[Energy and nutrient supply during childhood. V. Iron intake (author's transl)].

The iron intake of 2--14 year old children living at home is reported. The iron intake of 2--3 year old boys amounts to 7.5 +/- 1.2 mg/day, of girls to 7.1 +/- 1.3 mg/day. The iron intake increases to 13.0 +/- 2.4 mg/day in 12--14 year old boys and to 11.6 +/- 1.6 mg/day in girls. The iron content of the food is 4.7--5.6 mg/1,000 kcal, independent of age and sex. 1/3 of the iron comes from animal foodstuffs, 2/3 from vegetable foodstuffs. After an observation period of at least 4 weeks 50% of the observed children reached their individual mean iron intake.


[Follow-up results of neonatal renal vein thrombosis after heparin treatment (author's transl)].

The authors report on their experiences gained during follow-up studies in 3 children, who as neonates had had renal venous thrombosis, and had been treated with heparin. On the basis of the relevant literature and their own observations, the authors suggest heparinisation during the acute stage.


[Reference values of lipid metabolism in childhood (author's transl)].

Sera of 949 children were analyzed for cholesterol and triglycerides by enzymatic methods and for lipoprotein pattern by electrophoresis. For the first time all ages were examined. Two independent collectives were compared: healthy pupils and sick children without disturbances of lipid metabolism. The values of these groups showed no significant difference. In infancy cholesterol and triglycerides levels heavily depend on age, while later in childhood values change little. Highest reference values are 6.36 mmol/l (= 246 mg/dl) for cholesterol and 1.74 mmol/l (= 154 mg/dl) for triglycerides.


[Calcaneus osteomyelitis of newborns caused by diagnostical heel punction (author's transl)].

4 Cases of calcaneus Osteomyelitis caused by "diagnostical heel punction" are demonstrated. More attention should be paid to this complication which is not enough mentioned in literature.


[Aneurysmal bone cyst (author's transl)].

Aneurysmal bone cyst in two patients are described and some radiological and clinical problems discussed, especially some difficulties in establishing the X-ray diagnosis of the infrequent disease.


A first exploration of a Robertsonian translocation heterozygote in the mouse for its usefulness in cytological evaluation of radiation-induced meiotic autosomal non-disjunction.

In this report some data concerning the male meiotic system of mice heterozygous for Rb(11.13)4Bnr are presented and compared with those of a chromosomally normal Swiss random-bred stock. Change of the genetic background from a C3H/Swiss hybrid situation to the fourth backcross generation (to the Swiss random-bred stock), did not alter the average frequency of aneuploid secondary spermatocytes. This was confirmed by studies on post-implantation loss. Spermatogenic characteristics of Rb4/+ mice, such as testis weight, sperm production and the number of diplotene-metaphase-I figures found in stage XII of the seminiferous epithelium, suggest delay and cell death during this period. These data support our working hypothesis that such an aberrant chromosome system may be more prone to radiation effects and therefore is promising in our cytological studies into the causes of spontaneous and in our cytological studies into the causes of spontaneous and induced autosomal non-disjunction during meiosis in the mouse.


Characterization of DNA damages by filtration through nitrocellulose filters: a simple probe for DNA-modifying agents.

A simple technique for the detection of DNA-modifying agents is described. The double-stranded covalently closed circular DNA of phage PM2 is exposed to the modifying agent and then analysed for DNA damages by assays involving only incubation steps and filtration through nitrocellulose filters. The technique described allows the measurement of DNA modifications which lead to local denaturation of the DNA double helix, interstrand cross-links, single- and double-strand breaks, damages which render the phosphodiester bonds of the DNA sensitive to hydrolysis and damages which labilise the glycosylic bond between base and sugar moiety.


Induction of sister chromatid exchanges in the central mudminnow following in vivo exposure to mutagenic agents.

Sister-chromatid exchange (SCE) studies using the central mudminnow, Umbra limi, demonstrated its usefulness as a model in vivo system for the detection of genetically active substances (mutagens and/or carcinogens). 5 days following the injection of 500 micrograms/g of 5-bromodeoxyuridine (BrdU), SCE rates were found to be quite low in the gills (2.0--3.3 SCEs/metaphase), kidneys (2.6--3.4 SCEs/metaphase), and intestines (3.7--4.5 SCEs/metaphase). However, after i.p. exposure to microgram quantities of methyl methanesulfonate (MMS) or cyclophosphamide (CP), large linear dose-dependent increases in SCE rates were observed in all tissues examined. amined. On a microgram/g basis, CP was found to be a 2--4 times more potent inducer of SCE than was MMS. Studies involving the addition of neutral red dye (NR) to the fish's aquarium water revealed that the mudminnow could concentrate the dye in its gill and kidney tissues. This dye was found to cause significant increases in SCE rates at water levels of less than 0.1 ppm. However, the concentration of dye in the tissues did not show a correlation with the SCE rate. Possible explanations for this observation are presented in the text. These findings demonstrate the feasibility of using a fish such as the mudminnow to investigate cytogenetic consequences of aquatic pollution.


Induction of sister-chromatid exchanges in cultured human cells by an organophosphorous insecticide: malathion.

Because malathion is a widely used organophosphorous insecticide, the effects of non-toxic concentrations (2.5--40 micrograms/ml) on sister-chromatid exchange (SCE) frequencies were determined. Human fetal fibroblasts were exposed once or twice to malathion, with 20 h between exposures. A single exposure to a concentration of 40 micrograms/ml resulted in a highly significant increase in the number of SCEs. After a double exposure, a concentration of 20 micrograms/ml induced an even greater increase in SCE frequencies. Comparison of Sce frequencies after single and double exposures indicated a cumulative effect; the number of exchanges at concentrations of 5 micrograms/ml or higher was significantly greater after the double exposure. An analysis of SCEs by chromosome group showed that exchanges were distributed approximately according to chromosome length.


Mutagenicity of vinyl chloride, vinylidene chloride and chloroprene in V79 Chinese hamster cells.

The mutagenicity of vinyl chloride, vinylidene chloride (1,1-dichloroethylene) and chloroprene (2-chloro-1,3-butadiene) was tested in V79 Chinese hamster cells in the presence of a 15 000 x g liver supernatant from phenobarbitone-pre-treated rats and mice. Mutations in terms of 8-azaguanine and ouabain resistance were induced in a dose-related fasion by exposure to vapour of vinyl chloride in the presence of liver supernatant from phenobarbitone-pretreated rats. Vapours of vinylidene chloride and chloroprene induced a dose-related toxicity in the presence of liver supernatant from phenobarbitone-retreated rats, but these two compounds were not mutagenic in V79 Chinese hamster cells under the present assay conditions. The results are discussed with regard to the metabolic activation of the compounds and to the correlation with their carcinogenicity in man and experimental animals.


The use of in vitro technics to study drug-induced pancytopenia.

The confirmation of drug-induced marrow aplasia is difficult since rechallenging the patient can lead to serious morbidity. We used marrow-culture technics to challenge in vitro the bone marrow of a patient with marrow aplasia after ingestion of quinidine. There was no clinical or laboratory evidence of quinidine-mediated destruction of erythrocytes, leukocytes or platelets. By contrast, use of quinidine in combination with the patient's serum substantially inhibited in vitro growth of allogeneic marrow granulocytic and erythroid series. Furthermore, use of quinidine in combination with acute-phase serum (but not acute-phase serum alone or quinidine in combination with recovery-phase serum) inhibited growth of the patient's marrow. This observation suggests that both a transient serum factor and quinidine were responsible for the marrow aplasia. These technics could be applied with minimal risk to similar patients and would permit in vitro rechallenge with the suspected drug.


Change in the content of oxidation and oligomeric products of sunflower oil during hydrogenation.

Oxidation and oligomeric products of sunflower oil were determined by gel permeation chromatography after transformation into methyl esters and prefractionation by urea. During oil refining the content of oxidation monomeric products increased from 0.9% to 1.5%, the dimer content from 0.06% to 0.32%, and the trimer content from 0.02% to 0.10%. During hydrogenation the content of polar monomeric oxidation products decreased to 0.9%, the dimer content to 0.28% and that of trimers to 0.03%. Oligomers were partly adsorbed on the surface of catalyst and carrier, because fat isolated from the catalyst contained more than 3% of oligomers. The content of oligomers established in the refined sunflower oil and in the hydrogenated sunflower oil produced on an industrial scale was lower than values given as limiting with respect to hygiene safety, sensory value and stability against oxidative rancidity.


[Square-wave polarographic determination of heavy metals in vegetables with special regard to cadmium].

The cadmium contents of 104 foods mostly of vegetable origin (market samples from a highly industrialized area in the GDR) were determined by means of square-wave polarography. The values obtained are in good agreement with literature data about the cadmium contents of foods, and they are not indicative of an increased contamination of the products under investigation compared to other industrialized countries.


[Determination of the quality of injuries of potato tubers due to damage and rot].

A new method is presented for determining damage to potato tuber tissue. It is based on the fact that starch can be leached with water from the damaged tissue. The starch content of the washing water informs about the extent of tissue damage. Damage assessments of the same samples yielded correlation coefficients ranging from r = 0.8 to r = 0.9 between the determinations and the assessments. The method considers both the mechanical tissue damage and the rot.


[Dietary interview. I. Comparison between dietary history versus repeated daily recalls].

In the course of 12 months, 43 men and 53 women aged 30-40 years were subjected to 14 24-hours recalls and one dietary history concerned with their individual dietary habits. The mean values yielded by the first and the second method for energy, 4 nutrient groups and 8 food groups were statistically evaluated and compared with each other, from which the following conclusions can be drawn as to the reliability and the precision of the dietary history: 1. The dietary history permits the quantitative estimate of the energy and nutrient intake in groups of about 50 subjects with an error of less than 10%. Underestimation of the actual food intake is more likely than overestimation. 2. The same holds true for the quantitative estimate of the consumption of foods from great food groups. The method is considerably less precise in case of single food or irregularly consumed foods. The differences between the results from the two methods ranged from 0 to 25%. 3. The precision of the individual results obtained for energy and nutrient intake from the dietary history was +/- 20% with a probability of 80-90%. In 75% of the cases, the differences in the consumption of food groups as determined by the two methods were smaller than 20%. As to single foods, however, individual misestimations ranging from 30 to 50% are to be expected.


