Biomedical subjects

R Mark

Publications and source records attributed to R Mark.

At least 37 records · Page 2Linked to original sources

PubMed1984

Effect of frequency of plasma adsorption over protein A-containing Staphylococcus aureus on regression of rat mammary adenocarcinomas: modification of antitumor immune response and tumor histopathology.

Adsorption of the plasma of Sprague-Dawley rats having 7, 12-dimethylbenzanthracene (DMBA)-induced primary mammary adenocarcinomas with protein A-containing Staphylococcus aureus Cowan I (SAC) and reinfusion of the adsorbed plasma caused significant (p less than 0.05) regression of mammary adenocarcinomas. Adsorption of plasma was done at different intervals--weekly, biweekly, and on alternate days. Of these protocols, alternate-day adsorptions induced very fast (within a week) tumor regression (p less than 0.001). Other protocols also produced tumor regression; however, the effect was delayed. In long-term studies, the responding animals showed fewer tumor nodules than did the untreated controls. The plasma of the treated animals showed (a) a reduction in blocking activity, (b) an increase in antibody- and complement-mediated cytotoxicity, and (c) potentiation of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs). Histopathological analyses of biopsied sections of tumors from treated animals showed (a) disruption of tumor cell architecture, (b) loss of glandular structure, (c) shrinkage of epithelial cells, and (d) moderate mononuclear cell infiltration. Thus, adsorption of the plasma of DMBA tumor-bearing rats with SAC allows an indigenous immune mechanism to function against autochthonous tumors to control their growth and cause regression.

Adenocarcinoma↗

PubMed1983

Enhancement or inhibition of tumor growth by interferon: dependence on treatment protocol.

MSC cells are tumor cells originally induced in BALB/c mice by Moloney sarcoma virus. In these studies we demonstrated that, although these tumor cells are sensitive in vitro both to lysis by NK or NK-like cells and to the growth-inhibitory effect of murine L-cell interferon (IFN), the growth of the tumor in vivo could be either inhibited or enhanced by IFN. The outcome of in vivo IFN treatment was dependent on the timing and route of IFN administration relative to tumor challenge. IFN given systematically at the same time as tumor challenge resulted in enhancement of primary tumor formation, rate of tumor growth and subsequent progressive tumor growth. In contrast, IFN administered at the site of tumor inoculation on days 1-3 after tumor challenge inhibited tumor formation and growth. Histopathology of tissue sections obtained from the site of tumor challenge confirmed these results. Similar studies performed in mice given 450 rads of X-irradiation showed that IFN could still inhibit tumor growth when administered at the site of tumor inoculation on days 1-3 after tumor challenge. IFN administered simultaneously with tumor challenge, however, did not enhance tumor growth in irradiated mice. These results are consistent with the interpretation that 1) inhibition of MSC-induced tumor growth by IFN has a radioresistant component and 2) the enhancement of MSC-induced tumor formation by IFN is dependent on interaction with a radiosensitive population of cells, possibly lymphoid cells.

Animals↗

PubMed1983

Ambulatory ventricular tachycardia: characteristics of the initiating beat.

One hundred ten 24-hour Holter ECG recordings from 82 ambulatory patients with 341 episodes of ventricular tachycardia (VT) were analyzed. Most VT was precipitated by ventricular premature beats (VPBs) with prematurity indices (coupling interval/QT) between 1.0 and 2.0. However, a disproportionate number of VPBs initiating VT occurred early and late in the cardiac cycle compared with isolated VPBs. VT rate was not related to preceding heart rate, but faster basic rates appeared to protect against VT of extended duration. Approximately 80% of episodes of VT were initiated by VPB forms also seen in isolation. Of the 20% of VT initiated by a VPB of new morphology, one third occurred late in the cardiac cycle; almost none were early cycle.

Adult↗

PubMed1982

Extracorporeal immunoadsorption of plasma from a metastatic colon carcinoma patient by protein A-containing nonviable Staphylococcus aureus: clinical, biochemical, serologic, and histologic evaluation of the patient's response.

