Search PubMed⌕ Search

Biomedical subjects

M Busch

Publications and source records attributed to M Busch.

At least 145 records · Page 8Linked to original sources
PubMed1984

A major anti-myoglobin idiotype. Influence of H-2-linked Ir genes on idiotype expression.

A rabbit antiidiotypic antiserum raised against an A.SW IgG1K monoclonal anti-sperm whale myoglobin (Mb) antibody, HAL19, and extensively absorbed with normal mouse immunoglobulin and MOPC 21 (IgG1K), was found to detect a common or major anti-Mb idiotype expressed by some but not all anti-Mb monoclonal antibodies, regardless of immunoglobulin G (IgG) subclass, and by 40-50% of the anti-Mb antibodies in immune serum from five high responder strains of mice representing five different Igh allotypes. It did not inhibit antibodies to three unrelated protein antigens. The fraction of antibodies expressing this idiotype, denoted IdHAL19, was regulated by H-2-linked genes that correlated exactly in four independent haplotypes and an F1 with the known Mb immune response (Ir) genes and may be identical to these. Whereas less than 50% of antibodies from high responder mice were inhibitable by anti-IdHAL19, greater than 80% of antibodies from low responder mice, tested at comparable final antibody concentration, were inhibitable. This result was true for both low responder haplotypes, H-2b (B10) and H-2k (B10.BR). The idiotype was found to be present on antibodies that bound to native Mb but not fragments 1-55 or 132-153 of Mb or a denatured form, S-methyl Mb. This specificity for native Mb paralleled that of the monoclonal idiotype HAL19 itself. Therefore, the production of antibodies specific for native in contrast to denatured Mb was studied in H-2-congenic high and low responder strains. Strikingly, low responders produced antibodies that reacted almost exclusively with the native conformation, whereas a larger proportion of antibodies from high responder mice also reacted with the denatured form, S-methyl Mb. Bypassing of the Ir gene defect by immunization with Mb attached to a carrier, F gamma G, resulted in low responder antisera resembling higher responder sera in both idiotype expression and conformational specificity. The simplest explanation of these results is that H-2-linked Ir genes control antibody fine specificity, which is reflected in the idiotypes of the variable regions expressed. We suggest that low responder mice produce a more limited repertoire of antibodies consisting primarily of IdHAL19-positive antibodies specific for the native conformation of Mb. High responder mice produce a greater diversity of antibodies to Mb, so that the IdHAL19-positive, conformation-specific population represents a smaller proportion of the total. Similarly, the use of carrier-specific helper T cells in low responder mice results in a greater diversity of antibodies, which dilutes out the IdHAL19 subset.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Bovine regional brain blood flow during sojourn at a simulated altitude of 3500 m.

Regional distribution of brain blood flow (15 micron diameter radionuclide labelled microspheres injected into the left atrium) was studied in 6 unanesthetized calves during the 7th-8th weeks of exposure to a simulated altitude of 3500 m (PB = 500 mm Hg). Measurements were made during chronic hypoxemia (PaO2 = 48 +/- 1 mm Hg) and acute normoxemia (PaO2 = 91 +/- 1 mm Hg). Five calves, born and raised at sea level, were also studied in a similar manner during normoxemia (PaO2 = 86 +/- 2 mm Hg) and at 12 and 22 min of acute hypoxemia (PaO2 = 49 +/- 1 mm Hg) to serve as controls. Acute hypoxemia in sea level calves resulted in a marked uniform increase in blood flow to all regions of the brain and the brain O2 delivery remained similar to its normoxemic value. By comparison, however, blood flow in all regions of the brain in calves sojourning at 3500 m remained unchanged between hypoxemia and normoxemia. In these calves brain O2 delivery decreased during hypoxemia. These experiments demonstrated that blood flow in the bovine brain-stem and cerebellum behaved in the same manner as in the cerebrum during exposure to acute as well as chronic hypoxia. It is suggested that there are likely to be differences in adaptation of bovine cerebral circulation to acute vs chronic hypoxia.

Acute Disease↗
PubMed1984

Interstitial high dose-rate brachytherapy: principle, practice and first clinical experiences with a new remote-controlled afterloading system using Ir-192.

In our newly developed remote-controlled afterloading system, a single Ir-192-source is moved within hollow stainless steel needles, which are arranged strictly parallel and are uniformly spaced. Dose calculation is performed by an especially designed computer program using geometrical bodies (ellipsoid, cylinder and plane parallel body) as idealized tumor shapes. Reference points for calculation are defined on the surface of the chosen geometrical body. Theoretical base, principles of dosage, handling and first clinical experiences after treatment of 28 patients are presented.

Brachytherapy↗
PubMed1984

Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma.

