The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. I. Recessive lethal mutations and translocations in Drosophila. The relationship in Drosophila males between chemical reaction pattern of mono-functional alkylating agents (AA), described in terms of primary alkylation pattern with DNA and proteins as well as the Swain--Scott s factor, and their biological effectiveness were investigated. The agents chosen for comparative analysis were the nitrosamides ENU and MNU, the methanesulfonic esters iPMS, EMS and MMS, the dialkylsulfate DMS, and the nitrosamines DEN and DMN. Parameters of their biological activity were mortality (LC50) of treated adult males, induction in post-meiotic stages of X-chromosomal recessive lethal mutations and 2--3 translocations after either adult feeding or injection. Induced frequencies of recessive lethals, determined for each AA with a range of concentrations, served as biological dosimeter for interaction with target DNA in the germ line. The results are interpreted as indicating for these AA a causal connection between the pattern of primary alkylation of DNA and the quality of genetic damage observed. 1. The agent with the lowest s value, ENU, and its pendant DEN, failed to produce translocations at mutation frequencies that reached 44% for ENU. The highest chromosome-breaking activity was attributed to AA with high s, MMS and DMS. For MMS, the proportions of translocations (T) to mutations (M) approximately reached a 1 : 1 ratio in stored spermatozoa, at a recessive-lethal frequency of 14%. Ability to break chromosomes, as indicated by the T : M ratios, decreased in the sequence MMS greater than or equal to DMS, MNU greater than DMN greater than EMS greater than iPMS greater than ENU = DEN. 2. Nearly the reversed sequence in relative mutagenci effectivenss was obtained when the (directly acting) AA were arranged on the basis of their CM4/LC50 ratios (CM4, the exposure condition producing 4% recessive lethals after injection): ENU greater than EMS greater than iPMS, MNU greater than MMS = DMS. 3. Among the AA, EMS had a somewhat unique position, in that it was slightly less effective in the translocation test, and also less cytotoxic but more mutagenic in the recessive-lethal test than one would expect from its s value. This is taken as an indication of the influence on biological effectiveness of factors other than the s value, e.g. methylation versus ethylation and the lipid/water partition ratio. An example of the latter was also provided by DMS which, although having the same s as MMS, with its 5-fold higher lipid/water partition ratio, was more toxic than MMS. 4. For those AA that were clearly active in the translocation tests--MMS, DMS, MNU, DMN and EMS--delayed formation of exchanges was observed. Only in 17 out of 555 translocation tests with positive response translocations were already found in progeny from unstored spermatozoa. Consequently, it was concluded that performance of storage experiments in Drosophila is an absolute necessity for the detection of this type of rearrangement by AA. 5...


Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II. cis-Dichlorodiamminoplatinum-II (cis-DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of cis-DDP was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis-DDP. Significant increases in SCE rate were observed at 0.25 micrograms/ml and higher, showing a clear dose-response relation between SCE rate and cis-DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis-DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis-DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.


Neural hyperexcitability in hyperkalemic periodic paralysis. An electrophysiologic study of peripheral nerve excitability was performed in patients with hyperkalemic periodic paralysis (HPP) and in normal controls. It was found that a marked degree of neural hyperexcitability existed in all patients with HPP who showed cold sensitivity. The results suggest involvement of the nerve cell membrane in the proximal segments of peripheral nerve. This testing method may be of value in differentiating the cold-sensitive variant of HPP.


Protein synthesis in skeletal muscle following acute exhaustive exercise. Cell-free and whole-tissue protein synthesis was studied in skeletal muscle of untrained male guinea pigs that had undergone a treadmill run to exhaustion. Experiments using explants from the gastrocnemius muscle maintained in organ culture demonstrated that the ability of the acutely exercised muscle to incorporate amino acids into protein had increased. Compared to polyribosomes prepared from several lower hind limb muscles of nonexercised guinea pigs, polyribosomes from the same muscle in exhausted guinea pigs had incorporated almost 50% more radioactive leucine into protein. However, the polysome profiles of control and exercised muscle were identical, and no difference in the total polysome RNA content could be detected. The efficiency of in-vitro protein synthesis using washed membrane-bound polyribosomes (microsomes) isolated from acutely exercised skeletal muscle was 50% greater than with microsomes from rested control muscle.


Amplitude of the surface electromyogram during fatiguing isometric contractions. Five voluntee subjects held isometric handgrip contractions at specific submaximal tensions until the required tension could no longer be maintained. At the start of those contractions, the amplitude of the surface electromyogram (EMG) was linearly related to the tension exerted; the amplitude of the EMG increased linearly throughout these substained contractions by a constant amount--about 30% of the maximum. During sustained contractions, brief, intermittent maximal efforts showed that strength declined linearly at all tensions. At 25% maximal voluntary contraction (MVC), there was a linear fall in the EMG amplitude associated with the brief maximal efforts, but the fall in strength was more rapid than the fall in EMG amplitude. At 70% MVC, there was no fall in the EMG amplitude in response to the brief maximal efforts, while the muscle strength fell linearly.


Contractile responses of rat fast-twitch and slow-twitch muscles to glucocorticoid treatment. In an attempt to determine whether chronic glucocorticoid treatment affects speed- and strength-related properties of fast-twitch muscle and slow-twitch muscle, in-situ contractile properties of soleus and gastrocnemius muscles were measured in rats after 14 days on a regiment of triamcinolone acetonide injected at a dosage of 2 mg/kg/day. No effects on contractile speed or strength were noted for either muscle. The time to peak tension in soleus muscle was significantly longer in the treated group (43.0 +/- 1.0 msec) than in the control group (38.7 +/- 0.7 msec); however, this was attributed to a prolongation of "active state" duration, as suggested by the fact that treated muscles also showed significantly elevated twitch-tetanus ratios. The treatment-induced enhancement of the specific twitch tension was more pronounced in the gastrocnemius muscles (198% +/- 19% of control) than in the soleus muscles (153% +/- 9% of control). The difference in response to steroid treatment may reflect structural and functional differences in fast- and slow-muscle membrane systems.


Cylindrical spirals in human skeletal muscle. Muscle biopsies from two patients revealed that numerous type 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific.


Morphologic changes in extraocular muscles of the dystrophic hamster. Cardiomyopathic hamsters (UM-X7.1 strain) have demonstrable myopathy involving both skeletal and cardiac muscle. In addition, they have multiple ocular abnormalities. In this study, extraocular muscles were examined by light and electron microscopy. Changes observed within affected muscle fibers were variable and included coagulation necrosis, lysis of myofibrils, mitochondrial changes, and infiltration by phagocytic cells. Regenerative changes included duplication of myoblast nuclei, proliferation of sarcoplasmic reticulum, and myofibrillogenesis. The lesions are presumably myogenic in origin. The cardiomyopathic hamster may be useful as an animal model for certain types of ocular myopathy in man.


Reinnervation of rat extensor digitorum longus muscles after free grafting. Free grafts of the extensor digitorum longus (EDL) muscle of the rat are invaded by regenerating nerve fibers during the second postoperative week. Neuromuscular junctions are established during the third week. Levels of choline acetyltransferase (CAT) activity parallel the invasion of the graft by nerve fibers, but this activity never returns to control levels. We conclude that incomplete reinnervation of free muscle grafts may be a factor in the failure of such grafts to reattain the mass of control muscles.


Weakness from magnesium-containing cathartics: electrophysiologic studies. The case history of a patient with severe muscular weakness resulting from magnesium intoxication following oral and rectal administration of magnesium citrate cathartics is reported. The findings of the electrophysiologic studies were characteristic of the neuromuscular blockade seen in this disorder, including marked reduction in evoked muscle action potential amplitude which progressively decline on nerve stimulation at low rates, and a striking degree of facilitation of evoked muscle action potential after exercise or on high-frequency stimulation. When the hypermagnesemia was corrected, strength returned to normal.


Serum creatine kinase and pyruvate kinase in Duchenne muscular dystrophy carrier detection. The incidence of elevated serum creatine kinase (CK) and pyruvate kinase (PK) activities was compared in 20 definite carriers of Duchenne muscular dystrophy (DMD), 47 possible carriers, and 42 female controls. When adult age was not regarded as a variable, 70% of the definite carriers had elevated PK, 55% had elevated CK, and 75% had elevated PK or elevated CK or both, 38% of the possible carriers had elevated PK, 19% had elevated CK, and 40% had elevated PK or elevated CK or both. The detection efficiency of the CK test was influenced by the age of the subjects: the upper normal limit of serum CK in the adult controls was at the minimum between 21 and 35 years of age, and CK activity in some carriers declined from elevated to normal levels with increasing age. With these considerations, 70% of definite carriers had elevated CK and 80% had elevated PK and/or CK; 34% of the possible carriers had elevated CK and 43% had elevated PK and/or CK. On the basis of the PK and CK measurements, only 16 of 24 possible carrier mothers were likely to be DMD carriers, implying that the other 8 were non-carrier mothers of new mutant sons.


New muscle transplant method produces normal twitch tension in dystrophic muscle. Grafting newborn muscle is an innovative method of muscle transplant. This method overcomes hypoxia in the deeper fibers and facilitates reinnervation and revascularization of the grafted muscle fibers, thus promoting the survival and development of the characteristics of the donor muscle. The result achieved is superior to that obtained from mature muscle grafts or from minced muscle transplants. When an intact soleus from a 1-day-old normal mouse was grafted into a recipient soleus of a 20-day-old dystrophic C57BL/6J-dy2J mouse, the actively developing normal graft helped to improve the structure and function of the dystrophic muscle. When compared to the intact dystrophic solei, the test dystrophic muscles five to six months after operation showed increases in cross-sectional area, in wet weight, in twitch and tetanic tension, and in the number of muscle fibers with high resting membrane potentials. This is the first procedure to have raised the muscle twitch tension in an adult dystrophic mouse to the normal level.


Experimental myotonia induced in denervated muscles by 2,4-D. Rats were denervated in one hind limb and injected with 2,4-dichlorophenoxyacetic acid (2,4-D). Isotonic tetanic contractions of the muscles treated with 2,4-D after more than 10 days of denervation revealed prolonged relaxation times similar to those of the intact side and characteristic of clinical myotonia. No myotonic discharges were observed in the muscles denervated for more than 10 days and treated with 2,4-D. The increase in threshold for action potential generation secondary to denervation is suggested as the factor limiting the initiation of the repetitive discharges.


