PubMed Health⌕ Search

Biomedical subjects

Z Adam

Publications and source records attributed to Z Adam.

At least 55 records · Page 3Linked to original sources
PubMed1998

Herpes simplex infection as possible etiology for febrile neutropenia and mucositis in patients treated for hematological malignancies.

Mucositis is a common complication following chemotherapy. Clinical findings similar to herpetic infection are observed in some patients. Acyclovir administered in addition to empirical, antibiotic treatment improves the course of mucositis, and can also bring down the temperature. The aim of our study was to define the etiological influence of herpetic infection on the course of febrile neutropenia in patients with mucositis. A total of 34 patients with febrile neutropenia were divided into 2 groups: 15 with typical herpetic eruption, and 19 with non-specific mucositis. Both groups received 5-10 mg/kg acyclovir every eight hours together with empiric antibiotic treatment. The effect of acyclovir was studied, and results compared in the two patient groups. Body temperatures decreased in both groups, clinical symptoms, however, disappeared more slowly in the group with non-specific mucositis. The beneficial effect of acyclovir treatment was particularly well expressed in seropositive patients. In this group of patients, herpetic infections may recur under further chemotherapy. Thus, it would be useful to administer acyclovir to them prophylactically during risk periods.

Acyclovir↗
PubMed1998

[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

Adolescent↗
PubMed1998

[Schnitzler's syndrome].

The authors describe the development of disease in a patient with monoclonal immunoglobulin IgM, urticarial morphoeae and intensive pain in the region of the pelvic bones due to osteolysis and osteosclerosis. The combination of these symptoms corresponds with the so-called Schnitzler syndrome which is analyzed in detail in the discussion. The urticarial manifestations diminish only temporarily during corticoid treatment, other drugs have no effect. 2-chlorodeoxyadenosine, the most effective drug in treatment of m. Waldenström, suppressed the skin manifestations temporarily. However, the concentration of monoclonal IgM did not decline even after two cycles and therefore the authors did not proceed with it during subsequent cycles. The severity of urticaria called for a permanent daily dose of Prednisone. The second symptom, bone pain, was however influenced by the administration of pamidronate (Aredia), using an initial dose of 120 mg per month. Now the patient takes a maintenance dose of 60 mg/month. The authors describe the case to draw attention to a rare cause of urticaria and the possibility to treat bone pain with bisphosphonates.

Humans↗
PubMed1998

Current role of immunotherapy in multiple myeloma.

Myeloablative chemotherapy improved the results of multiple myeloma treatment but the disease remains incurable. Residual disease eradication is one of the main clues for further improvement of the prognosis of myeloma patients. Interferon alpha maintenance therapy has controversial results. New methods, such as consolidation therapy, antibodies, gene therapy, interleukins, immunotoxins, dendritic cells, vaccines and induction of graft-versus-tumor effect, are tested in the phase I/II clinical trials. This article briefly reviews the new treatment modalities of immunotherapy. Progress in adoptive cellular immunotherapy and progress in induction of graft versus myeloma effect are very promising. We are still not able to transfer very good preclinical results of immunotherapy into clinical results in vivo measured by event free and long-term survivals. Combination of myeloablative therapy followed a new type of immunotherapy focusing on residual disease eradication evaluated in the setting of sensitive disease may be optimal. Such approach could improve the current controversial status of immunotherapy in MM.

Clinical Trials as Topic↗
PubMed1997

Light-stimulated degradation of an unassembled Rieske FeS protein by a thylakoid-bound protease: the possible role of the FtsH protease.

Unassembled subunits of the cytochrome b6f complex as well as components of other unassembled chloroplastic complexes are rapidly degraded within the organelle. However, the mechanisms involved in these proteolytic processes are obscure. When the Rieske FeS protein (RISP) is imported into isolated chloroplasts in vitro, some of the protein does not property assemble with the cytochrome complex, as determined by its sensitivity to exogenous protease. When assayed in intact, lysed, or fractionated chloroplasts, the imported RISP was found to be sensitive to endogenous proteases as well. The activity responsible for degradation of the unassembled protein was localized to the thylakoid membrane and characterized as a metalloprotease requiring zinc ions for its activity. The degradation rate was stimulated by light, but no involvement of ATP or redox control was observed. Instead, when the RISP that was attached to thylakoid membranes was first illuminated on ice, degradation proceeded in either light or darkness at equal rates suggesting a light-induced conformational change making the protein prone to degradation. Antibodies raised against native FtsH, a bacterial, membrane-bound, ATP-dependent, zinc-stimulated protease, effectively inhibited degradation of the unassembled RISP, suggesting a role for the chloroplastic FtsH in this process.

