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Biomedical subjects

E Eriksson

Publications and source records attributed to E Eriksson.

At least 163 records · Page 9Linked to original sources
PubMed1994

In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair.

This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell). After gene transfer an external sealed fluid-filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair.

Amino Acid Sequence↗
PubMed1994

Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds.

Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components. Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repair in the mouse, consistent with a role for syndecans in regulating cell proliferation and migration in response to these effectors. Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specificity for mesenchymal cells, and selectivity for syndecan-1 and -4. We have purified and synthesized a 4.8-kDa proline-rich protein from wound fluid that reproduces this induction of syndecan-1 and -4 in cultured cells. This peptide, identical to the antibacterial peptide PR-39, is released into the wound by the cellular infiltrate and induces syndecan expression at the same peptide concentrations that lyse bacteria. These results indicate that wounds contain a multifunctional protein that induces mammalian cells to express cell surface heparan sulfate proteoglycans as part of the wound repair process and that kills bacteria as part of a nonimmune defense mechanism.

3T3 Cells↗
PubMed1994

Genetically modified keratinocytes transplanted to wounds reconstitute the epidermis.

Normal and retrovirally transfected keratinocyte suspensions expressing either the beta-galactosidase gene or the human growth hormone (hGH) gene were transplanted into chamber-enclosed skin full-thickness wounds of Yorkshire pigs. Immunostaining of sequential skin biopsies obtained for 4 weeks after transplantation showed survival of the transplanted keratinocytes as well as expression of beta-galactosidase. Transfected keratinocytes were first seen in the neodermal portions of the wounds, then in the regenerating basal epidermal layer, and finally in the terminally differentiating cells of the stratum spinosum. When keratinocytes transfected with the hGH gene were transplanted into similar wounds, hGH was detected for 10 days in wound fluid. In contrast, hGH was detected in vitro for 47 days. Wounds transplanted with either transfected or normal keratinocytes restored the epithelial barrier function significantly faster than nontransplanted controls (P < 0.05). The study confirms the successful transplantation of keratinocyte suspensions, their reconstitution of the epidermis, and their acceleration of repair. Further, this apparently normal incorporation of genetically engineered transplanted keratinocytes expressing either beta-galactosidase or hGH suggests the possibility of introducing other genes expressing therapeutic proteins into wounds to favorably affect healing. Wound fluid detection of the expressed peptide provided early demonstration of successful transfer of the hGH gene.

Animals↗
PubMed1994

Correlation between stromelysin-3 mRNA level and outcome of human breast cancer.

The expression level of stromelysin-3 (ST3) mRNA was analyzed by in situ hybridization of formalin-fixed, paraffin-embedded primary breast-tumor samples from 76 patients. Digital image analysis of the dark-field in situ hybridization signal was used to measure the maximal level of ST3 expression in each tumor. All 55 invasive ductal carcinomas and 9 of 10 invasive lobular carcinomas were positive for ST3. Invasive tumors had significantly higher levels of ST3 than in situ tumors. Furthermore, ST3 levels were higher in invasive ductal carcinomas than in invasive lobular carcinomas. The ST3 expression level was significantly correlated to fatal metastatic disease (mean follow-up 104 months). ST3 levels of < 2,500 units were associated with distant metastasis in 46% of patients, whereas levels of > 2,500 units were associated with metastasis in 79% of patients selected for study. ST3 mRNA levels did not correlate with tumor size, microvessel density, DNA ploidy or estrogen-receptor levels. Studies of ST3 expression may provide information valuable for the understanding of breast cancer biology and for prognosis.

Adult↗
PubMed1994

Breast reconstruction.

Breast reconstruction after mastectomy is becoming more common despite the general trend toward breast conserving therapy with lumpectomy and radiation. Reconstruction at the time of mastectomy can be done safely and eliminates the disadvantages associated with a second operation under general anesthesia. There are also some psychologic benefits to immediate reconstruction. Autologous reconstruction with flap tissue usually is preferred by the authors. In a woman with small breasts or when autologous tissue is not available, a prosthetic reconstruction is an acceptable choice. The authors prefer the use of textured saline implants in a submuscular position. Nipple and areola reconstruction is performed at least 3 months later as an outpatient procedure under local anesthesia. In 216 consecutive patients with immediate reconstruction, the patients with autologous reconstruction with transverse rectus abdominis or latissimus dorsi flaps ranked their level of symmetry as well as their level of overall satisfaction significantly higher than did the patients with prosthetic reconstruction. Similarly, the surgeons ranked the results from the autologous reconstructions higher. In the patients who underwent autologous reconstruction, 6% had necrosis of a significant portion of the flap. Prosthetic reconstructions were complicated by infections, hematomas, and chest-skin necrosis, resulting in removal of the implant in a total of 8% of the patients in this group. Thirty-four percent of the patients received adjuvant chemotherapy, and the reconstructive surgery did not result in a delay of the onset of this treatment. The authors conclude that breast reconstruction is a safe procedure with an acceptable morbidity when done either as an immediate or a delayed procedure. Patient satisfaction rates are high, particularly with autologous reconstructions.

