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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Surgical prevention of post-traumatic infection by immediate necrectomy of burn wounds].

Sepsis is the commonest cause of death following burn injuries. The main source of the bacteria which cause the onset of sepsis is the burn wound itself. We evaluated the question of whether immediate necrectomy versus early necrectomy leads to a decrease in septic complications, as well as posttraumatic lethality. We evaluated 66 patients, 33 of whom underwent immediate necrectomy (i.e., within the first 3 days posttraumatically, group 1); the remaining 33 patients underwent necrectomy in the early posttraumatic phase (from the fourth posttraumatic day, group 2). Following immediate necrectomy (group 1), septic complications developed in 12.1%, as compared to 33.3% in group 2 (p < 0.01). Lathality was significantly reduced in group 1 with 9.1% compared to 21.2% in group 2 (p < 0.01). In this study it was demonstrated that immediate necrectomy versus early necrectomy in young patients leads to a significant decrease of septic complications and lethality following burn injury.

Adult↗
PubMed1996

Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma.

A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.

Adult↗
PubMed1996

Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody.

A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving </=9 mCi/m2, 55% had grade 1 or 2 leukopenia and/or thrombocytopenia. Two of three patients treated with 12 mCi/m2 experienced grade 3 thrombocytopenia and leukopenia. One patient treated with 12 mCi/m2 had grade 4 neutropenia. The maximum tolerated dose of 90Y-CYT-356 was 9 mCi/m2. Only one patient developed a human anti-mouse antibody 4 weeks after treatment. No patient attained a complete or partial response based on prostate-specific antigen and/or radiological criteria. Three patients had transient subjective improvement in the symptomatology of their disease. In addition, patients treated with 12 mCi/m2 of 90Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of 90Y-CYT-356 </=9 mCi/m2.

Aged↗
PubMed1995

Multiple courses of high-dose total skin electron beam therapy in the management of mycosis fungoides.

PURPOSE: A retrospective analysis was undertaken to determine the indications for, the efficacy of, and the long-term complications of two courses of total skin electron beam therapy for mycosis fungoides. METHODS AND MATERIALS: A retrospective analysis of 15 patients with the pathologic diagnosis of mycosis fungoides treated in the Department of Radiation Oncology at Stanford University Medical Center between 1968 and 1990 was performed. All patients received two courses of high-dose electron beam therapy to the skin. The mean dose for the total skin treatment for the first course was 32.6 Gy and 23.4 Gy for the second course of treatment. RESULTS: Following the first course of total skin electron beam therapy, 11 of 15 had a complete response, with a mean duration of 11.6 months. All patients received adjuvant therapies between the first and second courses of high-dose total skin electron beam therapy. The mean interval between the first and the second courses of therapy was 41.3 months. Patients were restaged prior to commencement of their second course of high-dose total skin electron beam therapy, resulting in upstaging in six. The second course of therapy resulted in six complete responses and nine partial responses. Twelve of these patients have since died, 1 is lost to follow-up, and 2 are living with disease. The long-term side effects in the two living patients include pigmentation changes, alopecia, and diffuse xerosis. CONCLUSION: Delivery of two courses of total skin electron beam therapy is technically feasible, tolerable, and efficacious. The dose to the total skin was reduced for the second course of therapy in all cases. The criteria used to screen patients included initial good response to total skin electron treatment, long disease-free interval, exhaustion of other therapeutic modalities, and generalized skin involvement at relapse. Long-term toxicities were mild in severity and generally consisted of generalized xerosis, scattered telangiectasias, pigmentation changes, and partial alopecia.

Adult↗
PubMed1995

Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with Src and P85 alpha.

