Search PubMed⌕ Search

Biomedical subjects

S Jensen

Publications and source records attributed to S Jensen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reproductive toxicity in mink (Mustela vison) chronically exposed to environmentally relevant polychlorinated biphenyl concentrations.

Female mink were exposed to a technical polychlorinated biphenyl (PCB) preparation (Clophen A50 [A50]; 0.1 or 0.3 mg/animal/d), one fraction of A50 containing the non- and mono-ortho-chlorinated congeners (0-1-ortho-chlorobiphenyls [CBs]), another fraction of A50 containing the congeners with two to four ortho-chlorines (2-4-ortho-CBs), or an organic extract from Baltic gray seal blubber. The animals were exposed for 18 months, including two reproduction seasons. Among the animals given the highest dose of A50, the whelping frequency was reduced in the second reproductive season, and all kits died within 24 h of birth. Reproduction was also impaired by the lower dose of A50. Daily exposure to the 0-1-ortho-CBs separated from 0.3 mg A50 severely reduced kit survival. Reproduction was not significantly impaired by daily exposure to the 2-4-ortho-CBs separated from 0.3 mg A50 or by exposure to the blubber extract. We conclude that the reproductive toxicity in chronically PCB-exposed mink is caused by the aryl hydrocarbon (Ah) receptor agonists. The lowest-observed-effect level for reproductive impairment was 2.4 ng 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) per kilogram body weight and day (22 pg TEQs/g feed). Ethoxyresorufin-O-dealkylase (EROD) was strongly induced by the 0-1-ortho-CBs and pentoxyresorufin-O-dealkylase by the 2-4-ortho-CBs. High EROD activity was correlated with low kit production, and consequently EROD may serve as a marker for reproductive toxicity by Ah receptor agonists in mink.

Administration, Oral↗
PubMed2001

Musculoskeletal causes of chest pain.

BACKGROUND: Chest pain is a common presenting problem to general practitioners and accident and emergency departments. Such a symptom generates anxiety in both patients and their medical attendants, for fear that this symptom represents a life threatening event. Numerous investigations often ensue, adding to the physical and financial burden on an already stressed health system. Musculoskeletal causes of chest pain are common but frequently overlooked. OBJECTIVE: This article aims to outline some of the more common musculoskeletal problems which may present as chest pain, and to present a practical approach to their diagnosis and management. DISCUSSION: It is estimated that somewhere in the vicinity of 20-25% of noncardiac chest pain has a musculoskeletal basis. Careful history taking to identify red flag conditions differentiates those who require further investigation. Historical features suggesting a musculoskeletal cause include pain on specific postures or physical activities. A musculoskeletal diagnosis can usually be confirmed by clinical examination alone, the key to which is reproducing the patient's pain by either a movement or more specifically palpation over the structure that is the source of the pain. Confirming the diagnosis, explanation and reassurance allay anxiety. Management strategies include manual therapy, the provision of analgesia and anti-inflammatory agents, either topically, orally or by injection. Focal injection of local anaesthetic alone may also be a useful diagnostic and therapeutic tool.

Adult↗
PubMed2001

[Reconstruction of mental health services in Bosnia and Herzegovina].

