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Biomedical subjects

C Haworth

Publications and source records attributed to C Haworth.

At least 37 records · Page 2Linked to original sources
PubMed1989

T cells and lymphokines.

T lymphocytes are one of the richest sources of protein mediators. Many of their effects, such as T cell help, growth stimulation, macrophage activation or suppression are caused by the release of these molecular mediators, which include the interleukins IL-2, IL-3, IL-4, IL-5, IL-6, interferons alpha and beta (IFN alpha and beta), tumour necrosis factor (TNF), lymphotoxin (LT), granulocyte macrophage colony stimulating factor (GM-CSF) and transforming growth factor beta (TGF beta). These molecules are only produced transiently after activation of the cells, and the CD4 (cluster differentiation antigen 4) cells are the richest sources of cytokines.

Animals↗
PubMed1988

Role of HLA class II and cytokine expression in rheumatoid arthritis.

HLA class II expression is notable in rheumatoid arthritis. We have investigated the mechanism of HLA class II regulation in the joints and found local synthesis, as judged by mRNA levels to be high. The role of antigen presentation in maintaining class II mRNA was explored, and blocking presentation by using monoclonal antibodies to HLA class II inhibited synthesis of mRNA for HLA-DR alpha chain. HLA class II expression is maintained by cytokines and so cytokine production in rheumatoid joints was investigated. It was chosen to use mRNA analysis by slot blotting as a screening assay, and the expression of many cytokines was detected. Levels of these were maintained in culture in the absence of extrinsic stimulation.

Antibody Formation↗
PubMed1988

Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid leukemia.

The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in chronic myeloid leukemia (CML) but is less common in acute lymphoblastic leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+ ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the BCR gene; this results in a smaller chimeric gene which encodes a P190 BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a "masked" Ph chromosome in association with extensive karyotypic changes. The leukemic cells initially showed rearrangement of the bcr, presence of a hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent in remission. These results support the concept that the BCR-ABL chimeric gene plays a crucial role in leukemogenesis but suggest that factors other than the position of the breakpoint in the BCR gene determine the lineage of the target cell for malignant transformation.

Blotting, Southern↗
PubMed1985

Serial incidence of bone marrow GM-CFC prior to the development of acute non-lymphoblastic leukaemia in a child treated for non-Hodgkin's lymphoma.

A child treated for NHL developed acute non-lymphoblastic leukaemia 27 months after stopping treatment. Serial in vitro bone marrow studies showed a normal incidence of GM-CFC following treatment. However, GM-CFC incidence dropped at least 15 months prior to the development of leukaemia. This was associated with an asymptomatic neutropenia but no disturbance of bone marrow morphology. It is concluded that sub-clinical disturbances of bone marrow function may play an important part in leukaemogenesis.

Acute Disease↗
PubMed1985

Intracranial pressure after atracurium in neurosurgical patients.

In order to investigate the usefulness of atracurium for neurosurgical anesthesia, we studied its impact on intracranial pressure (subarachnoid bolt) mean arterial pressure (radial artery catheter) and cerebral perfusion pressure (mean arterial pressure-intracranial pressure) in 20 patients undergoing elective craniotomy for brain tumor excision. General anesthesia was induced with thiopental, 4 mg/kg intravenously, and maintained with 70 percent nitrous oxide in oxygen. Ventilation was controlled by face mask, with end-tidal CO2 held constant. Once intracranial pressure and mean arterial pressure had stabilized, the response to atracurium, 0.5 mg/kg intravenously, was continuously recorded for 5 min in 10 patients. An additional 10 patients received no atracurium and served as matched controls. Thiopental caused reductions in ICP in both groups of patients. Comparing the responses of the patients who received atracurium with those who did not, we found that atracurium had no significant effect on intracranial pressure, mean arterial pressure or cerebral perfusion pressure. Based on these data we conclude that atracurium appears to be preferable to the other available neuromuscular blocking agents that have been evaluated for neurosurgical anesthesia.

Adult↗
PubMed1982

Long-term bone-marrow damage in children treated for ALL: evidence from in vitro colony assays (GM-CFC and CFUF).

We have studied granulocyte-macrophage progenitor cells (GM-CFC) in serial bone marrow aspirates from 43 children who had been treated for acute lymphoblastic leukaemia (ALL). All patients were in full remission, not receiving anti-leukaemic therapy and 42 out of the 43 had normal peripheral blood counts. Thirty-seven patients have received standard amounts of chemotherapy and 6 have received additional therapy for relapses occurring in the first treatment-free interval. In the former group estimation of GM-CFC incidence did not provide evidence of long-term residual bone-marrow damage. In the latter, however, the mean incidence of GM-CFC was significantly reduced. This reduction was also apparent when the incidence of GM-CFC was related to the incidence of non-haemopoietic progenitor cells within the marrow (CFU-F).

Antineoplastic Agents↗
PubMed1982

Thiamine responsive anaemia: a study of two further cases.

A brother and sister of Pakistani origin suffered from sensorineural deafness, diabetes mellitus and a macrocytic anaemia. Their bone marrows showed megaloblastic erythropoiesis and contained many ringed sideroblasts. Electron microscope studies of the bone marrow revealed (1) iron-laden mitochondria in many erythroblasts, (2) non-specific abnormalities indicative of dyserythropoiesis in some erythroblasts, and (3) evidence of ineffective erythropoiesis. The deoxyuridine suppression test indicated that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. Studies of nucleic acid synthesis in the bone marrow cells showed that the rate of incorporation of [3H]thymidine into DNA was increased and that the rates of incorporation of [14C]glycine and [14C]adenine into both DNA and RNA were essentially within the normal range. The anaemia did not respond to therapy with hydroxocobalamin, folic acid or pyridoxine but responded to 25 mg thiamine, daily, by mouth. In one of the cases a post-thiamine marrow aspirate showed a considerable improvement in both the megaloblastic and sideroblastic changes.

