Cardiovascular and respiratory mechanisms in anaphylactic and anaphylactoid shock reactions

Summary Different mediators such as histamine, leukotrienes, prostaglandins and bradykinin are involved in different reaction mechanisms such as cytotropic anaphylaxis (CA), immune complex anaphylaxis (ICA), reactions due to direct histamine liberation or activation of the complement system or hyperosmolarity induced anaphylactoid reactions.In the monkey CA induces systemic vasodilatation, a transient pulmonary hypertension and increase of cardiac output followed by peripheral blood pooling and depression of cardiac output. ICA induces peripheral vasoconstriction, a severe increase in pulmonary vascular resistance and decreased cardiac output, the latter possibly being partially due to decreased cardiac contractility.In hypersensitivity reactions in man cutaneous vasodilatation as well as vasoconstriction may occur alternatively. Peripheral blood pooling and increased vascular permeability are the cause of severe relative and absolute hypovolemia, respectively. Pulmonary vasoconstriction seems to occur in connection with serious bronchospasm. Decreased venous return, myocardial ischemia and hypoxemia can contribute to a reduction of cardiac performance. The most frequent changes in the ECG are sinus tachycardia, sinus bradycardia, extrasystoles, conduction disturbances as A-V block and bundle branch block; lethal or sublethal shock is often associated with malign arrhythmias or cardiac arrest.Almost normal blood gas values are seen in anaphylactic shock without clinical signs of respiratory obstruction. The very few documented cases of anaphylactic shock with respiratory obstruction indicate that increased airway resistance and reduced lung compliance may be present as well as mild to moderate hypoxemia with normal or subnormal CO₂ values.     

Efferent connections of the cingulate gyrus in the rhesus monkey

Summary Efferent cortical connections of the cingulate gyrus are investigated in rhesus monkey using autoradiographic technique. The results indicate that the rostralmost part of the cingulate gyrus (area 32) sends projections to the lateral prefrontal and midorbitofrontal cortex and to the rostral portion of the superior temporal gyrus. In contrast, the other two major subdivisions of the cingulate gyrus, areas 24 and 23, have widespread connections within the cortex. Area 24, for example, projects to the pre-motor region (areas 6 and 8), the fronto-orbital cortex (area 12), the rostral part of the inferior parietal lobule, the anterior insular cortex, the perirhinal area and the laterobasal nucleus of amygdala. Area 23, likewise, sends its connections to the dorsal prefrontal cortex (areas 9 and 10), the rostral orbital cortex (area 11), the parieto-temporal cortex (posterior part of the inferior parietal lobule and the superior temporal sulcus), the parahippocampal gyrus (areas TH and TF), the retrosplenial region and the presubiculum. It seems that the connections of the rostralmost part of the cingulate gyrus resemble the efferent cortical connectional patterns described for lateral prefrontal and orbito-frontal cortex, whereas the projections of areas 24 and 23 are directed to the neocortical, the paralimbic and the limbic areas.This study was in part supported by NIH Grant NS09211 and V.A. Research Project No. 6901Preliminary results of this investigation were presented in abstract form (Pandya et al. 1979)     

Changes in T,B, and NK Lymphocyte Subsets During and After Normal Pregnancy

PROBLEM: Pregnancy affects the maternal immune system and the clinical course of maternal diseases. Here we report the changes in the detailed lymphocyte subsets of helper T cells, suppressor T cells, CD5⁺ B cells, T cell receptor (TCR) αβ-positive T cells (Tαβ cells), TCRαβ-negative T cell (Tγδ cells), and others during and after pregnancy through to one year postpartum, and discuss the significance of the changes. METHOD: The absolute numbers of helper T cells, suppressor T cells, cytotoxic T cells, TCRαβ-negative T cells (Tγδ cells), CD5^— B cells, CD5⁺ B cells, and NK cell subsets were examined by two-color flow cytometry in peripheral blood from 51 healthy non-pregnant women, 106 healthy pregnant women, and 148 healthy postpartum women. RESULTS: In early pregnancy, the numbers of suppressor T cells and NK cells with strong cytotoxicity (NK⁺⁺⁺ cells) increased, and the number of cytotoxic T cells decreased. In late pregnancy, the helper T cell and NK⁺⁺⁺ cell numbers decreased. Tαβ, CD5^— B and CD5⁺ B cells decreased during pregnancy. After delivery, helper T cells and cytotoxic T cells increased from 1 to 4 months postpartum, and suppressor T cells increased at 7 months postpartum. TCRαβ-negative T cells increased at 4 to 10 months postpartum. Both CD5^— and CD5⁺ B cells decreased further at 1 month postpartum, but CD5⁺ B cells increased markedly at 7 to 10 months postpartum. CONCLUSIONS: These data indicate that 1) early increases of suppressor T cells and NK⁺⁺⁺ cells during pregnancy may be related to the mechanism to accept or reject the fetus in early pregnancy, respectively; 2) late decreases of helper T cells and NK⁺⁺⁺ cells may be related to the maintenance of pregnancy: 3) postpartum increases of helper T cells, cytotoxic T cells, TCRαβ-negative T cells (Tγδ cells), and CD5⁺ B cells may be related to the postpartum aggravation of autoimmune diseases; and 4) the immunological effects of pregnancy remains until about 1 year after delivery.     

