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L Weber

Publications and source records attributed to L Weber.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Dermatomyositis-like skin changes with long-term hydroxyurea (Litalir) therapy].

We report on dermatomyositis-like adverse cutaneous reactions following long-term maintenance therapy with hydroxyurea in two patients suffering from chronic myelogenous leukaemia (CML). In addition to non-specific side effects, such as xerosis, pruritus and hyperpigmentation, both patients presented with more specific skin changes, i.e. erythematous lesions, scaling, and partially atrophic areas distributed in a linear fashion on the dorsal aspects of the hands and fingers. In addition, teleangiectatic erythema of the face was present in both patients, and this was associated with oedema of the eyelids in one patient. Despite these dermatomyositis-like features there were no clinical signs of muscular involvement, and muscle-specific enzymes were within normal ranges. Skin biopsy specimens revealed an interface dermatitis characterized by a lichenoid cell infiltrate, vacuolar alteration of basal cells, necrotic keratinocytes within the spinous zone, focal hypergranulosis, ortho-hyperkeratosis and telangiectases in the upper part of the dermis. Analogous histopathological findings have been documented in lichen planus-like skin changes on the hands following hydroxyurea therapy. It seems doubtful whether there are actually any major differences between those skin changes described as dermatomyositis-like and those interpreted as lichen planus-like in patients receiving long-term hydroxyurea therapy.

Aged↗
PubMed1995

Amelanotic lentigo maligna melanoma.

Only five cases of the amelanotic variant of lentigo maligna melanoma of the face have been reported. We describe an additional four patients observed within the past 5 years, suggesting a much higher incidence of this variant than previously suspected.

Aged↗
PubMed1995

Limitations of a pencil beam approach to photon dose calculations in lung tissue.

A common limitation in treatment planning systems for photon dose calculation is to ignore the impact on electron transport and photon scatter from patient heterogeneities. The heterogeneity correlation is often based on scaling operations along beam rays as for the method according to Batho or the more novel approach of 1D convolutions along beam paths applied in pencil-beam-based systems. The effects of the limitation have been studied in a mediastinum geometry for a wide range of beam qualities by comparing the results from a pencil-beam-based treatment planning system with the results from Monte Carlo calculations. As expected, the deviations within unit-density volumes are small while deviations in low-density volumes increase with increasing beam energy from approximately 3% for 4 MV to 14% for 18 MV x-rays as a result of increased electron disequilibrium.

Humans↗
PubMed1995

Modeling transmission and scatter for photon beam attenuators.

The development of treatment planning methods in radiation therapy requires dose calculation methods that are both accurate and general enough to provide a dose per unit monitor setting for a broad variety of fields and beam modifiers. The purpose of this work was to develop models for calculation of scatter and transmission for photon beam attenuators such as compensating filters, wedges, and block trays. The attenuation of the beam is calculated using a spectrum of the beam, and a correction factor based on attenuation measurements. Small angle coherent scatter and electron binding effects on scattering cross sections are considered by use of a correction factor. Quality changes in beam penetrability and energy fluence to dose conversion are modeled by use of the calculated primary beam spectrum after passage through the attenuator. The beam spectra are derived by the depth dose effective method, i.e., by minimizing the difference between measured and calculated depth dose distributions, where the calculated distributions are derived by superposing data from a database for monoenergetic photons. The attenuator scatter is integrated over the area viewed from the calculation point of view using first scatter theory. Calculations are simplified by replacing the energy and angular-dependent cross-section formulas with the forward scatter constant r2(0) and a set of parametrized correction functions. The set of corrections include functions for the Compton energy loss, scatter attenuation, and secondary bremsstrahlung production. The effect of charged particle contamination is bypassed by avoiding use of dmax for absolute dose calibrations. The results of the model are compared with scatter measurements in air for copper and lead filters and with dose to a water phantom for lead filters for 4 and 18 MV. For attenuated beams, downstream of the buildup region, the calculated results agree with measurements on the 1.5% level. The accuracy was slightly less in situations where the scatter component is very large, as for very large fields with very short filter to detector distances. The implementation of the model into treatment planning systems is discussed.

Air↗
PubMed1995

In situ detection of cyclosporin A: evidence for nuclear localization of cyclosporine and cyclophilins.

