Sewall Wright's contributions to physiological genetics and to inbreeding theory and practice.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E S Russell.
Explore the source record for details and available documents.
Three hundred and seventy-eight patients from 4 chronic pain populations have been examined by self-assessment questionnaire methods to estimate the amount of psychiatric morbidity present. Using the General Health Questionnaire-28 scaled version (GHQ-28) the findings for probable psychiatric illness by clinic were: for anaesthetists' pain clinics serving a mixed urban and rural population--37%; for an oral medicine facial pain clinic--30%; for a rural hospital pain clinic--37%; and for a psychiatrists' pain assessment and treatment service--51%. These findings demonstrate the effects of selection upon the psychiatric characteristics of different pain populations. On the subscales of the General Health Questionnaire the psychiatric clinic patients were significantly more depressed than those in the other 3 groups (P less than 0.001) and also showed more social dysfunction (P less than 0.001). On the Irritability/Depression and Anxiety Questionnaire (IDA), depression and inward irritability were higher in the psychiatric clinic patients (P less than 0.001) but the amount of anxiety did not differ by clinic or by diagnosis (P greater than 0.05). These findings are taken to indicate that the extent of somatic complaints and anxiety does not differentiate the majority of pain patients in pain services with psychological illness from others attending for treatment. However, in the patients who have definite psychological symptoms, depression, social dysfunction and irritability provide a characteristic pattern. The psychiatric clinic patients were demonstrably more introverted or obessional on the Hysteroid/Obsessoid Questionnaire (HOQ) than those in other clinics. Childhood experience as seen by the patients did not differ by clinic or diagnosis and did not correlate significantly with personality as measured by the HOQ. It did correlate very significantly with measures of the current mood represented by the IDA. This effect was relatively weak, permitting the inference that the major portion of those psychological abnormalities which were found to be present was related to other factors such as the occurrence of painful lesions.
Pleiotropic effects on germ cell number, hematologic status, and body size are described in 12- to 15-day WBB6F1 normal (+/-) and defective (an/an) mouse fetuses, with special emphasis on gametogenesis. Differences between genotypes were apparent by Day 12. At 12 days, normal testes contained many germ cells and frequent normal mitoses, and the number of germ cells increased rapidly from Day 12 to Day 15. By contrast, 12-day an/an testes contained fewer germ cells, frequently degenerating, and many abnormal mitoses. Their number of germ cells decreased rapidly, so that almost none persisted to Day 15. Normal ovaries contained many germ cells, with much normal mitosis on Day 12 and 13, followed by meioses, but the smaller an/an ovaries contained few germ cells, with little mitosis, some meiosis, and very much degeneration. The erythrocyte counts of both normal and anemic fetuses increased approximately fourfold between 12 and 15 days, but at comparable ages, total counts were always lower in an/an fetuses than in normal littermates. At all ages, Hertwig's anemic (an/an) fetuses were somewhat smaller than their normal littermates. Although both W/Wv and Sl/Sld mice also show macrocytic anemia and germ cell failure, the great difference in etiology of their germ cell defects indicates that an/an gene action must be qualitatively different from that in either W/Wv or Sl/Sld mice.
Explore the source record for details and available documents.
Mice carrying two mutant W alleles usually have severe macrocytic anemias which result from deficiencies of hematopoietic stem cells (CFUs) (1). Anemic W39/W39 and W41/W41 homozygotes (2) have deficiencies in the numbers of femoral stem cells which correspond to the severities of their anemias. The non-anemic W44/W44 homozygote (2) has a few stem cells as the W41/W41 mouse. Nevertheless, bone marrow implants from W44/W44 donors cure the anemias of W/Wv recipients while implants from anemic W39/W39 and W41/W41 donors do not. The peripheral hematologic differences between W41/W41 and W44/W44 homozygotes probably arise from qualitative differences intrinsic to their stem cells rather than from extrinsic hematopoietic factors. The hematopoietic environments of all three W homozygotes are relatively normal in that they support normal erythropoiesis when injected with congenic +/+ marrow. Even non-anemic W44/W44 recipients are repopulated with +/+ donor red cells, indicating that W44/W44 stem cells are at a disadvantage when competing with normal counterparts.
In addition to their anemia, sterility and lack of coat pigment (1,2), W/Wv mice are mast cell deficient (3,4). Our analysis of three recently described W alleles (5) confirms reports (3,6) that (a) W mutations alter skin mast cell number in parallel with their influence on red cell number (but not with pigmentation), (b) that mast cells arise from hematopoietic tissue (7) and (c) that injections of normal bone marrow cells, which cure the anemias of W/Wv recipients, also alleviate the deficiency of skin mast cells in these mice. Transplants of bone marrow cells from mice homozygous for two new anemia-causing W alleles, W39 and W41, fail to cure the anemias of W/Wv recipients (companion paper) or increase the number of mast cells in their skin. Marrow cell implants from non-anemic W44/W44 mice cure the anemia, but do not change the number of mast cells in the skin of W/Wv recipients. The fact that the bone marrows of all three new homozygotes have fewer than normal numbers of CFUs hematopoietic stem cells (see companion paper) and have reduced mast cell-regenerating capacities, supports Kitamura's contention (8) that mast cell precursors may be closely related to or identical with the CFUs.
