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Biomedical subjects

J Caro

Publications and source records attributed to J Caro.

At least 91 records · Page 5Linked to original sources
PubMed1987

Serum erythropoietin in rheumatoid arthritis and other inflammatory arthritides: relationship to anaemia and the effect of anti-inflammatory treatment.

Serum erythropoietin (s-Epo) was measured with a sensitive radioimmunoassay method in 58 patients with classical rheumatoid arthritis (n = 41) or seronegative spondyloarthropathies (n = 17). Epo was significantly (P less than 0.001) increased and on an average two times higher than in a healthy population. A correlation was found between Hb and s-Epo (r = -0.46, P less than 0.005), indicating that these patients respond to anaemia with an increase in s-Epo. In order to investigate if inflammation has a direct influence on s-Epo levels a short period of corticosteroid treatment was given to rapidly decrease inflammatory activity. No increase in s-Epo was seen after 1 week. Furthermore, there was a correlation between s-Epo and ESR in all patients (r = 0.59, P less than 0.01). These results indicate that s-Epo is directed by the Hb level, which in turn is influenced by the inflammatory activity: a higher inflammatory activity gives a lower Hb and an increase in s-Epo. In comparison to previously published figures for the relation between Hb and s-Epo these patients seem to have an ordinary Epo response. We conclude that the anaemia of patients with chronic inflammatory joint disease is not caused by a diminished Epo production.

Adult↗
PubMed1987

Regulation of erythropoietin production in a human hepatoblastoma cell line.

Production of immuno and biologically active erythropoietin was documented to occur in the human hepatoblastoma cell line HepG-2. The expression of the erythropoietin gene was further verified by Northern blot analysis using a single stranded RNA probe. In vitro studies showed that erythropoietin production by these cells was not stimulated by hypoxia or cobalt chloride, but was related to the proliferative activity of the cells in culture. In addition it was found that the secretion of erythropoietin was almost completely abrogated by tunicamycin, an inhibitor of N-linked glycosylation. This effect of tunicamycin was also observed in a permanently transfected cell line that secretes erythropoietin in large quantities.

Animals↗
PubMed1987

Erythropoietin titers in anemic, nonuremic patients.

Erythropoietin titers when related to the hematocrit percentage and measured by bioassay in 33 normal volunteers and in 61 patients with anemias not complicated by renal or chronic disease were found to overlap with titers measured by radioimmunoassay in 20 normals and 28 patients with similar anemias. Erythropoietin titers measured by radioimmunoassay in 34 patients with rheumatoid arthritis, 25 patients with sickle cell anemia (58 separate samples), and 28 patients with erythroid hypoplasia caused by hematologic malignancies were compared with those in the control group of patients with uncomplicated anemias and found not to differ significantly from titers in this group. Erythropoietin titers measured by bioassay in 12 patients with aplastic anemia also fell within the range of those in the control group. Consequently, erythropoietin titers in these anemias appear to be determined primarily by the degree of anemia and not by any specific effect of these illnesses on the production of erythropoietin.

Anemia↗
PubMed1987

Long-term marrow cultures from mice with busulfan-induced chronic latent aplasia.

Mice treated with busulfan develop chronic latent marrow aplasia characterized by near-normal peripheral leukocyte counts, hematocrits, and marrow cellularity but very reduced stem cell (CFU-S) and progenitor cell (CFU-GM) populations. To determine whether the lesion is primarily in the stem cells or whether there is also a microenvironmental component we have used the Dexter-type long-term marrow cultures. Normal marrow maintains hemopoiesis for several weeks to months in such cultures, whereas "busulfan-marrow" will not support long-term growth. When normal marrow cells were transplanted onto an established adherent layer, whether derived from normal or busulfan marrow, normal hemopoiesis was established. However, busulfan-treated marrow cells would not establish hemopoiesis even when transplanted onto a normal stem cell-depleted adherent layer. It appears, therefore, that the primary lesion induced by busulfan is in the stem cells rather than in the microenvironment.

