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Biomedical subjects

A Horak

Publications and source records attributed to A Horak.

At least 19 recordsLinked to original sources

Cancer vaccines with emphasis on a viral oncolysate melanoma vaccine.

Biotherapy of malignant diseases has become the fourth treatment modality besides surgery, chemo- and radiotherapy. Whole cell melanoma vaccines with or without BCG and other adjuvants, purified ganglioside and shed antigens, recombinant viruses carrying tumor antigens, dendritic cells pulsed with antigenic peptides etc. are in clinical trials. Efficacious viral oncolysate vaccines induce the host to mount tumor-specific cytotoxic T-cell response and prevention of relapses is supported by clinical trials. The use of "polyvalent" whole cell vaccines vs. purified or genetically engineered single antigen vaccines is justified as i. only very few single tumor antigens are present in all tumors of a given histological type; and ii. antigen modulation occurs in tumors rendering them resistant to immune attack generated by vaccine against a single antigen. Thus polyvalent vaccines immunize against several antigens vs. against a selected antigen.

Adjuvants, Immunologic↗

The origin and evolution of viruses (a review).

Viroids and prions might have existed early at the border of inanimate and living worlds. Most extant viruses can be characterized as derivatives of ancestors originating from episomal elements of prokaryotes (DNA phages) and later from eukaryotes. Retroviruses very likely originated from cellular retrotransposons. Retrograde evolution of some large viruses from obligatory intracellular bacteria is possible but the ontogenesis of extant bacteria does not include a viral form of existence (the filterable L forms are not viruses) and well-defined viruses do not regenerate back into vegetative bacterial forms. Biologists experimenting with the evolution of prokaryotic and eukaryotic ancient cells cannot ignore the earliest appearance of viruses within or outside the living matter. Viruses participated in and gave direction to the evolution and natural selection by coexisting with uni- and multicellular organisms for billions of years. The coevolution of viruses and their host cells is characterized by incessant attacks and counterattacks through gene rearrangements and mutations (induced in the virus by an immunological counterattack of the host or by transgression of species barriers by the virus) and recombinations. Recombinations occurred between viral and viral or viral and host genes. Acts of "molecular piracy" as practiced by ancient viruses endowed the virus with the expression of several host genes for the advantage of the virus in its replicative cycle and host-to-host spread. Probably the first immortalized and malignantly transformed cells were induced by viruses as viruses evolved anti-apoptotic measures. While infected cells resort to apoptotic death before the assembly of a new viral progeny, prominent are the anti-apoptotic measures viruses evolved in order to assure the completion of their full replicative cycle. Further, viruses may escape neutralization by host antibodies and may survive a counterattack by the host's T cells directed at virally infected cells of its own. Viruses may induce a form of tolerance and coexist with their host without inducing disease. Persistent and apparently or deceivingly apathogenic or even attenuated viral "quasi-species" populations may contain individual particles that regain virulence due to recombinations and/or gene rearrangements, especially when transgressing species barriers. Xenotropic viruses of animals may replicate in human cells and vice versa confounding experiments with xenotransplants or with use of veterinary viral vaccines for the treatment of human diseases.

Animals↗

Equilibrium radionuclide angiocardiography prior to elective abdominal aortic surgery.

Equilibrium radionuclide angiocardiography (ERNA) was employed preoperatively in 183 patients undergoing elective abdominal aortic reconstruction to measure left ventricular ejection fraction (LVEF) and to detect abnormal regional wall movement. Abnormal ejection fractions were virtually confined to the 97 patients who had clinical, electrocardiographic or radiographic evidence of heart disease. An operative mortality of 8.7% was recorded. Major cardiac events (defined as myocardial infarction, cardiac failure or malignant ventricular arrhythmia) occurred in 15 of 86 abdominal aortic aneurysm patients (17.4%) and six of 96 (6.25%) patients with aorto-iliac occlusive disease. Patients with an abdominal aortic aneurysm and abnormal LVEF or regional wall motion abnormality were more likely to suffer a cardiac event (p less than 0.001), the event rate exceeding 60% in patients whose LVEF was less than 35%. An abnormal LVEF failed to predict a cardiac event in patients with aorto-iliac occlusive disease. While not indicated in patients lacking clinical evidence of heart disease, ERNA can refine the assessment of cardiac risk, particularly in patients with previous myocardial infarction and define a high risk group in whom aortic reconstruction should be avoided except for the most compelling of indications.

Aorta, Abdominal↗

The plant mitochondrial F1-ATPase. The identity of the delta' (20 kDa) subunit.

The N-terminal amino acid sequence of the 20 kDa (delta') subunit of the turnip (Brassica napus L.) mitochondrial F1-ATPase has been determined. Comparison of the sequence obtained with those of the epsilon subunits of chloroplast CF1, E. coli F1 and the delta subunit of bovine F1 shows that the turnip delta' subunit is another member of this family of homologous proteins. The delta' subunit of sweet potato F1-ATPase [(1989) J. Biol. Chem. 264, 3183-3186] is very similar to the turnip sequence and thus can also be considered to belong to this family.

Amino Acid Sequence↗

Three different schedules of low-density lipoprotein apheresis compared with plasmapheresis in patients with homozygous familial hypercholesterolemia.

PURPOSE: To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low-density lipoprotein apheresis compared with plasmapheresis. PATIENTS AND METHODS: Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran-sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study. RESULTS: On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients. CONCLUSION: Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol.

Adolescent↗

Plant mitochondrial F1-ATPase. The presence of oligomycin-sensitivity-conferring protein (OSCP).

