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Biomedical subjects

A Weinreb

Publications and source records attributed to A Weinreb.

At least 37 records · Page 2Linked to original sources
PubMed1990

Left-handed Z-DNA and intramolecular triplex formation at the site of an unequal sister chromatid exchange.

An unequal sister chromatid exchange (USCE) in the mouse myeloma cell line MPC-11 between 3' regions of the C gamma 2a and C gamma 2b heavy chain genes results in duplication of the C gamma 2a heavy chain gene and generation of a novel recombination joint. The USCE occurs between (TC)n tracts adjacent to alternating purine-pyrimidine tracts. We have investigated the capacity of both the donor regions and the recombinant product involved in this event to adopt left-handed Z-DNA and intramolecular triplexes. The results of chemical probing with diethylpyrocarbonate and osmium tetroxide at the base pair level demonstrate that under the influence of negative supercoiling the alternating purine-pyrimidine regions of these plasmids can adopt Z-DNA at neutral pH, and the oligopurine.oligopyrimidine (pur.pyr) regions of these regions can adopt intramolecular triplexes at low pH (less than or equal to pH 6.0). At intermediate pH values, mixtures of both structures are present. Increasing the negative superhelical density of the plasmid does not increase the amount of triplex present at neutral pH indicating that the presence of long Z-DNA segments adjacent to pur.pyr tract prevents intramolecular triplex formation. In summary, we conclude that the sequences involved in the USCE can form either an intramolecular triplex in the (TC)n tract or Z-DNA in the alternating purine-pyrimidine tract and that Z-DNA will predominate under physiological conditions. The presence of segments which adopt Z-DNA at a site of USCE suggests that formation of this structure may enhance recombination between adjacent pur.pyr tracts.

Animals↗
PubMed1988

An evaluation of the SCM test for the diagnosis of cancer of the breast.

The SCM test (structuredness of the cytoplasmic matrix) consists of measuring the fluorescence polarization of fluorescein which is introduced into a particular sub-group of peripheral lymphocytes. The test has a non-specific part for the general detection of cancer and a specificity procedure which is based on the use of specific cancer extracts. In this article we deal only with the latter in relation to breast cancer. Blood samples from 94 patients have been tested; six of these had mastectomy performed previously; 83 underwent consecutively a surgical procedure and histology was obtained; five were only clinically examined. In 45/49 (92%) patients, correlation between a positive specificity test and tissue malignancy was found. Out of 35 patients with non-malignant proliferative lesions (as found by histology), 25 reacted positively in the test. Two out of five patients with non-malignant, non-proliferative lesions reacted positively in the test. Five patients who were defined as normals by clinical examination reacted negatively in the test. These results indicate the potential of the SCM test for detecting breast malignancy. The clinical implications of the test for cancer diagnosis are discussed.

Adolescent↗
PubMed1988

Site of unequal sister chromatid exchange contains a potential Z-DNA-forming tract.

Previous studies from this laboratory have provided evidence that the duplication of the IgG2a heavy chain constant region gene (C gamma 2a) in the murine myeloma cell line MPC-11 occurred via unequal sister chromatid exchange. We now report the determination of the DNA sequences of the germ-line regions in which this exchange has occurred. The two donor sequences have long regions of virtual identity. Furthermore, both chromatids contain stretches of T-C and T-G dinucleotides; the latter has the potential to form Z-DNA. Localization of the actual breakpoints via genomic Southern blot analysis suggests a novel mechanism for the recombination and strongly implicates the simple sequence in the process.

Animals↗
PubMed1988

Mechanism of class switching.

We have documented the action of unequal sister chromatid exchange on antibody genes, and our studies provide the first molecular description of an unequal sister chromatid exchange event. We delineated the sequences that mediate class switch recombination in normal B cells through genomic Southern analysis of five IgG2-producing hybridomas. Successive subclass switching was documented in two of eight maps and may possibly account for interposed DNA in three additional maps, implying that subclass switching may be a relatively frequent occurrence in normal B cells. As in most other myelomas and hybridomas, the 5' breakpoint of switch recombination in our panel of hybridomas falls 5' to Cmu-associated tandem repeats, whereas the 3' breakpoint falls within C gamma-associated tandem repeats. We consider various hypotheses in the text, the most interesting of which is that deletion of Cmu-associated tandem repeats is a necessary first step before class switch recombination in mature B cells. This hypothesis suggests that Cmu-associated tandem repeats may be a separately regulated DNA element.

Animals↗
PubMed1987

The relative significance of trabecular and cortical bone density as a diagnostic index for osteoporosis.

