[Notes on the transmitter histochemistry of the cortex cerebelli of rat].

The cortex cerebelli of the normal, adult rat was investigated fluorescence histochemically by means of the paraformaldehyde method according to FALCK and HILLARP (1962) for visualization of catecholamines and a modified ninhydrin-reaction for the demonstration of GABA (PFISTER and GORNE 1978), respectively. The Purkinje neurons were shown to display a considerable variability of the fluorescent GABA reaction product. Noradrenergic boutons were shown to be arranged mostly in a punctate manner around the somata of the Purkinje cells. The Purkinje cell pericarya would thus be under the inhibitory influence of cerebellar bascet neurons as well as of Locus coeruleus neurons.


Proteoglycans and their relationship with the other components of the rabbit aorta wall observed in two different experimental conditions.

An electron microscopic study of the aorta wall of rabbit was carried out employing electron microscopic histochemical methods aimed at examining the distribution of proteoglycans and their correlation with the other structural components of the aorta wall. The ultrastructural evidence of the proteoglycans has been obtained by treating the arterial wall with alcian blue stain and supporting this staining procedure with control enzyme treatments. Moreover, in order to attain a better interpretation of the ultrastructural findings, the arterial wall has been studied under 2 different experimental conditions, the 1st one being represented by an accentuated contraction of the vase's wall, following immersion in the fixator, the other one by an extreme distension of the wall, reached prior to fixation, subjecting the tissue to its tension limit of 700 dyn/mm2. This type of electron microscopic visualization of the proteoglycans following alcian blue treatment leads on to think that at least 2 distinct macromolecular entities of proteoglycans exist, each one having an unusual relationship with the other components of the arterial wall. Different site and types of interaction are to be noted for each of the 2 distinct ultrastructural proteoglycans entities.


[On the localization of sorbitol dehydrogenase in the rat kidney (author's transl)].

We have investigated the localization and demonstration of sorbitol dehydrogenase activity in the rat kidney by comparative histochemical-electrophoretical technique. Under histochemical conditions an adequate demonstration of the activity of the sorbitol dehydrogenase in native sections is possible by membrane incubating technique in presence of PMS and KCN. In the glomerulum the strong and uniform reaction with regard to the specifity is not clear. In the glomerula of semithin sections from glutaraldehyde fixed, incubated and Epon-embedded cryostate sections the reaction product is localized predominantly in the maesangium cells. By micropolyacrylamidgel gradient electrophoresis of the supernatant from the kidney cortex and of isolated glomerula 2 sorbitol dehydrogenase fractions were found. The results are discussed in connection with the specifity of the reaction.


beta-Glucuronidase activity in the developing uropygial gland.

The presence of sterolic compounds and beta-glucuronidase activity have been studied in the uropygial glands of chick embryos (18th day of inc.), chickens (3 weeks after hatching) and young fowls (5 months old). Sterols are histochemically detectable only after hatching and beta-glucuronidase activity, very faint before hatching, reaches its maximum in chicken glands with a peculiar inner localization coincident with sterolic localization. It is suggested that beta-glucuronidase has in uropygial gland a double functional significance: a certain amount of activity is developed to cell proliferation whereas a more strong activity is involved in the hydrolysis of sterol glucuronides.


Occurrence of somatostatin-like immunoreactivity (SLI) in the dorsal hippocampus of the sand rat (Psammomys obesus).

Somatostatin-like immunoreactivity (SLI) was demonstrated in neurons of the dorsal hippocampus of the sand rat by means of the immunofluorescence technique.


Vascularization of the endochondral layer with respect to the otic capsule. A comparative anatomical study.

The otic capsules of several species were examined morphometrically and compared with the otic capsule of man. Area, perimeter and diameter of vessels, radius of tissue cylinder, circumscribing hexagon, intervascular distance, and O2 exchange area were evaluated. A correlation between occurrence and expansion of the interglobular spaces ('Interglobularräume') on the one hand and vascularization of the endochondral layer on the other hand was found. This corresponds to results of other authors concerning the persistence of cartilage observed in tissue cultures and long bones.


Experimental endocarditis in rabbits. 3. Significance of the proteolytic capacity of the infecting strains of Streptococcus faecalis.

Insertion of a polyethylene catheter into the left ventricle of the heart was used for regular establishment of sterile endocarditis, and bacterial endocarditis was established by injection of approximately 10(8) Streptococcus faecalis into the blood stream at the same time as removal of the catheter which had been in place for 3 days. 100 out of 102 rabbits died spontaneously of bacterial endocarditis. Evidence is produced that the host-parasite interaction is influenced by the proteolytic property of S. faecalis in this experimental model. Two distinct types of clinical course are described: 1) A predominantly acute and damaging illness, characterized by a high level of bacteraemia, small amounts of soft, friable vegetations in the left side of the heart, high frequency of kidney infarcts and shorter survival time in rabbits infected with proteolytic strains. 2) A relatively subacute illness, characterized by a lower level of bacteraemia, large, hard, non-friable vegetations on the aortic valves, less pronounced destructive changes in the substance of valve leaflets, relatively lower frequency of kidney infarcts and longer survival time in rabbits infected with non-proteolytic strains. The results suggest that proteolytic strains of S. faecalis cause partial dissolution of the vegetations resulting in a more severe clinical picture.


Comparison of two selective media in the cultural diagnosis of Gonorrhoea.

A "chocolate" agar medium (CA-NCV) containing nystatin, colistin and vancomycin, was compared with the MNYC medium which contain lincomycin, colistin, amphotericin and trimethoprim. A total of 277 clinical specimens were cultured for gonococci, and 120 of these showed positive cultures on either or both of the media. The MNYC medium detected 96.6 per cent of the total number of positive cultures and 92.5 per cent of the patients and the CA-NCV medium after 80 and 79 per cent, respectively. Nearly half the positive cultures were detected on the MNYC medium after 24 hours of incubation. It is concluded that the MNYC medium is superior to the CA-NCV medium in the diagnosis of gonorrhoea.


Effect of centrophenoxine on acetylcholine release in perfused cerebral ventricles of cats under dynamic electrophysiological control.

The effects of centrophenoxine on the release of acetylcholine and on the changes in the bioelectrical activity are determined in experiments on non-anaesthesized cats subjected to perfusion of the anterior horn of the lateral cerebral ventricle and simultaneous recording of the bioelectrical activity of cortical and subcortical structures. Centrophenoxine is tested in doses of 25, 50 and 100 mg/kg intravenously. Most characteristic changes are found to occur after the dose of 50 mg/kg, when centrophenoxine markedly increases the amount of the released acetylcholine and changes the bioelectrical activity (synchronous changes in the cortex and hypothalamus). The parallelism between the increase release of acetylcholine and the bioelectrical changes continued until the time of the peak effect of centrophenoxine (45 min), followed by dissociation between them (the level of the released acetylcholine gradually approached the initial level, while the changed bioelectrical activity persisted for a longer time.


Comparison of effects of pentobarbital and ethanol on the neuronal activity in the posterior parietal association cortex.

The problem of this study was whether the effects produced by alcohol in the posterior parietal association cortex are specific to this drug or shared by other centrally acting depressant drugs such as barbiturates. The effect of graded doses of pentobarbital on multineuronal impulse activity was recorded with transdural microelectrode technique in 30 expts. in Brodmann's area 7 of five stump-tailed monkeys (Macaca speciosa). The results were compared with those from 32 expts. performed with alcohol and published separately. The dosage of the two drugs was determined on the basis of the monkeys' sensori-motor coordination which was assessed with a rating scale of reaching accuracy for food rewards. There were several recording sites where the actions of the two drugs were similar at similar behavioural levels of intoxication. However, in the distribution of effects among various functional types of recording sites a significant difference was found between pentobarbital and alcohol. Alcohol commonly diminished cellular activity related to motor behaviour (reaching, grasping) and only rarely responses to somesthetic stimuli, whereas the effects of pentobarbital were the opposite being most common on somatosensory responses and least common on activity related to motor behaviour. Also responses to visual stimuli were more sensitive to pentobarbital than to alcohol. The actions of pentobarbital and alcohol on responses evoked by sensory stimulation differed significantly (P less than 0.01). We conclude that significant differences exist in the mechanisms of action of alcohol and barbiturate on the associative systems of the brain.


Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats.

Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other groups of rats. These changes may partly explain the demonstrated training-induced increase in glucose tolerance. None of the findings could be ascribed to differences in foold intake or body weight.


Comparison between saliva and serum lithium concentrations in patients treated with lithium carbonate.

The relation between serum and saliva lithium concentration was studied in patients treated with lithium carbonate. In 23 patients a highly variable saliva/serum ratio was found in simultaneous saliva and serum samples. In five patients studied during a period of 4-8 weeks three patients showed a high fluctuation in saliva/serum lithium ratio. In 20 patients saliva lithium concentrations varied unexpectedly in a second sample produced after 15 min. Although some authors report a high and stable relation between saliva and serum lithium concentration, we consider the saliva lithium level unreliable as a prediction of the serum lithium level in patients treated with lithium carbonate.


Neuroendocrine correlates of testosterone-induced changes in brain evoked responses to afferent input.

Evoked responses (ER) to stimulation of spermatic nerve were picked up in conscious monkeys from hypothalamic limbic and cerebral cortical regions. The effect of intravenous injection of testosterone propionate (TPss; 0.4 mg/kg) on ER was examined in the same animal. Hormone administration caused inhibition or potentiation of ER in different regions of brain. The duration of hormone effect also suggested area specificity. A significant, immediate reduction in ER amplitude was produced by hormone injection in the ventromedial nucleus. On the contrary an increase of ER was observed in the anterior hypothalamus and in several limbic areas. Genital sensory motor cortex showed slight potentiation. The results support the hypothesis proposed in earlier EEG studies that TP and genital afferent input probably play a selective role in brain mechanisms underlying organized and integrated expression of reproductive functions.


Synchronization of EEG activity of male Rhesus monkeys Macaca mulatta treated with ovocyclin.

Bipolar stainless steel electrodes were stereotaxically implanted in hypothalamus and cortex of six male monkeys. The effect of intramuscular injection of estradiol dipropionate (ovocyclin) in a dose of 10 mg/d was observed on EEG activity on 3 successive days. On the first day, slow waves appeared only in preoptic and on the second day also in posterior hypothalamus. Generalized slowing with an increase in amplitude appeared in all the hypothalamic areas and cortex on the third day. This suggest estrogen to possess (i) cumulative effect on brain and (ii) inhibitory action in the form of synchronization of EEG activity.


