The HLA-A,B gene frequencies in the world: Migration or selection?

Multivariate methods make it possible to condense much of the information available for a large number of alleles into one or a few synthetic variables. The geographic distribution of synthetic variables can be analyzed and plotted by the same technique used in analyzing and mapping the gene frequency of a single allele. The information contained in 21 HLA-A and HLA-B alleles from 116 world populations is condensed in principal components and discriminant functions which describe the global variation of gene frequencies along longitudes and along latitudes.

Most genetic variation is associated with longitude and shows a center of symmetry in Asia. Thus Asia, or some part of it, may have been the center, both geographically and historically of late Pleistocene migrations. However, latitude also plays a significant role (perhaps 10% of the genetic variation). A remarkable symmetry of the latitude variation in opposite (north and south) hemispheres suggests that climatic factors exercise selective pressure for certain HLA alleles. More specifically A1, A3, B7, B8, and B27 show about equally high correlation coefficients (between 0.45 and 0.55) with distance from equator. This results supports the idea that the well-known linkage disequilibria between A1 and B8, A3 and B7 are probably kept by selective pressure.     

Behavioral development in mice: Effects of maternal environment and the albino locus

We examined the interaction of the albino locus with the maternal environment on the behavioral development of two coisogenic strains of mice. Subjects of the pigmented C57BL/6 strain (=B6^+/+) and of the albino C57BL/6^c2J strain (=B6^c/c) were either fostered by a mother of their own strain or cross-fostered at birth to an F₁ hybrid dam. They were compared for the amount and daily distribution of activity displayed during 48 h in a seminatural device at weaning and when 75 days old. Food hoarding in the nest and food consumption at the food-search place were also recorded in adult subjects. When animals were fostered by a mother of their own strain, albino mice were more active and less nocturnal than pigmented mice at both ages. They hoarded less food in the nest and ate more at the food-search place. Most of these differences disappeared when both strains were fostered by an F₁ dam. The amount of activity displayed during 48 h increased between 21 and 75 days of age. This increase was affected by cross-fostering to an F₁ dam in B6^c/c mice only. The developmental pattern of daily distribution of activity was changed by F₁ dams in B6^+/+ mice only. Whereas these influences of F₁ dams produced subjects resembling the mother's phenotypic score, maternal effects on hoarding behavior in B6^c/c mice produced subjects which did not resemble their foster mother. The results are discussed in terms of different possible ways of hereditary transmission of behavior and some methodological consequences are emphasized.     

HLA-B alleles of the Navajo: no evidence for rapid evolution in the Nadene

New HLA-B locus alleles have been found in South American Amerindian populations but were largely absent in North American Amerindian tribes also descended from this first Paleo-Indian migration. We have now extended these studies to the Navajo, descendants of the second Nadene migration. No new functional alleles were found at the B locus of this tribe. This limited study supports the notion that while new B locus variants are common in South American Amerindians, it is more difficult to find new B locus alleles in North American native peoples. Whether this dichotomy is due to differences in pathogen environment and/or population structures between North and South America remains a subject of speculation.     

Correspondence between the dopamine islands and striosomes of the mammalian striatum

During the development of the mammalian striatum, the early-forming dopamine innervation is broken up into macroscopic patches called "dopamine islands". These express high tyrosine hydroxylase-like immunoreactivity and are also rich in acetylcholinesterase activity. The mature striatum has prominent macroscopic compartments called "striosomes" that were first characterized by their low acetylcholinesterase activity and since have been related to heterogeneities in striatal input-output organizations. This report describes two sets of experiments designed to determine the relationship between the dopamine islands and the striosomes. The distributions of striatal tyrosine hydroxylase-like immunoreactivity and acetylcholinesterase activity were first compared in a series of kittens and young cats ranging in age from 1-228 postnatal days. During this time, the pattern of tyrosine hydroxylase-like immunoreactivity changed from islandic (patchy) to diffuse, and the pattern of acetylcholinesterase staining changed from one of acetylcholinesterase-rich patches to one of acetylcholinesterase-poor striosomes. The dopamine islands were in register with the acetylcholinesterase-poor patches at early developmental stages and at later stages the islands matched striosomes. These observations establish a correspondence between the dopamine islands and striosomes and demonstrate that the acetylcholinesterase-rich patches of the immature caudate nucleus become the acetylcholinesterase-poor striosomes of the adult. In a second set of experiments, cat fetuses were exposed to [3H]thymidine at embryonic days 22-29 in order to label the clustered subpopulations of striatal neurons known from previous experiments to lie in striosomes [Graybiel and Hickey (1982) Proc. natn. Acad. Sci. U.S.A. 79, 198-202]. The [3H]thymidine-labeled brains were examined at late fetal (embryonic days 50-52), early postnatal (days 1-21) and later postnatal (days 62-199) ages. The clusters of [3H]thymidine-labeled neurons were aligned with tyrosine hydroxylase-rich, acetylcholinesterase-rich patches early in development, and with acetylcholinesterase-poor striosomes at later stages. There were marked dorsoventral differences in the intensity of tyrosine hydroxylase-like immunoreactivity in the dopamine islands and this was confirmed in neonatal rats. A "dorsal islandic system" was defined as having crisp, highly immunoreactive islands; ventrally, regions of low and medium tyrosine hydroxylase-like immunoreactivity formed a mosaic.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma antiviral activity and interferon-gamma production by superantigen-stimulated lymphocytes during normal human pregnancy

