The comparison of counterimmunoelectrophoresis with indirect haemagglutination test for detection of antibodies in experimentally infected guinea pigs with Toxocara canis.

The humoral response of guinea pigs infected with doses of 500, 1000, and 1500 infective Toxocara canis ova were measured by counterimmunoelectrophoresis and indirect haemmagglutination tests one to five weeks after infection. The antigens used in these measurements were prepared from adult T. canis. Counterimmunoelectrophoresis showed lower titres than haemagglutination method, but it was performed rapidly and with ease. The possible use of these techniques for immunodiagnosis of human visceral larval migrans is discussed.


A key to cercariae of British strigeoids (Digenea) for which the life-cycles are known, and notes on the characters used.

From original observations and from data in the literature, a key to cercariae of British strigeoids for which life-cycles are known has been compiled. The value of various characters of systematic importance is discussed.


Mediation of macrophage cytolytic and phagocytic activities by antibodies of different classes and class-specific Fc-receptors.

The classes of antibodies that mediate the phagocytosis and cytolysis of 51Cr-labeled chicken erythrocytes by IC-21 macrophages, an established line of mouse peritoneal macrophages, were identified. The phagocytic activity of IC-21 macrophages, as determined by a functional inhibition assay with mouse myeloma proteins, depended mainly on IgM and IgG2a antibodies and to a lesser extent on IgG2b antibodies. Extracellular cytolysis of target cells was mediated solely by IgG2b antibodies. These results correlate with the previously documented specificities of discrete Fc-receptors for IgG2a and IgG2b immunoglobulins on IC-21 cells. Thus, phagocytosis and cytolysis appear to be mediated by antibodies of different classes operating through separate and distinct sites on the surface of IC-21 macrophages.


Transient suppression of the humoral immune response mediated by a factor derived from specifically activated, doubly primed lymphoid cells.

In cultures of sheep erythrocyte- (SRBC) stimulated spleen cells from mice immunized with tetanus toxoid (TT) and horse erythrocytes (HRBC) 30 to 90 days earlier, the addition of both HRBC (day 0) and TT (day 2) resulted in significant suppression of the anti-SRBC plaque-forming cell (PFC) response compared to the response of similar cultures maintained without the priming antigens. The observed inhibition was due to the presence of a soluble factor that was released into the supernatant fluid of the specifically stimulated, primed population of lymphoid cells between 72 and 120 hr after culture initiation. The active mediator, a macromolecule of approximately 24,000 daltons as determined by gel filtration over Sephadex G-150 and Ultrogel AcA 44, was suppressive when added within 24 hr, but not 48 hr, of assay for PFC against the reference SRBC antigen. The transiently acting soluble suppressor (TASS) was not overtly cytotoxic since total cell recovery and viability were unaffected in its presence. The results presented here are discussed in relation to a possible mechanism of action in which the negative regulation of immunoglobulin production is favored once a minimum level of immune reactivity is reached.


Binding of N-acetylgalactosamine-containing compounds by a human IgM paraprotein.

A serum that contains a monoclonal human IgM paraprotein (McG) agglutinates protease-treated human erythrocytes and binds glycosphingolipids that possess a terminal nonreducing N-acetylgalactosaminyl residue in either the alpha or beta anomeric configuration. The approximately equal reactivity of McG with both anomers of N-acetylgalactosamine was unexpected because most immunoglobulins that bind saccharides exhibit a marked preference for one anomeric configuration. The major receptor for this protein in normal group O erythrocytes is globoside, the blood group P antigen: Ga1NAc( beta, 1 leads to 3)Gal(alpha,1 leads to 4)Gal(b,1 lead to 4)G1c-ceramide. Erythrocytes of the rare Pk and p phenotypes lack globoside, and the former are not agglutinated by McG. The McG receptor in p erythrocytes, which are agglutinated as strongly as normal cells, appears to be a crossreactive glycolipid that contains a much larger number of sugar residues than globoside.


Hereditary C5 deficiency in man: genetic linkage studies.

Genetic linkage studies were performed on the only reported kindred with genetic deficiency of the fifth component of complement (C5). Thirty family members in four generations were studied for C5 defiency and 32 genetic marker systems. Of these marker loci, 13 were informative in this pedigree. Most importantly, C5 deficiency was excluded (lod score greater than -2.0) from linkage with the major histocompatibility locus (HLA) from a recombination frequency of greater than 15% (in females). Other marker systems excluded from linkage with C5 deficiency included the ceruloplasmin and Duffy loci at a recombination frequency of less than 15%, and the erythrocyte glyoxalase, MN, and Lewis loci at a recombination frequency of less than 5%. The most positive lod score (1.07, theta=0.05) was for linkage between C5 and haptoglobin, but this score does not reach statistical significance. Thus, among the genes for complement components which can be mapped because of deficiency states or polymorphic gene products, C5 joins C1r, C3 and C6 in not being closely linked to HLA. In contrast, close HLA linkage has been demonstrated for C2, C4, properdin factor B and, in one of two families, C8.


The nature of immune complexes in human cancer sera.

Sera from 517 patients with various types of malignancies were assayed for immune complexes (ICs) by the Raji cell radioimmune assay. The incidence of immune complexes in these patients ranged from 16 to 52% as compared to 19% in normal controls. Increases in tumor mass and metastatic disease were associated with high levels of circulating ICs. Immunization of melanoma patients with BCG and tumor-cell vaccine produced an increase in levels of ICs. Cancer sera contained complexes of intermediate size. Tumor antigens and IgG, presumably in the form of complexes, were identified by immunofluorescence and radiolabeled antibody techniques on the surface of Raji cells incubated in ICs-containing cancer sera.


In vitro lysis of target cells by rat polymorphonuclear leukocytes isolated from acute pyelonephritic exudates.

Polymorphonuclear (PMN) leukocytes from acute pyelonephritic exudates of rats were examined for cytoxicity against various target cells. Pyelonephritic PMN leukocytes caused lysis in vitro of syngeneic renal epithelial cells in 24 to 48 hr. They also caused lysis of allogeneic and xenogeneic target cells. The susceptibility to PMN-induced cytolysis was different among various target cell lines. Cell lysis proceeded at low ratios of effector to target cells and was not dependent on the addition of antibody or lectins. PMN isolated from peritoneal exudates (starch or endotoxin induced) were also cytoxic for the target cells. Cell-free supernatants from pyelonephritic PMN-target cell mixtures, or pyelonephritic PMN leukocytes cultured alone contained cytolytic substances which were nondialyzable and heat stable Finally, the urine of pyelonephritic rats was cytotoxic. These results suggest that PMN leukocytes and their cytotoxic mediators are directly involved in the pathogenesis of renal injury in pyelonephritis.


Temperature-sensitive mutants of influenza virus. XIII. Evaluation of influenza A/Hong Kong/68 and A/Udorn/72 ts and wild-type viruses in tracheal organ culture at permissive and restrictive temperatures.

For development of an in vitro assay of attenuation for virus vaccine candidates, tracheal ring organ cultures from young ferrets were infected with influenza A/Hong Kong/68 and A/Udorn/72 temperature-sensitive (ts) recombinant and wild-type viruses and observed for 21 days at permissive (33 C) and restrictive (37 C) temperatures for effects on ciliated epithelium and viral replication. Results were compared with the known effects of these viruses in humans. Viruses that damaged ferret cilia and grew to high titers at 37 C were insufficiently attenuated for humans, and viruses that failed to damage cilia and grew to low titers at 33 C were excessively attenuated for humans. This system did not completely differentiate the relative virulence of A/Hong Kong/68 ts recombinants for humans but was successful for the A/Udorn/72 ts recombinants. This organ culture system has adjunctive usefulness for detection of most insufficiently attenuated influenza A vaccine candidates and for identification of excessively attenuated candidates that might contain non-ts lesions.


Improved method for collection of nasal mucus.

Specimens of nasal mucus obtained after stimulaton of the mucosa with water and nasal washings from 20 volunteers were compared for content of IgA. The median concentration of IgA was 70 mg/dl in nasal mucus and 17 mg/dl in nasal washings concentrated 10-fold. The use of nasal mucus should allow for more accurate determination of nasal secretory antibody activity.


Quantitative effects of immunosuppression on bronchoalveolar cells.

The use of immunosuppressive chemotherapy is associated with an increased incidence of pneumonia. An animal model is described in which drug-induced defects in pulmonary host defense may be evaluated. Guinea pigs receiving cyclophosphamide (15 mg/kg) plus cortisone acetate (100 mg/kg) daily for seven days developed leukopenia (1.5 X 10(3) cells/mm3), neutropenia (0.4 X 10(3)/mm3), and lymphocytopenia (0.7 X 10(3)/mm3) and also lost prior skin hypersensitivity to purified protein derivative. No animal bled or died unexpectedly during immunosuppression. Transtracheal bronchoalveolar lavage of normal and immunosuppressed animals revealed a significant decrease in the number of pulmonary alveolar macrophages during immunosuppressed periods. Cell viability, phagocytosis of latex particlex, and adherence to plastic surfaces were not decreased in immunosuppressed alveolar macrophages. This animal model should allow further studies of cellular and humoral pulmonary immune parameters during a variety of immunosuppressive drug regimens.


Spontaneous leprosy-like disease in a chimpanzee.

The clinical and laboratory findings of a spontaneous disease, resembling human leprosy, in a chimpanzee are described. The disease was a chronic progressive dermatitis characterized by nodular thickenings of the dermis and involving the  ears, eyebrows, nostrils, and lips. A maculopapular rash was also present. Numerous acid-fast organisms were found in nasal swabs and in dermal lesions, including nerves. Attempts to culture acid-fast organisms in artificial media have failed. At this time, the only features of the etiologic agent of this disease that are inconsistent with those of Mycobacterium leprae are failure of the organisms to oxidize 3, 4-dihydroxyphenylalanine and failure to pyridine to remove the acid-fast staining property of the bacilli.


A prospective study of acute respiratory tract infections among children in a kibbutz: the role of secretory IgA and serum immunoglobulins.