Following ligand binding, the epidermal growth factor receptor (EGF-R) autophosphorylates itself on tyrosine residues located in its carboxyl terminus; in vitro, three sites are highly phosphorylated, while two other sites are phosphorylated to lesser extents. In the presence of the Src protein-tyrosine kinase, in vitro phosphorylation of the minor autophosphorylation sites was increased, and four additional residues were phosphorylated. Following EGF stimulation, two (Tyr-891 and Tyr-920) were found to be phosphorylated in a colorectal cell line (DLD-1) and in a breast tumor cell line (MCF7). The remaining in vitro sites were not found to be highly phosphorylated in vivo. The sequences surrounding Tyr-891 and Tyr-920 match the reported consensus binding sequences for the SH2 domains of Src and the regulatory domain of phosphatidylinositol 3-kinase (p85 alpha), respectively. In vitro, both of these proteins were found to bind to Src-phosphorylated EGF-R with approximately 100-fold greater affinity than to autophosphorylated EGF-R, demonstrating that Src creates new sites for SH2 binding. Furthermore, Csk-inactivated Src was activated by interaction with Src-phosphorylated EGF-R but not by autophosphorylated EGF-R. Upon EGF treatment of MCF7 or three colorectal carcinoma cell lines (WiDr, DLD-1, and LS174T), the EGF-R coimmunoprecipitated with both p85 alpha and Src. Evidence is also presented that suggests that an EGF-R-related protein, ErbB2, may be involved in similar Src-mediated interactions. These data demonstrate that EGF-R is phosphorylated in vivo at non-autophosphorylation sites and that these novel sites can act as docking sites for Src, P85 alpha, and potentially other SH2-containing proteins. In addition, the data suggest a tyrosine phosphatase-independent mechanism for the elevation of Src activity in cells exposed to growth factors. Overexpression of Src, EGF-R, and/or ErbB2 in breast and colorectal tumor cells suggests the potential that such interactions may contribute to the transformed phenotype of these carcinomas.

Amino Acid Sequence↗
PubMed1995

Mobilization of peripheral blood stem cells with chemotherapy and cytokines in multiple myeloma.

In an attempt to offset the impaired hematopoietic progenitors' mobilization and collection which are frequently encountered in multiple myeloma (MM), we have started a pilot study to evaluate the ability of a combination of high-dose melphalan (HDM) and sequential s.c. administration of recombinant human interleukin 3 (rhIL-3) and rh-granulocyte colony-stimulating factor (G-CSF) to mobilize blood cells (BC) in MM patients. Two different schedules for administration were successively tested. Schedule A consisted of IL-3 (5 micrograms/kg/d) from day 7 to day 11 after HDM followed by G-CSF (5 micrograms/kg/d) from day 12 to day 20. Under schedule B, HDM was followed by IL-3 alone at the same dosage from day 1 to day 3, IL-3 and G-CSF (idem) from day 4 to day 7 and G-CSF alone from day 8 until completion of apheresis. Two patients (one previously untreated, one having received prior chemotherapy for one year) underwent schedule A; three patients (one previously untreated, two pretreated) underwent schedule B. The post-HDM aplasia was not shortened in schedule A patients in comparison to what we usually observed following HDM alone (25 days) correlated with a very moderate two- to three-fold CD34+ cell increase. Only one patient was further transplanted with apheresis products: the post-transplant granulocyte recovery was slower than usual (16 days versus 12 days) while platelet count never recovered over 20 x 10(9)/l. In contrast, the post-HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Static fundus perimetry using the scanning laser ophthalmoscope with an automated threshold strategy.

PURPOSE: The purpose of this study was to develop software that allows the performance of routine static threshold perimetry using the scanning laser ophthalmoscope (SLO) and the comparison of the results with conventional computerized cupola perimetry. The original software does not allow performance of static threshold perimetry within a reasonable examination time. METHODS: Static perimetry was performed in random order on 50 healthy eyes using our SLO staircase threshold perimetry technique and the Octopus 500 (program 38). We compared the relative sensitivities for each of 25 corresponding visual field locations. RESULTS: Mean sensitivity in the SLO perimetry amounted to 32.7 dB (range 25-37 dB) while it was 28.7 dB in the Octopus. For all test locations the SLO showed higher dB values on average. The mean difference between both methods was 3.7 +/- 0.8 dB (range 1.4-5.8 dB) when the test locations at the blind spot were excluded (linear regression between the two methods: r = 0.843, P < 0.0001). The mean time interval between two stimulus presentations was 2.5 s with the SLO perimetry. CONCLUSION: With the Heidelberg software, automated static threshold perimetry using the SLO is possible within reasonably short examination times. The mean time interval between two test point presentations is about one tenth of that necessary using the original Rodenstock software. There is a systematic difference between SLO and Octopus fields of about 4 dB which was not very much influenced by the stimulus locations.

