Effect of phosphatidylcholine vesicles on the activity of DNA polymerase-alpha. Phosphatidylcholine vesicles stimulate the activity of the DNA polymerase-alpha from calf thymus. This effect is dependent upon the way of addition to the Mg ions, and the extent of the 3H-dTTP incorporation is closely related to the concentration of the vesicles. A role of phospholipids on the activity of the DNA-related enzymes is suggested.


Temperature dependence of the fluorescence of pyrene labeled crab nerve membranes. A method, using albumin-pyrene complexes, has been developed for labeling, in a controlled manner, crab leg nerves whose excitability was preserved. The excimer-to-monomer fluorescence intensity ratio of pyrene, embedded in nerve membrane lipids and in their crude lipid extracts, is a fluidity parameter which displayed the following features with temperatures. a--a temperature-dependent increase of fluidity b--three breaks (6 degrees, 19 degrees and 37 degrees C) in the physiological medium c--In Ca++-depleted sea water, the 37 degrees characteristic temperature vanished. These breaks may reflect some lateral phase separations of the lipid components of nerve membranes. The calcium dependent temperature break may involve a segregation of acidic phospholipids while the other two breaks (6 degrees and 19 degrees C) may be due to neutral lipids phase separation. The relationship of these findings to nerve function is discussed.


[Selective screening for organic acidurias (author's transl)]. The difference between mass screening of all newborns and selective screening of certain sick newborns is defined and the characteristic clinical features of organic acidurias are outlined. According to own experiences during the last 5 years, the author pleads for the introduction of a systematically performed selective screening for organic acidurias by gas chromatography on all hospitalized pediatric patients showing symptoms suggesting inborn errors of metabolism. Two or three well equipped laboratories should be enough to cover demands for all the pediatric beds in the Federal Republic of Germany. Some results of our selective screening for organic acidurias are presented.


[Is the intake of palm oil (palmitic acid) in meals associated with the low incidence of respiratory distress syndrome in Nigeria? (author's transl)]. Comparative gaschromatographic assays of different domestic oils used in West Germany and the domestic oil (palm oil) used in Nigeria and other West African countries were performed. It was discovered that the palm oil contains extremely high amounts of palmitic acid and linoleic acid compared to the other oils used in Germany. In view of the fact that previous studies have shown that palmitic acid is required for the biosynthesis of lung lecithin, which is closely related to fetal maturation, we performed animal experiments with rabbits to determine the incorporation rate of 3H-marked palmitic acid into various fetal organs: (fetal lung, placenta, fetal liver, fetal intestine etc.) after a previous intravenous injection of the 3H-marked palmitic acid to the mother rabbit. The radiochromatogram showed high incorporation rates of palmitate into the lecithin by fetal lung and placenta. These results seem to document that the high content of palm oil in Nigerian meals can partly be related to the low incidence of respiratory distress syndrom in Nigerian premature infants.


[The effect of iron on globin chain synthesis during the first six months of extrauterine life (author's transl)]. The mechanism regulating the formation of the globin-chains of hemoglobin is unknown. We have examined the formation of the alpha-, beta- and gamma-chains during the first 6 months in 10 healthy infants. Immediately after birth the ratio between rates of synthesis of alpha- and non-alpha-chains was 0.94 +/- 0.16. At 6 weeks the ratio was alpha/gamma + beta = 1.22 +/- 0.29. After oral therapy with iron (2 mg/kg) between ages 3 and 6 months the ratio alpha/gamma + beta became 0.92 +/- 0.14. Whether the imbalance at 6 weeks is due to a depression of alpha-chain synthesis or to a stimulation of gamma-chain and beta-chain synthesis remains unclear. Possibly in infants without iron therapy the gamma-chain synthesis is stimulated as was suggested by the comparison of the gamma/beta ratios in infants with and without iron therapy.


[Micromelic type of spondylo-meta-epiphyseal dysplasia (author's transl)]. A 3 6/12 years old girl with micromelic type of spondylo-meta-epiphyseal dysplasia combined with hepatosplenomegaly and muscular hypotonia is described.


[Enteritis due to yersinia enterocolitica in children (author's transl)]. 1922 stool specimens of children aged less than 14 years were screened for enteropathogenic bacteria over the past two years. In 24 cases Yersinia enterocolitica serovar 03 and 09, respectively, was identified. 16 of them suffered from acute gastroenteritis, 8 showed symptoms of pseudoappendicitis. All patients exhibited high agglutinin titers against the respective reference strains which were maintained for up to 4 months. All isolated strains had identical sensitivity patterns against the chemotherapeutics tested. Other enteropathogenic bacteria isolated at the same time are mentioned.


[Pericarditis and lymphangioma of the mediastinum (author's transl)]. Case report of a child with pericardial effusion and septic fever. Increasing mediastinal enlargement and osteolytic lesions were obviously not caused by inflammation. Open thoracic surgery revealed a lymphangioma inaccessible to resection.


[The radiolucent esophageal foreign body in children (author's transl)]. The symptoms of radiolucent esophageal foreign bodies in small children may be predominantly respiratory with stridor and dyspnea. In a 1 3/12 years old girl who suffered from inspiratory stridor and only later from dysphagia as well this diagnosis was delayed for 2.5 months. Air in the upper part of the esophagus was the first striking roentgenologic symptom of the foreign body which was then clearly outlined by a barium swallow examination. The foreign body was a plastic lid of a candy tube.


[Nutrition in preschool and school age (author's transl)]. The results of energy and nutrient consumption surveys of 2--14 year old children in their families are described. It is shown that the average energy and nutrient consumption of an age-group is not obligatory for a single child. Based on menus the amount of the different foodstuffs for the average energy and nutrient supply of preschool and schoolchildren is demonstrated. Children receive on average, independent of their socio-economic background, a mixed diet which, in our present knowledge, guarantees a good supply with energy and nutrients. The risk factors in the modern trend in nutrition, as increasing consumption of skimmed milk and skimmed dairy products, carbohydrate rich foodstuffs of low biological value and sweetened drinks are discussed.


[Leukocyte function in colostrum (author's transl)]. Breast milk, especially colostrum was analysed quantitatively and qualitatively as well as the function of various cell types in it. The phagocyte activity of the mass of leukocytes consisting predominantly of macro- and microphages approaches the phagocyte index of leukocytes of the newborn infant, however, neither of them reaches the level of adults.--The lymphocytes traceable in a minor proportion produce secretory IgA as well as IgG.--On the basis of literary data the authors discuss the literature and their own results regarding the immunobiological significance of breast milk.


[Spontaneous secretion of growth hormone in children with constitutional delay of growth and adolescence and with early normal puberty (author's transl)]. The spontaneous secretion of hGH (plasma-hGH levels, 1/2-hourly determined) during the first 5 1/2 h of sleep was measured in 18 prepubertal children with constitutional delay of growth and adolescence (cDGA), in 14 controls (matched pairs) and 1 girl with early normal puberty (enP). The mean value of the highest individual peaks of the children with cDGA as well as their planimetrically assessed total secretion of hGH amounted to 56% of that of the controls (p less than 0.01 and less than 0.001). The girl with enP showed enhanced hGH maxima and an increased total secretion. Therapeutic trials with hGH, 10 i.u./m2/week lead to a growth velocity twice as fast as before. Treatment with a long acting testosterone preparation caused a manifold increase of the hGH-secretion.


[Colonoscopy in children and juveniles (author's transl)]. Colonoscopy, as an established endoscopic procedure in adults, is thought to be of great value in children and juveniles as well. The main indications for its use are intestinal hemorrhage, polypectomy, diarrhoea of uncertain origin, uncertain x-ray findings as well as the confirmation of a diagnosis made by biopsy. The choice of instruments used, preparations prior to the examination and premedication are dependent upon the child's age. 32 children, aged between 1--14 years, and 41 juveniles between 15 and 18 years were examined. Most common diagnoses were Crohn's disease (29), polyps (7) and ulcerative colitis (4). Others were unspecific colitis (3), follicular hyperplasia of the terminal ileum (2), lymphangiectasia (2), one hemangioma and one rectal ulcer. In 24 patients endoscopy revealed nothing pathological within the colon. Examinations should be performed only by skilled endoscopists with special experience of the problems of colonoscopy in children.


[Idiopathic hypercalciuria due to primary decrease in the renal tubular reabsorption of calcium. Hypercalciuria type 2 according to Bordier (author's transl)]. A persistent hypercalciuria and normal serum levels of calcium were measured in a 5-year-old boy suffering from recurrent macro- and microhaematuria and bilateral nephrolithiasis (stone analysis was positive for calcium-oxalate). No growth retardation or any other relevant clinical parameters concerning hypercalciuria e.g. vitamin D-intoxication or renal tubular acidosis could be observed. A slight secondary hyperparathyroidism and increased calcium excretion during fasting or calcium depleted diet indicates a primary failure of calcium reabsorption as previously described by Bordier (hypercalciuria type 2). Treatment with a combination of hydrochlorothiazide (Esidrix) and sodium chloride depleted diet resulted in a long-lasting normalization of calcium excretion and thus disappearance of symptoms in the child.


[Idiopathic osteolysis type Hajdu-Cheney in early childhood (author's transl)]. Severe clinical and radiological signs of the rare idiopathic osteolysis, type Hajdu-Cheney were manifest in a seven year old girl. A peculiar aspect of her face was evident since birth. The acroosteolysis and a general osteoporosis were radiologically visible when she was three years old. During the following 4 years there was a fast progression of the bone abnormalities and the shape of the skull became dolichocephalic.


Host-cell reactivation of UV-irradiated adenovirus in Cockayne syndrome. Measurements of the host-cell reactivation (HCR) of mutagen-treated virus provides a very sensitive tool for detecting abnormal DNA repair. The best example of the utility of HCR studies in the examination of the DNA-repair capacity of human cells has come from studies of cells from the UV-sensitive repair-deficient xeroderma pigmentosum (XP) patients. We have examined the HCR of UV-treated adenovirus type 5 (Ad5) and type 2 (Ad2) in cells from patients with Cocayne syndrome (CS), another sun-sensitive syndrome whose cells also exhibits UV-sensitivity in culture. Comparisons with obligate heterozygotes and normal controls failed to reveal an abnromality in the HCR capacity of the CS cells. As the abnormality in DNA metabolism in CS appears to be in a late step in excision repair, a bypass mechanism may exist in these cells for circumventing the defect in the repair of viral DNA.