[Method for identifying and determining polycyclic aromatic hydrocarbons in foods, soil and drinking water].

A method is described for identifying and determining polycyclic aromatic hydrocarbons in foods, soil and drinking water that, owing to the combination of extractive, chromatographic and spectrophotometric techniques, permits to detect 0,01 microgram of bezo(a)pyrene/kg in the presence of other polycyclic aromatic hydrocarbons. The preparation, pretreatment and concentration of the samples depend upon their nature. The isolation and separation of the polycyclic aromatic hydrocarbons are achieved with the aid of two consecutive thin-layer chromatographic systems, silica gel and acetylated cellulose. The subsequent identification and determination are based on the ulta-violet spectra (limit of detection, almost 0,5 microgram/ml) and, in the nanogram range, on the in situ fluorescence spectral analysis (limit of detection, 0,005 microgram of benzo(a)pyrene/spot). Fluorescence excitation and emission spectra obtained directly from the acetylated cellulose plate permit not only the reliable identification but also the determination of the polycyclic aromatic hycrocarbons; fluorescence transfer loci obtained under various conditions, the simultaneous determination. Depending upon the kinds of sample material, the recovery values range from 75 to 99.6% with a variation coefficient between 10.3 and 22.1%. Furthermore, a limiting value method is presented that permits to take yes-no decisions, by means of thin-layer chromatographic screening without using complicated measuring techniques, indicating whether or not the respective sample complies with the benzo(a)pyrene standard.


Bases and consequences of the newly recommended daily intakes of vitamins for the population of the German Democratic Republic.

In 1977 the official recommendations of the GDR for the daily intakes of essential nutrients were revised and extended. The criteria used to establish the revision and the extension in regard to the recommended vitamin intakes are given. For assessing the adequacy of food supplies and intakes vitamin intake data from national food consumption surveys and the weighted average recommended intakes for the entire population were compared. To give a true representation of vitamin amounts actually consumed, different forms of calculating losses on the way from harvesting or producing foods to the gullet have been applied. With the exception of tocopherol the daily intake of all vitamins considered permanently increased within the 10 years' period regarded, and the average levels of vitamin intake may appear satisfactory. Nevertheless, it is not valid to conclude that the vitamin needs of all individuals have been met.


The post-harvest fruit rots of tomato (Lycopersicum esculentum) in Nigeria.

A survey of the post-harvest fruit rot diseases of tomato was conducted in five states of Nigeria. During severe infections, the diseases could cause 25% loss at harvest and 34% loss of the remaining product in transit, storage and market stalls; thus giving an overall loss of about 50% of the product. Two types of rots, soft and dry were recognised. The soft rot was found to account for about 85% and the dry rot about 15% of the overall loss. Erwinia carotovora, Rhizopus oryzae, R. stolonifer, Fusarium equiseti, F. nivale and F. oxysporum were established as the soft rot pathogens; while Aspergillus aculeatus, A. flavus, Cladosporium tenuissimum, Corynespora cassiicola, Curvularia lunata, Penicillium expansum P. multicolor and Rhizoctonia solani were established as the dry rot pathogens of tomato fruits in Nigeria.


[Hygienic significance of sterigmatocystin in vegetable foods. 1. Analytical detection of sterigmatocystin].

The present paper gives a survey of the chemical, physical and biological properties of the mycotoxin sterigmatocystin. It must be regarded as toxic to warm-blooded animals and as cancerogenic. It is likely to occur in foods; therefore, its analytical detection is necessary. With reference to known confirmatory reactions, a method is described for the semi-quantitative determination of sterigmatocystin in fruit and vegetables. This method permits to detect 20 microgram/kg of food by means of thin-layer chromatography, after column-chromatographic purification on silica gel. The identity is confirmed by derivatization to the semi-acetal by treatment with trifluoro-acetic anhydride. The method is suited especially for the routine control of foods.


[Hygienic significance of sterigmatocystin in vegetable foods. 2. Production of sterigmatocystin by Aspergillus versicolor].

To test the suitability of fruit as an appropriate substrate for the formation of the mycotoxin sterigmatocystin, various fruit products were inoculated with a suspension of spores of a toxicogenic strain of Aspergillus versicolor. After incubation at 22 degrees C for 14 days, the fruits and juices overgrown with mould were homogenized with ethyl acetate and subjected to thinlayer chromatography. Sterigmatocystin had been formed on most products, the largest amounts being found in gooseberry preserves (9.4 microgram/g) and in grapes (10 microgram/g). The experiments show that fruit is generally suited as a substrate for the formation of sterigmatocystin; consequently, the latter is likely to occur in the presence of Aspergillus versicolor.


[Hygienic significance of sterigmatocystin in vegetable foods. 3. Occurrence of sterigmatocystin].

A total of 142 samples of vegetable foods was examined for the occurrence of sterigmatocystin. The samples examined were fruits and vegetables which had spontaneously gone mouldy or begun to rot under natural conditions on the one hand, and organoleptically impeccable fruit juices and maize specimens on the other hand. The samples were taken at the manufacturing plant or procured on the market in the framework of operative controls. Sterigmatocystin was detected in none of the samples under investigation. From this it may be concluded that the risk of its occurrence in vegetable foods is not very great in our country. Nevertheless, due to its cancerogenic and toxic properties, sterigmatocystin should remain included in the examination for mycotoxins in the framework of food control.


[Hygienic significance of patulin in foods. 1. Analytical detection of patulin].

The authors describe a thin-layer chromatographic method for determining patulin in fruit and vegetable products which is suited for routine work in hygiene practice. The samples are extracted with ethyl acetate, and the extracts are purified on a Florisil column. Separation is performed by means of a one-dimensional technique, using toluene/ehtyl acetate/formic acid (5 + 4 + 1), or, in the presence of interfering contaminants, by means of a two-dimensional technique, using benzene/methanol/glacial acetic acid (90 + 5 + 5) for the first run, and toluene/ethyl acetate/formic acid (5 + 4 + 1) for the second run. Patulin is detected by spraying with a benzidine solution, after chlorination. The limits of detection are 5 microgram/l of juice and 5 microgram/kg of fruit or vegetable. Derivatization with acetic anhydride/pyridine is used for corroborating the results obtained. The significance of 5-hydroxymethylfurfural as an interfering substance in apple juices is discussed.


[Hygienic significance of patulin in food. 2. Occurrence of patulin in fruit and vegetables].

The analyses of more than 200 samples of various foods of plant origin showed that patulin was contained in 36% of the fresh and canned fruits infested with mould, and in 7% of the vegetables. Besides apples, pears, plums, peaches and tomatoes contained also patulin. In organoleptically impeccable fruit juices, the contamination rates were 40% (for apple juice) and 16% (for the other juices, such as sour cherry, currant, sea buckthorn juices). The patulin content varied from 20 to 200 microgram/l, the mean value being 80 microgram/l. It ranged from 0.1 to 5 microgram/g in apples and sterile apple preserves. The authors discuss the hygienic-toxicologic significance of these findings, and suggest to include patulin in the examination of foods for mycotoxins, stipulating a permissible value.


[Dietary interview. 2. Comparison of the results obtained with different numbers of daily recalls].

From energy, nutrient and food intake data obtained with 14 24-hours recalls from 43 male and 53 female employees, aged from 30 to 40 years, the authors calculated and compared the single and group means for 1, 3, 5, 7, 10 and 14 days, respectively. It is tried to deduce from them the lowest number of interviews necessary for reliable statements. As the intra-individual variances were greater than the variances within the groups, the diet of such a group cannot be characterized on the basis of a single interview. Statements regarding the mean intakes of energy, nutrients and high-aggregated food groups could be made for groups of subjects on the basis of 3-5 interviews, with a tolerance of +/- 5%. The stable estimation of the consumption of single foods (with a tolerance of +/- 10%) required at least 7 interviews. 10 interviews were necessary for estimating (with a tolerance of +/- 10%) the mean intakes of energy, nutrients and great food groups of single persons. These results will hold true only when the workdays and weekends are in due proportion.


[Kinetics of furfural formation as related to heating, concentration and storage of orange juices and concentrates].

According to studies on an orange concentrate diluted back with distilled water to the desired extract content, the formation of furfural follows the pattern of a consequent reaction. After the induction period, the reaction curve takes a linear course cooresponding to a reaction of a zero order. The temperature dependence of the resultant reaction constant k obeys the ARRHENIUS equation and yields the same energy of activation for all the extract contents under investigation. This is a case of specific acid catalysis, because the reaction velocity is directly proportional to the hydronium ion activity. On a semilogarithmic scale, the dependence of the k values of the extract contents of the concentrates and of the re-constituted juice can be presented for various temperatures in the form of parallels. According to the literature, the amount of the furfural produced correlates with the quality of the orange juices and concentrates. Consequently, this amount might be used as an indicator in evaluating quality deteriorations due to unsuitable manufacturing and storage on the one hand, and for the computation and optimization of the manufacturing processes and parameters on the other hand.


[Analytical methods for nitrate and nitrite in feeds. 1. Spectrophotometric determination of nitrate with o-cresol].

The o-cresol procedure which is used for determining nitrate in feeds is tested for precision. The treatment of the samples and the course of analysis are rationalized. The method is recommended as a standard procedure for biological materials; it is suited as a reference technique in elaborating new analytical procedures.


[Determination and the hygienic-toxicologic significance of patulin in fruit and fruit products].

The combination of extracting, chromatographic and fluorescence densitometric steps permits to determine patulin in fruits and fruit products with great precision and sensitivity. The limit of detection is 10 microgram/kg; the recovery rates range from 86 to 92% with a variation coefficient lying between 5.6 and 13.6%. Interferences due to patulin-simulating substances are widely excluded. Patulin concentrations ranging from 0.3 to 42 mg/kg were found in the brown-rotten portions of apples. Juices domestically prepared from healthy fruits and fruits rid of rotten portions, respectively, contained no patulin. On the contrary, patulin concentrations ranging from 0.02 to 0.3 mg/l were observed in commercial apple juices. As to products with subsequent mould infection, patulin values up to 50 mg/l were found in apple juices, and up to 0.4 mg/kg in peach preserves. In a further 24 commercial fruit and vegetable juices, patulin was not detectable even not in cider, in cereals which had gone mouldy spontaneously, and in bread samples. The fruits and fruit products were analysed not only for patulin, but also for aflatoxin and ochratoxin; the latter two, however, were found in none of the samples examined. The possibilities of manufacturing patulin-free products are discussed.


