The Involvement of Dopamine in Strengthening Cortical Signals Activating NMDA Receptors in the Striatum (a hypothetical mechanism)

A possible mechanism is proposed for the enhancement/weakening of those cortical signals in the cortex-basal ganglia-thalamus-cortex neural network which induce/do not induce opening of NMDA channels in the spiny neurons of the striatum and which can be regarded as strong/weak in terms of this measure. The mechanism is based on the modulatory influences of dopamine on changes in the efficiency of corticostriatal inputs. In the absence of dopamine, relative increases in the intensity of strong (weak) cortical signals can lead to the induction of long-term potentiation (depression) of corticostriatal synapses. In this case, because of the differently directed influences on thalamic cells of signals passing via strionigral and striopallidal cells, strong signals at the output of the thalamus are weakened, while weak signals are strengthened. Activation of dopamine D₁ (D₂) receptors on strionigral (striopallidal) neurons may facilitate increases in the extent of long-term potentiation/depression (decreases in the extent of long-term potentiation/depression or induction of long-term potentiation/depression). The consequence of this is that strong signals at the output of the thalamus can be strengthened synergistically, while weak signals cab be weakened synergistically. Background cortical signals evoking tonic release of dopamine in the striatum can decrease strengthening because of weakening of the modulatory influence of dopamine on the modification of corticostriatal synapses.     

On the terms “reticulosis” and “reticulum cell sarcoma” with regard to the modern concept of the monocyte macrophage system

Summary The terms reticulosis and reticulum cell sarcoma (= malignant lymphoma, histiocytic type) are discussed regarding the modern concept of the monocyte macrophage system which today has replaced the ancient theory of the reticuloendothelial system. The monocyte macrophage system is not independent, but closely related to the myeloid system. Thus, a third blood forming system as was believed in the case of RES does not exist. Phagocytic reticulum cells of the various hematopoietic organs are highly activated monocyte-derived macrophages. All those conditions formerly termed reticuloses have been found to belong either to the myeloid or to the lymphatic system. Considering the reticulum cell sarcomas or malignant histiocytic lymphomas, most of them seem to be of lymphatic rather than of macrophage origin, representing highgrade malignant lymphomas, possibly immunoblastic sarcomas. No relationship between these tumours and the monocyte macrophage system has been established, so far. Therefore, the terms reticulosis and reticulum cell sarcoma should be no longer used in order to avoid confusion, in order to stimulate sufficient diagnostic efforts which will really clarify such cases, and in order to give full credit to modern results of hematopathology.     

Biophysical studies of teschen disease virus (Talfan strain)

Summary Studies have been made of the heterogeneity of infectivity and CFA in Teschen virus (Talfan strain) suspensions. Most of the infectivity was contained in two components of densities 1.46 gm./ml. and 1.35 gm./ml. The physical, chemical and immunological properties of these components have been compared. It was possible, however, to convert a large proportion of 1.46 component to 1.35 component by treating the 1.46 component with sodium dodecyl sulphate. This would indicate that the 1.46 component was a complex formed between the infective particles and cellular debris.Further studies on the growth characteristics and electron microscopy of the virus have been made.     

The problem of detection of tissue antigens

Summary Utilization of the anaphylactic reaction for distinguishing tumor antigens from antigens of normal tissues requires the preliminary investigation of 2 problems: 1) how should desensitization against major antigens be performed in order to be sure of its completeness, and 2) how does such desensitization affect the sensitivity of the animal to minor antigens? Experiments were carried out on guinea pigs which were sensitized by mixtures of two antigens (foreign serums, tissue nucleoproteins) mixed in different proportions. It was demonstrated that the desensitizing dose of a major antigen is several times as great as the shocking dose, and therefore that repeated injection is necessary to bring about complete desensitization. This causes a pronounced decrease of the sensitivity to the minor antigen. Therefore it is necessary to increase the dose of the preparation containing the mixture of antigens (for example, a tumor extract) in order to obtain a definite anaphylatic reaction. These findings should be taken into consideration in employing anaphylaxis for the demonstration of antigenic differences between tumors and normal tissues.     

