Purine base transport in normal and mutant erythrocytes. The uptake of adenine and hypoxanthine in HGPRT-deficient and normal human erythrocytes was measured using a rapid filtering centrifugation technique. The transport of hypoxanthine as well as of adenine is impaired in the mutant cells. The transport of hypoxanthine into HGPRT-deficient erythrocytes differs from that into normal cells with respect to a higher accumulation capacity, to lower initial velocities and to the kinetic properties of the translocator. In addition, a higher accumulation capacity and lower initial velocities of adenine uptake could be demonstrated in  mutant cells. A linkage of the purine translocator with purine phosphoribosyltransferases associated with the erythrocyte membrane is discussed.


Human saliva as a source of biochemical genetic markers. I. Techniques. The number of genetic markers identified in human saliva is still small compared to known genetic markers of blood. Enzyme activities that can be detected in human saliva by spectrophotometric techniques are listed. The methodologies currently available for the detection of biochemical genetic markers by polyacrylamide-gel electrophoresis are summarized.


Anthropometric and physiological properties in the determination of biological distances. The investigation of anthropometric dimensions of the body and head, lung function tests and blood pressure was carried out in 3 separate groups. The analysis of 'distances' between particular pairs of the analyzed groups was performed by Penrose's CH2 and its components CQ2 and (v-l/v)CZ2. It is pointed to various ways of diversification of particular characteristics, which is likely to depend on different selective inertia of particular traits, that is, on different intensity of the effect of genetic and/or ecological factors on their formation. It is shown that as many different biological characteristics of human groups as possible should be taken into consideration for the calculation of 'distances'.


Inheritance of Indian childhood cirrhosis. Detailed pedigree charts were prepared from 120 index patients suffering from Indian childhood cirrhosis (ICC). Of the 120 families, 84 were informative for segregation analysis. Since families were ascertained through patients who came to hospital for treatment, the data were analyzed according to a single-selection model. The observed segregation ratio for the entire data was significantly lower than the one expected under the hypothesis of autosomal recessive inheritance (p = smaller than 0.005). On the other hand, the segregation data for families with at least two affected children (multiplex families) were compatible with autosomal recessive inheritance. On this basis, however, at least 50% of all the cases of ICC would have to be of nongenetic origin. Alternatively, analysis of the data by the Falconer method indicated that ICC could be of multifactorial origin with very strong genetic determination (over 85%).


Some aspects of the occurrence of new mutations in haemophilia. Using the data available on a group of carriers of haemophilia, the mutation rate in the male germ line was compared with that of the female germ line. The mutation rate among the male germ line was about 1-2 times that in the female germ line. An assessment of grandparental ages as a factor in the production of new mutations of haemophilia was also investigated.


Anthropometric differences between sicklers and nonsicklers in Zairian adults. From a sample of 1,079 male adult Zairians living in regions where falciparum malaria is endemic 212 sicklers and 867 nonsicklers were compared for eight anthropometric variables. The two groups did not differ significantly in their variances. The sicklers had a higher mean for seven variables, but significantly so for head breadth only. These results are discussed in terms of the balance of the possible effects of the AS genotype on growth and of the possible selective effects of death from malaria in infancy.


The importance of stroma in morphogenesis and functional activity of urogenital epithelium. Urogenital morphogenesis and cytodifferentiation are presented in the context of the epithelial-stromal interaction. The essential role of stroma in the processes is reviewed.


[Cell kinetics in experimental rheumatoid lesions and application in antirheumatic drug research (author's transl)]. The kinetics of chronic inflammatory cellular infiltrates in antiglobulin-induced arthritis, peritonitis and subcutaneous fibrin granuloma were investigated. Only small numbers of the mononuclear cells were labeled after 3H-thymidine impulse labeling, whereas a high labeling index results after 3H-thymidine labeling of the bone marrow. It is concluded that in experimental arthritis the inflammatory so-called cellular hyperplasia consists in bone marrow derived mononuclear cells. In experimental peritonitis glucocorticoid treatment decreases the 3H-thymidine labeling indices. By means of such labeling studies the antiproliferative and antiexsudative properties of steroids were demonstrated quantitatively. Therefore we suggest to make use of experimental cell kinetics for the recognition of anti-rheumatic drugs.


[Phagocytosis and nitroblue-tetrazolium reduction. Methodical variation (author's transl)]. A variation of the method of Preisig and Hitzig (18) for the determination of phagocytosis and NBT-reduction of polymorphonuclear granulocytes and monocytes in the peripheral blood is described. Contact with infectious cultures of Candida albicans is avoided by the use of baker's yeast for phagocytosis. Methylgreen is replaced by nuclear fast red for staining. The dye solution can be used over a longer period, the stained slides do not lose their colour, the contrast with the reduced blue NBT is more intense. The application of the method is demonstrated by the results of the test in the family of a boy suffering from CGD.


[Complement-fixing antibodies to chlamydia in the population (author's transl)]. 2,213 sera of normal persons and of men with nongonococcal urethritis were tested by CF. 4.5% of the males, 9.2% of the females, and 10.8% of the urethritis-patients had titers of 1 : greater than or equal to 16 when tested against a group-specific chlamydial antigen. The usefullness of the CFT for seroepidemiological studies was confirmed.


Abnormality of spontaneous lymphokine synthesis by lymphocytes of patients with connective tissue disorders. Forty-seven patients with various connective tissue disorders were studied to evaluate the spontaneous release of lymphocyte factors affecting the in vitro migration of guinea pig macrophages. In the assay used the lymphocytes from 8 patients produced an excessive amount of factors inhibiting macrophage migration while the lymphocytes from 12 patients produced an enhancement of migration. There were no differences in the delayed hypersensitivity skin test responses between the 2 groups of patients. The data are consistent with either an abnormality of suppressor lymphocyte function or an altered lymphocyte subpopulation relationship as a factor in this in vitro abnormality.


Kinetics of cellular and humoral response of rabbits immunized with mycoplasma pneumoniae. The cellular and humoral responses of rabbits immunized with Mycoplasms pneumoniae antigen in saline or incorporated in Freund's complete adjuvant were examined. Peripheral blood leukocytes were used for the leukocyte migration inhibition (LMI) test. Both groups of animals showed significant LMI activity in the presence of M. pneumoniae as well as cross-reacting M. salivarium antigens but response to M. pneumoniae antigen was more pronounced. In the humoral response no such cross-reactivity was observed. Although some of the animals (3/8) demonstrated antibodies to M. salivarium prior to immunization the titers were not influenced by the immunization with M. pneumoniae antigen. Both groups of animals produced antibodies to M. pneumoniae antigen only, but significantly higher titers were observed in the adjuvant group. Cold hemagglutinins in both groups appeared earlier than the specific antibodies to mycoplasma. The adjuvant had no effect on the production of the cold agglutinins.


The relative capacity of corneal, heart, kidney and skin cells to stimulate allogeneic lymphocytes. In stimultaneous experiments, the ability of inbred Wistar-Furth rat corneal cells to stimulate inbred Fisher rat lymphocytes in mixed culture was compared with the stimulatory capacity of the same number of Wistar-Furth skin, kidney, heart and lymphocyte cells. The tissue cells were dissociated and after inhibition by mitomycin C cultured with an equal number of allogeneic spleen lymphocytes for 5 days. In all of these mixed cell cultures, the allogeneic lymphocytic response was mainly to the major Ag-B2 histocompatibility antigen. The stimulatory effect of corneal cells was found to be the same as that of heart, kidney and skin cells. The data indicate a lack of differences between the density of histocompatibility antigens on the surfaces of these cells.


Stability of peripheral blood lymphocyte count and E-rosette forming lymphocytes in healthy adults. Highly reproducible peripheral blood lymphocyte (PBL) count and percent E-rosette forming lymphocyte (%E-RFL) assays were developed by modifying existing procedures. PBL count assay variation was reduced by using replicate electronic white blood cell (WBC) counting and 2,000 WBC differentials. The %E-RFL assay modifications reduced variation and include the use of: (a) a capillary buffy coat isolation procedure that recovered more than 85% of the PBL without the use of chemical separation media, (b) centrifugation temperatures of 20--22 degrees C, and (c) toluidine blue staining that allowed enumeration of %E-RFL and not E-rosette forming cells, by exclusion of nonlymphoid cells. Day-to-day variation of PBL count and %E-RFL was defined by making serial determinations over a period of months. The data indicate that healthy adults maintain PBL counts and %E-RFL within narrow ranges that are specific for each individual.


Isolation of stable aggregates of IgG by zonal ultracentrifugation in sucrose gradients containing albumin. Soluble heat aggregates of [125I]IgG (A-IgG) were prepared and separated by gel filtration or by zonal ultracentrifugation, and fractions containing different size aggregates were then analyzed by reultracentrifugation. A-IgG formed single narrow peaks with constant S rates when isolated, stored and analyzed in solution containing 0.5% serum albumin. Thus, stable homogeneous aggregates of IgG of known size can be simply prepared and should prove useful both as a model for immune complexes of specified sizes and as a standard for immune complex assays.


Uptake of 125I-labelled C3a by cultured human endothelial cells. The interactions of C3a anaphylatoxin with vascular endothelium were studied in vitro using human endothelial cells in culture and 125I-labelled human C3a. Cultured endothelial cells took up 125I-C3a in a time- and concentration-dependent manner and inactivated it. Uptake was not associated with binding to specific receptors since the amount of radioactivity accumulated by the cells was not influenced by treatment with excess unlabelled peptide, metabolic inhibitors or by low temperature. Further, we observed that uptake was not saturated during 90 min of incubation or within the concentration range of C3a tested (10(-9)--10(-6) M). C3a was taken up more rapidly than other labelled, less basic compounds, including Tyr5-bradykinin, lysozyme and albumin. Examination of the cells by autoradiographic electron microscopy revealed labelled material within the cell cysoplasm but not within specific intracellular structures, such as vesicles or vacuoles. C3a was partially inactivated after incubation with endothelial cells for 15 min, but some spasmogenic activity was retained even after 90 min incubation. Since the peptide is readily inactivated by the cells, the radioactivity in the cytoplasm may be inactive C3a and possibly C3a fragments. The combination of uptake and inactivation of C3a by endothelial cells may be an effective means of removing the peptide from circulation.