[Chemical modification of proteins. 5. Modification of the 11-S-globulin from sunflower seed by reaction with dialdehyde starch].

Dialdehyde starch (DAS) reacts unspecifically with the amino acid residues of the 11 S globulin from sunflower seed. The modification of the protein causes a decrease of the content of each amino acid. Their blocking reaches maximum values at high pH levels (9,5) and high concentration of protein (5%). Especially high reactivity is shown by arginine as well as by the hydrophobic amino acids isoleucine, valine, and proline, and furthermore by histidine, lysine, asparagine (aspartic acid), and glutamine (glutamic acid). By reaction with DAS at pH 8.0 70% of the amino groups are blocked within 6 h; on the contrary, glyoxale blocks only 30% of the amino groups. Owing to the blockage of charged amino acid groups, a shift of the isoelectric point of the protein to a lower pH (4,3-4,4) takes place; this effect can be followed for 2 days. As a result of the reaction with DAS, only small amounts (10-15%) of intermolecular crosslinkage products with sedimentation coefficients of 17 S and greater than 17 S were formed. But by means of SDS-gel electrophoresis, dimers and trimers of the polypeptide chains in the protein were detected.


In vitro formation of a complex between cytoskeletal proteins of the human erythrocyte.

The formation of a high-molecular weight complex between spectrin and F-actin depends on the presence of a third cytoskeletal constituent, protein 4.1. Electron microscopy shows that in this ternary complex the actin filaments are linked by bridges, which have the appearance of spectrin. The spectrin must be in the tetrameric state for such bridges to form: the dimer is evidently univalent, for it binds but forms no cross-links. G-actin also fails to form extended complexes. It is inferred that in the native cytoskeleton the spectrin is tetrameric and associated with 4.1 and probably oligomers of actin.


Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen.

DNA extracted from hepatitis B virus Dane particles has been cloned in bacteria using a plasmid vector. A full-length clone has been examined by restriction endonuclease analysis, and the nucleotide sequence of an 892-base pair fragment from cloned hepatitis B viral DNA encoding the surface antigen gene is reported. The amino acid sequence deduced from the DNA indicates that the surface antigens is a protein consisting of 226 amino acids and with a molecular weight of 25,398. The portion of the gene coding for this protein apparently contains no intervening sequences.


Chicken ovalbumin contains an internal signal sequence.

Ovalbumin is shown to contain an internal rather than an amino-terminal signal sequence. This internal signal can be recovered in a tryptic fragment which comprises residues 229--276 of mature ovalbumin and contains a region of striking sequence homology to amino-terminal cleaved signals of two other oviduct secretory proteins. The isolated tryptic fragment is used as a probe to demonstrate that a signal receptor is present in membrane vesicles derived from the rough but not in those derived from the smooth endoplasmic reticulum.


'Square arrays' in the sarcolemma of human skeletal muscle fibres.

Fast twitch fibres of rat and rabbit show rectangular patterns of intramembrane particles in freeze-fracture preparations of the sarcolemma. These 'square arrays' are almost totally absent in the slow twitch coleus muscle of rat. I report here differences in the incidence of square arrays in human fetal and adult muscle and in different fibres within a human muscle. Square arrays probably classify fast and slow twitch fibres in freeze-fracture preparations of mixed muscles.


Use of chlorotetracycline fluorescence to demonstrate Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum of skinned cardiac cells.

It has been proposed that the trans-sarcolemmal influx of Ca2+ occurring during the plateau of the mammalian cardiac action potentials is insufficient in itself to activate the myofilaments, but can trigger a release of Ca2+ from the sarcoplasmic reticulum (SR) which is sufficient for activation. The demonstration of this Ca2+-induced release of Ca2+ relied entirely on experiments in which the tension developed by the myofilaments was used as a sensor of the changes of myoplasmic free Ca2+ concentration ([free Ca2+]) in segments of single cardiac cells from which the sarcolemma had been removed by microdissection (skinned cardiac cells). The small size of these preparations has previously prevented the use of more direct methods for the detection of myoplasmic Ca2+ movements. The present study is a direct demonstration of Ca2+-induced release of Ca2+ from the SR of skinned cardiac cells treated with chlorotetracycline (CTC), a fluorescent chelate probe which enables changes in the amount of Ca2+ bound to a variety of biological membranes or micelles to be monitored. The fluorescence increases when more Ca2+ is bound.


Specific tricyclic antidepressant binding sites in rat brain.

The discovery of high-affinity binding sites for psychoactive drugs such as benzodiazepines, opiates and neuroleptics has opened up new approaches to the study of these drugs and their mechanisms of action. Although most tricyclic antidepressants inhibit neuronal uptake of noradrenaline and serotonin, their mechanism of action remains unclear. Changes in the sensitivity of the beta-receptor after chronic tricyclic antidepressant treatment suggest that they modulate noradrenergic neurotransmission. Tricyclic antidepressants also act directly on cholinergic, histaminergic, alpha-adrenergic and serotonergic receptors. It is not clear, however, which, if any, of these effects are related to the primary antidepressant effect or whether they are simply responsible for some of the side effects. We have thus investigated the possibility that specific binding sites for tricyclic antidepressants exist in the central nervous system. So far, binding studies using 3H-labelled tricyclic antidepressant drugs have only detected binding to histaminergic H2 and cholinergic muscarinic receptors and low-affinity binding. We demonstrate here a population of specific high-affinity binding sites for 3H-imipramine on brain membranes which may be responsible for the antidepressant effects of these drugs.


Evidence that three structural genes code for human alkaline phosphatases.

The number of structural gene loci that code for the different molecular forms of human alkaline phosphatase is unknown. Physical properties of the enzymes, immunological data, chemical inhibition and genetic studies suggest that at least three structural genes are involved: one coding for alkaline phosphatase from placenta, another for the enzyme from intestine, and one or more for the enzymes from liver, kidney and bone. Badger and Sussman have shown that alkaline phosphatases from human liver and placenta are products of different structural genes, and Greene and Sussman have shown that alkaline phosphatase from a metastasised bronchogenic carcinoma was nearly identical to the enzyme from placenta. However, other tumour-associated alkaline phosphatases and the enzymes from normal tissue other than placenta and liver have not been identified by conclusive structural criteria, and thus it is not known whether these onco-alkaline phosphatases represent ectopic production or unusual post-translational modification of the enzymes found in normal tissues. We present here, using a sensitive peptide-mapping technique, structural evidence that the enzyme forms from liver, kidney and serum from a patient with Paget's disease of bone (osteitis deformans) are products of the same structural gene and can be easily distinguished from either the intestinal or placental isoenzymes. The technqiue seems to be useful for the classification of tumour-associated alkaline phosphatases on a structural basis.


Interaction of C-reactive protein with artificial phosphatidylcholine bilayers.

C-Reactive protein (CRP), the most characteristic of the 'acute phase proteins' (ref. 1) is thought to participate in the mediation and/or modulation of acute inflammatory processes, but its exact function is unknown. CRP has a Ca2+-dependent binding specificity for phosphorylcholine, the polar head group of two widely distributed lipids, lecithin (phosphatidylcholine, PC) and sphingomyelin (SM). A number of observations suggest that at least some of the biological activities of CRP depend on its interaction with phospholipids of cell membranes. In addition, interaction of CRP with PC- and SM-containing lipid dispersions and with PC-containing liposomes can activate the complement system. We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC). Thus, a disturbance of the molecular organisation of the bilayer appears to be necessary for binding of CRP. These findings provide a possible biochemical explanation for binding of CRP to damaged but not intact cell membranes and might be relevant to its biological function.


Evidence for the bilobal nature of diferric rabbit plasma transferrin.

Plasma transferrin is involved in iron transport within the circulatory system of vertebrates, and provides an iron source for haemoglobin synthesis and other metabolic requirements. However, despite extensive studies by spectroscopic, biochemical and physiological techniques, the nature of iron binding and the mechanisms of uptake and release of iron are not fully understood. Plasma transferrins are monomeric glycoproteins with a molecular weight of approximately 80,000 (ref. 2); they have two similar and very strong binding sites for Fe(III), together with two associated anion binding sites. Fragmentation studies on various transferrins have shown that the polypeptide chain is composed of two domains formed from the N-terminal and C-terminal halves of the polypeptide chain. Each domain contains one metal binding site. The marked sequence similarities which exist between the two halves may reflect a doubling of an ancestral structural gene during the phylogenetic development of the protein. Preliminary crystallographic investigations of diferric rabbit plasma transferrin have been reported from this laboratory. We now report initial studies of the X-ray structure determination of dife-ric rabbit plasma transferrin which have led to a 6-A resolution electron density map.


Comparison of sodium nitroprusside and isoprenaline aerosols in histamine-induced bronchial asthma of the guinea pig.

1. Sodium nitroprusside (NP) is a potent relaxant of the guinea pig's tracheal smooth muscle contracted by carbachol or histamine. 2. At high doses, aerosols of NP delay the occurrence of symptoms of bronchial asthma in guinea pigs subjected to a histamine aerosol. However, the beta-adrenergic bronchodilator isoprenaline is at least 2,600 times more potent as an anti-asthmatic than NP on a molar basis. 3 NP and isoprenaline both reduce the blood pressure in rats when given either as infusion or as aerosol. The aerosol/infusion dosage ratio for comparable reductions of blood pressure were 1 for isoprenaline, and 10 for NP. After cessation of the application of the NP aerosol, the blood pressure rose more than twice as fast (t1/2 of blood pressure recovery) than after cessation of the application of the isoprenaline aerosol. 4. The poor antiasthmatic effect of NP aerosols may result from low permeability of the bronchial epithelium to the NP anion, from partial destruction in the airways or during tissue permeation, and from short half life of NP in the circulating blood. 5. Because of its inferiority to known bronchodilators, aerosols of NP cannot be recommended for the treatment of acute bronchial asthma.


The affinity of atropine for muscarine receptors in human sphincter pupillae.