Adult↗
PubMed1994

Late follow-up results of operative ankle arthroscopy in patients under local anaesthesia.

The purpose of this study was to evaluate our long-term results of operative ankle arthroscopy in local anaesthesia, without tourniquet and antibiotic prophylaxis, and to see whether we could produce the same results other investigators had published using general anaesthesia. Between 1987 and 1992, 51 operative ankle arthroscopies were performed--all as out-patient procedures. Thirty-six patients had local anaesthesia, 7 had general anaesthesia, one had spinal anaesthesia and one had epidural anaesthesia. No prophylactic antibiotics were given. Indications for surgery were the same for patients who had local anaesthesia as for those who had the other types of anaesthesia. Nineteen patients had partial synovectomies, 8 had removals of osteophytes, 7 had debridements of osteochondral fractures, 6 had debridements of mild degenerative osteoarthritis, 3 had loose bodies and 2 had septic arthritis. After a mean of 3 years (range 1-8) the patients were sent a questionnaire. They were asked to rate activity level, pain, swelling, and limb stiffness on a four-grade scale pre- and postoperatively and to rate their total subjective improvement. They were also asked if they would undergo the same procedure again knowing the outcome of the procedure. Forty-five patients (88%) were available for follow-up. Thirty-four patients (76%) were improved, 10 remained unchanged, and one became worse after surgery. No correlation existed between preoperative symptom duration, sex, trauma, type of anaesthesia, postoperative diagnosis or type of surgical procedure. Minor complications occurred in 11% of patients. Eighty-four percent of the patients said they would undergo the same procedure again. The type of anaesthesia used did not influence this decision.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood.

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.

Aged↗
PubMed1994

Cerebrospinal fluid levels of monoamine metabolites. A preliminary study of their relation to menstrual cycle phase, sex steroids, and pituitary hormones in healthy women and in women with premenstrual syndrome.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) were measured in a group of drug-free non-depressed women with premenstrual syndrome (PMS) (late luteal phase dysphoric disorder) (n = 13) and in controls with no premenstrual complaints (n = 13). In six patients and eight controls, CSF samples from both the luteal and the follicular phase were obtained, whereas in the remainder of the subjects, samples from either the follicular phase (patients: 4, controls: 2) or the luteal phase (patients: 3, controls: 3) were taken. The following observations were made: (1) Neither in the follicular phase nor in the luteal phase did the mean concentrations of CSF monoamine metabolites in the PMS group differ from the corresponding values in the control group. (2) Neither in the PMS group nor in the control group did the mean concentrations of monoamine metabolites in CSF samples obtained in the luteal phase differ from the corresponding values obtained in the follicular phase. (3) The intraindividual, intersample variations of CSF HVA and 5-HIAA concentrations were significantly smaller in the PMS group than in the control group. (4) CSF HVA correlated strongly to CSF 5-HIAA in the luteal phase of both patients and controls whereas in the follicular phase, particularly in controls, this correlation was much weaker. (5) In the luteal phase, the CSF HVA/5-HIAA ratio correlated negatively to serum levels of estradiol, progesterone, and testosterone. (6) The CSF HVA/5-HIAA ratio was significantly lower in PMS patients than in controls. (7) A positive correlation between CSF MHPG and serum luteinizing hormone was observed in the follicular phase. (8) A positive correlation between CSF HVA and serum prolactin was observed in the luteal phase. Because the study was comprised of a small number of subjects, the reported findings until replicated should be interpreted with caution.

Adult↗
PubMed1994

Fibronectin gene expression differs in normal and abnormal human wound healing.