Chloroquine-induced cytosomes with curvilinear profiles in muscle. A patient with systemic lupus erythematosus (SLE) was treated with chloroquine therapy for four years after the onset of her illness. Nine years after cessation of chloroquine, muscle weakness developed as part of the SLE. Four muscle biopsies performed for diagnostic purposes revealed varying degrees of inflammatory change as well as distinctive cytosomes with curvilinear profiles (CCPs). These CCPs were identical to those reported in Batten disease, a degenerative disorder of children which has a clinical course different from SLE. The CCPs seen in this case of SLE are thought to result from the effect of chloroquine on membrane systems within muscle cells. This report calls attention to the fact that CCPs are not unique to Batten disease bu may also occur in muscle of SLE patients treated with chloroquine.


Defective oxidative metabolism of myodystrophic skeletal muscle mitochondria. A small-scale procedure for preparing tightly coupled intact skeletal muscle mitochondria from myodystrophic (myd/myd) mice is described. Mitochondrial preparations derived from heart, liver, and skeletal muscle of myd/myd and their littermate (+/?) controls are characterized with respect to their cytochrome content and their oxidative and phosphorylative capacities. Our data indicate that there is an impairment in the NADH CoQ region of the respiratory chain of myodystrophic skeletal muscle mitochondria. Both heart and liver mitochondria of myd/myd exhibited normal activities of respiratory chain-linked oxidative phosphorylation.


Congenital muscular dystrophy: case reports and reappraisal. We report four cases of congenital muscular dystrophy; all demonstrated hypotonia and multiple contractures at birth. Strength remained stationary or improved, but the tendency for contracture formation persisted. Brief small amplitude polyphasic potentials were recorded on electromyography, and muscle biopsy revealed extensive fat and/or collagen replacement, which was out of proportion to fiber necrosis or patient strength. The consistent clinical and pathologic features of these patients and others described in the literature justify considering this disorder to be a specific nosologic entity.


The importance of serum pyruvate kinase in neuromuscular diseases and carrier states. Serum pyruvate kinase activity was measured in several myopathic and denervating illnesses as well as in 86 potential carriers of Duchenne dystrophy. These data showed that in potential Duchenne carriers, the serum pyruvate kinase assay is more sensitive in younger patients, especially those under 20 years of age.


Saturated phosphatidylcholine in amniotic fluid and prediction of the respiratory-distress syndrome. The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is widely used to predict the risk of respiratory-distress syndrome. However, the results are unreliable if the specimen is contaminated or obtained during a complicated pregnancy. We therefore compared the predictive value of the L/S ratio with that of the concentration of saturated phosphatidylcholine (SPC) in 322 amniotic-fluid samples, 75 per cent of which were contaminated or obtained during complicated pregnancies or both. A positive result is one that predicted the development of respiratory-distress syndrome, taken as an L/S ratio equal to or less than 2/1 or an SPC below 500 mug per deciliter. The respiratory-distress syndrome was correctly predicted in 25 of 45 cases (55.5 per cent) with L/S ratios equal to or less than 2/1, and in 35 of 42 cases (82 per cent) with SPC's less than 500 mug per deciliter. When L/S ratios were greater than 2/1, there were 13 of 277 (4.7 per cent) false negatives, and when SPC's were above 500 mug per deciliter, there were three of 280 (1.1 per cent) false negatives. We conclude that determination of SPC is both more specific and more sensitive as a predictor of the respiratory-distress syndrome than the techniques currently in use.


Ventricular fibrillation in the Wolff-Parkinson-White syndrome. To examine the risk of ventricular fibrillation in patients with the Wolff-Parkinson-White syndrome, we compared patients who had this syndrome and a history of ventricular fibrillation related to preexcitation with patients who had the syndrome without this history. Ventricular fibrillation occurred during atrial fibrillation, with rapid conduction over the accessory pathway, and these patients had a higher prevalence of both reciprocating tachycardia and atrial fibrillation (14 of 25 vs. 18 of 73, P = 0.004) and multiple accessory pathways (five of 25 vs. four of 73, P = 0.012). The shortest preexcitation R-R interval during atrial fibrillation was less in the group with ventricular fibrillation (mean shortest R-R, 180 vs. 240 milliseconds, P less than 0.0001) as was the average R-R interval (mean average R-R, 269 vs 340 milliseconds, P less than 0.0001). Patients with Wolff-Parkinson-White syndrome who are most susceptible to ventricular fibrillation have a history of atrial fibrillation and reciprocating tachycardia, demonstrate rapid conduction over an accessory pathway during atrial fibrillation and have multiple accessory pathways.


Evaluation of acromegaly by radioimmunoassay of somatomedin-C. We measured serum concentrations of somatomedin-C by radioimmunoassay in 57 acromegalic patients and compared them with various indicators of disease activity. The mean fasting somatomedin-C concentration was 6.8 U per milliliter (range, 2.6 to 21.7) for the acromegalics and 0.67 U per milliliter (range, 0.31 to 1.4) for 48 normal, fasting adults. The somatomedin-C concentration correlated significantly with: heel-pad thickness (r = 0.73), fasting glucose (r = 0.74), and one-hour postprandial glucose (r = 0.77). In contrast, "glucose-suppressed" growth hormone correlated weakly (r = 0.34, 0.36, 0.34) with these clinical indexes of severity. Fasting growth hormone levels showed no correlation (r = 0.14). Five active acromegalics had "normal" growth hormone levels after glucose suppression, but they had elevated somatomedin-C. In 15 patients studied one year after treatment, changes in somatomedin-C concentrations paralleled the degree of clinical improvement. Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations.


Detection of early cardiac dysfunction in patients with severe beta-thalassemia and chronic iron overload. To detect early left ventricular dysfunction, we used radionuclide cineangiography to determine left ventricular ejection fraction during exercise in 24 patients with transfusion-dependent, congenital anemias, 21 of whom had severe beta thalassemia. Ejection fraction at rest was normal in 21 patients (greater than 45 per cent) and in all patients was 53 +/- 2 per cent (mean +/- S.E.M.)--not significantly different from the value in normal subjects. However, ejection fraction during exercise was normal in only 11 patients (53 +/- 3 per cent in all patients, P less than 0.001 as compared with the normal value). All eight patients who had received fewer than 100 transfusions but only three of 16 (19 per cent, P less than 0.001) who had received 100 or more transfusions had normal responses during exercise. Whereas echocardiographic fractional shortening at rest was normal in 16 of 19 patients studied, eight patients with normal fractional shortening had abnormal ejection-fraction responses to exercise. Thus, radionuclide cineangiography during exercise is a highly sensitive technique for detecting preclinical myocardial dysfunction in patients with systemic iron overload.


Studies on the air-borne fungal spores in Amritsar: their role in keratomycosis. An aerial survey for fungal spores in Amritsar has been carried out by petri plate exposure method for a period of one year. A total of 23 fungi appeared in the plates. Out of these Aspergillus was the commonest fungus representing 21.69% of the total colony count followed by Alternaria, Curvularia and Fusarium. There was seasonal variation in the prevalence of fungal spores. A comparison of the prevalence of fungi in diseased and healthy eyes and the atmosphere of Amritsar appears to support the view that these fungi are transient residents in the eyes depending on their availability in the atmosphere.


[Rheological properties of a calcium alginate-potato starch hydrolysate-water system]. The rheological properties of liquid solutions and gels of sodium alginate, calcium gluconate and gelling maltodextrin were investigated and compared with the behaviour of pastes and gels of non-degraded potato starch. The dependence of the rheological properties upon the calcium gluconate concentration is extreme. A marked increase in the viscosity of the liquid solutions and maximal values for the hardness and the breaking strength of the gels are obtained at a calcium gluconate/sodium alginate ratio of 0.3. As to breaking strength, elasticity and hardness, the maltodextrin-based gels are many times inferior to the potato starch-based gels. The breaking strength, hardness and elasticity of maltodextrin gels are increased by the addition of sodium alginate and calcium gluconate, which increases their effectiveness when used in foods.


[Improvement in the quality of rape seed by combining silage with fodder sugar beets. 2. Changes in glucosinolate derivatives and fat contents]. Industrial and laboratory-scale studies showed that the combined silage fermentation of rape-seed flakes with half sugar mangels leds to a very beneficial reduction in the content of glucosinolate derivatives, especially during the first week of fermentation and storage processes on the qualitative and quantitative fatty-acid parameters were but significant.


[Analysis of nitrate and nitrite in feed. 2. Potentiometric nitrate determination with ion sensitive electrodes]. Nitrate-sensitive PVC matrix membrane electrodes produced in the German Democratic Republic are suited for determining nitrates in feeds and plants if the different causative parameters are taken into account. A rational determining method is presented. Comparisons with the o-cresol method showed statistically confirmed agreement.


[The Maillard reaction between beta-lactoglobulin and lactose. 2. Effect of thiol and disulfide groups on the properties of the macromolecular reaction products]. If a protein takes part in the Maillard reaction as the amino component, other functional groups in the protein molecule are also expected to react in addition under appropriate conditions. The beta-lactoglobulin-lactose system, first used by Freimuth and Trübsbach, served to demonstrate that the properties of the products from the Maillard reaction are affected by thiol and disulphide groups in a low-water medium at high temperature. The amount, solubility, swelling capacity and composition are modified in dependence of the presence or absence of these reactive groups.


[Use of the combined Kjeldahl-wet digestion/Berthelot-reaction for determining nitrogen in biological materials. 2. Design and testing of a partially automated apparatus for routine determination of nitrogen]. The authors describe the design and the mode of operation of a partially automated analyzer system, based on the combination of the Kjeldahl wet digestion with the Berthelot reaction, for the determination of nitrogen in biological materials. The results from three years of operation are discussed from the view-points of variability of the materials to be tested, of accuracy and of precision. This analytical technique (with an accuracy of 98% and a precision of 4%) is suited for determining amino and amido nitrogen as well as non-aromatically bound ring nitrogen. The statistical evaluation of the analytical results revealed that the deviation of the measured values is mainly caused by the high-temperature digestion.


Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential. Extrinsic optical probes have become important tools for monitoring membrane potential, with probes now available for many tissue or cell suspension systems. In each case that has been studied in detail, it seems that the mechanism involves a shift in the equilibrium population of the probe from one chemical environment to another in response to the transmembrane potential; the environments perturb the probe's spectrum differently. As this indirect mechanism involves a redistribution of dye between chemical environments that are likely to vary if a given probe is transferred from one membrane to another, a potential probe that is effective and calibrated for all membrane systems has not been realised. We present here evidence for a direct response of a probe chromophore to the electric field across membrane systems. The results suggest it might be possible to develop a universal set of membrane probes.


The molecular structure of lecithin dihydrate. Lecithin is a major structural component of biological membranes. Because of their amphipathic nature, lecithin and related phospholipids tend to aggregate as bilayer structures in which the hydrophilic head groups are orientated towards the surface and the hydrophobic hydrocarbon chains towards the interior. A detailed knowledge of the three-dimensional structure of lecithins will aid in the understanding of their role in membrane structure and function, but is still lacking. To this end we have now crystallised and solved the molecular structure of 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC), a lecithin species in the naturally occurring configuration. This compound crystallises from a water-containing solution, with two water molecules (5% w/w) of hydration.


Heat-shock induced proteins present in the cell nucleus of Chironomus tentans salivary gland. The heat shock (HS) system has been largely studied in Drosophila but the molecular mechanisms responsible for the induction of the heat shock genes as well as the function(s) and the intracellular localisation of the induced proteins is still unknown. It has previously been shown that the HS puff induction is accompanied by a local increase of nuclear nonhistone proteins (NHP) but the nature of most of the proteins accumulating is unknown. We have investigated the effects of a heat shock on Chironomus tentans salivary glands, a system where it is possible to study constituents in various subcellular or intranuclear regions including individual puffs, by microdissection. We report here evidence that at least two of the polypeptides synthesised in response to the heat shock migrate to the nucleus. Furthermore, these two proteins appear to have a broad intranuclear distribution, as shown by their presence in the various microdissected nuclear fractions.


Quaternary structure-induced photoreduction of haem of haemoglobin. Spectroscopic studies have provided extensive information on the primary process of visual pigments and photoexcitation of chlorophyll as well as their effects on photoreactivity on the higher-order structures of protein has been observed only rarely. Resonance Raman spectroscopy can reveal the vibrational frequencies of the chromophore in a molecule provided the excitation wavelength is in the absorption band of that molecule. As the visible absorption bands of haemproteins are due to pi pi* transitions of the porphyrin ring, we can selectively observe the vibrational frequencies of iron porphyrin during in situ interactions with immediate amino acid residues of protein when the wavelength of excitation light is close to the Soret or Q band. Correlation of some vibrational frequencies of haem with the oxidation and spin states of the haem iron has been studied in detail and an empirical rules has been established. This method is therefore especially suitable for the study of an effect of higher-order structures of protein on the chromophore. We report here a photoreaction facilitated by a particular quaternary structure of protein--in various haemoglobins resonance Raman spectroscopy showed that reversible photoreduction of haem took place in the T state but not the R state.


Heart attacks and geomagnetic activity.

Heart attacks and geomagnetic activity. Malin and Srivastava reported a remarkable correlation between daily variations in the geomagnetic field strength and daily admissions to the cardio-thoracic wards of hospitals in Hyderabad and Secunderabad, for cardiac emergencies, during 1967--72. We have now carried out a similar enquiry in the West Midlands region of the UK for the years 1969--70, but were unable to confirm the Indian results.


Immunoreactive forms of human erythrocyte ankyrin are present in diverse cells and tissues. Ankyrin is a polypeptide of molecular weight (MW) 200,000 which is tightly bound to the cytoplasmic surface of the human erythrocyte membrane and has been identified as the high-affinity membrane attachment protein for spectrin. This protein has also been shown to be associated with band 3 (ref. 4), the major transmembrane protein which links a cytoplasmic structural protein to an integral membrane protein. A water-soluble, 72,000-MW, proteolytic fragment of ankyrin has been purified which retains the ability to bind to spectrin, and competitively inhibits reassociation of spectrin with membranes. Monospecific antibodies directed against this fragment have been prepared and demonstrated to cross-react only with ankyrin among the erythrocyte membrane proteins. The present study reports the use of these antibodies to develop a radioimmunoassay capable of detecting femtomolar quantities of ankyrin, and demonstrates the presence of small but significant amounts of immunoreactivity in a variety of types of cells and tissues.


A mutation in Caenorhabditis elegans that increases recombination frequency more than threefold. In higher organisms the rate of recombination between genetic loci is presumably responsive to selective pressure. Recently, selective pressures and mutational events that influence recombination have been reviewed. Mutational sites and chromosomal rearrangements that enhance or suppress recombination frequency in specific regions are known, but general mechanisms that enhance recombination have not yet been discovered. We describe here the isolation and characterisation of a strain of the hermaphroditic nematode, Caenorhabditis elegans, that has a recombination frequency at least threefold higher than that found in the wild type. In this strain, rec-1, the number of reciprocal recombination events between linked loci is increased. This is true for all pairs of linked loci studies so far. The high recombination strain behaves as if it carries a classical recessive mutation, although a second mutation exists which can alter the recessive behaviour of rec-1.


Suppression of the nonsense mutation in homozygous beta 0 thalassaemia. The common form of beta thalassaemia associated with elevated haemoglobin A2 levels can be broadly classified as beta + or beta 0 type according to the presence or absence of beta-globin chain synthesis in the homozygous state. The molecular pathology of each type is heterogeneous. Apart from a subgroup of Indo-Pakistani patients, the beta-globin structural gene is intact in the majority of patients with beta 0 thalassaemia. The amount of beta-globin mRNA present in the reticulocytes of these patients varies: in some it is absent or barely detectable; in others, a substantial amount is present, but it is nonfunctional. We recently demonstrated that the molecular lesion in a Chinese patient with nonfunctional beta-globin mRNA was due to the mutation of the normal lysine codon AAG at amino acid 17 to the amber terminator codon UAG, which prematurely terminates the beta-globin chain. In the present study we demonstrate the first example of a nonsense mutation in humans which can be suppressed in vitro by the suppressor tRNA, as has been found in other eukaryotic cells and viruses.


Evolutionary nucleotide replacements in DNA. With the increasing availability of analytical information on mRNA molecules, it is now possible to compare homologous nucleotide sequences from different organisms and to draw conclusions about their evolution. Such comparisons have shown that silent changes in codons occur more frequently than nucleotide replacements that produce changes in amino acid sequences (code-altering changes). Furthermore, there is an important difference between amino acid sequence comparisons and nucleotide sequence comparisons. The former show only differences in amino acid residues, but the latter show several types of differences when corresponding codons are compared. Single-base replacements may be degenerate (silent) or expressed as amino acid replacements. Two-base codon changes may be degenerate, single-base changes, or be visible as such. Three-base codon changes may be degenerate (involving serine), simulate either single-base or two-base changes or be visible as such. All nine types of change are found in comparisons of genes from the viruses phi X174 and G4. The relative numbers of these nine types as based on all possible interchanges between all 61 amino acid codons were listed by Holmquist et al. and are shown in Table 1. We discuss these results in the light of the significance of nucleotide changes in molecular evolution.


Localisation of the G gamma-, A gamma-, delta- and beta-globin genes on the short arm of human chromosome 11. Human-mouse somatic cell hybrids have proved invaluable in assigning human genes to their respective human chromosomes. To date, the success of this approach has depended on identifying human proteins which are synthesised in hybrid cells containing a small number of human chromosomes. Consequently, chromosome assignment has been limited mainly to human proteins which are expressed in man-mouse somatic cell hybrids and for which a suitable assay, usually electrophoretic or immunological, exists to distinguish between the human and murine homologous proteins. This technique is therefore unsuitable for the assignment of those human genes which are expressed only in differential cells and not in hybrid cells. Here, we describe how nucleic acid hybridisation and restriction endonuclease mapping of DNA can be combined to test for the presence of human structural gene sequences within hybrid cell DNA. This method can be used to assign any purified human DNA sequence to a human chromosome, and does not require the DNA sequence to be expressed in man-mouse hybrid cells.


Genetic defect in secretion of complement C5 in mice. A genetic deficiency of the fifth (C5) component of complement1-3, a serum glycoprotein of molecular weight (MW) 220,000 (ref. 4), has been found in 39% of inbred strains of mice3. Sera of deficient mice lack detectable C5 activity and protein2,3. In addition deficient mice produce antibody to mouse C5 when injected with sera from C5 sufficient (normal) strains. Levy et al.5 showed that somatic cell hybrids between C5 deficient (B10.D2/old line) macrophages and either C5 sufficient (B10.D2/new line) mouse kidney or chicken erythroblasts secreted haemolytically active mouse C5 in vitro. Several possible molecular mechanisms to account for the findings were considered, but insufficient direct data were available to choose among them. We recently reported that mouse (CD.1 strain) peritoneal cells in culture synthesise and secrete a single chain precursor, pro-C5 (MW approximately 210,000), of the two-chain (alpha chain, 125,000 and beta chain 83,000 MW) C5 protein6. Radiolabelled precursor C5 was contained within the cells and was secreted into the tissue culture media. Using similar methods, we now find that C5 deficiency in each of five different mouse strains (AKR, SWR, DBA/2J8 A/HeJ and B10.D2/old line) is due to a failure in secretion of C5 protein and not to a failure in biosynthesis of pro-C5.


Bombesin suppresses feeding in rats.

Bombesin suppresses feeding in rats. Bombesin (BBS) is a tetradecapeptide originally isolated from amphibian skin1. BBS-like immunoactivity is widely distributed in mammalian gut2-5, and plasma levels have been shown to rise sharply following feeding (ref. 6 and V. Erspamer, personal communication). The physiological actions of BBS are unknown. We have previously shown that the classic gut hormone cholecystokinin (CCK) is a powerful and specific suppressor of food intake7-9. Although CCK and BBS lack common amino acid sequences, they have certain common actions on gut viscera10,11. We have now shown that BBS also suppresses food intake, and we compare its action with that of CCK.