Absolute concentrations of IgA in nasal secretions and concentrations of immunoglobulins in serum were determined in a prospective study of acute respiratory tract infections. The study was carried out in 48 children aged six months to four years liveing in a kibbutz with a homogeneous environment. No correlation was demonstrated between mean base-line levels of secretory IgA or serum IgA and number of episodes of acute resporatory tract infection. However, children who responded to infection by the production of higher levels of secretory IgA had a lower incidence of acute respiratory tract infection than those who did not. Thisfinding supports the hypothesis that the responsiveness of the host in the production of secretory IgA during infection is important in protection against mucosal infections.


The capsular polysaccharide of Bacteroides fragilis as a virulence factor: comparison of the pathogenic potential of encapsulated and unencapsulated strains.

The pathogenic potentials of encapsulated and unencapsulated strains of Bacteroides fragilis were compared by use of a rat model of intraabdominal sepsis. Implantation of encapsulated B. fragilis alone resulted in abscesses in most recipients, whereas unencapsulated strains seldom produced this effect unless they were combined with another organism. Implants of heat-killed, encapsulated B. fragilis also resulted in abscess formation. Subsequent experiments suggested that the abscess-potentiating ability of encapsulated B. fragilis is related to the capsular polysaccharide. Implantation of 200 microgram of the purified capsular material alone or in conjuction with unencapsulated strains caused abscess formation in a majority of animals. Comparable results were not obtained with capsular polysaccharide from Escherichia coli O7:K1(L)"NM or with heat-killed Streptococcus pneumoniae type III. The capsular polysaccharide of B. fragilis appears to potentiate abscess formation and may represent a virulence factor for this species.


Magnitude of lead intake from respiration by normal man.

Lead metabolism of five normal men was studied in a hospital metabolic unit in order to measure the daily intake of lead by respiration in urban adults. Subjects ingested a constant diet, and samples of blood, urine, feces, and diet were analyzed periodically for lead isotopic abundances by mass spectrometry. Three men were fed daily a stable isotope tracer of lead for 83 to 124 days in order to distinguish ingested from respired lead. Also, three men lived in rooms with filtered, low-lead air for 25 to 50 days in order to examine the response of blood lead levels to a change in airborne lead exposure. The quantity of respired lead intake was determined from the lead balance data, labeling of blood lead with a dietary lead tracer, and the response of blood lead levels and lead balances to exposure to low-lead air. The results indicate that these men absorbed a mean of 14 +/- 4 (S.D.) microgram/day of lead while exposed to the ambient levels of about 2 microgram/m3 of airborne lead. About twice this amount was absorbed from the diet.


Evaluation of tetracycline in the neutrophil chemotactic response.

The chemotactic response of human neutrophils was examined in the presence of tetracycline. High concentrations of the antibiotic decreased chemotaxis in vitro but did not have an inhibitory effect on the ability of neutrophils to respond to the chemotactic components of human complement. Mixtures of human serum and endotoxin had decreased chemotactic ability when they were preincubated with various concentrations of tetracycline, the decrease being concentration dependent. This inhibitory effect of tetracycline on the chemotactic response of human neutrophils was not time dependent. Eight different tetracycline compounds were found to produce similar inhibitory effects on the chemotactic response of human neutrophils in vitro. The results indicated that tetracycline either inhibits the generation of neutrophil chemotactic factors of human serum or binds with the chemotactic factors after their generation to cause inactivation.


Renal porphyrinuria during chronic methyl mercury exposure.

These studies demonstrate altered activities of renal heme biosynthetic pathway enzymes and elevated levels of urinary uroporphyrin and coproporphyrin in rats during chronic exposure to 3, 5, or 10 ppm methyl mercury hydroxide (MMH). Porphyrinuria appears to occur as a result of inhibition of renal ferrochelatase and uroporphyrinogen I synthetase, with secondary induction of delta-aminolevulinic acid (ALA) synthetase in kidneys but not livers of mercury-exposed rats. Since the renal heme biosynthetic system appears to be highly sensitive to MMH during continuous exposure to levels below those which elicit overt general organ damage, these results may have clinical utility in diagnosing pre-toxic biological responses to mercury in human populations.


Detection of homozygotes and heterozygotes with methylenetetrahydrofolate reductase deficiency.

Specific enzyme assay is required for the diagnosis of homocystinuria due to methylenetetrahydrofolate reductase deficiency. A rapid and accurate method has been developed using "pure" peripheral lymphocyte preparations. Triplicate determinations showed highly reproducible results. With the use of the mean of triplicate determinations in the presence of flavinadenine dinucleotide, there was complete segregation among the homozygotes, heterozygotes, and normal subjects. This method provides a rapid diagnosis in affected subjects and a simple means for the determination of heterozygotes for genetic counseling.


Lymphocyte mitogen stimulation studies for patients with lung cancer: evaluation of prognostic significance of preirradiation therapy studies.

The responses of lymphocytes to stimulation by three common plant mitogens (PHA, Con A, and PWM) have been studied prior to irradiation treatment in 65 patients with bronchogenic carcinoma. The lymphocyte mitogen stimulation (LMS) responses of these patients were determined to be normal or abnormal based on data obtained from similar studies in healthy volunteers. The data for the patients with lung cancer were analyzed for correlations between the lymphocyte responses and (1) the stage of disease, (2) prognostic significance, and (3) period of survival. Statistically significant correlations were observed between the responses of lymphocytes and the stage of disease and the period of survival. However, this study indicates that these correlated responses will be of limited prognostic clinical value for individual patients.


Factors affecting serum and urinary guanidinosuccinic acid levels in normal and uremic subjects.

Guanidinosuccinic acid (GSA) was measured in serum and urine from six normal subjects, 26 chronically uremic patients, and 17 patients undergoing maintenance hemodialysis. All normal subjects and 22 chronically uremic patients were fed diets providing 21 gm of essential amino acids or 20, 40, or 60 gm/day of protein. Serum GSA was usually undetectable in normal subjects and was increased in uremic patients (0.99 +/- S.D. 044. mg/100 ml). Serum creatinine and urea nitrogen were each correlated with serum GSA in the normal and uremic subjects combined and in uremic patients alone. Serum GSA was greater in hemodialysis patients (1.43 +/- 0.56 mg/100 ml) than in uremic patients (p less than 0.02) and decreased by 39% +/- 21 during hemodialysis in five patients. Serum GSA and the serum GSA/creatinine ratio tended to decrease with low protein intake in the uremic patients. Urinary GSA was increased in uremic patients (30.5 +/- 12.9 mg/day) as compared to that in normal subjects (7.5 +/- 1.9 mg/day), was greater in uremic patients than in normal subjects at each level of protein intake, and was directly correlated with protein intake and urinary urea and total nitrogen in both normal and uremic subjects. In three uremic patients who developed intercurrent illnesses, urinary GSA rose transiently. These results indicate four factors which affect serum or urinary GSA levels: (1) renal function, (2) protein intake, (3) catabolic stress, and (4) hemodialysis therapy.


Effects of potassium chloride on plasma renin activity during sodium restriction in normal man.

Previous studies have suggested that large intakes of potassium (K) will suppress plasma renin activity (PRA) in normal man. The effect of more modest intakes of K on PRA is unclear. The present study was designed to compare the PRA in 11 normal volunteers maintained on an electrolyte-free diet (7000 J), with and without the addition of 50 mEq/day of potassium chloride (7000 J + KCl), well within the limits of usual dietary consumption. Control recumbent and 2 hr of upright PRA determinations were made by radioimmunoassay prior to the initiation of either the 7000 J diet or the 7000 J + KCl diet and on the fourth day of the diet, at a time when urinary sodium, K, and chloride excretions were near intakes. Mean (+/- S.E.M.) PRA's are indicated in Table II. There are significant (p less than 0.01) differences between (1) all respective recumbent and upright posture positions and (2) before and after the administration of 7000 J and 7000 J + KCl. However, there are no significant differences between (1) control periods or (2) before and after the addition of KCl to the electrolyte-free diet. We conclude from these studies that K, given in modest amounts, has no inhibiting effect on PRA.


Tubular effects of acute metabolic acidosis in the rat.

Micropuncture and clearance studies were performed to evaluate the effects of acute NH4Cl-induced metabolic acidosis. Studies were performed in four groups of rats: controls, urea-saline, saline, and NH4Cl. Acidosis (pH: 7.25 +/- 0.02[S.E.M.], HCO3- = 12.4 +/- 0.7 mEq/L) was associated with increased fractional sodium excretion, 9.13% +/- 0.52 and calcium excretion, 1.32% +/- 0.43, which was significantly greater than controls, 0.30% +/- 0.07 and 0.30% +/- 0.07; urea-saline, 0.54% +/- 0.1 and 0.54% +/- 0.13; saline, 0.71% +/- 0.17 and 0.47% +/- 0.09. In the proximal tubule, however, fractional reabsorption was less with saline, 41.5 +/- 1.7, than either urea-saline, 51.1 +/- 1.3, or the NH4Cl-infused group, 46.9 +/- 0.4. The data indicate that natriuresis of acute NH4Cl loading is associated with but cannot be accounted for by inhibition of proximal tubular reabsorption. The mechanism of inhibition of transport at sites beyond the proximal tubule is not clear but cannot be either volume expansion or increased solute load due to urea excretion.


Adsorption of human erythrocyte surface glycoprotein onto polystyrene latex spheres.

Exposure of polystyrene latex spheres to purified human red blood cell glycoprotein type MM confers upon them the agglutinability of type MM red blood cells by rabbit antisera to human erythrocytes. Thus a property of the RBC outer surface can be transferred onto a synthetic substrate.


Effect of aminonucleoside on transport maximum of para-aminohippurate and intrarenal blood flow distribution in rats.

