bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Long-Term Effects of Heroin-Assisted Treatment: The Results of a 6-Year Follow-Up
Authors: Güttinger Franziska , Gschwend Patrick , Schulte Bernd , Rehm Jürgen , Uchtenhagen Ambros
Published: April 2003

Since January 1994, heroin-assisted treatment for opiate addicts has been available in Switzerland. This is the first report of the long-term effects of this form of treatment. The report examines subjects who entered a study involving medical prescription of opiates (Projekt zur ärztlichen Verschreibung von Betäubungsmitteln; PROVE) in Switzerland between January 1994 and March 1995 (n = 366). Opiates were dispensed in eight treatment centres. A follow-up was conducted 6 years after treatment entry. Two groups were assessed: clients who have continuously been on heroin-assisted treatment since entry into the PROVE study or who re-entered this treatment, and ex-clients who had discontinued heroin-assisted treatment at the time of follow-up. Two kinds of comparisons were conducted. Firstly, conditions at treatment entry were compared to 6-year follow-up outcomes, and secondly, outcomes were compared between clients still on heroin-assisted treatment and those who had been discharged. It was found that 46% of the clients still alive were on heroin-assisted treatment at the time of follow-up. A comparison of the present living conditions showed very little difference between those in treatment and those who had terminated treatment. Compared to the situation at entry, the results of the follow-up showed a significant decrease in the use of illegal substances, illegal income and most other variables concerning social conditions, but they also showed an increase in unemployment and reliance on social benefits. Heroin-assisted treatment is thus efficacious in the long-term course of treatment and is still effective after termination of treatment with respect to living conditions and use of illicit substances.
Simultaneous Laparoscopic Cholecystectomy and Percutaneous Papillary Balloon Dilatation for Cholecystocholedocholithiasis
Authors: Chikamori Fumio , Kuniyoshi Nobutoshi , Shibuya Susumu , Takase Yasuhiro
Published: April 2003

Aim: We evaluated the effectiveness of simultaneous laparoscopic cholecystectomy (LC) and percutaneous papillary balloon dilatation (PPBD) under general anesthesia in the treatment of cholecystocholedocholithiasis in elderly patients in poor general condition. Patients and Methods: We treated 17 patients (group 1) with LC and PPBD as separate procedures and 21 patients (group 2) with simultaneous LC and PPBD under general anesthesia. We compared the success rates, complications, durations of percutaneous transhepatic biliary drainage (PTBD) and hospital stays of the 2 groups. Results: The stones were successfully pushed out into the duodenum in all patients in both groups. All patients in group 1 complained of transient pain caused by balloon dilatation of the papilla. In group 2, PPBD was performed comfortably in all patients because of the general anesthesia. The mean postoperative stay of patients in both groups was 9 days. The overall duration of the hospital stay and the duration of PTBD were 28 ± 5 and 25 ± 9 days, respectively, in group 1, and 18 ± 7 and 15 ± 8 days in group 2 (significant difference: p < 0.01 and p < 0.01, respectively). There were no deaths or major complications, although transient hyperamylasemia occurred in both groups. Conclusions: Cholecystocholedocholithiasis can be treated by simultaneous LC and PPBD under general anesthesia without laparotomy, sphincterotomy, choledochotomy or the discomfort arising from papillary dilatation.
Serum of Patients with Behçet’s Disease Induces Classical (Pro-Inflammatory) Activation of Human Macrophages in vitro
Authors: Alpsoy E. , Kodelja V. , Goerdt S. , Orfanos C.E. , Zouboulis Ch.C.
Published: April 2003

Background: Although several immunological abnormalities have been demonstrated in Behçet’s disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation. Objective: To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro. Methods: Serum of 15 patients (8 women, 7 men; mean age 33 ± 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients’ serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or γ-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcγRI: CD64) and class III receptor binding the Fc part of IgG (FcγRIII: CD16). Results: Macrophages treated with patients’ serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease. Conclusion: Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.
Malignant Melanoma Arising in a Radiotherapy Field: Report of Two Cases and Review of the Literature
Authors: Trefzer U. , Voit C. , Milling A. , Audring H. , Sterry W.
Published: April 2003

We report 2 patients who developed melanoma or melanoma metastases in radiation fields 6 and 43 years after radiation therapy, respectively. One of the patients had received adjuvant hyperfractionated photon therapy for Ewing sarcoma, while the other patient had received X-ray therapy for a hemangioma. While postradiation secondary cancers with a long latency period are not uncommon, the development of melanoma is exceedingly rare.
Measurement of Electrical Current Perception Threshold of Sensory Nerves for Pruritus in Atopic Dermatitis Patients and Normal Individuals with Various Degrees of Mild Damage to the Stratum corneum
Authors: Kobayashi Hiromi , Kikuchi Katsuko , Tsubono Yoshitaka , Tagami Hachiro
Published: April 2003

