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Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, md. The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on md yielded a fitted line m(a) = .922md, r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European-Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population.

It has been suggested that the long-standing association of variability in the human nasal index [100 x (nasal breadth)/(nasal height)] with climatic variation is spurious evidence for natural selection in humans (Hoyme, 1965; St. Hoyme and Işcan, 1989). The argument is based principally on the observation that nasal height is globally more variable than nasal breadth, with nasal breadth thus contributing little to variation in the index. This argument does not take into account the confounding effect of absolute size of these variables on their variances. In this study we compare the intrinsic variation in skeletal nasal height and breadth within and among 26 mixed-sex populations (N = 2,408) at globally diverse localities (Howells, 1989), using 2 x 2 variance-covariance matrices of the logarithmically transformed variates. Hypothesis tests for homogeneity of matrices and equal-variance/equal-covariance indicate that the intrinsic variation in nasal breadth is greater than that for nasal height within populations, and that nasal breadth and nasal height exhibit equivalent intrinsic variation among populations. The argument that nasal breadth contributes little to the world-wide variation in the human nasal index is rejected. Given our present understanding of nasal physiological morpho-function, these results support, but do not demonstrate, an adaptive role for human nasal index variation. Promising methods for elucidating natural selection on human nasal form are suggested.

Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedical, and evolutionary concerns. New genetic typings on 730 Arizona Mexican Americans for the HLA-A, HLA-B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each model. The following admixture estimates were obtained: Amerindian, 0.29 +/- 0.04; Spaniard, 0.68 +/- 0.05; and African, 0.03 +/- 0.02. The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion. An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.

Susman (Am. J. Phys. Anthropol. 75:277-278, 79:451-474; Science 240:781-784; In FE Grine (ed): Evolutionary History of the "Robust" Australopithecines. New York: Aldine de Gruyter, pp. 149-172) has attributed the morphologically similar SK 84 and SKX 5020 hominid first metacarpals to Homo erectus and Australopithecus robustus, respectively, and has inferred that both species exhibited derived pollical morphologies, indicating refined precision grips. Consideration of the structure of his taphonomic arguments indicates that there are no adequate nonmorphological reasons to attribute these specimens securely to one or the other of the craniodentally represented species at Swartkrans. His morphological arguments fail to note any significant differences between the two specimens. Only the contrast in size between the small SK 84 and large SKX 5020 bones might warrant a species distinction; yet comparison of their length ratio to distributions of modern human first metacarpal length ratios indicates that it is not possible to reject conclusively the null hypothesis that they are conspecific. Therefore, early hominid adaptive scenarios based on a derived Homo-like manual functional morphology in A. robustus remain without a secure paleontological basis.

The evolutionary histories and relationships among African, Eurasian, and Pacific Island populations are investigated by using observations on five polymorphic restriction sites in the beta-globin gene cluster. We present new data on 222 chromosomes from a global sample and combine these with previously published observations on 591 chromosomes. It is shown that the data are rich in rare haplotypes and that rare variants are not helpful for standard methods of population structure analysis. Consequently, a new approach is developed. We first consider the phylogeny of beta-globin haplotypes. The roles of mutation, gene conversion, and recombination in the generation of haplotype diversity are specifically focused upon. The relationships among human populations are then inferred from the phylogenetic relationships among the haplotypes, their presence or absence, and frequencies within populations. Questions regarding whether or not a phyletic process can account for relationships among the major geographical populations and whether or not an extant human population exhibits the qualities that would be expected of an ancestral group are addressed. The results of this analysis support an African origin for modern Homo sapiens and a phyletic structuring of the major geographical regions. However, it is shown that divergence times for the various populations cannot be determined from these data.

