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B Glass

Publications and source records attributed to B Glass.

At least 19 recordsLinked to original sources
PubMed1992

Influence of cell dose and graft-versus-host reactivity on rejection rates after allogeneic bone marrow transplantation.

The number of cells transplanted and their capacity to induce graft-versus-host reactivity (GvHR) are two factors that are suspected to influence the engraftment of allogeneic bone marrow. We have investigated their impact on graft rejection rates in busulfan-treated LEW rats. In a series of experiments, we varied (1) the number of marrow cells transferred (1, 5, 10, 20, 30, and 40 x 10(7)), (2) the degree of pretransplant immunosuppression (1.5, 3.0, and 4.5 Gy of total body irradiation [TBI]; 0, 30, 60, 90, 120, and 180 mg/kg cyclophosphamide), and (3) the ability of the marrow graft to induce classical GvHR against major histocompatibility complex (MHC) antigens [semiallogeneic (CAP x LEW)F1 or CAP rats as marrow donors]. Reducing either the immunosuppressive pretreatment or the number of cells transplanted resulted in a stepwise increase in rejection rates. However, every reduction in the size of the marrow inoculum was compensated by increased immunosuppression and vice versa. While 60 mg/kg cyclophosphamide was sufficient to prevent rejections after grafting of 40 x 10(7) cells, 90 mg/kg was necessary to ensure 100% engraftment after transplantation of 20 x 10(7) cells, 120 mg/kg after 10 x 10(7) cells, and 180 mg/kg after 1 x 10(7) cells. Since CAP marrow leads to GvHR-mediated immunosuppression in LEW recipients, in contrast to (CAP x LEW)F1 marrow, we had supposed that lower cell numbers or cyclophosphamide doses are sufficient to achieve engraftment of CAP marrow. Although severe GvHR was present in all animals receiving escalating doses of CAP cells, the rejection rates were the same as for (CAP x LEW)F1 marrow. In conclusion, we have demonstrated that there is a sensitive balance between the immunosuppression of the host and the number of marrow cells transferred. We were not able to number of marrow cells transferred. We were not able to detect a beneficial effect of classical GvHR against MHC antigens on the engraftment of allogeneic marrow. Thus, our results do not support the hypothesis that the loss of GvHR-mediated immunosuppression is responsible for higher rejection rates following transplantation of T-cell-depleted bone marrow.

Animals↗
PubMed1992

Graft-versus-leukemia activity after bone marrow transplantation does not require graft-versus-host disease.

Clinical data have suggested that graft-versus-host disease (GVHD) plays a crucial role in the antileukemic effects of bone marrow grafts. We investigated (a) whether bone marrow cells unable to induce GVHD can effect graft-versus-leukemia (GVL) activity and (b) whether such antileukemic capacity depends on the presence of T lymphocytes in the graft. Balb/c mice were inoculated with A20 cells, a B-cell lymphoma/leukemia of Balb/c origin. Four weeks after tumor inoculation the animals were lethally irradiated and received a bone marrow graft. Cells from (Balb/c x C57) F1 or (C3H x Balb/c) F1 hybrids were transplanted into parental-strain Balb/c mice. Since lymphocytes from F1 hybrids are unable to cause graft-versus-host reactivity against a parental-strain animal, we used this experimental setting to explore GVL effects in a GVHD-free system. In vitro incubation with monoclonal anti-Thy-1.2 antibody plus complement was used to eliminate Thy-1+ cells. After syngeneic transplantation, the death rate due to leukemia remained unchanged (91%) compared with that among untreated animals (86%). Following transplantation of F1 marrow cells of either (C57 x Balb/c) F1 or (C3H x Balb/c) F1 origin, death rates of 40% and 50% were observed; these were significantly lower. Depletion of Thy 1+ cells from bone marrow graft caused only a slight increase in the leukemic death rate after transplantation of bone marrow of (C57 x Balb/c) F1 hybrid origin (50%), but a high leukemic death rate was seen after transplantation of (C3H x Balb/c) F1 bone marrow (100%). Additional experiments with fully allogeneic, T-cell-depleted C57 bone marrow transplantation suggest an antileukemic effect that is comparable to that seen after transplantation of unmanipulated F1 bone marrow. Taken together, our results indicate that GVL activity can be dissociated from graft-versus-host reaction.

Animals↗
PubMed1992

[Characteristics of changes of personal odor after experimental bone marrow transplantation].

In an operant conditioning paradigm 4 Balb/c inbred strain mice were conditioned to discriminate between urine samples of two other inbred strains. The purpose was to examine whether or not the known stimulus configuration during training had any effect upon the rate of recognition of other stimuli. On the basis of this procedure, we subsequently investigated the extent to which an allogeneic bone marrow transplantation interferes with the olfactory identity of an individual. For the transplants a strain was inbred which had no contact to the animals tested, a procedure used for the first time here. Furthermore, also for the first time, it was possible to demonstrate in a direct comparison, the role played by donor versus recipient characteristics on the olfactory composition of the recipients odor.

Animals↗
PubMed1991

Ifosfamide and ACNU in experimental allogeneic bone marrow transplantation.