Background: Patients with atopic dermatitis (AD) are well known to be sensitive to irritation from the environment due to the impaired function of the stratum corneum (SC). Electrical current perception threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of the sensory nerves. Objective: To study the CPT in a noninvasive fashion using Neurometer® CPT/C, together with measurements of various functions of the SC. Methods: We measured the CPT on the flexor forearm and cheek of AD patients and normal individuals. Subsequently, we evaluated the CPT and skin sensitivity to a 30% aqueous solution of lactic acid after the infliction of various mildly disruptive measures on the SC on the flexor forearm of healthy individuals by the following three methods: (1) removal of the superficial sebum with acetone/ether, (2) scarification with a needle and (3) tape stripping of the SC. Finally, we examined the effect of topical applications of emollients such as petrolatum or a moisturizing cream to the scratched skin. Results: AD patients showed a lower barrier function and lower CPT than normal individuals. In subsequent studies conducted in normal individuals, the CPT was found to be inversely correlated with transepidermal water loss (TEWL) levels after tape stripping. However, most of all, the partial superficial scarification with a needle decreased the CPT and increased the lactic acid stinging response. Prolonged removal of lipids from the SC with acetone/ether for 30 min that increased the TEWL levels for only 1 day decreased the high-frequency conductance value for 2 days and the CPT only on the 2nd day after treatment. Topical applications of emollients were effective to prevent the increased sensitivity caused by scratching. Conclusions: AD patients showed functional abnormalities of the SC and tended to have more sensitive skin on the cheek and flexor forearm than healthy controls. Even focal SC damage caused by superficial cracking may lead to further disruption of the already damaged SC in AD patients, by eliciting scratching and facilitating the permeation of various environmental allergens and also the induction of hypersensitive skin.
Neonatal Coagulopathy in Preterm, Small-for-Gestational-Age Infants
Authors: Hannam Simon , Lees Christoph , Edwards Rebecca J. , Greenough Anne
Published: April 2003

Our aim was to determine if antenatal hypoxia was associated with liver dysfunction and coagulation abnormalities in small-for-gestational-age (SGA) infants. Sixteen SGA infants, median gestational age 30 (range 26–32) weeks, who consecutively had had umbilical artery Doppler studies in the week before delivery, were compared to appropriate-for-gestational-age (AGA) controls, who were each matched to an SGA infant for gestational age. The median international normalised ratio (INR) was significantly higher (1.9 vs. 1.3, p < 0.001) and the neutrophil (p = 0.003) and platelet counts (p < 0.001), alkaline phosphatase (p < 0.001) and albumin (p < 0.02) levels significantly lower in the SGA compared to the AGA group. The umbilical artery pulsatility index (PI) was elevated, indicating antenatal hypoxia, in all but 1 of the SGA infants. Multiple linear regression analysis demonstrated that the INR was significantly related to the umbilical artery PI independent of the other variables (p = 0.0002, R2 = 0.71). These results suggest that the coagulopathy seen in preterm SGA infants might at least be partially explained by antenatal hypoxia affecting the liver and hence vitamin K-dependent coagulation.
Cyclic ADP-Ribose Contributes to Contraction and Ca2+ Release by M1 Muscarinic Receptor Activation in Coronary Arterial Smooth Muscle
Authors: Ge Zhi-Dong , Zhang David X. , Chen Ya-Fei , Yi Fu-Xian , Zou Ai-Ping , Campbell William B. , Li Pin-Lan
Published: April 2003

The present study determined the role of cyclic ADP-ribose (cADPR) in mediating vasoconstriction and Ca2+ release in response to the activation of muscarinic receptors. Endothelium-denuded small bovine coronary arteries were microperfused under transmural pressure of 60 mm Hg. Both acetylcholine (ACh; 1 nmol/L to 1 µmol/L) and oxotremorine (OXO; 2.5–80 µmol/L) produced a concentration-dependent contraction. The vasoconstrictor responses to both ACh and OXO were significantly attenuated by nicotinamide (Nicot; an ADP-ribosyl cyclase inhibitor), 8-bromo-cADPR (8-Br-cADPR; a cADPR antagonist) or ryanodine (Ry; an Ry receptor antagonist). Intracellular Ca2+ ([Ca2+]i) was determined by fluorescence spectrometry using fura-2 as a fluorescence indicator. OXO produced a rapid increase in [Ca2+]i in freshly isolated single coronary arterial smooth muscle cells (CASMCs) bathed with Ca2+-free Hanks’ solution. This OXO-induced rise in [Ca2+]i was significantly reduced by pirenzepine (PIR; an M1 receptor-specific blocker), Nicot, 8-Br-cADPR or Ry. The effects of OXO on the activity of ADP-ribosyl cyclase (cADPR synthase) were examined in cultured CASMCs by measuring the rate of cyclic GDP- ribose (cGDPR) formation from β-nicotinamide guanine dinucleotide. It was found that OXO produced a concentration-dependent increase in the production of cGDPR. The stimulatory effect of OXO on ADP-ribosyl cyclase was inhibited by both PIR and Nicot. These results suggest that the cADPR signaling pathway participates in the contraction of small coronary arterial smooth muscle and Ca2+ release induced by activation of M1 muscarinic receptors.
The Roles of Nitric Oxide in Dilating Proximal and Terminal Arterioles of Skeletal Muscle during Systemic Hypoxia
Authors: Edmunds N.J. , Marshall Janice M.
Published: April 2003