BACKGROUND: The immunosuppressant cyclosporin A (CsA) forms a trimolecular complex with cyclophilin (CPH) and calcineurins (CN) and inhibits CN phosphatase activity. Inhibition of CN phosphatase by CsA prevents the dephosphorylation of a nuclear factor in the cytosol and its nuclear translocation to the nucleus. EXPERIMENTAL DESIGN: The intracellular distribution of CPH and CN was investigated in permeabilized Jurkat T lymphocytes and MRC fibroblasts using biochemical techniques and confocal microscopy. The site of CsA binding was identified in situ using a photoaffinity label derivative of CsA followed by immunodetection. RESULTS: Cyclophilin A (CPH-A) and CN display essentially a cytosolic localization by immunofluorescence, and additional nuclear CPH-A and CN are evidenced by Western blot analysis of purified nuclei and immunofluorescence. By contrast, cyclophilin B (CPH-B) has a punctuate and reticular distribution pattern in cytoplasm, indicating an association with the endoplasmatic reticulum, but its main location is in the nuclear matrix, sparing the nucleolar region. For the in situ detection of CsA binding sites, a photolabile cyclosporine derivative (PL-CS) was used that allowed the detection of covalently bound CsA by Ab. Using the biologically active PL-CS, a punctate cytoplasmatic and nuclear immunoreactivity was obtained, which was specific and competed only with active cyclosporine derivatives. Nuclear CPH-A and -B were labeled by PL-CS, and trimolecular complexes of labeled CPH and CN were obtained by chemically cross-linking nuclear extracts. CONCLUSIONS: We describe herein the accessibility of CsA to the nucleus, the presence and labeling in situ of nuclear CPH and CN. The current models of CsA action predict that CsA-CPH complexes inhibit CN activity in the cytosol. However, our present findings invite the hypothesis that CPH may capture the drug into the nucleus and target regulatory proteins or transcriptional control elements.

Amino Acid Isomerases↗
PubMed1995

Caloric restriction and aging as viewed from Biosphere 2.

The low-calorie nutrient-dense diet consumed for 2 yr by the eight persons sealed inside the closed ecological space known as Biosphere 2, near Tucson, AZ, constituted a unique "experiment of nature," amounting to the first well-monitored application of a nutritional regimen proven in animals to substantially inhibit and delay time of onset of most age-related diseases, induce physiological changes characteristic of a functionally "younger" age, and extend both average and maximum lifespans. Over the 2 yr the eight persons demonstrated a substantial weight loss, remarkable fall in blood cholesterol, blood pressure, fasting blood sugar, and low white blood cell counts--exactly as seen in rodents on such a regimen. Studies in progress involving levels of cortisol, insulin, and glycosylated hemoglobin support the rodent similarity. Further studies will seek to determine whether additional among the large battery of physiologic changes induced in animals by caloric restriction are also induced in humans on a similar nutrient-dense, calorie-limited diet. Such evidence will pertain to the question whether the increased disease resistance and aging retardation shown by calorie-restricted rodents might also be expected to occur in humans.

Aging↗
PubMed1994

Large bowel cancer following gastric surgery for benign disease: a cohort study.

Early studies suggested that gastric surgery for benign ulcer disease was associated with a subsequent increase in the risk of large bowel cancer. Dietary fats, altered bacterial flora, and secondary bile acids are considered to play a major role in the disease etiology. Gastric surgery is known to alter bile salt metabolism as well as bacterial flora in the colon. This cohort study was designed to investigate the risk of large bowel cancer following gastric surgery for benign ulcer disease and to identify potential patient and treatment characteristics that may be associated with this risk. A cohort of 15,983 males was selected from Department of Veterans Affairs hospital admissions in 1970 and 1971. The exposed group (n = 7,609) included all males treated with gastric surgery (resection or vagotomy and drainage) for benign ulcer disease. The unexposed group (n = 8,374) was a random sample of all other male patients from the same time period and database. All subjects were followed through 1989 to identify vital status and cause of death. Deaths were identifiable by computerized linkage of the subjects' social security numbers with the Department of Veterans Affairs Beneficiary Identification Record Locator System and the National Death Index. The cause of death was documented by two certified nosologists from the death certificates of 99% of the deceased patients. Statistical analyses included estimations of risk based on standardized mortality ratios and standardized risk ratios. In this selected cohort, no increase in large bowel cancer risk was detected (risk ratio = 0.81, 95% confidence interval 0.62-1.05). The type of surgical procedure, ulcer diagnosis, age at the time of surgery, and length of follow-up did not alter the risk estimates. Unlike the previously identified increase in gastric cancer risk following ulcer surgery, no elevation in the risk of large bowel cancer following such surgery was detected in this study. Factors that may alter gastric surgery sequelae and resultant site-specific cancer risks deserve further investigations.

