Topical tobramycin therapy of experimental Pseudomonas keratitis: an evaluation of some factors that potentially enhance efficacy.

We evaluated several therapeutic modifications in an attempt to improve efficacy of topical therapy with tobramycin of experimental Pseudomonas keratitis in guinea pigs. Removal of corneal epithelium enhanced efficacy of topical therapy with 0.3 mg/ml and 3 mg/ml tobramycin sulfate but did not influence therapy with 40 mg/ml or 400 mg/ml tobramycin. The highest concentration of antibiotic was the most effective; 7 of 12 infected corneas treated with 400 mg/ml tobramycin were sterile in 48 hours. Therapy begun soon after the infection was established, when there were relatively few organisms present, was more effective than therapy begun later, when there were many more bacteria in the cornea. Our results are consistent with a basic therapeutic concept. The most effective regimen is one that achieves the highest safe concentration of antibiotic at the site of infection as early in the course of infection as possible.


Corticosteroid in experimentally induced Pseudomonas keratitis: failure of prednisolone to impair the efficacy of tobramycin and carbenicillin therapy.

The effect of prednisolone on tobramycin and carbenicillin therapy for experimentally induced Pseudomonas keratitis was evaluated. Results were assessed quantitatively by determining the number of bacteria that survived in the cornea. Simultaneous administration of prednisolone did not adversely alter results of treatment with carbenicillin or tobramycin. In another trial, pretreatment with prednisolone for 48 hours before antibiotic therapy was begun did not change significantly the results of therapy with intramuscular tobramycin or carbenicillin. We conclude that corticosteroid therapy does not affect adversely results of antibiotic therapy with tobramycin or carbenicillin in this experimental model.


Diphtheria corneal ulcers.

An adult with cutaneous diphtheria was admitted with bilateral purulent conjunctivitis and a perforated eye with most of the cornea absent due to Corynebacterium diphtheriae. At the time of admission of grayish patch of corneal epithelium was noted in the other eye, and in the next 24 hours there developed a large corneal perforation with dissolution of much of the cornea. Involvement of the external eye in diphtheria is rare but it is usually associated with cutaneous forms of the disease. Cutaneous diphtheria has been prominent in several recent outbreaks in the United States. Prompt recognition, early antibiotic treatment, and neutralization of the toxin with antitoxin are required for successful therapy.


Optokinetic nystagmus and vestibular stimulation in squirrel monkey model.

Simultaneous application of the rotatory stimulus with a constant angular acceleration (1 degree/sec2) did not clearly improve the optokinetic pursuing ability in squirrel monkeys, even though the directions of vestibular and visual stimuli matched. When the directions of vestibular stimulus and visual stimulus conflicted, the optokinetic pursuing ability markedly declined regardless of the stimulus magnitude. The inter-individual difference was large in that situation. For the vestibular-visual coordination, the active head movement condition is considered to be natural and important as a biological function.


Diverticulum hypopharyngis lateralis with a record of one case.

A case of lateral hypopharyngeal diverticula is reported. This type of diverticula is comparatively rare. The diagnosis can be made clinically and confirmed by x-ray examination and hypopharyngoscopy. A pharyngocoele is of differential importance as this may be present in many patients during Valsalva, but does not indicate treatment. The reported case is most probably caused by a development defect in the third branchial cleft.


Apparent fusion of the TOL plasmid with the R91 drug resistance plasmid in Pseudomonas aeruginosa.

The TOL catabolic plasmid was shown to be compatible with the R91 drug resistance plasmid. However, the TOL plasmid was extremely unstable in mutant PA03 of P. aeruginosa. By selecting for stabilization of the TOL plasmid in PA03 harbouring R91, it was possible to isolate a strain in which markers from both R91 and TOL appeared to exist in a single recombinant plasmid. This plasmid, pND3, encoded resistance to carbenicillin, was able to transfer at the same frequency as the R91 plasmid and encoded the ability to grow on m-toluate, p-toluate, m-xylene, p-xylene and toluene. In addition, it was shown to be incompatible with the NAH catabolic plasmid and it could be transferred by transduction. The TOL plasmid could stabilize in PA03 harbouring R91 without fusion with R91, and could stabilize in PA03 in the absence of R91. PA03 harbouring either the recombinant plasmid or the stable TOL plasmid in the absence of R91 could promote bacterial chromosome transfer between mutant derivatives of P. aeruginosa strain PA0.


Chemotactic activity of L-forms and mycoplasma.

L-forms of Streptococcus faecalis, Escherichia coli and Proteus mirabilis showed significantly less chemotactic activity for normal human leucocytes than did parent bacterial forms which were strongly chemotactic. Mycoplasma pneumoniae and Mycoplasma hominis did not demonstrate chemotactic activity.


Rat lung hyper-reactivity to stress.

Rats have been used frequently as a model for determining the pulmonary response to various stressful situations. It has been shown in the literature that rat lungs are remarkably sensitive to factors which result in the development of gross pulmonary injury, such as stress from exposure to hyperbaric oxygen. Similarly, a high degree of pulmonary reactivity was found in rats after administration of various CNS, convulsants and also exposure to mechanical vibration. The present study was confined to a determination of the gross pulmonary response of rats exposed to mechanical CNS traumatization compared to that of 10 other laboratory species. The frequency and severity of pulmonary injury from CNS traumatization, as indicated by lung weight/body weight ratios and gross appearance, was very striking in the traumatized rats, but we found little or no change in cats, dogs, rabbits and guinea pigs, in Rhesus, squirrel, vervet, and cynomolgus monkeys or in baboons and chimpanzees. Previous studies showed that the gross pulmonary injury from this mechanical head injury in rats, as well as from hyperbaric oxygen exposure, vibration, and CNS convulsants, was ameliorated by the prior administration of various sympathetic blocking agents. The results from the present comparative study tend to suggest that rat lungs are hyper-reactive to this stress.


Application of a fluid-filled spherical sandwich shell as a biodynamic head injury model for primates.

In this paper, two areas are investigated: first, the effect of pulse duration on skull fracture and brain injury and, second, under what conditions a scaling can be considered between subhuman primates and human. The skull is modeled as a spherical sandwich shell representing the general structure of the skull bones as being the compact inner and outer tables separated by a porous diploë layer. The brain and surrounding cerebrospinal fluid are modeled as an acoustic fluid with properties similar to those of water. The fluid-shell system is subjected to a local axisymmetric and arbitrary time-dependent external pulse and the transient response of the system is determined by numerical methods. The effect of pulse duration is investigated by choosing the pulse as the Heaviside function. Pulses with short duration are found to be less damaging as far as skull fracture and brain injury are concerned. Human head impact tolerance curves are obtained. For the second part of the investigation, a more realistic pulse containing both exponential and sine components is chosen to study the responses of the models of the human head and four species of primates. The numerical results are obtained for the same magnitude of the pulse as well as for equal magnitudes of initial acceleration after impact.


Empirical model of intracranial pressure and head motion resulting from a vibrating seated rhesus.

A series of experiments was designed to measure the head X and Z accelerations and the intracranial pressure in the unrestrained head of a rhesus monkey. The subject was exposed to a continuum of vibration frequencies from 2 to 35 Hz and peak acceleration amplitudes of 5, 10, 20, and 40 m/s2. The resulting data was used to build a frequency response model relating the head accelerations and pressures to the torso acceleration. The head-to-torso relationships, based upon a single subject, were both repeatable and invariant for torso acceleration amplitudes of 10, 20, and 40 m/s2. At frequencies above the 10Hz, the model strongly suggested the presence of linear system, and the inherent advantages of superposition. The model demonstrates the validity of the experimental method, involving a slow sweep through a range of frequencies, and of the analysis procedures used. More importantly, it promises to be a useful approach to the study of human response to vibration.


Inter- and intrapopulational variation in digging in Drosophila melanagaster larvae.

The digging behavior of larvae from the following strains of Drosophila melanogaster was studied: Oregon R-c, taxi, yellow, and vestigial. It was found that the time of stay of preadults in the culture medium, the number of larvae, and the illumination conditions can modify this behavior. The presence of this characteristic depends on the genetic composition of the population: the larvae of each strain used exhibited their own particular pattern of dispersal throughout the culture medium, independent of the experimental conditions under which this behavior was surveyed.


Phototactic and geotactic behavior of countercurrent defective mutants of Drosophila melanogaster.

Ten behavioral mutations, originally isolated in the countercurrent fractionation device, were tested in phototaxis and geotaxis mazes. While none of the mutations caused an altered ERG, they all caused photomaze behavior to differ from that seen in Canton-S controls. Eight of the mutants showed altered geotactic behavior. There was no correlation between the kind of change in phototactic behavior and the geomaze behavior of a given mutant. Certain mutations cause flies to be more photopositive and more geonegative than Canton-S; others result in behavior that is photo- and geopositive. The results suggest that certain mutations may be affecting visual components other than the ERG while other mutations may be more centrally or generally acting.


Genotypic differences in larval olfactory discrimination in two Drosophila melanogaster strains.

Wild-type (+B) and compound chromosome mutant (bB) Drosophila melanogaster larvae were tested in a U-maze. Fresh Drosophila food or food and larvae were placed in each of the two goals (+B only in goal 1, bB in goal2) and served as stimulus. Separate trials were conducted using +B and bB larvae to test for preference in the maze. Significantly more test larvae went to the arm of the maze containing their own strain as stimulus when (1) both goals contained larvae, (2) one goal contained homogenetic larvae and the other fresh food only, and (3) the goals contained biotic residues of stimulus larvae. The strength of the stimulus necessary to elicit the response differed for the two strains, the +B strain apparently being more sensitive. As the density of the stimulus larvae was increased, the choices of the test larvae became statistically nonsignificant and the number of larvae remaining in the starting arm of the maze increased. The data suggested that the strains of larvae utilized here have the capacity for olfactory discrimination.


Developmental patterns of 3-hydroxykynurenine accumulation in white and various other eye color mutants of Drosophila melanogaster.

