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Biomedical subjects

R Gottschalk

Publications and source records attributed to R Gottschalk.

At least 55 records · Page 3Linked to original sources
PubMed1991

Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration.

Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS.

Animals↗
PubMed1990

Non-invasive quantitation of liver iron-overload by magnetic resonance imaging.

A standard magnetic resonance imaging (MRI) system allowing spin echo times of 10 ms was used to quantitate liver iron concentration in nine healthy normal subjects and 13 patients with various grades of iron overload. Body iron status was estimated by measuring the serum ferritin concentration. In 11 subjects (two normal healthy controls, eight patients with HLA-related hereditary haemochromatosis and one patient with thalassaemia major) non-haem hepatic iron concentration was determined chemically in biopsy specimens (dry weight), in parallel to serum ferritin and MRI-T2 relaxation times. A moderate correlation (r = 0.79) was obtained for the correlation of the T2-relaxation rate (1/T2) and serum ferritin of the 22 subjects investigated. A much closer correlation (r = 0.98) was observed for the 1/T2 liver iron relationship in the 10 subjects analysed by liver biopsy. It is concluded from these preliminary observations, that MR-imaging may provide a useful non-invasive tool for the quantitative determination of liver iron in iron overload-syndromes.

Adult↗
PubMed1988

Lipid granulomatosis: Erdheim-Chester disease.

Twenty-six cases of lipid (cholesterol) granulomatosis, Erdheim-Chester Disease (ECD), have been described in the literature to date. A new case of ECD in a 33-year-old man with an unusual presentation of exudative ascites following a four year history of abdominal pain is reported. The radiographic and bone scan findings in this disease have been established and Ga-67 scan findings are reported. The Tc-99m sulphur colloid bone marrow and In-111 chloride scan findings are presented.

Adult↗
PubMed1988

Effect of blood transfusion on IL-2 production.

Spleen cells from B10.A mice transfused with B10.D2 blood suppress the immune responses of normal B10.A to B10.D2 in coculture as early as 2 days posttransfusion. In addition, the ability of B10.A mice to respond in cell-mediated lymphocytotoxicity (CML) is significantly impaired as early as 2 days after B10.D2 transfusion. Experiments were performed to characterize the cells mediating the suppressive effect and to determine whether the inability of transfused mice to generate a cytotoxic response is due to an inhibition of IL-2 production. To characterize the suppressor cells, spleen cells from B10.A mice were assayed 2 or 16 days after B10.D2 transfusion for the ability to suppress mixed lymphocyte culture (MLC) and CML responses of normal B10.A mice in coculture. The putative suppressor cells were either passed over a Sephadex G-10 or nylon wool column, treated with anti-Thy antibody or left untreated before addition to the coculture. Untreated cells from transfused mice suppressed the CML response of normal B10.A both 2 and 16 days posttransfusion, while the effect on the MLC response was inconsistent. Passage of the cells over Sephadex G-10 or nylon wool before assaying abrogated the suppressive effect, while treatment with anti-Thy antibody had no effect. These results suggest that the suppressor cells appearing shortly after blood transfusion have the characteristics of macrophages and not T lymphocytes. To determine the effect of transfusion on IL-2 production, cells from transfused mice were assayed for their ability to produce IL-1 and IL-2 and for the formation of IL-2 receptors. In addition, the effect of exogenous IL-1 and IL-2 on restoring the CML response of transfused mice to normal was assayed. The production of IL-1 by transfused mice was normal, while the production of IL-2 was significantly suppressed both 2 and 16 days posttransfusion. Activated cells from normal and transfused mice showed equal ability to absorb IL-2, indicating that IL-2 receptor formation is normal after transfusion. The addition of exogenous IL-2, but not IL-1, to CML cultures containing cells from transfused mice as responders restored the response to normal. These results indicate that the inability of transfused mice to respond in CML is due, at least in part, to an inability to produce IL-2. This could be mediated by prostaglandins released by activated macrophages.

Animals↗
PubMed1988

Identification of glucose and nucleoside transport proteins in neonatal pig erythrocytes using monoclonal antibodies against band 4.5 polypeptides of adult human and pig erythrocytes.