Indirect evidence suggests that dilatation evoked by systemic hypoxia in proximal and terminal arterioles of skeletal muscle is mediated by adenosine acting on A1 receptors, but that the dilatation of proximal arterioles requires the presence of nitric oxide (NO), whereas that of terminal arterioles is mediated by NO. In the present study, we showed that primary and terminal arterioles of spinotrapezius muscle (diameters: 45 ± 4 and 9 ± 1 µm, respectively) in anaesthetised rats dilated by 15 ± 7 and 48 ± 24%, respectively, during hypoxia (breathing 12% O2). Inhibition of NO synthesis with intravenous nitro-L-arginine methyl ester attenuated these responses (to –2 ± 3 and –4 ± 4%, respectively). However, when a tonic level of NO was subsequently restored by infusion of NO donor, hypoxia evoked dilatation of primary arterioles (+24 ± 8%) but not terminal arterioles (0 ± 4%). The adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (intravenous) attenuated this ‘restored’ primary arteriolar vasodilatation (to +6 ± 3%). Similar results were obtained with 8% O2. We propose that (1) proximal arteriolar dilatation evoked by systemic hypoxia depends on a background level of NO, which facilitates the action of adenosine on A1 receptors, and (2) hypoxia-evoked dilatation of terminal arterioles is mediated by NO synthesised via A1 receptor stimulation.
Isoprostane 8-Epi-Prostaglandin F2α Decreases Lymph Capillary Pressure in Patients with Primary Lymphedema
Authors: Amann-Vesti Beatrice R. , Gitzelmann Gabriele , Koppensteiner Renate , Franzeck Ulrich K.
Published: April 2003

In patients with lymphedema, reduced lymph drainage capacity results in an overloaded superficial microlymphatic network and microlymphatic hypertension. In in vitro experiments, it has been shown that 8-epi-prostaglandin F2α (PGF) induced contractions in human lymphatics. Since lymphatic contractility plays a crucial role in the regulation and generation of lymph transport, we studied the effect of PGF on microlymphatic dynamics by measuring lymph capillary pressure (LCP). Twenty healthy volunteers and 13 patients with primary lymphedema were studied after either PGF or placebo was applied to the skin and occlusively covered for 30 min. Glass micropipettes (7–9 µm) were inserted under microscopic control into initial lymphatics visualized by fluorescence microlymphography and pressure measurements were performed using the servo-nulling technique. The mean LCP in patients with lymphedema was significantly higher (19.8 ± 12.1 mm Hg) than that in healthy controls (8.4 ± 4.1 mm Hg) at the placebo-treated site and decreased to normal values after PGF (10.0 ± 7.7 mm Hg). In healthy volunteers, there was no significant decrease of LCP with PGF compared to placebo. PGF normalizes microlymphatic hypertension in patients with lymphedema by improving lymph transport into deeper channels.
Impact of Epidermal Growth Factor and Transforming Growth Factor Beta-1 on the Release of Fibrinolytic Factors from Cultured Endometrial and Ovarian Endometriotic Stromal Cells
Authors: Guan Yong-Mei , Carlberg Magdalena , Bruse Christine , Bergqvist Agneta
Published: April 2003

We have investigated whether there are any differences in the release of urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) from cultured endometrial and endometriotic stromal cells, and whether the release is regulated by epidermal growth factor (EGF) or transforming growth factor β1 (TGFβ1). The cells were isolated from endometriomas and endometrium from women with and without endometriosis. After treatment with EGF or TGF and in untreated controls, incubated media collected at 0, 24, 48 and 72 h were analyzed by ELISA. Stromal cells from all three types of tissues released uPA and PAI-1, but the soluble receptor of uPA was not measurable in any group. The basal release of uPA and PAI-1 from endometriotic cells was higher than from endometrial cells. The uPA release in endometriotic cells was reduced with and without the addition of EGF (p < 0.05) or TGFβ1 (p < 0.05). EGF increased the release of PAI-1 from stromal cells from women without endometriosis (p < 0.05) but decreased the release of PAI-1 from stromal cells from endometriotic women (p < 0.05). TGFβ1 increased the release of PAI-1 from endometriotic cells (p < 0.05) but had no effect in endometrial cells.
Management of Central Retinal Vein Occlusion
Authors: Hayreh Sohan Singh
Published: April 2003

The management of central retinal vein occlusion (CRVO) is discussed briefly. Since the prognosis, complications, visual outcome and management of nonischemic and ischemic CRVO are very different, the first essential step in the management of CRVO is to determine which type of CRVO one is dealing with. The various parameters which help to differentiate the two types reliably are described briefly. In this connection, the most important thing to remember is that the conventional, very prevalent use of a 10-disc area of retinal capillary obliteration is an invalid parameter to differentiate ischemic from nonischemic CRVO, or to predict ocular neovascularization (NV). Ocular NV is a complication of ischemic CRVO only. Relevant issues about the natural history of CRVO are summarized; the natural history of the disease must not be mistaken for a beneficial effect of treatment. Various advocated modes of treatment of CRVO and their relative merits are discussed, particularly photocoagulation, which is widely advocated. Controversies with regard to various aspects of CRVO management are examined. Finally, it is noted that apart from routine systemic and hematologic evaluations, the vast majority of patients with CRVO do not need an extensive and expensive workup. In conclusion, in spite of enthusiastic claims of success for various therapies, the reality is that we currently have practically no proven safe and effective treatment for CRVO.
Inhibitory Effects on Selected Oral Bacteria of Antibacterial Agents Incorporated in a Glass Ionomer Cement
Authors: Botelho Michael G.
Published: April 2003

