PubMed Health⌕ Search

Biomedical subjects

F Zimmermann

Publications and source records attributed to F Zimmermann.

At least 19 recordsLinked to original sources
PubMed1992

Selective generation of antigen-specific human hybridomas optimized for large scale growth in serum-free medium.

The direct propagation of newly formed human hybridomas in serum-free medium selects for hybrids with a metabolism best suited to growth in this environment. Under optimal culture conditions, this procedure results in the generation of antigen-specific human hybridomas comparable in frequency, stability, and antibody secretion rate to that obtained with murine hybridomas. After a transient phase of a few days in the appropriate selection medium supplemented with 1% serum, hybridomas grow in serum-free medium in stationary cultures with a cell doubling time of 15-25 h and an antibody production rate averaging 12 micrograms/10(6) cells/day. Clones propagated in bioreactors exhibited a cell doubling time of 29-35 h and an antibody secretion rate of 10-21 micrograms/10(6) cells/day.

Antibodies, Monoclonal↗
PubMed1992

Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure. We report here the development of transgenic rats carrying the human angiotensinogen TGR-(hAOGEN) and human renin TGR(hREN) genes. The plasma levels and tissue distribution of the transcription and translation products from both genes are described. A unique species specificity of the enzyme kinetics was observed. The human RAS components in the transgenic rats did not interact with the endogenous rat RAS in vivo. Instead, infusions of exogenous human RAS components specifically interacted with human transgene translation products. Thus, infusion of human renin in TGR(hAOGEN) led to an increase of angiotensin II and an elevation of blood pressure, which could not be antagonized by the human-specific renin enzyme inhibitor Ro 42-5892. Rat renin also elevated blood pressure and angiotensin II in TGR(hAOGEN); however, this effect was not antagonized by the human renin inhibitor. Compared to mice, rats offer the advantage of chronic instrumentation and repetitive, sophisticated, hemodynamic, and endocrinological investigations. Thus, transgenic rat models with human-specific enzyme kinetics permit primate-specific analyses in non-primate in vivo and in vitro experimental systems.

Angiotensin II↗
PubMed1992

High blood pressure in transgenic mice carrying the rat angiotensinogen gene.

Transgenic mice were generated by injecting the entire rat angiotensinogen gene into the germline of NMRI mice. The resulting transgenic animals were characterized with respect to hemodynamics, parameters of the renin angiotension system, and expression of the transgene. The transgenic line TGM(rAOGEN)123 developed hypertension with a mean arterial blood pressure of 158 mmHg in males and 132 mmHg in females. In contrast, the transgenic line TGM(rAOGEN)92 was not hypertensive. Rat angiotensinogen was detectable only in plasma of animals of line 123. Total plasma angiotensinogen and plasma angiotensin II concentrations were about three times as high as those of negative control mice. In TGM(rAOGEN)123 the transgene was highly expressed in liver and brain. Transcripts were also detected in heart, kidney and testis. In TGM(rAOGEN)92 the brain was the main expressing organ. In situ hybridization revealed an mRNA distribution in the brain of TGM(rAOGEN)123 similar to the one in rat. In TGM(rAOGEN)92 the expression pattern in the brain was aberrant. These data indicate that overexpression of the angiotensinogen gene in liver and brain leads to the development of hypertension in transgenic mice. The TGM(rAOGEN)123 constitutes a high angiotensin II type of hypertension and may provide a new experimental animal model to study the kinetics and function of the renin angiotensin system.

Angiotensinogen↗
PubMed1991

Candidiasis visualised by proteinase-directed immunofluorescence.

The secretory aspartic proteinases of Candida albicans and C. tropicalis are potential factors for virulence produced during infection. By indirect immunofluorescence, we have demonstrated proteinase antigen on elements of both species in deparaffinized tissue sections derived from clinical cases of mucosal and deep-seated candidiasis. Occasionally, we observed a halo of fluorescence in the close vicinity of candidal cells, which may reflect secretion of the enzyme. In kidneys, a ring of amorphous fluorescent material surrounding candidal colonies may illustrate alkaline denaturation of secreted enzyme within a pH gradient, which is generated by the fungus. Our findings support the view that candidal proteinase may be a diagnostically relevant antigen.

