PubMed Health⌕ Search

Biomedical subjects

J Zipper

Publications and source records attributed to J Zipper.

At least 19 recordsLinked to original sources
PubMed1999

Water-soluble beta-sheet models which self-assemble into fibrillar structures.

Self-assembly of beta-sheet domains resulting in the formation of pathogenic, fibrillar protein aggregates (amyloids) is a characteristic feature of various medical disorders. These include neurodegenerative diseases, such as Alzheimer's, Huntington's, and Creutzfeldt-Jacob's. A significant problem in studying such aggregation processes is the poor solubility of these beta-sheet complexes. The present work describes water-soluble de novo beta-sheet peptides which self-assemble into fibrillar structures. The model peptides enable studies of the relationship between beta-sheet stability and association behavior. The peptides [DPKGDPKG-(VT)n-GKGDPKPD-NH2, n = 3-8] are composed of a central beta-sheet-forming domain (VT-sequence), and N- and C-terminal nonstructured octapeptide sequences which promote water solubility. Conformational analyses by circular dichroism and Fourier transform infrared spectroscopy indicate the influence of peptide length, D-amino acid substitution, and concentration on the ability of the peptides to form stable beta-sheet structures. The association behavior investigated by analytical ultracentrifugation and dynamic light scattering was found to correlate strongly with the stability of a beta-sheet conformation. Model peptides with n >/= 6 form stable, water-soluble beta-sheet complexes with molecular masses of more than 2000 kDa, which are organized in fibrillar structures. The fibrils examined by Congo Red staining and electron microscopy show some similarities with naturally occurring amyloid fibrils.

Amino Acid Sequence↗
PubMed1998

Effects of long term treatment with corticotropin releasing factor on corticotropic tumor cells in vitro.

hCRF inhibits proliferation of corticotropic tumor cells cultivated in serum-reduced medium via interaction with CRF-receptors. This effect was attenuated by the specific antagonist hCRF (9-41), but not by a variety of substances which are inhibitors of cAMP production or cAMP-dependent kinases, suggesting that the effect was not mediated via cAMP. The growth inhibiting effect of hCRH was developed after 4 h incubation, a longer hCRF treatment did not change the effect observed after 4 h. Simultaneously, after hCRF treatment for 4 days the cells were insensitive for ACTH release by hCRF stimulation despite of an increase in the number of secretory granules. The results show that the inhibition of proliferation of pituitary tumor cells by hCRF seems to be a rapid receptor-mediated process connected with morphological changes, but not mediated via activation of adenylate cyclase.

Animals↗
PubMed1998

Mechanism of peptide-induced mast cell degranulation. Translocation and patch-clamp studies.

Substance P and other polycationic peptides are thought to stimulate mast cell degranulation via direct activation of G proteins. We investigated the ability of extracellularly applied substance P to translocate into mast cells and the ability of intracellularly applied substance P to stimulate degranulation. In addition, we studied by reverse transcription--PCR whether substance P-specific receptors are present in the mast cell membrane. To study translocation, a biologically active and enzymatically stable fluorescent analogue of substance P was synthesized. A rapid, substance P receptor- and energy-independent uptake of this peptide into pertussis toxin-treated and -untreated mast cells was demonstrated using confocal laser scanning microscopy. The peptide was shown to localize preferentially on or inside the mast cell granules using electron microscopic autoradiography with 125I-labeled all-D substance P and 3H-labeled substance P. Cell membrane capacitance measurements using the patch-clamp technique demonstrated that intracellularly applied substance P induced calcium transients and activated mast cell exocytosis with a time delay that depended on peptide concentration (delay of 100-500 s at concentrations of substance P from 50 to 5 microM). Degranulation in response to intracellularly applied substance P was inhibited by GDPbetaS and pertussis toxin, suggesting that substance P acts via G protein activation. These results support the recently proposed model of a receptor-independent mechanism of peptide-induced mast cell degranulation, which assumes a direct interaction of peptides with G protein alpha subunits subsequent to their translocation across the plasma membrane.

Animals↗
PubMed1998

Hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors in murine skin.