Inhibition of platelet thrombus formation by chlorpromazine acting to diminish haemolysis. There is increasing evidence that the sudden, unpredicatable event initiating myocardial infarction is fissuring of an atherosclerotic plaque. The resulting haemorrhage into the arterial wall produces obstructive platelet thrombi, just as arterial haemorrhages elsewhere produce haemostatic platelet plugs. It has been suggested that such platelet aggregation depends on ADP originating in red cells which are subjected to excessive haemodynamic stress at the site of haemorrhage. The release of ADP from red cells has been demonstrated in vitro in equivalent condtions of shear stress; and other mechansims, such as activation by collagen, cannot account for the rapidity with which the platelets react. One of us (G.V.R.B.) has suggested that drugs capable of counteracting haemolysis might diminish the activating effect of erythrocytes on platelets and so inhibit their aggregation as thrombi. Thus, chlorpromazine, added to human blood at concentrations which diminish haemoylsis but do not directly affect platelet aggregation, prolonged the 'bleeding time' from small holes in artificial vessels where extravasation is terminated, as in living arterioles, by aggregated platelets. The bleeding time was also prolonged by apyrase, consistent with the conclusion that the chlorpromazine acted through decreasing plasma ADP. We show here that this occurs through the anti-haemolytic action of chlorpromazine.


Electron microscope evidence for an 80 A unit in collagen fibrils. Connective tissues are composite structures containing collagen, elastin, glycosaminoglycans, minerals, water and other minor components. In all cases the collagen exists predominantly in fibrillar form. The size distribution of the fibrils does, however, vary markedly with both age and the mechanical requirements of the tissue. Little is known about the mechanism of fibril formation in vivo, although some information is now available form in vitro polymerisation studies. We have now collected new and extensive electron microscope data on the size of collagen fibrils from tendon, skin, cornea and other tissues from both fetal and immature animals. The results reported here show that the diameters of the collagen fibrils thus measured lie close to a multiple of 80 A, a result which may be simply and readily interpreted in terms of the collagen microfibril and its mode of packing.


Renal conservation of antifreeze peptide in Antarctic eelpout, Rhigophila dearborni. In Antarctic notothenioid fishes large amounts (3% w/v) of small molecular weights of 2,600-23,500 and would be expected to be filtered into the urine, they remain in the blood because the kidneys of these fishes contain only aglomerular nephrons. Unlike the situation in most fishes, urine formation is the result of secretion rather than filtration and reabsorption. On the other hand, the peptide antifreezes in Northern Hemisphere fishes such as the winter flounder. Pseudopleuronectes americanus, are retained by the glomerular kidney even though inulin, of comparable weight, is rapidly filtered from the blood into the urine. The Antarctic eelpout (zoarcid), Rhigophila dearborni, which is unrelated to either the Antarctic notothenioids or P. americanus, also uses a peptide antifreeze (molecular weight 6,000) which is maintained at a concentration of 3% (w/v) in the blood plasma. We report here that the lack of antifreeze in the urine of R. dearborni probably reflects the fact that the glomeruli are not functional and cannot filter. We support this conclusion with morphological and physiological evidence and relate our findings to the conservation of biological antifreeze necessary for life in ice-laden polar waters.


[Regulatory proteins in chromatin of eucaryotes]. Experimental evidence for a role of histones and chromosomal nonhistone proteins in the regulation of transcription in eucaryots is described. A speculative model on the regulation of gene activity in higher organisms is presented.


Rat jejunum perfused in situ: effect of perfusion rate and intraluminal radius on absorption rate and effective unstirred layer thickness. In anaesthetized rats a jejunal segment was perfused in situ varying the perfusion rate (0.1, 0.2, 0.5 ml/min) in a randomized order. The intraluminal radius of the segments was small (1.7 mm) or enlarged (3.1 mm) by increasing the intraluminal pressure. The appearance rate of butanol, antipyrine, salicylic acid, D- and L-phenylalanine but not of urea in the venous blood of the jejunal segments was increased up to 35%, when the intraluminal perfusion rate was raised from 0.1 to 0.5 ml/min. Two factors contribute to this effect: the flattening of the concentration gradient down the segment and the reduction of the effective unstirred layer thickness. The length and the intraluminal radius of the perfused segments was not altered, when the perfusion rate was varied. Therefore, a change of the absorbing area did not contribute to the increase of the absorption rate induced by the increase of the perfusion rate. In the series with small intraluminal radius the experimental data corresponded to the theoretical predictions obtained for a laminar intraluminal flow. In the segments with enlarged intraluminal radius the increase of the absorption rate by raising the perfusion rate was less than expected for a laminar flow indicating that the flow might have been turbulent. The enlargement of the intraluminal radius from 1.7 to 3.1 mm increased the absorption rate up to 100%.


Reduced phallotoxin uptake by livers of young compared with adult rats. Using [3H]-demethylphalloin as a tracer the uptake of phallotoxins by the liver of young (6, 12, 16 days old) and adult rats was determined in relation to the dose of toxin administered. The maximum amount taken up by the livers of the young rats was only about 50% of that in adults. Nevertheless, with a dose as high as 55 mg/kg body weight the toxin concentration in the young liver reached more than 30 micrograms/g, being markedly higher than the minimum concentration (approximately 20 micrograms/g) required to cause irreversible damage of the liver in adult rats and death of the animals. This suggests that the tolerance of young rats to phallotoxins cannot solely be explained by the reduced uptake of the toxin.


Local tetanus in rats; concentration of amino acids as studied in spinal cord segments, spinal roots, and dorsal root ganglia. 1. The effect of tetanus toxin injected into one gastrocnemius muscle on the steady state concentration of several amino acids was investigated in spinal cord half segments, spinal roots and dorsal root ganglia of rats. Care was taken to ensure a symmetrical afferent input to the spinal cord and to localize the segment with the highest concentration of tetanus toxin. 2. In the spinal cord segments containing the highest concentration of tetanus toxin the steady state concentration of glycine was higher on the side of the tetanus than on the contralateral control side. Results obtained after intravenous injection of 14C-glycine do not indicate that the higher concentration of glycine on the side of the tetanus was due to a higher uptake of glycine. 3. The results obtained in the spinal cord contradict previous findings of other authors but lend support to the prevailing concept about the action of tetanus toxin in local and general tetanus.


Transient apnoea after systemic injection of GABA in the rat. 1. I. v. or i.a. injection of GABA produced a transient apnoea in rats under pentobarbital anaesthesia. The dose-response relationship and specifity of this effect were investigated. 2. Injection of GABA into the femoral vein led to an apnoea of dose-dependent duration, the dose-response curve showed an ED50 of about 5 mumoles GABA kg-1 and a maximum duration of about 8 s. 3. The depressant action of systemic GABA on respiration seems to be specific as only close structural analogues of GABA such as trans-4-aminocrotonic acid, beta-hydroxy-GABA, delta aminovaleric acid, beta-alanine, and taurine were able to mimic the action of GABA. 4. Injection of these structural analogues of GABA 15 s rior to an injection of GABA inhibited the respiratory depressant effect of GABA dose-dependently. Picrotoxin also antagonized the apnoic action of GABA. 5. The results indicate that the apnoea induced by systemic injection of GABA is mediated by an action on GABA receptors.


Effect of physostigmine and atropine on acetylcholine turnover in mouse brain. The effect of physostigmine salicylate (0.5 mg/kg, i.p.) alone and in combination with atropine sulfate (25 mg/kg, i.p.) on levels of acetylcholine (ACh) and choline (Ch) and turnover of ACh has been studied in whole brain and striatum of mice. The animals were killed by focussed microwave irradiation and the turnover of ACh was studied after i.v. injection of deuterium labelled Ch by employing mass fragmentography. Physostigmine increased the levels of ACh in whole brain from 24.5--28.0 nmol/g(P less than 0.001) whereas there was no significant increase in striatum. The levels of Ch were also increased. The turnover rate of ACh was decreased in whole brain from 15.4 to 8.4 and in striatum from 52.9 to 24.4 nmol/g . min. Physostigmine given before or after atropine did not completely block the ACh lowering effect of atropine. When atropine was given before physostigmine the turnover rate of ACh in whole brain was increased to 24.2 nmoles/g . min. The results seem to indicate that there is no clear cut relation between the turnover rate and level of ACh in vivo. The increase of the turnover rate induced by atropine is masked unless a cholinesterase inhibitor is given to protect the newly synthesized labelled ACh released by atropine.


Interaction of botulinum type A, B and E derivative toxins with synaptosomes of rat brain. Clostridium botulimum 125I-labelled derivative toxin immediately bound to rat synaptosomes. Of the two fragments of type B derivative toxin, the large-molecular-weight fragment (fragment I) inhibited the binding of labelled type B derivative toxin to synaptosomes in the same manner as unlabelled type B toxin did. The inhibition by the small-molecular-weight fragment (fragment II) was less than that by fragment I. These findings suggest that type B toxin binds to synaptosomes mainly with some part of fragment I. The binding of labelled type A and E derivative toxins was inhibited by either of the unlabelled type A or E derivative toxins, but not by type B derivative toxin. It is concluded that synaptosomes of rat brain possess relatively specific binding sites for botulinum toxin types.


Electrical excitability of motoneurones in early local tetanus. 1. After injection of tetanus toxin into the gastrocnemius muscle of the cat non-synaptic excitability of motoneurones was studied in early local tetanus. Antidromic stimulation of motoneurones was performed onthe toxin-treated side and on the control side of the same cat. 2. The mean resting membrane potential of the motoneurones on the toxin-treated side did not differ from that on the control side. 3. Similarly, no differences were found as to the amplitude of the action potential and its rate of rise as well as to the size and time course of the after-hyperpolarization. 4. The mean input resistance of the motoneurones of the toxintreated side did not differ from that of the motoneurones of the control side. 5. Tetanus toxin did not change the mean refractory period and latency of antidromic responses. 6. It is concluded that the action of tetanus toxin the spinal cord cannot be explained by an action of the toxin on the electrically excitable membrane elements of the motoneurones.


The estimation of the survival rate of tetanus-intoxicated mice. A model for screening anti-tetanus drugs. The estimation of the survival rate of tetanus-intoxicated mice is suggested to be a useful animal model for assaying the anti-tetanus potency of drugs. This model was tested with the four central depressants phenobarbitone, chlorpromazine, diazepam and halothane. In agreement with their clinical value, diazepam appeared to be the most, phenobarbitone the least effective agent.