Concentration-dependent contractions in response to carbachol were determined on isolated pieces of human iris. Atropine competivtively antagonized the effect of carbachol. An apparent dissociation equilibrium constant of 0.4--0.7 nM was estimated for the muscarine receptor-atropine complex.


Baclofen and muscimol: behavioural and neurochemical sequelae of unilateral intranigral administration and effects on 3H-GABA receptor binding.

Log dose-response curves for induction of contralateral rotational behaviour in the rat by unilateral intranigral injections of the GABA agonist muscimol and the GABA analogue baclofen have been compared. Baclofen, 5--1000 ng, produced a maximal rotational response that was only 40% of that produced by 0.25--100 ng muscimol, and log dose-response curves failed to show parallelism. The behavioural effects of both drugs were only weakly antagonised by haloperidol and were not antagonised by 6-hydroxydopamine lesions of ipsilateral dopamine (DA) neurons, indicating that these responses were independent of DAergic mechanisms. The effects of baclofen were weakly antagonised by picrotoxin. Intranigral muscimol and baclofen substantially elevated striatal DA concentrations. While muscimol also substantially elevated striatal dihydroxyphenylacetic acid (DOPAC) but not homovanillic acid (HVA), bactofen did not significantly effect either DOPAC or HVA. Baclofein, GABA and muscimol displaced specific 3H-GABA binding in vitro with IC50's of 40 micron, 400 nM and 40 nM respectively. These results indicate that muscimol and baclofen do not act via a unitary GABAergic mechanism, but suggest that baclofen may be a partial GABA agonist, at least at nigral GABA receptors.


Micropuncture studies on the renal handling of 2,4-diamino-6,7-dimethylpteridine.

The excretion of the diuretic substance DADMP (I,4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2 . 10(-4) cm . s-1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20--30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2 . 10(-13) mol . min-1 and 10(-9) mol . min-1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.


Decreased sensitivity of isolated hepatocytes from baby rats, from regenerating and from poisoned livers to phalloidin.

Isolated hepatocytes, prepared from 5 day old rats, from regenerating livers of from livers after poisoning with carbon tetrachloride, are less sensitive to phalloidin in vitro than hepatocytes from untreated adult controls. The time course of the reduced susceptibility to phalloidin was compared with the ability of hepatocytes to take up bile acids under various conditions. SDS-electrophoresis of cell lysates gave no evidence for decreased levels of actin in cells with reduced sensitivity to phalloidin. In contrast, there was a good relationship between the active uptake of bile acids and the sensitivity of hepatocytes to phalloidin. The decreased response of hepatocytes from baby rats, from regenerating livers or from poisoned livers to phalloidin is more probably related to differences in phalloidin uptake than to a reduced endowment with microfilamentous structures.


A material with opioid activity in bovine milk and milk products.

Chloroform-methanol extracts of lyophilized milk, of commercially available dried milk or baby food and of casein digests were tested for opioid activity on the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. Compounds with opioid activity--which proved to be resistant to peptidases--were detected in certain batches of baby food, casein digest, and cow milk in considerably varying amounts.


[Organization of neurons in the cat Clare-Bishop area which react to photic stimulation].

Organization of neurons in Clare-Bishop associative cortex was investigated by means of microelectrode vertical penetrations and recording of the neuronal responses to visual stimulation. Of 463 electrode penetrations 255 showed responses to visual stimulation. In 131 penetrations only 1 or 2 visually driven neurons were noted, in 55 cases more than 3 neurons were registered. Of 55 investigated penetrations 8 showed distinct columnar organization, i.e. all neurons in each column had similar characteristics. In 24 penetrations neurons were organized in groups of 2 or 3 similar neurons intermingled with neurons of other types. In 18 penetrations a great degree of overlapping of the receptive fields of neurons in a single column was observed. In 5 penetrations a chaotic organization of different neurons was found. A conclusion is made that the columnar organization of visually driven neurons as a functional cortical unit can not be regarded as a prominent feature in Clare-Bishop area.


[Comparative characteristics of the direct influences of the perforant pathway on neurons in hippocampal fields CA1 and CA3 in vitro].

The effect of the perforant path stimulation on the CA1 and CA3 neurons was investigated in incubated slices of the guinea pig hippocampus. Spike generation was observed in both fields during stimulation of the perforant path. The majority of the CA1 neurons followed rhythmic stimulation up to 30-80/c. The CA3 neurons responded only to low-frequency stimulation (up to 5/c). The posttetanic potentiation of responses to the perforant path stimulation was observed in both hippocampal fields.


[Myelo- and cytoarchitectonics of the cat pallidum].

600 thick serial frontal and sagittal sections of the cat cerebrum were made. Using the new controlled impregnation technique, it was shown that the pallidum is crossed by numerous transit axons bundles (TAB) consisting of thin myelinated and unmyelinated axons each 0.2-0.8 micron in diameter. TAB pass through the dorsal part of the putamen and the whole pallidum parallel to the sagittal plane and perpendicular to the frontal plane. Such TAB contain not less than 10 million axons in the pallidum of a hemisphere. The TAB are mainly related to the capsula interna and to the sensory-motor cortex. The cyto- and synaptoarchitectonics of the pallidum is described.


[Activity of interneurons of the lumbar region of the spinal cord during fictive locomotion of thalamic cats].

Impulse activity of lumbar interneurons was recorded extracellularly during fictious locomotion of thalamic cats. Neurons whose activity was modulated in the rhythm of fictitious locomotion were revealed in the lateral intermediate zone and in the lateral ventral born. 41.2% of these neurons were mainly activated at the phase of "flexion", 48.5%--at the phase of "extension" and 10.3%--at both phases. Neurons with tonically increasing or decreasing activity during rhythmic efferent discharges and neurons whose activity did not change during fictitious locomotion were also observed. All these types of neurons were similarly activated during late discharges in efferent nerves. But in this case the depth of modulation of neuronal activity was lower than during fictitious locomotion. Afferent inputs to the recorded interneurons were also investigated. The neuronal organization of the spinal locomotor generator is discussed on the basis of the obtained data.


[Types of skeletal muscle motor unit activity during cold tremor].

The impulse activity of 184 single motor units of the sartorius muscle was investigated in anesthetized cats during cold tremor. Motor units whose impulse activity was connected with respiration cycles and motor units functioning independently of respiration were detected. The functions of both types of the motor units are characterized by the same average rate (4-12 imp/s) and low variability of interspike intervals. Additional thermal stimulation of the vascular thermoreceptors and changes in the rate and amplitude of respiratory excursions caused similar responses of the motor units of both types. It is suggested that motor units of both types have the same thresholds and belong to the phasic slow motor units.


[Relationship between the magnitude of the inflowing current of isolated Limnea stagnalis mollusk neurons and the external concentration of the current-bearing calcium and strontium ions].

The dose-inward current relationships for current-carrying ions Ca2+ and Sr2+ were studied by means of intracellular dialysis and voltage clamp in isolated neurons of the mollusc Limnea stagnalis. For Ca2+ and Sr2+ ions these relationships had ceiling. The data obtained are explained in terms of activation theory using two-barrier model of calcium channel. Values of velocity constants vx for ion x2+ transition over the second energetic barrier and of constants Kx corresponding to effectiveness of binding in the channel's entrance were determined: vca:vsr = 1:2; KCa = 1400 M-1; KSr = 270 M-1.


[Electrophysiologic analysis of interaction between afferent inputs to the rat neostriatum].

The interaction of the efferent inputs of the caudate nucleus in the region of their maximal overlapping was studied by paired stimulation. The stimulation of the n. paracentralis and cortex resulted in an increased amplitude of the tested response. On the contrary, the tested responses to stimulation of substantia nigra (zona compacta) and n. raphe (dorsal region) were inhibited. The paired stimulation showed a particular hierarchy of different afferent inputs as to their mutual influence: frontal cortex--thalamic intralaminar nucleus--midbrain structures. The afferent inputs from higher levels, while molulating the activity of those from lower ones, do not reliably change their own activity under the action of the latter. Possible mechanisms of this modulation are discussed.


[Critical evaluation of the searching technic of the polarization-sensitive neurons of insects].

The demerit of the light stimulator used by the authors was the presence of lenses between the eye and the observed light source. Apart from the image of the aperture diaphragm, the images of some details and reflections were formed. The terminal lens of the stimulator and the eye optics can divide the main and secondary images of the retina. Therefore the reactions of insect neurons to polarized light described previously could be explored also as the responses to flickers in secondary images.


Calculations of theoretical indices of carcinogenic activity including the effect of medium.

Relation between the electronic structure of aromatic compounds and their carcinogenic activity has been correlated. Hypotheses of K, L regions have been employed. Possibilities of better theoretical description of carcinogenic activity have been examined by including the effect of medium and by using a more exact quantum--chemical method. Theoretical carcinogenic activity of some compounds so far experimentally not tested has been estimated.


Inhibitory effect of the antioxidant butylated hydroxyanisole on the activation of the carcinogen benzo(a)pyrene.

The effect of the antioxidant butylated hydroxyanisole (BHA) on benzo(a)pyrene (BP) metabolites binding to DNA, percentage of diols and phenols in the total amount of BP metabolites extracted to organic solvent, were studied in : incubation mixture of rat liver microsomes, cultured mouse embryo cells, human skin, and human lymphocytes. The amount of BP metabolites bound to DNA in mouse embryo cells and human skin decreased in the presence of BHA. No effect was found in human lymphocytes. Percent of phenols increased in mouse embryo cell cultures; percent of diols decreased in cultures of human skin and lymphocytes.


Differences in the purification effect of carcinoembryonic antigen (CEA) from the three different hepatic metastases of rectum carcinoma.

Carcinoembryonic actigen (CEA) was purified from three liver metastases of carcinoma recti by a conventional procedure involving perchloric acid extraction of tumor tissue and fractionation of the extract by gel filtrations on Sepharose 4B and Sephadex G-200. The preparations obtained showed a different degree of heterogeneity in SDS-polyacrylamide gel electrophoresis and crossed immunoelectrophoresis, and also a different antigenic activity. One of preparations obtained was a homogeneous CEA by all these criteria, and two others showed heterogeneity and lower antigenic activity. The most heterogeneous CEA preparation was further purified by the affinity chromatography on Concanavalin A-Sepharose 4B and by DEAE-Sephadex A-50 chromatography and the usefulness of these procedures for purification of CEA is compared.