We demonstrate the presence and hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors (CRF-R) in C57BL/6 mouse skin. To correlate this with a physiological, developmentally controlled tissue remodeling process, we have analyzed CRF and CRF-R expression during defined stages of the murine hair cycle with its rhythmic changes between growth (anagen), regression (catagen), and resting (telogen). Using reversed-phase HPLC combined with two independent anti-CRF radioimmunoassays, we have identified CRF in murine skin. Maximal CRF levels were found in anagen III-IV skin, and minimal values were detected in catagen and telogen skin. By immunofluorescence, maximal CRF immunoreactivity (CRF-IR) was seen in the basal epidermis, nerve bundles of skin, the outer root sheath and matrix region of anagen IV-VI follicles, and in defined sections of their perifollicular neural network, whereas catagen and telogen skin displayed minimal CRF-IR. Using quantitative autoradiography and 125I-CRF as a tracer, high-affinity binding sites for CRF were detected in murine skin. The highest density of specific binding sites was detected in the panniculus carnosus, the epidermis, and the hair follicle. CRF-R type 1 (CRF-R1) IR was detected by immunohistology mainly in the outer root sheath, hair matrix, and dermal papilla of anagen VI follicles, as well as in the inner and outer root sheaths of early catagen follicles. CRF-R1 expression was also hair cycle dependent. Therefore, in normal murine skin, the CRF-CRF-R signaling system may operate as an additional neuroendocrine pathway regulating skin functions, possibly in the context of cutaneous stress responses.

Animals↗
PubMed1998

Stimulation of endothelial angiotensin-converting enzyme by morphine via non-opioid receptor mediated processes.

In this study, we examined the influence of morphine and naloxone on the enzymatic activity of different ecto-peptidases located on the surface of endothelial cells. Morphine increased in a concentration dependent manner the degradation of Leu-enkephalin in cultivated bovine aortic endothelial cells. Naloxone, a morphine antagonist, did not prevent this effect, but caused it as well. The enhanced Leu-enkephalin degradation was due to an increase in the activity of angiotensin-converting enzyme (ACE), whereas the activity of other ecto-peptidases (aminopeptidase N and neutral endopeptidase) was not influenced. Despite a high non-specific binding of [3H]-morphine, no specific opioid receptor binding on the endothelial cells could be detected. Autoradiographic investigations with native, cryostat-sectioned cells demonstrated that [3H]-morphine was nearly exclusively located within the nuclei. The present results suggests that the morphine effect concerning ACE activity is not mediated via opioid receptors but presumably by interactions within the cell nucleus.

Cells, Cultured↗
PubMed1997

Proliferation of myocardial peroxisomes caused by several agents and conditions.

In view of considerable gaps in our knowledge of myocardial peroxisomes. the aim of the present study is, on the basis of extensive electron-microscopic investigations, to provide reliable results on the inducibility of a proliferation (increase in the number) of these organelles in rodents' heart by several agents and conditions. As far as possible, we compared the response of heart and liver peroxisomes. Morphometric investigations were performed to assess the effectiveness of the hypolipidemic agent HL 41, erucic acid, ethanol, nifedipine, chlorpromazine, two cardiotonic drugs, isoprenaline, adriamycin, and physical exercise. The study also included spontaneously hypertensive rats (SHR). A further objective was to determine synergistic or additive effects that might occur when two or three peroxisome-proliferating stimuli act simultaneously. In every case we observed a clear peroxisome proliferation, which was found to increase by between 10 and 97% under the influence of an additional inducer. The observed increase in peroxisome number ranged from almost 200% to nearly 400%. Our results suggest that very different agents and conditions can induce myocardial peroxisome proliferation when they lead to metabolic alterations associated with an increased need for a peroxisomal beta-oxidation of fatty acids as an energy source and/or for preventing toxic effects. Regulatory mechanisms of these adaptive processes are apparently also present in the heart via peroxisome proliferator-activated receptors (PPARs) and their activation by fatty acids, which can also stimulate the PPARs gene expression. The assumption that stimulated catalase gene expression might be responsible for the induction of peroxisome proliferation as a cellular response to an extraperoxisomal oxidative stress situation (isoprenaline, adriamycin, or physical exercise) poses some critical questions. These questions pertain especially to: (a) quantitative aspects with regard to the possible effectiveness of an increase in catalase activity by two-, three-, or four-fold enhanced peroxisome numbers; (b) the role of cytoplasmic catalase; (c) the existence and importance of a myocardial mitochondrial catalase; and (d) the co-operation between the two H2O2-destroying enzymes catalase and glutathione peroxidase.

Animals↗
PubMed1995

Quinacrine: sclerosing agent of the utero-tubal junction in women, with anticarcinogenic actions in transplanted tumors in mice.

