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J Adam

Publications and source records attributed to J Adam.

At least 73 records · Page 4Linked to original sources

The effect of stem cell proliferation regulators demonstrated with an in vitro assay.

Spleen colony formation after transplantation of bone marrow cells into irradiated mice has been used as an assay for hematopoietic stem cells (CFU-S), but has serious limitations intrinsic to an in vivo assay. In this report we describe experiments using an in vitro clonogenic assay that is especially suitable for studies of stem cell regulation as defined growth factors and normal untreated bone marrow can be used. We have demonstrated that the colony-forming cells have proliferative properties in common with CFU-S and respond to specific proliferation regulators previously detected using the spleen colony assay.

Animals↗

Patterns of recovery of high proliferation potential colony-forming cells after stressing the haemopoietic system--I.

The rates at which the number of high proliferation potential colony-forming cells and other haemopoietic cells recovered after different first stresses and a standard second stress were studied. The following first stresses were compared; different doses of sublethal irradiation (2.57, 4.84 and 5.5 Gy) followed by endogenous repopulation; lethal irradiation followed by exogenous repopulation; lethal irradiation of radio-protected mice followed by endogenous repopulation; and treatment with busulphan. Six to 16 weeks after these first stresses a standard second stress was applied. This was i.v. injection of fluorouracil. Two, four and six days later the number of high proliferation potential colony-forming cells in femora was determined and recovery curves for these cells were calculated. Their number increased exponentially in this period in all mice studied except radio-protected, lethally irradiated ones. In these, the exponential increase occurred between four and eight days after fluorouracil. The rate of increase was faster than normal in sublethally irradiated and radio-protected, lethally irradiated animals whose haemopoietic systems repopulated endogenously; in lethally irradiated, exogenously reconstituted animals it was the same as normal and in busulphan-treated animals it was slower than normal. The marrow from these differently stressed mice was also cultured with seven doses of two synergistic factors to contrast the growth of high proliferation potential colony-forming cells in the mice whose first stresses had differed. The cultures were assessed automatically by the CLIP 4 image processor. The high proliferation potential colony-forming cells of sublethally irradiated and busulphan-treated mice required more synergistic factor than normals to form a given number of cells/femur.

Animals↗

Biochemical investigations after burning injury: complement system, protease-antiprotease balance and acute-phase reactants.

Seventeen burned patients were investigated--Group I (n=10) with a mean burned area expressed as unit burn standard (UBS) of 69 +/- 24 and Group II (n = 7) with a mean UBS of 23 +/- 8. Blood samples were collected immediately after admission, 6-12 h after injury, during the morning and evening of day 1, and then daily for 2 weeks. This prospective study demonstrated complement activation in vivo in all burned patients, measured by C3d/C3 ratio index which was not related to the extent of the burned surface. A significant protease-antiprotease imbalance, correlated to the severity of burns, was found, leukocyte elastase was increased throughout the observation period, alpha 2-macroglobulin drastically decreased in severely burned patients, and alpha 1-proteinase inhibitor promptly decreased below the normal level in patients with more than 40 UBS. Finally, there was a delayed but then persistent acute-phase reactant protein response involving C-reactive protein, haptoglobin and alpha 1-acid glycoprotein, the concentrations of which reached a plateau on days 6 or 7.

Acute-Phase Proteins↗

Haemopoietic progenitors in different parts of one femur perform different functions during regeneration.