Neonatal thymus grafts. I. Studies on the regulation of the level of circulating thymic factor (FTS). The level of circulating thymic factor (FTS) tested by its action on spleen rosette-forming cells from adult thymectomized mice, has been shown to be stable in young animals. This stability suggests a regulatory mechanism. An approach of this regulation has been attempted by disrupting the FTS level either by neonatal thymus grafting in adult normal and thymectomized animals, or by injections of synthetic thymic factor into normal, thymectomized mice, grafted or ungrafted. In all cases, after an initial increase over the normal value, FTS levels returned close to the previous range, indicating the existence of some homeostatic mechanism of FTS secretion.


Neonatal thymus grafts. II. Cellular events. Neonatal thymus undergoes sequential necrosis and cell regeneration after grafting under the kidney capsule in normal and thymectomized recipients. This regeneration assessed in terms of cell number, response to mitogens, in vivo steroid sensitivity, level of antigen-binding cells, and cellular distribution on Ficoll gradient is not influenced by the presence of host thymus or by FTS injections. The grafted thymus shows a similar pattern of development as control thymus of the same age followed up in situ, with the exception of age-related involution the onset of which takes place earlier in the grafted thymus.


A theoretical approach to precipitin reactions: insight from computer simulation. The theoretical consequences of different hypotheses of the mechanism of precipitin reactions have been evaluated by means of computer simulation. It has been found that the formation of compositionally different complexes in different antigen/antibody mixtures provides a valid explanation of the zoning phenomenon, but this concept fails to explain the absence of free antigen and of antigen in soluble complexes at the point of maximum percipitation. It is found that the following hypothesis provides an improved qualitative and quantitative explanation of percipitin reactions. In the first stage of the total reaction a series of compositionally different complexes is formed. As the second stage of the total reaction two kinds of processes are proposed. Inherently insoluble complexes precipitate causing the remaining soluble complexes to participate in mutual rearrangements to re-establish a new state of equilibrium in the supernatant. The inherently insoluble complexes, moreover, create a hydrophobic phase, distinct from the supernatant and cause the remaining otherwise soluble complexes to distribute themselves between the two phases according to a partition coefficient. A mathematical apparatus to study the consequences of this hypothesis is presented, and it is demonstrated that the features of precipitin curves can be explained nearly completely this way.


Measurements of precipitin reactions by difference turbidimetry: a new method. A new method for the measurement of precipitin and flocculation reactions between antibodies and antigens has been developed. The technique, called difference turbidimetry, involves the use of tandem cuvettes providing the opportunity of using separated and unmixed antigen and antibody as blank solutions for spectrophotometric readings in the ultraviolet wavelength range. By use of this technique genuine difference turbidity spectra have been recorded for the reaction between human serum albumin and rabbit-anti-human serum albumin IgG. It was found that difference turbidimetry at low wavelengths (e.g. 280 nm) allows the construction of precipitin curves with a very clearly expressed zoning phenomenon at a sensitivity which in terms of antigen and antibody concentrations is more than twice the sensitivity of conventional procedures. It is of special interest that the zone of equivalence differs when the same reaction between an antigen and its antibody is measured by difference turbidimetry, by absorbance of washed and redissolved precipitate, and by amount of precipitated antigen.


The metabolism of nucleic acids in mice. The metabolism of three forms of nucleic acid, native-DNA (N-DNA), single strand DNA (SS-DNA), and polyinosinic-polycytidylic acid (poly I : C), was investigated in vivo in randomly bred Swiss-Webster mice. Clearance of these substances from the circulation and tissue localization were determined at selected time intervals following the intravenous injection of 125I-labelled compounds. N- and ss-DNA were removed from the circulation more rapidly than was poly I : C. All three materials localized principally in reticuloendothelial-rich organs, i.e. liver and spleen. N-DNA was degraded by the liver more slowly than was poly I : C or ss-DNA. At 4 h following injection, the liver contained 26%, 13%, and 10% of the injected doses, respectively. Three days after injection, 4.5% of the N-DNA persisted in the liver, as compared to only 0.6% of the poly I : C, and 0.2% of the ss-DNA. The possiblity that these differences in metabolism of N-DNA, poly I: C, and ss-DNA may be related to their differing immunogenic potentials in experimental systems is discussed.


Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. I. Aspects of the radiolabelling technique. A reliable and simple technique for the in vivo labelling of Trypanosoma brucei with [75Se]-methionine was developed. Between 97 and 99% of the radioactivity was protein bound in the trypanosomes and spontaneous elution in vitro was less than 10% over 4 h. The fate of the labelled trypanosomes after i.v. injection into normal and immune mice was studied. Whilst the vast majority of parasites remained in the circulation of normal animals they rapidly disappeared from the blood of immune animals. In the latter the liver was found to be the principal site of phagocytosis removing over 50% of the radiolabelled parasites within 15 min of injection.


Separation of cell-dependent antibody (CDA) and inhibitory antibody by protein-A affinity chromatography and the effect of fractions on antibody-dependent cellular cytotoxicity (ADCC). The nature of cell-dependent antibody (CDA) and the mechanism of inhibition of antibody-dependent cellular cytotoxicity (ADCC) were studied in the ADCC assay system in which culture cells of methylcholanthrene-induced rat fibrosarcoma (KMT-50) were used as target cells, xenogeneic antiserum (rabbit anti-KMT-50) as the CDA, and human peripheral blood leucocytes (PBL) as effector cells, respectively. By using protein-A Sepharose CL-4B affinity column chromatography of rabbit anti-KMT-50 serum, CDA was shown to bind protein A. Complement dependent-cytotoxicity (CDC), however, was demonstrated in both the adsorbed fraction (eluate) and the non-adsorbed fraction (effluent) to protein A from the same affinity column chromatography. These data confirmed that CDA was IgG with an intact Fc portion. Inhibition of ADCC occurred by pretreatment of effector cells with rabbit anti-effector (human PBL) serum even with extremely small amounts of antiserum. Such inhibition was demonstrated with the eluate but not with the effluent from protein-A Sepharose CL-4B affinity column chromatography of rabbit anti-effector serum. F(ab')2 fragments of the same eluate (IgG) did not inhibit the ADCC activity. These data showed that the inhibition of ADCC was induced by the blocking of Fc receptors of effector cells with the Fc portions of IgG in anti-effector serum. The data obtained indicate the usefulness of protein A in separation and analysis of CDA and in investigation of the inhibitory mechanisms of ADCC.


Genetic analysis of antibody responsiveness to sheep erythrocytes in crosses between lines of mice selected for high or low antibody synthesis. Two selective breedings of mice for minimal or maximal agglutinin response to heterologous erythrocytes were carried out (selection I and II). Preliminary reported data indicated that for both selections the heritability was between 0.18 and 0.36 and the number of relevant loci from 7--13. The results reported in this article are definitive since the data of ten to twenty generations at selection limit are available and large populations of interline hybrids F1, F2 and both backcrosses were analysed. The character 'high response' was partially dominant in F1 hybrids of both selections, the degree of this incomplete dominance was 0.27 in selection I and 0.54 in selection II. In selection I, 38% of the F2 variance was due to genetic factors (VG) and 62% to environmental effects (VE). The partition of phenotypic variance of F2 and backcrosses into additive variance (VA) and dominance variance (VD) was made according to three methods and the mean results were: VA = 0.72 and VD = 0.05. The resulting mean heritability was 0.35 and the number of relevant loci about ten. In selection II, 69% of the F2 variance was due to VG and 31% to VE. The three methods of variance calculation give somewhat discordant results. According to the more probable estimation (see discussion) VA = 0.95, the mean heritability was 0.23 and the number of loci, about 6. The results obtained in crosses between homologous lines of the two selections indicate that the two 'high' lines have probably identical homogeneous genetic constitution while the two 'low' lines contain some different 'high' effect loci.


A mechanism for secretory IgA-mediated inhibition of the cell penetration and intracellular development of Eimeria tenella. The ability of Eimeria tenella sporozoites to develop normally in cultured chick kidney cells was used as an indicator of the anticoccidial effects of sera and extracts of caecal contents or tissue. Pre-treatment of sporozoites with normal serum globulin enhanced the frequency of intracellular development but pre-treatment in balanced salt solution, without protein, damaged sporozoites so that most had lost the ability to differentiate, even when they were able to invade host cells. The same inhibitory effect was seen when sporozoites were incubated in extracts of caecal contents from non-immunized chickens, although parasitic development was unaffected when sporozoites were pretreated in similar extracts of mucosae. Extracts of immune caecal contents impaired both cell penetration and subsequent development. These results show that sporozoites can lose the ability to differentiate before the ability to penetrate cells and provide evidence of a possible synergism between non-specific factors and secretory antibodies in anticoccidial immunity.


Studies of macrophage function during Trichinella spiralis infection in mice. Studies were made to investigate the quantitative and functional changes which occur in peritoneal macrophage populations obtained from mice infected orally with Trichinella spiralis larvae. C57BL/6 mice infected with T. spiralis larvae became parasitized with adult worms which were rejected from the intestine from 14 to 20 days after infection. Infected mice developed a striking increase in peritoneal exudate cells, composed largely of macrophages, which was maximal at from 16 to 18 days after infection. T. spiralis larvae and eosinophils were not seen in the peritoneal exudates. Macrophages from mice infected more than 11 days earlier inhibited DNA synthesis of syngeneic and allogeneic tumour cells, a property atributed to activated macrophages. In addition, macrophages from T. spiralis-infected mice had the functional ability to kill EL-4 tumour cells as measured by 51Cr release. Unlike activated macrophages, however, macrophages from infected mice did not develop the ability to inhibit multiplication of the intracellular pathogen Toxoplasma gondii. These studies demonstrate that T. spiralis infection in mice induces changes in macrophage function that differ from changes associated with infections by intracellular pathogens.