Several points of biochemical similarity between white and scarlet mutants suggest that both are defective in the transport of xanthommatin precursors. In both, accumulation of 3-hydroxykynurenine is negligible during larval life and occurs at only a slow rate during adult development. Larvae of both mutants also excrete 3H-3-hydroxykynurenine and 3H-kynurenine rapidly, which probably accounts for the normal levels of kynurenine during larval life. 3-Hydroxykynurenine levels are abnormal in all white mutants which were studied, although in two alleles which are strongly pigmented (w(sat) and w(col)) accumulation is enhanced rather than diminished. In w(a), larval accumulation is normal but accumulation during adult development is greatly diminished, suggesting that this mutation has a tissue-specific effect. Similar levels were found in zeste females. Of the 11 other eye color mutants tested, abnormal levels of 3-hydroxykynurenine were found in eight. In four of these (claret, light, lightoid, and pink), larval accumulation is negligible, suggesting that these have defects in the kynurenine transport system like scarlet and white. In three others, however (brown, karmoisin, and rosy), accumulation during larval life is enhanced. In cardinal accumulation is normal during larval life but is excessive during adult development. This evidence supports the suggestion that the cd mutation blocks the final step of xanthommatin synthesis.


Genetic linkage studies of the human glycosphingolipid beta-galactosidases.

The genetic linkage relationships of the human glycosphingolipid beta-galactosidases were determined using human--mouse somatic cell hybrids. A new method was devised for the estimation of human galactosylceramide, lactosylceramide, and GMI-ganglioside beta-galactosidase activities in the presence of their mouse counterparts, which takes advantage of the reproducible specific activity of lysosomal hydrolases under a given set of culture conditions and is based on differences in both pH optima and sensitivity to chloride ion. Human and mouse chromosomes were identified by their characteristic banding patterns obtained after quinacrine staining, and the optimum glycolipid beta-galactosidase activity was determined for three different substrates. A ratio was defined for each activity which was the specific activity at the human pH optimum divided by the specific activity at the mouse pH optimum. Linear regression analysis was used to test for concordant segregation between pH ratios for each enzyme and the frequency of occurrence of different human chromosomes in the man--mouse somatic hybrid clones. The results obtained from two independent series of hybrid clones indicated that human beta-galactosidase activities consistently segregated with human chromosome 12 in these somatic cell hybrids.


Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins.

1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h).


Human plasma uridine diphosphate galactose-glycoprotein galactosyltransfertase. Purification, properties and kinetics of the enzyme-catalysed reaction.

The soluble galactosyltransferase of human plasma catalysed the transfer of galactose from UDP-galactose to high- and low-molecular-weight derivatives of N-acetylglucosamine, forming a beta-1-4 linkage. The enzyme was purified by using (NH4)2SO4 precipitation and affinity chromatography on an alpha-lactalbumin-Sepharose column. The galactosyltransferase was maximally bound to this column in the presence of N-acetylglucosamine, and the enzyme was eluted by omitting the amino sugar from the developing buffer. The molecular weight of the enzyme was estimated to be 85000 by gel filtration. The assay conditions for optimum enzymic activity was 30 degrees C and pH7.5. Mn2+ ion was found to be an absolute requirement for transferase activity. The Km for Mn2+ was 0.4 mM and that for the substrate, UDP-galactose, was 0.024 mM. The Km for the acceptors was 0.21 mM for alpha1-acid glycoprotein and 3.9 mM for N-acetylglucosamine. In the presence of alpha-lactalbumin, glucose became a good acceptor for the enzyme and had a Km value of 2.9 mM. Results of the kinetic study indicated that the free enzyme reacts with Mn2+ under conditions of thermodynamic equilibrium, and the other substrates are added sequentially.


Partial purification and properties of purine nucleoside phosphorylase from rabbit erythrocytes.

1. The partial purification of purine nucleoside phosphorylase from rabbit erythrocytes is described. 2. Analytical and preparative isoelectric focusing gave a pI value for the enzyme of 4.65. 3. Gel-chromatography and sucrose-density-gradient-centrifugation techniques gave estimates of the molecular weight in the range 75000-83000. 4. Lineweaver-Burk plots of kinetic data were non-linear at high inosine concentrations. Extrapolation of the linear part of such plots yielded a Km value for inosine of about 70 micrometer for the rabbit erythrocyte and liver enzymes. 5. A Hill interaction coefficient of 0.75 was obtained, suggesting negative co-operativity with respect to the binding of inosine. 6. Treatment of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) caused partial inactivation, and subsequent Lineweaver-Burk plots with inosine as substrate displayed complete linearity, with an increase in Km value for inosine to 200 micrometer. 7. Starch-gel electrophoresis did not reveal the presence of secondary isoenzymes; all tissue extracts examined gave electrophoretic patterns similar to those obtained with the partially purified enzyme from erythrocytes. 8. Results of hybridization studies with nucleoside phosphorylase from human foetal liver suggest that the rabbit enzyme is also a trimer.


The use of wheat-germ lectin-Sepharose for the purification of human haemopexin.

Haemopexin was prepared in 37% yield from normal human serum by a simple procedure involving fractional poly(ethylene glycol) precipitation and subsequent chromatography on DEAE-Sepharose CL-6B. One peak from the ion exchanger consisted of only haemopexin and transferrin. These proteins were separated by chromatography on wheat-germ lectin-Sepharose 6MB. Haemopexin was selectively bound and was subsequently desorbed by N-acetyl-D-glucosamine. No impurities could be detected in the final preparation by immunoelectrophoresis or by immunodiffusion against a range of antisera. The protein gave two partially separated bands in polyacrylamide-gradient-gel electrophoresis, corresponding to apohaemopexin and haem-haemopexin complex.


The immunological similarity of rat glandular kallikreins.

The immunological properties of the submandibular kallikrein, urinary kallikrein, pancreatic kallikrein and pancreatic prekallikrein of the rat were studied by immunodiffusion, immunoelectrophoresis and radioimmunoassay. Although they behaved differently electrophoretically, all the antigens showed identical immunological behaviour. The implications of this are discussed.


[Stability of liquid ergotalkaloid preparations as a function of the solvent polarity (author's transl)].

The degradation of dihydroergotamine-, dihydroergocornine-, dihydroergocryptine- (both isomers) and dihydroergocristine-mesilate in solution was studied as a function of the temperature and the dielectric constant of the composition. The degradation reactions of the studied hydrogenated ergopeptide alkaloids gave pseudo first-order kinetics. The pseudo first-order rate constants at room temperature were calculated using the Arrhenius equation. It was found that the stability of the studied hydrogenated ergopeptide alkaloids in solution is a function of the dielectric constant of the composition, and that stable solutions can be obtained by the use of water-alcohol mixtures having dielectric constants between 30 and 45. Solutions of the hydrogenated ergot alkaloids in predominantly organic media have the advantage that the degradation to the corresponding aci-forms, hydrolysis products and oxidation products is reduced. For this reason it is not necessary to carry out the filling operation under an inert gas atmosphere in order to protect the hydrogenated ergot alkaloids from oxidation. These results present an important technological advance.


[Antibiotic therapy with doxycycline in dogs with lung transplantations (author's transl)].

In contrast with kidney, heart and liver transplantations, lung transplantation involves an organ which has contact with the environment and bears a special risk of infection. This circumstance and the diminished resistance during immunosuppressive therapy makes long-term treatment with an effective broad-spectrum antibiotic advisable for lung  transplantations. Taking into consideration the different objectives and questions within the research project concerned the 182 lung allotransplantations carried out in dogs can be divided into two therapeutic groups in regard to postoperative treatment: lung allotransplantations with and without immunosuppressive therapy (methylprednisolone, azathioprine). Long-term doxycycline therapy was carried out in both groups. Those animals which were not treated with immunosuppressive drugs survived for an average of 9 days, those receiving immunosuppressive therapy survived for an average of 30 days. The longest survival period was 2.5 years. Clinically and histologically it could be demonstrated that doxycycline was successful both during the immediate postoperative period and in antibiotic long-term therapy after experimental lung transplantations.


Oxytocic activity of two dihydrogenated ergot peptide alkaloids on the rabbit uterus in situ.

The effect of two recently synthetized dihydrogenated ergot peptide alkaloids has been investigated on the rabbit uterus in situ. The method is described in detail. 6-Nor-6-isopropyl-9,10-dihydro-2'beta-methyl-5'alpha-benzyl-ergopeptine (DZ 26-474) and 6-nor-6-idopropyl-9,10-dihydro2'8-methyl-5'alpha-isopropyl-ergopeptine (28-377) possess 33% and 59%, respectively, of the oxytocic activity of methylergometrine (Methergine). The uterotonic effect of DZ 26-474 and 28-377 can be completely abolished by pretreatment with alpha-adrenoceptor blocking drugs, indicating involvement of alpha-adrenoceptors. Results obtained are discussed in relation to the concept that dihydrogenated ergot peptide alkaloids usually inhibit spontaneous contractions of the uterus and contractions induced by methylergometrine.


Methyl ester of N-formylmethionyl-leucyl-phenylalanine: chemotactic responses of human blood monocytes and inhibition of gold compounds.

N-formylmethionyl-leucyl-phenylalanine, a potent hemotactic peptide for human polymorphonuclear leukocytes, is less chemotactic for human blood monocytes. Esterification of the N-formylated tripeptide enhances its chemotactic activity for monocytes by more than 4 logs, whereas a decrease by 3 logs is observed for polymorphonuclear leukocytes. These results indicate the participation of the C-terminal carboxyl group in chemotaxis of different cell types. We have also observed the selective inhibition of chemotactic responsiveness of human blood monocytes by a clinically useful antirheumatic drug, sodium aurothiomalate. Since this is the first in vitro cell migration model of inflammation in which gold compounds have demonstrated activity in micromolar concentrations, it suggests a site of action for this antirheumatic drug.


Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus.

Data from a prospective study of the clinical course in 223 patients with systemic lupus erythematosus followed for 655 patient-years were analyzed by computer to determine the influence on frequency of infection of 1) corticosteroid dose; 2) azathioprine; 3) active disease, measured by new disease exacerbations, elevated ESR, hypocomplementemia, active urinary sediment, and proteinuria; 4) uremia; and 5) leukopenia. The frequency of all infections, and of bacterial and opportunistic infections specifically, increased progressively with increasing steroid dose. Azathioprine use, independent of steroid dose, did not account for an increased risk of bacterial, opportunistic, or nonspecific viral infections. Leukopenia did not predispose to infection, except possibly when associated with azathioprine-induced bone marrow suppression. Active renal disease, especially when manifested by abnormal urine sediment, was associated with an increase in infection frequency.