Anemia, Macrocytic↗
PubMed1981

Routine bone marrow examination in the management of acute lymphoblastic leukaemia of childhood.

Eighty-four children with acute lymphoblastic leukaemia (ALL) who had relapsed in bone marrow were studied to assess whether treatment would be more successful if relapse was detected before the disease became clinically evident. Patients whose relapse was detected by routine bone marrow examination before the disease became apparent were compared with those whose relapse was suspected from clinical examination or peripheral blood findings. In the former there was a lower percentage of blast cells in the marrow (p less than 0.02) and the patients suffered less from complications of the disease, but there was no difference in the incidence or duration of second remissions between the two groups.

Bone Marrow↗
PubMed1979

Viability of red cells stored in diminished concentration of citrate.

A comparison was made between the post-transfusion survival of red cells stored in standard ACD-A and in modified ACD-A, containing two-thirds the amount of citrate. Measurements of survival after 28 d storage in both solutions were made in each of six subjects. Mean post-transfusion survival with the two solutions was almost identical. When the results in one subject in whom survival was particularly bad with both solutions were omitted mean values at 24 h were 74.0% for standard ACD-A and 74.9% for modified ACD-A. It is concluded that viability is just as well maintained in modified ACD-A as in standard ACD-A. The results also provide further evidence of large differences between donors with respect to the maintenance of red cell viability during storage.

Adenosine Triphosphate↗
PubMed1979

The prognostic significance of morphological features in childhood acute lymphoblastic leukaemia.

A consecutive series of 209 children with acute lymphoblastic leukaemia (ALL) presenting to a regional referral unit between 1970 and 1977 was studied. The following morphological features in the initial bone marrow were recorded: blast size, percentage periodic acid-Schiff (PAS) and oil-red-O (ORO) positivity, percentage of blasts with vacuoles, and acid phosphatase positivity. The blasts were also coded according to the FAB (L13) classification. When analysed separately, increasing blast size was significantly related to the length of first remission (P = 0.01). However, this was almost entirely due to its association with the FAB L2 type of disease which also had a highly significant influence on length of first remission (P less than 0.0001) independent of all other factors. Patients with L3 disease had blasts with heavy vacuolation, ORO positivity and displayed monoclonal surface immunoglobulin and their prognosis was very poor. The percentage of vacuolated blasts and ORO positivity otherwise showed no influence on prognosis. Fine granularity of PAS staining in lymphoblasts showed no prognostic value but the trend of longer remission duration with increase in percentage of PAS coarse granularity and blocks, was statistically significant (P = 0.006). This relationship was partly due to a correlation with the presence of mediastinal mass and L2 disease, but was still independent of all other prognostic factors. In a smaller number (39) of the series of patients on whom cell surface markers were available, we were unable to demonstrate a correlation between T-derived blasts and the L1 and L2 classification; but there was a strong correlation with polar acid phosphatase positivity in T-derived blasts.

Acid Phosphatase↗
PubMed1978

A case of atypical polyagglutinability due to Tk-transformation.

A case of acquired transient polyagglutinability in a group O, Rh(D) positive female patient, Wa, is described. An unusual finding in the preliminary serological investigation was the non-reaction of the cells with peanut (Arachis hypogaea) extract. The patient's red cells were strongly agglutinated by normal human and rabbit sera from which anti-T had been removed. Electrophoretic mobility studies and tests with polybrene indicated that their sialic acid content was normal. The use of a specific antiserum raised in a rabbit to Wa cells and cross-absorption tests showed that the patient's erythrocytes shared similar antigenic determinants to red cells treated with supernatants from pure cultures of Bacteroides fragilis. The in vitro-modified red cells reacted strongly with BS II lectin prepared from Bandeiraea simplicifolia seeds thus providing confirmatory evidence for Tk transformation on Wa cells. It is concluded that the Tk receptor is probably a more frequent feature of acquired transient polyagglutinability than has hitherto been recognized.

Animals↗
PubMed1978

Fetomaternal transfer of glucose analogues by sheep placenta.

The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.

Animals↗
PubMed1976

Permeability of the sheep placenta to unmetabolized polar non-electrolytes.

1. The rate of appearance in uterine venous blood of radioactively labelled, polar, non-electrolytes has been measured following their injection into the foetal circulation in the chronically catheterized sheep near term. Uterine blood flow was measured by an antipyrine technique. 2. Estimates of a placental permeability constant not corrected for area were 61-2 +/- 5-5 ml. min-1 (mean +/- S.E. of mean) for [14C] urea, 1-85 +/- 0-16 for [14C]erythritol and 0-21 +/- 0-03 for [3H]mannitol. Results are also presented for [14C]ethylene glycol, [14C]L-glucose, [14C]mannitol, [51Cr] EDTA and [3H] and [14C]sucrose. 3. In four sheep, permeability measurements for several solutes were made and the results were analysed in terms of restricted diffusion via cylindrical, water-filled pores. Calculation of pore radius was made by a minimum variance method and values ranging from 0-43 to 0-45 nm were obtained. 4. Stability and absence of protein binding of probe molecules was investigated by gel permeation on Sephadex columns.

Animals↗