The objectives of the study were to investigate the antimicrobial efficacy, over time, of combining antibacterial agents with a glass ionomer cement (GIC). This was assessed using an agar diffusion test. Chlorhexidine hydrochloride, cetylpyridinium chloride, cetrimide and benzalkonium chloride were added to Fuji IX GIC at 0, 1, 2 and 4% w/w. Antibacterial-GIC specimens were placed onto agar plates inoculated with one of six bacterial species (Streptococcus, Lactobacillus and Actinomyces, two each) and the area of inhibition calculated after 24 h incubation. The experiment was repeated weekly and at week 11 the surface of the specimen was abraded prior to replacing on inoculated agar plates. Control specimens of the GIC produced no bacterial inhibition. The antibacterial-GIC combination specimens showed significant inhibition which decreased at different rates over the test period. Resurfacing of the specimens showed a dramatic increase of antibacterial action similar to levels produced on week 1. CT-GIC showed the greatest (p < 0.005) inhibitory effect throughout the experimental period for 4 out of 6 test bacteria. The addition of antibacterial agents to Fuji IX creates a GIC material with significant antimicrobial action in vitro which is dependent on concentration and type of antibacterial agent, and appears to be associated primarily with a release of the antibacterial from the surface layer of the specimen.
Chromosomal Insertions and Deletions in Streptococcus mutans
Authors: Robinson W.G. , Old L.A. , Shah D.S.H. , Russell R.R.B.
Published: April 2003

Many isolates of Streptococcus mutans lack the ability to ferment melibiose and other sugars. We previously reported that this was commonly due to a chromosomal deletion and, in the present study, sequence information from the S. mutans genome project was used to design PCR primers to explore the nature and extent of the deletion. In all melibiose-negative strains examined, there was an incomplete insertion element, ISSmu3, in place of the 18-kb stretch of chromosome encoding the msm and gal operons. Strains that were also unable to utilise β-glucosides were found to have a separate 4 kb deletion in the bgl regulon that is proposed to be due to homologous recombination between two short stretches of identical sequence. The evidence is consistent with all the melibiose-negative strains examined being derived from a common ancestor.
Response to Cisplatin-Etoposide Treatment and Survival in Patients with Small-Cell Lung Cancer in North Lebanon
Authors: Kalaajieh Wassim Khalil
Published: April 2003

Objective: To study the clinical features of small-cell lung cancer (SCLC) cases diagnosed in adults in North Lebanon. Patients and Methods: Descriptive analysis of 125 SCLC cases diagnosed in a tertiary care hospital in North Lebanon. Results: One hundred and twenty-five patients diagnosed with SCLC comprised the study group; 109 male and 16 female patients aged from 35 to 84 years with a mean age of 56 ± 7.4 years. 95.4% of male and 31.2% of female patients were current smokers. The most frequent symptoms were cough, dyspnea, and chest pain in 24.8, 18.4, and 16.8%, respectively. Staging procedures were performed in all patients: 49 (39.2%) patients had limited stage (LS) and 76 (60.8%) patients had extensive stage (ES) disease. Metastasis was most frequent to bones (40.8%) followed by liver (24.8%) and brain (14.4%). The response rates, including both complete and partial responses to therapy, were 80, 41.5, and 52% for LS, ES, and overall patients, respectively. Median survival was 311, 163, and 201 days for LS, ES, and overall patients, respectively. Conclusion: Clinical features of the patients were very similar to those reported in the literature except that there were lower median survival values and response rates to treatment, including both complete and partial responses for both LS and ES disease. The results should be considered preliminary with regard to the activity of the chemotherapy regimen, given the statistical limitation of the small number of patients.
Three-Year Prospective Randomized Study of Incidence of Posterior Capsule Opacification in Eyes Treated with Topical Diclofenac and Betamethasone
Authors: Tsuchiya Tadaharu , Ayaki Masahiko , Onishi Takeo , Kageyama Toshiyuki , Yaguchi Shigeo
Published: April 2003

Purpose: To investigate the incidence of posterior capsule opacification (PCO) in eyes treated with diclofenac sodium (DFNa) and betamethasone phosphate (BMS) ophthalmic solutions. Methods: A total of 200 eyes with silicone intraocular lens implantation were treated with topical agents for 3 months postoperatively. Twenty-six cases of the DFNa group and 34 of the BMS group met the criteria, and the severity of PCO was evaluated after 3 years. Results: The results of axial densitometry by Scheimpflug photography were 27.8 computer-compatible tapes (CCT) in the DFNa-treated group and 32.6 CCT in the BMS-treated group (p = 0.1539). Posterior capsulotomy was performed in 11.5% of the DFNa group and 17.6% of the BMS group (p = 0.8375). The photographic grading of PCO showed no difference. Conclusion: The incidence of PCO in eyes treated with DFNa appears to be equal to that after BMS treatment.
Ocular Delivery of Acetylsalicylic Acid by Repetitive Coulomb-Controlled Iontophoresis
Authors: Kralinger Martina T. , Voigt Monika , Kieselbach Gerhard F. , Hamasaki Duco , Hayden Brandy C. , Parel Jean-Marie
Published: April 2003

To investigate the potential of transscleral coulomb-controlled iontophoresis (CCI) for repetitive delivery of acetylsalicylic acid (ASA) into the eye, a total of 50 rabbits was included in this study. Fourteen animals received serial CCI treatment. Fourteen animals underwent CCI with either ASA or balanced salt solution (BSS) for at least 6 days at 24- and 48-hour intervals. Eighteen animals received a single CCI application, while 18 animals were injected with 15 mg ASA/kg body weight intravenously. HPLC analysis was performed to determine the levels of salicylic acid (SA) in ocular tissues. Apart from clinical follow-up, 2 rabbits in the ASA and BSS groups were examined by electroretinography, and 2 animals were examined histologically. Though high concentrations of SA were measured, no alterations were observed clinically, histologically and electrophysiologically. Repetitive CCI demonstrated its potential as a topical drug delivery system for ASA into the eye. This transscleral delivery of ASA resulted in significant and sustained intraocular concentrations of SA without side effects. Iontophoresis may be advantageous in clinical administration maintaining therapeutic levels of ASA while avoiding adverse effects associated with the systemic administration of nonsteroidal anti-inflammatory drugs.
Aktuelle Konzepte zur Alterungsprävention
Authors: Gruber Christian , Huber Johannes C.
Published: April 2003