Adenosine Triphosphatases↗
PubMed1997

[Autologous transplantation of peripheral hematopoietic cells in a patient with multiple myeloma and renal insufficiency].

High dosage melfalan chemotherapy with subsequent autologous blood stem cell transplantation in suitably selected patients with multiple myeloma greatly increases the probability that complete remission will be achieved and it prolongs the mean survival period as compared with classical chemotherapy. Till recently patients with multiple myeloma and renal insufficiency were not included in transplantation programmes. Only recently several papers were published abroad which indicate the possibility to implement transplantations also in these patients. The authors describe the treatment, incl. the first autologous transplantation of blood stem cells in a patient with multiple myeloma and renal insufficiency.

Adult↗
PubMed1997

[Detection of myeloma cells in the peripheral blood using flow cytometry].

Bone marrow plasma cells from patients with multiple myeloma express monoclonal cytoplasmic immunoglobulin, strongly express CD38 and usually coexpress CD56 and CD54. The aim of this study was to learn the relationship between the number of CD38+CD56+ and CD38+CD54 positive cells in peripheral blood with the activity of multiple myeloma. We evaluated the number of these cells in patients with monoclonal gammopathy and in the control group, as well. We used the two-color flow cytometry for this purpose. The peripheral blood of 57 patients with multiple myeloma and 4 patients with monoclonal gammopathy of unknown significance was repeatedly analyzed. Patients with high activity of multiple myeloma had the highest percentage of CD38+CD56+ and CD38+CD54+ cells. Patients with lower activity of the disease had lower count of these cells. But in 4 (11%) patients with high disease activity the count of CD38+CD56+ cells was zero. We conclude, that the longitudinal flow cytometric analysis of CD38+CD54+ and CD38+CD56+ cells is a useful method for estimation of disease activity in patients with multiple myeloma. Single analysis of these parameters cannot be used as a strict criterium for differential diagnosis.

ADP-ribosyl Cyclase↗
PubMed1996

Identification, characterization, and molecular cloning of a homologue of the bacterial FtsH protease in chloroplasts of higher plants.

In an attempt to identify and characterize chloroplast proteases, we performed an immunological analysis of chloroplasts using an antibody against Escherichia coli FtsH protease, which is an ATP-dependent metalloprotease bound to the cytoplasmic membrane. A cross-reacting protein of 78 kDa was found in the thylakoid membrane of spinach, but not in the soluble stromal fraction. Alkali and high salt washes, as well as trypsin treatment of thylakoid membranes, suggest that the chloroplastic FtsH protein is integral to the membrane, with its hydrophilic portion exposed to the stroma. The protein is not bound to any photosynthetic complex and is exclusively located in the stromally exposed regions of the thylakoid membrane. Its expression is dependent on light, as it is present in green pea seedlings, but absent from etiolated ones. An Arabidopsis cDNA was isolated, and the deduced amino acid sequence demonstrated high similarity to the E. coli FtsH protein, especially in the central region of the protein, containing the ATP- and zinc-binding sites. The product of this clone was capable of import into isolated pea chloroplasts, where it was processed to its mature form and targeted to the thylakoid membrane. The trans-bilayer orientation and lateral location of the FtsH protein in the thylakoid membrane suggest its involvement in the degradation of both soluble stromal proteins and newly inserted or turning-over thylakoid proteins.

ATP-Dependent Proteases↗
PubMed1996

Immunological detection of proteins similar to bacterial proteases in higher plant chloroplasts.