The density of the distal radius in the non-dominant forearm was measured non-invasively by Compton spectrometry in 234 post-menopausal women. The density of the trabecular tissue was determined almost independently from that of cortical tissue by horizontal and vertical scanning of the bone. It was found that the lower the density of the trabecular bone, the greater the difference between the density of the cortical and trabecular bone. As osteoporosis progresses, trabecular bone density in the distal radius seems to decrease faster than that of compact bone. Hence the severity of the disease is best determined by measuring the density of trabecular bone.

Adult↗
PubMed1986

Iron, copper, and zinc concentrations in normal skin and in various nonmalignant and malignant lesions.

The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively determined in vivo by diagnostic x-ray spectrometry. The skin of healthy controls was divided into two major groups based upon the distribution of the concentrations of these elements. In the face and upper neck, the following wet weight concentrations were recorded: Fe, 14.2 +/- 3.3 ppm; Cu, 1.3 +/- 0.3 ppm; and Zn, 6.7 +/- 1.1 ppm. In the chest, abdomen, arm, axilla, and lower neck, the concentrations of these elements were as follows: Fe, 10.2 +/- 2.5 ppm; Cu, 0.8 +/- 0.3 ppm; and Zn, 4.5 +/- 1.7 ppm. In most lesions of solar dermatitis, solar keratosis, basal and squamous cell carcinomas, variable elevations of Zn and Fe (up to significant levels) were recorded in most of the contralateral, apparently uninvolved skin. In the majority of pigmented nevi and malignant melanomas, the levels of Fe and Zn were elevated. In some of these, the Cu concentration also was increased.

Carcinoma, Squamous Cell↗
PubMed1985

Tumour specificity of the SCM test for cancer diagnosis.

Phytohaemagglutinin (PHA), a well-known mitogen, and encephalitogenic factor (EF) are recognized by lymphocytes of patients with different malignant diseases as non-specific antigens. Utilizing these two antigens, the SCM (structuredness of the cytoplasmatic matrix) test offers a means of discrimination between malignant and non-malignant diseases. The SCM test can also be used as a specificity test since lymphocytes from donors with a given malignant disease react exclusively with the tumour-associated antigen (TAA) of that disease. Results from 73 donors (15 healthy patients, 38 patients with different types of malignant disorders and 20 patients with autoimmune diseases) indicate the predictive value of the test. First, the non-specific test was applied in order to establish whether the patients suffered from an active malignant disease. The lymphocytes of those patients which were found to suffer from an active malignant disorder were then exposed to different types of tumour tissues. Twenty-five out of the 38 patients with malignant disorders were found by the SCM test to have an active disease. The lymphocytes of 24 out of these 25 patients showed a positive reaction when exposed to tumour tissue of the same type of cancer of which they were found to suffer by other clinical tests, and displayed no reaction with any other tumour tissues for which they were tested. One patient, with an inconclusive value of the SCM test, showed no reaction with any type of tumour to which he was exposed. The remaining 13 patients, who were diagnosed by the test as non-cancerous, did not show any clinical evidence of malignancy at the time of the test, after their tumours had been excised. Eighteen out of 20 patients with autoimmune diseases showed negative results when tested by the general test and by the various specificity tests.

Antigens, Neoplasm↗
PubMed1985

Optical properties of the sclera.

A relationship between the structure of the sclera and its light scattering properties is proposed. The relative optical density as a function of wavelength in the infrared was measured for three sclera and a good correlation with the predicted function was found. The angular distribution of the scattered light at 632.8 nm as well as the degree of polarisation of the scattered light at zero angle was measured for three sclera; from these results the total transmission of the sclera was determined.

Collagen↗
PubMed1984

Discrimination between human melanoma cell lines by fluorescence anisotropy.

The fluorescence polarization of diphenylhexatriene (DPH) and trimethylammonium diphenylhexatriene (TMA-DPH) was measured when these markers were imbedded in cells of the human melanoma cell lines IGR37, IGR39, IGR3 and IGR4, as well as in cells of the mouse melanoma cell lines B16F1 and B16 F10. These measurements were performed on cell cultures which were grown on quartz plates as well as on cell suspensions. Considerable differences are found between the polarization values of the human cell lines that are related to their different origins. Differences for the plated cells are considerably greater than those for the suspensions. No differences in the polarization values were found for the two mouse melanoma lines. It is concluded that differences in lipid structural order can be found between cell types endowed with different metastasizing capabilities.

Animals↗
PubMed1983

Photochemical changes of fluorescent probes in membranes and their effect on the observed fluorescence anisotropy values.