The clinical and histopathologic characteristics of 65 patients with nodular lymphoma seen at the Massachusetts General Hospital between 1962 and 1972 were reviewed. Five years after diagnosis 54% of these patients were alive, but only 18 percent remained free of disease. Younger patients fared much better (64 percent of those below the age of 50 survived 5 years) than the elderly (only 34 percent of those above the age of 50 survived this long), but histologic subtype by the Rappaport classification was not useful in predicting survival in this series. Individuals with localized disease (80% of those in Stages I and II survived 5 years) experienced better survival than those with dissemination (only 45% of those in Stages III and IV lived this long), but the high relapse rate in Stages I and II indicates that few who presented with localized disease are cured. At the time of death, the histologic pattern had become diffuse in 8 of 18 patients but remained nodular in the other 10. Ten patients treated by total nodal irradiation followed the same survival curve as the remainder treated less radically. It is concluded that nodular lymphoma is an indolent but usually fatal entity: though more than half of our patients survived 5 years, few were cured by the treatments employed.

Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.

Genetic exchange with a neighboring village of Ye'cuana Indians had introduced two alleles, Dia and ACPa, into the Yanomama Indian Village of Borabuk. After several generations, these alleles had reached frequencies of 0.08 and 0.10, respectively. These frequencies are puzzling because they are higher in Borabuk than in the Ye'cuana village from which they were derived. Single allele estimates of ancestral proportions obtained from either of these traits are biologically unrealistic and suggest that admixture is not a good explanation for genetic variation in Borabuk. Nevertheless, multiallelic admixture models are seen to produce credible estimates of ancestral proportions and to explain a large amount of allele frequency variation in Borabuk. When these results are compared with expectations derived froma formal pedigree analysis, good agreement is seen. Comparison of single allele estimates of ancestral proportions obtained from alleles at 11 loci, with multiallelic estimates obtained from the same 11 loci and with the pedigree-derived estimates, demonstrates the superiority of the multiallelic approach.

A patient had papular and nodular cutaneous deposits of mucin and cutaneous and systemic manifestations of lupus erythematosus (LE). Since many of the mucinous deposits occurred at sites that were clinically free of skin lesions of LE, we considered initially that the patient had both LE and papular mucinosis. However, after a review of the English literature and further study of the patient, it seemed more likely that the papular and nodular deposits of mucin were secondary to LE and not a previously unreported simultaneous occurrence of the two diseases in the same patient. To our knowledge, this is the third case report of a patient with papular and nodular cutaneous mucinosis secondary to LE. In addition to the case report, this article is concerned with a discussion of cutaneous mucinosis in LE and other "collagen vascular" diseases.

The internal patterning of allelic correlations in the Gainj and Kalam swidden horticulturalists of highland Papua New Guinea is examined within the context of Sewall Wright's F-statistic model. A multiallelic extension of the model is given first, and multivariate variance-component estimators for the parameters are suggested. Then, it is shown that the expectation of the F-statistic set depends on the age structure of the population and that knowledge of the population and sample age structure is critical for meaningful analysis. The array of F-statistics estimated jointly over five polymorphic enzyme loci reveals the following features of Gainj and Kalam population structure: (1) significant departures from panmictic expectations and (2) characteristics of a continuously distributed breeding population, rather than those expected for populations subdivided into demes with discrete boundaries. Finally, the F-statistics estimated for the Gainj and Kalam are briefly compared to estimates obtained from other tribal populations. It is seen that the level of differentiation observed in the Gainj and Kalam is only about one-third that observed in South American swidden horticulturalists. Consequently, some conventional wisdom regarding the interrelationship of socioecological settings and genetic structures may require reevaluation.

We examined 90 serums from patients with Hodgkin's disease for immune complexes and for reactivity with established monolayer tissue cultures prepared from the tumor. All 23 serums with immune complex levels greater than 20 microgram per milliliter were found to react with cultured cells of patients with Hodgkin's disease when tested with antiserums against immunoglobulin heavy and light chains and the C3 component of complement. Five of 11 serums with borderline elevations of immune complexes (10 to 20 microgram per milliliter) and only four of 56 with levels less than 10 microgram per milliliter reacted. Absorption of patients' serums with cultured cells removed immune complexes and eliminated binding to monolayers. Immune-complex-containing serums from 19 control patients did react with cultured cells of patients with Hodgkin's disease; none of serums reacted with normal cultured spleen. Antibodies within complement-containing immune complexes in serums of patients with Hodgkin's disease react with an antigen on the surface of cultured cells of such patients.