Changes in hexokinase properties during transformation and subsequent proliferation of liver cells.

The activity and subcellular distribution of hexokinase in liver and several hepatomas were studied. The differences were found in the behavior of this enzyme in spontaneous, primary induced and transplantable hepatomas as compared with normal liver.


DNA methylation in various growth phases of cultured L5178Y murine lymphoblasts.

The extent of methylation of DNA during the transition of cells from exponential phase of growth to the saturation density has been studied in cultured L5178Y mouse lymphoma cells by the comparison of the degree of 5-methylcytosine formation and the stability of this preformed base in various periods of their growth. It has been found that while the degree of 5-methylcytosine formation gradually fell down, the level of this base preformed during the exponential growth was stable during the subsequent periods until the saturation density was reached. At that state some small and variable loss of the base was found.


Nucleolar morphology in estimation of urinary bladder cancer in man: study on surface contact preparations.

The special feature of nucleolar morphology which reflects the intensity of ribosomal RNA precursor molecule formation and thus also the intensity of proteosynthesis was studied in contact surface preparations from tissue samples of 28 patients with epithelial tumors of the bladder and in tissue samples of bladder mucosa from 16 patients with prostata hypertrophy (7 of them suffered also from cystolithiasis). In malignant lesions of the bladder mucosa, especially in tumors of medium and high grade malignancy, very low values of metabolically resting cells with ring shaped nucleoli and micronucleoli were found.


Histologic changes in the human skin melanoma after intratumorous treatment with BCG.

Twenty six patients with malignant skin melanomas were treated with an intratumorous injection of 0.1 ml BCG applicated in certain time intervals. Histologic changes in tumor tissue starting with dystrophy and necrosis of the cells and ending with the formation of a granular tissue replacing the tumor are described. In one case the untreated satellite localized 2 cm from the injected tumor disappeared. The results indicate that the reaction of the cells on the applicated vaccine varied. In some tumors dystrophic changes and necroses were very large, in others they were of a lesser extent, but in all the process ended with the formation of a granular tissue. The mechanism of the action of BCG is discussed. For the time being, it seems that the intratumorous application of BCG is a useful adjuvant therapy.


Comparative porphyrin content in tumors with contiguous non-neoplastic tissues.

The porphyrin content in primary human carcinomas, their metastases and the contiguous non-neoplastic tissues were compared. The level of porphyrins in primary internal organ tumors was greater, and in endocrine gland tumors lesser, than in their contiguous non-neoplastic tissues. Neoplastic metastases to the liver contained less porphyrin than the host tissue. Metastases both to the liver and to the kidney were characterized by higher pyrrole pigment content than that in the primary tumors.


A beneficial effect of the in situ kidney on in vitro marrow erythropoiesis in chronic renal failure.

The effect of the in situ kidney on transfusion requirements and in vitro erythropoiesis was investigated in 20 patients with end stage renal disease undergoing hemodialysis. 6 of the 12 patients with in situ kidneys did not require transfusion, whereas the other 6 had an average monthly transfusion requirement of 277 ml of sedimented RBCs. All 8 anephric patients required transfusions with an average requirement of 352 ml of sedimented RBCs per month. Serum erythropoietin activity was inappropriately low for the degree of anemia in all but 1 patient, and bone marrow was uniformly hypocellular. Marrow cells from patients with in situ kidneys exhibited a greater response to erythropoietin than marrow cells from their anephric counterparts. The response was not improved by hemodialysis.


Therapy of iron deficiency anemia in patients on maintenance dialysis.

A controlled, prospective study compared the effectiveness of oral ferrous sulfate to intravenous iron dextran, each with and without concurrent intramuscular androgen for therapy of iron deficiency anemia in patients with chronic renal failure treated with maintenance hemodialysis. During the 12-week period of therapy, the patients who received oral ferrous sulfate and androgens showed an increment in their mean hematocrit of 16.3% and those who received oral ferrous sulfate alone had an increase of 8.3%. Patients treated with intravenous iron dextran androgens showed an increment in their mean hematocrit of 9.4% and those given iron dextran alone showed an increase of 3.5%. Serum ferritin levels increased with iron repletion but correlated inversely with the erythropoietic response. The serum ferritin assay provides a simple and reliable method to demonstrate iron repletion, and oral ferrous sulfate is the preferred method of iron repletion in compliant patients.


Minimal intermittent heparinization during hemodialysis.

Minimal dose heparinization inhibiting clotting factor IXa, Xa, XIa, as monitored by the activated partial thromboplastin time, was compared with conventional intermittent, continuous and regional heparinization during hemodialysis treatment. Blood loss in coil dialyzers was the same. Heparin dosage was reduced markedly. Protamine sulfate and infusion equipment were not required. No bleeding problems were encountered in high-risk patients.


A study of the renal countercurrent system by computer simulation.

A model of the renal medulla is formulated, taking into account the transport properties of each medullary structure. Using known data on inflow to the vascular and tubular systems and on urine output in normal man in hydropenia, and assuming medullary osmotic profiles similar to published data on hydropenic dogs, transport coefficients are calculated for each medullary structure. The calculated coefficients compare reasonably well with measurements made in the rat kidney. A normal hydration case is calculated by reducing the collecting duct permeability until a urine output and concentration of 1.0ml/min and 700 mosm/l is obtained. The coefficients are then kept constant, and medullary osmotic profiles and urine output corresponding to various system imputs are calculated. These studies show that medullary osmolarities decrease and urine flow increases with increasing medullary blood flow and that an optimal rate of proximal reabsorption exists for producing a maximally concentrated urine. Such results are consistent with observations on renal function reported both experimentally and clinically.


Renal tubular necrosis following cephalothin.

Renal tubular necrosis was observed following intramuscular injections of cephalothin into rats. Lesions were consistently produced with 5.0g/kg and were maximal in severity at the 2nd and 3rd days following injection. Renal tubular necrosis following cephalothin was similar in morphology to that produced by nephrotoxic doses (2.0 g/kg) of cephaloridine. The nephrotoxic potential of cephalothin has been demonstrated in the rat model and caution is urged in using large doses of cephalothin.


Renal sites of natriuretic and uricosuric activity of ticrynafen in the mongrel dog.

Following establishment of steady state plasma concentrations of ticrynafen in the mongrel dog, the intravenous injection of large doses of p-aminohippurate (PAH) or sodium salicylate reduced or blocked the urinary excretion of ticrynafen. In a similar manner, the intravenous administration of ticrynafen reduced the urinary excretion of PAH in preloaded dogs. Since PAH and salicylate are actively secreted by a renal tubular organic anion transport system, these data were interpreted as evidence of an active tubular secretion of ticrynafen. The natriuresis and uricosuria which result from the administration of ticrynafen to the mongrel dog were reduced by PAH and salicylate at doses of these compounds which effectively blocked the secretion of ticrynafen. These results demonstrate that in the dog, the natriuretic and uricosuric activity of ticrynafen results from the presence of ticrynafen in the tubular lumen.


Effects of MK-196 on urate and electrolyte excretion in the rat.

Clearance and micropuncture techniques were used to evaluate the effects of MK-196 on uric acid and electrolyte excretion by the rat kidney. The urinary excretion of sodium, uric acid, calcium and magnesium increased significantly following MK-196 administration. The major site of action with respect to sodium reabsorption was in the ascending limb of Henle's loop as revealed by depression of both free-water clearance and reabsorption. By contrast, microinjection studies with [2-14C]-urate revealed the major site of altered urate absorption to be in the proximal convoluted tubule, a site where sodium and water reabsorption was unchanged.


Ticrynafen: site of natriuretic activity.

Studies were performed with ticrynafen (tienilic acid) to determine its natriuretic site of action, detailed electrolyte excretion, and its effect on acid excretion and bicarbonate reabsorption. With 500 and 1,000 mg oral doses under conditions of water diuresis, there was a decrease in free water excretion as osmolar clearance increased. During hydropenia, there was no change in free-water reabsorption as osmolar clearance increased. Maximum sodium excretion reached 5.2% of the filtered load. At 500 mg doses, there was no effect on phosphate excretion; with 1,000 mg doses, there was a reduction in phosphate excretion. During bicarbonate infusion, there was no change in the absolute or percent reabsorption of bicarbonate. After chronic administration of ticrynafen, there was no impairment of excretion of al acute acid load. Uric acid excretion increased at least threefold in all studies. The studies indicate that at 500 and 1,000 mg oral doses, ticrynafen has the characteristics of a diuretic which is active in the cortical diluting segment of the distal nephron.


Elevated serum uric acid. A cardiovascular risk factor?

A critical survey of the literature suggests that elevated serum uric acid is definitely associated with hypertension and may function as an independent risk factor in the development of this disease. The possible role of an elevated serum uric acid as an independent risk factor for the development of ischemic heart disease remains controversial and the association of these two factors may depend on the relationship between uric acid and hypertension. There is no evidence available to define the metabolic turnover of uric acid in hypertensives. The exact mechanisms underlying elevated serum uric acid values during diuretic treatment are unclear, but depend initially upon diuretic-induced extracellular volume depletion.


Mechanism of the uricosuric activity of ticrynafen.

Studies employing pyrazinamide, which have included the measurements of clearances of pyrazinamide and pyrazinoate, as well as of ticrynafen itself and its principal metabolite, have lent support to the hypothesis that ticrynafen inhibits the tubular reabsorption of both filtered and secreted urate by nephrons of the human kidney. The inhibition of the reabsorption of secreted urate by ticrynafen appears to be quantitatively important for eliciting its uricosuric and hypouricemic responses. Because the uricosuric and natriuretic responses correlate with urinary ticrynafen concentrations, the drug appears to inhibit tubular reabsorption after gaining access to tubule fluid. As a consequence of its extensive binding to plasma proteins, clearance data suggest that tubular secretion of ticrynafen is necessary for its action.


Uricosuric response to increasing doses of the indanone diuretic MK-196 in healthy volunteers.