Cytochalasin B and nitrobenzylthioinosine (NBMPR), which inhibit membrane transport of glucose and nucleosides, respectively, have served as photoaffinity ligands that become covalently linked at inhibitor binding sites on transporter-associated proteins. Thus, when membranes from erythrocytes of neonatal pigs with site-bound [3H]cytochalasin B or [3H]NBMPR were irradiated with uv light, two labeled membrane polypeptides (peak Mr values: 55,000 and 64,000, respectively) were identified. Treatment of the photolabeled membranes with endoglycosidase F increased the mobility of [3H]cytochalasin B- and [3H]NBMPR-labeled material (peak Mr values: 44,000 and 57,000, respectively) and limited digestion with trypsin yielded different polypeptide fragments (Mr values: 18,000-23,000 and 43,000, respectively). Identification of the photolabeled polypeptides as transporter components was established using monoclonal antibodies (MAbs) raised against partially purified preparations of band 4.5 from erythrocytes of adult pigs and humans. MAbs 65D4 and 64C7 (anti-human band 4.5), raised in this study, reacted with [3H]cytochalasin B-labeled material from membranes of human erythrocytes and bound to permeabilized erythrocytes but not to intact cells. MAb 65D4 also bound to erythrocytes of mice and neonatal pigs and to a variety of cultured cells (mouse, human, rat), including AE1 mouse lymphoma cells, which lack an NBMPR-sensitive nucleoside transporter. Also employed was MAb 11C4 (anti-pig band 4.5), which recognizes the NBMPR-binding protein of erythrocyte membranes from adult pigs. When membrane proteins from neonatal and adult pigs were subjected to electrophoretic analysis and blots were probed with different MAbs, MAb 65D4 (anti-human band 4.5) bound to material that comigrated with [3H]cytochalasin B-labeled polypeptides (band 4.5) from neonatal, but not adult, pig erythrocytes, whereas MAb 11C4 (anti-pig band 4.5) bound to material that comigrated with [3H]NBMPR-labeled band 4.5 polypeptides of erythrocytes from both neonatal and adult pigs. These results, which indicate structural differences in the cytochalasin B- and NBMPR-binding proteins of pig erythrocytes, establish the presence of both proteins in erythrocytes of neonatal pigs and suggest that only the NBMPR-binding protein is present in erythrocytes of adult pigs.

Affinity Labels↗
PubMed1986

Immune reactivity in congenic mice after allogeneic or isogeneic transfusion.

Pretransplant donor-specific blood transfusion has a beneficial effect on subsequent skin graft survival in B10 congenic mice when donor and recipient differ at both the K and I regions of the H-2 complex, but has no effect on graft survival in donor-recipient combinations differing at the K region alone. Immune reactivity was studied in B10.A recipients after a single allogeneic transfusion from B10 donors differing either at both K and I regions or at K alone, or after a transfusion of isogeneic B10.A blood. Spleen cells were assayed for the ability to respond in mixed lymphocyte culture (MLC) and cell mediated lymphocytotoxicity (CML) assays against blood donor and third-party at 2, 9, 16, and 30 days after transfusion. MLC and CML responses were nonspecifically suppressed in recipients transfused with allogeneic blood from K or K and I region disparate donors. The responses of mice receiving K region disparate blood were partially recovered by 9 days posttransfusion and had returned to normal 16 days posttransfusion. Responses of mice receiving K and I region disparate blood remained suppressed 30 days post transfusion. Isogeneic transfusion induced a suppression of the MLC response. Two days posttransfusion, the MLC response was suppressed to a variety of stimulators representing disparity at K alone; K and I; or K, I, and D. The response to K region disparate stimulators had recovered 9 days after isogeneic transfusion, but the response to K and I or K, I, and D region disparate stimulators remained suppressed 30 days after transfusion. The suppression observed after allogeneic or isogeneic transfusion was not due to a shift in the day of peak response in the transfused mice. Kinetic studies showed that the day of peak MLC and CML responses in the transfused mice corresponded to that of normal controls, but the level of response was significantly lower in the transfused mice.

Animals↗
PubMed1985

Protein binding studies of furosemide and penbutolol.