Adult↗
PubMed1991

Markers for HIV-disease progression in untreated patients and patients receiving AZT: evaluation of viral activity, AZT resistance, serum cholesterol, beta 2-microglobulin, CD4+ cell counts, and HIV antigen.

In order to find parameters which allow the assessment of the clinical state of HIV patients with or without antiviral therapy, viral cultures on lymphocytes and monocytes/macrophages, CD4-cell counts, HIV antigen, beta 2-microglobulin and serum cholesterol were evaluated for their predictive value. As had been shown previously for lymphocytes, the efficiency of viral isolation on macrophages also depends on the disease stage (CDC) of the patients and thus has a high predictive value. A multivariant discriminant analysis showed that the combination of beta 2-microglobulin, viral antigen, CD4+ cell count and HDL cholesterol predicted the outcome of viral cultures with 80% accuracy. While viral antigen, CD4+ cell counts and beta 2-microglobulin had been known, HDL cholesterol deserves further evaluation as prognostic parameter. The analysis of HIV derived from patients with AZT showed a 20-200-fold in vitro drug resistance after seven to 24 months of therapy. DNA sequence determination of such strains isolated from AZT patients over time showed only two of the amino acid exchanges described in the literature for resistant strains and an additional Val60-Ile transition after 32 months of therapy.

CD4-Positive T-Lymphocytes↗
PubMed1991

[Freud's interpretation of the manifest dream. Attempt at theoretical historical and biographical motives of ambivalent dream devaluation].

Freud's description of the manifest dream is characterized by an implicit appreciation and an explicit devaluation of dream images. The theoretical motives for this ambivalent evaluation are, according to the author, already apparent in Freud's primacy of the written word evident in his preanalytical writings, which submit dream images to the standard of the written word and therefore devaluate them. According to the author the underlying biographic motive is an ambivalent internalization of the jewish law that prohibits the creation of idols which was conveyed to Freud by his father and the Philippson Bible.

Dreams↗
PubMed1991

Biochemical and genetical analysis of AZT-resistant HIV-mutants.

Sequential virus isolates from an HIV-1-infected woman treated orally with 3'-azido-3'-deoxythymidine (AZT) for over two years showed a 10-fold reduced sensitivity for AZT after 8 months and a 100-fold resistance after 24-32 months of drug therapy. These AZT-resistant mutants were totally sensitive in vitro to other reverse transcriptase (RT)-inhibitors like the AZT-analogue 3'-fluoro-3'-deoxythymidine (FdT) or the chemically less related nucleoside analogue 2',3'-dideoxycytosine (ddC). Even the benzodiazepin derivative 4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)-imidazo [4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO), a new drug specific for HIV-1 RT, was inhibitory for these virus strains. Moreover, compounds with different modes of action, e.g. polysulfated polyxylan, exhibited full antiviral activity as well. Thus, AZT resistance seems to be highly specific and should allow to develop further drugs to be used when AZT resistance has emerged. 5.9 kb fragments of the 5'-genomic halves of these sequential HIV-isolates were amplified by PCR and cloned. DNA sequence analysis revealed that the RT gene of the two highly AZT-resistant isolates carried two of the mutations described by Larder et al. [Science 246, (1989)], the Lys 70----Arg and the Thr 215----Tyr transitions. The isolate obtained after 32 months of AZT-therapy in addition contained a third mutation at position 67 (Asp----Asn); in contrast to Larder's report, no mutation was found at position 219. Thus, although these virus isolates showed at least a 100-fold reduced susceptibility for AZT in vitro, the four mutations postulated to be relevant for highly resistant strains were only partially confirmed.

Amino Acid Sequence↗
PubMed1989

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment.

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Androgen Antagonists↗
PubMed1988

The jungle and the aroma of meats: an ecological theme in Hindu medicine.

