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Biomedical subjects

A Stein

Publications and source records attributed to A Stein.

At least 289 records · Page 16Linked to original sources
PubMed1983

Histone H5 can correctly align randomly arranged nucleosomes in a defined in vitro system.

In eukaryotic cells, DNA is packed into regularly spaced chromatin subunits called nucleosomes. The average distance between nucleosomes (the repeat length) varies in a tissue- and species-specific manner, with values ranging from about 160 to 240 DNA base pairs (bp). Thus, it has been recognized that the repeat length could be one of the factors underlying selective gene expression. In cells growing in culture, the characteristic repeat length for that type of cell seems to arise from an immature chromatin structure in which nucleosomes are initially irregularly spaced or are arranged in small closely packed clusters. At present no in vitro system has been described which is capable of reconstituting the mature physiological nucleosome spacing from purified chromatin components. Moreover, neither the factors necessary for spacing nor the reaction mechanism are known. We describe here an in vitro system that can restore the native subunit spacing in rearranged chromatin samples which have irregularly spaced nucleosomes similar to the situation apparent in newly replicated chromatin.

Animals↗
PubMed1983

The spatiotemporal building blocks of X-, Y- and W-ganglion cell receptive fields of the cat's retina.

The spatiotemporal distribution of excitation and inhibition has been characterized in 283 X-, Y- and W- cat retinal ganglion cells. Cells were classified by their latency from optic chiasm stimulation, responses to moving bars and gratings and responses to flashed gratings. As expected from earlier LGN studies the responses of retinal X-cells and Y-cells had distinct spatiotemporal profiles. The Y-cells had a relatively constant or homogeneous spatial distribution of responses while X-cells had a heterogeneous spatial arrangement. As has been previously reported in LGN, retinal X- and Y-fields had four independent spatiotemporal components or response domains; primary excitation (PE), primary inhibition (PI), secondary excitation (SE) and, finally, secondary inhibition (SI). In contrast, W-receptive fields had a few as a single response domain or as many as eight. An unexpected discovery was that all of these W-receptive fields were constructed from spatiotemporal domains, identical to those found in X-receptive fields. Thus, taking on-center and off-center cells into account we have found a total of 16 different spatiotemporal response components or "building blocks" for X- and Y-cells and the X-building blocks appear to be used in the construction of W-receptive fields.

Animals↗
PubMed1983

The effect of topically administered carbonic anhydrase inhibitors on aqueous humor dynamics in rabbits.

Repeated topical administration of 2.5% trifluormethazolamide, a halogenated derivative of methazolamide, resulted in a unilateral decrease in intraocular pressure in rabbits. Mean (+/- S.E.M.) baseline intraocular pressure (19.8 +/- 2.1 mm Hg) was significantly (P less than .05) decreased 30 minutes (16.1 +/- 2.2 mm Hg) and 60 minutes (15.8 +/- 2.7 mm Hg) after drug administration. Trifluormethazolamide did not alter outflow facility. Aqueous humor flow calculated from the tonographic data was reduced 44% and flow measured by fluorophotometry was reduced 29%. Topical delivery of trifluormethazolamide decreased the level of carbon dioxide in the aqueous humor in the treated eye in a manner similar to that observed after systemic administration of carbonic anhydrase inhibitors. Topical administration of 10% acetazolamide did not decrease intraocular pressure. However, topical administration of either trifluormethazolamide or acetazolamide before oral administration of water resulted in a blunting of the water-induced ocular hypertensive response.

Acetazolamide↗
PubMed1982

A computer-assisted surgical pathology system.

SURPATH is a comprehensive, integrated computer-assisted system for service, research, and management in surgical pathology that has been in use at New England Medical Center (NEMC) since July 1, 1978. Functions of the system include: maintenance of patient-name and diagnostic files; generation, editing, and printing of preliminary and final specimen reports; SNOMED coding and indexing of diagnoses; retrieval and video display or printing of data on individual cases or groups of cases; billing and generation of billing reports; and, calculation of intervals between accession and signout of specimens. Use of the system has greatly facilitated the production of surgical pathology reports; increased the spread with which inquiries about individual specimens can be answered; provided rapid, accurate searches of the diagnostic files; improved timeliness, accuracy, and completeness of billing resulting in increased departmental revenue; reduced intervals between accession and reporting; and, improved the morale of the professional and support staffs.

Computers↗
PubMed1982

Shope fibroma virus. II. Role of the virion-associated nucleases.

The effect of Shope fibroma virus (SFV) infection on host DNA synthesis was investigated. The cytocidal strain, SFV-I, inhibited the incorporation of [3H]thymidine into nuclear DNA very shortly (2 h) after infection, whereas the noncytocidal strain, SFV-W, did so later (10 h postinfection) and to a lesser extent. Furthermore, a two- to threefold stimulation of host DNA synthesis was recorded in SFV-W-infected cells 3 to 4 h after infection. Since virion-associated nucleases have been implicated in the shutoff of host synthesis, these and other enzymatic activities were measured in purified virion preparations. The SFV strains and vaccinia virus contained equivalent amounts of DNA-dependent RNA polymerase, ATPase, and protein kinase activities. However, in SFV-W the pH 4.5 exonuclease activity was lower than in SFV-I and vaccinia virus, and the level of pH 7.8 endonuclease was almost undetectable. To test whether the lack of endonucleolytic activity had some effect on the removal of the cross-links in the parental DNA that occurs after viral penetration, the fate of the virion SFV DNA was followed. The majority (80%) of the SFV-I and SFV-W DNA molecules extracted after viral adsorption sedimented in alkaline sucrose gradients as cross-linked. After 3 h of infection, 75% of the SFV-I DNA molecules lacked cross-links, whereas 78% of the SFV-W DNA still remained cross-linked. The same results were obtained when the presence of cross-links was tested in restriction fragments. Taken together, these results indicate that virion-associated nucleases are involved in the early shutoff of host DNA synthesis and in the elimination of cross-links from the parental viral DNA.

