Allergic contact dermatitis to natural latex.
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Dermatitis, Allergic Contact↗
Biomedical subjects
M Wyss
Publications and source records attributed to M Wyss.
Identification of creatine kinase isoenzymes in the guinea-pig. Presence of mitochondrial creatine kinase in smooth muscle.
Isoenzymes of creatine kinase (CK, EC 2.7.3.2) in guinea-pig smooth, cardiac and skeletal muscles as well as in brain were analyzed by cellulose acetate electrophoresis and FPLC gel permeation chromatography. In crude tissue extracts of smooth muscles brain type BB-CK and the hybrid form MB-CK were detected, but in enriched mitochondrial fractions from different guinea-pig smooth muscles, mitochondrial type Mi-CK was unambiguously identified. Smooth muscle Mi-CK displayed the same electrophoretic mobility as Mi-CK from brain, which migrates slower than cardiac Mi-CK. Identical to parallel experiments with Mi-CK from cardiac muscle and brain, smooth muscle Mi-CK could be resolved into dimeric and octameric species, the latter being remarkably stable. In contrast to guinea-pig smooth muscles, Mi-CK was not detected in chicken gizzard tissue extracts nor in enriched mitochondrial fractions thereof. The presence of Mi-CK, predominantly in octameric form, in guinea-pig smooth muscles, but not in chicken gizzard, may represent a clue for the different physiological properties of these muscles and may provide the molecular basis for the dependence of the PCr production on oxidative metabolism observed in the guinea-pig taenia caeci.
Animals↗
ATP binding site of mitochondrial creatine kinase. Affinity labelling of Asp-335 with C1RATP.
The ATP binding site of mitochondrial creatine kinase from chicken heart has been studied by modifying the purified enzyme with a 14C-labelled ATP analogue, C1RATP, in which the reactive label was covalently bound to the gamma-phosphate group of ATP. The modified enzyme was digested by pepsin, and a single radioactive nonapeptide was isolated by HPLC. Amino acid analysis and direct sequence determination revealed that the isolated peptide corresponds to amino acids 335-343 within the C-terminal region of Mi-CK, this peptide being highly preserved throughout evolution. Asp-335 is very likely the site of modification by C1RATP. The specificity of the ATP analogue for the active site of creatine kinase was demonstrated by the inhibition of the enzymatic activity of Mi-CK by C1RATP and by the prevention of this inhibition bij ADP.
Adenosine Triphosphate↗
Mitochondrial creatine kinase from chicken brain. Purification, biophysical characterization, and generation of heterodimeric and heterooctameric molecules with subunits of other creatine kinase isoenzymes.
In a recent study it has been shown that mitochondrial creatine kinase from chicken brain (Mia-CK) and heart (Mib-CK) are two distinct isoenzymes differing in ten out of the thirty N-terminal amino acids (Hossle, J.P., Schlegel, J., Wegmann, G., Wyss, M., Böhlen, P., Eppenberger, H.M., Wallimann, T., and Perriard J.C. (1988) Biochem. Biophys. Res. Commun. 151, 408-416). The present article describes the purification and biophysical characterization of the mitochondrial creatine kinase isoenzyme from chicken brain (Mia-CK). Gel permeation chromatography, direct mass measurements of individual molecules by scanning transmission electron microscopy, and analytical ultracentrifugation confirmed the existence of two different oligomeric forms, dimeric and octameric Mia-CK, with molecular masses of 85 kDa and 306-352 kDa and with sedimentation constants of 4.9-5.3 and 11.6-12.0 S, respectively. In addition, it was tested if Mia- and Mib-CK can form heterodimeric and heterooctameric molecules with subunits of other CK isoenzymes. By denaturation in urea or guanidine hydrochloride and subsequent renaturation, MiaMib-CK and surprisingly also MiaM-CK heterodimers could be generated. In contrast, no heterodimers were obtained between Mib- and M- or B-CK. Furthermore, reoctamerization of a mixture of Mia- and Mib-CK homodimers led to the formation of MiaMib-CK heterooctamers. In these heterooctamers, the Mia- and Mib-CK homodimers remained the fundamental building blocks. No subunit exchange between adjacent dimers within the heterooctamer could be observed even after storage for 3 months at 4 degrees C. The relevance of these data on the structural organization of the Mi-CK octamer and on the physiological aspects of tissue-specific isoenzyme expression are discussed.
Amino Acid Sequence↗
Functional studies with the octameric and dimeric form of mitochondrial creatine kinase. Differential pH-dependent association of the two oligomeric forms with the inner mitochondrial membrane.
