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S Majewski

Publications and source records attributed to S Majewski.

At least 19 recordsLinked to original sources
PubMed2003

A 3D high-resolution gamma camera for radiopharmaceutical studies with small animals.

The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2mm in planar and 2-3mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.

Algorithms↗
PubMed2001

Mutation and abnormal expression of the p53 gene in the viral skin carcinogenesis of epidermodysplasia verruciformis.

Patients suffering from epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility to the oncogenic human papillomavirus type 5. Genotoxic sunlight ultraviolet B radiations are likely to be a cofactor. Lesions of two human-papillomavirus-type-5-infected epidermodysplasia verruciformis patients collected during an 8 y period were retrospectively studied for p53 mutations in exons 5 through 8 by a polymerase chain reaction single-strand conformation polymorphism technique and/or by DNA sequencing of amplified exons. Mutations were detected in 11 of 26 (42.3%) specimens, including five (62.5%) squamous cell carcinomas, three (33.3%) Bowen's carcinomas in situ, two (40%) actinic keratoses, and one (33%) benign lesion. The nine mutations characterized by sequencing were shown to be missense and to affect mutational hotspots in human cancers. Five were C-->T transitions at dicytidine sites considered as ultraviolet signature mutations. Two were transversions (C-->G and C-->A) at dicytidine sites and two were C-->T transitions at nondipyrimidine sites. A marked p53 immunoreactivity was disclosed in 72.7% of 11 invasive carcinomas, 55.6% of nine carcinomas in situ, 37.5% of eight actinic keratoses, and one of three benign lesions. This includes 81.8% of 11 specimens with a p53 mutation but also 50% of 14 specimens with no mutation detected. A dysfunction of the p53 gene is thus likely to play a part in epidermodysplasia verruciformis carcinogenesis, either due to ultraviolet-B-induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in epidermodysplasia verruciformis keratinocytes remains to be determined.

Adult↗
PubMed2001

Positron emission mammography-guided breast biopsy.

UNLABELLED: Positron emission mammography (PEM) is a technique to obtain planar images of the breast for detection of potentially cancerous, radiotracer-avid tumors. To increase the diagnostic accuracy of this method, use of minimally invasive methods (e.g., core biopsy) may be desirable for obtaining tissue samples from lesions detected with PEM. The purpose of this study was to test the capabilities of a novel method for performing PEM-guided stereotactic breast biopsies. METHODS: The PEM system consisted of 2 square (10 x 10 cm) arrays of discrete scintillator crystals. The detectors were mounted on a stereotactic biopsy table. The stereotactic technique used 2 PEM images acquired at +/-15 degrees and a new trigonometric algorithm. The accuracy and precision of the guidance method was tested by placement of small point sources of (18)F at known locations within the field of view of the imager. The calculated positions of the sources were compared with the known locations. In addition, simulated stereotactic biopsies of a breast phantom consisting of a 10-mm-diameter gelatin sphere containing a concentration of (18)F-FDG consistent with that reported for breast cancer were performed. The simulated lesion was embedded in a 4-cm-thick slab of gelatin containing a commonly reported concentration of FDG, simulating a compressed breast (target-to-background ratio, approximately 8.5:1). An anthropomorphic torso phantom was used to simulate tracer uptake in the organs of a patient 1 h after a 370-MBq injection of FDG. Five trials of the biopsy procedure were performed to assess repeatability. Finally, a method for verifying needle positioning was tested. RESULTS: The positions of the point sources were successfully calculated to within 0.6 mm of their true positions with a mean error of +/-0.4 mm. The biopsy procedures, including the method for verification of needle position, were successful in all 5 trials in acquiring samples from the simulated lesions. CONCLUSION: The success of this new technique shows its potential for guiding the biopsy of breast lesions optimally detected with PEM.

Biopsy, Needle↗
PubMed2000

Telomerase activity in melanocytic lesions: A potential marker of tumor biology.