Mutational mosaicism and genetic counseling in retinoblastoma.

Mutations may arise throughout an organism's life cycle. Typically, sporadic meiotic mutations give rise to individuals with all their germinal and somatic cells bearing the mutant gene. These mutations may be amorphs (with full penetrance and expressivity) or hypomorphs (with reduced penetrance and expressivity). Mutational mosaicism, however, involves the origin of mutations occurring during mitosis, whether in the parent at some stage prior to reproductive maturity or in the offspring at some time following fertilization. The phenotypic expression and transmission of these new mutations are dependent on the proportion of cells bearing the mutant gene as well as the location of these cells in somatic and/or germinal tissues. Mutational mosaicism was used as a developmental model to analyze 1,500 sporadic and 179 familial cases of retinoblastoma from the world literature. This model provided an interpretation for the origin, onset, and transmissibility of the sporadic unilateral retinoblastoma cases, which represent over 60% of all retinoblastoma patients. The model also permits a reclassification of all transmissible types of retinoblastoma; based on this classification, more accurate risk figures for genetic counseling can be offered. In addition, mutational mosaicism can be extended as a model to other autosomal dominant and X-linked mutations.


Histological and ultrastructural studies of the cornea in Maroteaux-Lamy syndrome.

The author presents the histologic and electron-microscopic examination of the cornea of a patient with Maroteaux-Lamy syndrome. Histochemic examinations established the absence of keratin sulfate and heparin sulfate in the accumulated material. By means of electron microscopy three cell types have been found in the stroma which may show, besides the storage of the accumulated glycosaminoglycans, the morphologic signs of the pathologic enzyme-substrate connection. Considering the presence of the lipidlike material, the question arises whether the Maroteaux-Lamy syndrome belongs to mucolipidoses.


[Dosage-problems in controlled sodium nitroprusside hypotension in oto-rhino-laryngological surgery (author's transl)].

During a study of 130 patients undergoing hypotensive anaesthesia for oto-rhino-laryngological surgery the most important dose problems with sodium nitroprusside (S.N.P.) were characterized. In 14% of the cases more than 15 mcg/kg body weight/min S.N.P. were required. Our data show, that the smallest S.N.P. consumption occurs during neuroleptanalgesia in combination with 0.3--0.8 Vol-% enflurane. On the other hand, during neuroleptanalgesia alone, in several cases toxic amounts of S.N.P. would have been necessary to produce adequate hypotension. In such cases about 0.5 mg/kg body weight dihydralazine must be employed as a supporting agent for hypotension. The influence of this drug on the manoeuvrability of the low pressure state and on the administration of S.N.P. was investigated. Although, the equivalent amount of sodium thiosulfate (S.T.) did not increase the S.N.P. sensibility, its routine use is reconviended, since the combination of S.Th, and even higher doses of S.N.P. were tolerated without metabolic acidosis. As an alternative substance after long-term use of S.N.P. nitroglycerine should be used.


[Leukoplakia and cancers of the buccal cavity. Immunofluorescence counting and typing of plasmocytes].

Immunofluorescent study of paraffin sections of 80 lesions of the buccal cavity, for the most part malignant or pre-malignant revealed marked plasmocytosis in premalignant or early malignant cases. This plasmocytosis, easily seen by the use of anti-immunoglobulin sera, is of polyclonal type, with marked preponderance of IgG secretors. In infiltrating carcinomas and in recurrences, the number of plasmocytes decreases and the percentage of IgG secretors falls markedly. By contrast, that of IgA immunocytes remains the same. The significance of these findings is considered and their practical value in the surveillance of cases of leukoplasia is stressed.


Drosophila melanogaster as an experimental host for study of multiplication and biology of the mycoplasma inducing the "lethargy of coleoptera".

The mulitplication of the mycoplasma responsible for the "lethargy of coleoptera" on a laboratory host, Drosophila melanogaster, was obtained on the first passage. Independant series of successive passages on D. melanogaster were performed without any apparent modifications of the properties of the microorganism. Pathogenicity for its natural host Melolontha melolontha was retained. The different forms of mycoplasma observed lead us to propose a probable cycle of development, composed of a succession of globular and rod-shaped bodies, these later being often sinuous. The infected Drosophila flies presented a reduced life span and fertility. Infection of the cephalic nervous system seems to be responsible for death. Horizontal transmission of the microorganism was not observed.


[Relationships between "Mycobacterium simiae" and the "M. avium-intracellulare-scrofulaceum" complex (author's transl)].

The 24 strains of Mycobacterium simiae described in this report were isolated from 12 black Africans, 6 from white Europeans, 5 from primates and 1 from a leprosy infected Armadillo. These strains form 3 groups having the similar morphologic and cultural properties as M. intracellulare. Two groups were similar with respect to pigmentation, urease activity and niacin production but differed serologically, the second group being of M. intracellulare serotype 18. The third group was less homogenous and was intermediate to M. simiae and M. intracellulare. Thus M. simiae belong to the M. avium-intracellulare-simiae-scrofulaceum (MAISS) complex. Two cases of well characterized pulmonary disease progressed like M. avium mycobacteriosis.


The rate of bursting strength gain in repaired nerves.

The sciatic nerve in 60 rats was transected and repaired with 9-0 nylon under magnification. The repairs were tested for bursting strength at 2, 3, 6, 9, and 12 weeks and expressed as a percentage of the bursting strength of a paired control from the opposite leg. The mean percent bursting strength was 25, 42, 53, 45, and 62, respectively. There was no statistically significant gain in bursting strength from the third to the ninth week after nerve repair. However, there was a significant difference in bursting strength at 3 weeks and 12 weeks after repair. A similar experiment was performed in monkeys. At 4 weeks, the repaired nerves had regained 77% of the bursting strength of the normal median and ulnar nerves. These studies call into question earlier claims that repaired nerves regain normal bursting strength within 3 to 4 weeks of repair.


["In vitro" activity of a new cephalosporin (CGP-7174-E or cefsulodin) against "Pseudomonas aeruginosa" (author's transl)].

The minimal inhibitory concentration (MIC) of four betalactamins (carbenicillin, ticarcillin, piperacillin and (CGP-7174-E) against 109 clinical isolates of Pseudomonas aeruginosa was determined by an agar dilution method. CGP-7174-E was the most active (MIC 3.4 micrograms/ml), followed in descending order by piperacillin (MIC 4.9 micrograms/ml), ticarcillin (MIC 22 micrograms/ml) and carbenicillin (MIC 36 microgram/ml). High correlation was found between the MIC of these betalactamins (r greater than 0.60). In 12 strains where MIC for carbenicillin was greater than or equal to 1,024 microgram/ml, MIC for CGP-7174-E was less than or equal to 128 micrograms/ml and less than 16 micrograms/ml in four strains.


[Isolation of free-living amoebae from the nasal mucosa of man. Potential risk (author's transl)].

From march 1976 until december 1978, we have analysed 1039 nasal swabs in order to discover the healthy free-living amoebae carriers. So, we have isolated 9 strains of which one Hartmannella vermiformis. From the 8 remaining Acanthamoebae, only one, ORL 561 (Acanthamoeba hatchetti) is as pathogenic for mice as the 2 other identical known strains and A. culbertsoni.


Trypanosoma (Megatrypanum) amileari n. sp., isolated from Oryzomys eliurus (Wagner, 1845) (Rodentia-Cricetidae).

A new species of trypanosome, Trypanosoma (Megatrypanum) amilcari, is described in the present paper. This new trypanosome was found in the circulating blood of a rodent species Oryzomys eliurus (Cricetidae). Some biological observations were made.


[Advantages of the Errecart's technique for the identification of Plasmodium (author's transl)].

Errecart (1945) proposed a modified technique for making thick films for the diagnosis of Chaga's disease. We applied his technique to the study of malaria in mammals; the morphology of the blood parasites is very well preserved and allows the identification of species which are frequently not identifiable in ordinary thick films.


Vestibular mechanisms.

It is apparent from this and other reviews of the subject that our knowledge of vestibular function is most complete for the primary canal and otolithic afferents. Relatively little progress has been made in the understanding of receptor mechanisms and the functional importance of the efferent vestibular system. Since most of it has been summarized previously the latter were not considered here. Considerably more knowledge has accumulated in the field of central vestibular mechanisms, particularly those related to eye movements. Recent advances in functional synaptology of direct and indirect vestibuloocular pathways are described. It appears that the indirect pathways are essential for the central integration of the peripheral head velocity into a central eye position signal. Candidates for the neural integrator are presented and discussed and their connectivity described both for the horizontal and the relatively poorly studied vertical eye movement system. This field will certainly be studied extensively during the next years. Another interesting field is the role of the cerebellum in the control the vestibuloocular reflex. Recent data and hypotheses, including the problem of cerebellar plasticity, are summarized and evaluated. That the vestibular nuclei are by no means a simple relay system for specific vestibular signals destined for other sensory or motor centers is evidenced in this review by the description of multiple canal-canal, canalotolith, and visual-vestibular convergence at the nuclear level. Canal-otolith and polysensory convergence in vestibular neurons enables them to correct for the inherent inadequacies of the peripheral canal system in the low frequency range. The mechanisms of polysensory interaction in the central vestibular system will undoubtedly be an important and interesting field for future research.


Thyroid function tests in thyroxine-binding globulin deficiency.

Results are presented on two patients with complete and two with partial thyroxine-binding globulin (TBG) deficiency. All four subjects had lowered serum thyroxine but were clinically euthyroid. While thyroid hormone uptake tests or TBG assay were effective in the recognition of such individuals, indices based on these tests were misleading in assessing their thyroid status. Results within the reference range were obtained with the Immophase Free Thyroxine assay.


Distribution of membrane-bound monoamine oxidase in bacteria.

The distribution of membrane-bound monoamine oxidase in 30 strains of various bacteria was studied. Monoamine oxidase was determined by using an ammonia-selective electrode; analyses were sensitive and easy to perform. The enzyme was found in some strains of the family Enterobacteriaceae, such as Klebsiella, Enterobacter, Escherichia, Salmonella, Serratia, and Proteus. Among strains of other families of bacteria tested, only Pseudomonas aeruginosa IFO 3901, Micrococcus luteus IFO 12708, and Brevibacterium ammoniagenes IAM 1641 had monoamine oxidase activity. In all of these bacteria except B. ammoniagenes, monoamine oxidase was induced by tyramine and was highly specific for tyramine, octopamine, dopamine, and norepinephrine. The enzyme in two strains oxidized histamine or benzylamine. Correlations between the distributions of membrane-bound monoamine oxidase and arylsulfatase synthesized in the presence of tyramine were discussed.


