New studies on the Macushi Indians of northern Brazil

Demographic data and genetic information concerning 40 genetic systems are reported for three populations of Macushi Indians, and have been compared to those already obtained for three other communities of this tribe. These are young populations (mean age, 19 years), with a low sex ratio (90), low percentages of non-Indian ancestry (1-2%) and of marriages between locally born persons (34). Intertribal unions (14%) are less frequent than among their neighbours, the Wapishana. Fertility is high (average of 8.2 children per woman who completed reproduction), but the variance in family size and the frequency of premature deaths relatively low for populations at this cultural level. This conditions the lowest Index of Opportunity for Selection (0.45) calculated thus far among South American Indians. No variation was observed in 20 genetic systems, limited variation in 3, and larger variability in the remaining 17. In 13 of the 29 comparisons (45%), the Macushi gene frequencies present values in the middle third of the range observed among South American Indians. The previously reported private genetic polymorphism of esterase A was encountered in one of the three villages. A comparison of the genetic distances between villages with and without this polymorphism, and a similar comparison for the villages of the neighbouring Wapishana, yields no clue as to the tribe in which this polymorphism originated.     

Cytogenetic and clinical studies in gonadal dysgenesis with 46,X,Xt(qter leads to p221::p223 leads to qter) karyotype: review and phenotype/karyotype correlations.

Chromosome analysis by Q, R, and C banding was performed in a case diagnosed clinically as gonadal dysgenesis and the karyotype was shown to be 46,X,Xt(qter leads to p221::p223 leads to qter). Localisation of the breakpoints in the fused X chromosomes and replication studies have led to a hypothesis on the origin of the translocation. A comparison of clinical and cytogenetical findings in this and other published cases has also been made in an attempt to detect some phenotype/karyotype correlations.     

Selective depletion of the OKT 4+ 4B4+ subset in lymph nodes from HIV+ patients

We have used 4B4 and 2H4 monoclonal antibodies in conjunction with OKT 4 to quantify T cell subsets in lymph node suspensions from human immunodeficiency virus (HIV) positive subjects with lymphadenopathy syndrome. The data indicate that the reduced OKT 4:OKT 8 ratio was due to a depletion of the OKT 4+ 4B4+ subset. In contrast, there were no differences compared to reactive controls, considering the OKT8+ subpopulation. These alterations may be related to the immunological deficiency associated with HIV infection.     

Blood platelets in human essential hypertension

Blood platelets of patients with essential hypertension display signs of both increased sensitivityin vitro to aggregating stimuli believed to contribute to thrombosis and of activationin vivo possibly expressing the release of vasoactive products. The mean features of the modified platelet profile in hypertension include an increased ₂-adrenergic receptor density, an enhanced rate of adhesion/aggregation in particular in response to ADP and arachidonic acid, a greater sensitivity for thrombin and adrenaline to stimulate increases in cytoplasmatic-free Ca²⁺, increased resting levels of cytoplasmatic-free Ca²⁺, a reduced content of serotonin often combined with a defective uptake mechanism, a facilitated efflux rate of noradrenaline, an exaggerated release reactionin vivo as indicated by the increased plasma levels of Betathromboglobulin and a shortened platelet life span. These changes occur to various extents in some, but not all, hypertensive patients and are not always strictly related to the degree of blood pressure increase. On the contrary, platelet cyclooxygenase and thromboxane synthetase activity are in the normal range.     

Oxatomide protectsTrichinella spiralis infected mice from lethal anaphylaxis

Infection withTrichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active antiallergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice.The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.     

Dissociation between onset of natural killer E-rosette forming cells and of T3-positive cells following HLA-mismatched T cell depleted bone marrow transplantation.

