for GPT and the pathological significance of the antibody in chronic hepatic disorders remained obscure, possible inhibition of GPT activity in serum is suggested in the presence of this antibody.


Effect of psychosocial stimuli and limbic lesions on prolactin at rest and following stress.

Many of the factors altering corticosterone in the rat have similar effects on prolactin. Resting prolactin, like corticosterone, is higher in animals housed singly than in those multiply housed. Unlike corticosterone, gentling did not lower prolactin. An exquisite sensitivity to environmental stimuli which results in rapid elevations in prolactin levels has been indentified in the rat which is considerably greater than that for corticosterone. Like corticosterone, the pattern of prolactin stress responses varies according to time of day. This differential sensitivity may well account for the diurnal variation in prolactin reported by some investigators. The limbic system has an important influence on prolactin. Lesions of the septal region do not modify resting levels but alter the pattern of prolactin stress responses in ways which are only partly similar to the effects of such lesions on corticosterone. In rhesus monkeys, individual variation in resting prolactin levels was observed, similar to that seen in the human. Levels are stable over periods of up to 50 days and are characteristic of the individual animal. In response to the stress of electric shock or shaping to a bar press response, prolactin elevation occurs only in animals with high resting levels, suggesting that a common mechanism is responsible for controlling both resting levels and magnitude of stress responses.


Is there any association between the pharmacologic control of prolactin release and its action on mammary carcinogenesis in the rat?

Pretreatment of female Wistar rats with various compounds (coumarin, 4-methyl-phenobarbital, carbon tetrachloride) on mammary tumour production by 7,12-dimethylbenz(a)anthracene (DMBA) has been studied. The test compounds brought about a variety of actions on DMBA tumours; their effect varied from none (phenobarbital, carbon tetrachloride) to decreased incidence and delayed appearance (coumarin, 4-methylcoumarin). In all cases studied increased prolactin level was found. The inhibitory action of coumarin on tumour incidence and multiplicity showed a dose-related association with elevated serum prolactin and reduced hepatic drug metabolism. These results indicate that the production of DMBA-induced mammary adenocarcinomas in the rat is not associated with serum levels of prolactin. Our results suggest that in this model for tumorigenesis, prolactin only plays the role of a promoter after the carcinogenic event.


Serum immunoglobulins in aborted and non-aborted bovine foetuses.

The concentration of immunoglobulin classes G, M and A (IgG, IgM and IgA) in the sera of 233 aborted and 201 non-aborted foetuses was measured. IgM was first detected in a foetus at day 90 of gestation while IgG and IgA were first detected on day 111 of gestation. Immunoglobulins were detected in 81.5% of aborted foetuses and 32.8% of non-aborted foetuses. Total immunoglobulin concentrations of 20 mg/100 ml or greater were found in 35.2% of aborted foetuses but only in 4.5% of non-aborted foetuses. It is suggested that factors resulting in antigenic stimulation of the foetus may play an important part in bovine abortion.


Cytotoxicity of human and baboon mononuclear phagocytes against schistosomula in vitro: induction by immune complexes containing IgE and Schistosoma mansoni antigens.

Normal human blood monocytes, pre-incubated at 37 degrees C with sera from patients infected with Schistosoma mansoni, strongly adhered to S. mansoni schistosomula in vitro, whereas no significant adherence was induced by sera from uninfected individuals. Comparable adherence occurred with normal baboon blood monocytes or peritoneal macrophages when these cells were incubated with sera from S. mansoni-infected baboons. Adherence of macrophages to schistosomula was associated with damage to the larvae, as estimated by a 51Cr release technique. Neither adherence nor cytotoxicity was induced by pre-incubation of the schistosomula, instead of the monocytes, with immune serum. The relevant factor in immune serum was heat-labile, but was not a complement component. Absorption and ultracentrifugation experiments showed that immune complexes, containing S. mansoni-specific IgE antibody and soluble parasite antigens, produced monocyte or macrophage adherence and cytotoxicity. Similar observations have been reported previously in the rat model. Since the production of large amounts of IgE is a predominant feature of schistosome infections in man and experimental animals, it is possible that this new mode of mononuclear phagocyte activation could act as an immune effector mechanism against S. mansoni.


Cell-mediated immune responses in owl monkeys (Aotus trivirgatus) with trachoma to soluble antigens of Chlamydia trachomatis.

The first temporal study of the cell-mediated immune responses (CMI) following ocular infections with Chlamydia trachomatis is presented. We examined the CMI of owl monkeys infected with trachoma to soluble antigens of C. trachomatis by leucocyte migration inhibition (LIF) and delayed hypersensitivity skin testing. Delayed hypersensitivity of a systemic nature developed after a local eye infection in owl monkeys; clearance of inclusions from conjunctival cells coincided with the onset of this response. The association of eye secretion and circulating antibodies with recovery from primary infection was not so striking. Both cellular and humoral immune responses persisted for at least 2 months, at which time all test animals were completely resistant to re-infection. The elicitation of cell-mediated immune reactions with solubilized chlamydial antigens may permit the isolation of specific antigens involved in the generation of protective immunity in the owl monkey model.


