Determination of gene organization in the human IGHV region on single chromosomes

Organization of the IGHV genes (n=108) on single human chromosomes has been determined by detecting these sequences in single sperm using multiplex PCR amplification followed by microarray detection. A total of 374 single sperm samples from five Caucasian males were studied. Three deletion/insertion polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1 to 0.3 were identified. Del I is a previously reported polymorphism affecting three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18 kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans approximately 21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous state, and therefore, could not be easily detected if haploid samples were not used in the study. Results of the present study indicate that deletions/insertions together with other possible chromosomal rearrangements may play an important role in forming the genetic structure of the IGHV region, and may significantly contribute to antibody diversity. Since these three polymorphisms are located within or next to the 3' half of the IGHV region, they may have an important role in the expressed IGHV gene repertoire during immune response.     

Uteroplacental blood flow measured by placental scintigraphy during epidural anaesthesia for caesarean section

The uteroplacental blood flow was measured before and during epidural anaesthesia for caesarean section in 11 women. The blood flow was measured with dynamic placental scintigraphy. After an i.v. injection of indium-113m chloride, the gamma radiation over the placenta was recorded with a computer-linked scintillation camera. The uteroplacental blood flow could be calculated from the isotope accumulation curve. The anaesthesia was performed with bupivacaine plain 0.5%, 18-22 ml and a preload of a balanced electrolyte solution 10 ml/kg b.w. was given. The placental blood flow decreased in eight patients and increased in three with a median change of -21%, not being statistically significant. No correlation between maternal blood pressure and placental blood flow was found.     

The effect on uteroplacental blood flow of epidural anaesthesia containing adrenaline for caesarean section

The effect on uteroplacental blood flow of an epidural anaesthesia containing adrenaline for caesarean section was investigated in ten healthy women using dynamic placental scintigraphy with indium-113m and a computer-linked gamma camera. The epidural anaesthesia was performed with 18-22 ml bupivacaine 5 mg/ml with adrenaline 2.5 micrograms/ml followed by an i.v. balanced electrolyte infusion of 10 ml/kg b.w. A significant median decrease in the total maternal placental blood flow of 34% was found (P less than 0.01). There was also a significant decrease in maternal mean blood pressure of 3 mmHg (0.4 kPa) (P less than 0.05) and a significant negative correlation between the change in maternal blood pressure and the change in uteroplacental blood flow (r = -0.69, P less than 0.05).     

The orphan receptor GPR55 is a novel cannabinoid receptor

BACKGROUND: The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes. EXPERIMENTAL APPROACH: Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgammaS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways. KEY RESULTS: We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgammaS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1 or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Galpha13 and can mediate activation of rhoA, cdc42 and rac1. CONCLUSIONS: These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).     

INTERRELATIONS BETWEEN PLASMA AND TISSUE CONCENTRATIONS OF 17 β-OESTRADIOL AND PROGESTERONE DURING HUMAN PREGNANCY

Oestradiol and progesterone concentration in plasma, decidua, myometrium and placenta obtained from women undergoing Caesarian section at term and abortion at weeks 16-22 of pregnancy were determined. There was a significant increase in oestradiol concentration (per g wet wt) both in placenta, decidua and myometrium from mid-term to term. Both at mid-term and term oestradiol concentrations in decidua and myometrium were much smaller than those in the plasma (per ml). Progesterone concentration in placenta and in myometrium did not increase from mid-term to term where it increased significantly in decidua. Decidual and myometrial progesterone concentrations at mid-term were 2-3 times higher than those in plasma, but at term the concentrations in both these tissues were lower than in plasma. The ratio progesterone/oestradiol in plasma, decidua, myometrium and placenta at mid-term was 8.7, 112.2, 61.4 and 370.0, respectively, and it decreased significantly in the myometrium and placenta but was nearly unchanged in plasma and decidua at term. The general conclusion to be drawn from the present study is the lack of correspondence between the plasma concentrations and the tissue concentrations of female sex steroids during pregnancy.     

Interethnic genetic differentiation: HLA class I antigens in the population of Mongolia

A total of 1668 individuals representing 10 major Mongolian ethnic groups were serologically typed for HLA-A, -B, and -C antigens. Antigens A2, A24, B61, B51, B58, Cw3, Cw7, and Cw6 were the most frequent specificities in Mongolians and no case of B42 was noted in all ethnic groups. The cluster analysis of Principal Components I and II shows that Mongolian speaking groups form one cluster vs Turkic-speaking Kazakhs. The analysis reveals a low, but significant differentiation of Mongolian ethnic groups as measured by F_ST = 0.0100 (P < 0.001). Gene diversity analysis shows that the genetic diversity of the Mongolian population can be attributed largely to its ethnic component, which makes up 64% of total genetic variation. The low degree of interpopulation variation and high level of intrapopulation diversity can be explained by the nomadic way of life of this indigenous population. Three-locus haplotypes A24-B61-Cw3, A33-B58-Cw3 are the most common haplotypic associations in Mongolians. The presence of antigens characteristic of Mongoloid, Caucasoid, and Negroid populations in Mongolians suggests a unique genetic background of this indigenous population. The three-locus haplotype distribution among Mongolians relative to other world populations supports the migration of ancient people from Central Asia to the New World, Korean Peninsula, and Southeast Asia. Am. J. Hum. Biol. 11:603–618, 1999. © 1999 Wiley-Liss, Inc.     

Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20–87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20–84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.