Trisomy 13 and myelodysplastic syndrome

The clinical and cytogenetic data of a patient with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) and trisomy 13 as the sole abnormality are presented. This appears to be only the second report of such a patient. The presence of trisomy 13 is confirmed by in situ hybridization using an alphoid repeat probe L1.26, which is specific for the centromeres of both chromosomes 13 and 21.     

Human T hybridoma-derived immunoglobulin-binding factors

A human T hybridoma was generated lacking demonstrable low-affinity IgE surface receptors. This cell line produces spontaneously immunoglobulin-binding factors. The factors have an affinity for human IgE and IgG as well as for IgG from other species. The binding factors were purified by concanavalin A affinity chromatography, an IgE immunoaffinity column and SDS-PAGE. This purification procedure resulted in five major proteins bands at 13, 15, 30, 60 and less than 150 kilodaltons. As judged by Western blot analysis, all bands were variably glycosylated and were capable of binding IgE. Biological activity resided even within the small molecular weight (13 kilodaltons) peptide in terms of inhibiting IgE synthesis of the U266 B cell line and net IgE synthesis of B cells from atopic blood donors. Additionally, semipurified binding factor preparations also inhibited the Pokeweed mitogen-induced IgG synthesis while stimulating IgE synthesis at the same time. At present it is not clear whether the different molecular entities are dimers or polymers of the same protein, or are all derived from one larger protein (proteolytically cleaved), or whether they are completely different peptides mediating similar immunoglobulin-binding capacities as well as similar biological activities. Glycosylation of binding factors is not responsible for binding to immunoglobulins, but might be important for its biological activity.     

Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients

The fragile X syndrome is the most frequent cause of inheritedmental retardation. The molecular mechanism of the disorderis based on the expansion of a CGG repeat in the 5' UTR of theFMR1 gene In the majority of fragile X patients. The instabilityof this CGG repeat containing region is not restricted to theCGG repeat Itself but expands to the flanking region as well.We describe four unrelated fragile X patients that are mosaicfor both a full mutation and a small deletion in the CGG repeatcontaining region. Sequence analysis of the regions surroundingthe deletions showed that both the (CGG)_n repeat and some flankingsequences were missing in all four patients. The 5' breakpointsof the deletions were found to be located between 75–53bp proximal to the CGG repeat. This suggests the presence ofa hot spot region for deletions in the CGG repeat region ofthe FMR1 gene and emphasizes the instability of this regionIn the presence of an expanded CGG repeat.     

Prolactin and propranolol prevent the suckling-induced inhibition of lactation in rabbits

The normal once-a-day frequency of suckling in the rabbit was increased on day 31 (late lactation) by the addition of two extra sucklings (8 and 16 hr after) the daily suckling. In confirmation of previous data, two additional sucklings significantly decreased milk yield acutely on day 31 in comparison with the average 4-day milk yield before and after day 31. The decrease in milk secretion after the two additional sucklings was prevented by a single injection of 3 mg prolactin (given 24 hr before the two extra sucklings) and/or by injections of the beta-adrenergic-blocking drug, propranolol (100 micrograms/kg b. wt. given 30 min before each additional suckling). Since prolactin secretion is decreased in these species and the mammary gland is less responsive to the hormone during late lactation, the present results suggest that in addition to these factors, suckling-induced activation of sympathetic influences may contribute to the decline in milk production at this stage of lactation. Taken together, these results suggest that suckling may regulate lactation in the rabbit through antagonistic mechanisms at different stages of lactation.     

Induction of immunological tolerance to the penicilloyl antigenic determinant. III. Suppression of benzylpenicilloyl-specific IgE antibody formation by cleavable penicilloylated dextran

The suppressive effect of cleavable penicilloylated dextran (BPO-DEX), whose directly bound penicilloyl groups undergo hydrolytic cleavage within 3 days under physiological conditions, on murine IgE antibody formation against the benzylpenicilloyl (BPO) determinant was investigated in BALB/c and C3H mice. Intraperitoneal administration of BPO-DEX during either primary or secondary IgE responses to BPO ascaris produced a reversible suppression of BPO-specific IgE, while not affecting carrier-specific IgE antibody formation. Suppression of longer duration, at least 10 weeks, was achieved, however, by repeated administrations of BPO-DEX. BPO-DEX itself did not generate detectable BPO-specific IgE antibodies. These results suggest that BPO-DEX might be one of the promising tolerogens in the prevention of penicillin allergy.     

