Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse. Osteopetrosis (op/op) is a new mutation in the mouse that is transmitted as an autosomal recessive linked with variant waddler (Va) on chromosome 12. Compared with normal littermates, young op/op mice have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic. Osteoclasts from op/op mice are small, few in number and have an abnormal cytoplasmic distribution of the lysosomal enzyme acid phosphatase. In contrast to the three other mutations that transmit osteopetrosis in mice, the skeletal signs of the disease slowly disappear in op/op animals after bone matrix  formation declines about 6 weeks after birth from 145 percent to 20 percent of that in normal siblings. The main skeletal defect in op/op mice appears to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates.


The masked rat. An X-ray induced mutant with chronic blepharitis, alopecia, and pasteurellosis. An autosomal recessive mutation had been previously X-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis.


Esterases in the house fly. Polymorphisms and inheritance patterns. Polyacrylamide gel electrophoresis was used to examine the variability and inheritance of esterases in five strains of the house fly, Musca domestica L. Individual zymograms exhibited 8 to 15 bands that could be assigned to one of five zones designated as A through E from anode to cathode. Correlations of P1-F1 banding patterns indicated the existence of at least 3 different loci in zone A. 2 each in zones B and C, and 4 in zone D; no clear inheritance patterns were discernable for the bands of zone E. Only the Es-5 locus of zone C was monomorphic in all of the strains studied. Eight loci possessed null alleles and codominant alleles were detected at six loci. The results suggest that esterases should prove useful for measuring relationships among fly populations or for various studies of population dynamics.


Use of blood typing to confirm principles of coat-color genetics in horses. The chestnut rule in equine coat-color genetics asserts that the inter se mating of chestnut horses never produces bay, black, brown or gray offspring. The gray rule asserts that a gray offspring must have at least one gray parent. Nine alleged exceptions to the chestnut rule, all involving bay offspring, and eight alleged exceptions to the gray rule, including four offspring that were also exceptions to the chestnut rule, were examined for parent-offspring genetic incompatibilities in as many as 17 genetic systems of blood-group markers. In all except one of the 17 cases it was possible to show that parentage had been incorrectly assigned. In 9 of the 16 exclusions it was possible to exclude the stallion irrespective of the mare and in one of the 16 exclusions it was possible to exclude the mare irrespective of the stallion. The percentage of exclusions, i.e., 94, was closely in line with expectation based on the established efficacy of these tests, about 90 percent, in excluding the incorrect stallion or stallions in paternity cases. Although the results strongly uphold the validity of the chestnut and gray rules in equine coat-color inheritance, they do not completely exclude the possibility that there could be rare exceptions to one or the other or both color rules. Insofar as equine registries may be concerned, the results clearly indicate that no alleged exception to the color rules should be considered eligible for registry in the absence of these tests.


Abnormal feathers of the micromelic syndrome in White pekin ducks. In an effort to provide further information concerning the pleiotropic effects of the gene mutation responsible for micromelia in White Pekin ducklings, a histological examination was made oq the abnormal feathers associated with the mutation. Abnormalities found in mutant feathers included decreased overall size, absence of prelumulae and prefiloplumulae feathers, an abnoramlly small rhachis with a disproportionally small medulla, thickening of the feather-sheath, and increased  abundance of pulp cells. Embryos having the most abnormally developed feathers and the thickest periderm and feather-sheaths. The nature of many of the abnormalities found in mutant feathers suggests a common source in defective embryonic mesoderm.


Reactions to rubella vaccine and persistence of antibody in virgin-soil populations after vaccination and wild-virus-induced immunization. Vaccination of two virgin-soil (without historical or serological evidence of past infection) populations of Amazon Indians with RA 27/3 rubella vaccine was followed by fever of greater than 100 F in 10% of the vacinees and by ephermeral arthralgia in 2%. These frequencies are not greater than those that have been reported for cosmopolitan populations of comparable ages. There was little or no secondary spread of the virus. Titers of hemagglutination-inhibiting antibody to rubella virus were prevalent in a third population of Amazon Indians, who had naturally acquired immunity and were unexposed to reinfection, and did not decline during a period of four to 12 years after infection. Antibody titers in the two virgin-soil populations immunized with RA 27/3 vaccine declined by twofold between four months and two and one-half years after vaccination but, at the end of that period, were not appreciably lower than antibody titers at four years in the naturally infected population. All age groups except children under one year of age responded to vaccination equally well.


Attenuated, streptomycin-dependent Salmonella typhi oral vaccine: potential deleterious effects of lyophilization. Four studies were done with streptomycin-dependent Salmonella typhi as an oral, attenuated vaccine. Studies 1 and 3 employed freshly harvested vaccine, whereas studies 2 and 4 involved lyophilized vaccine. Five to eight doses (3 x 10(10)-10(11) organisms/dose) were given; oral streptomycin (1.0 g) was administered concomitantly in studies 2 and 3, with only two of the doses of vaccine in study 1, and was not given in study 4. No adverse reactions were encountered in 179 vaccinated men, and 94% of the men excreted the vaccine. In challenge studies (which included the control groups) with 10(5) virulent S. typhi organisms (Quailes strain), the fresh vaccine was highly protective (66%-78% efficacy), while lyophilized vaccine gave no clinical protection. Fresh vaccine also interfered significantly with intestinal proliferation of virulent S. typhi; only 17% of the vaccinees excreted organisms as compared with 75% of the controls. Studies of protection in mice showed no difference between immunogen content of the fresh and the lyophilized vaccines. Field trials with streptomycin-dependent, oral typhoid vaccine must await development of a lyophilized product that will retain the protective properties of the vaccine.


False-positive rabbit ileal loop reactions attributed to Vibrio parahaemolyticus broth filtrates. Vibrio parahaemolyticus broth filtrates have previously been shown to produce positive reactions in rabbit ileal loops only if concentrated 10-fold by lyophilization. This method of concentration produces solutions that contain greater than 20% NaCl. In the present study, however, concentrations of NaCl of greater than or equal to 4% induced positive responses in ileal loops, and desalting rendered previously reactive, concentrated broth filtrates negative. Therefore, enterotoxin was not demonstrated in our broth filtrates of V. parahaemolyticus, a finding which suggests that previous studies require further evaluation. Since most culture media contain 0.5% NaCl, it is important to determine and to control the NaCl content and the osmolality of all lyophilized concentrates tested in the ligated rabbit ileum.


Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus. One- to eight-week-old mice were studied after subcutaneous inoculation of Sindbis virus. Local replication at the site of inoculation, transient viremia, and invasion of the brain were found in mice of all ages, although the quantities of virus were greater in younger mice. Death occurred in 100% of one-week-old mice, 28% of two-week-old mice, and none of the mice four weeks old or older. Pathologic examination of the brains on day 7 after infection revealed a mononuclear inflammatory infiltrate in all mice, with evidence of necrosis in the youngest. Neutralizing antibody was present by day 3 and reached high titers by day 6 in all age groups. Specific stimulation of cells from the draining lymph node by Sindbis virus antigen was also demonstrable by day 6 in all groups. There was no evidence for a primary role of humoral or cellular immune responses in the age-dependent resistance of mice to infection with Sindbis virus.


Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis. Quantitative blood cultures were obtained from 42 patients with acute Yersinia pestis infection to determine whether the concentration of bacteria in blood influenced the clinical severity and outcome of illness. In 17 bacteremic patients, colony counts in blood cultures ranged from less than 10 to 4 X 10(7)/ml. Three of five patients with colony counts of greater than 10(2)/ml died, and two patients survived episodes of hypotension. Results from plasma limulus tests were positive at the time of admission in three of 10 patients tested, and these three patients had bacteremia with colony counts of greater than 10(2)/ml. Meningitis developed in three patients and pneumonia in two patients; these five patients a-l had buboes in the axillary region. Endotoxin was detected with the limulus test in the cerebrospinal fluid in the three patients with meningitis. Ten patients randomly assigned to receive streptomycin or trimethoprim-sulfamethoxazole survived. Those treated with streptomycin had a shorter median duration of fever and a lower incidence of complications than did the patients treated with trimethoprim-sulfamethoxazole.


An enzymatic assay for chloramphenicol with partially purified chloramphenicol acetyltransferase. In an enzymatic assay for chloramphenicol, chloramphenicol acetyltransferase partially purified by affinity chromatography was used; [3H]acetyl coenzyme A served as a substrate. The purified enzyme was sensitive to p-hydroxymercuribenzoate but insensitive to 5,5'-dithio-bis-2-nitrobenzoic acid. The Michaelis-Menten constant was 10.5 muM. The operating range of the enzymatic assay was 0-30 mug/ml. The coefficient of variation was 1.9% at a concentration of 10 mug/ml. The method correlated well with a microbiological agar-paper disk method for mock unknown sera (r = 0.997) and serum or urine specimens (r = 0.993). The enzymatic assay was unaffected by the presence of any of 12 other antibiotics in tested serum.


Reassessment of Q waves in left bundle branch block. This study disputes a number of recent reports claiming that abnormal Q waves or a QS configuration in inferior leads (II, III and AVF) coexisting with left bundle branch block is highly suggestive of, and indeed specific for, myocardial infarction. Five patients reported herein demonstrate disappearance of Q waves in inferior leads on spontaneous reversal of LBBB to normal conduction. This necessitates the conclusion that these Q waves represent a postdivisional conduction variant most closely equivalent to left anterior fascicular block coexisting with predivisional LBBB. Absence of inferior R waves in the five patients demonstrating LBBB is explicable by as little as a 20 msec conduction delay in the posterior fascicle coexisting with a higher grade conduction defect in the anterior fascicle. It is concluded that LBBB with a QS configuration in II, III and AVF cannot be considered diagnostic of inferior wall infarction since it regularly results from impaired conduction of the left anterior and possibly the left posterior fascicle (to a lesser extent), which may be reversible.