Psychiatric services in Bosnia-Herzegovina before the war disaster was fairly developed and one of the best organized services amongst the republics of the former Yugoslavia. The psychiatric care system was based on psychiatric hospitals and small neuropsychiatric wards within general hospitals, accompanied by psychiatric services in health centers. The onset of war in B&H brought devastation and destruction in all domains of life, including the demolition and closing of numerous traditional psychiatric institutions, together with massive psychological suffering of the whole civilian population. Already during the war, and even more so after the war, the reconstruction and reorganization of the mental health services was undertaken. The basis of mental health care for the future is designed as a system where majority of services is located in the community, as close as possible to the habitat of the patients. The key aspect of the system of the comprehensive health care is primary health care and the main role is assigned to family practitioners and mental health professionals working in the community. Large psychiatric institutions were either closed or devastated, or have their capacities extensively reduced. There will be no reconstructions or reopening of the old psychiatric facilities, nor the new ones will be built. The most integrated part of the psychiatric system are the Community based mental health centers. Each of these centers will serve a particular geographic area. The centers will be responsible for prevention and treatment of psychiatric disorders, as well as for the mental health well being. Chronic mental health patients without families and are not able to independently live in the community will be accommodated in designated homes and other forms of protected accommodation within their communities. The principal change in mental health policy in B&H was a decision to transfer psychiatric services from traditional facilities into community, much closer to the patients. Basic elements of the mental health policy in B&H are: Decentralization and sectorization of mental health services; Intersectorial activity; Comprehensiveness of services; Equality in access and utilization of psychiatric service resources; Nationwide accessibility of mental health services; Continuity of services and care, together with the active participation of the community. This overview discusses the primary health care as the basic component of the comprehensive mental health care in greater detail, including tasks for family medicine teams and each individual member. 1. Comprehensive psychiatric care is implemented by primary health care physicians, specialized Centers for community-based mental health care, psychiatric wards of general hospitals and clinical centers in charge of brief, "acute" inpatient care; 2. Primary mental health care is implemented by family practitioners (primary care physicians) and their teams; 3. Specialized psychiatric care in community is performed professional teams specialized mental health issues' within Mental health centers in corresponding sectors; 4. A great deal of relevance is given to development of confidence and utilization of links between primary health care teams and specialized teams in Mental health centers and psychiatric in patient institutions; 5. Psychiatric wards within general cantonal hospitals, departments of psychiatric clinics in Sarajevo, Tuzla, and Mostar, and Cantonal Psychiatric hospital in Sarajevo (Jagomir) shall admit acute patients as well as chronic (with each new relapse). Treatment in these facilities is brief an patients are discharged to return to their homes, with further treatment referral to their family practitioner or designated Mental health center; 6. Chronic mental patients with severe residual impairment in social, psychological, and somatic functioning, shall live in the community with their families or independently. Those chronic patients without families and economic and other resources to live independently shall be placed in supervised Homes in the communities where they live. The above delineated strategy of mental health care program in B&H has several fundamental and specific objectives, among which the most important are: Reduction of incidence and prevalence of some mental disorders, particularly war stress-related disorders and suicide; Reduction of level of functional disability caused by mental disorders through improvement of treatment and care of individuals with mental health problems; Improvement of psychosocial well being of people with mental health problems, through implementation of comprehensive and accessible service for community mental health care; and Respect of basic human rights of individuals with mental health disabilities. The program has been updated since 1996, after the two-year pilot program. The main goals for current two- and five-year period are: Implement the mental health care reform program by launching all 38 Mental health centers in the Federation of BiH by 2002; Complete the 10-day education and re-education of at least 50% of all professionals employed in mental health services in FB&H by 2002; and Achieve that 80 percent of all mental health problems are treated by family medicine teams (primary care practitioners) and specialized mental health services (Community mental health care centers) by 2005.

Bosnia and Herzegovina↗
PubMed2000

Contribution of planar (0-1 ortho) and nonplanar (2-4 ortho) fractions of Aroclor 1260 to the induction of altered hepatic foci in female Sprague-Dawley rats.

The hepatic tumor promoting activity of the planar 0-1 ortho ( approximately 9.7% w/w) and the nonplanar 2-4 ortho ( approximately 90.3% w/w) fraction of the commercial PCB mixture Aroclor 1260 was studied using a medium-term two-stage initiation/promotion bioassay in female Sprague-Dawley rats. Fractionation was carried out on an activated charcoal column. The composition of the effluent from the column was tested by GC-ECD. The absence of planar compounds in the 2-4 ortho fraction was confirmed by GC-MS analysis. The dioxin-like toxic potency of the fractions was determined with the DR-CALUX assay. The animal experiment was started with the initiation procedure (diethylnitrosamine injection, 30 mg/kg body wt ip, 24 h after (2)/(3) hepatectomy), followed 6 weeks later by the promotion treatment, which consisted of a weekly subcutaneous injection during 20 weeks. Exposure groups (n = 10) received the following treatments (dose/kg body wt/week): Aroclor 1260 (10 mg), 0-1 ortho fraction (0.97 mg), 2-4 ortho fraction (1, 3, or 9 mg), a reconstituted 0-4 ortho fraction (9.97 mg), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153; 1 or 9 mg), 2,3,7,8-TCDD (1 microg; positive control) or corn oil (1 ml; vehicle control). One group did not receive a promotion treatment. All exposure groups exhibited a significantly increased volume fraction of the liver occupied by hepatic foci positive for the placental form of glutathione-S-transferase-p compared to the corn oil control, except for the groups treated with 0-1 ortho fraction and 1 mg PCB 153/kg body wt/week. Approximately 80% of the total tumor promoting capacity of the reconstituted 0-4 ortho fraction could be explained by the 2-4 ortho PCB fraction while the 0-1 ortho fraction had only a negligible contribution. These results suggest that the majority of the tumor promotion potential of PCB mixtures resides in the non-dioxin-like fraction, which is not taken into account in the toxic equivalency factor (TEF) approach for risk assessment of PCBs. This may result in an underestimation of the tumor promotion potential of environmental PCB mixtures.

