Biomedical subjects

G Lenz

Publications and source records attributed to G Lenz.

At least 19 recordsLinked to original sources

PubMed2006

Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes.

Inflammatory and degenerative pathophysiological processes within the CNS are important causes of human disease. Astrocytes appear to modulate these reactions and are a major source of inflammatory mediators, e.g. extracellular adenine nucleotides, in nervous tissues. Actions following extracellular nucleotides binding to type 2 purinergic receptors are regulated by ectonucleotidases, including members of the CD39/ecto-nucleoside triphosphate diphosphohydrolase family. The ectonucleotidases of astrocytes expressed by rat brain rapidly convert extracellular ATP to ADP, ultimately to AMP. RT-PCR, immunocytochemistry as well as Western blotting analysis demonstrated expression of multiple ecto-nucleoside triphosphate diphosphohydrolase family members at both the mRNA and protein level. By quantitative real-time PCR, we identified Entpd2 (CD39L1) as the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar astrocytes. These data in combination with the elevated ecto-ATPase activity observed in these brain regions, suggest that NTPDase2, an ecto-enzyme that preferentially hydrolyzes ATP, is the major ecto-nucleoside triphosphate diphosphohydrolase expressed by rat astrocytes. NTPDase2 may modulate inflammatory reactions within the CNS and could represent a useful therapeutic target in human disease.

Adenosine Diphosphate↗

PubMed2005

The RNA interference revolution.

The discovery of double-stranded RNA-mediated gene silencing has rapidly led to its use as a method of choice for blocking a gene, and has turned it into one of the most discussed topics in cell biology. Although still in its infancy, the field of RNA interference has already produced a vast array of results, mainly in Caenorhabditis elegans, but recently also in mammalian systems. Micro-RNAs are short hairpins of RNA capable of blocking translation, which are transcribed from genomic DNA and are implicated in several aspects from development to cell signaling. The present review discusses the main methods used for gene silencing in cell culture and animal models, including the selection of target sequences, delivery methods and strategies for a successful silencing. Expected developments are briefly discussed, ranging from reverse genetics to therapeutics. Thus, the development of the new paradigm of RNA-mediated gene silencing has produced two important advances: knowledge of a basic cellular mechanism present in the majority of eukaryotic cells and access to a potent and specific new method for gene silencing.

Animals↗

PubMed2005

[Psychosocial characteristics of deaf people: evaluation of data from a special outpatient clinic for the deaf].

In this publication, data from a special outpatient clinic for deaf patients in a general hospital are presented. All members of the treatment team have competency in sign language. From the patients who consecutively attended the outpatient clinic, 352 were investigated for medical and psychosocial problems. In social contacts, there is a strong orientation towards other deaf people, and communication is mainly based on sign language. Of the deaf patients, 85% of their partners are also deaf, whereas only 10.1% of children of the deaf group are also deaf. The prevalence of selected psychiatric disorders (ICD 10 F1, F2, F3, F4, F6) in deaf people was found to be similar to that in hearing populations, with the exception of somatoform disorders, which seem to be more frequent in the deaf. Deaf people also more often present with somatic and other complaints such as nervousness, anxiety, and stress. With specific outpatient clinics for the deaf in which members of the therapeutic team are competent in sign language, access to health services is equally possible for deaf people.

Adolescent↗

PubMed2004

[Current strategies in the treatment of advanced stage mantle cell lymphoma].

Advanced stage mantle cell lymphoma (MCL) with a median survival of only three years and virtually no long-term survivors represents the lymphoma subtype with the poorest prognosis and remains incurable with conventional chemotherapy. Recently two randomized trials of the German Low Grade Lymphoma Study Group (GLSG) demonstrated the superiority of a combined immunochemotherapy with the anti-CD20 antibody rituximab in first-line therapy (R-CHOP) as well as in relapsed disease (R-FCM). In addition, in a trial of the European MCL Network, intensified-consolidation with high-dose radiochemotherapy followed by autologous stem cell transplantation significantly improved the progression-free survival in patients up to 65 years of age. However, the vast majority of patients with MCL will eventually relapse. Thus, new strategies such as allogenic transplantation after dose-reduced conditioning or novel molecular targeting agents (e. g. proteasome inhibitors or radiolabeled antibodies) are urgently warranted to further improve the long-term outcome of MCL.