A 54 year old woman presented with acute lymphocytic leukemia. Following an initial response to chemotherapy with vincristine and prednisone, progressive pancytopenia developed coincident with intense bone marrow infiltration by abnormal histiocytes. At autopsy two months later, no evidence of leukemia was found, but the bone marrow was replaced by abnormal histiocytes showing active erythrophagocytosis, consistent with histiocytic medullary reticulosis. Detailed morphologic, ultrastructural and histochemical studies performed throughout the course of the patient's illness served to confirm the transition from leukemia to histiocytosis. Four similar cases of acute lymphocytic leukemia terminating in histiocytic medullary reticulosis have been reported. This association may represent a distinct clinicopathologic syndrome.

Two rare types of familial periodontitis, a localized form usually diagnosed in late adolescence, and a more generalized form with a latter mean age of diagnosis, have been analyzed with respect to genetic models currently favored in the dental literature. These include autosomal recessive and X-linked dominant (partial penetrance) inheritance. Since there is variation in severity, extent, age of onset, altered sex ratio of affected individuals, and a low population prevalence, it is not surprising that genetic mechanisms heretofore have not been revealed. We have compared the likelihoods of 33 kindreds ascertained through affected probands under the above genetic models. Our findings include (1) several families in which both forms of early onset periodontitis co-occur, making it unlikely that the clinical varieties of the disease have unrelated genetic causes; (2) the autosomal recessive model is far more likely than the X-linked dominant model. The superiority of the recessive hypothesis arises from the fact that there are only a few instances of affected individuals having affected parents and because the skewed sex ratio is shown to be incompatible with X-linked inheritance. These conclusions are largely insensitive to the assumptions of the analysis. We conclude that the X-linked dominant hypothesis is inadequate, and while the autosomal recessive model is by no means proven, it is clearly favored.

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified.

The surface of lymphocytes obtained from fresh biopsy specimens from 41 patients with malignant lymphoma and from 30 normal subjects or patients with non-neoplastic lymphadenopathy were investigated. Immunoglobulin on the cell surface was used to identify B cells, whereas T cells were recognized by their reactivity with an antithymocyte antiserum and their ability to form rosettes with sheep erythrocytes. Normal and inflammatory lymph nodes were composed predominantly of T lymphocytes, as were nodes from 14 patients with Hodgkin's disease. Two thymomas were T cell proliferations, whereas a node from a patient with ataxia-telangiectasia was devoid of T lymphocytes. The presence of immunoglobulin on the cell surface indicated that 19 of 21 lymphocytic lymphomas were B cell proliferations, whereas the cells from 3 histiocytic lymphomas (reticulum cell sarcomas) and 1 mixed histiocytic and lymphocytic lymphoma were devoid of surface immunoglobulin. In immunoglobulin-positive tumors, one predominant heavy chain and one predominant light chain could usually be identified, thus establishing the clonal character of the neoplastic proliferation. Ten of 11 diffuse poorly differentiated lymphocytic lymphomas were composed of cells with large amounts of surface immunoglobulin, whereas only 1 of 5 diffuse well differentiated lymphocytic tumors contained such abundant surface immunoglobulin. The surface immunoglobulin data indicate the existence of at least two subspecies of B cell neoplasms. A small lymphocyte with sparse surface immunoglobulin proliferates as diffuse well differentiated lymphocytic lymphoma and chronic lymphocytic leukemia, whereas a larger lymphocyte with abundant surface immunoglobulin proliferates as diffuse poorly differentiated lymphocytic lymphoma and lymphosarcoma cell leukemia.

