Antigen presentation by a B-cell line transfected with cloned immunoglobulin heavy- and light-chain genes specific for a defined hapten.

The rearranged genes encoding immunoglobulin heavy (mu) and light (kappa) chains specific for the hapten 2,4,6-trinitrophenyl (Tnp) were introduced into a B-lymphoma line that bears surface IgG with an unknown specificity and expresses surface Ia molecules. A transformant expressing surface IgM specific for Tnp was obtained. The transformant was found to present Tnp-proteins to antigen (protein)-specific T cells far more efficiently than the parenteral B-lymphoma line. This artificial system, utilizing recombinant DNA technology and gene transfer, provides several approaches for the study of T-cell-B-cell interactions.     

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early measurement of intracranial pressure in polytrauma with associated craniocerebral trauma. II: Clinical and therapeutic aspects

During the time from 1982/83 the intracranial pressure was continuously measured from patients who were polytraumatized and also had severe head injuries. In 53% of these cases the first readings could be obtained within 6 hours after the injury and in 33% first after 12 hours. During the time of evaluation this relationship shifted to earlier implantation. From 27% of these patients the intracranial pressure values fell into a range that instigated immediate therapeutical measures. This proves how important it is to have a direct reading from the intracranial pressure as soon as possible after injury. The aspects of therapy by increased intracranial pressure were discussed.     

Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study.

BACKGROUND: Overall neocortical gray matter (NCGM) volume has not been studied in first-episode schizophrenia (FESZ) at first hospitalization or longitudinally to evaluate progression, nor has it been compared with first-episode affective psychosis (FEAFF). METHODS: Expectation-maximization/atlas-based magnetic resonance imaging (MRI) tissue segmentation into gray matter, white matter (WM), or cerebrospinal fluid (CSF) at first hospitalization of 29 FESZ and 34 FEAFF, plus 36 matched healthy control subjects (HC), and, longitudinally approximately 1.5 years later, of 17 FESZ, 21 FEAFF, and 26 HC was done. Manual editing separated NCGM and its lobar parcellation, cerebral WM (CWM), lateral ventricles (LV), and sulcal CSF (SCSF). RESULTS: At first hospitalization, FESZ and FEAFF showed smaller NCGM volumes and larger SCSF and LV than HC. Longitudinally, FESZ showed NCGM volume reduction (-1.7%), localized to frontal (-2.4%) and temporal (-2.6%) regions, and enlargement of SCSF (7.2%) and LV (10.4%). Poorer outcome was associated with these LV and NCGM changes. FEAFF showed longitudinal NCGM volume increases (3.6%) associated with lithium or valproate administration but without clinical correlations and regional localization. CONCLUSIONS: Longitudinal NCGM volume reduction and CSF component enlargement in FESZ are compatible with post-onset progression. Longitudinal NCGM volume increase in FEAFF may reflect neurotrophic effects of mood stabilizers.     

Biochemical characteristics of 130 recent isolates from Haemophilus influenzae meningitis.

A total of 130 Haemophilus strains, comprising virtually all isolates from Danish and Norwegian cases of Haemophilus meningitis occurring in the period from October 1975 through September 1976, were examined by biochemical and serological means. All isolates were identified as H. influenzae and, except for one noncapsulated strain, possessed a capsule of serotype b. The vast majority of strains (93%) belonged to biotype I, which, in contrast to biotypes II and III, is rarely encountered as a commensal of the upper respiratory tract. This finding is a strong incentive for studies of possible additional virulence factors associated with biotype I organisms. The results are discussed in the light of North American reports, which have suggested changes in the etiology of Haemophilus meningitis.     

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.     

Lack of cleavage of immunoglobulin A (IgA) from rhesus monkeys by bacterial IgA1 proteases.

Bacterial immunoglobulin A1 (IgA1) proteases cleaving IgA1 and secretory IgA1 molecules in the hinge region are believed to be important virulence factors. Previous studies have indicated that IgA of humans, gorillas, and chimpanzees are the exclusive substrates of these enzymes. In a recent study, IgA from the rhesus monkey was found to be susceptible to the IgA1 protease activity of Streptococcus pneumoniae. In an attempt to reproduce this observation, we found that neither five isolates of S. pneumoniae nor other IgA1 protease-producing bacteria representing different cleavage specificities caused cleavage of rhesus monkey IgA. Hence, the rhesus monkey does not appear to be a suitable animal model for studies of IgA1 proteases as virulence factors.     

Retained antigen-binding activity of Fab alpha fragments of human monoclonal immunoglobulin A1 (IgA1) cleaved by IgA1 protease

Immunoglobulin A1 (IgA1) proteases may be important virulence factors of certain bacteria involved in the pathogenesis of meningitis, gonorrhea, destructive periodontal diseases, and some other infections affecting mucosal membranes. This study evaluated the antigen-binding activity of free Fab alpha fragments released from human myeloma IgA1 by IgA1 protease from Haemophilus influenzae. Six myeloma proteins with antibody activity against streptolysin O, alpha-staphylolysin, or streptococcal hyaluronidase were used. Complete cleavage of the IgA1 myeloma proteins in the hinge region of the heavy chain did not affect their antigen-binding capacity. The titers of neutralizing activity associated with free Fab alpha fragments were not significantly different from those of the intact IgA1 proteins. The retained antigen-binding capacity of cleaved IgA1 is an important factor in the understanding of how IgA1 proteases may interfere with the immune protection of mucosal membranes.