Photoactivation ratios for specification of high-energy x-ray quality: part II, 4-15-MV x rays. A sensitive and relatively simple method for obtaining an index of the spectral quality of x rays in the 4-15-MV range is presented. The method is based upon the simultaneous production of 115mIn by inelastic scattering of x rays by an indium foil and the production of 116mIn by neutron capture, where the neutrons are obtained from the photodisintegration of deuterium. Since the cross sections for the production of 115mIn and 116mIn have markedly different energy response functions, the ratio of radioactivities is very sensitive to the incident x-ray spectrum. Using a detector consisting of an indium foil sandwiched between two plastic bottles of D2O, photoactivation ratios (PAR) have been measured for 4-, 6-, and 10-MV x rays. It is shown that the PAR method offers a sensitive and practical means for quality control of x-ray spectra and comparison of high-energy accelerators.


Postmortem transition in the dynamic mechanical properties of bone. Measurements of dynamic shear compliance versus dead time at room temperatures are reported for a sample of rabbit bone and several samples of human bone, including an extracted wisdom tooth. In all cases an abrupt, second-order transition is observed in one or both components of the audio-frequency complex shear compliance, J*b = Jb; - iJb", at about 5 hours after death; this is considered to be an indication of the life-to-death transition in bones.


Verification timer for radiation therapy machines. Many cobalt and x-ray therapy machines use mechanical timers to control the given dose. There is no other timer on the machine to veryfy that the correct time was set or that the timer did not malfunciton. This article describes a digital timer that has been installed on the MIR therapy machines as a lapsed-time indicator.


Composition of A-150 tissue-equivalent plastic. In recent years, the use of tissue-equivalent materials has become quite common in fast-neutron dosimetry, with the A-150 plastic developed by Shonka et al. probably the most popular. Information on this specific plastic is scantily reported in the literature and as a consequence a preponderance of authors unknowingly reference an article by Shonka describing an early version of a tissue substitute plastic but having a different elemental composition than the present A-150 formulation. We have reviewed the results of 21 chemical analyses which have occurred over a time span of four years on a total of 14 samples of A-150 plastic and based on these data and the formulation of the plastic, have arrived at a suggested composition for A-150 tissue-equivalent plastic. The ambiguities of water absorption by nylon, one of the components of the plastic, and the uncertainty this reflects in the composition of the plastic were evaluated.


Dosimetry measurements and analyses of 10-MV x rays for Clinac-18. Radiation parameters for two Varian Clinac-18 10-MV x-ray units were measured and compared with the same parameters for the Toshiba LMR-13 and the Arco Mevatron XII. Comparison of the percentage depth dose, surface dose, and depth of maximum ionization as a function of field size are presented.


Computer simulation study of Siemens star x-ray image artifacts. In the Siemens star image, exact determination of the first disappearance frequency, which is used to measure the focal spot size, is difficult since the disappearance band has a finite width and the image also has other artifacts. The origin of these artifacts and their appearance was studied by Siemens star image simulation on a digital computer. The simulated images were manipulated by using many different modulation and phase transfer functions. It is shown that the bending of spokes is not related to zero contrast; exact triplet splitting can occur only at the disappearance frequency, and therefore splitting is a valuable indicator of that frequency.


Dependence of cytoplasmic on mitochondrial protein synthesis in K. Lactis CBS 2360. I. Biochemical analysis. In the "petite negative" yeast Kluyveromyces lactis (strain CBS 2360) growth is inhibited by the same Erythromycin concentrations on fermentable and non-fermentable carbon sources. The minimal inhibitory concentrations of Erythromycin does not affect respiration, but completely inhibits total aminoacid incorporation by the cells in conditions in which permeability effects can be ruled out. The effect of the antibiotic on the "in vitro" protein synthesis by cytoplasmic and mitochondrial systems shows that inhibition is effective only at the mitochondrial level. Results suggest that the inhibition of growth and of total protein synthesis is a consequence of the inhibition of mitochondrial protein synthesis.


Dependence of cytoplasmic on mitochondrial protein synthesis in K. lactis CBS 2360. II. Genetic studies. A few eryR mutants independently isolated from K. lactis CBS 2360 display a conditional lethal phenotype at the temperature of 36 degrees C. In addition to drug resistance, also conditional lethality shows a non-Mendelian pattern of inheritance and is affected by exposure of the cells to Ethidium Bromide, indicating that in this yeast mitochondrial DNA controls cell viability. The results obtained from biochemical analysis suggest that the cellular functions in which are involved the gene products of the mitochondrial mutants analized are cytoplasmic protein and RNA syntheses.


EcoRI-sensitive mutation of T7 phage.

EcoRI-sensitive mutation of T7 phage. It is known that DNA from phage T7 is not cleaved by restriction endonuclease EcoRI. However, DNA from phage T7am28 (gene 5) mutant (Studier, 1969) was found to be cleaved by the endonuclease at one site. The site is located at 0.46 fractional length from the left end of the molecule. The mutation which makes T7 DNA sensitive to the endonuclease is separable from the amber nutation and located between am28 and am233 (gene 6).


[Creatinine concentration, osmolar concentration and blank color as basis for concentration dependent values in urine (author's transl)]. The correlation between Creatinine concentration, osmolality and blank color of urines was investigated. Only values of creatinine concentration and osmolality allow an approximative inter-conversion. For urine analysis, especially in cases of a very high creatinine concentration, we recommend to measure osmolality as a control.


[Cerebrospinal fluid rhinorrhea in achondroplasia with hydrocephalus (author's transl)]. Cerebrospinal fluid rhinorrhea was observed in a 12-year old girl with achondroplasia and communicating hydrocephalus. The leakage ceased and did not recur after treatment by ventriculo-atrial shunting (Holter valve) without plugging the fistula. The pathogenetic factors in this case are discussed.


[Caries or fluoridation--a comparison between Hamburg and Vordingborg (Denmark)]. The struggle against caries and their consequences calls for continuing and considerable financial support by governments. The exact extent of caries incidence is evident in official statistics on Hamburg school children. Childhood caries leading to the physiologically damaging, premature loss of deciduous teeth often causes subsequent malocclusion of the remaining teeth, thereby requiring costly, time-consuming orthodontic treatment. The endogenous and exogenous effects of fluorides on the developing or mature hard tissues of the dentition can significantly reduce the incidence of caries. These caries-inhibiting properties can be mostly clearly seen in the example of Vordingborg (Denmark), where naturally occurring drinking water has a fluoride content of between 1.3 and 1.7 parts per million. Comparisons have shown that despite absolutely equivalent conditions, including identical school dental care, the incidence of caries among Vordingborg children is nevertheless only a third of that in parallel groups from Roskilde, where the fluoride content of drinking water is only 0;1 to 0.3 parts per million.


[Modern serology of rheumatic fever and glomerulonephritis (author's transl)]. For the assessment of the situation after streptococcal infection and thus for prevention of rheumatic fever and glomerulonephritis more simple and rapid serological tests are needed. The principle of indirect haemagglutination seems particularly suited for this purpose. A rapid slide test (streptozyme) for the simultaneous detection of antibodies against five streptococcal enzymes in capillary blood or serum was compared to four monospecific tests: latex-Asl, Antistreptolysin-O (ASL-O), antistreptokinase and anti NADase. Several lots of test kits and more than four hundred sera of adults and children with and without suspected rheumatic fever were tested. The number of falsely negative and falsely positive results was small as compared to single monospecific tests. Additional positive reactions were obtained when the ASL-O was within the normal range, but the titer against several exoenzymes were elevated, or, when the antibodies against a single exoenzyme were extremely strong. The precision of the polyvalent test may not be quite as high as if three monospecific tests are applied, It is however sufficient. Thus it seems unrealistic to require the performance of at least three monospecific tests under the present epidemiological conditions.


[Neuroblastoma: paraneoplastic diseases and late complications (author's transl)]. Only 40 out of 104 patients with neuroblastoma survived moronger than 5 years, and 7 longer than 10 years. This indicates a 2 year remission period of 38.4%. Of the 40 surviving children, only 11 (10,4%) showed no further complications, while 29 (72,5%) children suffered from severe later complications originating from the tumor or the therapy. The skeletal system was affected in 42.9%, the peripheral nervous system in 21.5%, and the central nervous system in 19.6%. In 4 patients, we observed a statomotoric retardation and intelligence deficiency, and in 3 other children, an Australian antigenemia. The possible reason of these later complications are discussed in the paper. The high number of such complications in patients with neuroblastoma raises the question whether or not a less radical therapeutic procedure would be more advisable for differentiated tumors.


[Outpatient management of diabetic children and adolescents: control of fractional 24-h glucosuria (author's transl)]. The optimal ambulatory treatment of diabetic children requires the cooperation of the patient and his family. Following a careful and extensive information about the course of diabetic mellitus, its management, and its possible complications, the patients and their parents have to take charge of an important part of the metabolic control. Fractionating 24-h-urines in three portions and estimation of the glucose excretion using the Clinitest-method proved to be a valuable tool to judge the metabolic control and to adjust the insulin doses. The comparison of the glucose excretion in 595 fractionated urines of 30 juvenile diabetics estimated with both the Clinitest-method and polarimetry in the clinical laboratory showed good agreement for low glucose conentrations. The discrepancies between the two methods increased with rising glucose concentrations and increasing urine volumes. 139 insulin-dependent diabetic children and adolescents were presented to the Children's Hospital outpatient clinic every 6-7 weeks for a physical examination and measurements of the 24-h-glucose excretions as well as the postprandial blood glucose concentrations. The average glucose excretion in two groups of patients with one or two daily injections of insulin was 24 and 30 g/day, respectively, which is higher than the recommended limit of 20 g/day. The glucose excretion was not significantly influenced by the frequency of insulin administration (one or two injections per day), by the age of the patient or by the duration of the diabetes mellitus. The good agreement of the evaluations of the 24-h-glucosuria using Clinitest on one side and polarimetry on the other proves regular controls at home by the patients and their parents to be useful and to facilitated the outpatients management of juvenile diabetics. Measuring the 24-h-glucose excretion at least 2-3 times a week seems desirable.


