Killer immunoglobulin-like receptors (KIR2DL2 and/or KIR2DS2) in presence of their ligand (HLA-C1 group) protect against chronic myeloid leukaemia.

We have analysed the frequency of killer immunoglobulin-like receptors (KIR) in cohorts of patients from Turkey with acute lymphocyte leukaemia (n = 52), acute myeloid leukaemia (n = 54) and chronic myeloid leukaemia (CML) (n = 52) and compared the results with 154 controls. We also examined the frequencies of human leucocyte antigen (HLA)-C groups, -Bw4, -Bw6 and where appropriate the combination of the KIR gene and its ligand. We found several statistically significant results between the patients and the controls. We proposed a model in CML of protection via KIR2DL2 and/or KIR2DS2 with the presence of the ligand HLA-C1 group and susceptibility via HLA-Bw4 homozygosity (i.e. absence of HLA-Bw6).

No association of KIR genes with Behcet's disease.

Behcet's disease (BD) is thought to be caused by multiple genetic, environmental and immunological factors, one of the most prominent being the strong association with human leucocyte antigen (HLA)-Bw51, an HLA-Bw4-associated allele. We examined the presence/absence of 14 killer cell immunoglobulin-like receptors (KIRs) and their ligands in 134 Turkish individuals with BD and compared the results with those of 154 ethnically matched controls. Although KIR3DL1 with its ligand (HLA-Bw4) was significantly increased in the patients with BD (P = 0.0003), this no longer applied when the patients and controls were categorised by HLA-Bw51 status. Thus, no association was identified between presence or absence of any of the 14 KIR genes studied and BD. In addition, we did not find any associations of KIR with various manifestations of the disease nor with gender or age of onset.

14th International HLA and Immunogenetics Workshop: report from the reproductive immunology component.

The aim of the study was to investigate whether human leukocyte antigen (HLA) allele sharing between partners or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) and repeated implantation failure after in vitro fertilization (IVF)/embryo transfer. From a total population of 158 RSA couples, 40 couples with repeated implantation failures (IVF) and 81 control couples, reported by five different laboratories, analysis was performed for (a) HLA sharing in 50 RSA, 31 IVF and 31 control couples, (b) DQA1*0505 sharing/homozygosity among partners in 108 RSA, 40 IVF and 36 control couples, and (c) the women's KIR repertoire in 46 RSA, 26 IVF and 36 control wives. RSA couples were divided into alloimmune aborter (RSAallo) and autoimmune aborter (RSAauto). The results oppose to the suggestion that increased HLA sharing per se or a limited maternal KIR repertoire predisposes to RSA or IVF failure. However, the observation of a slightly higher percentage of DQA1*0505 sharing in the RSAauto and the IVF group needs further investigation. The ratio of inhibitory to activating KIR (actKIR) was slightly lower in RSAallo and IVF women (1.9 vs 2.6 in controls), while in a high percentage of these women, the standard receptors of the KIR A haplotype were combined with actKIR/s of the haplotype B (66.6% and 45.4% vs 20% and 15.3% in RSAauto and control groups). This may suggest a possible involvement of actKIRs in embryo implantation and the maintenance of pregnancy and also requires further investigation.

Passage of spermidine across the blood-brain barrier in short recirculation periods following global cerebral ischemia: effects of mild hyperthermia.

Transport of a polyamine (PA), spermidine (SPMD) into rat brain at various early postischemic periods was studied. Rats underwent 20 min of four-vessel occlusion (4VO) followed by 5, 10, 30 and 60 min of recirculation (RC) periods with natural brain temperature. 3H-aminoisobutyricacid (AIB) and 14C-SPMD were utilised to search dual functions of the blood-brain barrier (BBB); barrier and carrier functions, respectively. Unidirectional blood-to-brain transfer constant (Kin) was calculated for AIB and SPMD in four brain regions-parieto-temporal cortex, striatum, hippocampus and cerebellum. Kin for SPMD ranged between 1.2+/-0.3 x 10(3) ml g(-1) min(-1) (for striatum) and 2.2+/-0.4 x 10(3) ml g(-1) min(-1) (for cerebellum) in controls. Kin for AIB showed similar values. At 5 and 10 min RC periods, Kin for both substances increased in a non-specific manner in all brain regions studied. In the cortex, Kin for SPMD at 5 and 10 min RC periods were 3.2+/-0.4 x 10(3) and 2.9+/-0.3 x 10(3) ml g(-1) min(-1), respectively, and found to be maximum with respect to other brain regions studied. 30 and 60 min RC groups showed specific transport for SPMD, whilst there were no changes for Kin for AIB, in all brain regions studied. Hippocampus showed the maximum increase in Kin SPMD at 60 min RC (2.7+/-0.3 x 10(3) ml g(-1) min(-1)), corresponding to a percentage rise of 121%. Intraischemic mild brain hyperthermia (39 degrees C) gave rise to a striking increase in Kin at 60 min postischemia for both substances. These results suggest that there is a specific transport of SPMD into brain at 30 and 60 min RC periods following 20 min of forebrain ischemia. Moreover, dual functions of the BBB were perturbed with intracerebral mild hyperthermia during ischemia.

