The laser guidewire experience: ''crossing the Rubicon''

When estrogen (1 mg/mouse) was subcutaneously administered once into mice, the number of liver MNC increased but the number of thymocytes decreased profoundly from Day 3 to Day 20. Phenotypic characterization revealed that the proportion of intermediate (int) TCR cells with IL-2 receptor beta-chain (IL-2R beta) was elevated in both the liver and the thymus. Attention was then focused on how forbidden clones were distributed among various T-cell subsets, including IL-2R beta+ int TCR cells and IL-2R beta-high TCR cells. IL-2R beta+ int TCR cells are generated through the extrathymic pathway in the liver and an alternative intrathymic pathway, whereas IL-2R beta- high TCR cells are generated through the mainstream of T-cell differentiation in the thymus. It was demonstrated that forbidden clones, V beta 3+ and V beta 11+ cells, in BALB/C mice (Mls-1b2a) were confined to IL-2R beta+ int TCR cells, irrespective of the administration of estrogen. Interestingly, the proportion of forbidden clones among int TCR cells increased in the liver but decreased in the thymus after the administration of estrogen. Liver MNC that contained a high level of forbidden clones showed unexpected high levels of spontaneous proliferation and of the proliferative response to immobilized anti-V beta mAb (even in the combination of forbidden clone stimulations). The present results reveal that the levels of both int TCR cells and forbidden clones that induce hepatocyte damage preferentially increase in the liver, one of the prime target organs in autoimmune diseases, when estrogen is administered.     

The correlation between symptomatic CMV infection and CMV antigenemia in heart allograft recipients

Previous studies have demonstrated that CMV-specific antigens detected from peripheral blood leukocytes correlate with active CMV infection in transplant patients. However, the clinical diagnosis of CMV infection is difficult, and the significance of a positive blood finding is unclear, while CMV antigenemia and viremia may also occur in asymptomatic patients. To investigate the clinical significance of CMV antigenemia after heart transplantation, 68 heart allograft recipients were monitored weekly. Altogether 501 blood specimens were analyzed. CMV was demonstrated in blood leukocytes by a monoclonal antibody and immunoperoxidase staining, and the antigenemia level was expressed as CMV positive cells/50,000 leukocytes. CMV antigenemia occurred in 28/68 patients, and 12 of them developed a symptomatic infection. Of all blood specimens 88/501 were CMV positive, and 30 of them related to the clinical manifestation of CMV. When antigenemia level exceeded > 100/50,000, a significant correlation between antigenemia and CMV-related clinical manifestation was reached (P < 0.001). Of the 28 antigenemia positive patients 16 never developed any clinical signs of CMV infection. Their maximal antigenemia level was low (median 23, range 30-90) compared with those with clinical manifestation (median 500, range 30-1000) (P < 0.002). In conclusion, high antigenemia levels (> 100/50,000) correlate with clinical manifestations of CMV infection. Patients with lower levels (< 100/50,000) do not necessarily ever develop a symptomatic infection. Quantitative monitoring of CMV antigenemia may, thus, be helpful in the clinical diagnosis of CMV infection in heart transplant patients.     

Linked genes for calmodulin and E2 ubiquitin-conjugating enzyme in Trichomonas vaginalis

In searching the genomes of early-diverging protists to study whether the possession of calmodulin is ancestral to all eukaryotes, the gene for calmodulin was identified in Trichomonas vaginalis. This flagellate is a member of the Parabasalia, one of the earliest lineages of recognized eukaryotes to have diverged. This sequence was used to isolate a homologous 1.250-kb fragment from the T. vaginalis genome by inverse polymerase chain reaction. This fragment was also completely sequenced and shown to contain the 3' end of the single-copy calmodulin gene and the 3' end of a gene encoding a protein with high similarity to E2 ubiquitin-conjugating enzymes, a family which has previously only been identified in animals, plants, and fungi. Phylogenetic analysis of 50 members of the E2 family distinguishes at least nine separate subfamilies one of which includes the T. vaginalis E2-homologue and an uncharacterized gene from yeast chromosome XII.     

The study of outcomes for CAPD versus hemodialysis patients

Tacrine [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA), Cognex] is a potent acetylcholinesterase inhibitor recently approved for treatment of mild-to-moderate Alzheimer's disease. The potential for THA and/or a metabolite of THA to accumulate in brain tissue was investigated by autoradiographic and metabolic profiling techniques in rats given single and multiple doses of [14C]THA. In addition, the brain-to-plasma distribution time course of orally administered 1-hydroxy-THA (1-OH-THA, 24 mg/kg), a primary rat metabolite with anticholinesterase activity, was also examined. Results from a 16 mg/kg single-dose study showed THA to cross the blood-brain barrier readily and concentrate in brain tissue, approximately 5-fold compared with plasma. The metabolite 1-OH-THA was found in much lower amounts relative to THA and when given separately at a similar dose the levels in brain tissue were comparable with plasma concentrations. After multiple-dose administration, THA concentrations in brain tissue were approximately 3-fold higher than those achieved after a single oral dose. However, concentration of 1-OH-THA metabolite increased only 50%. These data suggest a marked difference between the ability of THA and 1-OH-THA to accumulate in brain tissue and may reflect differences in lipophilicity as estimated by calculated log p values. The relevance of THA accumulation in brain tissue to delays observed in THA clinical management of Alzheimer's disease remains to be established.     

Secondary alveolar bone grafting--five-year periodontal and radiographic evaluation in 100 consecutive cases

A prospective study of secondary alveolar bone grafting based on the Norwegian (Oslo) team approach has been conducted by the CLP Unit at the Princess Margaret Hospital for Children in Perth, Australia, since 1982. The 5-year results of 100 consecutive cases of uni- and bilateral cases are presented according to periodontal and radiographic parameters of tooth support. The vast majority of cases grafted (98%) resulted in the eventual eruption of the cleft side cuspid/lateral incisor within acceptable parameters of tooth support. The results confirm the predictability of this safe procedure when utilized within a strict clinical protocol involving the whole CLP team.