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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 307 records · Page 17Linked to original sources

An improved method for T-cell depletion of allogeneic histoincompatible donor bone marrow.

Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation is the most significant limiting factor preventing the widespread application of transplant therapy in acute leukemia and aplastic anemia. GVHD is mediated by T cells that contaminate harvested marrow in proportions ranging from 5-50% of the mononuclear cell population. T cell depletion (TCD) of large volumes of human marrow by E-rosetting for 24 h at 4 degrees C with modified sheep erythrocytes achieves removal of greater than or equal to 97% of all T cells, as judged by cytofluorographic analysis of the T-depleted bone marrow population with a broad panel of anti-T cell monoclonal antibodies, and abrogates functional T cell activity. Although T-depleted bone marrow cell recoveries were 2 logs below total harvested buffy coat cell numbers, the TCD mononuclear population was more than 99% viable and was enriched twofold for Ia+ cells as judged by cytofluorographic analysis. This method is at least the equivalent of those employing lectin column or monoclonal antibody/complement lysis techniques and is simpler to perform. Successful engraftment of adult patients can safely be obtained with as few as 4 X 10(8) total mononuclear cells following the 24-h procedure suggesting that prolonged or repeated T-depletion procedures do not interfere with stem cell engraftment. Preliminary results suggest that this method of TCD may ameliorate GVHD in histoincompatible transplants.

Bone Marrow↗

Thorium concentration in human tissues from two U.S. populations.

The concentrations of natural alpha-emitting isotopes of thorium (228Th, 230Th and 232Th) have been determined in 22 sets of human tissue samples obtained at autopsy from Grand Junction, CO and in 10 sets from Washington, DC. Tissues included lung, pulmonary lymph nodes, liver, kidney, bone, a few gonads, spleen and thyroid. Personal data on each individual's age, sex, smoking history and occupation were obtained whenever possible. The concentrations of 228Th, 230Th and 232Th were highest in lymph nodes for both populations with 2.6 and 5.1 pCi/kg of 228Th, 4.60 and 11.10 pCi/kg of 230Th, and 2.8 and 7.8 pCi/kg of 232Th in Washington, DC and Grand Junction, CO, respectively. The order of concentrations of all three isotopes in all other organs for both populations was as follows: (formula; see text) The data suggest that the non-mining residents who lived in the vicinity of uranium mine tailings do not have elevated 230Th concentrations in their lungs, when compared to the residents of Washington, DC who are not exposed to such tailings. However, 230Th concentration in bone of Grand Junction subjects was just significantly higher (at p less than 0.1) than that for Washington, DC subjects after suitable age adjustments. The data also suggest that 230Th is more available for accumulation in skeleton than would be supposed from its relative geochemical abundance.

Adolescent↗

Curium excretion studies in man and baboon: a predictive animal model.

A major rationale for performing metabolic research in laboratory animals is to obtain useful information which is applicable to man. Since it is usually impossible to determine many of the kinetic parameters which are responsible for the fate of a contaminant in inadvertently-exposed individuals, it is essential that well-controlled laboratory experimentation in animals be performed. In the present case, we will demonstrate how our experimental protocol, i.e. curium in the adult baboon, can provide a model from which to derive important characteristics of curium in man. To accomplish this goal, we have compared the retention and excretion patterns of curium in several men accidentally exposed via inhalation, burns, or puncture wounds with that of 243,244Cm citrate injected i.v. in nine adult baboons. Although many of the exposure conditions are different in considering the two primate species (human and non-human), biokinetic research in the baboon may serve to estimate tissue burdens and dose commitments in man. Comparison of the excretion rates of the nuclide in the urine of man and the baboon gives similar half times between days 10 and 50 post exposure.

Animals↗

The thymus dependency of transplantation allotolerance in the metamorphosing frog Xenopus laevis.

