Seasonal effects on fetal selection related to AB0 blood groups of mother and child.

An association of AB0 blood groups and month of birth was examined in two groups, students and newborns in Tokyo. Among 4919 students born mainly in the 1960s, an apparent seasonal variation was shown in births of blood group B students. Among 3592 newborns at an obstetric clinic in the 1980s seasonal variation was also observed in all four blood groups. The ratio of 0 group to A group newborns (0/A ratio) from 0 mothers was lower than that from A mothers among the 0 and A pairs contrary to the expected effects of 0-A incompatibility. The 0/A ratio was apparently different by season and the 0/A ratio from 0 mothers was significantly lower than that from A mothers among those born during August-January. It is assumed that an association of birth season with AB0 blood group may be caused by some seasonally and secularly changing environmental "infertility factors" such as infectious microorganism which may have some common components with a particular blood group substance respectively and induce a loss of embryos selectively at a particular season.     

Potential side effects of insect-resistant transgenic plants on arthropod natural enemies.

Engineering genes encoding insecticidal proteins into crop plants offers numerous benefits to agriculture. However, like many conventional insecticides, this new technology has the potential to disrupt natural biological control through both direct and indirect side effects of the plants on the fitness or behaviour of arthropod predators and parasitoids. Interactions between transgenic plants and these beneficial insects are being assessed to avoid incompatibility.     

T-cell depletion and haematological side effects of two cytotoxic monoclonal antibodies.

We investigated two cytotoxic monoclonal antibodies of BL-series (BL-IIIB4 and BL-IIG2) according to T-lymphocyte depletion from bone marrow. Both antibodies work together with human complement similar Campath-1, which was tested parallelly. The extent of T-cell depletion is about 95% for all three antibodies. On the other hand the haemopoietic side effects tested by CFU-GM recovery and LTBMC are for the BL-antibodies not as strong as for Campath-1, especially in view of LTBMC. T-cell regeneration could be shown in long term cultures. Our results indicate a possible suitability of the two investigated antibodies for T-cell depletion of bone marrow.     

Hydrogen bonding of adenine derivatives to tyrosine side chain.

High resolution proton magnetic resonance measurements provide evidence for the formation of hydrogen-bonded complexes between 9-ethyladenine and p-cresol used as a model of tyrosine side chain in CDCl3. We have calculated the sum of the association constants corresponding to the three existing 1:1 complexes: K=6.3+/-0.15. By methylation of the amino group of adenine, we were able to calculate the ratio of the two strongest equilibrium constants K7/K1=1.6+/-0.3. Theoretical computations by the complete neglect of differential overlap (CNDO/2) method indicate that several hydrogen-bonded planar complexes can form between 9-methyladenine and phenol. The computed energy of the complexes with 6-dimethylamino adenine removes some ambiguity concerning the computed ratio of the association constants. Comparison of the calculated energies with free energies experimentally determined in organic solvent shows that despite the competition with CDCl3, which associates with both solute molecules, the preferential order of association is conserved. The small variations of charge density of adenine carbon atoms when complexed with phenol are in agreement with very small chemical shifts observed by 13C-nuclear magnetic resonance.     

Plasma exchange for removal of anti-A and anti-B group antibodies in AB0 major-incompatible bone marrow transplantation

Between 1980-1986 seven patients underwent AB0-major incompatible bone marrow transplantation. Incompatible anti-A and anti-B antibodies could be decreased by the plasma exchange from titers 8-256 down to 0-8. Our practice combined with additional depletion of erythrocytes from marrow allowed to transplant all patients successfully, however, one patient demonstrated an acute haemolytic reaction during infusion of marrow. Plasma exchange was fairly well tolerated, however, 4 patients developed slight urticarial reactions. Both thrombocytopenic patients overcompensated the platelet loss caused by the exchange.     

The antibody-enzyme analogy. Characterization of antibodies to phosphopyridoxyltyrosine derivatives.

Stable analogs of the crucial Schiff base intermediate of enzymatic and nonenzymatic pyridoxal phosphate catalysis have been used as haptens for induction of specific antibodies. N-(5-phosphopyridoxyl)-3'-amino-L-tyrosine and its conformationally distinct cyclized derivative resemble the Schiff base formed upon mixing tyrosine with pyridoxal phosphate. These compounds were covalently coupled to a protein carrier via the 3'-amino group so as to confer a prescribed orientation, with the coenzyme region farthest removed from the carrier. A third antigen, with the phosphopyridoxyl group alone as the hapten, was prepared by linkage of pyridoxal phosphate directly to free amino groups on the carrier protein. Antibodies elicited for each determinant were purified by means of appropriate affinity columns. Antibody heterogeneity was observed in that different species could be separated from a given serum by sequential elution from the affinity columns with 1 M sodium phosphate buffers of pH 7.6, 5.2, 2.6 and 1.5. In assays of quantitative precipitation, inhibition of precipitation, equilibrium dialysis, and fluorescence quenching, antibodies to the phosphopyridoxyltyrosine haptens showed specificity for the phosphorylated form of the coenzyme and binding activity for both the coenzyme and tyrosine portions of the hapten. Antibodies to the phosphopyridoxyl groups alone did not display a similar reactivity toward the tyrosine portion of the complex haptens. The cyclic and noncyclic conformations of the hapten were serologically distinct, as antibody to each reacted preferentially with the homologous form.     