The binding of rabbit IgG and its enzymatically derived fragments to homologous peritoneal macrophages. Rabbit IgG and its Fab, Fc and pFc' fragments, prepared by papain or peptic digestion, were assayed for binding to homologous peritoneal macrophages. The binding affinity of IgG for the peritoneal macrophages (Ka = 5.9 +/- 1.6 x 10(5) L/M) was comparable to that recorded with alveolar macrophages (7.6 +/- 1.8 x 10(5) L/M, Arend & Mannik, 1973) but the number of receptor sites per peritoneal cell (4.6 +/- 2.1 x10(6)) was about four-fold greater than on the latter. Of the fragments, only Fc bound to macrophages with an affinity comparable to intact IgG; pFc' bound weakly and Fab was totally inactive. These data, taken with a recent study involving rabbit IgG and guinea-pig macrophages (Ovary, Saluk, Quijada & Lamm, 1976), indicate that the primary IgG binding site for macrophages is located in the C gamma 2 domain.


Non-specific recognition in phagocytosis: ingestion of aldehyde-treated erythrocytes by rat peritoneal macrophages. Particles were chemically modified with aldehydes and incubated with rat peritoneal cells for phagocytosis. All dialdehydes and lower monaldehydes tested (methanal, ethanal and propanal) made sheep erythrocytes phagocytosable. Failure of higher monaldehydes to induce phagocytosis of treated erythrocytes was not due to lack of reactivity with red cell membranes. All erythrocytes tested (bird and mammal red cells were used) and rat thymocytes were phagocytosed by rat macrophages after incubation with aldehyde. Treatment of Candida albicans did not induce phagocytosis: this failure was not due to lack of aldehyde binding (as demonstrated with [14C]-methanal) nor to anti-phagocytic properties of the parasite membrane. Sheep erythrocytes were submitted to enzymatic treatment (pronase, trypsin, neuraminidase) or incubated with succinic anhydride (to block free NH2 groups) or iodacetamide (to block free SH groups) before aldehyde treatment: phagocytosis was not decreased, which suggested that aldehydes did not act by altering some definite surface structure of the treated particles. Treatment of erythrocytes with cross-linking compounds such as tetraazotized o-dianisidine (coupling occurs mainly on tyrosine and histidine residues) or l-ethyl(3-dimethyl aminopropyl) carbodiimide (a bivalent reagent binding free COOH groups) did not induce any substantial phagocytosis of erythrocytes. Phagocytosis of aldehyde treated erythrocytes was partly correlated with hydrophobicity of these cells, as measured with a two-phase partition system. It is concluded that aldehyde-mediated phagocytosis of erythrocytes is mainly due to cross-linking of red cell membrane structures, probably involving free OH groups, which must increase local rigidity and thereby modify hydrophobicity of the red cell surface.


The localization of allogeneic lymphoid cells in relation to antibody-mediated immunosuppression. Carbon blockade of mice did not affect cytotoxic antibody production after immunization with allogeneic cells, nor did it affect the immunosuppressive activity of alloantibody. Though it inhibited the alloantibody-mediated increase in hepatic localization of allogeneic lymphoid cells it had no effect on the normal hepatic localization of allogeneic lymphoid cells. Alloantibody administered before allogeneic cells or 6 h after was equally immunosuppressive, but anti-lymphocyte antibody only had potent immunosuppressive activity when given just before the antigenic cells. These results suggest than an afferent mechanism of suppression of the humoral antibody response can be exerted by anti-lymphocyte serum and that alloantibody may also act by this method when given before the antigen. As alloantibody is also highly potent when given after the antigen when an afferent mechanism is unlikely to occur, studies on the specificity of immunosuppression, particularly the likely requirement for antibody to I region determinants, would best be conducted by giving the antibody after the antigen, thereby avoiding any possible afferent inhibitory activity.


Metabolic studies on the uptake of [14C]-histidine and [14C]-histamine and histamine synthesis by guinea-pig basophils, in vitro. The uptake of [14C]-histidine and [14C]-histamine and the conversion of [14C]-histidine to [14C]-histamine was measured in suspensions of guinea-pig bone marrow cells rich in basophils. When comparable amounts of labelled histidine or histamine were added to equal numbers of basophils, the uptake of histidine was approximately forty-five times greater than that of histamine. Purified eosinophils, neutrophils and mononuclear cells incorporated only a small proportion of [14C]-histidine when compared to the basophil; [14C]-histamine uptake by all these cell types was virtually negligible. Histidine uptake and the amount of histamine formed de novo was directly related to the number of basophils, the time of incubation and the substrate concentration. Histidine uptake was decreased by agents which inhibit glycolysis, oxidative phosphorylation, Na + - K + -dependent ATPase, protein synthesis and RNA synthesis. Inhibition was demonstrable in a dose-dependent fashion and at concentrations which had no apparent effect on cell viability. Inhibitors of DNA synthesis, and of microtubule function, had no influence on histidine uptake. Cytochalasin B, an inhibitor of microfilament function, also decreased histidine uptake but only at concentrations previously showen to affect hexose transport. None of the agents tested affected the uptake of [14C]-histamine or the amounts of new histamine formed from the histidine that had been incorporated. These studies suggest that histidine is preferentially incorporated into the basophil; that the uptake depends on the integrity of a number of metabolic pathways, but that once the histidine is taken up these requirements do not apply to the formation of new histamine. In contrast, histamine appeared to diffuse passively, and in relatively small amounts, into all the cell types tested.


Induction of an Fc conformational change by binding of antigen: the generation of protein A-reactive sites in chicken immunoglobulin. Chicken antibody alone does not bind to Staphylococcus aureus or protein A-Sepharose. Immune complexes containing chicken antibodies do bind, however, showing protein A-binding sites exist on the molecules. Binding does not occur via the antigen contained in the complex. Complexes formed in far antigen excess also bind, suggesting that an induced conformational change in the Fc region of the immunoglobulin occurs but only a fraction of the total chicken antibody is reactive.


Synthetic peptide chemotactic factors for neutrophils: the range of active peptides, their efficacy and inhibitory activity, and susceptibility of the cellular response to enzymes and bacterial toxins. The chemotactic activity for neutrophil leucocytes of twenty-six peptides of varied sequence, of which the majority were N-formylated, was assessed by determining the concentration at which each was maximally active and the efficacy of each peptide at that concentration. These two measures of activity did not correlate with one another. Many formylated peptides with a wide variety of sequences were active. Of these, the formyl-methionyl peptides had highest efficacy, but many other peptides were active at concentrations as low as the formyl-methionyl tripeptides. Unrelated peptides, viz formyl-methionyl-leucyl-phenylalanine, acetyl-tri-alanine, formyl-tri--phenyla-lanine, cross-inhibit the cells' response to one another, and this inhibition is reversible. Inhibition is prevented if the cells are incubated throughout the experiment in levamisole or A23187. These experiments suggest that the leucocyte peptide receptor is capable of binding many ligands, and that activation of a response is not solely a function of binding affinity. They exclude a strict steric specificity for binding. Chemotactic responses to formylated peptides were shown to be reduced in cells pretreated with perfringolysin, a bacterial cholesterol-binding toxin, and with phospholipase C. Trypsin and pronase also reduced these responses when used at 500 micrograms per 10(6) cells but not at lower doses.


Functional heterogeneity of macrophages. The antibody-binding activities of rabbit peritoneal macrophages separated on discontinuous gradients of Ficoll were investigated. The antibody was rabbit anti-ovalbumin IgG labelled with 125I. Of the five fractions obtained, one macrophage fraction was found to bind substantially more antibody than the others. These macrophages possessed more Fc receptor sites than the others and the number of Fc receptors (n) and the association constant (K) of these cells was calculated. By electron microscopy, the phagocytic activity of the subpopulation with most Fc receptors was less than that of the others.


Generation and secretion of eosinophilotactic activity from human polymorphonuclear neutrophils by various mechanisms of cell activation. An eosinophil chemotactic factor(s) (ECF) can be generated from human polymorphonuclear neutrophils by the calcium ionophore, phagocytosis, arachidonic acid and hypotonic lysis. In kinetic studies it is observed that peak ECF activity is released prior to the maximum of lysosomal enzyme release with the calcium ionophore, phagocytosis and arachidonic acid, while under conditions of hypotonic exposure ECF activity appears after the maximum of enzyme release. The ECF obtained by hypotonic exposure shows a fluctuating pattern with sharp peaks and steep fall-offs in activity. The ECF-release for each stimulus is temperature dependent; extracellular calcium is required when the ionophore or phagocytosis are used as stimuli, while with arachidonic acid and hypotonic exposure no extracellular calcium is necessary for ECF-release. On Sephadex G-25 each preparation of ECF eluted in the low molecular weight range at approximately 500 daltons. Eosinophils can be deactivated and cross-deactivated with the various ECF-preparations indicating either a molecular identity or a common mode of action on eosinophils.


Arteriovenous shunting in the lymph node before and after antigenic stimulus. We have assessed the effects of antigenic stimulation on the regional blood flow of the lymph node. In seventeen New Zealand white rabbits, the regional blood flow to the popliteal lymph nodes was determined using 9 and 15 micron microspheres at 16, 40, and 144 h following antigen administration. The regional blood flow in the resting lymph node measured with 15 micron spheres was 0 . 46 +/- 0 . 07 ml g-1 min-1, with 9 micron spheres 0 . 26 +/- 0 . 03 ml g-1 min-1. There was a significant 'differential flow' (the difference in blood flow between the experimental and control nodes) measured with 15 micron spheres (P less than 0 . 05). This increase in blood flow was larger early (16 h) than late (144 h) following antigen administration (P less than 0 . 01). There was significant (P less than 0 . 05) 'shunt flow' (the difference in blood flow measured with 15 micron and 9 micron spheres) in the lymph node, with more shunting early (16 h) than late (144 h) following antigen administration. No significant shunting was seen in the kidney or thigh muscle. Thus, we have established: (1) a significant increase in blood flow following antigenic stimulus; (2) shunting of 9 micron microspheres in the resting popliteal lymph node; (3) increased shunting following antigenic stimulus; and (4) that the increase in nodal blood flow was, to a large extent, secondary to increased shunt flow. Both the increased blood flow and the shunting shortly after antigenic stimulus may be important in the evolution of the immune response.


