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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 199 records · Page 11Linked to original sources
PubMed1981

The role of abdominal computed tomography in lymphoma following treatment.

Two hundred and six patients with biopsy-proven lymphoma, 74 with Hodgkin's disease and 132 with non-Hodgkin's lymphoma had abdominal computed tomography for assessment of remission status (108 patients) or for investigation of relapse (98 patients). In 43 patients with diffuse large cell lymphomas scanned at a time of apparent complete remission CT was abnormal in 21. Sixteen of these patients have relapsed and died. Only one patient has relapsed in the group who have normal CT scans. This difference was significant (p=0.00001). This difference was not seen in nodular lymphomas. There were very few patients with Hodgkin's disease in whom the CT scan was abnormal and there is a suggestion that many abnormalities following treatment may represent inactive Hodgkin's disease or fibrosis only. CT played a major role in diagnosing the full extent of relapse in both non-Hodgkin's lymphoma and Hodgkin's disease. Over 50% of the abnormal sites detected by CT would not have been shown by any other non-invasive investigation. Five patients with treated Hodgkin's disease who had "B" symptoms only suggesting relapse were all shown by CT to have extensive intra-abdominal disease.

Follow-Up Studies↗
PubMed1981

Ultrastructural aspects of colchicine ultrasensitivity in CLL lymphocytes.

Circulating lymphocytes from patients with chronic lymphatic leukaemia show extreme sensitivity to colchicine, with 80%-90% cell death after exposure to 10(-7) M colchicine for 20 h in vitro. This is 100,000-times greater than the dose required (10(-2) M) for a similarly toxic effect on normal lymphocytes. A time course series of fixations during the 20-h exposure of chronic lymphoid leukaemia (CLL) lymphocytes to 10(-7) colchicine revealed an entire spectrum of ultrastructural alterations well in advance of any sign of cell death, previously only ascertained by nuclear pycnosis in the light microscope. The changes included the appearance of large numbers of intermediate filaments, loss of surface microvilli, mitochondrial alterations and the formation of annulate lamellae. Mitochondrial changes included disruption of the cristae, swelling and tight clumping of the entire mitochondrial population into a single region of the cytoplasm.

Adolescent↗
PubMed1981

A method for following human lymphocyte traffic using indium-111 oxine labelling.

A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed.

Cell Movement↗
PubMed1981

Human lymphocyte traffic assessed by indium-111 oxine labelling: clinical observations.

Clinical studies using indium-111 oxine labelling of human peripheral blood lymphocytes are presented. Data from animal models of lymphocyte migration are compared with results found in healthy subjects and patients with malignant neoplasms. The physiological significance of bone marrow and liver localization on gamma camera imaging is discussed and the importance of considering the surface marker characteristics of the lymphocytes under study, when interpreting results, is emphasized. The possibility that the redistribution of lymphocytes within the body is a cause of the peripheral blood lymphopenia in patients with Hodgkin's disease and other malignancies is suggested, and the usefulness of indium-111 oxine labelling in clarifying this problem is proposed.

Cell Movement↗
PubMed1980

Relative activities of linear and cyclic electron flows during chloroplast CO2-fixation.

Evolution of oxygen and turnover of cytochromes b-563 and f were measured upon illumination of isolated intact spinach chloroplasts with a series of flashes. The flash yield of cytochrome f oxidation approximated the sum of the yields of cytochrome b-563 reduction and electron transfer through Photosystem II, regardless of whether HCO(-3), 3-phosphoglycerate or O2 served as the terminal electron acceptor. No absorbance contribution form cytochrome b-559 was discerned within the time range studied. Some pseudocyclic electron flow occurred when both HCO(-3) and 3-phosphoglycerate were omitted, and possibly also during induction of photosynthesis; however, the flash yield data suggest tht O2 is not reduced at a significant rate during steady state photosynthesis. The maximum rate of cytochrome f turnover (1000 microequiv./mg chlorophyll per h) was adequate to support the highest rates of photosynthesis observed in isolated chloroplasts. These results agree with the concept that cytochrome f is a component both of the linear and cyclic pathways whereas cytochrome b-563 functions only in the cyclic pathway. NH4Cl decreased the half time of cytochrome b-563 oxidation fro 11.6 to 8.2 ms and decreased the half time of cytochrome f reduction from 7.2 to 2.8 ms. The cyclic and linear pathways thus seem to be jointly regulated by a transthylakoid H+ gradient through a common control point on the reducing side of cytochrome f. Cyclic turnover also increased during the induction phase of photosynthesis, when linear throughput is limited by the rate of utilization of NADPH. The slow rise in the P-518 transient correlated with increased cyclic activity under the above conditions. It is proposed that flexibility in the utilization of linear and cyclic pathways allows the chloroplast to generate ATP and NADPH in ratios appropriate to varying needs.

Carbon Dioxide↗
PubMed1980

Advanced recurrent squamous cell carcinoma of the head and neck. Results of a chemotherapeutic regimen with adriamycin, bleomycin, 5-fluorouracil, methotrextate, and vitamin A.

