Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues.

Protectin (CD59) is a recently discovered 18-20 kDa glycoprotein that effectively inhibits lysis by the membrane attack complex of the homologous complement system. This glycoprotein is widely distributed on the membranes of human blood cells (erythrocytes and leukocytes). By using immunofluorescence microscopy, protectin was observed in vascular endothelia throughout the body and in extravascular tissues. Cells expressing protectin were also found in ductal epithelia of pancreatic, biliary, and salivary systems, bronchi, and kidney collecting ducts. Furthermore, protectin was expressed in the epidermis and in the syncytiotrophoblast of placenta. The expression of protectin in endothelia, in various epithelial cells, and in placenta presumably protects autologous tissues and the fetoplacental unit from complement-mediated damage.     

Respiratory Disease Markers in Porcine Bronchoalveolar Lavage Fluid

In bronchoalveolar lavage fluid (BALF) of pigs originating from different herds bacteria, cells and the antibacterial peptide PR‐39 were examined to gain information about the lung health status. In a high health nucleus herd 56% and in low health herds 20–100% of the examined pigs were found positive for potentially pathogenic bacteria. Based on these findings, a novel definition for bacterial respiratory tract disease was established using an 8% cut‐off for the relative number of neutrophils in bronchoscopic and a 40% cut‐off in transtracheal BALF in combination with the occurrence of potentially pathogenic microorganisms. The antibacterial peptide PR‐39 was highly correlated to this definition of respiratory disease. An assessment of the bacteriological respiratory health status appears to be possibly based on the determination of PR‐39 concentrations in BALF using different cut‐off values according to the lavage method (2.5 nM for bronchoscopic and 5 nM for transtracheal BALF).     

Immune privilege induced by regulatory T cells in transplantation tolerance

Summary:  Immune privilege was originally believed to be associated with particular organs, such as the testes, brain, the anterior chamber of the eye, and the placenta, which need to be protected from any excessive inflammatory activity. It is now becoming clear, however, that immune privilege can be acquired locally in many different tissues in response to inflammation, but particularly due to the action of regulatory T cells (Tregs) induced by the deliberate therapeutic manipulation of the immune system toward tolerance. In this review, we consider the interplay between Tregs, dendritic cells, and the graft itself and the resulting local protective mechanisms that are coordinated to maintain the tolerant state. We discuss how both anti-inflammatory cytokines and negative costimulatory interactions can elicit a number of interrelated mechanisms to regulate both T-cell and antigen-presenting cell activity, for example, by catabolism of the amino acids tryptophan and arginine and the induction of hemoxygenase and carbon monoxide. The induction of local immune privilege has implications for the design of therapeutic regimens and the monitoring of the tolerant status of patients being weaned off immunosuppression.     

Clinical immunology: past, present and future challenges and prospects.

Over the past four decades, immunology has undergone a revolution changing from a largely phenomenological science into a deeply analytical and technical field. Questions concerning the primary cell involved in cell-mediated immunity, the mechanisms responsible for antibody diversity as well as the molecules used by the network of immunological cells to communicate with one another that could barely be asked in the 1950s, have been definitely answered. A major contributor to this revolution in immunological knowledge has been the scientist focussing on patient-oriented clinical immunology, a form of clinical research requiring the presence of the patient or materials freshly derived from the patient. This type of research has led to the discovery of new diseases, the definition of new infectious agents causing disease and the delineation of functional defects using applied variables on mononuclear cells removed from the patient. Moreover, this type of research is absolutely required to test hypotheses concerning the pathogenesis of disease in humans and to provide the scientific basis for the development of new approaches to therapy. As I look to the future, there are great threats to patient-oriented clinical research. The road ahead seems long and daunting. Nevertheless, I am encouraged that the patient-oriented clinical research scientist in the future will make major contributions to the use of the immune system in preventing human disease, in the development of immunological methods for diagnosis, and in the use of immune intervention to provide a new perspective for the prevention of allograft rejection, and for the treatment of neoplastic, immunodeficiency, and autoimmune disease.     

Reshaping a therapeutic CD4 antibody.

An immunosuppressive rat antibody (Campath-9) against human CD4 has been reshaped for use in the management of autoimmunity and the prevention of graft rejection. Two different forms of the reshaped antibody were produced that derive their heavy chain variable region framework sequences from the human myeloma proteins KOL or NEW. When compared to a chimeric form of the CD4 antibody, the avidity of the KOL-based reshaped antibody was only slightly reduced, whereas that of the NEW-based reshaped antibody was very poor. The successful reshaping to the KOL-based framework was by a procedure involving the grafting of human framework sequences onto the cloned rodent variable region by in vitro mutagenesis.     

Heart wall rupture as a grave complication of acute myocardial infarct

The rupture of the heart wall is a severe complication of the acute myocardial infarction. We found it in 3.5% of the deceased patients with an acute myocardial infarction. The average age of these patients was 71 years. 75% of the patients died during the first five days after the event of the myocardial infarction. Apart from elderly patients with myocardial infarction such ones with a transmural myocardial infarction in the region of the left ventricle, an enlargement of the heart and signs of an insufficiency of the left heart, with a hypertension and diabetes mellitus seemed to be endangered. These patients need the most exact control and observation and in case of suspicion (symptomatology of angina pectoris which is continuing to exist) of a developing rupture of the heart wall and aimed diagnostics (echocardiography) and therapy must be begun immediately.     

Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene

An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients.     

The processing of prosody: Evidence of interhemispheric specialization at the age of four

Beyond its multiple functions in language comprehension and emotional shaping, prosodic cues play a pivotal role for the infant's amazingly rapid acquisition of language. However, cortical correlates of prosodic processing are largely controversial, even in adults, and functional imaging data in children are sparse. We here use an approach which allows to experimentally determine brain activations correlating to the perception and processing of sentence prosody during childhood. In 4-year-olds, we measured focal brain activation using near-infrared spectroscopy and demonstrate that processing prosody in isolation elicits a larger right fronto-temporal activation whereas a larger left hemispheric activation is elicited by the perception of normal language with full linguistic content. Hypothesized by the dual-pathway-model, the present data provide experimental evidence that in children specific language processes rely on interhemispheric specialization with a left hemispheric dominance for processing segmental (i.e. phonological) and a right hemispheric dominance for processing suprasegmental (i.e. prosodic) information. Generally in accordance with the imaging data reported in adults, our finding underlines the notion that interhemispheric specialization is a continuous process during the development of language.     

Two‐Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received Low‐Dose Intravenous Soybean Oil

Background: In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure–associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates. Materials and Methods: This is a single‐site prospective follow‐up study. Neonates with a gestational age ≤29 weeks were randomized to low‐dose (LOW) or standard‐dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age. Results: Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow‐up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12‐month follow‐up cognitive scaled score in the LOW group (P = .02). Conclusion: A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long‐term safety of SO dose reduction before this strategy can be adopted.