Enzymatic activities induced by interferon in human fibroblast cell lines differing in their sensitivity to the anticellular activity of interferon

IF^r, a subline of transformed human fibroblast cells, which is sensitive to the antiviral but resistant to the anticellular activity of interferon, was found to be equally well inducible as its parental cell line RSa for the two major interferon-mediated double-stranded RNA-dependent enzymatic activities, 2–5A synthetase and 73K phosphoprotein kinase. The induction of 2-5A synthetase as a function of interferon dose, the specific activity of the 2-5A synthetase, the nature of the 2-5A oligonucleotide products, and the activity of the 2-5A-activated endonuclease were essentially the same for both cell lines. The 73K phosphoprotein kinase was induced at a similar rate of activity, whether detected in solution or after immobilization on poly(I)·poly(C)-Sepharose. Our observations thus suggest that the induction of these two enzymatic activities are not sufficient for the anticellular activity of interferon.     

Macrophages in bronchoalveolar lavage fluid do not represent macrophages in granulomas of the lungs of BCG-infected mice

In normal mice the phenotype of macrophages in the BAL fluid accurately reflects the phenotype found for the macrophages in the alveoli, but in BCG-infected mice the macrophages in the BAL fluid do not resemble those occurring in either the alveolar spaces or the granulomatous lesions.     

Pheromones and novel male-induced pregnancy disruptions in mice: exposure to conspecifics is necessary for urine alone to induce an effect

Previous research indicates a role of pheromones in novel male-induced early pregnancy disruptions. Although some reports suggest that urine alone is sufficient to produce this effect, others raise procedural concerns and fail to replicate such effects. On Days 1 to 5 after insemination, female CF-1 mice had their nasal regions repeatedly painted with water, urine from males housed in isolation, or urine from males housed in proximity to females. Almost all (87.5%) of the control females delivered litters. There was a small nonsignificant reduction in proportion parturient (78.5%) among females exposed to urine of males housed without social contact. The proportion of females parturient (57.1%) after treatment with urine from males housed in proximity to females was significantly different from controls. The magnitude of the effect of socially stimulated male urine is substantially less than that recorded when males are housed directly above inseminated females separated by a wire-mesh grid. These data suggest that production of pregnancy-disrupting male pheromones is stimulated by contact with conspecifics.     

Use of ecarin clotting time in whole blood for monitoring recombinant hirudine treatment during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia

Lepirudin (Refludan is a recombinant hirudin, approved for anticoagulation treatment of heparin-induced thrombocytopenia patients with thrombosis. We report here our method for laboratory monitoring with ecarin clotting time (ECT) of hirudin therapy as anticoagulation for cardiac surgery. Ecarin is extracted from the Echis carinatus snake venom and directly converts prothrombin to its intermediate, meizothrombin. This one binds in a stoechiometric way to hirudin to be proportioned in whole blood. The activation of coagulation starts up only when the totality of the hirudin is bound to the meizothrombin. To minimize the effect of dilution related to the CEC on the prothrombin and fibrinogen levels, thus lengthening the ECT, the specimen to be tested is diluted with normal whole blood. In 1997, when we have performed our first surgery with cardiopulmonary bypass, only one team (P?tzsch et al., 1997) had described the use of the ECT in whole blood. We describe in this work our assay to dose hirudin with ECT after dilution in whole blood. This assay was used during 8 CEC among 7 patients affected with HIT (n = 6) or potentially sensitized with heparin (n = 1). Experimental conditions and interpretation of the assay are reported here. This test is fast enough to provide useful information for adjusting the dose during cardiopulmonary bypass.