Despite numerous demonstrations of protein degradation in chloroplasts of higher plants, little is known about the identity of the proteases involved in these reactions. To identify chloroplast proteases by immunological means, we investigated two proteins: ClpP, a protein similar to the proteolytic subunit of the bacterial ATP-dependent Clp protease, for which a gene is found in the chloroplast genome [Maurizi, M.R., Clark, W.P., Kim, S. H. & Gottesman, S. (1990) J. Biol. Chem. 265, 12546-12552] and PrcA, a cyanobacterial Ca2+-stimulated protease [Maldener, I., Lockau, W., Cai, Y. & Wolk, P. (1991) Mol. & Gen. Genet. 225, 113-120]. We expressed the clpP gene from rice in Escherichia coli, purified its product, and generated antibodies against the product. Western blot analysis revealed the ClpP protein in different leaf extracts. Analysis of fractionated barley chloroplasts revealed that the protein was associated with the stromal fraction. The expression of ClpP is light independent and tissue specific, as it was found in green and etiolated barley leaves, but not in roots. A second protein, similar to the cyanobacterial protease PrcA, was also detected in chloroplasts. Antibody against this protease recognized proteins in various leaf extracts. When pea chloroplasts were fractionated, the antibody only recognized a stromal protein. The expression of this protein is regulated by light, as it was found in green leaves, but not in etiolated leaves. The tissue specificity of PrcA was similar to that of ClpP in that it could not be detected in root extracts.

Adenosine Triphosphatases↗
PubMed1996

Degradation of mistargeted OEE33 in the chloroplast stroma.

OEE33, a component of the oxygen-evolving enzyme in chloroplasts, normally resides in the thylakoid lumen. In an attempt to study the fate of mistargeted proteins in chloroplasts, we substituted the bipartite transit peptide of OEE33 with that of CAB7, an integral thylakoid-membrane protein. As a result, when imported into isolated chloroplasts, the chimeric protein protein was targeted to the stroma instead of the thylakoid lumen. Whereas the wild-type OEE33 was totally stable for at least 2 h, the chimeric protein was rapidly degraded, with a half-life of 60 min. Degradation of the chimeric protein was stimulated by ATP supplementation. Degradation could also be observed in lysed chloroplasts, in an ATP-stimulated manner. When lysates were fractionated, the proteolytic activity was found to be associated mainly with the stromal fraction. This activity was very effectively inhibited by all tested inhibitors of serine proteases. Western blot analysis demonstrated that the stromal fraction active in degrading the chimeric OEE33 contains ClpC and ClpP, homologues of the regulatory and proteolytic subunits, respectively, of the bacterial, ATP-dependent, serine-type Clp protease.

Adenosine Triphosphatases↗
PubMed1996

Effects of light and temperature on expression of ClpC, the regulatory subunit of chloroplastic Clp protease, in pea seedlings.

Chloroplasts contain homologues to the proteolytic and regulatory subunits of bacterial ATP-dependent Clp protease. We tested the effects of light and temperature on the expression of ClpC, the chloroplastic homologue of the regulatory subunit. ClpC mRNA was present in all tissues of pea seedlings, most abundantly in leaves. Higher levels of the message were found in green leaves than in etiolated ones. Exposure of etiolated seedlings to light resulted in further accumulation of the transcript. Similarly, ClpC protein level was lower in etiolated leaves, and increased upon exposure to light. Transferring seedlings from 25 degrees C to either 17 or 37 degrees C resulted in a decrease in both ClpC mRNA and protein, with the lower temperature being the most effective.

Adenosine Triphosphatases↗
PubMed1996

Molecular cloning of a carotenoid-associated protein from Cucumis sativus corollas: homologous genes involved in carotenoid sequestration in chromoplasts.

Chromoplasts are carotenoid-accumulating plastids found in the corollas and fruits of many higher plants. In most cases, the pigment in these plastids is accumulated with the aid of carotenoid-associated proteins located within unique structures. This paper reports the isolation and characterization of the cDNA (CHRC) from Cucumis sativus corollas which encodes the chromoplast-specific carotenoid-associated protein CHRC. The transit peptide cleavage site was determined and, using a chloroplast uptake system, it is shown that CHRC can be post-translationally targeted to these plastids where it is peripherally associated with thylakoids. Analysis of CHRC transcript level in Cucumis sativus revealed its temporal and tissue-specific regulation: the transcript was detected only in corollas, where its level increased in parallel to flower development, peaking just before anthesis. CHRC shares significant homology (59%) with the gene coding for fibrillin-a protein in Capsicum annuum red fruits whose function is essentially identical to that of CHRC. A CHRC fragment including the potential active site of the protein was used as a probe in Northern blot analyses of floral and fruit tissues from various plants containing chromoplasts of different types: CHRC homologs of similar sizes were revealed in all cases. The existence of a group of homologous genes coding for chromoplast-specific proteins which aid in the sequestration of carotenoids within specific structures is proposed.