The overproduction of fibronectin and type I collagen in keloids and hypertrophic scars implicates altered regulation of extracellular matrix components as an important aspect of these wound healing pathologies. However, little is known about the similarities and differences in extracellular matrix gene expression during normal and abnormal wound healing. This study compared the content of fibronectin messenger RNA and rates of fibronectin protein biosynthesis in fibroblasts derived from normal skin, normal scar, keloid, and hypertrophic scar. Fibronectin expression was enhanced in cells from both normal and abnormal wounds relative to cells from quiescent normal skin. Matched pairs of normal and keloid fibroblasts from the same individuals were also compared, and three of the four pairs showed higher fibronectin expression by the keloid cells at the levels of messenger RNA and protein synthesis. This was consistent with previous studies showing elevated steady state content of fibronectin in keloid cells relative to normal cells from the same individual. Fibronectin messenger RNA and protein content in the tissues from which these cells were derived was examined by in situ hybridization and immunohistochemistry. These studies revealed that in vivo, the steady state content of fibronectin messenger RNA and protein was highest in abnormal wounds, less in most normal scars, and lowest in normal skin. Thus, fibroblasts from keloids and hypertrophic scars overexpressed fibronectin in vivo relative to normal skin and normal scar and retain this characteristic in vitro relative to normal skin. Although normal scars contained little fibronectin protein and messenger RNA, cultured fibroblasts derived from these scars had contents of fibronectin messenger RNA and rates of biosynthesis in vitro similar to those of keloid fibroblasts. This indicates that the fibronectin regulatory pathway in scar fibroblasts is influenced by the tissue environment. These results are discussed with respect to the relationship of fibronectin expression in keloids, hypertrophic scars, and normal wounds in human beings.

Journal Article↗
PubMed1994

Postmastectomy complications in breast reconstruction.

In a group of patients where breast reconstruction was performed at the time of mastectomy, the incidence of complications was studied. One hundred one consecutive patients had an autologous reconstruction using the transverse rectus abdominis musculocutaneous flap, and 115 consecutive patients had a prosthetic reconstruction with tissue expanders or with tissue expander and/or implant. One patient in the autologous reconstruction group had a cardiac arrhythmia requiring monitoring, but there were no other serious complications. Infection was more common in the group undergoing prosthetic reconstruction (5% compared with 3% in the autologous reconstruction group). A total of 8% of the patients in the group undergoing prosthetic reconstruction had to have their implants removed because of infection or exposure of the implant. Seven percent of the transverse rectus abdominis musculocutaneous flap patients had significant necrosis of a portion of the flap. Secondary surgical revision of the reconstructed breast was much more common (20%) in the prosthetic reconstruction group compared with 6% in the autologous reconstruction group.

Adult↗
PubMed1994

Can laboratory testing improve screening strategies for deep vein thrombosis at an emergency unit?

OBJECTIVES: To study various markers of blood coagulation and fibrinolysis in relation to the extension of deep vein thrombosis (DVT), and to compare the diagnostic usefulness of these markers as screening tests for excluding DVT. DESIGN: A clinical study of patients admitted to an emergency unit. SETTING: Ostra Hospital, Göteborg, Sweden. SUBJECTS: One hundred and five patients with a clinical suspicion of DVT. MAIN OUTCOME MEASURES: Phlebography was used as the reference method for a diagnosis of DVT. Small distal thromboses as well as large proximal thromboses were included. Plasma D-dimer as well as other markers of coagulation and fibrinolysis were analysed. RESULTS: Twenty-eight proximal and 20 distal DVTs were found. Plasma D-dimers (one ELISA and two latex assays), fibrin monomer, prothrombin fragment 1 + 2 (F1+2), thrombin-antithrombin III complex (TAT) and the t-PA-PAI-1 complex were all significantly correlated to the extension of DVT, whilst fibronectin, tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scru-PA) and plasminogen activator inhibitor 1 (PAI-1) were not. The sensitivity was 94% for the D-dimer ELISA and one of the latex methods (latex-B), at a specificity of 60% and 68%, respectively. The negative predictive value was 92% for ELISA and 93% for latex-B, and both assays showed a negative predictive value of 100% for proximal DVTs. Fibrin monomer, F1+2, TAT, D-dimer (latex-S) and the t-PA-PAI-1 complex all showed lower negative predictive values (88, 84, 79, 78 and 65% respectively). CONCLUSIONS: Sensitivity and negative predictive values for a latex assay (D-dimer latex-B) was similar to that of a D-dimer ELISA: With a sensitivity of 94% (100% for proximal DVTs) such a latex assay may be included in a screening strategy for DVT at an emergency unit. However, the safety of such an approach has to be tested in other prospective studies.