Adult↗
PubMed1995

Biosynthesis of (1,3)(1,4)-beta-glucan and (1,3)-beta-glucan in barley (Hordeum vulgare L.). Properties of the membrane-bound glucan synthases.

Mixed membrane preparations from the coleoptiles and first leaves of young barley (Hordeum vulgare L. cv. Triumph) plants catalysed the synthesis of 55% methanol-insoluble labelled material from UDP-[U-14C]glucose, the main components of which were identified as (1,3)(1,4)-beta- and (1,3)-beta-D-glucans. The membrane preparations also catalysed the transformation of UDP-glucose into labelled low-molecular-weight products, mainly glucose (by phosphatase action), glucose-1-phosphate (by phosphodiesterase action) and glyco(phospho)lipids (by glycosyltransferase action). The formation of (1,3)(1,4)-beta-glucans, (1,3)-beta-glucans, and the other reactions competing for UDP-glucose, were monitored simultaneously and quantitatively by a novel procedure based on enzymatic analysis, thin-layer chromatography and digital autoradiography. Thus it was possible (i) to optimise conditions to obtain (1,3)(1,4)-beta-glucan synthesis or (1,3)-beta-glucan synthesis in isolation, and (ii) to study the influence of temperature, pH, cofactors, substrate concentration etc. on the (1,3)(1,4)- and (1,3)-beta-glucan synthesis reactions even when both occurred together. The synthesis of both beta-glucans was optimal at 20 degrees C. In Tris-HCl buffer, the pH optima for (1,3)(1,4)-beta-glucan synthesis and (1,3)-beta-glucan synthesis were pH 8.5 and pH 7.0, respectively. Both glucan-synthesis reactions required Mg2+: (1,3)-beta-glucan synthesis was optimal at 2 mM, whereas (1,3)(1,4)-beta-glucan synthesis continued to increase up to 200 mM Mg2+, when the ion was supplied as the sulphate. (1,3)-beta-Glucan synthesis was Ca2+ dependent and this dependence could be abolished by proteinase treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Conformation↗
PubMed1995

Unimanual motor learning impaired by frontomedial and insular lesions in man.

We correlated impaired unimanual motor learning with the lesion site in 53 patients with chronic lesions predominantly of the frontal lobe. The lesions were assessed using computed tomography (CT), then transferred to standard templates of nine slices parallel to the canthomeatal plane and digitized with a raster matrix of 3 mm by 3 mm width. The learning task was to track a moving target on a computer screen with a dot guided by the preferred hand, while the horizontal coupling between hand movement and screen was inverted. The mean tracking error was recorded over eight successive trials of 80s duration. If the mean error of the last three trials was not lower than that of the first three trials, impaired motor learning was assumed. We correlated performance and lesion with a contingency table analysis for each raster element. Impaired motor learning was associated with a lesion within the supplementary motor area and adjacent anterior cingulate, and within the anterior insular region. Our results indicate that these regions are critical for motor learning and functional plasticity in man. Our data support activation patterns obtained with positron emission tomography.

Adolescent↗
PubMed1995

Plasma cell granuloma of the supraglottic larynx.

The occurrence of plasma cell granuloma of the larynx appears to be unusual. Review of the literature revealed only two previously reported cases. We present an additional case of plasma cell granuloma of the larynx. The diagnosis was made by histological and immunohistochemical examinations. The tumour was successfully treated by radiation therapy.

Granuloma, Plasma Cell↗
PubMed1995

Preservation of peripheral nerve grafts: a comparison of normal saline, HTK organ preservation solution, and DMEM Schwann cell culture medium.

The regeneration of peripheral nerve grafts was evaluated in a rat model, after pretreating the grafts with Schwann cell culture medium, HTK organ preservation solution, and normal saline, under cold ischemic conditions for different time periods. Following orthotopic replantation of the grafts into donor animals, the quality of regeneration was assessed after 6 weeks, compared to positive controls (autologous transplantation) and negative controls (acellular grafts). The regenerative quality in the Schwann cell culture groups with ischemic periods of 32 and 72 hr was comparable to normal controls. Significantly minor regeneration was detected in specimens undergoing 14 and 120 hr of ischemia in the Schwann cell culture medium and in the HTK and normal saline groups, regardless of ischemic time. Among the conclusions was that controlled proliferation of Schwann cells seems to be a basic principle for preservation of peripheral nerve grafts.