Effects of hypotension induced by halothane, on the cerebral circulation in baboons with experimental renovascular hypertension.

The effect of graded, progressive hypotension on the autoregulation of cerebral blood flow was studied in anaesthetized baboons with experimental renovascular hypertension. Graded hypotension was induced over a period of 5-6 h by the administration of increasing concentrations of halothane. In these chronically hypertensive animals cerebral blood flow remained constant until the mean arterial pressure had decreased to approximately 90 mm Hg. At mean arterial pressures of less than this value cerebral blood flow was pressure passive. At the completion of the investigation the brains were fixed by perfusion and submitted to neuropathological examination. Evidence of chronic hypertension and of ischaemic brain damage was found in every animal.


The effect of sodium cromoglycate, beclomethasone diproprionate and salbutamol on the ventilatory response to cotton dust in mill workers.

A double-blind placebo controlled study of sodium cromoglycate, beclomethasone dipropionate and salbutamol by inhalation was designed to test their effect on respiratory symptoms and changes in ventilatory capacity in cotton mill workers. All three drugs showed some beneficial effect. Salbutamol was the most effective drug studied, in all groups of workers. Beclomethasone dipropionate was also significantly effective particularly in workers with byssinosis or exertional dyspnoea. Sodium cromoglycate was the least effective of the three. Possible mechanisms of action of these drugs are described.


The biosynthesis and characterization of unreleased IgM in a case of CLL.

Intracellular IgM k is described in a case of CLL. The intracellular immunoglobulin occurred as amorphous spherical globules enclosed by rough endoplastic reticulum in the cytoplasms of the neoplastic lymphocytes. No abnormal IgM paraprotein could be found in the serum nor was there any Bence Jones protein detectable in concentrated urine. Biosynthetic studies confirmed the cells were able to synthesize IgM k immunoglobulin. On sizing gel analysis the intracellular IgM occurred as 7S monomer. The biosynthesis studies did not indicate secretion of IgM and was consistent with the serological findings. However, cells in culture secreted k light chain into the supernatant medium. It appears in this case that the secretory block is operating against heavy chain and not against free light chain. Some explanations for these findings are discussed.


Acute folate deficiency associated with intravenous nutrition with aminoacid-sorbitol-ethanol: prophylaxis with intravenous folic acid.

Preoperative folate levels were initially normal in 30 patients with gastrointestinal tract disease but fell within 48 h by 60-95% in 20 patients who received intravenous nutrition for 6-12 d with aminoacid-sorbitol-ethanol (ASE). This depression persisted in patients not given folate supplements. Folate levels in 10 control patients not given ASE showed only minimal decline. Haematological changes were reduced to a minimum in 10 patients given 0.5 mg i.v. folic acid daily whilst eight unsupplemented patients showed evidence of megaloblastic haemopoiesis. Three of these eight patients developed thrombocytopenia and/or leukopenia which was fatal in one patient.


Distribution of rhesus antigens on red cell surfaces.

Two pieces of evidence suggest different conclusions about the arrangement of the rhesus antigens on the surfaces of red cells. Indirect evidence suggests an ordered arrangement; electron-microscopic evidence has been interpreted visually as essentially random. Re-analysis of electron-microscopic material, using a form of computer spectral analysis, suggests that the visual interpretation was mistaken, and that the pattern is orderly. The material suggests that the maternally derived and paternally derived proteins are linked into couplets, and that the couplets may be regularly linked or packed, at least at shorter ranges. The material does not at present illuminate the question of longer range periodicity.


Structural elucidation of the 3-deoxy-D-manno-octulosonic acid containing meningococcal 29-e capsular polysaccharide antigen using carbon-13 nuclear magnetic resonance.

The capsular polysaccharide antigen from Neisseria meningitidis serogroup 29-e contains equimolar quantities of 2-acetamido-2-deoxy-D-galactose and 3-deoxy-D-manno-octulosonic acid (KDO), the latter of which is rarely found in biopolymers other than lipopolysaccharides. Carbon-13 nuclear mangetic resonance in conjunction with other chemical data indicated that the polysaccharide is composed of an alternating sequence of these two residues, the linkages being at C-3 of galactosamine and C-7 of KDO in the alpha-D and beta-D configuration, respectively. The native 29-e polysaccharide is O-acetylated, the O-acetyl groups being located at C-4 and C-5 of the KDO residues. Assignments of signals in the 13C nuclear magnetic resonance spectrum of the 29-e polysaccharide were made by consideration of those in the spectra of the monomer models, which necessitated the first recorded syntheses of methyl-alpha- and beta-D-3-deoxy-manno-octulopyranosonic acid. Like the methyl alpha- and beta-D-ketosides of sialic acid (Na+ salts), the equivalent methyl alpha- and beta-D-ketosides of KDO exhibit large chemical shift differences in the exocyclic C-8 position dependent on anomeric configuration. This can again be attributed to hydrogen bonding between the axial carboxylate group of the methyl beta-D anomer of KDO (C1 conformation) and the primary hydroxyl group at C-8. This phenomenon is also exhibited by the beta-D-linked KDO units of the 29-e polysaccharide.


Alteration by cereolysin of the structure of cholesterol-containing membranes.

When erythrocyte membranes were treated with cereolysin, negatively stained and examined by electron microscopy, ring and arc-shaped structures were observed in the membrane. The outside diameter of the rings varied from 33 to 50 nm with a border thickness of 6.7 to 8.3 nm. The arcs varied in length from 33 to 170 nm with a border thickness of also 6.7 to 8.3 min. When right-side-out erythrocyte ghosts which had been treated with cereolysin were examined by electron microscopy after freeze-fracture, structures with a diameter of 31 to 63 nm were seen in the fracture face of the exoplasmic half of the membrane, but no alterations were visible in the fracture face of the protoplasmic half of the membrane bilayer. Thus the ring structures did not appear to form holes through the membrane. At cereolysin concentrations above 6 microgram/ml rings and arcs were seen when purified toxin alone was examined. At or below 6 microgram/ml toxin rings and arcs were seen only if toxin was incubated with free or membrane-bound cholesterol. Our interpretation is that cereolysin tends to aggregate into ring and arc-shaped structures, and that the tendency to aggregate is increased by cholesterol. Rings and arcs were not seen when erythrocyte ghosts were treated with low, but lytic amounts of cereolysin that significantly altered the premeability of the ghosts.


The primary structure of rabbit, calf and bovine liver tRNAPhe.

Highly purified tRNAPhe from rabbit liver, calf liver and bovine liver were completely digested with pancreatic ribonuclease and ribonuclease T1. The oligonucleotides were separated and identified. The tRNAPhe from rabbit liver and calf liver were partially cleaved with ribonuclease T1 or by action of lead acetate. We describe the analyses of the large fragments and the derivation of the primary structure of these mammalian tRNAsPhe.


Mammalian tyrosinase. Structural and functional interraltionship of isozymes.

The isozymes of tyrosinase from normal and malignant melanocytes were studied; the data indicates that each consists of a basic tyrosinase polypeptide, and differs by post-translational modifications. T3 represents the de novo form of the enzyme; it is converted to T1 in vivo by the addition of sialic acids and neutral sugars, and in turn, to T4 by complexing with mealanosomal membrane constituents. The T2 isomer is suggested to be an artefact of the electrophoretic procedure, and due to deamidation of T3. It is shown that the apparent kinetics of enzyme activity are unafffected by any of these modifications.


Purification of jack bean meal beta-D-galactosidase by a new affinity adsorbent.

A simple procedure has been developed for the purification of jack bean beta-D-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) by affinity chromatography employing a new affinity adsorbent. The ligand 6-N-beta-(4-aminophenyl)-ethylamino-3-O-beta-D-galactopyranosyl-6-deoxy-L-gulitol was prepared by the reaction between lactose and beta-(4-aminophenyl)-ethylamine and was coupled to cyanogen bromide activated Sepharose 4B via the amino groups of the 4-aminophenyl moiety. This affinity gel resulted in a 111-fold purification of beta-D-galactosidase with a 64% recovery of the enzyme. With p-nitrophenyl-beta-D-galactopyranoside as the substrate the apparent Km and V values were 0.59 mM and 1.87 mumol/min per mg, respectively. The method for purification of beta-D-galactosidase may be applicable to other glycosidases depending upon the choice of specific di- or oligosaccharides of known structures to be used in the preparation of ligands.


[Study of the binding of thyroxine by thyroxine-binding prealbumin by a dialysis method using a fixed free concentration of ligand (author's transl)].

In order to study ligand-protein binding in solution, a dialysis method was used in which the free concentration of ligand can be controlled. The method has certain advantages and was applied to the binding of thyroxine by thyroxine-binding prealbumin, a system about which the results found in the literature are not in good agreement. From the isotherm drawn according to the Scatchard plot, it was found that thyroxine-binding prealbumin only presents a single binding site for thyroxine per molecule, the association constant being 1.7 . 10(8) M-1.


Glycosylation of endogenous lipids and proteins by preparations of chicken embryo fibroblasts.

Glycosylation of endogenous phosphoisoprenyl lipids and membrane-associated proteins was shown to occur in preparations of chicken embryo fibroblasts incubated with GDP[14C]mannose and UDP-N-acetylglucosamine. The two preparations used were cells released from the culture dishes by buffered saline containing EDTA and crude membranes from those cells. Both beta-mannosyl-phosphoryldolichol and oligosaccharide-phosphoryl lipids with five to eight sugar residues were labelled under the conditons employed. The oligosaccharide isolated from the octasaccharide-lipid fraction was shown to be heterogeneous after an analysis of the products formed by treatment of the oligosaccharide with glycosidases. Some of the oligosaccharides appeared to contain N-acetylglucosamine at positions external to that of [14C]mannose. Lipids with oligosaccharide moieties of different structures were made by the two preparations. The results of pulse-chase experiments were consistent with the glycosylated lipids being intermediates in glycoprotein biosynthesis.


Coenzyme M and methylcobalamin in methane biosynthesis: results of model studies.

