Hemoglobin levels in high altitude Tibetan natives of northwest Nepal.
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Adaptation, Physiological↗
Biomedical subjects
J W Larrick
Publications and source records attributed to J W Larrick.
Population differences in cutaneous methacholine reactivity and circulating IgE concentrations.
We evaluated the incidence of allergic and vasomotor symptoms, serum IgE concentrations, and the cutaneous responses to allergens and/or methacholine in 229 Waorani Indians residing at 300 m altitude near the headwaters of the Amazon River, 39 Tibetans residing at 4000 m in the Himalayas, and 84 healthy subjects residing at 150 m in the piedmont region of North Carolina. The Waorani Indians had a high level of intestinal parasitism, an intermediate level of parasitism occurs in Tibetans, and parasitism is rare in the control population. One Waorani Indian (less than 1%), six Tibetans (15%), and 59 North Carolina subjects (88%) had a past history of allergic or vasomotor symptoms. The prevalence of positive epicutaneous allergen skin tests among the Waorani was 40 in 2910 tests and was significantly less (chi-squared = 184.5; p less than or equal to 0.0001) than the 151 in 1344 incidence in the North Carolina subjects. Large highly significant differences (p less than or equal to 0.0001) were detected between the geometric mean IgE concentrations (international unit per milliliter) and methacholine-induced cutaneous flare responsiveness (millimeter) elicited, respectively, in comparisons between the Waorani Indians (9806 IU/ml; less than 1.0 mm), Tibetans (2930 IU/ml; 2.06 mm), and North Carolina subjects (108 IU/ml; 4.49 mm). Differences in methacholine sensitivity were small and not significant. A highly significant inverse relationship (r = -0.50, p less than or equal to 0.0001) was detected between the circulating IgE concentrations and the methacholine-induced cutaneous flare responsiveness in this cross-cultural, cross-environmental comparison of three populations.(ABSTRACT TRUNCATED AT 250 WORDS)
Altitude↗
Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2.
Patients with lepromatous leprosy (LL) but not borderline tuberculoid leprosy (BT) have defective cell-mediated immune responses to Mycobacterium leprae, despite normal responses to other stimuli, as judged by in vivo skin testing and in vitro lymphocyte transformation. To investigate the basis of the immune defect in LL patients, we studied the ability of patient mononuclear leukocytes to produce interleukin 1 (IL 1) and interleukin 2 (IL 2) upon stimulation with M. leprae, and determined the ability of exogenous IL 1 and IL 2 to reconstitute the LL patient response to this antigen in vitro. Equal numbers of adherent non-T cells from LL and BT patients produced similar amounts of IL 1 upon challenge with M. leprae, and addition of IL 1 to the culture medium failed to reconstitute the response of lymphocytes from LL patients to M. leprae. On the other hand, T cells of LL patients failed to express receptors for IL 2 or to produce IL 2 in response to M. leprae, whereas similarly treated T cells of BT patients both expressed IL 2 receptors and produced IL 2. Finally, recombinant human IL 2 purified to homogeneity as well as crude supernatants of mitogen-activated lymphocytes failed to reconstitute the response of LL patients to M. leprae. These results suggest that T cells of LL patients fail to respond to M. leprae despite an ability to produce IL 1 and that their failure to express receptors for IL 2 may explain both defective proliferation and the failure of exogenous IL 2 to reconstitute the response.
Animals↗
Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor.
We report a case of anemia due to autoantibodies to the transferrin receptor interfering with iron incorporation by erythroid progenitors. A previously healthy woman with severe acquired microcytic anemia had increased serum iron levels, electrophoretically normal transferrin concentrations, and very high levels of free protoporphyrin in red cells. The bone marrow had no stainable iron but had an excess of normal-appearing plasma cells. Erythroid precursors stained with fluorescent mouse antihuman IgM. The serum contained an antibody that reduced 59Fe incorporation by erythroleukemia K562 cells in vitro but did not inhibit iron transferrin binding. An IgM fraction of the patient's serum immunoprecipitated the human transferrin receptor obtained from solubilized [35S]methionine-labeled K562 membranes. Binding of [59Fe]transferrin or fluorescent iron transferrin was not diminished by the patient's serum at 4 degrees C, but at 37 degrees C uptake was markedly reduced, as was the binding of fluorescent monoclonal antibodies to either surface transferrin or the human transferrin receptor. A complete clinical and hematologic remission occurred with azathioprine and prednisone therapy. We conclude that the patient's autoreactive IgM down-regulated the number of transferrin receptors and diminished iron incorporation by erythroblasts, leading to an iron-deficiency anemia.
