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Diversity of some gene frequencies in European and Asian populations. V. Steep multilocus clines.

Regions of abrupt genetic change, which result from either rapid spatial change of selective pressures or limited admixture, were investigated in Europe and Asia on the basis of eight red cell markers typed in 960 samples. Two methods were employed, one based on genetic distances and one on evaluation of the first derivative of the surfaces representing allele-frequency variation. Genetic divergence tends to be maximal between populations that are separated by physical factors (mountain ranges and seas) but also separated by cultural barriers (different language affiliation). This suggests that mating isolation, rather than adaptive response to environmental change, accounts for spatially abrupt genetic change at the loci studied and that cultural differences associated with language contribute to isolating populations. Although selection may have determined two wide allele-frequency gradients, the genetic structure of European and Asian populations seems primarily to reflect isolation by distance when investigated on a small scale and migration patterns (or absence of migration) when investigated on a larger scale.

Alleles

Changing patterns of migration between metropolitan and nonmetropolitan areas in the United States: recent evidence.

Data from the 1975 Current Population Survey confirm that, during 1970-1975, there was a reversal of the traditional net migration stream between metropolitan and nonmetropolitan areas in the United States. During this period, there was net in-migration of 1,600,000 persons to nonmetropolitan areas, in contrast to net out-migration of 350,000 persons from these areas in 1965-1970. Reversal was caused by a 12 percent decrease in the number of nonmetropolitan out-migrants and a 23 percent increase in the number of SMSA residents moving to nonmetropolitan territory over 1965-1970 levels. While some changes in the size of migration streams were due to changes in age structures and population bases in metropolitan and nonmetropolitan areas, they were caused primarily by real shifts in out-migration propensities at practically all ages in both areas.

Age Factors

Lymphocyte traffic and the skin.

Lymphocyte migration patterns into and within lymphoid organs and nonlymphoid organs such as the skin as highly regulated and controlled by a variety of factors, some of which we are beginning to understand at a basic cellular and molecular level. In the case of lymphocyte migration into lymphoid organs, recirculatory patterns and preferences appear to be mediated by selective recognition via lymphocyte membrane receptors of distinctive determinants expressed by specialized endothelial cells in different organ sites. A similar model in which endothelial cells in the skin share common determinants with endothelial cells in peripheral lymph nodes can be developed to explain the migration patterns of lymphocytes from the blood into the skin. Cells that have undergone blast transformation in the microenvironment of the skin or peripheral lymph nodes, or both, appear to recirculate selectively within this particular sphere of immunologic influence, whereas other cells that undergo this transformation in the microenvironment of the gastrointestinal tract and its draining mesenteric lymph nodes selectively recirculate within that sphere of immunologic influence. This preferential recirculation increases the probability that the immunologic defense needs of a given region or tissue such as the skin will be met efficiently and appropriately. Finally, some of the phenotypic characteristics favoring the movement of lymphocytes from the bloodstream into the dermis (such as recent stimulation and the presence of T-cell surface markers) also seem to favor lymphocyte migration into or retention in the epidermis. However, under appropriate circumstances, epidermotropism can be exhibited by both major subsets of T cells as well as a variety of non-T cells.

Animals

Characterization of rotavirus electropherotypes excreted by symptomatic and asymptomatic infants.

Human rotavirus isolates from 1100 stool samples were analyzed by polyacrylamide gel electrophoresis, and 48 different migration patterns were detected. Heterogeneity in the migration of segment 10 was observed in both long and short electropherotypes in which three long and two short patterns were identified. In spite of these variations all short and long electropherotypes were subgrouped by enzyme immunoassay as subgroups I and II respectively. Mixed infections were detected in 17% of cases and the subgrouping correlated with the corresponding electropherotypes. The same electropherotypes were present in severe, mild and asymptomatic cases and no electropherotype was particularly associated with greater virulence. Furthermore, the electropherotypes isolated from nosocomial asymptomatic cases were the same as those detected from those admitted with severe diarrhea. It seems unlikely that electropherotyping can be used to identify more virulent strains of rotavirus.

Carrier State

Isolation of two human tumor epithelial cell lines from solid breast carcinomas.

