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Biomedical subjects

A Stein

Publications and source records attributed to A Stein.

At least 307 records · Page 17Linked to original sources

Folding of DNA by histones which lack their NH2-terminal regions.

HeLa chromatin core particles were digested with trypsin to excise the NH2-terminal histone regions. The resulting nucleoprotein complexes were dissociated in 2.5 M NaCl; the DNA and polypeptides were then allowed to reassemble by lowering the NaCl concentration. Eighty per cent of the DNA reassociated with the polypeptides. The reassembled nucleoprotein complexes sediment at 9.7 S, have a molecular elipticity at 280 nm of 3000 degrees cm2/dmol of PO4, and contain DNase I-susceptible sites at 10 nucleotide intervals. The pattern of products generated by cross-linking the polypeptides with dimethylsuberimidate is very similar to the pattern generated by cross-linking native core particles. The results indicate that histones which lack their HN2-terminal regions retain both the features necessary for correct protein-protein interactions and the ability to fold DNA into a nucleoprotein complex resembling the chromatin core particle.

Amino Acid Sequence↗

Early restenosis after carotid endarterectomy.

Restenosis within 24 months of carotid endarterectomy was discovered in 3.6% of 361 operations. The patients in this group of restenosis tended to be younger than the overall group. Hypertension and hyperlipidemia were also more frequent. Restenosis recurred within an average of 12.5 months of the first operation, with a range from five to 24 months. No surgical technical causes could be found. Restenosis is attributed to rapid, exuberant myointimal proliferation. This process is histologically distinct from the atherosclerotic plaque which is the cause of late restenosis. Reoperation on this group of patients with the fibrous myointimal proliferative type of lesion was difficult and was infrequently associated with improvement in the patients' signs and symptoms.

Aged↗

Rokitansky-Kuster-Hauser syndrome and leiomyoma uteri.

A large leiomyoma found in a patient with Rokitansky-Kuster-Hauser syndrome 8 years following McIndoe's procedure for the creation of an artificial vagina emphasizes the need for continued long-term gynecologic care of these patients who are theoretically at average risk for the development of myometrial or ovarian neoplasia. The fact that with the syndrome leiomyomata have been reported only three times previously and ovarian malignancy never suggests that these patients are often lost to long-term followup.

Adolescent↗

Gastric cancer. Contemporary aspects.

Records of 403 patients with gastric cancer seen between 1957 and 1966 at the Lahey Clinic Foundation have been analyzed. While the operability rate was 94 per cent and the resectability rate was 58 per cent, the cure rate was only 11 per cent and was unchanged from the previous decade. Significant correlation occurs with location, clinical type, histologic type, size of tumor, and number of lymph node metastases. The surgical approach is aggressive in exploration and in treating extensive but resectable cancers but is conservative for the average cancers and does not include resection of spleen, omentum, pancreas, and total stomach if possible. The histologic differentiation into diffuse and intestinal varieties provides additional prognostic information as well as clues to the etiology of varieties of gastric cancer.

Aged↗

Crosslinked histone octamer as a model of the nucleosome core.

When histones in chromatin core particles were crosslinked with dimethylsuberimidate, the resulting particles had properties closely similar to those of native core particles. A crosslinked octameric histone complex was isolated from these particles under nondenaturing conditions. Upon reaction with DNA, this octameric protein folded the DNA into a structure closely resembling that of native core particles as verified by various techniques; protein denaturants were necessary for reassociation. The histone octamer is useful as a model of the nucleosome protein core and for studying histone-DNA interactions that occur in nucleosomes.

Chromatin↗

Allosteric interpretation of Mg2+ binding to the denaturable Escherichia coli tRNAGlu2+.

