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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 91 records · Page 5Linked to original sources
PubMed1999

Resectable esophageal carcinoma: local control with neoadjuvant chemotherapy and radiation therapy.

PURPOSE: To evaluate the usefulness of neoadjuvant chemotherapy and radiation therapy before esophagectomy for invasive cancer of the esophagus or gastroesophageal junction (GEJ). MATERIALS AND METHODS: The authors conducted a retrospective analysis of 154 patients who underwent esophagectomy for invasive cancer between September 1, 1991, and December 31, 1995. The end points evaluated were overall, disease-free, local-regional relapse-free, and systemic relapse-free survival. RESULTS: Seventy of the 154 patients received neoadjuvant combined-modality therapy (CMT) consisting of concurrent cisplatin and fluorouracil administration and accelerated, hyperfractionated radiation therapy. The remaining 84 patients underwent immediate esophagectomy. With a median follow-up of 34.7 months, the 3-year overall, disease-free, and distant metastatic relapse-free survival rates were 38.0%, 41.9%, and 56.0%, respectively. Although neoadjuvant therapy did not appear to prevent distant metastases, there was a dramatic effect on local control. After CMT, the 5-year local control rate was 90% compared to 64% after surgery (P < .001). Tumors in the GEJ recurred more frequently (P = .01); however, multivariate analysis showed CMT was the only independent predictor of local control. Postoperative mortality was 15.7% after CMT versus 5.9% without CMT (P = .05). CONCLUSION: Local control of esophageal cancer is excellent following neoadjuvant chemotherapy and radiation therapy. However, the effects of CMT on overall and disease-free survival are less clear due to significant differences between the treatment groups.

Adenocarcinoma↗
PubMed1999

The Wisconsin Quality of Life Index: a multidimensional model for measuring quality of life.

The Wisconsin Quality of Life Index (W-QLI) is a multidimensional model for measuring quality of life. This model assumes that quality of life is comprised of 9 dimensions: life satisfaction, occupational activities, psychological well-being, physical health, social relations, economics, activities of daily living, symptoms, and the patient's own goals. The W-QLI takes into account the different perspectives of the patient, the patient's family, and the clinician, both currently and over time. An accompanying taxonomy and patient outcome report can be used in clinical practice to group the patient's goals and to track the attainment of the goals over time, as well as to show the agreements and disagreements between the patient and clinician in terms of how satisfied each is with the patient's progress. The W-QLI, taxonomy, and outcome report can also incorporate the service provider's goals and can be used to examine program results.

Activities of Daily Living↗
PubMed1999

Anticancer drug sensitivity and expression of multidrug resistance markers in early passage human sarcomas.

We have established new human sarcoma lines and examined their sensitivity to common antitumor drugs and expression of putative multidrug resistance (MDR) proteins. Eighty-two sarcoma samples were transplanted in nude mice. Fourteen of these sarcomas were established as tumor cell lines. We determined a chemosensitivity profile to antitumor drugs (MDR drugs = doxorubicin, mitoxantrone, and vincristine; non-MDR drugs = cisplatin, ifosfamide, and bleomycin) for each tumor line in vivo. Response to chemotherapy with doxorubicin and ifosfamide was observed in 30-50% of these tumor lines. Our results obtained with xenotransplants are similar to the results documented in clinical trials in which doxorubicin and ifosfamide are effective in 30-50% of the patients. Furthermore, we examined expression of MDR-relevant markers like P-glycoprotein, MDR-associated protein, lung resistance protein, and mdr1 mRNA in these xenotransplants. A relationship between mdr1 mRNA expression and response to doxorubicin was demonstrated in >90% of our tumor lines. In six sarcomas with mdr1 mRNA expression, five were resistant against doxorubicin and cross-resistant against several other drugs, whereas from eight sarcomas, which lacked detectable mdr1 mRNA, seven were sensitive to doxorubicin and other drugs. We found lung resistance protein or MDR-associated protein expressed in three resistant and mdr1 mRNA-positive sarcomas. These results demonstrate that mdr1 mRNA expression is a putative marker for drug resistance in our sarcoma lines. We conclude, therefore, that inherent P-glycoprotein expression might be also responsible for drug resistance occurring in treatment of patients with sarcomas. The established tumor lines are useful for additional investigations on mechanisms of drug resistance in sarcomas and as models for preclinical screening of new antitumor drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

A potent protein-tyrosine kinase inhibitor which selectively blocks proliferation of epidermal growth factor receptor-expressing tumor cells in vitro and in vivo.