Computer characterization of sinus rhythm. Sinus rhythm tracings, including sinus tachycardia and bradycardia, are characterized quantitatively by means of an ECG measurement program which has been subjected to rigorous evaluation. The analysis is performed on tracings of short duration (10 sec). The features of regularity and stability are considered for the R wavetrain. Regularity is evaluated from the normalized differences between sucessive RR intervals. Stability is determined by the ratio of maximum and minimum RR interval durations. Due to the difficulities of automatic beat-to-beat detection and measurement of P waves, an estimate of the PR interval is obtained from a pseudo-PR interval determined from certain features of the P and R wavetrains. The constancy of this pseudo-PR interval is evaluated, and its absolute value is uded as a characteristic of the type of sinus rhythm.


Angular velocity of the QRS loop of the vectrocardiogram in the normal heart. Angular velocity expressed in radians/sec of the rotation movement of the QRS loop at intervals of 2.5 msecs was calculated from a computer program written in Fortran IV. Frontal, horizontal and left sagittal planes were recorded in 125 normal subjects for analysis. The range of angular velocity for 375 QRS loops was from a few radians/sec to a maximum of 95 radians/sec. Average values of maximum angular velocities were: frontal plane, 46.2 radians/sec, horizontal plane, 41 radians/sec, and left sagittal plane, 34.1 radians/sec. Angular velocity expressed as a periodic function of the vector loop is characterized by polyphasic curves. In the frontal plane, curves tend to be more symmetrical with maximum values in the middle. Angular velocity curves are an alternate expression of analysis of planar vector loops employed in clinical practice. Their normal ranges are given in this paper.


Left ventricular parietal block: diagnostic and clinical study. Fifty-five patients with widened QRS complexes due to the presence of slurred S waves or of terminal slurrings on R waves, in more than three leads, with no infarction or bundle branch and fascicular blocks, were studied with the usual clinical examinations as well as vectorcardiographic recording. A parietal block of the left ventricle was diagnosed when, in the presence of a normal development of ventricular depolarization in the initial and middle phases, the terminal QRS loop was delayed, sometimes irregular and displaced leftward and posteriorly. When this delay was directed to the right, the ventricular localization was puzzling. The comparison of the electrocardiographic (ECG) and vectorcardiographic (VCG) data on the terminal part of ventricular depolarization showed some discrepancies and revealed the greater importance of VCG investigation for the study and the localization of parietal blocks. The pathogenesis of such minor conduction disturbances is not yet clear, since the experimental data on the anatomical-functional structures are different: the Purkinje network, Purkinje fiber-muscle junction or common myocardium. In some cases we think it is possible to localize the structure concerned; in any case we can always localize it at the level of the free ventricular wall.


T-wave changes secondary to left anterior hemiblock as shown by study of intermittent and alternating patterns. T-wave changes in spontaneous intermittent and alternating LAH have been described. Attention has been called to the fact that, with the onset of LAH conduction, the T-wave axis shifts oppositely to that of the QRS, thus widening the QRS-T angle in the frontal plane by about 95 degrees. This has the effect of causing T-waves to become upright in leads II, III and AVF, even in those in whom T-waves were previously inverted. This described dicordance of QRS and T-wave axes is considered as evidence that LAH conduction is in fact a true conduction abnormality. As a corollary, an inverted T-wave in leads II, III or AVF in the presence of LAH is a primary abnormality and may be an indication of inferior wall myocardial ischemia or infarction. T-waves are lowered but not inverted in lead I as a result of LAH conduction and precordial leads are variably but not significantly altered.


An easily applied and removed dry annular suction electrode. A new type of self-retaining dry metal electrode for the electrocardiogram (ECG) is described which adheres to the skin by the application of negative pressure to an annulus surrounding the electrode, which is a bare silver. Data are presented for the factors which govern the adherence to the skin and the range of initial impedance and the values obtained at 2, 5, 10 and 20 minutes and with tap water under the electrodes. The initial impedance is usually high (0.18 to 10 megohms) and decreases progressively with time. Tap water placed under the electrodes dramatically reduces the initial range of impedance. Such electrodes, when used with an amplifier with an adequately high input impedance, can be used for recording electrocardiograms in a variety of situations.


Sinoventricular conduction in atrial standstill. Sinoventricular rhythm implies preserved sinus node function with conduction of impulses to the A-V junction without generalized atrial excitation. Impulse propagation in such cases is presumably via specialized internodal tracts. In this present case, synchronized but localized activation from an area of the right atrium preceded each QRS, without generalized atrial depolarization. These recordings are offered as further evidence for the clinical occurrence of sinoventricular rhythm in humans.


Effects of the pacing site in sinus node reentrant tachycardia. His bundle recordings and premature atrial stimulation from coronary sinus, mid-right atrium and high-right atrium were performed in a patient with repetitive supraventricular tachycardias. Regardless of the paced site, there was a range of coupling intervals during which testing stimuli elicited short runs of premature beats. The corresponding P waves were positive in leads I, II and III and had a high-to-low right atrial activation sequence. Their morphology was similar to that of sinus beats. However, sustained tachycardia occurred only when pacing was performed from the coronary sinus. Therefore, it is postulated that the site of stimulation might be important in the genesis and (perhaps) perpetuation of this arrhythmia by changing the site and (or) mode of entry into the area where this type of tachycardia occurs. Though sinus node reentry was the most likely mechanism, it could not be determined whether the circuit involved the sinus node per se or the so called perinodal fibers.


The R-on-T phenomenon during supraventricular tachycardia in childhood. The electrocardiographic R-on-T phenomenon was observed in the absence of Wolff-Parkinson-White syndrome during recurrent episodes of supraventricular tachycardia (SVT) with rates between 240 to 275 per minute in a 5 year old boy. The rapid ventricular response during SVT corroborates the recent finding of a short refractory period of the A-V node in children. The demonstration of the R-on-T phenomenon in this child may be important in attempting to understand the pathogenesis of sudden death in children.


Spontaneous atrial premature depolarizations during paroxysmal reentrant tachycardia. The spontaneous onset and termination of many episodes of paroxysmal tachycardia, each initiated by an atrial premature depolarization, were studied in one patient. Surface electrocardiograms alone were inadequate to define the mechanisms underlying the frequent irregularity of atrial and ventricular cycle lengths during the tachycardia and the nature of spontaneous termination of the tachycardia. Unipolar atrial electrograms demonstrated that the irregularity during the tachycardia was due to premature atrial depolarizations that reset the reentrant cycle sustaining the tachycardia, and each spontaneous termination was due to an even more premature atrial depolarization interrupting the reentrant pathway. The genesis of the atrial premature depolarizations resetting and terminating the tachycardia, and their relationship to those initiating the tachycardia, are discussed.


Temporary unipolar pacing using a dual cathode. Using standard biopolar, temporary pacing catheters, thresholds were measured in four configurations: (1) bipolar (distal electrode negative, proximal electrode positive); (2) distal unipolar (distal electrode negative, right arm electrode positive); (3) proximal unipolar (proximal electrode negative, right arm electrode positive); (4) dual-cathode unipolar (distal and proximal electrodes negative, right arm electrode positive). With one exception, the bipolar threshold was the lower of the distal or proximal unipolar thresholds, suggesting that bipolar temporary pacing is reliable because one of the two electrodes is in good contact with the endocardium. In both the distal and proximal unipolar configurations there were numerous instances of high threshold and failure to pace. However, with one exception, in all cases either the distal or proximal unipolar threshold was normal and thus pacing was possible and effective in the dual-cathode configuration. Dual-cathode unipolar pacing combines the excitation and sensing advantages of unipolar pacing with the reliability of bipolar stimulation.


Colchicine stimulation of pyrogen production by human blood leukocytes. The effect of colchicine, an anti-inflammatory agent, on endogenous pyrogen (EP) production by human blood leukocytes in vitro was examined. Colchicine not only failed to suppress EP production by human leukocytes stimulated by phagocytosis, but, in the absence of other stimuli, micromolar concentrations of the drug induced pyrogen production and release by both polymorphonuclear (PMN) and mononuclear leukocytes. The response was dose related, occurring at concentrations above 0.1 muM. Colcemid and vinblastine, other agents which bind to microtubular protein, also induced pyrogen release from human leukocytes, whereas lumicolchicine, a light-alerted derivative of colchicine without affinity for microtubules, was ineffective. Colchicine did not induce EP production by rabbit leukocytes, even at 100 muM concentration. Studies of the mechanism of PMN leukocyte activation by Colcemid indicated that although the time required for contact between drug and leukocyte was brief, pyrogen production and release did not begin for 6 or more hours. If added during this time, puromycin prevented subsequent production and release of pyrogen. These results indicated that agents which interfere with the assembly of microtubules induce EP production and secretion by human leukocytes in vitro.


Mutant lines of guinea pig L2C leukemia. I. Deletion of Ia alloantigens is associated with a loss in immunogenicity of tumor-associated transplantation antigens. Five different lines of a strain 2 guinea pig leukemia (L2C) which had been carried in different laboratories share certain chromosomal markers and have a common surface immunoglobulin idiotypic determinant indicating that they have a common origin. All these leukemic lines have on their surface of the B alloantigen (equivalent of the murine H-2K and H-2D antigens) and four of these five lines have on their surface the Ia alloantigens normally present on the strain 2 lymphocytes. The result of a study of the growth and rejection patterns of these leukemias in inbred and random-bred guinea pigs of selected histocompatibility type indicates that both the B and Ia antigens can act as transplantation antigens in guinea pigs. Immunization protection tests in syngeneic animals demonstrated that the four Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-negative leukemia by this criteria did not appear to have TATA. However, crisscross immunization protection tests demonstrated that preimmunization of syngeneic animals with an Ia-positive L2C line lead to a subsequent protection against challenge with the Ia-negative leukemia. Immunization with the Ia-negative line never protected against a subsequent challenge with any of the leukemic cells of L2C lines. These results strongly suggest that the Ia-negative leukemia possessed a TATA that can be recognized but is not itself immunogenic, and also indicate that Ia antigens on L2C cells are functionally associated with TATA and can act as immunological carries for tumor transplantation determinants.