The relation between induced mutation frequency and cell survival--a theoretical approach and an examination of experimental data for eukaryotes. Many mutagens are known to induce a variety of different types of lesions in DNA. Cellular repair systems may eliminate some of these; some unrepaired lesions may lead to loss of reproductive capacity and others to viable mutations. Simple considerations of these three alternative fates of an exposed cell show that there should be a linear relation between the logarithm of the surviving fraction (log S/SO) and log (1-M) where M is the mutant frequency. For low frequencies the relation assumes the simpler form M=-m log S/SO. The published literature on experimental mutagenesis in eukaryotes confirms these expectations. Observed differences in the slope m when different mutagens induce the same mutation in a given kind of cell (or a given mutagen induces the same mutation in different kinds of cell) imply that mutation and cellular inactivation do not arise from one type of DNA lesion only.


Ultrastructural observations of X-ray induced chromatid gaps. A combination of light microscopy, transmission electron microscopy of whole-mount preparations and sectioned material, and scanning electron microscopy was employed to examine the fine structure of X-ray induced gaps and breaks in mammalian chromosomes, in an effort to determine the true nature of these aberrations. The results suggest that, rather than being completely separate phenomena, gaps and breaks are different manifestation of the same events and that gaps may be incomplete breaks. It was determined that light microscopy alone is inadequate for making accurate quantitative assessments of these aberrations, and it is therefore proposed that electron microscopy be used to supplement light microscopy for the analysis of gaps and breaks.


Dominant lethal assays in male mice: evaluation of experimental design, statistical methods and the sensitivity of Charles River (CD1) mice. Male CD1 mice were dosed by intraperitoneal injection of 20, 40 or 80 mg of methyl methanesulphonate (MMS) per kg body weight or with the solvent, water. After dosing, each male was caged with (a) 2 or (b) 3 females per week for 8 consecutive weeks and 13 days after mating the females were killed and examined for evidence of dominant lethal mutations. Results were analysed to determine (1) the sensitivity of CD1 mice to the mutagenic effect of MMS. (2) the influence of the number of females mated with each male. (3) the adequacy of the experimental design and (4) the adequacy of the statistical methods. A dose-related increase in early foetal deaths was induced in females mated to male mice in the first week after dosing with 20, 40 and 80 mg/kg MMS. A reduction in foetal implants was demonstrated in females in the 40 and 80 mg/kg MMS groups but not after dosing males with 20 mg/kg. Thus dominant lethal mutations were induced in male CD1 mice dosed IP with 20, 40 and 80 mg/kg giving a degree of sensitivity which compares favourably with that obtained with other strains of mice in other laboratories. For a given number of male mice, the greater precision obtained with 3 rather than 2 females arose directly from the numbers used. For a given number of female mice, the allocation of 2 per male (rather than 3 per male) is a more efficient design in that 50% more treated animals are available for estimation of the relevant error. Also more information would be available as a result of the probable increase in pregnancy rate. The experiment did not suggest the need for any modification in the statistical approach.


Prospects for evaluating genetic damage in mammalian cells in culture. Starting from some general considerations on cultured mammalian cells as a biological material for the detection of genetic changes, information is given on cell lines and genetic markers that have been the subject of extensive research. The experimental variables of mutation assays are then considered, with special reference to those involved in the system resistant to 8-azaguanine. Work now in progressin the field of environmental mutagenesis is mentioned at the end of the article.


The incidence of sister chromatid exchanges in cultured human lymphocytes. The incidence of sister chromatid exchanges (SCE) in cultured human lymphocytes from 50 normal individuals was studied using the BUdR-Giemsa technique. The mean SCE frequency per metaphase was 7.9 with a standard deviation of 1.36 and a range of 1-21. The incidence of exchanges was not influenced by the age of the donor nor did the exchange rate differ between sexes. The results of this study are compared with those of previous reports and reasons for the wide variation between results discussed.


Th induction of thioguanine-resistant mutants of Chinese hamster cells by gamma-rays. The induction of mutation to purine analogue resistance was assessed in Chinese hamster V79-4 cells exposed to gamma-radiation. After irradiation, the cells were grown in non-selective medium for different time intervals before respreading into medium containing 0.5-0.7 mug/ml thioguanine. In some experiments colonies arising in thioguanine-medium were counter-selected in medium containing the glutamine analogue azaserine, which distinguishes mutants with very little activity of the enzyme hypoxanthine-guanine phosphoribosyl transferase. Only these mutants were increased in frequency by radiation, the maximum measured frequencies occuring in cells respread after 2 days growth in non-selective medium. With longer intervals of post-irradiation growth in non-selective medium a fraction of the induced mutants was lost, and after large doses of radiation it is doubtful if the maximum frequency observed after 2 days post-irradiation growth represents the true induced frequency. The detection of freshly-induced mutants seemed to depend upon the dilution and decay of products formed from the genes prior to their mutation by radiation, since (a) selection of mutants in a higher concentration of thioguanine (2 mug/ml) increased the post-irradiation growth interval required to detect the maximum frequency of induced mutants, and (b) with increasing duration of post-irradiation growth in the non-selective medium, induced mutant cells were able progressively to overcome the growth-limiting effects of the analogue, to give large colonies when respread in thioguanine-medium. The radiosensitivities of 7 isolated mutant lines were indistinguishable from that of wild type cells, but the mutants were at a slight disadvantage when grown in competition with wild type cells. This disadvantage was consistent with the expected fitness of mutants relative to wild type cells calculated from estimates of the spontaneous mutation rate and the mean spontaneous mutation frequency. The induction of mutation to thioguanine resistance was non-linear with dose, yielding induced frequencies per rad of 5-10(-8) to 3-10(-7), but a plot of induced mutation frequency against log surviving fraction gave an approximately linear relationship. The same linear relationship holds for recently-published data on human and mouse cell cultures, so that all three mammalian cell types  exhibit the same fixed probability of mutation induction relative to the extent of inactivation caused by ionising radiation.


Cytogenetic hazards from agricultural chemicals. I. A preliminary study on the responses of root meristems to exotoxin from Bacillus thuringiensis a constituent of a microbial insecticide, thuricide. It reported for the first time that the exotoxin, thuringiensin A, from Bacillus thuringiensis, a component of the insecticide thuricide, inhibits spindle and cytokinesis and induces micronuclei, chromocentric nuclei and minor deviations in spindle activity. The binucleate cells also undergo mitosis yielding biprophases and bimetaphases. Spindle seems to have been inhibited even in bimetaphase. Microtubular systems and chromosomes are implicated as the primary targets. Most effects resemble those of caffeine, colchicine, aminopyrin, chloral hydrate and vinblastine to different extents, and are therefore suggestive of the anti-neoplastic and mutagenic potentialties of the exotoxin. The extensive use of thuricide on crop plants, in view of its mutagenic potential, may be hazardous. The results also suggest that the exotoxin may be used as a pre-treating agent in chromosome analysis and as a candidate-tagging tool for synchronization and cell cycle analysis, besides its probable utility in studies on cancer cells.


Liver homogenate-mediated mutagenesis in chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins. Several chemical carcinogens that require metabolic activation have been examined for their cytotoxic and mutagenic activity in Chinese hamster V79 cells. Mutagenic activity was measured as the induced frequency of 6-thioguanine-resistant colonies. Metabolic activation was provided by the 9000 g supernatant fraction of rat liver plus cofactors. The cytotoxicity and mutagenicity of aflatoxin B1 and B2, benzo(a)pyrene, 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene, dibenz(a,h)-anthracene, dibenz(a,c)anthracene, and benz(a)anthracene were examined as functions of concentration. Except for the two isomers of dibenzanthracene, the mutagenic activity in general paralleled the carcinogenic activity. An assay of this type may be useful as a prescreen for environmental chemicals that require metabolic activation.


Reduction in mortality from coronary heart disease in men residing at high altitude. In New Mexico, where inhabited areas vary from 914 to over 2135 m above sea level, we compared age-adjusted mortality rates for arteriosclerotic heart disease for white men and women for the years 1957-1970 in five sets of counties, grouped by altitude in 305-m (1000-foot) increments. The results show a serial decline in mortality from the lowest to the highest altitude for males but not for females. Mortality rates for males residing in the county groups higher than 1220 m in order of ascending altitude were 98, 90, 86 and 72 per cent of that for the county group below 1220-m altitude (P less than 0.0001). The results do not appear to be explained by artifacts in ascertainment, variations in ethnicity or urbanization. A possible explanation of the trend is that adjustment to residence at high altitude is incomplete and daily activities therefore represent greater exercise than when undertaken at lower altitudes.


Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine,  L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea, and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or pituitary tumor, stopped galactorrhea in over 50 per cent, restored menses in over 70 per cent, and allowed pregnancy in three.


Administration of education programs in academic health centers. Because of their expanding budgets, facilities, enrollments and staff, and because of increasing responsibilities for rendering health services, academic health centers must make major administrative decisions. We believe that these centers should remain within the university structure to facilitate interdisciplinary education, should better integrate the activities of the faculties of their component schools, and should prepare more purposefully for the multiprofessional teams that will deliver primary care in the future. Basic-science departments should also improve institutional programs for serving students in all the health sciences. A center's chief administrative officer, a vice-president for health affairs, should have clearly defined lines of authority over the center's operations, including those of the university hospital. In spite of burdensome governmental regulations, centers should cooperate with legislative efforts in health planning, in developing experimental models for new delivery systems and in supporting studies that will underlie equitable rate regulation.


Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. During hemodialysis, cardiopulmonary decompensation may appear in uremic patients, possibly caused by plugging of pulmonary vessels by leukocytes. In 34 patients we noted leukopenia (20% of initial levels) during hemodialysis that in 15 was associated with impaired pulmonary function. When we infused autologous plasma, incubated with dialyzer cellophane, into rabbits and sheep, sudden leukopenia and hypoxia occurred, with doubling of pulmonary-artery pressures and quintupling of pulmonary-lymph effluent. Histologic examination showed severe pulmonary-vessel-leukostasis and interstitial edema. The syndrome was prevented by preinactivation of complement but was reproduced by infusions of plasma in which complement was activated by zymosan. Thus, acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis.


