Particle movement in heliozoan axopods associated with lateral displacement of highly ordered membrane domains.

Freeze-fracture studies reveal that extrusive organelles displaying saltatory particle movements in centrohelidian axopod are attached to highly ordered domains within the plasma membrane. It is postulated that the motive force for lateral displacement of these membrane domains with the adhering organelle is located immediately underneath the plasma membrane being either part of the peripheral membrane proteins or attached filaments alined parallel to the axopodial microtubules. The attachment domain is interpreted as a "frozen" membrane area preventing untimely organelle discharge by membrane fusion.


[Coalpha/Cobeta-isomerism of corrinoids. Partial synthesis and Escherichia coli activity of further isomer pairs of the (Co-methyl)-corrinoids (author's transl)].

In 2-methyladenyl-(Cobeta-methyl)-cobamide and in adenyl-(cobeta-methyl)-cobamide the nucleotide base is coordinated to the cobalt atom in neutral and weak acidic aqueous solutions (in the corresponding adenosylcorrinoids the nucleotide base is not coordinated). 2-Methylthioadenyl-(Cobeta-methyl)-cobamide resembles, with regard to the coordination of the nucleotide base, the benzimidazole-corrinoids. The partial synthesis via cobalt (I) corrinoids results in a variable proportion: (Coalpha-methyl) isomer/(Cobeta-methyl) isomer, e. g. 7/93 (cobalamin) and 50/50 (p-cresylcobamide). This proportion is generally low, if in the corresponding cyanocorrinoid the nucleotide base is firmly coordinated; it is high, if the coordination in the corresponding cyanocorrinoid is weak or absent. These results are compatible with the assumption that in the cobalt (I) corrinoids the nucleotide base is to a certain extent coordinated. In Escherichia coli 113-3 the examined (Coalpha-methyl)-corrinoids show a weaker bioactivity than the corresponding (Cobeta-methyl)-corrinoids.


Studies on optically active pesticides, I synthesis and herbicidal activity of d(+) and 1(-) methyl-2-chloro-3-(4-chlorophenyl)-propionate.

d(+) and 1(-) Methyl-2-chloro-3-(4-chlorophenyl)-propionate (common name chlorfenprop-methyl; trade mark Bidisin) were prepared and their herbicidal activities studied on Avena fatua L. and Avena sativa L. ("Flämingskrone"). The 1(-) enantiomer was found to be twice as active as the racemate; the d(+) form almost inactive.


[6.7-Dihydroxycoumarin (Aesculetin) as a substrate for catechol-o-methyltransferase (author's transl)].

6,7-Dihydroxycoumarin (Aesculetin) was found to be a substrate of rat liver Catechol-O-methylfransferase (COMT) (EC 2.1.1.6). Incubation of this substrate with S-Adenosyl-L-[methyl-14C]methionine and/or S-Adenosylmethionin-hydrogensulfate in the presence of COMT yields the highly fluorescent compounds 7-hydroxy-6-methoxycoumarin (Scopoletin) and 6-hydroxy-7-methoxycoumarin (Isoscopoletin) in the ration of about 2:1. The O-methylated products obtained from Aesculetin were identified after separation by thin layer chromatography mainly by the reversed isotope dilution technique. The fluorescence of the isolated methylethers was proportional to concentration within the range from 10(-5)-10(-7) M. A reciprocal plot of activity versus substrate concentration gives a Km of 1 X 10(-6) M.


[Polymer linked N-(hexyl)-5-azido-2-nitro-benzoic acid amide; a photoreactive resin for the immobilization of ligands (author's transl)].

The preparation of a new photochemically-activatable polymer was accomplished by condensation of aminohexyl-6-yl-agarose with the N-hydroxysuccinimide ester of 5-azido-2-nitro-benzoic acid. The latter compound was obtained by diazotization of 5-amino-2-nitro-benzoic acid, exchange of the diazonium group through azide and condensation with N-hydroxysuccinimide. As shown for the photolysis on the monomer level, irradiation of the polymer led to the intermediate formation of a highly reactive nitrene, which is able to immobilize ligands e. g. L-phenylalanine to the polymer.


Nutritional requirement for 4-aminobenzoate caused by mutation of dihydropteroate synthetase.

Aerobacter aerogenes mutant 62-1 AC requires high concentrations of 4-aminobenzoate for growth. The mutant accumulates N-glucosyl-4-aminobenzoate and has an intact 4-aminobenzoate synthetase (Bacher, Gilch, Rappold, and Lingens, Z. Naturforsch. 28 c, 614-617 [1973]). On the other hand the ability of the mutant to synthesize dihydropteroate is markedly reduced. The dihydropteroate synthetase level of mutant 62-1 AC is 1% as compared to the parent strain. Spontaneous revertants of mutant 62-1 AC show wild type levels of dihydropteroate synthetase. We conclude that the requirement for 4-aminobenzoate in mutant 62-1 AC is due to poor utilization of 4-aminobenzoate as a consequence of the low level of dihydropteroate synthetase activity.


Properties of an antiserum against Streptomyces hydrogenans 20beta-hydroxysteroid dehydrogenase.

Antiserum against crystallized 20beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans was used for different immunodiffusion and immunoprecipitation tests to quantify the bacterial enzyme in cell-free supernatants of the microorganism. After immunoprecipitation and gel electrophoresis the molecular weight of the subunits of 20beta-hydroxysteroid dehydrogenase was calculated to be 27 300 +/- 700.


[Effect of N-methyl-N-beta-chloroethylhydrazine and its benzaldehydhydrazone on RNA-and protein synthesis as well as metabolism of synchronously growing yeast cells (Saccharomyces cerevisiae) (author's transl)].

N-methyl-N-beta-chloroethylhydrazine and its benzaldehydhydrazone inhibit the influx of [6-3H]-uracil and L-[U-14C]leucin in yeast cells as well as the incorporation in RNA and protein. Experiments with synchronously and asynchronously growing cells showed the N-methyl-N-beta-chloroethylhydrazine essentially influences the dividing phase while the benzaldehydhydrazone is more effective in the growth phase. The effect of these two substances on respiration, glycolysis and the concentration of fructose-1,6-diphosphate, triose phosphate, and adenosine triphosphate is small.


Pyramidal cells with different densities of dendritic spines in the cortex of the mouse.

Neighbouring pyramidal cells in the mouse cortex sometimes have different densities of dentritic spines. This was shown by a quantitative analysis of 10 neurons. For this, a method was worked out which corrects for the spines hidden behind (and in front of) the dendrite. The main result is that there is a positive correlation between the spine densities on different parts of the dendritic tree of one neuron. The possible functional meaning of these findings is briefly discussed.


[Effect of N-methyl-N-beta-chloroethyl-hydrazine-HCl on the growth and multiplication of yeast cells (Saccharomyces cerevisiae) (author's transl)].

N-Methyl-N-beta-chloroethyl-hydrazine-HCl and its benzaldehydhydrazone inhibit growth and multiplication of yeast cells. The DNA-synthesis is partially blocked. After removal of the substances the rate of this synthesis is much more increased than that of RNA and protein. The both substances we tested are more effective than simple alkylhydrazines.


Light and dark adaptation of crayfish visual cells depending on extracellular calcium concentration.

Lowering of extracellular Ca2+-concentration from 14 X 10(-3) M to ca. 10(-6) M (using 1 mM ethyleneglycol bis (beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)) results in weaker light adaptation by a 2 s light exposure and faster dark adaptation (half time 45 +/- 1%) of crayfish visual cells.


[Occurrence of an acetylcholinesterase (E.C. 3.1.1.7) in the haemolymph of the mussel Mytilus edulis (author's transl)].

A cholinesterase deriving from the hemolymph of the mussel Mytilus edulis was partially purified by use of gel-permeation and ion-exchange chromatography; the specifity to different substrates or inhibitors indicates clearly the occurrence of a "true" acetylcholinesterase.


1H and 13C NMR study of proton transfer in azoles. Mechanism of proton transfer in pyrazole in solutions containing bis-(acetylacetonato) nickel (II).

Proton transfer in pyrazole systems involving interaction with a paramagnetic transition metal complex has been studied with 1H and 13C NMR techniques. Kinetics of the ligand exchange in the pyrazole complex of bis-(acetylacetonato)nickel (II) has been investigated, and hyperfine coupling constants for the interaction of the nickel unpaired electron with the ligand nuclei in the complex have been determined. Catalytic admixtures of bis-(acetylacetonato)nickel (II) are shown to modify the mechanism of the proton transfer in pyrazole. The spectral data are discussed in terms of outer-sphere coordination and cooperative proton transfer effects.


[The distribution space of physically dissolved oxygen in aqueous solutions of organic substances].

In order to evaluate the distribution of molecular oxygen in biological systems, the oxygen solubility (ml/ml atm) at 37 degrees C in aqueous solutions of thirty organic substances with different concentrations was measured by the classical Van Slyke principle. The oxygen solubility always (with the exception of hemoglobin) decreases exponentially with increasing concentration of the respective substance. In all cases this behavior is described highly significant by a simple empiric exponential function, when the substance concentration as well as the oxygen solubility of pure water is given. The influence of one substance on oxygen solubility contributes additively to the over-all solubility value of a solution of several dissolved substances. Changes in oxygen, solubility and, therefore, oxygen distribution in aqueous solutions may be related to three main phenomena: 1. restriction of the free water volume by the specific partial volume of a dissolved substance (e.g. urea solutions), 2. existence of non-solvent water for oxygen especially in solutions of amino acids), 3. adsorption of oxygen at the interphase in a heterogenous system (e.g. protein solutions).


[Synthesis of 5-azido-3-nitro-omega-bromo-acetophenone- a photochemically active bifunctional reagent for the cross-linking of biopolymers].

The photochemically activatable heterobifunctional reagent 5-azido-3-nitro-omega-bromo-acetophenone (3) was synthesized by condensation of 3,5-dinitrobenzoyl chloride with diethyl malonate, acid-catalyzed decarboxylation of the formed malonester derivative 1 to 3,5-dinitro-acetophenone (2a), selective reduction of one nitro group in 2a to 5-amino-3-nitro-acetophenone (2b) and diazotization to 2c. Nucleophilic displacement of the diazonium group in 2c by sodium azide forms 5-azido-3-nitro-acetophenone (2d) which gives 3 after bromination. Compound 3 is photochemically labile and forms an highly reactive nitrene during ultraviolet irradiation. Since compound 3 is able to alkylate amino- or mercapto-groups of amino acids or nucleosides via its bromoacetyl residue, the bifunctional reagent 3 should cross link proteins or nucleic acids after nitrene generation.