The present study examined intrarenal blood flow distribution and possible involvement of tubular elements in rats with aminonucleoside (AMN)-induced nephrotic syndrome. Tubular maxima of para-aminohippurate (T M PAH) were determined during mild saline expansion in control rats and in rats on days 4, 5, 6, and 14 following a single intravenous injection of AMN (10 mg/100 gm of body weight). T M PAH and glomerular filtration rates (GFR's), unchanged from controls on day 4, were equally depressed on days 5, 6, and 14; minimum values were reached on day 6. Composite linear regression analysis of controls and AMN-treated rats showed that T M PAH and GFR's were significantly correlated (r = 0.704, p less than 0.001). Microsphere studies in animals with chronic carotid catheters demonstrated a decrease in the ratio of outer to inner cortical blood flow 6 days following AMN. The data suggest that AMN produces primarily glomerular lesions and that outer cortical blood flow is more susceptible to AMN than is inner cortical blood flow.


An improved method for the in vitro evaluation of monocyte leukotaxis.

An adaptation of the double-filter technique has been developed for the in vitro evaluation of monocyte leukotaxis. The assay, which employs a sandwich of a cell-permeable polycarbonate and a cell-impermeable cellulose nitrate filter membrane, is more reliable, reproducible, and sensitive than previous techniques without sacrificing their rapidity and simplicity. Leukotactic responses were directly proportional to monocyte concentrations varying from 1 X 10(5)/ml to 6 X 10(6)/ml. Kinetic studies indicated that there was a linear increase in leukotactic responses at incubation periods from 60 to 180 min. At incubation periods less than 60 min, leukotactic responses also increased linearly but at an accelerated rate. The leukotactic and chemokinetic effects of a leukoattractant may be discriminated and appear to exert antagonistic effects in this assay system.


A urinary double-radioisotope technique for the detection of fat malabsorption.

The possibility that the unreliability of urinary excretion of radioactivity after the administration of oral 131I-triolein, as a measure of fat absorption, is due to variable renal clearance of iodide prompted investigation of a double-radioisotopic method. Intravenously administered radioiodide should be cleared identically with radioiodide split from absorbed fat and serve as an internal standard. Oral 131I-triolein was given in an 80 gm fat liquid meal; 125I-iodide was given intravenously; urine was collected fractionally for 72 hr. Accepted stool fat excretion data and stool radioactivity excretion data developed in this study were used to define groups of normals (less than 5.4 gm of fat or less than 7.8% 131I) and malabsorbers (greater than 5.4 gm of fat or greater than 7.8% 131I). In 26 normals urinary 131I ranged from 24.6% to 77.1% in 48 hr and 27.7% to 86.8% in 72 hr; in the malabsorbers these values lay between 0.6% and 62.8% in 48 hr and 1.0% and 66.8% in 72 hr, showing much overlap with normal. An index of the cumulative percentage of urinary 131I/125I X 100 at either 48 or 72 hr completely separated the groups, the index in normals ranging from 68.7 to 100 in 48 hr and 72.5 to 100 in 72 hr, whereas the malabsorbers varied between 2.0 and 64 in 48 hr and 2.2 and 67.5 in 72 hr.


Serum 25-hydroxyvitamin D concentrations in patients receiving chronic corticosteroid therapy.

Serum 25-hydroxyvitamin D (25OHD) concentrations were measured by competitive protein-binding assay in 21 patients who were receiving chronic prednisone therapy and who demonstrated radiologic osteopenia. Results were compared to values obtained in 19 matched non-steroid-treated control subjects. Serum 25OHD values in control and steroid-treated subjects were virtually identical and showed a similar positive correlation with vitamin D intake. To rule out possible assay interference by postulated steroid-induced abnormal vitamin D metabolites, 25OHD was specifically isolated from pooled extracts of control and steroid-treatment patient sera by silicic acid column chromatography. 25OHD levels were again identical in both groups, and there was no evidence of radioassayable abnormal metabolites. It is concluded that the maintenance of normal serum levels of 25OHD is not altered by chronic moderate dose corticosteroid therapy.


Static equilibrium configurations of a model red blood cell.

The membrane of the red blood cell is modeled as a fluid shell which resists bending and changes in area. The differential equations governing the mechanical equilibrium of such a membrane are derived and axisymmetric solutions are obtained numerically.


Persistence and convergence of ecosystems: an analysis of some second order difference equations.

Three second order difference equation models are analyzed and numerical solutions computed. It is shown that two concepts of ecosystem stability, the local property of convergence and the global property of persistence, do not coincide, and that the exislity are obtained and shown as parameter space diagrams. Examples of solution trajectories representative of different regions of this space are computed and discussed. A wide range of oscillatory behavior, as noted in recent papers by several authors, results. In addition, the erratic nature of regions of convergence to stable solutions is discussed.


Excitable chemical reaction systems. II. Several pulses on the ring fiber.

The parameters of the Field, Noyes and Körös model for the Belousov-Zhabotinskii reaction were chosen in such a way that the given system is excitable. It is shown by simulation that several pulses on the ring fiber, contrary to experience with known excitable media, may arrange themselves in a non-symmetrical manner while the equilibrium distances are stable. The condition for such behavior is the non-monotonic dependence of the propagation velocity, v, on the time, T, elpased since the previous excitation at that point.


A solvable selfreproductive hypercycle model for the selection of biological molecules.

By introducing a modified enzyme coupling in Eigen's hypercycle equations we have produced an exactly solvable selfreproductive hypercycle model. The model shows explicitly how collections of different macromolecular information carriers may coexist, through internal couplings, in the presence of constraints. We show how the "selective value" concept is manifested in the model and give simple criteria for selection among competing hypercycles.


When are two qualitative taxonomic characters compatible?

A proof is given of a procedure that has previously appeared claiming to determine when two amino acid positions on a protein could both possibly be divergent taxonomic characters. An algorithm for executing this procedure is described.


The dynamics of density dependent population models.

The dynamics of density-dependent population models can be extraordinarily complex as numerous authors have displayed in numerical simulations. Here we commence a theoretical analysis of the mathematical mechanisms underlying this complexity from the viewpoint of modern dynamical systems theory. After discussing the chaotic behavior of one-dimensional difference equations we proceed to illustrate the general theory on a density-dependent Leslie model with two age classes. The pattern of bofurcations away from the equilibrium point is investigated and the existence of a "strange attractor" is demonstrated--i.e. an attracting limit set which is neither an equilibrium nor a limit cycle. Near the strange attractor the system exhibits essentially random behavior. An approach to the statical analysis of the dynamics in the chaotic regime is suggested. We then generalize our conclusions to higher dimensions and continuous models (e.g. the nonlinear von Foerster equation).


[Changes in the extracellular matrix of the cranial cartilages of amphibians (author's transl)].

During the differentiation of cranial cartilages the composition of perichordal and perineural extracellular matrix changes: at first only collagen and hyaluronic acid can be detectese while the concentration of hyaluronic acid is decreasing. The possible effects of these substances not only on the chondrogenetic cells but also between themselves are discussed.


[Importance of limb tissue associations in the development of nerve-induced supernumerary limbs in the newt Pleurodeles waltlii Michah (author's transl)].

Brachial nerve tip deviation has been carried out at various points in the upper arm and close to the limb. Some associations of cutaneous or muscular tissue from two opposite sides - dorsal and ventral or anterior and posterior - of the upper arm were made at these points. Various degrees of development of the nerve-induced supernumerary limbs were observed. When a nerve deviation was not followed by grafting of tissue from the opposite side, the supernumerary limbs did not develop or were strongly hypomorphic. A normal limb to development can occur when tissues from opposite side are associated with the ones located at the nerve tip. Such associations allow a harmonious nerve-induced supernumerary limb to develop and consequently allow all transverse axes to be established. Orientation of nerve-induced supernumerary limbs is determined by the orientation of the tissues in the area of nerve deviation. In terms of positional information, since an absence of contact between tissues from two opposite sides results in a lack of normal development, we can conclude that positional values located on either side of, the centre of, at least, one transverse axis should be in contact to allow limb development, i.e. a regenerated limb or nerve-induced supernumerary limbs or supernumerary limbs. It appears that contact between such values along any transverse axis, under sufficient nervous stimulation may give rise to a supernumerary limb.


Preleptotene chromosome condensation stage in human foetal and neonatal testes.

A preleptotene stage of chromosome condensation analogous to that already described in various plants and in the oocytes of several animal species has been observed in the human foetal testis. Contrary to what has been previously described, this stage in the testis is not followed by decondensation leading to leptotene filaments. This observation underlines the problem of the precise significance of this stage and its relation to initiation of meiosis. It is suggested that meiosis may be initiated during this condensation phase and that the male germ cell, despite its XY chromosome constitution, tends to evolve towards meiosis. This proposal pleads in favour of both the role of somatic cells in the inhibition of meiosis in the male foetus and the role of environmental factors rather than genetic constitution of the germ cell in meiotic induction.


In vitro development of palatal tissues from embryonic mice. II. Tissue isolation and recombination studies.

The epithelial and mesenchymal tissues of the secondary palate from 12-, 13-, and 14-day embryonic mice were enzymatically separated and cultured in isolation and in homochronic and heterochronic recombinations. In both homochronic and heterochronic recombinations, epithelial differentiation was similar to that in vivo. In heterochronic recombinations, epithelium differentiated according to a schedule appropriate for the age of the epithelium rather than for the age of the mesenchyme, suggesting that differentiation of palatal epithelium is temporally 'determined' as early as 12 days of gestation. Palatal epithelium cultured in isolation was capable of limited differentiation. Potential for differentiation therefore exists within the isolated palatal epithelium at an early stage of palatal development, and epithelial-mesenchymal interactions are required during palatal development to support full epithelial differentiation.


Blood formation in a clonal cell line of mouse teratocarcinoma.

Pluripotent cells of a teratocarcinoma clonal line differentiate into various tissues when they are cultivated in submerged cultures. We describe here the formation of endodermal vesicles and blood islands in organotypic cultures of such cells. These are the first macroscopically visible tissues to appear in organ culture and they give rise to megalocytes, the ultimate stage of blood cell evolution in the normal mouse embryo yolk-sac. As in the normal embryo yolk-sac, the formation of haemoglobin-containing cells stops after a while, but it is not replaced by adult haemopoiesis in culture.


Studies on the development of F1 embryos from inter-strain cross involving DDK mice.

