Multilocus sequence typing of Swedish invasive group B streptococcus isolates indicates a neonatally associated genetic lineage and capsule switching

Streptococcus agalactiae, also designated group B streptococcus (GBS), is an important pathogen in neonates, pregnant women, and nonpregnant adults with predisposing conditions. We used multilocus sequence typing (MLST) to characterize 158 GBS isolates that were associated with neonatal and adult invasive disease and that were collected in northern and western Sweden from 1988 to 1997. Five major genetic lineages (sequence type [ST] 19, ST-17, ST-1, ST-23, and ST-9 complexes) were identified among the isolates, including serotype Ia, Ib, and II to V isolates, indicating a highly clonal population structure among invasive GBS isolates. A number of STs were found to contain isolates of different serotypes, which indicates that capsule switching occurred rather frequently. Two distantly related genetic lineages were identified among isolates of serotype III, namely, clonal complex 19 (CC19), and CC17. CC19 was equally common among isolates from adult and neonatal disease (accounting for 10.3% of GBS isolates from adult disease and 18.7% from neonatal disease), whereas CC17 significantly appeared to be associated with neonatal invasive disease (isolated from 21.9% of neonatal isolates but only 2.6% of adult isolates). The distribution of the mobile elements GBSi1 and IS1548 reveals that they can act as genetic markers for lineages CC17 and CC19, respectively.     

Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus erythematosus.

Dogs can develop systemic lupus erythematosus syndromes that are clinically similar to those seen in humans. In contrast, previous observations suggest differences in their autoantibody reactivity patterns against histones and DNA which are components of the nucleosome in chromatin. The objective of this study was to assess comprehensively the levels of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus and control dog sera were determined using IgM- and IgG-specific reagents in an ELISA against a variety of chromatin antigens. When compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosome in lupus dogs. There was no significant increase in any of the IgM specificities tested. Therefore, the reactivity pattern to nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands in contrast with human and murine lupus, where autoantibodies are directed against a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in canine lupus. The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA antibodies are not required for the development of this complication, whereas IgG anti-histone antibodies may be relevant to its pathogenesis.     

Dynamics of Local Changes and Oscillations in Energy Metabolism in the Rabbit Cerebral Cortex during the Formation of a Conditioned Defensive Reflex

Brain energy metabolism associated with different functional states and different types of human and animal activity is accompanied by dynamic changes in the degree of linkage between glycolysis and oxidative phosphorylation in different cell compartments [20–23, 25]. These processes are reflected in the redox state of brain tissue [27] and can be recorded potentiometrically as changes in the redox state potential (E) of brain tissue [24]. Studies of E in the cortex of rabbits using implanted platinum electrodes showed that during the acquisition of a conditioned defensive reflex using a combination of a light and a mild electric shock to one of the rabbit's ears, cortical E showed oscillations with periods of several seconds after 5–15 combinations. This number of combinations started to be accompanied by generalized changes in E in the cortex, which, at 20–100 combinations, could be either an increase or a decrease in E. As the number of combinations increased, increases in E were gradually replaced by decreases. By 200–400 combinations, oscillations in E disappeared and the episodes of decreased E accompanying combinations acquired a stable local character. These results suggest that there is a change in the balance of the major sources of brain tissue energy supply during the formation and stabilization of a conditioned defensive reflex: at the initial stages of acquisition of the conditioned reflex a number of cortical points have an energy supply dominated by tissue respiration, while the main energy source for brain function during performance of the acquired conditioned defensive reflex is glycolysis.     

Use of immunoblotting to characterize the mitochondrial antigens recognized by anti-mitochondrial autoantibodies

Sera with anti-mitochondrial autoantibodies detected by indirect immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA) were examined by immunoblotting against pig heart mitochondria. Seven types of reactions were defined, according to the pattern of the labelled bands. Type I sera reacted with 12 bands located within four zones. The most intensively labelled bands were located at 70, 67, 58, 63 and 43 kDa. Other types gave decreasing band numbers. When beef heart mitochondria were used, sera belonging to each of the above types had a profile of labelled bands which sometimes differed from those obtained with pig heart mitochondria. When the chloroform extracted F1-ATPase from beef heart mitochondria was used to prepare the immunoblots, primary biliary cirrhosis (PBC) sera with anti-mitochondria antibodies reacted with all the bands although zone A bands were less labelled. Rat liver mitochondria gave seven bands with type I sera among which the 57 and 35 kDa bands were specific for rat liver mitochondria, as shown by absorption tests. Sera of PBC patients were also tested in immunoblotting against rat liver subcellular fractions including mitoplasts, submitochondrial particles, inner membrane, outer membrane, matrix proteins and inter-membrane proteins. Antigenic bands of A and B zones were localized in the inner membrane and/or in the matrix proteins and the 35 kDa band in inter-membrane proteins. The outer membrane gave no reaction. The most frequent anti-mitochondrial autoantibody types in PBC were type II, then I, whilst for chronic active hepatitis type III was the most common. Type V was only seen in a patient suffering from a typical PBC. Some sera from patients with syphilis, collagenous colitis or progressive systemic sclerosis labelled one or two bands distinct from those labelled by the PBC sera. Sera from patients with drug-induced hepatitis with endoplasmic reticulum antibodies and with systemic lupus erythematosus were generally found negative by immunoblotting.     

Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers?

The aim of this study was to identify significant prognostic factors by using unrelated genomically HLA-A, -B and -DRB1-identical donors. Such data could help to choose the best donor. We studied 136 consecutive patients with hematologic malignancies and a median age of 32 years (range, 0-55 years) who received hematopoietic stem cell transplantation. Bone marrow grafts were given to 83 and peripheral blood stem cells to 53 patients. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 30% and of chronic GVHD was 54%. At 5 years, the overall transplant-related mortality (TRM) was 34%, and patient survival was 50%. In Cox multivariate analysis, 32 potential risk factors were analyzed. Monoclonal antibody OKT-3 during conditioning was correlated with grade II to IV acute GVHD, chronic GVHD, and TRM. HLA-DP mismatch was associated with poor TRM and poor survival. Cytomegalovirus-seropositive patients with a seronegative donor had a decreased leukemia-free survival. Five-year TRM was 14% with no risk factor, 38% with 1 risk factor, and 87% with 2 risk factors. The 5-year survival was 72%, 48%, and 30% with 0, 1, and 2 risk factors, respectively. We concluded that unrelated hematopoietic stem cell transplantation may be improved if an optimal donor and immunosuppression are chosen.     

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.     

Immunoreactivity of aqueous extracts of rat and mouse tissue with anti-thymosin alpha 1, anti-bovine thymopoietin and anti-thymulin antibodies. Studies using immunoblotting

Anti-thymosin alpha 1 monoclonal antibodies recognized, on immunoblots, 1 to 2 bands corresponding to molecules of 34 and 35 Kd when using aqueous extracts of thymus, spleen, kidney, liver, brain, pituitary and adrenal glands from rats or mice. Anti-bovine thymopoietin polyclonal antibodies, in the same conditions, labelled analogous 34, 35 and 35.5 Kd molecules in brain and thymus extracts but also a 40 Kd molecules in thymus and a 90 Kd in brain extracts. Anti-synthetic thymulin monoclonal antibodies recognized irregularly and poorly a 52 Kd molecule from thymus and brain extracts. These results suggest that thymopoietin, thymulin and specially Thymosin alpha 1 are first synthesized in large precursors. Finally, other organs seem capable of synthesizing thymosin alpha 1 and probably thymopoietin, but for thymulin, the results are too irregular to conclude.     

Autonomic Nervous System Function and Essential Hypertension: Individual Response Specificity With and Without Beta-Adrenergic Blockade

The aim of the present research was to study individual response specificity in 22 male patients having essential hypertension (HT) and to compare these patients with age-matched male normotensive controls (NT). Four stimuli, letter identification, mental arithmetic, cold pressor and isometric exercise, were administered while recordings were made of: systolic and diastolic blood pressures, heart rate, respiration, forearm and hand blood flows, and skin conductance level and fluctuations. After each session urine samples were collected and epinephrine and norepinephrine levels were analyzed. Twelve subjects in the HT group were given beta-adrenergic blocking agents and retested 1 to 21 months (X?= 12 months) after the first session. Each response was standardized, using NT as the reference group. Intraclass correlations were computed to evaluate whether HT males reacted with a more consistent hierarchy of responses than did NT. Intraclass correlations were significantly higher among the patients than in the control group, regardless of whether the blood pressure response was included or excluded in the computation of the intraclass correlations. Thus, we conclude that male HT patients show more individual response specificity than NT controls. Beta-adrenergic receptor antagonists reduced levels of cardiovascular activity and attenuated reactivity but did not affect amount of specificity. Thus, intraclass correlations provide unique and useful information, since they are not related to blood pressure reactivity or to urinary catecholamine levels, nor affected by beta-adrenergic blockade.     

Learned control of heart rate during exercise in patients with borderline hypertension

Summary Twelve patients with borderline hypertension [⩽21.33/12.6, ⩾18.6/12.0 kPa (⩽160/ 95; ⩾ 140/90 mm Hg)] participated in an experiment aimed at testing whether they could learn to attenuate heart rate while exercising on a cycle ergometer. Six experimental (E) subjects received beat-to-beat heart-rate feedback and were asked to slow heart rate while exercising; six control (C) subjects received no feedback. Averaged over 5 days (25 training trials) the exercise heart-rate of the E group was 97.8 bt min⁻¹, whereas the C group averaged 107 bt min⁻¹ (P=0.03). Systolic blood pressure was unaffected by feedback training. Generally, changes in rate-pressure product reflected changes in heart-rate. Oxygen consumption was lower in the E than in the C group late in training. We conclude that neurally mediated changes associated with exercise in patients with borderline hypertension can be brought under behavioral control through feedback training.