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Biomedical subjects

T Franz

Publications and source records attributed to T Franz.

54 records · Page 3Linked to original sources
PubMed1991

Unusual cell specific expression of a major human cytomegalovirus immediate early gene promoter-lacZ hybrid gene in transgenic mouse embryos.

Transgenic mice carrying the human cytomegalovirus immediate early gene promoter driving the E. coli lacZ gene displayed an unusual cell specific expression of beta-galactosidase during development. LacZ expression was first detected in cells lining the apex of the neural fold of day 8.5 embryos. By day 10 of gestation, expression was prominent in the spinal ganglia, the ganglia of cranial nerves V, VII, VIII, IX, and X, in a line of cells marking the ventrolateral pathway adjacent to the dermamyotome, and in a column of differentiated cells in the entire ventrolateral neural tube posterior to the mesencephalon. Expression was also found in the myotomes. Neural tube explants from day 8.5 embryos cultured in vitro showed lacZ expression in cells migrating away from the explant. We conclude that the HCMV-IEP-lacZ transgene is expressed in a subpopulation of neural crest cells and its early derivatives.

Animals↗
PubMed1991

Immortalized fibroblastoid cells of osteopetrotic mutant mice (op/op) do not secrete CSF-1 and do not inhibit CSF-1 activity released by normal cells.

Osteopetrotic mutant mice (op/op) are deficient in osteoclasts and macrophages. In this report, the establishment of clonal permanent fibroblastoid cell lines from spleens of op/+ and op/op mice is described and conditioned medium obtained from these cell lines examined for release of growth factor that stimulates the proliferation and differentiation of macrophage precursor cells. It is shown that conditioned medium of op/+ fibroblastoid cells contains CSF-1 activity, whereas conditioned medium of op/op fibroblastoid cells does not. Conditioned medium of op/op cell lines does not inhibit colony-stimulating factor 1 (CSF-1) activity in conditioned medium of op/+ cells. Hybrids between op/op and op/+ fibroblastoid cells release CSF-1 activity in amounts similar to op/+ cell lines alone. These results confirm that op/op mice do not produce any CSF-1 activity. The data further suggest that predicted truncated proteins expressed from the mutated CSF-1 gene in op/op mice are functionally not relevant and that there is no evidence for trans-acting factors in op/op that might inhibit CSF-1 expression.

Animals↗
PubMed1990

Defective ensheathment of motoric nerves in the Splotch mutant mouse.

Mouse embryos, homozygous for mutations at the Splotch locus, are afflicted with spina bifida and disturbances of neural-crest-derived tissues, e.g. spinal ganglia and pigment cells. The development of Schwann cells is affected in homozygotes to a varying degree along the rostrocaudal axis. In cervical motoric roots, nerves are associated with apparently normal Schwann cells. At the thoracic level, nerve-associated cells become more scarce and resemble the surrounding mesenchymal cells. They are not enveloped by a basal lamina and frequently show wide gaps between neighbouring cells. Lumbar motoric roots are mostly devoid of any associated cells. The Splotch mutant embryo is proposed to be a new animal model for the study of peripheral nerve ensheathment. The implications for Schwann-cell-mediated axon guidance are discussed.

Animals↗
PubMed1990

Hydralazine induced lupus and Sweet's syndrome. Report and review of the literature.

This is the second case report of hydralazine induced Sweet's syndrome and lupus erythematosus. Our patient had the characteristic rash of Sweet's syndrome, confirmed histopathologically, as well as laboratory features consistent with drug induced lupus, including positive serum antinuclear and antihistone antibody tests. The association between these 2 clinical entities is discussed and a review of the literature is presented.

Acute Disease↗
PubMed1989

Persistent truncus arteriosus in the Splotch mutant mouse.