Enhancement by transition metals of unscheduled DNA synthesis induced by isoniazid and related hydrazines in cultured normal and xeroderma pigmentosum human cells. In combination with transition metals (Mn(II), Cu(II), and Fe(III)), isoniazid and related hydrazine compounds induced unscheduled DNA synthesis (DNA repair) in cultured human fibroblasts. Manganese at 10(-5) and 10(-4) M strongly enhanced DNA repair induced by isoniazid, iproniazid, nialamide and hydrazine. Peak levels of DNA repair occurred at 5 x 10(-4)--10(-3) M of the 4 hydrazine compounds. Copper caused less enhancement of DNA repair while iron had no detectable effect. Without added metal, unscheduled DNA synthesis was not observed in cells treated with any of the 4 freshly-prepared hydrazine compounds. However, following preincubation in medium for 6--12 h, isoniazid alone at high concentrations (10(-2) M--10(-1) M) induced DNA repair. With isoniazid/manganese mixtures, preincubation did not further enhance DNA repair except at low concentrations of isoniazid (2--5 x 10(-4) M). Catalase reduced the DNA damage caused by preincubated isoniazid and by the isoniazid/metal mixtures. Exposure of repair-deficient xeroderma pigmentosum cells to isoniazid plus manganese resulted in a DNA-repair profile similar to that of normal cells. The results are consistent with hydrogen peroxide being a critical intermediate for the production of free radicals which cause the observed DNA damage.


In vivo induction of sister-chromatid exchanges in liver and marrow cells by drugs requiring metabolic activation. A highly sensitive method for the detection of in vivo induction of sister-chromatid exchange (SCE) has been developed in mice subjected to partial hepatectomy. SCE induction by either acetylaminofluorene (AAF) or cyclophosphamide, drugs requiring metabolic activation, is significantly greater in both regenerating liver and bone-marrow cells of partial hepatectomized animals than in marrow cells of unhepatectomized mice. These experiments have confirmed the ability of AAF, a well known mutagen-carcinogen, to induce SCE formation, even though the cytogenic effects of this drug on non-hepatectomized mice is very small. The in vivo system described has demonstrated the influence of the liver on drug-induced damage to extra-hepatic tissues. The procedures developed should facilitate the detection of drug-induced cytogenic damage and permit the comparison of inter-tissue differences in SCE induction with tissue-specific differences in drug-activation pathways.


Cytogenetic effects of methotrexate on human cells in vivo: comparison between results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test. Cytogenetic studies were performed in 22 patients treated with methotrexate (MTX). In some patients, metaphases from both bone-marrow cells and peripheral blood cells were studied. In the bone-marrow preparations an increased number of structural chromosomal aberrations was present, whereas abnormalities were not observed in the peripheral blood cells. An examination of the bone-marrow chromosomes must therefore be included in the study of the possible chromosome-breaking effect of chemical agents. The results obtained with the micronucleus test and chromosome studies were compared in 10 patients treated with MTX. The micronucleus test was more sensitive than the chromosome analysis as regards the clastogenic effect of MTX.


Sister-chromatid exchanges in oral contraceptive users. The effect of the use of an oral contraceptive on the frequency of sister-chromatid exchanges (SCEs) was investigated. Oral contraceptive users showed significantly higher mean SCE per cell compared with both normal and pregnant women. This result obviously means an increased mutagenic environment in these cells--due either to the pill itself or to a metabolite(s).


Chromosomal aberrations in bone-marrow cells of mice given a normal or a calcium-deficient diet supplemented with various heavy metals. Mice kept on a normal (1.1% calcium) or low-calcium (0.03%) diet were exposed for one month to zinc chloride (0.5% Zn), lead acetate (0.5% Pb) or cadmium chloride (0.06% Cd) or to a mixture of these salts at half the above concentrations. These concentrations, given in a poor calcium diet, represent an LD 50/30 days. After the mice were killed bone-marrow cells were assayed for chromosomal aberrations, and serum calcium was determined. Chromosomal aberrations were detected in the mice maintained on a low-calcium diet and exposed to lead, zinc or a mixture of lead, zinc and cadmium. The possible mechanism for the synergistic action on genetic effects of the lack of calcium and intoxication by heavy metals are discussed, and it is recommended that routine attention be given to the state of calcium metabolism in heavy-metal intoxication.


Induction of unscheduled DNA synthesis in mouse germ cells following 1,2-dibromo-3-chloropropane (DBCP) exposure. Acute toxicity studies of 1,2-dibromo-3-chloropropane (DBCP) in mice demonstrated that the respective LD50 values for prepubertal and adult male mice were 180.7 mg/kg (154.0-197.5 mg/kg body weight) and 123 mg/kg (100.5-141.5 mg/kg body weight) which were significantly different. The slopes of the dose-response curves (1.2) were steep and essentially the same, indicating a narrow margin of safety. A single maximally tolerated dose of DBCP (100 mg/kg) administered intraperitoneally to prepubertal male mice induced significant unscheduled DNA synthesis in the premeiotic germ cells but not in spermatozoa.


On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males. The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I.  12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations per cell were estimated as 0.1, 0.16 and 0.2 for the 4 applied doses illustrating a dose-response relationship for the doses: 1, 2 and 4 mg, whereas with the higher dose, 6 mg, an abrupt decrease was apparent (0.05). This study calls for concern regarding the possible genetic hazards this drug may impose upon human populations.


Mutagenicity of metal cations in cultured cells from Chinese hamster. The mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) locus in Chinese hamster V79 cells induced by metal cations were examined by the development of resistance to 8-azaguanine (8AG). The spontaneous frequency of 8AG resistance was 5.8 per 10(6) cells, and the frequency was enhanced to 2-6 times that of the control by treatment of cells with the chlorides of beryllium and manganese. About 75% of 8AG-resistant colonies were sensitive to amethopterin, and 86% of the resistant colonies showed less than 3% of the HGPRTase activity of the wild-type cells. The mutant frequency in cultures treated with cobalt and nickel chlorides were slightly increased, and mutation induction was only detectable at very low rates of cell survival.


Amosite, chrysotile and crocidolite asbestos are mutagenic in Chinese hamster lung cells. Chinese hamster lung cells cultured in the presence of amosite, chrysotile or crocidolite displayed inhibition of cell growth. Phagocytosis of asbestos by cells was observed. Amosite and chrysotile appeared to be twice as toxic as crocidolite based on an equal weight/volume basis. Induction of 6-thioguanine resistance was studied. After treatment at 10 microgram/cm2 for 24 h, and with a 48-h expression time, numerically the cells did not change significantly from 6-thioguanine-sensitive to 6-thioguanine-resistant for each pair of control and experimental mutation frequencies. When all data points were considered as a whole, use of Student's t-test on paired samples showed that all 3 types of asbestos were mutagenic in Chinese hamster lung cells. It was reported that benzo[a]anthracene was an organic contaminant of abestos. Used as a positive control compound, 7,12-dimethylbenz[a]anthracene was metabolized by rat-liver microsomes and was found mutagenic in Chinese hamster lung cells. Microsome activation did not increase the mutagenic potential of asbestos. These findings point to the weak mutagenic potential of asbestos. Chinese hamster lung cells phagocytize particles and are ideal materials to study mutagenesis of environmental agents that exist in a particulate form.


The afferent influence on the voluntary firing range of individual motor units in man. The firing ranges of 50 normal anterior tibial or short toe extensor motor units in sustained isometric voluntary contraction were studied in electromyographic recordings. The afferent inflow was decreased by compression of the sciatic nerve, thereby blocking large afferents before alpha efferents. Motor units with low minimum and low maximum rates before blockade had higher minimum and maximum rates before blockade had a lower minimum but an unchanged maximum rate on blockade. The firing range recorded for both types of motor unit on blockade was also recorded for all tonically firing motor units during early reinnervation after traumatic lesion to the muscle nerve in 14 patients. It is concluded that both facilitating and inhibiting proprioceptive afferent activity is involved in the differentiation of motor unit firing ranges in sustained isometric voluntary contraction.


Thenar hypoplasia with associated radiologic abnormalities. We report on five patients who presented with unilateral or bilateral hypoplasia of the thenar eminence. X rays of the affected limbs showed varying degrees of malformation and underdevelopment of the thumb phalanges and first metacarpal bone, and of the carpal bones at the base of the thumb, indicating a developmental abnormality. Our electrodiagnostic findings were compatible with this interpretation. We suggest that this condition is part of the clinical spectrum of radial club hand (radial dysplasia) and that when seen in adults, its recognition is important in the differential diagnosis of carpal tunnel syndrome.


F waves in patients with hand wasting caused by a cervical rib and band. In five patients with unilateral wasting of the hand muscles as a result of cervical rib and band, F waves were recorded from the hypothenar muscles following stimulation of the ulnar nerve at the wrist. Twelve healthy control subjects were also examined. F-wave latency was consistently increased in the affected hands of the patients, compared with results from the unaffected and control hands. This increase persisted after removal of the cervical band in four patients and was thought to be mainly due to degeneration of fast-conducting fibers. In the fifth patient, F-wave latency decreased after operation, suggesting recovery of a local conduction block in the proximal part of the nerve.


Split genes and muscular dystrophy.

Split genes and muscular dystrophy. Recent developments in molecular biology have shown that some genes are split into segments, each coding for part of a protein. The intervening segments are transcribed but later excised, and the messenger RNA is spliced back together again before translation into protein begins. Abnormalities in the nontranslated segments would not be reflected in abnormal protein structure but, presumably, in the control of syntehsis of a particular protein. The muscular dystrophies may be an example of this class of disease. They are particularly amenable to investigation of this idea because muscle produces large amounts of relatively few proteins, facilitating isolation of the appropriate messenger RNA.