Vascular lesions in testes associated with male infertility in Cameroon

Summary Testicular biopsies in 40 of 41 infertile males with severe oligospermia in Cameroon presented massive subendothelial fibrinoid deposits in the small and medium sized vessels. Fibrinogen, complement and IgM were demonstrated in these deposits by immunofluorescence. Evidence strongly suggestive of parasitic testicular involvement was also observed in 2 cases.It is postulated that the fibrinoid deposits are the result of repeated formation and deposition of circulating immune complexes by reaction of antibodies with antigens. These antigens could be of various origins and in the cases described here they could be derived from living or dying parasites in the region. The accumulation and incorporation of the fibrinoid deposits may lead to vascular stenosis resulting in chronic ischaemia, tubular atrophy and fibrosis, and finally oligospermia.     

Elektronenoptische Untersuchungen zur in vitro-Wirkung von Dipyridamol auf das Pseudorabiesvirus

Dipyridamole at a concentration of 50 μM/ml displays no activity on adsorption and penetration of pseudorabies virus in chicken embryonal cells. Furthermore, first stages of virus replication take place within the nucleus, whereas incomplete virus cores defective in DNA content are found within the nucleoplasm at times when the regular viral replication has been finished in controls. Defective pseudorabies virus particles lacking in DNA-content of the core, can be observed at the end of normal replication time. Consequently, the antiviral activity of dipyridamole may be due to blocking of the synthesis or of the incoporation of infectious viral DNA into the virus core.     

Electrophysiological evidence for connections between septal neurones and the supraoptic nucleus of the hypothalamus of the rat

Summary In order to see whether septal neurones are connected to the hypothalamic neurones secreting vasopressin or oxytocin, neurones in different regions of the septum were recorded during electrical stimulation of the supraoptic nucleus. The position of the stimulating electrode within the latter was verified using lactating rats in which milk ejections could be induced by a train of electrical pulses applied to the nucleus. The responses of septal neurones to single pulse stimulation were then analysed by post-stimulus time histograms.In the septum ipsilateral to the site of stimulation, 42% of the neurones were antidromically invaded, 20% were orthodromically excited and 21% were inhibited following supraoptic stimulation. In the contralateral septum, 2% of the cells tested were antidromically invaded, 3% were excited and 16% inhibited. In the medial septum, 14% of the neurones were orthodromically excited, and 48% were inhibited.These results provide electrophysiological evidence for direct connections between septal neurones and the ipsilateral supraoptic nucleus of the hypothalamus, and give further support to the hypothesis of a septal influence on the activity of vasopressin- or oxytocin-releasing cells in the magnocellular system.Supported by grants I.N.S.E.R.M. CRL 79.5.372.6     

Cardiac and vascular effects of elliptinium in guinea pigs. Involvement of a histaminergic mechanism

This work reports a study of the effects of elliptinium on heart rate, arterial blood pressure and capillary permeability in guinea-pigs. The variations in capillary permeability are determined by spectrophotometric assay of skin Evans blue. Elliptinium induces dose-independent tachycardia and dose-related hypotension. For the highest dose (6 mg/kg), elliptinium induces lethal collapsus. Elliptinium increases capillary permeability and this effect, particularly marked at 1 mg, i.d., is partially antagonized by mepyramine-cimetidine association. These results are discussed in comparison with those obtained with elliptinium on other parameters, with histamine and with different antitumoral agents. The increase in capillary permeability raises the question of its relevance to the anticancer activity of elliptinium.     

In vitro stimulation with mitogen and antigen in patients with monoclonal gammopathy

Summary Peripheral blood lymphocytes from 32 patients with defined paraproteinaemia (16 IgG, 9 IgA and 7 IgM) and from 15 healthy donors were studied for their in vitro response to various stimuli, including unspecific mitogens such asPhytohaemagglutinin (PHA),Pokeweedmitogen (PWM) and Concanavalin A (ConA) as well as specific antigens such as purified Tuberculin, Candida, Varidase, Tetanus Toxoid, Vaccinia antigen and Vaccinia-control antigen.Mitogens and antigens were lyophilized in Microtiter plates. The lymphocytes of all tested patient-groups responded (measured by H3-Thymidin-up-take) significantly lower towards the unspecific mitogens than those of the control group. If the patients' lymphocytes were stimulated by the specific antigens, their in vitro response was significantly diminished to candida and vaccinia. Macroglobulinaemia showed significantly lower response to ConA if compared to myelomas of IgG- and IgA-type. No correlation was found between mitogen and antigen response and the serum concentration of the paraproteins or immunoglobulins. The results show that monoclonal gammopathy and especially macroglobulinaemia are associated with abnormalities of the cellular immunity which correlates with the clinical observation of increased fungal and viral infections.Supported in part by SFB 37 München and Euratom/GSF BIAD I 031-64