Molecular characterization of human immunodeficiency virus (HIV)-1 and -2 in individuals from guinea-bissau with single or dual infections: predominance of a distinct HIV-1 subtype A/G recombinant in West Africa.

Guinea-Bissau in West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but recently the HIV-1 prevalence increased rapidly with the subsequent appearance of HIV-1 and HIV-2 dual infections. Information about the genetic subtypes of HIV in the region is limited. Therefore, we characterized the env V3 region of HIV-1 and HIV-2 variants through direct DNA sequencing of peripheral blood mononuclear cell samples from 18 individuals with HIV-1 only and 9 individuals with dual infection. Phylogenetic analyses of these new sequences and database sequences from other West African countries showed that all HIV-1 and HIV-2 sequences from singly as well as dually infected individuals, except one, clustered among HIV-1 subtype A and HIV-2 subtype A, respectively. Importantly, a majority of the HIV-1 sequences from Guinea-Bissau and neighbouring countries were closely related with the isolates IbNG, DJ263, and DJ264, which share a common subtype A/G recombination pattern. Analysis of pol gene sequences from selected HIV-1 variants showed that "IbNG-like" viruses in Guinea-Bissau are also recombinant, indicating that the HIV-1 epidemic in Guinea-Bissau and neighbouring countries is dominated by an epidemic spread of a distinct subtype A/G recombinant, which is strikingly similar to the epidemic spread of a subtype A/E recombinant in Southeast Asia. Furthermore, the HIV-1 and HIV-2 variants carried by individuals with dual infection were intermixed with variants from singly infected individuals, indicating that variants involved in dual and single infections have common epidemiological histories.     

Effects of subacute treatment with toluene on cerebrocortical alpha- and beta-adrenergic receptors in the rat. Evidence for an increased number and a reduced affinity of beta-adrenergic receptors

Subacute treatment with toluene (80-1500 p.p.m.) produces a dose-dependent reduction of affinity and increase in density of the beta-adrenergic antagonist [3H]dihydroalprenolol binding sites in the frontoparietal cortex of the male rat, while the binding characteristics of alpha 1-adrenergic ([3H]WB 4101) and alpha 2-adrenergic ([3H]p-aminoclonidine) binding sites in the same region is unaffected by this treatment as evaluated in vitro. Therefore, it is suggested that the cortical beta-adrenergic receptors are particularly vulnerable to the action of toluene in vivo. It is speculated that as a result cortical beta-adrenergic neurotransmission may be altered following exposure to low concentrations of toluene, possibly related to the physico-chemical properties of toluene, leading to changes in membrane fluidity.     

Molecular identification of T cell-specific antigens on human T lymphocytes and thymocytes

We have identified membrane glycoproteins which carry T cell-specific antigens on human T lymphocytes and thymocytes. Purified cells were surface-labeled with NaB³H₄ after treatment with neuraminidase and galactose oxidase. Immunoprecipitations were performed with rabbit anti-human T cell-specific antibodies using co precipitation with protein A-containing staphylococci strain Cowan I. The labeled membrane glycoproteins and the precipitates were subjected to polyacrylamide slab gel electrophoresis and visualized by fluorography. The antibodies specifically precipitated 4 proteins called GP200, GP180, GP165 and GP160 (mol. wts. = 200000, 180000, 165000 and 160000) from surface-labeled T lymphocytes and low-density (medullary) thymocytes. The GP200 and GP180 were not labeled on high-density (cortical) thymocytes. A protein with a mol. wt. of 45000 was precipitated from thymocytes. Another glycoprotein on T lymphocytes and thymocytes with a mol. wt. similar to that of mouse and rat Thy-1 or Θ antigen (mol. wt. 25000) reacted with the antibodies.     

POLYMORPHISM OF BOVINE MHC CLASS II GENES. JOINT REPORT OF THE FIFTH INTERNATIONAL BOVINE LYMPHOCYTE ANTIGEN (BOLA) WORKSHOP,INTERLAKEN, SWITZERLAND, 1 AUGUST 1992