«Anti-Aging» bedeutet keineswegs, das Leben mit Gewalt und mit Mühe um einige Monate zu prolongieren. Die «Anti-Aging-Medizin» soll die zweite Lebenshälfte so optimieren, dass man ohne chronische Gesundheitsschäden auch im höheren Alter eine gute Lebensqualität geniessen kann. Sinnvolle Strategien zur Alterungsprävention müssen daher in viele wichtige Lebensbereiche eingreifen. Dementsprechend verwenden wir in Wien derzeit ein 4-Säulen-Programm, das interdisziplinär den Patienten angeboten wird. Das Programm besteht aus den Säulen «Lifestyle-Modifikation», «Kalorienrestriktion», «Phytotherapeutika» und der individualisierten Hormonersatztherapie. Von der Weltgesundheitsorganisation liegen Untersuchungen vor, nach denen ab dem Jahr 2010 mit einem sprunghaften Anstieg der über 85jährigen gerechnet werden muss. Eine Medizin, die sich um die zweite Lebenshälfte kümmert, egal ob sie «Anti-Aging-» oder «Präventivmedizin» getauft wird, wird in Zukunft unverzichtbar sein.
Anti-Aging oder ‘Better Aging’ – Ein Beitrag zur Alterungsprävention?
Authors: Haller U. , Hepp H. , Winter R.
Published: April 2003

Anti-Aging will die Qualität der zweiten Lebenshälfte so beeinflussen, dass chronische Gesundheitsschäden auch im höheren Alter bei hoher Lebensqualität vermieden werden können. So soll auch auf Grund von molekularbiologischen Tests die Grundlage für eine individualisierte, präventive Hormontherapie gelegt werden. Dabei stellt sich die Frage, ob aus dem Muster der Polymorphismen für die einzelne Frau bereits ein Risikoprofil für Störungen des Hormonhaushaltes im Klimakterium erkannt werden kann, nachdem eine wissenschaftliche Evidenz bis jetzt nicht nachgewiesen ist. Auch das Thema der Adrenopause, welche u.a. als alterstypische, partielle Nebenniereninsuffizienz charakterisiert ist, darf im Zusammenhang mit dem Anti-Aging-Problem nicht unerwähnt bleiben.
Physical Performance Effects of Low-Intensity Exercise among Clinically Defined High-Risk Elders
Authors: DeVito Carolee A. , Morgan Robert O. , Duque Maurice , Abdel-Moty Elsayed , Virnig Beth A.
Published: April 2003

Background: Falls are among the leading causes of injuries and deaths. Results from a number of studies have suggested that a community-based exercise program may be effective in improving lower body strength, although some have shown only limited improvements. However, the impact of these programs on gait and balance are equivocal. Further, studies that have specifically targeted deconditioned elderly individuals, rather than individuals drawn from the general community, either showed limited or no improvements in gait and balance. Objective: This study examined the effectiveness of a community-based, short-term, low-intensity exercise intervention strategy on measures of mobility skills, gait and balance, and muscle strength for a clinically targeted group of elderly individuals at high risk of falls. Methods: 245 men and women aged 60 years or older were randomized into either an intervention or control group and received a baseline (T1) assessment. Subjects in the intervention group received up to 24 sessions (45 min long) of low-intensity standard exercise modalities tailored to the individual patient over an 8- to 10-week period. At the conclusion of the program, the participants in the intervention group were instructed to continue performing the exercises at home until 1 year after T1. Measures of physical function and performance were collected for all subjects at three different points of study enrollment. Results: Of the subjects assessed at baseline, 138 (56%) also had a postintervention assessment (T2), 128 (52%) had a 6-month follow-up assessment (T3), and 105 subjects had assessments at all time points. Primary analyses were based on the 105 subjects who had assessments at all time points. Intervention and control subjects did not differ in any of the physical function or performance measures at baseline. Between T1 and T2, the intervention subjects showed significantly greater improvement than the control subjects on all outcomes, with improvements plateauing for most measures between T2 and T3. Gait and balance scores continued to improve throughout the study period for both groups of subjects. Conclusions: This easily implemented, low-intensity exercise program may lead to improvements in physical functioning that are retained over the long term and effectively targets a clinically defined population of deconditioned elders at high risk of falling and sustaining serious injury.
Altered Plasma Nerve Growth Factor-Like Immunoreactivity and Nerve Growth Factor-Receptor Expression in Human Old Age
Authors: Antonelli A. , Bracci-Laudiero L. , Aloe L.
Published: April 2003