Animals↗
PubMed2000

A critical reappraisal of the fossil record of the bilaterian phyla.

It has long been assumed that the extant bilaterian phyla generally have their origin in the Cambrian explosion, when they appear in an essentially modern form. Both these assumptions are questionable. A strict application of stem- and crown-group concepts to phyla shows that although the branching points of many clades may have occurred in the Early Cambrian or before, the appearance of the modern body plans was in most cases later: very few bilaterian phyla sensu stricto have demonstrable representatives in the earliest Cambrian. Given that the early branching points of major clades is an inevitable result of the geometry of clade diversification, the alleged phenomenon of phyla appearing early and remaining morphologically static is seen not to require particular explanation. Confusion in the definition of a phylum has thus led to attempts to explain (especially from a developmental perspective) a feature that is partly inevitable, partly illusory. We critically discuss models for Proterozoic diversification based on small body size, limited developmental capacity and poor preservation and cryptic habits, and show that the prospect of lineage diversification occurring early in the Proterozoic can be seen to be unlikely on grounds of both parsimony and functional morphology. Indeed, the combination of the body and trace fossil record demonstrates a progressive diversification through the end of the Proterozoic well into the Cambrian and beyond, a picture consistent with body plans being assembled during this time. Body-plan characters are likely to have been acquired monophyletically in the history of the bilaterians, and a model explaining the diversity in just one of them, the coelom, is presented. This analysis points to the requirement for a careful application of systematic methodology before explanations are sought for alleged patterns of constraint and flexibility.

Animals↗
PubMed2000

Changes in ventricular repolarization during percutaneous transluminal coronary angioplasty in humans assessed by QT interval, QT dispersion and T vector loop morphology.

OBJECTIVES: Based on clinical, epidemiological, and experimental data, transient cardiac ischaemia is one of the major triggering factors of malignant ventricular arrhythmia. According to animal studies, increased dispersion of repolarization is of pathophysiological relevance in this context. Therefore we explored the impact of myocardial ischaemia during single vessel coronary angioplasty on the change in ventricular repolarization, measured by QT and JT intervals and their dispersion in the 12-lead electrocardiogram. We also assessed a novel method, the 3-dimensional T vector loop, to find out whether it was sensitive to changes in ventricular repolarization during ischaemia, and whether there was any correlation with changes in the dispersion of the QT and/or JT intervals. DESIGN: This study was prospective with consecutive patients. Only patients in sinus rhythm and without bundle branch block were included. SETTING: All coronary angioplasties were performed at Norrlands University Hospital, Umeå. The analysis of the material was performed at the Karolinska Hospital, Stockholm. SUBJECTS: Twenty-nine consecutive patients went through 30 elective one-vessel percutaneous transluminal coronary angioplasty (PTCA) procedures. PTCA was performed in 10 stenoses of the left anterior descending, 10 of the left circumflex, and 10 of the right coronary artery. INTERVENTIONS: A 12-lead electrocardiogram was recorded continuously as part of routine monitoring of the patient during PTCA and the T vector loop was calculated from the simultaneously recorded. X, Y, Z leads. MAIN OUTCOME MEASURES: Repolarization was assessed by the QRS, QT and JT intervals as well as by the T vector loop parameters (Tarea, Tavplan, and Teigenv) before and at the end of the first occlusion during PTCA. RESULTS: PTCA, with an average occlusion time of 171 +/- 60 s (mean +/- SD), induced ischaemia on the 12-lead electrocardiogram in 73% of cases. The overall response for the 30 procedures was a significantly increased dispersion of ventricular repolarization, both corrected and uncorrected for heart rate. QT dispersion increased by, on average, 19% from 74 +/- 35 to 88 +/- 36 ms, QTc dispersion by 27% from 71 +/- 39 to 90 +/- 42 ms, and JTc dispersion by 19% from 78 +/- 32 to 94 +/- 43 ms (P < 0.05). The T vector loop became more circular and bulgy during occlusion (all three parameters changed by between 33% and 59%). There was a significant correlation between changes in one of the T vector loop parameters (Teigenv), and changes in JT and QT dispersion in the left anterior descending group. CONCLUSIONS: Transient ischaemia during PTCA induced significant changes in ventricular repolarization, especially during occlusion of the left anterior descending artery and resulted in a significant increase in both QT and QTc dispersion. The degree of QT dispersion was such that several patients were at risk of ventricular arrhythmia, if a proper triggering extrasystole had occurred. In addition, and as an original observation, the 3-dimensional T vector loop morphology seemed even more sensitive to coronary occlusion than QT dispersion.