Telomerase activation, being a cardinal requirement for immortalization, is a crucial step in the development of malignancy. With a view toward diagnostic and biological aspects in melanocytic neoplasia, we investigated the relative levels of telomerase activity in 72 nevi and 16 malignant melanomas by means of a modified telomeric repeat amplification protocol (TRAP) assay, including an internal amplification standard. We further compared telomerase activity with the expression of two different proliferation-specific proteins, Ki-67 and repp86, a protein expressed exclusively in the cell cycle phases S, G2, and M. Telomerase activity was associated with the overall growth fraction (Ki-67) but showed a closer correlation with the expression of repp86. Both telomerase activity and proliferation indices discriminated clearly between malignant melanomas and nevi, but not between common and dysplastic nevi. Nonetheless, a portion of nevi exhibited markedly elevated telomerase activity levels without proportionally increased proliferation. This was independent of discernible morphological changes. Clinicopathological correlations showed an association between high telomerase activity and early metastatic spread in melanomas, linking telomerase to tumor biology. Our results provide arguments in favor of an occasional progression from nevi to melanomas and imply that proliferation measurements in combination with telomerase assays may help to elicit early malignant transformation that is undetectable by conventional morphology.

Adolescent↗
PubMed2000

Communication: papillomavirus DNA in basal cell carcinomas of immunocompetent patients: an accidental association?TITLE.

DNA of human papillomaviruses has frequently been detected in nonmelanoma skin cancers, raising the question of a possible causal contribution of these tumor viruses to skin carcinogenesis. Basal cell carcinomas are the most common nonmelanoma skin cancers; however, so far they are only poorly analyzed with regard to human papillomavirus infection. We searched for human papillomavirus-DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two geographic locations in Europe using six different polymerase chain reaction primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the tested tumors. Human papillomavirus positivity did not seem to correlate with the duration of disease or patients' age. The vast majority of virus types in the biopsies belonged to the group of epidermodysplasia verruciformis-associated human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in tumors as well as in perilesional healthy skin, seven carried viral sequences in lesional and healthy skin and three only in the basal cell carcinoma. Six of the seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs contained identical human papillomavirus types in tumors and histologically normal tissue. Forty basal cell carcinoma patients were additionally analyzed for IgG antibodies against virus-like particles of three representative epidermodysplasia verruciformis-human papillomavirus types: 8, 15, and 36. No statistically significant differences could be detected between human papillomavirus antibody prevalences of basal cell carcinoma patients and of dermatologically healthy individuals. Moreover, serologic findings did not correlate with the detection of specific human papillomavirus types in tumors. Our results seem to suggest that the occurrence of human papillomavirus-DNA in basal cell carcinoma does not reflect a major etiologic role of human papillomavirus in this cancer.

Aged↗
PubMed2000

Antibodies to human papillomavirus type 5 are generated in epidermal repair processes.

We reported previously that patients with psoriasis harbored at a very high frequency DNA sequences of the oncogenic human papillomavirus type 5 (HPV5) associated with epidermodysplasia verruciformis. Moreover anti-HPV5 antibodies were detected in 25% of the cases. Our aim was to find out whether keratinocyte hyperproliferation and/or autoimmunity could be responsible for HPV5 expression in psoriasis. We found that epidermal repair in patients with extensive second degree burns (n = 19) is frequently associated with the generation of anti-HPV5 antibodies. In patients with autoimmune bullous diseases (n = 118), a condition in which keratinocyte proliferation is involved in repair mechanisms, the prevalence of anti-HPV5 antibodies (15%-25%) was similar to that reported in psoriasis and significantly higher than that (5%) observed in individuals with no known history of human papillomavirus infection (n = 119). A high detection rate (57.9%) of HPV5 DNA was observed in patients with bullous diseases. Anti-HPV5 antibodies were found in patients with autoimmune connective tissue disorders with cutaneous involvement (n = 40) as frequently as in patients with bullous diseases. HPV5 DNA was detected in one of the 10 patients studied. In contrast, the prevalence of anti-HPV5 antibodies in patients with autoimmune neurological disorders (n = 47) and in patients with common warts (n = 28) or invasive carcinomas of the skin (n = 40) was as low as in the general population. It is worth stressing that a similar prevalence of antibodies against HPV1 was found in all groups studied. Our data strongly suggest that extensive keratinocyte proliferation is a major factor for the generation of anti-HPV5 antibodies and that autoimmunity may contribute to this phenomenon. It remains to be determined whether HPV5 and other human papillomavirus genotypes associated with epidermodysplasia verruciformis contribute to the hyperproliferation of keratinocytes occurring in epidermal repair and in psoriasis.

