Biomedical subjects
Publications and source records attributed to A Stein.
A patient with wrist pain and cystic changes of the ulnar head is presented. This x-ray finding has not previously been reported in patients without rheumatoid arthritis. At the time of operation a tear of the triangular fibrocartilage was present.
We present a case of bilateral renal cell carcinoma occurring simultaneously with a single lymph node metastasis clearly demonstrated by angiography. Radical nephrectomy, blunt enucleation of the cortical tumor in the controlateral kidney and removal of a large lymph node metastasis were performed simultaneously.
We have investigated the average nucleosome spacing in the chromatin from several simian virus 40 virion assembly mutants temperature-sensitive in the major capsid protein VP1. Viral assembly intermediates that accumulate in cells infected with mutants that block virion assembly at the propagation step (tsB) have an average nucleosome repeat length similar to that of wild-type SV40 chromatin, approximately 198(+/- 4) base-pairs. This repeat length is longer than that of the host (BSC-40) cellular chromatin, which has a value of 187(+/- 4) base-pairs. In contrast, SV40 chromatin from cells infected with virus containing a mutation that blocks virion assembly at the initiation step (tsC) has a significantly shorter average repeat length of 177(+/- 4) base-pairs. At the permissive temperature (33 degrees C), tsC chromatin has a nucleosome spacing periodicity essentially the same as that of wild-type SV40 chromatin. In addition to possessing a chromatin structure with nucleosomes that are, on the average, closer together, tsC chromatin contains a nuclease-hypersensitive or open region in nearly all molecules, but apparently the same number of nucleosomes. These findings suggest that nucleosomes are deposited initially on newly replicated SV40 chromatin in such a way as to leave the DNA region containing the origin of replication and transcription enhancers uncovered. Subsequent interaction with capsid proteins appears to increase the average nucleosome spacing and consequently to cover the open region for encapsidation.
Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high-dose cytosine arabinoside therapy. While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status. The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset.
The relationship of lead exposure to blood pressure has been examined in a longitudinal study of a cohort of 89 Boston, Massachusetts, policemen. At the baseline examination, subjects had a blood lead determination and three consecutive blood pressure measurements. Triplicate blood pressure measurements were also taken at years 3, 4, and 5. Multivariate analysis revealed that, after correction for previous systolic blood pressure, body mass index, age, and smoking, a high level of blood lead was a significant predictor of subsequent elevation of systolic pressure. Bootstrap simulations of these models provided supporting evidence for the observed associations. These data suggest that lead exposure can significantly affect systolic pressure.
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Addition of core histones to chromatin or chromatin core particles at physiological ionic strength results in soluble nucleohistone complexes when polyglutamic acid is included in the sample. The interaction between nucleosomes and added core histones is strong enough to inhibit nucleosome formation on a closed circular DNA in the same solution. Complexes consisting of core particles and core histones run as discrete nucleoprotein particles on polyacrylamide gels. Consistent with the electrophoretic properties of these particles, protein cross-linking with dimethyl suberimidate indicates that added core histones are bound as excess octamers. Histones in the excess octamers do not exchange with nucleosomal core histones at an ionic strength of 0.1 M and can be selectively removed from core particles by incubating the complexes in a solution containing sufficient DNA. Under conditions where added histones are confined to the surface of chromatin, the excess histones are mobile and can migrate onto a contiguous extension of naked DNA and form nucleosomes.
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A system was constructed to allow direct visualization of the coronary microcirculation of a beating rat heart under a microscope. An electrocardiogram (EKG) triggered strobe is used on the video recording and display system to "stop" the action of the beating heart so the surface microvessels can be directly observed. Experimental results are recorded on videotape and played back for frame-by-frame analysis of the data using digital image extraction, image enhancement and edge detection. The digital image processing techniques are designed for multi-purpose applications using recorded video images.
This case of a bilateral complete cleft lip with minimal alveolar cleft illustrated that recession of the protruding premaxilla will occur following lip closure even if no cleft of the secondary palate or other void exists.