Serum protein binding of furosemide and penbutolol, the active principles of Betasemid (Hoe 9358), was studied by equilibrium dialysis. Membranes from commercial dialysis tubes were used within commercially available cells. Serum drug and portion unbound in buffer were determined by quantitative thin-layer chromatography. In the range of 1-20 micrograms drug/ml serum, 96 +/- 0.3% of furosemide vs. 88 +/- 4% of penbutolol were bound to proteins. The same results were obtained, when the two substances simultaneously interacted with proteins. Thus, specific protein binding sites for both compounds were demonstrated. For both drugs, Scatchard plots revealed two classes of specific binding sites with statistical mean values/protein of 0.4 and 5 in the case of furosemide and 0.04 and 0.3 in the case of penbutolol. Binding energies were 27.6 and 19.6 kJ/mol furosemide vs. 31.5 and 23.9 kJ/mol penbutolol. Further, serum protein binding of furosemide was studied by ultrafiltration. A micropartition system MPS-1 was used. Results were the same as those from equilibrium dialysis.

Blood Proteins↗
PubMed1984

Comparison of immune responsiveness in mice after single or multiple donor-specific transfusions.

Immune responsiveness was compared in B6AF1 mice after one, two, three, or four donor-specific DBA/2 blood transfusions (DST). Ten days after the last transfusion, the spleen cells of transfused mice were assayed for direct lymphocyte-mediated cytotoxicity, for the ability to respond in mixed lymphocyte culture (MLC) and cell-mediated lymphocytotoxic (CML) assays to DBA/2 and C3H/He antigens, and for the ability to inhibit the MLC and CML response of normal B6AF1 to DBA/2 and C3H/He antigens. Immune responsiveness was also tested in B6AF1 2 to 80 days after a single DBA/2 DST. The MLC response of transfused mice was specifically suppressed to the blood donor after both single and multiple transfusions. The CML response to DBA/2 was suppressed after a single DST, but returned to normal after multiple transfusions. Spleen cells from transfused mice did not inhibit the MLC response of normal B6AF1 mice to DBA/2 or C3H/He antigens after one or two transfusions regardless of time tested, but were able to inhibit the response to both stimulators after three or more transfusions. The MLC response remained specifically suppressed to the blood donor for as long as 80 days after a single DST, while the CML response was suppressed up to 50 days after transfusion, but had returned to normal by 80 days.

Animals↗
PubMed1984

Immunofluorescent and immunoperoxidase staining of antibodies to fibrous keratin. Improved sensitivity for detecting epidermal cancer cells.

Microscopically controlled surgery (Mohs' surgery) is a widely accepted technique because it provides total extirpation of skin tumors with maximum conservation of tissue. However, in poorly differentiated tumors it is often difficult microscopically to recognize individual tumor cells in the midst of an inflammatory cell infiltrate, in fibrotic tissue, in connective tissue around blood vessels, in nerve sheaths, and in fascial planes. We have developed techniques to differentiate tumor cells, derived from the epidermis, from the normal nonkeratinizing tissue of mesodermal origin or the inflammatory cell infiltrate. In frozen sections, indirect immunofluorescence techniques with polyclonal antibodies to fibrous keratin allowed rapid identification of tumor cells of basal and squamous cell carcinoma. Immunoperoxidase staining proved to be a remarkably sensitive method for the identification of such carcinoma cells in both frozen and paraffin-embedded sections. When used in combination with the precise mapping techniques of Mohs' surgery, these reliable and specific stains permitted greater accuracy in assessing the total resection of an invasive tumor.

Animals↗
PubMed1983

The effect of timing of multiple donor-specific or nonspecific blood transfusions on skin allograft survival in ALS-treated mice.

The effect of timing of multiple transfusions on skin allograft survival in antilymphocyte serum (ALS)-treated mice was studied using donor-specific or nonspecific transfusions. Transfusions were given every 4, 7, 14, or 21 days and skin grafting was done 10 days after the last transfusion. To study the effect of donor-specific transfusion, four DBA/2 transfusions were given to ALS-treated B6AF1 recipients followed by grafting with DBA/2 skin. To study the effect of nonspecific transfusions, five CF1 transfusions were given to ALS-treated B6AF1 mice, followed by grafting with C3H/He skin. Transfusions of both donor-specific and nonspecific blood every 4 days had no effect on prolonging graft survival, compared with ALS-treated controls. Transfusions of both types of blood every 7, 14, or 21 days significantly prolonged graft survival, with maximum survival observed in the group receiving transfusions every 14 days. The effect of varying the interval between the last transfusion and skin grafting was studied using multiple transfusions of nonspecific blood. Five weekly CF1 blood transfusions were given to ALS-treated B6AF1 mice. Skin grafting with C3H/He skin was done 2, 5, 10, 30, or 60 days after the last (5th) transfusion. Maximum graft prolongation was achieved when grafting was done 2 days after the last transfusion. Significant graft prolongation was also achieved when grafting was done 5, 10, or 30 days after the last transfusion. Of the mice grafted 60 days after the last transfusion, 60% showed no graft prolongation compared with controls, and survival of 40% of the grafts in this group was prolonged.