Background: Nerve growth factor (NGF), discovered because of its action on cells in the peripheral and the central nervous system, is now known to act also on immune cells in developing and adult subjects. Whether peripheral lymphocytes of aged subjects are responsive to this molecule is less clear. Objective: Aim of our study was to investigate whether or not plasma NGF undergoes any significant changes during aging and whether or not NGF receptors on peripheral lymphocytes are affected in old subjects. Methods: To address these questions, we used RT-PCR, immunohistochemistry, and immunoenzymatic analysis to evaluate the expression of NGF receptors in human peripheral lymphocytes and NGF-like immunoreactivity. Results: These results revealed a low amount of NGF in the plasma of old subjects associated with a reduced expression of mRNA for NGF receptor trkA in peripheral lymphocytes. They also showed elevated levels of circulating interleukin-1beta (IL-1β), and interleukin-6 (IL-6) in the bloodstream of adult and aged subjects. Conclusion: Our data indicate that peripheral lymphocytes are targets for circulating NGF and suggest that changes in NGF-receptor expression on lymphocytes might be potential marker for aging lymphocytes.
Discontinuous Variability of Brain Composition among Domestic Chicken Breeds
Authors: Rehkämper Gerd , Kart Emriye , Frahm Heiko D. , Werner Christian W.
Published: April 2003

In 80 domestic chickens from 8 breeds, the volumes of 12 brain parts were identified as dimensions in a cluster analysis. Based on Euclidean metrics and the Ward algorithm at least 2 groups were found that are congruent with the breeds ‘White Crested Polish chicken’ and ‘Breda’, although the breed identity was not a variable used in the cluster analysis. Domestication is interpreted as evolution which includes the possibility of speciation. It is hypothesized that White Crested Polish chickens and Bredas are becoming new species in terms of a biospecies concept.
Left Ventricular Mechanical Unloading Restores Beta-2-Adrenergic Receptor mRNA Expression and Decreases Susceptibility to Ischemia and Reperfusion in the Failing Heart
Authors: Nakahara K. , Horimoto H. , Nakai Y. , Mieno S. , Nomura Y. , Sasaki S.
Published: April 2003

Objectives: Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of failing LV, resulting in improved myocyte contractility. This study was designed to examine effects of LV unloading on β-adrenergic receptor (BAR) expression and ischemic susceptibility to ischemia reperfusion. Methods: Five groups were studied: group 1 [unloading myocardial infarction (MI), n = 6], MI hearts 2 weeks after coronary ligation subjected to LV unloading by heterotopic heart transplantation for 2 weeks; group 2 (2-week MI, n = 6), MI hearts left for 2 weeks without unloading; group 3 (4-week MI, n = 6), MI hearts left for 4 weeks without unloading; group 4 (control, n = 6), normal (non-MI) hearts as a control with no interventions, and group 5 (unloading control, n = 5), normal (non-MI) hearts subjected to LV unloading for 2 weeks.Then, all hearts were isolated and subjected to 20 min of global ischemia and 60 min of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. Either total BAR density or β2-adrenergic receptor (B2AR) mRNA expression in the noninfarcted myocardium was determined by radioligand binding assays or real-time quantitative RT-PCR, respectively. Results: LV unloading improved postischemic functional recovery (unloading MI vs. 2-week MI vs. 4-week MI: 74 ± 6 vs. 54 ± 5 vs. 51 ± 4%; p < 0.05 vs. unloading MI). LV unloading restored B2AR mRNA expression (unloading MI vs. 2-week MI vs. 4-week MI: 4.78 ± 0.21 vs. 2.80 ± 0.19 vs. 2.24 ± 0.17 × 107 copy/µg total RNA; p < 0.05 vs. unloading MI). Conclusion: LV mechanical unloading restored B2AR mRNA expression and improved postischemic functional recovery.
Acceleration of Gastric Ulcer Healing by Omeprazole in Portal Hypertensive Rats
Authors: Takeuchi Y. , Kitano S. , Bandoh T. , Matsumoto T. , Baatar D. , Kai S.
Published: April 2003

Background: Gastric ulcer healing is delayed in patients with portal hypertension (PHT) and often responds poorly to histamine H2 blockers. Although proton pump inhibitors are more effective anti-ulcer agents, there is little information regarding their efficacy for gastric ulcer in cases of PHT. Therefore, we investigated the effects of a proton pump inhibitor, omeprazole, on the healing of acetic-acid-induced gastric ulcer in PHT rats. Methods: Animals studied were 80 male Sprague-Dawley rats aged 7 weeks, of which half underwent two-staged portal vein ligation (PHT rats) and half underwent a sham operation (SO rats). Gastric ulcers were induced by acetic acid. Starting from day 4 after ulcer induction, rats received omeprazole or vehicle orally (50 mg/kg) for 5 or 10 days. Ulcer area, proliferating cell nuclear antigen labelling index (PCNA LI), and serum gastrin levels were recorded. Results: PHT significantly inhibited epithelial cell proliferation and delayed gastric ulcer healing as indicated by a decreased PCNA LI at the ulcer margin and almost 2-fold larger ulcer area in PHT versus SO rats 14 days after ulcer induction. Ten-day treatment with omeprazole (vs. vehicle) significantly accelerated ulcer healing to a similar extent in both PHT and SO rats. Serum gastrin levels were significantly higher in PHT rats than in SO rats following treatment with omeprazole. Omeprazole (vs. vehicle) restored the decreased PCNA LI at the ulcer margin in PHT rats to that noted in SO rats. Conclusions: In PHT rats, omeprazole accelerates gastric ulcer healing, stimulates epithelial cell proliferation at the ulcer margin, and increases serum gastrin levels. Since gastrin is a potent stimulator of gastric epithelial cell proliferation, increased serum gastrin levels may be an important factor in omeprazole-induced stimulation of epithelial cell proliferation and acceleration of gastric ulcer healing in conditions of PHT.
Classical Friedreich’s Ataxia and Its Genotype
Authors: Martin J.-J. , Martin L. , Löfgren A. , D’Hooghe M. , Storm K. , Balemans W. , Palau F. , van Broeckhoven C.
Published: April 2003

