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Neurogenesis and cell migration into the sexually dimorphic preoptic area/anterior hypothalamus of the fetal ferret.

A sexually dimorphic male nucleus (MN) of the preoptic area/anterior hypothalamus (POA/AH), comprising large, estradiol-receptor containing neurons, is formed in male ferrets due to the action of estradiol, derived from the neural aromatization of circulating testosterone, during the last quarter of a 41-day gestation. Two experiments were conducted to compare the birthdates and the migration pattern of cells into the sexually dimorphic portion of the dorsomedial POA/AH as well as the nondimorphic ventral nucleus (VN) of the POA/AH of males and females. In experiment 1 the thymidine analog, bromodeoxyuridine (BrdU), was injected into the amniotic sacs of fetuses of different mothers between embryonic (E) days 18 and 30. Kits from all mothers were sacrificed on E38, and brains were processed to localize BrdU immunoreactivity (IR) for determining the birthdates of neurons in the POA/AH. Cells in the MN-POA/AH of males and in a comparable region of females were born between E22 and E28; cells in the nondimorphic VN-POA/AH of both sexes were born between these same ages. These results suggest that cells in the sexually dimorphic as well as the nondimorphic subdivision of the ferret POA/AH are born during the same embryonic period. This is well before the ages (E30-E41) when administering testosterone to females can stimulate, and blocking androgen aromatization in males can inhibit, MN-POA/AH differentiation. In experiment 2 BrdU was injected on E24, and kits from different litters were perfused on E30, E34, or E38. Brains were processed for BrdU-IR as well as glial fibrillary acidic protein (GFAP), which served as a marker for radial glial processes. The orientation of radial glial processes in fetal brains of both sexes suggested that cells migrate into the dorsomedial POA/AH from proliferative zones lining the lateral as well as the third ventricles. Quantitative, computer-assisted image analysis of BrdU-IR in groups of male and female brains supported this hypothesis. There were no significant sex differences in the distribution of BrdU-IR over the three ages studied, suggesting that formation of the MN-POA/AH in males cannot be attributed to an effect of estradiol on the migration of those cells born on E24 into this sexually dimorphic structure. Finally, total BrdU-IR did not change significantly in the POA/AH of male and female kits killed at E30, E34, or E38 while the area of the POA/AH increased more than 2.5-fold over this period, suggesting that few of the POA/AH cells born on E24 die during this period in either sex. In the absence of evidence that formation of the male ferret's MN-POA/AH depends on steroid-induced changes in neurogenesis, cell migration, or death, we suggest that the specification of a particular neuronal phenotype (e.g., large somal size; capacity to produce some undetermined neurotransmitter or neuropeptide) may be responsible.

Animals↗

Parasite genotypes identify source populations of migratory fish more accurately than fish genotypes.

DNA-based assignment of individuals to their population of origin has many applications such as mixed-stock analysis, identifying individuals from protected populations, and elucidating migration patterns. However, low genetic differentiation among populations will cause misassignments. Thus, an alternative means of determining an individual's population of origin is needed in cases where there is little or no neutral differentiation among source populations. Here, we test the hypothesis that parasite genotypes can be used to identify the origins of hosts more accurately than host genotypes. Using microsatellite markers from steelhead trout and their trematode parasites, we show that the odds of correct assignment are four times greater with the parasite's genotypes than with the host's genotypes. Our analyses show that this result is simply explained by the greater genetic structure among populations of the trematode parasite. Recent studies on the comparative genetic structure of other host and parasite species suggest that our results are not unusual or unique to the host-parasite system we studied. Thus, our work indicates that parasites will be useful for a wide range of applied and basic research that requires the assignment of individuals to source populations.

Animal Migration↗

Lifetime migration to the major cities of the United States, Asia, and Africa.

