Biomedical subjects

B Fritz

Publications and source records attributed to B Fritz.

35 records · Page 2Linked to original sources

PubMed1998

Pigmentary mosaicism in hypomelanosis of Ito. Further evidence for functional disomy of Xp.

We report on a female with mental and motor retardation, facial dysmorphism, abnormal pigmentation reminiscent to hypomelanosis of Ito (HI), and karyotypic mosaicism involving a small supernumerary marker chromosome. The marker chromosome was defined by fluorescence in situ hybridisation (FISH) as a ring X chromosome with breakpoints in the juxtacentromeric region. FISH analysis showed that the ring does not include the XIST locus at the X-inactivation centre and, therefore, may not be subject to X inactivation. X-inactivation studies with the HUMARA (human androgen receptor) and FMR1 assay showed a skewed X-inactivation pattern (85:15) with preferential inactivation of the paternal X chromosome. These results are discussed with respect to the role of functional disomy of Xp in the pathogenesis of HI.

Child, Preschool↗

PubMed1997

Microdeletion 22q11 in complex cardiovascular malformations.

Besides DiGeorge, velocardiofacial and conotruncal anomaly face syndromes, some of the isolated congenital heart diseases have also been associated with a chromosomal deletion in 22q11. These disease entities, which had originally been considered to have a different genetic background, are now included in the CATCH-22 microdeletion complex. CATCH 22 is an acronym for cardiac defect, abnormal facies, thymic hypoplasia or aplasia and T-cell deficiency, cleft palate, hypoparathyroidism, and hypocalcemia. In the present study, we focused on the complex cardiovascular defects (CCVD) and screened 40 patients for a microdeletion of 22q11 by fluorescence in situ hybridization using the D22S75 DNA probe and for associated CATCH features. The patients were from genetic counseling (n = 15) or fetopathology (n = 3) of the Clinical Genetics Department in Marburg and from the Pediatric Cardiology Department (n = 22) in Mainz. Monosomy 22q11 was detected in 9 cases (= 22.5%). Familial transmission with one mildly affected parent and one affected sib each was proven in two cases. The CCVDs comprised complex conotruncal defects such as tetralogy of Fallot, double outlet right ventricle, transposition of great arteries and truncus arteriosus communis, or anomalies of the derivatives of the branchial arch arteries in association with a ventricular septal defect, including one case of atresia of the ductus arteriosus with pulmonary artery aneurysm and resulting in fetal hydrops. All 13 patients with a deletion of 22q11 showed at least one additional CATCH symptom. Most consistently, facial dysmorphy was apparent (92%), while hypocalcemia, mostly at threshold values, was present in 62% and thymic hypoplasia including borderline low T-lymphocyte numbers was observed in 41%. None of the patients presented with a cleft palate. A high intrafamilial variability in expression was also evident with respect to the CCVD. Our findings indicate that seemingly isolated complex cardiovascular defects associated with a 22q11 microdeletion most probably do not represent a distinct subgroup within the CATCH-22 complex but are syndromal in nature with extracardiac features that are often overlooked.

Adolescent↗

PubMed1997

Effect of endogenous biotin on the applications of streptavidin and biotin in mice.

The use of streptavidin-conjugated antibody to pretarget tumors in animals and patients, prior to administration of radiolabeled biotin, has provided encouraging results, in part because of the high affinity of biotin for streptavidin and the rapid whole-body clearance of biotin. However, binding of endogenous biotin to streptavidin may interfere with the clinical potential of this approach. This report evaluates the effect of endogenous biotin on an antibody-streptavidin conjugate in a mouse tumor model. Tumored nude mice were depleted of endogenous biotin by sequential intraperitoneal injections of streptavidin. The assay of serum biotin levels indicated less than 0.5 ng of biotin per mL of serum in treated mice versus 4 ng per mL in untreated animals. Flow cytometric analysis was used on single-cell suspensions of tumor from animals receiving streptavidin-conjugated IgG to detect the presence of the antibody on the cell membrane (with fluoroisothiocyanate-conjugated goat anti-mouse antibody), and to detect biotin binding sites on streptavidin (with biotin-phycoerythrin). Both treated and untreated mice demonstrated the presence of antibody on tumor cells through 48 h postadministration, but only in treated animals were biotin binding sites observed. These results in the mouse model suggest that the small concentration of streptavidin delivered to a tumor via a specific antibody may be saturated with endogenous biotin and therefore not able to be targeted subsequently with radiolabeled biotin.

Animals↗

PubMed1993

Improved tumor localization with (strept)avidin and labeled biotin as a substitute for antibody.

