The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency

Four patients with alpha-1 antitrypsin (alpha-1 AT) deficiency are presented: one woman with severe (phenotype PiZ) and 3 men with moderate (phenotype PiMZ) deficiency of alpha-1 AT. The variability of clinical presentation of hereditary emphysema is described. In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined.     

Effects of estrone on N-methyl-D-aspartic acid- and staurosporine-induced changes in caspase-3-like protease activity and lactate dehydrogenase-release: time- and tissue-dependent effects in neuronal primary cultures

A growing body of evidence indicates that estrogens affect apoptotic processes in neuronal cells. However, their effects seem to depend on type of neuronal tissue, stage of development and apoptosis inducing factors. In the present study we compared effects of estrone (100 and 500 nM) on N-methyl-D-aspartic acid (NMDA) (1 mM)- and staurosporine (1 microM)-induced caspase-3-like activity and lactate dehydrogenase (LDH)-release in primary cultures of rat hippocampal and neocortical neurons. Fluorometric and colorimetric determination of enzyme activity was performed 6 h, 14 h, and 24 h after exposure to apoptotic agents. In the hippocampal cell cultures on 7 days in vitro (DIV), a time-dependent NMDA-induced activation of caspase-3-like proteases was accompanied by increased LDH-release. In neocortical cell cultures on 7 DIV NMDA did not affect caspase activity and decreased LDH-release. In neocortical cell cultures on 12 DIV NMDA inhibited spontaneous caspase activity, but was toxic to neurons after 24 h exposure suggesting that these cells underwent necrotic rather than apoptotic death. Estrone has attenuated both pro- and anti-apoptotic NMDA-induced changes in rat primary neuronal cultures acting independently of estrogen receptors, as detected with ICI 182, 780. In hippocampal neurons estrone antagonized not only the NMDA-induced caspase-3-like activity, but also NMDA-mediated LDH-release. However, in neocortical neurons estrone either attenuated NMDA-induced inhibition of caspase-3-like activity (12 DIV) or partly blocked NMDA-mediated decrease in LDH-release (7 DIV). In contrast to NMDA, staurosporine elevated caspase-3-like activity and LDH-release in a time-dependent manner in all used culture systems. Estrone inhibited pro-apoptotic effects of staurosporine in neocortical neurons, but only at later stage of development in vitro, which points to the protective role of estrogens during the brain tissue maturation. Since estrone triggered its effects via non-genomic mechanisms, it suggests that the other estradiol metabolites exhibiting low affinity to hormone receptors may be potent neuroprotective agents, which could retain the favorable and minimize the adverse side effects of estrogens.     

The relation between lymphocyte profile in BALF and the course of sarcoidosis based on short term observation

The aim of this study was to assess how the extent of the number and percentage of lymphocytes in BALF and also the CD4 to CD8 ratio can help to predict the short outcome in sarcoidosis. Material consisted of 74 patients, 39 men and 35 women in the age from 23 to 58 years. 11 patients had chest lesions in stage I, 43 in stage II and 20 in stage III. Clinical markers of activity (fever, erythema nodosum) were present in 22 cases. Extrathoracic lesion were present in 31 and abnormal pulmonary function in 30. In all patients BAL was done before treatment and lymphocyte count, percentage and CD4/CD8 ratio was calculated. 50 patients were treated with corticosteroids and 24 were observed without treatment. After 6-12 month of observation regression of sarcoid lesions was observed in 46 of 50 patients treated with corticosteroids and in 17 out of 24 patients observed without treatment. There were no differences in lymphocyte count and percentage in BALF and in the short term outcome between group treated with corticosteroids and without treatment. The patients in whom regression of lesions was observed have however significantly higher CD4/CD8 ratio than others.     

