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Biomedical subjects

J E Harris

Publications and source records attributed to J E Harris.

At least 145 records · Page 8Linked to original sources
PubMed1985

Adjuvant tamoxifen treatment of elderly women with stage II breast cancer. A double-blind comparison with placebo.

One hundred seventy elderly women with stage II breast cancer, stratified on the basis of the number of positive axillary nodes and estrogen receptor status, were randomly assigned to receive tamoxifen or placebo for 24 months in a prospective, double-blind, adjuvant trial. The median age was 71 years with a range from 65 to 84 years. The overall percentage of patients disease-free at 4 years was 76% for those given tamoxifen and 52% for those given placebo (p = 0.0004). Benefit was seen in all subgroups of patients treated with tamoxifen. Two years of tamoxifen therapy represents an effective postoperative adjuvant treatment for elderly women with stage II breast cancer, resulting in improved time to relapse, statistically fewer distant first recurrences, and minimal toxicity. No improvement in overall survival has been seen yet.

Aged↗
PubMed1985

A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial.

A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.

Adenocarcinoma↗
PubMed1984

The separation of cytotoxic human peripheral blood monocytes into high and low phagocytic subsets by centrifugal elutriation.

Mononuclear cells (4 X 10(8) in a 5-ml volume) were loaded onto a Beckman JE-6B elutriator rotor spinning at 2,000 +/- 10 rpm with a flow rate of 10.0 ml/min. After lymphocytes were removed at flow rates between 10 and 11 ml/min with 500 ml of buffer, the flow rate was increased by 0.5 ml/min/fraction to collect 100-ml fractions. Highly enriched monocytes as judged by nonspecific esterase staining and morphology (70-95%) were found in each of eight fractions collected with flow rates between 11.5 to 15.0 ml/min. When stimulated with phorbol myristic acetate, these fractions mediated equivalent levels of cytotoxicity against 51Cr-labeled Chang liver cell line. Similarly, each monocyte-containing fraction was found to mediate the same level of cytotoxicity against antibody-sensitized 51Cr-labeled Chang liver cells. In contrast, cytotoxicity against the natural killer cell-sensitive K-562 cell line was found in only those fractions that contained a high percentage of lymphocytes. The fractions that were enriched in monocytes were found to differ in their ability to ingest latex. Those monocyte fractions that were collected between 11.0-12.0 ml/min consisted primarily of low numbers of latex-ingesting monocytes (less than 30%). Those monocyte fractions that were collected between 12.5 and 15.0 ml/min consisted primarily of latex-ingesting monocytes (50-70%). These data show that cytotoxic monocytes can be separated by centrifugal elutriation into at least two subsets that can be distinguished by their phagocytic activity.

Animals↗
PubMed1984

Effect of cytotoxic antineoplastic chemotherapy on immunoregulatory leukocytes measured with monoclonal antibodies.

The influence of cytotoxic chemotherapy on immunoregulatory leukocyte subsets measured by monoclonal antibodies was evaluated in the peripheral blood mononuclear cells from 15 patients with nonlymphoreticular solid tumors. The results obtained were correlated to changes in sheep erythrocyte-receptor-bearing T cells, active T cells, and latex-ingesting cells; also, these leukocyte values were correlated with changes in phytohemagglutinin (PHA)-induced lymphoproliferative responses and indomethacin-sensitive suppressor cell function. The results obtained demonstrated the cytotoxic chemotherapy did not consistently influence percentages of T cells whether these were measured as sheep erythrocyte-binding cells or as OKT.3+ cells. Similarly, consistent effects on OKT4 and OKT8 cells were not observed. Chemotherapy often led to suppression of the OKT4/OKT8 ratio and tended to restore abnormal percentages of active T cells at some point following initiation of drug treatment. The effects of chemotherapy on these leukocyte values could not be consistently correlated with changes in PHA-induced lymphocyte DNA synthesis or indomethacin-sensitive regulation of PHA reactivity.

Adult↗
PubMed1984

Memory failures in everyday life following severe head injury.