[Synthesis of a fragment of the active center of the streptococcal proteinase (EC 3.4.22.10), IX].

The synthesis of the protected pentapeptide tert-butyloxycarbonly-Gln-Ile-Met-Lys(X)-Gly-p-nitrobenzylester (X = benzyloxycarbonyl, 3-chlor-benzyloxycarbonyl) which is part of the carboxylend of a partial sequence of the active center of the streptococcal proteinase is described. Side reactions are observed if the tert-butyloxycarbonyl-protective group is cleaved by trifluoroacetic acid, not with HC1/dioxane. Obviously the presence of methionine is responsible for the formation of by products. Formation of methioninesulfoxide of tert-butylsulfoniummethionine could not be proved. tert-butyloxycarbonyl-Gln-1-hydroxybenzotriazolylester was obtained in a crystalline state from the reaction of tert-butyloxycarbonyl-Gln, dicyclohexylcarbodiimid and 1-hydroxybenzotriazol.


X-ray diffraction studies on the structure of alpha-chitin.

The structure for alpha-chitin originally proposed by Carlström is generally considered to be the true structure. However, it fails to account for several remaining problems of chitin structure which include a complete explanation of the infrared spectrum and also the different properties of alpha- and beta-chitins. We have reexamined the structure by X-ray diffraction using automatic rigid subunit least-squares refinement and also the difference Fourier method. The R-value was reduced from 0.31 to 0.22 by a number of small modifications to the structure proposed by Carlström. Consideration of symmetry suggests that two distinct types of statistical modifications could be present in the structure, both of which would allow complete intersheet hydrogen bonding between O6H groups within the general framework of Carlström structure. The X-ray results give some support to one of these modifications. However, it is predictable that both would affect the X-ray diffraction only marginally so that a clear proof lies beyond the present sensitivity of the method. The proposed extra hydrogen bonding in alpha-chitin provide the first clear explanation for the different properties of these kinds of chitin.


[Activity of aminotransferases in the blue green alga Anacystis nidulans].

The blue-green alga Anacystis nidulans (strain L 1402-1) was grown at +37 degrees C in air (0.03 vol% CO2 and in air enriched with 3.0 vol% CO2. The effects of several inhibitors on the activity of aminotransferases, 14CO2 fixation and radioactive photosynthetic products of Anacystis were studied. No serine-pyruvate aminotransferase activity could be found in 10-2 M isonicotinyl hydrazide (INH); under the influence of this inhibitor aspartate and alanine aminotransferase were decreased about 49% respectively 17.6%. Serine-pyruvate and alanine aminotransferase activity decreased to more than 50% in 10-3 M glyoxalbisulfite. The obtained inhibitory effect of 10-4 M HPMS on serine-pyruvate aminotransferase (35%) was stronger than one the other aminotransferases. DCMU (5 x 10-6 M) inhibition on alanine aminotransferase activity was 83.7%. Under the influence of 10-3 M glyoxalbisulfite no 14C-labelled amino acids could be detected after 5 min photosynthesis; 14C-labelling of phosphoenolpyruvate, malate, phosphoglycolate and glycolic acid increased. Isonicotinyl hydrazide (10-2 M) caused in comparison to the control experiment a lower radioactivity in aspartate glutamate and phosphoenolpyruvate. The results are discussed with reference fo the operation of the glycolate pathway and a carboxylation reaction of phosphoenol-pyruvate in the blue-green alga Anacystis nidulans.


[Structure-reactivity relationships and delayed neurotoxicity of organophosphorus compounds].

A correlation has been found between the reactivity in the alkaline hydrolysis reaction of a new series of organophosphates and their ability or disability to produce the clinical manifestations of delayed neurotoxicity in hen. At a dose of 1000 mg/kg only compounds exceeding a lower limit of reactivity (about 6x10-2 M-1S-1) are active.


[On the protein composition of ribonucleoprotein particles before and after fertilization fo sea urchin eggs (Echinus esculentus)].

Experiments indicate that eggs and embryos of the North Sea sea urchin Echinus esculentus are excellent material to investigate the regulation of protein synthesis before and after fertilization. The dormant egg contains several proteins which are absent from embryos. Such additional proteins have been detected on the small ribosomal subunits, in the salt wash of whole ribosomes, and associated with cytoplasmic messenger ribonucleoprotein particles.


Detachment of segments from DNA double strands as detected by time resolved Rayleigh light scattering.

Calf thymus DNA was irradiated oxygen saturated 0.01 N NaCl solution with 2 mus pulses of 15 MeV electrons. By monitoring the decrease of light scattering intensity after the pulse, two modes of decrease were detected: The fast decrease (tau 1/2 approximately 0.8 ms) is ascribed to the separation of DNA fragments produced by double strand breaks at positions directly opposite to each other. The slow decrease (tau 1/2 approximately 8 s) is attributed to the detachment of segments generated by single strand breaks at sites on the alternate strands being separated by about 10 nucleotide units.


Studies on the host-parasite interaction and role of esterases during biting of the Indian cattle leech, Poecilobdella granulosa.

Histochemical localization of acetylcholinesterase and butyrylcholinesterase in the salivary glands has unfolded the significant fact that salivary glands are of two types, one being enzymatically negative and the other showing positive activity. Activity of these enzymes has been linked with the operation of glandular dynamics, particularly concerning the synthetic and secretory processes. The enzymes have been seen localized in the core of jaw. Contrary to it they are absent in the papillary and interpapillary zones of the jaw. Absence of esterases in the papillary and interpapillary ductules has been correlated with its possible non-involvement in the synthesis of vasodilating and anticoagulating materials. The experiments on effect of biting on host tissue give a faint indication of vascular dilation due to bite. Likewise, experiments on enzymatic state of a salivary gland after leech-bite reveal that the diminution of the reactive coverage area in the salivary glands reaches its maximum in the case of ATPase, indicating thereby its more involvement in salivary functions than those of esterases and acid phosphatase.


Nucleoside triphosphate levels in Streptomyces hydrogenans during growth and induction of 20beta-hydroxysteroid dehydrogenase.

Levels of the purine nucleoside triphosphates are decreasing towards the end of log phase growth of Streptomyces hydrogenans. Induction of 20beta-hydroxysteroid dehydrogenase by addition of 11beta,21-dihydroxy-4,17(20)-pregnadien-3-one to the growth medium leads to a pronounced drop in purine nucleoside triphosphate levels with is irreversible in contrast to the initial loss and later accumulation of RNA.


Sulfated macromolecules in early embryos of Limnaea.

An attempt has been made to partially characterize the substance responsible for the rhythmic incorporation of 35S (inorganic sulfate) in the course of the cell cycle in early Limnaea embryos. This trichloroacetic acid (TCA) insoluble substance is partly pronase sensitive, and dissociable into two fractions after treatment with NaCl. One of these remains TCA-insoluble while the other is TCA soluble but precipitable by cetyl pyridinium chloride. Thus, unlike in some other higher organisms, the major part of the inorganic sulfate is incorporated here into a fraction which is not a single mycopolysaccharide, but is more likely to be a protein-mucopolysaccharide complex, rather like the chondromucoprotein of chick-embryo cartilage.


[Studies on the rectal pads of the honey bee Apis mellifca].

According to earlier investigations young bees show a rectal fluid hypo-osmotic to the haemolymph. It had been assumed, however, that in certain situations honey bees have to be economical with water and simultaneously form a rectal fluid hyperosmotic to the haemolymph. The latter has been confirmed by the present investigation.


[Quantitative determination of immunoglobulins in the saliva. Comparative studies in squamous cell carcinomas of the mouth mucosa].

Immunological processes have been increasingly gaining in importance in the development and proliferation of tumours inhuman. Quantitative determinations of immunoglobulins IgG and IgA in the saliva of patients with squamous cell carcinoma of the oral mucosa showed a significant difference in IgG concentration as compared with patients affected with inflammatory intraoral diseases.


[A contribution to the problem of reducing the size of the tongue for orthodontic purposes].

After a summary of the theoretic basis for the indication of an operative reduction of the tongue by the therapy of malocclusion, the results of the tests were individually analysed. A sure influence of the reduction of the tongue can only be proved for the averting of a threatening relapse after an operation of progenia. The ability of speech stayed without any influence in 12 cases and in 3 cases it got better or worse. The numerous late sequels in form and function of the tongue make it necessary to be carefully in indication of the reduction of the tongue by the therapy of malocclusion.


[Genetic and gynecologic prevention of congenital developmental disorders].

The authores investigated 273 women who bore one or more children with birth defects. These defects were classified genetically as polygenic inherited. The authors describe the bases and results of preconceptional care as a method to reduce the risk of polygenic inherited birth defects.


[Problems, methodology and 1st results in the prenatal cytogenic diagnosis of genetic defects].

24 patients were admitted for the prenatal diagnostics of genetic defects. In 20 patients a culture of amniotic fluid cells was necessary; Indicators for a culture of amniotic fluid cells were: state after the birth of a child with mongolism (12), D/G-translocation in the mother (1), familial burden of mongolism (2), sex determination for X-chromosomally inherited progressive muscular dystrophy and haemophilia (4), and the influence of exogenic noxae (1). For sex diagnostics only a smear preparation was obtained in one case. 3 women had an abortion before admission to the hospital and amniocentesis. No indication for cultivation of amniotic fluid cells exists in 4 cases. Therefore a culture of amniotic fluid cells was performed in 16 patients. In one patient the culture of amniotic fluid cells was unsuccessful. Problems and indications are considered in detail.


[Flow fluorescence-photometry in ovarian carcinomas with and without effusion].

By flow microfluorometry the DNA distribution curve of the cell nuclei of 39 adnex tumors, mainly ovarian carcinomas, was measured. 47% of the malignant tumor cell populations were diploid, the other ones were heteroploid (i.e. polyploid, tetraploid, aneuploid stem lines). Heteroploid tumors had the worse prognosis. In 8 cases effusions were analysed (7 ascites, 1 pleura). It is possible to diagnose a malignant tumor from effussion fluid by impulse cytophotometry. But in one case a great difference was found between the primary tumor and the ascites fluid, which only shows the DNA distribution of an irritative effusion. The value of impulse cytophotometry for clinical purposes is discussed.


[Rupture of the mitral chordae tendinae].

Twenty-seven cases of ruptured chordae tendineae have been discovered during surgery for mitral regurgitation (9,3 %) : the highest incidence of ruptured chordae tendineae has been found among pure mitral insufficiency (36 %). In thirteen cases, the rupture was isolated, without any other valvular lesion. The syndrome described as characteristic of rupture was present in one third of our patients : isolated cases do not differ clinically from the others but for a more frequent acute evolution. In pure or predominant mitral regurgitation, surgery seems needed when clinical aggravation, acute or progressive, cannot be explained by arrhythmia, anaemia, pulmonary embolism, hyperthyroidism.