Metabolic aspects of a protein-sparing modified fast in the dietary management of Prader-Willi obesity. Four adolescents or young adults with the Prader-Willi syndrome (hypotonia, mental retardation, hypogonadism and obesity) received a protein-sparing modified fast consisting of 1.5 g of meat protein per kilogram of ideal body weight and meeting vitamin, mineral and fluid requirements. Evaluation of nitrogen and energy metabolism revealed the development of starvation ketosis and a positive nitrogen balance. Serial whole-body potassium measurements in two patients confirmed preservation of lean tissue despite continuing loss of weight. Clinical diabetes mellitus in two subjects was rapidly ameliorated by the regimen. Short-term weight loss greater than 18 kg occurred in three of the four subjects, and reduced weight persisted during observation periods of 26 to 44 months. This degree of outpatient diet adherence by mentally deficient subjects, who do not normally experience satiety, suggests that hunger is eliminated or at least reduced by modified, protein-sparing fasting.


[Modern analytical methods in forensic chemistry]. The use of modern chemical and physical methods in forensic chemistry and crime investigation is steadily increasing and gaining in importance. For forensic purpose special modifications of the procedures are generally required in order to give results which are acceptable to legal authorities as proof of some specific points. The chemical toxicology can also help in cases of acute intoxications or in environmental problems.


Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery. A search was performed for presynaptic, release-modulating receptor systems on the post-ganglionic sympathetic nerves of rabbit pulmonary artery. Strips of the artery were preincubated with (-)-3H-noradrenaline and then superfused and stimulated transmurally. 1. Tetrodotoxin, guanethidine, and omission of calcium all suppressed the stimulation-evoked overflow of tritium, thus confirming selective release from noradrenergic neurones. 49% of the stimulation-evoked overflow of total consisted of 3H-noradrenaline, 22% of 3H-3,4-dihydroxyphenyglycol (DOPEG), and 9% of 3H-normetanephrine. Cocaine virtually abolished the evoked overflow of 3H-DOPEG; further addition of corticosterone also abolished that of 3H-normetanephrine. In the presence of cocaine plus corticosterone, unmetabolized 3H-noradrenaline accounted for 86% of the stimulation-evoked overflow of total tritium. The overflow evoked per pulse was 2.2 X 10(-5) of the tritium content of the tissue (1 Hz); it increased 2-fold when the frequency was raised to 8 Hz. 2. Presynaptic alpha-adrenoceptors have previously been demonstrated in this tissue (Starke et al., 1975b). High concentrations of isoprenaline reduced the stimulation-evoked overflow of tritium, presumably by alpha-adrenergic inhibiton. No presynaptic effect of up to 10(-5) M normetanephrine and metanephrine was found. 3. Dopamine slightly diminished the stimulation-evoked overflow of tritium, but only at 100 times the inhibitory threshold concentration of noradrenaline (which is 10(-8) M; Starke et al., 1975b), probably through activation of presynaptic alpha-adrenoceptors. Apomorphine failed to reduce the evoked overflow whether the superfusion medium contained cocaine and corticosterone or not. 4. Isoprenaline (10(-9) -10(-6) M) did not change the evoked overflow whether the medium contained cocaine and corticosterone or not, and whether the frequency was 1 or 2 Hz. Propranolol also had no effect. 5. Angiotensin II increased the stimulation-evoked overflow both in the absence and in the presence of cocaine and corticosterone. Equieffective concentrations of angiotensin I were 10 times higher. Saralasin had no effect, whereas 1-Sar,8-Ile-angiotensin produced a small increase. Both of the latter peptides behaved as presynaptic antagonists of angiotensin II. A presynaptically supramaximal concentration of the alpha-adrenergic agonist oxymetazoline prevented the facilitatory action of yohimbine, but not that of angiotensin II. Separation of 3H-compounds showed that angiotensin II caused a proportionate increase in stimulation-evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine; this finding rules out any inhibition of noradrenaline uptake mechanisms. 6. 10(-4) -10(-3) M acetylcholine caused hexamethonium-sensitive acceleration of basal tritium outflow. Much lower concentrations (10(-7) M and higher) reduced the overflow evoked by electrical stimulation. The evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine was proportionately decreased...


Specific action of narcotics on reflex activation of rat alpha-motoneurones. Specific effects of narcotics (opiates) were studied on rat extensor alpha-motoneurones. The animals were anaesthetized with halothane, artificially ventilated and immobilized with N,N'-diallyl nortoxiferinium-HCl. The alpha-motoneurones were activated by tetanic stimulation of the cut ipsilateral gastrocnemius-soleus (GS) nerve. Morphine (2 and 4 mg/kg) administered intravenously, significantly increased the frequency of reflex discharges. In most of the neurones tested, naloxone (0.25 mg/kg) given intravenously, abolished the effect of morphine. In some neurones, however, naloxone induced a further activation. The dose of naloxone employed was ineffective when given alone. The effect of morphine was mimicked by an intravenous injection of levorphanol (1 mg/kg), but not by an equimolar dose of the stereoisomer dextrorphan, which suggests that the activating effect on alpha-motoneurones is a specific one. An intraperitoneal injection of apomorphine (1 mg/kg) reduced the effect of morphine. The effect of narcotics on alpha-motoneurones parallels narcotic-induced catalepsy and muscular rigidity, with regard to dose-dependence as well as to the antagonism of naloxone and apomorphine, and suggests that both catalepsy and muscular rigidity are mainly due to an activation of extensor alpha-motoneurones. Since this activation can be inhibited by spinalization of the rats, it can be inhibited by spinalization of the rats, it can be concluded that the activation is due to a supraspinal action of morphine, resulting in a decreased dopaminergic neurotransmission in the brain.


Effect of convulsant and anticonvulsant agents on level and metabolism of gamma-aminobutyric acid in mouse brain. 1. The effect of the convulsant agents pentetrazole, picrotoxin, bicuculline, strychnine and isoniazid on the central level of gamma-aminobutyric acid (GABA) and the activity of the enzymes glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) from mice brain was studied in vivo and vitro. In vivo, convulsant doses of picrotoxin and isoniazid lowered the level of GABA and the activity of GAD, whereas strychnine and bicuculline had no such effect. Pentetrazole inhibited GAD, but did not alter the GABA content. In vitro, all convulsants, except bicuculline, inhibited the activity of GAD; however, the concentrations of strychnine were far beyond the range that is reached in vivo by convulsant doses. Only isoniazid inhibited the activity of GABA-T in vivo as well as in vitro. 2. Phenobarbital, ethosuximide and trimethadione were about equally active in preventing convulsions induced by strychnine and picrotoxin, whereas diazepam was 9 times, and sodium valproate 3.5 times more active against convulsions elicited by picrotoxin. Phenytoin up to 100 mg/kg was ineffective against all chemoconvulsants. 3. Diazepam, sodium valproate, ethosuximide and trimethadione antagonized the inhibition of GAD and the decrease in GABA concentrations caused by isoniazid. Phenobarbital and phenytoin prevented the decrease of GABA but did not reverse the inhibition of GAD. 4. The results suggest a role played by the transmitter pool of GABA in the convulsant action of chemoconvulsants and in the anticonvulsant effect of antiepileptics clinically used in petit mal epilepsy.


The role played by the extraneuronal system in the disposition of noradrenaline and adrenaline in vessels. The role played by extraneuronal sites in the disposition of noradrenaline and adrenaline was studied in the saphenous vein and in the mesenteric artery of the dog, taking as parameters the influence of blockade of these sites on the sensitivity to and on the time for half-relaxation (t50) (both in oil and in Krebs solution) of these agonists. Preliminary experiments have shown that the t50 values are not significantly changed by the changes in the height of the contraction provided the contraction is caused by the same concentration of the agonist. The results obtained permit us to conclude that in both vessels the removal of amines depends on the concentrations used. In low (0.023 and 0.23 muM) or in moderately high (2.3 muM) concentrations, adrenaline is removed preferentially by extraneuronal sites, whereas noradrenaline "preferred" neuronal sites. The selectivity of adrenaline for extraneuronal sites was present for such low concentrations that a possible physiological role of these sites in the inactivation of circulating adrenaline must be considered. The results obtained by studying the relaxation in oil in Krebs solution and by using cortexone (60 muM) or U-0521 (dihydroxy-2-methyl propiophenone; 0.1 mM) support the view that, at least in the vein, adrenaline may accumulate in extraneuronal cells and diffuse back into the biophase during the relaxation, thereby slowing the latter. Both in the veins and in the arteries noradrenaline was inactivated more rapidly than adrenaline. The difference in the rate of inactivation of these amines, already observed in controls (when all inactivation pathways are operative) became more marked when both neuronal and extraneuronal sites were blocked. The existence of an important pathway not blocked by cocaine + cortexone + iproniazid which may preferentially inactivate noradrenaline cannot be ruled out.


Effects of dopamine on whole kidney function and proximal transtubular volume fluxes in the rat. The renal effects of dopamine were studied using clearance and micropuncture techniques in rats. Intravenous infusion of dopamine (4.7 - 10(-6) mol - kg-1 - h-1) increased glomerular filtration rate and renal blood flow. Renal blood flow was measured by an electromagnetic flowmeter. The increase in filtered fluid and sodium was nearly completely matched by increased tubular reabsorption. Thus, only a small rise in urine flow and in urinary sodium excretion was observed. The micropuncture experiments using the split oil droplet method of Gertz demonstrated a stimulation of the transepithelial fluid transfer after injection of dopamine (10(-4) M) into the proximal tubular lumen. This effect was abolished by simultaneous injection of propranolol (10(-3) M) which, by its own, did not affect transtubular volume fluxes. It is concluded that dopamine, by stimulation of beta-adrenoceptors, may increase reabsorptive capacity of the proximal tubular epithelium independent of changes in renal hemodynamics.


Mescaline-induced changes of brain-cortex ribosomes. Mescaline demethylase activity of brain-cortex soluble supernatant. Brain-cortex slices demethylate mescaline and p-methoxyacetanilide, a reference O-demethylating substrate, though the rate of demethylation of mescaline is about one third that of the reference substrate. The demethylase activity is localized mostly in the soluble supernatant (105 000 x g). It is purified 47-fold with respect to the demethylation of mescaline by ammonium sulfate precipitation and DEAE cellulose chromatography. The partially purified demethylase, which is stable for 3-5 days at -5 degrees C in the presence of dithiothreitol and glutathione and is inhibited by p-chloromercuribenzoate, has maximal activity at pH between 7.2 and 8.0. It demethylates mescaline into 3,4-dimethoxy-5-hydroxyphenethylamine and 3,5-dimethoxy-4-hydroxyphenethylamine and some unidentified derivatives.


