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Biomedical subjects

N V Dimitrov

Publications and source records attributed to N V Dimitrov.

At least 55 records · Page 3Linked to original sources

Leukocyte interferon as a possible biological response modifier in lymphoproliferative disorders resistant to standard therapy.

In vitro and in vivo studies utilizing a combination of leukocyte interferon-alpha (IFN) and chlorambucil (CLB) were done to investigate possible synergism between a biological response modifier and a chemotherapy drug. In vitro studies utilized a human myeloid leukemia cell line (K-562) pretreated with IFN and then exposed to CLB. The combination resulted in significant depression of cell growth compared with use of IFN or CLB alone. In vivo studies involved eight heavily pretreated patients given 6 million units IFN for 5 days followed by oral CLB (16 mg/m2) for 5 days repeated every 4 weeks. Three myeloma patients had reduction in immunoglobulins and experienced clinical responses. Three of four patients with Hodgkin's disease responded after relatively short periods of treatment. One patient with a diffuse lymphocytic lymphoma had a complete unmaintained remission lasting 6 months. Toxicity was minimal, with mild fever, nausea, and vomiting. These preliminary studies suggest that IFN may be a biological response modifier when used in combination with a cytotoxic agent.

Adult↗

Pancreatic islet cell carcinoma associated with multiple hormone secretion and pancytopenia. Evidence of a serum factor suppressing hematopoiesis.

A case of metastatic islet cell carcinoma of the pancreas associated with the production of multiple polypeptide hormones (insulin, glucagon, and gastrin) is described. Three years prior to the histologic diagnosis the patient presented with a gastric ulcer and an androgen responsive pancytopenia with hypoplastic bone marrow. Discontinuation of androgen therapy resulted in relapse of pancytopenia. After the diagnosis of islet cell carcinoma of the pancreas was established, the patient was treated with 5-fluorouracil (5-FU) and streptozotocin and subsequently elevated serum polypeptide hormones returned toward normal levels. Concurrent with the normalization of peptide hormones another complete hematologic remission was achieved without use of androgens. Injection of the patient's serum into female rats produced a significant fall in leukocyte (P less than 0.02) and platelet counts (P less than 0.005), but no significant decrease in hematocrit. The clinical course and laboratory findings in this case suggest the presence of a previously undescribed serum factor released by an islet cell tumor capable of suppressing hematopoiesis.

Adenoma, Islet Cell↗

Interferon as an in vitro modifier of immune responses induced by combined vaccine (DTP) in mice.

The ability of DTP (diphtheria, tetanus, pertussis) vaccine to stimulate IgG-plaque forming cells (PFC) in mice was markedly inhibited by human leukocyte and mouse fibroblast interferon (IF). This effect of IF was not dose-dependent. The maximum inhibitory effect of human IF was observed on Day 10 after the administration of the vaccine. The inhibition of IgM-PFC was more severe when human IF was used. Although IF abrogated the effect of DTP vaccine on IgG-PFC, at the same time it stimulated PFC in the control group of non-vaccinated animals. The administration of DTP vaccine decreased IgM-PFC on Day 5, the effect was enforced by the addition of both human and mouse IF. IF decreased IgM-PFC in the control group. Small and large doses of DTP suppressed the leukocyte adherance inhibition (LAI) on Day 5 after administration of the vaccine, the effect was not affected by addition of IF. The suppressive effect of DTP was lost on Day 10 when addition of IF increased the percent of LAI in all experimental groups. Thus IF appears to interfere with the effect of DTP and selectively modulate the different immune responses.

Animals↗

High-dose methotrexate with citrovorum factor and vincristine in the treatment of malignant mesothelioma.

The incidence of malignant mesothelioma has increased greatly in the last 40 years. Current and recent past exposure to asbestos is expected to substantially increase this incidence. We report nine cases of malignant mesothelioma which temporarily responded to treatment with high-dose methotrexate-citrovorum rescue and vincristine. Further clinical trials of high-dose methotrexate with citrovorum rescue appear indicated in this disease.

Adult↗

Megakaryocytic leukaemia as a phase of myeloproliferative disorders.