Because of its short physical half life, the use of anti-tumor antibodies radiolabeled with 99mTc has necessitated early (i.e. 2-6 h post-administration) imaging. It is possible that at these early times localization of antibodies in certain tumors may be largely due to non-specific processes. If so, other proteins or agents may be preferred for early imaging of solid tumors. We have investigated tumor localization with labeled biotin administered subsequent to unlabeled and unconjugated streptavidin. Nude mice bearing anti-CEA tumors (LS174T) received 10 micrograms of 111In-labeled anti-CEA antibody (C110) or 111In-labeled streptavidin with sacrifice 5 h later. In an examination of pretargeting, other animals received 50 micrograms of unlabeled streptavidin followed 3 h later with 1 micrograms of 111In-labeled biotin (EB1) and sacrifice 2 h later. The biodistribution of labeled streptavidin was similar to that of labeled specific antibody except for lower blood and higher kidney levels. Tumor levels were also lower with labeled streptavidin but, because of still lower levels in liver and blood, the tumor/normal tissue ratios were improved. When unlabeled streptavidin was administered and followed by labeled biotin (pretargeting), tumor levels were further reduced modestly; however, normal tissue levels were greatly reduced such that the tumor/blood and tumor/liver ratios were 10.6 and 2.2 vs 1.5 and 0.5 for the specific antibody. Improvements were seen in all tissues sampled with the exception of kidney and muscle. A further control of labeled biotin alone (without the preinjection of streptavidin) showed minimal accumulations in all tissues with the exception of kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

A combined pseudoreplica-immunochemical technique for research and diagnostic virology.

Pseudoreplica and immunochemical techniques were combined in a single protocol for identification of virus in research and clinical specimens. Stock preparations of vesicular stomatitis virus (VSV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were used to develop the technique. Traditional pseudoreplicas of viral stock solutions were prepared but not negatively stained. The virus was then immunolabeled in two stages. Virus-specific polyclonal antisera were used in the first stage; colloidal gold conjugated antibodies were used as indicator antibody in the second stage. After immunolabeling, the grids were negatively stained. As a demonstration of the clinical usefulness of this approach, it was employed to antenatally identify human parvovirus B19 particles in ascites from a 22 week gestational fetus with nonimmune hydrops fetalis. The combined pseudoreplica-immunochemical approach offers several advantages over both the pseudoreplica and immunochemical methods when used in isolation. Advantages include relative purification of samples, concentration of virus, morphological preservation, and enhanced diagnostic specificity.

Cytomegalovirus↗

PubMed1992

Localization of infection using streptavidin and biotin: an alternative to nonspecific polyclonal immunoglobulin.

Since favorable images of infection are obtained with radio-labeled nonspecific IgG, streptavidin has been considered as an alternative protein in this investigation. The advantage of streptavidin is that once localized it may be targeted with radiolabeled biotin. Studies were conducted in a mouse model with an Escherichia coli infection in one thigh. Indium-111-labeled streptavidin showed equivalent localization to the infection as that obtained with 111In-labeled polyclonal nonspecific IgG, however blood levels with streptavidin were lower at all time points; consequently, target-to-blood ratios were improved. Pretargeting with unlabeled streptavidin followed 3 hr later with 111In-labeled biotin showed equivalent localization in the target and reduced activity in all organs sampled. As such, infected thigh-to-normal thigh ratios were improved 3-fold for pretargeting versus either labeled IgG or streptavidin. Improvements in infected thigh-to-liver and blood ratios were greater than 8-fold. Only in the case of kidneys was the ratio unimproved. In conclusion, we have shown that by preadministration of unlabeled streptavidin followed by labeled biotin, infectious lesions in a mouse model may be imaged earlier with lower background levels relative to the administration of labeled nonspecific IgG.

Animals↗

PubMed1991

New indium-111 labeled biotin derivatives for improved immunotargeting.

Investigations into the use of streptavidin-conjugated antibodies and labeled biotin to improve radioimmunotargeting have shown background levels drastically reduced over the conventional approach. Nevertheless, accumulation of 111In-biotin in normal tissue as well as streptavidin-independent accumulation in tumor, was observed. In this work, the effect of altering the biotin molecule to reduce this nonspecific uptake without decreasing specific localization has been investigated. Three EDTA and DTPA derivatives of biotin have been synthesized and investigated along with a commercial biotin derivative (DTPA-B2). The labeled biotin chelates were administered i.p. to normal mice implanted with avidin beads in one thigh. A wide variation in biodistribution was seen among the biotin derivatives. The most favorable results were obtained with biotinyl-hydrazino-EDTA (EDTA-B1), which showed the lowest accumulation in normal tissues but equivalent uptake in the target with respect to the other compounds. Averaged over 8 tissues sampled, the target-to-nontarget ratio was 140 vs 9 for EDTA-B1 vs DTPA-B2 (N = 6) at 24 h post administration. Similar observations have been made in culture with two tumor cell lines: positive accumulation of both DTPA-B2 and EDTA-B1 was measured in tumor cells independent of streptavidin-antibody conjugate, however in the case of the latter derivative, this accumulation was 3-5 fold lower. These studies show that modification of the biotin species can alter accumulation in normal tissues as well as the antibody-streptavidin independent accumulation in tumor tissue.

Animals↗

PubMed1989