A calculated 3-D model of the kinase domain of the epidermal growth factor receptor (EGF-R) protein-tyrosine kinase (PTK) was used to develop a pharmacophore model for ATP-competitive inhibitors and, subsequently, a new class of selective EGF-R kinase inhibitors. CGP 59326A, a highly selective and potent inhibitor of the EGF-R in vitro, inhibited the proliferation of EGF-R-expressing epithelial lines, while having little anti-proliferative activity against EGF-R-negative lines. In contrast to previously described inhibitors, CGP 59326A had potent and selective in vivo anti-tumor activity at well-tolerated doses against EGF-R-expressing tumors (e.g., ED50 of 0.78 to 1.5 mg/kg for inhibition of A431 tumor growth). CGP 59326A inhibited growth of human tumor xenografts expressing the EGF-R but showed little activity against EGF-R-negative xenografts. Combination of CGP 59326A with cytotoxic agents resulted in tumor regression and cures. The high selectivity and attractive biological profile of CGP 59326A suggest that it could have therapeutic value in the treatment of proliferative diseases which involve mitogenic signaling from the EGF-R.

3T3 Cells↗
PubMed1998

Mutations of the DPC4/Smad4 gene in biliary tract carcinoma.

A candidate tumor suppressor gene, DPC4, located at 18q21.1, has recently been shown to be inactivated in half of pancreatic adenocarcinomas. The close developmental relationship of the pancreas and biliary tract prompted us to determine the role of DPC4 in the multistep carcinogenesis of biliary tract carcinoma. A search for mutations in the genomic sequence of the highly conserved COOH-terminal domain of DPC4 (exons 8-11) was performed by single-strand conformational polymorphism analysis. Five of 32 (16%) primary biliary tract carcinomas had point mutations in the DPC4 sequence. Interestingly, inactivation of DPC4 was especially common in carcinomas originating from the common bile duct (four of eight specimens analyzed), suggesting an important role for DPC4 in the development of this subtype of biliary tract tumor.

Amino Acid Sequence↗
PubMed1998

Protection from Plasmodium berghei infection by priming and boosting T cells to a single class I-restricted epitope with recombinant carriers suitable for human use.

The desirability of inducing cytotoxic T cell responses to defined epitopes in humans has led to the development of a variety of recombinant delivery systems. Recombinant protein particles derived from a yeast retrotransposon (Ty) and the modified Ankara vaccinia (MVA) virus can deliver large epitope strings or even whole proteins. Both have previously been administered safely in humans. Immunization with recombinant Ty and MVA containing a single Plasmodium berghei class I-binding epitope provided 95% sterile protection against malaria in mice. The sequence of immunization, Ty followed by MVA, was critical to elicit high levels of IFN-gamma-producing cells and protection. The reciprocal sequence (MVA/TY) or homologous boosting was not protective. Both constructs (Ty and MVA) contain the H-2Kd-restricted pb9 CTL epitope from the circumsporozoite protein of P. berghei among a string of 8-15 human P. falciparum-derived CTL epitopes restricted through 7 common HLA alleles as well as widely recognized CD4 T cell epitopes. Thus, the novel recombinant Ty/MVA prime/boost combination with these constructs provides a safe alternative for evaluation for human vaccination against P. falciparum malaria.

Animals↗
PubMed1998

Crystallization of phycoerythrin 545 of Rhodomonas lens using detergents and unusual additives.

Phycoerythrin 545 from the cryptomonad alga, Rhodomonas lens, has been crystallized under a wide variety of conditions. Although this type of photosynthetic light-harvesting protein is water soluble, detergents were always required for crystallization. The crystals were typically poorly ordered, or ordered in only two dimensions. However, crystals that were well-ordered in three dimensions could be obtained under two different conditions. Both used polyethylene glycol as precipitant and the detergent lauryldimethylaminoxide, but the additives that were critical for obtaining well-ordered crystals were propionamide in one case and Cs+/Br- in the other. Crystals obtained in the presence of propionamide have the space group P2(1)2(1)2(1), with cell constants of a = 85.6 angstroms, b = 108.2 angstroms, and c = 131.0 angstroms, and contain two dimers [i.e., 2 x (alpha2beta2)] in the asymmetric unit. They show diffraction to at least 3.0 angstroms resolution. The crystals grown with Cs+/Br- are nearly isomorphous. Both types of crystals show intense, strongly polarized fluorescence, suggesting that energy transfer in the crystals is highly efficient. This should provide a basis for quantitative investigation of the role of exciton interactions in energy transfer in cryptomonad phycobiliproteins.