Intravascular clotting preceding crescent formation in a patient with Wegner's granulomatosis and rapidly progressive glomerulonephritis. Rapidly progressive glomerulonephritis is thought to be a proliferative reaction common to a number of disorders. Animal experiments implicate clotting or a product of it as its cause. In the human, the presence of fibrin in crescents, as well as the response to heparinization in some cases, support the role of coagulation in the genesis of extracapillary cell proliferation. We describe the clinical and histologic course in a patient with Wegener's granulomatosis who presented with a picture of intracapillary clotting which evolved into rapidly progressive glomerulonephritis. The patient had a remarkable return of renal function.


125I-iothalamate and creatinine clearances in patients with chronic renal diseases. In 196 adult patients with chronic renal disease or primary hypertension, the evaluation of glomerular filtration rate (GFR) by means of creatinine clearance, 'predicted' creatinine clearance and [125I]-iothalamate clearance was performed. Iothalamate clearance was evaluated after subcutaneous injection of the substance . In patients with normal or upper borderline plasma creatinine values, the iothalamate clearance ranged from 44 to 117 ml/min/1.73 m2 and the overestimation of GFR from creatinine clearance was negligible. In patients with mild or advanced renal failure, the overestimation of GFR from creatinine clearance increased up to 18 and 32%, respectively. The clinical usefulness of iothalamate clearance is evident especially in patients with mild renal failure, in whom an accurate evaluation of GFR is often important for a correct dietary and therapeutic approach.


Hepatitis B virus markers in 97 long-term hemodialysis patients. A study was undertaken to assess the state of hepatitis B virus (HBV) infection in hemodialysis patients. From 97 hemodialysis patients tested, 51 were found to have at least one hepatitis B virus specific marker. 18 were HBsAg carriers, 12 of these carriers have to be regarded as infectious as judged from the presence of HBeAg and/or HBV-specific DNA polymerase activity in the serum. Antinuclear antibodies (ANA) were found in the sera of approximately 20% of the hemodialysis patients with a high prevalence in cases which lacked HBV markers. We conclude from our study that HBsAg-positive hemodialysis patients should be dialyzed in a separate unit and preferably served by personnel which is anti-HBs-positive. The question whether patients in which anti-HBc represents the only HBV marker should be separated is still open and needs further work. The role of non-A/non-B infection is difficult to determine and further studies are needed to elucidate this question.


Granulocyte adherence in uremia and hemodialysis. To evaluate granulocyte function in uremia and hemodialysis we studied granulocyte adherence, an important step in chemotaxis. Our studies demonstrate that patients with severe impairment in renal function had normal granulocyte adherence (72.1 +/- 21 vs. 72.9 +/- 14% controls) while patients with end stage renal disease undergoing hemodialysis (45 +/- 30%) had significant impairment (p less than 0.001). Adherence worsened during dialysis (p less than 0.001) but returned towards the abnormal baseline values at the end of the procedure. There was a significant correlation between adherence and potassium (r=0.77; p less than 0.05) and adherence and sodium-potassium ratio (r=-0.78; p less than 0.05) before and after dialysis. Other factors such as changes in creatinine, urea nitrogen, osmolality, calcium, phosphorus or (H+) did not correlate with adherence. It is concluded that the abnormality in adherence is not the result of the basic disease process but a consequence of dialysis.


Fixed-bed uncoated charcoal hemoperfusion in the treatment of intoxications: animal and patient studies. We examined the efficacy of a new, fixed-bed, uncoated charcoal device in experimentally intoxicated dogs and in drug-intoxicated as well as chemically poisoned patients. In the animal studies, 4 h of hemoperfusion resulted in a significant decrease in the blood level of phenobarbital, salicylate, pentobarbital and glutethimide. The drug clearances varied between 97 +/- 10 and 129 +/- 6 ml/min. However, the total amount of drug removed was higher for phenobarbital and salicylate which have a small apparent volume of distribution (AVD) than for pentobarbital and glutethimide which have an AVD greater than total body water. We next treated 14 patients suffering from a wide variety of intoxications. Patients intoxicated with phenobarbital, methsuximide, chlordane and Amanita muscaria all showed a significant improvement in their clinical status. Patients intoxicated with ethchlorvynol, glutethimide, methaqualone, podophyllin and fluoroacetamide did not improve. Charcoal hemoperfusion may be useful in patients poisoned with drugs characterized by an AVD smaller than total body water. No major complications were encountered during the hemoperfusions.


Effect of experimentally induced chronic renal failure upon the behavior of rats. Two groups of rats were submitted to a 2-hour training session under a free operant avoidance of shock contingency 23 weeks after surgery, which provoked a state of chronic renal failure (experimental group) or after a sham operation (control group). Subjects in the control group had superior performances than those from the experimental group when total of shocks received and total numbers of avoidance and escape responses were compared. Results of biochemical blood analyses obtained from samples taken immediately after the avoidance training session indicate that the experimental group showed higher plasma urea concentration, higher levels of creatinine and osmolarity. The data show that the procedure used to provoke chronic renal failure was successful, and results in general confirm and extend findings relative to the effects of acute renal failure on behavior.


Response of insulin, glucagon and growth hormone to arginine infusion in patients with chronic renal failure. To determine whether glucose intolerance in patients with chronic renal failure could improve by hemodialysis, the effects of arginine infusion on the concentration of blood sugar, insulin, glucagon, growth hormone were examined in healthy volunteers, undialyzed and dialyzed patients with chronic renal failure. Plasma concentrations of sugar and hormones in undialyzed and dialyzed patients responded similarly to arginine infusion. While blood samples were collected at 30, 45, 60, 90, 120 and 180 min after beginning infusion of arginine, the concentrations of sugar and hormones in both patients had no statistically significant differences. However, plasma concentrations of growth hormone in both patients 180 min after beginning of arginine infusion gave statistically significant differences. In the present study, the results suggest that hemodialysis might not improve the glucose tolerance in the patients with chronic renal failure.


Effect of calcitonin on bone lesions in chronic dialysis patients. The effects of synthetic salmon CT, administered subcutaneously and intermittently (1 MRC U/kg/day for 15 days/month over 6 months) were investigated in 15 uremic patients on regular dialysis treatment (RDT), all presenting various degrees of osteodystrophy. Clinically, osteoarticular pain disappeared in 8 out of 10 cases; 1 patient with rib fractures had a rapid calcification of the bone fracture repair tissue. No significant changes were found in serum calcium and PTH levels. Phosphotemia showed a significant decrease within the first 20 days. The varying individual hypophosphatemic response proved to be related to the initial level of phosphatemia. The alkaline phosphatase, when increased, showed a decrease to the normal range. A significant decrease in osteoclastic hyperactivity (active resorption surface, osteoclast index) and a slight increase in osteoblastic pool (active osteoid surface) were documented. No change was noted when osteomalacia predominated. Side effects included: anorexia, nausea, vomiting, face flushing. Our data suggest that salmon CT may be usefully employed in chronic uremic patients on RDT, when secondary hyperparathyroidism predominates.


Progression of medial fibroplasia of the renal artery and the development of renovascular hypertension. A 33-year-old normotensive white women was rejected as a kidney donor because arteriography disclosed medial fibroplasia of the right renal artery. 44 months later she became hypertensive and arteriography revealed progression of the lesion. When renal venous renin assay demonstrated lateralization, a saphenous vein aortico-distal right renal arterial bypass graft was done; her blood pressure has been normal for more than 2 years since. Such patients should not donate kidneys because the course of renal arterial dysplastic lesions cannot be predicted.


Treatment of metabolic alkalosis with hemofiltration in patients with renal insufficiency. Hemofiltration using the postdilution technique and a modified saline solution as the replacement fluid succeeded in treating the metabolic alkalosis of two patients with renal failure.


A new aspiration-needle syringe for percutaneous renal biopsy. We report a renal biopsy technique utilizing the disposable Jamshidi Aspiration Needle-Syringe. The equipment and procedure described greatly simplify and speed up the procedure while ensuring adequate sampling of tissue and decreasing the likelihood of complications.


Effects of intraperitoneal nitroprusside on peritoneal clearances in man with variations of dose, frequency of administration and dwell times. Clinical studies with intraperitoneal nitroprusside were designed to examine drug effects on peritoneal clearances as a function of dose, frequency of administration and dwell times. Increases in clearances and protein losses were seen with 1 mg of nitroprusside per liter of dialysis solution, with progressively greater effects up to maximum doses of 4.5 mg/1. Maximum effects were seen at the high dose after 3 or more consecutive exchanges. Clearance effects promptly returned toward control during postdrug exchanges and, in some studies, even during alternate exchanges. Proportional effects on solute clearances appeared independent of dwell time, supporting previous studies suggesting area permeability alterations. Series of 12 or more consecutive exchanges showed little change in blood pressure. Increases in serum thiocyanate were not detected after multiple exchanges. Dialysate cell counts showed no evidence of chemical irritation.


Ferritin- and apoferritin-induced immune complex glomerulonephritis in mice. In order to study the effects of the protein moiety independent of the protein-iron complex in the development of ferritin-induced glomerulonephritis, we compared the effects of ferritin, equimolar amounts of apoferritin, and equimolar amounts of iron dextran in Swiss albino mice. The results were compared to both saline-injected and non-injected controls. Ferritin resulted in a glomerulonephritis associated with predominantly mesangial deposition of immune complexes. Tubulo-interstitial changes occurred as well. Iron dextran resulted in similar but less severe tubulo-interstitial changes and evoked no glomerular alterations. Apoferritin resulted in an immune complex glomerulonephritis usually associated with membranous deposits. No tubular or interstitial changes occurred. Proteinuria developed in animals receiving apoferritin. Since the protein-iron complex caused tubular and interstitial damage, apoferritin may provide a more suitable model of immune-complex-mediated glomerulonephritis.


The relationship between hematocrit and erythrocyte magnesium concentration in patients on regular hemodialysis. Plasma and erythrocyte magnesium (Mg) concentrations were measured in uremics on regular hemodialysis, in healthy persons and in patients with anemia due to causes other than renal failure. The mean plasma Mg concentration was found to be significantly higher in the uremic patients than in other subjects. The erythrocyte Mg concentration in anemic uremics and in nonuremic anemics was found to be higher than in normal subjects and a close inverse relationship was found between this figure and the hematocrit. It seems reasonable to argue that anemia, rather than renal failure, is related to the high concentration of Mg in erythrocytes.