Evoked responses of the elbow flexors in control subjects and in myopathy patients. Electrical and mechanical responses were evoked in the elbow flexors (EFs) of normal subjects and myopathy patients by maximal stimulation of the musculocutaneous nerve by a wire electrode in the axilla. In normals, the decrement in the mechanical responses during short trains of twitches was small (10%). The potentiation during a staircase decreased with increasing frequency of stimuli, but the potentiation 30 sec after the 100-sec staircase was the same at all frequencies. Posttetanic potentiation was twice as large as the maximal potentiation attained during the staircase. The staircase phenomenon probably results from two opposing events, diminution and potentiation. Findings in 11 patients with myopathy varied according to the severity of involvement. Slight weakness of the EFs was associated with an increased twitch:tetanus ratio, decreased tetanic tension, and decrease in the staircase and posttetanic potentiation. Additionally, severe weakness of the EFs was associated with a diminution in twitch tension.


A new regional curare test of the elbow flexors in myasthenia gravis. Electrical and mechanical responses of the elbow flexors (EFs) and the adductor pollicis muscle (ADP) were evoked in 31 patients with myasthenia gravis (MG). Thirteen patients with moderate or severe involvement showed a decrement during trains of repetitive stimuli in both muscle types, greater in the proximal ones than in the distal one. Seven of 18 patients with mild generalized or ocular MG showed abnormalities in the EFs, and 4 patients showed abnormalities in the ADP. A regional curare test was performed in the EFs of 11 patients with borderline or no abnormalities in the EFs and the ADP. All patients were more sensitive to curare than were control subjects; in 2, a decrement outside the range of controls could only be provoked in the partly curarized muscle during posttetanic exhaustion. Excitation-contraction coupling, as evidenced by the staircase phenomenon and after correction for blackade of fibers, was abnormal in 5 of 31 patients in the EFs, and in 11 patients in the ADP. In both muscles, the action potential was a more sensitive criterion of abnormality than the mechanical response. The decrement in the action potentials during 3/sec stimuli gave the largest diagnostic yield.


Role of plasma membrane defect of skeletal muscle in malignant hyperthermia. Halothane, at clinical concentrations, depolarizes the plasma membrane of skeletal muscle from Poland China pigs susceptible to malignant hyperthermia but does not affect the resting membrane potential of muscle from normal poland China pigs, mice, or frogs. The depolarization is reduced or partially reversed in the presence of dantrolene sodium. We suggest the possibility that malignant hyperthermia may be initiated by this abnormal depolarization of skeletal muscle by halothane.


Recurrent hypoglycemia associated with glutaric aciduria type II in an adult. Repeated episodes of hypoglycemia accompanied by elevated serum concentrations of free fatty acid without ketosis, fatty infiltration of the liver, hepatic dysfunction, and proximal myopathy in a 19-year-old woman, prompted us to analyze her urine for organic acids. Greatly increased quantities of glutaric acid, ethylmalonic acid, dicarboxylic acids with six to 10 carbons, and isovalerylglycine were consistently found in her urine. The ability of cultured skin fibroblasts from the patient to oxidize [1(-14)C]butyrate and [2(-14)C]lysine was reduced. These urinary and in vitro findings indicated defective activity of several acyl coenzyme A dehydrogenases, including glutaryl, isovaleryl, and butyryl coenzyme A dehydrogenases -- establishing a diagnosis of glutaric aciduria Type II. Carnitine concentrations in the skeletal muscle and liver were moderately reduced, but carnitine deficiency was considered a secondary biochemical abnormality. Although glutaric aciduria Type II has previously been described only in a neonate, the disease must be considered in the differential diagnosis of hypoglycemia in adults.


[Mass spectroscopy-gas cromatographic identification of chlorinated hydrocarbons in trout]. The PCB-content and the content of chlorinated hydrocarbons in trout was examined by GC-MS. PCBs ranging from trichlorobiphenyls to hexachlorbiphenyls, chlordan, DDE, DDD, DDT and dieldrine were found and identified by mass spectrometry. We suppose that less chlorinated PCBs in trout are not deposed or will be excreted very quickly.


[Determination of residues of the fungicide benzimidazole carbamic acid methyl ester and its metabolites 2-aminobenzimidazole and benzimidazole]. The authors describe a method for extracting and determining benzimidazole carbamic acid methyl ester (MBC) in the presence of its metabolites 2-aminobenzimidazole and benzimidazole. The determination is performed thin-layer and paper chromatographically using visual spot comparison. A sensitive biological method is employed for the detection of MBC. The metabolites are assayed by chemical procedures. The smallest amounts of residues that the authors could detect were: 0.01 p.p.m. of MBC and approximately 0.2 p.p.m. of the metabolites, the recovery rate ranging from 70--85%.


[Enzymatic determination of glucose and saccharose in selected dietetic foods]. The need to enlarge the offer of dietetic foods requires more sensitive methods for the determination of certain food constituents. Thus, the exact estimation of glucose and saccharose in foods for diabetics is of particular importance. The enzymatic determination of the two sugars is suited for these purposes. The enzymatic method used by the authors is described. On the basis of results from their own investigations, the authors compare the values yielded by the enzymatic method with those obtained by means of the Luff-Schoorl procedure. The differences observed were more or less great from one food to another.


[Contamination of foods and feeding stuffs from selected areas of the Erfurt district with lead and cadmium. I. Determination of lead and cadmium in vegetable material by inverse voltammetry]. An inverse voltammetric method is used for determining the trace elements lead and cadmium in vegetable foods and feeding stuffs. The organic meterials are mineralized by nitric acid vapour and, in the second stage, with the addition of perchloric acid. The procedure is very sensitive and suited for routine work. The detection limits are: 0.66 ng/ml for lead, and 0.30 ng/ml for cadmium. The error of the method is: VPb = 20.5% and VCd = 28.6%. The respective recoveries of amounts of lead and cadmium added to the samples prior to digestion were: 102.0 +/- 10.8% and 101.6 +/- 11.4%.


Molecular structure of a left-handed double helical DNA fragment at atomic resolution. The DNA fragment d(CpGpCpGpCpG) crystallises as a left-handed double helical molecule with Watson-Crick base pairs and an antiparallel organisation of the sugar phosphate chains. The helix has two nucleotides in the asymmetric unit and contains twelve base pairs per turn. It differs significantly from right-handed B-DNA.


Non-retinotopic arrangement of fibres in cat optic nerve. Fibres in the mammalian optic nerve are generally thought to be organised retinotopically. Recording electrophysiologically from the cat optic nerve, we found little evidence to support this notion, which led us to investigate the problem by anatomical methods. We made a localised injection of horseradish peroxidase into the lateral geniculate body of the cat, labelling a small clump of retinal ganglion cells and their axons in the optic nerve. These fibres, emanating from neighbouring cells in the retina, became widely scattered through the optic nerve, indicating that retinotopic order is essentially lacking.


A central role for denervated tissues in causing nerve sprouting. One of the oldest known forms of neuronal plasticity is the ability of peripheral nerves to grow and form functional connections after damage to neighbouring axons. Yet the source of the signal which elicits this "sprouting" remains unknown. In mammalian muscles, paralysis-which gives rise to many of the changes which occur in denervated muscles-causes motor nerve terminals to sprout. Could the inactive muscle fibres (rather than nerve degeneration products, another likely source) be responsible for some of the sprouting found in partial denervation? We confirm in this paper that direct stimulation of a partially denervated muscle inhibits sprouting and show that stimulation does so by activating the denervated fibres. Consequently after partial denervation the same signal as that which causes terminal sprouting in a paralysed muscle is able to spread from the denervated muscle fibres to the nerves on the innervated fibres and initiate terminal sprouting.


Competition between foreign and original nerves in adult mammalian skeletal muscle. It is well established that a normally innervated, uninjured mammalian skeletal muscle does not accept further innervation from a foreign nerve transplanted on to the muscle's extrasynaptic region. Because synapse formation under these circumstances would require the induction of new postsynaptic specialisations, it is not clear whether foreign axons could make connections if they were allowed instead to compete for existing synaptic sites. The capacity of individual endplates to accept multiple inputs has in fact been demonstrated during both normal development and reinnervation of adult mammalian muscle, that is, in conditions involving interactions among recently formed synapses. We report here that even in adult muscles whose normal innervation remains fully intact, a similar susceptibility to further innervation can be expressed following appropriate placement of a transplanted foreign nerve. Moreover, the establishment of foreign synapses can lead to suppression of original inputs.


Contractile force measured in unskinned isolated adult rat heart fibres. A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.


Suppression of natural antitumour defence mechanisms by phorbol esters. Chemical carcinogenesis in certain tissues occurs in at least two stages: initiation, producing irreversible tissue alterations, and promotion (by agents, themselves non-carcinogenic), enhancing the outgrowth of transformed cells. Among the various tumour-promoting compounds isolated from croton oil, phorbol-12-myristate-13-acetate (PMA), is the most potent. Cell culture studies have shown that the phorbol diesters and structurally related substances induce a variety of dramatic changes in diverse eukaryotic cells. Spreading, differentiation, metabolism, DNA synthesis, expression of cell surface glycopeptides, deoxyglucose transport, as well as polyamine, plasminogen activator and ornithine decarboxylase activity are altered. These findings indicate that tumour promoters potentiate expression of the transformed phenotype in cells already malignantly transformed and also induce reversible manifestations of the transformed phenotype in normal cells. It is not known whether these agents additionally influence host effector systems involved in antitumour resistance. The present study is concerned with the effects of PMA on spontaneous in vitro cytotoxicity by macrophages and/or natural killer (NK) cells, and on the resistance to rat fibrosarcoma in vivo considered to depend on these normal effectors, in particular on mononuclear phagocytes.


Glucocorticoid hormones inhibit DNA synthesis and enhance interferon production in human lymphoid cell line. Although buffy coat leukocytes have been the prime source of human interferon, cells of the Burkitt lymphoma line Namalwa are increasingly used for the large scale production of interferon. On induction with Sendai virus or Newcastle disease virus, Namalwa cells produce a substantial quantity of interferon which contains predominantly the leukocyte antigenic species and minor amounts of fibroblast-type interferon. We have recently demonstrated that inducers of erythropoietic differentiation in Friend cells are able to enhance interferon synthesis in Namalwa cells when added to cultures larger than or equal to 24 h before interferon induction by Sendai virus. The most potent compounds, n-butyrate, stimulated interferon production about 30-fold and has also been independelty described by others. All active compounds inhibited DNA synthesis in Namalwa cells and the extent of inhibition apparently paralleled the stimulatory potency of the respective compound. Induction of differentiation of Friend cells can be antagonised by various steroid hormones, which by themselves have no measurable effects on these cells. In contrast, we report here that glucocorticoid hormones inhibit DNA synthesis in Namalwa cells and augment Sendai virus-induced interferon synthesis.