Quinacrine, an acridine derivative that was in widespread use as an anti-malarial, has been shown to have both sclerosant and anticarcinogenic actions. The sclerosant action of quinacrine has been used to produce occlusion of Fallopian tube in both experimental animals and women, and several clinical studies are reviewed. Both actions of quinacrine are potentiated by steroidal and non-steroidal antiprostaglandins as well as by ionic copper. Combinations of quinacrine with antiprostaglandin drugs, and also with copper, improved the efficacy of quinacrine when used for female sterilization and reduced side effects. A review of the experimental and epidemiological evidence suggests that quinacrine has no carcinogenic effects.

Animals↗
PubMed1995

Transcervical quinacrine sterilization: clinical experience.

OBJECTIVE: To review the use of quinacrine pellets for non-surgical female sterilization. BACKGROUND: The transcervical insertion of quinacrine pellets has been under study for over 15 years. It could potentially expand access to sterilization services, because it is relatively simple to administer, with the use of a modified IUD inserter, and is inexpensive. METHODS: Published and unpublished data are reviewed. RESULTS: The short-term safety of transcervical quinacrine appears to be better than surgical sterilization, but it is less effective, especially among women under 35, and there are virtually no data on its reversibility. Thus, it is probably most appropriate for older women, aged 35 and over, but it could be an option for others where access to surgical sterilization is limited. CONCLUSION: The use of quinacrine pellets for female sterilization needs to be reviewed by appropriate regulatory authorities, especially with regard to long-term safety issues, and additional clinical studies are needed to better define a standardized regimen.

Cervix Uteri↗
PubMed1995

Cancer risk among women sterilized with transcervical quinacrine hydrochloride pellets, 1977 to 1991.

OBJECTIVE: To determine whether a cluster of eight cancers among 572 women who had received transcervical quinacrine hydrochloride was a random occurrence or evidence of an increased risk of cancer. DESIGN: Retrospective cohort study using interviews and reviews of medical records. Cancer cases were evaluated using cohort analyses and space-time cluster methods. SETTING: Santiago and Valdivia, Chile. SUBJECTS: Fourteen hundred ninety-two women who received transcervical quinacrine pellets for sterilization between 1977 and 1989. MAIN OUTCOME MEASURE: Age- and site-specific incidence of invasive cancers. RESULTS: Eight hundred two women were interviewed. From 1 to 14 years of data were available on 600 of the noninterviewed women from clinic records. During 7,852 women-years of follow-up, 17 invasive cancers were identified, compared with 11.8 expected, based on age-specific rates from the Cali, Colombia cancer registry. Five cases of cervical cancer were observed, compared with 3.96 expected. Only one other uterine cancer was observed, a leiomyosarcoma, compared with 0.2 or 0.3 other uterine cancers expected. CONCLUSIONS: The occurrence of an unusual cluster was confirmed, but no evidence was found of excess cancer risk associated with quinacrine pellet sterilization. However there was a single provocative observation (the leiomyosarcoma), and surveillance of the cohort is continuing.

Adult↗
PubMed1995

Prevalence and standardized incidence rates of preclinical cervical pathology among 1,061 women sterilized with transcervical quinacrine hydrochloride pellets.

OBJECTIVE: To determine whether the incidence of in situ cervical carcinoma was increased among a cohort of women who received transcervical insertions of quinacrine hydrochloride pellets into the uterine cavity as a method of nonsurgical sterilization. DESIGN: Retrospective review of Papanicolaou (Pap) test results, comparing incidence of high-grade lesions among quinacrine acceptors with a comparison population. SETTING: Outpatient clinics, Santiago, Chile. SUBJECTS: Women attending a family planning clinic (quinacrine acceptors) and a comparison population from another area of Santiago. MAIN OUTCOME MEASURE: Incidence of in situ cervical carcinoma. RESULTS: During 3,668 woman-years of follow-up, 8 women in the quinacrine group were found to have in situ carcinomas for an age-adjusted rate of 2.62 per 1,000 woman-years. The incidence in a comparison population was 1.62 per 1,000 woman-years, but the difference was not statistically different. CONCLUSIONS: The age-standardized incidence of in situ carcinoma among the quinacrine sterilized women was not significantly different from the rate in a comparison population of women in Santiago. However, the study has a number of limitations.

Adolescent↗
PubMed1994

Quinacrine and copper, compounds with anticonceptive and antineoplastic activity.