[Responses of neurons of the medial group of thalamic nuclei to stimulation of the fronto-basal portions of the neocortex]. Neuronal and focal responses of medial thalamic nuclei (mediodorsal, central lateral, parecentral, centrum medianum, parafascicular) to stimulation of frontobasal cerebral cortex (proreal, posterior orbital, basal temporal regions) were studied in acute experiments on cats narcotized by nembutal mixed with chloralose. Proceeding from the data on the number of neurons responding to cortical stimulation and on the duration of the response latent period, three functionally heterogeneous sections of medial nuclei were distinguished: the microcellular and magnocellular regions of the mediodorsal nucleus, and the intralaminar nuclei with the parafascicular complex. Neurons were recorded which could be activated antidromically during stimulation of another region. On this basis a suggestion is made on the integrating function of medial nuclei providing unification of the frontobasal regions of the neocortex.


[Excitability of the senso-motor cortex and red nucleus of rabbits with different levels of cortical potential spatial synchronization]. The motor reaction of the rabbit to the threshold electrical stimulation of the sensomotor cortex and red nucleus was studied to determine excitability of these structures. Under conditions of the computer-controlled experiment the excitability of the two structures was compardd for situations characterized by different levels of cortical potential correlation. An increase in the spatial synchronization of the cortical potentials is shown to be accompanied by intensification in excitability of the sensomotor cortex and red nucleus. This intensification seems to be one of possible neurophysiological mechanisms of the probability increase for the effector reaction to sensory stimuli when the cortical spatial synchronization rises.


[Comparison of the influence of the amygdaloid complex and the midbrain central gray substance on the neuronal activity of the lateral hypothalamus]. The influence of stimulation of stria terminalis and midbrain central gray substance on the neuronal activity of the lateral hypothalamus was studied in acute experiments on curarized rats. Five types of neuronal responses were found: 1) phase activation; 2) phase inhibition;3) diffusive activation; 4) diffusive inhibition; 5) two-phase responses. Stimulation of stria terminalis produced inhibition in 62.7% of the lateral hypothalamus neurons. 87% of those neurons were activated after stimulation of the central gray substance. The convergence of impulses from the amygdaloid complex and midbrain central gray substance was observed in 14.4% of reactive neurons. 84.6% of cells showed antagonistic convergent effects.


[Age and changes in the latent periods of the slow human auditory potential]. Regular changes in latencies of slow auditory evoked potentials were found with age. In particular, peak-latencies of comparatively early deflections, i.e. P1, N1 and P2, progressively diminished. The shortening of latencies was 50-60 ms for the age between 3-7, 8-13, and 25-35 msec further on. The latencies of the later waves, namely P3, N3 and P4, increased by 35-65 ms for the age between 3-7 and 8-13. After these ages, the latency of deflection P3 did not change, while deflections N3 and P4 disappeared. Of all the evoked potential components deflection N2 was the most stable, its latency negligibly shortened with age. In children aged 3-7 two complexes of waves (P1N1P2 and P2N2P3) often overlapped, forming a broad nondifferentiated deflection. The division of the latter was completed at the age of about 8. Long-term developmental changes in wave-shape and parameters of the slow evoked potentials are considered as supporting their mainly nonspecific (extralemniscal) orgin. Basing on correlation revealed between the late evoked potential components and EEG synchronization level, a hypothesis is advanced according to which these components are generated with participation of the nonspecific synchronizing system.


[Responses of bat cochlear nucleus neurons to ultrasonic stimuli]. The responses of cochlear nuclei single units in Vespertilionidae and Rhinolophidae were studied by means of ultrasound stimuli of different frequencies. Most neurons were found to have one or two complementary response areas with best frequencies equal to 1/2 and 1/3 of the highest one (which we regard as the basic best frequency). In Vespertilionidae which emit frequency-modulated signals some neurons have complementary areas with upper thresholds. The latency of responses do not correlate with the stimulus frequency. This suggests that there is no correlative reception of echosignals at this level of auditory system in bats.


[Acetylcholinesterase in the glial elements of the cat spinal cord]. The Karnovsky-Roots method was used for the light and electron cytochemical detection of acetylcholinesterase distribution in the cat cervical spinal cord. A specific reaction was found not only in nervous elements of the motor nuclei, but also in some astrocytes, satellite glial and Schwann cells. AChE activity was demonstrated in satellite cells accompanying both cholinergic and noncholinergic neurons. An electron microscopic analysis showed electron-dense end-products in the reaction (copper ferrocyanide) in nucleous, on the surfaces of the inner and outer leaves of the nuclear membrane and in its pores, in the perinuclear space and in the pericaria of satellite glial cells on the inner and outer surfaces of the cytoplasmatic membrane of the Schwann cells.


[Rhythmic activity in the retina of fish evoked by adequate stimulation]. Distribution of evoked rhythmical responses over the retinal surface and depth was investigated in carp and tench by recording the local electroretinogram and spike activity of ganglion cells. The dependence of the response amplitude-frequency characteristics upon the stimulus intensity and duration was also studied. The rhythmical responses to light "on" and "off" stimuli differed in a number of features, particularly in patterns of their distribution among cellular and synaptic retinal layers. It was found that frequency, amplitude and the number of waves in the response were functions of the stimulus parameters. The "on", "off" and "on-off" retinal ganglion cells were represented in the records. Their discharges corresponded to the wave phase angle close to pi/2. Blocking conduction in the optic nerve by cold made it possible to show that the retinal rhythmic activity system is independent of the centres although tonically influenced by them.


[Model for the feedback mechanism between horizontal cells and photoreceptors of vertebrate retinas]. A model is proposed which is based on the hypothesis that the feedback between horizontal cells and photoreceptors is fulfilled by electric current generated by the subsynaptic membrane of horizontal cells and flowing partially through receptors. An important element of the model is nonlinearity of the presynaptic membrane of photoreceptors. The model reproduces such experimental data as depolarization of cones evoked by hyperpolarization of horizontal cells with a light annulus or extrinsic current, as well as some properties of current-voltage relations in cones and rods.


[Post-synaptic responses of cat visual cortex neurons to stimulation of the lateral geniculate body]. Intracellular responses of 50 neurons in the striate cortex to lateral geniculate body stimulation were studied in cats immobilized with d-tubocurarine. Activation without subsequent inhibition was determined in 22 per cent of the cells. Initial activation was followed by inhibition in 32 per cent of the cells and primary inhibition was found in 46 per cent of the cells. The difference between the shortest latencies of IPSP and EPSP was 0.9 ms. A conclusion is made that in the striate cortex there exists a mechanism of afferent inhibition. The neurons responding with primary activation may play the role of inhibitory cells in such inhibition.


The use of serial determination of blood serum glycoproteins for indirect evidence of the sensitivity and resistance of malignant tumor cells to clinical chemotherapy. Sialic acid and mucoprotein tyrosine (MPT) as two important and sensitive indicators of blood serum glycoprotein changes were used for the dynamic follow up of the tumor growth in humans. Their determination was performed before and during chemotherapy with the aim to evaluate indirectly the sensitivity or resistance of malignant cell to the clinical chemotherapy. A total amount of 16 cases with gynecological malignancies was investigated. According to the results of the laborabory findings the patients were divided into three groups: a) with decreased values after chemotherapy, b) with no changes or increased values, c) uncertain results. The laboratory findings corresponded well with the clinical course of the disease.


Cytotoxic activity of macrocyclic metabolites from fungi. The cytotoxic effect of 7 macrocyclic fungal metabolites on HeLa cells has been determined. The authors noted great differences in the cytotoxic activity of the substances investigated. Least effective had proved the metabolites curvularin and zearalenone which kept exhibiting ED50 at a concentration of 2 X 10(-4)M and at a concentration of 7.5 X 10(-5)M respectively, whereas the most effective cyanein and monorden gave rise to 50% inhibition of multiplication of HeLa cells at a thousandfold lower concentration than zearalenone. Cytochalasins A, B and D brought about 50% inhibition of proliferation of HeLa cells at concentrations of the same order, with ED50 ranging between 1.2-2.1 X 10(-6)M. The different biological activity of the studied macrocyclic fungal metabolites is discussed in connection with their chemical structure.


Effect of hydroxyurea and vinblastine on the proliferation of the pluripotential stem cells. The population of the pluripotential hemopoietic stem cells in mice, i. e. those cells forming colonies in the spleens of lethally irradiated mice (colony forming cells CFc) is proliferating relatively slowly. After a partial damage the population regenerates which is achieved by means of the increased proliferation rate. The effect of damage caused by different doses of hydroxyurea or vinblastine on the proliferation of the CFc has been investigated. CFc population was measured in femur bone marrow after grafting the sample of the bone marrow into the lethally irradiated mice recipients (spleen colony method). The proliferation rate was estimated either according to the magnitude of the fraction of cells synthesizing DNA in the S phase of the cell cycle, or according to the sensitivity of the population to the repeated injections of vinblastine. Data showed that even after very minute damage caused by hydroxyurea the stem cells started to proliferate intensively. The effect was dose dependent. The comparable damage caused by vinblastine had a significantly weaker effect on the proliferation of the stem cells. From the results it is concluded that the proliferation response of the pluripotential stem cells depends on two factors: one being the extent of the damage caused to the hemopoietic tissue and the second the position of the killed cells in the cell cycle.


Cinemicrographic analysis of the cellular changes of the stabilized cell line HeLa provoked by l-aminoadamantane. The effect of antiviral compound l-aminoadamantane on HeLa cell culture has been studied. Morphological changes were observed at the concentration 300 and 500 mug/ml. The concentration of 150 mug/ml exerted a delay in the process of cell adhesion and dilatation (spreading).