A patient with a metastatic colon carcinoma was treated by immunoadsorption (IA) therapy using heat-killed, formalin-stabilized protein A-containing Staphylococcus aureus Cowan I as the immunoadsorbent. The patient experienced both subjective and objective positive clinical response without undue morbidity. The patient's response correlated well with laboratory findings of decreased concentrations of carcinoembryonic antigen (CEA), immunoglobulin G (IgG), immune complexes (IC) and histopathologic data. The patient underwent surgery following 15 IA treatments; she lived for eighteen months, post-treatment.

Adenocarcinoma↗

PubMed1979

Demonstration of effective antitumor immunity in an autochthonous host bearing primary colon tumors induced by 1,2-dimethylhydrazine dihydrochloride.

The role of host defense mechanisms in preventing the development of subclinical tumors into invasive tumors in an autochithonous host was studied in a model of rat colon carcinoma induced by 1,2-dimethylhydrazine dihydrochloride (DMH). Multiple gastrointestinal (GI) tumors were induced in inbred WF female rats exposed to DMH. In vitro and in vivo data suggested that the excision of the "first" GI tumor induced specific antitumor immune responses. After a complete excision of the first GI tumor, only 2 additional GI tumors were observed in 10 rats, whereas 13 and 12 additional GI tumors in 10 and 9 rats, respectively, were observed if the first GI tumor was left in situ or permitted to grow in an isolated segment of the colon. Furthermore, immunosuppression with antithymocyte globulin decreased the effectiveness of antitumor immunity induced by the immunizing first GI tumor. These experiments supported the view that an effective antitumor immunity is induced against successive tumors of an organ after a complete excision of a tumor originating in the same organ. The results of these experiments are discussed in relation to the observations of multiple primary neoplasms in humans.

Animals↗

PubMed1978

Ex vivo removal of serum IgG in a patient with colon carcinoma: some biochemical, immunological and histological observations.

Plasma of a patient with metastatic colon carcinoma was perfused over Formalin and heat-killed S. aureus, in an extracorporeal filtration apparatus, in order to nonspecifically remove IgG and its complexes. Twenty ex vivo absorption procedures were done, over a five-month period, with a minimum of discomfort to the patient. Extracorporeal perfusion of plasma on S. aureus effectively reduced the levels of IgG and immune complexes in the perfused plasma. The nonspecific removal of IgG resulted in 1) slight biochemical alterations in the serum, 2) a transient reduction in the serum blocking activity and appearance of complement-dependent serum cytotoxicity, 3) an increase in the serum IgM levels, 4) a transient increase in the Ig surface-bearing lymphocytes and a decrease in "E" rosetting lymphocytes in the first 24-48 hours postperfusion, particularly during the early treatments, 5) an improvement in general condition of the patient and decrease in tumor size, and 6) histological changes in the tumor consistent with tumor destruction. The potential problems and clinical applications of procedures involving ex vivo specific or nonspecific immunoabsorbents are discussed.

Adenocarcinoma↗

PubMed1978

Immunologic surveillance against chemically induced primary colon carcinoma in rats.

A 1,2-dimethylhydrazine dihydrochloride-induced rat gastrointestinal tract tumor model was used to study the phenomenon of immunologic surveillance. In two different sets of experiments, a properly timed administration of antithymocyte globulin resulted in earlier tumor appearance, increased numbers of tumors, and increased multiplicity of gastrointestinal tumors. Results obtained from histologic examination of the gastrointestinal tract at different times after the last dose of 1,2-dimethylhydrazine dihydrochloride suggested that a normally functioning immune system effectively suppressed the growth of some nascent tumors. However, the immunosuppression of the host with antithymocyte globulin allowed the development of foci of microtumors into grossly visible neoplasms. Our experiments supported the concept that immunologic surveillance against neoplasia depends on the thymus cell system, although other possible mechanisms were not excluded.

