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Biomedical subjects

J Fleischer

Publications and source records attributed to J Fleischer.

At least 19 recordsLinked to original sources
PubMed2006

The sense of smell: multiple olfactory subsystems.

The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of 'OR37' neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a 'mini-nose' with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.

Amino Acid Sequence↗
PubMed2005

Design and evaluation of a handheld impedance plethysmograph for measuring heart rate variability.

Heart rate variability (HRV) analysis from 10s ECGs has been shown to be reliable. However, the short examination time warrants a user-friendly system that can be used for ad-hoc examinations without normal preparation, unlike ECG. A handheld device has been developed that can measure ultra-short HRV from impedance plethysmographic recordings of the pulse wave in distal superficial arteries. The prototype device was made user-friendly through a compact, pen-like design and the use of integrated metal electrodes that were especially designed for dry operation. The main signal processing was performed by a digital signal processor, where the discrete heart beats were detected using a correlation algorithm that could adapt to individual pulse wave shapes to account for biological variation. The novel device was evaluated in 20 mainly young volunteers, using 10 s time-correlated ECG recordings as the reference method. Agreement between the two methods in measuring heart rate and root mean square of successive differences in the heart beat interval (RMSSD) was analysed using correlation coefficients (Pearson's R2), mean differences with 95% confidence intervals and 95% limits of agreement, and Bland-Altman plots. The correlation between the two methods was R2 = 1.00 and R2 = 0.99 when heart rate and RMSSD were measured, respectively. The Bland-Altman plots showed suitable agreement between the novel device and standard 10 s ECGs, which was substantiated by 95% limits of agreement of the difference of +/- 0.1 beats min(-1) and approximately +/- 10 ms for heart rate and RMSSD, respectively. Therefore the evaluation showed no significant systematic error of the novel device compared with ECG.

Adult↗
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2001

Identification of a nonmammalian Golf subtype: functional role in olfactory signaling of airborne odorants in Xenopus laevis.

Attempts to identify the Galpha subtypes in the two compartments of the olfactory system from Xenopus, which are supposed to be specialized for detecting aquatic and volatile odorous compounds, revealed that a Galpha(o1) subtype is characteristic for the "water nose," the lateral diverticulum, whereas a novel Galpha(s) subtype predominates in the "air nose," the medial diverticulum. The newly identified Galpha(s)-type is more closely related to Galpha(olf) of rat and human than to the known Galpha(s)-isoform of Xenopus; it is therefore considered the first identified nonmammalian Galpha(olf) subtype. Sequence comparison of Galpha(olf) from amphibia and mammals revealed a particular conservation within the alpha-helical domains, which are supposed to control the GDP/GTP-exchange rate. The selective expression of different Galpha subtypes in the two anatomically separated and functionally specialized nasal compartments parallels the expression of distinct classes of olfactory receptors. Moreover, biochemical analysis revealed that stimulation with appropriate odorous compounds elicits the formation of inositol trisphosphate in the lateral diverticulum. In contrast, cyclic adenosine monophosphate signals were induced in the medial diverticulum, and this response appears to be mediated by the novel Galpha(olf) subtype. The data indicate that olfactory sensory neurons in each of the nasal cavities are equipped not only with defined sets of receptor types but also with a distinct molecular machinery for the chemo-electrical transduction process.

Amino Acid Sequence↗
PubMed2001

Characteristic features and ligand specificity of the two olfactory receptor classes from Xenopus laevis.

Amphibia have two classes of olfactory receptors (ORs), class I (fish-like receptors) and class II (mammalian-like receptors). These two receptor classes correspond to the two classes identified in other vertebrates, and amphibians thus provide a unique opportunity to compare olfactory receptors of both classes in one animal species, without the constraints of evolutionary distance between different vertebrate orders, such as fish and mammals. We therefore identified the complete open reading frames of class I and class II ORs in Xenopus laevis. In addition to allowing a representative comparison of the deduced amino acid sequences between both receptor classes, we were also able to perform differential functional analysis. These studies revealed distinct class-specific motifs, particularly in the extracellular loops 2 and 3, which might be of importance for the interaction with odorants, as well as in the intracellular loops 2 and 3, which might be responsible for interactions with specific G-proteins. The results of functional expression studies in Xenopus oocytes, comparing distinct receptor types, support the idea that class I receptors are activated by water-soluble odorants, whereas class II receptors are activated by volatile compounds.

Amino Acid Sequence↗
PubMed2000

A possible role for caveolin as a signaling organizer in olfactory sensory membranes.

Fast kinetics and sensitivity of olfactory signaling raise the question of whether the participating proteins may be associated in supramolecular transduction complexes. We found evidence that caveolin proteins could play an important role in organizing signaling elements in olfactory sensory neurons. Western blot analysis indicated that caveolins are highly enriched in olfactory sensory membranes, where they co-localize in detergent-insoluble complexes with key components of the signaling pathways. Furthermore, the results of immunoprecipitation experiments suggest that G proteins and effector enzyme form preassembled subcellular complexes with caveolins. Since anti-caveolin antibodies and synthetic peptides derived from the scaffolding domains of caveolin-1 and caveolin-2 effectively attenuated second messenger responses in sensory cilia preparations in a characteristic manner, the data led to the suggestion that caveolins could mediate the assembly of signaling complexes within specialized membrane microdomains of olfactory sensory neurons.