"The purpose of this paper is to compare and contrast the lifetime migration patterns into the major cities of selected developed and developing countries. This study was confined to cities in...the United States and certain Asian and African countries with relevant published data.... This paper has shown that some lifetime population movements were exceptionally high. Two-thirds of the residents of the major U.S. cities in 1970 were born elsewhere. The major cities in sub-Saharan Africa were second highest with 60 percent. Asian cities followed with 48 percent of their residents being lifetime migrants and the cities of North Africa were lowest with less than a third. Finally, the native population born and reared in most urban agglomerations will probably comprise a larger percentage of the total population in those areas in the future." (SUMMARY IN FRE AND ITA)

Africa↗

New monoclonal antibody (4E9R) identifies mouse neural crest cells.

In order to analyze migration patterns of mouse neural crest cells, we produced a rat anti-mouse monoclonal antibody (4E9R) which identifies these cells. The distribution of 4E9R-immunoreactive cells was examined in migratory stages of mouse neural crest cells, ranging from embryonic day (Ed) 8.5 to 10.5. In the cephalic region of Ed 8.5 embryos, some mesencephalic mesenchymal cells close to neural folds were 4E9R-positive. In Ed 9.0-9.5 embryos, streams of 4E9R-immunoreactive cells extending from cranial neural tubes to maxillary processes and to first visceral arches were found in the lateral region and some of these cells were localized in presumptive trigeminal ganglia. In the same embryonic stages, 4E9R-positive cells were present in mesenchymal cells around the optic and otic vesicles. In the trunk region of Ed 9.5-10.5 embryos, 4E9R-positive cell masses were observed in dorsolateral spaces adjacent to neural tubes. The presence of 4E9R-immunoreactive cells in somitic segments was restricted within the anterior halves and these cells were seen under the dermomyotome and/or in the medial portion of the sclerotome. These cells colonized in presumptive dorsal root ganglia and in the surroundings of the dorsal aorta, the embryonic area in which sympathetic ganglia are formed. 4E9R-positive cells were also found just under the epidermis. These observations indicate that the distribution of 4E9R-positive cells is similar to that of amniote neural crest cells reported previously. Furthermore, the data suggest that the migratory behavior of mouse neural crest cells at trunk levels may be different between rostral and caudal levels within an anterior half of the sclerotome, and that sympathetic ganglia may be formed by neural crest cells migrating along "ventromedial pathways" as well as "ventrolateral pathways" at hindlimb-bud levels of mouse embryos. In primary cultures of mouse neural crest cells, approximately 80% of the cells were 4E9R-positive on culture day 2. Further, we have shown in cultures treated with colchicine or cytochalasin B that 4E9R antigens are present in intermediate filaments. When image analysis with a confocal laser scanning microscope was performed on primary cultures of mouse neural crest cells, the intracellular localization of 4E9R antigens in these cells was comparable to that of vimentin, which is a typical intermediate filament in most mesenchymal cells in embryonic stages examined. Since the distribution of 4E9R-positive cells and anti-vimentin-immunoreactive cells was different in mouse embryos, it is suggested that 4E9R antigens are vimentin-related and specifically expressed in a few cell types including mouse neural crest cells. These results indicate that a rat anti-mouse monoclonal antibody 4E9R is useful for the identification of mouse neural crest cells during the migratory stages.

Animals↗

Endogamy and inbreeding since the 17th century in past malarial communities in the Province of Cosenza (Calabria, Southern, Italy).

