Magnetic reorientation transition of Gd(0001)/W(110) films.
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Journal Article↗
Biomedical subjects
A Berger
Publications and source records attributed to A Berger.
Sphingosylphosphocholine, a signaling molecule which accumulates in Niemann-Pick disease type A, stimulates DNA-binding activity of the transcription activator protein AP-1.
Sphingosylphosphocholine (SPC) is the deacylated derivative of sphingomyelin known to accumulate in neuropathic Niemann-Pick disease type A. SPC is a potent mitogen that increases intracellular free Ca2+ and free arachidonate through pathways that are only partly protein kinase C-dependent. Here we show that SPC increased specific DNA-binding activity of transcription activator AP-1 in electrophoretic mobility-shift assays. Increased DNA-binding activity of AP-1 was detected after only 1-3 min, was maximal after 6 hr, and remained elevated at 12-24 hr. c-Fos was found to be a component of the AP-1 complex. Northern hybridization revealed an increase in c-fos transcripts after 30 min. Since the increase in AP-1 binding activity preceded the increase in c-fos mRNA, posttranslational modifications may be important in mediating the early SPC-induced increases in AP-1 DNA-binding activity. Western analysis detected increases in nuclear c-Jun and c-Fos proteins following SPC treatment. SPC also transactivated a reporter gene construct through the AP-1 recognition site, indicating that SPC can regulate the expression of target genes. Thus, SPC-induced cell proliferation may result from activation of AP-1, linking signal transduction by SPC to gene expression. Since the expression of many proteins with diverse functions is known to be regulated by AP-1, SPC-induced activation of AP-1 may contribute to the pathophysiology of Niemann-Pick disease.
3T3 Cells↗
Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling pathways of sphingosine 1-phosphate.
Sphingosine 1-phosphate, a sphingolipid metabolite, was previously reported to increase DNA synthesis in quiescent Swiss 3T3 fibroblasts and to induce transient increases in intracellular free calcium (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167). In the present study, pretreatment of Swiss 3T3 fibroblasts with pertussis toxin reduced sphingosine 1-phosphate-induced DNA synthesis. Sphingosine 1-phosphate decreased cellular cAMP levels and also caused a drastic decrease in isoproterenol- and forskolin-stimulated cAMP accumulation. Pertussis toxin treatment prevented the inhibitory effect of sphingosine 1-phosphate on cAMP accumulation, suggesting that a pertussis toxin-sensitive Gi or Gi-like protein may be involved in sphingosine 1-phosphate-mediated inhibition of cAMP accumulation. Mitogenic concentrations of sphingosine 1-phosphate stimulated production of inositol phosphates which was inhibited by pertussis toxin, while the response to bradykinin was not affected. Furthermore, calcium release induced by sphingosine 1-phosphate, but not by bradykinin, was also attenuated by pertussis toxin treatment. However, sphingosine 1-phosphate-induced phosphatidic acid accumulation was unaffected by pertussis toxin. The increase in specific DNA binding activity of activator protein-1, which was induced by treatment of quiescent Swiss 3T3 fibroblasts with sphingosine 1-phosphate, was also inhibited by pertussis toxin. These results suggest that some of the sphingosine 1-phosphate-induced signaling pathways are mediated by G proteins that are substrates for pertussis toxin.
3T3 Cells↗
Retinal pigment epithelial repopulation in monkeys after submacular surgery.
BACKGROUND: Transplantation of retinal pigment epithelium may be a treatment for retinal diseases, such as age-related macular degeneration and hereditary macular degeneration. Before transplantation studies are undertaken, questions concerning repopulation of retinal pigment epithelial cells in situ and photoreceptor repair after submacular surgery need to be addressed. METHODS: We removed the retinal pigment epithelium from Bruch's membrane in the macaque monkey in the macula and outside the vascular arcades. This model allowed the study of in situ retinal pigment epithelium regrowth and photoreceptor repair for 9 months following débridement. RESULTS: Fluorescein angiography revealed a window defect in the area of denuded retinal pigment epithelium. Histologic studies revealed repopulated nonpigmented retinal pigment epithelial cells in the denuded areas in both the early and late periods. At 9 months, the repopulated retinal pigment epithelium was associated with repaired, normal-appearing photoreceptor outer segments. Retinal pigment epithelium regrowth was observed only if Bruch's membrane was intact. CONCLUSIONS: Repopulation of retinal pigment epithelium in the adult primate can occur rapidly and can support the repair of damaged photoreceptors following submacular surgery.