14C-most-probable-number method for enumeration of active heterotrophic microorganisms in natural waters.

A most-probable-number method using 14C-labeled substrates is described for the enumeration of aquatic populations of heterotrophic microorganisms. Natural populations of microorganisms are inoculated into dilution replicates prepared from the natural water from which the organisms originated. The natural water is supplemented with a 14C-labeled compound added so as to approximate a true environmental concentration. 14CO2 evolved by individual replicates is trapped in NaOH and counted by liquid scintillation techniques for use in scoring replicates as positive or negative. Positives (14CO2 evolution) are easily distinguished from negatives (no 14CO2 evolution). The results from a variety of environments using the 14CO2 procedure agreed well with previously described methods, in most instances. The 14C-most-probable-number method described here reduces handling procedures over previously described most-probable-number procedures using 14C-labeled substrates. It also appears to have advantages over other enumeration methods in its attempt to approximate natural conditions more closely.


Simple agar block slide culture suitable for varying the environment of bacteria during time-lapse cinephotomicrography.

A simple paper wick agar block slide culture is described for use in experiments which vary the chemical environment of bacteria during time-lapse cinephotomicrography.


Pesticide and PCB residues in the upper Snake River ecosystem, Southeastern Idaho, following the collapse of the Teton dam 1976.

The Teton Dam in Southeastern Idaho collapsed on June 5, 1976. The resulting flood damaged a large area and caused the release of toxicants into the Snake River. A pesticide recovery team in a helicopter worked the flooded area for three weeks and collected 1,104 containers, about 35% of which contained toxicants. It was estimated that less than 60% of the lost pesticide containers were recovered. This paper addresses the results of a one-time sampling effort designed to determine the magnitude of the chemical contamination. Over 300 samples of fish, plankton, waterfowl, sediments, water, stream drift, aquatic plants, and soil were taken. Pesticide residues were measured as microgram/kg (ppb) wet weight, whole animal basis. Rainbow trout had as much as 1432 micrograms/kg total DDT plus analogs, 66 micrograms/kg dieldrin, and 1010 micrograms/kg PCBs. Utah suckers had up to 1420 micrograms/kg total DDT plus analogs, 32 micrograms/kg dieldrin, and 1800 micrograms/kg PCB. Rocky Mountain whitefish had as much as 2650 micrograms/kg total DDT and analogs, 30 micrograms/kg dieldrin and 1400 micrograms/kg PCBs. These PCB and DDT levels were high, approaching the 2,000 micrograms/kg FDA proposed tolerance, but were below the 5,000 micrograms/kg present tolerance. Dieldrin levels were low and organophosphates were undetectable. An undeveloped area (the Fort Hall Bottoms) showed higher levels of contaminants than did an industrialized area (the lower Portneuf River). This apparent discrepancy remains unexplained. Very little pre-flood data on a whole fish basis were available for comparison (Johnson et al 1977). However, it does not appear that any human health hazard due to pesticide levels exists in this portion of the Snake River.


Mercury and chlorinated hydrocarbons in zoobenthos of Lake Päijänne, Finland.

The average amounts of mercury, PCBs, and sigma DDT (primarily DDE), found in macrozoobenthos, on the wet basis, in Lake Päijänne, Finland, for the time period 1972-1974, were 79 ng/g, 29 ng/g, and 8 ng/g, respectively. Lindane was found in negligible amounts in only 2% of the samples examined; aldrin was present in 10% of the samples; no dieldrin was detected. Mercury and PCB concentrations varied regionally in the lake. PCB and sigma DDT concentrations were greater in the predatory bottom animals than in the herbivores or detritus feeders, and the amounts of chlorinated hydrocarbons were greater in profundal animals than in littoral animals. No significant correlation was apparent between the amount of residues found and the weight of the animal (e.g. Anodonta). A significant positive correlation was evident in the amounts of PCBs and sigma DDT in most of the taxonomical groups. Spongilla lacustris and Anodonta piscinalis were excellent species for monitoring purposes.


Fate of chloroalkylene-9-14C in carrots, sugar beets, and soil under outdoor conditions.

Immediately after application of chloroalkylene-9-14C to soil (1.32 ppm, based on dry weight of soil in the upper layer of 0 to 10 cm) under outdoor conditions, carrots were sown; in the following year, sugar beets were grown. About 80% of the radioactivity applied volatilized within one vegetation period. Most of the remaining radioactivity was still in the upper soil layer; 0.8% had dispersed to a depth of 40 cm, and 3.3% was taken up by the carrot plants. In the second year, no more decreases of soil residues was observed; uptake by sugar beets was 0.1% of the applied radioactivity. In the first year, the residues in the upper soil layer consisted of 41% unchanged chloroalkylene-9, 19% soluble metabolites, and 40% unextractable residues; the amount of unextractable residues rose to 68% in the second year. The following conversion products were characterized in the soil extracts: a monohydroxylated dichlorobiphenyl, a monomethoxylated dichlorobiphenyl, and two isomeric monohydroxylated, monoisopropylated dichlorobiphenyls; in carrot roots, a monomethoxylated dichlorobiphenyl was detected. Conjugates occurring in the soil yielded, after acid hydrolysis, a monohydroxylated dichlorobiphenyl among other compounds.


Responses of rats exposed to polychlorinated biphenyls for fifty-two weeks. II. Compositional and enzymatic changes in the liver.

Male Sprague-Dawley rats consumed a diet to which 100 ppm of various polychlorinated biphenyl (PCB) mixtures (Aroclors 1248, 1254, and 1262) were added for one year. Rats were hepatectomized at 13, 26, and 52 weeks during feeding and at 13 weeks following the discontinuation of the PCB diets. The liver homogenates of these rats had an increase in protein and RNA on a DNA basis and an increase in lipid and a decrease in DNA on the liver weight basis. The hepatic microsomes from these livers also had an increase in protein and cytochrome P-450. The RNA/microsomal protein levels were decreased, and no marked alterations were recorded for the phospholipids and cholesterol on a microsomal protein basis. Increased enzymatic activity was recorded for N-demethylase and nitroreductase. However, the specific activity of glucose-6-phosphatase was decreased throughout the treatment period.


Residues of DDT in a Norwegian fruitgrowing district two and four years after the termination of DDT usage.

This study describes the extent of DDT contamination in a typical fruit growing district in Norway two and four years after the DDT ban. Residues of DDT in man, dairy cows and soil were about five to one hundred times higher than in the control groups, while residues found in samples from the marine biota were the same or moderately higher (Figure 3). The residues of DDT in cows, gulls and parts of the marine samples showed a significant decrease from 1972 to 1974, while the level in soil was almost constant. The amount of DDE had increased considerably in 1974 for all the species except for the gull, although not to the same degree. The distribution of DDE, DDD and DDT in soil were almost constant during the two years of sampling.


Antimalarial activity of Floxacrine (HOE 991) I. Studies on blood schizontocidal action of Floxacrine against Plasmodium berghei, P. vinckei and P. cynomolgi.

Floxacrine (HOE 991), 7-chloro-10-hydroxy-3-(4-trifluoromethylphenyl)3,4-dihydroacridine-1,9-(2H, 10H) dion, shows a high level of antimalarial action against blood-induced infection of drug-sensitive and drug-resistant lines of Plasmodium berghei in mice, rats and Syrian hamsters. The drug is also a potent blood schizontocide against drug-sensitive P. vinckei strains in rodents and P. cynomolgi in rhesus monkeys. The CD50/CD90 values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice were 4.3/6.7 mg/kg after the oral route and 1.7/3.6 mg/kg after the subcutaneous (sc) route. In the 'two- and four-day test' the ED50 against sensitive P. vinckei was 0.7 mg/kg in both mice and rats. A moderate prophylactic effect could be demonstrated after the sc route probably due to a 'depot effect' of the water-insoluble active principle. Floxacrine was also highly active against P. berghei-lines which were resistant to chloroquine, mepacrine, dihydrofolate reductase inhibitors, sulfadoxine and dapsone. Resistance to HOE 991 could be developed in P. berghei and P. cynomolgi when the compound was used alone and administered repeatedly in subcurative doses. The antimalarial activity of the compound was not influenced by p-aminobenzoic acid or folic acid supplements in diets. Structural changes induced by floxacrine on pigment cytoplasm and nucleus in erythrocytic stages of P. berghei differed in some aspects from those of mepacrine and chloroquine. It is therefore assumed that the mode of action of floxacrine differs from that of the known antimalarial drugs. The general tolerance of the compound in rodents and rhesus monkeys is good and there is a wide range between the effective and maximum tolerated doses. Floxacrine was also effective at 100 ppm against pathogen Eimeria species in chickens, at 1000 mg/kg orally against Fasciola hepatica in rats and at 300-800 mg/kg orally against Heterakis spumosa in rats.


[Intracorporeal cardiac pacemakers for refractory tachycardia (excluding atrial disease). Apropos of 18 cases].

The treatment of paroxysmal tachycardia by the use of permanent pacing to prevent or terminate attacks is discussed. The series comprises 18 patients with follow-up periods ranging from 1 to 12 years. In 6 cases the indication for pacing was atrial tachy-arrythmias favourised by bradycardia (5 of whom had vagally- induced atrial arrythmias). The atrial pacemaker successfully prevented attacks in 4 out of 6 cases. Three cases of chronic reciprocating tachycardia were successfully treated by simultaneous atrial and ventricular pacing or using sequential pacing with a very short P-R interval. Eight cases of paroxysmal orthodromic reciprocating tachycardia in the WPW syndrome were paced: in 5 cases pacing was employed to terminate attacks by atrial (3 cases) or ventricular (2 cases) stimulation, in the other 3 cases pacing was used to prevent the bradycardia which favourised the initiation of tachycardia. Good results were obtained in all 8 cases. Ventricular stimulation was used to terminate attacks in one patient with refractory ventricular tachycardia but the patient had a sudden death probably caused by the pacemaker. The place of these different pacing techniques with respect to medical treatment and specialised arrhythmia surgery is discussed.


[Contribution of ultrastructural analysis to the knowledge of the neuromuscular relationships in the nodal and conduction tissue].

The ultrastructure of the atrio-ventricular junction in the rat heart fixed in situ was studied on serial fine sections. The relationships between the specialized tissue and the nervous system were studied after labelling adrenergic endings with 5-OH-dopamine. Among the various types of nerve endings a distinction may be made between: 1) adrenergic or cholinergic free endings; 2) large "cluster" endings of the cholinergic types, seen mainly in the equatorial regions of nodal cells; 3) small diameter cholinergic before the development of heart failure or significant card synaptic images; 4) afferent neurons, whose endings, rich in glycogen and mitochondria supply the conduction tissue fibres, getting into or through the muscle fibre. The intermembrane space is then 20 nm. The analogy between the images observed and the ultrastructural aspects of intrafusorial fibres in skeletal muscle is discussed.


