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Biomedical subjects

M Reich

Publications and source records attributed to M Reich.

At least 19 recordsLinked to original sources
PubMed2006

Activity patterns of proteasome subunits reflect bortezomib sensitivity of hematologic malignancies and are variable in primary human leukemia cells.

Proteasomal proteolysis relies on the activity of six catalytically active proteasomal subunits (beta1, beta2, beta5, beta1i, beta2i and beta5i). Applying a functional proteomics approach, we used a recently developed activity-based, cell-permeable proteasome-specific probe that for the first time allows differential visualization of individual active proteasomal subunits in intact primary cells. In primary leukemia samples, we observed remarkable variability in the amounts of active beta1/1i-, beta2/2i- and beta5/5i-type of subunits, contrasting with their constant protein expression. Bortezomib inhibited beta5- and beta1-type, but to a lesser extend beta2-type of subunits in live primary cells in vitro and in vivo. When we adapted the bortezomib-sensitive human acute myeloid leukemia cell line HL-60 to bortezomib 40 nM (HL-60a), proteasomal activity profiling revealed an upregulation of active subunits, and residual beta1/beta5-type of activity could be visualized in the presence of bortezomib 20 nM, in contrast to control cells. In a panel of cell lines from hematologic malignancies, the ratio between beta2-type and (beta1 + beta5)-type of active proteasomal polypeptides mirrored different degrees of bortezomib sensitivity. We thus conclude that the proteasomal activity profile varies in primary leukemia cells, and that the pattern of proteasomal subunit activity influences the sensitivity of hematologic malignancies toward bortezomib.

Animals↗
PubMed2005

Economic burden associated with multi-resistant Gram-negative organisms compared with that for methicillin-resistant Staphylococcus aureus in a university teaching hospital.

The aim of this study was to investigate the hospital costs of patients with multi-drug-resistant Gram-negative bacilli (MR-GNB) compared with those for patients with methicillin-resistant Staphylococcus aureus (MRSA), using the Austrian performance-related hospital financing system (LKF). The study was performed retrospectively at Vienna General Hospital, a 2,160-bed university teaching hospital, from January to June 2002. There were 99 patients in the MR-GNB group (median age 58 years) and 74 patients in the MRSA group (median age 60 years). More patients in the MR-GNB group (59 patients, 60%) were treated in the intensive care unit compared with patients in the MRSA group (25 patients, 34%) (P<0.01). The median hospital stay (42 and 37 days, respectively) and mortality (18 and nine deaths, respectively) of the two groups were similar. The total hospital cost for patients in the MR-GNB group was higher [4 915 712 LKF credit points (median: 34,180) equivalent to 2,605,327 pounds (median: 18,115 pounds )] than that for patients in the MRSA group [2,088,904 LKF credit points (median: 12,650) equivalent to 1, 093, 906 pounds (median: 6,624 pounds)] (P<0.01). This study is limited by being retrospective and having charge-based costings. However, it suggests that the hospital costs of patients with MR-GNB are substantial and may be greater than those of patients with MRSA.

Adolescent↗
PubMed2004

Open-label dose-escalation study of oral 1-octanol in patients with essential tremor.

Twenty-one single oral doses of 1-octanol were given to patients with essential tremor (ET) in an open-label dose-escalation study. The drug was well tolerated up to 64 mg/kg. The main side effect was an unusual taste. No overt intoxication was seen. There was evidence for efficacy, with a significant reduction in tremor amplitude as measured by accelerometry and handwriting that was maximal at 2 hours. Higher doses may produce more sustained benefit.

1-Octanol↗
PubMed2004

GeneCluster 2.0: an advanced toolset for bioarray analysis.

SUMMARY: GeneCluster 2.0 is a software package for analyzing gene expression and other bioarray data, giving users a variety of methods to build and evaluate class predictors, visualize marker lists, cluster data and validate results. GeneCluster 2.0 greatly expands the data analysis capabilities of GeneCluster 1.0 by adding classification, class discovery and permutation test methods. It includes algorithms for building and testing supervised models using weighted voting and k-nearest neighbor algorithms, a module for systematically finding and evaluating clustering via self-organizing maps, and modules for marker gene selection and heat map visualization that allow users to view and sort samples and genes by many criteria. GeneCluster 2.0 is a stand-alone Java application and runs on any platform that supports the Java Runtime Environment version 1.3.1 or greater. AVAILABILITY: http://www.broad.mit.edu/cancer/software

Algorithms↗
PubMed2004

[Selective serotonin reuptake inhibitors (SSRIs) antidepressants use in hot flashes in oncology].