Rise in dehydroepiandrosterone and oestrogens during clomiphene administration in normal men.

Serum concentrations of LH, FSH and testosterone, and urinary excretion of individual 17-ketosteroids, oestrogenic substances and free cortisol was investigated in 12 normal men after a daily administration of 50 mg clomiphene citrate for 14 days. A significant increase in the serum concentrations of LH, FSH and testosterone was seen after 8 days with a further increase when measured a week later. The percentual increase in urinary excretion of oestrogens and dehydroepiandrosterone was of the same order as the increase in serum testosterone concentrations whereas the increase in androsterone and a aetiocholanolone was significantly lower. The excretion of free cortisol was unaltered. The study that measurements of oestrogens in the urine might be used as a parameter of the stimulatory effect of clomiphene on the hypothalamic - pituitary - gonadal axis in man. In addition, of the results support the hypothesis of an independent effect of clomiphene on adrenal steroidogenesis, not related to the production of glucocorticoids.


"Timing" of ovulation by laparoscopy and evaluation of some physico-chemical parameters.

The Authors describe the laparoscopic aspects of spontaneous human ovulation and correlate it with the evaluation of basal body temperature, the total urinary oestrogens, pregnanediol and urinary LH and some hematic values of 17-beta-estradiol, 17-alpha-Hydroxyprogesterone and rogesterone. They find that the rise in temperature and the oestrogenuria peak precede ovulation by some hours in the great ovulation by sompe hours in the great majority of cases. They analyze the validity of the other parameters studied, and show a relatively constant behavior, with regard to ovulation, in the mean evaluation of several cases. In the individual analysis, on the contrary, this relation is difficult to find and less significant. The Authors stress the importance of comparing the physico-chemical evaluations with the biological phenomenon of ovulation directly ascertained by means of laparoscopy.


Histological and histochemical aspects of the mucosa of the nasal conchae in the zebu (Bos indicus).

In various respiratory areas of the mucosa of the nasal conchae of the zebu (Bos indicus) there is a quantitative variation of goblet cells. The glands are tubular or tubulo-alveolar, having morphologically serous and mucous cells. The excretory ducts are formed by non-secreting cells. The goblet cells and glands elaborate a glycoprotein. The carbohydrate portion is probably an association of neutral mucopolysaccharides, sulphated acid mucopolysacchardies and sialic acid and its proteic portion contains alpha-amino radicals. Tryptophan- and tyrosine-rich proteins are demonstrated only in the glandular secretion.


Chemo-architectonic studies in a submammalian brain. Adenosine triphosphatase and simple esterase in the diencephalon and mesencephalon.

The present report deals with the histo-enzymological mapping of adenosine triphosphatase and simple esterase in the diencephalon and mesencephalon of Uromastix hardwickii. The enzymatic make-up, in both cases, does not differ markedly in the various nuclei; few variations, of course, occur in some midbrain areas like pretectal nuclei. The latter are intensely positive for ATPase, while these nuclei are moderate to simple esterase. Nevertheless, one of the most interesting results pertaining to simple esterase activity is of a high order in the fiber tracts in comparison to ATPase. The other interesting feature relates to the fact that generally intensely positive nuclei, in ATPase preparations, are those which have extensive efferent fibres. The metabolic significance of high degree of ATPase activity vis-a-vis extensive efferent connections has been exhaustively discussed, besides the possible significance of the general data obtained.


Cysts of the semilunar cartilage of the knee. A light and electron microscopic study.

The semilunar cartilages of the knee of six cases showing various degrees of mucoid degeneration with cyst formation were studied with the light microscope. Three cases were selected for electron microscopic observation which revealed that some of the cystic spaces filled with mucoid material were lined by synovial cells. Masses of mucinous, alcian bluc positive material (acid mucopolysaccharides) were observed also among degenerated and intact bundles of collagen. It is concluded that the accumulation of acid mucopolysaccharides in meniscial cysts is at least in part a product of secretion of synovial cells. This observation explains the high incidence of recurrence of meniscial cysts after incomplete surgical excision and supports the concept that it is an active rather than a degenerative process.


Muscle spindle control during locomotor movements generated by the deafferented spinal cord.

In acute spinalized (Th 12) cats, treated with DOPA, curarized or with all lumbosacral dorsal roots transected, stepping patterns were elicited in the hindlimbs by continuous electrical stimulation of the dorsal roots. Single primary endings in dorsal root filaments or single gamma and alpha efferents in muscle nerve filaments from flexors and extensors were recorded together with the efferent nerve activity to various hindlimb muscles. The experiments showed a clear coactivation of the intra- and extrafusal system to the same muscle. The alpha efferent discharges typically started with a very short first interspike interval. It is concluded that there exists a central spinal alpha-gamma-linkage for locomotion in the hindlimbs.


[Study of the cerebral circulatory resistance by the Döppler effect and rheography (author's transl)].

A correlation is made between the index of circulatory resistance given by ultrasonic flow-measurement and rheography. Patients with normal and increased blood pressure were studied. The characteristics of the transient and of the permanent ischaemic attacks are defined.


Quantitative measures of enzyme activities in type I and type II muscle fibres of man after training.

The effect of 7 to 8 weeks of physical training on oxidative and glycolytic enzyme activities in the 2 major fibre types of human quadriceps femoris muscle has been investigated. 2 groups of 4 and 5 subjects respectively were trained at the same total work-load on a bicycle ergometer 3 days per week using interval exercise with maximal intensity (I.T.) or continuous exercise with submaximal intensity (C.T.). Succcinate dehydrogenase (SDH) and phosphofructokinase (PFK) activities were determined on crude homogenates of muscle biopsy samples and on pools of type I and type II fibres dissected from freeze-dried samples taken before and after training. Crude homogenate SDH activity increased to the same extent in both groups, average increases were 27.5% (I.T.) and 22% (C.T.) respectively. Only type I-SDH increased in the C.T. group (p less than 0.01), the average increase being 32%. On the other hand only type II-SDH increased in the I.T. group (p less than 0.01), with an average increase of 49%. No changes in PFK activity could be detected. The results of the present study emphasize the great adaptability in oxidative potential of both the two major human skeletal muscle fibre types and further that this adaptation seems to be related to the pattern of fibre recruitment during exercise.


Sectorial posterior rhizotomy, a new technique of surgical treatment for spasticity.

After their experience of Foerster's operation and its technical modifications in 80 cases the authors report a new concept of analysis and treatment of spasticity in lower limbs. Spasticity of the different muscle groups is classified either as "useful spasticity" or "handicapping spasticity". The first has to be preserved, the second must be reduced. In order to achieve this purpose a new technique is presented, based on operative sectorial identification of the posterior rootlets subserving the "handicapping spasticity" by electrophysiological stimulation, muscle testing, and E.M.G. studies. The conus medullaris and cauda equina are exposed by T 11-L 1 laminectomy, performed in the lateral position. The clinical and E.M.G. evaluation of responses to stimulation enables the surgeon to establish a map of rootlet groups which are marked with coloured threads. Selective resection of "handicapping posterior rootlets" is then performed after several tests of the mapping. The rootlets subserving useful spasticity are carefully preserved. Ten cases are reported, comprising five cases of cerebral palsy operated upon since 1974 and five cases of posttraumatic spastic paraplegia from the same period. Pre and postoperative findings are summarized. The technical features of this procedure are discussed and compared with other surgical procedures. The problem of the rootlet reflex arch is considered in the light of the effects of stimulation of anterior and posterior rootlets at the same level.


Oxidation and reduction of copper ions in catalytic reactions of Rhus laccase.

1) It was demonstrated by colorimetric as well as EPR measurements that the native (aerobic, resting state) Rhus vernicifera laccase contains both Cu2+ and Cu+ (total Cu content was 4.0 gram atoms/mole). The ratio of Cu2+ to total Cu in laccase varied (42-90%) in samples of latex collected from various districts. The absorption maximum at 615 nm was proportional to the content of total Cu in the enzyme sample. Laccase activity was found to almost parallel the content of the Cu2+ form. The oxidized minus reduced difference absorbance of the enzyme at 330 nm shoulder was proportional to the amount of Cu2+. 2) Steady state level of oxidation of laccase copper during the laccase copper catalytic action, the rates of reduction by substrates and the oxidation by O2 were determined by following absorbance changes at 615 and 330 nm by the stopped flow method. 3) All the results from titrimetric and kinetic experiments were consistent with the laccase model previously proposed by Makino and Ogura in which a laccase molecule contains 1 Cu(615) and 3 Cu(330). Our expanded model states that a laccase sample originally contains active as well as inactive enzymes. In the active enzyme, Cu ions are reactive to O2 but in the inactive enzyme, Cu can be oxidized only by oxidizing agents such as H2O2 or ferricyanide, or by a slow intermolecular electron transfer from Cu(615) to the active enzyme. In both species of enzyme rapid reduction of Cu2+ ions by substrate takes place. In comparative studies of the reactivities of Cu ions in various copper proteins, we would like to suggest that oxidatic activity of a copper protein is due to the Cu+ form of the enzyme ions with O2.


Platelets, Arthus-type reactions and inflammatory mediators.

The release of inflammatory mediators and the appearance of necrohaemorrhagic lesions induced by subcutaneous implantation of sponges containing antiplatelet serum globulins were studied in control and thrombocyto-penic rats. In thrombocytopenic animals, antiplatelet globulins caused a greater release of prostaglanding-like material and 5-hydroxytryptamine as well as larger inflammatory lesions. Thus, platelet integrity is not necessary for the induction of lesions by antiplatelet globulins and the mediators in the sponge exudates must have originated from leucocytes or damaged tissues. Mast cells seem not to be involved in the production of 5-hydroxytryptamine in this inflammatory reaction. It is suggested that in idiopathic thrombocytopenic purpura (ITP) an Arthus-type hypersensitivity reaction, rather than the thrombocytopenia itself, is the cause of the vascular lesions and their manifestations.


Reappraisal of the functional significance of the coronary collateral circulation.

A review of data in 465 patients with complete obstruction of either the left anterior descending or right coronary artery was undertaken to evaluate the functional role of the collateral circulation. Complete obstruction of a dominant right coronary artery was observed in 288 patients, 83 percent with distal filling and visualization of the posterior descending artery by way of collateral vessels. Complete obstruction of the left anterior descending artery was noted in 177 patients, 71 percent with filling and visualization distal to the obstruction by way of collateral vessels. Among patients with obstruction of the left anterior descending artery, there was a significantly greater frequency of congestive heart failure and cardiomegaly in those without collateral vessels than in those with collateral vessels. The former also had a significantly greater frequency of both electrocardiographic evidence of an anterior wall myocardial infarction and angiographic findings of anterior wall asynergy. The frequency of inferior myocardial infarction and inferior wall asynergy was not influenced by the presence of collateral vessels. These observations indicate that the collateral circulation plays a significant protective role in the presence of obstruction of the left anterior descending artery, which is not apparent with obstruction of the right coronary artery.