Most of the available human breast tumor cell lines have been derived from pleural effusions. The two cell lines herein described, BT-474 and BT-483, were derived from solid, invasive ductal breast carcinomas. Both are epithelial and neoplastic as judged by their general morphology, their fine structure, and their ability to produce growing nodules in nude mice and colonies in soft agar and methocel. BT-474 and BT-483 are human as expressed by chromosome morphology and aneuploid with a modal number of 55 and 72 chromosomes, respectively. Trypsin-Giemsa banding did not reveal the presence of obvious HeLa markers, and the glucose 6-phosphate dehydrogenase electrophoretic migration pattern was of the B-type. Furthermore, the migration of lactic dehydrogenase, malic dehydrogenase, and 6-phosphogluconate dehydrogenase isoenzymes was consistent with a human pattern and different from that of the mouse, rat, or hamster. Quarterly tests to detect the presence of aerobic and anaerobic mycoplasmas were repeatedly negative. A culture medium containing insulin, increased amounts of amino acids, vitamins, and glucose facilitated the isolation of the tumor cells. Cell replication was maintained with 10% fetal calf serum absorbed with activated charcoal and dextran. No production of alpha-lactalbumin was detected by radioimmunoassays, but high levels of progesterone receptors were found in both cell lines.

Animals

Migration properties of circular DNAs using orthogonal-field-alternation gel electrophoresis.

The migration of a series of supercoiled plasmids ranging in size from 4 to 91 kilobases (kb) has been analyzed by orthogonal-field-alternation gel electrophoresis (OFAGE). These circular DNAs enter OFAGE gels and are resolved over the same region of the gel as linear DNAs from 260 to 2200 kb. Furthermore, a distinct triphasic migration pattern was observed for the supercoiled DNAs. The migration of plasmids between 6 and 20, and 60 and 91 kb is inversely proportional to size, whereas the mobilities of plasmids between 20 and 60 kb increase with size. Unlike linear DNA molecules, the relative mobilities of these plasmids are constant over a broad range of pulse times, from 10 to 120s. Electrophoresis of supercoiled, relaxed, and nicked open circular forms as well as topoisomers of small plasmids shows that the extent of supercoiling has a dramatic effect on plasmid migration on OFAGE. Several practical applications for exploiting the different migration properties of circular and linear DNA molecules on OFAGE are presented.

Animals

Alcohol dose and low density lipoprotein heterogeneity in squirrel monkeys (Saimiri sciureus).

The present study was designed to determine whether normolipidemic male squirrel monkeys (Saimiri sciureus) exhibit low density lipoprotein (LDL) heterogeneity similar to that observed in humans and if present, whether LDL subfractions are altered by consumption of low vs. high dose ethanol (EtOH). Primates were divided into three groups designated control, low, and high EtOH and fed isocaloric liquid diets containing 0%, 12% and 24% of calories as EtOH, respectively, for 6 months. The 12% EtOH caloric level resulted in a modest, non-significant increase in high density lipoprotein (HDL) cholesterol and no change in LDL cholesterol or plasma apolipoprotein B (apo B), while the 24% dose produced significant elevations in plasma, LDL and HDL cholesterol and apo B. Using a single-spin density gradient ultracentrifugation procedure developed for humans, three distinct LDL subclasses designated LDL1a (d = 1.031 g/ml), LDL1b (d = 1.038 g/ml) and LDL 2 (d = 1.046 g/ml) were isolated from all three treatment groups. Monkey LDL subfractions were nearly identical to very light, light and heavy LDL subspecies isolated from human plasma in terms of their: (1) isopycnic densities following ultracentrifugation; (2) co-migration as single bands with beta-electrophoretic mobility in cellulose acetate and agarose electrophoretic gels; (3) size-dependent migration pattern in polyacrylamide gradient electrophoretic gels; (4) co-migration as a single band corresponding to apo B-100, following SDS polyacrylamide gel electrophoresis; and (5) decrease in total cholesterol/protein ratios with increasing LDL subclass density. Although there were no treatment differences in LDL particle size, within each treatment group, mean particle size for each LDL subfraction was significantly different from every other subfraction. Low (12%) dose alcohol had no effect on LDL subfraction mass relative to controls while high alcohol consumption resulted in marked increases in all lipid (except triglyceride) and protein of the larger, buoyant LDL subspecies (LDL1a and LDL1b). Moreover, the best correlation between plasma apo B and LDL subfraction total mass was demonstrated with LDL1b (r = 0.735). Since neither the lipid nor the protein concentration of the small, dense, purportedly more atherogenic, LDL2 changed with the 24% EtOH dose, we propose that the LDL subfraction alterations associated with high alcohol intake in squirrel monkeys (increased LDL1a, increased LDL1b, LDL2 no effect) may represent a compensatory response to modulate the overall atherogenic lipoprotein profile associated with elevations in total LDL cholesterol and plasma apolipoprotein B.