INTRODUCTION: Menopausal women or patients treated by chemotherapy or hormonotherapy for breast cancer have often disabled hot flashes. Men with prostate cancer confronted to castration can also suffer from the same problem. In both situations, many arguments go against implementation of estrogenic treatment. Albeit, many complementary therapeutics exist, they are often unsatisfying. CURRENT KNOWLEDGE AND KEY POINTS: Since some years, anecdotal case reports and controlled studies have reported interest of selective serotonin reuptake inhibitors (SSRIs) antidepressants in this indication. These treatments often appear efficient and well tolerated. FUTURE AND PROJECTS: Through a review of literature and clinical vignette, we will specify physiopathology and prescription modalities in this new type of indication.

Female↗
PubMed2004

Remaining problems and controversies in the management of childhood head and neck soft tissue sarcomas: Retrospective (national) Multicenter Study of the Polish Pediatric Solid Tumors Group.

Soft tissue sarcomas in children are a heterogeneous group of malignant diseases. Among these, tumors localized in the head and neck region are especially difficult to treat. While multidisciplinary care has dramatically improved the prognosis of sarcoma patients, their treatment remains uncertain because of demand on radical surgical resection of the tumor. Achieving cure without deforming or mutilating the child remains the primary goal of treatment. This study is the multicenter (nationwide, 11 Polish centers) retrospective analysis of the treatment results in children having soft tissue sarcoma in the head and neck region during the previous decade (from 1991 to 2001). Late effects of the treatment are documented in long-term survivals. Eighty-five children from 1 to 212 months of age were included. Different multimodal treatment protocols were utilized (CWS-91, SIOP-MMT-91, and CWS-96). The median observation time was 25 months. Data on long-term effects were collected in 34 long-term survivals. Complete remission was achieved in 68 (80%) patients. Primary treatment failure occurred in 13 (15.3%) patients, all of whom succumbed in disease progression. Relapse occurred in 21 (30.9%) patients primarily achieving complete remission. Second primary neoplasm occurred in 3 children. The estimated 5-year event-free survival and the 5-year total survival rates for the whole group are 0.38 and 0.55, respectively. The main late effect documented in long-term survivals were cosmetic defects in 12 (35.3%) and visual field deficit or blindness in 8 (26.5%). Despite substantial improvement of the prognosis of pediatric soft tissue sarcomas, the multimodal treatment of head and neck region tumors remains controversial. Improved long-term outcome and focusing on psychosocial difficulties raise the important and difficult problem of functional results and cosmesis. Tumors localized in the orbit carry an excellent prognosis. However, the main late sequela is vision impairment and cosmetic defect due to the therapy given many years earlier. Two other tumor localizations--the parameningeal and nonparameningeal ones--still have bad prognosis. The observations made in this study confirm that main prognostic factors are the size of the primary tumor and the tumor stage. The worst prognosis remains invasive tumor (T2-stage) with a size over 5 cm. Individually adjusted multimodal therapy, which imperatively needs to be radical, though not mutilating, might minimize the late effects. Psychosocial problems in long-term survivors need to be focused on at the national level and better support must be provided in the future, involving a team of different medical and paramedical profiles.

Adolescent↗
PubMed2003

Nonspecific plasma proteins during sublingual immunotherapy.

Usually, specific allergy-related plasma proteins such as immunoglobulin E (IgE) and immunoglobulin G (IgG) are used for estimating the grade of sensitization and follow-up of immunotherapy. In recent years, several nonspecific inflammatory markers, such as sICAM-1 and sIL-2R, have been shown as being suitable for therapy control in allergy. In our investigation of patients under sublingual immunotherapy (SLIT), plasma from 42 healthy controls and 133 children with single inhalation allergies to grass pollen, birch pollen or house dust mites was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis and allergic asthma with one single RAST class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), sE-selectin, interleukin-12 (IL-12) and specific IgG4 were analyzed with the ELISA technique. After 1 year of SLIT, concentrations of sICAM-1, sIL-2R and sE-selectin declined significantly when results from all patients were taken as one group. Regarding the single allergen groups, the sICAM-1 and sIL-2R decrease was significant in the grass and mite group, but not in the birch group, while the sE-selectin decline was only significant in the birch group after 1 year of SLIT, but not in the grass and the mite group. No difference was observed in IL-12 and IgG4 expression. In two groups of controls with a mean age of 9.5 versus 17.5 years, the analyzed parameters were not age-dependent. The increased proteins may be useful as additional markers for the evaluation of immunological effects and follow-up investigations of allergy therapies.

Administration, Sublingual↗
PubMed2003

[Conspiracy of silence in oncology: a situation not to be overlooked].