Questionnaires concerning the incidence of memory failures in everyday life were used in a postal survey of the aftereffects of severe head injury. Several years after a severe injury, 50 patients were compared to 33 patients a similar period after a very mild injury. A questionnaire completed on behalf of each patient by someone living in daily contact with him appeared to have some validity as a memory measure. The pattern of memory failures reported was similar to that found in a previous study and this may primarily reflect the ease with which certain forms of memory failure can be observed. A questionnaire completed by the patients themselves had little validity, possibly because severely injured patients could not recall their own memory failures. Only a minority of severely injured patients were reported to be significantly handicapped by memory failures at this stage in their recovery.

Adolescent↗
PubMed1984

Isolation and characterization of a novel thermophilic, freshwater methanogen.

A novel thermophilic, coccoid methanogen isolated from nonthermal freshwater sediments is described. Hydrogen plus carbon dioxide and formate were substrates for methanogenesis, and methane production was stimulated by yeast extract, Casamino Acids, and tryptose. Growth also occurred autotrophically. Elevated levels of sodium chloride were not required for maximum growth and were inhibitory above 2%. The minimum doubling time occurred at 57 degrees C, and the upper and lower limits for methane production were 62 and 26 degrees C, respectively. The optimum pH for growth was between 7.0 and 7.5. Inhibitory antibiotics included metronidazole, anisomycin, chloramphenicol, and lasalocid. Colonies were circular, dark yellow, shiny, and convex with entire edges. Cells were 1 to 2.5 mum in diameter, nonmotile, occurring singly or in pairs, and fimbriated. Cells were lysed by pronase or trypsin digestion, glass-distilled water, and 1% sodium dodecyl sulfate. Electron micrographs of thin sections showed a monolayered cell wall ca. 20 nm thick. The DNA base ratio was 49.2 mol% guanine plus cytosine. The whole cell protein pattern differed from that of other named coccoid methanogens.

Journal Article↗
PubMed1984

Regulation of natural killer cell function by glass-adherent cells in patients with primary intracranial malignancies.

Natural killer (NK) cell function against the NK cell-sensitive myeloid leukemia cell line, K562, was measured in the peripheral blood mononuclear cells (PBMCs) of 17 patients with primary brain tumors (4 diagnosed as having low grade tumors and 13 diagnosed as having high grade (malignant) tumors). The ability of monocytes to control the levels of NK cell function in PBMCs from these patients was assessed in glass-adherent cell depletion studies. Most patient assessments were performed before surgical biopsy and diagnosis; most but not all patients were receiving dexamethasone at the time of immunity assessment. The results demonstrate that patients with primary malignant brain tumors have depressed levels of NK cell function in their PBMCs due to the suppressive actions of glass-adherent monocytes, whereas patients with low grade tumors have normal levels of function shown by this assay.

Adult↗
PubMed1984

Relationship of arachidonic acid metabolism to indomethacin-sensitive immunoregulatory function and lymphocyte PGE sensitivity in peripheral blood mononuclear cells of disseminated solid tumor cancer patients.

The relationship between the conversion of arachidonic acid (AA) to E series prostaglandins (PGE), indomethacin-sensitive immunoregulation and lymphocyte PGE sensitivity was investigated in the peripheral blood mononuclear cells (PBMC) of normal subjects and disseminated solid tumor patients. Production of PGE was assessed by thin layer chromatography of ether-extracted glass adherent cells following a 24-hour pulse with 3H-AA. Immunoregulatory cell function was assessed in PHA-stimulated PBMC cultured in the presence of the prostaglandin synthetase inhibitor, indomethacin. Lymphocyte PGE sensitivity was assessed in PHA stimulated glass nonadherent cells cultured in the presence of 10(-8) M PGE. The cells from cancer patients demonstrated greater AA conversion to PGE and greater indomethacin sensitive immunoregulatory cell function than the cells of normal subjects. However, lymphocyte PGE sensitivity was comparable for both groups. When levels of arachidonic acid conversion to PGE were correlated to levels of indomethacin-sensitive immunoregulatory cell function by linear regression analysis, a significant correlation was found. These data suggest that the increased indomethacin-sensitive immunoregulatory cell function seen in PBMC from cancer patients can be directly correlated with increased production of E series prostaglandins by cancer patient peripheral blood monocytes.