We have tested ifosfamide and ACNU for their effectiveness in preventing graft rejection following allogeneic bone marrow transplantation. The engraftment-promoting potency of both was compared to that of the standard agent cyclophosphamide. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) (CAP x LEW) F1 marrow cells, which are unable to induce a graft vs host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte count either until death of the animal or until day 80. Surviving animals received a donor-type skin graft to confirm the persistence of allogeneic haematopoiesis. Because of its weak immunosuppressive properties, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, ifosfamide and ACNU and cyclophosphamide as the standard agent could be tested for their capacity to prevent marrow graft rejection. The following rejection rates were observed: cyclophosphamide: 30 mg/kg 100%, 60 mg/kg 60%, 90 mg/kg 20%, 120 mg/kg and 180 mg/kg 0%; ACNU: 3, 5, 7, and 10 mg/kg 100%, 15 mg/kg 45%, 20 and 30 mg/kg 0%; ifosfamide: 60-120 mg/kg 100%, 180 mg/kg 68%, 240 and 360 mg/kg 0%. Thus, 240 mg/kg ifosfamide or 20 mg/kg ACNU is nearly equivalent to the standard dose of 120 mg/kg cyclophosphamide in engraftment-promoting potency in allogeneic bone marrow transplantation.

Animals↗
PubMed1991

High-dose cytostatic agents in allogeneic bone marrow transplantation: comparison of the engraftment promoting potential.

We investigated the potential of various cytostatic agents for preventing graft rejection following allogeneic bone marrow transplantation. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) F1(CAP x LEW) marrow cells, which are unable to induce a graft-versus-host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte counts. Due to its weak immunosuppressive activity, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, agents administered in addition to busulfan can be tested for their capacity to prevent marrow graft rejection. 120 mg/kg of cyclophosphamide, 20 mg/kg of ACNU and 240 mg/kg of ifosfamide completely prevented rejection of the allogeneic marrow. Maximum doses of BCNU applicable in conjunction with busulfan reduced the rejection rate to 12% (30 mg/kg) and 17% (40 mg/kg), whereas the antitumour agents thiotepa, melphalan, and carboplatin exhibited a very limited engraftment-promoting potential in this experimental setting. Thus, BCNU (carmustine), ACNU (nimustine), and ifosfamide might be suitable candidates for conditioning of allogeneic bone marrow graft recipients.

Animals↗
PubMed1989

Failure of prediction of liver function test abnormalities with the urine urobilinogen and urine bilirubin assays.

A prospective observational study of 229 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. Both urine tests exhibited remarkably similar characteristics overall once they were adjusted to maximize accuracy and predictive values (occurring at a normal or abnormal "threshold," respectively, of 3.4 or 5.07 mumol/d for urobilinogen and 0 or 1+ for urine bilirubin). The percentage of cases correctly identified were 81% to 83% for serum bilirubin assays, 68% to 72% for other LFTs, but only 62% to 63% for screens for cases with at least one abnormal LFT finding. Poor sensitivities (47% to 49%) limited the detection of abnormal findings by the screen; both screens were reasonably specific (79% to 89%), but negative predictive values were suitable (89%) for serum bilirubin results only and were prohibitively lower (49% to 50%) in predicting all patients without LFT abnormalities. We conclude that spot urine urobilinogen and urine bilirubin determinations, although good screens for isolated serum bilirubin elevations, have unacceptable statistical properties as predictors of other LFT results due to a high proportion of false-negative results.

Bilirubin↗
PubMed1988

Abnormalities of urine urobilinogen and urine bilirubin assays and their relation to abnormal results of serum liver function tests.

A prospective observational study of 324 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. High positive predictive values (88% for at least one abnormal LFT) make the evaluation of positive urine screens detected during routine health care maintenance examinations imperative. Because extraneous factors may influence both urine and serum test results, however, urine assays obtained as a screening parameter in clinical presentations (abdominal pain, jaundice, constitutional symptoms, etc) have only limited clinical utility. The high proportion of false-negative results for both urine assays renders their statistical properties unacceptable as screens in these clinical situations.

Adolescent↗
PubMed1984

Some aspects of virus shedding by rainbow trout (Salmo gairdneri Rich.) after waterborne infection with viral haemorrhagic septicaemia (VHS) virus.

VHS virus shedding after experimental waterborne infection of rainbow trout was quantified by measuring virus infectivity in blood, faeces, and urine of catheterised fish. Virus shedding by urine with relatively high yields of infectious virus could be demonstrated during acute VHS until death, but not by faeces. Trout, which were vaccinated against VHS or had survived the disease but showed no detectable humoral antibodies, may excrete infectious virus via urine for more than 30 days and without any signs of VHS after a secondary challenge infection. These results reveal the development of a carrier status of rainbow trout after VHS exposure.

Animals↗
PubMed1979

Milestones and rates of growth in the development of biology.

An attempt has been made to examine the exponetial rate of increase of the great discoveries, the "milestones," in the rise of biology from the beginning of the seventeenth century, and particularly in the rise of genetics from the beginning of the twentieth century. The biological sciences in general, during the three centuries named, exhibit a doubling of the number of great discoveries in each fifty years. Genetics, in the twentieth century, has risen much faster. Its doubling time for the most significant discoveries has been about twenty-two and a half years. Either of these rates is of course far slower than the exponential rise in the total output of biological science, the number of scientists, or the cost of science, which have been generally reported to double about every ten years or less. It follows that, as time passes, and until these exponetial rates become considerably altered, a relationship of diminishing returns is quite evident. As time passes, even though the most significant discoveries continue to increase exponetially, it takes a greater total output, a greater number of (assisting?) scientists, and greater amounts of money to yield a set quantity of major new findings. The rapid rise of the life sciences cannot continue its present course into the twenty-first century without meeting ineluctable limits to expansion. It may be argued that as in other human spheres of activity, so too in natural science there are limits to growth which we are rapidly approaching. From the predictable asymptote only unpredictable breakthroughs might deliver us.

Animals↗