Many authors stressed the importance of considering mating patterns, migration and consanguinity when analysing micro-geographic differences in the distribution of the frequency of genetic traits (thalassaemia and glucose 6 phosphate dehydrogenase deficiency (G6PD) in populations living in areas of past malarial endemy. Therefore, the present work was aimed at estimating the reproductive isolation of Calabria, an Italian region that experienced endemic malaria until very recently. The research was carried out on 15311 records of marriage from Parish Books of four villages located in the past malarial area, and four situated in the non-malarial region. Endogamy rates were high in every village and decreased only in the present century as a consequence of the breakdown of isolation. In the earlier periods, the rates ranged between 93-84% in non-malarial villages, and between 96-66% in the past malarial area. The rate of consanguineous marriages was low in all villages: in the malarial area it was 2.15% on average, whereas in the non-malarial villages it ranged between 2-16%. Its trend increased with time almost everywhere. Concerning values, differences between past malarial and non-malarial villages in earlier periods are not consistent as they ranged from 0.1 x 10(-3) to 1 x 10(-3). In the present century, however, a was higher in the non-malarial villages. Observed changes of the coefficient a since the 19th century are due to the increased frequency of first cousin marriages. Isonymy rates were lower than 2% in all past malarial towns in all periods, whereas in nonmalarial villages they ranged between 1.2-9.5% and increased with time. Inbreeding coefficients F are always higher than alpha values, but show the same trend with time. They were between 0.0006-0.0045 in past malarial towns, and between 0.0017-0.024 in non-malarial villages. In non-malarial villages Fn displayed noticeable negative values in two situations in the earlier periods. In conclusion, given the above mating patterns and the observed distribution of frequencies of G6PD deficient hemizygous and thalassemic heterozygous in the investigated villages, there is clear evidence in this area for the absence of any specific role of reproductive isolation and consanguinity on the distribution of genetic traits related to past malaria presence.

Consanguinity↗

Migration and differentiation of bone marrow lymphocytes: development of surface immunoglobulin, Fc receptor, complement receptor, and functional responsiveness as studied with anti-allotype serum.

Immunofluorescent studies using fluorescein isothiocyanate-conjugated mouse anti-allotype antibody were carried out to study the migration pattern and the development of surface Ig (SIg), Fc receptor for IgG (FcR gamma), and complement receptor (CR) or mouse bone marrow lymphocytes following intravenous injection into congenic mice. After transfer of bone marrow cells from CSW mice into untreated congenic CWB mice, the absolute number of donor-type SIg-bearing (SIg+) cells and the proportion of either FcR gamma- or CR-bearing (FcR gamma+ or CR+) cells in donor-type SIg+ cells were evaluated in the recipient spleen and the results were compared with those obtained after the transfer of CSW spleen cells. After injection of donor bone marrow cells, detectable donor-type SIg+ cells, although few initially, increased from day 1 to Day 2 and reached a plateau thereafter. The proportion of FcR gamma+ cells in donor-type SIg+ cells, although very low in the donor marrow inoculum, increased progressively after 1 day to reach a maximum at Day 5 (90%). On the other hand, following the transfer of spleen cells, the proportion of FcR gamma+ cells remained at high levels (90%) for 5 days after transfer. Likewise, the proportion of CR+ cells in donor-type SIg+ cells was very low (less than 1%) in the original donor bone marrow cells but high (60%) in the donor spleen cells. However, in transferring bone marrow cells this proportion also increased in the recipient spleen to reach a maximum (49%) at Day 5 although it was lower compared to the percentage of FcR gamma+ cells in donor SIg+ cells. Furthermore, the ability of functional responsiveness to antigen was also examined in the same system by detecting plaque-forming cells (PFC) from donor origin. In transferring donor bone marrow cells into recipient, the participation of donor cells in the PFC response was very low when the recipients were primed with sheep red blood cells at Day 3 after transfer. However, when the recipients were primed at Days 7 to 21 after transfer, increasing numbers of the donor marrow-derived cells were involved in the PFC response. Thus, the present study demonstrates that the bone marrow-derived lymphocytes, albeit lacking both distinctive surface receptors (IgM, FcR gamma, CR) and the functional responsiveness to antigen, continue their development along the B-cell lineage after migrating into the spleen, as evidenced by the surface receptor expression and participation in the antibody response.

Animals↗

Symmetry-breaking in mammalian cell cohort migration during tissue pattern formation: role of random-walk persistence.

