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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 55 records · Page 3Linked to original sources
PubMed2001

Adult skeletal profile in isolated cleft palate: a comparison of the von Langenbeck and Wardill procedures for primary repair of the palate.

Sixty-four adult patients operated on for isolated cleft palate were evaluated with regard to facial skeletal morphology using conventional radio-cephalometry. Dental occlusion was assessed clinically. Forty-two had had a von Langenbeck repair at the age of 7 months and 22 a Wardill repair at 18 months. The mean error of the method was 0.7 degree for angular, and 0.9 mm for linear, measurements. The group with clefts had less maxillary prognathism (s-n-ss), more maxillary inclination (NSL/NL), more retroclined lower incisors (ILI/ML), and shorter total and upper facial heights (n-gn, n-sp) compared with the reference group. Multiple regression analysis was used to evaluate differences between the two treatment regimens. Explanatory variables in addition to surgical technique were sex, severity of cleft, and presence of a velopharyngeal flap. Only one variable, lower incisor inclination (ILI/ML), was different for the two regimens. Ten (24%) in the von Langenbeck group had a lateral cross-bite compared with one (5%) in the Wardill group. Other variables in a multivariate regression analysis were affected by sex and severity of cleft to various degrees. This study showed no obvious differences in facial skeletal morphology that could be attributed to surgical technique. Factors other than technique, including sex, age, and severity of cleft merit attention.

Adult↗
PubMed2001

Dopamine fails to inhibit Na,H-exchanger in proximal tubules of obese Zucker rats.

Dopamine via the activation of D1-like receptors inhibits Na,K-ATPase and Na,H-exchanger and subsequently increases sodium excretion. We have previously reported that dopamine failed to inhibit Na,K-ATPase in the proximal tubules (PTs) of obese Zucker rats. The present study was designed to determine the effect of dopamine on Na,H-exchanger in PTs of lean and obese Zucker rats, and examine D1-like receptor-coupled signal transduction pathway mediating the inhibition of Na,H-exchanger. We found that dopamine inhibited Na,H-exchanger in the PTs of lean rats but this response was absent in obese rats. In brush border membranes, [3H]SCH 23390 binding revealed a approximately 45% reduction in D1-like receptor binding sites in obese compared to lean rats. Dopamine stimulated cAMP accumulation in PTs of lean but not in obese rats. Forskolin-mediated stimulation of cAMP was similar in lean and obese rats. Dopamine as well as forskolin and dibutyryl cAMP-mediated stimulation of protein kinase A (PKA) was reduced in PTs of obese compared to lean rats. The data suggest that reduction in D1-like receptor binding sites, defective coupling with signaling pathway and inability of PKA activation may be responsible for the failure of dopamine to inhibit Na,H-exchanger in PTs of obese rats. This phenomenon may contribute to an increase in sodium reabsorption and development of hypertension in obese Zucker rats.

Animals↗
PubMed2001

Interaction of cisplatin, paclitaxel and adriamycin with the tumor suppressor PTEN.

Due to its pivotal role in signal transduction, the universal tumor suppressor PTEN (also termed MMAC or TEP) is one of the putative candidates for involvement in tumorigenesis of several tissues. Although involvement of PTEN in tumorigenesis was shown in different tissues, no data are available concerning PTEN activity in response to antineoplastic agents. Therefore, we assayed the PTEN activity exposed to either blank medium or the commonly used anti-cancer drugs cisplatin, adriamycin or paclitaxel, respectively, in three different concentrations. PTEN activity was determined using the Malachite Green assay basing upon dephosphorylation of phosphatidylinositol-3,4,5-triphosphate (PIP3) by the PTEN enzyme and subsequent determination of inorganic phosphate released. Although the three different anti-cancer drugs assayed act with different cellular modes, the antineoplastics influenced PTEN activity in a similar manner: at low concentrations tested all three antineoplastics significantly increased PTEN activity. However, increasing drug concentrations exhibited a decline but not a total loss of PTEN activity. The data indicate that PTEN activity is increased following cytotoxic drug exposure and, thereby, exhibits its suppressive function. However, the decrease of PTEN activity in response to increasing drug concentrations suggests an aberration of total functional activity. As far as the regulative checkpoint PTEN is abolished, tumor cells might evade cell death pathways resulting in increased proliferation of cancer cells. This might be a general event in refractory tumor cells surviving chemotherapy.

Antineoplastic Agents↗
PubMed2001

Detection of experimental hepatic tumors using long circulating superparamagnetic particles.