Coenzyme M (2-mercaptoethanesulfonate, HS-CH2CH2SO3-) reacts with methylcobalamin nonenzymatically in the pH-range between 6 and 14 to yield the S-methyl derivative (CH3-S-CH2CH2SO3-). In addition, and also at lower pH, methane is produced by reductive cleavage of the Co-C bond. With methylcobaloximes as the methyl group donors, methane production predominates, with insignificant S-methylation. The initial rates of methane production from methylcobaloximes with coenzyme M as the reductant correlate with the rates of methane production from these substrates with active cell extracts of Methanobacterium M.o.H.


[Investigation of tyrosinase activity and phospholipid composition in Harding-Passey melanoma microsomal fraction].

Alteration in DOPA-oxidase activity of Harding-Passey melanoma microsomal fraction tyrosinase, activation of tyrosinase after partial delipidization of the microsome, phospholipid composition of both native microsomes and the ones after delipidization have been studied. In the course of tumor growth (starting on the 14th day after tumor transplantation) the tyrosinase activity has been shown to decrease monotonously both in native microsomes and in the ones after delipidization. The phospholipid composition alters both in the process of tumor growth and after delipidization. Alteration in the tyrosinase activity in native microsomes as well as after their delipidization has been found to depend on the relative composition of certain phospholipids. In those cases a linear correlation between the enzyme activity and the phosphatydylethanolamine of phosphatydylcholine ratio has been found. This interrelationship may be accounted for by either simultenous presence of inhibitors and activators of the enzyme activity in the lipids or by changes in the membrane structure depending on the relative phospholipid composition.


[Quaternary structure of glycogen synthetase I from rabbit skeletal muscles].

Glycogen synthetase I from rabbit skeletal muscles was studied by electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate. The presence of glycogen in the preparation prevented the destruction of the quaternary structure of the enzyme. In order to separate glycogen synthetase I from glycogen, alpha-amylase from saliva, pig pancrease and bacterial amyloglucosidase were used. The subunit composition of the total preparation and that of the individual glycogen synthetase forms separated ultracentrifugally in the sucrose density gradient, were shown to be identical. The molecular weight of the minimal subunit of glycogen synthetase I from rabbit skeletal muscles was shown to be 36,000. A comparison of the subunit composition of the enzyme preparations stored in the presence and in the absence of phenylmethylsulfanylfluoride did not show that the preparation possesses proteolytic activity.


[Transfer of proteins synthesized in the cytoplasm into mitochondria. Stimulation of mitochondrial protein synthesis by microsomal fraction].

The in vitro transport into mitochondria of proteins synthesized in the cytoplasm was studied. The system, in which the microsomes synthesize protein in the presence of mitochondria directly during the experiment proved to be the most efficient one. The microsomal fraction significantly stimulated the incorporation of 14C-valine into the isolated mitochondria proteins. The effects of EDTA treatment of the mitochondrial fraction, the dependence of protein synthesis stimulation on the ratio of mitochondria and microsomal proteins and the kinetic pattern of the reaction suggest that the stimulation of the labelled precursor incorporation into mitochondrial proteins is not probably due to the labelled microsomes adsorption on the mitochondria.


[Relation of cyclic and noncyclic electron transport in Rhodospirillum rubrum chromatophores. I. Experimental study of the kinetic characteristics of dark reduction of P870 with different donor concentrations in the medium].

The kinetics of the dark recovery of photo-oxidized bacteriochlorophyll P870 was studied as a function of the intensity and duration of actinic light illumination at different concentrations of a donor in the medium. From the comparison of the experimental data with the results of mathematical modelling of the processes under investigation [1] it is concluded that electron transport is triggered for another pathway, whenever the concentration of the donor in the medium attains a certain critical level.


[Cryoresistance of rat liver endoplasmic reticulum membranes].

The effects of freezing of microsomes in liquid nitrogen and those of storage of microsomal suspensions at 2-4 degrees C and -3 - -5 degrees C for 24 hrs, on the enzymatic activities and hydrophobicity of membranes were studied. The hydrophobicity was determined by fluorescence of bound 1,8-anilino-naphthalene sulfonate. Rapid freezing of the microsomal suspension in liquid nitrogen followed by rapid warming did not change the hydrophobicity of the membranes, the rate of enzymatic lipid peroxidation, the level of cytochrome P-450 and the activity of NADH- and NADPH-cytochrome c reductase. A considerable decrease in the rate of enzymatic lipid peroxidation and membrane hydrophobicity was observed in the microsomes stored for 24 hrs at 2-4 degrees C. The 24-hr storage at -3 - -5 degrees C with subsequent thawing resulted in a rapid aggregation of the microsomes.


Hyperglycemia and glycogen storage in the rabbit fetal liver. Role of age and hormonal status.

A 2-hour glucose infusion to pregnant rabbits resulted in fetal hyperglycemia. The question was studied whether this hyperglycemia would induce an increase in the concentration of glycogen in the fetal liver. The result depended upon the age of the fetus. In 24- or 25-day-old fetuses hyperglycemia did not increase the liver glycogen. On the contrary, on day 26, 27 and 28, the glycogen content in the liver was approximately twice as high as in controls. However, in fetuses which were decapitated on day 24 and studied on day 26, the maternal glucose infusion did not increase the glycogen stores. But in those fetuses decapitated on day 25 hyperglycemia provoked glycogen deposition. The activity of liver glycogen synthetase (active form alpha and total form a + b) increased between days 24 and 28 in control fetuses. Some increase of the alpha form already occurs between days 24 and 25. In fetuses decapitated on day 23, the alpha form was found almost as low on day 31 as it was on day 23. The incapacity of the liver of fetuses under 26 days of age or of those decapitated before day 25 to store glycogen under conditions of hyperglycemia probably results from a low glycogen synthetase activity.


The development of pyruvate dehydrogenase in the subhuman primate Macaca mulatta.

The development of total pyruvate dehydrogenase activity in the subhuman primate, Macaca mulatta, was investigated in brain, liver, kidney cortex, and skeletal and cardiac muscle. Newborn primates delivered prematurely at 135 days of gestation had only 32% of this enzyme activity present in the brain compared to the full-term animal. Full-term animals were similar to adults. All tissues showed high activities of enzyme at 1 year of age compared either with neonates or adults. Kidney cortex showed an increase in activity from 807 +/- 74 mumol/g/min in prematurely delivered neonates to a maximum of 3,769 +/- 275 mumol/g/min in 1-year-old animals. The results are discussed in relation to the developing energy requirements of the tissues concerned.


Effect of cortisone or L-triiodothyronine administration to pregnant rats on the activity of fetal intestinal disaccharidases and lysosomal acid beta-galactosidase.

Activities of maltase, sucrase, lactase and acid-beta-galactosidase were studied in jejunum and ileum of term rat fetuses obtained by cesarian section. Female rats were either untreated or injected daily in the last (3rd) week of pregnancy with cortisone acetate (10 or 50 mg/100 g body weight) or L-triiodothyronine (20 or 50 microgram/100 g body weight). Two other control groups were injected with appropriate solvents. Cortisone or T3 treatment to mothers increased sucrase and maltase activity in jejunum and ileum of the offspring. Generally, higher doses of hormone were more effective. Lactase activity was increased by 25% in the jejunum by the higher dose of cortisone. Both doses of cortisone increased ileal lactase. Jejunal acid-beta-galactosidase activity was decreased in fetuses of T3-treated mothers.


Heart rate and body temperature in separated monkey infants.

Heart rate (HR) and body temperature (BT) were recorded from ten unrestrained group-living M. nemestrina (pigtail) monkey infants, using totally implantable multichannel biotelemetry systems, during a 4-day base line (preseparation) period, during the agitation-depression reaction accompanying 4 days of maternal separation, and for several days following reunion with the mother. Quantified behavioral data were collected in nine of the ten infants. Mean daytime (1000 to 1600 hr) and nightime (2200 to 0400 hr) HR and BT values were computed for each infant, and for the group as a whole. The behavioral agitation reaction immediately following separation was accompanied by increases in both HR and BT. Beginning with the first night of separation, both HR and BT showed marked decreases from base line. Whereas group mean HR and BT changes were maximal early in the separation, behavioral indices of depression tended to be maximal later in the separation period. Reunion with the mother tended to normalize HR and BT in most infants. Two infants exhibited sudden transient reversible drops in nocturnal BT well into the separation period, suggesting an impairment in thermoregulatory mechanisms during the period of depressive behavior. One infant had a prolonged separation-induced decrease in HR that persisted throughout reunion, indicating that the stress of maternal separation may induce physiological changes that considerably exceed the duration of the effective stress.


Recent aspects of prostaglandin biosynthesis: a review.

Some recent aspects of prostaglandin biosynthesis of physiological importance are reviewed. Particular attention has been placed on phospholipase functioning and inhibition, endoperoxides, thromboxane and prostacyclin (PGX) synthesis since these compounds are likely to be the potent biological derivatives of prostaglandin biosynthesis. Because of some recent studies, peroxidative reactions have been detailed; their intervention in prostaglandin biosynthesis is of importance and could explain some regulatory aspects of this process, as well as the action of several cofactors and prostaglandin synthetase inhibitors.


Comparison of the restoration effect of Pseudomonas aeruginosa, BCG and poly I: poly C on cancer patients non responsive to recall antigen delayed hypersensitivity.

A preparation of 10 serotypes of Pseudomonas aeruginosa has restored skin delayed hypersensitivity reactions to recall antigens in about fifty per cent of cancer patients not previously immunodepressed by radiotherapy or chemotherapy, but anergic. This proportion is similar to that obtained by given modalities of administration of BCG, C. parvum or levamisole, while other modalities of application of BCG or administration of poly I: poly C do not induce such an immuno-restoration in a significant number of patients.


Heat-killed Pseudomonas aeruginosa as a systemic adjuvant in cancer immunotherapy.