Effects of spermidine treatment on neurobehavioral development in intrauterine growth retarded (IUGR) rats.

It was previously shown that polyamine treatment could induce precocious development of several somatic and neurobehavioral functions in newborn rats. This study investigates the effects of daily injections of spermidine (SPMD) 50 microl/10 g s.c. on neurobehavioral development of newborn rats experiencing undernutrition. Neurobehavioral development was assessed by measurements of gripping and righting reflexes. SPMD treated intrauterine growth retarded (IUGR) rats reached righting reflex control values at 30 days postnatal (1.87 +/- 0.78 s vs 1.75 +/- 0.66 s). Beginning from 7 days postnatal, gripping reflex values of SPMD treated IUGR rats declined, reaching that of controls at 30 days postnatal (1.77 +/- 91 degrees vs 1.82 +/- 65 degrees). These results suggest the utility of exogenous SPMD in rats experiencing undernutrition, thus indicating a clinical relevance.

Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat.

This study was designed to investigate the possible protective actions of nicotine on cerebrovascular permeability in convulsions during nicotine-induced seizures. We have measured the permeability changes in the blood-brain barrier (BBB) macroscopically and spectrophotometrically by using Evans blue dye. Specific gravity measurements were also performed to assess brain edema which develops after blood-brain barrier opening. The experiments were carried out on Wistar rats. Rats were divided into two groups. They received acutely a convulsive dose of nicotine 3, 5, 8 and 9 mg kg(-1)i.p. or pretreated with a low dose of nicotine (0.8 mg kg(-1)i. p.) for 21 days followed by the procedure mentioned in the first group. Acute nicotine injection induced a significant increase in blood pressure and Evans-blue passage, despite a decline in specific gravity values. Low doses of chronic nicotine administration markedly reduced both the leakage of dye, and brain water content. Chronic treatment with low doses of nicotine (0.8 mg kg(-1)day(-1)s. c.) lessened the intensity of tonic-clonic seizures observed with a single dose of 3, 5, 8 or 9 mg kg(-1)nicotine. The data presented here demonstrate that nicotine pretreatment results in decreased sensitivity to nicotine-induced seizures in rats.

Changes in the permeability of the blood-brain barrier in acute hyperammonemia. Effect of dexamethasone.

This study was designed to determine the contribution of elevated plasma ammonia levels to blood-brain barrier (BBB) abnormalities in the presence of intact liver. The permeability changes of the BBB were investigated grossly with Evans blue (EB) and quantitatively by measuring the blood-to-brain transfer content for alpha-aminoisobutyric acid (AIB) in normal rats and rats subjected to sublethal doses of ammonium acetate (NH4OAc) (750 and 600 mg/kg ip; at 30-min intervals). Some rats were pretreated with dexamethasone (DXN). Injection of NH4OAc increased both plasma and brain ammonia concentrations about 16-and 5-fold, respectively, above the control level. In rats receiving NH4OAc injection, the blood-to-brain transfer constant (Ki) for AIB was increased 3- to 11-fold. The elevated Ki values were limited to certain gray matter areas and less pronounced permeability changes were detected in white matter. Extravasation sites of EB were more restricted and were especially observed in thalamus and cerebellum, whereas cortex and white matter were unaffected. Dexamethasone pretreatment for 3 d reduced both leakage of EB and the Ki for AIB in NH4OAc injected animals, whereas acute treatment appeared ineffective. Dexamethasone did not prevent the development of coma but slightly decreased the ammonia concentration in plasma and brain. The results obtained indicate that hyperammonemia may disrupt BBB integrity not only to AIB and EB but also enhance the transport of other solutes.