Presence of α -Naphthyl Acetate Esterase Activity in Human Haematopoietic Cell Lines and in Fresh Biopsy Specimens of Lymphoma and Myeloma

We have previously shown that non-proliferating human T- but not B-lymphocytes contain demonstrable amounts of acid α-naphthyl acetate esterase (ANAE). The usefulness of this histochemical marker for the diagnosis and classification of malignant lymphoid tumors was investigated by use of a panel of established normal and malignant human haematopoietic cell lines and fresh biopsy cells from malignant lymphomas and myelomas. The results showed that not only the T-cell derived acute leukaemia lines, but also histiocytic lymphoma and myeloma lines and some of the lymphoma (Burkitt and lymphocytic) and non-neoplastic lymphoblastoid cell lines with B-cell surface markers expressed strong ANAE reactivity. Some but not all of the immunoglobulin producing myeloma and lymphocytic lymphoma biopsies were ANAE-positive. Inhibition experiments with sodium fluoride and E-600 demonstrated that although the T-lymphocyte specific esterase is predominantly of ‘A’-type, the malignant lines contain also non-specific ‘B’ esterase and pseudocholinesterase. As the presence of the various esterases did not demonstrate any specific distribution pattern among he haematopoietic cell lines of different origin, we concluded that the ANAE marker is no longer T-specific when malignant lymphoid cells are considered, and that the usefulness of this marker in routine diagnostic work therefore is limited.     

In vitro T- and B-cell reactivity in cartilage hair hypoplasia

We have investigated in vivo and in vitro parameters of cellular immunity in ten patients with cartilage hair hypoplasia, CHH. All ten patients displayed a negative skin test to 1 Tu tuberculin, eight patients did not respond to 10 Tu and seven not even to 100 Tu. Six patients were skin test-negative to 1:50 oidiomycin; and three were negative to even 1:10 oidiomycin. The absolute and relative distribution of blood T lymphocytes was normal. The absolute distribution of blood B lymphocytes was slightly decreased in three patients, but all patients had normal levels of IgM, IgG and IgA. Major changes were observed in the proliferative responses of blood leucocytes to mitogens and antigens. Five patients responded suboptimally to phytohaemagglutinin (PHA), two to concanavalin A, three patients were hyporesponsive to Staphylococcus aureus strain Cowan I bacteria, six to tuberculin (PPD) and six to oidiomycin. The in vitro responses of two patients were entirely normal. Except for three patients responding suboptimally to PPD or oidiomycin only, the reduced responses were all confined to the five patients responding suboptimally to PHA. The suboptimally responding patients displayed normal dose–response profiles to both PHA and Con A.

The in vitro hyporeactivity was a persistent phenomenon, as the pattern of PHA and Con A reactivity was essentially similar when the same patients had been tested to the same mitogens 5 years earlier. Except for the skin test hyporeactivity, none of these patients displayed any detectable clinical handicap, suggesting that the Finnish variant of the syndrome is dissimilar from the Amish variant, where the in vitro deficiency to mitogens and antigens is related to susceptibility to severe and often fatal infections, especially to varicella and vaccinia.

     

Humans as reservoir for enterotoxin gene--carrying Clostridium perfringens type A

We found a prevalence of 18% for enterotoxin gene-carrying (cpe+) Clostridium perfringens in the feces of healthy food handlers by PCR and isolated the organism from 11 of 23 PCR-positive persons by using hydrophobic grid membrane filter-colony hybridization. Several different cpe genotypes were recovered. The prevalence was 3.7% for plasmidial IS1151-cpe, 2.9% for plasmidial IS1470-like-cpe, 0.7% for chromosomal IS1470-cpe, and 1.5% for unknown cpe genotype. Lateral spread of cpe between C. perfringens strains was evident because strains from the same person carried IS1470-like cpe but shared no genetic relatedness according to pulsed-field gel electrophoresis analysis. Our findings suggest that healthy humans serve as a rich reservoir for cpe+ C. perfringens type A and may play a role in the etiology of gastrointestinal diseases caused by this organism. The results also indicate that humans should be considered a risk factor for spread of C. perfringens type A food poisoning and that they are a possible source of contamination for C. perfringens type A food poisoning.     