Adult↗
PubMed1994

The dosimetric verification of a pencil beam based treatment planning system.

A new three-dimensional treatment planning system (TPS) based on convolution/superposition algorithms (TMS-Radix from HELAX AB, Uppsala, Sweden) was recently installed at the University Hospital in Lund. The purpose of the present study was to design a quality assurance and acceptance testing programme to meet the specific characteristics of this convolution model. The model is based on parametrization of a non-measurable quantity-the polyenergetic pencil beam. However, the verification of the treatment planning model is still dependent on numerous comparisons of measured depth-doses and dose profiles. The test programme was divided in two basic parts: (i) model implementation and beam data consistency and (ii) model performance and limitations in special situations. The first part was scheduled for all photon beam qualities available before they could be used for clinical treatment planning. The second part was performed for selected energies only. The results indicate clearly that the model is well suited for clinical three-dimensional dose planning and that the TPS handles data as expected. For example, calculated depth-doses for open and wedge beams at depths larger than the depth of dose maximum and profiles for open beams shows a very good agreement with measurements. However, depth-dose deviations at shallow depths, especially for high energies, were found. Monitor units calculated by the system were accurate for most fields except for very large fields, where deviations of several per cent were found.

Algorithms↗
PubMed1993

Biochemical and immunological characterization of the human carcinoma-associated antigen MH 99/KS 1/4.

We have characterized the 38-kDa transformation-associated membrane glycoprotein MH 99, whose expression is highly elevated in many epithelial malignancies. A spontaneous cleavage of MH 99 into a 32- and a 6-kDa chain in some carcinoma cell lines was recently shown. Sequence homologies to nidogen, a matrix-adhesion molecule, support the suggestion of a receptor-like function. In this study, we characterized biochemical and immunogenic aspects of MH 99. Transformed epithelial cell lines which do not spontaneously cleave MH 99 were exposed to 8 proteases with distinct specificities. Each of the enzymes produced similar specific fragmentation into chains of about 30 to 32 and 6 kDa, indicating a characteristic cleavage site of MH 99. The fragments were not distinguishable from those in carcinoma cells showing spontaneous cleavage of MH 99. The specific fragmentation depends on the localization in intact membranes and is not shared by other membrane proteins. N-glycosylation of MH 99 of about 4 kDa was exclusively found on the 32-kDa fragment. Characterization of antigenic epitopes was performed using 16 different monoclonal antibodies (MAbs). Only 2 independent determinants were found. One is located on the 32-kDa chain and is recognized only by the MM 104 MAb. The other 15 antibodies bind to a dominant epitope on the 6-kDa fragment which can be divided into 3 overlapping sub-epitopes. The unique features of MH 99 indicate that its immunogenic epitopes are mainly located at its 6-kDa chain, and support the suggestion of a transformation-associated cell-surface receptor which might be proteolytically regulated.

Animals↗
PubMed1993

Determination of phenylmercapturic acid in urine of benzene-exposed BDF-1 mice.

This paper describes a procedure for the identification of phenylmercapturic acid in urine of benzene-exposed mice. Collected urine of benzene exposed mice was adjusted to pH 7 and applied to an anion exchanger. After extraction with diethyl ether and evaporation to dryness, the sample was dissolved in aqueous phosphoric acid and injected into the HPLC. HPLC conditions included an ODS column and an eluent consisting of tetrabutylammoniumhydrogensulfate-methanol (75:25, v/v), the absorbance wavelength was 255 nm. The detection limit of phenylmercapturic acid was 3 mg/l in mouse urine.

Acetylcysteine↗
PubMed1993

A cohort study of stomach cancer risk in men after gastric surgery for benign disease.

BACKGROUND: For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs. PURPOSE: This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk. METHODS: Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques. RESULTS: A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01). CONCLUSIONS: This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years.

Adult↗
PubMed1993

Immunoaffinity chromatography of recombinant Amb a I in the presence of a denaturing agent.