[Multicenter epidemiological survey of primary myocardiopathies. Apropos of 380 cases].

A retrospective study of adult congestive cardiomyopathy was carried out; the admission criteria being heart failure with cardiomegaly after the exclusion of known causes of heart failure. Coronary artery disease was excluded by forming two sub groups, one with proven normal coronary arteries at angiography or autopsy and the other with only assumedly normal coronary arteries. The results concern the study of the incidence of this disease which has been regularly seen over the last 10 years in departments with a large number of referrals of cardiomyopathy. --Professional factors are analysed to see if there is a higher incidence amongst the working classes. --Other factors are analysed by comparison with three control groups: normal, coronary and valvular disease, and diabetes which may be a predisposing factor, but not the serum cholesterol which is decreased in these patients. There is a significant association with smoking and alcoholism and the main biological sign of the latter condition, macrocytosis. This is also found in both coronary sub groups. The isolation of this alcohol factor in the genesis of congestive cardiomyopathy implies the possibility of reversing or stabilising the myocardial damage after its withdrawal, so changing the severe diagnosis associated with this disease.


[Two-dimensional echocardiography of ventricular aneurysm. Study of 38 cases with angiographic correlation].

This is a study of the data supplied by cross-sectional echocardiography in the diagnosis of post-infarction aneurysm. It involves 38 confirmed cases of myocardial infarction. The clinical, electrical, radiological and echocardiographic data (in M mode) were specified. Right anterior oblique ventriculography showed 21 posterior and 17 anterior aneurysms (4 antero-lateral, 5 apical, 8 antero-apical), and 14 mitral regurgitations. Cross-sectional echocardiography using a (30 degrees or 90 degrees) mechanical sector scanner allowed the study of the kinetics of 6 segments following 5 viewing angles: one longitudinal, two transversal, two apical. Each segment was classified according to its shape and motion: akinetic, dyskinetic or aneurysmal, and the papillary muscles of the mitral valve were assessed as normal or pathological (dense and motionless on the echogram). 35 of the 38 aneurysms seen at angiography, were detected by cross-sectional echocardiography; in one case the diagnosis could not be made for technical reasons; in two cases echocardiography was in favour of akinesia. An abnormal papillary muscle was observed in the 14 cases of mitral insufficiency. The causes of error in localisation were considered. In conclusion, cross-sectional echocardiography appears to be an excellent atraumatic procedure for the diagnosis of aneurysms and papillary muscle dysfunction.


[Aortocoronary bypass permeability explored by tomodensitometry. Preliminary study].

The patency of 24 aorto-coronary grafts was studied by tomodensitometry. --16 out of the 18 bypasses examined within the two weeks following surgery were seen. --4 older bypasses were not visible, either by scanner or by angiography and were therefore occluded: two more, performed more than a year previously, were patent on tomodensitometric examination. The interpretation of the results, discussed taking into account the small number of angiographic check ups does not permit any formal conclusion as to the validity of the procedure. The results of this technique seem satisfactory and quite comparable with other non invasive methods used in the study of aorto-coronary grafts.


[Traumatic coronary-cardiac fistulas. Apropos of a case].

The case of a 24-year old patient having suffered a bullet wound was reported. After a hemopericardium accompanied by minor signs of tamponade, a continuous murmur gradually appeared due to a fistula between the right coronary artery and the right atrium, which was strictly symptomless: surgical repair was performed eight years after the accident. This satisfactory spontaneous outcome, after surviving the life threatening danger of tamponade and myocardial infarction was also observed in the 21 cases of coronary-cardiac fistulae already published. The fistula, which almost always involves the right heart cavities, only gives rise to a continuous murmur which is often discovered at a later stage. The long term course of traumatic coronary-cardiac fistulae can only be assessed by comparison with congenital coronary-cardiac fistulae, which are much better known, and the consequences of which are on all accounts similar. Four complications are discussed: heart failure, coronary insufficiency, infectious endocarditis, and the rupture of the fistulized coronary artery due to aneurysmal dilatation. These risks are statistically small and more theoretical then real, and the justification of systematic repair of traumatic coronary-cardiac fistulae now rests essentially on the relatively low risk of the procedure.


[Hemodynamic effects of mexiletine].

The haemodynamic changes caused by intravenous mexiletine were studied in 12 patients. Initially the drug was given rapidly at the rate of 3 mg/kg/min for 10 minutes and then slowly at a rate of 0,06 mg/kg/min for 30 minutes. The plasma Mexiletine level measured after 20 minutes was used to divide the series of patients into two groups: in Group A the level was over 0,7 g/ml (0,961 +/- 0,109 microgram/ml) whilst in Group B the level was only 0,547 +/- 0,101 microgram/ml. The mean aortic pressure, heart rate and left ventricular end diastolic volume did not vary significantly in the two groups. The left ventricular end diastolic pressure rose, and the cardiac index and the ejection fraction fell in Group A. The indices of left ventricular contractility fell in all patients of the start of the injection. This depression only persisted to the end of the injection in Group A. Mexiteline did not cause significant changes in post extrasystolic potentialisation in the 5 cases in which this phenomenon was studied.


[Fibrinolytic treatment. First results during the early postoperative period].

Fibrinolytic treatment during the early post-operative period is associated with a real danger of hemorrhage. On the other hand, in palliative shunt procedures in Fallot's disease, especially in small children, the anastomoses may thrombose. In such cases the therapeutic lysis of the thrombus improves the child's condition and may defer further surgery. The authors describe five cases of children with Fallot's disease and thrombosis of Blalock-Taussig anastomoses who were successfully treated by streptokinase. They conclude that fibrinolytic treatment should be considered in early thrombosis following anastomosing operations.


[Pulmonary valve atresia with intact interventricular septum in the grown child and the adult].

Atresia of the pulmonary valve with an intact interventricular septum is a rare cyanotic congenital cardiac malformation. Rare at birth, it is exceptionally rare for cases to survive over 5 years. Three cases of porlonged survival aged eleven nineteen and thirty-four years are reported. In the latter case, the abnormality was probably aquired. Prolonged survival is related to a collateral pulmonary circulation. Surgical treatment is discussed with respect to the anatomical features. Good results were obtained in the two operated cases.


[Aneurysm of the interauricular septum by hernia of Vieussens' valve, and suspected coronary embolism].

During the hemodynamic evaluation of a young patient with heart failure whose electrocardiogram showed sequels of anterior necrosis, an aneurysm of the fossa ovalis was seen at cineangiography. Selective coronary angiography showed an interruption of filling of the anterior interventricular artery just distal to the branching of the first septal artery: it raised therefore the possibility of the embolic origin of that myocardial infarction. In connection with this case study, angiographic aspect, pathogenesis and the embolic role of the aneurysm of the fossa ovalis were discussed.


[Intranodal reciprocal dual rhythm].

In a patient with spells of paroxysmal supraventricular tachycardia of two types, the stimulation tests demonstrated a dual intranodal conduction responsible sometimes for "usual" reciprocal rhythms (slow anterograde pathway and rapid retrograde pathway), sometimes for "reversed" reciprocal rhythms (rapid anterograde pathway and slow retrograde pathway). The latter contrasted with the lack of discontinuity of the retrograde nodal function curve (V1-V2 versus A1-A2).


The cell cycle of Bacillus subtilis as studied by electron microscopy.

Bacillus subtilis strain Marburg was grown exponentially with a doubling time of 65 min. To follow the time course of various cell cycle events, cells were collected by agar filtration and were then classified according to length. The DNA replication cycle was determined by a quantitative analysis of radioautograms of tritiated thymidine pulse labeled cells. The DNA replication period was found to be 45 min. This period is preceded and followed by periods without DNA synthesis of about 10 min. The morphology and segregation of nucleoplasmic bodies was studied in thin sections. B. subtilis contains two sets of genomes. DNA replication and DNA segregation seem to go hand in hand and DNA segregation is completed shortly after termination of DNA replication. Cell division and cell separation were investigated in whole mount preparations (agar filtration) and in thin sections. Cell division starts about 20 min after cell birth; cell separation starts at about 45 min and before completion of the septum.


[Continuous feeding and the waking-sleeping rhythm in children].

Twelve children aged 1 to 8 months with severe intestinal disorders that had necessitated treatment from birth with continuous parenteral and/or enteral nutrition were recorded for 24 hours. The analysis of the EEG, their behaviour and their activity showed that the distribution of sleep and movement during the night was similar to that of normal babies fed on demand. The total duration of sleep and the longest sustained sleep were slightly reduced. The authors think that the suppression of feeding rhythms do not alter the pattern of waking and sleeping.


Response of peritoneal cells to horseradish peroxidase and aldehyde-fixed erythrocytes in the mouse: an electron microscope study.

In adult dd-mice, response of peritoneal free cells to either horseradish peroxidase (HRP) or glutaraldehyde-fixed erythrocytes were examined by electron microscopy. As reported previously (ABE et al., 1979), peritoneal free cells are classified into three types: type I, II and III cells. Type I cells are small lymphocytes, type II cells are medium-sized mononuclear cells, and type III cells are macrophages. The amount of HRP taken up is very large in type III cells. The cells contain numerous vacuoles filled with HRP. Type I and II cells also have vesicles containing HRP. The vesicles are fewer in type I cells than in type II. Type III cells rapidly enclose erythrocytes by thin cytoplasmic flaps and then ingest several erythrocytes. In type III cells, a labyrinth of ramifying tubes seen in the peripheral cytoplasm may serve as a reserve of the membrane system for allowing a rapid coverage and internalization of large foreign materials. A part of type II cells attach to erythrocytes and take them by a varying depth of invagination. Type I cells do not respond to erythrocytes at all. In conclusion, the three types of peritoneal cells can be differentiated by their response to foreign materials as well as by their cytologic features.


Ultrastructural and morphometric studies on the rat pituitary thyrotrophs and thyroid follicular cells following administration of thyrotropin releasing hormone.