Phosphate extraction of mitochondrial creatine kinase (Mi-CK, EC 2.7.3.2) from freshly isolated intact mitochondria of chicken cardiac muscle, after short swelling in hypotonic medium, yielded more than 90% of octameric and only small amounts of dimeric Mi-CK as judged by fast protein liquid chromatography-gel permeation analysis of the supernatants immediately after extraction of the enzyme. In extraction buffer, octameric Mi-CK displayed a tendency to dissociate, albeit at a slow rate with a half-life of approximately 3-5 days, into stable dimers. Experiments with purified Mi-CK octamers or dimers, or defined mixtures thereof, incubated under identical conditions with Mi-CK-depleted mitoplasts revealed that both oligomeric forms of Mi-CK can rebind to mitoplasts. However, the association of Mi-CK was strongly pH-dependent and, in addition, octameric and dimeric Mi-CK showed different pH dependences of rebinding. Therefore, it was possible under certain pH conditions to rebind either both oligomeric forms or selectively the octamers only. Furthermore, evidence is presented that Mi-CK dimers partially form octamers upon rebinding to the inner membrane. The differential association of the two oligomeric Mi-CK forms with the inner mitochondrial membrane together with the dynamic equilibrium between octameric and dimeric Mi-CK (Schlegel, J., Zurbriggen, B., Wegmann, G., Wyss, M., Eppenberger, H.M., and Wallimann, T. (1988) J. Biol. Chem., 263, 16942-16953) suggest that both oligomeric forms are physiologically relevant. A change in the octamer to dimer ratio may influence the association behavior of Mi-CK in general and thus modulate mitochondrial energy flux as discussed in the phosphoryl creatine circuit model (Wallimann, T., Schnyder, T., Schlegel, J., Wyss, M., Wegmann, G., Rossi, A.-M., Hemmer, W., Eppenberger, H.M., and Quest, A.F.G. (1989) Prog. Clin. Biol. Res. 315, 159-176.
Animals↗
Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study.
In an attempt to stimulate endogenous erythrocyte production and thereby provide an alternative to erythrocyte transfusions, we administered recombinant human erythropoietin (rHuEpo) in doses of 75 to 300 units/kg/wk to seven infants with the anemia of prematurity. Treatment was started between 21 and 33 days of life, maintained for 4 weeks, and was well tolerated. All the patients had low baseline serum erythropoietin levels. After rHuEpo therapy, the number of reticulocytes increased from a mean baseline count of 75 x 10(9)/L to 95, 141, and 165 x 10(9)/L on days 7, 10, and 14 of therapy, respectively. Correction or stabilization of the anemia was observed in six of seven patients, whose estimated total erythrocyte volume increased by 49% during therapy (vs a predicted increment of 18% in the absence of rHuEpo). In one patient, however, the hematocrit declined during the treatment, and in three of the responders a secondary fall in hematocrit was noted either during therapy or after its discontinuation. Serum iron and ferritin levels rapidly decreased after the initiation of rHuEpo therapy, and in most patients transient early thrombocytosis and late neutropenia were observed. These data suggest that rHuEpo may correct or stabilize the anemia of prematurity. Its effects, however, may be limited by a variety of factors, among which iron availability probably plays an important role. Controlled studies will be needed to confirm these preliminary observations.
Anemia↗
Subcellular compartmentation of creatine kinase isoenzymes, regulation of CK and octameric structure of mitochondrial CK: important aspects of the phosphoryl-creatine circuit.
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Animals↗
Topical skin anesthesia for venous, subcutaneous drug reservoir and lumbar punctures in children.
A new topical anesthetic ointment (EMLA, "eutectic mixture of prilocaine and lidocaine was studied in a double-blind, placebo-controlled trial to evaluate its efficiency in alleviating pain associated with venous, subcutaneous drug reservoir and lumbar punctures in children. Pain intensity was scored by the children themselves, using a visual analogue scale in which 0 corresponded to absence of sensation and 10 to the worst imaginable painful sensation. Venipunctures were performed on 18 children (6.1 to 12.2 years of age) equally divided in the study and control groups; EMLA cream was associated with lesser pain scores than those with placebo (means +/- SD: 2.8 +/- 2.4 vs 6.8 +/- 2.1, P less than .01). A crossover trial was used in the studies of subcutaneous drug reservoir and lumbar punctures, eight children (6.1 to 15.1 years of age) were tested for subcutaneous drug reservoir punctures; pain induced by this procedure was rated at 3.9 +/- 2.2 with placebo compared with 1.2 +/- 1.8 with EMLA cream (P less than .04). In lumbar punctures (14 children studied, 5.5 to 15.3 years of age), EMLA cream was again associated with less pain (1.9 +/- 1.9) than was placebo (5.6 +/- 3.0, P less than .01). It was concluded that the use of EMLA cream substantially reduces pain caused by venous, subcutaneous drug reservoir, and lumbar punctures in children and may therefore be offered to young patients, particularly those repeatedly submitted to such procedures.