Animals↗
Degeneration and regeneration in nerve autografts and allografts.
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Humans↗
Secondary surgery following brachial plexus injuries.
The favourable treatment of post-traumatic brachial plexus lesions based on our experience of 362 cases over a 12 year period is reported. Twenty-five percent of the patients needed secondary operations. The spectrum of the latter consisted of arthrodesis, tenodesis, and musculotendinous transfer, including free neurovascular tissue transfer partially innervated by nerve transposition. Functionally, secondary tendon transfer can help to improve the effect of nerve repair techniques. To restore shoulder function the trapezius transfer (n = 22) has been used mainly; elbow flexion has been regained by pedicled latissimus dorsi translocation (n = 22), triceps-to-biceps transfer (n = 18), bipolar latissimus muscle transfer, and free neurovascular tissue transfer (n = 8). The Steindler flexorplasty was performed in four plexopathies, and finally a pedicled serratus muscle transfer was used. A unipolar latissimus dorsi transfer results in an ability to lift 10-15 kg, whilst the bipolar latissimus transfer and the triceps-to-biceps transfer produced a maximal strength of 5-8 kg. Epitrochlear flexor-pronator mass transfer produced a strength of 2-5 kg, whereas free neurovascular latissimus dorsi transfer developed a maximal muscular strength of 2-4 kg in the unipolar variation and 1-2 kg for the bipolar LD. In 97 secondary procedures to the lower arm and hand the following secondary operations were indicated: in 29 cases of radial nerve palsy transfers according to Merle d'Aubigne, a further 21 wrist tenodeses and 8 wrist arthrodeses were performed. To restore median nerve function, coupling tendon transfer (n = 4) and free neurovascular gracilis transfer (n = 3) were selected.(ABSTRACT TRUNCATED AT 250 WORDS)
Arthrodesis↗
Morphometric changes in free neurovascular latissimus dorsi flaps: an experimental study.
This study was designed to investigate regeneration of reinnervated, free transplanted muscles. We used a rat model, consisting of eight rats per group, in which the latissimus dorsi muscle was transplanted orthotopically and then harvested and evaluated after 2 and 12 weeks. Age-matched control animals were used to oppose non-operated muscles. At date of removal the patency of the vascular anastomoses was checked clinically and histologically. Electrophysiological measurements were also performed and conventional and enzyme histochemical histological slides manufactured. Two weeks after the free neurovascular flap transfer the muscle was not yet innervated, and histologically a dissolved pattern of type 1 and type IIA muscle fibres was found. The muscle fibres demonstrated a decrease of more than 50% cross-sectional area. After 12 weeks the muscles were reinnervated again; muscle contraction was positive with electrical stimulation and the cross-sectional area had regained 80% of the activity of normal muscle fibres. With enzyme histochemical staining the typical type grouping of reinnervated muscles could be demonstrated.
Animals↗
Measurements of tissue blood flow by the hydrogen clearance technique (HCT): a comparative study including laser Doppler flowmetry (LDF) and the Erlangen micro-lightguide spectrophotometer (EMPHO).