Coordinated, cohort cell migration plays an important role in the morphogenesis of tissue patterns in metazoa. However, individual cells intrinsically move in a random walk-like fashion when studied in vitro. Hence, in the absence of an external orchestrating influence or template, the emergence of cohort cell migration must involve a symmetry-breaking event. To study this process, we used a novel experimental system in which multiple capillary endothelial cells exhibit spontaneous and robust cohort migration in the absence of chemical gradients when cultured on micrometer-scale extracellular matrix islands fabricated using microcontact printing. A computational model suggested that directional persistence of random-walk and dynamic mechanical coupling of adjacent cells are the critical control parameters for this symmetry-breaking behavior that is induced in spatially-constrained cell ensembles. The model predicted our finding that fibroblasts, which exhibit a much shorter motility persistence time than endothelial cells, failed to undergo symmetry breaking or produce cohort migration on the matrix islands. These findings suggest that cells have intrinsic motility characteristics that are tuned to match their role in tissue patterning. Our results underscore the importance of studying cell motility in the context of cell populations, and the need to address emergent features in multicellular organisms that arise not only from cell-cell and cell-matrix interactions, but also from properties that are intrinsic to individual cells.

Animals↗

Prehistoric juvenile rheumatoid arthritis in a precontact Louisiana native population reconsidered.

Descriptions of skeletal pathological conditions evident in the prehistoric Tchefuncte adolescent 16ST1-14883b are clarified. The basis is reaffirmed for assigning to the described pathological conditions a diagnostic perspective of juvenile rheumatoid arthritis or juvenile Lyme disease--a disease that mimics juvenile rheumatoid arthritis in its arthritic presentation--rather than of assigning them as representative of juvenile onset ankylosing spondylitis or other juvenile spondyloarthropathies. A hypothesis (Lewis [1994] Am. J. Phys. Anthropol. 93:455-475) is restated that 1) the spirochete Borrelia burgdorferi was the infectious agent responsible for prevalence of adult rheumatoid arthritis in prehistoric southeastern Native American populations, 2) that B. burgdorferi is a possible cause of the arthritis evident in individual 16ST1-14883b, and 3) that antibodies to B. burgdorferi provided partial immunity to the related spirochete Treponema pallidum for the 16ST1 precontact Tchefuncte population from Louisiana, protecting them from severe treponemal response. Given the probable widespread existence of Ixodid tick vectors for B. burgdorferi in prehistoric North America, coupled with the existence of treponematosis, it follows that the transition of Native American hunting-gathering economies to more sedentary economies would predictably be linked to an increased incidence of treponematosis due to the loss of benefits of the above-stated partial immunity. In other words, as prehistoric Native American exposure to tick vectors for B. burgdorferi decreased, susceptibility to treponematosis increased. Inferences regarding biological controls interacting with and influencing prehistoric Native American migration patterns are suggested from the link of B. burgdorferi to an Ixodid tick common to northeast Asia.

Adolescent↗

Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas.

To define the possible role of the VHL gene in the development of sporadic renal cell carcinomas, 91 different parenchymal tumours of the kidney have been investigated for mutation of the VHL gene by single strand conformation polymorphism (SSCP) and/or heteroduplex (HD) techniques. Chromosome 3p deletion was detected in 98 per cent of non-papillary renal cell carcinomas and in 25 per cent of chromophobe renal cell carcinomas. In 22 of the 43 non-papillary renal cell carcinomas, abnormally migrating DNA bands were detected by SSCP and/or HD analysis. No mobility shift was seen in any of the 23 chromophobe renal cell carcinomas. In addition, 15 papillary renal cell tumours and ten renal oncocytomas, which are characterized by genetic changes other than loss of chromosome 3p sequences, were analysed for mutation of the VHL gene. None of these tumours showed abnormal migration patterns. The results indicate that mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinoma.

Base Sequence↗

Analysis of the MEN1 gene in sporadic pituitary adenomas.