Disclosure of a cancer diagnosis and, more often that of a poor prognosis facilitates the creation of a conspiracy of silence, also called a collusive situation. It is often imposed by the patient's relatives. While the initial purpose is to protect a loved one from bad news, these situations are observed in the end to create psychological suffering for all of the protagonists: patient, family, care providers. In order to resolve conflicts and improve the lived experience of difficult moments, it is preferable to break into the collusion by initiating a dialogue. A clinical vignette illustrates an approach to take in everyday practice.

Attitude of Health Personnel↗
PubMed2003

Elevated nonspecific plasma proteins in allergic patients.

Several allergen-specific plasma proteins, such as IgE and IgG subclasses, are commonly used for the evaluation of grade of allergy. In the present investigation, we compared the concentration of various nonspecific plasma proteins, mostly known as inflammation markers, in an allergic and a healthy population. Plasma from 130 children with single inhalation allergies to grass pollen, birch pollen, or house dust mites as well as from 42 healthy children was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis, and asthma with one single radioallergosorbent test (RAST) class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1(sICAM-1), soluble interleukin-2 receptor(sIL-2R), sE-selectin, and soluble vascular cell adhesion molecule-1 (1sVCAM-1) were analyzed by enzyme linked immunosorbent assay (ELISA) technique. Concentrations of sICAM-1 and sE-selectin were significantly increased in all patients compared to controls. In the single allergen groups, sICAM-1 elevation was significant in the grass and mite groups, but not in the birch group; while sE-selection increase was significant in the birch and mite groups, but not in the grass group. The elevation of sIL-2R in the allergic patients was obvious in each single allergen group, but not significant. No difference was observed in sVCAM-1 expression. In two groups of patients with mean age of 9.5 years versus 17.5 years, the analyzed parameters were not age dependent. The increased proteins may be useful as additional markers for efficacy and follow-up investigations of allergy therapies.

Adolescent↗
PubMed2001

Multiclass cancer diagnosis using tumor gene expression signatures.

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.

Biomarkers, Tumor↗
PubMed2001

Mechanism of Tet repressor induction by tetracyclines: length compensates for sequence in the alpha8-alpha9 loop.

Natural Tet repressor (TetR) variants are alpha-helical proteins bearing a large loop between helices 8 and 9, which is variable in sequence and length. We have deleted this loop consisting of 14 amino acid residues in TetR(D) and rebuilt it stepwise with up to 42 alanine residues. All except the mutant with the longest alanine loop show wild-type repression, but none is inducible with tetracycline. This demonstrates the importance of the alpha8-alpha9 loop and its amino acid sequence for induction. The induction efficiencies increase with loop length, when the more tightly binding inducer anhydrotetracycline is used. The largest increase of inducibility was observed for TetR mutants with loop lengths between eight and 17 alanine residues. Since loop residues Asp/Glu157 and Arg158 are conserved in the natural TetR sequence variants, we constructed a mutant in which all other residues of the loop were replaced by alanine. This mutant exhibits increased anhydrotetracycline induction compared to the corresponding alanine variant. Thus, these residues are important for induction. Binding constants for the anhydrotetracycline-TetR interaction are below the detection level of 10(5) M(-1) for the mutant with a loop of two alanine residues and increase sharply until a loop size of ten residues is reached. TetR variants with longer loops have similar anhydrotetracycline-binding constants, ranging between 2.6 x 10(9) M(-1) and 8.0 x 10(9) M(-1), about 500-fold lower than wild-type TetR. The increase of the affinity occurs at shorter loop lengths than that of inducibility. We conclude that the induction defect of the polyalanine variants arises from two increments: (i) the loop must have a minimal length-to allow efficient inducer binding; (ii) the loop must structurally participate in the conformational change associated with induction.

Amino Acid Sequence↗
PubMed2001

Dose schedule of recombinant murine thrombopoietin prior to myelosuppressive and myeloablative therapy in mice.