Buffers↗
PubMed1998

Monitoring local disposition kinetics of carboplatin in vivo after subcutaneous injection in rats by means of 195Pt NMR.

The anticancer drug carboplatin has been monitored in rats during treatment by means of in vivo 195Pt NMR spectroscopy at 2.0 T. The purpose of the study was to assess local disposition kinetics in intact tissue following subcutaneous injection of a platinum-containing drug. Serial 195Pt NMR measurements have been carried out in four animals after administration of carboplatin solutions with doses ranging from 37.1 to 59.4 mg per kg body weight. A surface coil of 2 cm diameter tuned to 18.3 MHz was placed over the injection site (back of the neck of the animals). To optimize measurement parameters of the single-pulse-acquire sequence and to determine chemical shifts and the detection threshold, in vitro 195Pt NMR experiments have been performed on model solutions of potassium tetrachloroplatinate(II), carboplatin, and cisplatin with different solvents such as H2O, DMSO, and DMF. Resonances of PtCl2-4, carboplatin, cisplatin, and cis-[Pt(NH2)Cl(DMSO)]+ were observed at chemical shift positions delta = -1623 ppm, -1705 ppm, -2060 ppm (cisplatin in DMSO), and -3120 ppm, respectively, relative to the reference signal of Na2PtCl6 at delta = 0 ppm. A spin-lattice relaxation time of carboplatin of T1 = (0.103 +/- 0.02) s was measured. The threshold for NMR detection of platinum-containing compounds estimated from the in vitro experiments was 10 micromol (corresponding to approximately 4.8 mM). In vivo 195Pt NMR spectra obtained in four rats after administration of carboplatin showed a broad resonance at delta = -(1715 +/- 8) ppm. The signal-to-noise ratio of this peak (starting 2 min after the injection) was approximately 9:1 for a measurement time of 6 min (TR= 13 ms, 28672 transients). The elimination rate constant of local disposition of carboplatin was kel = 0.017 (0.008-0.025) min-1 (median and range).

Animals↗
PubMed1998

[Diagnosis and staging of laryngeal tumors with CT and MRI].

Cross-sectional imaging with CT and MRI plays an indispensable complementary role to endoscopy in the pretherapeutic workup and staging of laryngeal neoplasms. Adequate interpretation of the CT and MR images requires a thorough knowledge of the patterns of submucosal spread and familiarity with the diagnostic signs of neoplastic invasion as seen with each modality. In addition, the radiologist should be aware of the implications of imaging for staging and treatment. Both CT and MR imaging are highly sensitive for the detection of neoplastic invasion of the pre-epiglottic space, paraglottic space, subglottic region and cartilage. The high negative predictive value of both CT and MRI allows exclusion of neoplastic cartilage invasion quite reliably. The specificity of both CT and MRI is, however, limited and both methods may therefore overestimate the extent of tumor spread. Nevertheless, both cross-sectional imaging methods significantly improve the pretherapeutic staging accuracy of laryngeal tumors if used in addition to clinical examination and endoscopic biopsy. In the presence of a submucosal mass, CT and MRI play a key role for the diagnosis, as they may characterize the lesion, reliably depict its submucosal extent, and guide the endoscopist of perform deep biopsies that allow a definitive histological diagnosis.

Humans↗
PubMed1998

Atypical squamous cell carcinoma of the larynx and hypopharynx: radiologic features and pathologic correlation.

