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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 451 records · Page 25Linked to original sources

Immunological monitoring and immunotherapy in carcinoma of the lung.

One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).

Adenocarcinoma↗

Cytotoxic antibody complicating platelet support in acute leukemia. Response to chemotherapy.

Lymphocytotoxic or thrombocytolytic antibodies were detected in 11 of 25 thrombocytopenic patients receiving repeated platelet transfusions. Platelet survival times were reduced in these patients (half-life [T/2], 32 hours) as compared to patients without antibody (T/2, 51 hours, P less than .05). In one woman with acute myeloblastic leukemia and a potent platelet antibody, combination chemotherapy resulted in a profound decrease in circulating gamma-globulin and concurrent disappearance of the cytotoxic antibody. The survival of transfused platelets in this patient was dramatically improved, and bleeding was controlled.

Adolescent↗

Absence of ristocetin aggregation factor from the skin of a patient with von Willebrand's disease.

Samples of apparently normal skin from one patient with von Willebrand's disease (vWD) and five patients without vWD were examined with fluorescein-tagged antiserum to the component of factor VIII required for aggregation of platelets by ristocetin (VIII-R.A.F.). No evidence of VIII-R.A.F. was found in the vWD skin, while bright granules were seen on and/or in the endothelial cells of dermal capillaries in all patients without vWD. VIII-R.A.F. granules were also found in the interstitial vasculature of all of twelve renal-biopsy specimens from patients without vWD. These observations support the concept that an abnormality of the vascular endothelium is involved in the pathogenesis of vWD.

Blood Platelets↗

Failure of AHF concentration to control bleeding in von Willebrand's disease.

A newly available dried concentrate of antihemophilic factor (Profilate, Abbott Laboratories) was compared with standard, blood-bank prepared cryoprecipitate in the control of bleeding in a patient with von Willebrand's disease. Profilate effectively raised plasma levels of factor VIII but produced only half the expected increase in plasma ristocetin aggregation factor (RAF), and this RAF did not bind readily to the platelets in the presence of ristocetin. Furthermore, the Profilate had little effect upon the bleeding time or the clinical hemorrhage. In contrast, the cryoprecipitate did increase plasma RAF to the expected level, and this RAF bound readily to the patient's platelets in the presence of ristocetin. Cryoprecipitate promptly controlled bleeding. We conclude that the RAF present in Profilate retains in vitro activity but is incapable of augmenting platelet function in vivo.

Adult↗

Cytogenetic effects of protracted exposures to alpha-particles from plutonium-239 and to gamma-rays from cobalt-60 compared in male mice.

Adult C3H X 101 hybrid male mice were injected intravenously with 4 muCi of 239Pu citrate per kg body weight and examined for evidence of cytogenetic damage to the testis after exposures of 21, 28 and 34 weeks, with average doses from alpha-particles estimated as 13, 18 and 18 rad respectively (mean dose rate 0.00006 rad/min). Results were compared with those obtained when equivalent males were exposed continuously and concurrently to 1128 rad 60Co gamma-irradiation over 28 weeks (0.004 rad/min). The following estimates of the relative effectiveness of the alpha- and gamma-radiation were made: 24 for reciprocal translocations and for chromosome fragments, 22 for dominant lethal mutations acting after implantation. These values (with mean of 23) are based on average testis doses, with no correction for probable non-homogeneity of alpha dose distribution. In the mice exposed to gamma-irradiation there were significant reductions in testis mass and epididymal sperm-count. Although corresponding differences from control were not significant in the alpha series, consideration of results from a previous experiment by the same authors [2] allowed the relative effectiveness of the alpha- and gamma-irradiation for testis mass reduction to be estimated as roughly 10-15. Existing data on translocation induction in mouse spermatogonia by low dose-rates of gamma-rays (down to 0.003 rad/min) were analysed. They suggested that minimum rates of induction at very low intensities were not less than 1 X 10(-5) translocations per rad. A comparison of the frequencies of induction of fragments and of sperm-head abnormalities obtained after chronic gamma-ray exposures in the present experiment with those found by other workers after acute X-ray exposures suggested that there were no marked dose-rate effects with these types of mutational effect. Finally, the special problems associated with cytogenetic studies on alpha-emitters are discussed.

Alpha Particles↗

Urinary loss of clotting factors due to hereditary membranous glomerulopathy.