Doses of 20, 40, 60 and 80 mg of the indanone diuretic MK-196 and 40 mg of frusemide were administered in random order to 5 healthy volunteers in a stable metabolic state, on the same day for 5 consecutive weeks. Diuresis, natriuresis and kaluresis increased with increasing doses, the natriuresis lasting for about 12 h and the kaluresis for about 24 h. Uricosuria increased with increasing doses of MK-196 and lasted for about 6 h. The uricosuria was followed by urate retention, so that there was little net change in the renal excretion of urate. Significant weight loss occurred, so that there was probably some associated plasma volume contraction, which would promote urate retention. By contrast, frusemide caused a reduction in renal excretion of urate at all times.


Comparative effects of ticrynafen and hydrochlorothiazide on blood pressure, renal function, serum uric acid and electrolytes, and body fluid spaces in hypertensive man.

25 hypertensive subjects underwent a double-blind, randomized study to compare the effects of ticrynafen (TCNF) with hydrochlorothiazide (HCTZ) on blood pressure (BP), renal function, serum uric acid (UA) and electrolytes, and body fluid spaces. BP was similarly lowered by TCNF and HCTZ. Neither TCNF nor HCTZ had a significant effect on true or regular creatinine, inulin, or PAH clearances. TCNF lowered UA, whereas HCTZ elevated UA. Both produced similar electrolyte disturbances. Neither TCNF nor HCTZ, according to our methods, had a significant effect on plasma volume, extracellular fluid, or total body water. The primary advantage of TCNF compared with HCTZ is its profound hypouricemic effect.


[Importance of dynamics of scintigraphic changes in the brain for prognosis in stroke].

The results of scintigraphic investigations of the brain were analysed in patients with ischaemic strokes. In all cases scintigraphic investigation was done twice at least. Particular attention is called to the dynamic development of changes in the size of pathological foci in relation to the degree of improvement in the neurological condition of the patients over one year of follow up. Among patients with considerable neurological improvement control investigations carried out after 4 to 8 weeks of the disease demonstrated return of normal scintigraphic findings or a considerable reduction in the size of pathological foci. On the other hand, in patients without neurological improvement pathological scintigraphic changes persisted much longer, they were present in the investigations performed after 4 to 8 weeks, and even after 3--4 months. The presented observations point out that scintigraphic investigations of the brain can have a prognostic significance for the prognosis in brain strokes. These investigations must be done, however, at least twice between the 2nd and 3rd weeks and between the 4th and 8th weeks of the disease. Normalization of scintigraphic findings or a considerable reduction in the size of the pathological changes in the second investigation may suggest good prognosis.


[Differences in basic rheoencephalographic studies in healthy persons depending on age].

The method of rheoencephalography (reg) was applied for assessing brain circulation in 40 healthy subjects divided into two age group. The age in the first group was from 20 to 45 years (mean 34.3), in the second group from 46 to 73 years (mean 52.3). Reg records were assessed visually calculating the pertinent indices and arithmetical means of 10 waves on each side. The obtained results point to reduced elasticity of blood vessels in the older age group.


[Leukergy in multiple sclerosis before and after treatment with sodium salicylate and dexamethasone (preliminary report)].

The authors determined the leukergic reaction in the blood of multiple sclerosis patients treated with dexamethasone and sodium salicylate. The investigations were done in two groups of 25 patients each. Dexamethasone was used in a daily dose of 4 mg, and sodium salicylate in a dose of 2.0 g. A significant effect of dexamethasone on reduction of the leukergic forms of leucocyte in the peripheral blood of these patients was observed. There was no significant effect of sodium salicylate on leukergy.


[Pneumoencephalographic appearance of cerebral ventricles in spontaneous tremor].

Three patients of different ages with evidence of essential tremor of familial origin are reported. Pneumoencephalography demonstrated in these cases presence of hydrocephalus. The size of the cerebral ventricles was assessed by means of the index of Schiermann and Evans. No correlation was observed between the degree of changes in the ventricular system and the duration of the disease. Abnormalities moencephalograms concerned only the Evans index.


[Analysis of changes in the incidence of seizures in pregnant women with epilepsy].

Sixty-five (41%) of 153 pregnant women with epilepsy were selected for analysis because the course of the disease changed in them during pregnancy. In 43 of these women (67%) the frequency of seizures decreased and in 21 cases the seizures disappeared completely. In 22 patients (33%) the frequency of seizures increased in pregnancy. An unfavourable influence of pregnancy was observed more frequently in patients with vourable influence of pregnancy was observed more frequently in patients with severe epilepsy with evidence of organic changes in the central nervous system and mental changes. The prognosis was better in women with less severe disease continuing anticonvulsant treatment.


[Comparison of the changes in bioelectric activity recorded simultaneously from the amygdaloid body and the hippocampus and from the cranial surface during the stereoelectroencephalographic examination in epilepsy].

The authors analysed 95 SEEG records in epileptics with prevalent temporal-lobe changes comparing the bioelectric activity of the brain recorded simultaneously in the amygdala, hippocampus, temporal cortex and cranial surface during these investigations and relating them to EEG records obtained before the operation. In these records pathological elements typical of epilepsy were found occurring in different variants synchronously or asynchronously in leads at three above mentioned levels. In the findings reported attention is called to occurrence of seizure discharges in the amygdala and hippocampus which had no equivalent in cortical or cranial bioactivity records. In the light of these SEEG observations and a survey of the literature the authors stress the diagnostic importance of SEEG investigations in epilepsy.


[Disorders of dopamine and 5-hydroxytryptamine metabolism in the early period after cranio-cerebral injuries].

In patients with signs of intracranial hypertension caused by subdural haematoma or brain oedema following craniocerebral trauma significantly increased concentrations of HVA and 5-HIAA were found in the cerebrospinal fluid obtained by means of lumbar punction in relation to a control group comprising patients with lumbar disc prolapse. In patients after craniocerebral injuries with open fracture of cranial bones without disturbances of consciousness dopaminergic system hyperactivity was observed lasting up to the 7th day after injury. In patients with symptoms of brain commotion after craniocerebral trauma a significant rise in 5-HIAA concentration was observed in the cerebrospinal fluid on the 7th day after trauma. This may suggest increased serotonin turnover early after trauma.


[Value of the neuropsychological examinations in the diagnosis of supratentorial gliomas].

The authors report an analysis of the results of neuropsychological investigations of patients treated for supratentorial gliomas. A syndrome of the most frequently observed disturbances of higher nervous activity has been outlined. The diagnostic, localizatlry and differential diagnostic value of neuropsychological investigations has been assessed and found to a useful auxiliary clinical method.


[Subarachnoid hemorrhage and circulatory disturbance of cerebrospinal fluid--scanning electron microscopid study in clinical and autopsy cases (author's transl)].

The scanning electron microscopy (SEM) gives intersting information about the changes of the subarachnoid space. In this study, specimens from 16 patients (one during surgery and others at autopsy) were examined by SEM: 11 cases of subarachnoid hemorrhage, 2 of posterior fossa brain tumor operated and 3 of control cases without CNS diseases. In cases of subarachnoid hemorrhage, there seemed to be three stages of the obstruction in the subarachnoid space: a) obstruction by blood clots mainly consisted of red blood cells, b) obstruction by subarachnoid fibrosis with thickening of arachnoid, c) obstruction by arachnoid adhesion obliterating subarachnoid space. Specimens from parietal parasagittal area, lateral cerebral fissure and temporal base on both sides were systematically examined by SEM, and the degree of the obstructive changes of the subarachnoid space were classified into five grades: 0) no changes 1) minimal changes--slight thickening of arachnoid and perivascular fibrosis in subarachnoid space 2) moderate changes--thickening of arachnoid and fibrosis in subarachnoid space with patent meshwork 3) severe obstruction of subarachnoid meshwork 4) complete obstruction of subarachnoid space--no space for CSF circulation. We found high incidence of communicating hydrocephalus after SAH in those cases in which epicortical CSF circulation was obstructed more than grade 3 in the parasagittal area bilaterally.


[Large abdominal pseudocyst as a complication of ventriculoperitoneal shunt--diagnosis by ultrasonography and whole body CT scan (author's transl)].

We report a case in which a large abdominal pseudocyst developed following a ventriculo-peritoneal shunt (V-P shunt) for hydrocephalus due to pineal germinoma. A 24-year-old man had undergone a V-P shunt and radiotheraphy for unbiopsied posterior third ventricle tumor. Four years after operation he was readmitted because of double vision, conjugate upward gaze palsy and a large abdominal mass. Preoperative diagnosis of abdominal pseudocyst was made by abdominal computed tomography and ultrasonotomography. The shunt tube was clearly deomonstrated in the cavity by computed tomography. It is suggested that, in a patient suspicious of having abdominal pseudocyst who developed abdominal symptoms and signs following V-P shunt, abdominal computed tomography and/or ultrasonotomography provide a definitive diagnosis of this entity.


[Two cases of azygos anterior cerebral artery aneurysm (author's transl)].

Two cases with azygos anterior cerebral artery were reported from an analysis of 37 cases of distal anterior cerebral artery aneurysm. Case 1 was a 57-year-old woman. She had an attack of subarachnoid hemorrhage two months before admission to our clinic. The anterior cerebral artery was not demonstrated on the right carotid angiogram, and an azygos anterior cerebral artery was visualized on the left carotid angiogram. The aneurysm was situated at the distal end of the azygos artery. Case 2 was a 71-year-old hypertensive woman. Subarachnoid hemorrhage occurred 6 days before admission to our clinic. The left carotid angiography with contraleteral compression revealed an azygos artery and an aneurysm in its middle part. The azygos arteries in both cases were confirmed at operation and aneurysmal necks were managed without any serious deficit. The distal anterior cerebral artery aneurysm is frequently accompanied by azygos artery. This vascular anomaly may cause a hemodynamic change and may be one of the factors of aneurysmal formation at this part.


[Central prolapse of the Th12 -L1 nucleus pulposus with radiological signs of tumor of the conus medullaris].

The authors report a 42-year-old patient with excruciating pains felt in the interscapular and lumbar regions and both lower extremities without symptoms of root involvement. Myelography suggested presence of a tumour of the conus medullaris or epidural tumour in this area, at the Th12--L1 level. During the operation a central prolapse of the nucleus pulposus was found in the midline on the anterior wall of the vertebral canal below the longitudinal ligament. After operation all symptoms disappeared and the patient resumed work.