PROBLEM: Plasma interferon (IFN)-beta levels, lymphocyte responsiveness, and evaluation of the relationship between circulating antiviral activity (AA) and IFN-gamma production were studied in pregnant women and nonpregnant age-matched controls with the objective of elucidating the downregulation of IFN-gamma production in successful pregnancy. METHOD OF STUDY: In plasma and supernatants of peripheral blood mononuclear cell (PBMC) cultures, stimulated with staphylococcal enterotoxin A (SEA) superantigen, from 43 pregnant women with a history of normal pregnancy and 30 healthy nonpregnant age-matched controls, levels of AA were measured in a micromethod by inhibition of the cytopathic effect (CPE) caused by vesicular stomatitis virus (VSV) in the human amnionic cell line (WISH). RESULTS: Significantly higher plasma AA (60% was IFN-gamma and residual activity was acid-labile IFN-like) was present in pregnant women than controls. On the other hand, SEA-activated PBMCs from pregnant women produced significantly lower IFN-gamma levels than those of nonpregnant women. Furthermore, maternal plasma AA levels correlated negatively with IFN-gamma production by SEA-stimulated PBMCs. CONCLUSION: The hypothesis that successful pregnancy requires downregulation of IFN-gamma is only partially sustained, suggesting that the immunology of pregnancy is more complex and that murine and human pregnancy have different cytokine profiles.     

Definition of HLA-C alleles using sequence-specific oligonucleotide probes (PCR-SSOP)

Abstract: Many new HLA-C locus alleles have recently been identified by DNA sequencing, and a molecular based method for their detection using PCR with sequence specific primers has been reported. However, other methods may be more appropriate for the identification of C locus alleles in larger studies. Here we describe one such system, based on PCR sequence specific oligonucleotide probes, (SSOP) for C locus typing. Advantages of SSOP typing compared to SSP are that it is easier to detect new alleles, more cost effective and less time consuming. We have developed a DNA typing method to identify the broad C locus antigens (including those not yet defined serologically) using a minimum of probes with one amplification. We use a C locus specific sense primer in exon 2 and a consensus antisense primer in exon 3, in a two-step PCR, giving a product of 710 bp. Probes were designed with similar melting temperatures (54–56C) that would identify as many alleles as possible. The method was established using DNA from B lymphoid cell lines of known C locus type, mostly 10th workshop homozygous cell lines, plus as many other sequenced cell lines as possible. The system was able to correctly identify their C locus types using only 26 probes. DNA was tested from a panel of serologically typed individuals which included many different heterozygous combinations. We found a high concordance of results, with all discrepancies being additional antigens identified by molecular typing, filling in serological blanks. We can identify all common heterozygote combinations using this method.     

大鼠蓝斑内P物质、神经降压肽和生长抑素样神经元的上行投射

本实验采用HRP逆行追踪与免疫细胞化学相结合的方法,对大鼠蓝斑内P物质(SP)、神经降压肽(NT)、生长抑素(SOM)三种肽能投射神经元的纤维联系及其局部关系进行了探讨。结果证实:1.HRP注射至丘脑或尾壳核后,大鼠蓝斑内均可见到双标记神经元。2.存在SP样和NT样蓝斑—丘脑纤维,前者终止于丘脑腹后核和板内核,后者终止于丘脑板内核。3.蓝斑至尾壳核的投射呈SOM样免疫反应。4.蓝斑内三种肽能投射的起始和终止部位有所不同,其中SP样和NT样神经元主要位于蓝斑后部背侧区,其纤维终于丘脑;而SOM样投射神经元则见于蓝斑前部背侧区,纤维终止于尾壳核。上述肽能通路均为双侧性,而以同侧占优势。5.蓝斑内三种肽能单标记神经元中以NT样免疫反应阳性胞体最为丰富。以上结果表明;蓝斑上行性投射中除含去甲肾上腺素纤维外,还含有SP样、NT样和SOM样纤维,并存在一定的局部定位投射关系。     

Skewed T cell receptor V{alpha} repertoire among superantigen reactive murine T cells

Reactivity of murine T cells with viral or bacterial superantigensis clearly correlated with the expression of TCR V_ßdomains. Thus, T cells responding to the minor lymphocyte stimulatorylocus (Mls-1^a) or staphylococcal enterotoxin B (SEB) expresspredominantly TCR V_ß6 or V_ß8.2 respectively.We have investigated the involvement of the other major variableelement of the TCR, the V domain, in these superantigen responses.Using a panel of anti-TCR V mAbs, It is demonstrated that theTCR V repertoire among superantigen stimulated V_ß6⁺or V_ß8.2⁺ blasts (responding to Mls-1^a or SEB respectivelyin vitro) is altered in comparison with anti-CD3 stimulatedcells expressing the same V domains. Furthermore, the TCR Vrepertoire is strongly skewed in TCR V_ß8.2 transgenicmice that have undergone extensive peripheral clonal deletionafter SEB injection. These data imply that the V domain influencessuperantigen recognition by sthe TCR.     

Induced recombination and reversion of theCDC8 gene in relation to the cell cycle of yeast

Summary The induction of mitotic recombination in theCDC8 locus was studied in a diploid strain heteroallelic forcdc8 mutations (cdc8-1/cdc8-3); mitotic reversion was studied in strainscdc8-1/cdc8-1 andcdc8-3/cdc8-3. Conversion and reversion did not occur in those cells blocked at the S stage of the cell cycle by exposure to a nonpermissive temperature. In stationary phase cells irradiated just prior to exposure to temperature stress, the induction of recombinants was rather low and the induction of revertants was minimal. Conversely, a significant induction ofcdc ⁺ occurred in logarithmic phase cells subjected to the same treatment. Irradiation of synchronously dividing cultures revealed that intragenic recombination occurs at all three stages of the cell cycle- G₁, S and G₂. It was also found that UV-induced gene reversion can occur during the S and G₂ stages, but not during the G₁ stage of the cell cycle.