Adult↗
PubMed1994

High levels of free testosterone in women with bulimia nervosa.

Women with normal-weight bulimia nervosa (n = 11) displayed significantly higher serum levels of free testosterone than age-matched controls (6.0 +/- 0.7 vs 3.9 +/- 0.8 pmol/l; P = 0.03). The possible importance of androgens, in women, for the pathophysiology of conditions characterized by an impairment in impulse control is being discussed.

Adult↗
PubMed1994

Osseointegration from the perspective of the plastic surgeon.

This review summarizes some aspects of osseointegration. The principles, implant type and design, surgical technique, and results are reviewed. A large number of patients have been followed after intraoral reconstruction using osseointegrated implants. The success rates are 95 percent in the maxilla and 99 percent in the mandible. In craniofacial reconstruction, results vary from 98 percent success in the temporal area to as low as 48 percent in the radiated orbit. Some early experience with finger joint reconstruction, bone-anchored finger prostheses, and major amputations are reviewed.

Equipment Design↗
PubMed1993

A high dose of EEDQ reduces pituitary dopamine D2 receptor density and the prolactin suppressive potency of agonists.

In male rats, a high dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 30 mg/kg s.c., 24 h) caused a reduction of pituitary dopamine D2 receptor density by 27% as measured by means of in vivo radioligand binding (using a single dose of the ligand [3H]spiperone). The same dose of EEDQ reduced the potency, but not the maximal response, of the dopamine D2 receptor agonists R-(-)-N-n-propylnorapomorphine (NPA), (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP), and 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5]azepine (B-HT 920) with respect to suppression of prolactin release after pretreatment with gamma-butyrolactone. The measured reduction in dopamine D2 receptor density after EEDQ was of the same magnitude as the reduction in receptor number predicted from the EEDQ induced shift in the dose-response curve of the full dopamine D2 receptor agonist NPA. The findings are discussed in relation to our previous observation that a somewhat lower dose of EEDQ (20 mg/kg s.c., 24 h) effectively reduces the efficacy of partial dopamine D2 receptor agonists while affecting neither the prolactin response to full dopamine D2 receptor agonists nor the density of pituitary dopamine D2 receptors.

Animals↗
PubMed1993

Reactive oxygen intermediates and ischemia-reperfusion injury release tissue plasminogen activator from isolated rat hearts.

Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t-PA.

Animals↗
PubMed1993

Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury.

Wound fluid was obtained from porcine partial-thickness excisional wounds and analyzed for heparin-binding growth factors. Two heparin-binding growth factor activities were detected, a relatively minor one that was eluted from a heparin affinity column with 0.65 M NaCl and a major one that was eluted with 1.1 M NaCl. These activities were not present in wound fluid 1 hr after injury but appeared 1 day after injury, were maximal 2-3 days after injury, and were not detectable by 8 days after injury. The heparin-binding growth factor eluted with 0.65 M NaCl was identified as a platelet-derived growth factor (PDGF)-like activity by the use of specific anti-PDGF neutralizing antibodies. The heparin-binding growth factor eluted with 1.1 M NaCl was shown to be structurally related to heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) by several criteria, including binding to heparin affinity columns and elution with 1.1 M NaCl, competition with the binding of 125I-EGF to the EGF receptor, triggering phosphorylation of the EGF receptor, immunodetection on a Western blot, and stimulation of fibroblast and keratinocyte growth. It was concluded that HB-EGF is a major growth factor component of wound fluid and, since it is mitogenic for fibroblasts and keratinocytes, that it might play an important role in wound healing.

3T3 Cells↗
PubMed1993

Haloperidol increases prolactin release and cyclic AMP formation in vitro: inverse agonism at dopamine D2 receptors?

Haloperidol (30 nM, 3 microM) was found to increase prolactin release from GH4C 1 cells transfected with the D2 receptor cDNA (GH4ZR 7) and from wild-type (untransfected) GH 3 cells, but not from wild-type GH4C 1 cells. In addition, haloperidol (3 microM) stimulated cAMP formation in GH 3 cells. It is suggested that haloperidol may act as an inverse agonist rather than as a neutral antagonist at dopaminergic D2 receptors.

1-Methyl-3-isobutylxanthine↗