Shear-induced concanavalin A agglutination of human erythrocytes. The mechanism by which cell suspensions are agglutinated by plant lectins remains obscure. The agglutination of a particular cell line in the presence of a specific plant lectin probably depends on several factors including the number and valence of lectin molecules bound to the cell surface, the mobility of receptor molecules in the membrane, the surface morphology and charge and the metabolic state of the cell1-6. The assay system used to assess cell agglutination also seems to be important, since many laboratories studying the same agglutination reaction have reported dissimilar or contradictory results. To provide further information on the molecular mechanism of agglutination we have begun a systematic study on the aggregation of human red cells by the lectin concanavalin A (Con A). By using an adaptation of our previously described aggregation assay which provides a continuous measure of both the rate and degree of intercellular adhesion in the presence of controlled shear forces, we have found that the agglutination of erythrocytes by Con A can be resolved into three stages, two of which are observed only if the system is exposed to shear.


Diethylcarbamazine enhances antibody-mediated cellular adherence to Brugia malayi microfilariae. Treatment with the antifilarial drug diethylcarbamazine (DEC) results in a rapid decline in the number of microfilariae circulating in the blood of infected hosts. DEC induces morphological changes in the surface layers of microfilariae, but these alterations alone are probably insufficient to cause the death of the parasite, because the drug fails to reduce microfilaraemia in animals lacking filarial antibodies, and also does not shorten the survival of microfilariae in vitro. The effect of DEC in vivo is thought to result from the trapping of microfilariae in the liver, where they undergo lysis.


Genomic rearrangements correlated with antigenic variation in Trypanosoma brucei. The capacity of African trypanosomes to express sequentially a large repertoire of different surface antigens during an infection enables the parasite to evade the immune response of its host, and makes attempts to produce a vaccine against the disease difficult. It is evident that point mutations cannot account for antigen diversity. Variable antigens like immunoglobulins are derived from an extensive family of genes of which only one is expressed in a given cell. As somatic tic recombination is involved in the immunoglobulin gene system, this similarity prompted us to search for somatic rearrangements in trypanosome variable antigen genes. We have constructed a recombinant plasmid containing approximately half the DNA sequence coding for a Trypanosoma brucei variable antigen and hybridised the inserted sequences to various restriction enzyme digests of nuclear DNA from different trypanosome clones. Differences in the sizes of restriction tion fragments hybridising to the inserted variable antigen coding sequence show altered positions of enzyme sites relative to this sequence, indicating different arrangements of DNA sequences around this gene in different trypanosome clones.


Acetylcholine synthesis by mesencephalic neural crest cells in the process of migration in vivo. Specific to the vertebrate embryo, the neural crest is a transitory structure whose constituent cells migrate extensively through the developing animal and ultimately give rise to many distinct cell types, including the components of the peripheral nervous system. The earliest clear indices of their differentiation have so far been detected only when cells from the crest have reached their destination. This is exemplified by the acquisition of the ability to synthesise and store catecholamines; absent from crest cells before and during their dorso-ventral migration, this ability appears concomitantly with their aggregation into the primary sympathetic ganglia. The chronology of cholinergic maturation, however, is less well defined. Appropriate biochemical markers are demonstrable as soon as parasympathetic or enteric ganglia are formed, but the lack of a suitable cytochemical method is a major obstacle to the identification of any cholinergic cells before then. Although acetylcholinesterase (AChE) is present in migrating neural crest, choline acetyltransferase (CAT), the enzyme catalysing acetylcholine (ACh) synthesis, is a much more relevant correlate, and definitive evidence for cholinergic differentiation should include the demonstration of ACh-synthesising activity in intact cells or their extracts. We show here that neural crest, as soon as it begins migration, can synthesise ACh.


Incorporation of inositol hexaphosphate into intact red blood cells. I. Fusion of effector-containing lipid vesicles with erythrocytes. Fluid charged lipid vesicles loaded with an inositol hexaphosphate solution were used to transport this allosteric effector into human intact red blood cells. Rate and extent of uptake of the vesicles and of the effector by the red blood cells were measured as changes in the O2 half-saturation pressure and the 31P-NMR spectra of the intracellular inositol hexaphosphate-haemoglobin complex.


Single ionic channels observed in tissue-cultured muscle. The extracellular patch clamp technique developed by Neher et al. to record the responses of single channels in skeletal muscle has provided firm evidence for the two-state nature of the conductance event in nicotinic endplate channels. We report here the use of the extracellular patch technique to record single-channel responses from tissue-cultured chick skeletal muscle cells. The temperature dependence of channel conductance and gating kinetics shows no evidence of discontinuous behaviour between 17 and 37 degrees C.


Single postsynaptic channel currents in tissue cultured muscle. Some of the most compelling evidence for the existence of ionic channels in cell membranes comes from direct recording of quantised current jumps generated by the opening and closing of individual channels. Single-channel jumps have been extensively studied for lipid bilayer membranes doped with various channel-forming additives. Recently agonist-induced single-channel currents were detected in denervated frog muscle by use of extracellular electrodes, which can isolate the current from a small area of membrane. The current jumps provide a means for the direct test of many of the inferences about ionic channels which have come from electrical noise analysis. In this report we present measurements of single-channel currents induced by the agonist carbamylcholine in tissue-cultured mammalian muscle. These measurements confirm the earlier noise studies on tissue culture preparations. Recordings of single-channel currents induced by the agonist, suberyldicholine, in avian muscle are presented by Nelson and Sachs.


X-ray crystallography of the binding of the bacterial cell wall trisaccharide NAM-NAG-NAM to lysozyme. Hen egg white lysozyme was the first enzyme whose structure was determined by X-ray crystallography. The proposed mechanism based on this structure involves the distortion of the saccharide residue (2-acetamido-2-deoxy-D-muramic acid, NAM) in the natural substrate (an alternating beta (1 leads to 4) linked oligomer of 2-acetamido-2-deoxy-D-glucose (NAG) and NAM residues) bound to site D in the binding cleft. The importance of substrate distortion has prompted numerous enzymatic, chemical, theoretical, and physical studies, but there is little direct crystallographic evidence on the conformation of a NAM residue bound at site D. We now present the X-ray structure of the non-hydrolysed trisaccharide NAM-NAG-NAM bound in subsites B, C, D. Our interpretation of the 2.5-A resolution difference map does not involve distortion of this residue in site D. Comparison with the structure of the delta-lactone derived from tetra N-acetylchitotetraose (NAG)3NAL) bound to lysozyme suggests we may be looking at a Michaelis complex.


Quasi-hexagonal molecular packing in collagen fibrils. Collagen molecules in native 66.8 nm (D) periodic fibrils are widely believed to be assembled into discrete, rope-like substructures, or microfibrils. Several types of microfibril have been proposed (2, 4, 5, 7- and 8-stranded) mainly on the basis of information contained in the medium angle X-ray diffraction patterns of native tendon fibres. These patterns show a series of equatorial and near-equatorial Bragg reflections which indicate that the collagen molecules are arranged on a three-dimensional crystalline lattice. The 4-stranded, 5-stranded and 8-stranded microfibrils are D-periodic with approximate diameter 3.8 nm, and these and the 2-stranded model are supposed to be packed on a three-dimensional lattice whose basal unit cell, (approximately) perpendicular to the fibril axis, is tetragonal (or quasi-tetragonal)with side a, a square root 2 or 2a, where a is approximately 3.8 nm. In this paper we describe a re-interpretation of the X-ray data which leads to a new model for the crystalline regions of the fibril, based on quasi-hexagonal molecular packing without microfibrillar sub-structures, and hence having the character of a molecular crystal.


X-ray diffraction from the side-by-side model of DNA. An intriguing topological problem posed by the double-helical Watson-Crick model of DNA is that of unwinding the intertwined strands during replication. Several workers have recently proposed novel side-by-side (SBS) structures for DNA. In all these models the two strands are joined by complementary Watson-Crick base pairs and the antiparallel polynucleotide strands alternate between short segments of right- and left-handed helix, thus both reducing the amount of intertwining and alleviating the unwinding problem. We show here that there are unacceptable discrepancies between the observed diffraction pattern of B-DNA and that calculated for the original SBS structure. We also describe a simple modification of this model which resolves some of the more serious discrepancies. However, the agreement is still markedly inferior to that obtained for a Watson-Crick model of DNA.


[Receptive fields of the visual cortex--detectors or filters of spatial frequencies?]. Spatial frequency characteristics of the complex cortical visual receptive field were studied in curarized cats. It is shown that, besides the main maximum, they also have additional maxima and negative regions as predicted by the theory of piecewise Fourier-analysis. Comparison of responses of the complex receptive field to sinusoidal grating entering the field completely or incompletely together with the comparison of responses to sinusoidal and squarewave gratings shows the linear properties of the receptive field as a spatial frequency filter. The response of the complex receptive field increases with the number of periods constituting the sinusoidal grating. Several periods of optimal spatial frequency matched the size of the complex receptive field. In the columns of neurons, the receptive fields were found tuned to a broad band of spatial frequencies. The data confirm the hypothesis according to which the complex receptive fields are rather spatial frequency filters than detectors.


[Habituation in the cortical division of the visceral analyzer]. Reactions of neurons without background activity ("silent" neurons) on long-lasting stimulation of mesenteric nerves were studied in cats anesthetized with chloralose 65-70 mg/kg) and paralyzed with flaxedile. It is shown that the "silent" neurons of the parietal and first projections areas are characterized by habituation during long-lasting stimulation of visceral nerves. Habituation developed faster in the parietal cortex and in the focus of maximal activity of the first somatosensory areas as compared to the second somatosensory area. The particularities of neuronal habituation in the cortex on visceral stimulation are discussed.