The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). The purification of human C8 in milligram quantities from outdated human serum was achieved by ammonium sulfate precipitation (37.5-50% saturation) and ion exchange column chromatography employing CM-32 cellulose and QAE-Sephadex. The yield of C8 activity ranged from 2-9%, and the average purification was 1,700-fold. Fully reduced C8 was shown by SDS polyacrylamide gel electrophoresis to have three polypeptide chains which were present in equimolor ratios: alpha, 77,000 daltons; beta, 63,000 daltons; and gamma, 13,700 daltons. C8 denaturation by SDS and urea in the absence of reducing agents revealed two noncovalently linked subunits: alpha-gamma, 99,000 daltons, and beta, 75,000 daltons.


The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. 24 di-, tri-, and tetrapeptides have been synthesized as a start of a systematic study of the structural requirements for chemotactic activity and lysosomal enzyme-releasing ability in rabbit neutrophils. All but two of them are N-formyl methionyl peptides. Using the method of Zigmond and Hirsch (10), two representative peptides, F-Met-Leu-Phe and F-Met-Met-Met, were shown to stimulate directed, as well as, random locomotion; thus, they were truly chemotactic. The various peptides showed a wide spread in activity. F-Met-Leu-Phe, the most active peptide studied, had an ED50 for induced migration of 7 X 10(-11) M and for lysozyme and beta-glucuronidase release of 2.4 X 10(-10) M and 2.6 X 10(-10) M, respectively; the least active, Met-Leu-Glu was 26 million times less active in these respects. The relation of activity to structure is exceedingly specific, very small changes in structure making large changes in activity. Moreover, this specificity exhibits a definite regularity and pattern; the activity of a given peptide depends not only on its constituent amino acids but on the position of the amino acid in the peptide chain. Most striking in this last regards is the high activity conferred by phenylalanine when it is in the carboxyl terminal position of a tripeptide, whereas, as the second amino acid from the NH2 terminal end whether in a tripeptide or a dipeptide, it contributes no more to the activity than other amino acids with hydrophobic side chains such as leucine or methionine. The high activity and the specificity and nature of the structural requirements strongly suggest that the primary interaction of peptide and neutrophil leading to either chemotaxis or lysosomal enzyme release is a binding of the peptide with a stereospecific receptor on the neutrophil surface. Whether all chemotactic factors act through the same receptor is not known. An essentially exact correlation exists between the concentrations of the various synthetic peptides required to induce migration and their ability to induce release of lysozyme or beta-glucuronidase. This implies that these two neutrophil functions are triggered by teh same primary interaction; possibly, the binding of the peptides to the same putative receptor. A higher concentration of a given peptide is required to stimulate lysosomal enzyme release than a corresponding migratory response. A slightly but significantly higher concentration of peptide is required to induce beta-glucuronidase secretion than lysozyme release.


Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes. The DNA released into the culture medium after phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes has been purified and characterized. It is double stranded, sediments at 7-8S in alkaline sucrose, and has a Tm determined optically and by thermal elution from hydroxyapatite that is substantially lower than that found for lymphocyte cell DNA. Media DNA contains a major component reassociating with an average Cot-1/2 of 87 mol X s/liter, compared to a Cot-1/2 of 770 mol X s/liter for the unique fraction of cell DNA as measured by reassociation in 0.6 M Na+. This component of media DNA consists of unique sequence elements which are largely shared in media DNA preparations from cultures derived from different cell donors. The marked difference between media DNA and cell DNA indicates that media DNA is not derived from cell death and lysis, rather than some unique portion of lymphocyte DNA is apparently excreted from the cells during PHA-stimulated growth.


Inhibition of maturation of human precursor lymphocytes by coformycin, an inhibitor of the enzyme adenosine deaminase. High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes.


The HLA system in the families of patients with juvenile diabetes mellitus. The HLA and Bf genotypes were determined in 10 families with one or more children with JDM. A statistically significant association was found between HLA-D-identity and the chance to present JDM within a sibship. No such association was detectable with the SD antigens. A highly significant increase in the frequency of intra-HLA recombination was also found in these families.


Spatial probability learning by alcoholic Korsakoff patients. Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.


The effects of divided attention on information processing in manual tracking. Six subjects performed a manual tracking task concurrently uith each of two secondary tasks: in input task (auditory signal detection) and an output task (application of a constant force). A feedback-control analysis of tracking performance was utilized to analyze the time-sharing decrements observed in mean squared errer, in terms of components due to processing delay, addition of internal processing noise, and change in response bias (tracking gain). The results indicated that only the parameters measuring noise and gain were sensitive to time-sharing conditions, and these only to concurrent performance of the force application task. It is concluded that limits of attention in dual-task performance are more severe in output than in input stages of processing, but that these limits are not necessarily those of a single-channel bottleneck. Instead, a broader conception of attention is proposed: one that included changes in processing noise and shifts in response bias, as attention-related phenomena.


Color vision and hue categorization in young human infants. Two studies examined the organization of color perception in 4-month-old human infants. In Study 1, infants looked at selected spectral stimuli repeatedly until their visual attention waned. The stimuli represented instances of basic adult hue categories - blue, green, yellow, and red. Following habituation, infants were shown a series of wavelengths which were the same as or different from the stimuli first seen. Analyses of infant attention during this dishabituation phase of the study indicated that infants categorize wavelengths by perceptual similarity; that is, they see hues in the spectrum much as adults do. In Study 2, a group of infants who looked at the alteration of two wavelengths from the same hue category habituated as did the group of infants who looked at the repitition of a single wavelength from that category, but a group of infants who looked at two wavelengths from different categories habituated at a slower rate. Data from the two studies suggest a high degree of organization of the color world prior to language acquisition.


Irrelevance of figural identity for resolving ambiguities in apparent motion. In order to examine the degree to which form perception affects the formation of apparent-motion experience, subjects were presented with nine ambiguous apparent-motion situations, where the elements of each single flash were various figures. One of the interpretations of each situation preserved the figural identity of the figures across flashes. It was found that figural identity does not have any effect on determining the type of motion experienced, except when the figural analysis involved is relatively simple.


The role of pattern goodness in the reproduction of backward masked patterns. Four experiments investigated the role of pattern goodness in backward masking using five- and four-dot patterns constructed by placing dots in the cells of a 3 x 3 matrix. In Experiment 1, subjects rated the goodness of these patterns and the results replicated previous work showing that good patterns had few alternatives. In Experiment 2, the dot patterns were the target stimuli in a backward masking task using a variety of masking stimuli. For all masking, good patterns were reproduced more accurately than poor patterns. In Experiment 3, the goodness of the masking stimulus was varied. The results indicated that good patterns were reproduced more accurately (replicating Experiment 2) and that good patterns were less effective as stimulus than were poor patterns. In Experiment 4, a long interstimulus interval which precluded masking was used to determine whether goodness affected encoding or memory. At these intervals, there were no differences among patterns, suggesting that the effect of pattern goodness was on rate of encoding. These results demonstrate the importance of configural properties in pattern perception.


Attending to forty-nine spatial positions at once. Simultaneous attention to 49 spatial positions resulted in the processing of threshold information from one of those positions essentially identical to the processing when the subject knew in advance that that position would be tested. This result held true when the task consisted of detection of the presence of a briefly presented dot. The same result held true for 9 spatial positions when the task consisted of report of the briefly presented letter in the target position.


Separate "what" and "where" decision mechanisms in processing a dichotic tonal sequence. Right-handed subjects were presented with a dichotic tonal sequence, whose basic pattern consisted of three 800-Hz tones followed by two 400-Hz tones on the channel and simultaneously three 400-Hz tones followed by two 800-Hz tones on the other. All tones were 250 msec in duration and separated by 250-msec pauses. On any given stimulus presentation, most subjects reported the sequence of pitches delivered to one ear and ignored the other. They further tended significantly to report the sequence delivered to the right ear rather than to the left. However, each tone appeared to be localized in the ear receiving the higher frequency, regardless of which ear was followed for pitch and regardless of whether the higher or lower frequency was in fact perceived.


Preliminary letter identification in the perception of words and nonwords. Words with mixed uppercase and lowercase letters (e.g. fAdE) were perceived more accurately than mixed-case pseudowords (e.g. gAdE), and mixed-case pseudowords were perceived more accurately than mixed-case unrelated letter strings (e.g. eFdT). In addition, same-case words were perceived more accurately than their mixed-case counterparts. The same held true for pseudowords but not for unrelated letter strings. The results are compatible with the view that both letter identify and visual form information are used in word perception.


Locomotion of bluefish.