Analysis of wall dynamics and directional components of left ventricular contraction in man.

The extent and rate of left ventricular wall thickening during systole has previously been shown to be a useful measure of regional ventricular function and to play an important role in the ejection of blood from the left ventricle. The relation among systolic wall thickening, the directional components of contraction, ejection fraction and force velocity measurements is therefore of interest in understanding the dynamics of contraction of the intact ventricle. This report describes a theoretical basis and method for using ventricular angiograms to quantify the separate contributions of longitudinal shortening, circumferential shortening and systolic wall thickening to overall ventricular performance in man. One hundred twenty-two patients with valvular, coronary or myocardial heart disease were studied with biplane angiocardiography during diagnostic cardiac catheterizations. The percent contribution of directional components to total work or power developed by a mid-wall equatorial element of myocardium was shown to be: longitudinal, 14 percent in normal and diseased ventricles; circumferential, 45 percent in normal, increasing to 55 percent in dilated ventricles (P less than 0.005); wall thickening, 40 percent in normal, decreasing to 31 percent in dilated ventricles (P less than 0.001). Thus, left ventricular contraction, which is expressed as systolic wall thickening, quantified separately from inward wall displacement due to mid-wall circumferential shortening, accounts for nearly half of segmental left ventricular work and power. The rate and extent of ventricular wall thickening correlated closely with ejection fraction (r = 0.92 and 0.95, respectively) and with velocity of circumferential shortening (r = 0.90 and 0.80, respectively). Previous models of ventricular and myocardial mechanics that include computations of mid-wall longitudinal and circumferential stress and strain do not appear to account for the large contribution of systolic wall thickening to the performance of the intact heart. Force-velocity relations as heretofore described may therefore be partial descriptors of myocardial function in the intact ventricle.


Prolapse of the mitral valve is described in two patients with the Ebstein's anomaly of the tricuspid.

Prolapse of the mitral valve is described in two patients with the Ebstein's anomaly of the tricuspid valve. This association has not been described previously. It is probable, however, that this association is not a rare one, but that clinical features of the prolapsing mitral valve are obscured by those resulting from the malformed tricuspid valve. Opportunity also was provided to study anatomically the mitral valve of a patient known to have a systolic click and a late systolic murmur (the Barlow syndrome). Although there have been several anatomic descriptions of floppy mitral valve at necropsy, they have been extremely rare in patients known to have the classic auscultatory features of the Barlow syndrome.


T and B lymphocytes in patients with Down's syndrome.

Individuals with Down's syndrome are thought to have abnormalities of immune function. Studies to quantify the number of peripheral blood T and B lymphocytes and serum immunoglobulins in 12 individuals and 12 sex and age matched control subjects were performed. Hepatitis B antigen and antihyroglobulin antibodies as markers of possible immune dysfunction were determined. The numbers of circulating T and B cells, and the level of serum immunoglobulins in children with Down's syndrome did not differ from nonretarded control children. Circulating hepatitis B antigen and antihyroglobulin antibodies were not present. These studies indicated that quantitative abnormalities of T and B cells are not present in children with Down's syndrome. The data did not exclude the existence of qualitative abnormalities.


Hysterosalpingographic follow-up of laparoscopic sterilization.

Two hundred and fifty of 323 laparoscopically sterilized patients had hysterosalpingographic (HSG) follow-up. A Foley catheter was used in hysterosalpingography. Of these patients, 3.6 per cent demonstrated fistula; 1.2 per cent were found to have round ligament burns, and 0.618 per cent became pregnant. Mechanism of fistula formation, prevention, and management is discussed. The incidence of intrauterine pregnancy and ectopic pregnancy after laparoscopic sterilization is discussed, and the literature is reviewed. Based on these data, it is concluded that HSG follow-up is helpful in teaching institutions and where the laparoscopic sterilization is carried out by inexperienced operators. Routine HSG follow-up is not recommended.


Disposition and regulation of body potassium: an overview.

Most of filtered K+ is reabsorbed passively in the proximal tubule since the tubular fluid (TF): plasma (P) concentration ratio is almost identical to the equilibrium value calculated from the transtubular potential difference. In the loop of Henle, K+ also moves passively along chemical and electrical gradients. Only 5-10% of the filtered K+ remains in the early distal convoluted tubule. In the distal convoluted tubule TF/P K+ is lower than the calculated equilibrium value suggesting that K+ is passively secreted and actively reabsorbed. Most of the excreted K+ had been secreted by the end of the distal convoluted tubule. Aldosterone increases K+ secretion in this segment, an effect that may be dissociated from the effect on Na+. The relation between K+ secretion and Na+ absorption is the consequence of the luminal electronegativity produced by Na+ absorption and is not stoichiometric. Acidosis and alkalosis decrease and increase K+ secretion in the distal tubule respectively; this is not due to reciprocal changes in H+ secretion. Normally, some K+ is reabsorbed in the collecting duct. During K+ deprivation and loading the collecting duct may participate in the conservation or elimination of K+ respectively. Adaptation to chronic K+-loading consists of renal and extrarenal factors. The extrarenal mechanism is aldosterone-dependent and consists of rapid uptake of K+ by muscle. The renal mechanism consists of increased K+ secretion by the distal tubule. Luminal electronegativity and increased K+ pool in the distal tubular cell play a crucial role.


Left atrial size in patients with atrial fibrillation: an echocardiographic study.

Left atrial dimensions were recorded echocardiographically in 50 patients with atrial fibrillation. Fibrillatory wave amplitude (f wave) was measured in lead V1 of standard electrocardiograms for all patients. Left atrial dimensions (LAD), LAD compared to body surface area (LAD/M2) and the ratio of LAD to aortic root diameter (LAD/AR) were calculated. There was no significant correlation between f wave size and LAD (p = 0.6480), between f wave size and LAD/M2 (p = .6721), or between f wave size and LAD/AR (p = .1157), nor was there any association between LAD and the etiology of the heart disease. F wave size did correlate (p = .0073) with the age of the patient, the older the individual, the more likely was he to have fine atrial fibrillation (peak to trough f wave less than 0.5 mm).


Mechanics and electrolyte composition of arterial smooth muscle in developing dogs.

The effects of age on arterial smooth muscles (SM) mechanics and electrolyte composition were studied during growth and development in six litters of puppies and their mothers from isolated segments of carotid, renal, mesenteric, and iliac arteries. An increase in the maximum wall stress following both norepinephrine (NE) and potassium (K) was found with age at all sites. The ratio of the stress response for K/NE was found to decrease with age. The maximum stress response for both NE and K shifted to lower values of wall strain with age in the same manner that passive stress-strain curves were shifted. The maximum diameter re3 (3 SM activator to SM activator were not significantly altered with age, but they were better maintained at higher transmural pressure in older animals. Chemical analysis indicated "cell" water, Mg, and K contents decreased with age, as did extracellular water, Na, and Cl. Na anhe suggest that changes in SM excitation-contraction coupling occur with age. Passive wall elements appear to interact with the contractile elements in determining wall responses to SM activation.


DDE feeding and plasma osmoregulation in ducks, guillemots, and puffins.

To assess the possibility that organochlorine pesticide disruption of osmoregulation is responsible for recent large kills of young seabirds, we have studied the effects of DDE feeding (10-250 ppm) on plasma osmoregulation and nasal gland function in the following species: mallared and white Pekin ducks (both Anas platyrhynchos), black guillemot (Cepphus grylle), and common (Fratercula arctica). Other investigators have recently reported that dietary DDE (10-1,000 ppm) inhibits nasal gland secretion in freshwater-maintained mallards; our initial experiments with white Pekins showed no such inhibition during either freshwater or seawater maintainance. Moreover, DDE had minimal effects on plasma electrolyte levels and total nasal gland Na-K-ATPase activities in all species studied. Liver DDE levels in experimental ducks and guillemots were comparable to those reported for seabirds found dead after kills; levels in starved experimental puffins were much higher. Thus DDE at environmental levels does not affect osmoregulation or nasal gland Na-K-ATPase either in ducks or in two species of oceanic birds.


Attempted experimental cross infections with mammalian guinea-worms, Dracunculus spp. (Nematoda: Dracunculoidea).

Dracunculus medinensis and D. insignis are morphologically indistinguishable. Experiments to test the susceptibility of various mammalian hosts to these two guinea worm species are described. Infective 3rd-stage larvae of D. medinensis were administered to each of four raccons (Procyon lotor): infective 3rd-stage larvae of D. insignis were administered to a rhesus monkey (Macaca mulatta), two dogs, two ferrets (Mustela putorius furo), and a marten (Martes americana). D. medinensis was not found in the raccoons when necropsies were performed on days 247, 283, 354, and 390 post-infection, respectively. Nine female D. insignis containing eggs, embryos, and motile 1st-stage larvae were found in the rhesus monkey 180 days post-infection. Lesions had not formed and the larvae were presumed to be immature and not yet infective as they were comparatively inactive and attempts to infect suitable copepods failed. D. insignis was not found in the dogs or the marten, although both ferrets were successfully infected. Variations in susceptibility of various mammalian species to the guinea worm are discussed together with comments on variations in migration routes and sites of emergence in hosts which may be partially refractory. D. insignis and D. medinensis may represent physiological strains of a single species, or they may in fact be two distinct species which have evolved in different geographical locations.


Fluorimetric method for the detection of anti-DNA antibodies in serum.

A method for the detection of native anti-DNA antibodies in serum is described. The method is based on the reactivity of fluorescein isothiocyanate with DNA, forming a complex capable of combining with anti-DNA antibodies. The fluorescein content of the precipitated fluorescein-DNA anti-DNA complex is then measured in a fluorometer. The assay is accurate, highly reproducible, and inexpensive to perform. Comparative studies performed with the Farr assay show the fluorimetric method to be more sensitive in detecting anti-DNA antibodies in the serum of SLE patients.


Exploding the myths of hernia repair.

Sacred prinicples guiding surgical repair of groin hernias have remained basically unaltered since their inception. This may explain the failure of results to improve significantly over the years. Ten hallowed concepts have been critically analyzed in the light of modern technology and contemporary experience. Although challenging established surgical traditions invariably invites debate, it is essential to scientific progress.