The MEN1 gene on chromosome 11q13 is mutated in patients afflicted with multiple endocrine neoplasia syndrome type 1 (MEN1). These patients develop endocrine tumours of the pancreas, the parathyroid, and the anterior pituitary. In order to determine the role of MEN1 in sporadic pituitary adenomas, 61 pituitary adenomas were analysed from patients without evidence of a familial tumour syndrome. Single strand conformation polymorphism (SSCP) analysis was performed for the entire coding sequence of MEN1. Fragments with aberrant migration patterns were sequenced bidirectionally. Only a single somatic mutation was detected in this series. In addition, several previously reported and three novel polymorphisms were observed. Loss of heterozygosity analysis with 12 polymorphic markers, however, identified 13 pituitary adenomas with allelic deletions on chromosome 11. Allelic losses occurred significantly more often in pituitary adenomas with hormone secretion than in non-functioning adenomas. These data suggest that MEN1 mutations are rare events in sporadic pituitary adenomas. However, the discrepancy of only 1/61 adenomas with MEN1 mutation but 13/61 (22 per cent) with allelic loss on chromosome 11 may suggest the presence of a yet unknown tumour suppressor gene, relevant to the pathogenesis of sporadic pituitary adenomas.

Adenoma↗

Pathogenesis of retinoic acid-induced ear malformations in primate model.

13-cis retinoic acid (RA) is a causative agent for human/monkey retinoic acid embryopathy (RAE), in which the most common type of malformation is microtia or anotia. In the present study, malformed ears of monkey fetuses exposed to RA during early embryogenesis were analyzed and revealed a subtype of defects., i.e., apparent duplication of the external/middle ear. A part of the posterior auricle appeared to be ectopically formed in the anterior auricular region or in the region posterior to the auricle. Additionally, there was duplication of the zygomatic arch, malleus, and incus. In order to characterize possible pathogenetic events underlying these malformations, embryos at selected stages were collected after dosing dams with RA at 5 mg/kg/day during gestational days 12-27. Cellular retinoic acid binding protein I whole-mount immunostaining showed that RA induced specific alterations in the migration of cranial neural crest cells (NCC). NCC en route to the second pharyngeal arch were bifurcated, and some of these NCC migrated abnormally into the first and/or third arches, which may underlie external ear duplication. Scanning electron microscopy and neurofilament immunostaining provided evidence that there was partial duplication of trigeminal nerve/ganglion following RA insult. The duplication of NCC neuronal derivatives in the first pharyngeal arch is consistent with duplication of NCC mesenchymal components (zygomatic arch, malleus, and incus). Therefore, RA-induced alterations in cranial NCC migration patterns are likely to be a pathogenetic event underlying ear malformations (including duplication) of RAE in monkeys.

Animals↗

Tyrosine phosphorylation of myelin protein PO.

Po (M(r) 30 kDa), the major protein component of peripheral nervous system (PNS) myelin, is known to be phosphorylated by protein kinase C on serine residues at multiple sites. This study was conducted to assess whether other amino acids might be phosphorylated in the protein. Segments of rat sciatic nerve were incubated with 32P in either the presence or absence of phorbol ester. Labeled Po was isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subjected to partial acid hydrolysis. Upon separation of the hydrolysis products by either thin-layer electrophoresis or thin-layer chromatography, a radioactive spot was detected which comigrated with authentic phosphotyrosine. In other experiments, nerves were incubated with the tyrosine phosphatase inhibitors vanadate or vanadyl hydroperoxide (pervanadate). When the nerve homogenate proteins were separated on gels and probed with a monoclonal antibody to phosphotyrosine on Western blots, a positive immune reaction was obtained for a protein species which migrated with the same mobility as PO on Coomassie Blue-stained gels. In the absence of 2-mercaptoethanol, this immunoreactive band displayed increased mobility on gels which is characteristic of the migration pattern of Po. The same immunostaining results were obtained using a purified peripheral myelin fraction prepared from nerve homogenates. Furthermore, the positions of immunoreactive bands produced by anti-Po and antiphosphotyrosine antibodies coincided on the same immunoblot of myelin proteins and purified Po. These data indicate that one or more tyrosyl residues in Po can be phosphorylated in intact sciatic nerve.