Electron microscopy of Fc receptors on human lymphocytes. The membrane receptor for Fc portions of IgG (FcR) was localized on the cell surface of humans lymphocytes by electron microscopy. The electron microscopic markers for FcR were soluble ferritin 7S anti-ferritin immune complexes prepared in forty times antigen excess than needed at equivalence. Fc receptors on the lymphocytes labelled at 0 degree in the presence of sodium azide were seen as discontinuous patches on the cell surface. In control experiments, no labelling was observed, which included lymphocytes treated with ferritin only or with F(ab')2 immune complexes as well as glutaraldehyde-fixed lymphocytes treated with 7S anti-ferritin immune complexes. The findings are discussed with relation to the widely accepted membrane fluidity model.


Proline-rich polypeptide from ovine colostrum: its effect on skin permeability and on the immune response. The effect of a proline-rich polypeptide from ovine colostrum on the humoral immune response in mice against sheep red blood cells (SRBC) was studied. It was shown that the polypeptide had a regulatory activity stimulating or suppressing the immune response. The proline-rich polypeptide also increased the permeability of skin vessels in guinea-pigs. Studies on the mechanism of the effect of the proline-rich polypeptide suggest that prostaglandins are involved in the activity of the polypeptide.


Cellular recognition of foreign-ness in two insect species, the American cockroach and the desert locust. Encapsulation of tissue implants by haemocytes was used as the assay for immune recognition in the insects studied. If haemocytes attach to and encapsulate an object implanted within the haemocoele, it may be assumed the implant is recognized as 'not-self'; lack of encapsulation of tissue implants may be assumed to indicate lack of recognition. The American cockroach, Periplaneta americana, and the desert locust, Schistocerca gregaria, were used both as donors of tissue, and as recipients of tissue implants from various insect species. Allografts were not recognized as foreign and encapsulated by haemocytes of either S. gregaria or P. americana, a phenomenon which has been reported frequently for other insect species. Haemocytes of S. gregaria recognized and encapsulated a smaller range of xenografts compared with haemocytes of P. americana, and it appears that the acuity of immune recognition by haemocytes differs between S. gregaria and the other species tested. Reasons for the different recognition responses of P. americana and S. gregaria are suggested and discussed with particular reference to the results for Nauphoeta cinerea tissue in P. americana, and Gryllus domesticus tissue in S. gregaria, where at least half the number of implants are totally but weakly encapsulated, and it is suggested that haemocytes do not react to 'difference' unless it surpasses a certain threshold.


Alterations of some chemical constituents in blood and liver of jowar fed chicks. The affect of feeding jowar (Sorghum vulgare) was investigated in day old chicks for the periods of 10 and 30 days. Similar chicks serving as controls were fed on Hindlever Poultry feed. The jowar fed chicks showed marked reduction in growth, poor development of comb and feathers, and symptoms of nicotinic acid deficiency. Biochemical investigations showed that plasma alpha-amino nitrogen was significantly reduced in jowar fed groups, indicating the deficiency of utilisable proteins in these chicks. The blood sugar levels in chicks fed on jowar for 10 and 30 days were significantly higher as compared to the respective controls. Liver glycogen in 10 days jowar fed chicks was significantly greater than in the control group. These observations have been explained to be due to reduced utilization of glucose through glycolysis.


Lognormal distribution in physical work capacity in young healthy males. This paper evaluates the statistical distribution of physical work capacity (Vo2 max) in young healthy males. For this purpose, the normally of Vo2 max data, collected on two random samples consisting of 123 and 120 young healthy male volunteers was tested. It is concluded that physical work capacity follows lognormal distribution and the quality of fit has been found to be good as tested by chi2 test.


The hypolipidemic effect of onion (Allium cepa Linn) in sucrose fed rabbits. Long term administration of sucrose significantly increased triglyceride levels in normal rabbits. Effects of an aqueous extract of onion on the sucrose fed rabbits have been investigated. Administration of onion extract significantly reduced serum, liver and aorta triglycerides and serum and liver proteins. On the other hand liver free amino acids have been significantly increased in the onion treated group as compared to the sucrose fed control. The effects of onion have been ascribed to its sulfur containing principles which oxidize thiol compounds either present free or combined in a protein and NADPH which are necessary for lipid synthesis.


Neuropharmacological actions of labetalol. Labetalol, an alpha- and beta- adrenoceptor antagonist was investigated for its central nervous system effects in rats and mice. A marked reduction in the spontaneous motor activity with no concomittant muscle weakness was produced. The drug caused closure of eyelids in rats. Labetalol caused hypothermia and prolonged the pentobarbitone-induced hyposis. In animals trained for conditioned avoidance response the drug blocked the SCR in all the animals and CAR in a few number of animals. The drug did  not protect the animals against electroshock convulsions. From the results it appears that labetalol is a central nervous system depressant.


Vagus stimulation effects during various doses of fluid infusion in dogs. Stimulation of caudal and cranial ends of vagi in vagotomised chloralose-urethane anaesthetised dogs with 7.5V, 30Cps pulses of 2 msec width after 0, 25, 50, 75 and 100 ml/kg body weight infusion dose of Ringer-Locke solution caused well known effects on heart rate, BP, amplitude of peripheral blood pressure waves, amplitude and frequency of respiration and amplitude of ECG waves. The vagal stimulation effects did not appear to be related to volume of fluid infused into circulation except that caudal end stimulation effect on QRS amplitude was prominent during higher infusion doses while its effect on amplitude of peripheral blood pressure waves and respiration was prominent during lower infusion doses.


Towards substantiation of intact nephron hypothesis. A prolonged study on sheep and goats; whose 83% of total renal mass was removed, revealed that even an extremely heterogenous kidney not only performed the regular function but remained responsive for the demands of the body.


Electrolyte changes in plasma and urine during tender coconut water infusion in dogs. Intravenous infusion of tender coconut water to paraldehyde and chloralose-urethane anaesthetised dogs at a rate of 0.5  ml/kg/min to a total dose of 100 ml/kg body weight decreased serum Na and increased K and Ca levels. Simultaneously, urinary Na excretion decreased and K and Ca excretion increased and there was glycosuria. Serum electrolyte changes were more prominent in paraldehyde anaesthetised dogs.


Histologic explaination for reduced fetal urine production and for reduced amount of amniotic fluid in complicated pregnancy. Reduction in the production of fetal urine and amniotic fluid has been recognised to have resulted from increased tubular mass in the kidneys of sub-acutely or chronically stressed fetuses and from reduced arteriolar luman size in kidney of acutely stressed fetuses.


Lung function tests in Rajasthani subjects. Various lung volumes and ventilatory tests (TV, ERV, IC, MV, MVV, VC, FEV1, MMFER and PEFR) were determined and BR, DI and AVI (Air velocity Index) calculated in 241 Rajasthani subjects of either sex ranging from 17 to 40 years of age. Most of the values (Mean +/- SEM) are higher in males than in females, and also higher in the younger age groups (17 to 27 years) than in the older age groups (28 to 40 years) for the same sex.


Outcome of Listeria monocytogenes infection in compromised and non-compromised adults; a comparative study of seventy-two cases. The mortality in listeric meningitis and septicaemia, the two main clinical manifestations of the infection, is generally considered to be high. However, co-existing disorders rather than the listeric infection itself seem to determine the outcome. In the present study of 72 listeric infections among non-pregnant adults, 28 patients without co-existing disease had a fatality rate of 10.7% as compared to 57.9% among 19 immunocompromised individuals. Finally, in a third group of listeric patients, including alcoholics and people with heart disease or diabetes mellitus, the fatality rate was 24.0%.


[The behaviour of serotonin in blood, the activity of monoaminooxidase in serum and of 5-hydroxyindoloacetic acid in twenty-four hour urine in patients with viral hepatitis (author's transl)]. The level of serotonin in blood, the activity of MAO in serum and the value of 5-HIAA in 24 hour urine were estimated in 76 patients with viral hepatitis divided according to clinical parameters into three groups (mild, mild to severe and severe clinical course). A statistically significant increase of serotonin level in blood compared with the healthy control group was found. Highest values were observed in patients with the severe form of viral hepatitis. Decreased values of 5-HIAA in 24 hour urine in the early course of the disease showed a tendency to increase in later examinations. The activity of MAO in serum was significantly lowered in all clinical forms of viral hepatitis.


Clinical, epidemiological and therapeutical experience with human tularaemia: the role of hamster hunters. Fifty patients suffering from tularaemia were treated in our department. The most frequent occupation of the tularaemia patients was hamster hunter. The most important source of the tularaemic infection (90%) was the hamster (Cricetus cricetus). We observed the cutano-glandular form in 90% of the patients and internal tularaemia in 10%. The antibiotics used (streptomycin i. m., oxytetracycline and doxycycline per os) were effective.


Isolation of H1N1 influenza virus in Munich. During an outbreak of a mild upper respiratory tract infection in a university children's hospital in Munich, an H1N1 influenza virus was isolated. Serological analysis of the isolate showed that antigenically the virus resembled the USSR/90/77 strain of influenza A virus which has been isolated in many parts of the world during the last two years.


[Infections caused by the so-called atypical mycobacteria (author's transl)]. A number of cases of patients in whom the so-called atypical mycobacteria were identified in our institute are presented briefly in this report. Predisposing factors such as occupation and existing tissue damage, particularly in prolonged respiratory tract diseases, play a significant role in the establishment of the infection in the host organism. The bacteriological culturing, testing and typing of these organisms is an important adjunct to the clinical picture.


[In vitro testing of newer cephalosporins (author's transl)]. The spectrum of activity of the newer cephalosporins is considerably wider and includes a number of gram-negative bacteria. Test results using cephalothin as 'class disc' of a class of antibiotics is therefore no longer valid for the newer members. Like cefazoline, all of the above-mentioned antibiotics are more effective against Escherichia coli. Cefuroxin and cefoxitin also display increased effectiveness against Klebsiella, as do cefoxitin against Serratia and indolpositive Proteus species, and cefamandole and cefuroxime against Enterobacter. Cefotaxim is superior to all other agents, as was also demonstrated in our own inhibition zone tests; in addition cefotaxim is effective against Pseudomonas aeruginosa. Since the various pathogens do not exhibit a uniform pattern of resistance to these antibiotics, the four new agents should for the time being be tested independently of cephalothin and cefazoline.