The development of the early mouse embryos was investigated from 36 to 84 h after the presumed time of fertilization. The mean number of cells constituting the embryo from the intra-strain crosses of three strains at 84h of development was as follows: DDK, 22-7; BS, 43-1 and ITES, 62-0. A significance was observed in the cleavage rate of the embryo between DDK and the other two strains. The F1 embryos from the crosses of BS females X DDK males and ITES females X DDK males showed almost the same progress of development as BS and ITES embryos, respectively. Therefore, it is concluded that the early development of the F1 embryos iss, DDK females X BS males, showed conspicuously small cell numbers as compared with their litter-mates that developed to the blastocyst stage. It is inferred that the discrimination is already made during cleavage between the fortunate survivors and the lethal embryos due to the incompatibility between the cytoplasmic factor of DDK eggs and alien spermatozoa.


Mandibular growth retardation as a cause of cleft palate in mice homozygous for the chondrodysplasia gene.

Defective chondrogenesis in C57BL mice homozygous for the chondrodysplasia gene leads to deformity of limbs, ribs, trachea, mandible and palate. Since formation of the secondary palate depends upon coordinated development of several craniofacial structures, the presence of micrognathia and cleft palate in cho/cho newborn mice suggested a cause-and-effect relation between these two deformities. To determine whether or not lower jaw shortening coincided with the time of palate closure, heads from mutant control littermates previously rated morphologically were examined in median sagittal section. Of six parameters analyzed, growth rates for mutant mandible and anterior vertical dimension were significantly less than those of controls from the beginning of control palate closure. Since there is evidence that intrinsic shelf force is normal, these observations suggested that, during palatogenesis, growth retardation of Meckel's cartilage did not allow forward displacement of the tongue, and that the consequent failure to straighten the tongue impaired shelf movement. The data support the concept that growth of Meckel's cartilage is necessary for normal palate formation.


Karyotype analysis of teratocarcinomas and embryoid bodies of C3H mice.

Karotype and capacity for differentiation were determined in four transplantable teratomas, and their embryoid bodies, derived from C3H mouse embryos. An apparently normal karyotype was retained by one tumour and one subline that were able to differentiate into a wide range of tissues, but some chromosomal alterations were found in the two tumours and one subline that showed almost identical restrictions in their capacity for differentiation. Trisomy for chromosome 11 was shared by all three restricted tumours; two of the tumours had similar length changes in the same two chromosome (1 and 14) while the third was generally trisomic for four other chromosomes.


An experimental investigation into the early development of the chick elbow joint.

The theory that differential growth of opposed chondrogenic centres is important in early joint formation has been tested experimentally by removing structures in relation to the chick elbow joint. The humerus and its cap of differentiating joint cells were found to develop independently of structures distal to them. Removal of the presumptive joint region at early stages resulted in fusion of the humerus with the radius and ulna. Results are discussed in terms of concepts concerning pattern formation of cell types in the early wing-bud.


Developmental precocity after asynchronous egg transfer in mice.

Asynchronously transferred ova were found to implant 6-8 h earlier than did non-transferred eggs, indicating that the endometrium was receptive to implantation several hours before the native blastocysts were prepared to implant. This developmental precocity was also preserved on day 14, according to the results of a morphological rating study on day 14. Synchronously transferred ova showed no such developmental precocity. No statistically significant difference in implantation time or development on day 14 was found between the two strains, CBA and A/Jax. The importance of precocious development for planning teratological studies is emphasized.


Experimental studies on a mutant gene (p) causing premature death of Ambystoma mexicanum embryos.

The premature death (p) mutation is a recessive lethal, which, in the homozygous condition, gives rise to a complex of abnormalities. The mutant embryos develop only to stage 37, at which time disintegration of superficial tissue begins. Many of the abnormalities observed in sections of the stage-37 mutant embryo are related to its failure to establish a functioning circulatory system, or to the resulting edema and/or ascites that distend the abdomen and flanks. There are, however, abnormalities of heart, liver, gill and muscle development which cannot be attributed to lack of circulation and edema. All of these abnormalities can be indirectly related to the endoderm, particularly the anterior and dorsal endoderm. The findings, therefore, suggest that the mutation leads to a fairly general defect of the endoderm.


Determination of anteroposterior polarity in the axolotl forelimb by an interaction between limb and flank rudiments.

1. It is shown that the mesoderm in the prospective forelimb-bud of the axolotl embryo is thickened and divided into somatic and splanchnic layers, while that of the flank is thinner and divided. The first sign of the limb-bud itself appears at stage 38. 2. A whole, a half or a third of a limb rudiment can develop into a normal or reduplicated limb when transplanted to the flank. 3. An anterior half of a limb rudiment fails to develop when transplanted to the head but will do so if accompanied by a small piece of flank tissue. 4. Small pieces of tissue from a wide area of the flank will cause reduplication of the forelimb if grafted to the anterior margin of the rudiment. It is shown that the whole of the reduplication is formed from host tissue and has the morphological character of the host. 5. Reduplications have posterior structures arranged symmetrically on both sides of midline. Both muscles and cartilages are duplicated. 6. It is suggested that the same interaction between prospective flank and limb is responsible for the capacity for growth on the head, the induction of reduplications and the formation of the anteroposterior pattern of the limb in normal development. 7. A simple rule is proposed which explains the occurrence of reduplications in classical work on the amphibian limb.


Control of anteroposterior pattern in the axolotl forelimb by a smoothly graded signal.

(1) It is shown that the number of cartilage elements in an experimentally produced reduplicated limb depends on the width of competent tissue between pieces of flank tissue. (2) Seventy well formed reduplications were examined on the assumption that the difference in the number of elements between them results from small differences in graft position. (3) All the reduplications are symmetrical along their entire length. (4) All possess the most posterior structures at both edges with other elements arranged in between in the correct serial order. (5) The existence of vestigial and of branched elements in the midline suggest that the cases examined come from a potentially continuous series. (6) All these characteristics can readily be explained by assuming the existence of a continuous U-shaped anteroposterior gradient, and of threshold responses by the cells which together control the pattern of cell differentiation. (7) It is suggested that the gradient "deepens" as more distal levels of the limb are laid down. (8) Most but not all of the cases can be arranged in a single series in which proximal and distal levels expand coordinately. (9) Possible mechanisms for the establishment and maintenance of the gradient are discussed.


Cell lineage and cell determination in the developing compound eye of the cockroach, Periplaneta americana.

By grafting between eye colour mutants of the cockroach Periplaneta americana we have investigated (i) the hypothesis that cells within an ommatidium of the fused rhabdom type are clonally derived from a single mother cell and (ii) we have tested the suggestion that cells from non-prospective eye epidermis can form ommatidia when grafted next to eye tissue. Mosaic eyes containing cells of the two genotypes contain ommatidia with unpredictable combinations of the two sorts of cells at the host/graft border. This finding is inconsistent with the first hypothesis. Using grafts of prothoracic epidermis and head epidermis from non-prospective eye regions we have shown that only cells from the prospective eye region can form ommatidia. Possible ways that eye cells could be determined are discussed in the light of these findings.


A technique for introducing localized long-lasting implants in the chick embryo.

A technique is described for making chronic, localized implants of drug-impregnated Silastic in early chick embryos. This silicone material has been shown to gradually and uniformly release its impregnated contents under such conditions. Following implantation of pieces of Silastic treated with the metaphase-blocking drugs colchicine and vinblastine into the wing-buds of 41/2-5 day chick embryos, 53-75% survived 4-5 days, at which time they were sacrificed. Non-impregnated (control) Silastic was also implanted in a group of embryos. In this group, 90% survived 4-5 days. The antimitotic effects of the drugs were very well localized to implanted wings, which were reduced in size by approximately 55% at the time of sacrifice (day 8-9 of incubation). In control embryos, the implanted wings were normal in size and general morphology. It is suggested that the technique could have numerous applications for the study of neuroembryology or other aspects of embryogenesis.


Inhibition of cranial neural crest cell development by vitamin A in the cultured chick embryo.

Chick embryos at stage 8, prior to neural crest cell migration, were explanted on whole egg medium with or without vitamin A and cultured for 3 days. Sections through the head regions showed that the cranial neural crest cells had migrated into the first visceral arch in the controls but were absent from this structure in the treated embryos. These observations suggest that vitamin A inhibits neural crest cell development or migration, an effect which may in part account for the facial malformations produced by excess vitamin A.


Trophoblastic vesicles of preimplantation blastocysts can enter into quiescence in the absence of inner cell mass.

Preimplantation mouse blastocysts were dissected into inner cell mass (ICM) and trophoblast cells. These fragments were transferred to pseudo-pregnant mice which were left intact or ovariectomized. The latter group received progesterone to permit blastocysts and the dissected fragments to enter into quiescence, prior to injection of oestradiol to induce implantation. Trophoblastic vesicles, without ICM, entered into quiescence and implanted whereas the ICM did not. The entry of trophoblast into quiescence does not appear therefore to be governed by the ICM.


Ultrastructural observations on stumpy (stm), a new chondrodystrophic mutant in the mouse.

Stumpy (stm) is a new chondrodystrophic mutant in the mouse. Light microscopy of cartilage reveals a slightly increased mitotic rate, more chondrocytes than is usual per lacuna and a wide zone of hypertrophy. Electron microscopy shows that many chondrocytes are in close approximation with some tight junctions: in cartilage from 14-day-old mice there is much interdigitation and folding of the cell membranes of adjacent chondrocytes.


Further studies on skull growth in achondroplasic (cn) mice.

The morphology of the basioccipital, basisphenoid and mandibular bones in achondroplasic (cn/cn) mice was compared with that of normal siblings. The two bones of the cranial base were markedly reduced in length but not in width. The percentage reduction in the basisphenoid was twice that in the basioccipital bone and of the same magnitude as that previously observed in the long bones of the limbs. This difference may arise because the basisphenoid, like the long bones, grows in length from two cartilaginous growth sites while the basioccipital grows from one cartilaginous and one periosteal site. The mandible of the cn/cn mice was also reduced in size, although to a lesser extent than were the cranial bones and without the ensuing disproportion. The scale of the mandibular changes suggests that they are largely attributable to regulatory responses to the shortened cranium. The finding that the condylar cartilage of the cn/cn mice is reduced in thickness indicates, however, that the cn gene may have a direct effect on condylar chondrocytes.