Human malignant melanoma cells: morphological and immunological variations. When cultured in vitro, human malignant melanoma cells proliferated in two patterns: In one the cells were polygoneal or spheroidal unequal in form and size, whereas in the other, the cells were elongated, fusiform, poorly delimited, with various degrees of atypism. Antisera to each of these two types of malignant melanoma cell cultures were raised in rabbits. The antiserum cytotoxic activity was assessed against 10 cultures of malignant melanoma cells, 10 mammary carcinoma, 2 fibrosarcoma and 10 normal skin fibroblasts. Prior and at intervals post surgery, the cytotoxic activity of serum from 10 patients with malignant melanoma was assessed against the above cell cultures. Based on their cytotoxic activities, the sera drawn from patients with melanoma thirty days after surgery had the highest cytotoxicity and could be classified into two groups similar to the rabbit antisera. Glycoprotein fractions were isolated from 3 M KCl extracts of the two melanoma cell types, i.e. from patients ShA and ZBJ. These glycoproteins stimulated 14C-2-thymidine uptake and DNA-polymerase activity of peripheral blood lymphocytes from post surgery melanoma patient. The glycoproteins had no effect on peripheral blood lymphocytes from normal donors.


Arachnoid cyst and cord compression in association with tangential shrapnel injuries of the spine. Seven cases of tangential shrapnel injury of the spine with sensory and motor paralysis were discovered to have subdural arachnoid cysts with compression of the cord also. In one of them an extradural cyst coexisted. Detection of the cysts was only possible after myelographic screening of all cases of tangential trauma. The clinical, laboratory, radiological, surgical and histopathological data were studied. Follow-up for eight weeks was recorded including one case of recurrence of a cyst. A theory of the mechanism of injury and of the formation of the cysts is given. The number of cyst cases constituted about 33% of all tangential injuries, and 8.8% of all shrapnel injuries received in Maadi Hospital during the October Middle East Conflict, 1973. Removal of the cysts improved the prospects of neurological recovery.


Cerebrospinal fluid lysozyme activity in patients with central nervous system tumours. The presence of lysozyme in the CSF is considered with regard to its value in the early diagnosis of primary or secondary CNS Tumours. Since the appearance of this enzyme in the CSF is secondary to the increase of protein in the fluid, the search for lysozyme in the CSF is of no practical help in the diagnosis of CNS tumours.


Simultaneous occurrence of spinal tumor and lumbar disk herniation. Eight cases are reported where spinal tumor occurred simultaneously with hernited lumbar disks in a series of 609 lumbar disk operations. The value of the diagnostic procedures is discussed and the literature is reviewed.


Evaluation and revision of ventriculo-gastric shunts by gastroscopy. The authors have found that gastroscopy is a relatively easy and safe technique for evluating the function of , and relieving distal obstruction in, ventriculo-gastric shunts.


[Cerebral blood flow determination with the use of a Standard ZM 703 device]. The authors report a method of determination of regional blood flow in the brain with a Polish ZM 703 apparatus produced by United Nuclear Equipment Works POLON. The authors found that ZM 703 is useful for determination of brain blood flow but it should be equipped with detection crystals and collimators of smaller size for simultaneous examination of greater number of brain regions.


[Familial EEG abnormalities in children of epileptics]. The purpose of the study was to establish the frequency of EEG abnormalities in mother and child when one of them has epilepsy. The incidence and type of EEG abnormalities were analysed in 2 groups: 33 epileptic children and their 31 healthy mothers, and 28 epileptic mothers with their 46 clinically healthy children. For illustration of data distribution in EEG the examined subjects were divided in both groups into mother-child pairs comparing the features of the records as well as morphological similarity of the curves in mother and child. It was found that the probability of abnormalities in the bioelectric activity of the brain is the same in a healthy child of an epileptic mother (67.3%) as in a healthy mother of an epilepitic child (51.6%). The frequency of EEG pathology was greater in daughters than in sons of epileptic mothers. Similarities in morphological patterns of EEG occurred in only 3 cases in mothers of epileptic children and in 8 children of epileptic mothers.


[Syphilis of the central nervous and cardiovascular systems in Poland in the light of epidemiological data of the Institute of Venerology in Warsaw]. The authors describe the epidemiological situation with regard to late syphilis in the period of 25 years with particular reference to the last decade (1965--1974). The activities of consultation services for late syphilis and their role in prevention of late organ involvement are discussed.


[Value of cerebrospinal fluid protein study by the polyacrylamide gel electrophoresis method]. The methods of cerebrospinal fluid electrophoresis used as yet are surveyed briefly with particular reference to the method using polyacrylamide gel. In the light of own results it has been found that the method is superior because only small amounts of material are required and the sensitivity and separating ability of the method are much higher.


[Clinical pattern of epilepsy with abortive temporal lobe attacks]. The purpose of the present work was to evaluate the clinical course of epilepsy with infrequent partial attacks with complex manifestations derived from the temporal lobe. Thirty patients aged 14 to 64 years treated on an outpatient basis and discovered during epidemiological investigations were followed-up. In half the cases only attacks without generalization occurred, in the remaining cases isolated generalized seizures appeared during many years of disease duration. In both groups a decrease was observed in the frequency of seizures in patients treated systematically or irregularly, as well as in those who had never been treated. Despite a long duration of the disease (above 6 years in 24 cases) the patients had normal mental level and good social adaptation.


[Epilepsy and self evaluation of health conditions in subjects with a history of severe head injury in childhood]. Follow-up study of 309 subjects were carried out. They gave a history of severe head trauma in childhood (with cerebral concussion or cranial fracture). The mean age of these subjects at the time of trauma was 6.3 years and at the time of examination -- 19.3 years, the mean duration of follow-up being about 13 years. The frequency of epilepsy in this group was 3.2/1000 before head trauma. In follow-up prevalence of epilepsy in this groups was 25.9/1000, and of suspected epilepsy prevalence was 13/1000. The prevalence of epilepsy in subjects after severe head trauma was three times the expected one (9/1000). The most frequent complaint in this group were headaches. They were twice as, frequent as in the general population at the same age. The proportion of subjects regarding their health state as poor  was nearly twice as high as expected, and that of subjects regarding it as good was by one-third lower than expected. Despite these differences in self-evaluation of the health state and frequency of complaints it was found that a higher proportion of subjects in this group had not visited doctors in the year preceding the investigation than in the general population. This may indicate that many subjects in this group have lost motivation for treatment.


[Incidence of seizures and therapy course in the light of a follow-up study of 2 representative groups of epileptics]. The follow-up study reported covered two representative groups of epileptics: 289 known epileptics (group Z) and 82 cases found in a sample of general population in Warsaw (group T). During 2--3 years of follow-up the frequency of seizures has changed in 40% of cases: the percent of patients improved exceeding significantly that of patients with worsening or relapse. The remaing 60% of cases consisted of two almost equally numerous groups: patients with unchanged frequency of seizures and those free from seizures for years. Cases of milder epilepsy were underrepresented among the patients on medication but it is stressed that it was particularly difficult to obtain data on such cases (migrations, refusals). The frequency of relapses in the untreated group reached 10% in group Z and 5% in group. T. Many untreated epileptics continue to have epileptic seizures, usually rare.


[Behavior of nervous tissue during long-term administration of diphenylhydantoin to cats]. The purpose of the study was to assess the morphological changes in the brain of cats reveiving diphenylhydantoin in therapeutic doses during several weeks. The material included 20 cats: 14 experimental and 6 control. In conditioned behaviour the animals showed a steady reduction in the number of correct responses to positive stimuli, statistically significant prolongation of the mean time of latent reaction and disappearance of reaction in intervals between signals. The general condition of the animals changed also, they became somnolent, refused to take food or water. Trophic changes included weight loss, spot-like loss of hair and loss of hair lustre, mucosal bleeding. These changes developed already in the first weeks on the drug administration independently of the dose. Morphological investigations of cat brains showed greatest cell loss and different grades of damage of the surviving cells in Ammon's horn, amygdala and in brain stem reticular formation. Glial proliferation and hypertrophy were slight. The authors discuss the problem of importance of the observed changes for development of "clinical" syndrome in experimental cats.


[Study of children of mothers treated with anticonvulsants during pregnancy]. Forty children of mothers with epilepsy treated with anticonvulsants during pregnancy were investigated. Medical documentation and history data permitted to gain information concerning the course of the disease and treatment during pregnancy, the course of pregnancy and labour and the neonatal condition of the child. The children had medical, psychological and EEG investigations. It was found that in the group studied disturbances in the course of pregnancy occurred much more frequently than in the general population (pregnancy disturbances in 20.5%, premature labour -- 25.6%, complicated labour -- 15.4%). Numerous so-called minor malformation syndromes were found in these children (37.5%) and somatic development was deficient in 52.5% of cases. EEG abnormalities were present in 65.6% of children. No abnormalities were observed in mental development. It seems that these abnormalities were most frequent when the mothers had been treated with derivatives of phenytoin and phenobarbital. The observed group is, however, too small for reaching reliable conclusions.


[Effects of clonidine on various blood-coagulation parameters in hypertension]. The effect of oral clonidine on prothrombin time, partial thromboplastin time, blood fibrinogen, fibrinolytic activity and platelet count was investigated in 25 hypertensive and 7 normal subjects. High plasma fibrinogen levels were present in 80% of the hypertensive patients and prolonged lysis time in 28%; the means values were 487 +/- 135 mg % and 223 +/- 62 min., respectively. The other coagulation tests were normal. 0,300-0,450 mg/day clonidine per os for 15 days both decreased fibginogen levels (mean 406 +/- 149; p less than 0.05) and shortened lysis time (mean 153 +/- 78 min; p less than 0.005). No changes were noted in the normal subjects. The pathophysiological mechanism of these findings is discussed and their possible implications for the treatment of hypertension are emphasised.


[Arterial hypertension as a medico-social disease. Etiopathogenetic aspects and therapeutic possibilities]. The increased incidence of arterial hypertension raises important medicosocial problems, since it has been shown that the prognosis for those who receive treatment is different from that of those who do not. Mass education is required to ensure that as many sufferers are aware of their condition before complications set in. Those detected should be properly classified in accordance with the nature, type and degree of their form and treated on the basis of its aetiopathogenesis. It has, in fact, been shown that, apart from secondary forms, even those of a primary nature can be differentiated in the light of their predominant aetiology: hyperincretion of catecholamines, hyporeninaemia, hypercorticoidism, etc. These, of course, require specific, directed drug management: anti-adrenergic treatment, diuretic treatment, administration of spironolactone, etc.