Previous studies had revealed that DNA with partial similarity to the myc oncogene (N-myc) is frequently amplified in human neuroblastoma cell lines and neuroblastoma tumors. We show here for one patient that N-myc amplification is confined to the neuroblastoma tumor and is not present in normal tissue. N-myc mRNA approximately equal to 4.0 kilobases in size is detectable in neuroblastoma cell lines and tumors and in a retinoblastoma cell line. By contrast, appreciable amounts of this RNA were not present in a number of cell lines derived from other human tumors and in fibroblasts from a normal individual and from a neuroblastoma patient. Low levels of N-myc RNA were found in human and murine neuroblastoma cell lines lacking amplification of this gene, up to 80-fold greater levels in all cell lines carrying amplified N-myc. In situ hybridization to sections of neuroblastoma tumors revealed high expression of N-myc predominantly in undifferentiated neuroblasts. We hypothesize that amplification and consequent elevated expression of N-myc may be related to malignant progression.

Cell Line↗
PubMed1984

Antigen conformation determines processing requirements for T-cell activation.

We studied the difference in requirements for processing and presentation to a single T-cell clone of four different forms of the same epitope of sperm whale myoglobin--namely, on the native protein, on two conformationally altered forms of the protein, or as a 22-residue antigenic peptide fragment. The T-cell clone was I-Ed-restricted and specific for an epitope on the CNBr fragment 132-153 involving Lys-140. As inhibitors of macrophage processing of antigen, we used several agents that inhibit lysosomal function: the weak bases chloroquine and NH4Cl, the cationic ionophore monensin, and the competitive protease inhibitor leupeptin. When these agents were used to inhibit processing of antigen by presenting cells and then washed out before T cells were added to culture, they inhibited the presentation of native antigen but not of fragment 132-153. To our surprise, the intact but denatured form, S-methylmyoglobin, behaved like the fragment not like the native protein. Apomyoglobin was intermediate in susceptibility to inhibition. Thus, native myoglobin requires a processing step that appears to involve lysosomal proteolysis, which is not required by fragment 132-153 or the denatured unfolded forms. For an antigen the size of myoglobin (Mr 17,800), it appears that unfolding of the native conformation, rather than further reduction in size, is the critical parameter determining the need for processing. Since a major difference between native myoglobin and the other forms is the greater accessibility in the latter of sites, such as hydrophobic residues, buried in the native protein, we propose that processing may be necessary to expose these sites, perhaps for interaction with the cell membrane or the Ia of the antigen-presenting cell.

Ammonium Chloride↗
PubMed1984

[Optimized application of afterloading in epipharyngeal tumors].

In case of carcinoma of the epipharynx , the superfractionated and computer-optimized intracavitary radiotherapy with a highly active radiation source moved by steps of 5 mm is an easily tolerated local measure to boost teletherapy. This field of irradiation and application techniques, of dosage and optimization represents an improvement of methods well-known since some thirty years.

Brachytherapy↗
PubMed1984

[Interstitial afterloading therapy. Principles, practical application and first clinical experiences].

The principle and practical application of an afterloading system for interstitial therapy is reported. The system works with a single Ir-192 source with high dose rate and achieves the optimum dose distribution by gradual displacement and variable position times. A specially developed computer program serves to calculate the stopping times of the source. The implantation is performed with hollow needles made of refined steel, which are held in parallel position by means of jigs fixed to the patient. 28 patients with 36 tumors have been treated. The dose was determined according to the experiences in gynecologic afterloading therapy with high dose rate sources and dosage prescriptions in teletherapy. The authors present the therapeutic results of this pilot study, discuss the new system and show practicable possibilities for further development.

Brachytherapy↗
PubMed1981

[Determination of the galactokinase activity of erythrocytes of swine of various ages].

In view of the fact that the ability of pig erythrocytes to use galactose will decrease with growing age, the galactokinase activity in pig erythrocytes of different age was determined by means of a spectrophotometrical method. A total of 5 pig fetuses (112th day of gestation) and 45 piglets at the age of 8 hours to 35 days belonging to different broods as well as 10 pigs for slaughter whose blood was collected after slaughtering out were included in the examination. In 5 piglets of one brood a progress examination was made during the suckling period. In the erythrocytes of all examined animals of different age groups the activity of the enzyme could be identified. There are great differences in the galactokinase activity of haemolysates of pig erythrocytes in different broods irrespective of their age. Therefore, an enzyme age dependence can only be recognized as a tendency from the comparison of the enzyme activities in erythrocytes of animals taken from different broods. In the erythrocyte haemolysate of 5 piglets of one brood the age dependence on galactokinase activity during the suckling period was determined in such a way that newborn piglets show a 30% higher enzyme activity than piglets at an age of 35 days. The enzyme activity in them, however, is still 1.6 times higher than in pigs for slaughtering. Thus, it may be concluded tht a postnatal decrease of galactokinase activity will occur in pig erythrocytes similarly to human erythrocytes. However, it is not responsible for a decrease of galactose utilization because no direct relations exist between both procedures. Parallel to glucose the decrease of galactose membrane permeability is assumed to play the decisive role here.

Age Factors↗
PubMed1979

[Three dimensional optimization method for the interstitional afterloading therapy (author's transl)].

The authors present a new method for the interstitial therapy working with an Ir-192 source which is displaced step by step. After having been fed with the tumor parameters, the computer calculates for every stopping point the duration of stay of the source which provides a threedimensional optimization. The practical application of the method is discussed and the optimization procedure is compared with other similar methods.

Computers↗