Intercellular contacts at the epithelial-mesenchymal interface of the developing rat submandibular gland in vitro.

An ultrastructural study of the development of the rat submandibular gland (SMG) analage in vitro was undertaken to determine if epithelial-mesenchymal and epithelial-nerve contacts were integral events in the differentiation of the gland in vitro as they are in vivo. SMG rudiments were removed at the stalk-bulb stage (15 days in utero) and cultured for 6 days on a millipore filter in supplemented McCoy's 5A media. Rudiments were taken at daily intervals, fixed and processed for electron microscopy. The overall development of the explanted rudiments closely paralleled their maturation in vivo although cultured glands lagged 24-36 h behind their normal counterparts. Direct epithelial-mesenchymal contacts were seen after the morphogenetic patterning of the gland had been established but prior to functional differentiation of the rudiment. Epithelial-nerve contacts were not seen although healthy axons were seen in the stroma throughout the culture period. The study indicates that epithelial-nerve contacts are probably not required for morphogenesis of cytodifferentiation of the rat SMG. However, direct epithelial-mesenchymal contacts appear to be an integral part of the developmental sequence of the rat SMG.


Morphologic alterations in the parietal yolk-sac of the rat from the 12th to the 19th day of gestation.

The rat parietal yolk-sac and its adherent epithelial cells were examined at various stages of gestation using an en face technique. Specimens were observed a both the light and electron microscopic level. Diastase pretreatment and PAS-staining were used to determine the presence of glycogen. As early as the 12th day of gestation the cytoplasm of the parietal yolk-sac cells contained numerous ribosomes and mitochondria and a large amount of endoplasmic reticulum. The glycogen content of the epithelial cells increased from the 12th day of gestation and accumulated in large quantities by the 16th day. By the 17th day many cells exhibited variable degrees of degeneration. Cellular elements of degenerating cells appeared to be trapped within Reichert's membrane. Contrary to the reports of other investigators, the present study indicates that the capsular portion of the parietal yolk-sac consisting of Reichert's membrane and its adherent epithelial cells remained intact until at least the 18th day of gestation. Some of the unique characteristics of the parietal yolk-sac provide experimental models to study the effects of environmental factors on (1) the synthesis of basement membranes, (2) the ageing of cells and (3) the correlation of these histologic changes with the functions of the parietal yolk-sac.


Magnesium deficiency in embryos of Xenopus laevis.

Embryos of Xenopus laevis reared in media with various low (less than or equal to 10(-5) M) magnesium ion concentrations will exhibit differing degrees of a potentially lethal magnesium starvation syndrome depending on the ion concentration and rearing temperature. The higher the rearing temperature or the lower the magnesium ion content of the medium the more severely the syndrome will be expressed. (Normal development can be expected at temperatures 13-30 degrees C and magnesium ion concentrations greater than 10(-5)M to 10(-2) M.). The magnesium deficiency syndrome in Xenopus embryos is described in detail and compared with the normal and anucleolate conditions. The deficiency condition becomes manifest after hatching as retarded growth and differentiation with progressive paralysis and edema. At the same time alterations are observed in the pattern of soluble proteins. The use of magnesium ions as a probe for investigating developing systems is discussed.


Attention and visual dominance: a chronometric analysis.

Three chronometric experiments, each comparing vision and kinesthesis, were conducted to study visual dominance. The time required to switch attention from vision and from kinesthesis was equal, while switching to kinesthesis was faster than switching to vision (Experiment 1). Responses to a combined visual-kinesthetic stimulus were slower than responses to a kinesthetic stimulus alone when the subject was expecting the bimodal stimulus. The visual dominance effect was shown to depend on the subject knowing the modality of the stimulus in advance (Experiment 2). When subjects were instructed to attend one modality they had equal difficulty with conflicting visual and kinesthetic information (Experiment 3). These findings suggest that visual dominance results from a bias to attend vision when that modality seems adequate for the task. Te bias to attend vision may develop to overcome a deficiency in visual alerting.


Attention and reaction times to signals of uncertain modality.

Visual, auditory, and tactile reaction time (RT) signals were used in an a-reaction task. The main independent variable was the predictability of signal modality, which was varied by cuing the relevant modality or modalities before each trial. The response requirement was nondiscriminative with respect to modality. Three experiments showed that (a) RT's were longer when signal modality was uncertain, the more so with three possible modalities than with two; (b) this effect of uncertainty was approximately the same whether varied within subjects or between subjects; and (C) the effect of uncertainty was somewhat smaller on tactile RTs than on visual or auditory RTs. Experiment 4 examined change in this uncertainty effect with practice. The uncertainty effect declined over 11 daily sessions to the point of virtual absence from auditory and tactile RTs but was restored or increase will respect to all three signals following one session of discrimination RTs ("respond if visual, refrain if auditory or tactile"). The results are interpreted as showing that attention can be allocated to sensory modalities and that the implied selective process is concerned with modality "identification," though not in a way consistent with a channel-switching model thereof.


Perception of wholes and of their component parts: some configural superiority effects.

Theories of visual pattern recognition frequently assume that processing begins with an analysis of the pattern into component parts, which are often assumed to be line segments of particular orientations, lengths, positions, and curvatures. The present experiments measured discriminability of these simple parts when presented either in isolation or within configural contexts that provided no formal information useful for the discrimination. Certain contexts either impaired or did not affect performance. Other contexts were found, however, which dramatically improved discriminability. Thus, two patterns which differed only in a single part could be discriminated from each other more quickly than could their distinguishing parts shown in isolation. Further experiments suggest that this "configural superiority" effect influences perceptual components of processing rather than memorial components. The mechanism underlying configural superiority appears to be the detection of novel and distinguishing features, such as corners and intersections, which emerge when parts are placed in close proximity to each other. The outlines of a model for preattentive feature discrimination are presented.


Classifying intergral stimuli.

Two reported experiments support holistic, as opposed to analytic, processing models for integral stimuli. Speeded classification data from different information-processing tasks (univariate and correlated) were predicted by distance between stimuli in similarity space but not by redundancy. The results of the filtering and condensation tasks and the notion of configural stimuli are also explicable in these terms. It is shown that some operational definitions commonly used to define integral stimuli are usually confounded with stimulus similarity. The assumption of independence between the attributes that combine to form multidimensional stimuli is not always met and is always an empirical question. When these attributes are not independent, physical and psychological spaces are not necessarily the same. Similarity structure is a crucial concern if inferences of cognitive processing are to be based on information-processing task results.


Backward pattern masking can vary as a nonmonotonic function of target duration: on the influence of intratraget metacontrast.

The magnitude of backward masking is usually found to vary inversely with the amount of information about a target that is made available to the visual system. Contrary to these findings, we report a nonmonotonic relation between the magnitude of backward pattern masking and target duration. Specifically, masking decreased as target duration was increased to about 8 msec and, then, became more severe as target duration was further increased to a value of at least 40 msec. The occurrence of the nonmonotonic function depended on (a) the degree of definition of the target's edges, (b) the luminance levels within the target stimulus, and (c) the state of adaptation of the eye. It is hypothesized that the source of the nonmonotonic function was metacontrast interference that originated from within the target stimulus configuration. This hypothesis was supported by data that indicated that in the absence of any mask presentations, the apparent contrast between the target and its immediate background varied as a nonmonotonic function of target duration.


Perceived shape at a slant as a function of processing time and processing load.

Shape and slant judgments of rotated or frontoparallel ellipses were elicited from three groups of 10 subjects. A masking stimulus was introduced to control processing time. Backward masking trials were presented with interstimulus intervals of 0,25 and 50 msec. Reduction of processing time altered shape judgments in the direction of projective shape and slant judgments in the direction of frontoparallelness. This finding is consistent with the shape-slant invariance hypothesis. In order to study the effects of processing load, one group of subjects was given prior knowledge of the kind of judgment to be made on each trial, one group had no prior knowledge, and a third group made both judgments on each trial. The effects of the processing load manipulation were interpreted in terms of the role of attention in perceptual encoding. Consistent with previous findings, allocation of attention did not affect perceptual encoding.


Differential visual persistence between the two eyes: a model for the Fertsch-Pulfrich effect.

By presenting moving bars of different widths to the two eyes, an attempt was made to model the differential visual persistence produced by differential intensity filtering in the two eyes (the Fertsch-Pulfrich effect). If the phase of the two moving bars was controlled so that the thinner bar lined up with the leading edge of the wider bar, a clear depth effect was seen, which was the same as that produced by placing a filter in front of the eye seeing the wider bar. The depth effect was reversed, for example, from clockwise to anticlockwise, when the trailing edges of the targets were in alignment. These effects were additive to those produced by differential intensity filtering. When observers were permitted to control the phase relation between the two target bars in order to null the depth effect, they placed the thinner bar in alignment with the geometrical center of the wider bar. Widening the variable bar led to a reduction in its luminance, but this did not in itself seem to entail a Fertsch-Pulfrich effect. The classical latency explanation of the differential filtering effect is questioned, and a model involving spatial averaging of visual direction in conditions of differential persistence is proposed in its stead. Possible differences in the mechanisms of static and dynamic stereopsis are discussed.


Influence of spatial stimulus-response compatibility on reaction time of ipsilateral and contralateral hand to lateralized light stimuli.

In a simple reaction time task, key-pressing responses to unpatterned light stimuli presented in the right and left visual fields were faster for the hand ipsilateral to the visual stimulus than for the hand contralateral to the stimulus. The superiority of the ipsilateral reactions was seen also when responses were made with the hands crossed, so that such a superiority cannot be attributed to spatial compatibility between the side of the stimulus and the position of the response device. Similar results were obtained in a reaction time task of the Donders's c-type. It is argued that these laterality effects in visuomotor reaction time tasks are best explained by the anatomical relationships between the visual fields, the cerebral hemispheres, and the hands. The possible interaction between these effects and the effects of spatial compatibility between side of stimulus and side of response device are discussed in relation to reaction time tasks of the Donder's b-type.