Rabbits were immunized with an antigen of specific gravity, 1.15-1.21 isolated by density gradient sedimentation of the centrifuged medium of long-term monolayer cultures derived from spleens involved by Hodgkin's disease. The globulin fraction of the antiserum was absorbed to reduce reactivity with normal cellular antigens and tissue culture components, and was tested by the indirect fluorescent antibody technique with cells from 18 different Hodgkin's disease cultures, and 16 normal cultures derived from adult spleen and fetal spleen and thymus. With anti-Hodgkin's disease globulin diluted 1:40 and 1:80, positive surface staining was observed in 48% and 41%, respectively, of viable cells from Hodgkin's disease cultures, and in less than 5% of cells cells from normal cultures. Fluorescent staining of the cytoplasm without nuclear staining was observed in 51% of acetone-fixed cells from the Hodgkin's disease cultures and in 4-8% of cells from normal cultures. Reactivity of the antiserum with Hodgkin's disease target cells could be removed by absorption of the antibody with additional antigen of density 1.15-1.21 obtained from other Hodgkin's disease cultures. Antisera to fractionated medium from a normal spleen culture and to noncultured Hodgkin's disease tumor tissue were used as controls: 2-10% of viable and acetone-fixed target cells reacted and no difference was observed between Hodgkin's disease and normal cell cultures. In vitro propagation of tumor cells from patients with Hodgkin's disease is needed for detection of the Hodgkin's disease tissue culture antigen; the antigen could not be demonstrated in noncultured Hodgkin's disease tissue.

An antigen in tissue cultures derived from Hodgkin's disease tumors was investigated by polyacrylamide gel electrophoresis, column chromatography, and isotopic antibody techniques. Fourteen long-term, serially passaged monolayer cultures prepared from tumor nodules of Hodgkin's disease in the spleen were studied; 11 monolayers derived from normal adult spleen and human fetal spleen and thymus were used as controls. Cell-free medium from Hodgkin's disease and normal cultures were centrifuged, and the pellet fractions were sedimented in a discontinuous sucrose gradient, solubilized with dodium dodecyl sulfate, and labeled with radioiodine. Gel filtration and electrophoresis revealed a component in samples prepared from medium of Hodgkin's disease cultures that was not observed in medium from normal cultures. An antiserum made in rabbits against this component reacted by radioiodine-labeled antibody assay with an antigen on the surface on cells from Hodgkin's disease cultures that was present in very small amounts, or in a cryptic state, on normal cultured cells. This antigen, intimately associated with propagation of cells obtained from the tumor in vitro, was not demonstrable in noncultured Hodgkin's disease tissue...

An antiserum was prepared in rabbits against an antigen obtained by density gradient sedimentation of centrifuged medium from monolayer cultures of spleens involved by Hodgkin's disease. The antiserum was tested by isotopic antibody techniques with cells from each of eight cultures derived from spleens involved by Hodgkin's disease, four cultures derived from normal adult spleen, and one culture each of fetal spleen and thymus. By an indirect radioiodine-labeled antibody assay, anti-Hodgkin's disease globulin reacted with an antigen on the surface of cells from the Hodgkin's disease cultures, the quantity of which was related to the number of target cells and the amount of antibody used. This Hodgkin's disease tissue-culture antigen did not react with a rabbit antiserum against fractionated medium from a normal spleen culture, nor against noncultured Hodgkin's disease tumor tissue. The tumor specificity of the Hodgkin's disease tissue-culture antigen was assessed by a direct technique using (125)I-labeled anti-Hodgkin's disease globulin absorbed with either cultured Hodgkin's disease cells or with cultured normal cells. By this method the quantity of antigen on cells from Hodgkin's disease cultures was 15- to 30-fold greater than that on cells from normal cultures. The Hodgkin's disease tissue-culture antigen is intimately associated with the propagation of the tumor in monolayer cultures, but its identity has not been established: it could be a viral component, a tumor or fetal antigen, or a normal tissue constituent.

