Transplantation of cells in an immunoisolation device for gene therapy.
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Animals↗
Biomedical subjects
D R Boggs
Publications and source records attributed to D R Boggs.
A modification of cellulose that facilitates the control of complement activation.
Complement activation by Cuprophan hemodialysis membranes has been linked to a variety of pathological sequelae (neutropenia and various cardiopulmonary manifestations) seen in the clinical setting. The modification of reactive surface hydroxyl groups on regenerated cellulose with various dicarboxylic-acid anhydrides has been found to significantly limit the complement-activating potential of these materials. Of the anhydrides tested, maleic anhydride appears to display the most dramatic and consistent diminution of complement activation compared to unmodified cellulose (0-10% of control values for C3b deposition and C3a/C5a production). Current evidence suggests that this maleated derivative facilitates the factor-H control of C3 and C5 convertase activity and thus may help limit complement activation by normal regulatory mechanisms. In addition, this modification may help limit the production of other inflammatory mediators that may result in diminished levels of cellular activation.
Biocompatible Materials↗
The effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice.
Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of 59Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and 59Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen 59Fe and a decrease in marrow 59Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen 59Fe uptake but the marrow 59Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.
Animals↗
Conversations with a Chinese editor.
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China↗
Search for eosinopenia in hospitalized patients with normal blood leukocyte concentration.
Hospitalized patients were studied prospectively in an attempt to determine whether idiopathic eosinopenia in the absence of other major changes in blood cells is rare or is more frequent than is commonly recognized. Strict criteria for eosinopenia were used; patients with more than 10.0 X 10(9)/liter total leukocyte count, or less than 4.0, as well as those with any form of hematologic cancer, or those receiving any form of cancer chemotherapy, were excluded from the study. With those criteria and exclusions, only 24 patients with eosinopenia were found among 24,300. Twenty were receiving some form of adrenal glucocorticosteroid (steroid) and of the other four, three had serious organic diseases for which they were receiving various drugs. The remaining patient, whose primary problem was depression, could have had drug-induced eosinopenia. Thus, unexpected eosinopenia appears to be a very rare event or syndrome. A normal range for eosinophils was defined from studies of 740 medical students, which was 0.015 to 0.65 X 10(9)/liter and was quite similar to previously reported values. The effect of acute or chronic steroid administration on eosinophils in normal human subjects was studied. Confirming studies reported for man and many other mammals, eosinopenia developed promptly, but disappeared within hours unless repeated doses were given. Literature on various types of eosinopenia was reviewed.
Eosinophils↗
Chronic lymphocytic leukemia in China.
Chronic lymphocytic leukemia (CLL) is a very common form of leukemia among middle-aged and elderly persons in Western countries. In the Japanese, or in those with Japanese ancestry born and living in the USA, CLL is rather rare. It is also rare in China, but convincing data to support this statement are found primarily in the Chinese literature. We have reviewed previously unpublished data from Peking Union Medical College (PUMC) concerning the frequency of CLL among adult patients with the four common types of leukemia. Of 4,174 such patients (1952-1986), 4.6% had CLL; 22.9% chronic myeloid leukemia (CML); 50.3% acute myeloid leukemia (AML); and 22.3% acute lymphoblastic leukemia (ALL). This low frequency of CLL is none the less higher than that found in a multiinstitutional collection of Chinese patients with leukemia. Various clinical and laboratory aspects of a carefully studied, previously published group of patients with CLL from PUMC were compared to similar published findings in patients from the University of Utah. No differences in the overall nature of the disease were detected between these groups. However, not unexpectedly, the duration of symptoms before the diagnosis was made longer in Chinese than in USA patients and the proportion diagnosed at a time when no CLL related symptoms had been noted was less in Chinese. Neither differences in life span in the two populations nor an excess of CML, AML, and ALL at the expense of CLL were viable hypotheses to explain the rarity of CLL in China. We suggest that the dearth of CLL in Chinese is on a genetic basis, as it is thought to be in the Japanese.
Adult↗
Fate of a ferrous sulfate prescription.
