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Biomedical subjects

S Bram

Publications and source records attributed to S Bram.

At least 19 recordsLinked to original sources

Vitamin C preferential toxicity for malignant melanoma cells.

Vitamin C has been suggested and disputed as an anti-cancer agent. For cells in culture, no preferential effect against any type of cancer has yet been demonstrated. Our aim here is to show that vitamin C is selectively toxic to at least one type of malignant cell--a melanoma--at concentrations that might be attained in humans. Copper ions react with ascorbate and generate free radicals in solution. Ascorbate when combined with copper rapidly reduces the viscosity of DNA solutions and has exhibited some carcinostatic effects on transplanted sarcoma 180 tumours in mice. We reasoned that the elevated copper concentration in melanoma could result in a more selective toxicity for ascorbate.

Animals

Chromatin freeze fracture electron microscopy: a comparative study of core particles, chromatin, metaphase chromosomes, and nuclei.

Chromatin gels, metaphase chromosomes, and intact nuclei were studied by freeze fracturing followed by electron microscopy. The results complement and extend those obtained by classical electron microscopy techniques as they are obtained without fixation or dehydration. The freeze fracturing technique permits a determination of the hydrated diameters of nucleosomes in chromatin and in nuclei to be 13 nm by comparing to simultaneously studied test objects. Nucleosomes in chromatin fibers are closely spaced but are discrete particles in all conditions studied. In the presence of divalent ions, most chromatin in solution, chromosomes, and nuclei is organized into fibers whose thickness is larger than 40 nm. The images are not at all compatible with a super bead organization of the nucleofilament. Freeze fractures of intact nuclei provides information on the distribution of chromatin in a hydrated unfixed state. The images suggest that most of the chromatin is localized in large domains in contact with the inner nuclear membrane.

Animals

Neutron scattering on nuclei.

Very small angle neutron scattering studies have been made on intact nuclei under a variety of solution conditions. Scattering maxima are observed at 30 to 40 nm and at 18 nm in most environments. Although the spacing, intensity and presence of the maximum near 40 nm varies considerably with environment the 18 nm is rather constant. The 30 to 40 nm maximum appears to be best interpreted by the presence of 35 to 50 nm diameter fibers in nuclei. An important result is that no scattering maximum was observed near 11 nm, suggesting that a tightly super coiled nucleofilament with such a pitch is not present.

Animals

Chromatin fiber dimensions and nucleosome orientation: a neutron scattering investigation.

Chromatin fibers were studied in solutions of mM monovalent salt by small angle neutron scattering. The variation of the cross section radius of gyration with H2O/D2O contrast shows that DNA is at much larger average radial distances from the fiber axis than histone. Consequently, the coils of DNA in a core particle must be approximately parallel to the fiber direction. The radii of gyration suggest that the maximum diameter of chromatin and nucleosomes is approximately 14 nm and that the DNA id distributed in two radial layers. The concentration dependence of the scattering maxima near 14 nm spacings furnishes independent support for a 14 nm external diameter and can be interpreted by a double DNA layer configuration.

Animals

A relationship between motor control and language development in an autistic child.

Recent work in both experimental and clinical psychology indicates an important link exists between the development of motor control and language development. Diagnostic and therapeutic work with autistic children reveals a high incidence of gross motor dysfunction along with language deficits. A study to evaluate the effectiveness of behavior modification techniques in eliciting speech from nursery-age autistic children yielded new data to confirm the importance of the relationship. Results from a case study of one autistic child demonstrated that the child most frequently vocalized when motorically quiet, and engaged in motor activity when not speaking and especially prior to speech. Data from 30 half-hour behavior modification sessions and an intensive clinical interview indicated that limiting the child's gross motor activity was effective in increasing the frequency of vocalization. Several theoretical interpretations of this phenomenon as well as implications for treatment and further research are offered.

Autistic Disorder

Chromatin very small angle neutron scattering: further evidence for a 30 nm diameter super coil in dilute solutions.

Intact chromatin, chromatin minus histone H1, and nuclease digestion fragments have been studied by very small angle neutron scattering. The results are not consistent with a straight chain of nucleosomes and require the presence of a higher order coiling in monovalent salt solutions. The data are interpretable by a structure having a cross section radius of gryration of 8.5 +/- 1 nm, which suggests an outer diameter for a coil of nucleosomes of 27 +/- 3 nm.

Animals

[Preliminary studies on chromatin subunits by freeze-etching].

We show that freeze-etching electron microscopy preserves and visualizes chromatin structure at level 25 A. Chromatin depleted of histone H 1 is observed to consist of subunits each having a central asymmetric core of DNA and protein 100 by 120 A. Around this core is wound a loop of DNA containing about 130 base pairs and perhaps some protein.

Animals

Quaternary structure of chromatin.

Neutron scattering experiments on chromatin solutions have been carried out at Bragg spacings several times larger than in any previous x-ray work. A new series of very low angle reflections at about 400, 200, and 140 A were observed. These reflections demonstrate the existence of a higher order structure of the 100 A unit fibril. A coiled-coil model with a major pitch of 500 A and a radius of center to fibril center of 130 A is proposed to explain the results.

Animals

Variation of type-B DNA x-ray fiber diagrams with base composition.

Eight natural DNAs of widely differing base composition have been studied by x-ray diffraction in fibers at high relative humidity. The resulting type B diffraction diagrams showed that all of the DNAs had a 34-A pitch and 3.4-A interbase pair separation. However, the intensity distribution on the inner three layer lines was a strong function of the base content. In diffraction diagrams of very AT-rich DNA, the intensity of the first and third layer line was 2- or 3-times stronger than in the patterns of GC-rich DNA. These high humidity diffraction patterns agree with x-ray scattering from solutions of DNA. The results are interpreted to imply that each AT base pair may have a different cross section than a GC pair. If this is so, it would appreciably alter the currently held ideas concerning DNA recognition.

Animals