The investigation was undertaken to define the features of lymphoblastic lymphoma. Fifteen lymph node biopsies from a group of 82 specimens studied for the enzyme terminal deoxynucleotidyl transferase (TdT) fulfilled morphological criteria for this diagnosis. These criteria required a diffuse infiltrate of relatively uniform, immature lymphoid cells with basophilic cytoplasm; round, oval or lobulated nuclei with evenly dispersed chromatin; rare or inconspicuous nucleoli; and numerous mitotic figures. Examination of 1-micron thick, plastic-embedded, Giemsa-stained tissue sections revealed convoluted nuclei in more than 50% of neoplastic cells in four cases: in six specimens there was an admixture of cells with grooved, hyperlobulated, and round nuclei, and in five the round or oval nuclei were non-convoluted. Specimens from all 15 patients were positive for TdT by fluorescent antibody and biochemical assays. The percentage of cells from involved nodes reacting by indirect immunofluorescence with an antiserum against bovine TdT ranged from 4 to 90% (mean of 52%), and the mean level of biochemically measured enzyme activity was 8.7 units/g of tissue (range of 1.9 to 27.5). Cytochemical stains for acid phosphatase were positive in 13 of the 15 cases. In eight samples more than 50% of cells formed rosettes with sheep erythrocytes, while the E rosettes varied from 14 to 38% in the other seven. The percentage of cells with complement receptors varied widely (range of 6 to 80), but cells bearing surface immunoglobulin or IgGfc receptors were not increased. All patients presented with supradiaphragmatic lymphaedenopathy, eight with an anterior mediastinal mass. Two-thirds of the patients were male, and the mean age was 20 years (range 4 to 46 years). None were leukemic at the time of diagnosis, but eight patients subsequently developed acute lymphoblastic leukemia. Involvement of the central nervous system was observed in four of the 15, and of the testes in two. Ten patients have died of their disease with a median survival of 8 months (range 4 to 20), and five are alive 3--8 months after diagnosis. We observed no differences in clinical findings at presentation, incidence of mediastinal involvement or leukemic dissemination, content of TdT, acid phosphatase staining, or immunologic cell surface characteristics between the convoluted and non-convoluted types of lymphoblastic lymphoma. Distinctive morphologic, cell surface, biochemical, and clinical features of lymphoblastic lymphoma can be identified irrespective of the presence or absence of convoluted nuclei.

Cells from 9 monolayer tissue cultures prepared from Hodgkin's disease tumors in the spleen were examined in the electron microscope. Three established culture lines (carried in vitro for greater than 3 years and passaged greater than 200 times) that contained aneuploid karyotypes were composed of oval cells with numerous interdigitating surface microvilli. The nuclei were complex and convoluted with multiple large nucleoli and dispersed chromatin. The cytoplasm contained lysosomes, microfilaments, a complex Golgi apparatus, nondilated rough endoplasmic reticulum, polyribosomes, fat, and glycogen. One Hodgkin's disease monolayer with aneuploid chromosomes examined from the 4th to 48th passage in culture was composed of larger cells with fewer microvilli and numerous multinuclear giant cells. Two monolayers derived from transplanted tumors in nude mice inoculated with Hodgkin's disease cultured cells were similar to the original cell lines. The ultrastructural features of these 6 cultures with aneuploid karyotypes differed from those of 3 monolayers which, although prepared from Hodgkin's disease splenic tumors, were composed of fibroblastic cells with diploid chromosomes. The aneuploid Hodgkin's disease cultures did not resemble 6 normal spleen, thymus, or lung monolayers, Raji lymphoblastoid suspension cultures, or Hela cells. Our electron microscopic studies indicate that adherent cells which replicate in some monolayer tissue cultures derived from Hodgkin's disease tumors are related to and possibly derived from neoplastic macrophages.

The patterning of allele frequency variability among 18 local groups of Gainj and Kalam speakers of highland Papua New Guinea is investigated using new genetic distance methods. The genetic distances proposed here are obtained by decomposing Sewall Wright's coefficient FST into a set of coefficients corresponding to all pairs of population subdivisions. Two statistical methods are given to estimate these quantities. One method provides estimates weighted by sample sizes, while the other method does not use sample size weighting. Both methods correct for the within-individual and between-individual-within-groups sums of squares. Genetic distances among the Gainj and Kalam subdivisions are analyzed with respect to demographic, geographic, and linguistic variables. We find that a demographic feature, group size, has the greatest demonstrable association with the patterning of genetic distances. The pattern of geographic distances among groups displays a weak congruence with the pattern of genetic distances, and the association of genetic and linguistic diversity is very low. An effect of differences in group size on genetic distances is not surprising, from basic theoretical considerations, but genetic distances have not often been analyzed with respect to these variables in the past. The lack of correspondence between genetic distances and linguistic and geographic differences is an unusual feature that distinguishes the Gainj and Kalam from most other tribal populations.