Prescriptions for ferrous sulfate, 300 mg, were filled with eight different preparations by 15 pharmacies. Only three types of pills had a reasonably rapid dissolution time in acid media and these were all obtained from university-associated pharmacies. Some form of "slow release" or "enteric coat" feature was present in the pills and capsule supplied by private pharmacies and the Veterans Administration Hospital pharmacy. Adding the phrase "not enteric-coated" to the prescription effected no change in the type of pill supplied. Prices were highly variable, even for the same preparation, and although all generic pills were cheaper than brand-name pills, the "supermarket" type pharmacies charged as much or more for the pills as individually owned pharmacies.
Costs and Cost Analysis↗
Marrow mass and distribution in murine skeletons cleaned by beetles as compared to cut up carcasses and a further simplification of the latter technique.
Distribution of 59Fe into various bone groups of the complete murine skeleton was studied using two methods of dividing up the bones: 1) our previously reported technique of simply cutting up a skinned, eviscerated carcass and 2) separating bones from skeletons cleaned of overlying tissue by beetles, Dermestes species. The total percentage of injected 59Fe recovered in the sum of all skeletal parts, the percentage of total skeletal 59Fe found in each bone group, and the overall accuracy of determining these values were quite similar for the two techniques. The only statistically significant difference shown was a modest decrease in the percentage of total skeletal iron found in ribs plus sternum plus cervical and thoracic spine in beetle-cleaned as compared to cut up groups and we would not consider this to be of biological significance. Cutting up carcasses is the simpler of the two techniques but there are circumstances in which beetle digestion would be advantageous. In addition, we collected data on the reproducibility and precision of determining the percentage of 59Fe injected which is found in a "pulled off" foreleg plus scapula and of the distribution of 59Fe within three cut up pieces from the leg and within the scapula. These data can be used as a measure of overall changes in marrow mass and/or distribution, or at least they can be used as a screening procedure to detect such. This simple procedure adds potentially useful values for fully interpreting hematopoietic changes in the mouse.
Anatomy↗
Cytobiologic and clinical aspects in a patient with chronic neutrophilic leukemia after thorotrast exposure.
A patient with fairly typical chronic neutrophilic leukemia, as represented by some two dozen such reported cases, had been given Thorotrast more than 20 years before. Typical myeloblastic crisis developed with remarkable terminal leukocytosis. Mature blood neutrophils had normal function with respect to phagocytosis, bacterial killing, metabolic activation, and chemotactic response. The number of cells producing colonies of neutrophils and monocytes in in vitro semisolid cultures was normal in the blood and increased in marrow. Colony size was smaller than is usually observed in normal patients or in typical patients with chronic myeloid leukemia. Termination in blast crisis, also seen in a few other patients with chronic neutrophilic leukemia, indicates that this is indeed a form of leukemia and not a "leukemoid" reaction of obscure cause. The differential diagnosis of extreme neutrophilia is discussed.
Aged↗
Hematopoiesis and aging. V. A decline in hematocrit occurs in all aging female B6D2F1 mice.
Longitudinal studies of hematocrits were done in aging B6D2F1 female mice at 54, 64, 91, 105 and 115 weeks of age. A modest decline in hematocrit was observed in 41/42 mice; we have previously shown that the decreased hematocrit of aged as compared to young mice is due to an expansion of plasma volume. Mice which died spontaneously after 91 weeks had lower hematocrits at 91 weeks and 105 weeks than did those which survived to 115 weeks. At each time interval, a sub-group of mice was killed and uptake of 59Fe into blood, foreleg, spleen and liver was studied and total nucleated cells per humerus was determined. The results were generally compatible with the thesis that aging mice maintain normal rates of erythropoiesis under basal conditions. Thus, it would appear that a decrease in hematocrit can be considered an expected part of the aging process in this mouse.
Aging↗
Jehovah's Witnesses with leukemia.
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Adolescent↗
Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice.
Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27-28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43% vs 49% (p less than .001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20-25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal-appearing hair; the latter was subdivided into those weighing less (25-26 g) or more (30-34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild "dilutional" anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process.
Aging↗
Amegakaryocytic thrombocytopenia.
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Humans↗
Suppression of hepatic hematopoiesis with radioactive gold (198Au).
A patient with idiopathic myelofibrosis of some 20 yr duration developed esophageal varices and ascites. No explanation for increased portal pressure other than hepatic hematopoiesis was found. Consequently, a trial of cobalt irradiation to the liver was undertaken with definite but transient decrease in ascites. Subsequently, two courses of radioactive colloidal gold were given, again with definite but transient beneficial effects on the degree of ascites. This latter benefit occurred without suppression of marrow function.