[1 year of automatic management of an analytical laboratory using a part-time computer]. This paper is a report on a one year-automatic management of the Clinical Lab. of the Hospital of Gallarate (Italy) by means of a "part-time" computerization system. Technologies and procedures used for in-patients and out-patients are analysed: by this kind of management many advantages are obtained but some partly unremovable drawbacks, are identified which are mainly caused by the current management of clinical Departments.


[Bilateral occlusion of the internal carotid artery with compensatory circulatory through the ophthalmic arteries]. This study is referred to a patient with bilateral occlusion of the internal carotid artery with anastomotic compensatory circle through ophthalmic arteries.


[Ultrasonic diagnosis of aneurysms of the abdominal aorta]. The principles of ultrasound diagnosis are briefly explained and the technique of the examination is described with particular reference to the measures taken to ensure the exact measurement of diameters. The modalities for the echographic presentation of the normal and aneurysmatic aorta is illustrated, together with the respective pictures. It is suggested that echography be employed both as a preliminary technique and as a supplement to angiography, which is not itself particularly applicable in the case of aneurysms. Above all, it can be considered as the sole and resolutive examination on account of the findings it offers.


[Antigenic hemagglutinating characterization of influenza virus A/Torino/1/75 (H3N2)]. An A strain influenza virus isolated in Turin during the winter of 1974-75 was antigenetically related to the A/Port Chalmers/1/73 strain and dominant with respect to it. In addition, it was dissimilar and antigenically distant from the A/Scotland/840/74 strain.


[Research on the immunity status of the Turin population with respect to 3 recent variations of influenza A virus]. Measurement of influenza A/Torino/1/75, A/MRC 11 and A/Scotland/840/74 viruses h.i. antibodies in a sample of the Turin population represented by 200 non-vaccinated adults, showed that the percentage of subjects carrying antibiodies at the minimum titre of 1/10 was respectively 83, 78,5 and 52 and respective mean titres were 1/65, 1/65 and 1/43. These results confirm the antigenic affinity between A/Torino/1/75 and A/MRC/11 strains and their diversity with respect to A/Scotland/840/74. It is emphasized that vaccines should include the Scottish variant of the influenza virus also.


[Problems of periodical health controls in the light of experience of Italian Diagnostic Center]. The medical, social and economic problems and implications involved in periodic health check-ups are considered. The starting point is the early experience of the Italian Diagnosis Centre and the examination of what has been done by Centres working in the field for some time. The intention is to stress the importance of defining in detail those pathological factors worthy of investigation and of showing that the purpose of the check-up is to pinpoint the correct diagnosis as quickly as possible. "Early diagnosis" is considered to be an area of primary importance in the struggle against disease. Finally, the social importance of the check-up in reducing the incidence of hospital admittances and average hospitalization is stressed.


Pregnancy in women over forty.

Pregnancy in women over forty. In a retrospective review of 440 pregnancies occurring in women over the age of 40, increased frequencies of both perinatal and maternal complications were noted. The perinatal mortality rate of the study group was three times greater than that of the general obstetric population. There were increased incidences of both low and high birthweight infants. Neonatal morbidity was increased. Congenital abnormalities were noted in 12 infants, including 2 infants with cytogenetic abnormalities. Hypertensive disorders complicated one-third of the pregnancies. Diabetes mellitus and abruptio placentae occurred with increased frequency. Cesarean section was required in 12.2% of the deliveries.


Assessment of factors constituting an "inducibility profile". A survey of 440 patients examined vaginally during the last month of pregnancy showed a correlation between quantitative assessment of the pelvic score features described by Bishop and the duration of induced labor. Cervical dilatation was as useful as the total Bishop score in this respect. Cervical dilatation and station of the head together were especially predictive for long labor and these two factors together with length of cervix were especially predictive for shorter labors. It was also apparent from this study that previous cervical surgery or vaginal termination of pregnancy was associated with a lower incidence of low Bishop scores. The changes in individual components of the Bishop score during the last month of pregnancy are described.


Fetal lung maturity. I. Mode of onset of premature labor. Influence of premature rupture of the membranes. In a prospective study of 133 spontaneous premature deliveries the relation between premature rupture of the membranes (PRM) and development of respiratory distress syndrome (RDS) in newborn infants is examined. PRM is associated with a significantly decreased incidence of RDS in newborn infants (P less than 0.002). This relation is valid at a gestational age of 28 weeks or more and a birthweight greater than 1000 g. Total respiratory morbidity in newborn infants (transient tachypnea + RDS) is also significantly decreased when labor is associated with PRM (P less than 0.005). Assessment of the influences of sex of the infant, fetal asphyxia, and delivery by cesarian section shows that PRM bears a stronger relation than each of these individual factors to a decreased incidence of RDS. Duration of the latent period has no influence on protection from RDS, and it is suggested that fetal lung maturity occurs before the membranes rupture.


Maternal serum unconjugated estriol and urine estriol concentrations in normal and high-risk pregnancy. Serum unconjugated estriol levels and urinary estriol levels of concurrent specimens were compared for 6 normal and 6 high-risk subjects throughout the last trimester of pregnancy. Free estriol values in serum exhibited a close correlation with urinary estriol values for both the normal (r = 0.91) and high-risk (r = 0.92) groups. The results of this study indicate that the assessment of high-risk pregnancies now accomplished principally by urinary estriol assays may be performed by more convenient and rapid radioimmunoassays developed for quantification of free estriol in serum.


The diagnosis and management of intrauterine growth retardation. Twenty-eight pregnant patients exhibiting subnormal fetal growth patterns by serial ultrasonic cephalometry were studied. Only 12 (43%) delivered small-for-gestational-age (SGA) infants indicating a poor correlation between the prenatal assessment of intrauterine growth retardation (IUGR) by ultrasonic cephalometry and the neonatal evaluation of the newborn as SGA. The most important factors in the evaluation of the fetus with subnormal serial ultrasonic cephalometry were: 1) the type of ultrasonic growth pattern ("late flattening" vs "low growth profile"), 2) the presence or absence of maternal high-risk factors, and 3) the gestational age of the fetus at the time of detection of the growth abnormality. A pregnancy showing a late flattening type of growth pattern by serial ultrasound in the presence of maternal high-risk factors and with the growth abnormality being detected before 35 weeks of gestation, almost certainly will terminate with the birth of a SGA infant. On the contrary, serial plasma free estriol determinations were not useful in predicting the fetal status at birth. All but 4 of these patients were delivered at term and there was neither perinatal mortality nor significant morbidity. It is suggested that the existence of an abnormal cephalometric pattern is not an indication for early delivery unless fetal distress is detected by means of an oxytocin challenge test.


Serum free estriol and estriol glucuronide fractions in hydatidiform mole measured by radioimmunoassay. Serum or plasma total unconjugated estriol and total estriol glucuronide fractions were measured in 14 patients with unaborted hydatidiform mole between 11 and 25 weeks of gestation and in 20 normal pregnant patients between 8 and 17 weeks of gestation. The estriol fractions were separated by solvent partition, and the estriol was measured by radioimmunoassay using antiserum against estriol-16-17-dihemisuccinate conjugated to bovine serum albumin. The values (means and ranges) found in normal pregnant patients were as follows: estriol 1.3 ng/ml (0.3-2.9); estriol glucuronide, 11.1 ng/ml (4.7-24.8). Wide ranges of values were found in patients with molar pregnancies compared to those with normal pregnancies of equivalent gestation, some values being within the upper range of normal and others being well below the normal range. Of the 14 molar pregnancies studied, 9 (64%) were associated with serum estriol values which were below the ranges for normal pregnancy, and 8 (57%) were associated with similarly low estriol glucuronide values. The incidences of low estriol and estriol glucuronide values were less than those reported for low urinary estriol excretion in hydatidiform moles. No correlation was found between any of the serum estriol fractions and the serum hCG values or with the presence of theca lutein cysts in the ovaries. It was suggested that the trophoblast was the principal source of estriol in these molar pregnancies.


Plasma hormones in human gonadotropin induced ovulation. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone (E1), estradiol-17beta(E2), progesterone (P), androstenedione (A), and testosterone (T) were analyzed in daily plasma samples of seven cycles of human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) induced ovulation. Plasma FSH rose gradually and remained at a higher level (20 to 30 mlU/ml) during hMG injection while LH stayed at a low tonic level. The FSH/LH ratio of plasma gonadotropins was consistently higher than 1 in spite of injecting an hMG preparation with FSH/LH ratio of 1. A pharmacologically induced high RSH/LH ratio in the late follicular phase is contradictory to the low ratio seen in the normal ovulatory cycle. This may be one of the causes of multiple follicular maturation and ovulation frequently encountered in the hMG-hCG induced ovulation. Higher than normal levels of plasma progesterone commonly seen in the hMG-hCG induced cycle is attributed to the multiple ovulation. Plasma androgen levels, both A and T, in these therapy cycles stayed consistently within normal range. This is a strong contrast to the clomiphene induced cycle in which A and T were frequently elevated in parallel with elevated LH. No significant differences in plasma hormones were observed between the pregnant and nonpregnant patient following hMG-hCG induced ovulation. A consistent and similar ovarian response to hMG-hCG was noted in 1 individual who had 3 consecutive therapy cycles studied. The plasma hormone levels in the multiple ovulation did not show a significant difference from those in the single ovulation with the exception of a higher plasma P level in the former.


Embolization of the hypogastric arteries in the control of massive vaginal hemorrhage. Percutaneous, transcatheter Gelfoam embolization of the hypogastric arteries was utilized in a patient to control vaginal hemorrhage secondary to far-advanced carcinoma of the cervix. The advantages of this method are outlined, and consideration of its use is recommended for patients in similar situations. The various types of particulate material used in transcatheter embolization and the situations in which they have been used are reviewed.


