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Biomedical subjects

F Zimmermann

Publications and source records attributed to F Zimmermann.

At least 55 records · Page 3Linked to original sources

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↗

[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↗

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↗

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↗

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↗

[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↗

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↗

[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↗

Acidic "peptidophospholipids", a new class of hapten-bearing cell surface modifying reagents.

Covalent coupling of glutamyl-glutamic acid to the amino group of ether-phosphatidylethanolamine (EPE) yields an acidic "peptidophospholipid" (Glu2-EPE) which is water-soluble above pH 7.0 and stable to phospholipase A. The terminal amino group of Glu2-EPE is free for coupling with amino-reactive determinants. We describe the synthesis of various hapten-substituted peptidophospholipids as well as of an intermediate compound, coupled with the heterobifunctional reagent 3-(2'-pyridyl)-dithiopropionic acid N-hydroxysuccinimide ester. The latter derivative allows binding to sulfhydryl-containing molecules, e.g. peptides or proteins. So far, beef and pig insulin as well as trinitrophenyl-substituted ribonuclease A have thus been linked to Glu2-EPE. All derivatives of Glu2-EPE are water-soluble at physiological pH and readily adsorb to cell surfaces from aq. solution. Binding to cells is fast, stable and "non-toxic" over a wide range of concns. The adsorbed determinants are accessible to specific antibodies and facilitate complement-mediated cell lysis. Glu2-EPE thus appears to be a universal carrier molecule for fast, simple and mild modification of cells with foreign determinants, e.g. for Jerne plaque assays.

Animals↗

Contribution to the understanding of oxicam ionization constants.

Determinations of the pKa-values by the spectrophotometric method indicate significant differences in the acidic behaviour between piroxicam and tenoxicam on the one hand and isoxicam on the other. In the case of the first named 2-pyridyl-substituted substances the two measurable and due to the UV-shift individually assignable pKa-values might be explained by the existence of zwitterionic species. In contrast to this isoxicam exhibits only one pKa-value for the enole-enolate system in the pH-range 1-14.

Chemical Phenomena↗