Changes in the evolution of a malignant transplantable tumor in mice to whom quinacrine, copper and zinc were supplied in drinking water are reported. Male AJ mice were inoculated in the right thigh with 1,000,000 TA3 or TA3 MTXR tumoral cells. Three experiments were designed with different types of tumors and different schedules of quinacrine and cations administered in drinking water. The animals that received quinacrine or quinacrine plus copper in drinking water had significantly smaller tumors, and some groups had a high rate of complete tumor regression (up to 60%). Quinacrine and copper have synergistic antineoplastic activity. Zinc salts do not improve the antitumoral effect of quinacrine. The relevant fact of this experiment lies in the fact that a large number of women using IUDs with copper could occasionally be treated with quinacrine.

Animals↗
PubMed1993

Effects of salsolinol on cultivated endothelial cells.

In view of neurotoxic properties of tetrahydroisoquinolines (TIQ's) there are open questions also in regard to the disturbance of the blood-brain barrier. Because endothelial cells are an important element of this barrier the present study was designed to assess the influence of salsolinol (a TIQ formed by condensation of dopamine and acetaldehyde) on cultivated endothelial cells by physiological, biochemical and morphological investigations. For the investigations we used aortic endothelial cells because of a variety of similarities in physiology and biochemistry to brain capillary endothelial cells. Cytotoxic effects estimated by cell counting after 72 h treatment with salsolinol (IC50 = 38 mumol/l) were possibly caused by mitochondrial damages. Already after 2 h severe ultrastructural alterations of many mitochondria could be observed. The respiration activity of the cells was always inhibited after treatment with salsolinol for some hours. The damage of the mitochondria by salsolinol was not connected with inhibition of the activity of succinate dehydrogenase and cytochrome c + c1. Nevertheless the damages of mitochondrial integrity support the hypothesis that the neurotoxic effect of salsolinol is primarily caused by damaging the endothelial cells associated with a disturbance of blood-brain barrier.

Animals↗
PubMed1993

[Female non-surgical sterilization: use of endo-uterine quinacrine and betamethasone pellets. Review of the subject: experimental bases--pharmacology--toxicology--efficacy].

Quinacrine produces obstruction of the region of the uterine tube by its fibroblastic granulomatous action. Factors such as the Zn++ and Cu++ content of tubal tissue, as well as the use of anti-prostaglandins, potentialise this action. Two groups of patients were evaluated in this study: Group A--95 women. 180 mg of quinacrine +0.6 mg of betamethasone were inserted into the uterine cavity, on the basis of two insertions separated by a one month interval. Two pregnancies were found by the end of the 2nd year, the percentage failure rate being 2.2 and the Pearl index 0.58. Group B--129 women. 216 mg of quinacrine +1.2 mg of betamethasone were inserted into the uterine cavity, on the basis of two insertions separated by a one month interval. Two pregnancies were found by the end of the 1st year, the percentage failure rate being 0.59 and the Pearl index 0.54. Iatrogenic adverse reactions associated with quinacrine only were not seen in either of these two study groups. None of the pregnancies was ectopic.

Adult↗
PubMed1993

[Non-surgical female sterilization using quinacrine: efficacy of two insertions of quinacrine pellets].

In a group of 159 women at Santiago du Chili, fertility control by means of chemical occlusion of the utero-tubular junction was assessed. Two transcervical intra-uterine insertions of 216 mg of quinacrine, carried out at an interval of one month and associated with 50 mg of intra-uterine diclofenac and 150 mg of intra-muscular diclofenac resulted in a pregnancy rate after 12 months of 2.1 per 100 women and a Pearl index of 1.63 at 27 months after the sterilization process. The complications and adverse events appear to be similar to those which occur during insertion of an IUD and were minor and transient, disappearing within a few hours or at most 2 days after the procedure.

Adult↗
PubMed1988

[Interaction of liposomes with vascular endothelial cells].

Confluent monolayers (3 days old) of cultured calf aortic endothelial cells (line BKEz-7) were incubated for 30, 60 or 120 min with liposomes (reverse-phase evaporation vesicles) in order to investigate by electron microscopy whether and how they interact. This study demonstrates such interactions on a large scale. Electron micrographs show different ways by which liposomes interact with vascular endothelial cells. The observed mechanisms are adsorption, fusion, endocytosis and a transcellular passage of intact liposomes.

Adsorption↗