Anemia, Hypochromic↗
Production of human monoclonal antibody in mouse ascites.
Human B-cell hybridomas were grown in nude mouse ascites. The growth of cells in ascites requires prior subcutaneous (SC) adaptation, but the amount of antibody harvested is 100-fold that produced in in vitro culture. The relative merits of in vitro versus in vivo production of human monoclonal antibodies are discussed.
Animals↗
Studies of endemic cretinism in Papua New Guinea: digital and palmar dermatoglyphic patterns.
We have tested the hypothesis that the abnormal development of the central nervous system seen in endemic cretinism might be accompanied by concurrent abnormal dermatoglyphic patterns. We compared digital and palmar dermatoglyphics of normal individuals and endemic cretins inhabiting the Huon Peninsula of Papua New Guinea. The population sampled from the Irumu River Valley included 118 males and 114 females with 22 male cretins and 23 female cretins. The population sampled from the Wantoat River Valley included 72 males and 38 females with 12 male cretins. No pathognomonic patterns were found that could identify the endemic cretin subpopulation. However, the occurrence of a number of differences between controls and cretins suggests that subtle changes in dermatoglyphic patterns accompany the anomalous development of the CNS secondary to maternal iodine deficiency. We discuss the significance of these findings and compare the dermatoglyphic patterns of normal Irumu and Wantoat natives and 21 other populations of Papua New Guinea.
Congenital Hypothyroidism↗
Does hyperimmunoglobulinemia-E protect tropical populations from allergic disease?
The Waorani Indians of eastern Ecuador have the highest blood concentration of IgE reported in a human population. Evidence obtained by medical history, physical examination, and immediate hypersensitivity skin tests suggests that pollen allergy and other atopic diseases are rare among the Waorani. A similar association between parasite-induced hyperimmunoglobulinemia-E and a low prevalence of conventional atopic disease has been reported in numerous other tropical populations. Saturation of mast cell IgE receptors with antibodies directed to the parasite and/or other antigens and competitive inhibition of passive binding of pollen allergen-specific IgE is one hypothetical cause of this association. We have tested this interesting conjecture by passively sensitizing the skin of Waorani Indians with serum containing pollen allergen-specific IgE antibodies. Waorani Indians with hyperimmunoglobulinemia-E can be adoptively sensitized with human ragweed or rye grass hyperimmune IgE antisera. This suggests that the cutaneous mast cells of healthy Waorani have active IgE receptors. The high circulating plasma concentrations of IgE in the Waorani do not prevent adoptive cutaneous sensitization with pollen-specific IgE antibodies.
Ecuador↗
Characterization of human hybridomas secreting antibody to tetanus toxoid.