Delayed and recurring infection in postoperative abdominal wounds.

Delayed and recurring wound infection in the abdominal wall of twenty-five patients, producing a variety of signs and symptoms months or years after original operations, were most frequently associated with silk sutures and endogenous infection due to Escherichia coli. The restorative procedures employed at a small community hospital varied from incision and drainage to en bloc wound excision. Timing of operations, culture data, pre- and postoperative antibiotics, and changes in the type of suture material were important adjuncts to therapy.


Prosthetic arteriovenous fistula for vascular access in hemodialysis.

Vascular access through subcutaneous prosthetic arteriovenous fistulas was studied in eighteen dogs. Dacron velour and woven Dacron grafts (6 mm diameter) were constructed across the lower abdomen between the common femoral artery and the opposite common femoral vein. In heparinized animals 197 percutaneous punctures were made with a "14 guage hemodialysis cannula at weekly intervals. Over a period of one and a half years there was no instance of infection. One of the fourteen Dacron velous and all four woven Dacron fistulas thrombosed. These data suggested the feasibility of achieving repetitive blood access through Dacron velour vascular prostheses. Nineteen Dacron velour fistula bypasses between the brachial artery and median basilic vein were performed in fifteen selected patients for a total dialysis period of ninety-six months. Failed standard subcutaneous fistulas or absence of suitable vessels in the upper extremity were indications for the primary procedure. Of three looped forearm fistulas, two thrombosed at twenty-two and two months. Complications among sixteen straight bypasses in the arm included two graft infections and one cannula tract infection. There were no instances of thrombosis in this group. The advantages of single needle dialysis in these high risk patients have been emphasized. Eleven grafts are presently functioning two to nine months postoperatively. Our preliminary results suggest that a Dacron velour fistula merits consideration as an alternative for vascular access in maintenance hemodialysis.


The HLA linkage group and disease susceptibility.

The HLA linkage group, located on chromosome 6, is composed of serologically defined (SD-) loci (HLA-A, -B and -C) and of a MLC (= mixed lymphocyte culture-) or lymphocyte defined (LD-) locus (HLA-D). Different alleles of these loci are linked together as well as with loci for the synthesis of some complement components and the properdin factor B (= Bf-system) by strong positive linkage disequilibria (gametic association). The indication of a HLA linked genetic control of immunoresponsiveness makes the HLA system one of the biologically most important immunogenetic systems in man. The associations, found between single HLA determinants and diseases, can be explained in different ways, but may contribute to a better understanding of the etiopathogenesis of diseases and of the biological role of the HLA linkage group.


Histochemical evaluation of enzymes in the rabbit corneal endothelium after short-term storage.

Isolated rabbit corneae were stored at a temperature of 4 degrees C in McCoy's 5a medium (modified) containing 5% dextran T 40 and gentamycin sulphate (250 mug/ml) for a varied number of days. The endothelium of the corneae was examined by light- and electron-microscopic histochemical methods for ATPase, TPPase, and SDH. The activity of each enzyme in the endothelia, stored for 6 days, was found to resemble the enzyme activities in the fresh corneal endothelium. By 8 days, the SDH activity was lowered and specific staining for ATPase and TPPase was decreased. In the 12 day-stored endothelium, the SDH and TPPase activities could not be detected. From these results, it was gathered that the isolated cornea stored in the medium for 6 days may be used in keratoplasty.


Allergic reaction to allopurinol with cross-reactivity to oxypurinol.

A 25-year-old white man with gout and nephropathy and with a previous reaction to allopurinol was given a trial dose of oxypurinol. He developed malaise, a generalized erythematous reaction with edema, pruritus, and emesis; this was clinically identical to the reaction he experienced with allopurinol. When the patient's lymphocytes were exposed in vitro to oxypurinol and allopurinol, increased DNA synthesis was observed, suggesting an immunologic basis for the reaction. This patient indicates that clinical cross reactivity to allopurinol and oxypurinol does occur and may be of an immunologic basis. There is a need for additional xanthine oxidase inhibitors for such patients.


[Mongolism: an encephalopathy "not like others"].

Considering ancient and new aspects to Langdon Down's disease, the author points out: the varieties of evolution, due to associate physical and sensorial defects and peculiarly to the differences of intellectual level and ego structuration. They are under dependence of social and familial factors. A demonstration is given in Lyon by a sheltered workshop where mongolian adults have found good possibilities. Sexual and sentimental life is a problem of great difficulties connected with conscient and inconscient reactions of normal adult (parents and "educateurs").


Studies on the nature of autoimmunity in myasthenia gravis. Evidence for an immunodeficiency type.

Clinical and laboratory data continue to support the concept of a genetically determined breakdown of immunological tolerance in myasthenia gravis with immunological damage to the motor end plates. The demonstration of impaired function of thymus-derived lymphocytes and of IgA deficiency correlate well with the clinical data in which there is an increase incidence of autoimmune diseases associated with anergy. Whilst the exact pathogenesis of myasthenia gravis is unknown, the available data support the concept of an immune deficiency disorder.


Selective arteriography of the celiac artery in patients with thoracic sarcoidosis.

In this paper on hepatosplenic sarcoidosis the authors confirmed currently accepted concepts and further refined the examination of liver and spleen by selective arteriography of the celiac artery. In addition, they emphasized the frequency of hepatosplenomegaly in sarcoidosis as well as the speckled aspect of the parenchyma of both organs, which appeared dotted with innumerable small lacunae. This appearance was not strictly pathognomonic of sarcoidosis. Cortisone treatment caused reversion to a normal pattern in the patients.


[Use of BrdU in the study of cell cycle in normal and abnormal subjects].

Chromosome modifications induced by BrdU allow a study of the cell division cycle during, at least, three consecutive generations. Among normal lymphocytes, the cell cycle varies in duration, but for the majority of cells, is a little shorter than twenty hours. In trisomy 21 individuals, the mean cell cycle is shorter, around 16 hours. In Fanconi's anemia, the cell cycle is slowed down and its duration is approximatively twice that of normal individuals. Endoreduplicating cells seem to have the cycle of longest duration.


Calcium-binding proteins.

Calcium binding, which appears to be either specific or physiologically significant, has been reported for 70 norminally "different" proteins. First, I catalog these proteins. Only a few recent or general references can be cited. Those proteins that serve critical physiological functions or that may be regarded as chemical prototypes are discussed in more detail. Second, I present several generalizations. Inevitably the logic here is cyclic in that the generalizations dictate which data from all those available are actually presented. In order to focus our attention in the catalog, I outline these generalizations: 1. An examination of the five calcium-binding proteins of known structure does not reveal a correlation between ligand type and/or geometry and Ca2+ affinity or selectivity. 2. For many of the enzymes supposedly activated or stabilized by Ca2+ the available data dot not allow one to judge the physiological significance of the calcium binding or its contribution of the enzymic mechanism. 3. Of the enzymes requiring Ca2 and concanavalin A, only the nuclease of Staphylococcus and possibly phospholipase appear to bind Ca2 at the active site. 4. The calcium affinities of most of the extracellular enzymes are low, pKd = 3 to 4. This is consistent with the fact that the Ca2+ concentration of the extracellular environment is about 10(-3) M. 5. The cytosol concentration of free Ca2+ in most if not all eukaryotic cells is from 10(-6) to 10(-8) M. Following a stimulus to the cell after which Ca2+ functions as a second messenger, the free Ca2+ may rise to 10(-6) to 10(-5) M. The reported affinities of most enzymes of the cytosol are too low to be physiologically significant. 6. Several intracellular enzymes or enzyme activators have pKd values between 5 and 8. These enzymes therefore may be turned on and off or "modulated" in response to extracellular stimuli. 7. There is a distinct conceptual difference between extracellular enzymes that are "activated" by Ca2+ and those intracellular enzymes that are modulated by Ca2+. The activated proteins bind Ca2+ upon secretion or upon incorporation into a secretory vesicle and retain it throughout their functional lifetimes. The modulated proteins may bind and release Ca2+ many times in response to varying concentrations of this second messenger. 8. Several of the calcium-modulated proteins contain a characteristic conformation, consisting of a helix, calcium-binding loop, and second helix, referred to as the "EF hand". These proteins are homologous, that is, evolutionarily related.


Clindamycin vs placebo as adjunctive therapy in moderately severe acne.

Eighty-three patients with moderately severe acne were entered into a double-blind study utilizing clindamycin and placebo. Counts of comedones and pustules were made at intervals during a 13-week period. Clindamycin resulted in noticeable improvement of acne in 85% of subjects while in the placebo group improvement was present in 38%. There was also an unexplained reduction of total comedone count in the clindamycin-treated group. Severe side effects occurred in two of 44 patients receiving clindamycin (diarrhea, 1 and rash, 1); although an additional eight patients receiving clindamycin experienced mild diarrhea, discontinuation of therapy was not required. Clindamycin appears to be a valuable additional drug in the treatment of acne.


[The acquisition of antibody diversity studied in anuran amphibians (author's transl)].

For T and B lymphocytes, the capacity of recognizing diverse antigens is acquired early in ontogeny. This is shown for T cells by graft rejection and mixed leucocyte reaction experiments and for B cells by the heterogeneity of antibody response in young larvae which only possess a small number of lymphocytes. Thus any proposed mechanism for the generation of antibody diversity in frogs has to take into account: (a) that such diversity is acquired within about 21-30 days after fertilization in larvae whose lymphocyte generation time is 36-40 h; (b) that genetically identical animals have similar immune responses as revealed by mixed leucocyte reaction for T cell responses and by isoelectric focussing patterns for anti-dinitrophenyl and anti-sheep red blood cells antibodies for B cells.


Alopecia areata and Down syndrome.

The skin of 214 institutionalized patients with the Down syndrome was carefully examined. There were 19 cases of alopecia areata and four cases of vitiligo. Since persons with the Down syndrome are predisposed to immunological deficiency in thymus-dependent (T-cell) function, findings from the skin examinations suggest that immunologic factors might contribute to the increased incidence of vitiligo and alopecia areata seen in the Down syndrome. Syringoma was also common and affected female patients twice as frequently as male patients.


Epidemic Norwegian scabies.

Norwegian scabies is an ectoparasitic infestation by Sarcoptes scabiei, characterized by hyperkeratotic lesions of the hands, feet, ears, and scalp, which contain many mites. An epidemic of Norwegian scabies involved 22 patients in a 25-patient ward of mentally and physically handicapped persons (mostly mongoloids). The pathogenesis of the prolific mite population is unclear, but either a specific immunologic deficit or the inability to effectively eliminate the mites by scratching is a plausible possibility.


Topically applied antibiotics in acne vulgaris: clinical response and suppression of Corynebacterium acnes in open comedones.