Animals↗
PubMed2000

The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages.

Unstimulated monocytes rapidly undergo physiological changes resulting in programmed cell death (apoptosis) while stimuli promoting differentiation of these cells into macrophages were shown to inhibit apoptotic processes. In the present study, we report that the platelet-derived alpha-chemokine platelet factor 4 (PF4) induces the differentiation of monocytes into macrophages, as is evident from morphological changes as well as from the up-regulation of differentiation markers (carboxypeptidase M/MAX1 and CD71). Significant alterations of the phenotype were observed after 72 hours of culture in the presence of the chemokine and required a minimal concentration of 625 nmol/L PF4. PF4-induced macrophages were characterized by a lack of HLA-DR antigen on their surface but showed a strong increase in the expression of the CD28 ligand B7-2. Furthermore, PF4 stimulation prevented monocytes from undergoing spontaneous apoptosis during 72 hours of culture as determined in an annexin-V-binding assay. Although PF4 induced the secretion of relevant amounts of TNF-alpha, neutralizing antibodies directed against TNF-alpha or granulocyte-macrophage colony-stimulating factor (GM-CSF) did not revert PF4-induced rescue from programmed cell death, suggesting that PF4 exerts its antiapoptotic effects in a TNF-alpha- or GM-CSF-independent fashion. On the basis of these results, we propose a novel role for PF4 in the control of monocyte differentiation during an inflammatory process in vivo. (Blood. 2000;95:1158-1166)

Antibodies, Monoclonal↗
PubMed2000

[Surveillance of group illnesses with Norwalk-like viruses (NLV) in Baden-Württemberg. Isolation and detection of Norwalk-like viral RNA from fecal samples with RT-PCR].

Between the turn of the years 98/99 and 99/2000, stool samples from various health departments in the south of Germany were sent to the LGA (Landesgesundheitsamt Baden-Württemberg). Different testings as bacteriological routines for enterobacteriaceae and virological antigen screenings of the stool samples for adeno-, astro- and rotaviruses lead to negative results. Additional RT-PCR tests for the presence of Norwalk-RNA showed nearly 40% of positive samples. From 14 group infections between december 98 and january 2000, 286 samples in total were sent to the LGA, 118 of them gave positive results for the norwalk agent. For the verification of the analysis, some random samples were sent to the Robert-Koch-Institut, div. of molecular virology at Berlin, where the results were confirmed.

Caliciviridae Infections↗
PubMed2000

Burgers' turbulence with self-consistently evolved pressure

The Burgers' model of compressible fluid dynamics in one dimension is extended to include the effects of pressure back-reaction. The system consists of two coupled equations: Burgers' equation with a pressure gradient (essentially the one-dimensional Navier-Stokes equation) and an advection-diffusion equation for the pressure field. It presents a minimal model of both adiabatic gas dynamics and compressible magnetohydrodynamics. From the magnetic perspective, it is the simplest possible system which allows for "Alfvenization," i. e., energy transfer between the fluid and magnetic field excitations. For the special case of equal fluid viscosity and (magnetic) diffusivity, the system is completely integrable, reducing to two decoupled Burgers' equations in the characteristic variables v+/-v(sound) (v+/-v(Alfven)). For arbitrary diffusivities, renormalized perturbation theory is used to calculate the effective transport coefficients for forced "Burgerlence." It is shown that energy equidissipation, not equipartition, is fundamental to the turbulent state. Both energy and dissipation are localized to shocklike structures, in which wave steepening is inhibited by small-scale forcing and by pressure back reaction. The spectral forms predicted by theory are confirmed by numerical simulations.

Journal Article↗
PubMed1999

Course of platelet counts in cirrhotic patients after implantation of a transjugular intrahepatic portosystemic shunt--a prospective, controlled study.

BACKGROUND/AIMS: The pathogenesis of thrombocytopenia associated with advanced liver disease is still controversial. To study the impact of portal decompression on this hematologic complication, we conducted a prospective, controlled study to compare the course of platelet counts in patients after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) with matched controls without shunts. METHODS: Fifty-five TIPS patients and 110 controls matched for age, sex, Child-Pugh class, etiology of liver disease and baseline platelet count were included, and followed for 1 year. Follow-up visits were scheduled after 1 month, after 3 months, and at 3-month intervals thereafter. RESULTS: Nonparametric Mann-Whitney U-tests revealed significantly higher platelet counts for TIPS patients as compared to controls from the 1st through the 12th month (p<0.01). During the study period, the median platelet count of TIPS patients increased by 19.7%, from 104.0/nl (IR: 68.0) to 124.5/nl (IR: 41.0). In contrast, during the same period the median platelet count of controls decreased by 17.1%, from 102.5/nl (IR: 66.0) to 85.0/nl (IR: 67.5). In the group of cases with baseline platelet counts < or =100/nl, platelet counts had increased by at least 25% at month 12 in 65% of TIPS patients, but in only 5% of controls (p<0.001). However, normalization of platelet counts, i.e. > or =150/nl, was not achieved in any case. Neither the portosystemic pressure gradient after TIPS implantation, nor the percentage of portosystemic pressure gradient reduction during the procedure was predictive of platelet response. CONCLUSIONS: TIPS implantation increases platelet counts significantly. However, portal hypertension is clearly not the only mechanism contributing to thrombocytopenia in advanced liver disease.