Adult↗
PubMed2000

Detection of Methane Oxidizing Bacteria in Forest Soil by Monooxygenase PCR Amplification.

Atmospheric methane oxidation by a spruce forest soil from Norway at 15 degrees C was found to be maximal at a depth of ca 7 cm. Examination of the kinetics of this methane oxidation revealed an apparent K(m) of 403.1 nM and a V(max) of 2.2 nmol g(-1) dry weight soil h(-1). The low apparent K(m) suggested the presence of active methane oxidizing bacteria with a high affinity for methane. DNA was extracted from the 5-10 cm horizon, purified, and subjected to PCR amplification with primers directed toward the monooxygenase genes pmoA and amoA, which are essential for methane oxidation. Hybridization analysis of the clone library subsequently constructed revealed that 49% of the 76 cloned PCR fragments were putative methanotroph pmoA sequences and 16% were putative ammonium oxidizing nitrifier amoA sequences. Sequencing of 28 clones identified three major groups showing homology to pmoA from Methylococcus capsulatus, beta-subdivision ammonia-oxidizers (amoA), and a new group of monooxygenase pmoA/amoA sequences.

Journal Article↗
PubMed1999

A comparative study of Mono Mac 6 cells, isolated mononuclear cells and Limulus amoebocyte lysate assay in pyrogen testing.

Pyrogen induced secretion of interleukin 6 (IL-6) in Mono Mac 6 (MM6) cells was measured. The ability of the MM6 cell culture to detect pyrogens was compared to the Limulus amoebocyte lysate (LAL) test and isolated mononuclear cells (MNC). The detection limit of MM6 for lipopolysaccharide (LPS) and Staphylococcus aureus was comparable to that of MNC. Aspergillus niger and Candida albicans induced IL-6 in isolated MNC, but not in MM6. The detection limit for Salmonella typhimurium in the MM6 assay was comparable to that of the LAL assay. As expected, S. aureus and C. albicans did not show any LAL activity. A. niger and Influenza virus showed some activity in the LAL test, but could not be detected by MM6 cells. In conclusion, the MM6 assay is a good supplement to the current pyrogen assays for detection of LPS, S. aureus and S. typhimurium, but the MM6 assay could not detect A. niger, C. albicans and Influenza virus.

Biological Assay↗
PubMed1999

Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha.

Eukaryotic topoisomerase II is a nuclear enzyme essential for DNA metabolism and chromosome dynamics. The enzyme has a dimeric structure, and subunit dimerization is vital to the cellular functions and activities of the enzyme. Two biochemical approaches based on metal ion affinity chromatography and immunoprecipitation have been carried out to map the dimerization region(s) in human topoisomerase IIalpha. The results demonstrate that two regions spanning amino acids 1053-1069 and 1124-1143 are both essential for dimerization. The regions correspond to the interaction domains revealed in yeast topoisomerase II after crystallization of a central fragment of this enzyme, indicating that the overall C-terminal dimerization structure of eukaryotic topoisomerase II is conserved from yeast to human. Furthermore, linker insertion analysis has demonstrated that the two dimerization regions are located in a highly flexible part of the enzyme. Topoisomerase IIalpha mutant enzymes unable to dimerize via the C-terminal primary dimerization regions due to lack of one of the defined dimerization regions can still be forced to dimerize if DNA and an ATP analog are added to the reaction mixture. The result indicates that secondary interactions occur by ATP analog-mediated clamp closing when the subunits are brought together on DNA.

Amino Acid Sequence↗
PubMed1999

Taming of transposable elements by homology-dependent gene silencing.

