Mhc-E polymorphism in Pongidae primates: the same allele is found in two different species

The results of 93 de la Caffinière thumb joint replacements in 71 patients were reviewed between 6 and 16 years. The survival rate was 89% at 16 years. Eleven thumb joints had failed requiring revision. The commonest reason for failure was aseptic loosening of the trapezial component. The failure rate was higher in men of working age than any other group, which possibly reflects the increased demands on the prosthesis of these patients. We support the use of this implant for degenerative osteoarthritis, but caution against its use in men under 65 years.     

A multivariate approach to affected-sib-pair analysis using highly dense molecular maps

Adaptation of the Bacillus subtilis strain 2335/105 (Km Inf+) containing a recombinant plasmid encoding the extracellular human interferon alpha 2 was studied under various conditions. Stability of the plasmid in the population of B. subtilis 2335/105 was estimated under nonselective conditions. The plasmid-free cells and cells with a low number of plasmid copies were found to accumulate progressively, constituting 80% of the population after 10 culture passages, indicating the poor competitiveness of cells carrying a high number of plasmid copies. The behavior of vegetative cells of the recombinant strain introduced into aquatic microcosms differing in trophic chain length was studied. Within the first 10 days, the lysis of vegetative cells of B. subtilis 2335/105 occurred; the number of viable spores was very low but remained constant for half a year.     

The proliferative response of HIV+ T-cells (CD4+ and CD8+) are severely suppressed via CD28 coactivation

Several studies have suggested that regulation of expression of the costimulatory molecule CD28 on the T-cell surface may play an important role in AIDS pathogenesis. In a study of T-cells from HIV+ donors, we find that activation with anti-CD3 plus anti-CD28 results in a mitogenic response which was approximately 86% suppressed for both CD4+ and CD8+ T-cells when compared to normal control cells. With PMA costimulation (instead of anti-CD28), the anti-CD3 response was suppressed much less, by 64 and 61%, respectively. With Con A as opposed to CD3 stimulation, the degree of suppression was less with either coactivator but still more severe with CD28 than with PMA coactivation. It has been reported that the CD28 subset of CD8+ T-cells is diminished in HIV+ individuals and could account for these results. It is possible as well that the CD28 costimulatory pathway in the CD4+ T-cells particularly is altered due to intervention by the HIV. While our data do not differentiate between these two possibilities, it show that the immune status is compromised in the HIV+ individual not only in terms of number of CD4+ T-cells, but in their activation response as well.     

Leukocytes modulate 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in human granulosa-lutein cell cultures

A randomised clinical trial was performed to investigate whether there is a need or advantage to splint two implants in the mandible retaining a hinging overdenture. Furthermore, patient satisfaction was evaluated for different attachment systems retaining the overdenture. Thirty-six edentulous patients were randomised into three groups of equal size and treated with either magnets, ball attachments or straight bars (reference group). After 3 years of observation no implants were lost in any of the groups. Besides, no statistically significant differences were noted for the peri-implant outcome. Although the bar group presented the highest retention force, the general satisfaction of the patients in the three groups did not differ. The patients with bar retentions showed less prosthetic complications of the retention elements but more at the level of the denture-supporting mucosa. Finally, the clinical outcome of all groups confirms that overdenture treatment demands regular controls with limited time intervals.     

Variable region domain exchange influences the functional properties of IgG

In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human Ckappa and the variable region of the light chain on different human gamma constant regions (creating inside-out molecules). Although fully assembled molecules were secreted, this variable region exchange slowed the kinetics of Ab assembly. Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowing both the on and off rates. When effector functions were evaluated, inside-out IgG1 and IgG3 were more effective in complement-mediated cytolysis than their wild-type counterparts. Variable region domain exchange may be one approach to obtaining Abs of identical specificity with altered binding characteristics.     

Histamine synthesis and content in benign and malignant breast tumours. Its effects on other host tissues

We studied 100 patients: 40 with breast cancer, 41 with benign breast tumours and 19 non-cancer-bearing cholecystectomy patients, in order to measure the histidine decarboxylase activity and histamine content in benign and malignant breast tumours, and to determine whether the histamine metabolism affected skin and muscle tissue distant from the tumour. The HDC-activity of cancerous tissue was significantly higher (P < 0.01) than that registered in the healthy mammary gland tissue of the same patient, being even more pronounced in benign tumour tissue (P < 0.001). However, the histamine content was found to be significantly lower (P < 0.01) in malignant tumours, but higher in benign tumoural tissue as compared with the healthy tissue of the same patient. We also found that the histamine content in muscle tissue was significantly higher in cancer patients than in non-cancer patients. These findings highlight the fact that intracellular histamine metabolism varies in benign and malignant tumours, and that high histamine synthesis of malignant tumours affects other host tissue.     

Sensitive assay for midazolam and its metabolite 1'-hydroxymidazolam in human plasma by capillary high-performance liquid chromatography

A sensitive high-performance liquid chromatographic method is described for the quantification of midazolam and 1'-hydroxymidazolam in human plasma. Sample (1 ml plasma) preparation involved a simple solvent extraction step with a recovery of approximately 90% for both compounds. An aliquot of the dissolved residue was injected onto a 3 microm capillary C18 column (150 mm x 0.8 mm I.D.). A gradient elution was used. The initial mobile phase composition (phosphate buffer-acetonitrile, 65:35) was maintained during 16 min and was then changed linearly during a 1-min period to phosphate buffer-acetonitrile, 40:60. The flow-rate of the mobile phase was 16 microl/min and the eluate was monitored by UV detection. The limits of quantification for midazolam and 1'-hydroxymidazolam were 1 ng/ml and 0.5 ng/ml, respectively. The applicability of the method was demonstrated by studying the pharmacokinetics of midazolam, and its major metabolite 1'-hydroxymidazolam, in human volunteers following i.v. bolus administration of a subtherapeutic midazolam dose (40 microg/kg).