Noninvasive intermittent positive pressure ventilation in treatment of chronic respiratory disease exacerbation

Noninvasive intermittent positive pressure ventilation (NIPPV) via nasal mask became a routine method of treatment of severe exacerbations of chronic respiratory failure. The aim of the study was to apply NIPPV in patients with COPD admitted to hospital due to exacerbation of the disease who on standard treatment developed progressing respiratory acidosis (pH < 7.30). Fourteen COPD patients were treated with NIPPV. Arterial blood gases at the beginning of treatment were: PaO2 41 +/- 9 mmHg, PaCO2 = 87 +/- 17 mmHg, pH = 7.30 +/- 0.05. In 10 patients NIPPV applied quasi continuously resulted in clinical improvement and an amelioration of arterial blood gases. PaO2 rose from 41 +/- 9 mmHg to 56 +/- 12 mmHg, PaCO2 fell from 85 +/- 17 to 57 +/- 9 mmHg and pH rose from 7.30 +/- 0.05 to 7.41 +/- 0.04. In 4 patients NIPPV did not prevent further progression of respiratory acidosis. They were intubated and mechanically ventilated. Three patients survived and were discharged home. One patient died from septic shock. We conclude that NIPPV is an effective method to treat respiratory acidosis developing during exacerbation of severe COPD.     

Effect of IFN-gamma on expression of HLA in bare-lymphocyte syndrome-like cell line HAJ

We compared HLA antigen expression on new B-lymphoblastoid cell line (B-LCL) HAJ with that on B-LCLs expressing normal HLA levels as well as on B-LCLs derived from bare lymphocyte syndrome (BLS) patients and in vitro mutated B-LCLs of BLS-like phenotype. HAJ cells had no expression of HLA class II and low expression of class I antigens similarly to some of BLS B-LCLs, although HAJ cell line was derived from lymphocytes of HLA class I- and class II-normally expressing donor. HAJ cells displayed B lymphocyte markers, surface immunoglobulin and CD19. Culture of HAJ cells in the presence of interferon y resulted in HLA class I antigen upregulation, but did not restore class II expression. The cell line HAJ may prove useful for studies on factors influencing HLA class I cell surface expression.     

Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis

INTRODUCTION: Oxidative modification of proteins affects their biological properties. Previously we have shown that hypochlorite (HOCl), the product of activated neutrophils, enhances protein immunogenecity. Collagen type II, a primary component of cartilage, is commonly used in the induction of arthritis in animals (CIA). The aim of this study was to examine whether HOCl may affect immunogenic, tolerogenic, and arthritogenic properties of collagen. MATERIALS AND METHODS: DBA/J mice were injected with either native (CNAT) or chlorinated collagen (CHOCl) to induce arthritis. The effect of chlorination on collagen properties was measured by evaluation of incidence and severity of CIA. Moreover, the concentration of serum anti-collagen IgG antibodies and myeloperoxidase (MPO) activity in inflamed joints was determined. RESULTS: Mice immunized with CNAT in adjuvant developed arthritis (CIA) with an incidence of 69%. CNAT also exerted tolerogenic properties when injected intravenously either before or shortly after primary immunization, resulting in decreased incidence and severity of CIA, reduced MPO activity in inflamed joints, and lowered serum levels of anti-CNAT IgG anti-bodies. Chlorination of collagen significantly diminished its ability to induce CIA and to trigger generation of anti-CNAT IgG antibodies. Interestingly, chlorination did not affect tolerogenic properties of collagen administered prior to primary immunization with CNAT. CONCLUSIONS: These results suggest that chlorination of collagen may selectively affect functional epitopes of collagen. It is likely that in inflamed joints, neutrophil derived HOCl, in some circumstances, will destroy arthritogenic and immunogenic B cell epitopes, while regulatory T cell epitopes will be preserved.     

Imidazopyrimidodiazepines--new heterocyclic system; synthesis and properties

The synthesis of the new tricyclic system ring 6-methyl-2,3,10,11-tetrahydroimidazo (1',2',3'-CD) pyrimido (5,4-b) (1,4) diazepinediones-5,8 is described. The 4-aryl- and 5-amino-imidazopyrimidodiazepines have also been obtained. The synthesis started from derivatives of 2-hydroxy-6-methyl-5-pyrimidine carboxylic acids. Some of the chemical and biological properties of new compounds are described.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.