The effect of heat-killed Pseudomonas aeruginosa (10 serotypes) on antibody formation, macrophage activation and leukemia growth was investigated in relation to the dose injected and to the time and the route of administration. It appeared that intravenous administration of the preparation (10(9) bacteria per ml) was the most efficient at the dose of 0.1 ml since: 1) it increased the number of PFC against SRBC when injected 10 days before the antigen (higher doses and shorter time intervals resulted either in no modification or an significant inhibition of the PFC response; 2) it induced a slight activation of peritoneal macrophages as measured by their cytostatic activity for tumor cells in vitro, when injected 3 or 7 days before testing whereas higher doses were ineffective; 3) it increased the survival time of leukemic mice when administered 2.5 days before the injection of L1210 tumor cells, and higher doses were also effective in this immunoprophylaxis assay. When the subcutaneous route was used, large doses appeared to be the most effective: 1) potentiation of the PFC response was obtained only when 0.5 or 0.2 ml were given 10 days before the antigen; 2) macrophage activation was demonstrated 7 and 10 days after 0.5 ml; 3) leukemia growth was retared when 0.5 or 0.2 ml was injected 2.5 days prior to L1210 tumor cell inoculation and also when 0.2 and 0.1 ml were injected 7 days before tumor cells. No correlation between macrophage activation and the inhibition of tumor growth could be found.


Diffusion control in reversible enzyme reactions. Applications to carbonic anhydrase.

The limit to the possible rate of reversible enzymatic reactions set by the diffusional motion has been considered. It is found that not only the diffusion of the reactants to the enzyme but also the diffusion away of the products can be rate limiting. To avoid assumptions about the detailed nature of the enzyme only diffusion in the bulk aqueous medium is treated. By such an approach one obtains an upper limit to the possible rate. In the latter half of the paper the derived general equations are applied to the possible suggested reaction schemes for the enzyme carbonic anhydrase. It is found that a scheme involving HCO3- as substrate for the dehydration process and a direct reaction between buffer and enzyme is comsistent with the limits set by the diffusional motion, while several other possibilities can be ruled out.


[Cross microbial antigens of the human bronchopulmonary apparatus].

The work was undertaken to assess the antigenic affinity of some Neisseria perflava, Klebsiella pneumoniae, Staphylococcus aureus strains serving as active sensitinogen of the human broncho-pulmonary apparatus. With the aid of the complement fixation test, precipitation after Ouchterolony, and immunoelectrophoresis there was established the presence of a series of similar antigenic determinants common for all the three microbes and for determinant responsible for the cross reactions of two microbes only.


[Analysis of the types of chromosome aberrations in the combined action of chemical mutagens].

Types of chromosome aberrations were studied in human lymphocyte cultures in combined action of different concentrations of thiophosphamide and dipine in different proportions. The mutagens acted at the Go stage. The range of the concentrations studied was from 3.17-10(-5) M to22.19-10(-5) M. As compared with dipine, the equimolar concentrations of thiophosphamide induced more chromatid exchanges and less sister (isolocus) unions, and also a greater part of single breaks and the part of breaks in the chromatid exchanges of the total number of chromosomal breaks. Both absolute and relative frequencies of chromosome aberrations depended on the mutagens concentration. A change of the thiophosphamide and dipine proportion with a constant total number of molecules of the two mutagens at different concentration levels led to the effect, the level of which was between the effect of action of equimolar concentrations of pure mutagens. This effect depended upon the part of each mutagen in combined treatment. A conclusion was drawn on the additivity of thiophosphamide and dipine action.


Microscopic platelet size and morphology in various hematologic disorders.

Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.


The actions of diazepam and phenytoin on a low dose penicillin epileptiform focus in the anaesthetised rat.

1 A technique is described for the induction of an acute short-lived epileptiform focus by the local injection of benzyl penicillin 25 units into the cerebral cortex of rats anaesthetized with urethane. The effects of anticonvulsants on this microfocus have been studied. 2 Phenytoin 20 mg/kg and diazepam 1 mg/kg intravenously significantly reduced the frequency of the normally occurring surface positive electrocorticogram (ECoG) plateaux and caused a greater decrease in the frequency of the epileptiform spikes normally associated with these plateaux. 3 A novel effect was seen in that both anticonvulsant drugs significantly reduced the amplitude of the epileptiform spike within the focus, as well as causing an even larger decrease in the amplitude of the propagated spike. The contribution of the anticonvulsant drug effect on the focal spike to its effect on propagated activity is discussed.


Build-up and depth-dose characteristics of different fast neutron beams relevant for radiotherapy.

Build-up and central axis depth-dose curves have been obtained for d(50) + Be and d + T neutron beams. Measurements carried out with the collimator opening covered with a layer of lead showed that for all three neutron beams the entrance dose is approximately 60% of the dose at the maximum. Consequently the skin-sparing properties of these neutron beams will be approximately equal and comparable to those for electron beam therapy. Central axis depth-dose curves have been established for d(50) + Be neutrons at 129 cm SSD, for p(42) + Be neutrons at 125 cm SSD and d + T neurtons and 60Co gamma rays at 80 cm SSD. The 50% dose values in a water phantom are at depths of 12.7 cm, 12.0 cm, 9.7 cm and 12.7 cm respectively, for field sizes of approximately 15 cm x 20 cm. Insertion of a 6 cm thick nylon filter in the p(42)+Be beam increases this value from 12.0 cm to 13.5 cm. The gamma component for the d+T neutron beam is higher than for the cyclotron beams.


Subarachnoid haemorrhage above the age of 59: are intracranial investigations justified?

Out of 186 patients aged over 59 referred to a neurosurgical department after spontaneous subarachnoid haemorrhage, 143 underwent cerebral angiography; only 28 (15%) of the patients had surgery, of whom 16 were independent one year later. The doubtful benefit of surgery and the small proportion of patients who underwent surgery have economic and ethical implications; in particular, neurosurgical beds and neuroradiological facilities should not be occupied by such patients if this delays the admission of younger patients and those requiring investigation of intracranial space-occupying and spinal lesions.


Cell-mediated immune response in gonococcal infections.

Peripheral blood lymphocyte (PBL) transformation stimulated by gonococcal and meningococcal antigens was studied in 29 men and 21 women with uncomplicated gonorrhoea. The blastogenic responses of PBLs from these men and women were substantially higher than from normal controls. Cross-reactivity between Neisseria gonorrhoeae and Neisseria meningitidis was manifested by the PBL transformation responses in patients with gonorrhoea to non-purified meningococcal antigen (MGC-I). In both male and female patients the PBLs were stimulated by non-purified gonococcal antigen (GC-I) and by non-purified meningococcal antigen. The extent of the blastogenic response in women was much greater than in men. Partial purification of these antigens by gel chromatography resulted in reduced cross-reactive responses to the semi-purified meningococcal antigen (MGC-II). Female patients demonstrated marked stimulation with the semi-purified gonococcal antigen (GC-II), while male patients showed slight stimulation with GC-II. It is possible that cell-mediated immunity may act to limit the spread of gonococcal infection beyond the genital mucous membranes.


Release of enzymes from human leucocytes during incubation with Neisseria gonorrhoeae.

The effect of Neisseria gonorrhoeae on release of enzymes from human leucocytes was determined. Supernatants from incubation mixtures containing leucocytes and gonococci were assayed for activity of the cytoplasmic enzyme, lactic acid dehydrogenase, as well as for activity of the hydrolytic enzymes, β-glucuronidase and lysozyme, which are found primarily in leucocyte granules. Thirty-minute incubation of leucocytes with pilated T1 gonococci resulted in a negligible release of lactic acid dehydrogenase and little release of β-glucuronidase even at bacteria to leucocyte ratios as high as 50 to 1. Lysozyme release, however, was significant at this ratio and at 20 to 1 but not at 5 to 1. Incubation with non-pilated T4 bacteria yielded no significant release of lactic acid dehydrogenase or β-glucuronidase, but it caused a significant release of lysozyme at bacteria to leucocyte ratios as low as 2 to 1. These results suggested that the lysozyme release might be related to the degree of phagocytic activity since, at low ratios, T4 was readily ingested but T1 was not. Consistent with this hypothesis, serum which promoted the phagocytosis of the pilated gonococci also stimulated lysozyme release at low ratios of T1 to leucocyte. Absorption of the serum with T1 abolished the opsonic effect and markedly diminished the amount of lysozyme released.


Which Neisseria?

A case of disseminated gonococcal infection in which the gonococcus was isolated from the blood and genitalia and the meningococcus from the throat is described. A second patient, in whom the meningococcus was isolated from the throat and the gonococcus from the genitals but in whom no organisms were recovered from the blood, had lesions resembling those of a disseminated infection. The results of 150 throat cultures from patients who were examined at a clinic because they had a history of oral sexual intercourse are presented. The meningococcus was isolated nearly six times more often in patients with genital gonorrhoea than in those in whom genital cultures were negative, while the gonococcus was found 2 1/2 times more often in those who carried the meningococcus in the throat than in those who did not. If these findings can be confirmed it could indicate an individual susceptibility to the acquisition of Neisserian organisms that would merit further investigation.


Defects in accuracy of reaching after removal of posterior parietal cortex in monkeys.

We measured the capacity of monkeys to project the arm to visually located targets under conditions differing in the nature of visual control allowed during reaching. This capacity was impaired by a unilateral posterior parietal lesion which increased the magnitude and variability of errors in projecting the contralateral arm to targets located on either side of the midline. Furthermore, accurate projections of the arm were often accompanied by misorientations of the fingers of the hand. These errors occurred whether reaching with or without visual guidance of the limb. The presence or absence of vision influenced the direction of errors in arm projection. Under conditions permitting a view of the limb and sight of the target, errors occurred in a direction toward the side of the lesion. When all visual cues were eliminated during reaching, errors were directed away from on-target toward the midline as they are in normal monkeys, but were greater in magnitude following the lesion.


Heterosexual, autosexual and social behavior of adult male rhesus monkeys with medial preoptic-anterior hypothalamic lesions.