Animals↗

Sensitivity of the denaturing gradient gel electrophoresis technique in detection of known mutations and novel Asian mutations in the CFTR gene.

More than 500 mutations have been identified in the CFTR gene, making it an excellent system for testing mutation scanning techniques. To assess the sensitivity of denaturing gradient gel electrophoresis (DGGE), we collected a representative group of 202 CFTR mutations. All mutations analyzed were detected by scanning methods other than the DGGE approach evaluated in this study. DGGE analysis was performed on 24 of the 27 exons and their flanking splice site sequences. After optimization, 201 of the 202 control samples produced an altered migration pattern in the region in which an alteration occurred. The remaining sample was sequenced and found not to have the reported mutation. The ability of DGGE to identify novel mutations was evaluated in three Asian CF patients with four unknown CF alleles. Three novel Asian mutations were detected-K166E, L568X, and 3121-2 A-->G (in homozygosity)-accounting for all CF alleles. These results indicate that an optimized DGGE scanning strategy is highly sensitive and specific and can detect 100% of mutations.

Alleles↗

Temperature and pH effects on single-strand conformation polymorphism analysis by capillary electrophoresis.

We investigated the effects of temperature and pH on single strand-conformation polymorphism (SSCP) analyzed by capillary electrophoresis (CE) using short-chain linear polyacrylamide as the sieving medium. Nine different mutations (in factor V, cystathionine beta-synthase, and methylenetetrahydrofolate reductase genes), including both transitions and transversions, were investigated. We confirmed that low temperature in general increased the number of detectable single-strand conformations and thereby the sensitivity of the analysis. The pH effects of the separation matrix on the migration pattern, and thus the assay sensitivity, varied markedly between the different DNA fragments. Seven of nine single point mutations were detected at the ordinary pH of 8.3, whereas the CBS T833C mutation was discriminated at the extreme pH values of 9.0 and 6.4, and the CBS G797A mutation could not be detected at any pH value within the range 6.4--9.0. These data emphasize the importance of the pH of the separation matrix in detecting certain mutations by SSCP.

Base Sequence↗

C283Y mutation and other C-terminal nucleotide changes in the gamma-sarcoglycan gene in the Bulgarian Gypsy population.

Sarcoglycanopathies, affecting the dystrophin-associated sarcoglycan (SG) complex, are a heterogeneous group of neuromuscular disorders. A subgroup of these disorders, limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive disorder, clinically manifested as an early onset, severe Duchenne-like muscular dystrophy. LGMD2C is caused by mutations in the gamma-SG gene, localized on 13q12. Recently, a number of mutations have been described in that gene, among which C283Y, a "private" Gypsy mutation (eight codons before the 3' end of the gene) is detected. In this article, we report on a single-strand conformation polymorphism (SSCP) method for fast C283Y mutation detection, using direct dry blood spot amplification. The method permits a large number of samples to be easily screened. To check heterozygote carriers of C283Y mutation among Gypsy population in Bulgaria, the SSCP analysis was applied on 400 Gypsy newborns from northeast Bulgaria. Our results show 2.25% of heterozygosity, which means that 1 in 50 Gypsies carries the mutation. Moreover, new SSCP migration patterns were detected that revealed two polymorphisms still unavailable in the literature. One of these changes was 984G-->A, leading to substitution of conserved serine at position 287 with asparagine and the second one is 1049C-->G at the 3' UTR (untranslated region). The present data could help the understanding the role of these sequences for the protein function.

Base Sequence↗

Mississippians in motion? A population genetic analysis of interregional gene flow in West-Central Illinois.