Purified pea (Pisum sativum) cotyledon F1-ATPase contains six subunits rather than the five usually reported for F1-ATPases. The additional 26.5 kDa (delta) subunit is shown by immunoblotting and N-terminal amino acid sequencing to be similar to bovine oligomycin-sensitivity-conferring protein (OSCP). It is concluded that the delta subunit of plant mitochondrial F1-ATPase is the plant OSCP. This OSCP subunit occurs in all mono- and di-cotyledonous species of plants tested (maize, oats, peas, potatoes, sweet potatoes and turnips).

Adenosine Triphosphatases↗

Reconstitution of Oxidative Phosphorylation and of Oligomycin-Sensitive ATPase by Five- and Six-Subunit Forms of Pea Mitochondrial F(1)-ATPase.

Five- and six-subunit forms of F(1)-ATPase were purified from pea (Pisum sativum L. cv Homesteader) cotyledon submitochondrial particles. Apart from the usual complement of five subunits, the six-subunit enzyme contained an additional 26,500-dalton protein. Both forms of the F(1)-ATPase were used to reconstitute oxidative phosphorylation in F(1)-depleted (ASU) as well as in F(1) and oligomycin-sensitivity conferring protein (OSCP)-depleted (ASUA) bovine mitochondrial membranes. The six-subunit enzyme was considerably more efficient in reconstituting the ATP synthesis than the five-subunit enzyme. Both forms of the enzyme were also able to reconstitute the ATPase activity in ASU- as well as in ASUA-particles. There were substantial differences, however, in the oligomycin sensitivity of the ATPase bound to the ASUA-particles: 20 and 60% inhibition by oligomycin was obtained in the case of the five-subunit and six-subunit enzyme, respectively. We conclude, that the 26,500-dalton protein present in the six-subunit F(1)-ATPase is responsible for the increase in oligomycin sensitivity of the bound enzyme and functions, therefore, as the plant OSCP.

Journal Article↗

Surgery in patients with heart transplants. Anaesthetic and operative considerations.

As cardiac transplantation becomes more common, so an increasing number of patients with functioning heart transplants may require surgery for related or unrelated non-cardiac conditions. Fifteen patients who have undergone a total of 39 operations (excluding retransplantation) since heart transplantation were reviewed; 36% were for infective conditions and 23% each for gastro-intestinal and vascular lesions. There was one postoperative death in a patient undergoing leg amputation for overwhelming Clostridium welchii infection. There were no major non-fatal complications. The conditions for which operation may be necessary, the specific problems of anaesthesia and surgery in such patients, and the prophylactic measures which may be undertaken to ensure an uncomplicated clinical course are discussed. A clear understanding of the physiology and pharmacology of the denervated heart is essential if these patients are successfully to undergo major operations requiring general anaesthesia.

Adolescent↗

Coupling factor activity of the purified pea mitochondrial F1-ATPase.

The pea cotyledon mitochondrial F1-ATPase was released from the submitochondrial particles by a washing procedure using 300 mM sucrose/2 mM Tricine (pH 7.4). The enzyme was purified by DEAE-cellulose chromatography and subsequent sucrose density gradient centrifugation. Using polyacrylamide gel electrophoresis under non-denaturing conditions, the purified protein exhibited a single sharp band with slightly lower mobility than the purified pea chloroplast CF1-ATPase. The molecular weights of pea mitochondrial F1-ATPase and pea chloroplast CF1-ATPase were found to be 409 000 and 378 000, respectively. The purified pea mitochondrial F1-ATPase dissociated into six types of subunits on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Most of these subunits had mobilities different from the subunits of the pea chloroplast CF1-ATPase. The purified mitochondrial F1-ATPase exhibited coupling factor activity. In spite of the observed differences between CF1 and F1, the mitochondrial enzyme stimulated ATP formation in CF1-depleted pea chloroplast membranes. Thus, the mitochondrial F1 was able to substitute functionally for the chloroplast CF1 in reconstituting photophosphorylation.

Adenosine Triphosphate↗

Mucocutaneous lymph node syndrome in a young adult. A case report.

The mucocutaneous lymph node syndrome, first noted in 1961 by Kawasaki in Japan, is an acute, febrile mucocutaneous condition accompanied by cervical lymphadenopathy, which affects infants and young children. More recently it has been recognized in other countries, but not before 1979 in South Africa.

Adolescent↗

Studies on photophosphorylation utilizing methylene diphosphonate analogs of ADP and ATP.

Spinach chloroplasts were able to photophosphorylate the ADP analog alpha,beta-methylene adenosine 5'-diphosphate (AOPCP). Phosphorylation of AOPCP was catalyzed by chloroplasts that were washed or dialyzed to remove free endogenous nucleotides. In the presence of glucose, hexokinase, AOPCP and 32Pi, the 32P label was incorporated into alpha,beta-methylene adenosine 5'-triphosphate (AOPCPOP). In contrast to photophosphorylation of AOPCP, the ATP analog AOPCPOP was a poor substrate for the ATP-Pi exchange reaction and its hydrolysis was neither stimulated by light and dithiothreitol nor inhibited by Dio-9. Photophosphorylation of AOPCP was inhibited by the alpha,beta- and beta,gamma-substituted methylene analogs of ATP, while phosphorylation of ADP was unaffected by them. The ATP-Pi exchange was also unaffected by both ATP analogs, while the weak AOPCPOP-Pi exchange was inhibited by the beta,gamma-methylene analog of ATP. Direct interaction of methylene analogs with the chloroplast coupling factor ATPase was indicated by the enzymatic hydrolysis of AOPCPOP on polyacrylamide gels.

Adenosine Diphosphate↗