Blood antigens in the AB0 system and susceptibility of humans to diphtheria

The analysis of a large number of diphtheria cases (1326) at the peak of diphtheria morbidity in Russia (1993-1994) revealed that the intensity of antidiphtheria antitoxic immunity was age-dependent with a sharp immunodeficiency in the population aged 35 years and older. As adaptive capacity of the organism decreases, the positive associative links between immunity to diphtheria and the AB0 blood groups become evident. Populations with phenotype B (III) had the largest diphtheria immune stratum at the age of 35 years and over as compared to 3 other phenotypes. The genotypic analysis of serological data may be of practical importance for the detection of the degree of predisposition of humans to infectious diseases.     

In vivo effects of a treatment with antibodies to adipocyte plasma membranes in the rabbit

Antibodies against rabbit adipocyte plasma membranes were injected in 6-week-old rabbits. Controls received normal IgG. Animals were killed 1, 2, 5 or 9 weeks after treatment. Body weight and food intake were reduced significantly until the 7th week for the live weight and the 5th week for the intake. Whatever the anatomical location considered, adipose tissue was markedly reduced: -75% for week 1 and -20% for week 9 respectively for the total adipose mass. Cell volume and enzymatic activities of G3PDH, LPL and LDH were highly decreased during the first 2 weeks after treatment. Simultaneously the plasma levels of triglycerides and plasma free fatty acids were increased. As shown by others in the rat, it is possible to induce a long-term fatness reduction in the rabbit by treatment with antibodies to adipocyte plasma membranes. The cytotoxic effects of antibodies have also been discussed.     

The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics

Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability.     

Potential application of aromatic plant extracts to prevent cheese blowing

This study aimed to inhibit the growth of Escherichia coli and Clostridium tyrobutyricum, common bacteria responsible for early and late cheese blowing defects respectively, by using novel aqueous extracts obtained by dynamic solid–liquid extraction and essential oils obtained by solvent free microwave extraction from 12 aromatic plants. In terms of antibacterial activity, a total of 13 extracts inhibited one of the two bacteria, and only two essential oils, Lavandula angustifolia Mill. and Lavandula hybrida, inhibited both. Four aqueous extracts were capable of inhibiting C. tyrobutyricum, but none were effective against E. coli. After extracts’ chemical composition identification, relationship between the identified compounds and their antibacterial activity were performed by partial least square regression models revealing that compounds such as 1,8 cineole, linalool, linalyl acetate, β-phellandrene or verbene (present in essential oils), pinocarvone, pinocamphone or coumaric acid derivate (in aqueous extracts) were compounds highly correlated to the antibacterial activity.     

Genetic risk assessment towards warfarin application: Saudi Arabia study with a potential to predict and prevent side effects

Warfarin doses are greatly affected by polymorphism altering cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) gene. This study evaluated the prevalence of alleles (either single or double) and carriers of single nucleotide polymorphisms (SNPs) in both genotypes CYP2C9 and VKORC1 in alkharj area, Saudi Arabia and its association with warfarin use risk. Total 112 samples were collected and genotyped using FlexiGene DNA Kit for isolation and StepOnePlus Real-Time PCR System by TaqMan allelic discrimination methods. The results indicated the frequency of 11%, 8% and 45% for CYP2C9 *2 *3 and VKORC1-1639 G > A polymorphism. And as a combination genotype it was 15.18% For both CYP2C9 and VKORC1 polymorphism, 27.67% for CYP2C9 and 42.86% for VKORC1. Non-carriers rate came to be at 30.3%. According to previously published dosing changes in warfarin for polymorphism carriers (single-double-triple). The predicted warfarin doses reduction in order of 1–1.6, 2–2.9, 2.9–3.7 mg/day. It was found that 72.3% of the study population was carrier of a type of polymorphism, 15.18% for two types of polymorphisms. These findings predict changes in warfarin metabolism and eventually dosing alteration among patients on warfarin. Both genotypes (CYP2C9 and VKORC1) require different dosing of warfarin than non-carriers in order to minimize the risk of warfarin overdosing and avoidance of the drug-related problems (DRPs).