Topical antibiotics were used on patients with acne vulgaris. Corynebacterium acnes organisms from open comedones were quantitated during treatment, and the progress of the disease was evaluated. Clindamycin lotion completely suppressed the growth of C acnes organisms, whereas erythromycin and tetracycline did not depress the C acnes counts. Taken as a group, these antibiotics gave a substantial improvement of the disease on the treated side as compared with paired untreated sides  of the face and back.


Leukocytoclastic vasculitis.

Patients with leukocytoclastic vasculitis have purpuric, palpable lesions, most commonly on the lower part of the legs. Systemic involvement, particularly of the kidneys, is found frequently. Characteristic pathological features include necrosis of small vessels within the dermis, infiltration by polymorphonuclear leukocytes within and around the vessel walls, hemorrhage, and occasionally thrombosis. Immunofluorescence study frequently shows granular deposits of immunoglobulins and complement in vessel walls. Etiologic agents that have been implicated include infection, foreign proteins, chemicals, drugs, and a variety of diseases. The mechanism causing tissue damage is thought to be mediated by immune complexes, although specific antigens have only occasionally been unequivocally identified. Treatment includes bedrest, corticosteroids, and sometimes, cytotoxic agents.


[Disturbed distribution of surface glycoconjugates of the plasma cell membrane in psoriasis. Cytochemical detection using the alcianblue-lanthan-reaction (author's transl)].

Lanthanum has been used as a tracer for the intercellular space and the surface coats in different epithelia including human epidermis, however, lanthanum compounds may or may not penetrate into skin specimes and reaction product may or may not be present in the intercellular space. After treatment with alcian blue prior exposure to lanthanum the trilaminar plasma membrane was more regularly stained and a thin coat of reaction product corresponding to superficial glycoconjugates outlined the cell surface and filled the narrow intercellular space in normal epidermis. In psoriatic epidermis the quantity of superficial membrane-bound glycoconjugates was rather reduced, their distribution and compartmentalization was profoundly changed and the outer leaflet of the trilaminar plasma membrane was not always clearly seen, having a "moth-eaten appearance" in some places. These findings show once more that alterations of the cell membranes and their surface architecture are present in psoriasis. They may play a major role in the pathogenesis of the disease, influencing the activities of membrane-bound enzymes and the flow of the epidermal growth control mechanism. The glycocalyx may serve in this mechanism as an accumulator of energy rich compounds or as a receptor site of membrane-bound ezymes. According to our views it represents a "ground substance" of epidermal origin, which controls the social behaviour of the keratinocytes in tissue.


Chemotherapy for malignant Zollinger-Ellison tumors: successful treatment with streptozocin and fluorouracil.

Streptozocin is of value in the treatment of malignant insulinomas, but has not previously been shown to be effective against Zollinger-Ellison tumors, which secrete gastrin. This patient's malignant gastrinoma responded to treatment with streptozocin and fluorouracil. Tumor regression was verified by the disappearance of the epigastric mass, improvement of liver function, and reduction of serum gastrin levels to one third of the pretreatment level. The patient has been in remission for more than two years and has had no further treatment since the first year.


[Activities and properties of adenosine triphosphatase (ATPase) in homogenates of renal cortex, liver, myocardium and small-intestine mucosa in sheep].

Studies conducted into the activity of adenosine triphosphatase (ATPase) in homogenate of several tissues of sheep and against the background of pH 7.5 (tris-HCl buffer) have shown highest enzyme activity to develop in renal cortex and cerebral cortex followed, in declining order of quotation, by liver, myocardium, and mucous membrane of small intestine. ATPase activities were studied also in the presence of pH-values between 7.2 and 8.95 (tris-HCl buffer) and between 8.6 and 11 (piperazine buffer), with the pH optimum of ATPase in the above tissues having been found to lie at approximately 9.0. Different concentrations of Mg ions were added, and maximum ATPase activity of 2 mMol ATP was obtained by adding 2 mMol Mg. Decline in ATPase activity should be expected in the case of hypomagnesaemia. Addition of different concentrations of sodium and potassium ions gave in most of the tissues tested maximum activity in response to 10 mMol potassium and 68 mMol sodium. Na-K ATPase could be inhibited by oubain particularly in cerebral and renal cortex.


Preexisting glomerulonephritis in allografted kidneys. Occurrence in man.

Biopsy specimens were taken from 43 renal allografts after completion of the anastomoses. In five kidneys from four donors, mesangial lesions compatible with preexisting glomerulonephritis were found. Immunofluorescence study of three kidneys indicated immunecomplex pathogenesis. In one donor, congenital heart disease was present: the others were free of manifest (renal) disease. Clinical follow-up data and repeated renal biopsy specimens indicated an uneventful course of these allografts. Awareness of this kind of lesions is useful for interpretation of glomerular lesions in biopsy specimens from renal transplants.


Virus "Tamdy"--a new arbovirus, isolated in the Uzbee S.S.R. and Turkmen S.S.R. from ticks Hyalomma asiaticum asiaticum Schulee et Schlottke, 1929, and Hyalomma plumbeum plumbeum Panzer, 1796.

Eleven virus strains were isolated from ticks Hyalomma asiaticum asiaticum Schulce et Schlottke, 1929, and Hyalomma plumbeum plumbeum Panzer, 1796,collected in 1971-1974 in desert regions of the Uzbee S.S.R. and the Turkmen S.S.R. According to CF test the strains were closely related to each other and not antigenically connected with viruses from antigenic groups A, B, California, CHF-Congo, Bakau, Bunyamwera, Gajam, Kaisodi, Qalyub, Kemerovo, Quaranfil, Simbu, Turlock, Hughes, Uukuniemi, Tete and 21 ungrouped viruses isolated from ticks. The virus was named "Tamdy" after the place of isolation of a prototype strain LEIV-1308 Uz. The virus does not agglutinate goose erythrocytes, it is pathogenic for suckling mice and 3 weeks old mice by intracerebral infection. Replication of a virus with CPE in cell cultures--L, Rh, A1--and without CPE--in pig embryo kidney cell cultures--was demonstrated. According to ultrafiltration and electron microscope data the size of the virus is about 90 nm. It is rather sensitive to lipid solvents and is an RNA-virus. Morphologically the virus resembles the Bunyaviridae.


Evaluation of patients with progressive intellectual deterioration.

Sixty consecutive patients with progressive intellectual deterioration were evaluated by a specific protocol. Eighteen (30%) were found to have an underlying disease potentially reversible by medical or surgical therapy. Sixteen patients had a specific diagnosable but untreatable disease as a cause of dementia. The laboratory and radiologic tests of the protocol that uncovered treatable illnesses were the radioisotope brain scan (two cases of bilateral subdural hematoma), the pneumoencephalogram (seven patients with normal-pressure hydrocephalus), thyroid function screen, and liver function studies (one case each). Unrewarding tests included serum barbiturate, bromide, vitamin B12, and folate levels.


Occupational contact dermatitis in 100 consecutive patients.

One hundred consecutive cases of occupational contact dermatitis diagnosed in Warsaw are discussed. In 79 subjects allergic and in 21 patients irritant occupational dermatitis was found. The most numerous group were workers employed with epoxy resins (20 persons), next came masons (14 subjects), and third medical staff members (12 persons). In 46 patients the standard series was sufficient for diagnosis of allergic occupational contact dermatitis, but in thirty three cases it was indispensable to test them with additional subsances.


[Nickel sensitization in  women and its relevance to occupation].

213 women and 26 men out of 7835 persons examined in the course of 9 years (1967--1975) had a positive reaction to nickle sulfate. The frequency of the sensitization to nickel increased during this time, from 0.9 to 5.01%. 121 of the sensitized women were less than 30 years old. The first manifestations of that contact eczema due to metal ions appeared on the earlobes, the fingers in the ring-region, the hands, the wrists and the neck. In most of the men but only in 20 women (1 photograph, 19 metallists), a professional cause could be revealed, and an occupational disease was recognized. In the other women, a non-professional cause was found. No hair-dresser had been sensitized to nickel, by an occupational contact. The increase of the allergy ot nickel from 1967 to 1975 was mainly due to wearing costume-jewelry since the localisation of the contact eczemas ofter corresponded to the trend of fashion. Before demanding the recognition as an occupational disease in case of positive tests, the relevance of the latter to the occupation of the subject should be elucidated.


Cartilage proteoglycans. Structure and heterogeneity of the protein core and the effects of specific protein modifications on the binding to hyaluronate.

Purified proteoglycans extracted from pig laryngeal cartilage in 0.15 M-NaCl and 4 M-guanidinium chloride were analysed and their amino acid compositions determined. Selective modification of amino acid residues on the protein core confirmed that binding to hyaluronate was a function of the protein core, and was dependent on disulphide bridges, intact arginine and tryptophan residues, and epsilon-amino groups of lysine. Fluorescence measurement suggested that tryptophan was not involved in direct subsite interactions with the hyaluronate. The polydispersity in size and heterogeneity in composition of the aggregating proteoglycan was compatible with a structure based on a protein core containing a globular hyaluronate-binding region and an extended region of variable length also containing a variable degree of substitution with chondroitin sulphate chains. The non-aggregated proteoglycan extracted preferentially in 0.15 M-NaCl, which was unable to bind to hyaluronate, contained less cysteine and tryptophan than did other aggregating proteoglycans and may be deficient in the hyaluronate-binding region. Its small average size and low protein and keratan sulphate contents suggest that it may be a fragment of the chondroitin sulphate-bearing region of aggregating proteoglycan produced by proteolytic cleavage of newly synthesized molecules before their secretion from the cell.


The electrophoretic heterogeneity of bovine nasal cartilage proteoglycans.

1. Proteoglycans were extracted from bovine nasal cartilage with 2.0M-CaC2 or with 0.15M-KCl followed by 2.0M-CaC2.. Proteoglycan fractions were prepared from the extracts by density-gradient centrifugation in CsCl under 'associative' and 'dissociative' conditions. 2. The heterogeneity of the proteoglycan fractions was investigated by large-pore-gel electrophoresis. It was concluded that extracts made with 2.0M-CaCl2 or sequential 2.0M-CaCl2 contain two major species of proteoglycan 'subunit' of different hydrodynamic size, together with proteoglycan aggregates. Both 'subunits' have mobilities that are greater than those of proteoglycans obtained from pig articular cartilage McDevitt & Muir (1971) Anal. Biochem. 44, 612-622] and are therefore probably smaller in size than the latter. 3. Proteoglycan fractions isolated from cartilage extracted lith 0.15M-KCl separated into two main components on large-pore-gel electrophoresis with mobilities greater than those of proteoglycans extracted with 2.0M-CaCl2. Proteoglycans extracted at low ionic strength from bovine nasal cartilage are of similar hydrodynamic size to those extracted from pig articular cartilage under the same conditions [McDevitt & Muir (1971) Anal. Biochem. 44, 612-622]. 4. The role of endogenous proteolytic enzymes in producing proteoglycan heterogeneity, particularly in low-ionic-strength cartilage extracts is discussed. 5. Hyaluronic acid and 'link proteins' were present in the proteoglycan fraction separated from KCl extracts as well as in the fraction separated from CaCl2 extracts. Hyaluronic acid can only be identified in proteoglycan fractions by large-pore-gel electrophoresis after proteolysis and further purification of the fraction. 6. Collagen was extracted by both salt solutions and was tentatively identified as type II. Small amounts of collagen appear to be associated with the proteoglycan-aggregate fraction from the high-ionic-strength extract but not with the corresponding fraction from the KCl extract.