Adolescent↗
Native mitochondrial creatine kinase forms octameric structures. I. Isolation of two interconvertible mitochondrial creatine kinase forms, dimeric and octameric mitochondrial creatine kinase: characterization, localization, and structure-function relationships.
The mitochondrial isoform of creatine kinase (Mi-CK, EC 2.7.3.2) purified to homogeneity from chicken cardiac muscle by the mild and efficient technique described in this article was greater than or equal to 99.5% pure and consisted of greater than or equal to 95% of a distinct, octameric Mi-CK protein species, with a Mr of 364,000 +/- 30,000 and an apparent subunit Mr of 42,000. The remaining 5% were dimeric Mi-CK with an apparent Mr of 86,000 +/- 8,000. Octamerization was not due to covalent linkages or intermolecular disulfide bonding. Upon dilution into buffers of low ionic strength and alkaline pH, octameric Mi-CK slowly dissociated in a time-dependent manner (weeks-months) into dimeric Mi-CK. However, the time scale of dimerization was reduced to minutes by the addition to diluted Mi-CK octamers of a mixture of Mg2+, ADP, creatine and nitrate known to induce a transition-state analogue complex (Milner-White, E.J., and Watts, D. C. (1971) Biochem. J. 122, 727-740). The conversion was fully reversible, and octamers were reformed by simple concentrations of Mi-CK dimer solutions to greater than or equal to 1 mg/ml at near neutral pH and physiological salt concentrations in the absence of adenine nucleotide. After separation of the two Mi-CK species by gel filtration, electron microscopic analysis revealed uniform square-shaped particles with a central negative-stain-filled cavity in the octamer fractions and "banana-shaped" structures in the dimer fractions. Mi-CK was localized inside the mitochondria by immunogold labeling with polyclonal antibodies. A dynamic model of the octamer-dimer equilibrium of Mi-CK and the preferential association of the octameric Mi-CK form with the inner mitochondrial membrane is discussed in the context of regulation of Mi-CK activity, mitochondrial respiration, and the CP shuttle.
Animals↗
Mitochondrial creatine kinase from cardiac muscle and brain are two distinct isoenzymes but both form octameric molecules.
Mitochondrial creatine kinase (Mi-CK) from chicken cardiac muscle and brain, recently shown to differ in their N-terminal amino acid sequences and to be encoded by multiple mRNAs (Hossle, H.P., Schlegel, J., Wegmann, G., Wyss, M., Böhlen, P., Eppenberger, H. M., Wallimann, T., and Perriard, J.C. (1988) Biochim. Biophys. Res. Commun. 151, 408-416) were separated on two-dimensional nonequilibrium pH-gradient electrophoresis gels and visualized as two distinct protein spots by immunoblotting. Analysis of the two proteins purified by specific elution from Blue-Sepharose with ADP (Wallimann, T., Zurbriggen, B., and Eppenberger, H. M. (1985) Enzyme 33, 226-231) followed by fast protein liquid chromatography cation exchange chromatography showed obvious differences in peptide maps, in immunological cross-reactivity with monoclonal antibodies, and in kinetic parameters. However, even though the two proteins were different, tissue-specific mitochondrial isoforms, both formed regularly-sized, perforated cube-like octameric structures with Mr of 364,000 +/- 25,000 and 352,000 +/- 20,000 for the cardiac and brain isoform, respectively. Electron microscopy of cardiac and brain Mi-CK octamers revealed cube-like molecules with a central cavity or transverse channel filled by negative stain. The octameric molecular structure of Mi-CK isoforms differs from the generally accepted dimeric arrangement of "cytosolic" muscle MM- and brain BB-CK.
Animals↗
[Super intensive treatment followed by bone marrow autograft in cases of hematologic neoplasms and solid tumors].