Studies on the use of Coulter Chemistry in the veterinary laboratory: day-to day reproducibility and the effects of storage, hemolysis, lipemia, hyperbilirubinemia and anticoagulants on test results.

A study was done to determine the variations in clinical chemistry test results that might be due to day-to-day changes in laboratory testing conditions or to variations in specimens submitted. Laboratory precision and specimen storage conditions had relatively little effect on the test results, except for a few specific instances. Other variables, such as the presence of anticoagulants in the specimen and sample discoloration due to hemolysis, hyperbilirubinemia or lipemia were more often responsible for inconsistencies in test results.


The effects of unilateral or bilateral removals of the second somatosensory cortex (area SII): a profound tactile disorder in monkeys.

Three groups of monkeys were studied; one with bilateral removals of the second somatosensory projection cortex (SII); another with similar unilateral removals; and an unoperated control group. Both lesion groups were significantly impaired on tasks of tactile learning and tactile retention. However, there were no differences between groups on the great majority of tasks of motor learning, nor on spatial alternation in the dark. The animals with unilateral removals were generally impaired whether using the hand contralateral to or ispilateral to the removal.


Disturbance of cage-finding in the monkey.

Qualitative and quantitative observations were made on two monkeys with unilateral or bilateral removals of areas 5 and 7 of Brodmann. The task was to return to the home cage in the light or in the dark. Both animals were slower in the dark, and also qualitatively abnormal in the light.


Characterization of restriction nuclease prepared chromatin by electron microscopy.

Chromatin was solubilized from rat liver nuclei by digestion with the restriction nuclease EcoRI or HaeIII in the presence or absence of EDTA and sodium chloride. The samples were investigated by electron microscopy after positive and negative staining with uranyl acetate under a number of conditions. Depending on the salt concentration during solubilization the chromatin appeared as beads on the string or in more compact form. Solenoid- and superbead-like structures were seen as had been reported for chromatin solubilized with micrococcal nuclease.


Heat-shock DNA homology in distantly related species of Drosophila.

Polytene chromosomes of D. melanogaster and D. virilis were hybridized in situ with 125I labeled mRNA isolated from polysomes of D. melanogaster tissue culture cells incubated at 37 degrees C. 125I mRNA hybridized preferentially with subdivisions 87A and 87Cl of the D. melanogaster 3R chromosome; grains were also observed at regions 93D, 95D and over the chromocenter. A considerable cross hybridization of this mRNA with D. virilis polytene chromosomes was observed. The 29C region of the D. virilis second chromosome was the main site of hybridization. Significant grain numbers also appeared in region 20F of the same chromosome. The two regions mentioned belong to heat shock loci in the latter species. Based on label intensity we conclude that region 29C of D. virilis contains DNA sequences retaining molecular homology with those at subdivisions 87A and 87Cl of D. melanogaster. SDS-polyacrylamide gel electrophoresis revealed similar distributions of heat shock proteins in the two species studied.


Possible effects of normetabolites on the subjective and reinforcing characteristics of opioids in animals and man.

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.


[Autotransplantion of Langerhans islets after total duodeno-pancreatectomy in a patient with chronic pancreatitis (author's transl)].

Total duodenopancreatectomy was performed in a 36-year-old man because of global chronic pancreatitis. Islets cells were isolated by collagenase digestion from the resected pancreas and re-implanted into the liver via the portal vein. Until the sixth postoperative day the amount of insulin required fell from 54 IU initially to 10 IU per day. Serial insulin determination demonstrated secretion by the implanted cells.


Polychlorinated terphenyls as an environmental pollutant in Japan.

This paper summarizes the results of the studies made by our group and other investigators in Japan on the residue levels of polychlorinated terphenyls (PCTs) in a variety of items in the environment including the human body. In contrast to widespread distribution of PCBs in the environment, PCT residues were seldom found in samples from aquatic environments such as water and sludge and waterfowl and fish, and, if found, the levels of PCTs were so low as to be practically negligible. Similarly, no significant levels of PCTs were detectable in foodstuffs such as edible oils, vegetables, dairy products and meat and in prepared diets. These findings may be explained by the fact that PCTs are much less volatile and soluble than PCBs and the total industrial output of PCTs was as small as 2700 tonnes which is 1/20 of PCBs produced in Japan. However, the levels of PCTs in human fat and blood were shown to be almost equivalent to PCBs, despite a negligible amount of PCTs being found in food. No clear explanation of human contamination by PCTs has been proposed so far.