The purpose of this study was to compare the hydrogen clearance technique (HCT) with two different, well-established techniques, i.e., the laser Doppler flowmetry (LDF) and the Erlangen micro-lightguide spectrophotometer (EMPHO), for tissue blood flow measurements in an experimental setting. For the animal experiments, we chose a rat model for arterial and venous flap thrombosis, using the epigastric groin flap. Forty male dark Aguty rats were included in the study. The animals were divided into eight groups, each with a different vascular thrombotic model. HCT was used to collect 1,467 measurements, and 2,934 graphs were recorded; 27 measurements (54 graphs) had to be discarded due to faulty electrode placements and electronic noise. In 19 of the 27 discarded measurements the cause of failure was moving of the awaking animal with disruption of the decay signal. The LDF and EMPHO measurements were performed continuously during each measuring phase. Simple and multiple linear regression and paired t-tests were used to compare the three techniques. The reproducibility of registered blood flow values in phases 1, 3, 6 and 7 varied between 7.8% and 13.6% which is in about the same range as LDF and EMPHO. We could not find a significant difference between the three techniques in this regard. The correlation coefficient for HCT and LDF was r = 0.89. For HCT and EMPHO we found r = 0.67. Sensitivity and specificity values for HCT were both 1.0 in detecting arterial and venous flap thrombosis; for LDF we found values of 0.89 and 0.92, respectively. Sensitivity and specificity values for EMPHO were 0.92 and 0.95, respectively. After careful evaluation of three different techniques (HCT, LDF, and EMPHO) for measurements of local tissue blood flow we came to the conclusion that HCT must be favoured as a reliable tool for quantitative measurement of local tissue blood flow and early diagnosis of arterial and venous flap thrombosis.
Animals↗
Neonatal urinary uric acid/creatinine [correction of ceratinine] ratio as an additional marker of perinatal asphyxia.
UNLABELLED: The diagnosis and evaluation of perinatal asphyxia can be problematic and objective means of assessing its severity are lacking. To study the validity of urinary uric acid as a marker of the degree of perinatal asphyxia, the ratio of urinary uric acid to creatinine (UA/Cr) in urine specimens obtained after birth was measured in two groups of infants. Eighteen term infants with Apgar scores < or = 5 at 5 min and/or an umbilical cord blood pH < or = 7.2, and a base deficit > or = 12 meq/l were compared to 50 healthy controls. The severity of the perinatal asphyxia was determined by using an ASPHYXIA SCORE. The UA/Cr was higher in the asphyxiated group when compared to controls. (2.06 +/- 1.12, vs. 0.64 +/- 0.48; P < 0.001). Within the perinatal asphyxia group, a significant correlation was found between the UA/Cr ratio and the asphyxia score. (r = 0.86, P < 0.01). CONCLUSION: Infants with perinatal asphyxia have a significantly higher urinary UA/Cr ratio. This may be used as an indicator of the severity of perinatal asphyxia.
Asphyxia Neonatorum↗
Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.
Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia.
Administration, Oral↗
Hartmann's operation--back to the future?
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Humans↗
Chest wall reconstruction by free latissimus dorsi flap 25 years after accidental exposure to a source of industrial irradiation.
25 years after successful plastic surgical closure of a large, radiation-induced ulcer of the chest wall the patient developed recurrent ulceration and unstable scars requiring a second procedure. A quarter of a century of progress in plastic surgical procedures is demonstrated.
Adult↗
Iliac compression syndrome treated with stent placement.
Iliac compression syndrome is usually diagnosed during the third and fourth decades of life when the patient has iliofemoral deep vein thrombosis. Catheter-directed thrombolytic therapy is an accepted method of treatment for iliofemoral deep vein thrombosis, which has been reported to afford greater success with clot dissolution than with system therapy. Although this method is not new, this is the first case, to our knowledge, reporting successful treatment of computerized tomographically demonstrated iliac compression syndrome with stent placement after lysis and insufficient response to balloon angioplasty.
Constriction, Pathologic↗
Seroprevalence of HCV, HAV, HBV, HDV, HCMV and HIV in high risk groups/Frankfurt a.M., Germany.