Animals

New temperate bacteriophage for Bacillus subtilis, rho 11.

A new temperate bacteriophage, rho11, isolated by J. Hoch, has been characterized. This new phage is very similar to the temperate phage phi3T in size (380 nm), host range, homoimmunity, DNA buoyant density (1.694 g/ml), antigenicity, and molecular weight (around 6.0 X 10(7)) as determined in gels. Like phi3T, rho11 converts thymine auxotrophs to prototrophy at high frequency (250 out of 250 tested). Phage rho11 differs from phi3T in plaque morphology and in the endonuclease R-EcoRI digest pattern. Sixteen of the 20 rho11 DNA fragments have migration patterns corresponding to those of the 21 fragments of phi3T. The close similarities yet clear differences between these phages suggest that the two phages have a common ancestor.

Bacillus subtilis

Trends in return migration to the South.

The rate of return migration to the South rose by nearly 19 percent between the late 1950's and the late 1960's and was an important factor in changing the South's overall migration pattern. But an increase in the rate of return migration was somewhat less important in changing Southern migration than (1) a decline in the rate of out-migration of native Southerners and (2) an increase in the rate at which non-Southern-born persons move to the South. The probability of former migrants returning to the South was over four times greater for whites than for blacks in the 1955-1960 period and three and one-fourth times greater in the 1965-1970 period. Since 1970 the rate of return migration has apparently continued to rise at a faster rate for blacks, but the black rate of return migration is still below the white rate.

Adolescent

Genetic variation at the immunoglobulin allotype loci in Creoles of Trinidad.

The sera of a sample of 204 Creoles from Trinidad were tested for the presence of polymorphic gene complexes occurring on immunoglobulin light- and heavy-chain molecules including the allotypic markers IGKC 1, IGHA2 1 and 2, IGHG1 A, X, F, and Z, and IGHG3 G, G5, B0, B1, B3, B4, B5, C3, C5, S, and T. Nine IGHG (GM) haplotypes occur in polymorphic frequencies (greater than .01) in this population, including known African, Asian, Caucasian, and Amerindian marker haplotypes. Significant differences (P less than .01) were found in the frequency distributions of three IGHG (GM) haplotypes and the frequency of IGKC*1 in these data and data from Creole populations of Belize and St. Vincent. The Creoles of Trinidad and St. Vincent are more similar in IGHG (GM) haplotype distributions than are Trinidad and Belize populations. Previous testing has revealed no significant differences between St. Vincent and Belize Creoles at the Ig allotypic loci. Analysis of migration patterns in the Caribbean suggests that different rates of Asian migration have maintained regional diversity at these loci, while continuous gene flow from the eastern Caribbean to Trinidad has had a relative homogenizing effect on the gene pools of this area.

Chi-Square Distribution

Importance of rotavirus and adenovirus types 40 and 41 in acute gastroenteritis in Korean children.