Femoral haemopoietic tissue was divided into cells released by flushing and cells released by grinding and washing flushed femora. The flushed femur contained 5 times more nucleated cells than the ground femur, 40 times more macrophage colony-forming cells and 6 times more developmentally late, day 8, and developmentally early, day 13, spleen colony-forming cells. However, the ground femur contained 2 times more developmentally early high proliferation potential colony-forming cells and 3 times more late ones. Haemopoietic regeneration of mice treated with fluorouracil was compared in samples obtained by flushing alone and grinding flushed femora. The number of nucleated cells recovered by flushing fell thirteen-fold by the sixth day after administration of the drug and the number recovered by grinding fell six-fold by the eighth day. Developmentally early high-proliferation-potential colony-forming cells which were recovered by grinding doubled their number in half the time taken by similar cells recovered by flushing. These observations are consistent with haemopoietic cells in different parts of the same bone performing different functions during regeneration. Large numbers of high-proliferation-potential colony-forming cells were not found in the circulation until 8 days after treatment with fluorouracil. Five days after mice had been treated with fluorouracil, when their blood forming systems were regenerating, early high-proliferation-potential colony-forming cells in one sample of marrow were derived from different founder cells than were late cells in the same sample. At the same time, early high-proliferation-potential colony-forming cells in the ground sample of a femur were derived from different founder cells than were cells at the same stage of development in the flushed sample of the femur. These observations are consistent with the view that haemopoietic regeneration after treatment with fluorouracil is due to the growth of few founder cells whose progeny have migrated little within 5 days of drug treatment.

Animals↗

Assessing cultured colonies automatically.

The number of colonies formed by macrophage colony-forming cells and high proliferation potential colony-forming cells was assessed by an image processor. The processor counted and sized colonies accurately, reproducibly, rapidly (2 s/dish) and objectively. The processor also measured the amount of light (in grey levels) the colonies transmitted. The optical density of a colony (the sum of its grey levels) was related to its cellularity. Thus the image processor compared both the number of colonies in samples and their cellularity. Samples of marrow containing high proliferation potential colony-forming cells of different proliferative capacity were prepared by injecting fluorouracil into mice and collecting their marrow 2-10 days later (marrow samples called FU2-FU10). These samples were cultured with one of three sources of synergistic factor titrated over seven dilutions. Colonies contained approx. 5 X 10(4) cells after 11 days culture but the way that FU2-FU10 marrow grew depended on the interval between treating donors with fluorouracil and collecting their marrow. Samples collected 2-4 days after fluorouracil formed more colonies containing more cells with small increases of synergistic factor whereas samples collected after 8-10 days did neither. It was important to culture samples of marrow with the appropriate synergistic factor for the interval after fluorouracil. Factor(s) derived from the 5637 cell line acted optimally on high proliferation potential colony-forming cells in samples collected 2-8 days after fluorouracil, and factor(s) derived from Wehi 3B cells on high proliferation potential colony-forming cells in samples collected 6-10 days after fluorouracil. Factor(s) derived from placental conditioned medium acted well on samples collected between 2 and 10 days. The proliferative capacity of samples of marrow could also be compared by estimating growth curves for high proliferation potential colony-forming cells in samples collected at successive intervals after fluorouracil.

Animals↗

What does a trainee see?

The experience of a trainee was documented in detail for a complete training year and the data were stored and analysed using a suite of purpose-written computer programs. The results indicate that the experience of the trainee was extremely similar to that of the trainer and that continuity of care must be considered in planning a training programme. The findings also emphasize that general practice deals with a wide range of problems many of which occur infrequently and therefore may not be adequately covered during the training year.

Continuity of Patient Care↗

Assessment of adequacy of pancreatic enzyme replacement with the multiple-phase carbon-14-triolein test.

The carbon-14-triolein absorption test was used to investigate fat absorption and its response to pancreatic enzyme replacement therapy in 10 men with pancreatic steatorrhoea. Absorption was increased in all, from 1,14 +/- 1,2% of the dose per hour (group mean +/- SD) to 2,85 +/- 2,33% (P less than 0,01) by the simultaneous administration of 8 tablets of enteric-coated pancreatic enzymes (Nutrizym; Merck). In patients with normal or high gastric acid secretion, neutralization of gastric acid with 30 ml magnesium trisilicate had no effect on absorption while the addition of an extract of gastric secretions (Enzynorm; Noristan) to the therapy of the 1 achlorhydric patient improved absorption from 2,2% to 3,81%. The 14C fat test offers a rapid and more acceptable alternative method for determining individual response to pancreatic enzyme replacement therapy than the conventional 72-hour faecal fat excretion measurement. The enteric-coated pancreatin preparation used in this study appears to be optimally effective under conditions of normal gastric acid secretion.

Adult↗

Haemopoiesis by clonal succession?