Locomotion of bluefish. 1. Pressure previously measured on the body surface of swimming bluefish were resolved into their backward vectorial components to allow calculation of profile drag. It was 0.18 kg at a speed of 1.8 m/sec. Tangential drag was calculated as if for a thin plate of an area equal to that of the fish. It was 0.08 kg at 1.8 m/sec. Net drag, 0.26 kg, was the sum of profile and tangential drag. 2. Thrust and drag also were calculated from the changes of acceleration measured during steady swimming, assuming that thrust took place only during the acceleration phase, whereas drag occurred during both acceleration and deceleration. This drag was 0.08 kg at a speed of 1.1 m/sec. It is compatible with the drag of 0.26 at 1.8 m/sec calculated from profile and tangential drag provided drag varies as the square of velocity. 3. The force required to produced maximal acceleration was measured during a scare. It was calculated to be 6.9 kg at a peak acceleration of 3 g. 4. The compression strength of th vertebrae was found to be approximately 20 kg per cm2, or roughly three times the force encountered during maximal acceleration. This safety factor of 3 would be reduced when the back was curved, or if opposing groups of muscles were under tension. 5. The finding that a bluefish can accelerate at 3 g and that the vertebral column is strongg enough to withstand this force indicates that the muscles and body structure of a bluefish would be able to withstand the force of gravity if the fish were otherwise equipped for terrestrial life. This fish may have evolved these strengths simultaneously with land animals. It is speculated that other fish may have evolved some degree of strength to overcome inertia and drag during aquatic locomotion, and this evolution may have been a prelude to terrestrial locomotion.


Induction of antler growth in a congenitally polled Scottish red deer stag. A congenitally polled red deer stag was captured from a Scottish deer forest and kept in an enclosure for observations. The animal had rudimentary antler pedicles but no antlers, and during five years of study no significant antler development occurred. Amputation of the apex of one antler pedicle in May 1974 when the stat was 12 years of age resulted in the growth of a complete antler on the operated side, and this antler was subsequently cleaned and cast in the normal way and a new antler cycle was initiated. The result illustrates that the primary abnormality in this polled stag lay not in his inability to grow antler, but in his inability to develop fully formed antler pedicles from which normal antler tissue could differentiate. Traumatizing the rudimentary pedicle had the effect of stimulating growth of antler tissue, and once this was formed the process of cleaning, casting and regrowth occurred spontaneously. The incomplete development of the antler pedicles is considered to be responsible for the absence of antlers in the majority of "hummels" in Scotland, and the etiology of the condition is discussed.


Mitotic activity and nucleic acid precursor incorporation in denervated and innervated limb stumps of axolotl larvae. Mitotic activity and DNA and RNA precursor incorporation were compared in innervated regenerating limbs and in denervated, non-regenerating limbs on days 8 and 9 post-amputation. Innervated limbs had well-developed cone stage blastemas which showed high cellular mitotic indices and H3-thymidine labeling indices of 0.40-0.50 and H3-uridine labeling indices of 0.50-0.75. In contrast, denervated limbs showed dedifferentiated cells distally under thickened wound epithelia, but essentially no mitotic activity and no blastema formation. These dedifferentiated cells showed lower levels of H3-thymidine (0.10 index) and H3-uridine (0.50) incorporation than regenerating limbs. Labeling indices of wound epithelia are also compared.


Furrowing in altered cell surfaces.

Furrowing in altered cell surfaces. Understanding the process which established the cell division mechanism requires analysis of the role of the responding surface as well as that of stimulatory subsurface structures. Cell surface was altered by the expansion which occurs during exovate formation. Exovates appear on the surface of fertilized Arbacia lixula, Paracentrotus lividus and Echinarachnius parma eggs in response to extreme flattening. They result from cytoplasmic outflow initiated in a very restricted portion of the egg surface. Observations of the formation process in pigmented A. lixula eggs revealed that the original surface may be expanded about 100 fold as the exovate swells. When exovates formed 15-30 minutes after fertilization contain the mitotic apparatus, they divide synchronously with flattened controls. If nucleated exovates are established after the beginning of first cleavage, furrows appear in ten minutes. Exovates established after the beginning of second cleavage develop furrows four minutes after the entrance of the the mitsotic apparatus. Cytoplasm beneath damaged exovate surfaces sometimes develops partial constrictions independently of the surface in the plane the furrow would have occupied. These results suggest that normal surface structure is unnecessary for furrow establishment and function.


Polarizing activity in the developing limb of the Syrian hamster. The transplantation of small pieces of tissue from the limb buds of 9 1/2 -10 day hamster embryos to the wing bud of the chick results in the induction of supernumerary wing structures. The anteroposterior polarity of these induced structures is under the control of the transplanted hamster tissue. The developing hamster limb thus has limb polarizing activity similar to that found in avian species and, as in the chick, the activity is found primarily in the posterior region of the limb bud.


Optimal temperatures for inner-ear performance in gekkonoid lizards. Temperature effects on the cochlear alternating potentials are described in lizards of the Eublepharidae (4 spp. and subspp.), Diplodactylinae (2 spp.), Gekkoninae (7 spp. and subspp.) and Sphaerodactylidae (1 sp.). Pure tones (50-15,000 Hz) were applied to the anaesthetized gecko's external ear. Sound intensity needed for a standard response was plotted (db versus frequency). A total of 249 such sensitivity functions were obtained from 50 animals, at temperatures of 15-40 degrees C. For each species, an optimal sensitivity function is definable by its extreme sensitivity and relative smoothness. This is obtained throughout a specific optimal temperature range. At lower temperatures, the function is less sensitive and its best sensitivity is at a lower frequency. The specific optimal cochlear temperature range resembles the specific ecological temperature preferendum where known. Both are broader in gekkonoid than in iguanid lizards. The temperature effects on the sensitivity function occur even with aerial or mechanical stimulation at the oval window after middle ear extirpation. Hence they arise in the inner ear. Their magnitude (db/ degrees C) is half that known from auditory nerve potentials. When accurate auditory data are desired, the specific optimal temperature and its possible seasonal variation require consideration. This increases the need for proper identification of subjects by name and origin, and for monitoring experimental thermal parameters, including pre-experimental acclimation.


Irradiation inhibits the regeneration of aneurogenic limbs. The developing arms of axolotl larvae from the 2-digit stage onward and the aneurogenic arms of surgically denervated larvae maintained in parabiosis are able to regenerate after amputation. Such regeneration is uniformly inhibited by local irradiation of the arm, whether innervated or not. This demonstration refutes a recent hypothesis that X-rays interfere with a special activity of nerves required for regeneration, and supports the earlier concept that X-rays act directly on those cells which must proliferate to form the regenerated tissues.


Morphology and kinetics of spermatogenesis in Xenopus laevis. The light microscopic characteristics of spermatogenic stages of the germ cell line in the anuran, Xenopus laevis, have been described as they appear in both nuclear squash preparations and plastic embedded thick sections of intact testes. Tritiated thymidine autoradiography was employed to unequivocally identify stages. Using this methodology, it was determined that the premeiotic DNA synthetic period occurs in a cell which is morphologically indistinguishable from a late secondary spermatogonial cell. In addition, kinetic studies with tritiated thymidine were employed to determine the duration of meiotic prophase and spermiogenesis in Xenopus. Results indicate that at 18 degrees C, the most rapidly matururing cells in the testis spend four days in leptotene, six days in zygotene, twelve days in pachytene, one day in diplotene, one day in meiotic division, and twelve days in spermiogenesis. An estimate for the duration of the premeiotic S stage was indirectly calculated from combined data to yield a value of six to seven days. Pooled spermatocyte counts measuring the frequency of occurrence of individual stages produced results which correlated closely with estimates obtained by tritiated thymidine labelling. Individual counts, however, show wide variations between testes from single animals and between testes from different animals, whether sacrificed together or at different times of the year. Nevertheless, in all cases, both morphology and labelling patterns indicate that spermatogenesis is continuously active. The variation observed in individual testes appears to be the result of waves of non-random entry of spermatogonial stem cells into the population of cells irreversibly committed to differentiation.


In vivo and in vitro fertilization of hamster, rat and mouse eggs after treatment with anti-hamster ovary antiserum. Rabbit antiserum against hamster ovary was examined on agargel diffusion plates against several hamster tissues, and also against rat and mouse ovarian extracts. Unabsorbed anti-hamster ovary antiserum showed eight to nine precipitin bands for hamster ovary and four to eight bands for other tissue extracts, but no bands against sperm antigens. Anti-hamster ovary antiserum also showed three to four bands for rat and one to two bands for mouse ovarian extracts. The present experiments confirmed previous reports for the hamster and mouse that treatment of eggs with anti-ovary antiserum blocked in vitro fertilization and that the extent of the inhibition was related to the formation of a precipitate on the zone pellucida. A single injection of anti-hamster ovary antiserum inhibited fertilization in mice but not in rats. In vitro fertilization of mouse eggs was also inhibited in the presence of such antiserum.


Gallium-67 distribution in pregnant mammals. Studies on the distribution of 67Ga in pregnant rabbits showed a marked concentration of the isotope in uterine tissue and flushings of 5-day pregnant rabbits 24 hours after isotope injection. The isotope no longer localized throughout the uterine tissues and flushings on injection of 7- to 8-day pregnant rabbits but was specifically associated with the blastocysts and sites of implantation. As the gestation time progressed 67Ga increasingly concentrated in placental and mammary tissue while the concentration in serum and thymus tissue decreased. The marked concentration in placental tissue was readily discernible on total-body scans of pregnant rabbits. Column chromatography of uterine washings and placental extracts from pregnant rabbits and thymus extracts from estrous rabbits showed most of the isotope associated with moieties greater than or equal to 200,000 MW whereas the isotope in "milk" and extracts of mammary tissue was bound to components of 25,000-35,000 MW. Extracts of thymus from pregnant rats showed a marked, selective loss of 67Ga binding in two peaks of approximately 50,000 and 120,000 MW compared to the chromatographic profile of extracts from normal rat thymus.