The objective of this study was to analyze the radiologic features of atypical forms of squamous cell cancer and correlate them with clinical, endoscopic, and histopathologic findings. The CT and MRI images of 31 patients with atypical forms of squamous cell carcinoma were reviewed retrospectively and the radiologic findings were correlated with clinical, endoscopic, and histopathologic findings. Histopathologic diagnoses included undifferentiated carcinoma of nasopharyngeal type (n = 8), verrucous carcinoma (n = 18), spindle cell carcinoma (n = 3), and basaloid cell carcinoma (n = 2). Undifferentiated carcinoma of nasopharyngeal type was located in the supraglottis or piriform sinus beneath an intact mucosa and initial endoscopic biopsy was most often negative. The discrepancy between an intact mucosa at endoscopy and a solid mass with homogenous enhancement at CT or MRI was characteristic for these tumors and warranted further investigations to obtain the definitive histologic diagnosis. Verrucous carcinoma displayed characteristic clinical, radiologic, and pathologic features, namely, an exophytic tumor arising from the glottic level displaying a rugged surface with finger-like projections but with only minor submucosal infiltration. Spindle cell carcinoma appeared as a polypoid mass with a thin stalk arising from the supraglottis. Basaloid cell carcinoma displayed a distinct lobulated enhancement pattern which was observed on contrast-enhanced T1-weighted SE images. Although the MR and CT features of atypical forms of squamous cell carcinoma cannot be considered pathognomonic they should raise the differential diagnosis even if endoscopic biopsy has been negative. The radiologist's awareness of the appearance of these unusual tumors on CT and MR images may greatly facilitate the diagnostic work-up and helps to guide the endoscopist to the adequate biopsy site in order to establish the correct diagnosis.

Aged↗
PubMed1998

[Prognostic factors in surgery of macular holes].

UNLABELLED: Idiopathic macular holes are today treated surgically with good results. The prognostic value of factors predictive for the anatomical and functional outcome has not been completely evaluated. PATIENTS AND METHODS: One hundred and thirty-five eyes with penetrating macular holes (stage II-IV) were investigated prospectively. The mean follow-up was 19.5 months (6-50 months). RESULTS: In 86% of cases the hole was closed postoperatively. The age of the macular hole proved to be a significantly predictive factor for the outcome; the age of the patient did not. The diameter of the hole showed no influence on the results. Application of autologous serum in front of the hole did not significantly improve the anatomical, but the functional results. The strongest improvement of visual acuity was seen in eyes with poor preoperative function. In 118 eyes a prefoveal membrane could be peeled off. Seventeen eyes without detectable membrane showed identical results. CONCLUSION: Some predictive factors in macular hole surgery are proven, others remain uncertain. Identical results in eyes with and without prefoveal membranes support the assumption of different pathomechanisms in macular hole formation.

Follow-Up Studies↗
PubMed1998

[Familial juvenile macular dystrophy with congenital hypotrichosis capitis].

BACKGROUND: Our knowledge about the pathogenesis of hereditary macular diseases is still very circumscript. For genetic determination, a knowledge of the coincidence of eye symptoms and other defined common symptoms is helpful. The purpose of this paper was to present two sisters of a family of consanguineous parents with the combination of hypotrichosis of the head and macular dystrophy in the context of a tricho-ocular malformation of an ectodermal dysplasia. A review of the recent literature is included. PATIENTS AND METHODS: Two 13- and 17-year-old sisters presented at our hospital with reduced visual acuity because of symmetrical central changes of the retinal pigment epithelium and chorioatrophic scars according to macular dystrophy combined with hypotrichosis capitis. We performed fundus perimetry and histological examinations of the hair. RESULTS: The 13-year-old patient exhibited central changes of the retinal pigment epithelium leading to a relative central scotoma for Goldmann 1/4 during fundus perimetry in both eyes (visual acuity 0.125 and 0.4). We found central chorioatrophic scars, followed by absolute central scotomas, with unstable fixation in the upper retinal hemisphere in her 17-year-old sister with reduced visual acuity (0.16 and 0.2). CONCLUSION: There are few descriptions of the association of macular dystrophy and hypotrichosis. The combination of hypotrichosis and macular dystrophy could make genetical analysis easier. Mutational analysis of the TIMP-3 gene that has previously been associated with Sorsby fundus dystrophy did not reveal any disease-causing mutations in our patients.

Adolescent↗
PubMed1998

Risk indicators for malnutrition are associated inversely with quality of life for participants in meal programs for older adults.