We have studied immunological reconstitution following partially HLA-incompatible T cell depleted bone marrow transplantation, compared with reconstitution following HLA identical T cell depleted and HLA identical untreated bone marrow transplantation. We often observed an early emergence of E-rosette forming cells that were T3 negative and displayed strong natural killer activity in the first group of patients. This activity was shown with fresh leucocytes as well as interleukin 2 grown cells. The appearance of T3+ cells was delayed in this situation compared to that observed in HLA identical bone marrow transplantation. The delay in T3+ cell differentiation and in cellular immune function development probably explains why NK rosette forming cells are early detected within 3-4 months following HLA mismatched bone marrow transplantation. This NK subset is likely to be present at an early stage in all types of bone marrow transplantation, but is most commonly observed simultaneously with the T3+ cells in HLA identical untreated bone marrow transplantation. The respective role of T cell depletion and HLA incompatibility in this phenomenon are discussed while patients' conditioning, cyclosporine A and graft-versus-host disease have been shown to be irrelevant for the dissociation between NK E-rosette forming cells and T3+ subset onsets.     

Impaired H-2 expression in B16 melanoma variants

We studied the expression of H-2b alloantigens in three different B16 melanoma lines cultures in vitro. Cell lines were B16-F1 and two cell cultures (named B16-A and B16-B) newly derived from two different in vivo sublines of B16 melanoma. The assays used were in vivo tumour growth in allogeneic (BALB/c and B10.BR) as compared to syngeneic mice, in vitro cell-mediated cytotoxicity by anti-H-2b immune lymphocytes and absorption of anti-H-2b antisera activity. The B16-F1 line was able to efficiently kill allogeneic hosts, could not be lysed by anti-H-2b cytotoxic effectors and did not express any serologically detectable amount of H-2b alloantigens. The B16-A line was H-2 positive during the early in vitro passages, then, at the 8th-10th passages, it acquired the capacity to kill allogeneic hosts, lost the sensitivity to anti-H-2b cytotoxic effectors and the H-2Kb antigens became undetectable The expression of H-2Db was reduced, although at a lower degree. Similar data were obtained with B16-B cells, which after 10 in vitro passages grew and killed allogeneic hosts, showed a decreased sensitivity to cytotoxic anti-H-2b effectors and a very low expression of the K region antigens. The results indicate that H-2 expression is altered in B16 melanoma lines and this may influence the different metastatic capacity of such cells.     

Failure of primary breast cancer neoangiogenesis to predict pattern of distant metastasis

In the present study, the primary tumor angiogenesis characteristics of 81 stage IV previously untreated breast cancers with synchronous metastasis to different distant sites (10 patients with soft tissue metastases, 31 with bone metastases, and 40 with visceral metastases) were analyzed. The primary intratumor microvessel density was assessed by immunohistochemical assay on paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody. The mean primary intratumor microvessel density (at 400× fields) was 78±39 (SD) microvessels per field. The microvessel density was not significantly related to the main clinical/pathological features of the tumor (age, cytohistological grade, DNA ploidy, diameter, and receptor status). The percentage of tumor cases with high primary intratumor microvessel density (cut-off median value of the series 73±39 microvessels/field) did not significantly differ in patients with bone, soft tissue, or visceral metastatic disease. Aanalysis of clinical outcome showed a significantly shorter time to progression and overall survival for patients with visceral metastases (P<0.001 and P<0.0002 by log-rank, respectively). Presence of visceral metastases was confirmed to be the only independent prognostic factor related to a worse TTP (hazard risk 2.15, 95% confidence interval 1.14–4.03, P<0.02) and overall survival (hazard risk 1.81, 95% confidence interval 0.98–3.35, P<0.06) by multivariate analysis. In conclusion, the assessment of neoangiogenesis of primary breast cancer by CD34 expression does not provide information predictive of different distant sites of metastasis. Received: 15 June 2001 / Accepted: 12 September 2001     

Allograft rejection results from a failed attempt by the immune system to protect foreign tissue

The focus of our research is to understand the immune response to foreign tissue. We believe that adichotomy exists within the immune response to an allograft such that part of the response is dedicated to the protection of the graft. Nevertheless, in a dominantly graft-aggressive environment, rejection typically ensues. In this article, we describe models that have been set up to test directly the ability of potentially protective aspects of the immune response to prevent allograft rejection. We discussour data in the context of a growing body of exciting and often controversial literature.