Prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection among Spanish drug users measured by HTLV-1 assay and HTLV-1 and -2 assay. HTLV-1 and HTLV-2 Spanish Study Group.

The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection in 1992 and 1993 was determined by testing 2,152 specimens from injection drug users living in 11 geographic areas in Spain. Results obtained by an authentic HTLV-1 and -2 test were compared with those obtained by an HTLV-1 assay. HTLV infection was identified in 7 of 11 regions, with an overall prevalence of 2.5% (range, 0.4 to 11.5%). Fourty-four (81%) of 54 subjects were infected with HTLV-2; the viral strains in the remaining 10 subjects could not be serologically typed. Underestimation of HTLV infection because of the low sensitivities of HTLV-1 enzyme immunoassays for HTLV-2 antibody was relatively low (< 20%). Therefore, previous epidemiologic findings generated with HTLV-1 enzyme immunoassays appear to be reasonably accurate. Our results suggest that the rate of HTLV infection may have been increasing recently among Spanish drug users.     

Early Response of Lung to Low Levels of Ozone

The epithelial response in the terminal bronchioles and alveoli was examined after exposure to approximately 0.5 and 0.9 ppm ozone (O₃). Loss of ciliated cells from the terminal bronchiole was pronounced after 6 to 10 hours of exposure; however, nonciliated cells were resistant to injury from O₃. In contrast, type 1 alveolar lining cells were very sensitive to O₂ and were severely damaged or removed from significant areas of the proximal alveoli after as little as 2 hours of exposure to 0.5 ppm. The basement lamina was left devoid of an epithelium with the exception of type 2 cells, which were very resistant and retained a relatively normal appearance. Under continuous exposure, repair of the lesion area was accomplished in approximately 48 hours through proliferation of the type 2 cells. The new cells were cuboidal at first but subsequently became more squamous in appearance. Exposure for 8 to 10 hours followed by residence in clean air resulted in a proliferative response at 48 hours, about equal to that observed after continuous exposure.     

Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB.

Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure.     

Distress and DNA repair in human lymphocytes

This research assessed differences in DNA repair in lymphocytes from high-and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.This research was funded in part by General Molecular Applications, Inc., the Bremer Foundation, the Samuel J. Roessler Fund, and Comprehensive Cancer Center Core Grant CA-16068-09.     

Pathogenesis and diagnosis of human meningococcal disease using immunohistochemical and PCR assays

Neisseria meningitidis remains the leading cause of fatal sepsis. Cultures may not be available in fulminant fatal cases. An immunohistochemical assay for N meningitidis was applied to formalin-fixed samples from 14 patients with meningococcal disease. Histopathologic findings in 12 fatal cases included interstitial pneumonitis, hemorrhagic adrenal glands, myocarditis, meningitis, and thrombi in the glomeruli and choroid plexus. Meningeal inflammation was observed in 6 patients. Skin biopsies of 2 surviving patients showed leukocytoclastic vasculitis and cellulitis. By using immunohistochemical analysis, meningococci and granular meningococcal antigens were observed inside monocytes, neutrophils, and endothelial cells or extracellularly. By using real-time polymerase chain reaction (PCR) on formalin-fixed tissue samples, meningococcal serogroup determination was possible in 11 of 14 cases (8 serogroup C, 2 Y, and 1 B). Diagnosis and serogrouping of N meningitidis can be performed using immunohistochemical analysis and PCR on formalin-fixed tissue samples. Immunohistochemical analysis determined the distribution of meningococci and meningococcal antigens in tissue samples, allowing better insights into N meningitidis pathogenesis.     

Inhibition of synovial fluid lysosomal glycosidases by anti-Arthritic gold preparations

The ability of currently available anti-arthritic gold preparations to inhibit lysosomal glycosidases from rheumatoid synovial fluid and normal human serum was studied in vitro.It was shown that these preparations differ markedly in their ability to inhibit the enzymes. Gold thioglucose (Solganal) did not inhibit -glucuronidase (-GLUC), -N-acetylglucosaminidase (-NAG) or hyaluronidase (HASE). Chloro(triethylphosphine)gold (SK&F 36914) was a potent inhibitor of -NAG only. Sodium aurothiomalate (Myochrysine and sodium 3-aurothio-2-propanol-1-sulphonate (Allyochrisine) were inhibitors of all three enzymes, notably -GLUC.Kinetic analysis of inhibition by aurothiomalate demonstrated apparent competitive inhibition with -GLUC, but non-competitive inhibition with HASE and -NAG -GLUC was also strongly inhibited by silver and copper thiomalates.The concentrations of these drugs required for effective inhibition of lysosomal glycosidases probably exceed those attained in serum and therefore preclude this action extracellularly. It is suggested that durg sequestration and retention within phagocytic cells facilitates inhibition of glycosaminoglycan catabolism that mediates cleavage of glucuronidic linkages of hyaluronic acid and chondroitin sulphates.The hypothesis that gold dompounds act in vivo by attenuating the activity of lysosomal enzymes is discussed in relation to these and previous findings.     

Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury

Whole-mount airway preparations isolated from the lungs of mice treated by intraperitoneal injection of naphthalene and allowed to recover for 5 days were examined for the distribution and abundance of solitary pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) along the main axial pathway of the right middle lobe. Sham mice treated with corn oil vehicle were examined in a similar manner. An antibody to calcitonin gene-related peptide, a neuroendocrine cell marker, was used to identify the location, size, and number of PNECs and NEBs in the airways. After naphthalene treatment and epithelial repair, NEBs were significantly increased along the walls of the airways as well as on branch point ridges. The surface area covered by NEBs composed of 20 or fewer PNECs was significantly enlarged after naphthalene treatment compared with control NEBs of an equivalent cell number. The PNEC number per square millimeter was also increased more than threefold above control values after naphthalene treatment. These findings provide further support for a key role of neuroendocrine cells in the reparative process of airway epithelial cell renewal after injury.     

Life-threatening community-acquired methicillin-resistant Staphylococcus aureus infection in Australia

Eight patients with invasive bacteremic community-acquired methicillin-resistant Staphylococcus aureus infection in southeast Queensland, Australia, are reported. One patient died of septic shock. Haematogenous seeding to lungs, bone, and other sites was common. All isolates carried the virulence factor Panton-Valentine leukocidin and were either the southwest Pacific clone or the newly described Queensland clone. Clinicians should consider community-acquired methicillin-resistant Staphylococcus aureus infection in any patient presenting to hospital with severe staphylococcal sepsis or pneumonia.