Adult↗
PubMed1984

Abnormal indomethacin-sensitive suppression in peripheral blood mononuclear cells of cancer patients restricts augmentation by interleukin-2.

The capacity of the immunomodulators interleukin-2 (IL-2) and indomethacin to augment phytohemagglutinin (PHA)-induced lymphoproliferation in the peripheral blood mononuclear cells (PBMC) of cancer patients was evaluated. Ficoll-Hypaque-isolated PBMC from 20 patients with disseminated non-lymphoreticular solid tumors were stimulated with PHA in the presence of IL-2, indomethacin, or IL-2 plus indomethacin. Augmentation of PHA responsiveness by each immunomodulator was additive. There was a significant negative correlation between PHA reactivity and immunomodulation by indomethacin. There was no correlation between PHA reactivity and immunomodulation by IL-2. A significant negative correlation was also found between indomethacin-induced augmentation and IL-2-induced augmentation in patients with significantly impaired reactivity to PHA. Still, the combined effects of IL-2 and indomethacin could not prevent the suppressive effects of prostaglandin E2 added to PHA-stimulated cultures containing both immunomodulators. These results suggest that the presence of abnormal indomethacin-sensitive immunoregulation in PBMC from cancer patients limits lymphocyte responsiveness to IL-2 and suggests that these two immunomodulators might be combined in certain cancer patient therapies.

Adult↗
PubMed1984

Effect of combination chemotherapy on PGE-mediated immunoregulation in the peripheral blood mononuclear cells of solid tumor cancer patients.

The effect of cytotoxic chemotherapy on phytohemagglutinin (PHA)-induced lymphocyte DNA synthesis was monitored in the peripheral blood mononuclear cells (PBMC) of drug-treated solid tumor cancer patients. The results obtained were correlated with changes in indomethacin-sensitive immunoregulatory function, prostaglandin E (PGE) levels, and PBMC PGE sensitivity. Those patients who demonstrated "rebound-overshoot" recovery of PHA responsiveness following their drug treatment did so in association with a significant reduction in levels of indomethacin-sensitive immunoregulation. This was associated with a significant decline in PGE-levels in PBMC. This was not consistently associated with a reduction in the sensitivity of PBMC to suppression by PGE. These data show that immune function recovery in drug-treated cancer patients is dependent in part on the effects of chemotherapy on PGE synthesis by PBMC.

Arachidonic Acid↗
PubMed1983

The immunological response of Wistar rats to the intracranially implanted C-6 glioma cell line.

The immune response of Wistar rats to the intracranial inoculum of 1 X 10(5) C-6 glioma cells was evaluated. The growth of these cells disrupted the blood-brain barrier by day 9. The rats with the implanted tumor cells died between three to four weeks following injection. No significant cell-mediated cytotoxicity against 51Cr labelled C-6 cells was seen in the short term (4 hours) cytotoxicity assay with spleen cells obtained from glioma-bearing rats at any stage of tumor growth. In the long term (18 hours) cytotoxicity assay, significant activity was detected using whole, adherent and nonadherent spleen cells from glioma-bearing rats at every assessment point during the growth of the tumor, but this cytotoxicity was also seen in normal rat splenocytes. The lack of cell mediated cytotoxicity above normal values was not due to a generalized immunosuppression since splenocytes from glioma bearers were found to have responses to Con A comparable to normal controls. However, normal or glioma-bearer splenocytes showed augmented cytotoxicity in the presence of serum obtained from rats bearing a glioma tumor starting by day 13 of tumor growth and rising in cytotoxic activity until death. This activity was not seen with normal serum. The glioma-bearer serum, though not cytotoxic to the C-6 cells alone, became cytotoxic with the addition of rabbit complement. These data indicate that the growth of intracranially implanted glioma cells in rats elicits primarily a humoral cytotoxic immunity without a significant cell-mediated immunity. This humoral immunity develops after the breakdown of the blood-brain barrier.

Animals↗
PubMed1983

Serial immune testing in surgically resected lung cancer patients.