Animals↗

PubMed1978

Effect of embryonic tissue immunization on chemically induced gastrointestinal tumors in rats. I. Can embryonic antigens act as rejection antigens?

Inbred WF rats were inoculated with crude suspensions prepared from liver and gut tissue of 12- to 15-day fetuses of the same strain. Rats previously unsensitized to syngeneic embryonic tissue were inoculated with fetal material sc three times during exposure to 1, 2-dimethylhydrazine dihydrochloride (DMH), a gastrointestinal (GI) carcinogen in rodents. Properly timed immunization inhibited the development, growth, and metastasis of primary GI tumors. This effects was observed in both sexes; however, it was more prounced in male rats. Nine WF rats with DMH-induced carcinoma of the GI tract were inoculated sc with syngeneic fetal tissue. Of 9 rats, 7 rejected the embryonal tissue implants, which thus demonstrated the presence of a concomitant immune response to embryonic antigen(s). Two rats in which fetal tissue grew out to palpable nodules had multiple GI tumors with metastasis and extra-GI tumors, i.e., a massive tumor load. Ten other rats with DMH-induced GI tumors were treated with unblocking serum. The unblocking serum was inoculated to counteract serum-blocking factors in vivo. These rats were inoculated intradermally with syngeneic fetal tissue. In all 10 rats, inflammation and necrosis were noted at the inoculation site after 24-72 hours, which thus demonstrated a delayed hypersensitivity reaction to embryonic antigens. Our experiments suggest that embryonic antigens common to fetal and tumor cells can induce immunity in an autochthonous host and can act as rejection antigens.

Adenocarcinoma↗

PubMed1978

Effect of unblocking therapy and levamisole on primary gastrointestinal tumors in rats: immunologic and histologic correlation.

The effect of multimodal immunotherapy was studied in WF rats bearing primary gastrointestinal (GI) tumors induced by 1,2-dimethylhydrazine dihydrochloride. The alterations induced in antitumor immune responses of the treated rats were studied in vitro and were correlated with tumor status in vivo. Multimodal immunotherapy consisted of unblocking serum, unblocked lymphoid cells, and levamisole. Such immunologic intervention resulted in significant inhibition of tumor growth, inhibition of metastases, and prolonged survival of the host. Serum blocking activity could be completely counteracted in 6 rats, all of which showed complete tumor regression. Of 20 rats, 8 showed inadequate counteraction of serum blocking activity and transient appearance of cytotoxic antibodies. All 8 rats showed marked tumor inhibition and prolonged survival. Six remaining rats succumbed from either GI or extra-GI tumors, although they survived significantly longer than untreated rats; these 6 rats had only transient counteraction of their serum blocking activity. All 20 tumors in 14 rats of the therapy group showed histologic evidence of tumor rejection. Our studies suggested that a complete counteraction of blocking activity in conjunction with methods capable of improving the specific and nonspecific immune competence of the host may be important to achieve optimal antitumor effects.

Animals↗

PubMed1978

Ex-vivo removal of mammalian immunoglobulin G: method and immunological alterations.

We have described a clinically feasible method capable of rapidly and repeatedly removing mammalian IgG extracorporeally by adsorption onto heat-killed, formalin-stabilized Staphylococcus aureus Cowan-I. In dogs, 2-13 grams of IgG were removed in 60-70 minutes, lowering the serum concentration of IgG by 30-70 percent. Serum IgG levels returned to pre-run values within 48-72 hours and, in some cases, were higher than pre-run levels at 48-72 hours. Serum biochemical alterations were generally transient and relatively modest. Peripheral lymphocyte counts showed minimal changes but the percentage of erythrocyte rosette forming cells appeared to increase with successive runs. This method is safe and efficient, and can be repetitively performed at short intervals in dogs. This method may prove useful in diseases in which rapid removal of circulating IgG is desired.

Animals↗

PubMed1978