Evaluation of mouse monoclonal antibodies raised against an isolate of the variant avian paramyxovirus type 1 responsible for the current panzootic in pigeons

Summary Nine monoclonal antibodies raised against pigeon variant avian paramyxovirus type 1 isolate pigeon/England/617/83 were tested for their ability to react with classical and other pigeon variant isolates. Two of the monoclonal antibodies appeared to be specific for 617/83 reacting with no other virus. The remaining seven monoclonal antibodies bound to cells infected with all other pigeon isolates in indirect immunoperoxidase (IIP) tests but four distinct groups of other PMV-1 viruses were formed on the basis of the binding patterns. One of the monoclonal antibodies 161/617 caused haemagglutination inhibition (HI) of all the pigeon isolates tested but none of the other PMV-1 viruses and these results reflected the IIP results with this monoclonal antibody.161/617 was also shown to inhibit viruses of the avian paramyxovirus type 3 serogroup in HI tests. This reaction and the ability to bind to infected cells in IIP tests appeared to be restricted to PMV-3 viruses isolated from exotic birds and did not occur with viruses of ostensively the same serotype from turkeys.     

Modelling of electrolyte transport in renal and intestinal epithelia

Summary Epithelia can be classified as leaky and tight epithelia due to their conductive properties and their modes of solute transport. Both the proximal segment of the nephron and the intestinal tract are leaky whereas the distal nephron and the colon are tight. Consequently, inborn errors and exogenous disorders of solute transport often involve both the proximal tubule and the small intestine. In addition, effects on ion and water transport in the distal nephron closely resemble those in the large intestine. Models of solute transport in leaky and tight epithelia are presented employing porter systems known in mammalian tissues. These porter systems are discussed as possible sites of transport defects and as targets for pharmacological agents.     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Ribonuclease activity of the “myofibrillary” fraction of normal and autolyzed muscle tissue

The separation in a sucrose gradient of the myofibrillary fraction of normal and autolyzed muscle tissue gave 4 components. During post-mortem destruction of the tissue there was observed a slight decrease of the myofibrillary fraction yield and also certain changes in the distribution of protein between different components. Under the selected conditions RNase activity was found in all 4 components. During the course of autolysis enzymatic activity increased in the whole myofibrillary fraction, as well as in the lysosomal-mitochondrial components of myofibrils.Research Laboratory, Ministry of Health of the USSR, Moscow. Translated from Buylleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 533–537, May, 1978.     

Application of the polymerase chain reaction to study the M protein(-like) gene family in beta-hemolytic streptococci

Evaluation of homologous regions of published M protein (emm) gene sequences from group A streptococci (GAS; Streptococcus pyogenes) was used to design three primer pairs for polymerase chain reaction (PCR) and three oligonucleotide probe sequences internal to the amplified products. One set of primers and corresponding probe should detect and lead to amplification of emm(-like) genes of virtually every type (all M), another (SOR^-M) should only amplify emm(-like) genes from GAS negative for serum opacity reaction (SOR) and the third (SOR⁺M) should expand only emm(-like) genes from SOR⁺ GAS. Using the all M primer pair for PCR on the genomic DNA from GAS of 29 different M types as well as from a group C and a group G streptococcal isolate, DNA fragments within the expected size range were amplified in every assay. All PCR products reacted with the all M probe. Related sequences were not detected in genomic DNA of an S. agalactiae and an Enterococcus faecalis isolate. Applying the SOR^-M and SOR⁺M primers to identical assays led to mutually exclusive amplification products. The SOR⁺M and SOR⁺M probes hybridized only to their corresponding products. Exceptions to this exclusivity were the SOR⁺ GAS of M types 3, 8, 27, 34, 42, 67, and 69, which consistently reacted only with the SOR⁺M primer/probe set. Analysis of sequence data from the amplified emm(-like) 2, 3, 18, and 19 genes revealed interesting specific features such as conserved gaps in the C-terminal sequence regions from SOR⁺ and the exceptional SOR^- GAS strains. These data indicate the existence of a subgroup of strains among SOR^- GAS and may advance our understanding of phylogenetic relationship between different serotypes of GAS.     