Ten years' survey of dialysis-associated tuberculosis. Tuberculosis associated with dialysis was studied at the Renal Unit of the Tokyo Medical and Dental University and Yokosuka Mutual Aid Hospital Kidney Center, in both of which the treatments of chronic renal failure are the same. There are 12 tuberculosis patients out of 367 patients on maintenance hemodialysis from January 1967 to December 1976, an incidence of 3.3%. This was 6-16 times greater than that in the general population of this country according to yearly statistics. The characteristics of dialysis-associated tuberculosis include a high incidence of miliary tuberculosis, especially in aged patients and difficulty in establishing the diagnosis before death. Clinical features which are helpful in the early diagnosis are intermittent high fever of unknown origin, weight loss, anorexia, abnormalities of the central nervous system, erythrocyte sedimentation rate over 100 mm/h, leukocytosis and high value of the C-reactive protein. With the increasing number of dialysis patients, an increase of dialysis-associated tuberculosis is expected and this will be one of the major problems of dialysis patients in future.


Serum-cholesterol-binding reserve in patients with the nephrotic syndrome. Hyperlipidemia and premature atherosclerosis are known metabolic complications in patients with the nephrotic syndrome. In this study, we have measured serum levels of cholesterol, triglycerides and serum-cholesterol-binding reserve (SCBR) in 22 patients (14 men, 8 women) with the nephrotic syndrome and in 21 hyperlipidemic men who served as control subjects. Serum cholesterol levels were higher (p less than 0.005) in patients when compared to those of controls while triglyceride levels did not differ significantly between the groups. SCBR levels were lower (p less than 0.001) in the nephrotic subjects. The abnormally low SCBR values may be an important risk factor for atheroclerosis as suggested by previous studies in patients surviving premature myocardial infarction.


Effect of low protein diet and surplus of essential amino acids on the serum concentration and the urinary excretion of methylguanidine and guanidinosuccinic acid in chronic renal failure. 20 patients with moderate renal failure (serum creatinine 4.5--12.0 mg/dl) and some uremic symptoms on a diet ad libitum were treated with a high caloric diet containing 0.5--0.7 g/kg/day protein, supplemented with eight essential amino acids and histidine in the form of solution and/or granules. During the treatment uremic symptoms subsided or diminished without the signs of malnutrition, SUN and the ratio SUN/S-creatinine fell and the nitrogen balance and the ratio N-balance/intake N improved. The serum concentration and the urinary excretion of MG and GSA of the 12 patients were determined by Stein's method using the modified Sakaguchi reaction. In all patients, the serum concentration and the urinary excretion of MG and GSA diminished remarkably during the treatment with a low protein diet alone and furthermore with a low protein diet and essential amino acid supply. We concluded that conservative treatment -- low nitrogen diet supplemented with sufficient calories and essential amino acids -- improved the nutritional state of uremic subjects, and decreased the metabolic production of MG and GSA. The results show that the supplementation of essential amino acids to uremic patients may be a useful treatment.


Dopamine-beta-hydroxylase activity and catecholamine levels in the plasma of patients with renal failure. In 25 patients with end-stage renal failure and 9 patients treated with hemodialysis an increase in norepinephrine (NE) and epinephrine (E) concentrations in the plasma and a decrease in the dopamine-beta-hydroxylase (DBH) activity was ascertained. DBH, NE and E concentrations were determined in some patients before and after commencement of the chronic hemodialysis program. NE concentration increased further both before and after single hemodialysis comparing to previous levels, E increased only after single dialysis but DBH levels did not change. NE concentration in the blood showed a positive correlation with DBH activity in healthy persons and hemodialysed patients. The observed increase in the catecholamine concentrations and decrease in the DBH activity is an evidence of dysfunction in the autonomic nervous system.


[Large aneurysms of the internal carotid artery in its infraclinoidal intracranial portion (author's transl)]. Two new cases of large aneurysms of the infraclinoidal intracranial portion of the internal carotid artery are reported. After a survey of the literature, the authors emphasize the rarity of these malformations, their particular clinical picture with involvement of the cranial nerves. Among the various surgical techniques which were suggested for the management of these large aneurysms, the ligation of the internal carotid artery in the neck is favoured by the authors as the best procedure.


[Bilateral cervical internal carotid artery aneurysms (author's transl)]. Aneurysms of the cervical internal carotid artery are not rare lesions although they often remain symptomless. The authors describe the case of an eighteen-year-old boy presenting bilateral cervical internal carotid artery aneurysms of probable traumatic origin and treated conservatively. Etiology, pathogenesis, difficulties in diagnosis and choice of treatment are discussed.


[Primary intra-cerebral hemorrhage in the new born, nursling and child (author's transl)]. The authors report 6 cases of intracerebral hemorrhages in 6 children, of what appears to be, of primary origin. 3 cases concern children between the ages of 4 and 14 years; the 3 others are situated shortly after birth or during the first months of life. A review of the literature emphasizes the sporadic nature of these cases and the persistance of diagnostic and etiological problems as to the cause of these hemorrhages. In the course of reviewing articles as well as our own personal series, it is evident that the cat scanner has demonstrated its qualifications as a diagnostic tool in the early detection of the lesions, permitting a better adapted treatment, thus improving their prognosis. The prognosis appears to be linked : --to an early diagnosis --to whether or not the hemorrhage is of massive nature or not --to the precise location of the hematoma --to the neurological state of the patient at the time of treatment --to the absence of an associated pathologie (severe prematurity, coagulation pathology). The long distance prognosis in the case of these apparently primary hemorrhages remains uncertain, due to the high rate of recidivism at a later unpredictable date (one month or several years later); to the occurence or not of a hydrocephalus especially in the case of young infants; and frequent sequels affecting superior functions. This long distance prognosis seems, however, to be little affected by the recent acquisitions in diagnostic testing.


[Use of haemodilution in the treatment of cranio-cerebral injuries (author's transl)]. By decreasing blood viscosity and vascular resistance normovolemic haemodilution increases cerebral blood flow and improves microcirculation. This eliminates the symptoms of anoxia of cerebral tissue. The extent of disturbances of the blood brain barrier is decreased. The case presented in this paper illustrates the use of the above-mentioned properties of haemodilution and concerns a patient with chronic subdural haematoma. The patient's status in the pre-operative period was very poor. Craniotomy and avacuation of the haematoma did not result in a visible improvement of the patient's state. He did not regain consciousness and even lost spontaneous respiratory function. Haemodilution /Hct 29%/ was performed using Dextran 60 and 5% human albumin in the proportions 1 : 1. As a result, spontaneous respiration was restored and there was a gradual improvement in the patient's status. 29 days later it was possible to communicate with the patient. The authors are of the opinion that haemodilution could find a much application in neurosurgery than has been the case up to now.


[Anastomosis between subclavian artery and V. A. at C1-C2 level. Case report and reappraisal of surgical possibilities on the third portion of the vertebral artery (author's transl)]. A reappraisal of surgical possibilities on the third portion of the Vertebral Artery (V.A.) above C2, have been done from an anatomical study on 20 autopsied specimen. A route passing between the Internal Jugular Vein and the Sternocleido-mastoidian muscle allows a rather simple approach of the transverse process of C1. After dividing two muscles taking insertion on this process, 1,5 cm of the V.A. can be exposed. For larger exposure of the artery, the Foramen Transversaris of C1 must be unroofed and the artery dissected in the guttering of the posterior arch of Atlas. This surgical route was used in a case of aneurismal dysplasia at C3 level. An anastomosis between Subclavian Artery and V.A. at C1-C2 level was realized with an autologous saphenous vein graft. The keypoints are the highest possible freeing of the XI nerve and the head position. Rotation and extension move the transverse process and the posterior arch of Atlas superficially and anteriorly.


[Germinoma (ectopic pinealoma) with double location : supra-sellar and the cerebellum without pineal tumour (author's transl)]. The now nine years old girl with growth retardation, started to be ill with otitis and then diabetes insipidus of central origin at 1974. A treatment with lysin-vasopressin is prescribed. The PNEG in May 1976 shows a little, pea like, suspicious, supra-sellar nodule who is not surgically explored since they was no ophtalmologic symptoms and because a normal CT scan. Corticoid and thyroid substitutive therapy is added until September 1977 when the general status becomes impaired and vomiting starts. Also because some visual loss, a new neuroradiological study is performed showing a supra-sellar tumour and a fourth ventricle mass. The CT scan asserts the double intracranial expansive process and a posterior fossa craniotomy is done with subtotal resection of a vermian tumour and Torkildsen drainage. The histology is : Immature Dysembryoma (seminoma type) or germinoma. The follow-up was good under hormonal care. X Rays Therapy over the posterior fossa, the suprasellar region, the brain and the spinal channel was instaured. Four months later, the CT scan shows normal sized ventricles and no tumour mass at all. This case gives the authors opportunity for comments and to study the concerned literature.


[Solitary vertebral osteochondroma with spinal cord compression (author's transl)]. Solitary vertebral osteochondromas with spinal cord compression are very rare. Here we report a case of an osteochondroma of the 5th cervical vertebra protruding into the spinal canal. The therapeutic approach is discussed in relation to the natural evolution and the favourable prognosis of these lesions. The usefullness of the C.T. scan is shown both in diagnosis and post-operative follow-up.


[Intraventricular hemorrhage : relation between the symptomatology and computed tomography (author's transl)]. The author gives a description of 60 patients with a ventricular hemorrhage. In most of the cases an intracerebral hematoma or a vascular malformation (aneurysm, angioma) are the causes of the ventricular hemorrhage. Frequently the symptomatology is caracterised by a sudden coma (ictus apoplecticus) or the clinical picture of a subarachnoid hemorrhage without important disturbances of consciousness. With computed tomography a ventricular hemorrhage can be diagnosed very easily. Three formes can be distinguished : haematocephalus totalis, haematocephalus partialis and intraventricular hemorrhage. Most of the patients were treated conservatively. Only 11 patients received surgical treatment. The mortality is very important : 58,3%. Nevertheless this study shows that not all ventricular hemorrhages have a bad prognosis. In one third of the patients the consciousness was normal or only mildly disturbed. These patients had a good recovery. It seems that the ventricular hemorrhage is not the only factor which influences the clinical picture. The origin, the localisation and extent of the primary hemorrhage are essential prognostic factors for morbidity ahd mortality. Above all the direct or indirect lesions of the brain stem seems to be an important factor.