Population genetic and biological distance studies of Late Woodland and Mississippian populations from west-central Illinois have provided insight into a number of prehistoric demographic processes at the regional level. However, a formal analysis of diachronic interregional gene flow has not been attempted within a population genetics framework. In this study, cranial measurements of 489 individuals from 13 skeletal samples across the central and lower Illinois valleys are analyzed to address two central issues. First, the potential impact of Cahokia's decline and associated demographic events on the population structure of west-central Illinois Mississippians is examined. Second, the Mississippian and Late Woodland interregional migration patterns are compared to determine if geographic and/or cultural boundaries affected local population structure. Following Relethford and Blangero ([1990] Hum Biol 62:5-25), R matrix methods are utilized to calculate observed and expected phenotypic variances, minimum genetic distances, and F(ST) values in order to detect patterns of differential external gene flow over time. The results indicate that Late Woodland peoples had a larger sphere of biological interaction than Mississippians. In the Mississippian period, culturally imposed barriers paralleled geographic boundaries between regions such that the geographic distribution of biological variation closely adheres to a classic isolation-by-distance model. Further, intraregional population movement was a more significant contributor to Mississippian population structure than interregional gene flow, even during periods of sociopolitical strife. Small-scale intraregional shuffling is consistent with other recent studies of prehistoric Mississippian biocultural and geographic landscapes in the southeast United States.

Adolescent↗

Mechanisms of immunosuppression in tumor-bearing mice: a multifactorial analysis.

Neoplastic growth results not only from the inherent proliferative potential of the neoplasm, but also from the neoplasm's ability to survive within a host whose immune responses may be activated to destroy it. It has been proposed that several mechanisms enable a neoplasm to outgrow the host. The present work describes a system for probing tumor-associated immunosuppression by utilization of the delayed hypersensitivity response to dinitrochlorobenzene (DNCB). Mice of the Balb/c and C3H/HeJ strains were sensitized with a subcutaneous injection of 2 mg DNCB followed 5-10 days later by the subcutaneous injection of a 0.05 mg challenge dose of DNCB in the hind footpad. The footpad response measured 24 hours after challenge is a delayed hypersensitivity reaction by virtue of the histology and kinetics of that response and because it is transferred by spleen cells but not by serum. DNCB sensitization is inhibited by spontaneous, chemical- and virus-induced syngeneic tumors in Balb/c and C3H/HeJ mice. Three mechanisms of immunosuppression are elucidated in the present experiments: (1) serum from tumor-bearing mice inhibits primary sensitization of normal mice to DNCB upon passive transfer; (2) spleen cells from tumor-bearing mice inhibit primary sensitization of normal mice to DNCB and appear to be macrophages in the C3H/HeJ system; and (3) an alteration of lymphocyte migration patterns exists in tumor-bearing mice that removes effector cells from the blood and prevents the initiation of a footpad response. The interrelationships of these three mechanisms are discussed. Correlations are also made with tumor-associated immunosuppression observed in cancer patients.

Animals↗

Occupation and the high risk of lung cancer in Northeast Florida.

A case-control study involving interviews with 321 male patients with lung cancer and 434 controls, or their next of kin, was undertaken to identify reasons for the high lung cancer mortality along the northeast coast of Florida. In Duval county (Jacksonville), the age-adjusted rate for lung cancer, 1970-1975, among white males was the highest of all urban counties in the United States. Increased risks on the order of 40-50% were associated with employment in the shipbuilding, construction, and lumber/wood industries, particularly among workers with reported exposures to asbestos or wood dust. Excess risks were also linked to fishing and forestry occupations, although the numbers of cases involved were small. Occupational factors did not appear to fully account for the area-wide excess of lung cancer, but no evidence was found to implicate smoking habits, migration patterns, or diagnostic and reporting practices as factors responsible for the exceptional mortality rates.

Aged↗