Fourteen patients with classical features of Friedreich’s ataxia (FRDA) were examined. The clinical diagnosis of FRDA was afterwards confirmed in all patients by the appropriate DNA investigation which showed markedly increased amounts of GAA repeats on both alleles of the frataxin gene. None of our patients presented with atypical features such as late-onset FRDA, FRDA with retained deep tendon reflexes or with a very slow course. Five of them are not yet confined to a wheelchair. But for 1 patient who died at age 36 years and had the largest number of GAA repeats on both alleles, there was no significant correlation between number of repeats in the shortest allele, age at onset, age at wheelchair dependence, duration of the disease and main clinical signs. All patients but 3 had between 500 and 1,050 GAA repeats. The 3 patients with, respectively, 400, 450 and 500 repeats on the shortest allele had a clinical course comparable to the other patients. Even in the case of variations in the number of repeats in the same sibship, there were only modest differences between the siblings concerning age at onset of the disease, symptoms and signs and age at wheelchair dependence. There were no qualitative differences in the main clinical features and laboratory investigations in the full-blown phase of the disorder. Molecular biology has become a major element in the diagnosis of FRDA. DNA testing for FRDA should be applied to every case of idiopathic autosomal recessive or sporadic ataxia. However, the clinical features of FRDA remain fully characteristic in many patients and keep their diagnostic value.
Influence of an Interferon Inducer on Bone Marrow Transplant Reconstitution in Irradiated, Leukemic Mice: Elevated Natural Killer Cell Numbers and Improved Life Span
Authors: Currier N.L. , Miller S.C.
Published: April 2003

Interferon-γ and interferon inducers such as polyinosinic-polycytidylic acid (poly I:C) promote natural-killer (NK)-cell-mediated killing of a wide range of tumor cells both in vitro and in vivo. The aim of the present work was to administer poly I:C to irradiated, leukemic mice, both before and after syngeneic bone marrow transplant with the intent of boosting the host’s natural immunity in the critical peritransplant period. Briefly, DBA/2 mice were injected with Friend-virus-induced erythroleukemia cells. After 5 days of tumor growth, some mice received daily injections of poly I:C for the next 4 days while control, leukemic mice received the saline vehicle only. All mice were then irradiated (450 R × 2 at 4-hour intervals) and transplanted 1 day following irradiation with bone marrow from age- and sex-matched, normal DBA/2 donor mice. After transplant, daily injections of poly I:C (or vehicle) continued for 8 more days. On day 9 after transplant, treated and control mice were killed, and the total cellularity, total numbers of lymphoid cells, the total numbers of NK cells (identified by the presence of an immuno-labelled, specific cell surface marker) were obtained from both the spleen and the bone marrow. Other identically treated mice subjected, however, to several additional rounds of poly I:C treatment were sampled 3 and 6 months after irradiation and bone marrow transplant. The results indicated that (a) poly I:C administered in the peritransplant period (before and after transplant) significantly increases the absolute numbers of NK cells in both the bone marrow and spleen of the transplanted host at all time intervals studied, (b) no erythroleukemic tumor cells were found, even as late as 6 months after transplant in the poly-I:C-treated hosts in spite of the fact that poly I:C treatment in this group had been terminated more than 2 months prior to tissue sampling, and (c) survival was significantly improved by pre- and posttransplant treatment with poly I:C.
Natural Killer Cell Frequency and Function in Pigs Selectively Bred for High or Low Antibody and Cell-Mediated Immune Response: Response to Vaccination with Modified Live Transmissible Gastroenteritis Virus
Authors: Raymond Claudine , Wilkie Bruce N.
Published: April 2003

Porcine NK cells are small to medium lymphocytes which are lytic for tumours and virally infected cells when co-cultured for long periods (≈16 h). The frequency and function of NK cells were examined in generation 8 of pigs genetically selected for high (H), low (L), and control (C) antibody (Ab) and cell-mediated immune response (CMIR). The NK phenotype was identified using a pan-species NK-specific murine monoclonal antibody (5C6) and both binding and lysis of the NK target, K562. Vaccination with modified live transmissible gastroenteritis virus (TGEV) had no effect on blood leucocyte NK cell frequency. In interactions with K562 targets, NK cells of H and C pigs responded similarly in frequency of conjugate formation and lytic activity, while L pigs had very little or no response. Therefore, in pigs selected for high Ab and CMIR, there was no correlated enhancement of NK-cell-related traits following vaccination with TGEV, while selection for low immune response was associated with reduced NK response in pigs. This may suggest that low immune response can reflect reduced contribution of NK cells in pigs.
Lack of Natural Killer Cell Precursors in Fetal Liver of Ikaros Knockout Mutant Mice
Authors: Boggs Sallie S. , Trevisan Maryanne , Patrene Kenneth , Geogopoulos Katia
Published: April 2003