Age Factors↗

PubMed2004

Erythroblastic synartesis in a patient initially diagnosed with myelodysplastic syndrome.

Explore the source record for details and available documents.

Anemia↗

PubMed2004

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Craniocerebral Trauma↗

PubMed2003

Mantle cell lymphoma: established therapeutic options and future directions.

During the last few years, new insights into the biology of mantle cell lymphoma have been obtained. However, with a median survival of only 3 years, mantle cell lymphoma remains the lymphoma subtype with the poorest prognosis. At initial diagnosis most patients present with advanced Ann Arbor stage III or IV and conventional chemotherapy hardly alters the continuously declining survival curve. Recently, two prospective randomized studies of the German Low Grade Lymphoma Study Group (GLSG) clearly confirmed the superiority of a combined immunochemotherapy. In a randomized study of the European mantle cell lymphoma Network, consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation improved the progression-free survival in patients younger than 65 years. However, relapses are still observed at a high frequency. Thus, new therapeutic strategies such as radioactively labeled antibodies or molecular targeting agents (e.g. Bortezomib or flavopiridol) are urgently warranted to further improve the clinical outcome of mantle cell lymphoma.

Antibodies, Monoclonal↗

PubMed2003

[Evolution of inflammatory parameters after fibroid embolization].

PURPOSE: To describe the rise of classical laboratory tests for inflammation following transarterial uterine fibroid embolization (UFE) in order to monitor the normal course following UFE. MATERIALS AND METHODS: In 20 females, white blood cell (WBC) count and C-reactive protein (CRP) were determined before and up to 5 days after UFE. With the exception of one noninflammatory complication, the post-procedure course was uneventful in all patients. The measured values were correlated with both the total uterine volume and the amount of instilled embolizing agent. RESULTS: Following UFE, an increase in the WBC count to an average maximum of 10.8 +/- 3.5/wL (range 5.9 - 18.6/wL) was found. In 13 of 20 patients, the WBC count was above normal on at least one day following UFE. The increase reached the maximum on the third post-interventional day and subsided within 5 days after the UFE. The CRP values increased significantly to an average maximum of 41.9 +/- 28.8 mg/l. The maximum was found on the 2nd post-interventional day in 8 patients, on the 3rd day in 11 patients and on the 4th day in one patient. No correlation to the total uterine volume or to the amount of the instilled embolizing agents was detected. CONCLUSION: Following uncomplicated UFE, a steep increase in CRP occurs with no or only a mild increase in the WBC count, which does not indicate an infected fibroid. The maximum is reached on the 3rd or 4th post-interventional day, followed by a decline in CRP and normalization of the WBC count.

Adult↗

PubMed2002

St. John's wort (Hypericum perforatum)--is it safe during breastfeeding?

Both doctors and patients often treat postnatal depression with herbal preparations derived from St. John's wort. Because these preparations are available to patients as "natural" over-the-counter drugs for depression, they are popularly assumed to be safe. However, no systematic information exists regarding treatment of postnatal depression, infant's safety or pharmacokinetics of hypericum constituents in human breast milk or infant plasma. A mother with post-natal depression was admitted at our service. Her pharmacist had recommended taking a St. John's wort preparation three times a day (Jarsin 300, Lichtwer Pharma AG, Berlin, Germany). Four breast-milk samples (fore and hind milk) during an 18-hour period were analyzed to measure concentration of hypericin and hyperforin. Only hyperforin is excreted into breast milk at a low level, hyperforin and hypericin (two major active components) were below the lower limit of quantification (BLQ: below lower limit of quantification, LQ hypericin: 0.20 ng/ml, LQ hyperforin: 0.50 ng/ml) in this infant's plasma. No side effects were seen in the mother or infant. Before recommending St John's wort for the treatment of depression to women who breastfeed, long-term studies of outcome in infants are needed.