The forensic taxonomic debate on Cannabis: semantic hokum. It has been asserted that there are legal species of marihuana plants, and this contention has generated frequent court challenges of criminal prosecutions involving marihuana. Invariably the claim is made that the name C. sativa used in legislation is insufficiently comprehensive to proscribe all forms of marihuana. The maneuver being used, alarmingly, is potentially applicable to innumerable other materials, but its success is based on a failure to appreciate the subjective nature of taxonomy and the little-known but critical ambiguities which are inherent in scientific names. The complex principles and operational conventions of biological nomenclature are presented in elementary fashion. Despite important technical constraints on the use of scientific names, some facts are clear: these names are used subjectively, they may be highly ambiguous, the consensus on use of these names is liable to change with time and, most important, quite permissibly they may have substantially different meanings to different users. The claim that there are legal species of Cannabis merely amounts to a semantic ploy in which certain of the variants of Cannabis that have customarily been understood to be denoted by the species name C. sativa, and which are clearly understood to be proscribed, are simply arbitrarily redefined as different species. This ploy has proven unsuccessful in all cases where scientific evidence was adequately presented by the state and in all important court cases where the issue was critically examined.


Detection of urinary Cannabis metabolites: a preliminary investigation. Cannabinol and 11-OH-delta9-THC have been detected in the individual urines of five professed marihuana or hashish smokers. Both compounds exist primarily as urinary conjugates with the concentration of cannabinol being substantially greater than 11-OH-delta9-THC in all urines. These findings are discussed in light of present knowledge of delta9-THC metabolism and in view of current analytical procedures for the determination of delta9-THC and its metabolites in physiological fluids.


Extraction procedures for some common drugs in clinical and forensic toxicology. The results of four extraction systems for 86 drugs are reported. These systems were investigated with the view to obtaining a rapid, reliable, and efficient extraction technique in clinical and forensic toxicology.


A fatal case involving proparacaine.

A fatal case involving proparacaine. A 16-year-old female died soon after inhaling proparacaine. Analysis of the tissues revealed an amphoteric compound consistent with a hydrolysis product prepared in the laboratory by reacting proparacaine with HCl in the presence of heat.


Mass spectrometry as an aid in the detection and identification of piperidyl benzilates and related glycolates. On the basis of the data presented above the following conclusions may be drawn. 1. The molecular ion peaks of most of the compounds examined are relatively weak but usually easily discernible to permit molecular weight determination. 2. The mass spectra of benzilate esters exhibit a relatively intense peak at m/e 183, and monitoring of this ion can serve as a means for preliminary screening for the presence of this type of a system. 3. Related esters exhibit a similar type of fragmentation resulting in a fragment ion analogous to m/e 183 but shifted by the appropriate number of mass units according to the substituents present. 4. Cleavage of the piperidine ring-ester oxygen bond in 3 and 4-substituted isomers is followed by selective losses of hydrogen radicals to produce ions of type e, f, and g as indicated above. It is significant that in a related piperidine ring system (methylphenidate) substituted in the 2 position, the same type of cleavage results in no further hydrogen losses [16] because of charge stabilization from the ring nitrogen (ion j, Fig. 17) [17]. In other words, the tendency to form a conjugated ion following initial bond cleavage can serve as a means for identifying the position of substitution on the ring and for distinguishing positional isomers.


Elemental analysis by energy dispersive x-ray: a significant factor in the forensic analysis of glass. Eighty-one glass samples were analyzed by EDX; two were indistinguishable. However, when the physical properties of the glass samples were considered, all glass samples were distinguishable from each other. The need to examine glass with respect not only to physical properties but also to elemental composition has been demonstrated. The authors believe that if glass is examined only by density and refractive indexes it is quite possible to conclude incorrectly that glass samples with the same physical qualities could have originated from the same source. To confirm that the glass specimens may have in fact originated from the same source their elemental compositions in addition to density and refractive indexes must be determined. The analysis by EDX of glass samples can selectively eliminate most specimens on the basis of elemental differences. If this step is performed prior to refractive index or density measurements considerable time savings can be realized in casework situations.


Preparing samples for the recording of infrared spectra from synthetic fibers. An improved technique for recording infrared spectra from minute amounts of synthetic fibers by using KBr micropellets is described. The procedure is the same for all commonly encountered synthetic fiber varieties; hence, no preliminary identification is required.


Concentrations of ethanol in two segments of the vascular system. The time courses of capillary and venous blood concentrations of ethanol after oral administration of 0.30 and 0.34 g/kg doses of ethanol to two normal human subjects indicated that, by interpolation, equal capillary and venous concentrations are reached at only one time, and this time varied with the subject. The capillary/venous blood concentration ratios varied markedly as a function of time in both subjects over the entire observation period of 4 h.


The computer and the law: coordinate analysis of skull shape and possible methods of postmortem identification. Mechanisms accelerating or retarding the disintegration of soft tissues are briefly discussed, as well as the need to reconstruct the missing profile for postmortem identification purposes. The application of X-ray and computer-based analyses is discussed in the context of providing data to predict and reconstruct the most probable soft tissue profile of a dry skull. In addition, information from extensive studies of the facial bones and profiles of veterans has been applied to methods in forensic medicine of determining age, sex, and racial background of unknown subjects.


An experimental study of powder tattooing of the skin. Test firings were conducted on specially prepared live rabbits to determine the approximate maximum ranges at which powder tattooing occurs for different forms of gunpowder. For .38 caliber, powder tattooing from cartridges loaded with flake powder disappears at a range of 18 to 24 in. (0.4 to 0.6 m). Powder tattooing with flattened ball powder extends to 36 in. (0.9 m), while that due to ball powder extends to 48 in. (1.2m) of range. In .22 caliber, powder tattooing was observed out to 24 in. (0.6 m) with flake powder and 18 in. (0.4 m) with flattened ball. Attempts to reproduce the animal powder tattoo patterns on paper revealed that the paper patterns are consistent with skin tattoo patterns only up to 18 in (0.4 m) of range.


Soft tissue radiography in determining contact and near-contact gunshot wounds. Contact and near-contact gunshot wounds ordinarily show distinctive gunpowder patterns, muzzle imprints, or tearing of the skin. Microscopic and chemical examination have been used to estimate firing distances. A new method that utilizes soft tissue radiography is described. Nonjacketed lead bullets deposit a pattern of fragments and residues in tissue circumscribing contact and close gunshot wounds. Various patterns are presented to contrast the appearance of contact from distant gunshot wounds using various firearms and different types of bullets. This procedure may be used as an adjunct in the determination of contact and close gunshot wounds.


Sex-chromatin bodies in penile washings as an indicator of recent coitus. A technique for the collection and examination of penile washings for the possible presence of vaginal cells is presented. Various characteristics of cellular form and structure are discussed insofar as they pertain to the primary goal of this study--the detection of evidence of recent sexual intercourse on the part of a male by the examination of cellular content of penile washings.


Excepted substances: a comparison of Federal and state laws. A state law has placed an obligation on the criminal investigation laboratories to screen and quantitate all preparations, both pharmaceutical and illicit, that fall under the provisions of "Excepted Substances." Without complete screens on these preparations, there is room for erroneous indictments as well as possible acquittals on technicalities.


A potential young murderer.

A potential young murderer. Longitudinal study of six people who committed homicides or exhibited a potential for homicidal behavior was undertaken over a period of ten years. The data were obtained through psychiatric interviews, psychological testing, and examination of all available records. The material thus obtained was analyzed from the psychoanalytic point of view. Three specific points were identified as being common and applicable to a lesser or greater degree in all six cases studied. First, as children each of these six people suffered actual physical abuse perpetrated by their parents. Second, they actually saw during childhood violent and destructive behavior by their parents. Third, the sequelae of such exposure to violence interfered with the phase specific resolution of the basic conflicts of childhood, specifically Oedipus complex. These traumata of violence set up a predisposition for regression to the preoedipal levels of psychic organization and functioning. From the structural point of view, ego functions of impulse control were lacking due to profound states of regression whenever these patients experienced extreme anger, which in turn would precipitate homicidal behavior. None of the patients had childhood history of pyromania, enuresis, nor cruelty to animals. On the basis of the aforegoing material, one may conclude that in some instances it is possible to establish "homicidal proneness" as a clinical entity. Homicidal proneness can be anticipated in people who as children suffered from physical and emotional abuse, witnessed violence, and were sexually traumatized through incestuous experiences or their equivalents.


Ionic selectivity of the sodium channel of frog skeletal muscle. The ionic selectivity of the Na channel to a variety of metal and organic cations is studied in frog semitendinosus muscle. Na channel currents are measured under voltage clamp conditions in fibers bathed in solutions with all Na+ replaced by a test ion. Permeability ratios are calculated from measured reversal potentials using the Goldman-Hodgkin-Katz equation. The permeability sequence was Na+ approximately Li+ approximately hydroxylammonium greater than hydrazinium greater than ammonium greater than guanidinium greater than K+ greater than aminoguanidinium in the ratios 1:0.96:0.94:0.31:0.11:0.093:0.048:0.031. No inward currents were observed for Ca++, methylammonium, methylguanidinium, tetraethylammonium, and tetramethylammonium. The results are consistent with the Hille model of the Na channel selectivity filter of the node of Ranvier and suggest that the selectivity filter of the two channels is the same.