[The role of chlamydiae in male urethro-adnexitis (author's transl)]. Chlamydiae belonging to Subgroup A occur in both the normal male urethra and in patients with urethro-adnexitis, which means that Chlamydiae must be attributed with a significant pathogenetic role in certain cases of abacterial urethroadnexitis. Susceptibility to erythromycin therapy confirms this.


Chemotaxis inhibition induced in polymorphonuclear neutrophils by soluble immune complexes. Complement-independent chemotactic factor(s) may be generated in fresh guinea pig serum by contact with soluble Ab1Ag1 immune complexes. This activated serum is equally efficient in inducing an unresponsive state in polymorphonuclear neutrophils (PMN) to subsequent chemotaxis challenge with sera containing C-dependent or C-independent chemotactic factors. The unresponsiveness persists long after the removal of serum. Reagents which are inactive on complement but which prevent the generation of C-independent chemotactic factors in fresh serum (diisopropyl fluorophosphate, synthetic esters, kaolin) inhibit both the induction of PMN chemotaxis and the PMN deactivation. Conversely, serum from a guinea pig decomplemented in vivo retains its ability to generate C-independent factors active in PMN attraction and desensitization. The opposition of two pathways for the production of chemotactic factors in serum, one depending on complement, the other on the contact system of coagulation, is again emphasized. A different procedure for inducing unresponsiveness in PMN with soluble complexes in the absence of serum is also presented here.


Allergenicity of concanavalin A in mice. Concanavalin A (Con A) is a potent allergen in certain strains of mice and in particularly the H-2Kk mice, A/J, CBA/H, and C3H/He. Using a dose of 100 microgram, the subcutaneous route of injection was the most effective means of inducing high, persistent titers of T cell-dependent circulating anti-Con A reagins without the addition of the classical IgE adjuvants, aluminium hydroxide and Bordetella pertussis vaccine. Haptenated Con A induced reagins with antihapten specificity. In the discussion, one possible contributing factor in Con A allergenicity in genetically responder strains of mice is emphasised, namely, persistence in subcutaneous injection sites.


Nephelometric detection of soluble immune complexes: methodology and clinical applications. We have developed a method for the detection of immune complexes by laser nephelometry which is simple, reproducible, suitable for automation, and generally adaptable for diagnostic testing. Light dispersion by antigen-antibody complexes in the test samples is measured after addition of polymeric buffer, which enhances the aggregation of complexes but does not significantly affect unbound immunoglobulins. The method was used to measure immune complexes formed in vitro by incubation of tetanus toxoid with serum from a rabbit previously hyperimmunized with the same antigen, and to compare the levels of immune complexes in human sera obtained from normal adults and from 37 patients with collagen vascular diseases or endocarditis. When precautions were taken to avoid interference produced by the presence of lipoproteins or by freezing of the samples, the results obtained with human sera were consistent with those expected for normal controls and for patients with conditions thought to be associated with the presence of soluble immune complexes.


Release of slow-reacting substance from anaphylactic lung tissue and its modification by beta-sympathomimetics. Anaphylactic release of slow-reacting substance of anaphylaxis (SRS-A) from chopped guinea pig lung was studied. The antibodies mediating the anaphylactic reaction were classified as IgG antibodies by PCA technique. Isoprenaline was found to inhibit the release of SRS-A in the concentration range 10-8-10-6M, while the beta2-selective agonist terbutaline showed inhibition in the concentration range 10-6-10-5M. The beta1-selective beta-agonist tazolol was ineffective when tested in the concentration range 10-7-10-5M. The rank order of inhibitory potency of the compounds on SRS-A release agree with that for histamine release.


Circulating immune complexes and prognosis in human malignant lymphoma, a prospective study. Sera from 53 patients with Hodgkin's disease (HD) and 56 patients with non-Hodgkin malignant lymphoma (NH) were investigated, prior to treatment, for the presence of circulating immune complexes (CIC) by the 125I-C1q-binding radioassay. The patients were then followed for 14-31 months. No significant association was found between the presence of CIC and achievement of complete remission in any of the groups. In none of the groups could a difference be found between the survival rates of patients with and without CIC in their sera prior to treatment. About half of the patients were retested for the presence of CIC after completion of initial therapy. No significant association was found between the presence of post-treatment CIC and lack of complete remission in any of the patient groups. In the HD group, both pre- and post-treatment CIC appeared to be most frequent among patients over 50 years. No such association was found in the NH group.


Homogeneously staining regions on marker chromosomes in malignancy. Direct chromosome analysis with G-banding revealed homogeneously staining regions (HSR) in five of 16 human solid malignant tumours of different histological types. The HSR's were localized either terminally or interstitially on the marker chromosomes. The great stability of the HSR-carrying markers in the tumour cells suggests an interrelationship of malignant cell proliferation with the HSR. In a single case the HSR showed a moderate staining intensity for C-heterochromatin.


Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma. Aryl hydrocarbon hydroxylase activity in lymphoblasts from normal Finnish adults and from patients with pulmonary carcinomas and other types of malignancy has been studied by a modification of previously used techniques. High absolute induced aryl hydrocarbon hydroxylase activity was found in 39% of patients with untreated lung cancer but only in 15% of normal people. No increased frequency was found in the control group comprising other malignancies. The diagnosis of pulmonary carcinoma was made at a lower mean age (4.9 years younger) in the individuals with high aryl hydrocarbon hydroxylase activity than in those with low activity. High absolute aryl hydrocarbon hydroxylase activity was dominantly inherited in normal individuals, and the frequency of athe Ahb gene in the Finnish population was 8%.


Aryl hydrocarbon hydroxylase inducibility is not altered in bladder cancer patients or their progeny. We investigated the possible influence of aryl hydrocarbon hydroxylase (AHH) on susceptibility to bladder cancer in humans. AHH inducibility was measured in the cultured lymphocytes of 16 patients who were being followed after successful treatment for bladder cancer, in 53 progeny of bladder cancer patients, and in matched controls. In both the progeny and patient populations, no evidence was found for a difference between the distribution of AHH inducibility or induced AHH activity compared to the distribution among control individuals. Thus, AHH acitivity or inducibility does not appear to be a major determinant of bladder cancer risk in humans.


Aryl hydrocarbon hydroxylase inducibility and lymphoblast formation in lung cancer patients. Aryl hydrocarbon hydroxylase (AHH) inducibility and lymphoblast formation were studied in lymphocytes from healthy control subjects and from lung cancer patients undergoing radiotherapy. The relationship between AHH inducibility and percentage lymphoblasts was statistically significant only for the pre-treatment patients (r = 0.598; p less than 0.05). In the control group and in patients undergoing radiotherapy the correlation between AHH inducibility and lymphoblast formation was positive but statistically it was not significant. Our data do not suggest a linear relationship between AHH inducibility and lymphoblast formation.


Burkitt's lymphoma in Ghana: urban-rural distribution, time-space clustering and seasonality. Epidemiological data are summarized from 236 cases of Burkitt's lymphoma (greater than 90% cytologically or histologically confirmed) seen from 1970 through 1975 at Korle Bu Hospital, Accra, Ghana. The rate of referral from rural areas was greater than that from urban areas, despite a probable bias toward referral from urban areas. The distribution of cases in Ghana appeared to be non-random but we attribute this to variable access to medical care and physician interest. Rainfall did not appear to be an important factor. Seasonal variation and time-space clustering were not observed. The incidence here seems lower than that reported in East Africa. We found no evidence of an environmental influence with a short incubation period, as has been postulated for this disease in East Africa. The higher risk among rural patients is consistent with severe malaria being a factor in the etiology of Burkitt's lymphoma.


Dissociation of anti-tumor immune responses in rats immunized with solubilized tumor-associated antigens from a methylcholanthrene-induced fibrosarcoma. Soluble tumor antigens were prepared from chemically-induced rat fibrosarcoma KMT-17 cells by various methods [Na-deoxycholate (DOC), 3 M-KCI extraction, and crude membrane preparations by mechanical disruption]. Soluble tumor antigens prepared by DOC extraction (DOC-STA) could be detected by a radioisotopic footpad assay (FPA) and they showed the strongest antigenic activity in KMT-17 immune rats. Anti-tumor immune responses in rats previously immunized with DOC-STA were measured by FPA, Winn assay, and transplantation resistance. Significant responses detected by the FPA and Winn assay were demonstrated in rats immunized with DOC-STA. However, rats previously immunized with DOC-STA showed a significant enhancement of tumor growth when challenged with KMT-17 cells. This enhancement was specific for the tumor line used. Normal rats which received adoptive transfer of thymus and spleen cells from rats immunized with DOC-STA produced specific enhancement of tumor growth as compared with non-treated rats. Administration of cyclophosphamide before immunization with DOC-STA abrogated the enhanced tumor growth in the host. These results suggest that immunization with soluble tumor antigens specifically enhanced tumor grwoth by the induction of immunosuppressor cells. Dissociation between the anti-tumor immunity detected by the FPA and Winn assay and the enhanced tumor growth detected by transplantation resistance in rats immunized with DOC-STA is discussed.


Enhancement of tumor outgrowth by tumor-associated blocking factors. Transplanted lines of 3-methylcholanthrene (MCA)-induced BALB/c sarcomas were used for experiments in which tumors were mechanically suspended in Waymouth's culture medium, the suspensions centrifuged and filtered and the remaining cell-free "tumor fluids" (TF) tested for activity in vitro and in vivo. TF were found to inhibit ("block") cell-mediated cytotoxicity to tumor target cells in vitro with specificity for each tumor tested and even at high dilutions (1:1,000-1:10,000). In vivo, TF enhances the outgrowth of subcutaneously transplanted tumors in non-immune syngeneic mice. This enhancement had both specific and non-specific components, with the non-specific component being most apparent. Enhancement was best demonstrated when the TF were inoculated together with the tumor inocula. In one of two experiments in which TF were given intraperitoneally, specific enhancement was seen, whereas in the other, inhibition of tumor outgrowth was observed.