Adult↗

PubMed2001

[Health care services for women with postpartum mental disorders--assessment of current options in Austria].

For many women childbirth is one of the most impressive life-events, but this period of life may also be a phase of increased vulnerability for psychiatric illness. 10-15% of women develop a postnatal depression (PND) after the birth of a child, and 1@1000 suffer from a puerperal psychosis. Despite the high prevalence, with estimates of approximately 10,000 women suffering annually from postnatal psychiatric disturbances in Austria, there has been a lack of medical attendance for these women and their children. Motivated by a research initiative from the EU on transcultural aspects of postnatal depression (PND) with 17 participating research centers world-wide, a research team at the Vienna University Clinic for Psychiatry initiated the investigation of conditions for mother-child-admissions at 31 psychiatric wards in Austria. These departments were asked about the possibility of conjoint mother-child-admission, and their experiences with this form of admission; 23 departments (74.2%) provided information. A total of 12 departments responded that they theoretically accepted mothers with their babies; however, they also indicated that until now these conjoint admissions had been performed only very rarely or not at all. Based on many years of experience in the field of postpartum mental health in Great Britain, British researchers have developed guidelines for need assessment and health care provision for women with postpartum psychiatric disorders. With the help of these guidelines, the Viennese team of psychiatrists tried to develop fundamental concepts for need assessment, diagnosis, and treatment of patients suffering from postpartum mental illness in Austria.

Austria↗

PubMed2001

Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells.

The absence of immunoglobulin (Ig) expression in B-cell-derived Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD) was initially suggested to be caused by crippling mutations in the Ig promoter or coding region. More recent investigations have, however, challenged this concept. This study addressed the role of mutations in the Ig promoter region in HRS cells. Nine cases of cHD and 3 B-cell-derived HD lines were analyzed for mutations in the TATA box and octamer motif of the Ig promoter. Mutations in the octamer motif were found in only 1 of the 9 cases and in 1 of the 3 HD cell lines (L1236). Furthermore, in all cases either a complete lack or strong reduction in the expression of the Oct2 transcription factor and the BOB.1/OBF.1 coactivator were found. The relevance of the rare promoter mutations was investigated by assaying the activity of Ig promoter reporter constructs transfected into the HD cell line L1236, which harbors a mutated octamer motif. These Ig reporter constructs were completely inactive in L1236 cells; however, their activity could be reconstituted by the cotransfection of a BOB.1/OBF.1 expression vector. The additional transfection with an Oct2 expression vector did not further enhance the Ig promoter activity. The conclusions drawn from these results are that crippling mutations in the Ig promoter and coding region are not the sole cause for the lack of Ig expression in HRS cells and that defects in the transcription machinery such as absence of BOB.1/OBF.1 are more important for this phenomenon.

Carrier Proteins↗

PubMed2001

Immunologic recovery after autologous blood stem cell transplantation in patients with AL-amyloidosis.

We prospectively studied absolute lymphocyte (ALC) and monocyte counts (AMC), lymphocyte subsets and proliferative in vitro responses to mitogen and antigen in 12 patients with AL-amyloidosis (AL) undergoing autologous blood stem cell transplantation (SCT) with high-dose i.v. melphalan. Myeloid and lymphoid recovery (>500 per microl) occurred in a median of 10 days post SCT. While there was a continuous decline in the number of CD4+ T cells at 3 months, ALC, AMC, B cells (CD19+), CD8+ T cells, and NK cells (CD16+/56+) returned to baseline. While T cell proliferative responses to phytohemagglutinin (PHA) remained depressed, B cell function measured by the proliferative response to staphylococcal antigen returned to baseline by 3 months. To supplement our findings, we retrospectively evaluated ALC, AMC and serum immunoglobulin levels in a separate group of patients treated with the same protocol at our institution. ALC and AMC recovery was similar to the pattern observed in the initial study group. Immunoglobulin levels remained within normal ranges at 3 and 12 months after SCT. Of 50 patients who were followed for a minimum of 1 year following SCT, seven (14%) developed shingles and one (2%) had PCP pneumonia. In conclusion, cellular immune function, reflected by absolute numbers of CD4+ T cells and PHA responsive T cell proliferation, is significantly suppressed at 3 months after SCT in patients with AL, and this post-transplant immunosuppression is associated with a low but clinically meaningful occurrence of opportunistic infections typical of T cell immunosuppression.

