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Biomedical subjects

M Hajdúch

Publications and source records attributed to M Hajdúch.

30 records · Page 2Linked to original sources

Induction of apoptosis and regression of spontaneous dog melanoma following in vivo application of synthetic cyclin-dependent kinase inhibitor olomoucine.

This case report describes a dog with spontaneous melanoma of the orofacial region which was treated by a synthetic inhibitor of cyclin-dependent kinases, i.e. olomoucine (OC). The drug was applied i.v. in a single dose of 8 mg/kg/day for 7 days in succession. Repeated bioptic examinations of metastatic cervical lymph nodes showed rapid induction of apoptosis in tumor cells as early as on the third day of treatment. Standard clinical and laboratory examinations did not reveal side effects of the therapy. There were no detectable manifestations of myelosuppression, hepatotoxicity, nephrotoxicity or neurotoxicity. However, transient anemia developed following bleeding from a devitalized tumor mass. For this reason, the dog underwent surgery to minimize tumor load as well as to eliminate the source of bleeding. Two kilograms of primary tumor were extirpated in the course of surgery, including cervical node metastases. Unfortunately, the dog died soon after surgery due to respiratory depression. Histological examinations of the tumor tissue showed marked apoptosis of melanoma cells in both the primary tumor and metastases. The induction of programmed cell death of cancer cells by OC resulted in rapid eradication of at least 68% of the tumor cells. The remaining melanoma cells retained at least equally well in vitro sensitivity to OC as to drugs currently used in clinical practice.

Animals↗

Differential chemosensitivity of leukemic cells in the myeloid and lymphoid phases of stem cell leukemia (a case report).

A five-year-old girl, initially diagnosed as having acute lymphoblastic leukemia (ALL; FAB-L1) relapsed with ALL 4 months after completion of chemotherapy (BFM 83). The initial ALL presentation and subsequent ALL relapse were analyzed using conventional morphology, cytochemistry, cytogenetics and immunophenotyping. The results were consistent with a diagnosis of B-lymphocyte precursor ALL. Bone marrow leukemic cells revealed a 46, XX karyotype at diagnosis and a 46, XX, del(7) (q22; qter) when the girl first relapsed. The case was managed with a BFM REZ-ALL 90 protocol. Upon completion of the first cycle of the protocol, severe myelosuppression developed. This was treated with GM-CSF. Three days later, however, GM-CSF was stopped because the WBC reached 1.1 x 10(9) per liter with 60% of blasts in peripheral blood. Laboratory characteristics were typical of AML. Cytogenetic analysis revealed 46, XX, del(7) (q22; qter) karyotype as before. The bcr-abl fusion gene was not detected. Myeloid blasts were placed in a culture and maintained at 37 degrees C and 7.5% CO2 for two weeks. During this period, formation of hemopoietic colonies was observed and subsequently analyzed using histology and electron microscopy. This showed that the colonies consisted of differentiating erythroid, megakaryocytic and myeloid cells. Further, the chemosensitivity of leukemic cells was examined in both "lymphoid" and "myeloid" relapse instances. While the "lymphoid" phenotype was characterized by good sensitivity to corticosteroids, a typical feature of the "myeloid" phenotype was a high resistance to corticosteroids with marginally increased sensitivity to ARA-C.

Antineoplastic Combined Chemotherapy Protocols↗

Decreased in vitro chemosensitivity of tumour cells in patients suffering from malignant diseases with poor prognosis.

The aim of the study was to assess the predictive value of MTT in vitro assay for evaluation of tumour cell resistance/sensitivity to cytotoxic drugs. We analyzed 105 samples of malignant cells of different origin. The study included patients with a diagnosis of acute and chronic lymphatic leukaemia, acute and chronic myeloid leukaemia, non-Hodgkin lymphoma, carcinoma of the lung, stomach and liver, rhabdomyosarcoma and breast carcinoma. The results demonstrate outstanding chemosensitivity in the majority of childhood acute lymphoblastic leukaemias, medium chemosensitivity of adult haematopoietic malignant diseases and chemoresistance of solid tumour cells. Our preliminary data suggest a good correlation between in vitro MTT assay and clinical curability of individual malignant diseases.