Inverse correlation between cell-surface adhesiveness and malignancy in mouse fibroblastoid cell lines. The correlation between tumorigenicity and cell-surface adhesiveness was investigated in eight mouse fibroblastoid cell lines. Four of the lines (Mc 11-Mc 15) were derived from mouse MC-induced fibrosarcomas, two were derivatives of L cells (A9, A9HT), and two (clone 3 and clone 7 H7F4) were obtained by fusion of A9HT cells with normal diploid mouse lymphocytes. Quantitative comparison of cellular adhesive properties by the Latex particle adherence assay indicated that higher malignancy of some lines (Mc 11, 13, 14, A9HT cl 7 H7F4) was regularly associated with lower cell-surface adhesiveness and conversely, lower malignancy of the other lines (Mc 15, A9, cl 3) with high cell-surface adhesiveness. The differences in adhesiveness of cell lines of high and low malignancy were determined by cell subsets not attaching and Latex particles (24.6-61.9% of cells in highly and 4.6-12.0% in slightly tumorigenic lines) and cell subsets attaching more than 25 Latex particles per cell (14.6-17.2% in highly and 46.1-71.4% in less tumorigenic lines).


Discrepant effects of interferon murine syngeneic ascites tumors and their solid metastasizing counterparts. The effects of interferon on mice with syngeneic tumors growing either intraperitoneally or as solid tumors were analyzed. The same dose that depressed the growth of ascites tumors, enhanced growth and in one case metastasizability of the corresponding solid tumors. The possibility that this was due to some host reaction is discussed. It seems important to develop animal models for analyzing interferon effects before treatment is initiated in human tumor disease.


Influence of the mouse hepatitis virus (MHV) infection on the growth of human tumors in the athymic mouse. The growth characteristics and histological appearance of tumors resulting from transplantation of the tumor lines HEp-2 and SW480 into pathogen-free and mouse hepatitis virus infected athymic mice were studied. Subcutaneous or intraperitoneal implantation 1 x 10(6) neoplastic cells into pathogen-free animals resulted in tumor growth. Subcutaneous transplants grew locally, surrounded by a capsule of connective tissue. The fibrovascular stroma supporting the neoplastic tissue was minimal and infiltration of tumor capsule was observed. Intraperitoneal tumors grew in a multifocal pattern, were not encapsulated, showed marked invasiveness and metastasized. The same number of neoplastic cells (1 x 10(6)) transplanted into hepatitis-positive animals failed to develop into grossly visible tumors. When the number of transplanted cells was increased to 2 x 10(7), tumors appeared in a few animals. All tumors, regardless of the site of transplantation, were characterized by the presence of severe fibrohistiocytic reaction at the site of implantation that possibily influenced the tumor growth. No evidence supporting T-cell-mediated tumor rejection was observed. It is concluded that the state of health of the athymic mice is critical for the growth of human tumors and may account for the variations in reporting successful transplantation of such tumors in nude mice.


Oesophageal cancer and alcohol consumption; importance of type of beverage. The role of alcohol consumption in oesophageal cancer in Normandy has been studied by a retrospective study of 312 male cases and 869 controls. The linear relationship between the logarithm of risk and overall daily alcohol consumption was confirmed after adjustment for tobacco. The role of each specific alcoholic beverage was further investigated by computing relative risks for individuals consuming a given beverage and for those drinking other beverages only, within each overall alcohol consumption category. It is concluded: (1) that there is a linear relationship between the logarithm of risk of oesophageal cancer and overall daily ethanol consumption, whatever the beverage; (2) that the effect is more marked for strong beverages; (3) that there is an additional risk related to apple brandy and cider.


Some environmental and bodily characteristics of melanoma patients. A case-control study. A case-control study including 78 patients with malignant melanoma of the skin and 131 controls with the diagnoses of malignant lymphoma, testicular cancer or bone and soft-tissue sarcoma, was performed at the Norwegian Radium Hospital 1974-1975. The questionnaire contained questions for evaluating the comparability between cases and controls, and questions bearing on the relation between sun exposure and malignant melanoma. No essential difference between cases and controls was found as regards hair and eye colour, time spent outdoors during leisure, and degree of solar exposure. The melanoma patients liked sunbathing less than controls, worked more outdoors, more often went to Southern Europe for sunbathing and more often used sun lotions. These differences, however, were not clearly statistically significant. Highly significant differences were demonstrated as regards the tolerance of sun exposure and propensity to freckling. The melanoma patients tolerated sun exposure less well and freckled more easily than the controls. Although attempts were made to eliminate bias, there are still limitations and loop-holes in the study, and the relative risks demonstrated are not large enough to be of great immediate practical or scientific value. It seems justified, however, to advise persons with a low sun exposure tolerance to be cautious in following the sun-tan-demanding fashions. The study may also provide certain clues for the planning of future epidemiological and clinical studies regarding the etiology of malignant melanoma.


Murine natural anti-tumor antibodies. I. Rapid in vivo binding of natural antibody by tumor cells in syngeneic mice. A competitive radioimmunoassay (RIA) for the detection of cell-bound antibody was used to study the in vivo acquisition of immunoglobulin (Ig) by tumor cells. Several tumor lines acquired Ig rapidly between 3 and 18 h after intraperitoneal implantation into normal syngeneic mice and this Ig was recovered by elution with basic or acid buffers. The Ig eluted from the L5178Y lymphoma showed higher binding to the L5178Y than to thymocytes, bone-marrow cells, 1509a sarcoma and P-815-X2 mastocytoma. In addition, binding of the eluates to the L5178Y was specifically inhibited by L5178Y cells or by solubilized membrane antigens of the L5178Y. The in vivo acquisition of Ig by the L5178Y could also be blocked by the IV and IP injections of tumor antigen although both L5178Y and 1509a solubilized membrane antigens were effective. Some of the Ig acquired by the tumor cells was found to be complement-fixing antibody since normal rabbit complement lysed 80% of L5178Y cells obtained from the peritoneal cavity of syngeneic mice 18 h after implantation, but did not lyse in vitro L5178Y cells. The in vivo binding of the complement-fixing antibodies was also inhibited by tumor antigens in the same way as the acquisition of Ig detected by RIA. It was shown that the acquisition of Ig during the first 18h of IP growth was a T-independent phenomenon because tumor cells acquire as much Ig in AT X BM mice as in sham-thymectomized controls. In a study with 11 different clones derived from the L5178Y lymphoma, a high correlation (r = 0.75, p less than 0.005) was found between the amount of Ig acquired after in vivo implantation and the amount of Ig bound to the cells after in vitro incubation with normal syngeneic serum. It is suggested that the rapid in vivo acquisition of Ig was due to the in vivo binding of natural antibodies to tumor cells.


Treatment of micrometastases from Lewis lung carcinoma with abrin and cyclophosphamide, given singly and in combination. The effect of the plant toxin abrin and of cyclophosphamide given as adjuvant chemotherapy after irradiation of the primary tumor was studied in mice bearing intramuscularly growing Lewis lung carcinoma. The chemotherapy was given immediately after irradiation performed 9 days after inoculation of 10(5) tumor cells. The drugs were given in bolus injections either as single agents or concurrently. The therapeutic effect was assessed by recording the appearance of lung metastases on day 21 or the number of long-term survivors, i.e. animals alive at day 60. In the control group 21 +/- 3.4 (SD) macroscopic lung colonies was recorded on day 21. Mean survival time was 25.5 days with none of the mice alive at day 60. The optimal abrin dose (612.5 ng/kg IV) reduced the number of lung metastases to 2.6 +/- 0.8 and yielded 37% long-term survivors (11/30). The optimal dose of cyclophosphamide (150 mg/kg IP) reduced the number of lung colonies to less than 1 and yielded 61% survivors (14/23). Small to moderate doses of abrin significantly potentiated the therapeutic effect of cyclophosphamide without increasing the toxicity. The best results (18/20 or 90% long-term survivors) were obtained when the optimal dose of cyclophosphamide, 150 mg/kg, was combined with 350 ng/kg of abrin. The results obtained in this highly resistant tumor suggest that combinations of the two drugs may be useful also in other tumor types.


Neuroendocrine cells in serially passaged rat stomach cancers induced by MNNG. Five gastric carcinomas, induced in inbred Wistar rats by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water, were successfully transplanted to isologous rats. The transplants grew to a size of 10 to 35 mm in diameter within 8 to 25 weeks of implantation. In one case, serial transplantation were maintained up to the 11th generation, with occurrence of distant metastasis in the 3rd generation. Histological histochemical, and electron microscopical comparison of the original and transplanted tumors revealed that (1) the original tumors were quite well differentiated, forming either papillary or tubular structures, whereas the transplants were more anaplastic and pleomorphic showing often solid nests; and (2) tumor cells with gastrointestinal differentiation and cells with neuroendocrine differentiation were present and evenly distributed in both the original and the serially transplanted tumors. As it is unlikely that the normal and neoplastic neuroendocrine cells are growing side-by-side with and independently of the epithelial neoplastic components in the present series of transplants, the findings strongly suggest (1) the multidirectional potency of the inbred rat stomach carcinoma cells and (2) the common neoplastic origin of the epithelial and neuroendocrine components.


Circadian rhythmicity in rat intestinal villus length and cell number. Circadian rhythmicity has been reported in various small intestinal digestive-absorptive functions and in the mitotic activity of intestinal crypt cells. These functional activity rhythms and perhaps the mitotic rhythms are cued by the feeding schedule. We now report that circadian rhythms also occurred in both the villus height and cell number in rats maintained on morning or afternoon feeding schedules for 7 days. Villus width was constant. In afternoon-fed rats both villus height and cell number were 50% greater just before feeding than 12 h later. The amplitudes of the two rhythms in the morning fed rats were decreased, the general shape of the cycles were changed and the average number of cells was increased. These changes between morning and afternoon feeding are attributed to incomplete phase shifting due to an insufficient adaptation span for the morning fed rats. We conclude that circadian rhythms occurring in villus height and cell number are affected by the feeding schedule. Similarities to some previously reported functional rhythms suggest that fluctuations in cell number and/or villus length might be related to the functional changes.


Circadian rhythm of cholesterol biosynthesis: dietary regulation in the liver and small intestine of hamsters. Sixty three hamsters were divided into two groups which were exposed to the same rigid lighting schedule (06(00)--18(00)) but fed at different time intervals (18(00)--22(00), and 08(00)--12(00), respectively) for five weeks. The cholesterol synthetic activity was then determined in liver, gastrointestinal tract, and kidney by in vivo incorporation of (1--14C)-acetate into cholesterol at different hours of the day. A remarkable circadian rhythm of the activity was found in the liver and small intestine, but not in other organs. Regardless of the lighting schedule, the nadir occurred, in both groups, always at the end of the fasting period and the peak four to six hours after feeding. The study clearly indicated the major role of diet in regulation of such phenomenon.


