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Biomedical subjects

Z Adam

Publications and source records attributed to Z Adam.

101 records · Page 6Linked to original sources

[Therapy of refractory multiple myeloma. II. Therapy using high doses of alkylating cytostatic agents and radiotherapy in addition to interferon and bone marrow transplantation].

The author presents part II of his review on the treatment of refractory myeloma. Treatment with large doses of melphalane, 140 mg/m2, was associated with a high death rate and therefore it is used nowadays only in combination with autologous transplantation or treatment with leucocytic growth factors (GM-CSF and G-CSF). Medium doses of melphalane (25 mg/m2 to 70 mg/m2) are tolerated better and are one of the possible approaches. Another possible therapeutic procedure is whole-body irradiation. The advantage of extensive irradiation is rapid regression of pain. Interferon-alpha achieves a therapeutic response in some 20% of refractory patients. Finally the author presents some data on transplantation of bone marrow in patients with multiple myeloma.

Bone Marrow Transplantation↗

[Therapy of refractory multiple myeloma. I. Monotherapy with glucocorticoids and combined cytostatic therapy].

Treatment of refractory myeloma is still a problem. For patients where treatment with melphalan and prednisone had no effect, many therapeutic procedures were suggested and tested. Some were more, others less successful. In the first part of this review the author summarizes clinical studies which evaluate the importance of glucocorticoids and various combinations of cytostatics administered in this indication. He considers a continual four-day infusion of vincristine and adriamycin or mitoxantrone with large doses of glucocorticoids the most effective treatment. In the primarily resistant form glucocorticoids are the most important component of treatment. Finally the author presents a review of therapeutic patterns. In the second part of the paper the author will deal with the therapeutic results of large doses of cytostatics, interferon and discuss experience with transplantation of bone marrow in patients with myeloma.

Antineoplastic Combined Chemotherapy Protocols↗

Deletion Mutants of Chlorophyll a/b Binding Proteins Are Efficiently Imported into Chloroplasts but Do Not Integrate into Thylakoid Membranes.

Chlorophyll a/b binding polypeptides (CABp) are integral thylakoid membrane proteins containing three membrane-spanning helices. We have created a series of mutations in tomato CABp to test whether individual membrane helices with hydrophilic flanking sequences, when fused to a transit peptide, can be imported into chloroplasts and correctly targeted to thylakoid membranes. All of the mutated precursors, including those with large C-terminal and internal deletions, were imported successfully, showing that these regions of the mature CABp are not required for import into chloroplasts. All mutants tested, containing either one or two membrane helices, were found primarily in the stroma and not in the thylakoids. The small amount of protein found associated with the thylakoids was largely resistant to alkali extraction but was sensitive to protease, unlike wild-type protein, which is resistant to both treatments. When incubated with thylakoids in the absence of stroma and/or ATP, a significant amount of wild-type protein assumes a form that is resistant to alkali extraction but is protease sensitive, like the imported deletion proteins. This form of the wild-type protein is not chased into a protease-resistant form by adding stroma and/or ATP. These results suggest that CABp can spontaneously associate with membranes as an aberrant species that is not an intermediate in the process of integration. The inability of the deletion forms of CABp to assume a protease-resistant conformation suggests that correct integration is afforded by elements within the entire protein that collectively contribute to the proper conformation of the protein. The ability of deletion mutants to associate with thylakoids in a nonphysiological way suggests that the study of such mutants may not be useful in elucidating thylakoid-targeting signals.

Journal Article↗

[Subphrenic abscess--a complication of intensive cytostatic treatment in acute leukemia].

The authors describe the slow development of an abscess in the left subphrenic space in a patient with acute myeloid leukaemia. The patient suffered several months before the diagnosis was established from pain in the left subcostal region and was on account of this pain examined repeatedly by clinical methods and sonography. During the last sonographic examination in this area a hypoechogenic formation was detected. The diagnosis was than established more accurately by computer tomography by visualization of the abscess cavity. The case-history and relatively thick wall of the cavity suggested a long-term process. The abscess cavity was evacuated surgically, however, the patient suffered a relapse later and died from septicaemia. In the discussion the authors analyze the problem of development of metastatic abscesses in leukopenic patients, early diagnosis and treatment.

Acute Disease↗

On the interaction between cytochrome f and plastocyanin.

The interaction between cytochrome f and its electron acceptor plastocyanin (PC) was studied. To address the question of which specific regions and which of the positively charged residues of cytochrome f are important for the interaction with the negatively charged residues of PC we have used two different experimental approaches. Cytochrome f was proteolytically cleaved and fragments that could bind to a PC-affinity column were isolated. The smallest of these fragments was analysed to give information on the minimum structural requirement for binding to PC. By this procedure, we identified a peptide of approx. 11 kDa, containing the heme binding site, and having an N-terminal sequence identical to that of the mature cytochrome f. This finding suggests that the first 90 amino acids of cytochrome f contain at least some of the residues interacting with PC. The second approach involved modification of Arg residues of cytochrome f with the specific chemical modifier, hydroxyphenylglyoxal (HPG). Cytochrome f modification was performed in the absence of PC to enable identification of residues that are protected from modification when PC is bound to cytochrome f. Two peptides containing Arg residues which are modified in the absence of PC, but are not modified when PC is present, were isolated. Sequence analysis of these two peptides revealed that Arg residues no. 88 and 154 of cytochrome f are the residues that are protected from modification when cytochrome f is bound to PC, suggesting a role for these residues in the binding of cytochrome f to PC.