Polymorphism of the bovine DRB, DQA, DQB, DYA, DOB and DIB genes was investigated using restriction fragment length polymorphism (RFLP) analysis, isoelectric focusing (IEF), class II serology and polymerase chain reaction (PCR) based typing techniques. The simultaneous application of multiple typing techniques and the characterization of multiple genes resulted in a greatly enhanced picture of the bovine class II regions. Thirty-eight class IIa (DR-DQ) and 5 class lib (DYA-DOB-DIB) haplotypes were defined. It was found that IEF types were associated with DRB3 polymorphism defined by DRB3 PCR-RFLP and DRB3 microsatellite PCR. Serologically defined polymorphism was associated with distinct molecular/IEF motifs and, therefore, DR and DQ specificities could be tentatively distinguished. Although the DR and DQ genes are tightly linked, neither DR nor DQ typing defined all of the class IIa region polymorphism. Furthermore, even the most powerful DRB3 typing technique, DRB3 PCR-RFLP, failed to detect all expressed DRB3 polymorphism. All detected DRB3 polymorphism could, however, be distinguished with a combination of two molecular techniques: DRB3 PCR-RFLP and DRB3 microsatellite PCR. RFLP typing with transmembrane probes detected significantly less polymorphism than typing with cDNA or exon probes. However, the transmembrane probes were useful because they were locus specific. The presence of only 5 of 12 possible class lib haplotypes was unexpected and indicates that the DYA, DOB and DIB genes are tightly linked.     

Long-term corticosteroid treatment in giant cell arteritis

Ninety patients with giant cell arteritis were followed up 9-16 years (median 11.3 years) after diagnosis. The mean duration of corticosteroid therapy was 5.8 years (range 0-12.8 years). Together, the patients had received corticosteroids for 492 patient-years. Five years after diagnosis, 43% of the patients were on corticosteroid therapy. After 9 years, 15 of 60 surviving patients (25%) were still being treated with 1.25-10 mg of prednisolone daily (median dose 5 mg). The relapse rate was about 50%, regardless of the time after diagnosis, when an attempt to withdraw the treatment was made. Forty-six per cent of the relapses occurred within one month and 96% within one year of the end of treatment. Most of the flare-ups occurred during the first year of therapy and in 55% of the patients on a prednisolone dosage of 5 mg or less. We did not find any increase in morbidity in our patients compared to the general population. Nor did we see any significant complications which we could attribute to the steroid treatment.     

Regional and species differences in vascular reactivity to extracellular potassium

In-vitro vasoreactivity to extracellular potassium (Ko+) was tested in isolated human pial and mesenteric arteries as well as basilar and mesenteric arteries from rabbits and rats. Contractions were induced by stepwise increases in [K+]o and were measured isometrically with a force-displacement transducer, in small-volume organ baths. Significant differences between species as well as between regions were found. The threshold of [K+]o for eliciting contraction in human cerebral arteries in hyperosmotic solutions was 10 mM, in rabbit cerebral arteries 17 mM and in rat cerebral arteries 27 mM. The threshold concentration for contraction in mesenteric arteries was significantly higher compared to cerebral arteries in humans and rabbits, but lower in rats: 20 mM in humans, 26 mM in rabbits and 25 mM in rats. In all species the contractile amplitudes were significantly higher in both cerebral and mesenteric arteries when [K+]o was increased under isotonic conditions in the buffer solution than when hyperosomolality was created. This difference increased with increasing hyperosmolality. In hyperosmotic solutions, the EC50 for [K+]o was lower in cerebral and mesenteric arteries from man than in vessels from rabbit and rat. When the solutions were isotonic, this pattern was seen only in mesenteric arteries. It is concluded that significant species and regional differences in vascular responses to [K+]o exist. Considering that [K+]o is increased in cerebral ischaemia, the observed significantly lower threshold for K+-induced contractions in human cerebral arteries may be of importance, especially in human cerebral ischaemic events.     

Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.     

[H]Paroxetine binding in human platelets in relation to age and sex

The binding of [³H]paroxetine to serotonin uptake sites in human platelets from 47 individuals between 15 and 95 years of age was investigated. There were no significant age-related changes in maximal binding capacity (B_max) or apparent binding affinity (K_d). There were no significant differences in binding between males (n = 19) and females (n = 28).     

Use of Antibodies in Lymphocyte Secretions for Detection of Subclinical Tuberculosis Infection in Asymptomatic Contacts

We have previously demonstrated that Mycobacterium bovis BCG-specific immunoglobulin G antibodies in lymphocyte secretions (ALS) can be employed as a marker for active tuberculosis (TB). We aimed to determine whether the ALS method allows detection of subclinical TB infection in asymptomatic individuals. A prospective study of family contacts (FCs) of patients with active TB and healthy controls was performed. Thirteen of 42 FCs had high ALS responses, including 6 FCs who subsequently developed active TB. No correlation was observed between the tuberculin skin test and the ALS responses in the FCs (r = 0.1, P = 0.23). Among patients with active TB, BCG-specific ALS responses steadily declined from the time of diagnosis through 6 months following antimycobacterial chemotherapy (P = 0.001). The ALS assay enabled detection of infection in exposed symptom-free contacts, who are at greater risk for developing active TB. The method may also allow discrimination between effective treatment of active infection and suboptimal response to therapy.