Animals↗
PubMed1987

Physiologic regulation and tissue localization of renal erythropoietin messenger RNA.

Although erythropoietin (Epo) is produced primarily by the kidneys in response to hypoxia, the precise cell type(s) and mechanisms by which these cells regulate production are poorly understood. In the experiments we report, the kinetics of renal Epo production in response to acute hypoxia and the intrarenal localization of cellular Epo synthesis were studied at the level of Epo mRNA. Erythropoietin mRNA expression was determined by Northern blot analysis of rat kidney RNAs using a probe derived from the mouse Epo gene. Renal Epo mRNA content increased as early as 1 hour after initiation of hypoxia and continued to accumulate during 4 hours of stimulation. Discontinuation of the hypoxic stimulus resulted in rapid decay of mRNA levels. Kidney and plasma Epo levels measured by radioimmunoassay paralleled, with respective lag times, the changes in renal Epo mRNA content, suggesting that Epo production in response to acute hypoxia represents de novo synthesis and is regulated by changes in Epo mRNA. Northern blot analysis of RNAs extracted from separated glomerular and tubular tissue fractions revealed Epo mRNA in the tubular fraction, whereas glomerular tissue did not contain Epo mRNA. Thus, the site of cellular Epo synthesis is located in the renal tubule or its interstitium and not in the glomerular tuft.

Animals↗
PubMed1987

Erythropoietin titers in response to anemia or hypoxia.

The normal response to anemic or hypoxic hypoxia is synthesis and release of erythropoietin in accord with the concept that erythropoietin production is controlled by a renal oxygen sensor. In this study, erythropoietin production, as predicted, was abrogated in patients with renal impairment (55 cases), but normal in nonuremic individuals. Specifically, patients with rheumatoid arthritis (34 cases), sickle cell anemia (25 cases), aregenerative anemia (27 cases), and aplastic anemia (13 cases) had erythropoietin titers overlapping with those observed in simple anemia (61 cases) at corresponding hematocrits. The response of polycythemic laboratory animals to hypoxia is more difficult to fit within the concept of an oxygen sensor responsive both to anemic and hypoxic hypoxia. If the polycythemia was induced by hypertransfusion, erythropoietin production in response to hypoxia was, as predicted, less than that observed in normal animals. If, however the polycythemia was induced by previous exposure to hypoxia, the animals responded to hypoxia as though they were not polycythemic. An explanation for this challenging observation may provide a clue as to the operation of the oxygen sensor.

Anemia↗
PubMed1986

Granulopoiesis in long-term culture by marrow from mice with busulfan-induced chronic latent aplasia.

Mice given high-dose busulfan therapy develop a chronic latent marrow aplasia characterized by normal peripheral blood neutrophil numbers, hematocrits and marrow cellularity but reduced numbers of pluripotent hemopoietic stem cells (CFU-s) and granulocyte-monocyte progenitor cells (CFU-gm). To study the pathogenesis of this lesion, bone marrow was propagated in long-term marrow cultures (LTMC). Small amounts of normal marrow readily established and sustained long-term granulopoiesis in vitro. In contrast, inocula of marrow from busulfan-treated animals containing three to five times as many stem and progenitor cells failed to establish long-term granulopoiesis in vitro. These results suggest that high-dose busulfan therapy produces a qualitative defect in either the hemopoietic stem cells, the stromal-forming elements, or both, rendering them incapable of establishing long-term granulopoiesis in vitro. Furthermore, mixing experiments employing normal and busulfan-damaged marrow demonstrate that this qualitative defect is not due to the emergence of a suppressor cell population. LTMC can show types of marrow damage not detectable by other techniques currently available and represent a powerful tool for studying latent bone marrow failure.

Anemia↗
PubMed1986

Physiologic and molecular biology of erythropoietin.