[Horseradish peroxidase labelled neurons of nonspecific thalamic nuclei projecting to the cat brain somatosensory zone I]. The morphology and topography of neurons whose axons form the thalamic nonspecific input to the primary somatosensory cortex were studied in the cat thalamus by the method of the retrograde transport of the horseradish peroxidase. The labelled cells were found in the dorsolateral part of the nucleus ventralis anterior, in the nucleus centralis lateralis, in the lateral part of the nucleus dorsalis medialis, in the dorsal part of the nucleus centrum medianum. A very small number of slightly stained cells were found in the nucleus paracentralis. The variety of the shape, size and intensity of labelling of the HRP-positive cells was observed in each thalamic structure. The results of the experiments indicate that not only the ventrobasal complex but also the nonspecific thalamic nuclei are projected to the primary somatosensory cortex. These data demonstrate the existence of multiple afferent thalamic inputs to the primary somatosensory cortex.


[Configuration of the electrical field of an evoked potential in in the superiod colliculus of the rabbit brain upon punctiform afferent stimulation]. Evoked potentials were studied in the rabbit superior colliculus to punctiform light stimulation of the receptive field. The evoked potentials were of negative polarity and did not show potential reversion. The depths of recordings were from 0.1 to 1 mM. The 4-6 degrees shift of the punctiform stimulus from the optimal position led to the disappearance of the evoked potential. If large (more than 5-6 degrees) or diffuse stimuli were used the evoked potentials reversed from surface-negative to deep-positive at a depth of 0.3-0.4 mM. It is suggested that the evoked potential to punctiform stimuli indicate more precisely the location of afferent synapses.


[Laminar distribution of sources of ascending spinocerebral fiber systems in the spinal cord of cats]. Cells of origin of the spinobular, spinomesencephalic and spinothalamic tracts in the cat brain were identified by the retrograde horseradish peroxidase transport technique. A conclusion is made that neurons in laminae IV and V give rise to ascending fibres to the ipsilateral dorsal column nuclei and neurons in the lateral parts of laminae V and VI and in lamina VIII establish direct connections with the contralateral thalamus (CM, MD, CL) and reticular formation of the brain stem. Throughout the spinal cord the labelled neurons were present in the intermediate zone of both sides.


[Effect of the alkaloid lappaconitine on ion currents through the somatic membrane of Helix pomatia neurons]. The effect of alkoloid lappaconitine on ionic currents through the somatic membrane of identified neurons of the mollusc Helix pomatia was studied under voltage-clamp conditions. It is shown that 4 mM lappaconitine causes a reversible blocking action on the calcium channels. Concentration exceeding 4 mM causes irreversible changes. Lappaconitine had either an insignificant or no effect on sodium currents.


[Electrophysiologic study of the properties of the cholinoreceptors of frog sympathetic ganglion neurons]. The effect of the perfusion with cholinomimetics and cholinolytics on the membrane potential and membrane conduction of the isolated frog sympathetic ganglion neurons was studied using the intracellular microelectrodes. The activation of nicotinic cholinoreceptors with carbachol, suberildicholine and tetramethylammonium evoked depolarization with an increase in membrane conduction. The activation of muscarinic receptors with carbachol and 5-methylfurmethide evoked depolarization accompanied with a decrease or less frequently with an increase in the membrane conduction. It is found that atropine caused no changes in the membrane electric parameters when used as the perfused first drug, but it caused a short-lasting depolarization with the membrane conduction increase when used after carbachol.


[Polarization and spectral sensitivity of individual house cricket photoreceptors]. Polarization and spectral sensitivities of single photoreceptors of a house-cricket were measured. Morphologically, the cricket rhabdom is a symmetric model in which the polarization sensitivity of a single photoreceptor is equal to the dichroic ratio of a single microvillus. The spectral sensitivity curves of all the photoreceptors measured (24 cells) appeared to be similar and showed the main peak of sensitivity at 500 nm and the secondary peak at 360 nm--the situation reminding properties of vertebrate rhodopsin. The polarization sensitivity measured was equal to 2.28 +/- 0.85 (mean for 70 cells +/- standard deviation). This value is in favour of small preferential orientation of the dipole moments of the pigment molecules along the microvillar axes.


[Frequency potentiation in newborn rabbit hippocampus]. Ontogenetic development of the frequency potentiation in the entorhinal afferent input of the hippocampus was studied on unanesthetized rabbits 1--15 days after birth. In the fields CA1 and CA3 of the new-born rabbits rhythmical electrical stimulation (1--20 Hz) of the perforant path led to a 20--100% increase in the amplitude of local potentials as compared to the control value and to an increase in the probability of the mass discharge response from 0--0.5 (in control) to 0.8--1.0 (during tetanization). In 1--3-day-old rabbits the potentiation was especially pronounced at frequencies of 4--6 Hz. The frequency optimum of 4--15 Hz appeared on the fifth day after birth. The frequency potentiation of the mass discharge was observed on the 8th--10th day of life. The results show that the frequency potentiation in the cortical afferent connections of the hippocampus can be recorded already in new-born rabbits and achieved the mature pattern at the beginning of the second week of the postnatal life.


[Squirrel visual cortex neurons selective for contour orientation]. The receptive field organization of orientation-selective neurons was studied in the squirrel visual cortex. Neurons with mutual inhibiting on- and off-areas of the receptive field, partially and completely overlapping excitatory and inhibitory mechanisms were observed. Neurons of the second group are the most typical. They reveal orientation selectivity if the stimuli are in the excitatory area of the receptive field, the inhibitory areas outside the excitatory area sharpen the selectivity. It is supposed that no obvious differentiation between simple and complex neurons exist in the squirrel visual cortex.


[Hypothalamic influences on the activity of superior colliculus neurons in cats]. Experimens on immobilized unanesthetized cats showed that hypothalamic stimulation effectively modifies background and evoked activity of superior colliculus neurons. Some differences in the nature of influences from different hypothalamic areas were revealed. Stimulation of the AHA and HL often caused depression of the background impulsation with initial inhibition, especially during stimulation of HL. Cyclic modulation of background activity was also revealed. The influence of these structures on the activity evoked by light was mostly of modulating character. Stimulation of the ventromedial nucleus produced both inhibitory and excitatory effects on the activity of tectal neurons with a tendency to an increased rate of the latter when using repetitive stimulation.


[Depolarization of the terminals of different groups of afferent fibers of the lumbar region of the spinal cord during fictive scratching]. Kinetics of lumbar primary afferent depolarization was investigated during fictitious scratching of decerebrated and decapitated cats. Fictitious scratching was accompanied by tonic and phasic primary afferent depolarization. Periodic depolarization of primary afferents was synphasic in different segments of the lumbosacral spinal cord. Tonic depolarization was observed in the terminals of all the investigated groups of fibres (low-threshold cutaneous and of groups 1a and 1b). Phasic changes took place in terminals of low-threshold cutaneous fibres and fibres of group 1b. Physiological significance of modulation of primary afferent depolarization by the spinal scratching generator is discussed on the basis of the data obtained.


[Effect of beta-phenylethylamine on the dopaminergic system of rat brain]. Using a quantitative fluorescence-histochemical analysis the dynamics of changes of the dopamine level in dopaminergic neurons of the nigro-neostriatal and mesolimbic systems of the rat brain was studied during an hour after intraperitoneal injection of beta-phenylethylamine (100 mg/kg). The temporary increase in the dopamine level in the terminals coincided with a sharp decrease in the dopamine level in the neuron bodies, and conversely, the depletion of dopamine in the terminals after 30 min was accompanied by an increase in the dopamine level in the neuron bodies. The obtained results enable a suggestion that the increase in locomotor activity of animals after injection of beta-phenylethylamine described in the literature is due to the effect of phenylethylamine on catecholaminergic brain systems, the dopaminergic systems in particular.


[Possibility of using an analgesic (fentanyl) for electrophysiologic studies of the cerebellar cortex]. The effect of the central analgetic, fentanyl, on evoked potentials and Purkinje cells discharges in the cerbellar cortex to stimulation either the cerebral cortex or somatic nerves were studied in nonanaesthetized cats. It was found that the analgetic dose fentanyl (10-30 microgram/kg) did not affect the evoked potentials. The fentanyl dose of 30 microgram/kg suppressed the resting discharges and responses of Purkinje cells while the dose of 10 microgram/kg facilitated them. However these effects were substantially weaker as compared with those of nembutal. Therefore fentanyl can be used for analgesia during electrophysiological study of the cerebellar cortex in nonanaesthetized cats.


[Disulfide bonds in the cholinoreceptors of frog sympathetic ganglion neurons]. The effect of dithiotreitol (disulfide bonds reducing agent) and potassium ferricyanide (oxidative agent) on the nicotinic and muscarinic receptors of frog's sympathetic ganglion neurons were studied using intracellular electrodes. Dithiotreitol inhibited the responses evoked by carbachol, suberildicholine and 5-methylfurmethide. Ferricyanide if applied after dithiotreitol increased the inhibited responses to suberildicholine and decreased those to 5-methylfurmethide. Using protectors it was shown that both acetylcholine and tetramethylammonium protected nicotinic and muscarinic receptors from the action of dithiotreitol, the acetylcholine was more effective than tetramethylammonium in the case of nicotinic receptor. It was suggested that there are disulfide bonds in the active centres of nicotinic and muscarinic receptors located in the anionic centres as well as outside of those centres.


[Activity of cerebellar fastigial nucleus neurons during the fictive scratching reflex in cats]. The activity of neurons in the rostral part of the fastigial nucleus was recorded during fictious scratch reflex (FSR) in immobilized cats. During FSR the discharge frequency of many fastigial neurons was rhythmically modulated in relation to the scratch cycle: most of them fired in bursts at the end of the flexor phase or at the extensor phase of the cycle. The firing pattern of fastigial neurons was similar during both ipsilateral and contralateral FSR. Therefore the fastigial nuclei exert bilateral influences on the brain stem structures during one-sided motor activity.