The incidence of spina bifida in Sweden 1973-2003: the effect of prenatal diagnosis

BACKGROUND: Many studies have been conducted on the accuracy of prenatal ultrasound diagnosis of foetal CNS-malformations. These studies were mostly hospital-based or, sometimes, multicentre studies. We present here a population-based study of the prenatal diagnosis of spina bifida in Sweden over a period of 31 years. METHODS: We compared the number of newborns with spina bifida and the elective terminations because of the prenatal diagnosis of spina bifida for different periods. RESULTS: The rate of spina bifida among newborns diminished gradually from 0.55 per 1000 to 0.29 per 1000 during the study period. In M county the rate of spina bifida at birth decreased very rapidly and from 1993 onwards was about half of that in the rest of the country. CONCLUSION: There has been a decline in the rate of spina bifida at birth. This decline can be seen earlier in the southern part of the country, M county. The decline is probably, to a great extent, a consequence of prenatal ultrasound screening.     

Phage Treatment Trial to Eradicate LA-MRSA from Healthy Carrier Pigs

The increase of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) causes a threat to human health. LA-MRSA can be transmitted from animals to animal caretakers, which may further spread MRSA to communities and health care facilities. The objective of this work was to study the efficacy of phage treatment in the eradication of LA-MRSA from healthy carrier pigs. A total of 19 MRSA -positive weanling pigs were assigned to a test (n = 10) and a control group (n = 9). A phage cocktail containing three Staphylococcus phages, or a control buffer was administered to the nares and skin of the pigs three times every two days, after which the phage and MRSA levels in nasal and skin swab samples were monitored for a three-week period. The sensitivity of the strains isolated during the follow-up period to the phage cocktail and each phage individually was analyzed and the pig sera were tested for antibodies against the phages used in the cocktail. The phage treatment did not cause any side effects to the pigs. Phages were found in the skin and nasal samples on the days following the phage applications, but there was no reduction in the MRSA levels in the sampled animals. Phage-resistant strains or phage-specific antibodies were not detected during the experiment. The MRSA load in these healthy carrier animals was only 10–100 CFU/swab or nasal sample, which was likely below the replication threshold of phages. The effectiveness of phage treatment to eradicate MRSA from the pigs could thus not be (reliably) determined.     

Repeatability of exhaled nitric oxide measurements in patients with COPD

The assessment of the presence of eosinophilic airway inflammation may help in predicting the steroid response in subjects with respiratory symptoms. Unlike patients with asthma, only a subset of patients with chronic obstructive pulmonary disease (COPD) benefits from steroid treatment. Fractional exhaled nitric oxide (FENO) is a useful surrogate marker for eosinophilic airway inflammation, but data on the repeatability of FENO measurements in COPD needed for the assessment of significant change are insufficient. The aim of this study was to assess the short-term repeatability of FENO measurement in subjects with moderate to very severe chronic airway obstruction compared to that in healthy subjects. We studied 20 patients with stable COPD and 20 healthy subjects, and determined FENO (flow rate 50 ml s(-1) ) three times: at baseline, 10 min and 24 h after baseline. Spirometry was performed on the first study day after the FENO measurements. The median FENO concentration in patients with COPD was 15·6 ppb, and in healthy subjects, 15·2 ppb. The coefficient of variation (CoV) for 24-h measurements was 12·4% in COPD patients, and 15·9% in healthy subjects. Among COPD patients with global initiative for chronic obstructive lung disease stage 2 disease, the CoV was 13·7%, and among those with stage 3-4 disease, 10·5%. The findings indicate that the short-term repeatability of FENO measurement in patients with moderate to very severe COPD is equally good as in healthy subjects. A change in FENO exceeding 24% is likely to reflect a minimum measurable change in COPD.     

Clinicopathological characterization and genomic aberrations in subcutaneous panniculitis-like T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) represent a rare, difficult-to-diagnose, and poorly characterized subtype of cutaneous T-cell lymphomas (CTCLs) affecting younger people more than the other CTCL forms. We performed a thorough clinical, immunohistological, and molecular analysis of nine Finnish SPTL patients. Specifically, we performed single-cell comparative genomic hybridization (CGH) from laser microdissected, morphologically malignant SPTL cells, as well as loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analysis for the NAV3 (neuron navigator 3) gene. CGH revealed large numbers of DNA copy number changes, the most common of which were losses of chromosomes 1pter, 2pter, 10qter, 11qter, 12qter, 16, 19, 20, and 22 and gains of chromosomes 2q and 4q. Some of the DNA copy number aberrations in SPTL, such as loss of 10q, 17p, and chromosome 19, overlap with those characteristic of common forms of CTCL (mycosis fungoides (MF) and Sezary syndrome (SS)), whereas 5q and 13q gains characterize SPTL. Allelic NAV3 aberrations (LOH or deletion by FISH), previously found in MF and SS, were identified in 44% of the SPTL samples. This study demonstrates that SPTL is also moleculocytogenetically a uniform entity of CTCL and supports the current World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification defining SPTL as a subgroup of its own.