The fluorescence intensity of diphenylhexatriene (DPH) and of trimethylammonium-diphenylhexatriene (TMA-DPH) is measured when these probes are embedded in vesicles of dipalmitoyl- and dioleoylphosphatidylcholine (DPPC and DOPC), in mixtures of these vesicles as well as in vesicles of the mixed phospholipids, in trout intestinal brush border membranes and in mitoplasts of rat liver cells. The intensity in DOPC vesicles is found to be significantly higher than in DPPC vesicles. When these systems are irradiated with strong ultraviolet light radiation, a decrease in the fluorescence intensity is observed; this effect is much stronger in DOPC than in DPPC vesicles. The fluorescence anisotropy values in the mixture of vesicles as well as in the membranes show an initial increase with irradiation which is followed by a significant decrease. A transfer of DPH molecules between DPPC and DOPC vesicles is observed. For TMA-DPH this transfer takes place only from DPPC to DOPC vesicles, but not vice-versa. These results are related to intensity and anisotropy measurements of these probes in cell cultures.

Animals↗
PubMed1983

Validation of the SCM-test for the diagnosis of cancer.

The basic aspects of the SCM-test are summarized. A derivation of the fluorescence intensity vs time curve is given as well as that of the polarization as a function of time. These curves are found to be in excellent agreement with the experimental results. The test is applied to the lymphocytes of twenty-six healthy individuals and of thirty-three cancer patients. No false negative results were obtained. Seven cancer patients were found to be negative after various intervals from the removal of the tumour. The most important technical difficulties and pitfalls are discussed in order to facilitate the reproduction of the test by other researchers.

Cytoplasm↗
PubMed1983

A new method of measuring bone density in the lower tibia of normal and postinjury limbs. A quantitative and comparative study.

In osteoporosis, a pathologic state of diminution of bone mass, radiography is the most widely used diagnostic method, but it is only descriptive and mainly depicts changes in the compacta. Based on the Compton photon-scattering phenomenon, a noninvasive yet quantitative measuring method for analyzing bone density was developed. The values of repeated measurements taken at identical locations did not vary by more than 2%. Using this technique, bone density of the lower tibia was measured in 39 men and 36 women; 14 had been affected by an injury to a knee or calf and immobilized five to eight years prior to this investigation. The measured values demonstrated an impressive equality between the tibiae of each individual and between the two sexes up to 50 years of age. However, these values correlated poorly with the bone density of the distal radius. In women older than 50 years of age, bone density decreased. Bone density was also low in all postinjury limbs. When compared with radiographic and bone mineral content (BMC) measurements of the same limb at the same location, the bone density measurements were useful and reduced the range of uncertainty of diagnosing osteoporosis by radiography only. Little or no correlation was found between bone density values and BMC measurements. The Compton scattering technique may become a precise and sensitive method for the clinical diagnosis of postinjury osteoporosis and quantitation of the long-term effects of limb injuries.

Adolescent↗
PubMed1982

The relationship between bone density, mineral content, and mechanical strength in the femoral neck.

The bone density, mineral content and average shear stress in bending at failure were measured in vitro in 33 femoral necks of women and men of different ages. The correlations between these three parameters as well as their correlation with the Singh index were carefully analyzed and found to show that the Singh index is of no clinical value. The best correlation exists between bone density and shear stress at failure. Practically no correlation is found between the breaking stress and Singh index. The breaking stress decreases with age much faster than the bone density or bone mineral content. The correlation between the work to fracture and the bone density or its mineral content is only moderate. The bone density is best indicator for the compressive bone strength. The changes of bone strength are apparently influenced by factors other than the bone density and mineral content, although the possibility that small changes in bone density or mineral content cause large changes in bone strength cannot be excluded.

Absorptiometry, Photon↗
PubMed1981

Iron content of skin before and after thalidomide treatment of lepra reaction. A preliminary report.

THe concentration of copper, zinc and iron in the skin of patients suffering from lepra reaction was measured by diagnostic X-ray spectrometry (DXS) at the sites of the lesions before and after treatment with thalidomide. The results were compared with the levels of these elements in the skin of healthy individuals. No significant changes in the copper level of leprous skin were found. The zinc levels showed significant elevations in some lesions with no apparent trend. The iron level in the affected areas had highly elevated values in all cases of lepra reaction. However, in contrast to the fast clinical improvement which followed the treatment with thalidomide, the iron levels did not decrease for prolonged periods.

Adult↗
PubMed1981

In vivo measurements of iron, copper and zinc in the skin of prurigo nodularis patients treated with thalidomide.

The concentration of iron, cooper and zinc in the skin of patients with prurigo nodularis was measured by diagnostic X-ray spectrometry before and after treatment with thalidomide. Before treatment, larger skin lesions were associated with significantly higher zinc levels and higher iron levels than the smaller ones. Upon treatment the zinc and iron content in these lesions decreased towards normal range. Copper values were found to be within the normal range in lesions before and after thalidomide treatment.

Adult↗