Bilateral radiofrequency lesions were made in the medial preoptic-anterior hypothalamic (MP-AH) area of 6 adult male rhesus monkeys; 5 sham-lesioned subjects served as controls. Behavioral analysis consisted of observations on copulatory behavior, yawning, masturbation and some aspects of social behavior. MP-AH lesions reduced or completely eliminated the display of manual contacts of the partner, mounts, intromissions and ejaculations without interfering with masturbation. Yawning, a sexually dimorphic behavior, was not affected either, Measure of several social behaviors indicated no evidence of social withdrawal or other aberrance of social interactions, which might have led to the decline in heterosexual behavior. The results with regard to copulatory behavior were consistent with the effects of MP-AH lesions in rats, cats and dogs. In rhesus monkeys it appears as though the MP-AH region is specifically involved in the mediation of heterosexual copulation and is not vital to the performance of other forms of male sexual activity such as masturbation. Also the MP-AH is not critical for the display of all sexually dimorphic behaviors. The types of behavioral change in MP-AH lesioned subjects differed to some extent from those following castration, indicating that the effects of the lesions cannot be explained as basically that of functional castration.


The use of osmolality as an aid to establishing consistent fixation quality: studies on the kidney of the domestic fowl.

1. Using the proximal convoluted tubule of the fowl kidney as indicator tissue the immersion application of fixatives of differing composition and osmolality was studied. 2. The best results were obtained with Dalton's buffered osmium tetroxide and with sodium cacodylate buffered glutaraldehyde followed by osmium post-fixation. 3. The most satisfactory component concentrations in both cases were those which most reproduced a total osmolality close to that of fowl plasma. With both types of fixation the ultrastructural image of the kidney tubule was sensitive to changes in fixative osmolality and differences were clearly identified over a 30 to 50 mOsm range. 4. With glutaraldehyde/osmium double fixation it was found that it was the total osmolality of the glutaraldehyde buffer combination that was to be considered in a study of osmolotic effects, not the osolality of the buffer vehicle alone. 5. The 30 to 50 mOsm difference in fixative osmolality that was able to be detected by studying the image of the kidney tubule was of the order of magnitude commonly experienced as experimental error in the laboratory as a result of changes in reagent batches or error in making up the solutions. The measurement of osmolality therefore provides an ideal quality control to the laboratory make-up of fixative solutions.


Comparison of radiotherapy with and without razoxane (ICRF 159) in the treatment of soft tissue sarcomas.

Comparison of the recurrence rates of soft tissue sarcomas treated by radiotherapy (14 patients) or radiotherapy and synchronous administration of razoxane (19 patients) has shown a statistically significant benefit for those patients treated by the combination. No increase in tissue reactions or adverse side-effects (apart from a readily reversible leukopenia) was observed. The implication is that razoxane acts as a well tolerated adjuvant for radiotherapy.


Comparison of the convulsant effects of cocaine and pseudococaine in the rhesus monkey.

The convulsant effects of cocaine and its C2-epimer, pseudococaine on EEG, respiration, heart rate and behavior were studied in the rhesus monkeys with electrodes implanted in the brain. Intravenous injections of cocaine (3.0 to 8.0 mg/kg) and pseudococaine (3.0 to 7.0 mg/kg) in the animals produced a similar pattern of clonic convulsions accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. However, both isomers showed different effects on the EEG and animal's behavior following convulsions; e.g., the cocaine-induced convulsions were followed by low-voltage fast waves in the EEGs associated with behavioral hyperexcitation, while pseudococaine-induced convulsions were followed by high-voltage slow waves associated with behavioral depression and drowsiness with intermittent sleep. Pseudococaine was more potent than cocaine in producing convulsions in the same monkeys. The durations of convulsions produced by these drugs were dose-dependent.


Radition therpay control of nine patients with malignant thymoma.

Malignant thymoma is a relatively rare condition and a review of the literature reveals approximately 100 reported cases. Only a small percentage of these have been treated with megavoltage radiation therapy; therefore, it is difficult to find the necessary information to establish a proper time-dose relationship for treatment. This report deals with the radiation therapy and survival data concerning nine patients treated for malignant thymoma during a ten year period at the Medical University of South Carolina. Megavoltage irradiation in the dose range of 3500-4800 rads was employed in all patients. All gross tumor was completely resected in only three patients, two had a biopsy only, and the remaining four had subtotal resections. Local tumor control has been 100% with the average follow-up being 5.5 years and a minimum of 30 months. Three patients are dead; one from intercurrent disease, one from myasthenia gravis, and one from radiation injury to the spinal cord. One patient is alive with metastatic disease controlled by chemotherapy. The technique of radiation therapy is outlined, as well as suggested treatment policy.


Tumor promotion and the induction of epidermal ornithine decarboxylase activity in mechanically stimulated mouse skin.

Wounding by incision was a promoting stimulus in mouse skin previously initiated with 7,12-dimethylbenz-(a)anthracene. Skin massage elicited a marked proliferative response in skin but was not a promoting stimulus. Wounding mouse skin, either by multiple scalpel incisions or by stripping with silicon carbide paper, led to a marked induction of ornithine decarboxylase activity. In both instances activity was maximal between 20 and 26 hr after wounding, with a secondary rise at 72 hr. Skin massage did not lead to a detectable increase in ornithine decarboxylase activity over the same time period.


Formation of a mutagenic drug metabolite by intestinal microorganisms.

A new broad-spectrum antiparasitic agent, 4-isothiocyano-4'-nitrodiphenylamine, is devoid of mutagenic activity in vitro, either alone or in the presence of activating enzymes of rat liver. However, six species of mammals receiving this drug excrete as as yet unidentified mutagenic metabolite. Several observations suggested that one or several constituents of the enteric bacterial flora, rather than the metabolic activities of the host, are involved in the formation of this mutagen. Unequivocal demonstration for such a mechanism was provided by germ-free rats that do not form this metabolite, in contrast to their conventional littermates. Only a relatively moderate and apparently quite selective reduction in the total number of microorganisms of the intestinal flora is needed to elminate this mutagenic transformation. For example, following administration of a single dose of erythromycin or erythromycylamine, conversion of the isothiocyanate to a mutagen can be prevented completely, while antiparastitic activity is maintained. There is no obligatory association between chemotherapeutic activity and the formation of the mutagenic metabolite, and these two activities can be dissociated completely. This suggests a new approach for increasing the safety of pharmacological agents.


Relationship between insulin and estrogen binding to growth response in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors.

Insulin and estrogen binding have been determined in 7,12-dimethylbenz(a)anthracene-induced mammary tumors of rats in various endocrine states. Hormonal therapy, such as diabetes and ovariectomy, resulted in differential effects on growth patterns and hormone binding of tumors coexisting in the same host or in different hosts. It was observed that tumors that continued to grow after the host was made diabetic (insulin independent) or started to regress after ovariectomy (ovarian dependent) demonstrated decreased insulin binding. Tumors that regressed in diabetic hosts (insulin dependent) or continued to grow in ovariectomized animals (ovarian independent) showed an increased insulin-binding capacity. No significant change in insulin binding was observed in tumors that remained static after ovariectomy or induction of diabetes. Estrogen binding in tumor cells from diabetic rats paralleled the pattern of tumor growth response to diabetes; insulin-independent tumors demonstrated a significant increase in binding compared to tumors from intact hosts, and insulin-dependent tumors showed decreased estrogen receptor levels. From these results, we conclude that (a) insulin plays a positive role in regulating estrogen-binding capacity, (b) ovarian hormones may play a role in regulating insulin-binding capacity, and (c) a relationship between insulin and ovarian hormones and the growth of 7,12-dimethylbenz(a)anthracene-induced tumors is strongly suggested and may have therapeutic implications.


Harmonic analysis of the left ventricular pressure waveform of the primate.

Most attempts to quantitate myocardial function rely on morphologic features of complex pressure waveforms to reflect the functional properties of the ventricular myocardium. Relationships between waveform components and the function of the organ generating them were examined in 38 rhesus monkeys by harmonic analysis of left ventricular pressure waveforms. In the basal state, harmonic content was closely correlated (r=0.98) with hemodynamic state, as quantitated by heart rate, systolic and diastolic pressures, left ventricular end-diastolic pressure and maximum contractile element velocity. Hemodynamic indices were expressed as significant linear functions of harmonic terms (r=0.71--0.83), in patterns consistent with the principle of superposition. In 20 animals, infusions of dextran, methoxamine, propranolol or ouabain were used to further assess this relationship. Results demonstrated (1) significant correlation between changes in hemodynamic and harmonic parameter (4= 0.99), (2) correlations between each harmonic term and the set of hemodynamic indices such that specific terms varied directly with contractility but not with loading, whereas others correlated significantly only with loading, and (3) that the patterns in these correlations were of such specificity as to permit construction of significant discriminant functions (p less than 0.0001) that accurately characterized the pharmacologically induced hemodynamic change in 85% (56/67) of trials.


Intracoronary versus intravenous nitroglycerin on the transmural distribution of coronary blood flow.

The effect of intracoronary versus intravenous administration of nitroglycerin (GTN) on the transmural distribution of coronary blood flow (epi/endo) was studied in an isolated canine heart preparation and intact dogs. The distribution of blood flow between epicardium and endocardium of the left ventricle was determined by use of radioactive microspheres (15 micrometer diameter). Intracoronary infusion of GTN in the isolated heart significantly increased epi/endo during a constant coronary blood flow, whereas no change in epi/endo was observed during a constant coronary perfusion pressure. When maximal coronary vasodilatation was produced by chromonar, the epi/endo increased significantly, however intracoronary GTN produced no further vasodilatation and did not improve epi/endo. In contrast, intravenous infusion of GTN in intact hearts significantly decreased epi/endo. These results suggest that intracoronary GTN does not enhance endocardial perfusion and may even produce a coronary steal, whereas intravenous GTN may improve endocardial perfusion via indirect haemodynamic actions.


The posterior horn and collateral trigone of the lateral ventricle of the monkey brain (Macaca speziosa). A scanning electron microscopic study.

The posterior horn of the lateral ventricle in the monkey brain varies in size in different individuals. In this part of the ventricle, the ependymal cells bear cilia, microvilli, microblebs and supraependymal, axon-like cell processes. Only slight differences are seen in the different parts of the posterior horn: The roof has densely packed cilia and microvilli. Supraependymal axons are almost absent. The lateral wall has axons which are irregularly arranged. Subependymal vessels are partly covered by polygonal ependymal cells. The collateral trigone has some regions with densely packed cilia and some with widely spaced cilia. The regions with widely spaced cilia have polygonal cells whose surfaces differ in shape and are surrounded by a border of microvilli. The meshwork of supraependymal axons is wide-spread on polygonal cells. The medial wall shows no regional differences. Though larger areas are free of supraependymal cell processes, all ependymal structures (cilia, microvilli, microblebs) are present. In the posterior horn of only two animals were these larger spherical protrusions present which could be the result of a secretory process.