Electromechanical coupling in tubular muscle fibers. II. Resistance and capacitance of one transverse tubule. In tubular muscle fibers of the yellow scorpion the transverse tubules are arranged in a radial symmetry. This particular morphology, enables one to derive values for electrical components of one transverse tubule (TT) by treating the TT as a core conductor rather than a complex network. The electrical properties of tubular muscle fibers were completely characterized and analyzed by measuring two independent functions of frequency, i.e., the characteristic impedance and the propagation function. The impedance of a single tubular muscle fiber was determined with microelectrodes over the frequency range 1 Hz to 1.5 kHz. The results were fitted to a possible equivalent circuit model which is based on morphological evidence. The average component values for this model are: Ri = 209 omega-cm, Rm, and RT = 980 omega-cm2 (referred to unit area of surface membrane), Cm and CT = 0.9 muF/cm2, and RL = 103 omega-cm. Relating the equivalent circuit to ultrastructure shows that the average component values are consistent with the hypothesis that the TT is open to the extracellular medium, the electrical capacity of surface and TT membranes is about 1 muF/cm2, and the spread of surface depolarization into the TT is attenuated by about 25%.


Grayanotoxin, veratrine, and tetrodotoxin-sensitive sodium pathways in the Schwann cell membrane of squid nerve fibers. The actions of grayanotoxin I, veratrine, and tetrodotoxin on the membrane potential of the Schwann cell were studied in the giant nerve fiber of the squid Sepioteuthis sepioidea. Schwann cells of intact nerve fibers and Schwann cells attached to axons cut lengthwise over several millimeters were utilized. The axon membrane potential in the intact nerve fibers was also monitored. The effects of grayanotoxin I and veratrine on the membrane potential of the Schwann cell were found to be similar to those they produce on the resting membrane potential of the giant axon. Thus, grayanotoxin I (1-30 muM) and veratrine (5-50 mug-jl-1), externally applied to the intact nerve fiber or to axon-free nerve fiber sheaths, produce a Schwann cell depolarization which can be reversed by decreasing the external sodium concentration or by external application of tetrodotoxin. The magnitude of these membrane potential changes is related to the concentrations of the drugs in the external medium. These results indicate the existence of sodium pathways in the electrically unexcitable Schwann cell membrane of S. sepioidea, which can be opened up by grayanotoxin I and veratrine, and afterwards are blocked by tetrodotoxin. The sodium pathways of the Schwann cell membrane appear to be different from those of the axolemma which show a voltage-dependent conductance.


Isolation, properties and taxonomic relevance of lipid-soluble, iron-binding compounds (the nocobactins) from Nocardia. Representative strains of the genus Nocardia, when grown on iron-deficient media, produce intracellular lipid-soluble, iron-binding compounds known as nocobactins. However, strains representing the 'rhodochrous' taxon fail to form such compounds. The formation of the nocobactins is completely repressed in bacteria grown on iron-sufficient media. Procedures for purifying the nocobactins are described. From their various properties (u.v. and visible spectra of the the ferri- and desferri-materials, mobility upon thin-layer chromatography, and dissociation patterns in HCl), they can be distinguished from the mycobactins (related compounds from mycobacteria) and divided into three main classes. The classes correspond to the three well-described species of the genus Norcardia: N. asteroides, N. brasiliensis and N. caviae. The correlation of the nocobactin data with previous results of conventional numerical taxonomy is high. Two strains of N. asteroides, however, did not produce nocobactins of the group type.


Deoxyribonucleic acid reassociation in the classification of flavobacteria. DNA-DNA reassociation studies showed that Flavobacterium emningosepticum strains had a genetic relatedness of 91 to 100% with inter-strain duplexes having high thermal stabilities. The only exception, strain NCTC10016, had an average relatedness of only 43% to other strains of F. meningosepticum. The apparent divergence in DNA base sequence of this strain was reflected in the structural differences of some enzymes. There was a gradation of DNA relatedness among the Flavobacterium group II-b strains, but three strains were sufficiently related to constitute a species. Low levels of genetic relatedness were confirmed between F. meningosepticum and strains of Flavobacterium group II-b, group II-f, F. aquatile, F. breve, F. heparinum, F. pectinovorum, F. odoratum and Moraxella saccharolytica. All strains had base compositions in the range 32 to 46% guanine plus cytosine. The genome sizes of representative strains of F. meningosepticum and Flavobacterium group II-b were 2-50 X 10(9) to 3-52 X 10(9) daltons. The taxonomic implications of these findings are discussed.


Conditions affecting boundary response to messages out of awareness. Multiple studies evaluated the role of the following parameters in mediating the effects of auditory subliminal inputs upon the body boundary: being made aware that exposure to subliminal stimuli is occurring, nature of the priming preliminary to the input, length of exposure, competing sensory input, use of specialized content messages, tolerance for unrealistic experience, and masculinity-feminity. A test-retest design was typically employed that involved measuring the baseline Barrier score with the Holtzman bolts and then ascertaining the Barrier change when responding to a second series of Holtzman blots at the same time that subliminal input was occurring. Complex results emerged that defined in considerably new detail what facilitates and blocks the boundary-disrupting effects of subliminal messages in men and to a lesser degree in women.


Identity of emotional triggers in epilepsy. This communication describes a technique of stimulated recall and video replay which has reduced the frequency of seizures in five epileptic patients. Each of the patients had long standing partial epilepsy with complex symptomatology of the psychomotor type. It was generally acknowledged that emotional factors played an important role in their poor seizure control. Previous psychotherapeutic efforts had been without benefit because ictal amnesia had erased the memory of the stressful antecedent message-input which had triggered the seizures. Creation of empathetically stressful responses to presentation of audio and video tape recordings of specific problematic social interactions was sufficient to induce seizures in these patients. Video tape recording of the seizure and the antecedant events provided by means by which the patients could acquire otherwise unrecognized or forgotten information. Once equipped with the identity of the specific emotional trigger, the patient could avoid the kinds of events which might be expected to induce a seizure and be better able to cope with threatening environmental cues when encountered in the future.


Treatment of chronic post-traumatic organic brain syndrome with dextroamphetamine: first reported case. In view of its therapeutic efficacy in the treatment of children with minimal brain dysfunction syndrome, dextroamphetamine was administered to a young adult with a chronic organic brain syndrome secondary to cerebral trauma. That D-amphetamine was critical to the resulting marked diminution in confusion, paranoia, and deficit in short term memory was confirmed by the occurrence of a relapse coincident with placebo administration as part of a double blind evaluation. Amitriptylline appeared to potentiate the therapeutic effects of D-amphetamine. The results achieved, although observational and subjective in nature, warrant replication in controlled, quantitative clinical studies.


Variation in monoamine oxidase activity in rat brain crude mitochondrial fractions prepared by rate zonal centrifugation. Rat brain crude mitochondrial fractionated by rate zonal centrifugation using an iso-osmotic gradient of Ficoll and sucrose. The results demonstrated that the isolated fractions were biochemically heterogeneous with regard to the enzymes, monoamine oxidase (MAO), NADH dehydrogenase and succinate dehydrogenase. When the activity of MAO was plotted as % of the highest specific activity towards tyramine, kynuramine oxidation remained fairly constant in fractions 10 to 30 but tyramine and dopamine showed separate peaks of activity in fractions 21 and 32 respectively. Sonic oscillations of separated particulate fractions did not change the ratios of various monoamine deamination when compared to the intact particles.


Apomorphine in the rat nucleus accumbens: effects on the synthesis of 5-hydroxytryptamine and noradrenaline, the motor activity and the body temperature. Apomorphine (10 mug) was injected bilaterally into the nucleus accumbens or the neostriatum of rats. The application of apomorphine to the nucleus accumbens, but not to the neostriatum, enhanced the accumulation of 5-hydroxytryptophan in the central nervous system following inhibition of the aromatic L-amino acid decarboxylase. The effect was greatest in the brain stem particularly in the pons plus medulla oblongata. Similar but smaller rises were observed for the accumulation of DOPA in noradrenalinerich regions. The motor activity was increased and the body temperature was decreased by apomorphine in the nucleus accumbens, whereas smaller or no effects were obtained from the neostriatum.


Separation of pineal extracts by gelfiltration. IV. Isolation, location and identification from sheep pineals of three indoles, identical with 5-hydroxytryptophol, 5-methoxytryptophol and melatonin. Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. A low molecular Sephadex G-25 fraction F4 was filtrated on Sephadex G-10. Several distinct peaks could be detected showing excitation and fluorescence maxima resembling those of indoles. A thinlayer chromatography study revealed that one Sephadex G-10 peak contained a spot identical with that of synthetic 5-methoxytryptophol, another a spot with the same Rf-values in different solvents as synthetic 5-hydroxytryptophol, while from a third peak a substance was isolated identical with synthetic melatonin. Mass spectra of the isolated compounds were recorded. These results are compared with those of previous isolation studies.


An ultrastructural study of sympathetic ganglion satellite cells in the rat. 2. Effect of preganglionic sympathectomy. The ultrastructure of satellite cells of the rat superior cervical ganglion was studied following preganglionic sympathectomy.Several distinct morphological alterations were observed: (a) enlargement of the intercellular space between the ganglion cells and the satellite cells, (b) dilation of the granular endoplasmic reticulum and loss of attached ribosomes, and (c) swelling of the mitochondria with disorganization of the cristae mitochondriales. The presence of degenerating nerve fibers and synaptic boutons was also noted.


Plethysmographic study in the patients with non-specific complaints in the head-cervico-brachial regions: with a special reference to laterality in vasomotor responses and "cervical sympathetic dysharmony". Bilateral vasomotor responses and sweat gland activities under the control of cervical sympathetic nerves were examined simultaneously by photo-electric plethysmogram (PTG) and skin potential reflex (SPR) in patients with nonspecific complaints in the head-cervicobrachial regions such as headache, dizziness, tinnitus, pain or stiffness of the neck and shoulder, and dullness or numbness of the arms. 137 out of those 355 patients (38.6%) were revealed to have laterality in vasomotor responses, but it was only 3 in 60 normal control subjects (5%) that showed the laterality in vasomotor responses. These results supported the assumption that the cervical sympathetic dysharmony--imbalance between the right and left sides of cervical sympathetic functions--played an important role in causing their various vegetative complaints in the head-cervicobrachial regions.