Right-hemisphere language processing in normal right-handers.

Three experiments were conducted to investigate the verbal performance of the right cerebral hemisphere in right-handed individuals with normal intact brains. A manual reaction time (RT) measure was used to assess the relative efficiency of lateral stimulus-response pathways (e.g., left visual field-right hemisphere-left hand) in processing linguistic information. Experiment 1 showed that the right and left hemispheres were equally efficient at recognizing concrete object nouns in a lexical decision task. The RT data also suggested that abstract nouns may be recognized only by the left hemisphere. Experiments 2 and 3 demonstrated the right hemisphere's ability to detect semantic relationships between concrete nouns and their superordinate categories. The findings were discussed in terms of their consistency with data from split-brain research and their implications for models of the functional organization of language skills in the normal brain. It was proposed that the right hemisphere in the intact brain can play a functional role in processing language.


Patient problems in the office practice of six family physicians in Louisiana.

Using the Royal College of General Practitioners (RCGP) classification of disease, the patient problems encountered in six family practice offices were classified. The top 20 diagnoses are identified, collectively and individually, and compared with the top 20 diagnoses encountered in a similar, but larger study done in Virginia. The present study includes a regional practice profile based on the disease categories of Royal College of General Practitioners, which was compared with the distribution of problems in the Virginia data. This study confirms the Virginia information on the most frequently encountered problems. Collectively, southeastern Louisiana profiles show fewer respiratory problems and more circulatory problems than the Virginia study. Individually, each practice has a distinct enough profile to warrant consideration of individual practice profiles at the time of re-certification examination or planning of continuing education programs.


An integrated medical record and data system for primary care. Part 3: the diagnostic index manual and computer methods and applications.

Manual and computer versions of the diagnostic of the index-E-Book are described. Methods for establisment and maintenance of both indexes are given and the relative merits of each are delineated. Uses of diagnostic indexes are presented which are appropriate to solo and group practices. The role of the diagnostic index in curriculum development within a family practice training setting is also illustrated.


Failure to thrive in infants and young children.

Failure to thrive is a syndrome of infancy and early childhood, characterized by growth failure for no apparent cause. A careful history, thorough physical examination, and relatively simple laboratory and radiographic studies will identify the cause of the problem in most instances. Prenatal, genetic, familial, constitutional, and environmental factors are most important. Hospitalization for diagnostic evaluation is often effective from a therapeutic standpoint as well. The family physician is in a favorable position to manage most pediatric patients who fail to thrive.


Placebos: a brief review for family physicians.

Placebos are as old as the practice of medicine and for thousands of years represented nearly the totality of medical therapeutics. Positive and negative placebo effects occur in about 35 percent and 10 percent of individuals, respectively. Without exception, all medical therapeutics may be assumed to have significant placebo components. Factors contributing to the success of placebos are many, but include the expectations of physician and patient, the doctor-patient relationship, and societal norms. Ethical issues regarding the use of placebos are not clear-cut but, in general, the use of placebos is contraindicated except as an adjunct to specific therapy, or as a research tool with informed consent.


Accumulation of glucocorticoids in regenerating areas of limbs of the newt, Notophthalmus viridescens.

Evidence is presented that regenerating portions of newt limbs preferentially accumulate 3H-labelled exogeneous cortisol and corticosterone. The ability of such regions to accumulate glucocorticoids is maximal about seven days after amputation and is abolished by interrupting the spinal nerves innervating the limb. Either hypophysectomy or ablation of interrenal tissue is without marked effect. The accumulation effect is not shown by aldosterone, testosterone, glucose, cholesterol, or leucine but estradiol does accumulate to a somewhat lesser extent than do the glucorticoids examined.


Polymorphism and reproductive mode in the rotifer, Asplanchna sieboldi: relationship between meiotic oogenesis and shape of body-wall outgrowths.

Sexuality and polymorphism are closely coupled in the rotifer Asplanchna sieboldi. In a graded response to dietary tocopherol, embryos develop body-wall outgrowths of various sizes and shapes. Also in a graded response to this compound, some of the affected females produce eggs undergoing meiotic instead of mitotic oogenesis. The haploid eggs of such mictic females develop parthenogenetically into males instead of females. The incidence of mictic females among animals with different shapes was studied among cohorts from mothers subjected to different inducing conditions. The hypothesis that external tocopherol concentrations absolutely fix the probability of meiotic oogenesis was rejected. The other extreme hypothesis, that the probability of meiotic oogenesis is fixed by morphotype, was rejected for animals at the low end of the morphotypic scale but accepted for the more strongly-affected individuals. The probability of meiotic oogenesis is thus constant for the higher morphotypes. The ascertainment of morphotype frequencies in natural or laboratory populations may suffice for estimating the incidence of sexual forms; furthermore studies of factors affecting the body-wall-outgrowth response may also bear directly upon regulation of sexual reproduction in this species.


Ontogenetic change in molecular and functional properties of blood of garter snakes, Thamnophis sirtalis.

At birth the blood of garter snakes (Thamnophis sirtalis) has high oxygen affinity (P50 at 25 degrees C and pH 7.2 = 21 mm Hg), low hematocrit (14%), and a high proportion of inactive hemoglobin (44%). Growth of the snakes is accompanied by a steady decrease in oxygen affinity (P50 = 44 mm Hg in adults), increased hematocrit (to 44%), and decreased inactive hemoglobin (to 3%). These adult values are reached in the second or third year of a snake's life. There is a continuous change in the electrophoretically separable hemoglobin fractions during this period, but there is no ontogenetic change in the oxygen affinity of phosphate-stripped hemoglobin in solution. Organic triphosphates do not fully explain the ontogenetic change in blood oxygen affinity. Similar ontogenetic changes in blood oxygen affinity were found in two other species of snakes. The unusual morphology of snake lungs and consequent changes in pulmonary pO2 and pCO2 during ontogeny may be the basis for the unusual relationship between body size and blood oxygen affinity in snakes.


Is the activated spermatozoon really capacitated?

A culture medium (7M) consisting only of salts and devoid of any macromolecule was prepared to test its effect upon survival, activation and acrosome reaction of golden hamster spermatozoa. Incubation of spermatozoa in medium 7N allowed a temporal separation of activation and acrosome reaction. Over seventy per cent of spermatozoa were activated after four hours at 37 degrees C while the acrosome reaction remained very low (8%). Activated spermatozoa with intact acrosomes were incubated with zona-free hamster oocytes at 37 degrees C for one to two hours. When these oocytes were examined with the electron microscope it was found that the spermatozoa were closely bound to the egg plasma membrane, mainly by the plasma membrane overlying the acrosome, but in no instance had the gamete membranes fused. Prolonged incubation resulted in an engulfment of the sperm by the oocyte in a phagocytic manner. The experimental evidence would indicate that an activated spermatozoon is not capacitated since it cannot fertilize oocytes.


Variations in macromolecular antifreeze levels in larvae of the darkling beetle, Meracantha contracta.

Overwintering larvae of the darkling beetle, Meracantha contracta, produce a macromolecular antifreeze that is similar in activity to the glycoproteinaceous and proteinaceous antifreezes found in some cold-water, marine teleost fishes. The antifreeze is not present in the hemolymph of the Meracantha larvae in summer, but its production begins by late September in the wild population. The antifreeze reaches a maximum concentration in February, decreases slowly through spring, and disappears by early June. The supercooling points of the larvae are lowest in February, when the antifreeze levels are highest, and increase as the antifreeze concentrations in the hemolymph decrease in the spring. Larvae collected in mid-February and warm-acclimated lost the antifreeze with-in 12 days. Larvae collected in early September and cold-acclimated required nearly two months to produce concentrations of antifreeze comparable to those of overwintering larvae. Temperature seems to be the major environmental factor responsible for the control of antifreeze levels in Meracantha; however, other environmental factors may also be involved.


Liver regeneration in normal and alloxan-induced diabetic rats.

The effects of alloxan-induced diabetes on liver regeneration were investigated. Normal and diabetic rats were sacrificed at eight time periods between 16 hours and 4 weeks following two-thirds partial hepatectomy or sham operation. The results indicate that alloxan-induced diabetes delays but does not prevent liver regeneration following partial hepatectomy. This delay is indicated by a depressed synthesis of RNA, DNA and protein during the first post-operative day and a lack of mitotic figures in the 24-hour sample. In addition, the synthesis of these three cellular constituents did not return to control levels as rapidly in the diabetics. Compared with the sham operated animals, the concentrations of total serum protein remained depressed longer in the diabetic hepatectomized animals. The data indicate that the metabolic alterations associated with alloxan diabetes delay the onset of the regenerative process and prolong the recovery period.


Carbohydrate composition of hepatitis B surface antigen.

The content and composition of carbohydrate in hepatitis B surface antigen HBsAg) were clarified by gas chromatography. A value of 75-8 microgram carbohydrate per mg of protein was obtained. The main components were N-acetylglucosamine, mannose, galactose and sialic acid and the minor one was fucose. No N-acetyl-galactosamine was detected. The fact that no sugar was detected in lipid fractions suggests that the sugar in HGsAg exists almost exclusively in the form of glycoprotein and there is no glycolipid.


Early diagnosis of Hepatitis B by Dane particle associated DNA polymerase assay.

We have studied prospectively 178 subjects exposed to hepatitis B and 120 haemodialysed patients for the presence of HGs antigen, e antigen and DNA polymerase as well as for anti-HBs and anti-HBc antibodies. The results suggest that the DNA polymerase assay enables us to diagnose hepatitis B earlier than the radioimmunoassay for HGs and that DNA polymerase might be present in the blood in the absence of HBs in cases of confirmed hepatitis B. A posititive correlation between e antigen and DNA polymerase was observed in 83% of the patients on haemodialysis who developed hepatitis B but only in 9% of normal patients developing the same disease.


Electron microscope observations on a virus transmissible from pinnipeds to swine.

Evidence from immunological tests and electron microscopy indicates that a virus isolated from an Alaskan fur seal is transmissible to swine. The virus is one of the San Miguel sea lion viruses and a member of the calicivirus groups.


Characteristics of a human cell line transformed by DNA from human adenovirus type 5.