Severe plasma deficiencies of clotting factors IX and XII developed in a 59-year-old woman with a nephrotic syndrome secondary to a laminated membranous glomerulopathy. Both these clotting factors were subsequently identified in the patient's urine. Chromatographic analysis of the urine revealed that the bulk of clotting activity attributed to factors IX ann XII was in early eluting gel filtration fractions containing predominately alpha-2 globulin and albumin. The unprecedented finding of two coagulation proteins in the urine is attributed to the marked proteinuria present in this case.

Biopsy↗

Function and ultrastructure of platelets of neonates: enhanced ristocetin aggregation of neonatal platelets.

We have investigated platelet morphology and function in human maternal-newborn pairs. Fibrinogen concentration and factor-VIII activity in plasma were also determined. Our results showed that, compared to maternal platelets, neonatal platelets were poorly responsive to adenosine diphosphate, adrenaline and collagen. Uptake of labelled serotonin by neonatal and maternal platelets was the same, but release of the radioactivity was reduced in the former. Phagocytic activity of neonatal platelets, demonstrated with latex particles, was similar to that of maternal platelets. Although the ultrastructure of neonatal platelets approximated that of maternal platelets, immature appearing platelets were occasionally found in the neonatal samples. An unanticipated finding was that platelet aggregation induced by ristocetin was more vigorous in neonatal than in maternal platelet-rich plasma samples. Furthermore, neonal -lasma, which had lower fibrinogen and factor-VIII content than maternal plasma, facilitated maternal platelet aggregation by ristocetin and showed a greater ability than maternal plasma to promote ristocetin-induced aggregation of platelets of a patient with von Willebrand's disease. These results indicate that the plasma of neonates contains large quantities of the ristocetin-dependent platelet aggregation factor (RAF), probably more than is in maternal plasma, despite the higher levels of factor-VIII procoagulant activity in the latter. Thus, in the newborn, there is a clear dissociation between factor-VIII clotting activity and the RAF activity.

Blood Platelets↗

Matching of histocompatibility (HL-A) antigens for platelet transfusion.

The average in vivo platelet survival was measured by both per cent recoveries (%R) and half-lives (t 1/2) of 51Cr-labeled platelets in 69 transfusions given to 43 thrombacytopenic patients. The results demonstrated that (1) increase in the number of HL-A incompatibilities in the platelet donor was significantly associated with decreased %R and t 1/2 of the infused platelets; (2) survival of transfused platelets from HL-A-matched single donors was consistently superior to those pooled from several grossly mismatched donors; and (3) survival of platelets infused when patients had circulating lymphocytotoxic antibodies was consistently lower than when patients did not have such antibodies, regardless of whether it was the first, second, or third such infusion.

ABO Blood-Group System↗

Platelet-bound ristocetin aggregation factor in normal subjects and patients with von Willebrand's disease.

Antiserum specific for that part of the factor VIII complex designated ristocetin aggregation factor (VIIIRAF) was prepared by immunizing rabbits with VIIIRAF derived from the plasma of a hemophilic patient with circulating antibody to factor VIII procoagulant activity (VIIIcoag). The rabbit antiserum prevented ristocetin-induced platelet aggregation and platelet retention by glass-bead columns. Although the antiserum also inactivated VIIIcoag in normal plasma, it did not inactivate VIIIcoag which had been dissociated from VIIIRAF by chromatography in 1 M NaCl, thus establishing the antigenic specificity of these two factors. When the VIIIRAF antibody was conjugated with fluorescein isothiocyanate and used to examine platelets from normal subjects and patients with von Willebrand's disease, the normal platelets showed a granular fluorescence similar to that observed with antifibrinogen serum whole von Willebrand platelets showed no fluorescent staining. The normal platelets retained the VIIIRAF granules during 18 hours incubation and 5 washings in artificial medium while the von Willebrand platelets failed to acquire granules after 18 hours in normal plasma. When the unstained platelets from patients with von Willebrand's disease were suspended in normal plasma and then aggregated by the addition of ristocetin, the aggregates not only stained brightly for VIIRAF, but fluorescent granules could be seen on individual platelets in the aggregates. These observations suggest that ristocetin causes the binding of VIIIRAF to platelets as well as platelet-to-platelet adhesion.

Blood Platelets↗