Thirty-one patients underwent autologous bone marrow transplantation (ABMT) after intensive radio and/or chemotherapy. On 18 occasions, bone marrows were treated in vitro with either Asta-Z 7557, Asta-Z 7654 or the rat monoclonal antibody Campath-1M and complement. Sixteen patients were transplanted for acute leukemia: 6 patients were in first complete remission (CR), 5 in CR greater than 1 and 5 in relapse. Twelve out of fourteen evaluable patients have relapsed. Two patients transplanted in CR 2 and CR 1 remain in CR after 9.5 and 12 months respectively. Nine patients were transplanted for aggressive lymphoma: four patients were in CR 1, 2 in CR greater than 1, 1 in first relapse and 2 refractory to best available second line chemotherapy. All 3 achieved CR after ABMT. Nine patients are evaluable: 4 relapsed and 5 remain in CR at 5, 6.5, 21, 25 and 39 months, this last patient transplanted in a refractory state, the others in CR 1. Four patients were transplanted for refractory Hodgkin's disease: 3 patients are evaluable. One patient achieved complete remission which lasted 9 months. Two patients were transplanted for relapsed solid tumors and achieved a partial response. In conclusion, the response rate is encouraging for patients transplanted during active and sometimes refractory phases of the diseases (8/13 evaluable patients achieved CR). However, for the whole group of patients, including those transplanted for acute leukemia in CR 1, the relapse rate was high. Durable remissions were achieved for patients with aggressive lymphoma who were transplanted early in the disease.
Acute Disease↗
Distinct tissue specific mitochondrial creatine kinases from chicken brain and striated muscle with a conserved CK framework.
cDNA clones for chicken mitochondrial creatine kinase (Mi-CK) were isolated from a lambda gt11 leg muscle cDNA library and sequenced. The deduced amino acid sequence showed 6 blocks of extensive homologies with the cytosolic creatine kinases and contained twenty N-terminal amino acids, with characteristic features of part of a mitochondrial presequence. The mature enzyme contained 380 amino acids with a calculated Mr of 43'195. RNA hybridization analysis showed corresponding Mi-CK transcripts in cardiac and skeletal muscle, but not in brain RNA. Within the 30 N-terminal amino acids purified brain Mi-CK contained 10 changes with respect to cardiac Mi-CK. Thus multiple isoproteins of mitochondrial creatine kinases of brain and striated muscle are encoded by multiple mRNA's.
Amino Acid Sequence↗
[Usefulness of the annual publication of numerical data on the health professions in Switzerland].
This article is an attempt to demonstrate how it is possible to obtain recent data on health manpower in a federal state where the management of the health services and the allocation of resources are not responsibilities of the central government. A practical solution is proposed considering the advantages as well as the disadvantages of national and cantonal data sources.
Data Collection↗
[Ewing's sarcoma of the chest wall. Apropos of 5 cases].
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Adolescent↗
[Transplantation of allogeneic bone marrow treated in vitro with Campath-1 monoclonal antibody].
Out of 14 bone marrow transplants, 12 patients received transplantations with allogeneic bone marrow after in vitro T-cell depletion with monoclonal Campath 1. The patients also received short term cyclosporin. This small series is in agreement with the results of larger series using T-depleted marrow as far as the prevention of graft versus host disease is concerned, and with respect to mixed chimerism, slow take, late rejection and, possibly, increased risk of recurrence.
Aged↗
[Intensive treatment and autologous bone marrow transplantation in cases of acute leukemia and lymphoma].
Experience with 19 autologous bone marrow transplantations shows that this approach may produce a high proportion of complete remissions in otherwise resistant tumours. Although most responses are of short duration, they suggest that longterm disease-free survival may be achieved in patients with poor prognosis if treated earlier in the course of disease.
Adult↗
[Health personnel in Switzerland: concept, sources and results].
Data concerning health manpower are recorded, in Switzerland, at different levels and in connection with various applications: at the national level, on the occasion of the Federal Census of Population; at the cantonal level, from the cantonal health authorities, which are recording data in connection with professional licences. Both of these main surveys are complementary, because the Federal Census is decennial, whereas cantonal data are continuously recorded. The present article makes by the way of examples some suggestions about how to use the professional data, describes a method for an interpretation of cantonal data and comments results at the national level. Health manpower constitutes a most important part of healths statistics. For instance many questions about controlling health costs and health planning cannot be treated without extensive knowledge of the structure and the development of the medical and paramedical professions.
Data Collection↗
Plasma exchange: an important part of the therapeutic procedure in a small child with autoimmune hemolytic anemia.
The case history of a child with autoimmune hemolytic anemia with complement activating warm antibodies of the pdl type is presented. This child also had giant cell hepatitis. Although plasma exchange is not curative in such a patient, the removal of antibodies and bilirubin by means of plasma exchange has alleviated the patient's condition on two occasions (at age 19 and 33 months respectively), and has permitted the institution of effective immunosuppression. A technique for plasma exchange is described, which by use of plasma filters and the usual hemodialysis equipment allows to safely perform the procedure in any pediatric hemodialysis unit. Its use in this patient stresses the technical practicability even in very young children. It is suggested that plasma exchange, if indicated, should be considered more often as part of a therapeutic concept.
Anemia, Hemolytic, Autoimmune↗