Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A,prednisolone and azathioprine

Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo treatment. Eight weeks' postgrafting medication with cyclosporin A, prednisolone and azathioprine had resulted in survival of 14 out of 15 grafts (93%), compared with 11 out of 14 (79%) in the group treated with cyclosporin A alone. Only 2 out of 13 grafts (15%) survived in placebo-treated animals. Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need for extended immunosuppressive and antiinflammatory therapies after intracerebral grafting of histoincompatible tissues.     

GABAA and GABAB receptor agonists, partial agonists, antagonists and modulators: design and therapeutic prospects

A large number of highly selective GABA_A and, more recently, GABA_B receptor ligands have been developed and used for receptor characterization. Whereas full agonists and antagonists at GABA_A receptors, for different reasons, may be difficult to use therapeutically, partial GABA_A agonists may have therapeutic interest. The efficacious partial GABA_A agonist, THIP, shows analgesic and anxiolytic effects in man, but THIP is ineffective as an antiepileptic agent, and PET studies have disclosed that THIP increases glucose metabolism in epileptic patients and human volunteers. In principle, GABA_A antagonists may be used therapeutically in Alzheimer's disease and schizophrenia, but low-efficacy partial GABA_A agonists may have particular interest in these disorders. Using the nonannulated THIP analogue, 4-PIOL, as a lead, a series of partial GABA_A agonists showing a broad spectrum of relative efficacies have been developed.     

Quantitative ultrasound tissue characterization in shoulder and thigh muscles – a new approach

Background  

The echogenicity patterns of ultrasound scans contain information of tissue composition in muscles. The aim was: (1) to develop a quantitative ultrasound image analysis to characterize tissue composition in terms of intensity and structure of the ultrasound images, and (2) to use the method for characterization of ultrasound images of the supraspinatus muscle, and the vastus lateralis muscle.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes

Cytolytic T lymphocytes kill target cells by two independentcytolytic mechanisms. One pathway depends on the polarized secretionof granule-stored proteins including perform and granzymes,causing target cell death through membrane and DNA damage. Thesecond cytolytic effector system relies on the interaction ofthe Fas ligand (FasL) on the effector cell with its receptor(Fas) on the target cell, leading to apoptotic cell death. Usingmixed lymphocyte culture (MLC)-derived primary T lymphocytesof perforin-knockout and gld (with non-functional FasL) mice,the molecular basis of the two killing mechanisms was compared.The activity of both pathways was dependent on extracellularCa²⁺. Incubation of MLC-stimulated primary T cells with proteinsynthesis inhibitors prior to TCR triggering impaired FasL cellsurface expression and abolished cytolytic activity, althoughthe cells exhibited an intracellular pool of FasL. The perforin-dependentmechanism induced cell death more rapidly, although both pathwaysultimately showed similar killing efficiencies. Both pathwaysinduced comparable levels of DNA degradation, but Fas-inducedmembrane damage was less pronounced. We conclude that upon TCRtriggering FasL may be recruited in part from pre-existing intracellularstores. However, efficient induction of target cell death stilldepends on the continuous biosynthesis of FasL molecules.     

Bone and joint tuberculosis in Denmark

Epidemiologic data on 100 patients with bone and joint tuberculosis reported in Denmark from 1980 to 1984 are presented. The annual incidence of skeletal tuberculosis remained unchanged during the period, although most other forms of tuberculosis showed a decreasing trend. Eighteen per cent of all the cases of bone and joint tuberculosis were found among young first generation immigrants, notably from Asia. In the native Danish population, bone and joint tuberculosis was almost exclusively found among the elderly. The lesions were most common in the spine and hip. Thirty per cent of the patients had a previous history of pulmonary tuberculosis.     

Colocalization of [H]muscimol and antisera to GABA and glutamic acid decar☐ylase within the same neurons in monkey retina

Two procedures have been used to test for the colocalization of different neuroanatomical γ-aminobutyric acid (GABA)ergic markers within the same neurons in primate retina. First, sequential immunocytochemical processing of sections was done using antisera to glutamic acid decar☐ylase and to GABA, and these antisera were visualized by peroxidase-antiperoxidase and fluorescein isothiocyanate techniques respectively. Colocalization of both antisera was found within the same neuron cell bodies. In the second experiment, immunocytochemical staining using GABA antiserum was performed on retinal tissue that had been previously incubated in vitro for neuronal uptake of [³H]muscimol. Both markers colocalized in 70% of the labeled cell body population.