Effect of photoperiod reversal on twenty-four hour patterns for dopamine levels in the corpus striatum and upper and lower brainstem of the rat. Dopamine levels were measured in the corpus striatum, upper and lower brainstem at 6 hour intervals for a period of 24 hours in rats adapted for 3 weeks to either of two concomitantly-conducted lighting programs. On the normal cycle the animals were illuminated from 08(00)--20(00); on the reverse cycle, from 20(00)--08(00). In the corpus striatum dopamine levels peaked during the dark phase of both illumination cycles indicating that 24 hour rhythm is exogenous. On the other hand, in the upper and lower brainstem, dopamine peaks occurred in both light cycles at 00(00) or 06(00) indicating that these 24 hour rhythms are endogenous in nature. Photoperiod reversal resulted in significantly elevated dopamine levels in the corpus striatum and lower brainstem. The existence of a stress as well as a seasonal factor which affects striatal dopamine is suggested.


Introduction to the theme--state intervention and the social wage: the politics of social services expansion. State intervention in the consumption process has become increasingly critical to economic growth on the one hand and to real family income on the other. The social wage thus tends to become a conflictual political issue. As a result, the articulation of state intervention with the changing requirements of economic growth is subject to continuous political challenge. This special issue examines the problematic relationship between state intervention in social services and the organization of the capitalist economy. Some contributors study the ways in which state inter ventions are structured so as to be consonant with the requirements of economic growth and profitability, as well as the difficulties such structures pose. Feshbach's analysis of the Hill-Burton Hospital Construction Program and Mollenkopf's study of San Francisco's public transit system both reflect this concern. Other contributors study the ways in which the organization of the economy constrains the development of democratically responsive social services. Sbragia's study of the capital market and public housing in Italy and Taylor's study of free medical clinics in the U.S. both reflect this concern. Finally, contributors study macroscopic transformations in the relationship between state intervention and the organization of the capitalist economy. Esping-Andersen's study of the political logic of increasing state intervention in production and Hirschhorn's analysis of the defunctionalization of social services attendent upon the disaccumulative tendencies in capitalism both reflect this concern. This introductory paper reviews four theories which attempt to explain how state intervention is insulated from democratic controls. For each theory, the mechanisms specified to perform this function are subject to weaknesses. An attempt is made to position the contributions to this volume with respect to these theoretical traditions.


Borrowing to build: private money and public welfare. The process of local government borrowing to finance the capital needs of social services has an impact on both central-local relations and the type of service which can be offered to the citizen-consumer. Based on an examination of these relationships in the United States, the United Kingdom, France, and Italy, it is postulated that different types of central-local relations are dependent on the nature of relations between central government and the investment community. Further, through use of material from a case study of public housing politics in Italy, it is shown how the investment criteria of the so-called "private" sector are transferred to the operations of the public sector through the mechanism of local borrowing. This transferal affects the manner in which social services are conceived and delivered.


Alternative services: the case of free clinics. The viability of a political mobilization and reform strategy based on the provision of care of alternative social service agencies is examined in the context of the achievements of free medical clinics in the United States. The development of genuine alternatives to the contemporary American health care system is limited by the monopoly of organized medicine, the scarcity of funds for preventive care, a class-based health insurance system, and the inadvertent role of free clinics in legitimating existing structures. American medicine constrains and shapes clinic activities through its control of certification, its specialist divisions and priveleges, and its pervasive ideology. Free clinics' responses to these constraints can engender: (a) high worker turnover, low morale, legal jeopardy, and curtailment of self-help programs; (b) the reproduction of medical hierarchies; and (c) patient-imposed limitations to the acceptability of alternative therapies and therapists. Clinics often pay dearly for the meager funds available to them; strings attached to special grants can change the character of free clinics, their social composition, and the treatment they offer. The usefulness of the free clinic as a safety valve and training facility may actually legitimate the current organization of health care. Free clinics provide an alternative form of care, but in the long run they cannot be a base for radical social change.


Comparative social policy and political conflict in advanced welfare states: Denmark and Sweden. There has developed an abundant literature on the social and political determinants of social policies, but few have addressed the question of how state policies, once implemented, affect the system of stratification in civil society. This article examines the political consequences of social policy in Denmark and Sweden, countries in which a social democratic labor movement has predominated for decades. Superficially, these two highly developed welfare states appear very similar. Yet the political and social contexts in which their social policies have evolved differ substantially. I shall demonstrate the argument that the traditional welfare state approach may be conducive to a new and powerful political conflict, which directly questions the legitimacy of the welfare state itself, unless government is successful in subordinating private capitalist growth to effective public regulation. In Denmark, where social democratic governments have failed to match welfare state growth with more control of private capital, social policy has tended to undermine the political unity of the working class. Consequently, the Social Democratic Party has been weakened. Social welfare programs, in effect, have helped create new forms of stratification within the working class. In Sweden, social democratic governments have been quite successful in shifting a decisive degree of power over the private market to the state. This has helped avert a crisis of the welfare state, and has also been an important condition for continued social democratic hegemony and working-class unity. I conclude that social reform politics tend to be problematic from the point of view of the future power of social democratic movements.


The theory of social services in disaccumulationist capitalism. The theory of social services today must be based on a more general theory of the "disaccumulation" of capitalist society. Capitalist society disaccumulates as new productive forces emerge within the framework of the capitalist labor market. These forces are expressed abstractly in new sources of productivity based on information and organization and concretely in a new organization of work. This new organization of work breaks down the old capitalist division between labor and non-labor time and poses instead a more fluid interaction and integration of work and non-work. Capitalist society, however, disaccumulates through social crisis. The reorganization of work is simultaneously expressed as the decay of the labor market. This decay delegitimates social services and creates the present social service crisis. Social services can find their new sources of legitimacy only if social classes can move past the crisis of disaccumulation and find the appropriate new forms of social life based on the emerging non-capitalist organization of work.


The use of a standardized battery of Luria's tests in the diagnosis of lateralized cerebral dysfunction. The present study was designed to examine the capability of a standardized battery of Luria's qualitative neuropsychological techniques in discriminating between right, left and diffuse brain-injured subjects. A total of sixty medically confirmed brain-damaged subjects were equally divided among the three groups. Subjects were assigned to two groups (right, left) according to medically proven lateralized brain injury to either the right or left hemisphere in the absence of verifiable insult to the opposite hemisphere. A third group was also selected in which medical evidence confirmed damage to both hemispheres (diffuse group). All three groups were matched for age and education. All subjects were tested on a standardized version of 269 Luria's qualitative neuropsychological test items. The items were divided into 11 sections based upon Luria's theory of brain function. Each of the 11 sections plus a right and a left hemisphere scale as well as an overall impairment scale yielded 14 summary measures of performance representing several areas of neuropsychological ability and overall severity of brain dysfunction. Analysis of variance and discriminant analysis were used to compare the three groups on these 14 summary measures. Analysis of variance revealed on significant difference between the three groups on the Left scale with the left group performing poorest. Discriminant analysis predicted the status of 59 of 60 subjects correctly (98% hit rate). The implication of the lack of significant simple relationships (ANOVA) and the complex interrelationships found using the discriminant analysis were discussed in terms of the support these results provide for Luria's theory of brain function. The specific qualitative aspects of the test battery and their use in the diagnosis of lateralized brain injury were also discussed. Indications for future research were pointed out.


Common dimensions of visual and auditory agnosia and an explanation of the auditory recognition deficit in aphasia. An experimental analysis of auditory recognition disturbances was performed; 81 patients with localized cerebral lesions were examined with a recognition test for meaningful sounds and with a nonverbal intelligence test (Block Design). Sensory stimulation was 5 or 15 sec for each sound. Nonverbal intelligence accounted for a considerable and significant amount of variance in recognition performance. The aphasic group was more impaired in auditory recognition than were both the other groups, i.e., patients with right or left hemispheric lesions without aphasia. The auditory recognition disturbance in the aphasic group depended to a significant extent on stimulus duration, which means a slowing down of the recognition process in aphasia. The analogies to studies on visual agnosia are striking. In both modalities, recognition depends on intellectual functioning, sensory disturbances or reduced sensory input, and the presence of aphasia.


Morphine and intracranial self-stimulation in the hypothalamus and dorsal brainstem: differential effects of dose, time and site. The purpose of this study was to examine if morphine, a drug of abuse, exerts site-specific effects on intracranial self-stimulation (ICSS). Rats, implanted with dorsal brainstem (DB) and hypothalamic (HYP) electrodes, bar-pressed for ICSS at two current intensities eight hours a day during six days each of predrug saline, morphine (2.5, 5.0, 7.5 or 10.0 mg/kg) and postdrug saline conditions. There were three patterns of drug effects: "pure" depressions, "pure" facilitations and a biphasic pattern (depressions followed by facilitations). Repeated morphine administration modified the temporal patterning of these effects: shortened duration of depressions and produced earlier onsets of facilitations. Within an animal, DB electrodes displayed more depressions than the HYP electrodes. Tolerance to the depressant effects, observed frequently, occurred occasionally to the facilitative effects of morphine. The drug effects on ICSS were dissociated from those observed on other behavioral measures, and thus are not artifacts of concomitant changes in activity levels.


Cultural hemisphericity: evidence from cognitive tests. Cultural differences in appositional abilities were investigated. Items from two gestalt completion tests were modified to examine the effects of stimulus manipulations (e.g., background color, presence of details) on previously observed ethnic differences in performance. Overall, black subjects again scored higher than white subjects; women scored higher than men. However, these differences varied with certain stimulus manipulations. These findings suggest that, by investigating gestalt completion, we can better understand the cognitive factors underlying appositional abilities.