During the period from August 1991 to April 1993, serum samples originating from different risk groups were tested for antibodies against hepatitis C virus (HCV), using a second-generation ELISA. The highest HCV seroprevalence levels were observed in haemophiliacs (87.0%) and intravenous drug abusers (IVDA) (78.9%). The HCV-seropositivity rates of polytransfused and organ transplant recipients were nearly identical (18.4% vs. 16.8%). Significantly lower HCV-seroprevalence rates were determined in chronic haemodialysis patients (8.1%) and homo/bisexuals (10.0%). The lowest HCV seroprevalence levels were found in the groups of female prostitutes (1.4%) and health care staff (0.8%). A strong correlation between HCV seropositivity and the presence of antibodies against HIV-1, HBc and HCMV was observed. There was also an association between HCV seropositivity and HAV. The seroprevalence of HDV and the proportion of HBsAg and HBeAg carriers was not significantly influenced by HCV serostatus. The incidence of HCV infection in renal transplant recipients was 3.9%. In 10 (6.5%) patients, anti-HCV seroconversion was observed in the immediate post-transplantation period followed by a decrease of the index value and finally, disappearance of antibodies at the end of the study. Antibodies passively acquired through intravenous immunoglobulin (IVIG) donation may account for overestimation of HCV seroprevalence in retrospective seroepidemiological surveys as established by our findings.
Adolescent↗
Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study.
Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.
Antineoplastic Combined Chemotherapy Protocols↗
Preservation of peripheral nerve grafts: a comparison of normal saline, HTK organ preservation solution, and DMEM Schwann cell culture medium.
The regeneration of peripheral nerve grafts was evaluated in a rat model, after pretreating the grafts with Schwann cell culture medium, HTK organ preservation solution, and normal saline, under cold ischemic conditions for different time periods. Following orthotopic replantation of the grafts into donor animals, the quality of regeneration was assessed after 6 weeks, compared to positive controls (autologous transplantation) and negative controls (acellular grafts). The regenerative quality in the Schwann cell culture groups with ischemic periods of 32 and 72 hr was comparable to normal controls. Significantly minor regeneration was detected in specimens undergoing 14 and 120 hr of ischemia in the Schwann cell culture medium and in the HTK and normal saline groups, regardless of ischemic time. Among the conclusions was that controlled proliferation of Schwann cells seems to be a basic principle for preservation of peripheral nerve grafts.
Animals↗
Macromolecular mechanisms of sputum inhibition of tobramycin activity.
Tobramycin, an aminoglycoside antibiotic, is used in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis patients. Tobramycin bioactivity, however, is antagonized by sputum. Glycoproteins (mucins) and high-molecular-weight DNA make up 2 to 3% (P. L. Masson and J. F. Heremans, p. 412-475, In M. J. Dulfano, ed., Sputum: Fundamentals and Clinical Pathology, 1973) and 3 to 10% (W. S. Chernick and G. J. Barbero, Pediatrics 24:739-745, 1959, and R. Picot, I. Das, and L. Reid, Thorax 33:235-242, 1978) of the dry weight of sputum, respectively. tobramycin binds to both mucins and DNA obtained from sputum (R. Ramphal, M. Lhermitte, M. Filliat, and P. Roussel, J. Antimicrob. Chemother. 22:483-490, 1988). In vitro, recombinant human DNase (rhDNase) hydrolyzes high-molecular-weight DNA of > 50 kb within sputum to fragments of 2 to 4 kb. Studying dialyzable tobramycin, we examined drug binding to whole sputum and to "mock sputum," which consisted of porcine gastric mucin and calf thymus DNA. We also studied the effects of rhDNase treatments of sputum, mock sputum, and calf thymus DNA on tobramycin binding. We found that treatments of sputum, mock sputum, and calf thymus DNA with rhDNase did not significantly increase the tobramycin bioactivity within the dialysates; surprisingly, sputum binding of tobramycin was increased by rhDNase. We conclude that rhDNase does not increase the bioactivity of tobramycin in sputum.
Adult↗
[Updated status of replantation services in Germany, Austria and Switzerland].
The revised survey involves the years 1991 and 1992 and includes 41 university and major civil hospitals. As in the years 1989 and 1990, replantation activity in the year 1991 still declined, whereas in 1992 we registered a sharp increase in replantations, especially in Germany. In numbers, 856 were reported for 1991 (72 macro- and 784 microreplantations), and 1091 in 1992 (85 macro- and 1006 microreplantations). A considerable number of amputation cases (617) were rejected mainly due to lack of operative manpower capacity.
Austria↗