Antibodies, Viral↗
PubMed2000

Performance of a PSPMT based detector for scintimammography.

In breast scintigraphy, compact detectors with high intrinsic spatial resolution and small inactive peripheries can provide improvements in extrinsic spatial resolution, efficiency and contrast for small lesions relative to larger conventional cameras. We are developing a pixelated small field-of-view gamma camera for scintimammography. Extensive measurements of the imaging properties of a prototype system have been made, including spatial resolution, sensitivity, uniformity of response, geometric linearity and energy resolution. An anthropomorphic torso phantom providing a realistic breast exit gamma spectrum has been used in a qualitative study of lesion detectability. A new type of breast imaging system that combines scintimammography and digital mammography in a single upright unit has also been developed. The system provides automatic co-registration between the scintigram and the digital mammogram, obtained with the breast in a single configuration. Intrinsic spatial resolution was evaluated via calculation of the phase-dependent modulation transfer function (MTF). Measurements of extrinsic spatial resolution, sensitivity and uniformity of response were made for two types of parallel hole collimator using NEMA (National Electrical Manufacturers Association) protocols. Geometric linearity was quantified using a line input and least squares analysis of the measured line shape. Energy resolution was measured for seven different crystal types, and the effectiveness of optical grease coupling was assessed. Exit gamma spectra were obtained using a cadmium zinc telluride based spectrometer. These were used to identify appropriate radioisotope concentrations for the various regions of an anthropomorphic torso phantom, such that realistic scatter conditions could be obtained during phantom measurements. For prone scintimammography, a special imaging table was constructed that permits simultaneous imaging of both breasts, as well as craniocaudal views. A dedicated breast imaging system was also developed that permits simultaneous acquisition and superposition of planar gamma images and digital x-ray images. The intrinsic MTF is nonstationary, and is dependent on the phase relationship between the signal and the crystal array matrix. Averaged over all phases, the MTF is approximately 0.75, 0.57 and 0.40 at spatial frequencies of 1.0, 1.5 and 2.0 cycles per cm, respectively. The phase averaged line spread function (LSF) has a FWHM value of 2.6 mm. Following uniformity corrections, the RMS deviations in flood images are only slightly greater than is predicted from counting statistics. Across an 80 mm section of the active area, the differential linearity is 0.83 mm and the absolute linearity 2.0 mm. Using an anthropomorphic torso phantom with detachable breasts, scatter radiation similar to that observed exiting the breast of scintimammography patients was observed. It was observed that scattered gamma rays can constitute the majority of the radiation incident on the detector, but that the scatter-to-primary ratio varies significantly across the field of view, being greatest in the caudal portion of the breast, where scatter from the liver is high. Using a lesion-to-breast concentration ratio of 6:1, a 1.0 cm3 simulated breast lesion was detectable in lateral images obtained with both the developmental camera and with a clinical camera, while a 0.35 cm3 lesion was detectable in neither. Utilization of the dual x-ray transmission, gamma emission breast imaging system greatly increases the conspicuity of scintimammographic lesions relative to prone imaging, as well as greatly facilitating the localization and identification of structures in the gamma image. The prototype imaging gamma detector exhibits spatial resolution superior to that of conventional cameras, and comparable uniformity of response and geometric linearity. Because of light losses in the crystals, the energy resolution is inferior to that of single crystal NaI(Tl) came

Equipment Design↗
PubMed2000

The potential role of positron emission mammography for detection of breast cancer. A phantom study.