[A case of congenital dermal sinus in the parietal region (author's transl)].

A congenital dermal sinus at the midline of the parietal region, which extends into the falx, is relatively rare. The following case is illustrative. A 3-year-old girl was noticed by her parents to have tumor at the midline of the parietal region without other disturbances and complaints. This girl had the normal mental and motor development, and was admitted to our clinic for cosmetic surgery. A round, elastic soft tumor, roughly 1x1x1 cm in diameter, was located at the midline of the parietal region. This tumor had a port wine cutaneous discoloration and an absence of normal hair growth in this area. Abnormal hair did not protrude from the sinus. This tumor had no dimple nor sinus opening. Skull XP showed a round lucent bone defect at the midline of the parietal region. This bone defect with sclerotic margin, was about 1 cm in diameter. Skull XP and tomography, with contrast medium injection into the tumor, showed that this tumor extended into the falx through bone defect. Angiography showed that there were no relations between the tumor and the superior sagittal sinus. PEG showed that there were no mass lesion nor dilatation of ventricles. Both spinal tap and EEG were normal. Operation for the congenital dermal sinus was performed on Nov. 4, 1977. This congenital dermal sinus extended into the falx and congenital cell rest tumor was not elicited.


[A case with giant aneurysm of distal portion of the posterior inferior cerebellar artery (author's transl)].

A case of a giant aneurysm of the distal posterior inferior cerebellar artery has been presented, in which the preoperative sympotoms were those of a space occupying lesion of the posterior fossa. CT scan revealed a round mass in the cerebellum. The wall of this round mass was not enhanced after an intravenous administration of iodine. At operation we found a large saccular aneurysm, about 3 cm in diameter, arising from the distal portion of the left posterior inferior cerebellar artery. By needle decompression and dissection around the aneurysm, we were able to place a Heifetz clip across the neck. After exicision, the aneurysm was found to contain a large thrombus.


[A case of choroid plexus angioma with subarachnoid hemorrhage--case report (author's transl)].

Authors report a case of choroid plexus angioma of lateral ventricle, in a 42 years old woman, initiated with an episode of subarachnoid hemorrhage. The localization of lesion, in the anterior horn and body of right lateral ventricle, producing primary intraventricular bleeding was revealed by pneumoencephalography, especially polytome pneumotomography. However, it was difficult to find by angiography. Patient was successfully removed angioma and showed good recovery. In review of the literatures, the choroid plexus angioma is found more frequently in children than adults, caused by primary intraventricular or subarachnoid hemorrhage and is ocasionally associated with other congenital anomalies. Otherwise, it is found incidentally at autopsy and show hydrocephalus or normal pressure hydrocephalus. Prognosis is excellent in operated case, but heavy mortality in non-operated case and combined with intraventricular hematoma.


Foetal brain development in the sheep.

The pattern of normal foetal brain development has been described for the Merino sheep. Controlled flock matings were used and foetuses removed by hysterotomy at 40, 54, 67, 81, 90, 95, 109, 121 and 150 days of gestation. Lambs at 7 days after birth and adults were also studied. The CNS was dissected, separated and weighed as four segments--cerebral hemispheres, brain stem, cerebellum and spinal cord. Determinations of DNA, RNA, protein, cholesterol and water content were subsequently carried out on each segment. Brain weight increased from 0.264 g (40 days) to 52.74 g at 150 days. The ratio to body weight decreased from 6.7% (40 days) to 1.5% (150 days). DNA increased more rapidly from 40 to 90 days in the cerebral hemispheres and brain stem than in the cerebellum and spinal cord and this increase preceded the main increase in weight. Increases in cholesterol and decreases in water content were also more marked in the cerebral hemispheres and brain stem. Increase in brain weight occurred in two phases, one up to 90 days followed by a more rapid and larger increase after 90 days which continued to birth. These two phases appear to reflect an increase in neuroblast multiplication followed by neuroglial multiplication and myelination respectively. At birth, brain weight had reached 50% of adult size, the cerebral hemispheres 52% of adult size, the cerebellum 40% and spinal cord 40%. The relative maturity of the brain at birth justifies the classification of the sheep as a prenatal brain developer.


The effects of postnatal lead exposure on Purkinje cell dendritic development in the rat.

Rat pups, suckled by mothers maintained after parturition on a diet containing 4% lead acetate, were killed at 30 days and their cerebella examined. The blood lead was greatly increased in these animals (258.20 +/- 6.72 micrograms/100 ml) as compared with controls (4.75 +/- 0.75 micrograms/100 ml) and their mean body weight was reduced by 28%. Cerebellar weight, however, remained unchanged. Histologically the vermis showed vacuolation of the white matter and an increase in the size of Purkinje cell bodies. The total number of Purkinje and granule cells and their densities were unchanged except in animals with encephalopathy when these parameters were reduced. Network analysis of the dendritic trees of Purkinje cells indicated a 34.8% reduction in total dendritic length, due to reduction in total segment number and in the length of distal segments. Dendritic density and the frequency of trichotomous branching were unchanged by the experimental treatment. The density of dendritic spines over the periphery of the network was normal. The topology of the dendritic trees of Purkinje cells was abnormal in that branching patterns deviated from the normal pattern generated by random terminal growth. These results suggest that lead causes changes in Purkinje cell metabolism which reduce the rate of dendritic growth and cause abnormal branching. It remains to be determined whether these are direct effects or secondary to the vascular changes known to occur in the cerebellum during lead intoxication.


Atypical axon-Schwann cell relationships in the common peroneal nerve of the dystrophic mouse: an ultrastructural study.

Several atypical features of myelination of the peripheral nervous system are reported in common peroneal nerve of dystrophic mice (129 Re J dy/dy): (i) central nervous system-like contact between myelin sheaths of adjacent nerve fibres; (ii) nodes and internodes of myelinated fibres enwrapped with cytoplasmic processes of Schwann cells from adjacent nerve fibres; (iii) Schwann cells of adjacent nerve fibres co-operating in formation of a single myelin sheath; and (iv) a single Schwann cell myelinating two separate axons. In view of the presence of similar features of myelination in the central nervous system, where the myelin producing cells lack basement membrane, we suggest that in the dystrophic peripheral nerves the development of these features can be attributed to the partial deficiency of the Schwann cell basement membrane. Two types of widened nodes of Ranvier are also identified: (i) nodes with paranodal damage; and (ii) nodes without paranodal damage. In addition, abnormal features of myelination are described which are likely to represent altered Schwann cell/axon relationships during demyelination and remyelination and/or decreased myelinating ability of Schwann cells. We interpret these findings as indicating a metabolic disorder of Schwann cells. They provide an experimental model for the investigation of factors involved in the origin and maintenance of the structural organization of peripheral nerve.


Vasoactive intestinal polypeptide in the pituitary pars nervosa.

Vasoactive intestinal polypeptide (VIP) is a widely distributed neuropeptide which has recently been found in the hypothalamus and in hypothalamo-hypophyseal portal blood. We have examined the pituitary of several mammalian species for the presence of VIP by immunocytochemistry and radioimmunoassay and report here that the pars nervosa contains a considerable quantity of VIP (100-250 fmol/mg) which, in the dog, can be shown to be present in nerve fibres. It is possible that neurohypophyseal VIP may be a local releasing agent for vasopressin.


Fine structure of muscle in human disuse atrophy: significance of proximal muscle involvement in muscle disorders.

The universal occurrence of weakness of skeletal musculature on disuse, however produced, and the paucity of published reports on the fine structural changes in human disuse atrophy, prompted the present investigation. The quadriceps muscle of a leg immobilized in plaster cast (for fracture) and of the opposite non-immobilized limb was biopsied in four adult males, after periods of immobilization from 50 to 75 days. These 8 muscle specimens were examined for histopathological changes, and muscle fibre diameters were measured by micrometry from paraffin sections. The histograms revealed a larger proportion of small fibres (less than 20 micron) and a smaller proportion of large fibres (greater than 40 micron) in the immobilized limb compared to the opposite. Thus, light microscopy showed only atrophic changes. This was confirmed by electronmicroscopy, where atrophy of few to several muscle fibres was seen in the form of loss of myofibrils, collapse and folding of the basement membrane and prominence of glycogen or muscle nuclei. The atrophic change was more severe in the immobilized limbs, but it was also noticeable in all the non-immobilized limbs. Degenerative changes, especially disorganization and breakdown of myofibrils, and fragmentation of plasma membrane, were also seen in occasional atrophied muscle fibres, again more frequently in the immobilized limb. Lipofuscin was often found accumulated in muscle fibres and occasionally in endothelial cells of intramuscular blood vessels; the latter showed prominent pinocytotic vesicles or thickened basement membrane. It is concluded that both atrophy and degeneration of fibres of proximal muscles can occur as non-specific consequences of disuse of the limb in man, that degeneration is a latter and more severe change, that muscles even of the non-immobilized leg are subjected to disuse atrophy during bed-rest, and that the proximal muscles in man seem to have a natural susceptibility to atrophy and degeneration in any muscular disorders.


Spinal cord transection: a quantitative analysis of elements of the connective tissue matrix formed within the site of lesion following administration of piromen, cytoxan or trypsin.

Long-Evans hooded rats were cordotomized at the T-5 level and given either (1) cyclophosphamide (cytoxan), an immunosuppressive, (2) piromen, a bacterial polysaccharide-nucleic acid complex, (3) topical and systemic trypsin, or (4) no further specific treatment. Because of past and present controversy surrounding the proposed ability of these agents to promote spinal cord regeneration, a systematic study, employing light and electron microscopy, and quantitative methods in a single animal model, was done in order to re-evaluate the effects of each treatment upon the connective tissue matrix which forms in the defect left by transection. After an initial inflammatory reaction during the first week after surgery, the lesion zone is characterized either by areas of dense collagenous connective tissue with occasional fibroblasts and macrophages, or a loose areolar tissue with numerous sheets and cords of mesodermal cellular elements but minimal collagen. By 45 days postoperatively (dpo), axons supported by Schwann cells invade and become entangled in the loose connective tissue matrix. With longer postoperative survival, cysts appear craniad and caudad to the lesion and erode much of the scar together with viable neural tissue. Giving cytoxan or piromen did not result in any qualitative alteration of the scar matrix as evidenced by electron microscopy. Quantitative analysis revealed a slight reduction in the fibrous connective tissue component of the scar at 45--90 dpo, but this was transient when longer postoperative periods were studied. Trypsin caused a significant reduction in the amount of fibrous connective tissue with a concomitant increase in loose connective tissue and the appearance of a few distinctive, compact bundles of unmyelinated axons lacking Schwann cells. Consistent behavioral changes were not observed in any group which could distinguish them from the controls. Our results appear to contradict the findings of Matinian and Andreasian (1976) who reported return of normal sensori-motor function in 80% of their animals treated with topical and systemic trypsin. It is concluded that a major impediment to whatever longterm regenerative potential exists within the spinal cord is the lack of axonal guiding elements within the scar, but more importantly, the severe erosion of the remaining spinal cord due to cyst enlargement.