Human embryonic kidney cells have been transformed by exposing cells to sheared fragments of adenovirus type 5 DNA. The transformed cells (designated 293 cells) exhibited many of the characteristics of transformation including the elaboration of a virus-specific tumour antigen. Analysis of the polypeptides synthesized in the 293 cells by labelling with 35S-methionine and SDS PAGE showed a variable pattern of synthesis, different in a number of respects from that seen in otheruman cells. On labelling the surface of cells by lactoperoxidase catalysed radio-iodination, the absence of a labelled polypeptide analogous to the 250 K (LETS) glycoprotein was noted. Hybridization of labelled cellular RNA with restriction fragments of adenovirus type 5 DNA indicated transcription of a portion of the adenovirus genome at the conventional left hand end.


Relationship of a virus from Tellina tenuis to infectious pancreatic necrosis virus.

The physicochemical and serological properties of a virus isolated from the bivalve mollusc, Tellina tenuis, have been examined. The virus has a diam. of 59 nm, sediments at 430S in sucrose gradients and bands at a density of I-32 g/ml in CsCl. The virus contains RNA with a mol. wt. about 2-8 X 10(6) as extimated by polyacrylamide gel electrophoresis but in sucrose gradients the RNA sediments at 14S. The virus RNA is resistant to ribonuclease under conditions in which ribosomal RNA and the single stranded Mengo virus RNA are completely hydrolysed. Two major polypeptides, mol. wt. 67 and 40 X 10(3), and minor polypeptide, mol. wt. 110 X 10(3), are present in the virus particle. These properties are similar to those found in different serotypes of infectious pancreatic necrosis (IPN) virus. Although there was only a very low level of cross-neutralization between Tellina virus and IPN virus. there was some cross-reaction in immune electron microscopy tests and in immunofluorescence tests with infected tissue culture cells. This cross reaction, together with the close similarity in morphology and physiochemical properties, suggests that Tellina virus and IPN virus belong to the same virus group.


Legibility of five-digit Arabic and Devanagri numerals as a function of their sizes.

The purpose was to test two hypotheses: (a) Arabic numerals would be more legible than Devanagri; and (b) among all the four type sizes, 10-point printing faces would be most legible. Five-digit stimuli of four printing sizes (8-, 10-, 12-, and 14-points), printed on white cards in deep black ink, were tachistoscopically presented to 16 students (eight males, eight females) of undergraduate and graduate classes. F ratios for within points, as well as for within scripts, were significant. In all point sizes Arabic was more legible. All but two pairs of means of Arabic numerals (8- X 10-points and 10- X 12-points), but only two pairs of means (8- X 12-points and 8- X 14-points) of Devanagri numerals were significantly different from each other. Legibility scores distinctly rose with increase in sizes in both the numerals.


The size-color illusion.

Slides were made from Munsell color chips in three sizes, four hues, and two chromas; all had the same intensity. A direct-comparisons, forced-choice procedure was used with 100 male and female volunteers from psychology courses. When pairs of slides had the same size and chroma, the order of decreasing apparent size was red-purple, yellow-red, purple-blue, and green. At chroma/8, all comparisons were significant except yellow-red over purple-blue. At chroma/4, the same order was found, but the effect was not pronounced. When pairs were made up of identical hues but different chromas, the square with chroma/4 (less saturation) appeared significantly larger.


Relation of auditory-visual integration to reading and intelligence.

The relation of auditory-visual integration to intelligence and reading achievement was studied in a sample of 165 fifth-grade boys and girls by means of (a) a test to match visual dot patterns to tape-recorded tones (b) a nonverbal intelligence test, and (c) a test of reading comprehension. Results showed that auditory-visual integrative ability was significantly related to intelligence and reading achievement. With the effects of intelligence controlled, intersensory transfer remained a significant predictor of reading achievement.


A controlled study of siblings of hyperactive children.

A controlled study of siblings of hyperactive boys resulted in the following findings. The hyperactive child syndrome is more common among brothers of hyperactive children than among brothers of controls (26 per cent vs. 9 per cent). Both probands and their brothers presented with more symptoms of depression-anxiety than controls. The probands, but not their sibs, presented with more antisocial symptoms than controls. Although differences in intelligence and achievement scores were found between probands, their sibs, and controls, both intelligence level and academic achievement were within normal limits in all groups.


The importance of psychiatric illness in newly arrested prisoners.

One hundred ninety-nine male prisoners without prior felony convictions were evaluated through a structured personal interview administered within 24 hours of this arrest. While 46 per cent met psychiatric diagnostic criteria, only 5 per cent demonstrated a need for acute treatment for their affective disorder or organic brain syndrome. It is felt that the alcoholics (15 per cent) and drug-abusing prisoners (12 per cent) might benefit from counseling but were not in need of emergency care. The characteristics of men in each diagnostic group are discussed.


Significance of crossed eye-hand dominance for the adult neuropsychological evaluation.

The variable of opposit eye and hand dominance is reviewed as a possible sign of learning problems and as an indication of congenital or early developmental brain impairment. It is considered as an independent variable in examining differences along several dimensions of psychological functioning as a possible discriminator of performance levels. It is also considered as a variable in discriminant function analysis to predict brain lesion process. Although few results were statistically significant, the numerous analyses were remarkably convergent in suggesting that crossed dominance is related to poorer verbal learning skills and is a useful variable in differentiating various process diagnostic groups.


Cardiac toxicity with thioridazine-tricyclic antidepressant combination.

Thioridazine-tricyclic antidepressant combination is frequently used in clinical practice. One reason for the choice of this combination may be its anticipated effectiveness in depressions which show both retarded and anxious features. Because both of these drugs have an adverse effect on cardiac repolarization, this may be a particularly hazardous combination. Two cases are presented illustrating life-threatening ventricular arrythmia in patients who have ingested both thioridazine and tricyclic antidepressants.


Dimensions of family therapy.

This article is a description of different approaches to therapy with a family orientation. There are general categories of family therpay which had their origins in individual therapy, such as the approaches based upon psychodynamic theory, those derived from experiential procedures, and the behavioral approaches. There are also family therapies which have not developed from individual therapy, such as the extended family system approach and the communication school of family therapy. The different therapy approaches are described within a set of dimensions which characterize most therapy. Such dimensions include whether the past or present is emphasized, whether the therapist uses interpretation or directives, whether the approach is in terms of growth or specific problems, whether hierarchy is a concern, and whether the unit is an individual, two people, three people, or a wider network. Illustrations of the different family therapy approaches are given in terms of the kinds of information that would interest the therapist of each school and the kinds of actions he or she would take to bring about change.


Impact of computerised axial tomography of the management of posterior fossa tumours in childhood.

Computerised axial tomography (CAT) has profoundly altered the management of most children with posterior fossa tumours. Fifty such children were operated on from October 1973 to December 1975, 20 of whom were explored after investigation by CAT only. Most recent experience suggests that CAT need by the only investigation in the majority of children suspected of having an expanding lesion in the posterior fossa.


Value of computed tomography in the diagnosis of intracranial abscess.

The computed tomography (CT) scans of 60 patients with intracranial infection have been reviewed. Computed tomography, particularly if used with contrast enhancement, is a valuable adjunct to the investigation of patients with suspected intracranial abscess. The false negative rate is 1%, but despite this, mortality from intracranial abscess remains unchanged.


Preservation of singing in Broca's aphasia.

Twenty-four right-handed, right hemiparetic patients with Broca's aphasia were examined for their singing capacity. Twenty-one (87.5%) produced good melogy. Twelve of these (57%) produced good text words while singing. It is speculated that the right hemisphere is dominant over the left for singing capacity. The relationship between melodic and text singing was also discussed.


Alexia without agraphia associated with right occipital lesion.

A 78 year old, right handed man developed the syndrome of alexia without agraphia due to a right occipital thrombotic stroke. The cerebral dominance test strongly suggests that his right hemisphere is dominant. This is believed to be the first case of alexia without agraphia secondary to a right occipital lesion in a right handed person.


A sensitive test for tactile extinction: results in patients with parietal and frontal lobe disease.

A simple test for detecting tactile extinction is described. In a population of parietal-damaged patients it yielded fewer false negatives than the classical clinical procedure. Contrary to expectations, lesions confined to the right frontal lobe produced no extinction, while those in right-handed, left frontal cases revealed ipsilateral extinction with the new test.


Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in normal subjects.

In the platysma of 34 normal subjects the amplitude of the action potential and twitch tension and tetanic tension were lower, the contraction time of the isometric twitch was 1.4 times shorter, and the potentiation of twitch tension in a staircase and after tetanus was two to four times greater than in m. adductor pollicis. Differences in twitch kinetics and potentiation were related to the four times higher incidence of fast fibres in the platysma than in the adductor pollicis muscle, as determined by histochemistry. Ninety-five per cent confidence limits were established for comparison with patients with myasthenia gravis.


Mediastinal paraganglioma causing spinal cord compression.

An invasive paraganglioma of the posterior mediastinum caused spinal cord compression in a 31 year old women. Electron microscopic examination of the paraganglioma invading the epidural space revealed numerous dense-cored granules in the cytoplasm of the tumour cells. We are reporting this case to present the ultrastructure of mediastinal paraganglioma, and to call attention to an unusual cause of spinal cord compression.


Familial idiopathic cerebral calcifications.

Nine members of a family spanning three generations showed bilateral calcifications of the basal ganglia with autosomal dominant inheritance. Two members developed chorea, dementia, and a characteristic speech disturbance (palialalia) in the third or fourth decade. A third member possibly shows the initial stage of a similar syndrome. Six members with calcifications but without neurological signs are younger than 25 years. All nine patients had normal calcium and phosphorus, and no evidence of endocrinological or somatic abnormalities. Thie 'isiopathic' picture must be differentiated from hypoparathyroidism and pseudohypoparathyroidism.


The place of ganglion or root alcohol injection in trigeminal neuralgia.

Of 157 patients with trigeminal neuralgia, referred for neurosurgery, 81 underwent 85 ganglion or root injections. The results, which are analysed with regard to pain relief and sensory loss, compare favourably with results from the literature of other forms of surgery, particularly open temporal root section.