Transposable elements can invade virgin genomes within a few generations, after which the elements are 'tamed' and retain only limited transpositional activity. Introduction of the I element, a transposon similar to mammalian LINE elements, into Drosophila melanogaster genomes devoid of such elements initially results in high-frequency transposition of the incoming transposon, high mutation rate, chromosomal nondisjunction and female sterility, a syndrome referred to as hybrid dysgenesis (for review, see refs 2-4); a related syndrome has also been described in mammals. High-frequency transposition is transient, as the number of I elements reaches a finite value and transposition ceases after approximately ten generations. It has been proposed that the I elements encode a factor that negatively regulates their own transcription, but evidence for such a mechanism is lacking. Using the hybrid dysgenesis syndrome in Drosophila as a model, we show here that transpositional activity of the I element can be repressed by prior introduction of transgenes expressing a small internal region of the I element. This autoregulation presents features characteristic of homology-dependent gene silencing, a process known as cosuppression. Repression does not require any translatable sequence, its severity correlates with transgene copy number and it develops in a generation-dependent manner via germline transmission of a silencing effector in females only. These results demonstrate that transposable elements are prone to and can be tamed by homology-dependent gene silencing, a process that may have emerged during the course of evolution as a specific defense mechanism against these elements.

Animals↗
PubMed1999

Engineering of conformations of plasminogen activator inhibitor-1. A crucial role of beta-strand 5A residues in the transition of active form to latent and substrate forms.

The serpin (serine proteinase inhibitor) family is of general protein chemical interest because of its ability to undergo large conformational changes, in which the surface-exposed reactive centre loop (RCL) is inserted as strand 4 in the large central beta-sheet A. Loop insertion is an integral part of the inhibitory mechanism and also takes place at conversion of serpins to the latent state, occurring spontaneously only in plasminogen activator inhibitor-1 (PAI-1). We have investigated the importance of beta-strand 5A residues for the activity and latency transition of PAI-1. An approximately fourfold increase in the rate of latency transition resulted from His-substitution of Gln324 (position 334 in the alpha(1)-proteinase inhibitor template numbering), which interacts with the underlying alpha-helix B. The side chains of Gln321 and Lys325 (template residues 331 and 335, respectively) form hydrogen bonds to the peptide backbone of a loop connecting alpha-helix F and beta-strand 3A. While substitution with Ala of Glu321 had only minor effects on the properties of PAI-1, substitution with Ala of Lys325 led to stabilization of the inhibitory activity at incubation conditions leading to conversion of wild-type PAI-1 to a substrate form, and to an anomalous reaction towards a monoclonal antibody, which induced a delay in the latency transition of the mutant, but not wild-type PAI-1. We conclude that the anchoring of beta-strand 5A plays a crucial role in loop insertion. These findings provide new information about the mechanism of an important example of protein conformational changes.

Amino Acids↗
PubMed1999

Cortical event-related potentials show the structure of hypnotic suggestions is crucial.

Electroencephalographic cortical event-related potentials (ERPs) are affected by information processing strategies and are particularly appropriate for the examination of hypnotic alterations in perception. The effects of positive obstructive and negative obliterating instructions on visual and auditory P300 ERPs were tested. Twenty participants, stringently selected for hypnotizability, were requested to perform identical tasks during waking and alert hypnotic conditions. High hypnotizables showed greater ERP amplitudes while experiencing negative hallucinations and lower ERP amplitudes while experiencing positive obstructive hallucinations, in contrast to low hypnotizables and their own waking imagination-only conditions. The data show that when participants are carefully selected for hypnotizability and responses are time locked to events, rather robust physiological markers of hypnosis emerge. These reflect alterations in consciousness that correspond to participants' subjective experiences of perceptual alteration. Accounting for suggestion type reveals remarkable consistency of findings among dozens of researchers.

Cerebral Cortex↗
PubMed1999

Cosuppression of I transposon activity in Drosophila by I-containing sense and antisense transgenes.

We have previously shown that the activity of functional I elements introduced into Drosophila devoid of such elements can be repressed by transgenes containing an internal nontranslatable part of the I element itself and that this repressing effect presents features characteristic of homology-dependent gene silencing or cosuppression. Here we show that transgenes containing a fragment of the I element in antisense orientation induce I-element silencing with the same characteristic features as the corresponding sense construct: namely, repression takes several generations to be fully established, with similar rates for sense and antisense constructs, and it is only maternally transmitted, with reversal of the effect through paternal transmission. We also show that transcription of the transgenes is necessary to produce the silencing effect and that repression can be maintained for at least one generation following elimination of the transgenes, thus strongly suggesting that a transgene product and not the transgene per se is the essential intermediate in the silencing effect. The data presented strongly support models in which the repressing effect of antisense transcripts involves the same mechanisms as cosuppression by sense constructs and emphasize the role of symmetrically acting nucleic acid structures in mediating repression.