The role of the autonomic nervous system in trigeminal neuralgia. The role of the autonomic nervous system in trigeminal neuralgia is discussed. While the trigeminal nerve is accompanied by both sympathetic and parasympathetic fibers, first and second branch phenomena are predominantly associated with sympathetic stimuli. Third branch phenomena, by contrast, primarily involved a parasympathetic component. Atropine sulfate and beta-receptor blockers are suggested as a therapeutic modality. On ancillary studies involving  30 patients with trigeminal neuralgia an abnormal glucose tolerance and/or increased cholesterol level was found to be present in 28 cases.


The isolated perfused chicken heart as a tool for studying acetylcholine output in the absence of cholinesterase inhibition. In chicken hearts, the acetylcholine (ACh) output in response to vagal stimulation was easily detectable by gas chromatography even in the absence of cholinesterase inhibition. Eserine 10(-6) M markedly increased the ACh output. In contrast, the ACh output from the perfused rabbit heart was not measurable in the absence of cholinesterase inhibition. Both ACh concentration and cholinesterase activity were higher in the chicken heart than in the rabbit heart. In conclusion, the isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition.


The metabolism of adenine derivatives in different parts of the brain of the rat, and their release from hypothalamic preparations on excitation. Five enzymes concerned with the metabolism of adenine derivatives were assayed in seven regions of the rat brain. A region which included the hypothalamus had the highest AMP deaminase and adenosine deaminase activities, while its 5'-nucleotidase activities were relatively low. The enzymes named and also the uptake of [14C]adenine by incubated tissue samples were more active with hypothalamic than with neocortical tissues. On superfusion with glucose-bicarbonate saline after assimilating [14C]adenine, the hypothalamic tissues released about 0.2 per cent of their 14C content per minute. This release was increased fourfold with electrical excitation but the presence of 0.25 muM tetrodotoxin prevented most of this increase. The compounds released during superfusion and electrical stimulation were preponderantly hypoxanthine, inosine, and adenosine, with only small amounts of adenine nucleotides. The output of all these compounds increased during the period of stimulation and also the proportion of adenine nucleotides increased when stimulation was carried out in the presence of tetrodotoxin. The output of the nucleotides and adenosine increased more promptly when stimulated than did that of the other compounds named. The results are discussed in terms of the metabolic roles of the enzymes concerned. and in relation to whether the enzymes are acting on intracellular or extracellular substrates.


Movement of glycine across the blood-brain barrier of the rabbit. The single pass clearance of glycine from the cerebral capillary bed was measured in the rabbit with the indicator diffusion method. It was shown that glycine was extracted to the same degree as fructose (ca..07). The concentration of glycine injected into the carotid artery was varied some 700-fold without significantly affecting the clearance of this amino acid in transit through the brain. Cross inhibition of the unidirectional movement of glycine was not demonstrable. These present results and most previous studies suggest that this putative neurotransmitter does not cross the blood-brain barrier by a carrier mediated process.


Electrophysiological study of corticocaudate projections in cats. The potential waves evoked in the caudate nucleus (CN) of cats by stimulation of the cerebral neocortex were sterotactically recorded. The head and the body of the caudate nucleus were systematically explored. Stimulation of the ipsilateral sigmoid gyrus and the orbitofrontal cortex evoked waves with the largest amplitude in the CN. Smaller potentials were evoked from the ipsilateral ectosylvian and suprasylvian gyri and from the sigmoid gyrus on the contralateral side. Antidromic conduction from the caudate nucleus to the cortex demonstrated the directness of the corticocaudate pathway. By stimulating the white matter and by amking lesions, the corticocaudate pathway was shown to pass, in part, through the subcallosal fasciculus and, in part, through the internal capsule. Corticocaudate connections were shown to be separate from the fibers of the corticospinal tract. A staggered and extensively overlapping topographic progression of the corticocaudate projections was demonstrable along the antero-posterior axis, but was less evident in the medio-lateral direction. It was concluded that the intranuclear distribution of functional synaptic connections must be more profusely branched than was suspected from anatomical data.


Observations on sensory and sympathetic function during intrathecal analgesia. A dilute solution of procaine in glucose solution was injected by slow drip into the lumbar theca of patients to cause a differential block. Vasodilatation of the skin vessels of the lower limbs always occurred before any change in sensibility. The first changes in sensibility were inability to fell painful stimuli and warm stimuli; these two forms of sensibility were usually coextensive and occurred at the same time. When this was not so, either form of sensibility could be more extensively disturbed than the other. When warmth sensibility was removed, cold sensibility was either normal or diminished or cold stimuli caused non-thermal sensations such as non-thermal wetness or pressure. It is concluded that the nerve fibres signalling warmth are the smaller delta fibres or non-myelinated fibres or both. As two groups of investigators who recorded from the non-myelinated fibres in man found no non-myelinated fibres responding to cold, it is condluded that fibres signalling cold cover the same delta range as those signalling warmth, together with a proportion of larger delta fibres. When fibres subserving pain, warmth, and cold were blocked, tactile sensibility could be normal. It is concluded that, if there are tactile fibres in man in the smaller delta and non-myelinated ranges, their contribution to tactile sensibility is insignificant. It is also concluded that the pre-galglionic B fibres are the most susceptible of all fibres of the nerve roots to local anaesthetic agents. On two occasions, piloerection occurred when the pre-ganglionic sympathetic fibres were blocked. In two patients spontaneous itching occurred when all peripheral nerve fibres were blocked except large tactile fibres.


Vertebrobasilar artery insufficiency in rheumatoid atlantoaxial subluxation. Cervical myelopathy has become commonly recognized as a complication of rheumatoid atlantoaxial subluxation. A small group of patients with atlantoaxial subluxation may have intermittent symptoms associated with change of head position and which are due to vertebral artery compression. Two such cases are reported, one with necropsy findings of infarction in the area supplied by the vertebrobasilar system. The pathogenesis of the symptomatology and infarction is discussed.


Measurement of regional cerebral blood volume by computerized axial tomography. Computerized tomography has been used for the estimation of regional cerebral blood volume in a group of 18 patients. Sodium iothalamate was injected intravenously (1.75 ml/kg) to increase the absorption of x-rays in the cerebral circulation. A mean value of 5.7 ml/100 g was found for the cortex and 5.1 for tha thalamus.


Muscle nuclear size in neuromuscular disease. Nuclear size has been estimated in muscle biopsy specimens from seven healthy individuals, eight patients with infantile spinal muscular atrophy (types I and II), and eight patients with Duchenne muscular dystrophy. The results indicate a great increase in nuclear size in Duchenne muscular dystrophy but not in spinal muscular atrophy when compared with controls. The reasons for this finding are discussed in relation to the pathogenesis of these two groups of diseases.


Prognostic significance of electrodiagnostic studies in the Guillain-Barré syndrome. Nerve conduction and needle electromyographic studies were carried out in 50 patients with the Landry-Guillain-Barré syndrome to assess the reliability of this procedure in predicting the prognosis. Two main groups were identified. The first group was characterized by gross abnormalities in nerve conduction and absence of fibrillation potentials during the entire course of the illness. Twenty-five of 31 patients (80.6%) belonging to this group recovered rapidly, and the quality of recovery was good. In 19 patients belonging to the second group, profuse fibrillations were noted within the first four weeks of the illness with or without associated nerve conduction deficits. Recovery in this group was poor (31.5%) and pronounced residual deficits were more common. Electrophysiological studies therefore are of value not only in the diagnosis but also as a reliable prognostic index in this syndrome.


Central effect of bladder filling and voiding. In normal subjects and in patients with spasticity and/or urological complaints changes in somatic muscle reflexes associated with filling of the urinary bladder were observed. Two different patterns of reflex changes occurred. One pattern was associated with easy initiation of voiding: it consisted of increasing H and T reflexes and decreasing flexor reflexes with concomitant decreasing sphincter muscle activity. The other pattern was associated with difficulty in initiation of voiding: it consisted of increasing flexor relfexes including sphincter muscle activity and decreasing H and T reflexes. The importance of these reflex patterns in disturbances of micturition is discussed. During voiding, decreasing flexor relfexes with increasing H and T reflexes occur as the general pattern.


Baroreflex sensitivity and responses to the Valsalva manoeuvre in subjects with diabetes mellitus. Baroreflex sensitivity was measured in a group of diabetic patients from the slope of the regression of pulse interval on systolic arterial pressure, during elevation of pressure induced by phenylephrine. The response to Valsalva's manoeuvre was assessed in the same subjects. There was a good correlation between the two tests in the identification of patients with a parasympathetic autonomic disturbance, but measurements of baroreflex sensitivity were more readily quantifiable than were the responses to Valsalva's manoeuvre. Furthermore, baroreflex sensitivity could be measured in patients with sympathetic nervous dysfunction in whom vagal function could not be assessed by means of the Valsalva manoeuvre. Measurement of baroreflex sensitivity is likely to be suitable for longitudinal studies of the progress of diabetic autonomic neuropathy.


Stroke associated with addiction to heroin. During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke.


The normal motor unit in man. A single fibre EMG multielectrode investigation. The motor unit in the normal EDC and biceps brachii muscle was studied with a multielectrode technique permitting recording from 44 sites 300 mum apart. It was found that the muscle fibres in man are scattered with no evidence of grouping, similar to the findings in glycogen depletion experiments in animals.