PURPOSE: Thrombopoietin is being investigated as a therapeutic agent for platelet recovery following myelosuppressive therapy. Little information is available, however, on the optimal dose of this drug or the timing of its administration. To develop these data, a series of studies were conducted to examine the effects that time of dosing has on the efficacy and safety of recombinant full-length murine thrombopoietin in murine myelosuppression and murine myeloablation models. METHODS: For the myelosuppression model, mice were exposed to 500 rad whole-body irradiation in a cesium irradiator and received an intraperitoneal dose of 1.2 mg carboplatin at time 0. For the myeloablation model, mice were exposed to 900 to 950 rad of whole-body irradiation at time 0. RESULTS: Significant increases in the number of platelets and red and white blood cells were observed by day 10 in mice that had received a single intravenous bolus dose of recombinant murine thrombopoietin from 2 h before until 4 h after myelosuppressive therapy compared to those had received myelosuppressive therapy alone. In the myeloablation studies, mice treated with 900 rad of whole-body irradiation alone had a mortality rate of 50% compared to 0% for mice that had received recombinant murine thrombopoietin 2 h prior to whole-body irradiation. When the whole-body irradiation dose was increased to 950 rad, the mortality rate of the control mice was 83% compared to 25% for mice that had received recombinant murine thrombopoietin 2 h prior to whole-body irradiation. Dosing with recombinant murine thrombopoietin 7 days prior to whole-body irradiation resulted in a mortality rate greater than or equal to that of control mice. CONCLUSIONS: These data suggest that pretreatment with thrombopoietin can dramatically affect recovery from myelosuppressive and myeloablative therapy. Therefore, the timing of thrombopoietin administration in relation to the therapy may be critical to the drug's safety and efficacy.

Animals↗
PubMed2001

[Disclosure of a diagnosis of cancer: paradoxes and misunderstandings].

INTRODUCTION: Announcing to a patient that he has cancer is a key moment both in the relationship between this patient and his doctor and in the setting up of quality communications. However, the quality of this communication is often impaired by the presence of paradoxes and misunderstandings. CURRENT KNOWLEDGE AND KEY POINTS: The particularities of cancer, the defense mechanisms of the different contributors and cancer representations can increase the sources of misunderstandings, which will leave an indelible mark on the patient at the beginning of the disease. FUTURE AND PROJECTS: What's at stake in that type of announcement in terms of compliance should not be neglected. Practitioners becoming aware of those phenomena and communication rules should improve the modes of announcement.

Communication↗
PubMed2001

Mineralogical and chemical interactions of soils eaten by chimpanzees of the Mahale Mountains and Gombe Stream National Parks, Tanzania.

Termite mound soils eaten by chimpanzees of the Mahale Mountains and Gombe National Parks, Tanzania, have mineralogical and geochemical compositions similar to many soils eaten by higher primates, but release very low levels of either toxic or nutritional inorganic elements to solution at acid pH. Comparison with control (uneaten) soils from the same areas showed lower levels of carbon and nitrogen in the eaten soils, a relationship confirmed by surface analysis. Surface analysis also revealed lower levels of iron on particle surfaces versus interiors, and higher levels of iron on ingested versus control soil particle surfaces. The soils can adsorb dietary toxins, present in the plant diet or those produced by microorganisms. Taking the toxic alkaloids quinine, atropine, sparteine, and lupanine as examples, it is evident that soils from Mahale have a very good adsorptive capacity. A new adaptive advantage of geophagy is proposed, based on the prevention of iron uptake. The behavior of the soils in vitro is consistent with the theory that geophagy has a therapeutic value for these chimpanzees.

Adsorption↗
PubMed2001

Molecular classification of multiple tumor types.

Using gene expression data to classify tumor types is a very promising tool in cancer diagnosis. Previous works show several pairs of tumor types can be successfully distinguished by their gene expression patterns (Golub et al. 1999, Ben-Dor et al. 2000, Alizadeh et al. 2000). However, the simultaneous classification across a heterogeneous set of tumor types has not been well studied yet. We obtained 190 samples from 14 tumor classes and generated a combined expression dataset containing 16063 genes for each of those samples. We performed multi-class classification by combining the outputs of binary classifiers. Three binary classifiers (k-nearest neighbors, weighted voting, and support vector machines) were applied in conjunction with three combination scenarios (one-vs-all, all-pairs, hierarchical partitioning). We achieved the best cross validation error rate of 18.75% and the best test error rate of 21.74% by using the one-vs-all support vector machine algorithm. The results demonstrate the feasibility of performing clinically useful classification from samples of multiple tumor types.

Algorithms↗
PubMed2000

Use of ultrasonic nebulizer with desolvator membrane for the determination of titanium and zirconium in human serum by means of inductively coupled plasma--mass spectroscopy.

A technique for the determination of titanium and zirconium in human blood serum, after pressurized digestion utilizing ICP-MS coupled to an ultrasonic nebulizer (USN) and desolvating membrane is described. As no CRM for titanium is available, zirconium has been determined in order to demonstrate the accuracy of the technique, as the limits in blood are well known. Bone cement consists basically of a polymer, namely polymethylmethacrylate (PMMA). For better X-ray contrast some manufacturers use incorporated ZrO2 with a volume fraction of 10 to 15%. Thus, the zirconium present in the PMMA matrix can be used as an indicator for the PMMA particulate debris.

Bone Cements↗