To examine the role of rotavirus (Rv) and adenovirus types 40 and 41 (Ad40/41) in Korean children with acute gastroenteritis, we evaluated 345 children with acute gastroenteritis and 90 children without acute gastroenteritis in Seoul, Korea, during a 29-month period. Stools were tested for group A Rv antigen and for Ad40/41 by using monoclonal antibody (MAb)-based assays. Rv was found in 68% of the ill children and 19% of the controls (P less than 0.001), whereas Ad40/41 was detected in 9% of the ill children and 2% of the controls (P less than 0.05). Also, 6% of the ill children and 0.01% of the controls excreted Rv and Ad40/41 simultaneously. Among the ill children, 96% of children with Rv and 94% of those with Ad40/41 were younger than 24 months. Although a peak of Rv infection was detected in early winter in both years of the study, there was no apparent seasonal trend with Ad40/41. Diarrhea with more than 10 stools per day, vomiting, or fever was most strongly associated with Rv shedding, whereas the first two manifestations were associated with coinfection of Rv and Ad40/41. To investigate the genetic and serotypic diversity of Rv strains, we tested 195 and 144 fecal Rv specimens isolated from the gastroenteritis cases, respectively, by polyacrylamide gel electrophoresis of the segmented RNA genome and by an enzyme-linked immunosorbent assay with serotype-specific MAbs. Of the 195 specimens, 154 yielded RNA patterns characteristic of group A Rv: 18% had short electrophoretic migration patterns, 81% had long patterns, and 1% had a mixture of short and long patterns. Of the 144 specimens, serotype specificity was determined in 51%: 89% were serotype 1, 10% were serotype 2, and 1% were serotype 3. Analysis of the specimens for which electropherotypes and serotypes were available indicated that a given RNA pattern corresponded to a particular serotype, except in one strain that showed short patterns but serotype 1. We suggest that Rv and Ad40/41 in stools be accepted critically as an important cause of diarrhea among young children in Korea.

Acute Disease

Effects of epidermal growth factor, fibroblast growth factor, and transforming growth factor-beta on corneal cell chemotaxis.

The effects of recombinant basic fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) on migration of human and bovine corneal cells were determined using checkerboard analysis in Boyden chambers. EGF, FGF, and TGF-beta each stimulated high levels of chemotactic migration. Each growth factor, however, induced a different dose-response pattern. Migration stimulated by FGF reached a plateau at a concentration between 100 and 200 ng/ml for endothelial, epithelial, and stromal fibroblasts. By contrast, chemotactic responses to EGF peaked between 10 and 50 ng/ml, then decreased at higher concentrations. TGF-beta also stimulated a peak in migration in all three corneal cells, but the peak of migration occurred at an approximately 1000-fold lower concentration (1 pg/ml) than for EGF. Checkerboard analysis demonstrated that FGF and EGF, but not TGF-beta, stimulated chemokinesis of bovine, stromal, and endothelial cells. These results demonstrate that FGF, EGF, and TGF-beta induce migration in pure populations of bovine and human corneal cells and support the concept that these growth factors may play key roles in corneal wound healing by regulating migration of corneal cells.

Animals

T-cadherin expression alternates with migrating neural crest cells in the trunk of the avian embryo.

Trunk neural crest cells and motor axons move in a segmental fashion through the rostral (anterior) half of each somitic sclerotome, avoiding the caudal (posterior) half. This metameric migration pattern is thought to be caused by molecular differences between the rostral and caudal portions of the somite. Here, we describe the distribution of T-cadherin (truncated-cadherin) during trunk neural crest cell migration. T-cadherin, a novel member of the cadherin family of cell adhesion molecules was selectively expressed in the caudal half of each sclerotome at all times examined. T-cadherin immunostaining appeared graded along the rostrocaudal axis, with increasing levels of reactivity in the caudal halves of progressively more mature (rostral) somites. The earliest T-cadherin expression was detected in a small population of cells in the caudal portion of the somite three segments rostral to last-formed somite. This initial T-cadherin expression was observed concomitant with the invasion of the first neural crest cells into the rostral portion of the same somite in stage 16 embryos. When neural crest cells were ablated surgically prior to their emigration from the neural tube, the pattern of T-cadherin immunoreactivity was unchanged compared to unoperated embryos, suggesting that the metameric T-cadherin distribution occurs independent of neural crest cell signals. This expression pattern is consistent with the possibility that T-cadherin plays a role in influencing the pattern of neural crest cell migration and in maintaining somite polarity.

Animals

Antigen-induced changes in lymphocyte circulatory patterns.

The effect of a splenic or lymph node anti-sheep red blood cell response on lymphocyte migration patterns in mice was studied. It was found that trapping of lymphocytes in these stimulated organs was indiscriminate and was followed by a period of restricted cell entry or localization; furthermore, reduced cell localization in the spleen, during the splenic response, was accompanied by a reduction in the number of cells localizing in unstimulated brachial and axillary lymph nodes. These results were taken to indicate that major changes occur in lymphocyte circulation during strong splenic immune responses.