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 microgram/ml +/- 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (less than 15 microgram/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.

Long, John C., AND Aisenberg, Alan C.: Richter's syndrome. A terminal complication of chronic lymphocytic leukemia with distinct clinicopathologic features. Am J Clin Pathol 63: 786-795, 1975. Two patients with chronic lymphocytic leukemia of 8 and 9 years duration had a terminal illness characterized by weight loss, persistent fever, lymphadenopathy, and dysglobulinemia. In both cases autopsy revealed a pleomorphic histiocytic lymphoma which contained multinucleate tumor cells and was associated with persistent chronic lymphocytic leukemia. These two cases are examples of Richter's syndrome, a clinically distinct complication of chronic lymphocytic leukemia that may be confused pathologically with Hodgkin's disease. Review of the medical literature suggests that this syndrome has frequently gone unrecognized. (Key words: Richter's syndrome; Chronic lymphocytic leukemia.)

The research presented focuses on genetic variation in the Gainj- and Kalam-speaking peoples of highland Papua New Guinea. The primary data are typings at 51 genetic loci observed on 600 individuals who reside in 21 census units, called parishes. These data are augmented by cultural and demographic information that has also been collected. Parish sizes are small, ranging from 20 to about 200 individuals. Direct Western contact with these people has been occurring only for the past three decades. Although Westernization is currently increasing, we find that much of the traditional settlement pattern and mate exchange system is preserved. There are segregating variants at 27 loci. Four rare variants are initially described: NP 4-Kalam, ADA 6-Kalam, PEPA 3-Kalam, and FUM 2-Kalam. We find evidence for a new Gm haplotype, a;-, that is recessive to all other Gm haplotypes. It occurs at a high enough frequency, f(a;-) = 0.119, to be considered a "private polymorphism." Average per locus heterozygosity is estimated to be 0.053. This value is not statistically different from levels observed on two modern urban populations. Thus, there is no evidence for a reduced level of genetic variation in these people, despite small parish sizes and a relatively unacculturated social structure.

We examined the binding of soluble immune complexes in sera from patients with Hodgkin's disease to established tissue cultures derived from the tumor. Circulating immune complex levels were determined by the Raji cell assay, and the reaction of serum with cultured cells was examined with a radioimmune assay and by immunoferritin electron microscopy. Serum with elevated immune complexes was found to react with cells of Hodgkin's disease monolayers when tested with radioiodine-labeled antisera against human IgG heavy and light chains and the complement 3 (C3) component. When examined with the electron microscope, monolayers incubated with Hodgkin's disease serum containing immune complex and labeled with ferritin-conjugated antiserum to C3 contained surface-bound ferritin particles with a uniform but discontinuous pattern. Absorption of Hodgkin's disease serum with monolayer cells reduced immune complexes and decreased reactivity of the sample with cultured cells by radioimmune assay. Sera of patients with other disorders and aggregated gamma-globulin with complement, despite markedly elevated immune complex levels, did not react positively with monolayers derived from Hodgkin's disease tumors, and none of the sera reacted with normal cultured spleen. The approximate size of serum components reacting with Hodgkin's disease monolayers was estimated by sucrose density gradient centrifugation. Sedimentation fractions in the 19S region reacted with monolayer cells when tested with 125I-labeled antisera to both IgG and C3 and contained immunoglobulin-complement complexes by gel diffusion and immunoabsorption. A component sedimenting at 7-9S contained immunoglobulin not complexed with complement; this component reacted with monolayer cells when tested with anti-IgG antiserum but did not react when tested with antibody to C3. The reaction of Hodgkin's disease monolayers with serum containing immune complexes differed from that of two suspension culture lines composed of cells with surface complement and IgG Fc receptors. Inasmuch as cells of our long-term Hodgkin's disease monolayers do not contain these surface receptors, possibly the antibody component of the immune complex reacts with antigens on the surface of cultured cells.

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.