The Splotch mutant mouse shows defects in neural crest-derived cell populations. The septation of the truncus arteriosus and the development of the aortic arch-derived blood vessels was studied in homozygotes of the Splotch mutant allele Sp1H. It is shown that in homozygous mutant embryos, the septation of the truncus arteriosus does not proceed normally, resulting in persistent truncus arteriosus. The ostium of the persistent truncus arteriosus opens to the right ventricle. Frequently, variations of the aortic arch-derived blood vessels are observed. The development of the thymus, the parathyroid and the ultimobranchial bodies are also variably affected in mutants. These results provide indirect evidence, that cells contributing to the aortic arches and the septum of the truncus arteriosus in mice are derived from the neural crest. The Splotch mutant mouse is proposed to be an animal model for persistent truncus arteriosus. The implications of the vascular malformations for the midgestational death of this mutant are discussed.

Animals↗
PubMed1987

Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans.

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.

Animals↗
PubMed1986

Retroviral mutants efficiently expressed in embryonal carcinoma cells.

The myeloproliferative sarcoma virus (MPSV) is a unique member of the Moloney murine sarcoma virus family. Due to mutations in the U3 region of its long terminal repeat, MPSV has an expanded host range that includes cells of the hematopoietic compartment. Using a MPSV recombinant containing the gene for neomycin-resistance (NeoR-MPSV), we demonstrate that the host range of MPSV also includes undifferentiated F9 embryonal carcinoma cells. Transfer of G418-resistance with NeoR-MPSV to F9 cells is almost as efficient as G418-resistance transfer to fibroblasts, in contrast to G418-resistance transfer to PCC4 embryonal carcinoma cells, which is at least 3 orders of magnitude lower. To isolate NeoR-MPSV mutants that are efficiently expressed in PCC4 cells, G418-resistant PCC4 cell lines were induced to differentiate, and the provirus was rescued by superinfection with murine leukemia virus. Viral isolates (PCMV-5 and -6; PCMV = PCC4 cell-passaged NeoR-MPSV) were obtained and assayed for expression in embryonal carcinoma cells. The efficiency of NeoR transfer was equally as high in both F9 and PCC4 as in fibroblasts. mos oncogene expression was unaltered as judged by transformation capability. No gross alteration in the coding region and in the long terminal repeat was detectable by restriction enzyme analysis. NeoR-MPSV and its mutants PCMV-5 and -6 can thus be utilized as vectors for the efficient transduction of genes into embryonic cells.

Animals↗
PubMed1986

Viral transfer, transcription, and rescue of a selectable myeloproliferative sarcoma virus in embryonal cell lines: expression of the mos oncogene.

A derivative of the myeloproliferative sarcoma virus (Neor-MPSV) carrying the mos oncogene and dominant selection marker for neomycin resistance (Neor) was introduced into embryonal carcinoma and embryo-derived cell lines by transfection and infection using pseudotypes with Friend helper virus (Friend murine leukemia virus [F-MuLV]). Cells resistant to G418 (a neomycin analog) were cloned and expanded. Transductants retained an undifferentiated phenotype as judged by morphology, tumorigenicity, and cell-surface antigen analyses. Nucleic acid analysis of infectants revealed both Neor-MPSV and F-MuLV proviruses, although no virus was released. G418-resistant transductants remained nonpermissive for the expression of other proviruses and for subsequent superinfection. Northern analysis showed expression of full-length Neor-MPSV, as well as mos-specific subgenomic RNA. mos sequences were deleted from Neor-MPSV (Neor mos-1), and pseudotypes were used to infect embryonal carcinoma cells. No morphological differences were observed in either mos+ or mos- transductants as compared with parental cell lines. However, mos+ transductants showed an enhanced anchorage-independent growth compared with that of mos- transductants in agar cloning. PCC4 transductants were induced to differentiate with retinoic acid and superinfected with F-MuLV. Infection with viral supernatant in fibroblasts and in mice confirmed the rescue of biologically active Neor-MPSV.

Animals↗
PubMed1985

Etretinate kinetics during chronic dosing in severe psoriasis.