The role of Ikaros in early stages of natural killer (NK) cell differentiation was investigated using an in vitro system that promotes proliferation and differentiation of NK cell precursors into mature NK1.1+ cells. Day 14.5 fetal liver cells from mice, either homozygous for Ikaros Null or dominant negative (DN) mutations, had severe 55- to 79-fold reductions in functional NK cell precursors. Although there was no statistically significant difference between values for +/+ and +/– Null mice, the mean precursor frequency for DN mutant (+/–) mice was significantly above that for DN –/– mice and below that for DN +/+ mice. The NK activity values for cells generated from the NK cell precursors followed the same respective relationships found for NK cell precursor frequencies. These data suggest that the deficiency of mature NK cells in Ikaros mutant mice is related to lack of functional precursors.
Age-Associated Hematopoietic Alterations in the Spleen of Tumor-Bearing Hosts
Authors: Khare Vineeta , Singh Sukh Mahendra , Sodhi Ajit
Published: April 2003

The present investigation was carried out to study the effect of tumor growth on the spleen of an aged host. Dalton’s lymphoma (DL), a spontaneous T cell lymphoma, was grown in mice of different age groups classified as young, adult or old on the basis of their reproductive status. Splenocytes obtained from normal and tumor-bearing young, adult and old mice were checked for an in vitro blastogenic response to concanavalin A (Con A), colony-forming ability and apoptosis. There was an enhanced apoptosis of splenocytes and a concomitant inhibition of splenocyte blastogenesis and their responsiveness to the mitogenic stimulus of Con A in aged mice. The counts of granulocyte macrophage- and macrophage-colony forming units were significantly enhanced in the spleen of tumor-bearing adult mice. It is proposed that the DL-growth-dependent increase in the size of the spleen in adult mice is due to an increased blastogenesis of splenocytes, which, however, may not be applicable in the case of old tumor-bearing mice. The role of splenic macrophages in the regulation of the functions of the spleen by macrophage-derived NO is shown.
Purification of Filaggrin from Human Epidermis and Measurement of Antifilaggrin Autoantibodies in Sera from Patients with Rheumatoid Arthritis by an Enzyme-Linked Immunosorbent Assay
Authors: Palosuo T. , Lukka M. , Alenius H. , Kalkkinen N. , Aho K. , Kurki P. , Heikkilä R. , Nykänen M. , von Essen R.
Published: April 2003

Background: The so-called antikeratin antibody (AKA) and the antiperinuclear factor (APF) that recognize proteins related to human epidermal filaggrin belong to the most specific serological markers of rheumatoid arthritis (RA). However, assays for the detection of AKA and APF are currently based on immunofluorescence, a method that is subject to arbitrary interpretation and inadequate standardization of the substrates. Methods: Proteins extracted from human epidermis were separated by reversed-phase high-performance liquid chromatography (HPLC). Filaggrin-containing fractions, identified in immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic digestion, amino acid sequencing and mass spectrometry were used to cornfirm the identity of the purified protein. Filaggrin was used as antigen in enzyme-linked immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies. Results: The filaggrin preparation obtained gave a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides analyzed were shown to originate from human filaggrin. Antifilaggrin antibody levels exceeded the 99th percentile level of 100 middle-aged blood donors in 26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA-positive. Conclusion: Human filaggrin can be purified by standard biochemical techniques, despite the heterogeneity of the protein, and used in ELISA for testing autoantibodies to filaggrin. The sensitivity of the assay equals that of the AKA test.
Human chromosome 3: integration of 60 NotI clones into a physical and gene map
Authors: Sulimova G.E. , Kutsenko A.S. , Rakhmanaliev E.R. , Udina I.G. , Kompaniytsev A.A. , Protopopov A.I. , Moisjak E.V. , Klimov E.A. , Muravenko O.V. , Zelenin A.V. , Braga E.A. , Kashuba V.I. , Zabarovsky E.R. , Kisselev L.L.
Published: April 2003

Sequence tagged sites generated for 60 NotI clones (NotI-STSs) from human chromosome 3-specific NotI-jumping and NotI-linking libraries were physically located using PCR screening of a radiation hybrid (RH) GeneBridge4 panel. The NotI map of chromosome 3 was generated using these RH-mapping data and those obtained earlier by FISH and sequencing of the corresponding NotI clones. The sequences of the NotI clones showed significant homologies with known genes and/or ESTs for 58 NotI-STSs (97%). These 58 NotI clones displayed 91–100% identity to 54 genes and 23 cDNA/EST clones. One known and two hypothetical protein-coding genes were localized for the first time and nine cDNA clones (unknown genes) were also carefully mapped only in this work. Three newly mapped genes are histone gene H1X (NR1-BK20C) and genes for hypothetical proteins THC1032178 and THC1024604 (NL1-243).
Mapping and microsatellite marker development for the porcine leukemia inhibitory factor receptor (LIFR) and epidermal growth factor receptor (EGFR) genes
Authors: Spötter A. , Drögemüller C. , Kuiper H. , Brenig B. , Leeb T. , Distl O.
Published: April 2003

Leukemia inhibitory factor receptor (LIFR), epidermal growth factor receptor (EGFR), and their respective ligands have been implicated in regulating growth and development of the early pig conceptus. We isolated a PAC clone containing the porcine gene for LIFR and a BAC clone with the porcine EGFR gene, respectively. On each of these clones one microsatellite marker was identified by sequencing a collection of subclones. These gene-associated markers were evaluated by genotyping of 202 unrelated boars of four different breeds. Based on fluorescence in situ hybridization and radiation hybrid mapping, the porcine LIFR gene was assigned to SSC16q13→q14. The EGFR gene mapped to SSC9q26.