Ectopic pregnancy following tubal sterilization surgery. In a consecutive study of 100 women with the surgical diagnosis of ectopic pregnancy confirmed by histologic examination, 7 women were found to have had prior tubal sterilization surgery. In 3 of these cases the sterilization procedure was bilateral tubal fulguration. The diagnosis of ectopic pregnancy must be given careful consideration if patients conceive after a tubal sterilization procedure of any type.


Preirradiation celiotomy and extended field irradiation for invasive carcinoma of the cervix. Epidermoid carcinoma of the cervix was treated in 120 patients by means of exploratory celiotomy (with semitherapeutic excision of involved lymph nodes) followed by irradiation. The size of the field used for irradiation was determined by the presence and site of lymph involvement. Of 64 patients, metastatic cancer in pelvic nodes was found in 40, and in common iliac or aortic nodes in 24. Of the 2 groups, 8 and 3 patients, respectively, survived for 2 years or more. Irradiation to extended fields (using 5500 rads at 850 rads per week) controlled the cancer satisfactorily within the treated area, but the incidence of bowel complications was high. Recurrent carcinoma usually appeared as distant metastases outside the treatment area which suggests that patients with bulky primary lesions and positive nodes actually already have systemic disease as treatment is started. A safe yet effective dosage level for radiation therapy to extended fields has not yet been established.


Histogenesis of pseudomyxoma peritonei. Review of 9 cases. Nine cases of pseudomyxoma peritonei associated with ovarian neoplasia have been reviewed specifically from the standpoints of histology and histogenesis. It is suggested that this disseminated intraabdominal neoplasia results from mucinification of the abdominal mesothelium and that the stimulant for this alteration lies in the mucinous fluid.


Elective abortion. Complications seen in a free-standing clinic. Experience is reported with the elective first trimester abortion of 16,410 pregnancies during a 31-month period by Reproductive Health Services of St. Louis, a free-standing clinic. Incidence of complications was 1.54%. The most common of these were incomplete evacuation, excessive postabortal bleeding, and uterine perforation. In patients with unquestioned perforation, the use of laparoscopy has been very valuable in ascertaining the exact nature of the perforation, in avoiding unnecessary laparotomy, and in giving intraabdominal visual guidance to concomitant suction evacuation in cases of an incomplete procedure. Aspects of the other complications are also discussed. In general, the findings support the view that even in the first trimester, the earlier in pregnancy that suction abortion is performed, the less likely it is to result in major complications. It is possible to perform first trimester abortions in a free-standing clinic with a satisfactorily low complication rate.


Nonpuerperal uterine inversion. Report of an unusual case. Total nonpuerperal inversion of the uterus is rare. A case caused by a fundal leiomyoma is presented. It is the first reported case that included the complications of acute obstruction of the urethra from upper vaginal inversion and bilateral hydronephrosis from traction of the prolapsed inverted uterus on the distal ureters. The various complications and the management of the condition are discussed.


Large endometrioma occurring in an adolescent. The occurrence of endometriosis and endometriomas in adolescent women is unusual. A large endometrioma of the ovary, occurring in a 19-year-old woman, with minimal symptomatology, is reported. The occurrence, etiology, and treatment are discussed.


Unusual uterine malformation. Double cervix with single corpus and single vagina. An unusual uterine malformation in which double cervix was the sole müllerian tube fusion defect is presented. It was associated with numerous other congenital anomalies in a 4-month-old infant with normal chromosome studies. The embryologic significance of this defective fusion is discussed.


Dyspareunia from auto suture staples. A report of two cases. The use of Auto Suture staples for closure of the vaginal vault after abdominal hysterectomy may result in postoperative dyspareunia and urinary urgency. Two cases are reported in which these complications occurred.


The in vivo and in vitro analysis of immunity to Trichinella spiralis in mice and rats. Wistar-Furth strain male rats and CFW strain male mice were immunized against Trichinella spiralis using an antigenic fraction derived from a cell-free homogenate of mature muscle larvae. In rats, animals immunized with 250 mug of antigen harboured significantly fewer (135000) muscle larvae 30 days after oral challenge than controls (231000). Further 7-day-old adult worms derived from immunized rats shed 48% fewer (P less than 0.001) newborn larvae over a 24h period in vitro than adult worms from non-immunized animals. Mice were injected with either 10 or 100 mug of antigen. In comparison with non-immunized controls, mice immunized with 100 mug of antigen harboured significatnly fewer adult worms at days 7 and 9 after oral challenge infection, while female worms recovered from immune mice on days 6-10 after challenge shed fewer newborn larvae in vitro. Finally, mice immunized with 100 mjg of antigen harboured significantly fewer (10391) muscle larvae at 30 days after challenge than did controls (47750). Immunization of mice with 10 mug of antigen did not induce a statistically significant reduction in adult worms at either day 7 or 9 after challenge (P less than 0.5). However, adult female worms from mice receiving 10 mug of antigen still shed fewer larvae than did adults from control mice (P less than 0.05). Mice immunized with 10 mug of antigen harboured significantly fewer (13700) recoverable muscle larvae than did controls at 30 days after challenge (39000).


Isolation of chick intestinal cells infected with second-generation schizonts of Eimeria necatrix. After infection with Eimeria necatrix, chick intestinal cells undergo a profound increase in size. Herein, we describe methods for isolating and purifying infected cells containing second-genration schizonts at various times post-infection. Our purification procedures depends upon three fundamental properties of infected cells: namely (1) large size, (2) resistance to shearing and (3) decreased susceptibility to osmotic shock in hypotonic solutions. The availability of simple techniques for isolating infected whole cells should prove valuable in elucidating various intracellular aspects of infection during schizogony.


Isolation of host-cell nuclei from chick intestinal cells infected with second-generation schizonts of Eimeria necatrix. A procedure is described for the preparation of purified nuclei of chick intestinal cells infected with Eimeria necatrix. During second-generation schizogony the host-cell membrane becomes resistant to homogenization, hypotonic shock and ultrasonication. However, brief treatment with a low concentration of trypsin (0.001%) will disrupt the cell membrane. Thereafter the nuclei can be selectively harvested from contaminating nuclear types and schizonts by a series of centrifugations. Electron microscopy and Feulgen-DNA microspectrophotometry showed that the nuclear preparations retained their integrity with little, if any, loss of DNA. Chemical determinations confirmed that host-cell nuclear DNA synthesis was stimulated by coccidial infection and further established that quantitatively there was a coincident increase in the amount of host nuclear RNA during schizogony. It is now feasible to examine directly the effects of coccidial infection upon the host's nuclear apparatus.


Trypanocidal activity of blood and tissue fluid from normal and infected rabbits treated with curative drugs. A new technique for determining the trypanocidal activity of body fluids has been devised, using very small quantities in the wells of plastic microtest plates. The activities of blood and tissue fluid of rabbits have been measured after the infection of melarsoprol, suramin, diminazene aceturate and isometamidium chloride. Activity against Trypanosoma (Trypanozoon) brucei persisted in body fluids for a shorter time in treated normal rabbits than in treated rabbits infected with the trypanosome. The difference was caused by the participation of the immune response of the infected animals. The new technique was sensitive enough to detect these interactions of chemotherapy and immunology and should be of use in the study of new trypanocidal compounds.


Cystathionine beta-synthase deficiency: a qualitative abnormality of the deficient enzyme modified by vitamin B6 therapy. The thermostability of cystathionine synthase and the effect of pyridoxal phosphate (PLP) on this thermostability were investigated in extracts of normal human liver and in extracts of liver, both before and during pyridoxine (vitamin B6) therapy, from members of a family with three clinically and biochemically typical, B6-responsive, synthase-deficient sibs. Incubation of crude extracts of normal liver at 55 degrees (preincubation) for 3-4 min before assay consistently resulted in a more than 2-fold increase in specific activity (activation) of cystathionine synthase (Fig. 1). With periods of preincubation longer than 4 min, thermal inactivation occurred. When PLP was added to the preincubation mixture, slightly more activation occurred in the first 3-4 min, and there was no observable loss of activity for an additional 25 min. The activation phenomenon was not observed in extracts of liver which had been obtained from three synthase-deficient sibs before therapy with vitamin B6 (Index of activation, Table 1). When extracts of liver obtained during vitamin B6 therapy were studied, however, significant activation was observed. Synthase activity in extracts of liver from the patients' parents, obligate heterozygotes for synthase deficiency, and from a potentially heterozygous sister demonstrated activation similar to that found in control liver extracts. With periods of preincubation longer than 5 min, the inactivation of synthase in liver extracts from patients receiving pyridoxine-HCl occurred at the same rate as in liver extracts from heterozygotes and from normal subjects (Index of inactivation, Table 1). PLP completely prevented heat inactivation of enzyme from normal liver.


Effects of oral glucose and protein load on plasma glucagon and insulin concentrations in small for gestational age infants. This paper reports portal and peripheral blood glucose, insulin, and glucagon levels in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns during the first 48 hr of life. These parameters were studied after an oral glucose and protein load (1 g/kg of each) after a 4-hr fast. In AGA and SGA infants, mean fasting blood glucose level was significantly higher in the portal vein than in the aorta (P less than 0.05). After the load, mean blood glucose level rose significantly in both vessels. The mean fasting plasma insulin level was low and was similar in both vessels. After the load in the AGA group mean plasma insulin level rose significantly at 45 min both vessels (P less than 0.05) (52.1 +/- 37.2 muU/ml in aorta and 91.8 +/- 75.3 muU/ml in portal vein). In the SGA group, the insulin response was minimal in the aorta and in the portal vein; the increase was significant only in the portal vein (P less than 0.05) at 180 min (47.1 +/- 25.3 muU/ml). The mean fasting plasma glucagon level was higher in the portal vein than in the aorta in both groups (P less than 0.05). After the load in AGA infants plasma glucagon rose significantly from 193 +/- 55 pg/ml at zero time to 290 +/- 76.8 pg/ml at 180 min (P less than 0.01) in the aorta but not in the portal vein. In the SGA group, the mean plasma glucagon did not rise significantly in the aorta or in the portal vein (from 231.2 +/- 54.3 pg/ml at zero time to 293.7 +/- 123.5 pg/ml at 180 min in the portal vein). The molar ratio of insulin to glucagon (I/G) rose significantly after the load in the portal vein in both groups of infants (AGA 2.48 +/- 2.06 at zero time to 5.08 +/- 4.06 at 180 min; SGA infants from 2.2 +/- 1.98 at zero time to 4.16 +/- 2.59 at 180 min). When both groups of infants were compared there was no significant difference either in the aorta or in the portal vein in mean blood glucose, mean plasma level, and plasma glucagon level. It is concluded that SGA and AGA premature infants are similar in regard to secretion of both pancreatic hormones in the first days of life.