Severe head injuries in three countries.

Methods for assessing early characteristics and late outcome after severe head injury have been devised and applied to 700 cases in three countries (Scotland, Netherlands, and USA). There was a close similarity between the initial features of patients in the three series; in spite of differences on organisation of care and in details of management , the mortality was exactly the same in each country. This data bank of cases (which is still being enlarged) can be used for predicting outcome in new cases, and for setting up trials of management.


Cytophotometric mapping of neuronal changes in senile dementia.

Results of a cytophotometric study have shown a widespread reduction in cytoplasmic RNA of nerve cells. It appears, therefore, that although certain aspects of the symptomatology of senile dementia may be accounted for by lesions in particular anatomical sites, the main part of the neurological disturbance is related to more broadly based changes in nerve cell metabolism affecting much, if not all, of the CNS.


Presenile dementia presenting as aphasia.

A focal aphasic syndrome was the first and outstanding manifestation of a degenerative, presenile dementia in a 67 year old man. Computerised axial tomography showed a strikingly dilated left Sylvian fissure--particularly in its posterior aspect--in the presence of moderate diffuse cortical atrophy. The radiographic findings correlated well with the clinical data. This is the first report of an aphasic disturbance of language as the initial symptom is presenile dementia.


Fatal measles encephalopathy with retinopathy during cytotoxic chemotherapy.

A 14-year-old boy receiving post-operative cytotoxic chemotherapy for a testicular rhabdomyosarcoma developed a fatal encephalopathy associated with retinal changes 2 months after an episode of acute measles. Post-mortem histological examination showed intranuclear inclusion bodies in the neurons and glial cells, but inflammatory cell infiltrations were absent. Electron-microscopic and immunofluorescent studies revealed intracellular masses of paramyxovirus nucleocapsid-like structures, which had the morphological and antigenic properties of measles virus. Recent reports have emphasized the possibility of occurrence of a similar encephalopathy in treated childhood leukemia. It is evident, however, that this potentially fatal complication must be borne in mind when measles is contracted during any form of cytotoxic treatment or immunosuppression. Retinal changes may be of value for the diagnosis during life. We propose the designation "measles encephalopathy during immunosuppression" (MEI) for this condition.


Crossed immunoelectrofocusing for identification of normal and abnormal cerebrospinal fluid proteins. A preliminary report.

Isoelectric focusing is a valuable method for the analysis of cerebrospinal fluid (CSF) proteins. Its high resolving power has, however, created problems in identifying the large number of protein bands separated. In an attempt to identify these bands, two-dimensional crossed immunoelectrofocusing has been used, where isoelectric focusing is combined with rocket immunoelectrophoresis. By these methods 9 of the normal proteins in the acidic pH interval have been identified. In addition the unusual CSF protein abnormalities occurring in Marie-Sanger-Brown's ataxia and alcoholic cerebellar degeneration have been shown to represent increases of different microheterogeneous forms of transferrin.


Myopathy with hyperaldosteronism. An electron-microscopic study.

In the case reported, an overproduction of aldosterone was accompanied by paretic attacks, a decrease in the serum potassium level, and in muscle tone and the deep tendon reflexes. The decrease of serum potassium level was consistent, but moderate, being to just below the normal lower limit. Loading with carbohydrate produced an attack, forearm ischaemic exercise resulted in less lactic acid production than normally. In the limb-girdle muscles there was also evidence of slight but permanent weakness. The results of histological and ultrastructural examination of a muscle biopsy are reported. It seems probable that the disturbance in the mineralo-corticoid metabolism led periodically to a decrease in the serum potassium, while in some muscle fibres the glycogen content increased and the SR became dilated and partially destroyed. In the attack-free periods tubular aggregates were produced, supposedly through an attempt at regeneration of the SR. During attacks portions of the muscle fibres were destroyed irreversibly and in consequence moderate permanent weakness resulted. Some spheromembranous degradation products which were observed might be regarded as remnants of degenerated tubular aggregates.


A quantitative technique for growing human adult skeletal muscle in culture starting from mononucleated cells.

A quantitative and reproducible technique for establishing primary surface cultures from normal and diseased human muscle is described. Successful cultures were prepared from both fresh muscle and that stored up to 96 hr at 4 degrees C. The CPK activity of the muscle cells ranged between 0.5-3.0 micronmoles creatine per min per mg protein at 30 degrees C, thus indicating a high degree of differentiation. Spontaneous contractions were observed in 4 out of the 22 cultures established. Nerve cells were not required to achieve this level of differentiated function. No gross differences in plating efficiency, rate of myotube formation or CPK specific activity were found for the diseased muscle cells cultured so far. However, a 5--10-fold higher cell yield was obtained from muscles of patients with an inflammatory myopathy. The advantages of this technique for carrying out comparative studies on normal and dystrophic muscle cells are discussed.


HLA in multiple sclerosis. Relationship to measles antibody, mitogen responsiveness and clinical course.

In our study of multiple sclerosis (MS) patients we have found significant increases in the A3, B7, and DW2 antigens. We have also studied immune responses in these same patients. There was elevation of measles antibodies in MS patients positive for A3, B7, and B18 as compared to MS patients without those antigens. The first study of mitogen responsiveness (31 patients) showed a decreased response in A3, and B7 positive patients. Study of a second and a larger group (62 patients), at a different time, failed to confirm this deficiency. We propose that there is a genetically linked (HLA) T cell deficiency in some MS patients and that this deficiency results in high humoral responses to measles antigens and an evanescent (or cyclical) reduced T cell response to mitogen.


Pathological changes in the optic chiasm of the cat following local injection of diphtheria toxin.

The optic chiasm in 14 cats was injected stereotactically with small amounts of diphtheria toxin and the morphological changes were examined by light and electron microscopy. Phagocytosis was already well-marked at 3 hr after injection and massive at 1 week. Intercellular oedema was extensive in the first week and, though diminished, was still present after 1 month. The oedema was most marked in the subendothelial regions in the early stages but was found among the nerve fibres and glial processes in those animals which survived for longer periods. Demyelination and Wallerian-type degeneration were established at 3 hr after injection and both processes continued up to 2 months and beyond. Scarring and an absolute loss of nerve fibres were present in the longer-surviving animals. Unequivocal evidence of remyelination was not obtained.


Changing mortality patterns of motor neuron disease in Japan.

The age-adjusted female death rate from motor neuron disease in Japan was noted to rise after 1952 and to fall rapidly since about 1960. A similar trend was also noticed in the males. Further study will show whether this was a part of a cyclical change or whether the mortality of the disease has entered a period of prolonged decline in that country. Death rates for neurological diseases in various countries were reported previously for 1953-58. Updating this study for 1966-71, a rising trend of deaths from motor neuron disease was identified in European countries, but the rate has been stationary in the United States. The rapidly changing patterns of the mortality seemed incompatible with a purely genetic causation of the disease. This indicates the need for extensive epidemiological studies to identify the extrinsic factors which induced such a trend, and were thus possibly the cause of the disease. In view of the results of the re-evaluation of the diagnosis in death certificates, mortality figures of motor neuron disease in females appeared reasonably reliable for an epidemiological study.


Hypocomplementaemic and normocomplementaemic multiple sclerosis. Genetic determinism and association with specific HLA determinants (B18 and B7).

Seventy-five patients with multiple sclerosis (MS) were treated for complement components C3, after factor B, C4, and tested for HLA-A and B-determinants. Levels of IgG, IgA, IgD, IgE and titres of measles antibodies were also determined. Correlations between these immunological values and HLA determinants could be obtained in siblings, parents and/or children of the patients in 13 families. B18 frequency is strongly associated with the hypocomplementaemic group (x2 = 8.9). An association of B18 with the population of cases with low B levels is also found (x2 = 8.02). Familial data showed that low C3 and/or low B levels are associated with the HLA haplotyes, especially with those containing B18. A "complement abnormality susceptibility gene", linked to the HLA genes, is postulated. Infections are significantly more frequent in families of hypocomplementaemic MS, the existence of a genetic immunodeficiency affecting the synthesis of the complement components, linked to the HLA determinants. In 1 case studied in this article, a heterozygous C2 deficiency linked to HLA-A10, B18 was found and might confirm this hypothesis.


Ultrastructural and histological studies of brains of ferrets inoculated with subacute sclerosing panencephalitis: similarities to human disease.

Similarities to human subacute sclerosing panencephalitis (SSPE) were revealed in a study of the brains of ferrets inoculated with a cell associated measles virus originally isolated from an SSPE patient. The similarities were greatest in animals that showed neurological signs 3-4 months after inoculation and had high titers of neutralizing antibodies against measles virus. These included dense core particles, nuclear bodies, alterations of basement membranes of small blood vessels, plasma cells, distorted myelin, and rod-like structures in some nuclei. Other abnormalities seen were Hirano bodies, tubular aggregates in cisternae of endoplasmic reticulum and clusters of cytoplasmic tubules. No cells containing viral inclusion bodies were observed by electron microscopy but cell cultures of the brains of these animals always yielded abundant measles virus nucleocapsids in typical SSPE multinucleated syncytia. These findings suggest that the ferret is a suitable animal model for the study of the pathogenesis of SSPE.


Fine structure of medulloepithelioma.

A survey of published cases of medulloepitheliomas indicates that this tumor is highly malignant (average course 6 months), occurs in early childhood (average age 4,4 years) and has no sex predilection. Although it may originate in any part of the central nervous system, it is most common in the cerebral hemispheres. The first case studied with the electron microscope is reported here. The fine structure of the tumor is similar to that of the fetal neural tube in showing a primitive epithelium having uniform nuclei rich in chromatin but little cytoplasm and sparse organelles; it rests on a distinct basement membrane. The epithelial surface lacks cilia or microvilli and is covered with an irregular amorphous coat which is probably the cause of the light-microscopic misinterpretation of an inner limiting membrane. The lateral cell surfaces lack interdigitations but show extensive primitive forms of cell junctions. The case presented is also unusual in being the second case on record originating in the cerebellum and the first showing massive seeding along the spinal canal.