Larval as well as adult frogs (Xenopus laevis) are immunocompetent. Yet, whereas adults will vigorously reject MHC-incompatible skin grafts, metamorphosing larvae may not. Previous studies have revealed that this graft survival reflects an immunologically specific host tolerance. The role of the thymus in the acquisition of this tolerance to MHC-disparate skin allografts by metamorphosing outbred and inbred frogs has been investigated. When thymectomy was performed during midlarval or late larval life, it markedly impaired tolerance, as judged by an increased frequency of hosts rejecting grafts and by a curtailed survival time of rejected transplants. The efficacy with which thymectomy affected tolerance in this way was dependent on the developmental stage at which it was performed, on the haplotype disparity between donor and host, and on the size of the transplant. These last two variables also affect tolerance in intact perimetamorphic animals. Thymectomy during larval life affected the survival of grafts transplanted during postmetamorphic life. This influence was also dependent on the particular MHC haplotype incompatibility involved, and on the size of the transplant.

Animals↗

Xerophthalmia in urban Bangladesh. Implications for vitamin A deficiency preventive strategies.

Eight per cent of children attending a nutrition unit in urban Bangladesh had the eye signs and symptoms of vitamin A deficiency. About 1 in 10 of children with xerophthalmia and moderate-to-severe protein-energy malnutrition (PEM) had corneal involvement (X2,X3A/B): seasonal variation in prevalence was striking. Xerophthalmia was commonest in the 2-3 years age group and was associated with gastro-enteritis and measles. Breast feeding rates were low for PEM children with or without xerophthalmia. Poverty and overall shortage of food are the common denominators for both PEM and xerophthalmia. Effective vitamin A deficiency preventive strategies in urban Bangladesh will need, therefore, to include a broad range of measures such as the present limited distribution of high potency vitamin A capsules (200 000 IU) to children aged 0-6 years, food subsidies and food fortification if the most vulnerable children in the slums are to be reached.

Bangladesh↗

Where did all the "No-Shows" go?

The pilot study examines the demographic profile, referral source, and presenting symptom of 40 families whose child was referred to and accepted for assessment by the Outpatient Psychiatry Department of the Hospital for Sick Children, but who ended up cancelling their initial assessment interview when an appointment time was set. These "No-Show" cases constitute a relatively small (13.6%) proportion of the total population accepted for assessment. the "No-Show" families did not differ markedly from the general intake population in terms of age, and presenting problem. However, girls, suburban residence and lower class background were more prevalent in the "No-Show" group. The length of time spent on the waiting list was given most frequently as the primary reason for cancelling the appointment.

Ambulatory Care↗

HLA-D "BG" in Israel. A Japanese related allele population and family study.

An homozygous typing cell for a local HLA-D determinant"BG", defined by family study, is described. HLA-D "BG" recognizes a specificity identical to the Japanese HLA-DHO (Dw12). Two families and 102 randomly selected healthy Israeli individuals were typed for the HLA-D "BG" determinant. HLA-D "BG" showed segregation as a single determinant within families. The gene frequency for this allele was 0.045, compared to the frequency of 0.148 for DHO in Japanese. In the Israeli population "BG" is in strong association with HLA-Bw52 (joint occurrence = 7.80%) and DR2 (joint occurrence = 8.80%), resembling the data reported foar DHO (Dw12) in Japan. The frequency of this allele may partially account for the low frequency of HLA-Dw2 in the Israeli population.

Alleles↗

Study of a family with Cerebrotendinous Xanthomatosis. No HLA linkage, but an informative recombination between HLA-B and Bf.

A large family with three children affected with the autosomal recessive disease of Cerebrotendinous Xanthomatosis (CTX) was studied for class I (HLA-A,B,C) and class II antigens (HLA-DR,D,SB), properdin factor B and glyoxalase. The extensive typing revealed an informative cross-over between HLA-B and Bf, indicating that Bf is located centromeric to the HLA-B locus and segregated in this family with HLA-D/DR. The parents in this family were first cousins and their parents were also first cousins. Three of their four haplotypes share B14, BfS, DR1, Dx and SB4 and may be identical by descent. The three affected children carried among them all four parental haplotypes, indicating that close linkage of the CTX locus to HLA is unlikely.

Adolescent↗

Decompression incidence in air- and liquid-breathing hamsters.