Serum calcitonin and blood mineral interrelationships in normal children aged six to twelve years. Simultaneous measurements of serum immunoreactive thyrocalcitonin (iTCT), immunoreactive parathyroid hormone (iPTH), calcium, inorganic phosphate, magnesium, and alkaline phosphatase were made in 37 normal children whose ages ranged from 6-12 years. Between the ages of 6 and 12 there is a statistically significant rise in serum iTCT levels (r = 0.4638; P less than 0.01), and a fall in serum iPTH levels (r = 0.4976; P less than 0.01). There is a highly significant inverse correlation between serum iTCT and iPTH levels (r = 0.5248; P less than 0.005). Serum iTCT levels were inversely correlated with phosphate levels (r = 0.4989; P less than 0.01), the latter being age dependent and falling significantly between the ages of 6 and 12 (r = 0.4802; P less than 0.001). There was no significant relationship between serum calcium levels and iTCT, iPTH, or age. Serum magnesium levels were not correlated with calcium, iTCT, or iPTH levels.


The in vivo use of dithiothreitol in cystinosis. Two male patients with late stage (uremic) infantile nephropathic cystinosis (INC) (Table 1) were treated by mouth with the reducing agent dithiothreitol (DTT), at doses not exceeding 25 mg-kg-1 body weight three times per day. Three sequential periods of observation were obtained in both patients: on thiol (8.5 months); off thiol (8-9 months); on thiol again (7 months or longer). Other than nausea and vomiting at the maximum dose range, no apparent toxicity was observed. One subject died in uremia in the 24th month of the study. The half-cystine concentration in peripheral blood leukocytes decreased during both treatment periods in each patient from initial pretreatment levels in excess of 8 nmol-mg-1 protein (normal less than 0.1 nmol-mg-1) to 10-20% of initial values (Table 2 and Fig. 1, A and B). Reduction in total number of blood leukocytes or in the neutrophil fraction, where cystine storage occurs selectively in cystinosis, did not occur (Table 3) as a possible explanation for these findings; nor did storage of samples, a possible artifact, influence the cystine content of cystinotic cells (Fig. 2). Multiple site rectal mucosa biopsy clearly revealed cystine storage but serial biopsies did not reflect a positive DTT response when compared with the leukocyte assay (Table 4). High intersample variation in cystine content, even between samples taken at one time, prevented measurement of a treatment response. DTT had no apparent detrimental effect on the concentration of representative proteins, including hemoglobin (Table 3), serum insulin, and serum immunoglobulin during the treatment trials. Renal function (glomerular and tubular) was severely depressed and did not improve during the period of observation in either patient (Table 2; Fig. 3, A and B). Postmortem tissues from one patient revealed 10-40-fold excess cystine accumulation in kidney cortex and liver (Table 5). However, these levels of accumulation are at the lower range of or even below published values for cystine in cystinotic kidney and liver. Whereas chemical methods are not reliable for detecting and measuring DTT in biologic fluids, preliminary evidence indicates that a silylated derivative of oxidized DTT can be detected in the urine of patients receiving DTT by mouth (Fig. 4). This finding suggests that the thiol is absorbed and excreted.


Studies on cystic fibrosis using isoelectric focusing. III. Correlation between cystic fibrosis protein and ciliary dyskinesia activity in serum shown by a modified rabbit tracheal bioassay. We have developed a modified rabbit tracheal bioassay for use in investigating a possible correlation between cystic fibrosis protein (CFP) and ciliary dyskinesia factor (CDF) in human serum. The bioassay requires high standards of tissue selection, and all epithelial tissue must be free of underlying connective tissue. When serum samples were collected and processed carefully and warmed to 37 degrees before assay, CDF could be reliably detected in 31 of 31 sera from cystic fibrosis (CF) homozygotes or obligate heterozygotes in 35 min or less without prior fractionation or concentration of sera, whereas 13 of 14 normal control sera were nonreactive. CDF-positive serum reacts in three consecutive phases: (1) initial increase in ciliary beat frequency, (2) ciliary dyskinesia, and (3) tissue destruction with extrusion of single ciliated cells, mucus, and debris. Our results confirm the association of CDF with cystic fibrosis. The bioassay is not specific for CF, however, when whole sera are bioassayed, since serum from several patients with bronchial asthma also caused ciliary dyskinesia. However, this finding need not preclude using rabbit tracheal ciliated epithelial tissue as an assay for following the purification of CDF. Isoelectric focusing showed that the presence or absence of CFP corresponded with that of dyskinesia activity in all sera tested except for the active samples from seven asthma patients, which were negative for CFP. The results indicate that CFP and CDF may be identical or closely related markers for the CF gene, and suggest that the activity detected by the rabbit tracheal bioassay in sera from patients with asthma and other diseases probably is caused by a substance different from a CF-specific CDF.


Hemoglobin alpha chain deficiency in black children with variable quantities of hemoglobin Bart's at birth. Hematologic and globin chain synthesis studies have been made in 21 children, aged 2 to 6 years, many of their parents, and several normal adults and alpha-thalassemia heterozygotes. At birth, 11 children had about 5% hemoglobin (Hb) Bart's, 5 had about 2% Hb Bart's, and 5 had no trace of Hb Bart's. A significant decrease in mean corpuscular volume. (MCV) and mean corpuscular hemoglobin (MCH) values and an increase in the beta/alpha ratio was observed in the first group; microcytosis and hypochromia were absent in the children of the second group although the beta/alpha ratio was significantly increased. The alpha chain deficiency is familial. Increased alpha/alpha ratios were present in many parents although only two parents of children with 5% Hb Bart's at birth had hematologic findings suggestive of the presence of the same type of defect as observed in the children with the larger amount of Hb Bart's at birth.


Plasma gonadotropins and estrogens in girls with idiopathic precocious puberty. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) estrone, and estradiol were measured radioimmunologically in more than 60 plasma specimens of 34 girls suffering from idiopathic precocious puberty. Although the median values of both gonadotropins in the plasma of the patients (LH = 1.0 ng/ml; FSH = 1.6 ng/ml) were higher than those from healthy prepubertal girls (LH = 0.6 ng/ml; FSH = 0.5 ng/ml), only 23 out of 64 LH levels and 30 out of 64 FSH levels exceeded the upper normal limit for age. While the median value of plasma estrone (13 pg/ml) was found to lie within the normal range for prepubertal girls (7-29 pg/ml) and only 13 out of 75 estrone values were pathologically elevated, the median value of plasma estradiol (22 pg/ml) was nearly 3 times higher than the normal median for prepuberty (8 pg/ml). Of 75 estradiol levels, 35 were above normal for age. Grouping the values according to the stage of sexual development revealed considerably lower gonadotropin and estrogen levels in the patients than in normally maturing girls of the same developmental stage. However, patients who were examined repeatedly at short intervals over a 1-month period showed an almost cyclic sequence of their estradiol levels similar to the pattern observed in healthy pubertal girls.


Origin and metabolic fate of plasma glycerol in the rat and rabbit fetus. On day 21.5 a pregnant rat received a single injection of [1-14C]glycerol. The purpose was to study the transfer of glycerol through the placenta from the maternal to fetal plasma. From 3-20 min after injection the specific activity of glycerol in maternal and fetal plasma was measured. The results indicate that the mother can provide this molecule to the fetus. Similar results were obtained with the rabbit on day 28 of pregnancy. The possibility of the conversion of plasma glycerol to glucose has been investigated in the rat and rabbit fetus. This molecule was chosen chiefly to see whether the gluconeogenic pathway was functioning in the fetus above the triose phosphate step. At two stages of fetal development the capacity of the fetus to incorporate [1-14C]glycerol into glucose plus glycogen has been shown in the two species. In the rat fetus the conversion of [1-14C]glycerol to [14C]glucose increases from 19.5 to 21.5 days of gestation. For the rabbit this parameter increases from 25 to 28 days of gestation. On day 25 in the rabbit and day 19.5 in the rat the liver glycogen was labeled, but it did not accumulate the [14C]glucose from [1-14C]glycerol during the time that we have studied. In contrast, on day 28 in the rabbit and day 21.5 in the rat the incorporation of radioactivity increased as function of the time. However, the relative importance of glycerol as precursor of the glucose plus glycogen in the fetus remains to be elucidated.


A biochemical concept of cellular production of paramyxoviruses. Previous analysis in vitro of the interaction between some paramyxoviruses and the chicken embryo has indicated that the cell most productive (MP) of virus is the heart cell whereas the liver cell is least productive (LP). More superior production of virus results from more efficient release of virions, whereas the kinetics of viral attachment and penetration and the production of interferon are similar for both types of cell. Since plasma membrane lipids may represent the structural key to enveloping and release of paramyxovirions, the lipid composition of MP and LP cells and purified plasma membranes was investigated. The plasma membranes of heart cells contain a high molar ratio of cholesterol to phospholipid (1.66 vs. 0.55), more phosphatidylethanolamine (34.8% vs. 24.0% of total phospholipid), and less phosphatidylcholine (39.7% vs. 55.0% of total phospholipid) than the plasma membranes of liver ce-ls. The fatty acids of heart and liver cellular plasma membranes are similar. The glycosphingolipid components of heart and liver cells are also the same, as is the content of gangliosides (6.18 mug vs. 6.49 mug neuraminic acid/mg protein) in these cells, but the heart cell contains one-fifth as much total cerebroside (34.3 mg vs. 174.3 mug cerebroside/mg protein), indicating a greater ganglioside to neutral glycolipid ratio for the heart cell. Comparison of these data with the monkey/hamster (MP/LP) renal cell-parainfluenza SV5 virus system of Klenk and Choppin suggests that essential molecular determinants of superior cellular production of paramyxoviruses are the relative concentration of phosphatidylethanolamine and the molar ratio of cholesterol to phospholipid in the plasma membrane.