Partial reversal of the defect in intestinal calcium absorption during the course of regular hemodialysis. The coefficient of true intestinal calcium absorption (a value) was measured by a double radioisotope technique in 24 patients treated by regular hemodialysis for 2--46 months. The mean a value of these patients was significantly below normal (p less than 0.001). 18 of them were studied a second time after an interval of 12 months. Values at 12 months were higher than the corresponding initial values (p less than 0.001). There was a trend to higher a values in the patients treated for longer periods of time. It is concluded that the defect in calcium absorption tends to reverse during the course of regular hemodialysis.


Intravenous pyelography in nonuremic diabetic patients. We studied the influence of intravenous pyelography (IVP) in 40 diabetic patients with a serum creatinine level of less than 2 mg/100 ml. None of the patients experienced irreversible renal function changes but 4 patients had an early significant rise in creatinine levels (greater than 0.2 mg/100 ml). In 3 of these it was only mild, but 1 patient sustained reversible serious damage with a creatinine rising from 1.6 to 3.8 mg/100 ml. 3 of these 4 patients had evidence of renal disease with mild creatinine elevations or proteinuria. Thus, IVP is a relatively safe procedure in nonuremic diabetic patients. This is different from IVP in diabetic patients who have creatinines over 2 mg/100 ml where 76% of the patients have serious acute renal failure and this is irreversible in one-third.


Peritoneal transport of vancomycin during peritoneal dialysis. The peritoneal transport of vancomycin during peritoneal dialysis was studied in 11 uremic patients following intravenous and intraperitoneal administration of vancomycin. The half-life of vancomycin was about 18 h and the clearance of vancomycin 6.1 ml/min (range 4.2--9.8) during the period of dialysis. Following intraperitoneal administration of vancomycin 50 micrograms/ml of dialysate, serum concentrations from 5.1 to 21.5 micrograms/ml were obtained and 35% of the instilled amount of vancomycin was absorbed during 15 h of dialysis. The peritoneal transport of vancomycin indicates that the dosage should be increased during peritoneal dialysis. Peritonitis caused by Staphylococcus aureus may be treated by peritoneal dialysis with vancomycin added to the dialysate.


Glucose-enriched dialysate and tolerance to maintenance hemodialysis. 10 patients entered a controlled 4-week study to evaluate the effect of a glucose-enriched dialysate (400 mg/100 ml) on hemodialysis tolerance. Headache during and after dialysis and post-dialysis fatigue decreased in a statistically significant manner. The average glycemia was only moderately increased with an adequate insulin response. Blood cholesterol and triglycerides did not vary signifcantly during this short study period.


Effect of indomethacin on renal function and plasma renin activity in dogs with chronic renovascular hypertension. The effect of indomethacin on plasma renin activity (PRA) and renal function was examined in conscious dogs with chronic renovascular hypertension before or after volume expansion. PRA did not change following the infusion of indomethacin: PRA was 5.18 +/- 1.46 ng/ml/h during control periods and was 5.01 +/- 0.95 ng/ml/h (p greater than 0.1) after 80 min of infusion of indomethacin. Mean arterial blood pressure (MABP) was 121.6 +/- 7.4 mm Hg during control periods and was 122.0 +/- 4.6 mm Hg (p greater than 0.1) after 80 min of infusion of indomethacin. Infusion of indomethacin into these dogs undergoing diuresis did not change inulin or p-aminohippuric acid clearance. Sodium excretion (UNaV) showed slight but not signifcant decreases with the infusion of indomethacin. UNaV was 109.3 +/- 25.7 muEq/min during control periods and was 69.6 +/- 21.0 muEq/min (0.05 less than p less than 0.1) after 80 min of infusion of indomethacin. The results suggest that renin release, sodium excretion, and blood pressure in the dog with chronic renovascular hypertension in uninfluenced by indomethacin.


Intrarenal prostaglandins: effect of sodium and indomethacin on PGE2 and PGF2 alpha in rabbits. The levels of prostaglandins (PGs) E2 and F2 alpha in different parts of the rabbit kidney were determined to observe the effect of sodium and indomethacin. After the pretreatment with injections of saline or with indomethacin, tissues from inner and outer medulla and cortex were separated, extracted, analyzed for PGE2 and PGF2 alpha by radioimmunoassay. In the normal rabbit kidney, the greatest amount of PG was found in the inner medulla. Saline injections appeared to increase PGE2 (but not PGF2 alpha), especially in the inner medulla. Repeated injections of saline, on the other hand, markedly reduced PGE2 in the inner medulla but increased outer medullary PGE2. Indomethacin reduced the production of PGs in all kidney segments. These results suggest the bidirectional effect of sodium on PG concentration in the rabbit kidney. Acute administration of sodium may directly stimulate the synthesis of PGE2 in the inner medulla but chronic stimulation with sodium may alter the pattern of PGE2 synthesis.


Behavior of amikacin in renal parenchyma of normal rats and of rats with acute obstructive renal insufficiency. Aminoglycosides show a remarkable tendency to accumulate and persist in the renal parenchyma. In order to study the kinetics of this phenomenon for amikacin, rats received 25 mg/kg of this antibiotic i. p. and were sacrificed in groups of 6 up to 15 days after the injection. At 6 h, while the other organs and the serum were almost completely freed of amikacin, concentrations in the renal cortex reached 156 +/- 21 micrograms/g, or 6 times the peak serum level (instead of 20 times the peak serum level for gentamicin or sisomicin, a difference which is reduced by the fact that amikacin is given in higher dosage). They then decreased very slowly, according to a half-life of 122 h. Although it decreases glomerular filtration, ligation of ureters 20 h before the injection quadrupled the concentration in the cortex. These data explain the characteristics of the nephrotoxicity of amikacin and the increased toxic risk in acute obstructive renal insufficiency.


Mitochondrial granulation in the proximal renal tubule in uremia. Mitochondria contain electron-dense particles, partly composed of an amorphous form of calcium phosphate. We have used electron microscopy from percutaneous renal biopsy material to analyze mitochondrial granulation in the proximal renal tubule of nonuremic and uremic children. Based on a technique of cutting mitochondria from ten electron micrographs per biopsy, counting the granules in each mitochondrion and weighing the paper, we found that mitochondria of nonuremic children averaged 23.7 +/- 1.2 granules/g paper while uremic children had only 11.8 +/- 1.1 granules/g. The number of granules per gram was unrelated to the serum calcium phosphate solubility product. A significant decrease in calcium granulation in uremia can also be produced experimentally in rats. Control rats averaged 14.7 +/- 1.5 granules/g, while rats made uremic by partial nephrectomy had 6.0 +/- 0.7 granules/g. Treatment of uremic rats with a pharmacological dose of vitamin D restored granulation to normal within 24 h. The significant decrease in calcium phosphate granulation in the renal proximal tubule in uremic children and in experimental animals is probably related to the documented loss of 1 alpha-hydroxylation of vitamin D in uremia.


Clinical analysis of arachnoid cysts in the middle fossa. This paper describes the clinical picture and radiological findings of 12 cases of "idiopathic" arachnoid cyst in the middle fossa which the authors have encountered during the past 12 years. Their results are as follows. 1) The age of the patient in 10 out of 12 cases was under 15 years of age, and 8 cases were males. The site of the cyst was on the left side in 9 cases. 2) On plain skull radiography, thinning and bulging of the temporal bone by the lesion, elevation of the lesser wing of the sphenoid, and forward projection of the greater wing of the sphenoid were observed in all cases. 3) On cerebral angiography, a characteristic elevation of the middle cerebral artery and hypoplasia of its insular and opercular portion were observed; and in the venous phase, a defect of the middle cerebral vein, backward deviation of the vein of Labbé, and elevation of the vein of Rosenthal were seen. 4) On Metrizamide (Amipaque) CT cisternography, there were two types, one which communicated and the other which did not communicate with the adjacent subarachnoid space.


[Opercular aplasia (author's transl)].

[Opercular aplasia (author's transl)]. The article reports on 11 cases of opercular aplasia in patients aged 5 to 44 years. Aplasia occurred to a greater extent in the frontal operculum than in the temporal operculum, and was always associated with space-requiring arachnoidal cysts. Symphyses and obstruction of the flow of the basal CSF spaces were also seen. In 91% of the cases, the aplasia was localized on the left side, 91% of the patients were males. The patients tend to decompensate after a cerebrocranial trauma, and in many cases surgery reveals a subdural haematoma which fills the aplastic region, due to detachment of the exposed cerebral veins effecting basal drainage. In the remaining cases, surgery was performed because of general signs of cerebral compression, exacerbation of an existing disease associated with attacks, or because of the space-occupying character of the concomitant arachnoidal cysts. In patients with opercular aplasia without space-occupying arachnoidal cysts, surgery is not performed for the time being; instead, regular neurological and CT control is effected.


The protective effect of steroid treatment on lysosomal enzymes after cold lesion of the cat brain. The effect of posttraumatic steroid treatment (6-methylprednisolone) on the stability of lysosomal membranes in the cat brain is studied. The share of free activity of the lysosomal enzymes beta-glucuronidase and N-acetylhexosaminidase indicates the grade of membrane stability. The results demonstrate an increased stability of lysosomal membranes in grey as well as in white matter after posttraumatic steroid treatment. This regarded as an important aspect of the protective effects of steroid treatment in posttraumatic brain edema.


Diagnostic aid of aspiration biopsy cytology in brain lesions. In a series of 28 neurosurgical cases we tried to assess the value of aspiration biopsy cytology from brain lesions during the operation. Cytological aspirates during craniotomy were compared with simultaneously performed frozen section biopsies. Cytology was correct in 24 out of 28 cases (86%). It is concluded that aspiration cytology permits a safe microscopic diagnosis provided the specimens are cellular and representative. Cases are mentioned where this technique can be very useful and/or the only way to obtain microscopic evidence of a malignant tumour before treatment.


[Etiology of parkinsonism. A verification of Poskanzer's and Schwab's hypothesis]. It was the purpose of this work to verify the hypothesis of Poskanzer and Schwab according to which nearly all cases of parkinsonism are consequences of clinical and subclinical lethargic encephalitis in the years 1917-1926. The investigated material included 495 patients with parkinsonism treated at the neurological hospital departments in Warsaw in the years 1967-1976 and 263 patients living in the City of Warsaw and treated as outpatients or inpatients in the years 1972-1976. The control group comprised patients with amyotrophic lateral sclerosis treated in the Warsaw hospitals in the years 1967-1976. The correlation between the mean age at the time of disease onset and the calendar year of disease onset was studied in different groups of patients. The indices of disease prevalence, first visits and mortality were calculated in the group of patients living in the City of Warsaw. Low values of correlation indices and persistence of approximately unchanged indices of first visits and mortality in the years 1972-1976 failed to confirm the hypothesis of Poskanzer and Schwab.