Fourteen patients with various forms of psoriasis participated in a clinical study to characterize the pharmacokinetics of etretinate before, during, and after 6 months of therapy. A single 100 mg dose was initially given, followed 2 days later by approximately 170 days of multiple dosing with 25 mg one, two, three, or four times a day depending on the subject's response and tolerance. Blood samples were drawn for 48 hours after the initial dose, for 12 hours after dosing at monthly intervals, and for up to 8 months after administration of the last dose. Blood concentrations of etretinate were determined by a specific reverse-phase gradient elution HPLC assay. Blood concentrations after the first dose declined with an apparent t1/2 of approximately 7 hours, whereas those after the last dose declined with an apparent t1/2 of approximately 120 days. The lengthening of the t1/2 during chronic dosing appears to result from the cumulation of blood concentrations in the measurable range rather than from time-related alterations in drug kinetics. This is substantiated by the fact that etretinate blood concentration--time data for the entire course of therapy were fit by a nonlinear least-squares computer program designed to accommodate changes in the dosing regimen. A single polyexponential kinetic equation described the entire 6-month course of therapy as well as the 8-month washout without the need to invoke nonlinear kinetics. Although single-dose kinetic data for etretinate may not be good predictors of steady-state blood concentrations, etretinate appears to follow linear kinetics during these dosing regimens.

Absorption↗
PubMed1984

Molecular cloning of Rauscher spleen focus-forming virus and biological properties of the cloned virus.

Rauscher virus (RV) induces acute erythroleukaemia and a myeloproliferative disease in adult mice. It consists of a replication-competent murine leukaemia virus (R-MuLV) which acts as a helper virus and a defective transforming component which causes spleen focus formation, Rauscher spleen focus-forming virus (R-SFFV). The integrated proviral DNA of R-SFFV was cloned molecularly. The cloned R-SFFV was compared to that of other viral components which are associated with RV-induced disease and also the cloned Friend SFFV (F-SFFV) and the myeloproliferative sarcoma virus (MPSV), both of which expand the erythroid (F-SFFV, MPSV) and myeloid (MPSV) compartment on infection of adult mice. The genome of R-SFFV differs, if analysed by restriction enzymes, from R-MuLV in the 3' end of the genome between the env gene and the long terminal repeat. The difference is most likely an alteration in the 3' part of the gp70-coding region of the env gene. Comparison with Rauscher mink cell focus-inducing virus (R-MCF) suggests that R-SFFV is derived from R-MCF by substitution of the 3' half of the env gene with a sequence of unknown origin. The molecularly cloned R-SFFV pseudotyped with Friend MuLV induces an increase in late erythroid precursor cells which still require erythropoietin for maturation. Host range studies of the molecularly cloned R-SFFV prove that the Fv-2r locus is required but not sufficient to restrict RV-induced haemopoiesis in adult mice, thus suggesting that R-SFFV has a different target cell range than F-SFFV and is similar to MPSV.

Animals↗
PubMed1981

Central nervous system myelin proteins and glycoproteins in vertebrates: a phylogenetic study.

CNS myelin was isolated by a conventional method from a wide range of vertebrate classes and analyzed by SDS-PAGE for proteins (Coomassie blue) and glycoproteins (concanavalin A (Con-A)-peroxidase). Mammalian, avian and reptilian myelin shared similar protein patterns (basic protein, BP; intermediate protein, DM-20; proteolipid protein, PLP; Wolfgram protein, W). Amphibians lacked DM-20 but were characterized by specific activities of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) higher than those of the other classes examined. The Con A-binding profiles were similar in the high molecular weight (HMW) regions of the classes listed above, while the typical myelin proteins in the low molecular weight (LMW) regions were devoid of Con A-binding properties. In teleost myelin a putative BP band ran well ahead of rat small basic protein (SBP), whereas the region corresponding to rat PLP was covered by several closely spaced bands, most of which bound Con A. In elasmobranch myelin, apart from bands corresponding to BP, Con A-binding glycoproteins were detected migrating in the region of rat DM-20 and PLP as well as with mammalian PNS P0 protein. Cyclostomates yielded only very small amounts of material in the myelin preparation and displayed undifferentiated Coomassie blue- and Con A-binding in the HMW region, while typical LMW myelin proteins were absent. These results demonstrate that CNS myelin from bony and cartilaginous fishes is characterized by containing several major Con A-binding proteins of low molecular weight. This is in striking contrast to myelin from phylogenetically higher classes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMedDate not supplied

Transformation of mononuclear phagocytes in vivo and malignant histiocytosis caused by a novel murine spleen focus-forming virus.