The pituitary thyrotrophs and thyroid follicular cells of rats were studied by electron microscopy and morphometric analysis at 5, 10, 20, 30 and 60 min after intravenous injection of 200 microgram of thyrotropin releasing hormone (TRH) and at 10 min after injection of 10 microgram TRH. Multiple granule extrusions in a group were often observed around the pituitary thyrotrophs at 5, 10 and 20 min after administration of 200 microgram TRH, as well as at 10 min after injection of 10 microgram TRH. The number of released granules reached its maximum at 10 min after 200 microgram TRH injection, but the total number of secretory granules in the cytoplasm of thyrotrophs did not show any significant variation throughout the experimental period. Percent area of the rough endoplasmic reticulum indicated the maximum value at 20 min and that of the Golgi apparatus at 10 min. These findings suggest that TRH stimulates the thyrotroph and accelerates synchronously the secretion as well as the synthesis of TSH. In the thyroid follicular cells after 200 microgram TRH injection, numerous small vesicles which might be secretory granules were found in the apical cytoplasm at 5 and 10 min. Pseudopod formation on the luminal surface and accumulation of colloid droplets and lysosome-like granules in the apical cytoplasm were most frequently observed at 20 and 30 min. The value of the mean ratio of the diameter of the colloid lumen to the cell height of follicular cells in the thyroid follicles of all experimental animals stimulated with TRH decreased much more than that of the control animals. This value may indicate the increased activity of follicular cells to reabsorb the colloid.


Animal models for an integrated approach to the pharmacologic control of atherosclerosis.

A system of animal models potentially useful for the discovery and evaluation of new effective antiatherosclerotic agents is described. The models consist of a series of lipoprotein and atherosclerosis assays in rats, SEA Japanese quail and cynomolgus monkeys. SEA quail are particularly useful for detecting compounds that inhibit arterial cholesterol deposition. The use of this integrated system of models is illustrated with data on clofibrate, adamantyloxyaniline (a hypobetalipoproteinemic agent), and o,p'-DDD. Male SEA quail appear to be a quite satisfactory model for testing the effects of large numbers of compounds on atherosclerosis and are available in limited numbers to all qualified investigators in the field of atherosclerosis research for evaluation in their laboratories.


Preventive, educational, and treatment priorities in a school dental programme.

Because of increased costs, school dental programmes should maintain the dental health of the maximum number of children possible. Suggestions are made on the priorities required in prevention and treatment provided for primary school children.


[A new case of D/D blood].

A second case of the -D-/-D- blood in this country is described. A woman, belonging to this rare blood group is from the same region, from which is the first our case published 15 years ago.


Human lysosomal genes: arylsulfatase A and beta-galactosidase.

The segregation of human lysosomal arylsulfatase A (ARS-A) has been evaluated in 50 primary hybrid clones derived from four separate fusions involving WBCs from two unrelated individuals and three hamster cell lines. ARS-A was expressed in the hybrids as a dimeric molecule of very similar or identical subunits. The expression of this enzyme was concordant with that of mitochondrial aconitase (ACON-M), an isozyme assigned to chromosome 22, in all 50 clones and with chromosome 22 segregation in all but one of the 29 karyotyped hybrids. No other human chromosome cosegregated with 22 in these clones, suggesting that this enzyme is specified in hybrid cells by a locus (or loci) on a single chromosome. beta-Galactosidase (B-GAL) expression was analyzed with two different electrophoresis systems and with a number of cell extract preparation methods in 39 of the primary hybrid clones. The B-GAL isozyme expressed in these hybrid cells was concordant with the expression of glutathione peroxidase-1 (GPX-1), an isozyme assigned to chromosome 3, in all 39 clones and with the segregation of this chromosome in 97% of the 29 karyotyped hybrids. These observations substantiate the prior tentative assignments of an ARS-A locus to chromosome 22 and a B-GAL locus to chromosome 3 (Bruns et al., 1978a, b). The implications of the chromosome assignments of loci for 12 human lysosomal enzymes for the cellular assembly of these organelles are discussed.


Characterization of the subunits of purine nucleoside phosphorylase from cultured normal human fibroblasts.

In previous communications we have demonstrated that the subunits of normal human erythrocyte purine nucleoside phosphorylase can be resolved into four major (1-4) and two minor (1p and 2p) components with the same molecular weight but different apparent isoelectric points (and net ionic charge). The existence of subunits with different charge results in a complex isoelectric focusing pattern of the native erythrocytic enzyme. In contrast, the isoelectric focusing pattern of the native enzyme obtained from cultured human fibroblasts is simpler. The multiple native isoenzymes obtained from human erythrocytes and human brain have isoelectric points ranging from 5.0 to 6.4 and from 5.2 to 5.8 respectively, whereas cultured human fibroblasts have two major native isoenzymes with apparent isoelectric points of 5.1 and 5.6. Purine nucleoside phosphorylase has been purified at least a hundredfold from 35S-labeled cultured human fibroblasts. A two-dimensional electrophoretic analysis of the denatured purified normal fibroblast enzyme revealed that it consists mainly of subunit 1 (90%) with small amounts of subunits 2 (10%) and 3 (1%). This accounts for the observed differences between the native isoelectric focusing and the electrophoretic patterns of the erythrocyte and fibroblast enzymes. The purine nucleoside phosphorylase subunit 1 is detectable in the autoradiogram from a two-dimensional electrophoretic analysis of a crude, unpurified extract of 35S-labeled cultured normal human fibroblasts. The fibroblast phosphorylase coincides with the erythrocytic subunit 1 of the same enzyme, and the cultured fibroblasts of a purine nucleoside phosphorylase deficient patient (patient I) lack this protein component, genetically confirming the identity of the purine nucleoside phosphorylase subunit in cultured fibroblasts.


Characterization of human carbonic anhydrase III from skeletal muscle.

A third form of human carbonic anhydrase (CA III), found at high concentrations in skeletal muscle, has been purified and characterized. This isozyme shows relatively poor hydratase and esterase activities compared to the red cell isozymes, CA I and CA II, but is similar to these isozymes in subunit structure (monomer) and molecular size (28,000). CA III is liable to posttranslational modification by thiol group interaction. Monomeric secondary isozymes, sensitive to beta-mercaptoethanol, are found in both crude and purified material and can be generated in vitro by the addition of thiol reagents. Active dimeric isozymes, generated apparently by the formation of intermolecular disulfide bridges, also occur but account for only a small proportion of the total protein and appear only when the concentration of CA III is particularly high.


Ontogeny, cell distribution, and the physiological role of NADP-malic enxyme in Drosophila melanogaster.

NADP-malic enzyme (NADP-ME) (E.C. 1.1.1.40) is situated in the cytosol of Drosophila melanogaster. Both the tissue activity and CRM level of NADP-ME parallel changes in the dosage of a gene, Men+, located in region 87C2-3 to 87D1-2 of the third chromosome. The tissue activity of NADP-ME is very high in early third instar larvae, providing about 33% of the NADPH at this life stage. The tissue activity declines during pupal development but increases as the adult ages. The concentration of NADP-ME CRM and tissue activity are coordinately increased in third instar larvae by dietary carbohydrate and decreased by dietary lipid.


Relationship of the oxidative pentose shunt pathway to lipid synthesis in Drosophila melanogaster.

The tissue activities of the oxidative pentose shunt enzymes, glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49) and 6-phosphogluconate dehydrogenase (E.C. 1.1.1.44), in the larvae of Drosophila melanogaster are not dependent on the amount of flux through the oxidative pentose shunt pathway. An oxidative pentose shunt deficiency effects about a 40% reduction in the NADPH concentration in early third instar larvae, resulting in a six-fold difference in the NADPH/NADP+ ratio between wild-type and pentose-shunt-deficient larvae. The capacity of pentose-shunt-deficient larvae to synthesize triglyceride in response to a high concentration of dietary sucrose is only 73% of the wild-type level. Environmental temperature influences on the fatty acid composition of larvae are not altered by an oxidative pentose shunt deficiency.


Genetic and biochemical aspects of sucrase from Drosophila melanogaster.

Isoelectrofocusing of abdominal extracts of Drosophila melanogaster revealed the existence of two forms of sucrase (E.C. 3.2.1.26). One form exhibited an isoelectric point of 4.63 +/- 0.02 while the other form exhibited an isoelectric point of 4.83 +/- 0.02. The localization of the structural gene for sucrase is proposed on the basis of enzyme determinations in a series of duplication- and deletion-bearing aneuploids. We suggest that the sucrase structural gene lies between 31CD and 31EF on the left arm of chromosome 2 and that the two forms of abdominal sucrase derive from a common protein coded for by a single sucrase gene designated Sucr+.


Genetic and cytogenetic studies of the malate dehydrogenases of Drosophila melanogaster.

Genetic and cytogenetic locations of the structural genes for the NAD-dependent malate dehydrogenases have been studied. The mitochondrial form (mMDH) is coded for by a gene (mMdh) found at 62.6 on the third chromosome and included in Df(3R)R14, which includes 90C2-91A3 in the salivary gland chromosomes. Based on its inclusion within several J (Jammed; 2-41.0) deficiencies, the structural gene (cMdh) for the cytoplasmic form (cMDH) was determined to lie in region 31B-E, confirming the earlier finding of Grell. Flies lacking any cMDH activity (cMdhn-gamma 10069/Df(2L)J-der-27) were both viable and fertile.


Isolation of 35S- and 3H-labelled proteoglycans from cultures of human embryonic skin fibroblasts.

35SO42- - and [3H]-leucine-labelled proteoglycans were isolated from the medium of a fibroblast culture, from an EDTA extract of the monolayer, and from consecutive dithiothreitol and guanidine hydrochloride extracts of the cells. Proteoglycans of different sizes were isolated from the extracts by gel chromatography on Sepharose 4B. In the medium and the EDTA extract the largest proteoglycans contained only 35S-labelled galactosaminoglycan, whereas all other fractions contained in addition heparan [35S-labelled galactosaminoglycan, whereas all other fractions contained in addition heparin [35S]sulphate. The galactosaminoglycan-containing proteoglycans of the various extracts were separated into a larger component, containing chondroitin sulphate-like side chains, and a smaller component, containing dermatan sulphate. The larger proteoglycan of the medium showed reversible association-dissociation behaviour when chromatographed on Sepharose CL2B in phosphate-buffered saline and 4M-guanidine hydrochloride respectively. This property remained after removal of extraneous proteins by CsCl-density-gradient centrifugation in guanidine hydrochloride. The association was markedly increased by the addition of high-molecular-weight hyaluronic acid.


beta-Galactoside-binding muscle lectins of man and monkey show antigenic cross-reactions with those of bovine origin.

Endogenous beta-galactoside-binding lectins were isolated from human heart and from human and rhesus-monkey skeletal muscles. Gel precipitation and radioimmunoassays with rabbit antisera to calf heart lectin revealed antigenic cross-reactions between the primate and bovine muscle lectins.