Animals↗
PubMed1999

Solvent effects on activity and conformation of plasminogen activator inhibitor-1.

We have studied effects of the solvent composition on the activity and the conformation of human plasminogen activator inhibitor-1 (PAI-1) from HT-1080 fibrosarcoma cells. Non-ionic detergents, includine Triton X-100, reduced the inhibitory activity of PAI-1 more than 20-fold at 0 degrees C, but less than 2-fold at 37 degrees C, while glycerol partly prevented the detergent-induced activity-loss at 0 degrees C. The activity-loss was associated with an increase in PAI-1 substrate behaviour. Evaluating the PAI-1 conformation by proteolytic susceptibility of specific peptide bonds, we found that the V8-proteinase susceptibility of the Glu332-Ser333 (P17-P16) bond, part of the hinge between the reactive centre loop (RCL) and beta-strand 5A, and the endoproteinase Asp-N susceptibility of several bonds in the beta-strand 2A-alpha-helix E region were increased by detergents at both 0 and 37 degrees C. The susceptibility of the Gin321-Ala322 and the Lys325-Val326 bonds in beta-strand 5A to papain and trypsin, respectively, was increased by detergents at 0 degrees C, but not at 37 degrees C, showing a strict correlation between proteinase susceptibility of beta-strand 5A and activity-loss at 0 degrees C. Since the beta-strand 2A-alpha-helix E region also showed differential susceptibility to endoproteinase Asp-N in latent, active, and reactive centre-cleaved PAI-1, we propose that a detergent-induced conformational change of the beta-strand 2A-alpha-helix E region influences the movements of beta-sheet A, resulting in a cold-induced conformational change of beta-strand 5A and thereby an increased substrate behaviour at low temperatures. These results provide new information about the structural basis for serpin substrate behaviour.

Humans↗
PubMed1998

Characterization of DNA topoisomerase II alpha/beta heterodimers in HeLa cells.

In mammalian cells, DNA topoisomerase II is the product of two distinct genes encoding the alpha and beta isoforms of the enzyme. Besides homodimeric topoisomerase IIalpha and IIbeta, we have recently shown that alpha/beta heterodimers constitute a third population of topoisomerase II in HeLa cells. We found that topoisomerase II heterodimers are not restricted to HeLa cells but exist in different mammalian cell types, and up to 25% of the total topoisomerase IIbeta population is involved in heterodimer formation. Studies of topoisomerase II phosphorylation in HeLa cells show that heterodimers are phosphorylated in vivo to a significantly lower level compared to homodimeric alpha enzymes, but in contrast to the latter neither heterodimers nor topoisomerase IIbeta homodimers coprecipitate together with a kinase activity that is able to mediate their phosphorylation. However, both enzymes can still be phosphorylated by exogenously added casein kinase II. The differential phosphorylation of topoisomerase II heterodimers suggests an alternative regulation of this topoisomerase II subclass compared to the homodimeric topoisomerase IIalpha counterparts.

3T3 Cells↗
PubMed1998

Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis.

Wound repair in the liver induces altered gene expression in stellate cells (resident mesenchymal cells) in a process known as "activation." A zinc finger transcription factor cDNA, zf9, was cloned from rat stellate cells activated in vivo. Zf9 expression and biosynthesis are increased markedly in activated cells in vivo compared with cells from normal rats ("quiescent" cells). The factor is localized to the nucleus and the perinuclear zone in activated but not quiescent cells. Zf9 mRNA also is expressed widely in nonhepatic adult rat tissues and the fetal liver. The zf9 nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine-proline clusters and leucines. The human zf9 gene maps to chromosome 10P near the telomere. Zf9 binds specifically to a DNA oligonucleotide containing a GC box motif. The N-terminal domain of Zf9 (amino acids 1-201) is transactivating in the chimeric GAL4 hybrid system. In Drosophila schneider cells, full length Zf9 transactivates a reporter construct driven by the SV40 promoter/enhancer, which contains several GC boxes. A physiologic role for Zf9 is suggested by its transactivation of a collagen alpha1(I) promoter reporter. Transactivation of collagen alpha1(I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all in D. schneider cells. Our results suggest that Zf9 may be an important signal in hepatic stellate cell activation after liver injury.

Amino Acid Sequence↗