[Acoustic neurinomas. Trans-labyrinthine approach (author's transl)]. The authors, supporters of a tight oto-neuro-surgical collaboration, show their tactical evolution in front of acoustic neurinomas which they operated at first in two stages, trans-labyrinthine then sub-occipital, and now they approach only by trans-labyrinthine way. They report their experience and their results to the point of a first serie of 30 cases : 10 combined approaches in two stages, and 20 trans-labyrinthine approaches. The mortality (3 cases-10%) for this first serie is still raised. One patient, after a softening of the pons, maintained important sequelles. On the other hand, among the remaining 26 patients, 13 kept a normal facial motricity and 5 recovered but with syncinesis. These first results are still perfectible : among the 20 last cases only trans-labyrinthine approached the facial nerve preservation was realised in 72% of the cases. The most frequent surgical complication is a cerebro-spinal fluid leak (7 cases) which fortunately the most often spontaneously dry up (6 cases) but which justify a very attentive closure technic. The authors show the arguments which convinced them of the interest of the trans-labyrinthine approach such it is done by W. House.


[Percutaneous thermocoagulation of sacral roots (author's transl)]. Following spinal cord lesions, signs of spasticity may be observed on bladder with decreased capacity and urinary leaks. We have attempted to associate the inocuity of anesthetic blocks and the selective precision of microsurgical rhizotomies by percutaneous thermocoagulation of sacral roots. Bilateral 53 root coagulation, under Rx control, vesical pressure monitoring and stimulation tests, is ususally efficient. Authors report the technic and the results of this simple method about the first nine cases with more than one year of follow up.


Activity of choline acetyltransferase and acetylcholinesterase in the goldfish optic tectum after disconnection. Activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were investigated in the goldfish optic tectum after disconnection of the optic afferents. Permanent disconnection was achieved by eye removal, and optic nerve crush produced a temporary disconnection until regeneration. There was a rapid loss in total activity per tectum for both enzymes under the two disconnection conditions. At longer intervals after optic nerve crush the levels of total activity for both enzymes returned toward control levels, as regeneration of the nerve proceeded. Total activity for both enzymes remained depressed after eye removal, however. Variable results were obtained in specific activity data, expressed per unit protein, although there was a 10% loss in specific activity of CAT at early intervals after eye removal. The data are interpreted as consistent with the possibility that at least a fraction of the axons in the retinotectal pathway of goldfish are cholinergic, and parallel our previous observations showing similar rapid losses of nicotinic-cholinergic receptor activity in this system.


Age-dependent changes in the specificity of tRNA methyltransferases in the cerebellum of the icteric and nonicteric Gunn rat. The activity of tRNA methyltransferases present in the cerebellum of 6- and 21-day-old nonicteric and icteric Gunn rats was compared using purified E. coli tRNAs as substrates. At 6 days the tRNA methyltransferases of the icteric animals were significantly more effective in methylating tRNAGlu2 and tRNAPhe than were those of their nonicteric counterparts. This relationship reversed itself at 21 days. The action of the tRNA methyltransferases from the 6-day-old icteric animals led to higher proportions of 1-methyladenine in tRNAGlu2 and tRNAPhe than were obtained using the corresponding enzymes of the nonicteric animals. The proportion of N2-methylguanine was also higher, yet only in tRNAfMet and not in tRNAPhe. The study reveals much more extensive fluctuations in the activity and in the substrate recognition specificity among the cerebellar tRNA methyltransferases of the icteric than among those of the nonicteric controls during the crucial 6--21 day period of cerebellar development.


Glutamate decarboxylase activity in chick brain and retina. Inhibition of the immature enzyme by Triton-X-100. We have studied the effect of Triton-X-100 on glutamate decarboxylase (GAD) activity in brain and retina from chick embryos of 12 and 16 days' incubation and from chicks 4--6 weeks old. GAD activity was measured in five different homogenization media. Triton-X-100 inhibited the enzyme by about 60% in both brain and retina of 12-day embryos and by about 50% in 16-day embryos, independently of the homogenization medium. In chicks only about 20% inhibition by the detergent was observed in brain whereas no effect was found in retina. These results indicate that the evaluation of the experimental conditions of enzyme assays at different ages is essential for developmental studies of GAD activity in nervous tissue.


Quantitative evaluation of two pathways for ethanolamine phosphoglyceride biosynthesis in rat brain in vivo. [3H]Ethanolamine and [32P]orthophosphate were injected intraventricularly into adult female rats. At varying time intervals after the injection (1--10 min), the animals were killed by means of a microwave apparatus, and phosphorylethanolamine and ethanolamine phosphoglycerides were extracted from the brains and counted after separation. The kinetic constants for phosphorylethanolamine incorporation into ethanolamine lipids were calculated both from 3H data and from 32P data. From our results, it seems that base exchange reactions for ethanolamine incorporation into ethanolamine lipids are a pathway active in brain in vivo.


Biopterin. VI. Purification and primary amino acid sequence of mammalian D-erythro-7,8-dihydroneopterin triphosphate synthetase. An enzyme that catalyzes the conversion of 2-amino-6-(5'-triphosphoribosyl)amino-5- or 6-formamido-6-hydroxypyrimidine, but not of guanosine triphosphate, to quinonoid 6-(D-erythro-1'-2'-3'-trihydroxypropyl)dihydropterin triphosphate and formic acid has been purified to homogeneity from some mammalian brain and liver. The enzyme of a single strand is a basic protein of 9177 daltons consisting of 68 amino acid residues--except the enzyme from rat brain, which has one additional aspartic acid as residue 7. The enzyme possesses three free SH groups and, in its most active form, 1 mol of phosphate per mole of enzyme. Peptides isolated after hydrolysis with trypsin, chymotrypsin, or weak acid were separated by thin-layer chromatography and sequenced manually by Edman degradation. The complete sequence of the molecule was established as follows: (formula: see text)


Effect of Met-enkephalin and (D-Met2,Pro5)-enkephalinamide on the adenylate cyclase activity of rat brain. Among opiatelike peptides, stimulatory as well as inhibitory effects are encountered on adenylate cyclase activity. These actions are dependent not only on the investigated brain region but also on the applied peptide. Met-enkephalin stimulates adenylate cyclase activity in the rat brain stem (D-Met2, Pro5)-enkephalinamide and beta-endorphin inhibited it, whereas all three peptides inhibited the activity of cortex. Naloxone antagonized the effects of the applied peptides in the presence of sodium chloride.


Uptake of para-tyramine and meta-tyramine into slices of the caudate nucleus and hypothalamus of the rat. The kinetics of the uptake of p-tyramine, m-tyramine, and dopamine were investigated in slices of the hypothalamus and striatum of the rat in the presence of nialamide. When uptake was analyzed by a least-squares fit to a Lineweaver-Burk plot, each amine appeared to be concentrated by both a "low"-affinity and a "high"-affinity system in both brain regions. The obtained Km and Vmax values for the "high"-affinity uptake system for each amine in both brain regions were similar. In general terms, the uptake systems in the striatum exhibited larger Km and Vmax values, with the velocity of uptake being in the order dopamine less than m-tyramine less than p-tyramine. 2,4-Dinitrophenol (DNP) and ouabain reduced all uptakes in the caudate, but reduced only the "high"-affinity uptake of m-tyramine and the "low"-affinity uptake of dopamine in the hypothalamus.


[Cerebrospinal fluid (CSF) cytology using "cytospin" in patients with brain tumors (author's transl)]. Cerebrospinal fluid (CSF) cytology was performed using cytocentrifugation method ("Cytospin") in 88 preoperative patients who had been known to have deeply seated brain tumors by CT. 20 cases (22.7%) among them showed positive findings and 11 cases (12.5%) probably positive findings. High incidence of positive results were obtained in germinomas (60.9%), ependymomas (50.0%), medulloblastomas (40.0%), followed by malignant lymphomas (20.0%), pontine gliomas (16.7%) and metastatic tumors (16.7%). In contrast, it was persistently negative in cerebral astrocytomas, glioblastomas, teratomas, epidermoids, meningiomas and neurinomas. This method was quickly prepared in 30 minutes and was superior in retaining detailed cytomorphology. It was concluded that the CSF cytology is a less invasive diagnostic investigation, can provide an additional information as regards the nature of some kinds of brain tumors and is still useful even in the CT era.


[Brain abscess (Part 5)--Brain abscess following internal carotid occlusion (author's transl)]. Three cases of brain abscess following an occlusion of the internal carotid artery were reported. Case 1: A 6-year-old girl with congenital heart disease was admitted with headache, disturbance of consciousness and left hemiparesis. Right carotid angiography revealed an occlusion of the right internal carotid artery. After 6 months, she was readmitted with high fever. CT scan revealed a low density area and a ring-like shadow at the same site of cerebral infarction. Case 2: A 69-year-old man was admitted in semicoma and with right hemiplegia. Left angiography revealed an occlusion of the left internal carotid artery. After 2 months, a brain abscess was noted in the infarcted area. Case 3: A 20-year-old man with congenital heart disease, was admitted due to headache, vomiting and high fever. CT scan revealed a brain abscess in the right frontal lobe. Carotid angiography showed bilateral internal carotid artery occlusion. We concluded that diminution of cerebral oxygen and encephalomalacia are predisposing factors to the evolution of brain abscess.


[A case of mesenchymal chondrosarcoma originating from the spinal dura (author's transl)]. A rare case of mesenchymal chondrosarcoma originating from the thoracic spinal dura was reported. A 10-year-old girl complained of paresis of the right leg in June 1977. Then she became unable to walk early in August, and a complete paraparesis developed on August 18. She was admitted to our department on August 22. On admission she had complete paraparesis, bilateral ankle clonus, upward plantar reflexes, sensory disturbance below T7, shincter disturbance and neck stiffness. Plain thoracic X-ray revealed bilateral decalcification of pedicles of T6. Myodil myelography showed a complete block between T6 and lower end of T7 vertebrae. Bilateral laminectomy from T3 to T8 was performed. A tumor originating from the spinal dura was located in the right dorsal extradural space. The tumor was totally removed together with a small area of the affected dura. Light microscopy showed mesenchymal chondrosarcoma. Her recovery from neurological deficiencies was excellent and now she can run 14 months after surgery. Metastasis or recurrence has not yet been seen.