Degradation of cytochrome P-450 haem by carbon tetrachloride and 2-allyl-2-isopropylacetamide in rat liver in vivo and in vitro. Involvement of non-carbon monoxide-forming mechanisms.

Degradation of intrinsic hepatic [(14)C]haem was analysed as (14)CO formation in living rats and in hepatic microsomal fractions prepared from these animals 16h after pulse-labelling with 5-amino[5-(14)C]laevulinic acid, a precursor that labels bridge carbons of haem in non-erythroid tissues. NADPH-catalysed peroxidation of microsomal lipids in vitro (measured as malondialdehyde) was accompanied by loss of cytochrome P-450 and microsome-associated [(14)C]haem (largely cytochrome P-450 haem), but little (14)CO formation. No additional (14)CO was formed when carbon tetrachloride and 2-allyl-2-isopropylacetamide were added to stimulate lipid peroxidation and increase loss of cytochrome P-450 [(14)C]haem. Because the latter effect persisted despite inhibition of lipid peroxidation with MnCl(2) or phenyl-t-butylnitrone(a spin-trapping agent for free radicals), it was concluded that carbon tetrachloride, as reported for 2-allyl-2-isopropylacetamide, may promote loss of cytochrome P-450 haem through a non-CO-forming mechanism independent of lipid peroxidation. By comparison with breakdown of intrinsic haem, catabolism of [(14)C]methaemalbumin by microsomal haem oxygenase in vitro produced equimolar quantities of (14)CO and bilirubin, although these catabolites reflected only 18% of the degraded [(14)C]haem. This value was increased to 100% by addition of MnCl(2), which suggests that lipid peroxidation may be involved in degradation of exogenous haem to products other than CO. Phenyl-t-butylnitrone completely blocked haem oxygenase activity, which suggests that hydroxy free radicals may represent a species of active oxygen used by this enzyme system. After administration of carbon tetrachloride or 2-allyl-2-isopropylacetamide to labelled rats, hepatic [(14)C]haem was decreased and haem oxygenase activity was unchanged; however, (14)CO excretion was either unchanged (carbon tetrachloride) or decreased (2-allyl-2-isopropylacetamide). These changes were unaffected by cycloheximide pretreatment. From the lack of parallel losses of cytochrome P-450 [(14)C]haem and (14)CO excretion, one may infer that an important fraction of hepatic [(14)C]haem in normal rats is degraded by endogenous pathways not involving CO. We conclude that carbon tetrachloride and 2-allyl-2-isopropylacetamide accelerate catabolism of cytochrome P-450 haem through mechanisms that do not yield CO as an end product, and that are insensitive to cycloheximide and independent of haem oxygenase activity.


Subcellular distribution of the different platelet proteins phosphorylated on exposure of intact platelets to ionophore A23187 or to prostaglandin E1. Possible role of a membrane phosphopolypeptide in the regulation of calcium-ion transport.

Exposure of 32P-labelled human platelets to ionophore A23187 results in an increased incorporation of 32P into polypeptides with apparent mol.wts. of 47 000 (P47) and 20 000 (P20), whereas exposure to prostaglandin E1 results in increased labelling of polypeptides with apparent mol.wts. of 24 000 (P24) and 22 000 (P22) [Haslam, Lynham & Fox (1979) Biochem. J. 178, 397-406]. Labelled platelets that had been incubated with ionophore A23187 or prostaglandin E1 were sonicated and rapidly separated into three fractions by differential centrifugation. Electron microscopy and measurement of marker enzymes indicated that the 1300-19 000 gav. particulate fraction was enriched in granules, mitochondria and plasma membranes, that the 19 000-90 000 gav. particulate fraction was enriched in both intracellular and plasma membranes and that the 90 000 gav. supernatant contained only soluble proteins. 32P-labelled phosphopolypeptide P47 was present almost exclusively in the 90 000 gav. supernatant, whereas phosphopolypeptide P20 was largely dephosphorylated under fractionation conditions that protected other phosphopolypeptides. 32P-labelled phosphopolypeptide P24 was enriched in both particulate fractions, but particularly in the 19 000-90 000 gav. fraction, and may therefore be present in both the intracellular and plasma membranes. Phosphopolypeptide P22 appeared to be similarly distributed. Both particulate fractions were capable of the ATP-dependent oxalate-stimulated uptake of Ca2+. When the 19 000-90  000 gav. membrane fraction was prepared from platelets that had been incubated with ionophore A23187, active uptake of Ca2+ did not occur, but when this fraction was isolated from platelets that had been exposed to prostaglandin E1, uptake of Ca2+ was significantly greater than observed with the corresponding membranes from control platelets. It is suggested that phosphorylation of polypeptide P24 (or P22) by a cyclic AMP-dependent protein kinase may promote the active transport of Ca2+ out of the platelet cytosol.


Postnatal development of uridine diphosphate glucuronyltransferase activity towards bilirubin and 2-aminophenol in human liver.

UDP-glucuronyltransferase activities towards 2-aminophenol and bilirubin were studied in a total of 70 human subjects, including premature and full-term newborn babies, infants, children and adults. These two activities have been reported in rat to develop latefoetally and neonatally respectively, but in man they both develop neonatally. There is a linear relationship between the logarithm of each liver transferase activity and the logarithm of the number of days after birth during the first 3 months of life, after which each activity remains constant.


[Respiration-stimulated activation of DNAase I associated with mitochondria].

The influence of respiration and Ca++ transport in the liver mitochondria on the activation of DNAase I, associated with these organelles, was studied. It was shown that 96% of the total activity of this enzyme in mitochondria is in the latent state. Aeration of the mitochondrial suspension leads to a sharp increase in the enzyme activity. The activation of DNAase I is inhibited by EGTA addition (optimal pH 8.0), and stimulated in mitochondria, releasing Ca++. It is concluded that the activation of DNAase I is dependent on the state of cellular energetics. Participation of mitochondrial phospholypase A, activated by the Ca++ release from mitochondria during DNAase I activation is suggested.


[Chloramphenicol and dextramycin, inhibitors of mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene].

In noninbred rats chloramphenicol and its optical isomer dextramycin diminished the blastomogenic effect of 7,12-dimethylbenz(a)anthracene on mammary glands. The protective effect was shown by a decreased tumor incidence at all periods of observation and an increase in the life span of rats and in the case of dextramycin this action consisted in a prolongation of the latent period of tumor emergence.


[Participation of the hypothalamus in the pituitary and testicular responses to administration of the antiandrogen 4-nitro-3-trifluoro-methylisobutyranilide].

The effect of the antiandrogen 4-nitro-3-trifluoro-methylisobutyranilide (flutamide, NFBA) on the content of follitropine, lutropine and testosteron in the blood plasma as well as on the testicular activity of the steroid delta 5-3 beta-Ol-dehydrogenase (SD) has been studied in male rats with intact and destroyed hypothalamic median eminence. In sham-operated rats with intact hypothalamus the levels of lutropin, follitropin, testosteron and the enzymatic activity were 5, 2, 4 and 3-4 times as increased, respectively, under the effect of NFBA. After destroyal of the hypothalamic median eminence NFBA treatment did not change follitropin secretion, while lutropin, testosteron plasma levels and SD activity were only 1 1/2-2 times higher, i.e. significantly less as compared to those in sham-operated animals. The data obtained suggest the most important role of the hypothalamus in pituitary and testicular responses to NFBA administration.


Psychiatric manifestations in temporal lobe epilepsy: a controlled study.

Psychiatric disorder was studied in 62 patients with temporal lobe epilepsy (study group) and 70 patients with grand mal epilepsy (control group), both diagnosed electroencephalographically. The two groups were similar as regards age, sex, socio-economic status, duration and frequency of fits, family history and premorbid personality. A significantly greater number of temporal lobe epileptics had emotional disturbances in childhood and psychiatric abnormalities at the time of study. Neuroses, schizophrenia and behaviour disorder occurred more commonly in the study group, while epileptic personality and confusional psychosis were seen more frequently in the controls. The findings of the study are discussed in the light of relevant literature.


[Development and control of liver amylo-1,6-glucosidase activity in the fetal rat].

The development of amylo-1,6-glucosidase activity is studied in fetal rat liver. The activity of control fetuses is high on day 17.5, decreases from day 17.5 to day 19.5, and then rises during the next days. In hypophysectomised fetuses, the increase of the activity is suppressed but not the decrease. Moreover, if the mother is adrenalectomized the decrease and the increase are abolished in hypophysectomised fetuses. Growth hormone administration is quite effective in preventing the decrease in enzyme activity but cortisol treatment does not prevent it. In contrast, cortisol produces a precocious decrease of the activity in intact fetuses. These findings suggest that during fetal life, two hormonal regulation mechanisms are involved in the regulation of amylo-1,6-glucosidase activity: cortisol has a repressive effect on the enzymic activity while growth hormone acts as an inducer.


A rapid technique for measuring calcium uptake in mitogen-induced T and B lymphocytes.

The procedures for lymphocyte activation and for removing the cells from the radioactive loading solution in incubation medium were modified to routinely obtain significant and reproducible 45Ca2+ uptakes in mitogen-induced mouse T and B lymphocytes. Factors such as mouse strain, lymphocyte origin, and media pH were not critical to the 45Ca2+ uptake measurements. In contrast, factors such as lymphocyte cell concentration during mitogenic activation, filtering the 45Ca2+:3H2O mixtures, and the nature and purity of the B-cell mitogens were critical for obtaining maximal and reproducible 45Ca2+ uptakes. Centrifugation through silicone oil into sucrose was an efficient and rapid procedure for separating the cells from the radioactive loading solution in the incubation medium. Using optimal conditions, an approximate twofold increase in 45Ca2+ uptake (representing an influx of approximately 97 amol per lymphocyte and an increase in average cellular Ca2+ of approximately 0.72 mM) was routinely obtained with purified mouse lymphocytes activated with a variety of T- and B-cell mitogens (using concentrations resulting in maximal [3H]thymidine incorporation). A larger 45Ca2+ uptake was routinely obtained with mitogenic concentrations of A23187, a divalent cation ionophore stimulating T cells. Experiments employing [14C]sucrose and [14C]inulin with control and mitogen-induced lymphocytes showed that the trapped extracellular fluid measurements in the cell pellets should be used to correct the magnitude of the 45Ca2+ uptake measurements.


A broth-disc technique for the assay of antibiotic synergism.