Recognition by peptide mapping of three different structural groups of outer membrane protein YOP-1 of Yersinia enterocolitica and Yersinia pseudotuberculosis

The structural relation of YOP-1 of european and american Yersinia enterocolitica serotypes O3, O9, O5, 27, and O8 and O20, respectively, and Y. pseudotuberculosis serotypes I, II, and III was compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis and peptide mapping using Staphylococcus aureus protease V8. Apparent molecular weights of YOP-1 ranged from 206,000 (O3) to approx. 180,000 (O8). According to their respective peptide maps YOP-1 of the european and american Y. enterocolitica serotypes and Y. pseudotuberculosis serotypes could be assigned to three different groups. Evaluation of several isolates of Y. enterocolitica serotypes O3, O9, and O8 by peptide mapping indicated that YOP-1 is conserved within a serotype. However, one serotype O8 isolate differed from the consensus peptide pattern of the other serotype O8 and O20 isolates. The similarity of the peptide patterns of Yersinia serotypes which predominate in certain geographical locations, i. e., european and american Y. enterocolitica serotypes, suggest common evolution of YOP-1 of these serotypes independent of the evolution of the other serotypes.     

Temperament as a potential predictor of mortality: Evidence from a 41-year prospective study

Psychological factors were hypothesized to influence mortality, in particular, early versus later mortality. To explore the relationship between temperament, a psychological factor, and mortality in a prospective study of 1337 medical students, we constructed a measure portraying three temperament types, using latent class analysis. Death occurred in 113 subjects over 25–41 years of follow-up. In univariate survival analysis, subjects tending to direct tension inward when under stress (Tension-In) had a higher risk of mortality than Tension-Out or Stable types. These associations persisted after adjustment for age, smoking, cholesterol level, and Quetelet Index. The relative risk (RR) of mortality for Tension-In was 1.56 (95% confidence interval, 1.00–2.44) compared with the Stable group. The risk was due entirely to the excess risk in persons under 55 years of age (RR, 2.59; 95% confidence interval, 1.46–4.62); the corresponding risk of death in older persons was 0.66 (0.30–1.48). Thus temperament is a significant risk factor for mortality, in particular, premature death.     

Resistance toTrypanosoma cruzi infection in relation to the timing of IgG humoral response

The Biozzi high (BH) and low (BL) responder mice (Selection III) differeed in their susceptibility toTrypanosoma cruzi. The BH strain responded quickly to the infection, similar to the reaction of (CBA×C57B1/10)F₁ mice but in contrast to the susceptible BL strain. We suggest that the IgG response mounted by the host during the prepatent period of the infection is crucial to the outcome of the infection.     

Vasodilator therapy enhances neutrophil tissue migration

Very little is known about the effect of vasoactive substances on migration of polymorphonuclear neutrophilsin vivo. We evaluated the effect of oral treatment with isosorbide dinitrate on neutrophil migration into a sterile skin inflammatory focus in man with the use of skin chamber technique. Isosorbide dinitrate increased the number of neutrophils harvested in the chamber as well as the granulocyte clearance. Thus, vasoactive agent may increase neutrophil extravasation and subsequent tissue migration.     

Über Fortschritte der Naturwissenschaften und Technik aus der Sicht Eines Klinikers

Ohne Zusammenfassung1. Vorsitzender der Gesellschaft Deutscher Naturforscher und Ärzte 1956/58Festrede aus Anlaß der Eröffnung der 100. Tagung der Gesellschaft Deutscher Naturforscher und Ärzte, Wiesbaden 28. 9. 58.     

The vertex-positive scalp potential evoked by faces and by objects

Summary The influence of stimulus form on the scalp-recorded vertex positive peak (VPP) evoked by images of faces (Jeffreys 1989a) was studied in seven subjects. In separate experiments, we recorded the responses to 2D images of: (1) many different depictions of human faces; (2) the heads of several different species; (3) many familiar non-face objects; and (4) stimuli where the configuration of objects were modified to produce an illusory or non-contextual subjective impression of a face. The results showed that every facial representation, including the illusory stimuli, and most of the non-face objects, evoked a VPP of corresponding form and scalp distribution. The object-evoked VPPs, however, were always smaller and usually later than those evoked by the faces. VPPs of longer latency but often comparable amplitude were also recorded for impoverished compared to well-defined facial representations; and for most non-human compared to human faces. Very consistent responses were recorded to repeated presentations of the same stimulus for the same subject, but there was considerable variation in latency as well as amplitude (but not form) of the VPP evoked under identical experimental conditions for different subjects. These response properties of the VPP, suggest that its underlying physiological generators are sensitive to basic configurai properties of the visual stimulus; and also that face- and object-related information are processed in the same brain area(s), although not necessarily by the same physiological mechanisms.     