We have selected a thioguanine-resistant lymphoblastoid cell line (LTR228) that forms human-human hybrids with high efficiency. Fusions with peripheral B cells consistently yield one colony per 10(5) cells plated. To produce antitetanus monoclonal antibodies, we withdrew blood from persons who had recently received booster injections of tetanus toxoid. T cells were separated from peripheral mononuclear cells by 2-aminoethylisothiouronium bromide-induced rosette formation, given 1,500 rads (1 rad = 0.01 gray), and cultured in a 1:1 ratio with nonrosetting cells. After 3 days of pokeweed mitogen stimulation, heterokaryons were produced by a plate-fusion technique and cultured in Iscove's Dulbecco's minimal essential medium for 24 hr prior to hybrid selection. Colonies appeared after 10-14 days in hypoxanthine/azaserine supplemented medium. A direct binding enzyme-linked immunosorbent assay with specific tetanus toxoid inhibition identified positive wells. The hybridomas were cloned twice in soft agarose and by limiting dilution. The subcloned hybridomas double every 26 hr (vs. every 16 hr for LTR228) and produce 1-5 micrograms of specific IgG, kappa antibody per 10(6) cells per ml per 24 hr. All subclones (almost 200) continue to secrete antibody after 11 months of continuous culture. Twelve representative subclones have near tetraploid amounts of DNA. From hybridomas grown in 5-liter spinner flasks, milligram quantities of the IgG, kappa antibody were purified by staphylococcus protein A affinity chromatography. Specific antibody from hybridoma cultures protected mice injected with 1,000 times the LD50 of tetanus toxin. Our cell line and associated techniques should permit the production of therapeutically important human monoclonal antibodies.
Antibodies, Monoclonal↗
Protective effect of snake venom antibodies in sera of previous snake bite victims.
Three out of seven serum samples from Ecuadorian Indians had very high antibody levels against Bothrops nasutus venom, and IgG concentrates of these sera effectively neutralized this venom when subsequently injected into mice. It is concluded that the high mortality rate among these Indians would be even higher if there were not such natural protection. Further research into active immunization of humans should be encouraged.
Animals↗
Co-migration and internalization of transferrin and its receptor on K562 cells.
The incorporation of iron into human cells involves the binding of diferric transferrin to a specific cell surface receptor. We studied the process of endocytosis in K562, a human erythroid cell line, by using tetramethylrhodamine isothiocyanate-labeled transferrin (TRITC-transferrin) and fluorescein isothiocyanate-labeled Fab fragments of goat antireceptor IgG preparation (FITC-Fab-antitransferrin receptor antibody). Because the antireceptor antibody and transferrin bind to different sites on the transferrin receptor molecule it was possible to simultaneously and independently follow ligand and receptor. At 4 degrees C, the binding of TRITC-transferrin or FITC-Fab antitransferrin receptor antibody exhibited diffuse membrane fluorescence. At 20 degrees C, the binding of TRITC-transferrin was followed by the rapid formation of aggregates. However, the FITC-Fab antitransferrin receptor did not show similar aggregation at 20 degrees C unless transferrin was present. In the presence of transferrin, the FITC-Fab antitransferrin receptor antibody formed aggregates at the same sites and within the same time period as TRITC transferrin, indicating co-migration. Although the diffuse surface staining of either label was removed by proteolysis, the larger aggregates were not susceptible to enzyme degradation, indicating that they were intracellular. The internal location of the aggregates was also demonstrated using permeabilized cells that had been preincubated with transferrin and fixed with 4% paraformaldehyde. These cells showed aggregated receptor in the interior of the cell when reacted with fluorescein-labeled antibody to the receptor. This indicated that the transferrin and the transferrin receptor co-internalize and migrate to the same structures within the cell.
Cell Line↗
Digital and palmar dermatoglyphic patterns among natives of extreme northwest Nepal.
A dermatoglyphic study was made of two high-altitude populations inhabiting the same ecozone in extreme northwest Nepal. Despite cultural and linguistic differences there appears to be a significant amount of dermatoglyphic homology between the Buddhist-Tibetan villages and their Hindu-Caucasian neighbors.
Dermatoglyphics↗
Gm and Inv (Km) studies of Melanesian people on the Huon Peninsula in Northeast Papua New Guinea: polymorphism for a Gm1,5,10,11,13,14,17,21,26 Haplotype.
Blood samples from 448 people living in six villages in the Huon Peninsula in northeast Papua, New Guinea, were tested for Gm(1,2,3,5,6,10,11,13,14,17,21,24,26) and Inv(1) [Km(1)]. All the people are non-Austronesian (NAN) speakers. As expected, there was a low frequency of the Gm1,3,5,10,11,13,14,26 haplotype, but in contradiction to expectations there was a complete absence of Gm1,2,17,21,26 haplotype. In addition, samples from people in one village (Yupna) and probably those for two other villages (Irumu 13 and 14) have the rare haplotype Gm1,5,10,11,13,14,21,26 at polymorphic frequencies. Two samples from people living in Yupna had the rare phenotype Gm(1,3,17,21,26), indicating the presence of any one of several rare haplotypes that had been observed in other populations. These are discussed.