Twenty-five patients with advanced squamous cell carcinoma of the head and neck were entered into this study. All patients had previously been irradiated and the majority had also undergone surgery for recurrent tumor. A low-dose regimen consisting of adriamycin, bleomycin, 5-fluorouracil, methotrexate, and vitamin A was prescribed, the median number of courses was four and a total of 95 were administered. Ten patients (40%) achieved objective responses (7 partial, 3 complete). The median duration of response was 14 weeks (range, nine to 60 weeks) with a median survival time of 38.5 weeks (range, eight to 72 weeks). The nonresponding patient group's survival time was significantly reduced (P = 0.002; median, 12 weeks; range, three to 40 weeks). The treatment was given on an outpatient basis and no serious hematologic toxic reactions were encountered. Mucositis was uncommon. This regimen produced an acceptable response rate without serious side-effects. The use of Vitamin A may have helped to prevent further impairment of the patient's nutritional status by ameliorating drug-induced mucositis.

Adult↗
PubMed1980

Anti-T antibody in malignant melanoma patients. Influence of response and survival following chemotherapy--changes in serum levels following C parvum, BCG immunization.

The level of anti-T antibodies directed towards the precursor T antigen of the MN blood group system was measured in the sera of 55 patients with disseminated melanoma, before and during chemoimmunotherapy. The anti-T titer was subnormal in patients before therapy; patients who responded to therapy had significantly higher titers than did nonresponders in sera taken before therapy, at regression/progression of disease, and during the last pulse of treatment. Higher pretreatment titers were associated with a significntly longer survival time. A single infusion of Corynebacterium parvum was given to 14 other melanoma patients and significant elevation of preimmunization titers was observed on days 14, 21, and 28 after infusion; Bacillus Calmette-Guerin, vaccination of 9 patients did not significantly alter the anti-T titer. The expression of the normally cryptic T antigen on melanoma cells would absorb naturally circulating anti-T antibodies. Less dense expression of T antigen on melanoma cells that were responsive to therapy, i.e., less "malignant," would explain the better prognosis for patients with higher titers. The increase in anti-T antibodies following administration of C parvum but not of BCG is of possible clinical relevance when C parvum is used as an immunotherapeutic agent.

Adult↗
PubMed1980

Computerised acquisition and analysis of flow cytometric data.

An interface between a commercial flow cytometer (Ortho Cytofluorograf 4800) and a Desk Top Computer (H.P. 9845S) is described. Programs for data acquisition and analysis have been developed. These include cell DNA content analysis, 2-parameter (3D) histograms and sophisticated sub-population selection. Although cell sorting is not possible using the facility, the data acquired per cell is optimised and detailed analysis can be carried out. The system represents a flexible, easily controlled and economical method for storing and analysing flow cytometric data.

Cells↗
PubMed1980

Computed tomography (CT) in the staging of patients with Hodgkin's Disease: a report on 136 patients.

One hundred and thirty-six patients with biopsy proven Hodgkin's disease (HD) had conventional staging investigations and CT carried out at presentation. CT did not detect 20 out of 24 positive spleens and did not detect disease at 16 involved lymph node sites proven at laparotomy. In 60 cases in whom lymphography was performed, CT detected all disease shown by lymphography and showed additional disease in 13 other cases (three within the lymphogram area). In 43 patients CT was the only investigation of the abdomen that could be performed and identified 31 unexpected areas of disease in this group. CT altered the stage of the patients in 16% of cases compared with 8% (lymphography) and 34% (laparotomy). The importance of CT as a baseline investigation for the subsequent monitoring of the complete remission of all known disease is discussed, and the routine use of CT when available as the primary non-invasive staging investigation of the abdomen in HD is recommended.

Abdominal Neoplasms↗
PubMed1980

Colchicine ultrasensitivity of peripheral-blood lymphocytes from patients with non-Hodgkin's lymphoma.

Incubation for 20 h in low concentrations of colchicine has been shown to kill the peripheral blood lymphocytes (PBL) of patients with chronic lymphocytic leukaemia (CLL), whereas at least a 10,000 x higher concentration of colchicine is required to kill lymphocytes from a normal donor. This ultrasensitivity of CLL lymphocytes to low doses of colchicine was confirmed in 19/20 PBL samples, 5/6 lymph nodes, and in the one totally replaced marrow studied. PBL from 75 patients with non-Hodgkin's lymphoma (NHDL) were examined for colchicine ultrasensitive (CUS) cells similar to those found in CLL. All the patients had less than 5 x 10(9)/1 morphologically normal circulating lymphocytes. PBL from 45 healthy donors and 39 patients with diseases other than leukaemia or lymphoma were used as controls. CUS cells were detected in 24 (32%) of the 75 patients. The CUS cells were considered to represent blood involvement with malignant lymphocytes for three reasons. First, there was an association with marrow involvement (P less than 0.05) which usually accompanies involvement of the blood with morphologically abnormal cells. Secondly, 23 (77%) of the 30 involved lymph nodes, marrows and spleens studied were CUS. Thirdly, there was a close correlation with the presence of a monoclone of B lymphocytes demonstrated by surface markers (P less than 0.01).