Nitrogenases from Klebsiella pneumoniae and Clostridium pasteurianum. Kinetic investigations of cross-reactions as a probe of the enzyme mechanism.

In combination with the Mo-Fe protein of nitrogenase from Klebsiella pneumoniae, the Fe protein of nitrogenase from Clostridium pasteurianum forms an active enzyme with novel properties different from those of either of the homologous nitrogenases. The steady-state rates of reduction of acetylene and H+ are 12% of those of the homologous system from C.pasteurianim. Acetylene reductase activity exhibited an approx. 10min lag at 30 degrees C before the rate of reduction became linear, consistent with a once-only activation step being necessary for acetylene reduction to occur. No such lag was observed for H2 evolution. The activity with N2 as a reducible substrate was very low, implying that acetylene reductase activity is not necessarily an accurate indication of nitrogen-fixing ability. This is of particular relevance to studies on mutant and agronomically important organisms. Stopped-flow spectrophotometric studies showed unimolecular electron transfer from the Fe protein to the Mo-Fe protein to occur at the same rate (k2 = 2.5 X 10(2)s-1) and with the same dependence on ATP concentration (apparent KD = 400 muM) as with the homologous Klebsiella nitrogenase. However, an ATP/2e ratio of 50 was obtained for H2 evolution, indicating that ATP hydrolysis had been uncoupled from electron transfer to substrate. These data indicate that ATP has at least two roles in the mechanism of nitrogenase action. The combination of the Mo-Fe protein of nitrogenase of C.pasteurianim and the Fe protein of K.pneumoniae were inactive in all the above reactions, except for a weak adenosine triphosphatase activity, 0.5% of that of the homologous K.pneumoniae system.


The formation of a stable complex between dissociated proteoglycan and hyaluronic acid in the absence of a link protein.

A proteoglycan fraction prepared from bovine articular cartilage under dissociative conditions was shown to interact with three purified hyaluronic acid preparations to form stable complexes in the analytical ultracentrifuge. It is concluded from these experiments that, although link proteins are associated with hyaluronic acid and proteoglycans in complexes between these macromolecular constituents.


The metabolic fate of intravenously injected peptide-bound chondroitin sulphate in the rat.

The degradation of intravenously administered chondroitin sulphate-peptide, obtained by trypsin digestion of rat cartilage preparations labelled in vitro with 35S (and, in some cases, with 3H), was studied in rats. As with free chains of chondroitin sulphate, the major site of accumulation and degradation in the body was the liver, although peptide-linked chains were taken up more rapidly than free chains. In the first 2h after intravenous injection of a chondroitin sulphate-peptide fraction, labelled macromolecular components were excreted in the urine. These were shown to be chondroitin sulphate-peptide of the same degree of sulphation but of smaller average size than the injected material. A similar observation was made when free chains of chondroitin sulphate from the same source were administered intravenously. An isolated perfused rat kidney failed to de-sulphate circulating chondroitin sulphate-peptide, but a component of lower average molecular weight was excreted in the urine. When a chondroitin sulphate-peptide fraction of relatively larger hydrodynamic volume was administered, very little chondroitin sulphate appeared in the urine in the first 2h. It was concluded that, depending on size and/or peptide content, the chondroitin sulphate-peptide released from connective tissues into the circulation would probably be subjected to one of two alternative fates. The smaller fragments are more likely to be excreted in the urine, whereas the larger ones are taken up by the liver and there degraded to inorganic sulphate and undefined carbohydrate components.


Comparative study of the hypoglycaemic and antilipolytic effects of four antidiabetic agents administered i.v.

The effects of i.v. administration of equipotent doses of glycodiazine, glibenclamide, desaglybuzol and glydiazinamide on the level of blood sugar and plasma free fatty acids (FFA) have been assessed in 30 diabetic patients and 24 healthy controls. Glibenclamide proved to have the most potent hypoglycaemic effect in diabetics. The decrease in blood sugar level was less sustained after glycodiazine as compared with the other three drugs. This is due mostly to differences in dynamics of insulin secretion. Glibenclamide also proved to have pronounced and most sustained antilipolytic action. In contrast, desaglybuzol, like phenformin (a biguanide), failed to cause a drop in the level of plasma FFA and hence can be recommended in obese diabetic patients.


Effect of fominoben-HCl on circulation, pulmonary gas exchange and acid-base balance at rest and during exercise.

The effect of 3'-chloro-2'-[N-methyl-N[(morpholino-carbonyl)methyl]aminomethyl]benzanilide-hydrochloride (forminoben-HCl, Noleptan) on pulse rates and blood pressures, ventilation and gas exchange, and acid base balance was studied in eleven patients aged 31 to 72 years at rest and during a standardised excercise. Mean systolic and diastolic blood pressures decreased at rest before and 10 min after work as well as during work. Mean alveolar ventilation was reduced by 9% at rest and was unchanged during work. No changes occurred in mean alveolar-arterial oxygen differences or in mean anatomical right-to-left shunt. In a few individual patients with grossly impaired intrapulmonary gas exchange, however, an improvement with regard to alveolar ventilation in relation to oxygen uptake and the alveolar-arterial oxygen tension difference could be demonstrated.


Effects of certain antirheumatic drugs on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine.

The effects of antirheumatic drugs on in vitro responses of normal human peripheral blood lymphocytes were examined and found to affect phytomitogen, antigen, and mixed lymphocyte responses. The drugs and concentrations (mumg/ml) at which 50% inhibition (ID50) of phytomitogen stimulation occurred were acetylsalicylic acid, 80; phenylbutazone, 150; indomethacin, 250; sodium aurothiomalate, 200; hydroxychloroquine, 75; D-penicillamine, 400; hydrocortisone, 50; naproxen, 350; and sodium meclofenamate, 175. Acetaminophen enhanced blastogenesis by 100% at 200 mug/ml, but was 50% inhibitory at 500 mug/ml. Other drugs had no effects. Numbers of viable cells in cultures with and without mitogens and drugs were generally similar at beginnings and ends of experiments. Stimulated cell cultures containing combinations of drugs exhibited greater inhibition than did cultures of individual drugs. Inhibition by drugs was greater when cells were cultured in medium alone than in medium with 20% plasma. Cells exposed overnight to phenylbutazone, indomethacin, sodium aurothiomalate, or sodium meclofenamate, then washed and stimulated, responded generally as well as did cells not exposed to drugs. Because some of these drugs exhibited effects at concentrations approaching therapeutic levels, these findings may be pertinent to clinical investigations of cellular immune responses of patients on drug therapy and to possible mechanisms of action for certain drugs.


Effect of some antirheumatics on connective tissue components.

The effects of a number of classical and modern antirheumatics on the biosynthesis of glycosaminoglycans and collagen were studied comparatively. The experimental results indicate that the antirheumatics deeply affect the metabolism of the main components of connective tissue. With regard to the methods used for testing, it may be stated that phenylbutazone, flufenamic acid, ibuprofen, mefenamic acid and trimetazone belong to the most effective of the entire series of antirheumatics tested.


[On the biological characterization of the outbred strain of Chbb : NMRI (SPF) mice / 1st comm.: Characterization of breeding stock under constant conditions of nutrition (Part II) (author's transl)].

The second part continued the biological characteization of the outbred strain Chbb : NMRI (SPF) (formerly NMRI/Tübingen/Kisslegg/Biberach) mice. The results obtained from 7 generations (F9 to F 15-generations) refer to the following parameters: loss of breeding animals, conception rate, ability to build a nest, litter size at birth and weaning, loss of young animals, litter weight at birth and weaning, intervals between two births and efficienty quota.


Carrageenin-induced arthritis. II. Effect of intraarticular injection of carrageenin on the synthesis of proteoglycan in articular cartilage.

An inflammation of the periarticular tissue induced by the intraarticular injection of carrageenin caused a 40-75% decrease in the rate of proteoglycan synthesis in the articular cartilage. This decrease was determined both in vitro and in vivo. Provided that the collagen network of the cartilage was not disrupted, the chondrocytes were able to recover this synthetic ability and exhibited rates of synthesis above those of the controls. This ability resulted in a net replacement of the proteoglycan lost during the initial period of inflammation.


[Studies on pharmacokinetics and biotransformation of ipratropiumbromide in man (author's transl)].

Studies into the human pharmacokinetics of (8r)-3alpha-hydroxy-8-isopropyl-1 alphaH, 5 alphaH-tropanium-bromide- (+/-)-tropate (ipratropium bromide, Sch 1000, Atrovent) following inhalation and oral and i.v. administration are described. The substance was labelled with 14C. The plasma level (total radioactivity) recorded following oral administration was characterised by a low but broad plateau persisting for several hours. After i.v. injection rapid elimination from the plasma was observed in the first phase. The plasma level following inhalation was characterised by an initially rapid absorption and the curve subsequently resembled that following oral administration. An equi-bronchodilatory dose following inhalation produced a blood level 1000 times lower than those following oral dosing. The half-life of elimination lay between 3.2 and 3.8 h for all routes of administration. The maxima were recorded at 3 h. Cumulative renal excretion was 9.3% following oral administration, 72.1% following i.v. route and 3.2% after inhalation. 88.5% were excreted via the faeces following oral dosing, 6.3% following i.v. application and 69.4% after inhalation. Ipratropiumbromide is partly metabolised. After 4 h, the percentage of unchanged substance in relation to total activity in the urine was 24% (oral), 46% (i.v.) and 13% (inhalation). One of eight metabolites-- six in very small amounts-- was identified as N-isopropyl-methyl-nortropiumbromide.


[On the problem of Side Effects of Anticholinergic Drugs Depending on the Route of Application/Inhalation versus intravenous injection of ipratropiumbromide].