Positron emission mammography (PEM) is a new, specialized imaging modality utilizing PET radiopharmaceuticals to detect breast cancer. The capabilities and limitations of PEM in detecting breast tumors were investigated with a series of phantom experiments. The PEM imager was mounted on a standard Lorad biopsy table (separated by 18 cm). In the initial phase of the investigation, basic scanner parameters (resolution, sensitivity, and scatter fraction) were measured. The effects of a number of breast imaging parameters (length of acquisition, breast thickness, and breast density) on detection of breast lesions were then explored utilizing special phantoms. Moderately compressed breasts were simulated with a block of gelatin containing amounts of FDG consistent with 370 MBq injections. Lesions were simulated with four hollow spheres (inner diameters=5 mm, 8 mm, 12 mm, and 15 mm) filled with amounts of FDG representative of uptake in malignant breast tumors (target-to-background concentration ratio=8.5:1). Resolution at the center of the imager was 3.9 mm, sensitivity was 0.059 kcps/kBq/ml and the Compton scatter fraction was approximately 12%. Objects as small as 8 mm in diameter could be detected after 30 s of data acquisition; 5 mm spheres were detectable after 300 s. Object detection capabilities were reduced with increasing breast thickness. In thin compressed breasts (2 cm) even the smallest sphere (5 mm in diameter) could be detected; increasing breast thickness increased the minimum detectable sphere diameter to 8 mm. Increased background activity caused by FDG uptake in metabolically active normal tissue more prevalent in radiodense breasts compared to "fatty" breasts was simulated and shown to reduce the minimum detectable lesion size to 12 mm for the densest breasts. These results demonstrate the potential of PEM for the detection of breast lesions. The addition of the system to a standard biopsy apparatus indicates its potential for use to guide some core biopsies of breast cancers.

Breast Neoplasms↗
PubMed2000

Parakeratosis variegata: a possible role of environmental hazards?

We report 2 cases of parakeratosis variegata (PV) evolving from lesions beginning with characteristics of ashy dermatosis. Both patients presented with a reticulated, poikilodermatous and hyperpigmented eruption with bizarre coalescent lichenoid papules. Histology showed lichenoid epidermotropic infiltrates, more pronounced in case No. 1, consistent with early malignancy. The course was chronic: after more than 10 years, systemic symptoms were not present. In patient No. 1, a monoclonal T-cell population was detected 12 years after the onset of the disease. Both patients had close contact with fertilizers and insecticides. In patient No. 2, the lesions spontaneously regressed within 3 years after cessation of exposure. PV may be a prelymphomatous stage of mycosis fungoides or some closely related cutaneous T-cell lymphoma and does not always evolve into overt malignancy. Gene rearrangement detection techniques may be helpful in predicting the course of the disease.

Environmental Exposure↗
PubMed2000

Vitamin D analogs in cutaneous malignancies.

In this article are reviewed available experimental and clinical studies and vitamin D analogs, and molecular and cellular mechanisms of their antineoplastic activity. In more detail are discussed the antiproliferative and pro-differentiative effects, inhibition of tumor-induced angiogenesis and induction of apoptosis. The use of vitamin D analogs is however hampered by their toxicity. In various experimental systems it was shown that the activities of vitamin D analogs can be enhanced by combined application with retinoids or other biological active compounds such as cytokines and growth factors. Retinoids and vitamin D analogs were found to have synergistic inhibitory effects on tumor cell proliferation and angiogenic capability, and both agents applied simultaneously are efficacious in small doses. Thus combined therapy could find application in clinical practice. There are up to now only very limited data on the treatment of cutaneous malignancies with vitamin D analogs and it appears that a combined therapy, preferably with retinoids, could be more beneficial. The new synthetic, more potent and less calcemic analogs might find wide application in chemotherapy of premalignant and early malignant cutaneous tumors and could be especially useful for chemoprevention in the high-risk groups, e.g., xeroderma pigmentosum, organ transplant recipients, arsenical keratoses and others.

Animals↗