Animals

Inhibitory effect of cetirizine 2HCl on eosinophil migration in vivo.

The effect of a potent antihistamine, cetirizine, was studied on allergic patients and normal subjects by means of an in-vivo 'skin window' technique. All subjects showed significant inhibition of skin-test responses to grass pollen, compound 48/80, histamine and methacholine, after administration of a single dose (10 mg) of cetirizine. Compared to placebo, cetirizine significantly decreased the eosinophils attraction at skin sites challenged with grass pollen and compound 48/80. In allergic patients no change in eosinophil migration pattern was noted with histamine and methacholine skin-tested sites. In normal subjects, compound 48/80 and histamine did not induce eosinophil accumulation and cetirizine did not modify cellular patterns as compared to placebo. These results suggest that cetirizine acts on eosinophil migration by inhibiting the release of mast cell mediators or inhibiting the eosinophilotactic mediators themselves.

Adult

Cells and immunoglobulins in lymph.

Studies of the free-floating lymphocytes and of the immunoglobulins in lymph collected over long periods of time from ducts draining individual tissues of the body as well as from the thoracic duct of the fetus in utero have been reviewed. The findings show that stimuli within the internal milieu act on different classes of lymphocytes to alter their migration pattern, morphology, metabolic activity, and range of immunological potentialities. As the lymphoid cells migrate between the blood, tissue fluid, and lymph, a continual process of reassortment occurs leading to the establishment of heterogeneous lymphoid cell populations in different regions of the lymphatic apparatus. It seems that the biological activities of these cells are not decided only in terms of a thymus or a bone-marrow origin. The immunoglobulins, like other proteins in lymph, are mainly derived by filtration from the circulating plasma. Some of the immunoglobulins and specific antibodies are synthesized, however, by lymphoid cells and secreted directly into the lymph.

Antibody-Producing Cells

Timing and patterns of astrocyte migration from xenogeneic transplants of the cortex and corpus callosum.

The timing, pattern, and pathway of astrocyte migration were investigated in vivo by transplantation of CD-1 mouse cerebral cortex (E13-14) or corpus callosum (P2-3) into neonatal rat cortex. A monoclonal antibody specific for a mouse astrocyte surface antigen (M2) was used to identify the location of the grafts and the migrated donor astrocytes. Within the host cortex, astrocytes from cortical grafts began migration at post-transplantation day (PTD) 7. Over the next 4 days, the most distant displaced donor cells were found progressively further away from the grafts, migrating at a rate of about 220 microns/day. After PTD 11, the migration rate for the farthest displaced donor cells slowed to 25 microns/day, and the cells appeared to stop at about PTD 16 at a distance of 1,100 microns from the edge of the graft. Astrocytes had a faster migration speed in the white matter and covered a longer distance (5 mm) than those in the gray matter, extending on occasion into the contralateral hemisphere. The patterns of astrocyte migration differed depending on local cues around the transplant. Donor astrocytes that had been implanted into the host cortex migrated toward the host cortical surface, sometimes in several radial lines. Astrocytes from grafts, especially callosal grafts, placed in the subcortical white matter migrated along the host fiber tracts. Many astrocytes transplanted into the hippocampus formed laminar patterns close to the hippocampal neuronal layers. These results suggest that the direction, pattern, and speed of astrocyte migration are influenced by local substrates in the host brain.

Animals

Elderly Hispanic migration in the United States.

The specific aim of this study was to extend the analysis of migration patterns to Hispanics (Mexican, Cuban, Puerto Rican, and Other Hispanic) over the age of 60. The 1980 Census public use sample provided the data for this study, which was structured by four research expectations derived from features of the Hispanic population and from migration concepts. First, because of population growth, migration from abroad was expected to be heavy, and about half came from abroad. Second, because of the pattern of Hispanic population concentration and the different settlement patterns of the four subgroups, a relatively small migration system with distinct subsystems for the four nationality groups was expected and found. Florida is the major ethnomagnet. Third, traditional family values, as reflected in dependent living arrangements, were expected to be more prevalent among migrants from abroad, and they were. Finally, returning to one's state of birth was highest among Mexican interstate migrants, as expected.

Aged