The effects of hyperbaric compression on heart rate, rectal temperature, respiratory rate, bubble formation, and survival were studied in three groups of anesthetized golden hamsters (Mesocricetus auratus). Group I (15 animals) breathed air while exposed to 7 ATA of pressure for 1 h in a hyperbaric chamber; Group II (13 animals), at the same pressure level (7 ATA) and for the same time period (1 h), breathed an oxygenated fluorocarbon liquid (temperature 27 degrees C) that was open to the chamber atmosphere; Group III (10 animals), at the same pressure and time period as the other groups, were sealed in a flexible plastic bag filled with oxygenated fluorocarbon as a breathing mixture. A fourth, Group IV (12 animals), breathed oxygenated fluorocarbon for 1 h at 1 ATA. Survival after rapid decompression in each group varied, 9 animals died in Group I, 12 animals in Group II, whereas none of the animals died in either Groups III or IV. Thirty minutes after decompression postmortem examinations of all the animals demonstrated the presence of large amounts of gas bubbles in the right ventricle and some gas bubbles in the left ventricle of all the hamsters in Groups I and II. No gas bubbles were found in the hearts of the Group III animals. Group III animals, breathing a liquid unsaturated by an inert gas, survived rapid explosive decompression without the signs and symptoms of decompression sickness. Immersion in the liquid fluorocarbon produced a profound decrease in heart rate, rectal temperature, and respiration in Groups II, III, and IV.

Air↗

Self-pituitary grafts are not rejected by frogs deprived of their pituitary anlagen as embryos.

In the present study, we have adopted the model of Triplett to reinvestigate the timing of development of immunological tolerance to self-organ-specific antigens. We have removed pituitary or eye analgen from embryos before development of the immune system and returned them at a later time as differentiated organ implants to their now immunocompetent larval or adult original owners. If immunological tolerance to these putative organ-specific self-antigens occurs at an early and fixed time period, than organ-deprived hosts, lacking the opportunity to become tolerant, would be expected to reject such implants. Our results show that self-implants were never rejected whereas control allogeneic implants were usually rejected by larval hosts and were always rejected by adult hosts. These data, which contrast with those reported by Triplett, suggest that frogs, and perhaps other higher vertebrates, can become tolerant to self-organ-specific antigens throughout life.

Age Factors↗

Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus.

Development of autoimmune disease in female New Zealand hybrid mice was dramatically modified by classical conditioning of immunosuppression. Groups of animals received each week a solution of sodium saccharin (conditioned stimulus). One group of conditioned animals received an injection of cyclophosphamide (the unconditioned stimulus) after half of the weekly occasions when they received the saccharin solution. The rate of development of proteinuria and mortality were significantly retarded in these conditioned mice relative to untreated controls and nonconditioned animals that received unpaired treatment with saccharin and cyclophosphamide.

Conditioning, Psychological↗

Immunogenetic aspects of in vivo allotolerance induction during the ontogeny of Xenopus laevis.

This study describes the ontogeny of allograft immunity in a partially inbred strain of frogs (Xenopus laevis). At various times during the frogs' premetamorphic, perimetamorphic, and postmetamorphic life, major histocompatibility complex (MHC) homozygous strain JJ Xenopus (MHC haplotype j) were grafted with skin from adult donors of defined MHC homozygous (j,f) and heterozygous (j/f,f/h) haplotypes. This protocol reveals that destructive allograft reactivity to MHC alloantigens in Xenopus matures slowly and that allotolerance can be induced to such MHC-encoded antigens throughout larval life. The ultimate fate of an MHC disparate transplant (survival or rejection) is dependent on several interacting variables, which include antigen dose, haplotype dose, and the developmental stage of the host frog at the time of transplantation. In contrast, minor H-locus disparate (MHC compatible) grafts never appear to be rejected by hosts grafted at any larval stage.

Age Factors↗

HLA-DR, D recombination in a kidney transplant recipient.

Immunogenetic studies of a consanguineous family revealed discordance in the inheritance pattern of the HLA-D and HLA-DR antigens in one offspring. The findings suggest a recombination between the HLA-D and HLA-DR loci in one of the paternal chromosomes. Results on segregation of B-cell alloantigens. MLC reactivity, and glyoxalase isoenzyme determination map the DR gene between the HLA-B and D loci.

Chromosome Mapping↗