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J M Yoffey

Publications and source records attributed to J M Yoffey.

At least 19 recordsLinked to original sources

Virus dissemination via the lymphomyeloid complex.

In the previous AIDS symposium organized by the Society, Witte and Witte (1) made a number of predictions, one of which was that in AIDS patients, "Lymph from the thoracic duct should be strongly positive for HIV." Though direct evidence for this is lacking, some early experiments of ours with vaccinia virus (2) are fully in accord with this prediction, to which they lend indirect support. In rabbits, nasally instilled vaccinia virus spreads via the lymphatic pathway (afferent peripheral lymph--deep cervical gland--efferent lymph--thoracic duct) in as short a time as nine hours. Virus is transported mainly in cells, for when the efferent lymph is centrifuged virus is found only in the cell sediment. It seems reasonable to assume that other viruses, including HIV, are similarly disseminated. Paradoxically, the lymphomyeloid complex both greatly facilitates the spread of virus, and at the same time, mounts the immunological defenses against the virus which it so effectively helps to disseminate. Whatever the portal of entry of the virus, its transport by migrating cells ensures its dissemination throughout the lymphomyeloid complex, including the bone marrow. The bone marrow is an integral part of the complex, as the prime source of B lymphocytes, T lymphocyte precursors, and many of the antigen-presenting cells as well as the granulocytes. There is some evidence concerning possible ways in which the bone marrow can contribute to the development of immune deficiency in AIDS patients. The bone marrow merits further study in this context.

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Stem cell kinetics: correlation of in vivo and in vitro data.

Comparisons have been made along three parameters between the observations of a number of workers regarding in vivo the transitional cell compartment, and in vitro observations of colony-forming units. The parameters used were size changes when the stem cell requirements are increased, the existence of three size groups in both the transitional cell compartment and in the colony-forming units examined, and the relation between cell size and the percentage of cells in DNA synthesis. On all these parameters there appears to be close correlation between the in vitro properties of stem cells and progenitor cells and the in vivo properties of the transitional cell compartment. Transitional cells appear to be the only cells in the marrow that can match the kinetic properties of a number of colony-forming units.

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DNA synthesis in peritoneal lymphoid cells. Indirect induction of changes.

Changes were observed in the DNA-synthesising cells of the murine peritoneal cavity after a single subcutaneous injection of (1) fluid thioglycollate medium, (2) guinea-pig serum, (3) pertussis vaccine, (4) fresh egg albumen, (5) bovine albumin Fraction 5, (6) normal saline as control. The subcutaneous route was chosen in order to avoid direct peritoneal irritation. A total of 180 animals was employed, in six groups of 30 each, and in each group five animals per day were examined for six days. In all cases except the controls there was a significant increase in the number of DNA-synthesising cells in the peritoneal fluid, as measured in autoradiographs following incubation with tritiated thymidine. The labelled cells were predominantly lymphoid, some resembling the transitional cells of bone marrow. There was also a smaller number of labelled macrophages. Changes were maximal after thioglycollate. The peak percentage of labelled cells occurred on Day 1 after thioglycollate and egg albumen, on Day 2 after guinea-pig serum, and on Day 4 after pertussis vaccine and bovine albumin.

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Phagocytic lymphoid cells and transitional cells in the peritoneal cavity.

In 71 mice, a study was made of the non-granular phagocytic cells in the peritoneal cavity, both after the intraperitoneal injection of India ink, and by incubation of the non-adherent cells with ink in vitro. Ink was taken up by a number of lymphoid cells, as well as by macrophages and monocytes, referred to jointly as macrophages. In addition, the presence of DNA-synthesizing cells was investigated by radio-autography after incubation of cell suspensions for 1 hour with tritiated thymidine. A small number of labelled macrophages was usually found in the normal peritoneal cavity, and also about 1% of labelled cells with the typical morphological features of the transitional cells seen in bone marrow. During 14 days after the intraperitoneal injection of ink, the combined population of lymphoid cells and macrophages showed an increase in the percentage of lymphoid cells, and a fall in the percentage of macrophages. The phagocytic lymphoid cells did not appear to develop into macrophages. It seems reasonable to assume that the haemopoietic stem cells known to be present in the peritoneal cavity are to be found among the transitional cells, some of which may also be macrophage or lymphocyte precursors.

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Studies on transitional cells. I. Kinetic changes in rat bone marrow during hypoxia and rebound.

Kinetic changes have been studied in the transitional cells of the marrow in normal, hypoxic (0.5 atm) and rebound rats. Suspensions of marrow cells were incubated with tritiated thymidine for 1 hour, and the percentage of labelled transitionals of all sizes, as well as of large transitionals, was couinted in radioautographs. From a normal labelling index of 55.4% +/- 6.0089 there is an initial fall after 1 day of hypoxia, followed by a significant rise to 69.233 +/- 2.8263% on day 3, when erythropoiesis is at its peak. This is followed by a sharp fall to a low level of 35% on day 2 of rebound, when erythropoiesis is depressed, returning to normal by day 7. The highest labelling index is found in the large transitional cells.

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The lymphocyte production pathway in bone marrow: possible significance of the size spectrum of lymphocytes and their precursors.

It is now generally accepted that transitional ('lymphoid') cells are the precursors of small lymphocytes. Such cells have a heterogeneous size spectrum and show high proliferative capacity. To facilitate the study of the kinetics of lymphocyte production, a detailed investigation of cell sizes of the transitional cell-lymphocyte compartment was carried out using a Coulter counter modified to permit a very rapid and accurate examination of cells in suspension. Enriched populations of 'lymphoid' cells, obtained after 10 d rebound from hypoxia at half an atmosphere, were enriched further by bovine albumin and Ficoll gradients to give density fractions containing two types of cells. Differential counts of stained smears of these fractions enabled a comparison to be made between the size distribution and the specific cell types. Four distinct cell types were characterized in terms of volume and density: small and intermediate-sized lymphocytes (volume 53-59 fl, albumin fractions 19-23%), small transitional cells (154-160 fl, 21-23%), medium transitional cells (206-218 fl, 17-19%) and large transitional cells (350-400 fl, 21-27%). These findings are consistent with the view that there are at least three mitoses in the course of the lymphocyte production pathway in the bone marrow.

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Successive stimulation of major cell groups in bone marrow. A preliminary approach to the problem of stem cell competition.

The existence of pluripotential haemopoietic stem cells raises the possibility of stem cell competition when two or more differentiating stimuli are given either simultaneously or in close succession. The experiments now reported deal with the effects on guinea pig bone marrow of successive stimulation and they fall into two groups. In one group, erythropoiesis was first stimulated by means of hypoxia, after which granulopoiesis was stimulated by the intraperitoneal injection of typhoid vaccine. In another group, these two stimuli were given in the reverse order. Bone marrow changes were evaluated both quantitatively and by differential counts. The experimental animals were compared with controls given only one stimulus, either hypoxia or vaccine, and also with normal untreated animals. As judged by the output of granulocytes or erythrocytes, no stem cell shortage developed in the experimental animals. A marked fall in transitional cells in the bone marrow of the experimental animals is consistent with the view, though not affording actual proof, that the pluripotential stem cells are to be found in the transitional cell compartment.

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