A broth-disc technique has been developed to demonstrate the antibiotic synergism of some broad-spectrum penicillins plus an aminoglycoside against Pseudomonas aeruginosa and enterococci. Utilizing the zone sites obtained from Kirby-Bauer susceptibility tests, approximate minimum inhibitory concentrations of each antibiotic upon individual isolates were derived using standard regression curves. One-fourth of each value was calculated and the approximate desired concentration then prepared in Mueller-Hinton broth through use of the labelled antibiotic disc content. Tubes were inoculated with a standardized suspension of organism and incubated at 35 degrees C for 18-24 h. Subsequently, inhibitory end points were recorded. This approach to synergy testing showed good correlation with the standard checkerboard method. The broth-disc synergistic assay is also reproducible, financially feasible, and less time-consuming to execute.


Thiocyanate utilization by an Arthrobacter.

An Arthrobacter species, which utilized thiocyanate (SCN-) as a nitrogen source, was isolated from soil by the enrichment culture method. The organism tolerated SCN- concentrations up to 0.1 M. On addition of nitrate or ammonium ion to cultures of the isolate growing in the presence of SCN-, the organism continued to degrade SCN-. Degradation could be followed by release of 14CO2 from SCN-(14C). The SCN- -degrading activity diminished to low levels as the stationary phase of growth was appraoched.


Catabolite repression-resistant mutants of Bacillus subtilis.

Mutants of Bacillus subtilis that are able to sporulate under the condition of catabolite repression were isolated by a simple selection technique. The mutants used in the present study were able to grow normally on minimal medium with ammonium sulphate as the nitrogen source and glucose as the carbon source. Studies carried out with these mutants show that there is no close relation between catabolite repression of an inducible enzyme, acetoin dehydrogenase, and that of sporulation. Certain mutants are able to sporulate in the presence of all the carbon sources tested but some mutants are resistant only to the carbon source used in isolation. It is suggested that several metabolic steps may be affected in catabolite repression of sporulation.


Dissolved organic matter utilization and oxygen uptake in algal-bacterial microcosms.

Under closed laboratory conditions, at non-limiting nutrient levels, the biomass of Anabaena variabilis, Anacystis nidulans, Chlorella pyrenoidosa, and Selanastrum capricornutum increased with increasing levels of dissolved organic matter (DOM) as a result of bacterially produced carbon dioxide (CO2) and (or) cofactors. Oxygen (O2) produced as a result of algal photosynthesis was sufficient to supply the najority of O2 required by the bacterial community. The percentage of DOM utilized by bacteria which was subsequently incorporated into algal biomass varied with individual species indicating that the association between individual algal species and the bacterial microbiota varied. Under natural conditions bacteria could provide CO2 and (or) cofactors for algal photosynthesis which in turn supplies O2 for bacterial respiration. This mutualistic association in aquatic environments could result in an increase in planktonic and epiphytic algal biomass if other nutrients are available.


The occurrence of Candida Albicans in Lake Ontario bathing beaches.

There are inherent weaknesses associated with currently used bacterial fecal pollution indicator systems. Fecal pollution indicator data would be more meaningful if supplemented with information relating to the occurrence of pathogens in recreational water. Through surveys of four bathing beaches on Lake Ontario, it was established that the opportunistically pathogenic yeast Candida albicans occurs in near shore waters. The beaches surveyed could be differentiated on the basis of bacterial fecal pollution indicator levels and numbers of the pathogens C. albicans and Pseudomonas aeruginosa. The occurrence of C. albicans and P. aeruginosa appeared to be related to elevated fecal pollution indicator levels. Maximum numbers of all parameters were observed in July and August in association with peak bather loads at the beaches. In only one instance does the data suggest that a beach was subjected to human fecal contamination.


The effect of nickel on the growth, photosynthesis, and nitrogenase activity of Anabaena inaequalis.

Anabaena inaequalis was sensitive to nickel ion in the order of decreasing sensitivity of growth, photosynthesis, and acetylene reduction. At a culture density of 9 x 10(4) cells per millilitre, growth after 12 days was completely inhibited by 0.125 ppm (microgram/mL) Ni2+. Nickel caused the increase of both the lag phase of growth and the culture doubling time, and caused the retardation phase to be sooner. Photosynthesis and acetylene reduction were completely inhibited by 10 and 20 ppm Ni2+, respectively, at a cell concentration of 1.3 x 10(6) cells per millilitre. Preincubation for 24 h in the presence of nickel ion significantly increased the sensitivity of photosynthesis and acetylene reduction. Under these conditions acetylene reduction was more sensitive than photosynthesis. Nickel ion reduced culture growth by 35% at a level of 0.05 ppm and inhibited that culture's acetylene-reducing ability by 29% while leaving photosynthesis unaffected. Nickel caused some damage to filament apical cells and induced pigment bleaching in aged cultures. Nickel toxicity was proposed to be due to poisoning of intracellular enzyme systems by nickel ions.


Methionine transport in Pseudomonas aeruginosa.

A high-affinity (Km = 2.7 x 10(-7) M) energy-requiring methionine-transport system has been characterized in RM 46 and RM 48, two different PAO methionine auxotrophs of Pseudomonas aeruginosa. After 8 s of transport 40--60% of the methionine label in the alcohol extract appears in S-adenosyl-L-methionine (SAM) with the remaining activity in free methionine. Methionine transport required a high degree of structural specificity for transport. Stimulation of transport occurred by addition of glucose or organic acids. The ability of a given substrate to stimulate transport was related to the type of carbon source used for growth. Transport was sensitive to sulfhydryl reagents and required oxidative phosphorylation, as indicated by the inhibitory effects of anaerobiosis, cyanide, and arsenate. The degree of inhibition by arsenate correlated with the level of ATP in the cell. Rapid transport in a SAM-deficient mutant (TM 1) and inhibition by arsenate of transport in this mutant suggested that SAM formation was not directly linked to transport and that ATP supplied energy for transport. Inhibition by arsenate was more severe in glucose- compared to citrate-stimulated cells. This result was also observed with proline transport indicating that this was not a peculiarity of the methionine-transport system. These data emphasize the close link between glucose metabolism, ATP levels, and transport. This ATP level is not so critical for transport in cells metabolizing citrate.


Chagas' disease: trends in immunological research and prospects for immunoprophylaxis.

Acute infection with Trypanosoma cruzi usually subsides spontaneously but the mortality rate encountered in individuals with the chronic infection is high. Much evidence has accumulated in the last five years that autoimmunity plays an important role in the pathogenesis of the myocarditis that is common in the chronic phase. A negative relationship has been observed between the demonstrable parasitaemia and the presence of severe cardiac lesions. This myocarditis is characterized by lymphocytic infiltrates and destruction of normal heart cells, in the absence of the parasite in situ. Furthermore, the demonstration in vitro of heart cell lysis by T. cruzi-sensitized T lymphocytes is strong evidence of autoimmunity in Chagas' disease.Acquired immunity plays a major role in the course that T. cruzi infections may run in the mammalian host. As a result of the immune mechanisms induced by the parasite, the infection is controlled at subpatent levels, and the immune host does not develop acute T. cruzi infection again. At present there are several means of achieving immunoprotection against experimental T. cruzi infections, but it is not known whether vaccinated animals might develop chronic Chagas' disease and die many months or years later. Studies on immunoprotection against Chagas' disease should therefore not be limited only to the acute phase of the infection. Furthermore, the involvement of autoimmunity in the production of the lesions of Chagas' disease indicates that research in this area should be conducted with caution. The definition of an animal model for chronic Chagas' disease is essential to further development of immunological research devoted to immunoprophylaxis.


An effective rabies treatment in exposed monkeys: a single dose of interferon inducer and vaccine.

Rhesus monkeys were injected with lethal doses of rabies virus and then treated with a variety of treatment combinations. The one found most successful was one dose of an interferon inducer (poly(I)-poly(C) complexed to poly-L-lysine and carboxymethyl-cellulose) and one dose of human diploid rabies vaccine. This combination proved to be as effective as hyperimmune serum and vaccine, and much better than vaccine alone. The combination of the interferon inducer plus vaccine could be administered at least up to 48 hours after the very severe challenge given and still provide marked protection.


Lower body negative pressure: a method to differentiate vasodilators in the intact rat.

1. In rats lower body negative pressure induced venous pooling in a reproducible manner. The response to LBNP in the pentobarbitone-anaesthetized rat appeared not to be influenced by the autonomic nervous system. 2. The hypotensive effect of arterial vasodilators was diminished at 5 mmHg LBNP, compared with effects at 3 mmHg, whereas the hypotensive effect of venous vasodilators was not changed at 5 mmHg LBNP, compared with that at 3 mmHg LBNP. 3. In the pithed rat dihydroergotamine caused venoconstriction. In the phenobarbitone-anaesthetized rat the hypotensive effect of venous vasodilators was decreased significantly by pretreatment with this drug, whereas it did not influence the hypotensive effect of arterial vasodilators. 4. Thus venodilatation by LBNP and venoconstriction by dihydroergotamine provide a method for differentiating arterial and venous sites of action of vasodilators in intact rats.


Glutathione and mercapturic acid conjugations in the metabolism of naphthalene and 1-naphthyl N-methylcarbamate (carbaryl).

The formation of glutathione (GSH) conjugate in the detoxification of [1-14C]-naphthalene and [naphthyl-14C]-carbaryl was investigated using rat liver homogenate. The mercapturic acid conjugate in rats was also investigated by collection of urine after intraperitoneal injection of 14C substrates. The formation of water-soluble metabolites in vitro from naphthalene was dependent on the amount of glutathione added, but this was not seen in carbaryl metabolism. In vitro, the metabolism of [1-14C]-naphthalene produced 50% GSH conjugates in the incubation mixture, whereas in vivo the metabolism of this compound produced 65% mercapturic acid conjugate in the urine. There was no evidence of GSH or mercapturic acid conjugate in the metabolism of [naphthyl-14C]-carbaryl in vitro and in vivo. This conclusion was made by comparing the nature and chemical characteristics of GSH and mercapturic acid conjugates formed in [1-14C]-naphthalene metabolism. With the aid of the specific enzyme (e.g. beta-glucuronidase and sulfatase) and acid hydrolysis, the water-soluble metabolites of [naphthyl-14C]-carbaryl were tentatively recognized as glucuronide or sulfate conjugated mainly with 5,6-dihydro-5,6-dihydroxycarbaryl or N-hydroxy-methyl carbaryl and their hydrolytic products. This data demonstrated that the substituent group on the naphthalene molecule may affect the significance of GSH conjugation.