Adolescent↗
PubMed1980

Relationship between the pretreatment proliferative activity of marrow blast cells and prognosis of acute lymphoblastic leukaemia of childhood.

Pretreatment marrow blast cells were studied in 38 boys and 27 girls (aged 1-14) with acute lymphoblastic leukaemia by flow cytometry after staining with propidium iodide.The percentage of blast cells in the S phase of the cell cycle ranged from 1% to 40% (median 6%). A correlation was found between the percentage of cells in S and the morphological classification of the French American British Cooperative Group (FAB), presence of T or B cell markers, haemoglobin concentration, blast size, bone pain, platelet count, and an inverse correlation with coarse granule and block staining with Periodic-acid-Schiff (PAS).63 of the 65 children attained complete remission. During the first 24 months of follow up there were fewer relapses (P = 0·054), and deaths (P = 0·004) in those children with 6% or fewer blasts in S phase. The difference was most marked in the first 12 months with 4 relapses out of 33 in the group with 6% or fewer cells in S compared with 13/30 in the group with > 6% cells in S.In order to investigate the prognostic significance of the pretreatment proliferative studies in greater detail, remission duration was correlated with 17 presenting features. Each feature was correlated individually and then the simultaneous effect of all the features was assessed by stepwise multiple regression.Only 3 features of the disease at diagnosis were individually correlated with duration of remission. These were% cells in S (P < 0·001), log white cell blood count (WBC) (P < 0·01) and the presence of T- or B-cell surface markers (P < 0·05). However, the multiple regression analysis showed that cell markers were not an independent prognostic feature, whereas the percentage cells in S and log WBC were independently and significantly correlated with duration of first remission (P < 0·001 in each case).

Acute Disease↗
PubMed1979

Electron transport pathways in spinach chloroplasts. Reduction of the primary acceptor of photosystem II by reduced nicotinamide adenine dinucleotide phosphate in the dark.

Addition of NADPH to osmotically lysed spinach chloroplasts results in a reduction of the primary acceptor (Q) of photosystem II. This reduction of Q reaches a maximum of 50% in chloroplasts maintained under weak illumination and requires added ferredoxin and Mg2+. The reaction is inhibited by (I) an antibody to ferredoxin-NADP+ reductases (EC 1.6.7.1), (ii) treatment of chloroplasts with N-ethylmaleimide in the presence of NADPH, (iii) disulfodisalicylidenepropanediamine, (iv) antimycin, and (v) acceptors of non-cyclic electron transport. Uncouplers of phosphorylation do not affect NADPH-driven reduction of Q. It is proposed that electron flow from NADPH to Q may occur in the dark by a pathway utilising portions of the normal cyclic and non-cyclic electron carrier sequences. The possible in vivo role for such a pathway in redox poising of cyclic electron transport and hence in controlling the ATP/NADPH supply ratio is discussed.

Chloroplasts↗
PubMed1979

Cytochrome function in the cyclic electron transport pathway of chloroplasts.

Flash excitation of isolated intact chloroplasts promoted absorbance transients corresponding to the electrochromic effect (P-518) and the alpha-bands of cytochrome b6 and cytochrome f. Under conditions supporting coupled cyclic electron flow, the oxidation of cytochrome b6 and the reduction of cytochrome f had relaxation half-times of 15 and 17 ms, respectively. Optimal poising of cyclic electron flow, achieved by addition of 0.1 microM 3-(3,4-dichlorophenyl)-1,1-dimethylurea, increased phosphorylation of endogenous ADP and prolonged these relaxation times. The presence of NH4Cl, or monensin plus NaCl, decreased the half-times for cytochrome relaxation to approximately 2 ms. Uncouplers also revealed the presence of a slow rise component in the electrochromic absorption shift with formation half-time of about 2 ms. Ths inhibitors of cyclic phosphorylation antimycin and 2,5-dibromo-3-methyl-6-isoprophy-p-benzoquinone abolished the slow rise in the electrochromic shift and prolonged the uncoupled relaxation times of cytochromes b6 and f by factors of ten or more. These observations indicate that cytochrome b6, plastoquinone and cytochrome f participated in a coupled electron transport process responsible for cyclic phosphorylation in intact chloroplasts. Estimations of cyclic phosphorylation rates from 40 to 120 mumol ATP/mg chlorophyll per h suggest that this process can provide a substantial fraction of the ATP needed for CO2 fixation.

Antimycin A↗
PubMed1979

Spinal-cord compression in myeloma.

Clinical records of 47 patients in whom spinal-cord compression was the presenting feature of plasma-cell myeloma were analysed retrospectively. Patients were referred during 1954-78. Median survival was 30 months and prognosis was best for those in whom the site of cord compression was the thoracic region. Early laminectomy and decompression followed by adequate radiotherapy resulted in complete or good partial response in over a third of patients who presented with complete paraplegia. Improvements in supportive care and more effective chemotherapy allow spinal-cord compression in myeloma to be treated promptly and vigorously, thus improving duration and quality of survival in a substantial proportion of patients.

Female↗