Animals↗
PubMed1981

Specific unresponsiveness to skin allografts in anti-lymphocyte serum-treated, marrow-injected mice: participation of donor marrow-derived suppressor T cells.

Sequential changes of cell-mediated immune reactivities were examined in anti-lymphocyte serum-(ALS) treated, C3H/He (C3H; H-2k) bone marrow-injected (C57BL/6 X A)F1 (B6AF1; H-2b/k.d) mice bearing enhanced C3H skin grafts. Spleen cells of these mice exhibited marked suppression of the proliferative response to phytohemagglutinin and concanavalin A. When the spleen cells were assayed for the direct lymphocyte-mediated cytotoxicity against H-2k targets, their lytic activity remained low until the time of graft rejection, in contrast to the increasingly high cytotoxic activity exhibited by spleen cells of control B6AF1 mice given only ALS and C3H skin grafts. When spleen cells of marrow-injected B6AF1 mice were cultured with mitomycin-C treated C3H spleen cells, the proliferative response was significantly suppressed the throughout the course, despite the early appearance of high "secondary-type" cytotoxic activity. Co-culture experiments demonstrated the presence of C3H antigen-specific suppressor cells in the ALS-treated, marrow-injected mice bearing intact allografts. Treatment of spleen cells with anti-H-2, anti-Thy 1 and anti-I-J sera and C revealed that the suppressor cells present late in the marrow-injected mice were T cells of donor C3H bone marrow cell origin.

Animals↗
PubMed1980

Effect of splenectomy on specific unresponsiveness to skin allografts induced in ALS-treated, marrow-injected mice.

The role of the spleen in the induction and maintenance of unresponsiveness to skin allografts and in the generation of suppressor cells has been studied in ALS-treated B6AF1 mice grafted with C3H/He skin and injected with C3H/He marrow. B6AF1 mice were splenectomized either before the induction of unresponsiveness or on day +13, +28, or +42 after unresponsiveness was induced. Graft survival in the splenectomized mice was compared to that observed in nonsplenectomized ALS-treated, marrow-injected controls. Graft survival was prolonged equally in all splenectomized groups and the nonsplenectomized controls. To study the effect of the spleen on the generation of suppressor cells, lymph node cells were removed at day +42 from splenectomized ALS-treated, marrow-injected B6AF1 mice bearing C3H/He skin grafts and transferred to ALS-treated B6AF1 recipientso ALS-treated BTAF1 recipients grafted with C3H/He skin. Graft survival in the secondary recipients receiving lymph node cells from splenectomized donors was compared to that observed in ALS-treated B6AF1 mice that received lymph node cells transferred from nonsplenectomized enhanced donors. Suppressor cell activity could be detected in the nodes of splenectomized mice, but a higher dose of lymph node cells was required to transfer unresponsiveness from splenectomized donors compared to nonsplenectomized donors. These results indicate that the spleen is not necessary for the induction or maintenance of unresponsiveness to skin allografts in ALS-treated, marrow-injected mice. In addition, suppressor cells can be generated in the lymph nodes of unresponsive mice in the absence of the spleen, although the production of suppressor cells appears to be less effective in splenectomized mice than in mice with intact spleens.

Animals↗
PubMed1979

Suppressor cells in specific unresponsiveness to skin allografts in thymectomized, ALS-treated, marrow-injected mice.

Spleen cells from thymectomized antilymphocyte serum (ALS)-treated B6AF1 mice bearing enhanced C3H/He grafts after the infection of C3H/He marrow were assayed for their ability to suppress the response to C3H/He grafts after transfer to syngeneic B6AF1 recipients. Cells were transferred from thymectomized ALS-treated B6AF1 mice that had received either a C3H/He graft alone, C3H/He marrow alone, or both a graft and marrow. Cells were removed from donors and transferred at either day +13, +42, +62, +100, or +150. Spleen cells from thymectomized mice were unable to transfer unresponsiveness regardless of donor treatment or time of transfer.

Animals↗