Adult↗

Bacterial immunomodulator Olimunostim inhibits degranulation of mastocytes in vitro.

A bacterial immunomodulator Olimunostim (OS) is one of the first Czech biologic response modifiers, which have been introduced into clinical practice. OS activates the mechanisms of non-specific immunity and is used for the most part in chronic infections. Since OS is indicated in patients suffering from infection complicated allergic diseases (asthma bronchiale, atopic eczema, etc.), (1) the concentration of histamine (Hi) and Hi-like compounds in OS, and (2) the possible role of OS in the process of histamine release from rat peritoneal mastocytes (PMC) were studied. The cells were preincubated with soluble fractions of OS. PMC degranulation was stimulated by the compound 48/80. The amount of Hi and Hi-like substances in the supernatant and in the pellet of PMC was determined by the fluorimetric method. Compounds of Hi nature were also evaluated in OS (lysate of S. aureus, K. pneumoniae, P. acnes) by original modification of high-performance liquid chromatography. The data provide the first evidence for a dose-dependent inhibitory effect of OS on the degranulation of rat PMC. Moreover, we found that 1 mg of OS itself contained 0.376 microgram of Hi and 0.142 microgram of 1-methylHi. Histamine was detected in P. acnes (0.672 microgram/mg), K. pneumoniae (0.136 microgram/mg), and S. aureus (0.175 microgram/mg), while methylHi was detected only in the case of K. pneumoniae (0.454 microgram/mg). The results of our in vitro study do not support the hypothesis of inducing type I allergic reaction by OS or facilitating OS in crossing the enteral barrier.

Adjuvants, Immunologic↗

[Histochemical differentiation of lymphatic organs during intrauterine development].

The activities of some enzymes (phosphatases, esterases peptidases, and dehydrogenases) were studied. The activities of the enzymes in the youngest embryos (4-8 weeks) were relatively low (ALP-activity on membranes of the primitive capillary endothelium, ACP and UE activities in the cytoplasm of the epithelial reticulum cells). The DPP IV activity was observed on membranes of the epithelial reticulum cells. The activities of GPDH and SDH were relatively strong in the epithelial cells of the primitive cytoreticulum. In the fetal period, the activities of the studied enzymes are gradually increasing. The immunohistochemical findings demonstrate that 95% of the lymphocytes in the thymus anlage (in the fetal period) are T-lymphocytes. The enzyme activities in other lymphatic organs (spleen, lymph nodes) were significantly lower.

Capillaries↗

Some biochemical characteristics of the early phase of immunomodulation.

The study estimates some biochemical changes of chosen immunological and biochemical parameters after intraperitoneal application of a) immunomodulators of microbial origin--Propionibacterium acnes and Geotrichum candidum, b) chemical substances--indomethacin and phenobarbital. The estimation was concentrated above all to the changes of chemiluminiscence, phagocytic activities, the amount of cAMP in peritoneal macrophages, the amount of liver cytochrome P-450 and cAMP in the liver, spleen and thymus. The experiments also included histological examination of the spleen, thymus, lungs and diaphragm. The effect of Propionibacterium acnes was evident as soon as 24 hrs after application. In the frame of studied parameters, there was manifested the nonspecific activation of the immune system by the mechanisms independent to oxygen. The early changes were accompanied by the increase of cAMP in macrophages. In contrary, the intraperitoneal application of Geotrichum candidum activated the release of oxygen radicals from peritoneal macrophages. The amount of the cytochrome P-450 correlated to the intensity of immunomodulation. On the other hand, the induction of cytochrome P-450 by phenobarbital decreased the value of several immunity indices.

Adjuvants, Immunologic↗

Effect of quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and fagaronine on some mammalian cells.

The effects of benzo[c]phenanthridine alkaloids sanguinarine (SA), chelerythrine (CHE), fagaronine (FA) and their dihydroderivates were tested on human leukocytes and lymphocytes, rat peritoneal mastocytes and primary cultured hepatocytes. The cytotoxicity of SA and CHE on hepatocytes is dose (35-100 microM) and time (1-3 h) dependent. Both alkaloids decrease chemiluminiscence of leukocytes and inhibit a creation of active E-rosets. The degranulation of mastocytes is inhibited only by CHE. Dihydroderivates of SA and CHE did not display any effect on studied cells, dihydrofagaronine exhibits a hepatotoxicity after 3 h.