Adult↗

PubMed2001

Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures.

ATP, acting via P2Y, G protein-coupled receptors (GPCRs), is a mitogenic signal and also synergistically enhances fibroblast growth factor-2 (FGF-2)-induced proliferation in astrocytes. Here, we have examined the effects of ATP and FGF-2 cotreatment on the main components of the extracellular-signal regulated protein kinase (ERK) cascade, cRaf-1, MAPK/ERK kinase (MEK) and ERK, key regulators of cellular proliferation. Surprisingly, ATP inhibited activation of cRaf-1 by FGF-2 in primary cultures of rat cortical astrocytes. The inhibitory effect did not diminish MEK and ERK activation; indeed, cotreatment resulted in a greater initial activation of ERK. ATP inhibition of cRaf-1 activation was not mediated by an increase in cyclic AMP levels or by protein kinase C activation. ATP also inhibited the activation of cRaf-1 by other growth factors, epidermal growth factor and platelet-derived growth factor, as well as other MEK1 activators stimulated by FGF-2, MEK kinase 1 (MEKK1) and MEKK2. Serotonin, an agonist of another GPCR coupled to ERK, did not inhibit FGF-2-induced cRaf-1 activation, thereby indicating specificity in the ATP-induced inhibitory cross-talk. These findings suggest that ATP stimulates an inhibitory activity that lays upstream of MEK activators and inhibits growth factor-induced activation of cRaf-1 and MEKKS: Such a mechanism might serve to integrate the actions of receptor tyrosine kinases and P2Y-GPCRS:

Adenosine Triphosphate↗

PubMed2001

LY294002, an inhibitor of phosphoinositide 3-kinase given into rat hippocampus impairs acquisition, consolidation and retrieval of memory for one-trial step-down inhibitory avoidance.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the CA1 region of the dorsal hippocampus. Once recovered from surgery, animals were submitted to one session of step-down inhibitory avoidance training (3.0 s, 0.4 mA footshock). Animals received a 0.5-microl infusion of saline, or of LY294002 (5, 50 or 500 microM), an inhibitor of the phosphoinositide 3-kinase (PI 3-K) family. Infusions were given 10 min before training, immediately post-training or 10 min prior to a 24-h retention test. In the pre- and post-training groups, the animals were tested twice: at 1.5 and 24 h after training, for short- (STM) and long-term memory (LTM), respectively. Pre- and post-training infusion of the drug inhibited both STM and LTM. Pre-test infusions impaired LTM retrieval. The effects can not be attributed to influences on locomotor, exploratory, pro- or anti-conflict behaviour, since LY294002 had no influence on elevated plus-maze behaviour. The results suggest that hippocampal PI 3-K is necessary for memory acquisition, consolidation and retrieval of the consolidation of step-down inhibitory avoidance in rats. This could be due to an interaction with the N-methyl-d-aspartate (NMDA) receptor complex or with activity of the extracellularly regulated protein kinase (ERK)-Ras signalling pathway.

Animals↗

PubMed2001

Interpersonal psychotherapy adapted for the group setting in the treatment of postpartum depression.