[Computed tomography in crossed aphasia (author's transl)]. Crossed aphasia, first described by Bramwell, is aphasia due to the hemispheric damage on the side of handedness. Crossed aphasia in a dextral is rare, and in Japan, there have not been more than ten cases in which the lesion is localized clearly. The cases reported till now have been verified mainly by necropsy. However, the time lag between the appearance of aphasia and the necropsy may affect the conclusion subtly. We consider that computed tomography (CT) can obtain almost the same findings as that by necropsy. However, at present there have been few cases diagnosed by CT except two cases reported by April et al. and Wechsler. We have reported a 47-year-old man in a dextral, who shows left hemiparesis and Broca's aphasia. His lesion is diagnosed by cerebral angiography and CT as the right hemisphere infarction due to right middle cerebral artery occlusion. CT localizes the lesion on the right hemisphere mainly sited deep region and sited wedge shaped cortical area of the fronto-parietal region. On the other hand, it localizes no lesion on the left hemisphere. CT in aphasia has been already reported by Hayward et al. In their report they concluded that correlation of lesion located by CT with aphasia type supported Geschwind's concept of aphasia. In this report we have discussed CT in crossed aphasia analysing our case and the two cases by April et al. and Wechsler. Three cases including our case are all Broca's aphasia, and we compare the lesion location of these three cases with Hayward's lesion located on Broca's aphasia. As the result of this, we can draw the conclusion that the lesion location by CT of these three cases and that of Hayward's report are almost symmetric.


[Cryptococcal granulomatous arachnitis of the spinal cord--a case report (author's transl)]. A case of cryptococcal granulomatous arachnitis of the spinal cord was reported. A 12-year-old boy suffered from sudden occipitalgia and left hemiparesis. The symptoms disappeared spontaneously in about a half year. The next year, he consulted an orthopedist because of lumbago and gait disturbance. Myelography through the cisternal route showed complete block at the level of L1. Exploratory laminectomy of D12 and L1 revealed adhesive arachnitis. Symptoms were improved immediately after the operation. At the age of 15, he was admitted to our clinic, because of sudden onset of headache and vomiting. Computed tomography showed marked hydrocephalus. He recovered by ventriculoperitoneal shunt, and was discharged. The next year, sudden back pain occurred. Gait disturbance, sensory disturbance of the legs and trunks below the mamilla, and dysuria appeared gradually. He was readmitted and laminectomy of D2-4 was performed. The arachnoid membrane was white and 2 mm in thickness diffusely. Thickened arachnoid membrane was removed at the level of D2-4. Histological diagnosis was granulomatous arachnitis. Cryptococcus was seen in the removed tissue. Symptoms were improved after operation. One thousand milligrams of amphoterisin B was injected intermittently. He was discharged on food. Spinal symptoms in cryptococcosis are rare. Operative procedures were effective before the administration of amphoterisin B.


[Choroid plexus carcinoma with metastasis to bone (author's transl)]. A very rare case of the choroid plexus carcinoma of the left lateral ventricle with metastasis to bone was reported. A two-month-old baby was suffering from irritability and vomiting. Her vital signs became progressively worse. On admission she showed an increased head circumference and meningeal irritation signs. An emergency tapping of the right lateral ventricle at the anterior fontanel revealed the bloody csf and an opening pressure of over 700 mm of water. All laboratory findings were negative. Cerebral angiograms showed only an internal hydrocephalus. CT scan and conray-ventriculography gave the finding of a tumor at the trigone of the left lateral ventricle. The tumor was removed "en bloc". Histological examination of the tumor revealed a choroid plexus carcinoma, which was considered met the criteria given by Russell and Rubinstein. The postoperative course was very complicated with metastasis to the right tibia, which was verified by needle biopsy. The patient died from a cachexia. This case was the youngest of all reported cases and very unique in the point of which the tumor metastasized to outside of the central neural axis.


[Oculomotor palsy due to aneurysm of internal carotid artery (author's transl)]. Sixty-five cases of berry aneurysm on the supraclinoid portion of internal carotid artery were reviewed on the viewpoint of oculomotor palsy. 27 of 65 patients (42%) showed oculomotor palsy. Most cases of complete oculomotor paralysis developed immediately after having subarachnoid hemorrhage, whereas the case of gradually developing oculomotor palsy tended to manifest diplopia first, and followed with blephaloptosis. The recovery rate from oculomotor palsy seemed to be correlated with the duration from the onset of symptom to surgery. The recovery from the complete oculomotor paralysis lasting for a long time seemed to be unsatisfactory unless the surgical direct procedure to the aneurysm was successful in early stage.


[Vasoconstriction of external carotid arteries after the rupture of intracranial aneurysm (author's transl)]. A patient in whom vasospasm of not only intracranial but also extracranial arteries was demonstrated after the rupture of an intracranial aneurysm was reported. A 55-year-old male was admitted with a ruptured left IC-PC aneurysm. Intracranial direct operation and continuous ventricular drainage were performed 33 hours after the rupture. Six days after the surgery, right hemiparesis and consciousness disturbances developed. Angiography revealed severe vasospasm of intra-and extracranial arteries, especially branches of the external carotid artery. The symptoms improved markedly following the superior cervical ganglionectomy and perivascular sympathectomy of cervical internal carotid artery on the left side. Vasospasm of the external carotid system, which has not been reported, was further investigated angiographically in 23 patients who had vasospasm of the intracranial arteries after aneurysm rupture. In about 50% of these patients was found vasospasm of the external carotid system too. These changes were not found in control cases without vasospasm of the intracranial arteries. Pathogenesis of the vasospasm of the external carotid system was discussed with particular emphasis on the relationship with the sympathetic nerves.


[The effect of mannitol in preventing the development of cerebral infarction--an electron microscopical investigation (author's transl)]. We have undertaken an electron microscopical investigation of the effects of mannitol on the development of cerebral infarction using an experimental model for thalamic infarction in dogs. 1) It was found that administration of 20% mannitol (2 g/kg) prior to arterial occlusion had significantly suppressive effects upon the formation of cerebral infarction following occlusion. 2) In the control group, only one animal with 30 minutes occlusion showed no pathological changes, but, in the mannitol group, dogs with normal brain tissue were seen even after 120 minutes occlusion. 3) All of the control animals with 60 minutes occlusion showed nerve cell shrinkage, but none of the mannitol treated animals showed such changes. 4) After 180 minutes of arterial occlusion, no notable differences were found between the control and mannitol groups. In one of the mannitol treated animals, cerebral infarction was more severe than in the control group.


[A case of giant choroid plexus carcinoma in a child (author's transl)]. A 1-year-and 4-month-old girl with giant choroid plesux carcinoma was reported from a viewpoint of surgical treatment. As this tumor develops in the ventricular system, rapid deterioration of the general condition due to marked intracranial hypertention is seen especially in children. Therefore, the first aid of the surgical treatment is the control of the intracranial pressure by continuous ventricular drainage in an attempt to improve the general condition of the patient. Because the tumor is very bloody, applying of the temporary clip on the feeding artery such as the anterior choroidal artery should be recommended prior to the dissection of the tumor during surgery.


[Giant optic glioma--case report (author's transl)]. A 3 1/2-year-old girl with a huge optic glioma was reported. On February 26, 1978, she was hospitalized for signs of increased intracranial pressure, namely headache, vomiting and consciousness disturbance. Before admission she did not complain of her visual disturbance. A huge mass lesion in the subfrontal-suprasellar region was found by neuroradiological examination. The operation was performed on March 7, 1978, and the tumor arising from the right optic nerve, about 170 grams in weight, was totally removed in piecemeals. Histopathological diagnosis was pilocytic astrocytoma. Immediately after operation diabetes insipidus and hypernatremia developed, but two months later these symptoms disappeared. Post-operative CT scan demonstrated no mass lesion in the subfrontal-suprasellar region. After radiation therapy, she was discharged with slight left hemiparesis on August 31, 1978. Though her right eye was blind, visual acuity remained 0.2 in the left eye. No other neurologic deficits could be found.


Effect of intraventricular infusion of catecholamines on luteinizing hormone release in ovariectomized and ovariectomized, steroid-primed rats. This study examined alterations in episodic LH release in response to prolonged, slow infusions of dopamine (DA), norepinephrine (NE), or epinephrine (EPIN) into the thire ventricle in adult, ovariectomized (OVX) rats, and the influence of priming with ovarian steroids on the LH response to the catecholamines. Unanesthetized rats with right atrial cannulae were bled continuously at slow rates for 1--1 1/2 h prior to infusion, 1--1 1/2 h during infusion, and up to 1 h afterwards. The amines were protected from oxidation by ascorbic acid, and infused in an artificial cerebrospinal fluid (CSF) vehicle (pH 7.29--7.33) into the third ventricle at a rate of 25--27 microliter/h. Blood samples were analyzed for LH by radioimmunoassay. In unprimed, OVX rats, infusions of artificial CSF, as well as low doses of DA (2--4 micrograms/h) or NE (0.3--0.6 micrograms/h), had no effect on episodic LH release or mean blood LH levels. However, administration of 8.5 and 17 micrograms DA/h, and 5.5 and 11 micrograms NE/h, resulted in a decrease in blood LH levels and, in most animals, prolonged intervals between peak blood LH levels during infusion or inhibitions which began rapidly and lasted for nearly the entire infusion period or longer. In contrast, infusion of 5.7 and 11.5 micrograms EPIN/h had no effect on blood LH levels in uprimed rats. In OVX rats primed 3 days prior to infusion with 50 micrograms estradiol benzoate and 25 mg progesterone (OEP), administration of CSF or the same doses of DA that previously inhibited episodic LH release had no effect on LH secretion. However, these steroids completely reversed the LH response to 11 micrograms NE/h, with increases in LH relase occurring during infusion. EPIN, in doses ineffective in unprimed rats (5.7 and 11.5 micrograms/h), also caused elevations in blood LH levels in EOP rats. Finally, in rats primed with 5 micrograms estradiol benzoate/100 g b.w./day for the 2 days prior to infusion, none of the three neurotransmitters had any effect on LH release.