Animals↗
PubMed1982

Shope fibroma virus. I. Biological and molecular properties of a cytocidal and a noncytocidal strain.

The biological and molecular properties of two strains of Shope fibroma virus (SFV) were compared. SFV-I was highly cytocidal to most of the cell lines tested and produced pocks in the chorioallantoic membrane of chick embryos. By contrast, SFV-W did not produce cytopathic effects in any of the cell lines or in the chorioallantoic membrane, but it induced characteristic foci 3 to 4 days after infection. Both strains produced tumors when inoculated into the skin of susceptible rabbits. Maximal infectivity in BSC-1 cells was reached by both strains between 24 to 48 h after inoculation. Viral DNA synthesis also took place at the same time, although cells infected with SFV-I incorporated three times more [(3)H]thymidine than cells infected with SFV-W. Sedimentation analysis and hydroxylapatite chromatography of the two viral DNAs indicated that their molecular weights were similar and that both were naturally cross-linked. Digestion with three restriction endonucleases, however, revealed that they had different restriction sites. When SFV-I and vaccinia DNA were compared, the restriction patterns were more alike. Analysis of the virion structural proteins by gel electrophoresis indicated that SFV-I, SFV-W, and vaccinia virus had many polypeptides in common, although there were distinctive differences among the three viruses. Finally, the results of plaque neutralization tests with different antisera showed that SFV-I and SFV-W shared common antigens and that vaccinia antiserum inhibited SFV-I but not SFV-W. We conclude that the SFV-I genome contains information for both cytolysis and tumorigenesis. This unusual virus may be a recombinant between an orthopoxvirus and a leporipoxvirus.

Animals↗
PubMed1981

Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique.

The 2-[18F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli (tactile, visual, or auditory) exhibited focal increases in glucose metabolism in response to the stimulus. Unilateral visual hemifield stimulation caused the contralateral striate cortex to become more metabolically active than the striate cortex ipsilateral to the stimulated hemifield. Similarly, stroking the fingers and hand of one arm with brush produced an increase in metabolism in the contralateral postcentral gyrus, compared with the homologous ipsilateral region. The auditory stimulus, which consisted of a monaurally presented factual story caused an increase in glucose metabolism in the auditory cortex in the hemisphere contralateral to the stimulated ear. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain.

Adult↗
PubMed1981

Technical note. Computer assisted analysis of tomographic images of the brain.

A computer system for the analysis of computed tomography and positron emission tomography scans of the brain is described. The system, called TOAP (Tomographic Overlay and Analysis Program), permits the registration of user specified slices from a digital brain atlas with the tomographic images. Regions of interest can then be defined with respect to the atlas. The system thus affords an objective and reproducible means for the analysis of tomographic images.

Brain↗
PubMed1980

DNA wrapping in nucleosomes. The linking number problem re-examined.

Chromatin was assembled in vitro from relaxed closed circular DNA (SV40) and core histones at histone to DNA ratios of 0.2 to 0.3 (g/g) and incubated with topoisomerase I to relax supercoils in DNA regions not constrained by protein. Addition of histones H1 + H5 to the chromatin at an ionic strength of 0.1 M, in the presence of the solubilizing agent, polyglutamic acid, and topoisomerase I, increased the magnitude of the DNA linking number change, relative to protein-free DNA. No change in the linking number distribution occurred for relaxed protein-free DNA under these conditions. Control experiments indicated that the increase in the absolute value of the DNA linking number change in the chromatin could not be attributed to an increase in the number of nucleosomes per DNA molecule. These data suggest a solution to the linking number problem associated with models of chromatin structure.

Animals↗
PubMed1980

Stability of DNA in nucleosomes.

Heats of thermal denaturation of chromatin core particles and core particles with covalently crosslinked histones were measured by differential scanning calorimetry. The additional stabilization of the nucleoprotein complex by crosslinking is not reflected in the transition enthalpy. The contribution of protein denaturation to the total heat was estimated by comparison of core particles with core particle DNA in a high-salt solution. By taking into account the temperature dependence of the transition enthalpy of DNA, we conclude that the enthalpy change for denaturation of DNA in core particles is nearly the same as that for naked DNA in solution.

Calorimetry↗
PubMed1979

Acidic polypeptides can assemble both histones and chromatin in vitro at physiological ionic strength.

We provide evidence that nucleosomes can assemble in vitro at physiological ionic strength (0.1-0.2 M NaCl/10 mM Tris . HCl, pH 8.0) in the absence of "assembly factors" and that poly(glutamic acid) greatly facilitates chromatin assembly under these conditions. We also show that in the presence of either poly(glutamic acid) or poly(aspartic acid), core histones assemble into octamers at physiological ionic strength. We suggest that it is a property of histones to assemble into octamers upon their interaction with macromolecules containing regions of high negative charge density, and we discuss several implications of this property.

Animals↗
PubMed1979

False negative biopsy in Pneumocystis carinii pneumonia.

Unlike most pneumonias, the diagnosis of Pneumocystis carinii pneumonia is based solely on identifying organisms by stain, usually with methenamine-silver. Because of technical problems involved with adequate staining, control samples usually are done concurrent with tissue specimens to be examined. Lung containing fungi often is used as a control. We recently observed false-negative biopsy specimens in a case of P carinii pneumonia where the Pneumocystis organism failed to stain with methenamine-silver on several occasions, although fungal controls were positive. This report emphasizes the importance of using P carinii as a control whenever attempting to diagnose P carinii pneumonia.

Adult↗