Alkaloids↗

Biochemical aspects of immunomodulation by Propionibacterium acnes.

The present paper deals with the effect of indomethacin and/or Propionibacterium acnes (Pa) on the cytochrome P-450 content in liver microsomal fraction, free fatty acids and lipase concentration in serum with respect to the phagocytic activities of monocytomacrophage system, changes in weight of the spleen and liver, survival after LD100 of Klebsiella pneumoniae, and histology of the spleen and liver. The results obtained indicate that INDO acts as an inhibitor of cytochrome P-450 and at the same time stimulates functions of the monocytomacrophage system in all the parameters studied. Pa, a classical immunomodulator, inhibits cytochrome P-450. After the initial suppression phase (3rd day after administration), it stimulates significantly the activity of monocytomacrophage system and increases the amount of FFA in the serum. The combination of both preparations also inhibits the cytochrome P-450 concentration in the liver and stimulates functions of the monocytomacrophage system in all the studied parameters. However, no temporary suppression of phagocytic activities was observed on the 3rd day of the experiment, in contrast to the animals administered Pa alone. Serum FFA concentration increased significantly. The application of both preparations accelerated markedly the onset of proliferation and differentiation processes in lymphatic follicles of the spleen.

Adjuvants, Immunologic↗

"Nude rabbit" with aplasia of B-lymphoid structures.

An original observation of the randombred nude rabbit with aplasia of B-lymphoid structures (absence of the follicles in lymph nodes and spleen, no Peyer's plaques). The thymus gland and the T-dependent structures in the spleen and lymph nodes were-on the contrary-well preserved. The nude skin of this genetic rabbit mutant contained large numbers of hair follicles showing almost intrafollicular retention of hairs with their subsequent dysplasia at the subepidermal and ostiopilar level.

Animals↗

Lymphocyte proliferation and T-lymphocyte subsets during experimental immunomodulation of Balb/C mice by Olimunostim.

To objectivize possible immunomodulatory effects of polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte proliferation and T-lymphocyte subsets were followed-up in Balb/c mice administered perorally the lysate or saline (controls). The enhanced spontaneous lymphocyte proliferation observed at the beginning of Olimunostim application preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the maximum five days after the administration of the last dose and returning back to the control levels ten days afterwards. This stimulation of lymphocyte proliferation was accompanied by Olimunostim induced increase of CD4+ splenic lymphocytes being most pronounced five days after the end of immunomodulation and later returning to the initial values. The last experiment revealed an enhanced response of the in vivo primed lymphocytes after the re-exposure to Olimunostim in vitro. It is concluded that mostly nonspecific activation mechanisms, plausibly also parallelly induced specific immunity, are involved in Olimunostim modulatory effects on the cellular immune response.

Adjuvants, Immunologic↗

Transient aplastic crisis in a leukemic child caused by parvovirus B19 infection.

Acute parvovirus B19 infection was confirmed in an 8-year-old girl with acute lymphoblastic leukemia on maintenance therapy by electron microscopy, DNA, and serological techniques. Clinical manifestations were typical of severe anemia, fever, leukopenia, and thrombocytopenia. Increased levels of serum erythropoietin were detected in the course of the infection. The patient's recovery was supported by corticosteroids, red blood cell transfusions, G-CSF, and commercial immunoglobulin preparations.

Acute Disease↗

Lung resection in a neoadjuvant protocol.

Neoadjuvant therapy was defined as a cytoreductive therapy administered prior to a definitive locoregional treatment--surgical resection. While surgical resection can be curative in patients diagnosed with localized early-stage non-small cell lung cancer, patients with nodal (N1, N2) disease are generally not candidates for exclusive surgery. Inductive therapy can improve the microscopic metastatic disease, eradicate the primary tumor and thereby improve survival.

Antineoplastic Combined Chemotherapy Protocols↗