Eales' disease with neurological involvement. Part 2. Pathology and pathogenesis. Detailed neuropathologic examination was carried out on 1 case of Eales' disease with CNS involvement, in the form of retinal vasculopathy, followed first by signs of brain stem and cerebellar disease and then by a myelopathy, with death 4 years later from retinal infection. There was mild chronic inflammation in the retina, and sub-total demyelination of one optic nerve. The brain stem and cerebellum showed extensive vasculopathy, with various stages of venous change extending from proliferation and dilatation to haemorrhage, or to thickening with hyalinisation. The perivenular brain tissue, particularly of the cerebellum, often showed demyelination, with relative axon preservation, but no inflammation. Similar, but less pronounced venopathy was seen in the dorsal cord. There was ascending degeneration of Goll's columns and descending degeneration of the lateral columns.


Glycine levels in the degenerated human spinal cord. Tissues from non-degenerated tissue of 18 patients were assayed for glycine concentration in grey and white matter in the thoracic, cervical and lumbar regions. Confirming earlier results, glycine concentration was found to be maximal in the grey matter of the lumbar segments of the lateral column. Analysis of tissue from 11 human spinal cords showing unilateral Wallerian degeneration, 4 cords with amyotrophic sclerosis and 4 cords with bilateral Wallerian degeneration failed to show statistically significant differences when compared with control values. The results argue against a supraspinal origin of glycine and suggest that glycine levels are regulated locally or at a segmental level in the spinal cord in man.


Testosterone-induced changes of choline acetyl-transferase and cholinesterase activities in rat levator ani muscle. One year after castration the activities of choline acetyltransferase (ChAc) and of cholinesterase (ChE) in the levator ani (LA) muscle of male rats were lowered by 42 and 79% respectively. The weight of the muscle corresponded to 15% of control values. These changes were not accompanied by a decrease in the number of the muscle fibres. Treatment with testosterone rapidly increased the activity of ChAc and the weight of the muscle near to control values; the restoration of ChE was less complete. Testosterone produced an increase in the size of the muscle fibres and increased the histochemically observed activity of ChE in the postsynaptic part of the motor end-plates. In non-castrated rats the administration of testosterone increased the weight ofthe LA muscle, but was not accompanied by an increase of ChAc above control values.


Effects of castration, testosterone and immobilization on the activities of choline acetyltransferase and cholinesterase in rat limb muscles. Thirteen months after castration of male rats the weight of their soleus muscles was lowered to 82% and their choline acetyltransferase (ChAc) activity to 83% of control values. The administration of testosterone lasting 5 weeks increased the weight of the soleus muscles of castrated animals by 19% and their ChAc activity bu 37%. Changes in the activity of cholinesterase occurring after castration and testosterone treatment were not statistically significant. It is assumed taht the effect of testosterone on the activity of ChAc was mainly due to an increase in the functional activity of the motoneurones innervating the muscle. Rapid developmental increase of ChAc activity was observed in the muscles of intact rats between the age of 48 and 82 days. During this period of development the activity of ChAc rose faster than the weight of the muscles. Testosterone had no effect on the weight and ChAc activity of the soleus and extensor digitorum longus muscles of non-castrated rats after 1 week's administration; after 5 weeks' administration the weight of the muscles and their ChAc activity were diminished. After the soleus muscles of non-castrated rats had been immobilized for 10 days, their ChAc activity was 56% and their weight 51% of control values. The administration of testosterone did not alter the effect of immobilization on the ChAc and weight of the muscle.


The metabolic and hormonal response to glucagon. Part 1. Normal subjects. Significant increases in mean plasma noradrenaline levels were observed 30-60 min and 150-180 min after a subcutaneous injection of 1 mg glucagon. The first peak coincided with the maximum blood glucose and plasma insulin levels and the second peak occurred after plasma growth hormone (GH) and cortisol levels had begun to rise. The first plasma noradrenaline peak may be important in inhibiting further insulin secretion. There was no evidence that glucagon stimulates adrenaline secretion in normal human subjects. It was also confirmed that there are significant increases in the levels of glucose, insulin, GH and cortisol and a significant decrease in FFA levels following subcutaneous injection of glucagon in normal human subjects.


The metabolic and hormonal response to glucagon. Part 2. In patients with migraine. The hormonal and metabolic changes following the subcutaneous injection of 1 mg glucagon have been studied in a group of 6 migraine patients, and the results indicate that the responses of these subjects differ from those of a control group. Three of the migraine subjects had raised basal plasma noradrenaline levels but all had been taking clonidine up to 12-24 hr before the test and the increased plasma noradrenaline levels were probably due to the effect of withdrawal of the drug.


Senile changes in the human neocortex and hippocampus compared by the use of the electron and light microscopes. The severity of certain "senile" changes, namely senile plaques, neurofibrillary tangles and granulovacuolar degeneration in the neocortex and hippocampus, was estimated by light microscopy, in brains obtained at autopsy from 16 cases aged 24 to 93 years. An assessment of certain features of plaques and tangles as well as Hirano-bodies (also associated with senile change) was made by electron microscopy. A statistically significant correlation was found between the electron-microscopic and light-microscopic findings. The findings in an additional 4 cases aged 39 to 65 years in which only the cortex was examined supported the correlation.


Chronic relapsing polyneuritis.

Chronic relapsing polyneuritis. Clinical, electrophysiological and pathological findings in 23 patients with subacute and relapsing idiopathic demyelinating polyneuropathies are described. In 17 patients with relapsing polyneuropathy, the neurological illness was unaccompanied by any systemic disturbances. The term preferred for the neuropathy in this group of patients is chronic relapsing polyneuritis. The findings in this group suggest that the common form of this syndrome is due to a single disease entity. Chronic relapsing polyneuritis differs from acute idiopathic polyneuritis chiefly in regard to the rate of evolution and the severity of the initial episode of polyneuropathy. If these two polyneuropathies have the same pathogenesis, the factor which determines whether the disease is acute and self-limiting or chronically relapsing is often present at the time of onset of the disease. The relationship of chronic relapsing polyneuritis to relapsing hypertrophic polyneuropathy and progressive hypertrophic polyneuropathy is also discussed and it is concluded that these diseases may constitute a spectrum of pathogenetically related disorders. In chronic relapsing polyneuritis, as in other demyelinating polyneuropathies, a marked segmental reduction in axon diameter accompanies demyelination. This corresponds to a more than 50% reduction in the volume of the affected region of the axon and it is associated with increased packing of axoplasmic organelles and wrinkling of the axolemma. It is suggested that in the normal myelinated nerve fibre, the Schwann cell and myelin sheath maintain fluid locally within the axon.


Multiple sclerosis amongst Chinese in Taiwan. Twenty-five cases of multiple sclerosis (MS), including 2 autopsy cases, collected during the past 20 years from amongst the Chinese of Taiwan, are reported. These cases fulfilled all the clinical diagnostic criteria of MS. The following observations were made: (1) Multiple sclerosis does exist among Chinese in Taiwan. It is uncommon, but is by no means a very rare disease. The prevalence rate in northern Taiwan near Taipei is estimated as 0.8/100.000 population. (2) Female preponderence was conspicuous (F:M = 3.2.:1) in our MS cases as well as in other demyelinating diseases. (3) On the whole, the onset of the disease was earlier in female patients, and those who had their initial symptoms before the age of 20 years were all females. (4) The optic nerve was most frequently involved at the onset, and it was involved in the majority of patients during the whole clinical course. (5) Involvement of the optic nerve and spinal cord, with or without the brain stem, was the commonest form of our MS cases, especially among female patients. (6) More malignant forms of MS, with acute onset and rapid clinical course leading to severe incapacity or fatality, were more common among female patients. (7) Painful tonic spasms were relatively frequently encountered, and they were usually seen in patients with severe spinal cord involvement. (8) Marked elevation of the CSF total protein and of leukocytes was relatively frequent during severe relapses in patients with spinal cord lesions. (9) Severe and extensive demyelinating lesions, both old and recent, in the optic nerve and spinal cord were seen in 2 autopsy cases. The relationship between MS and NMO in Oriental patients is briefly discussed. (10) It seems likely that cases of MS which are atypical as compared with Western MS are more frequently seen in Oriental countries, and perhaps also in tropical regions where MS is known to be rare.


A mathematical model of cerebrospinal fluid dynamics. The ability to solve systems of simultaneous non-linear differential equations by a combination of analytical and computational techniques has encouraged the development of valid mathematical models of biological phenomena. The dynamics of the cerebrospinal fluid (CSF) system has been the subject of closer scrutiny in recent years since the recognition of symptomatic low-pressure hydrocephalic states in man. A mathematical model has been derived from 7 assumptions: (1) That the brain is a spherical shell. (2) That CSF is secreted at a constant rate. (3) That CSF absorption is linearly dependent on pressure. (4) That flow between the CSF compartments is proportional to the pressure difference. (5) That Laplace's Law holds for the visco-elastic properties of the brain. (6) That there is compliance in the spinal compartment of the CSF system. (7) That vascular pulsations in the cranial and spinal compartments are capacitatively coupled. Using known data (and estimates of as yet unknown values) for the several parameters, the validity of the model has been successfully tested against 3 clinical conditions. This model extends our understanding of derangements of CSF dynamics and suggest where further research may yield data at present lacking.


[Proliferation of the transverse tubular system during a tardive and familial myopathy]. The authors report a case of non-progressive, late-onset, recessive, sex-linked myopathy. Electron microscopy reveals a striking proliferation of the T system. This proliferation might be interpreted as indicating an abortive attempt of muscle to regenerate, which could explain the clinical course. Some basic ultrastructural aspects concerning the T system are reported. The signification of the findings of numerous "zebra bodies" is discussed.