The gene for erythropoietin, the first growth and differentiation factor to be identified, has now been cloned and a recombinant erythropoietin is ready for clinical trials. This molecular achievement has also led to the identification of its mRNA in liver and especially in kidney tissue and here in the extra glomerular fraction. A radioimmune assay has been developed and its shows, as anticipated, low levels of erythropoietin in patients with kidney disease. However, in all other anemias, including the anemias of cancer, the levels of erythropoietin do not seem to be affected by the kind of disease but only by the degree of anemic hypoxia. The action of recombinant erythropoietin appears to be directed at surface receptors which increase in density on progenitor cells as they mature from early BFU-E to late CFU-E. These findings have led to an updating but not to a radical change in our concept of the feedback circuit which controls red cell production and the size of the red cell mass.

Animals↗
PubMed1986

Some comparative aspects of a longitudinal growth study in normal Spanish children and other longitudinal studies.

The differences existing among some european longitudinal growth studies make it necessary to be cautious in the use of standards constructed on different populations. The improvement of the environmental conditions during the last 20 years is probably the most important cause of the "catch-up" phenomenon of the spanish stature. It is probable that racial characteristics also play a role, even in the same country as can be appreciated on comparing two spanish longitudinal studies based on children originally from different regions. All of which indicates the need to use own standards in those countries which, like ours, have lived through a period of intense changes. Even exploratory studies of regional differences in the same country seem necessary.

Age Determination by Skeleton↗
PubMed1985

Effect of cyclosporine and delayed graft function on posttransplantation erythropoiesis.

The effect of delayed graft function and immunosuppressive drugs on posttransplant erythropoiesis was studied prospectively in 18 living-related (LR) and 84 cadaver-donor (CD) recipients. Eight of 18 LR and 20 of 84 CD recipients received antilymphoblast globulin (ALG) in addition to azathioprine and prednisone. Sixty-four CD recipients received cyclosporine (CsA) with prednisone. In the absence of rejection reticulocytosis began 6.7 +/- 0.2 days following graft implantation in azathioprine-only-treated LR recipients. This was lengthened by ALG to 9.4 +/- 0.3 and 9.9 +/- 0.7 days in LR and CD recipients, respectively, whose grafts functioned immediately. Delayed graft function prolonged onset of reticulocytosis to 15.9 +/- 0.9 days in ALG-treated but not in CsA-treated recipients (5.8 +/- 0.4 days). The shortest latency was noted in CsA-treated recipients (4.9 +/- 0.5 days) with immediately functioning grafts. The earlier onset of reticulocytosis of CsA-treated recipients was followed by statistically significant blunting of peak reticulocytosis, which correlated with a slower rate of correction of anemia (delta Hct = 0.19/day) compared with non-CsA-treated recipients (delta Hct = 0.34/day). Early rejection was associated with abrogation of reticulocytosis and correction of anemia without regard to immunosuppressive regimen) until rejection was reversed. Erythropoietin (EPO) was measured sequentially in 5 patients with immediate function. In 4 of 5 cases changes in EPO preceded those in reticulocytosis. EPO rose from a mean of 13 mU/ml pretransplant to a peak of 50 within 3 weeks and decreased to 18 mU/ml within 6 weeks of graft implantation. At six months posttransplant, normalized reticulocyte counts were only 55% higher (1.75 vs. 1.13%) but hematocrit had increased from 26 +/- 1% to 42 +/- 1%. Hematocrit varied inversely with serum creatinine, which was highest in CsA-treated patients with initial delayed graft function. We conclude that correction of anemia posttransplantation is driven by EPO but other factors may also be important, that neither ATN nor ALG-therapy have clinically important effects on erythropoiesis, and that CsA reduced "effective" erythropoiesis and influences correction of anemia--particularly if delayed graft function complicates the initial course posttransplantation.

Antilymphocyte Serum↗
PubMed1985

Why the kidney?

