Human amnion and chorion cells from term placenta can successfully engraft neonatal swine and rats. These results may be explained by the peculiar immunologic characteristics and mesenchymal stem cell-like phenotype of these cells. These findings suggest that amnion and chorion cells may represent an advantageous source of progenitor cells with potential applications in a variety of cell therapy and transplantation procedures.

Chimerism, defined as the co-existence of cells of different origin within the same organism, has received much attention in hematopoietic cell and organ transplantation because of the strict relationship between its establishment and the induction of specific tolerance. Traditional methods applied for chimerism detection, such as immunohistochemistry, cytogenetics, fluorescent-activated cell sorter analysis, and serological and biochemical testing, are limited by their sensitivity. We have established a highly sensitive molecular approach based on the amplification of the mitochondrial cytochrome B gene and tested its specificity and sensitivity level in six different mammalian species, including human, pig, mouse, rat, sheep and rabbit. Increased sensitivity of detection of specific amplification products was obtained by the non-radioactive Southern blot technique. This novel approach allows the detection of one cell against the background of 1 to 4 x 10(6) xenogenec cells and will be helpful for high-sensitivity analysis of donor cell engraftment after xenotransplantation procedures in these animal models.

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Excessive vascular tone and overresponsiveness to adrenergic stimuli characterize the hemodynamics of the greater and the lesser circulation in hypertension. We tested whether calcium entry blockade with verapamil (11 cases) or nifedipine (11 cases) may improve the vascular regulation in high blood pressure. Mental arithmetic and cold were used as adrenergic activators. The former stimulus produced obvious elevation of epinephrine plasma concentration, increase of cardiac output (CO), slight systemic vasodilatation, pulmonary vasoconstriction, and rise of blood pressure in both circuits. After calcium antagonists, the epinephrine reaction to the arithmetic test was significantly attenuated, variations in CO and systemic blood pressure were unchanged, pulmonary vasoconstriction was abolished, and the pressure rise in the lesser circuit was halved. The cold pressor test increased norepinephrine plasma concentration (NE pc), systemic and pulmonary blood pressure, and vascular resistance and did not alter CO. The attained NE pc during cold was unvaried after verapamil and significantly enhanced after nifedipine; pressure and resistance responses of the two circuits were almost unchanged after the former, whereas systemic and pulmonary vascular resistance rises were importantly attenuated after the latter compound, resulting in much lower pressure reactivity. A modulation of the sympathoadrenal reaction, per se, can explain changes in the systemic and in the pulmonary vasomotion with calcium blockade during arithmetic. It would seem that after verapamil the sympathetic system was still activated during cold to such an extent as to maintain the same vasoconstrictor potency. NE pc suggests that the sympathetic discharge was not reduced by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunosuppression, myeloablation, and the use of immunologically immature tissue can overcome major histocompatibility complex barriers by inducing tolerance. With the goal of inducing tolerance to BALB/c-derived murine hybridoma cells producing the 4C6 monoclonal antibody (mAb), we transplanted BALB/c fetal tissue into neonatal pigs during a regimen of low-dose conditioning with busulfan and cyclophosphamide. After the tolerance induction phase, animals received intraperitoneal injections of 4C6 mAb hybridoma cells. Evidence of persistence of injected cells over time was sought by molecular analysis of peripheral blood for the presence of mouse genomic sequences and circulating 4C6 mAb. Persistence of donor polymerase chain reaction signal during the entire duration of the study, detectable mAb titer for 6 weeks, and a twofold increase of mAb concentration after a boost hybridoma infusion was observed in one animal receiving six consecutive administrations of the conditioning regimen. Our model has the distinctive advantage of allowing functional monitoring of engrafted cells for studying tolerance induction strategies. In addition, this model could be the basis for approaches aimed at producing mAbs in tolerized large animals.

Squamous cell carcinoma of the oral cavity continues to be a major clinical problem, with about 100,000 new deaths each year worldwide. There is therefore a need to search for new tools to aid oral cancer treatment. We tested the inhibitory activity on chemical carcinogenesis of the three principal protein fractions of about 50, 14, and 8.5 kDa of the mixture UK101 derived from goat liver. These are composed principally of a glycoprotein rich in mannose residues, a protein with analogy to the heat shock protein family, and ubiquitin, respectively. The animal model employed was dimethylbenzanthracene-induced hamster cheek pouch carcinoma. Number of tumours per animal, tumour mass per animal, and proliferating cell nuclear antigen (PCNA) in non-tumour mucosa were quantified: the 14-kDa fraction was the most active; this was also confirmed by testing its corresponding recombinant material. The 50-kDa fraction was inactive, while the ubiquitin showed only low inhibitory activity. It is possible that the technique described and the results obtained could lead to an interesting clinical approach to the treatment of oral cancer.