RATIONALE AND OBJECTIVES: To evaluate the potential of an iron oxide-based MR contrast agent for the detection and delineation of experimental liver tumors during the early vascular phase of the compound. METHODS: Superparamagnetic blood pool agent (SBPA) was administered intravenously to rabbits bearing VX2 tumors. Images were acquired before the injection, immediately after, and 1 or 3 weeks later. The variations of signal intensity were measured in the tumors and in several tissues for various T1-weighted spin-echo, T2-weighted fast spin-echo, and T2-weighted gradient-recalled-echo sequences. RESULTS: Fourteen and 12 of the 16 tumors were detected immediately after SBPA injection using, respectively, the T2-weighted fast spin-echo and T2-weighted gradient-recalled-echo sequences. A significant decrease in signal intensity was observed in well-perfused organs, and blood signal was abolished even at the lowest injected dose and using a T1-weighted sequence. In the late phase, the loss in signal intensity of the liver was even more pronounced. CONCLUSION: The dominant T2 effect of SBPA induces an increase in the tumor-to-liver and tumor-to-blood contrast during the vascular phase, improving the detection of the tumors and allowing the distinction between small lesions and vessels through plane. This effect on the liver signal persists for several days because of the incorporation of SBPA in the reticuloendothelial system.

Animals↗
PubMed2001

Specificity of parotid sialendoscopy.

OBJECTIVE: To present our initial experience with sialendoscopy of the parotid duct. STUDY DESIGN METHODS: Diagnostic and interventional sialendoscopy procedures were performed in 79 and 55 cases, respectively. Diagnostic sialendoscopy was used to classify ductal lesions into sialolithiasis, stenosis, sialodochitis, and polyps. Interventional sialendoscopy was used to treat these disorders. The type of endoscope used, the type of sialolithiasis fragmentation and/or extraction device used, the total number of procedures, the type of anesthesia, and the number and size of the sialoliths removed were the dependent variables. The outcome variable was the endoscopic clearing of the ductal tree and resolution of symptoms. RESULTS: Diagnostic sialendoscopy was possible in all cases, with an average duration of 26+/-14 minutes and no complications. Interventional sialendoscopy was successful in 85% of cases, with an average duration of 73+/-43 minutes (+/- standard deviation). Multiple procedures were performed in 45% of cases, general anesthesia was used in 24%, and parotidectomy in 2%. Multiple sialoliths were found in 58% of ducts and associated with more procedures under general anesthesia and longer operations. The average size of sialoliths was 3.2+/-1.3 mm; larger stones were associated with more procedures under general anesthesia, longer and multiple procedures, use of fragmentation, and sialendoscopy failures. Sialolithiasis fragmentation was required in 10% of cases, with a success rate of 70%. Semirigid sialendoscopes performed better than flexible ones. Complications were mostly minor but were encountered in 12% of cases. CONCLUSIONS: Diagnostic sialendoscopy is a new technique for evaluating salivary duct disease, a technique which is associated with low morbidity. Interventional sialendoscopy allows the extraction of sialoliths in most patients, preventing open gland excision.

Adolescent↗
PubMed2001

Zinc cyanamide, Zn(CN2).

Single crystals of the title compound have been grown by annealing microcrystalline zinc cyanamide at 843 K in silver crucibles. Zn(CN(2)) crystallizes as colourless prisms. The crystal structure is composed of corner-linked ZnN(4/2) tetrahedra. Carbon and nitrogen form (CN(2))(2-) dumb-bells with the C atom on a twofold axis. Nitrogen is approximately trigonally planar, coordinated by two Zn atoms and one C atom.

Journal Article↗
PubMed2001

p21(waf) correlates with DNA replication but not with prognosis in invasive breast cancer.