Intercellular bridges in ovarian follicle cells of Drosophila melanogaster.

Intercellular bridges have been detected in ovarian follicle cells of Drosophila melanogaster. These bridges occur widely between follicle cells of previtellogenic chambers, while, in vitellogenic chambers, they become restricted to the columnar follicle cells. Usually, only one bridge is detectable between adjacent follicle cells, but a single cell may form two cytoplasmic continuities. The fine structure of the intercellular bridges is similar to that previously described in the development of Drosophila. The bridge wall consists of two layers of which the more external is more electron dense and thinner than the inner one. The role played by the intercellular bridges in the determination of asynchronous differentiation of the linked follicle cells is discussed in relation ot the known behaviour of these cells in the secretion of the egg covering precursors.


Drosophila: the genetics of two major larval proteins.

A series of irradiation-induced deficiencies covering 62 polytene chromosome bands in chromosome arm 3L of Drosophila melanogaster includes the loci of two abundant developmentally regulated larval proteins. The structural gene for larval serum protein 2 (LSP 2) lies at 68E3 or 4, and that for salivary glue secretion protein 3 between 68A8 and 68C11, coincident with a major intermoult puff active in the salivary gland at the time of glue synthesis. The structural genes for esterase 6 and four visible recessive loci lie within the same region.


[Morphological evolution of the first lower premolar of some higher primates].

Recent discoveries in Africa, in Asia and in Europe of new fossils attributed to the Ramapithecinae and/or to the Australopithecinae seem to point out the monocuspid origin of Man's first lower premolar the bicuspidy of the Gigantopithecidae, the Oreopithecidae' and the Hominidae' first lower premolar, reached at different geological ages, give an example of parallel evolution.


[The schizogony of Polychromophilus (Haemoproteidae), cosmopolitan parasite of Microchiroptera].

The schizogony of Polychromophilus was partially known by the findings of Schingarew, Mer and Goldblum who demonstrated microschizonts in the reticulo-endothelial tissue. The present work completes these data by showing the presence of macroschizonts in the lungs of both African and European species. These schizonts are characterized by their large size, the hypertrophy of the host cell and its nucleus and the evolution of the parasite apparently slow when young, becoming rapid later.


[Effects of hyperpolarizing currents on the action potentials of nodal and perinodal sino-atrial cells of the rabbit heart].

A technique of focal polarization allowed us to confirm that the action potentials of the true rabbit heart pacemaker cells possess a rapid sodium channel normally inactivated because of the low value of the take-off potential of this tissue. The latent pacemaker cells are regular sinocaval cells depolarized as a consequence of the proximity of true pacemaker cells.


[Presence of neurons synthesizing LH-RH in the anterior hypothalamus of the duck (Anas platyrhynchos)].

Using histochemical techniques with LH-RH anti-serum, a large number of LH-RH producing neurons were identified in the Duck hypothalamus, under different physiological conditions. The LH-RH pericaryas were localized in a well delimited area of the anterior hypothalamus, including the dorsal part of the periventricular preoptic nucleus. The LH-RH containing axons were directed downwards towards the infundibulum, and terminated within the external layer of the rostral and caudal median eminence, in close vicinity to the capillaries of the pituitary portal system.


[Acceleration of the speed of neuronal growth by a new neurotropic substance: N-isopropyl-amino-2-pyrimidine].

16 hrs. after per os administration of 14C N-isopropyl-amino-2-pyrimidine (IAP) in the Rat, radioactivity of the sciatic nerve is significantly higher than in plasma and other organs. In vitro IAP (base, orthophosphate or dichloracetate) accelerates neurite outgrowth of explained spinal ganglion after 48 hrs. of incubation in nutritive medium. Results suggest that IAP incorporated in nerve cell acts on cellular mechanisms controlling nerve growth.


[Detection of DDT in quail eggs: quantitative analysis].

Significant residues of DDT have been found in the albumin and vitellus of Quail eggs, after external treatment of the shell with an aqueous suspension of commercial DDT. The rate of pesticide crossing varies according to the shell porosity and thickness. Residues of DDT have also been found in the control eggs and in the Quail industrial food.


[Allergenic character of tetrahydrocannabinol (delta 9 THC), active principle of Indian hemp (Cannabis saliva var. indica)].

The maximization test applied on the Hartley Guinea Pig and the mast cell degranulation test performed on the sensibilised Guinea Pig serum resulted in: 1, extreme allergenicity; 2, the formation of circulating antibodies anti delta9 THC.


[A new method permitting the quantitative determination of virus present in surface waters].

With a 34% efficiency, not related to the amount of viruses, a simple and inexpensive apparatus allows quantitative recovery of enteroviruses from river-water.


[Survival of tumor fragments as a function of temperature: correlation with electric impedance].

The ability of small pieces of Rat Walker's tumour carcinome 256 to develop a subcutaneous tumour on another Rat is dependent on the value and the duration of heat treatment.


Effect of nitroglycerin and arterial hypertension on myocardial blood flow following acute coronary artery occlusion in the dog.

This study was designed to evaluate the effects of nitroglycerin and phenylephrine-induced arterial hypertension on regional myocardial blood flow in awake dogs with acute occlusion of the left circumflex coronary artery. Myocardial blood flow to four transmural layers from epicardium to endocardium was estimated with 7-9 micron radionuclide labeled microspheres in 1) the non-ischemic myocardium, 2) the central ischemic zone, and 3) the border zone separating ischemic from normally perfused myocardium. Measurements were repeated 1) during infusion of nitroglycerin, 0.015 mg/kg/min, 2) during phenylephrine administered to increase arterial pressure 60 mm Hg above the control measurements, and 3) during combined nitroglycerin and phenylephrine administration. Both nitroglycerin and phenylephrine increased myocardial blood flow to the central ischemic area; nitroglycerin significantly decreased the resistance of the collateral vascular system, while the increased flow during phenylephrine administration was accounted for entirely by the increased arterial pressure with no change in collateral vascular resistance. The increased blood flow to the central ischemic zone during nitroglycerin administration was delivered preferentially to the subendocardium, while the increased blood flow during phenylephrine administration was directed exclusively to the subepicardium. Neither nitroglycerin nor phenylephrine significantly altered computed vascular resistance of the border zone, but because of the increased driving pressure, blood flow to the border zone was significantly increased during phenylephrine administration.


Respiratory disease in workers exposed to solder flux fumes containing colophony (pine resin).

Twenty-one patients are described who developed asthma, or evidence of a peripheral airways reaction, while working in the electronics industry and exposed to solder flux fumes containing colophony (pine resin). This selected group contained five patients with pre-existing asthma. Fourteen patients had never smoked. Prick-testing with common environmental antigens gave one or more positive reactions in nine patients. The diagnosis was confirmed by occupational-type provocation tests in all workers with colophony-based cored solder, and reproduced by exposure to the fumes of heated colophony alone. Control subjects did not react to the test with colophony. The clinical findings and provocation test reactins have features of a hypersensitivity reaction, although so far specific antibodies have not been found.


Allergenic activity of fractions of cocksfoot (Dacylis glomerata) pollen.

A cocksfoot (Dactylis glomerata) pollen extract has been fractionated by isoelectric focusing in polyacrylamide gel, the separated components extracted from the gel and assayed by three methods: prick tests in human skin, RAST and PCA tests in monkey skin. Prick testing in human skin showed that subjects responded differently to the separated components, indicating the presence of more than one antigenic determinant, and a profile of antibody activity against each fraction could be constructed. In general, good agreement was observed between RAST profiles and skin test profiles, although some patients who gave positive skin tests lacked circulating IgE and consequently did not give a RAST profile or a monkey PCA. These studies emphasize the current difficulty in attempting to isolate a single pure allergen from cocksfoot which can be used either diagnostically for the detection of pollen allergy, or for the standardization of diagnostic extracts.


A practical radioimmunoassay of thyroglobulin.

We describe a reliable and convenient double-antibody radioimmunoassay for human thyroglobulin that can be performed within two days. Analytical recoveries were quantitative and immunological equivalence between several sources of human thyroglobulin was demonstrated. Cross reactivity with either thyroxine or triiodothyronine was insignificant. The between-day coefficient of variation in the 5--100 mug/liter range was 10%. The range observed for 68 normal individuals was 2--61 microgram/liter.


Electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay evaluated for quantification of human apolipoprotein B.

We examined three immunoassay techniques for measuring apolipoprotein B in serum and major lipoprotein density fractions from normolipidemic and hyperlipoproteinemic persons, comparing values by electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay with those determined gravimetrically. Electroimmunoassay is faster and simpler than radioimmunoassay, and equally precise (within- and between-assay coefficients of variation for both were 5 and 7%, respectively). All the immunoassays gave results that agreed with those by gravimetry for normolipidemic sera and the corresponding lipoprotein density fractions, but only electroimmunoassay results agreed with those by gravimetry for apolipoprotein B in lipoproteins of d less than 1.019 g/ml isolated from hypertriglyceridemic patients. Concentrations of apolipoprotein B in plasma, determined by electroimmunoassay in a population of normal persons and patients with primary hyperlipoproteinemias, were: normals, 980 +/- 200; type I, 700 +/- 160; type IIa, 2000 +/- 260; type IIb, 2180 +/- 300; type III, 1300 +/- 340; type IV, 1470 +/- 400; and type V, 1550 +/- 390 mg/liter (mean +/- SD). Lipoprotein density fractions from the hyperlipoproteinemic patients each had a characteristic distribution of free and associated forms of lipoprotein family B. The absolute concentration and distribution of apolipoprotein B between the free and associated forms of lipoprotein B may represent a useful indicator of the underlying biochemical defect(s).


A double antibody solid phase radioimmunoassay for placental alkaline phosphatase.