[Cerebrovascular disorders in the urban population of Kielce: incidence and mortality in the years 1973-1974]. During 1973 and 1974 in the urban population of Kielce 528 verified new cases of cerebro-vascular disorders (CVD) were found. The average annual incidence rates reached 203 for males, 176--for females, and 189 for both sexes per (100,000) 181, 167 and 174 respectively when cases of transient ischaemic attack were excluded. The mortality rates in those cases were estimated to be 103, 82 and 92 respectively. Nearly 70 percent of all cases were admitted to neurological departments, and 14 percent remained at home. Age-adjusted incidence rates for subarachnoidal haemorrhage and cerebral embolism were three times higher, and the total incidence rate--twice higher than the rates estimated previously for the Warsaw population. It can be concluded that the incidence rates for CVD based exclusively on data from neurological departments are underestimated by at least 30 percent, and this bias varies according to the type of CVD. Prospective studies aimed toward evaluation of factors which can influence risk of development or death of CVD should be initiated.


[EEG in offspring of epileptic mothers]. In a group of 134 children of epileptic mothers abnormal EEG tracings were found in 39.6% of cases, 7 of these children (5.2%) had epileptic seizures. In 92% of cases EEG changes had the character of paroxysmal dysrythmia, and they were significantly more frequent in children aged 5 to 14 years and significantly more frequent in the children of mothers who had had epilepsy before the age of 20 years. Pathological EEG changes were more frequent in daughters than in sons, and in the daughters generalized discharges of centrencephalic type were significantly more frequent. In all families with more than two children at least one child had pathological EEG tracings.


[Neural conduction velocity in patients on hemodialysis]. Fourteen patients with chronic glomerulonephritis and with Alport's syndrome were treated. Haemodialysis was performed 2--3 times weekly. The duration of treatment was from 10 months to 9 years. Serum levels of electrolytes, urea and creatinine were determined, the neurological condition was examined and nerve conduction velocity was measured in the lower and upper extremities. The determinations were done before and after haemodialysis. Subclinical manifestations of polyneuropathy were demonstrated with reduced motor-nerve conduction velocity in the lower extremities. A direct effect of single haemodialysis was far from uniform: usually the conduction velocity increased after haemodialysis and in some cases it decreased. There was no correlation between the serum levels of electrolytes, urea and creatinine and motor-nerve conduction velocity.


[Effectiveness of antifibrinolytic, edema-preventing and hypotensive agents in the prevention of recurrent bleeding from intracranial aneurysms]. On the basis of a material of 561 patients with ruptured intracranial aneurysms treated at the Department of Neurosurgery, Institute of Neurology, Medical Academy in Cracow in the years 1971 to 1977 the authors discuss the effectiveness of conservative treatment for prevention of recurrent bleeding from these aneurysms. The whole group of 561 patients were divied into two subgroups: 361 patients (group A) receiving standard antifibrilytic treatment, drugs preventing oedema formation and reducing the arterial blood pressure, and 254 patients (group B) who were not given antifibrinolytic agents and the other pharmacological agents were given to them only sporadivally. Recurrent bleeding developed in 8.86% of cases of group A and 11.02% in group B. The difference was not significant.


[Evaluation of the intelligence level in patients following craniocerebral injuries]. The purpose of the study was to find out whether persistent depression of intellectual functions after craniocerebral injuries occurs also outside the group of very severe traumas and what is the role played by the degree of injury, the age of the patient and the length of time after trauma. Using Wechsler's test for adults 150 men were tested who had had from 1 to 10 years earlier craniocerebral injuries. The sustained injuries were classified according to the severity and permanent neurological sequelae. A control group of 50 individuals was tested similarly. The study showed that craniocerebral injuries caused permanent depression of intellectual functions also in the cases of less severe injuries, and that the degree of trauma severity was not always correlated significantly with the degree of intellectual impairment. It was shown that in the subjects with skull trauma sustained at the age above 40 years intellectual impairment caused by trauma was greater (significance level p less than 0.002) than in younger subjects.


[Intraoperative electrocardiographic control of the position of the cardiac part of the ventriculoatrial valve catheter]. The author reports 86 cases treated surgically at the Department of Neurosurgery, Medical Academy in Warsaw in the years 1974--1977 for hydrocephalus of different aetiology, who had Pudenz and Hakim valves implanted and in whom the position of the intracardiac part of the device was checked by ECG during the operation. The method included filling of the cardiac portion of the device with 10% saline and connecting it to the ECG on which the ECG curve was recorded continaually during insertion of the catheter into the venous system. Obtaining of P wave in the record corresponding in height to the QRS complex was a reliable indicator of the end part of the catheter reaching the middle part of the right atrium. The described method is technically simple and no complications have been observed as yet connected with it.


Cytoarchitecture of the supraoptic nucleus. A Golgi study. A Golgi-Cox study of the supraoptic nucleus of the adult rabbit has revealed the presence of three major cell types: (1) large multipolar neurons; (2) large bipolar neurons, and (3) small interneurons. The multipolar and bipolar neurons demonstrated regional variation in the rostral and caudal aspects of this nucleus, while the interneurons appeared identical throughout the nucleus. This study provides detailed cytoarchitectural descriptions of the magnocellular neurosecretory cells in the supraoptic nucleus and establishes the presence of an interneuronal cell population through which incoming afferent messages could influence the neurosecretory neurons.


Hypothalamic injection of cycloheximide in the 4-day cyclic rat. Acute suppression of lordotic behavior and ovulation. The results of serveral studies imply that estrogen can act upon the central nervous system via a protein synthetic step. Our objective was to determine if the intrahypothalamic (preoptic area, POA) injection of cycloheximide (CHX), an inhibitor of protein synthesis, at 17.00 h on diestrus II of the 4-day cycle altered lordotic behavior and (or) ovulation in the intact rat (sexual receptivity to males normally begins on the evening of proestrus as herein defined; ovulation occurs on estrus of the cycle). CHX-treated females were tested for lordotic behavior at 23.00 h on proestrus, then killed at 17.00 h on the following day. None of the CHX-POA rats were receptive to the males and 90% of these rats did not ovulate. Thus, CHX significantly suppressed sex behavior and ovulation in the cyclic rat.


Altered neuroendocrine status of middle-aged rats prior to the onset of senescent anovulation. The incidence of senescent anovulation (constant estrus) in female rats increases sharply in the age interval 10--14 months. We have compared the neuroendocrine status of 12-month-old rats, which were still cycling, with that of 6-month-old rats in the reproductive prime. Norepinephrine content in the median eminence of the hypothalamus and circulating levels of FSh and androstenedione were significnatly higher in middle-aged rats (12 months old) than in young controls (6 months old). These increases were selective, in that ten other neuroendocrine parameters measured were unchanged. These results indicate that changes occur at multiple levels of the neuroendocrine system during the transitional phase prior to the onset of senescent anovulation.


Foetal thyroidectomy and brain development in the sheep. Sheep foetuses were surgically thyroidectomized at 50-60 days gestation, when thyroid function begins, and the pregnancy was then allowed to continue until 90, 120 or 150 days (term). At these times the foetuses were removed by caesarean delivery, exsanguinated, weighed and dissected. The central nervous system was divided--cerebral hemispheres, brain stem, cerebellum and spinal cord for subsequent analysis. Comparison was made with sham operations on seven foetuses. Thyroidectomy led to a fall in body weight (24.7%) and brain weight (11.7%) at 120 days and 150 days, 31.1% and 24.5% respectively. The hemispheres showed the greatest change and the cerebellum the least. DNA and protein contents were reduced in the hemispheres and cerebellum at 150 days, while in the brain stem and spinal cord the DNA content was not significantly affected. Protein content was, however, reduced indicating a reduced cell size, but not a reduced cell number as in the other two regions. Somatic changes included reduced wool growth, delayed osseous development in the limbs (X-ray assessment) a reduced heart weight (39.1%) and an increased pituitary weight (48.1%). The thyroidectomized lambs failed to survive for more than a few hours after birth or caesarean delivery at 150 days. The findings indicate significant effects of foetal thyroidectomy on brain development in the sheep late in pregnancy along with other evidence of foetal hypothyroidism.


Estradiol generates pulses of prolactin secretion in castrated male rats. Unrestrained, freely moving rats implanted with an atrial indwelling cannula were used to inject estradiol and to take blood samples. The effect of estradiol on prolactin secretion was monitored by taking blood samples every 2 min. When a single bolus of estradiol (100 micrograms/kg) was injected, no response was seen for approximately 2 h. There then followed a pulsatile pattern of plasma prolactin and this lasted more than 24 h. The elevation of the prolactin concentration was not accomplished by a gradual change but through frequent pulsatile bursts of secretion. The major slopes of the decay curves of these bursts, plotted on a semilogarithmic scale, were parallel to a theoretical curve with a slope of 7 min half-life. Such consistency of decay slopes indicates that prolactin secretion is accomplished through discrete bursts of secretion.


Effects of morphine and naloxone on serum levels of luteinizing hormone and prolactin in prepubertal male and female rats. The effects of morphine (M) and naloxone (N) on serum levels of luteinizing hormone (LH) and prolactin (PRL) in prepubertal male and female rats were investigated. N raised serum LH concentrations in female rats at 10, 15, 20, 25 and 30 days of age, but increased serum LH levels in male prepubertal rats only at 30 days of age. M significantly depressed serum LH values in both sexes only at 15 days of age. M increased serum PRL levels in immature rats of both sexes in all age groups, except in 25-day-old males, whereas N decreased serum PRL only in 25-day-old male rats. These data show that there are differences in the pituitary LH and PRL responses to M or N of immature as compared to the responses previously reported in mature rats, and suggest that the endogenous opioid peptides may have a role in regulating LH and PRL secretion in immature rats.