Severe erythrocytosis is associated with increased whole blood viscosity and impaired blood flow. Since a reduced blood flow will cause tissue hypoxia and since tissue hypoxia is associated with increased synthesis of erythropoietin, erythrocytosis per se should cause an increase in the rate of red cell production. This, however, does not occur and severe erythrocytosis in patients with polycythemia vera does not lead to increased synthesis of erythropoietin. We propose here that the reason for this discrepancy is that decreased blood flow to the kidneys, the site of erythropoietin synthesis, does not cause renal tissue hypoxia. The oxygen tension in the kidneys is to a great extent determined by the consumption of oxygen used for sodium reabsorption and since sodium reabsorption is roughly proportional to glomerular filtration, a decreased flow of blood should be matched by a decreased oxygen consumption leaving the tissue tension of oxygen unchanged. Consequently, the location of an oxygen sensor in the kidneys controlling erythropoietin production appears to be most fortuitous since it prevents the development of a vicious circle, with erythrocytosis causing more erythrocytosis.

Blood Viscosity↗
PubMed1984

Risk of large-bowel cancer in synthetic fiber manufacture.

In a previous study, the authors found an increased incidence of colorectal cancer among workers in a textile factory producing synthetic fiber. To answer the crucial question of whether the risk is confined to one section of the plant, a case-control study was done. For each of 43 cancers that occurred in the plant between 1965 and 1979, 3 controls were selected at random from company files of 24,270 current and past employees. They were matched for age, date of beginning employment, and duration of employment. Forty-four percent of the cancer patients worked in one of three departments: "extrusion D," "extrusion TM," and "textile," whereas only 21% of the controls worked in one of these departments (P less than 0.005). After 1974, when the peak incidence was observed, 10 of 21 patients had worked in either or both extrusion departments; only 8 of 63 controls had worked in these departments. (P less than 0.002). It took more than 10 years (10 of 33 cases versus 8 of 95 controls; P less than 0.002) before a risk became apparent. According to work areas, the relative risk was increased for those who had worked in building 3, where the extrusion D department was located (P less than 0.02). These results offer a basis for the prevention and surveillance of colorectal cancer in this industry.

Colonic Neoplasms↗
PubMed1984

Adrenocorticotropic activity of an extract from sheep placental tissue at term.

We have performed experiments to determine possible adrenocorticotropic activity in placental tissue of a sheep at term. The placental tissue was homogenized and extracted with 0.1 mmol/L of ammonium bicarbonate. The adrenocorticotropic activity of the term placental extract was compared to that of the vehicle (saline solution) and synthetic adrenocorticotropic hormone (ACTH). A single bolus injection of term placental extract had no significant effect on the plasma concentration of cortisol or progesterone. In a separate protocol, a bolus injection of ACTH was administered before and after a 48-hour continuous infusion of term placental extract, ACTH, or saline solution. The infusion of term placental extract or ACTH caused a significant increase in the basal cortisol and progesterone concentrations and a greater progesterone response following the second ACTH bolus. In vitro, the isolated adrenal cells from the term placental extract- and ACTH-infused animals showed a significantly greater ability to produce cortisol in the presence of exogenous substrate and ACTH. We concluded that placental tissue from sheep at term contains a substance which, when infused in vivo, has a corticotropic effect on the adrenal glands.

Adrenal Glands↗
PubMed1984

Asbestos-related fibrin formation in human plasma.

This study was designed to test the hypothesis that asbestos is responsible for the activation of clotting, for the reduction in activity of clotting factors and for the formation of fibrin when human plasma is exposed to asbestos chrysotile fibers in vitro. The recalcification time was accelerated in the early phase and was found to be greatly prolonged at 24 hours. The activated partial thromboplastin time showed marked changes at 24 hours only. One group of clotting factors, consisting of factors V, IX and X, showed the greatest decrease in their plasmatic activity. The factors least changed were factors XII and VIII; the other clotting factors were found in between these groups. Histologic examination demonstrated fibrin fibers in close proximity to the asbestos. Thus, chrysotile asbestos fibers activate clotting with the subsequent decrease in activity of some coagulation factors resulting in the formation of fibrin.

Adult↗