Aged↗
Effect of rabbit antimouse brain serum on marrow cells capable of curing W/Wv mice.
The W/Wv mouse has a recessively inherited defect in hematopoietic stem cells (HSC) but can be cured of its hematopoietic abnormalities by infusion of marrow from a co-isogeneic, +/+ mouse. The "curative" cell for the W/Wv is thought to be a subcompartment of the HSC that is capable of forming hematopoietic spleen colonies (CFU-S) in irradiated mice. The curative HSC must have a very high proliferative potential and it is known that HSC with variable degrees of proliferative potential are found within the CFU-S compartment. Rabbit antimouse brain serum (RAMBS) was used to treat +/+ marrow and its effect upon CFU-S and upon curative cells was compared with the effect of normal rabbit serum (NRS) or of sham treatment. CFU-S were reduced to 70%-79% of control by NRS and to 8%-9% by RAMBS. Curative cells for the W/Wv were not detectably reduced by NRS; they were reduced by RAMBS, but to only approximately 20%-30% of control. Thus, it appeared to a certain degree that RAMBS spared HSC with a high proliferative potential when compared with its effect on the entire CFU-S compartment.
Animals↗
Hematopoiesis and aging: IV. Mass and distribution of erythroid marrow in aged mice.
Aged mice are "anemic," i.e., they have a lower hematocrit than young adult mice, but this appears to be a "dilutional" anemia; the red cell mass is normal. Other observations have supported the hypothesis that basal erythropoiesis does not change as mice grow old. In the present study, the percentage of injected 59Fe found in the skeleton and spleen, 59Fe distribution between various bones and bone groups, and the number of nucleated erythroid cells per humerus were studied and the total mass of erythroid precursors was calculated. There was no significant difference in any of these values between mice aged 3-27 months. The variability of 59Fe distribution within various skeletal parts was no greater in aged than in young mice. Thus, these data further strengthen the case for normal basal rates of erythropoiesis in aged mice.
Aging↗
The total marrow mass of the mouse: a simplified method of measurement.
The total number of nucleated cells in the long bone of a mouse can be determined with some accuracy. Thus, in this species, values for marrow cells can be expressed as a total cell count per bone, a more meaningful number than values expressed as concentration as is done in most studies of other species. If the percent of total marrow in the skeleton that is contained in that bone is known, values can be expressed as "per mouse" (total marrow mass)--a still more meaningful value than values per bone. The total marrow mass of mice has been calculated previously on the basis of nucleated cells per humerus or per femur and the percent of the total marrow contained in that bone. However, that percent was based on rather tedious dissection of the entire skeleton and determining the amount of 59Fe that had been taken up by each bone. In the present study, mice were injected with 59Fe, skinned, and eviscerated. The carcass was then either cooked and all bones dissected out or simply cut into pieces containing various bones or bone groups. The percent of 59Fe taken up by various bones or bone groups as measured by the two techniques was virtually identical. The percent distribution between various bones was found to be fairly constant between 4 and 18 h after 59Fe injection and the same in mice aged 3 or 12 months. This simplified technique makes the measurement of total marrow mass a practical addition in studies of murine hematopoiesis.
Animals↗
Aging and hematopoiesis. II. The ability of bone marrow cells from young and aged mice to cure and maintain cure in W/Wv.
The proliferative ability of hematopoietic stem cells (HSC) was compared in young and aged mice. Infusion of coisogeneic marrow cures the hematopoietic defect of the W/Wv, a mouse with a recessively inherited defect in stem cells, including HSC. W/Wv were cured with equal frequency by relatively small doses of marrow (5 X 10(4) nucleated cells, an average of 2-3 "curative" HSC per aliquot) from 3-month-old or 27-month-old +/+ donors. After functioning in the originally cured W/Wv for 26 months, the marrow was used to cure other W/Wv. After functioning in secondary recipients for 16 months, it was, in turn, used to cure still other W/Wv. There was no difference between "old" and "young" bone marrow with respect to the frequency of cure in W/Wv, the duration of cure--or, in regard to marrow from cured W/Wv, the number of nucleated and peroxidase-positive cells per humerus and the number of cells capable of producing spleen colonies in irradiated recipients. Thus, these studies fail to disclose any evidence for a proliferative limitation for old as compared to young HSC.
Aging↗