Characterization of the pleiotropic effects of ten new putative W locus mutations, nine co-isogenic and one highly congenic with the C57BL/6J strain, reveals a wide variety of influences upon pigmentation, blood formation and gametogenesis. None of the putative alleles, each of which is closely linked to Ph, a gene 0.1 cM from W, gave evidence of complementation with W39, a new allele previously shown to be allelic to Wv. All W/W39 genotypes resulted in black-eyed-white anemics with reduced gametogenic activity. Homozygotes for seven of these mutations are lethal during perinatal life; anemic embryos have been identified in litters produced by intercross matings involving each of these alleles.--Phenotypes of mice of several mutant genotypes provide exceptions to the frequent observation that a double dose of dominant W alleles (e.g., W/Wv or W/W) results in defects of corresponding severity in each of the three affected tissues. One viable homozygote has little or no defect in blood formation, and another appears to have normal fertility. The phenotypes of these homozygotes support the conclusion that the three tissue defects are not dependent on each other for their appearance and probably do not result from a single physiological disturbance during the development of the embryo.--Although homozygosity for members of this series results in a wide range of phenotypes, the absence of complementation of any allele with W39, the close proximity of each mutant to Ph, and the fact that all alleles produce detectable (though sometimes marginal) defects in the same tissues affected by W and Wv, support the hypothesis that each new mutant gene is a W allele.
In alpha-thalassemia, the genetic locus for the alpha chains of adult hemoglobin is not expressed. We have examined the hemoglobins of a number of individual mouse embryos heterozygous for a particular alpha-thalassemia (Hbath-J) and find no decrease in the proportion of hemoglobins containing the alpha chain as compared to the hemoglobin containing the alpha-like embryonic globin chain. This result suggests that the locus for this embryonic alpha-like chain is inactivated or deleted in these embryos as well. Because a single mutational event inactivated adult and embryonic loci, we conclude that they are probably closely linked to one another on the same chromosome. We also present evidence that an unusual hemoglobin in the blood of these embryos is composed only of an embryonic beta-like chain, and is thus analogous to the hemoglobin H (beta 4 tetramer) of adult alpha-thalassemics.
Using a high-resolution isoelectric focusing system, we have been able to separate the products of the individual "nonallelic+ mouse hemoglobin alpha-chain genes. The hemoglobins of mice of inbred strains that make two structurally different, but electrophoretically identical, alpha chains resolve into two bands on isoelectric focusing. The hemoglobin from other strains that make only one type of alpha chain forms a single band. Two new "alleles" of haplotypes of Hba (the alpha-chain complex locus) are described that code for hemoglobins with solubilities similar to that of the hemoglobin of strain C57BL/6J, but that give demonstrably different isoelectric focusing patterns. Because this method allows Hba typing of strains with the Hbbd or "diffuse" allele at the hemoglobin beta-chain locus, we have also been able to classify a number of previously untyped stocks, including some recently derived from feral populations. Among these mice we have found new representatives of most of the extant Hba genotypes. The demonstration that it is possible to detect genetic differences involving only neutral amino acid substitutions between proteins suggest that careful application of appropriate isoelectric focusing systems to the analysis of other proteins will greatly increase the sensitivity of our ability to detect genetic variation.
Explore the source record for details and available documents.
Access to medical services in north Canada is limited by geography, climate, communication and transportation. A geostationary spacecraft, Hermes, was used to provide dependable, high-quality communication between a remote nursing station, a base hospital and a health science centre. Teleradiology formed an important component of the telemedicine services. Remote supervision of radiography and fluoroscopy was made possible; consultation services were shown to be 90% effective.
Mutant Ts/+ fetuses are developmentally retarded as compared to normal +/+ littermates. Mutant fetuses have less total hemoglobin than do normal fetuses of the same gestational age. However, when compared to +/+ fetuses of similar body weight, Ts/+ fetuses have the appropriate amount of total hemoglobin, suggesting that the apparent anemia observed in mutant fetuses is most likely the result of delay in growth and development. Changes in proportions of embryonic hemoglobins during fetal development are similar in Ts/+ and +/+ fetuses at day 12 and later of gestation. Moreover, adult hemoglobin is detected in circulating primitive nucleated erythrocytes in the developmentally retarded Ts/+ mutant fetuses at about the same chronologic age as their +/+ normal littermates.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Search for structural variants of three globin chains (x, y, z), synthesized only during mouse embryonic hematopoiesis, was carried out by electrophoretic analysis of blood from 12-day embryos, all with C57BL/6 mothers, and fathers from 115 inbred stocks selected for their diverse genetic origins. Structure of the beta-chains of adult hemoglobins differed among the tested strains, with 57 carrying the Hbbs allele, 56 the Hbbd allele, and two the Hbbp allele. The search revealed no x- or z-chain variants but confirmed and extended knowledge of a previously described y-chain variant. Blood of all embryos sired by males from the 57 Hbbs strains contained only y'-chains, while blood of au embryos sired by Hbbd or Hbbp males contained y2-chains as well as the y1-chains inherited from their C57BL/6 mother. The locus controlling structure of the y-chain of mouse embryonic hemoglobins is thus extremely closely linked to the locus controlling structure of adult hemoglobin beta-chain, with maximum possible recombination frequency less than 0.019.