Axon sprouting into segments of rat spinal cord adjacent to the site of a previous transection.

Transection of the spinal cord is adult Long-Evans Hooded rats is followed by the formation of a connective tissue matrix in the lesion site and the rapid erosion of the neural elements above and below this zone particularly within the dorsal white columns. In the period between 15--45 days after operation two significant events begin to occur. First the injured surfaces of the divided cord become invested by a glial limiting membrane (glia limitans) and, concomitantly, large numbers of axons ensheathed by Schwann cells sprout into the scar matrix and along the eroded dorsal column region. The injured surface of the spinal cord is highly irregular with deep, collagen-filled rifts into which the sprouting axons may probe and penetrate into the adjacent normal neuropil. Electron microscopic examination generally reveals the interposed glia limitans and that these fibres are usually restricted to the peripheral environment. However, as some axons approach the reconstituting glia limitans, they are enveloped by an astrocytic cytoplasmic process which may either displace the Schwann cell or encompass it together with the enclosed axons. This last phenomenon appears to precede the entry of some axons into the neuropil and suggests that the glia limitans may not necessarily represent an impenetrable barrier to the passage of regenerating axons into the CNS. Apparent maintenance of most of these fibres for periods of up to 3 months may suggest that viable, functional synapses were established upon available neuronal elements, but clear evidence of this could not be documented.


TSH secretion following acute heat exposure, in intact and in hypothalamic deafferentated male rats.

Male rats, intact (N) or with complete, anterior, or posterior hypothalamic deafferentations (CHD, AHD, or PHD, respectively), were acutely exposed to an environmental temperature of 36 degrees C, and serum TSH concentrations were determined by RIA. In intact animals, 30 min of exposure to elevated environmental temperature resulted in decreased serum TSH levels. In both CHD and AHD animals, basal serum TSH concentrations were reduced, and heat exposure produced further decreases. In the PHD group, no significant difference in resting serum TSH concentrations was observed, as compared to intacts. Exposure of these animals to 36 degrees C was followed by a reduction in this parameter, similar to that in intact rats. Exposure of intact animals to 3 nonthermal stress modalities produced no changes in serum TSH concentrations. These experiments demonstrate (1) that the hypothalamo-hypophyseal-thyroid axis responds specifically to heat exposure; (2) that extrahypothalamic centers which innervate the medial basal hypothalamus from the rostral direction maintain basal activity of the axis; and (3) that humoral factors, possibly extrahypothalamic thyrotrophin-releasing hormone carried to the median eminence via the CSF, may also mediate both basal and heat-induced secretory activity of the thyrotrophs.


Increased serum growth hormone and somatic growth in adult hamsters with hippocampal transections.

Somatic, endocrine, and behavioral correlates of growth and levels of voluntary running activity were measured in adult hamsters with hippocampal transections (HIPPO cuts) or in controls with transections of overlying cortex. Significant increase in serum concentration of growth hormone (GH) and decrease in pituitary concentration of GH were measured in HIPPO hamsters with a homologous radioimmunoassay method for hamster GH. HIPPO hamsters had increased: serum insulin concentration in fed state, food consumption, ponderal and linear growth, and percentage of body fat, and decreased levels of voluntary activity. Similarities between growth acceleration after HIPPO cuts and lesions of rostral medial septum suggest that fibers interconnecting, or passing through, the hippocampal formation and septum inhibit growth in adult hamsters.


The cellular origin of lysosomal enzymes in the plaque in multiple sclerosis. II. A histochemical study with combined demonstration of myelin and acid phosphatase.

Existing techniques have been adapted and it has been possible to demonstrate acid phosphatase (APP) and myelin, lipid or astrocytic fibres in the same histological section. In normal controls APP was demonstrated in neurons, astrocytes, ependyma including choroid plexus epithelium and in pericytes, but not in oligodendrocytes. In multiple sclerosis (MS), APP positive cells were found in the plaque, plaque edge and macroscopically normal white matter. Contrary to some previous reports, not only macrophages, but also astrocytes in the MS plaque were found to be APP positive, although the distribution of enzyme in these cells was predominantly diffuse, unlike the particulate distribution in normal astrocytes and other APP positive cells: the significance of this finding is discussed. It is concluded that astrocytes and macrophages are the main source of the elevated levels of APP found biochemically in MS and that in old plaques astrocytes make the major contribution.


DNA synthesis in the pituitary gland of the rat. Effect of sulpiride and postnatal maturation.

During development of the rat anterior pituitary gland (APG) there is a fall in DNA replication which is accompanied by a decline in the activity of the soluble DNA polymerase and of an endonuclease. This latter enzyme is capable of activating the DNA template for the DNA polymerase assay. Sulpiride sulfate, a drug known to produce prolactin release from the APG, increases thymidine incorporation in the APG 20 h after the injection. This drug also enhances the activity of the soluble DNA polymerase while that of the endonuclease and thymidine kinase does not change. The results suggest that the intracellular prolactin content regulates DNA replication in mammotrophs and that the soluble DNA polymerase plays an important role in this regulation.


Specificity of short-loop feedback of luteinizing hormone in the rabbit.

The specificity of the gonadotropin short-loop feedback mechanism was investigated in castrated rabbits by blood sampling from an indwelling jugular venous catheter for follicle-stimulating hormone (FSH) after the intravenous administration of purified human luteinizing hormone (hLH). Although we have previously shown that such hLH administration results in a decrease of rabbit LH, no decrease in rabbit FSH was seen in these experiments. This specificity of LH feedback is compatible with the site of feedback being at the (1) pituitary level or (2) at the hypothalamic level provided two separate LH and FSH releasing factors exist.


Pseudo-intracellular collagen tangles in human spinal ganglia.

A new structure was found in the spinal ganglia of 6 out of 215 human autopsy cases with various disorders. It was composed of ballooned cells fully packed with fibrillar structures showing the same staining properties as collagen. Ultrastructurally the fibrillar structures were bundles of collagen fibres with a striation of about 70nm periodicity, and they were enclosed by the cell membrane invaginated in a very complex manner into the cytoplasm. This structure, which we named 'pseudo-intracellular collagen tangle', was considered to result from a disturbance in the releasing process of collagen fibre from fibroblasts. The aetiology of the structure is unknown, but it might represent one of regressive or senile changes in human spinal ganglia.


Regulation of the tuberoinfundibular and nigrostriatal systems. Evidence for different kinds of dopaminergic neurons in the brain.

The tuberoinfundibular dopaminergic (TIDA) neurons appear to present remarkable differences from the nigrostriatal and mesocortical dopaminergic (DA) systems. The hormonal feedback of prolactin on TIDA neurons differs from the neuronal feedback system operating in the striatum and olfactory tubercles. The uptake of dopamine appears to present the characteristics of a high affinity process in the terminals of the striatum and olfactory tubercle, whereas in the median eminence this process exhibits a much lower affinity. The pharmacological properties of postsynaptic receptors in the different DA pathways appear to be similar. However, the intracellular events which are ultimately manifested as physiological responses to dopamine may be completely different in the postsynaptic cells in the neostriatum and in the lactotrophs of the anterior pituitary. In addition, there is evidence suggesting that dopamine receptors in the anterior pituitary are more sensitive to the actions of agonists and antagonists than are dopamine receptors in the striatum.


Adult metachromatic leucodystrophy: clinicopathological report of two familial cases with slow course.

Two cases of adult metachromatic leucodystrophy in one family are reported. The main clinical features in both were predominantly psychiatric with alcoholism and an extremely long duration of the illness. Neuropathological examination revealed a similar distribution of the lesions in both, and scanty metachromatic accumulation in the CNS and not at all elsewhere. The great variability of the lengths of the courses is stressed. The duration in no way seems to be linked to the age of onset, except in the typical infantile form. The authors argue that different lengths of history correlate with distinct neuropathological findings, and may possibly be related to qualitative differences in the involved enzyme disturbance. Therefore, the authors suggest that the classification based on the age of onset be enlarged with a further one distinguishing between 'rapid' and 'slow' course types.


Anatomical study of a posterior cerebral lesion producing dyslexia.

After an "occipital lobectomy" that resulted in a severe dyslexia and a moderate dysgraphia-dyscalculia, anatomical study showed damage to the posterior extremity of the angular gyrus and degeneration in the posteroinferior pulvinar. This is in contrast to an earlier case that had degeneration in the anterosuperior pulvinor associated with a small anterior temporoparietal infarct and a well-documented receptive-expressive aphasia. However, the role of the pulvinar in speech function remains uncertain. The surgeon should be aware of the short distance between the angular gyrus and both the midline and the occipital pole because a lesion here during an "occipital lobectomy" produces a distressing and durable speech impairment.


Correlation of absorption coefficients with intracranial fluid protein concentrations and specific gravities.

Samples of ventricular cerebrospinal fluid, tumor cyst fluid, and subdural fluid were obtained from 30 patients at operation. The protein concentration and the specific gravity of each sample were measured and the corresponding mean absorption numbers were calculated from the numerical printout of the preoperative computerized tomogram. For fluids with a specific gravity greater than 1.005, a linear relationship was demonstrated between protein concentration and specific gravity. For protein concentrations greater than 300 mg/dl, there was a linear relationship between protein concentration and the mean absorption number. As the precision of present instrumentation improves, it is expected that a noninvasive technique for estimating intracranial protein concentration will have a number of clinical application.