The study of retrovirus-induced leukaemias in mice is a powerful tool for the elucidation of the normal regulation of the haematopoietic system. The acute murine spleen focus-forming viruses (SFFV) can be classified according to the haematopoietic lineage on which they exert their effects in the adult mouse. Here we report a new SFFV isolate, the AF-1 virus, with the novel ability to transform cells of the mononuclear phagocyte lineage. The virus was isolated from sarcomas that were induced on passage of a cloned Friend helper virus (F-MuLV, 643/22F) in newborn BALB/c mice. We have cloned the transforming defective subunit of the AF-1 viral complex in NRK cells and isolated several subclones. Analysis of the proviral genome in two non-producer cell clones reveals that AF-1 virus contains Harvey v-ras-specific sequences (Fig. 1). Thus, AF-1 virus is closely related to Harvey murine sarcoma virus (Ha-MSV), and is, at present, the only tool by which permanent cell lines can be obtained from mononuclear phagocytes in the mouse.

Animals↗
PubMedDate not supplied

Effects of a decision support system on the diagnostic accuracy of users: a preliminary report.

OBJECTIVES: To assess the effects of incomplete data upon the output of a computerized diagnostic decision support system (DSS), to assess the effects of using the system upon the diagnostic opinions of users, and to explore if these effects vary as a function of clinical experience. DESIGN: Experimental pilot study. Four clusters of nine cases each were constructed and equated for case difficulty. Definitive findings were omitted from the case abstracts. Subjects were randomly assigned to one of four clusters and were trained on the DSS prior to use. SUBJECTS: The study involved 16 physicians at three levels of clinical experience (six general internists, four residents in internal medicine, and six fourth-year medical students), from three academic medical centers. PROCEDURE: Each subject worked up nine cases, first without and then with ILIAD consultation. They were asked to offer up to six potential diagnoses and to list up to three steps that should be the next items in the diagnostic workup. Effects of DSS consultation were measured by changes in the position of the correct diagnosis in the lists of differential diagnoses, pre- and post-consultation. RESULTS: The DSS lists of diagnostic possibilities contained the correct diagnosis in 38% of cases, about midway between the levels of accuracy of residents and attending general internists. In over 70% of cases, the DSS output had no effect on the position of the correct diagnosis in the subjects' lists. The system's diagnostic accuracy was unaffected by the clinical experience of the users.

Decision Making↗
PubMedDate not supplied

Decision making of clinical teams: communication patterns and diagnostic error.

This study examined the discussion of information among mixed-status clinical teams while constructing differential diagnoses. Twenty-four ad hoc teams, each consisting of a resident, an intern, and a third-year medical student, were given two hypothetical patient cases to discuss and diagnose. Prior to discussion, team members individually viewed different versions of a videotaped interview with a "patient" (trained actor). Each videotape contained some information that was present in all three versions (shared information) and some that was present in only that version (unique information). In addition, half of the time, the cases were constructed so that the unique information that appeared in only one tape was crucial for a correct diagnosis (a "hidden profile" condition). After viewing the videotapes, team members met to discuss the case and develop a differential diagnosis. Discussions were videotaped and analyzed. Overall, shared information was mentioned more often than unique information (p < 0.0001). Furthermore, teams offered incorrect diagnoses significantly more often for hidden-profile cases than for control cases (p < 0.01). The teams' overreliance on previously shared information (inability to appropriately utilize unique information) was detrimental when a correct diagnosis demanded the inclusion of such information. Clinical discussions that require the consideration of uniquely held information may be susceptible to error.

Adult↗