Immunoregulation of phytohemagglutinin (PHA) responsiveness by glass-adherent cells and prostaglandin-synthesizing cells was serially monitored in the peripheral blood mononuclear cells (PBMC) of surgically resected stage I and stage II lung cancer patients entered on a trial of adjuvant immunotherapy. The relationship between immunoregulatory cell function, immunocompetence, and disease relapse was determined. Immunoregulatory activity was measured in PHA-stimulated cultures in the presence and absence of 2 micrograms/ml indomethacin and in the presence and absence of glass-adherent cells. In each instance of disease relapse seen, an increase in immunoregulatory cell function to a level significantly different from normal was observed 3 months prior to or coincident with clinical confirmation of disease recurrence. This was usually associated with a decline in PHA responsiveness. In the patients who did not relapse, the levels of PHA responsiveness and immunoregulatory function persisted within normal limits throughout the course of study. Percentages and numbers of leukocytes and leukocyte subsets and delayed cutaneous hypersensitivity were also monitored in this study, but could not be consistently correlated with early changes in clinical disease status. These data suggest that the development of indomethacin-sensitive and glass-adherent suppressor cells may precede and predict for tumor recurrence in surgically resected lung cancer patients.

Cell Adhesion↗
PubMed1983

Chronic intratumoral chemotherapy of a rat tumor with cisplatin and fluorouracil.

In order to demonstrate the feasibility and efficacy of intratumoral chemotherapy, brain tumors in rats were treated by direct infusion of cisplatin or fluorouracil. Each animal was initially implanted in the midline cerebellum with a chronic stainless-steel cannula, and 2 weeks later 1 X 10(5) 9L cells were injected through the cannula. 8 days after tumor cell transplantation, a small implantable pump containing drug, or saline as a control, was connected up to the same cannula, and the solution was pumped into the tumor region for 7 days. The results showed that both drugs produced statistically significant increases in survival as compared to the controls.

Animals↗
PubMed1983

Effect of interferon therapy on indomethacin-sensitive immunoregulation in the peripheral blood mononuclear cells of renal cell carcinoma patients.

The effect of interferon (IFN) therapy on prostaglandin (PGE)-synthesizing immunoregulatory cell function was assessed in the peripheral blood mononuclear cells of renal cell carcinoma patients. Ten patients were treated daily for 28 days with either 1 X 10(6) IU (five patients) or 10 X 10(6) IU (five patients) of leukocyte IFN. Patient cells were assessed for phytohemagglutinin (PHA) responsiveness in the presence and absence of the PGE synthetase inhibitor indomethacin. Progressive impairment in PHA responsiveness was found in all patients by the end of 28 days of therapy. It was associated with increased levels of indomethacin-sensitive suppressor function. Change in any of the patients studied was not correlated with IFN dose level. There was no correlation between clinical response to IFN and alterations in these parameters of immune function. In co-culture experiments, preincubation of glass-adherent cells with IFN led to increased indomethacin-sensitive regulatory function. These results suggest that IFN can produce progressive impairment of PHA-induced lymphoproliferation by increasing PGE-synthesizing immunoregulatory cell activity.

Adenocarcinoma↗
PubMed1983

Cigarette smoking among successive birth cohorts of men and women in the United States during 1900-80.

Trends in cigarette smoking among successive cohorts of men and women were reconstructed from smoking histories of respondents to the 1978-80 Health Interview Surveys. Estimated smoking rates among the older cohorts were then adjusted for the differential mortality of cigarette smokers and nonsmokers. By 1920, over half of the young male population smoked cigarettes. Not until 1950 did more than a third of the young female population smoke cigarettes. The proportion of men who ever smoked cigarettes progressively declined with each successive cohort born after 1920. By contrast, the proportion of women who ever smoked declined only among cohorts born after 1940. Cessation of cigarette smoking from age 30 years onward was observed for all cohorts of men. Cessation rates accelerated for men who reached age 30 after 1960. By contrast, smoking cessation from age 30 was observed only for women who reached age 30 after 1950. Cessation rates accelerated only for women who reached age 30 after 1970. For each cohort, recent smoking cessation rates for men have exceeded those for women. Maximum exposure to cigarette smoking probably occurred among men who are now in their seventh and eighth decades. By contrast, peak exposure to smoking probably occurred among women who are now only in their fifth and sixth decades.

Adult↗