Inhibition of rat hepatic microsomal cytochrome P-450 system by cobaltous chloride and reversal of inhibition by iron in vivo.

The effects of preexposure of rats to cobaltous chloride (CO) mixed in iron-sufficient (I.S) and -deficient (I.D) diets on hepatic microsomal electron transfer system was investigated. Male Sprague-Dawley rats were fed for 4 weeks on I.D diets mixed with 0, 100 and 200 ppm CO. At the end of 4 weeks three rats from each group were transferred to I.S diets mixed with the same amount of CO. Liver microsomal NADPH - Cytochrome C reductase, NADPH - dehydrogenase, cytochrome P-450 and aniline binding were determined in both batches of rats. The rats receiving CO in the I.D diets showed a 35, 60, 75 and 40% decrease in NADPH - Cyt. C reductase, dehydrogenase, Cyt. P-450 and aniline binding respectively. The rats transferred from I.D diet to I.S diet showed a complete recovery of the inhibition of the microsomal electron transfer system. The rats receiving 200 ppm mixed with I.S diets did not show any changes in any biochemical parameter measured.


Bile acid metabolism in the fetus and newborn.

The development of bile acid synthesis, secretion and absorption was studied in laboratory animals and humans. Although there is species variation, a developmental pattern emerges. Bile acid pool size and synthesis rates increase during the final third of gestation and the perinatal period. Similarly, bile acid secretion is a developing function during the final third of gestation and is incompletely developed at birth. The ileal mechanism for active bile acid transport is absent at birth and only develops during the first 2--5 weeks or more of life. It is therefore possible that the intestinal conservation of bile acid is ineffective in the newborn. The combination of immaturity of bile acid synthesis, secretion and absorption probably contributes to the fat malabsorption especially evident in low birth weight infants. Finally, synthesis, secretion and absorption can be induced to develop early by the administration of adrenocortical steroid. The induction of mechanisms for bile acid metabolism raises the possibility of therapeutic intervention in severe cases of neonatal malabsorption of lipid.


Central nervous system mediated stimulation by thyrotropin-releasing hormone of microcirculation in thyroid gland of rats.

The blood flow of thyroid, adrenal cortex and renal cortex in the pentobarbital anesthetized rat was assessed from hydrogen gas desaturation curve. The microcirculation of thyroid was markedly augmented within 2 min after an intraventricular injection of Thyrotropin-Releasing Hormone (TRH) while Met-Enkephalin (ENK) failed to influence. Both TRH and ENK stimulated the microcirculation of adrenal cortex moderately. ENK diminished the microcirculation of renal cortex whereas TRH did not exert any effect. The response of thyroid to TRH was abolished by vagotomy, thus the existence of a specific TRH-vagus -thyroid connection was indicated.


Equitable considerations in balancing the energy equation.

Decisions concerning how we balance energy supply and demand should not be made by quantitative cost-benefit analyses alone. The distributions of costs and benefits among individuals, groups of individuals, nations, and generations raise questions of equity that need to be addressed forthrightly. Doing so can help rather than impede the decision-making process.


Relevance of animal experiments to humans.

The best evidence of an adverse human health effect is a properly conducted epidemiological study. But human beings should not be the sole test animal. Properly conducted animal studies have been shown to be preductive for carcinogenicity and toxicologic responses in human populations. We need to develop more efficient predictive animal tests for all the common serious toxic effects caused by chemicals. One particularly important use of epidemiological studies is to validate (or invalidate) the laboratory animal experiments. There is no more powerful tool than the combination of well conducted animal experiments and well conducted epidemiological experiments.


Role of scientific data in health decisions.

The distinction between reality and models or methodological assumptions is necessary for an understanding of the use of data--economic, technical or biological--in decision-making. The traditional modes of analysis used in decisions are discussed historically and analytically. Utilitarian-based concepts such as cost-benefit analysis and cannibalistic concepts such as "acceptable risk" are rejected on logical and moral grounds. Historical reality suggests the concept of socially necessary risk determined through the dialectic process in democracy.


Health effects of the gas-aerosol complex. Report to Special Committee on Health and Ecological Effects of Increased Coal Utilization.

Combustion products derived from the burning of coal are definitely capable of producing adverse human health effects. No single component of the combustion product mixture is solely responsible. Rather, effects are due to a group of compounds, both gases and aerosols, in the effluents of stationary source combustion processes. Although incompletely defined, the individual components of the gas-aerosol complex appear to be capable of interacting both in terms of atmospheric chemistry and health effects. The three primary air quality standards pertinent to regulating coal combustion all represent to some extent indirect, although reasonable, measures of this gas-aerosol complex. As a group, these standards appear to be adequate to protect human health. Conventional toxicological considerations suggest that the adverse health effects of any necessary increase in coal combustion effluents would be greatest per unit of coal in those areas which are most heavily populated and have the highest preexisting levels of the gas-aerosol complex. In order to decrease the degree of uncertainty for future decisions of this type, it is important that prospective epidemiological and air monitoring studies be initiated in conjunction with any large scale introduction of coal use.


Atmospheric CO2 consequences of heavy dependence on coal.

Accurate and regular measurements of the concentration of CO2 in the atmosphere during the past 20 years show an accelerating increase. Although clearing of tropical forests has released large amounts of carbon to the atmosphere, evidence is strong that a major contributor is the combustion of fossil fuels. Future energy demands of the world will require extensive further exploitation of fossil fuels, and projections show that without major development of nonfossil fuel alternatives, the atmospheric concentration will double within the next 75 years. Four issues require serious attention. The developing countries will require vastly increased amounts of energy. Major efforts to develop suitable (inexpensive) nonfossil energy sources to meet at least a portion of this demand are required. The distribution of carbon released from fossil fuels and from other anthropogenic sources among the reservoirs of the carbon cycle must be better defined. Uncertainties regarding the effect of the increased concentration of CO2 in the atmosphere on global climate must be reduced. Possible political and social responses to a substantial climate change must be studied in order to more fully understand all of the implication of increased atmospheric CO2.


Chemical exposure and intestinal function.

The particular substances that are ingested by individuals are the consequence of their environmental, residential, and occupational exposures. The possible effects of these exposures on intestinal functions can be examined by the evaluation of in vivo or in vitro exposure followed by an in vivo and/or in vitro monitoring of effects. Several examples of the in vivo exposure and in vitro monitoring approach are presented to demonstrate the consequences of oral exposure to either a heavy metal (arsenic), or a herbicide contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) or a jet fuel propellant (hydrazine) and the subsequent measurement of either a particular metabolic pathway, or a cell-specific enzyme induction or the development of brush border enzymes are presented.


Biotransformation of xenobiotics in human intestinal mucosa.

Drug-metabolizing enzymes, especially monooxygenases, play a major role in biotransformation and detoxification of many foreign compounds including environmental carcinogens. Although largely localized in the liver they are also found in the small intestine, which is the portal of entry of dietary toxins. Therefore cytochrome P-450 content as well as monooxygenase (7-ethoxycoumarin O-deethylase) and NADPH-cytochrome c reductase activities were determined in surgical specimens of the human small intestine and in jejunal biopsy material obtained from patients by use of a hydraulic biopsy instrument. Microsomes were prepared from surgical material; these ranged in P-450 content from 30 to 120 pmole/mg protein and in monooxygenase activity from 60 to 110 pmole/min-mg protein. In the 20,000g supernatant of the homogenized biopsy material, monooxygenase activity was undetectable in patients who had total villous atrophy, and low enzyme rates were found when the mucosa showed a partial villous atrophy. The mucosal monooxygenase activity of patients with normal jejunal histology and steatorrhea was significantly higher than in mucosa with villous atrophy but was only half of that observed in normal controls. These eight control patients had normal histology and no malassimilation. Our results suggest that monooxygenase activity in the human small intestine is dependent on the morphological integrity of the mucosa and that in normal mucosa the enzyme rates are reduced when malassimilation is present.


[Ischemic alterations of the regional mechanical performance of the left ventricle. Study of parietal deformation as a vectorial time-dependent parameter and of pressure-length loops (author's transl)].

A study was carried out on 59 patients with significant stenosis (greater than or equal to 75%) in at least one coronary vessel. For each parietal region of the left ventricle the pattern of contraction was defined through a study of the regional deformation as vectorial time-dependent parameter and of the construction of the pressure-length loops. The different models obtained in basal conditions and through intervention (nitroglycerin and post-extrasystolic potentiation) were correlated with experimental data on ischemic alterations of the regional mechanical performance.


[Criteria of the homology and phylogeny of facial muscles in primates including man. I. Prosimia and Platyrrhina].

The facial muscles of primates are derivates of sphincter colli profundus muscle and platysma myoides. A third superficial muscle layer which is present in primitive mammals is found as a rest in Tupaiiformes. The facial muscles of some Lemuriformes must be considered as a model from which originate the facial musculature of other primates. The new formation of muscles takes place at the margine of the original muscle layers; marginal muscle fibers assume another run and get individualized. So it can be seen in facial muscles of prosimians and platyrrhine monkeys that the profound muscles of mouth and nose and some of the rostral margine of the auricle have orginated from sphincter colli muscle, all others from platysma myoides. Primitive and modified muscle forms and intermediate muscle forms can be observed among prosimians as well as among platyrrhine monkeys and by this it is possible to see the homology of the facial muscles.


Pathogenesis of pathogenic Naegleria amoeba.

In brain sections of the Naegleria-caused cases of primary amoebic meningoencephalitis, extensive demyelinization was found in the white matter, besides the severe histopathological changes and large clusters of trophozoites in the grey matter. The myelinoclasis appeared to be a result of a specific phospholipolytic effect, unlike that in post-viral encephalomyelitis, which has been attributed to vascular blockade or hemorrhages. In monkey kidney cell cultures a very early cytopathic effect was observed and traced to the cytolytic property of the seeding culture fluid. Rat brain slices inoculated with Naegleria culture exhibited amoebic growth and demyelinization in 28-52 hours incubation at 35 degrees C. In a chemically defined medium containing sphingomyelin, casein and glucose, the Naegleria produced a limited growth parallelling the clearance of the lipid turbidity during a 72 hour incubation at 35 degrees C. Chromatographic analysis of the turbidity-cleared cultures revealed decomposition of sphingomyeline with liberation of choline, sphingosine and fatty acids. It is, hence, concluded that the pathogenicity of cytopathic effect of pathogenic Naegleria can be attributed to the latter's capacity to liberate a phospholipolytic enzyme or factor during active growth, which "makes holes" in the lipid-rich cytoplasmic membrane of cells as well as demyelinizes nerve tissue.