A solid-phase "direct" radioimmunoassay for determination of placental alkaline phosphatase in serum was developed. The assay is highly sensitive, with a minimum detectable dose of 9 ng protein per ml. The specificity for the placental type of the enzyme, in comparison to other serum alkaline phosphatases, was found to be convincing. The choice of genetic types of either placental alkaline phosphatase or antiserm was found not to influence the radioimmunoassay. With the described technique the serum concentration of this enzyme during normal pregnancy was measured. A 25-fold increase from low levels during the first trimester up to 252 +/- 70 ng/ml (mean +/- S.D.) in gestation week 40 was observed.


Biosynthesis and characterization of intracellular IgDkappa in a case of CLL.

A case of chronic lymphocytic leukaemia (CLL) with diffuse intracellular IgDkappa is reported. No serum paraprotein or urinary Bence-Jones protein were detected. No surface immunoglobulin was found on the neoplastic lymphocytes, but the cells had receptors for Fcgamma and the C3 component of complement consistent with other cases of CLL. Biosynthetic studies confirmed that the cells synthesized IgDkappa but there was no evidence for secretion of IgD into the culture medium. The cells did not produce Ig of any other class. The intracellular IgD occurred predominantly as deltakappa units with no covalent links between the chains. These findings are discussed.


Characterization of the IgA immunocyte population and its product in a patient with excessive intestinal formation of IgA.

An 11-year-old Norwegian boy presented with clinico-pathological features indicative of coeliac or alpha-chain disease. However, his major serum component (about 50 mg/ml) was found to be a polyclonal, polymeric (about 80% dimeric) IgA consisting mainly of the subclass IgA1 and showing a kappa:lambda ratio of 67:33. Also the serum concentration of IgA monomers was increased (about 9 mg/ml). The polymers were heterogeneous with regard to J-chain content--varying on a molar basis from 1.9 for the more basic fraction to at least 2.4 for the more acidic one. Both fractions showed non-covalent affinity for secretory component (SC) in vitro. Most of the serum IgA seemed to originate from the small intestine, which contained a five-times-increased population of IgA immunocytes. These cells were heterogeneous with regard to production of polymeric IgA; many of them showed definitely more J-chain synthesis than normal intestinal IgA immunocytes. The cell population had apparently not spread to the bone marrow, but the polymeric IgA product permeated the connective tissue throughout the body and appeared also in the urine, partly associated with SC. The possibility that such an excessively proliferating intestinal B-cell population may bear some relation to alpha-chain disease is discussed.


Antibodies reacting with salmon and human protamines in sera from infertile men and from vasectomized men and monkeys.

A micro-complement fixation test was modified for the detection of low-titred antibodies to protamines. Specific immunological reactions with salmon protamine were found with some sera obtained from infertile men and vasectomized men and monkeys. The possibilities that allergic reactions, observed in patients receiving salmon protamine, result from immunity to the fish protamine and from immunological cross-reaction between human and salmon protamines (in cases where auto-immunity to human protamine has developed prior to the administration of fish protamine) are discussed.


An immunoglobulin heavy chain variable region (VH) marker associated with cross-reactive idiotypes in man.

The VH specificities of two rabbit antisera raised against the H chains of two human IgM cold agglutinins were studied with the aid of proteins on which the VH sequence data are available. They were found to recognize a new VH antigen (VHMar), which may represent a subgroup of VHI. This antigen is found on anti-Ii antibodies which have cross-reactive idiotypes. It is moderately well-expressed in normal gamma globulin and strongly expressed on 8% of unselected myeloma and macroglobulinaemia proteins. There is evidence to suggest that a proportion of the cross-reactive idiotypes among the anti-Ii antibodies involve this VH antigen.


Cell-mediated immunity in Chagas' disease: Alterations induced by treatment with a trypanocidal drug (nifurtimox).

Peripheral leucocyte migration inhibition (LMI) with Trypanosoma cruzi-specific antigens, measured as a migration index (MI), was studied in chronic Chagas' disease patients. The MI of untreated patients with polymerized antigens from culture forms (epimastigotes) of T. cruzi was significantly lower than that of controls. In contrast, when chronic Chagas' patients were treated with nifurtimox, 10 mg/kg/day for 2 months, the MI was not different from control values. Treated and untreated patients had normal T- and B-lymphocyte markers, measured by the ability to form rosettes either with sheep erythrocytes (E-RFC) or with sheep erythrocytes--antibody--complement (EAC-RFC). In addition, the number of lymphocytes bearing surface membrane Ig (SMIg) was the same as that of controls. Non-specific functional assays, such as PHA-induced blastogenesis and antibody-dependent cell-mediated cytotoxicity (ADCC) to sensitized chicken erythrocytes were also normal, both in treated and untreated patients. Thus, nifurtimox produced a particularly effect on cell-mediated immunity, specially detectable using LMI.


Kidney lesions in baboons infected with Schistosoma mansoni.

Glomerular lesions in baboons (Papio anubis) infected with different dosage regimes of Schistosoma mansoni were studied by immunofluorescence and light microscopy on kidney sections and by countercurrent immunoelectrophoresis on kidney homogenates and tissue eluates. Mild lesions, characterized by focal and segmental deposits of immune complexes, developed in sixty-two out of 103 baboons, irrespective of the intensity and duration of the infection. Severe, diffuse lesions developed in six baboons after prolonged and heavy infections. Adult worm and soluble egg antigens, together with IgM, IgG and C3, were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in acid homogenates and eluates of kidneys which showed no deposits of immunoglobulins or complement. These observations indicate that renal lesions in S. mansoni infections may be attributable to the deposition of immune complexes pre-formed in the circulation. However, the demonstration of antigens alone in some animals may suggest an alternative possibility, namely that antigens are deposited first with a subsequent binding of antibody and complement.


Structure and biological functions of human IgD. XII. Anti-IgD enhancement of PHA responsiveness in patients with chronic lymphocytic leukaemia.

Specifically purifed anti-human delta stimulated the in vitro incorporation of [3H]thymidine by human peripheral lymphocytes from patients with chronic lymphocytic leukaemia (CLL). The peak response varied between individuals; those with 5--52% IgD-bearing lymphocytes exhibited maximum stimulation at 3 days, whereas a patient with only 1% IgD-bearing cells showed optimal activation at 6 days. In agreement with others, our data indicated that, in most instances, lymphocytes from patients with CLL respond poorly to PHA. One of the most important findings in this study is the enhancement of PHA responsiveness by anti-delta. Lymphocytes that exhibited reduced responsiveness to PHA alone, when pre-treated with anti-delta, showed transformation greater than the sum of the anti-delta plus PHA responses.


Nifurtimox-induced alterations in the cell-mediated immune response to PPD tin guinea-pigs.

Positive skin reactions to PPD in guinea-pigs immunized with Freund's complete adjuvant (FCA) were reversed after treatment with 10 mg/kg/day nifurtimox for 12 days. The in vitro migration of peripheral blood leucocytes from FCA-immunized guinea-pigs was inhibited with PPD, but it returned to normal values after nifurtimox treatment. Furthermore, the cell-free supernatant from PPD-stimulated lymphocytes from FCA-immunized nifurtimox-treated guinea-pigs did not inhibit the migration of normal cells. Thus the administration of nifurtimox impaired the specific cell-mediated immune response to PPD both in vivo and in vitro.


Fibrodysplasia (myositis) ossificans progressiva treated with disodium etidronate.

Two patients with fibrodysplasia ossificans progressiva (FOP) were treated with disodium etidronate, a disodium salt of ethane-1-hydroxy-1, 1-diphosphonic acid (EHPD) for two years; both had multiple ectopic ossifications of connective tissue. Regular follow-up showed no improvement in joint movement whilst laboratory examination revealed an increase in the serum phosphorus level. Serum calcium and urinary phosphorus excretion remained within normal limits. The urinary calcium excretion varied with the dose of EHDP. X-ray examination showed significant reduction in size and density of the ectopic ossifications, while the density of bones during and after EHDP therapy remained normal. Development of new ossification was inhibited in the active phase of the disease. Suspected side-effects of the drug were occult blood in stools, skin petechiae, and amenorrhoea. Previous reports on the EHDP treatment of disorders with ectopic ossification are summarised.


Visuo-spatial performance following posterior parietal and lateral frontal lesions in stumptail macaques.

Three groups of four monkeys were trained to negotiate a small hand ("stylus") maze, and to use a "pointer" to guide response in a two-choice position discrimination task. One group was given bilateral lesions of posterior parietal cortex, and the second bilateral lesions of lateral frontal cortex. Postoperative impairment on the maze was evident in three of the four parietal animals, and both operated groups showed impairment on the pointer task. Since maze performance was positively associated with speed of stylus recovery in a control version of the task but was not correlated with pointer task performance, it is suggested that the parietal deficit resulted primarily from a sensory-motor dyscoordination rather than a spatial perceptual disorder. The latter could however be the cause of parietal impairment on the pointer task. Error analysis suggests an interpretation of the frontal deficit on the pointer task in terms of perseveration on position.


Form perception in stumptail macaques following posterior parietal and lateral frontal lesions.

Monkeys with bilateral posterior parietal and lateral frontal ablations were compared with normal animals on a series of four tests for their ability to relate elements of a visual pattern on the basis of the Gestalt principle of proximity. The operated animals showed no clear impairment on these tests of perceptual grouping. The three groups of monkeys were then trained to discriminate two faces and tested for generalisation to different views of the same faces. The pariental-operated monkeys showed less generalisation than the other animals to lateral mirror-images of the training stimuli, but more generalisation to inverted mirror-images. It is concluded that any deficit in "gestalt" perception following such lesions must be at a relatively high level.


Reaction time variability in epileptic and brain-damaged patients.

Median reaction times and intra-individual variability were studied in epileptic (N = 63), brain-damaged (non-epileptic) (N = 25) and control patients (N = 25) using a six and one half minute visual, continuous reaction time task. Epileptic and brain-damaged groups were significantly slower than control patients on median reaction times at the 10th, 50th, and 90th percentiles and on the differences between the 10th and 90th percentiles. Thus both general slowing and greater intra-individual variability were found in the epileptic and brain-damaged patients. Reaction times were not related to presence, type and severity of EEG abnormality or to age of onset of epilepsy. Grand mal patients did have significantly greater variability than other types of seizure patients. Epileptic and brain-damaged patients did not differ significantly on any reaction time variables. Both groups were discriminated significantly from the controls on all reaction time measures, especially on the intra-individual variability measure.