Alloenzymes of phosphoglycerate kinase (Pgk-1A and 1B), an X-linked enzyme of the glycolytic pathway that is expressed on all somatic cells, were used to study properties of developmentally early haemopoietic cells of mice (high proliferation potential colony-forming cells, HPP CFC) This study showed that: The colonies formed by HPP CFC are clones; There are distinct populations of HPP CFC that can respond to different haemopoietic growth factors; There are substantial differences in the proportions of Pgk alloenzymes of similar sets of HPP CFC found in similar and neighbouring bones; and In the whole animal, there is no evidence of any single population of HPP CFC that is permanently derived from a limited set of precursors.

Animals↗

A correlational analysis of symmetry between the arrowhead and featherhead Müller-Lyer illusions.

Correlational methods were used to investigate symmetry of effect for the arrowhead and featherhead versions of the Müller-Lyer figure. Two control figures were compared in the determination of baseline levels for measurement of the illusions: a shaft presented without any inducing context, and a shaft with vertical inducing lines attached. In addition, results based on difference-score measures of the illusions were contrasted with results obtained by partial-correlation techniques. Overall, when one considers the results for either one of the arrowhead or featherhead versions, the evidence favours a common underlying mechanism. However, results across the two versions suggest that the mechanisms for the two versions differ fundamentally. In weighting the different kinds of evidence contributing to this conclusion, methodological issues were raised. By obtaining two judgments for each stimulus figure from a large number of subjects, it was possible to demonstrate not only that conventional difference-score measures of illusions are highly unreliable, but also that they can yield biased results.

Adolescent↗

Seasonal variations of carbon monoxide-induced polycythemia in rats.

Fluctuations of the extent of polycythemia in rats due to repeated exposure to carbon monoxide prompted us to study whether the differences were caused by seasonal variations. Data from 18 independent experiments involving the hemoglobin values of 206 CO-exposed and 208 control rats over a period of nearly 3 years were available. Because the experiments were not designed for chronobiological studies, several methods of quasilinear and nonlinear regression analysis were applied to fit periodic models to the data. The best fit was obtained by a single cosine function with a period of nearly 12 months and with maximum values in winter and minimum values in summer. Experiments to elucidate mechanism(s) of seasonal variations showed that following a single CO exposure to the nocturnally active rodents, the rate of CO release from the body was higher in the dark span, that reduced food supply produced a potentiation of the CO-induced hemoglobin increase, and that the adaptive CO response was not affected by testosterone or thyroidectomy, but inhibited by L-thyroxine. Thus it seems that influences of light, CO elimination rate, food intake, metabolic rate and related hormones play a role for seasonal variations.

Animals↗

Familial cerebral amyloidosis and spongiform encephalopathy.

Clinical and neuropathological investigations are presented of the "W" family in which there is a dominant inheritance of slowly progressive cerebellar ataxia and dementia. The disease is of insidious onset and its average duration more than 4 years. Pathological findings included amyloid deposition in cerebellar and cerebral tissue; vascular amyloid in one case; and spongiform encephalopathy and astrocytic hyperplasia typical of Creutzfeldt-Jakob disease. Neuritic plaques of the senile (Alzheimer) type were present to a lesser extent. This study confirms the familial association between cerebral amyloidosis and spongiform encephalopathy.

Adult↗

Control stimuli in investigations of the acute-angled and obtuse-angled Müller-Lyer illusions.

Over the past decade, attention has been drawn to the importance of intertip distance (the distance between the tips of the arrowheads or featherheads) as a possible determinant of the Müller-Lyer illusion. Investigation of this stimulus property for the arrowhead and featherhead components of the Müller-Lyer figure has indicated that the two components exhibit a lack of symmetry, a conclusion supported by other studies using rather different approaches to the investigation of symmetry. This article argues that the control stimuli used in previous investigations are inadequate. It is proposed that in addition to the conventional straight-line control stimulus, in which the standard shaft is stripped of the oblique inducing lines. H-shaped figures in which the inducing lines are vertical should be included. Results are reported of an experiment in which both types of control stimuli are used to investigate the effects of intertip distance, and the spatial separation of that distance from the standard shaft, upon the arrowhead and featherhead figures.

Adult↗