Adult↗
PubMed1998

[Sentinel lymph nodes in breast carcinoma].

Aim of the experiment is to select patients with positive axillary lymph nodes by means of the sentinel lymph node concept. In this way all other patients who would not benefit from a lymph node dissection are spared from this procedure and its morbidity. Till now the sentinel lymphadenectomy is, however, still an experimental technic with yet unproven utility.

Axilla↗
PubMed1998

[Surgical procedures in therapy of breast carcinoma with reference to the value of axillary endoscopy techniques].

During the last decades the surgical treatment of breast cancer has been dramatically changed. Today breast conservative treatment represents a therapeutic option applicable to nearly 70% of the women. In contrast to this, the technic of axillary dissection remained unchanged. Suzanne et al. proposed an axilloscopic technic to reduce this morbidity. The sometimes unacceptable low lymph node count in the specimen induced us to modify this procedure. In the future the sentinel lymph node concept perhaps offers the possibility to select NO-patients and to spare the axillary dissection completely to this sub-group.

Axilla↗
PubMed1997

Substance use disorder and the early course of illness in schizophrenia and affective psychosis.

The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.

Adult↗
PubMed1997

Acute and chronic complications after implantation of a transjugular intrahepatic portosystemic shunt--a prospective study in 53 patients.

Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with a broad spectrum of acute and chronic complications. Data concerning incidence and prognosis of these complications are conflicting but of great importance toward defining the role of TIPS relative to other therapeutic options. We conducted a prospective, uncontrolled cohort study in 53 patients to assess incidence, management and clinical outcome of complications occurring after TIPS procedure. Mean follow-up was 21.1 +/- 9.0 months. Technique-related mortality was 2%; 9% of patients died within 30 days after TIPS procedure. The overall survival rate after 18 months was 74%. The overall incidence of primary hepatic encephalopathy (HE) within the first year was 25%, and 77% of episodes could be managed successfully by medical treatment or implantation of a reducing stent. The rate of patients without rebleeding after 18 months was 84%. Rebleeding was associated with shunt abnormalities, and the bleeding was controlled by revision of the stent. Two patients died of variceal hemorrhage. The cumulative incidence of shunt stenosis or occlusion was 47% after 18 months. The technical success rate of shunt revision was 97%. TIPS implantation is associated with a considerable risk of HE and shunt stenosis or occlusion. Nevertheless most episodes of HE can be managed by medical treatment or implantation of a reducing stent. Angiographic revision of the stent is successful in nearly all cases of stenosis or occlusion. We therefore conclude that TIPS implantation in combination with careful follow-up examinations constitutes effective medium-term treatment of portal hypertension in a considerable proportion of patients.

Acute Disease↗
PubMed1996

Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes.

The interaction of CD28 with its ligands is important for T-cell activation. Recent studies demonstrated the existence of at least two ligands on accessory cells, CD80 (B7-1) and CD86 (B7-2). In this study we demonstrate that, although CD80 and CD86 are both expressed on monocytes, they seem to have different functions. Freshly isolated monocytes express CD86 but are CD80-negative. CD80 expression is weakly induced after 6-8 hr of in vitro culture and is enhanced by stimulation. CD86 expression is enhanced faster than CD80 expression and reaches the peak level after 4-6 hr in stimulated cells. Reverse transcription-polymerase chain reaction studies demonstrate that freshly isolated monocytes contain no CD80-mRNA. The mRNA of CD80 is induced after 4-6 hr of culture, which matches with the expression of the protein. Inhibition studies using different antibodies against both molecules and the fusion protein CTLA4Ig show that only anti-CD80 and CTLA4Ig could partially inhibit antigen-specific (tuberculin) and polyclonal (anti-CD3) lymphoproliferation and interferon-gamma (IFN-gamma) secretion of T cells cocultured with autologous monocytes. IFN-gamma secretion was more sensitive to blocking costimulation than proliferation. The antibody BB-1 did not inhibit proliferation and cytokine secretion, nor did the anti-CD86 clone IT2.2. CTLA4Ig, which binds both CD80 and CD86, has the same inhibitory capacity as the anti-CD80 antibody tested. From those findings we conclude that human monocytes use CD80 as a costimulatory ligand for CD28 and utilize other costimulatory mechanisms besides those mediated via molecules of the B7 family.

Antigens, CD↗