Morphometric studies of rat glial cell ultrastructure after urease-induced hyperammonaemia. The ultrastructure of astrocytes and oligodendrocytes was investigated in hyperammonaemic rats injected daily with urease for 4 days. Glial cells were randomly photographed and magnified x28 000. Cell and nuclear sizes were estimated by planimetry and mitochondrial size and density were measured by image analysis. After 4 days of hyperammonaemia the astrocyte cytoplasmic area was increased by 46%. Mitochondrial area was increased by 20%, but after correction for cytoplasmic oedema the number and size of mitochondria were not significantly increased. The nuclear and cytoplasmic areas of oligodendrocytes were unchanged. The mitochondria of oligodendrocytes were small in the hyperammonaemic group and so was their percentage area to cytoplasmic area, but their numbers were unchanged. It was concluded that hyperammonaemia induces astrocyte oedema and increases the astrocyte mitochondrial content. These findings support the assumption that the astrocytes are the active cells in the brain metabolism of ammonia. The decrease in oligodendrocyte mitochondrial content could be considered a point against an active function of oligodendrocyte mitochondria in ammonia metabolism in hyperammonaemia.


The fragility of cerebral lysosomes in multiple sclerosis. The possibility that cerebral lysosomes in the white matter from patients with multiple sclerosis (MS) are more fragile than in normal controls was investigated in tissue obtained at necropsy. In the MS cases no differences were found in results from samples obtained from histologically distinct areas of white matter, i.e. plaque, periplaque and macroscopically normal white matter. However, in comparison to white matter from a group of controls, certain differences were found. Firstly, the cerebral lysosomes in MS white matter appeared to be more fragile than those in the control cases. Secondly, the remaining intact lysosomes in MS cases showed different characteristics from those obtained in control cases. These results, in the light of earlier experiments in rat brain, were interpreted as further evidence of a greater fragility in the cerebral lysosomes from MS cases. The implications of these results in relation to current thinking on the aetiology of MS are discussed.


Observations on focal demyelinating lesions in cat optic nerves. A demyelinating perivascular condition has been observed in the optic nerves of three cats, the lesions of which included the following features: thinly myelinated and demyelinated axons, few normal oligodendrocytes, astroglial scar tissue, lymphocytes, plasma cells, mononuclear phagocytic cells and lipid-laden cells. Also present were tubular inclusion bodies which had morphological features similar to the nucleocapsids of some paramyxoviruses. These lesions are compared with some other demyelinating diseases of the central nervous system, and similarities to the lesions of multiple sclerosis are suggested.


Effects of neonatal ovariectomy upon 3H-estradiol uptake by target tissues of androgen-sterilized female rats. Tissue distributions of radioactivity were studied at 2, 4 and 6 h after intravenous injection of 3H-estradiol-17 beta (48.6 ng/100 g b.w.) in 4 groups of 10 or 11 adult female rats with the following neonatal treatments: Control = sham ovariectomy (ovx) on day 1, oil injection on day 5 (n = 10); ovx = ovx on day 1, oil on day 5 (n = 11); TP = sham ovx on day 1, 30 micrograms testosterone propionate (TP) on day 5 (n = 10); ovx-TP = ovx on day 1, 30 micrograms TP on day 5 (n = 11). Neonatal TP treatment significantly hastened vaginal opening in all animals. After ovariectomy, vaginal opening occurred in 20/22 rats regardless of hormonal treatment; ovariectomy did not significantly affect the time of vaginal opening in these 20 animals. All ovariectomized animals had diestrous vaginal smears after puberty, all controls cycled normally and all of the TP group used for the uptake part were in persistent vaginal estrus (sequence of vaginal smears with 70% or more containing no leukocytes) confirmed by ovarian histology to be anovulatory (11/13 injected). 72 h prior to radioisotope injection, intact females in the above groups were ovariectomized and the neonatally ovariectomized were sham operated. Tissue radioactivity was extracted from the anterior, middle and posterior hypothalamus, hippocampus, amygdala, cerebrum, anterior pituitary, uterus and plasma. Neonatal ovariectomy raised 3H-estradiol concentrations in all tissues, except hippocampus and anterior pituitary, suggesting an increase in nonspecifically bound hormone. Neonatal TP decreased 3H-estradiol concentrations in the anterior and middle hypothalamus and uterus only, in both the intact and ovariectomized group, demonstrating a selective effect of neonatal TP upon subsequent development of estrogen binding capacities of target tissues that is independent of the ovaries.


Pigment-filled appendages of the small spiny neurons: a severe pathological change of the striatum in neuronal ceroid lipofuscinosis. In neuronal ceroid lipofuscinosis, the small spinous nerve cells of the striatum show a conspicuous pathological change in that they develop spindle-shaped and pigment-filled appendages of the soma. The axon emerges from the tip of these expansions, the volume of which often exceeds that of the cell body. The aspiny neurons of the striatum do not show this alteration. The pigment-filled expansions close to the axon may be considered an early sign of neuronal degeneration. The small spinous nerve cell is the predominant cell type of the striatum which receives inputs from various sources. Its slowly progressive destruction might account for extra-pyramidal motor disturbances in the course of neuronal ceroid lipofuscinosis.


Multidirectional reconstruction of angiograms by stereogrammetry and computer. Application to computed tomography. A technique of reconstruction of angiograms in any projection, by stereogrammetry and computer, is described. Sections of the vessels may be obtained and superimposed on CT sections.


Diagnosis of small and micro pituitary adenomas by intercavernous sinus venography. A preliminary report. Intercavernous sinuses surround the pituitary gland and their form can be modified by small pituitary tumors. A preliminary report of the use of venography for the diagnosis of pituitary microadenomas is presented.


A qualitative comparison of two contrast media for cerebral angiography. A clinical method. A qualitative comparison of two contrast media for cerebral angiography with regard to contrast should, preferably, be based on a comparison made in two different hemispheres of one patient. Two problems then arise which made evaluation difficult. Vasodilation occurs after the first contrast injection as a result of which the second contrast medium to be compared flows into a dilated vascular tree. In addition, in the case of a comparison in two different hemispheres, variations of image geometry occur, resulting in differences of sharpness and contrast. The method of solving these problems is discussed and is illustrated by a comparison of two contrast media which might be expected to produce differences in contrast because of their physical properties. The results of this clinical comparison show that the expected differences can be partly demonstrated.


Foix-Chavany syndrome: CT study and clinical report of three cases. The Foix-Chavany syndrome is a neurological entity characterized by linguo-bucco-facial apraxia almost always caused by disturbed cerebral circulation. Three typical cases of this syndrome are described and the role of the CT scan to obtain a definite diagnosis is emphasized.


Delayed intracerebral hemorrhage as demonstrated by CT scanning. Three patients are presented who developed delayed intracerebral hematomas after head injury. Two patients had essentially negative CT scans on admission and developed intracerbral hematomas within 24 h after injury. They required surgical treatment and had fatal outcomes. The third patient presented with an epidural hematoma on CT scan, developed an intracerebral hematoma 48 h after evacuation of the epidural hematoma, and did well with conservative management.


Moyamoya disease and intracerebral hematoma. Clinical pathological report. This report concerns a hypertensive woman who suffered a stroke at the age of 51 and recovered from left hemiparesis after 3 to 4 months. During the subsequent 24 years she had four seizures which involved the left arm and face and became generalized, ending with left hemiparesis, from which she recovered after 4 to 5 days. Carotid angiography was performed in 1967, 1973 and 1974 and the characteristic picture of moyamoya disease was demonstrated. She died at the age of 77 with extensive vascular disease. The literature concerning 215 cases of moyamoya disease, in which there were 14 intracerebral hematomas, is reviewed and discussed.


CT and pneumographic studies of membranous occlusion of the aqueduct of Sylvius. A case report. A case of membranous occlusion of the aqueduct of Sylvius with malformation of the skull and associated hydrocephalus is reported. The diagnosis was made with the help of CT, pneumoencephalography and ventriculography. In the literature membranous occlusion of the aqueduct has been considered to be a rare cause of hydrocephalus.


Assessment of posterior fossa tumors in infants and children by means of computed tomography. The attenuation profiles before and after contrast enhancement were examined in 18 infants and children with posterior fossa tumors: eight cerebellar astrocytomas, six medulloblastomas, and four brainstem tumors. The astrocytomas, with one exception, had characteristic patterns, and all could be distinguished from the medulloblastomas, which have a distinct pattern of their own. The brainstem tumors had varying appearances, and were entirely low-attenuating, high-attenuating or had a ring shadow after enhancement. The nature of a posterior fossa tumor in a pediatric patient can usually be predicted fairly satisfactorily from a computed tomogram.


Clinical testing of Conray meglumine and Amipaque in cerebral angiography. Amipaque 280 mg I/ml and Conray meglumine 282 mg I/ml have been compared in a double-bind trial in cerebral angiography. Altogether 55 cerebral artery branches have been examined in 21 patients, who served as their own controls. The effect of the contrast injections on the intra-arterial blood pressure, pulse rate, ECG, circulatory rate and the patients' reactions were recorded under standardized conditions. The quality of the films was also evaluated. No significant difference in the cardiovascular effects of the two contrast media was found. There was a significant difference in favour of Amipaque in the discomfort of the patients--less pain and sensation of warmth. No serious side effects were observed.


The demonstration of the auditory ossicles by high resolution CT. The high resolution CT scanning system introduced by EMI in 1978 has added a new dimension to computerised tomography in otology. The apparatus used for this study was an EMI CT 5005 body scanner adapted for head and neck scanning and incorporating a high resolution facility. The latter has proved most advantageous in areas of relatively high differential absorption, so that its application to the demonstration of abnormalities in the petrous temporal bone, and in particular middle ear disease, has been very rewarding. Traumatic ossicular disruptions may now be demonstrated and the high contrast of CT often shows them better than conventional hypocycloidal tomography. The stapes is also better visualised and congenital abnormalities of its superstructure have been recorded. These studies have been achieved with a very acceptable level of radiation to the eye, lens and cornea and the technique is clearly a rival to conventional pluridirectional tomography in the assessment of the petrous temporal bone. With further design improvements high resolution CT could completely replace existing techniques.