2 cases of megakaryocytic leukaemia are presented as a variant of myeloproliferative disorders. The uncontrolled proliferation of the megakaryocyte-platelet cell line occurred after splenectomy and treatment of blastic phase. Applicability of the term megakaryocytic leukaemia is discussed as well as its relationship to similar disorders. It is suggested that an extensive neoplastic proliferation of megakaryocytes with abnormal maturation and thereby formation of large dysplastic platelets in extramedullary organs especially the liver in the end stage of myelofibrosis is a possible mechanism for this disorder. Treatment with platelet-pheresis may be an effective part of therapy.

Cell Division↗

Feminization in hepatocellular carcinoma corrected by chemotherapy: a case report.

A 17-year-old boy with metastatic hepatocellular carcinoma and feminization became asymptomatic after administration of antineoplastic agents. Serum estradiol level, urine estrogens, and tumor estrogen receptors were changed after the treatment. Achievement of partial remission resulted in normalization of the serum sex hormone profile and disappearance of the feminization in spite of the presence of residual tumor. Thus, serum hormone levels alone cannot be used as tumor markers for control of therapy. This suggests that chemotherapy may have altered the biological behavior of the tumor, which resulted in loss of its ability to synthesize estrogen estrogen receptors.

Adolescent↗

Effect of adriamycin and Corynebacterium parvum in tumor-bearing mice: modulation of response to sheep red blood cells.

Administration of adriamycin and Corynebacterium parvum alone in C57BL/6J mice bearing Lewis lung carcinoma stimulated the direct (19S) and indirect (7S) plaque-forming cell (PFC) response specific for sheep red blood cells. Thus adriamycin appears to possess some immunostimulatory effect on tumor-bearing mice with much less effect than C. parvum alone. Simultaneous administration of adriamycin and C. parvum decreased the PFC response compared to that for C. parvum alone. This decrease may indicate that drug-vaccine interaction could produce some inhibition of the strong immunostimulatory effect of C. parvum as measured by the PFC response in tumor-bearing mice. The immunostimulatory effect of adriamycin and C. parvum administered as a single agent or in combination was associated with significant splenomegaly. The results of this study could be helpful in clinical situations when these agents are used alone or combined.

Animals↗

Immunoproliferative alterations in lymphoid tissues and liver in mice stimulated with Corynebacterium parvum.

Morphological alterations in the spleen, liver, lymph nodes, thymus, bone marrow and blood were studied in DBA and Balb/C mice treated with Corynebacterium parvum. The spleen lymph nodes and liver increased in size and weight, whereas thymus showed decrease in weight compared to the control group. A marked, early proliferation of monocytes in the bone marrow preceded infiltrations by macrophages in lymph nodes, spleen and liver. These infiltrations were closely related to the vascular structures, became nodular and decreased around day 12 after the injection. A rapid increase in the number of monocytes and transformed lymphocytes of the peripheral blood were noted almost immediately after the administration of the vaccine. No relationship between the degree and duration of the histological changes, strain of mice, and number of inoculations was found. It is suggested that the increase in size and weight of the lymphoid organs and the liver is primarily caused by invasion of macrophages, perhaps secondary to a preceding proliferation of monocytes in the bone marrow.

Animals↗

Organ distribution of Corynebacterium parvum labeled with iodine-125.

Administration of iv, ip, single sc, multiple sc, and footpad injections of [125I]Corynebacterium parvum in mice revealed different patterns of radioactive vaccine distribution in various organs. High deposition and retention were found in the liver, spleen, and gastrointestinal tract and less in the lungs, kidneys, thymus, and bone marrow. Control animals given 125I showed very rapid clearance of the isotope and no retention in the organs. The pattern of distribution of [125I]C. parvum could be useful when protocols for clinical trials are designed.

Absorption↗

Effect of corynebacterium parvum on bone marrow cell cultures (38557).

The effect of C. parvum on in vitro colony-forming cell was evaluated. A single ip injection of the vaccine had no effect during the first 4 hr either on colony stimulating factor or on colony-forming cells. The enhancement of the colony-forming capacity of the bone marrow by C.parvum occurred after two injections of the vaccine within 48 hr. The stimulation of colony formation by C. parvum was time related function and occured 5 days after the initiation of the cultures. The results of this study indicate that C. parvum appears to be stimulant of bone marrow cells capable of proliferation and may be used as a valuable adjuvant against myelosuppressive agents.

Animals↗