Direct immuno-electron microscopy and some morphological features of hog cholera virus

Summary Characteristic particles of hog cholera virus were identified by direct immuno-electron microscopy. The virion is 40–50m, often asymmetrically shaped, and is enveloped in a membrane that bears 12–15 m surface projections. The surface projections are shear-sensitive and are antigenically different from the virion's envelope. They may represent hog cholera virus soluble antigen.     

Analysis of cell-associated recombinant hepatitis B surface antigen by flow cytometry

Summary Murine L cell lines secreting recombinant hepatitis B surface antigen (rHBsAg) of either the Adw or Ayw subtype were used as a model system to develop procedures for analysis of cell-associated HBV antigens by flow cytometry. Only weak membrane immunofluorescence was observed when viable Ad or Ay cells were reacted with monoclonal antibodies (MAbs) to either subtype specific or the common group specific a determinant of rHBsAg. Following fixation and permeabilisation to allow access of MAbs to the intracellular compartment, specific reactivity of cells with both anti-a and subtype specific MAbs was readily demonstrated by flow cytometric analysis. Comparison of the fluorescence histograms produced by analysis of Ad and Ay producing cells with the anti-a MAb demonstrated an increased proportion of cells with high levels of intracellular rHBsAg in the Ay line. The results of these studies demonstrate that flow cytometric analysis with MAbs is a useful tool for characterizing the expression of viral antigens at the cellular level. The application of this technique to monitoring the production of native viral proteins following in vitro infection should provide valuable insights into the process of viral replication.     

The ultrastructure of the “excretory” system of ascaris suum larvae

Summary Electron microscope observations of the excretory cell of the infective larva reveal that it contains a large nucleus surrounded by cytoplasm containing numerous organelles, multi-granular bodies, vesicles and granules typical of glandular cells. The proximal region of the excretory duct bears a number of scattered microvilli, on its adluminal surface, and the distal region is lined with a thin multilayered cuticle.In the liver stage larva 2 days after infection, 2 lateral excretory columns are present. These arise from the excretory cell body and extend posteriorly for about half the length of the intestine. Each column contains a narrow longitudinal canal surrounded by cytoplasm rich in mitochondria, granular endoplasmic reticulum, free ribosomes and large vacuoles. Evidence was obtained of the passage of substances through the wall of the canal but their chemical nature was not determined.Further extension of the lateral columns is seen in the 8-day, lung-stage larva, the columns now extending for more than two-thirds the length of the intestine. Their diameter is also increased but their internal structure is essentially similar to that of the 2-day liver-stage larva.The excretory duct which arises immediately anterior to the nucleus has a structure similar to that of the lateral columns for the first half of its length, the microvilli described in the infective larva being absent at this stage. The distal half of the duct is lined with cuticle.     

Destabilization of herpes simplex virus type 1 virions by local anesthetics,alkaline pH,and calcium depletion

Summary The infectivity of herpes simplex virus type 1 (HSV-1) was found to be markedly reduced by treating virions with the tertiary amine local anesthetics lidocaine, dibucaine and tetracaine. These treatments induced a characteristic shift in the buoyant density of the HSV-1 particles from a light to a heavy population. HSV-1 virions were unstable at alkaline pH, and alkali treatment caused the same shift in buoyant density. Ca²⁺ stabilized the light population. These results suggest that the physicochemical status of the HSV-1 envelope which is sensitive to the treatments described above plays an important role for the integrity of the virion.     

Lability in the responses of cells in the auditory cortex of squirrel monkeys to species-specific vocalizations

Summary The activity of 28 cells located mainly in the secondary auditory cortex (A II) of awake squirrel-monkeys, was extracellularly recorded for periods of up to 6 h. Seven different species-specific vocalizations, which were repeatedly presented to the monkey, were used as auditory stimuli. Twenty-six cells responded, at least once, to one or more vocalizations; 22 cells revealed some change in their response (pattern or strength) to at least one vocalization (change in response). Twenty-one cells exhibited a change in the number and/or type of vocalization to which they responded during the recording period (change in selectivity). At some time during the recording period all the responding cells exhibited a change in response and/or a change in selectivity (change in responsiveness). A change in response of a cell to a vocalization did not necessarily exclude a change in selectivity, associated with the same vocalization, later in time and vice-versa. A change in responsiveness to one vocalization was not necessarily correlated with changes in responsiveness to other vocalizations.