BACKGROUND/AIMS: p21(waf) plays a central role both in the regulation of the cell cycle and in DNA replication. Accordingly, p21(waf) is a putative tumour suppressor. The role of p21(waf) expression in breast cancer is still unclear, particularly with respect to the clinical situation. Therefore, this retrospective study was designed to investigate the value of immunohistochemically detected p21(waf) expression in invasive breast cancer. METHODS: Cellular expression of p21(waf) was assessed in 307 breast cancer tissues by immunohistochemistry using the monoclonal antibody, clone 4D10. The data were correlated to established and functional factors of prognosis (age, menopausal status, tumour size, nodal status, tumour grade, receptor status, proliferating cell nuclear antigen (PCNA) expression, Her-2/neu expression, and p53 expression), and to clinical follow up (median observation time, 82 months). RESULTS: Ninety nine of 307 (32.2%) tumour tissues were considered p21(waf) positive (nuclear staining). In the entire study group, p21(waf) expression correlated only with increased PCNA expression (chi(2) test: p = 0.029), and with none of the other investigated markers. In node negative patients (n = 134), p21(waf) expression correlated with increased tumour size and increased PCNA expression, whereas the node positive subgroup (n = 161) showed no correlation with these parameters (lymphonodectomy was done in 295 women). With respect to clinical outcome, p21(waf) expression showed a definite favourable trend in both subgroups (N0: p21(waf) negative, 23 of 87; p21(waf) positive, nine of 43. N+: p21(waf) negative, 63 of 107; p21(waf) positive, 23 of 52), but this observation was not significant (p > 0.05). Multivariate analysis for disease free survival as indicated by Cox regression analysis included all factors investigated. The most striking parameters were nodal status (relative risk (RR), 1.74; p = 0.00001), receptor status (RR, 0.59; p = 0.0085), tumour size (RR, 1.42; p = 0.02), and Her2/neu expression (RR, 1.56; p = 0.033). p21(waf) expression was not significant in the multivariate analysis (p > 0.05). CONCLUSIONS: p21(waf) expression is an independent factor but fails to be of prognostic or predictive value in multivariate analysis. These data confirm the hypothesis of a p53 independent p21(waf) induction and suggest a functional role in the inhibition of PCNA mediated DNA replication.

Breast Neoplasms↗
PubMed2001

Histopathology of submandibular glands removed for sialolithiasis.

We reviewed the clinical history of 48 consecutive patients who underwent submandibular gland removal for radiologically proven sialolithiasis. The specimens were examined by a pathologist blinded to the clinical data. A histopathologic classification into I of 3 grades was established by evaluating the degrees of atrophy, fibrosis, and inflammation. A correlation between the clinical and pathological variables was sought in order to define clinical variables that would predict abnormal submandibular glands that required extirpation. A significant percentage of the submandibular glands exhibited normal histologic findings. The patients with normal submandibular glands had a clinical evolution similar to that of other patients with severely damaged glands. The only clinical variable that correlated with increased histopathologic alteration was the patient's age. In view of the newly available diagnostic and therapeutic techniques for sialolithiasis, a conservative attitude to submandibular gland resection appears justified.

Adult↗
PubMed2001

How parents of premature infants gather information and obtain support.

PURPOSE: To identify the process by which parents of premature infants seek information, the kinds of information they seek, and the resources they use to meet their educational and support needs. DESIGN/SAMPLE: Descriptive study using 19 parent interviews and 64 questionnaires. MAIN OUTCOME VARIABLE; The process parents use to obtain information and support. RESULTS: Parents of premature infants make a transition from being passive recipients of information to actively seeking it. They spend 10-20 hours a week gathering information during the first month of the baby's hospitalization. They desire more information than is provided, particularly in the areas of infant health, infant care, and coping. Family is the primary source of support prior to birth and after discharge, but during the infant's convalescence, nurses are the main source of support and help for parents in understanding and adapting to their baby. Many parents would use a computer-based resource for information if it were available to them.

Adaptation, Psychological↗
PubMed2001

Quantification of human cells in NOD/SCID mice by duplex real-time polymerase-chain reaction.

BACKGROUND AND OBJECTIVES: The aim of this study was the development of a fast and reliable polymerase chain reaction (PCR) assay which quantifies the proportion of human cells in immunodeficient chimeric mice, for example transplanted with human hematopoietic stem cells. DESIGN AND METHODS: We developed a TaqMan chemistry-based, real-time duplex PCR assay to quantify human and murine DNA in a single-tube reaction in parallel (HUmu PCR). Two independent sets of primers and exonuclease probes, located in the tumor necrosis factor-a gene of both species, were selected to amplify specifically human and murine genomic DNA. Serial dilutions of defined numbers of human cells in mouse cells served to construct calibration curves. The test was applied to NOD/SCID mice transplanted with CD34(+) cells isolated from human cord blood and compared to FACS analysis. RESULTS: Analysis of DNA from human cells diluted stepwise into a fixed number of murine cells - and vice versa - led to calibration curves with good correlation for human and murine cells (r(2)>0.99) with a detection limit of 2% human cells. Results obtained with the HUmu PCR paralleled those of FACS analysis. However, in contrast to FACS analysis, which requires fresh single cell suspensions, the HUmu PCR can be carried out on already stored samples, even from solid organs and, moreover, the quantity of material required for analysis is very low. INTERPRETATION AND CONCLUSIONS: The HUmu PCR presented here is the first real-time PCR assay for simultaneous quantification of human and murine cells. It is extremely fast, accurate and is an interesting alternative method for quantifying the proportion of human DNA in organs of chimeric mice.