In four different trial series the effect of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH, 5alphaH-tropanium-bromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) on the stimulated salivary secretion and pulse rate in a total of 43 healthy volunteers was investigated in a cross-over comparison using atropine sulphate and placebo administered by inhalation (metered dose inhaler) and by i.v. injection. All the trial preparations were administered in increasing doses at 30-min intervals in a double-blind procedure. The maximal dose by inhalation in this context was 2.4 mg (60 times the single therapeutic dose), and the maximal i.v. dose was 0.28 mg. The stimulated salivary secretion was not influenced by doses up to 2.4 mg of ipratropiumbromide by inhalation. Following inhalation of 1.6 mg and 2.4 mg atropine sulphate by means of metered dose inhaler of linear, statistically significant inhibition of stimulated salivary secretion was observed (p less than 0.001). Following i.v. administration of ipratropiumbromide, a statistically significant decrease in stimulated salivary secretion was observed following a total dose of 0.28 mg (p less than 0.001). Following inhalation the changes in pulse rate all occurred within the placebo or confidence limits. Following i.v. administration the pulse rate showed a statistically significant increase after a total dose of 0.28 mg. Dryness of the mouth was observed by several volunteers following the maximum dose of ipratropiumbromide, All volunteers in this trial series observed dryness of the mouth inhalation of atropine sulphate.


[Short Communication: Rotation-viscosimetric determinations of the effect of ipratropiumbromide on bronchial excretion/a double blind study].

In a double blind cross-over study using randomized selection the effects of 3 x 2 puffs (8r)-3alpha-hydroxy-8-isopropyl-1aH, 5aH-tropaniumbromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) (0.02 mg per puff) from a metered dose inhaler were compared with placebo in 25 patients. The parameters studied were the amount of morning sputum, sputum viscosity as measured by rotational viscosimetry and total airways resistance (Rt) measured by whole-body plethysmography during 2 successive treatment periods, each of 5 days, sepraated by 2 rest days. The patient material consisted of 16 males and 9 females, ages 21-66 (mean 47), 15 of whom had bronchial asthma and 10 chronic bronchitis. Both groups received multiple supplementary viscosity or volume but the Rt was significantly decreased by 11-15% only after ipratropiumbromide when measured 10 min after inhalation. Non-characteristic side effects occurred with equal frequency in the ipratropiumbromide and placebo groups. Therefore ipratropiumbromide has a clear bronchospasmolytic action without secretion-inhibiting properties if used in therapeutic dosage.


[Ipratropium bromide in controlled clinical trials. Short communication (II): Time-response measurements of pulmonary function after ipratropium bromide and isoprenaline].

(8R)-3alpha-Hydroxy-8-isopropyl-1alphaH, 5alphaH, 5alphaH-tropaniumbromide (+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) was compared with isoprenaline in a cross-over study with randomized selection in 12 stable asthmatics, using total airways resistance (Rt) measured by whole-body plethysmography, peak expiratory flow (PEF) and pulse rate as parameters. 2 puffs ipratropiumbromide (0.02 mg per puff) or isoprenaline (0.1 mg per puff) were administered by metered dose inhaler and measurements taken at 5, 20, 35, 50, 90 min, 2, 3, 4, and 6 h later. Drugs were given on alternate days. Rt decreased significantly (p less than 0.001) for 4 h to 53% of the initial value after ipratropiumbromide and to 70% of the initial value after isoprenaline, but only for about 2 h after the latter. The maximum 20-min effect on Rt was almost the same for both drugs. The difference in the time course of the bronchodilation was also significant. The rise in PEF after 4 h following ipratropiumbromide was similarly highly significant (p less than 0.001); as for Rt the time course for both drugs ran nearly parallel. Neither substance caused a significant rise in pulse rate at the dosages used.


[Ipratropium Bromide, an Anticholinergic Bronchodilator/Behavior of airways resistance in patients with reversible respiratory obstruction following inhalation of various doses of ipratropium bromide].

A dose- and time-response study using different doses of an inhaled derivative of atropine, (8r)-3alpha-hydroxy-8-isopropyl-1 aH, 5aH-tropaniumbromide-(+/-)-tropate (Sch 1000, ipratropium bromide, Atrovent) was performed in 12 patients with reversible chronic obstructuve airways disease. The drug was shown to be an effective bronchodilator with the typical action of reducing airways resistance with 2 puffs (0.02 mg per puff). Increasing the dose to 4 and 8 puffs did not produce any relevant difference in time response. The onset of action was rapid and reached a maximum between 30 and 60 min after inhalation. The duration of bronchodilation was maintained during the observation period of 3 h. 30 min after inhalation the results corresponded to those following the inhalation of 2 puffs of orciprenaline (0.75 mg per puff). Isolated side-effects were independent of the dosage.


[A new method for technical synthesis of tertiary and quaternary d,1-tropic acid esters of some N-subsituted nortropan- and granatan-3-oles (author's transl)].

A new technically feasible method for synthesizing atropine is described. This method can also be applied to N-substituted nortropan- and granatan-3-oles. The quaternization of these basic tropic acid ester yields new substances which have a pharmacological profile different from that of atropine. The stereoselectivity of the quanternization reaction is discussed.


[General pharmacology and secretion inhibitory action of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropanium bromide-(+/-)-tropate (ipratropiumbromide) (author's transl)].

(8r)-3alpha-Hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide-(+/-)-tropate (ipratropiumbromide, Sch 1000) is a quaternary tropic acid tropane ester with pronounced anticholinergic activities (inhibition of secretion and spasmolysis). The effect of the substance of all parasympathetically innervated organs ist 1.4 to 2 times stronger than that of atropine. As an inhibitor of the secretion of free hydrochloric acid in the stomach it proved to be 5 times more effective than atropine. Central activities were not observed. The duration of action of Sch 1000 exceeds that of atropine by far.


[The effect of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide-(+/-)-tropate ((ipratropiumbromide) on tracheobronchial spasm, bronchial and salivary secretions, ECG and heart rate (author's transl)].

At very low doses (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) and atropine inhibit acetylcholine-induced bronchospasms in guinea-pigs and dogs. The dose ratio main effect vs. most sensitive side effect (inhibition of saliva secretion) is 1:10 for i.v. injection and 1:100 for aerosol application. When both compounds are administered in a nebulized form bronchodilatation occurs immediately. The maximum effect of Sch 1000 occurs somewhat later than that of atropine but the duration of action is much longer. Bronchial secretion in guinea-pigs is increased by small doses of Sch 1000 and atropine. These doses correspond to bronchodilating doses.


[Toxicological studies on ipratropiumbromide (author's transl)].

The acute, subacute and chronic toxicity of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide (ipratropiumbromide, Sch 1000, Atrovent) was studied on mice, rats, dogs and monkeys following oral, s.c., i.v. administration and inhalation. With toxic doses all typical symptoms of atropine or atropine derivatives were present, like mydriasis, dryness of the mucosa and meteorism with coprostasis. It was not possible to determine the LC50 of the substance due to its low toxicity.


[Reproductive toxicological investigations with ipratropiumbromide (author's transl)].

In investigations of the effect of the bronchospasmolytic (8r)-3alpha-e (ipratropiumbromide, Sch 1000, Atrovent) on the reproductive function in the mouse, rat and rabbit, no teratogenic effect was demonstrated following administration by either gavage or inhalation. Extremely high dose resulted in mortality in pregnant animals and reduction in foetal birthweight. Similarly, no evidence of impaired fertility or perinatal survival due to the substance was found. Postnatal development progressed normally.


[Studies on the pharmacokinetics and biotransformation of ipratropium bromide in the rat and dog].

The pharmacokinetics of the bronchodilator (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropanium-bromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) were studied in the rat and the dog after administering radioactive material (14C). The blood level of Sch 1000 following oral dosing showed plateaus in both the rat and the dog over a period of 2--8 h following administration. Subsequent elimination from the blood occurs with a half-life of 7h (rat) and 10 (dog). The half-life of elimination following i.v. administration is 1.9 h (rat) and 3.4 h (dog). In the rat biliary excretion occurs to the extent of 3.2% following oral dosing and 17.7% following i.v. application. In the same species renal excretion is 5.5% following oral administration and 58% following i.v. administration. Renal excretion in the dog, on the other hand, averaged 28% following oral and 55% following i.v. dosing, respectively. On the basis of a comparison of the areas under the blood level curves and also from the renal excretion following oral and i.v. dosing, i.e. disregarding absorption by gastrointestinal tissue, absorption was calculated as being 12% in the rat and 38% in the dog. Absorption in the rat after 1--3 h was calculated at 17--35% including the gastrointestinal tissue. Four metabolites and the unchanged substance could be detected in the 8-h urine of the rat. In the urine of the dog, the percentage of unchanged substance fell from a maximum of 81% (after 1 h) to 20% (after 47 h) in terms of radioactivity in the urine.


[Pharmacological influence on central serotonergic mechanisms in man and its consequences on sleep (author's transl)].

Central serotonergic mechanisms were investigated in three experiments: 1. Chronic administration (four weeks) of L-5-hydroxytryptophan (L-5 HTP 600 mg/day) plus decarboxylase inhibitor (Ro 4-4602) reduces slow-wave sleep (stages 3 + 4 = SWS) without influencing other sleep parameters. 2. Clozapine reduces SWS, increases paradoxical sleep (REM) and dissociates sleep mechanisms so that increased REM in NREM stage 1 occurs. Central serotonin levels seem to remain unaffected. 3. Parachlormethylamphetamine, a serotonin synthesis inhibitor, normalises irregular sleep and narcoleptic and cataleptic attacks of narcoleptic syndrome as well. 4. Central serotonergic mechanisms are described as having a boundary-setting function.


Prognosis in unstable angina.

A retrospective study was made of 158 patients with unstable angina admitted to a coronary care unit over a 4-year period. Twenty patients (13 per cent) had myocardial infarcts while in hospital, and of these 3 died; three others died without preceding evidence of myocardial infarction. There was thus an acute mortality rate of 4 per cent. Patients with persisting angina after the first 24 hours and those without a previous history of myocardial ischaemia were more likely to develop a myocardial infarct or to die in hospital. Follow-up information, ranging from 3 to 7 years, was available in 144 of 152 hospital survivors. Patients older than 60 years (P less than 0-05), with cardiomegaly (P less than 0-01) and with pulmonary venous congestion (P less than 0-05) were found to have significantly increased long-term mortality. Long-term mortality was also found to rise with increasing coronary prognostic index. The average mortality rate for the whole group of hospital survivors was about 5 per cent per annum. Of the 111 patients who were alive at follow-up, 19 (17%) had had a myocardial infarct after leaving hospital, and a similar number had moderate or severe angina.