Black People↗
Snake venom antibodies in Ecuadorian Indians.
Serum samples from 223 Waorani Indians, a tribe in eastern Ecuador, were investigated by enzyme-linked immunosorbent assay for antibodies to snake venom. Seventy-eight per cent were positive, confirming the highest incidence and mortality from snake bite poisoning yet recorded in the world. Most samples were positive for more than one venom antibody. Antibodies were found to venoms of Bothrops viper in 60% of positive cases, of Micrurus coral snake in 21%, and of the bushmaster, Lachesis muta, in 18%. Further studies are needed to determine whether high venom-antibody levels afford protection against further snake envenoming.
Adolescent↗
Transferrin receptors on leukaemic cells.
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Antigens, Neoplasm↗
Should mild hypertension be treated with drugs?
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Diet, Sodium-Restricted↗
Hyperimmunoglobulinemia E in the Waorani, an isolated Amerindian population.
The Waorani Indians of Eastern Ecuador have the highest blood levels of immunoglobulin E that have been recorded in a human population. Using a radial immunodiffusion technique for IgE determination, we found the mean plasma IgE concentration for the entire sample (n = 227) to be 11,975 International Units per milliliter (normal: 5--500 IU/ml). The reason for the elevated IgE concentrations is unclear, although genetic factors and a high prevalence of parasitic infection may be involved. Atopic disease is rare among the Waorani as determined by medical history, physical examination, and immediate hypersensitivity skin tests. Our data are consistent with the association between hyperimmunoglobulinemia E and low prevalence of atopic disease in tropical populations. The significance of the findings with regard to the control of allergic disorders is discussed.
Adolescent↗
Infectious disease patterns in the Waorani, an isolated Amerindian population.
The Waorani Indians of eastern Ecuador provide a unique opportunity for studying exposure of an isolated human population to various infectious disease agents. Using serologic tests to determine antibody prevalence, skin test data, and stool examination for parasites, we have been able to construct a profile of infectious diseases which are endemic, and others which have been introduced into the Waorani population. These findings are compared with similar data reported from elsewhere in the Amazon. Serologic studies demonstrating the presence of antibody to measles and poliovirus type 3 after vaccination indicate that the Waorani respond normally to viral challenge with these agents. The question of genetic inability among aboriginal Amerindians to respond to viral agents is discussed. Finally, general recommendations are made regarding the future health care of the Waorani.
Adolescent↗
Characterization of a human macrophage-like cell line stimulated in vitro: a model of macrophage functions.
When cells of human macrophage-like cell line U937 are cultured in the presence of medium conditioned by mixed lymphocyte culture (MLC), PHA- or Con A-stimulated lymphocytes they demonstrate morphologic and functional characteristics of stimulation. The cells become larger, their surface more villous, and the cytoplasm has increased numbers of lysosomes and phagosomes. There is a marked (at least 10-fold) increase in antibody-dependent cellular cytotoxicity (ADCC) against both erythroid and tumor targets accompanied by increased expression of Fc receptors (FcR). There is also an augmentation of antibody-dependent phagocytosis. Medium conditioned by unstimulated lymphocytes, a B lymphoblastoid cell line or a fibroblast cell line produce very little stimulation of U937 cells. U937 cells gradually lose their increased ADCC capacity if they are washed free of conditioned medium (CM) but can be maintained in a stimulated state for long periods of time by culturing them in medium supplemented with PHA-CM at a concentration of 2%. Stimulation of macrophage-like cell line U937 may provide a useful model for further study of mechanisms of macrophage cytotoxicity and its modulation by products of activated lymphocytes.
Antibody-Dependent Cell Cytotoxicity↗