Animals↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

Donor stromal cells from human blood engraft in NOD/SCID mice.

Little is known about the presence, frequency, and in vivo proliferative potential of stromal cells within blood-derived hematopoietic transplants. In this study, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were injected with human CD34(+) peripheral blood cells (PBCs) or cord blood cells (CBCs, either enriched for CD34 or density-gradient separated mononuclear cells). Flow cytometric analysis 5 to 11 weeks after transplantation revealed the presence of a human lymphomyeloid hematopoiesis within the murine bone marrow. Immunohistochemical staining of bone marrow cell suspensions using human-specific antibodies showed human cells staining positive for human fibroblast markers, human von Willebrand factor (vWF) and human KDR (vascular endothelial growth factor receptor-2) in mice transplanted with CD34(+) PBCs or CBCs, with mean frequencies between 0.6% and 2.4%. In stromal layers of bone marrow cultures established from the mice, immunohistochemical staining using human-specific antibodies revealed flattened reticular cells or spindle-shaped cells staining positive with human-specific antifibroblast antibodies (mean frequency, 2.2%). Cell populations of more rounded cells stained positive with human-specific antibodies recognizing CD34 (1.5%), vWF (2.2%), and KDR (1.6%). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and subsequent complementary DNA sequencing detected transcripts of human KDR (endothelial specific) and human proline hydroxylase-alpha (fibroblast specific) within the bone marrow and spleen of transplanted mice. Analysis of nontransplanted control mice yielded negative results in immunocytochemistry and RT-PCR. Cells expressing endothelial and fibroblast markers were also detected in the grafts before transplantation, and their numbers increased up to 3 log in vivo after transplantation. These results indicate that stromal progenitor cells are present in human cytokine-mobilized peripheral blood or cord blood that engraft in NOD/SCID mice. (Blood. 2000;96:3971-3978)

Animals↗
PubMed2000

Expression of the collagen receptor glycoprotein VI during megakaryocyte differentiation.

This study examined the expression of the platelet collagen receptor glycoprotein VI (GPVI) in megakaryocyte cell lines and primary megakaryocytes by reverse transcriptase-polymerase chain reaction and by flow cytometry and ligand blotting using the snake venom toxin convulxin. Expression of GPVI is increased in the megakaryoblastic cell lines HEL and CMK on differentiation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), along with the Fc receptor gamma-chain (FcR gamma-chain). The increase in GPVI expression is associated with marked potentiation of tyrosine phosphorylation and Ca(++) elevation in response to convulxin. Syk, linker for activated T cells, and phospholipase C gamma 2 (PLC gamma 2) are among the proteins tyrosine phosphorylated on convulxin stimulation in PMA-differentiated HEL cells. Studies on primary murine megakaryocytes grown in vitro confirmed that GPVI is up-regulated in parallel with functional activation, assessed by measurement of [Ca(++)](i), during differentiation. The results demonstrate that expression of GPVI is up-regulated along with the FcR gamma-chain during differentiation of megakaryocytes. (Blood. 2000;96:2740-2745)

Animals↗
PubMed2000

Identification and functional characterization of the human and murine fibroblast growth factor receptor 4 promoters.

Fibroblast growth factor receptors (FGFRs) play crucial roles in signal transduction of adult tissues and during embryonic development. To study the transcriptional control, we isolated and characterized the promoter of human FGFR4. Two transcription initiation sites were identified. The deletion analysis in different cell types defined a core promoter reaching from -9 to -198, lacking TATA and CCAAT boxes but displaying high GC content (77%) in a stretch of 300 bp upstream of the major mRNA start. This region harbors multiple binding motifs for transcription factors. Moreover, the region between -1085 and -1140 contains a potential repressor element, which downregulates transcriptional activity. To identify conserved regulatory elements, we isolated and analyzed also the murine FGFR4 promoter. Only one transcription start was identified using RNase protection assays. Sequence alignment of human and mouse shows a striking similarity in the core promoter region of both genes, encompassing conserved transcription factor binding sites and a splice acceptor site. Furthermore, the region containing the putative repressor element is also conserved suggesting a functional role for gene expression.