Animals↗
PubMed1995

[Kinetic fundus controlled perimetry with the scanning laser ophthalmoscope].

BACKGROUND: The detection of circumscribed visual field defects due to pathologic macular findings may be difficult even when modern conventional perimetry procedures are used. Using conventional clinical methods there exists no reliable correlation between morphology and function for follow-up and documentation. The Laser Scanning Ophthalmoscope enables a fundus-based examination and therefore allows exact comparison between morphologic appearance and corresponding function. PATIENTS AND METHODS: 50 eyes with pathologic macular findings were examined using a newly developed kinetic perimetry method based on the Scanning Laser Ophthalmoscope. The results were compared to those obtained with other clinical examinations such as Goldmann or Octopus visual field and Amsler-chart. RESULTS: Fundus-based examination with the SLO is preferable for detection especially when small pathologic findings at the posterior pole like macular holes or small serous detachments are combined with reduced stability of fixation. The detection of sharp borders of the scotomas is much better than with conventional perimetry. CONCLUSION: The Scanning Laser Ophthalmoscope allows several different types of fundus-based examinations. Concerning kinetic perimetry we were able to find the borders of scotomas within very short examination times. This method therefore is of valuable help in patients with circumscribed scotomas at the posterior pole combined with deterioration of the stability of fixation and allows documentation for follow-up and further comparison with other clinical findings.

Adult↗
PubMed1995

Characterization of kinectin, a kinesin-binding protein: primary sequence and N-terminal topogenic signal analysis.

Kinectin is a kinesin-binding protein (Toyoshima et al., 1992) that is required for kinesin-based motility (Kumar et al., 1995). A kinectin cDNA clone containing a 4.7-kilobase insert was isolated from an embryonic chick brain cDNA library by immunoscreening with a panel of monoclonal antibodies. The cDNA contained an open reading frame of 1364 amino acids encoding a protein of 156 kDa. A bacterially expressed product of the full length cDNA bound purified kinesin. Transient expression in CV-1 cells gave an endoplasmic reticulum distribution that depended upon the N-terminal domain. Analysis of the predicted amino acid sequence indicated a highly hydrophobic near N-terminal stretch of 28 amino acids and a large portion (326-1248) of predicted alpha helical coiled coils. The 30-kDa fragment containing the N-terminal hydrophobic region was produced by cell-free in vitro translation and found to assemble with canine pancreas rough microsomes. Cleavage of the N terminus was not observed confirming its role as a potential transmembrane domain. Thus, the kinectin cDNA encodes a cytoplasmic-oriented integral membrane protein that binds kinesin and is likely to be a coiled-coil dimer.

Amino Acid Sequence↗
PubMed1995

Neoplastic invasion of the laryngeal cartilage: comparison of MR imaging and CT with histopathologic correlation.

PURPOSE: To compare the usefulness of computed tomography (CT) and gadolinium-enhanced magnetic resonance (MR) imaging in the detection of neoplastic invasion of laryngeal cartilage. MATERIALS AND METHODS: In a prospective study, 53 patients with carcinoma of the larynx or piriform sinus underwent CT and MR imaging before total or partial laryngectomy. The findings at imaging and pathologic examination were compared. RESULTS: At histologic examination, neoplastic invasion of cartilage was present in 34 patients and absent in 19. MR imaging was more sensitive than CT (89% vs 66%; P = .001). Inflammatory changes and fibrosis, however, were indistinguishable from tumor on MR images, resulting in overestimation of neoplastic invasion in a large number of patients. Therefore, MR imaging was less specific than CT (84% vs 94%; P = .004). CONCLUSION: MR imaging is more sensitive than CT in detecting neoplastic invasion of cartilage, but the inability to differentiate between nonneoplastic inflammatory changes and tumor with MR imaging leads to overestimation of neoplastic invasion.

Carcinoma, Squamous Cell↗