How the nervous system determines the quantity of information delivered by signals. Starting from the finding that the brain responds to received signals according to the quantity of information (Restian, 1978), the author tried to answer the question: How does the brain discover the quantity of information brought by these signals? In order to reply to this question, the author appealed to two sources that emitted similar signals containing different information. It was found that although the signals brought different information at the beginning they functioned similarly. Only after a period of time did the signals come to function differently, according to the quantity of information delivered by them. This fact demonstrates that the brain operates neither on signals nor on source-emitted information. The brain operates on information discovered by it in the respective signals, and the discovery of the information the received signals is done according an internal model constructed by the brain concerning the respective source. It can be affirmed by the fact that together with the improvement of the model, the results of the received signals are modified.


A possible link between intelligence level and habituation of the GSR. An attempt was made to correlate the intelligence level of three well-defined groups (Gifted, IQ 140; Normal, 95 IQ 105: Mentally retarded, 45 IQ 55) and the habituation rate and pattern of a GSR response to a series of light stimuli. The results indicate that the gifted and normal groups yield systematic patterns of GSR responding in contrast to the mentally retarded, whose distribution of GSR response pattern differs. The mentally retarded seem to yeild a larger number of ill-defined, non-systematic GSR responses. These results indicate a possible link between the measured level of intelligence by IQ test and the habituation pattern in an autonomic nervous system response.


Structural and biochemical changes in vitamin A--deficient rat retinas. The levels of rhodopsin and opsin were investigated in relation to the maintenance of retinal structure in retinas of vitamin A--deficient rats in low levels of cyclic illumination (1.5 to 2 foot-candles). Rhodopsin levels decreased in the deficient retinas to approximately 20% of control at 9 weeks, and this level was retained through 39 weeks on the deficient diet. Opsin levels decreased at a slower rate but reached about 20% of control levels at 32 weeks. Despite the decrease in rhodopsin levels, obvious deterioration of disc structure was not observed until 16 weeks of deficiency, when opsin levels had already decreased to 60% to 70% of control. The structural disruption of photoreceptor outer segments was localized initially in discs of the distal third. Rod cell degeneration preceded cone cell degeneration in vitamin A--deficient retinas. Most of the rods and cones persisted in the posterior retina at 23 weeks on the deficient diet; however, by 40 weeks, only 11% of the rod nuclei remained. In contrast, about 63% of the cone nuclei were present at 40 weeks of deficiency. The photoreceptor cells were affected by the deficiency to a greater extent in the inferior hemisphere than in the superior hemisphere of the eye.


Sunlight and human cataracts.

Sunlight and human cataracts. Studies of the cataractous lenses of humans in three different geographic locations indicate that where the ultraviolet components of sunlight are more intense, dark brown cataracts result at a higher frequency than in locations where they are weak. Individuals exposed to sunlight regularly by virtue of their outdoor occupations seemed to develop this dark brown type of cataract much more frequently than those who work indoors. The biochemical characteristics of all brunescent cataracts were found to be very similar, whether derived from individuals exposed to high or low levels of sunlight. These findings support the idea that exposure to sunlight specifically enhances brunescent cataract development in humans.


Vision through an abnormal cornea: a pilot study of the relationship between visual loss from corneal distortion, corneal edema, keratoconus, and some allied corneal pathology. Visual function was assessed by classic acuity measures as well as contrast thresholds over a wide spatial frequency range for subjects with experimentally induced corneal distortion and induced corneal edema. These results were compared with similar results for patients with uniocular keratoconus, bilateral keratoconus, and allied corneal pathology. Distortion and edema were found to produce characteristically different types of contrast attenuation at threshold (amplitude) and have quite different suprathreshold abnormalities (phase) for objects within the resolution limit and therefore could form the basis of a useful functional classification of the visual degradation from corneal pathology.


Improved use of tapetal reflection for eye-position monitoring. A new technique is described for eye-position monitoring in species with strong tapetal reflections. A fiber optic is used to introduce light into the eye, whose optics then produce an image of the fundus on a tangent in front of the animal. The technique simplifies heretofore tedious measurement of cylotorsional changes, as well as providing a very wide view of the fundus. It has been used successfully in conjunction with single-unit recording from the visual system.


Abnormal saccadic substitution during small-amplitude pursuit tracking in amblyopic eyes. Small-amplitude, low-velocity, predictable triangular tracking was tested in patients having amblyopia without strabismus, intermittent strabismus, or constant strabismus amblyopia by means of a photoelectric eye-movement recording technique. In the majority of amblyopic patients, abnormal saccadic substitution was found; that is, abnormally large saccades rather than small-amplitude smooth movements were used by the amblyopic eye to follow a spot stimulus that moved horizontally with low to high frequencies. Pursuit for the same range of stimuli was normal for binocular tracking and for monocular tracking with the dominant eye, pointing to a sensory rather than motor basis for the defect. This abnormal saccadic substitution response appeared to be related to the presence of amblyopia rather than strabismus. Several possible mechanisms responsible for causing this unusual response are discussed, including impairment of direction sense over small central regions of the amblyopic eye.


Nuclear translocation of the cytoplasmic glucocorticoid receptor in the iris--ciliary body of the rabbit. The cytoplasmic glucocorticoid receptor of the iris--ciliary body of the rabbit has been shown to translocate to the cell nucleus within 30 min of an injection of cortisol. Over the next 2 1/2 hr the amount of receptor returns to the control value. The threshold of the loss of receptor from the cytosol was found at 0.04 mg of cortisol per kilogram body weight, with a maximal loss being reached at a cortisol dose of 0.5 mg/kg B.W. The inactive glucocorticoid tetrahydrocortisol and the major sex steroids, dihydrotestosterone, estradiol, and progesterone, had little or no effect on this translocation, indicating the specificity of the cortisol effect. Thus this receptor appears to migrate to the cell nucleus in a manner similar to that found in other steroid-sensitive tissues and is consistent with the accepted mechanism whereby these hormones regulate differential gene expression in the nucleus.


X-like and Y-like ganglion cells in the Necturus retina. The linearity of spatial summation within the receptive fields of Necturus retinal ganglion cells was examined with a counterphase-modulated split-field test stimulus. Modulation-locked histograms were constructed with the border at a variety of positions relative to the receptive field center. Most cells generated distinct, modulation-locked discharges when the border was 0.10 to 0.25 mm from the receptive field center. The discharges for more central border positions depended upon response type. Sustained-responding cells showed a sharp decrease in total response per cycle at the center position and increasing response for increasingly eccentric positions, i.e., nulling or X-like behavior. In contrast, the total response of transiently responding cells was largely independent of border position. For central positions of the border, these cells generated two bursts of impulses per cycle, i.e., frequency doubling or Y-like behavior.


Activation of initial wound healing responses in rat corneas in organ culture by mesodermal growth factor. In organ culture, mesodermal growth factor (MGF) from mouse submaxillary glands stimulates fibroblast formation, mitosis, and migration of cells into the dead-cell zone adjacent to the wound edge of rat corneal buttons. A classic dose-response relationship between the width of the stromal fibroblast zone and the dose of MGF suggests that fibroblast zone width may be used as a measure for screening agents which influence the initial stages of corneal wound healing.


A comparison of three methods for the measurement of corneal thickness. Four subjects who had never worn contact lenses underwent measurement of their corneal thickness by each of three measurement methods: Haag-Streit pachometer with/and without Mishima-Hedby attachment and the Syber specular microscope. Data were collected on three separate sessions, and at each session triplicate measurement trials were made for each method. The resulting 108 measurements were analyzed statistically. Significant differences were found among the measurement methods. Two of the methods were found to be consistent from session to session. In addition, the specular microscope was found to be the most precise method within a session. It was concluded that the specular microscope, which highly trained technicians can utilize to make the measurements, offers a valuable alternative to the measurement of corneal thickness in long-term prospective studies.


Measurement of corneal DNA content.

Measurement of corneal DNA content. The amount of DNA in the corneal epithelium, stroma, and endothelium of both rabbit and bovine tissue was measured by a diphenylamine assay procedure. The results indicate that hot perchloric acid extraction is required to effectively solubilize the corneal DNA for assay. Rabbit corneal epithelium, stroma, and endothelium were found to contain 53.8, 1.7, and 4.3 microgram of DNA per milligram of tissue dry weight, respectively. Bovine corneal epithelium contained 15.8 microgram/mg DNA, stroma 0.6 microgram/mg DNA, and endothelium 3.1 microgram/mg. These data provide a basis for an expression of the cellularity of corneal layers.


[Acute generalized pustular bacterid: a variety of pustular Andrew's bacterid]. Eight cases of acute pustular bacterid preceded by angina of beta-streptococcal origin are summarized. Although this disease appears to be an acute type of pustular bacterid Andrews, the elevated antistreptolysin titers and the histological features of vasculitis with perivascular deposits of C3 and IgM seem to be remarkable findings. One of the patients' skin symptoms were complicated by a glomerulonephritis. The skin lesions improved rapidly after systemic administration of glucocorticosteroids.


[Pseudoporphyria cutanea tarda in hemodialysis patients]. A bullous disease very similar to late onset cutaneous porphyria has been found in approximately 16 percent of the patients on intermittend hemodialysis. The bullae occur during the summer and are situated on exposed areas, particularly hands, head and neck. There is skin fragility and the bullae are transient, giving place to erosions and later to atrophic scarring. Even milia have been observed. Histology reveals a subepidermal bulla, the basis of which consists of spiky papillary dermis. Immunofluorescence shows immunoglobulin depoits in the vessels and basal membrans. All porphyrin measurements are negative. This disorder may be due to the precence of a non porphyrinogenic photosensitizing substance.


[Carpal tunnel syndrome in diffuse scleroderma]. A 61 year old female patient with diffuse scleroderma, complicated by carpal tunnel syndrome, is reported. The coexistence of carpal tunnel syndrome with dermatomyositis and lupus erythematodes is reviewed.


[Skin metastasis of an ovarian carcinoma imitating erythema anulare]. The histopathology of an anular erythemalike dermatosis unexpectedly showed metastases of a carcinoma of the ovary.


[Pathophysiology and clinical aspects of the venous low-pressure system]. The pathophysiology especially of the venous low-pressure system, the venous muscle pump, and the pressure-volume relation is represented. The clinical manifestations--varicous veins-varicophlebitis, phlebothrombosis, and chronic venous insufficiency--are described. Consecutively, the ways of possible therapy are shown.