Amino Acid Sequence↗
PubMed1996

[Treatment of inoperable non-small cell bronchogenic carcinoma with a combination of cisplatin and vinorelbine--preliminary evaluation].

The optimal therapeutic approach to patients with inoperable non-small-cell carcinoma is still a matter of discussion. The reason is that chemotherapy improves the quality of life only in some patients. It prolongs their life only by several weeks. In recent years in this indication a new cytostatic is tested--vinorelbine which when used in monotherapy achieves a therapeutic response in 16--30%. In clinical trials of phase 2 a combination of vinorelbine and cisplatinum was most effective and therefore it was selected for the third phase of clinical trials. In the Czech Republic a clinical investigation was made with the objective to verify published data on the success of treatment, evaluate undesirable effects and consider whether it is suitable for routine use. Cisplatinum (Platidiam Lachema) was administered--80 mg/m2 on the first day, vinorelbine (Navelbine Pierre Fabre)--30 mg/m2 on the first and eighth day. The cycle was repeated on the 22nd day. All patients were treated for 12 weeks. Then followed the first evaluation and treatment was continued only in patients with regression or stabilization of the disease. In the group of 126 patients in 44 (35%) partial and in 3 (2.3%) complete therapeutic responses were obtained. In 35 (27%) the disease was evaluated during treatment as stabilized, in 38 (30%) of the patients the disease progressed despite treatment. The tolerance of treatment was, when effective antiemetic treatment was used (ondansetrone or granisetrone), relatively satisfactory.

Antineoplastic Agents↗
PubMed1996

[Treatment of multiple myeloma--melphalan monotherapy after bone marrow transplantation].

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to three years. In the following three decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought contraverse results. The latest metaanalysis and data published by Ludwig support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trend are reviewed in this paper.

Antineoplastic Agents, Alkylating↗
PubMed1996

[Erythropoietin in hematology and oncology. I. Chronic anemia in malignant disease and the pharmacology of erythropoietin].

In many patients with malignant haematological and oncological diseases during the disease the haemoglobin concentration declines. Anaemia can be due to blood losses, less frequently to nutritional deficiency. One of frequent causes is the humoral effect of malignant disease on haematopoiesis and the development of anemia of chronic disease. Anemia of chronic disease has a complex etiology. Decreased production of erythropoietin is one of the participating factors and the pharmacological doses of erythropoietin can restore the number of erythrocytes to normal value. The authors present basic information on chronic anaemia of malignant diseases and principles of erythropoietin treatment of these patients.

Anemia↗
PubMed1996

[Treatment of multiple myeloma].

A new era of multiple myeloma management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Clinical trials have begun and the first results are promising, though preliminary. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Humans↗
PubMed1996

[Erythropoietin in oncology. II. Evaluation of the effectiveness of erythropoietin in hematologic and oncologic diseases].

Erythropoietin can be successfully used in the treatment of anaemia induced by chemotherapy and radiotherapy as well as for the treatment of anaemia induced by malignant disease without previous chemotherapy of radiotherapy. Erythropoietin administered during chemotherapy is effective in 50-70% patients, it has a more marked effect as a supplement to chemotherapy with cisplatinum and carboplatinum than non-platinum regimens. Erythropoietin reduces the consumption of red cell concentrates during chemotherapy on average by one half. Long-term administration of erythropoietin in anaemia caused by malignant disease alone proves most effective in multiple myeloma and in chronic lymphatic leukaemia or in non-Hodgkin lymphomas with a low malignity. The therapeutic responses defined as independence on transfusions and a rise of the haemoglobin level by at least 20 g/l, as compared with the pretreatment value, can be achieved in 60 to 80% of the patients. Erythropoietin is much less effective (10-20% therapeutic responses) in myelodysplastic syndrome, in myeloproliferative diseases or in aplastic anaemia. The authors give an account on the effectiveness of erythropoietin in different indications.

Anemia↗