OBJECTIVE: To evaluate the nature and strength of associations between quality of life and factors commonly linked with malnutrition in participants in a meal program for the elderly. DESIGN: A questionnaire that assessed quality of life, nutritional risk, quality of health, depression, social satisfaction, functional status, food security, and food enjoyment was administered. SUBJECTS/SETTING: All persons aged 60 years and older enrolled in the Title III-C meal program in Pepin County, Wisconsin, during a 1-month period were asked to participate. Of 180 eligible subjects, data were available for 155; 108 received meals at congregate sites and 47 received home-delivered meals. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were used to characterize the population. Independent-samples t tests and chi 2 analysis were used to test for differences between the congregate-meal group and home-delivered-meal group. Spearman correlation coefficients were used to determine the direction and magnitude of associations between scale variables and quality of life. RESULTS: Quality of life and quality of health were positively correlated (r = .83, P < .0001). Nutritional risk, food insecurity, decreased enjoyment of food, depression, and impaired functional status were all negatively associated with quality of life. This research offers evidence that there are measurable associations between nutritional factors and quality of life. APPLICATIONS: Our finding could be helpful to dietitians in justifying, planning, and evaluating nutrition programs and interventions. Quality of life in older adults may be further enhanced by programs that include social and psychological components in addition to elements oriented to reduce nutritional risk.

Aged↗
PubMed1998

Normal values for fundus perimetry with the scanning laser ophthalmoscope.

PURPOSE: To evaluate the normal light sensitivity values for fundus perimetry and their short time fluctuation (reliability) in normal volunteers of different ages. After the development of full-threshold static fundus perimetry, age-corrected sensitivity values for normal subjects are required to interpret results and to compare them with conventional computerized perimetry. METHOD: Full-threshold fundus perimetry of the central field (33 x 21 degrees) by means of the scanning laser ophthalmoscope was performed on 152 eyes of 99 healthy persons aged 16 to 77 years with normal vision and no eye disease. Fixation was simultaneously documented. Light sensitivity values were evaluated according to each subject's age and test point location. RESULTS: Linear regression analysis disclosed a significant (P < .0001) decrease of the mean sensitivity of 0.275 dB per decade of increasing age, starting with 16.6 dB at age 10 years. Standard deviation around the center of fixation was 0.287 degrees in the first decade, and it increased by 2.82 minutes of arc per decade (P < .0001). Variation in triple examinations of subjects did not differ from short time fluctuation. CONCLUSION: Visual fields examined with fundus perimetry show reliable measurements in a range comparable to conventional computerized perimetry. There is a significant correlation between increase of age and decrease of light sensitivity in fundus perimetry. Visual fields obtained with fundus perimetry seem to correlate well with known data from computerized static threshold perimetry. It should be recognized that even in normal subjects, the stability of fixation decreases with increasing age.

Adolescent↗
PubMed1998

Larynx and hypopharynx.

Cross-sectional imaging with CT and MR imaging plays an indispensable complementary role to endoscopy in the pretherapeutic work-up of laryngeal and hypopharyngeal cancer and is very valuable for the detection of tumor recurrence after surgery or radiation treatment as well. Close interdisciplinary co-operation and the radiologist's familiarity with therapeutic options and challenges are required in order to use these powerful diagnostic tools in an optimal fashion. Other indications for cross-sectional imaging of the larynx and hypopharynx include uncommon neoplasms, benign masses, inflammatory disorders, and trauma.

Anatomy, Cross-Sectional↗
PubMed1998

Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime.

Human immunodeficiency virus (HIV) vaccine candidates were previously constructed as a string of cytotoxic T lymphocyte (CTL) epitopes delivered and expressed using DNA and modified virus Ankara (MVA; an attenuated vaccinia virus) vectors. These vaccines were shown to induce interferon (IFN)-gamma-producing and cytolytic CD8+ T cells after a single vaccine administration. In the course of this work, immunization protocols were sought which would improve the levels of induced HIV-specific T cells. It was found that previous immunological exposure to MVA reduced the efficiency of subsequent priming and boosting using the same vaccine vehicle. However, a combined regime whereby the animals were first primed with the DNA vaccine and then boosted with MVA was the most potent protocol for the induction of both interferon-gamma-producing and cytolytic T cells against two CTL epitopes simultaneously. The general applicability of this novel vaccination method for induction of major histocompatibility complex class I-restricted T cells is discussed.

Animals↗
PubMed1998

Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara.

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.

Animals↗