Animals↗
PubMed2000

Solid-phase parallel synthesis of azarene pyrrolidinones as factor Xa inhibitors.

A focused library (4 x 14) prepared from 4-aminopyridine and 4-, 5-, and 6-azoindole templates was synthesized using 14 polymer supported 4-amido-2,3,5,6-tetrafluorophenyl (TFP) sulfonate esters inputs. Several compounds were identified as factor Xa inhibitors (IC50< or =0.1 microM) helping to establish the SAR among these four series of azarene pyrrolidinones.

Anticoagulants↗
PubMed2000

Cytoplasmic localization and the choice of ligand determine aggregate formation by androgen receptor with amplified polyglutamine stretch.

Polyglutamine tract expansion in androgen receptor is a recognized cause of spinal and bulbar muscular atrophy (SBMA), an X-linked motor neuronopathy. Similar mutations have been identified in proteins associated with other neurodegenerative diseases. Recent studies have shown that amplified polyglutamine repeat stretches form cellular aggregates that may be markers for these neurodegenerative diseases. Here we describe conditions that lead to aggregate formation by androgen receptor with polyglutamine stretch amplification. In transfection experiments, the mutant, compared with the wild-type receptor, was delayed in its cytoplasmic-nuclear translocation and formed large cytoplasmic aggregates in the presence of androgen. The cytoplasmic environment appears crucial for this aggregation, since retention of both the wild-type and mutant receptors in this cellular compartment by the deletion of their nuclear localization signals resulted in massive aggregation. Conversely, rapid nuclear transport of both receptors brought about by deletion of their ligand binding domains did not result in aggregate formation. However, androgen antagonists that altered the conformation of the ligand binding domain and promoted varying rates of cytoplasmic-nuclear translocation all inhibited aggregate formation. This demonstrates that in addition to the cytoplasmic localization, a distinct contribution of the ligand binding domain of the receptor is necessary for the aggregation. The finding that antiandrogens inhibit aggregate formation may provide the basis for in vivo determination of the role of these structures in SBMA.

Animals↗
PubMed2000

Feasibility and early results of accelerated radiotherapy for head and neck carcinoma in the elderly.

BACKGROUND: Accelerated radiotherapy (RT) represents a promising method with which to improve the treatment outcome in patients with head and neck carcinoma. However, its applicability to elderly patients has not been well established. This study assessed treatment toxicities, patient compliance, and oncologic results in patients age >/= 70 years who were treated with an accelerated concomitant boost RT schedule. METHODS: Between 1991 and 1997, 39 patients aged >/= 70 years (mean, 75 +/- 6 years) presenting with carcinomas of the oral cavity, pharynx, or larynx were treated radically with a modified concomitant boost RT schedule (planned dose of 69.9 grays [Gy] over 38 days). Based on American Joint Committee on Cancer staging, there were 14 patients with Stage I-II disease and 25 patients with Stage III-IV disease. Eighty-one patients age < 70 years who were treated with the same RT schedule served as a comparative group. The median follow-up for the surviving patients was 19 months (range, 3-65 months) and 23 months (range, 2-76 months), respectively, for the elderly and younger patient groups. RESULTS: The planned RT schedule was completed in all cases. Three patients (8%) in the elderly group and none in the younger group had an unplanned treatment interruption because of acute toxicity or lack of compliance (P = 0.03). The median tumor dose (69.9 Gy; range, 67-73 Gy) and the median overall treatment time (41 days; range, 36-60 days) were identical in both groups. According to the Radiation Therapy Oncology Group grading system, Grade 3-4 acute reactions were observed in 66% of elderly patients and in 71% of younger patients. Ten elderly patients (26%) and 19 younger patients (23%) required a nasogastric tube or a percutaneous gastrostomy for feeding, with a median weight loss of 4.1 kg and 4.4 kg, respectively, in the 2 groups. Grade 3-4 late complications were observed in 3% of the elderly patients and 10% of the younger patients (P = 0.43). Both elderly and younger patients had similar results with regard to 3-year actuarial overall survival (68% vs. 62%; P = 0.48) and locoregional control (73% vs. 68%; P = 0.31). CONCLUSIONS: The current study suggests that an accelerated concomitant boost RT schedule is feasible in elderly patients who are physically healthy enough to undergo curative treatment. The acute and late toxicities appear to be similar to those observed in younger patients, and treatment outcomes appear to be comparable.

Actuarial Analysis↗