We used 18-F-fluoro-2-deoxyglucose positron emission tomography (PET) and computed tomography (CT) to study eight patients with homonymous hemianopias or quadrantanopias due to ischemic lesions of the visual pathways. Four patients with ischemic damage to all or part of the occipital lobe had decreased glucose metabolism in the affected region. Three patients with ischemic damage limited to the optic radiations had decreased glucose metabolism in the portion of striate cortex appropriate for the visual field defect. Changes in glucose metabolism frequently occurred in the undamaged ipsilateral thalamus and visual association areas.
Poly[d(A-T)].poly[d(A-T)], when reconstituted with chicken erythrocyte core histones and subsequently incubated with sufficient histone H5 in a solution containing polyglutamic acid, forms structures resembling chromatin. H5 induces nucleosome alignment in about two hours at physiological ionic strength and 37 degrees C. The nucleosome spacing and apparent linker heterogeneity in the assembled nucleoprotein are very similar to those in chicken erythrocyte chromatin. Also, condensed chromatin-like fibers on the polynucleotide can be visualized. The binding of one mole of H5 per mole of core octamer is necessary to generate the physiological nucleosome spacing, which remains constant with the addition of more H5. The nucleosome repeat length is not a function of the core histone to poly[d(A-T)] ratio for values lower than the physiological ratio. With increasing ratios, in excess of the physiological value, nucleosome spacing first becomes non-uniform, and then takes on the close packing limit of approximately 165 base-pairs. In addition to eliminating possible base sequence effects on nucleosome positioning, poly[d(A-T)] allows nucleosomes to slide more readily than does DNA, thereby facilitating alignment. Evidence is presented that polyglutamic acid facilitates the nucleosome spacing activity of histone H5, primarily by keeping the nucleoprotein soluble. This model system should be useful for understanding how different repeat lengths arise in chromatin.
This report describes a computer system that generates reconstructions of film autoradiographs of the cerebral cortex. The reconstructions preserve 4 dimensions of the data including the (1) rostro-caudal and (2) medio-lateral cortical dimensions, (3) cortical thickness and (4) optical density value. This system is especially useful as it removes the subjectivity in analyzing the autoradiographs and provides a method for objectively reconstructing large amounts of data.
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Triple phase radionuclide bone imaging (TPI), a diagnostic study, consists of a blood flow evaluation by means of an intravenous bolus injection of radionuclide tracer and rapid sequential images which show the arterial pattern; an immediate static image reflecting the pooling of activity in the soft tissues; and delayed static images taken about one hour later which reflect bone localization of the radiotracer. TPI is not specific for a particular condition, but it will confirm or rule out the presence of disease.
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We show that ordinary (bulk) chicken erythrocyte nucleosomes are digested more rapidly by DNAase I when they are associated with high mobility group (HMG) proteins 14/17. Digestion of HMG 14/17-nucleosome complexes, under conditions where the DNA in control nucleosomes is digested to 10 to 20% acid solubility, results in a particular depletion of single-strand DNA fragments greater than 80 nucleotides in length, relative to the DNA fragments produced from control nucleosomes. Additionally, we show that staphylococcal nuclease digests of H1/H5-depleted chromatin contain an abundant subclass of nucleosomes that are not present in appreciable amounts in digests of native chromatin. These nucleosomes contain longer lengths of DNA and have lower electrophoretic mobilities than core particles. HMG 14/17 associates highly preferentially with these nucleosomes and renders them sensitive to DNAase I, similar to what has been found for active nucleosomes.
Chicken erythrocyte chromatin was assembled with inner histones at about 60% of the ratio found in vivo and subsequently incubated with histone H5 (or H1 + H5) in a solution containing 0.1 M NaCl and poly(glutamic acid). Micrococcal nuclease digestion produced dinucleosomes of 360-390 base pair (bp) DNA content, similar to those from native chromatin and contrasting with the 270-280 bp species found in material incubated without H5. On sucrose gradients a dinucleosome sedimenting at 16 S containing 360 bp DNA was isolated. Removal of H1 + H5 after reconstitution did not change these results; H5 thus can induce rearrangements of nucleosome cores with respect to their neighbors. The results are interpreted as an H5-induced "sliding apart" of histone octamers, complementary to the "sliding together" found in native chromatin after removal of H1 + H5.