Classics in oncology. Portrait of Arthur M. Sutherland, M.D.
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Biomedical subjects
Publications and source records attributed to M Braun.
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Cell migration inhibition of white blood cells in the presence of total protein lepromin (TPL) was studied in ten lepromatous patients, six tuberculoid patients, and ten normal controls; adding normal, tuberculoid, lepromatous, or no serum to the culture medium. Using normal or no serum, lepromatous patients and skin negative controls gave negative reactions, while tuberculoid patients and skin positive controls gave positive cell migration inhibitions. The addition of lepromatous serum gave a very significant overall increase of migration indices in all groups of subjects, turning to negative the positive reactions of lepromatous patients and positive controls. On the contrary, the addition of tuberculoid serum gave a decrease of migration index in all groups of subjects, turning to positive the reactions in lepromatous patients. The significance of these circulating factors, able to enhance or inhibit cell migration inhibition responses in patients and controls, is discussed.
The prevalence and activity of human herpesvirus-6 in patients with collagen vascular diseases (CVD) was determined. One hundred and fifty patients with CVD (56 with systemic lupus erythematosus-SLE, 92 with rheumatoid arthritis-RA, 1 with Sharp's syndrome and 1 with atypical polyclonal lymphoproliferation-APL and rheumatoid features) were screened serologically (IFA and ELISA) for antibodies against human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Virus isolation was attempted from peripheral blood lymphocytes (PBL) of 25 persons with various disorders. PBL were grown in tissue culture and tested with standard HHV-6-positive antisera for viral antigen expression. Supernatants of the patient's lymphocyte cultures were used to infect HSB2 cells, and virus infection in these cells was proven by IFA, in situ hybridization and by electron microscopy. Fifty-five percent of the SLE patients, 6.5% of the RA patients and both patients with Sharp's syndrome or with APL had antibody titers indicative of active HHV-6 infection. Virus cultures were positive in 9 of the 25 attempts with establishment of stable virus lines. These patients were 5 with SLE or UCVD, and one each with RA, CFS, APL as well as one healthy control. Reactivated and chronic active HHV-6 infections are frequent in SLE like EBV in RA. The role of these viruses in the pathogenesis of the diseases or in their reactivation still needs further investigation.
Double infection of cells by HHV-6, Epstein-Barr virus (EBV) and by human immunodeficiency virus (HIV-1) can enhance viral effects though genetic transactivation. It remained to be clarified, however, by which mechanism different viruses may enter the same cell. We have shown that HHV-6 infection of immature lymphoid cells rigidifies the cytoplasmic membrane and causes receptor proteins for viruses such as CD4 for HIV-1 and CR2 for EBV to be expressed. In our experiments, HHV-6 infected cells were superinfected by HIV1 and caused enhanced cell death. The mechanisms by which receptors were expressed after HHV-6 infection appears independent of cell membrane rigidification alone and is suppressed by cycloheximide only to a certain extent.
Follicular dendritic cells (FDC) are able to fix high amounts of immune complexes by C3b or Fc receptors without endocytosis and for long periods of time. In order to determine the function of this retention, we analysed the secretion of prostaglandin E2 (PGE2) by FDC in vitro; indeed, it is well-known that immune complex fixation on cells may induce PGE2 production. FDC were isolated by enzymic digestion of lymph follicles dissected under the biomicroscope from human tonsils or adenoids. Isolated FDC appeared as spherical clusters where they enveloped lymphoid cells with their cytoplasmic extensions. Tests were performed in synthetic culture media or in media supplemented with foetal calf serum. PGE2 production in FDC suspensions was compared to that of lymphocyte or macrophage-enriched populations prepared from the same human tonsils. In all experimental conditions, FDC and macrophage-enriched cell populations produced high levels of PGE2, inversely to lymphoid cell populations. This secretion was inhibited by indomethacin. At the ultrastructural level, we also showed that 3H-arachidonic acid was metabolized in cell membranes of all three cell types. The PGE2 produced in the culture media, according to our experimental conditions, do not influence cell proliferation, as assessed by 3H-thymidine incorporation tests on phytohaemagglutinin-stimulated lymphocytes.
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The dextrocerebral stroke is often underestimated as a result of its deficits--in contrary to the left cerebral stroke with the aphasia--because the patient's neglect of the plegic side is transferred to the therapist. A key to understanding this is the hypothesis that the anosognosia results in a loss of spatial analysis. After a survey of the different functions of the left and right hemispheres the author demonstrates the symptoms, diagnosis and therapeutic prognoses. The therapy needs to be continued for several months. In addition, the patient's social environment is important.
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Complement fragments (C3, C3d, C5a), thromboxane B2 (TxB2), 6-keto-PGF1 alpha and immunoreactive trypsin (IRT) were measured in 98 patients at risk of developing the adult respiratory distress syndrome (ARDS): 53 multiple trauma, 28 abdominal surgery and 17 acute pancreatitis. Sixty-five of these patients developed ARDS: 30 multiple trauma, 19 abdominal surgery and 16 acute pancreatitis patients. Forty of the 65 ARDS patients and 9 out of the 33 non-ARDS patients died. Mean value of the C3d to C3 ratio was abnormal in both ARDS and non-ARDS patients. C5a-like activity was detected in 70 out of the 98 patients (49 ARDS and 22 non-ARDS patients). TxB2 abnormal values (greater than 100 pg . ml-1) were found in 70% of the patients, especially when sepsis occurred. No correlation could be made between abnormal 6-keto PGF1 alpha values and ARDS or sepsis. The mean peak IRT value was 675 micrograms . 1(-1) for ARDS patients and 274 micrograms . 1(-1) for non-ARDS patients (p less than 0.05). A firm correlation was also measured between IRT and sepsis (p less than 0.01). C5a-like activity was regularly detected soon after injury, while TxB2 and IRT tend to appear later in patients developing ARDS. Neither C3d/C3, nor C5a-like activity, nor TxB2, nor IRT are specific markers of ARDS, since they also appeared in severely ill patients who did not develop ARDS.
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