Amino Acid Sequence↗

Reconstitution of isolated Rieske Fe-S protein into a Rieske-depleted cytochrome b6-f complex.

The Rieske Fe-S protein can be isolated from the cytochrome b6-f complex by means of chromatography on a hydroxyapatite column in the presence of detergent. Depletion of the cytochrome complex from the Rieske protein results in the loss of oxidoreductase activity, as well as the ability to reduce cytochrome b6. The Rieske Fe-S protein can be reconstituted into the Rieske-depleted complex by removal of the Triton X-100 molecules associated with the protein fractions, and their substitution by lipids. Upon reconstitution the complex is reactivated, and the role of the Rieske Fe-S protein in the reduction of both plastocyanin and cytochrome b6 can be demonstrated.

Chromatography↗

Age-Dependent Discrimination between Stereoisomers of 1-Amino-2-Ethylcyclopropane-1-Carboxylic Acid in Carnation Petals.

The ability of carnation petals (Dianthus caryophyllus L. cv White Sim) of different ages to convert the cis and trans isomers of 1-amino-2-ethylcyclopropane-1-carboxylic acid (AEC) to 1-butene was studied. Young petals, which produce ethylene at a low rate, convert both cis- and trans-AEC to 1-butene with low efficiency and at equal rates. In senescing petals, the rate of conversion of cis-AEC remains low, but there is a marked increase in the rate of trans-AEC conversion. Thus there is a clear evidence of stereodiscrimination between the isomers. Stimulating the rate of senescence by treatment with either 1-aminocyclopropane-1-carboxylic acid or ethylene further increases the rate of trans-AEC conversion. Delaying of petal senescence by silver thiosulphate or aminooxyacetic acid inhibits the rise in trans-AEC conversion.

Journal Article↗

Free radicals play little role in the conversion of 1-aminocyclopropane-1-carboxylic acid to ethylene in carnation membrane fraction.

The role of free radicals in the conversion of 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene by a membrane-bound enzyme from carnation petals was studied. The membrane preparation oxidized ACC more effectively than it oxidized cyclopropaneamine or 2-keto-4-methylthiobutyric acid (KMB). All these substrates were oxidized chemically by NaOCl to ethylene very effectively. Free radicals generated by the xanthine/xanthine oxidase system oxidized KMB far more effectively than it oxidized ACC; only 0.004% of the ACC included in the reaction mixture was oxidized in 1 h, compared with 0.9% of the KMB. Conversion of ACC to ethylene by the membrane-bound enzyme was inhibited by Co2+, ATP and EDTA, while the inhibition of the oxidation of KMB by the same inhibitors was much less pronounced. These results suggest that ACC, the natural immediate precursor of ethylene, is specifically oxidized by the membrane-bound enzyme rather than through a nonspecific oxidation by free radicals.

Adenosine Triphosphate↗

Chloroplast proteases: possible regulators of gene expression?

A wide range of proteolytic processes in the chloroplast are well recognized. These include processing of precursor proteins, removal of oxidatively damaged proteins, degradation of proteins missing their prosthetic groups or their partner subunit in a protein complex, and adjustment of the quantity of certain chloroplast proteins in response to changing environmental conditions. To date, several chloroplast proteases have been identified and cloned. The chloroplast processing enzyme is responsible for removing the transit peptides of newly imported proteins. The thylakoid processing peptidase removes the thylakoid-transfer domain from proteins translocated into the thylakoid lumen. Within the lumen, Tsp removes the carboxy-terminal tail of the precursor of the PSII D1 protein. In contrast to these processing peptidases which perform a single endo-proteolytic cut, processive proteases that can completely degrade substrate proteins also exist in chloroplasts. The serine ATP-dependent Clp protease, composed of the proteolytic subunit ClpP and the regulatory subunit ClpC, is located in the stroma, and is involved in the degradation of abnormal soluble and membrane-bound proteins. The ATP-dependent metalloprotease FtsH is bound to the thylakoid membrane, facing the stroma. It degrades unassembled proteins and is involved in the degradation of the D1 protein of PSII following photoinhibition. DegP is a serine protease bound to the lumenal side of the thylakoid membrane that might be involved in the chloroplast response to heat. All these peptidases and proteases are homologues of known bacterial enzymes. Since ATP-dependent bacterial proteases and their mitochondrial homologues are also involved in the regulation of gene expression, via their determining the levels of key regulatory proteins, chloroplast proteases are expected to play a similar role.

Chloroplasts↗

[Plasmacytoma and support therapy with calcitonin].

The author describes the excellent effect of two-years therapy of a female patient suffering from multiple myeloma, using the calcitonin preparation Miacalcic Sandoz. During the two and a half year follow up of the patient only a small progression of the bone affection occurred. The patient who on account of pain was treated with opiates was unable to walk unaided, now walks does not take analgesics.

Aged↗