In classical Ayurvedic medicine, the jungle is the dry land of the Punjab and the Delhi Doab, an open vegetation of thorny shrubs. The polarity of dry lands and wet lands framed not only the whole Ayurvedic materia medica, but also the more general conception of a cosmic physiology governed by Agni (the sun) and Soma (the dispenser of the rain). Clearing the land and draining the body were two aspects of one and the same art of managing the transactions of all sorts of vital fluids, saps, juices, savors and humors. Medicine in the context of thought and practice associated with the jungle was, and still is in modern India, a kind of agriculture.

Animals↗
PubMed1988

[Pharmacological characterization of the new highly potent beta-adrenergic receptor blocker soquinolol].

The present pharmacological test results characterize soquinolol (5-[3-tertiary butylamino-2-hydroxypropoxy]-2-formyl-1,2,3,4- tetrahydroisoquinoline mucate, We 704, Sertum) as a highly potent non-subtype-selective beta-adrenergic receptor blocker, which is devoid of any intrinsic sympathomimetic activity. Its localanaesthetic activity (membrane stabilizing effect) is very weak. It also shows good enteral efficacy and long duration of action. In binding studies with heart (Ki beta 1 = 3.25 nmol/l) and lung membranes (Ki beta 2 = 0.85 nmol/l) its binding profile was found to be similar to that of propranolol. Soquinolol inhibits the isoprenaline-induced tachycardia (EC50% = 48 micrograms/l) in the guinea-pig Langendorff heart in vitro to the same degree as propranolol. However, in the conscious dog soquinolol's beta 1-adrenergic blocking activity (ED 50%) on intravenous injection (5.5 micrograms/kg) and oral administration (5.8 micrograms/kg) is about twice as great as that of pindolol and 19 times (i.v.) or 138 times (p.o.) greater than that of propranolol. These results suggest 95% enteral efficacy for soquinolol (pindolol 88%, propranolol 13%). The differences in soquinolol's and propranolol's efficacy detected in vitro and in vivo are partially attributable to differences in their kinetic properties namely the lower protein binding and the higher distribution volume of soquinolol. In the conscious dog, soquinolol inhibits beta 1-(ED 50% = 4.0 micrograms/kg) and beta 2-receptors (ED 50% = 2.7 micrograms/kg) at dose levels which do not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

An antigen-independent physiological activation pathway for L3T4+ T lymphocytes.

The data presented in this report describe an antigen-independent activation pathway leading to reinduction of proliferation of class II major histocompatibility complex (MHC)-restricted murine T cell lines that after previous antigen-specific stimulation reverted to a resting state. Antigen-independent proliferation and interleukin 2 (IL2)-receptor expression occur in the presence of splenic accessory cells, exogenous IL2 and a soluble factor(s) provisionally termed T cell-stimulating factor(s) (TSF). Each of these components is essential for inducing growth. TSF is found in the supernatant of an autoreactive T cell line upon stimulation with syngeneic accessory cells. Neither TSF nor accessory cells can be replaced by IL1 and by some other cytokines. Monoclonal antibodies against class II MHC molecules, the T cell receptor and L3T4 do not block this antigen-independent stimulation. This demonstrates that the function of the accessory cell in this system is not MHC restricted and that the T cell receptor is also not involved. Furthermore, it is suggested that the blocking of L3T4 molecules by antibody will mediate a negative signal only if T cells are triggered via their antigen receptors.

Animals↗
PubMed1986

[Psychosomatic aspects of parent-child relations in atopic eczema in childhood. I. Psychodiagnostic test procedures in parents and children in comparison with somatic findings].

A total of 23 children with atopic eczema and 13 control children suffering from non-atopic dermatological disorders were studied. For children between 8 and 14 years the "Hamburg neuroticism and extraversion scale for children and adolescents" (HANES-KJ) was used. In this test no statistically significant differences were observed between children with atopic eczema and children with other dermatological disorders. The mothers and fathers of atopic children were examined for personality profiles using the "Freiburger personality inventory" (FPI). In the FPI, mothers of children with atopic eczema were shown to be less "spontaneous", more "under control" and less "emotional" than the normal population. The fathers of atopic children showed now significant differences compared with the normal population; however, there was a trend towards increased "irritability". In a comparison of FPI profiles within couples with atopic children, mothers showed less "somatic emotional response" in the FPI profile, while the feature "emotional control" was more prominent in the mothers as compared with the respective fathers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