Interpersonal psychotherapy (IPT) has demonstrated efficacy in the individual treatment of antepartum and postpartum depression. The current investigation extends prior work by examining the efficacy of a group IPT approach for the treatment of postpartum depression. Depression scores of 17 women diagnosed with postpartum depressive disorder (DSM-IV criteria) decreased significantly from pre- to post-treatment. Follow-up assessments at 6 months revealed continuation of the treatment effect. Results indicate that IPT adapted for a group model has positive implications for the treatment of postpartum depression, demonstrating both short-term and longer-term effects in the reduction of depressive symptomatology. Study limitations include the small sample size, absence of control group, possible bias in therapist's assessments, and lack of monitoring adherence, which may have jeopardized the accuracy of the results.

Adult↗

PubMed2000

Extracellular S100B protein modulates ERK in astrocyte cultures.

S100B is a calcium binding protein expressed and secreted by astrocytes. Extracellular S100B stimulates the proliferation of astroglial cells and the survival of neurons. Extracellular signal regulated kinases (ERK) are involved in the transduction of proliferating signals in astrocytes. Here we report that S100B significantly increases the activity of ERK in primary cultures of astrocytes, a result which may be related to previous observations of the effect of this protein on glial proliferation. We further confirm that conversion of S100B to its covalent dimer by oxidation of cysteine residues increases its extracellular activity. Although we cannot exclude S100B involvement in other mechanisms of signal transduction, these results suggest that ERK activity in astrocytes is modulated by extracellular S100B.

Animals↗

PubMed2000

Influence of volatile and intravenous anesthetics on the threshold of the acoustically evoked stapedius reflex.

The influence of volatile and intravenous anesthetics on the threshold of the acoustically evoked stapedius reflex (SR) was studied prospectively in 45 patients undergoing elective ENT surgical procedures. After premedication with flunitrazepam the patients were randomly assigned to one of nine groups. Group I: 70% nitrous oxide (N2O) in oxygen (O2); Groups II-VII: induction of anesthesia with intravenous thiopental, followed by mask inhalation with 100% O2 and 1.13% halothane (Group II), 2.52% enflurane (Group III) or 1.73% isoflurane (Group IV); or 70% N2O in oxygen, and 0.44% halothane (Group V), 0.86% enflurane (Group VI) or 0.75% isoflurane (Group VII): Group VIII: intravenous midazolam and ketamine; and Group IX: intravenous midazolam and alfentanil. Tympanometry and ipsilateral and contralateral SR measurements were performed when the effects of the anesthetics had achieved a steady state. Flunitrazepam raised the SR threshold only slightly. Substances applied during inhalation anesthesia either markedly increased the threshold contralaterally more than ipsilaterally (thiopental, N2O), or suppressed the reflex completely (thiopental, all volatile anesthetics with or without N2O). Under intravenous anesthesia the reflex was always present. The midazolam-ketamine combination influenced the threshold bilaterally only slightly, while the midazolam-alfentanil combination led to a pronounced, contralaterally significant elevation of the threshold. Based on its minimal influence on the SR threshold, flunitrazepam is especially suitable for sedation and the midazolam-ketamine combination for anesthesia in audiological diagnostic procedures.

Acoustic Impedance Tests↗

PubMed2000

Identification of brain ecto-apyrase as a phosphoprotein.

Ecto-apyrase is a transmembrane glycoprotein that hydrolyzes extracellular nucleoside tri- or diphosphates. Apyrase activity is affected by several physiological and pathological conditions indicating the existence of regulatory mechanisms. Considering that apyrase presents consensus phosphorylation sites, we studied the phosphorylation of this enzyme. We found an overlay of the immunoblotting and phosphorylated bands in three different preparations from rat brain: (a) hippocampal slices, (b) synaptic plasma membrane fragments and (c) cultured astrocytes. In addition, two-dimensional electrophoresis separations with human astrocytoma cells were done to identify unequivocally the coincidence between the immunodetected and phosphorylated protein. These observations indicate that apyrase can be detected as a phosphoprotein, with obvious implications in the regulation of this enzyme.

Animals↗