Recombinant proteins expressed in E. coli are often sequestered into inclusion bodies and require the use of denaturing agents in order to solubilize them. The recombinant form of Amb a I, the major allergen from short ragweed pollen, is one such protein. In some cases solubility can be maintained after the removal of the denaturing agent, particularly if the protein can be folded into its native conformation. However, not all proteins refold readily and after the removal of the denaturing agent the proteins will reaggregate and/or precipitate. In the case of Amb a I, the recombinant protein stays in solution at low concentrations but aggregates with itself and other proteins. The recombinant Amb a I is not expressed at high levels and may be toxic to E. coli. Therefore, isolation from a complex mixture of E. coli proteins was necessary. Monoclonal antibodies which recognize the denatured form of Amb a I were available, allowing for immunoaffinity purification. However, because the protein was not monomeric, this chromatographic technique did not provide an improvement in the purity level when run in normal buffer solutions. Analysis of one monoclonal antibody's stability to urea indicated it could tolerate the presence of 2 M urea and recover full activity. Use of this antibody as an immunoaffinity reagent in a column run in 2 M urea, which minimized aggregation of the E. coli produced proteins, gave a high degree of purification of recombinant Amb a I in one step. This illustrates the potential for the use of denaturing and other solubilizing agents in immunoaffinity chromatography of recombinant proteins.

Allergens↗
PubMed1993

The use of treatment progress scales in client monitoring and evaluation.

This article describes a multiple-use patient monitoring and evaluation system, the Treatment Progress Scales (TPS), which has been used for the last six years on 4,600 psychiatric and chemically dependent patients in a state-operated mental health facility. The system has been used for patient monitoring, management information, and program evaluation purposes. The article summarizes these and offers a brief overview of the TPS, its psychometric properties, and its advantages and disadvantages.

Hospitals, Psychiatric↗
PubMed1993

[Fine needle aspiration cytology of metastatic malignant melanoma. Improvement of results with ultrasound control].

A review of 315 fine-needle aspiration cytologies (FNAC) carried out from 1984 through 1992 in 157 patients with suspected metastatic melanoma was carried out: 176 results were confirmed by histological examination and 139 by clinical follow-up. In the first period, from 1984 through 1988, we observed 5 false-negative results out of 123 evaluable FNACs. All were caused by technical failure. In the second period, from 1988 through 1992, all fine-needle biopsies of impalpable masses were done with ultrasound guidance. Thus, we were able to avoid further false-negative results. No errors in interpretation were found. We obtained 219 true-positive and 91 true-negative results with 97.8% sensitivity, 100% specificity, 98.4% accuracy, 100% positive and 94.8% negative predictive value. In 3 cases with metastatic melanoma the cytological diagnosis only was 'malignant tumor', while in another 5 patients the cytodiagnosis of melanoma was not definitive. Immunocytology was helpful in these cases in identifying melanoma. FNAC allowed the correct diagnosis of a second malignancy in 4 cases (one papillary thyroid cancer, one Hodgkin's disease, two non-Hodgkin's lymphomas). No complications occurred. In our opinion, FNAC--for poorly defined lesions with ultrasound guidance--is a very rapid, safe and accurate method that allows reliable diagnosis of metastatic melanoma.

Adolescent↗
PubMed1993

[Osteoma cutis. Multiple miliary osteoma of the face].

Primary and secondary forms of ossification can be distinguished on the basis of the skin, with osteoma cutis occurring in primary forms. Three entities can be differentiated: solitary and generalized osteoma cutis and multiple miliary osteoma of the face. Clinically, multiple papules 2-3 mm in diameter are present, which histologically consist of bony trabeculae enclosing mature fat cells and, occasionally, marrow cells. We describe the clinical, radiological and histological features of a case of multiple miliary osteoma of the face in an otherwise healthy 55-year-old woman.

Biopsy↗
PubMed1992

Determination of benzene metabolites in urine of mice by solid-phase extraction and high-performance liquid chromatography.

A method was developed for quantitative measurement of trans,trans-muconic acid, catechol, hydroquinone and phenol in urine. Hydrolysis of esterified and glucuronized phenolic compounds was effected by specific enzymes. The hydrolysed mixture was purified and separated by solid-phase extraction with an anion exchanger, followed by extraction with diethyl ether. By using a clean-up procedure the natural background from mouse urine could be reduced, so that the detection limit of the metabolites was in the range 3-60 mg/l. Optimization of the chromatographic conditions resulted in a short high-performance liquid chromatography analysis time. Phenol had the longest retention time of about 10 min. The clean-up procedure could also be used for phenylmercapturic acid, an additional benzene metabolite, but for sensitive high-performance liquid chromatographic detection of phenylmercapturic acid other conditions are necessary.

Animals↗