The Mg2+ binding properties of the denaturable tRNAGlu2 from E. coli in 0.1 M Na+, pH7, are characterized by equilibrium dialysis. At 34 degrees C, where the native and denatured conformers are in equilibrium, Mg2+ binding is cooperative. By trapping the tRNA completely in the native conformation at 4 degrees C it is shown that native tRNAGlu2 possesses one strong binding site, K1 = 7.5 x 10(4) M-1 and approximately 36 weak sites with K2 = 8.3 x 10(2) M-1. A significantly lower affinity for the denatured conformer is indicated. We show that Mg2+ effects an allosteric transition from the low affinity denatured conformational state to the high affinity native state and develop the appropriate equations to fit the Mg2+ binding data with physically meaningful parameters. Our results also suggest the previously reported cooperative cation binding to tRNA arises from a cation induced conformational change to the native tRNA conformation and does not reflect the inherent Mg2+ binding properties of the native conformer.

Allosteric Site↗

Equilibrium binding of magnesium(II) by Escherichia coli tRNAfMet.

Equilibrium dialysis measurements show that tRNAfMet1 in 0.17 M Na+ has one strong Mg2+ binding site, K = 3 X 10(4) M-1, and approximately 26 weak binding sites with K = 4 X 10(2) M-1, with RNA concentration measured in moles of tRNA per liter and T = 4 degrees C. The data fit significantly less well to a model with two strong sites and a large class of weak sites. Binding is noncooperative. Our results differ from previous experiments showing cooperative binding because the binding equilibrium is not coupled to a cooperative conformational change of the macromolecule. Measurements at relatively high Na+ concentrations and low temperature ensure that the tRNA is in the "native" region of the conformational phase diagram for all Mg2+ concentrations.

Binding Sites↗

Conformational changes of transfer RNA. The role of magnesium(II).

Magnesium ions added to tRNAfMET1 selectively stabilize the dihydrouridine helix-tertiary structural region. Low Mg2+ levels have little direct effect on the remaining three cloverleaf helices, but these are prevented from melting independently when their intrinsic Tm is surpassed by the Tm of the tertiary structure. At high Mg2+ concentration the thermal unfolding of tRNAfMet1 is approximately a two-state, concerted transition from the globular native structure to the random coil, in contrast to the sequential unfolding observed without Mg2+. We interpret the kinetics of refolding to mean that the D helix serves as a required nucleus for the rate-limiting step of tertiary structure formation. We found that unfolding of the tertiary structure leads to loss of the tightly bound Mg2+ ions, and showed with a Mn2+-sensitive fluorescent indicator that the rate of Mn2+ release is the same as the rate of unfolding the tertiary structure. Hence the tightly bound divalent ion must be located in a site formed by the tertiary structure-D helix region of the molecule.

Binding Sites↗

Diaphragmatic hernia as a long-term complication of stab wounds of the chest.

The suggestion that early exploratory operation be performed in all patients with stab wounds of the left lower chest in whom the diaphragm is likely to be injured is examined in detail. The incidence of stabs in this situation is reported on an analysis of 1,000 consecutive cases of stab wounds of the chest. Thirteen cases of diaphragmatic hernia as a long-term complication of stab wounds of the chest are discussed.

Female↗

Changing epidemiology of lung cancer. Increasing incidence in women.

Recent worldwide reports show a large increase in the incidence of lung cancer in both men and women. To detail changes in the epidemiology of lung cancer relating to the incidence in men and women, we reviewed the patterns of diagnosis of 1145 patients with lung cancer seen at the Lahey Clinic between 1956 and 1972, during which time the proportion of all men and women seen was unchanged. The total number of women with lung cancer increased greatly and has almost doubled during this period. Lung cancer in women is now increasing at a faster rate than in men so that the male to female incidence has decreased from 6.8/1 (1957 to 1960) to 2.4/1 (1969 to 1972). We reviewed in detail the case histories and pathology of 231 women with lung cancer. No significant change was evident in cell type distribution during the study years. The most frequently seen tumors in women were adenocarcinoma (31 per cent), undifferentiated large cell cancer (22 per cent), epidermoid carcinoma (16 per cent), and undifferentiated small cell carcinoma (12 per cent). Among those women with known smoking histories, the group most responsible for the recent increase in women with lung cancer was comprised of smoking women in whom Kreyberg group 1 (smoking-related) tumors developed.

Adenocarcinoma↗

Quantitation of membrane sites in aggregating Dictyostelium cells by use of tritiated univalent antibody.

Cell-to-cell adhesion during aggregation of Dictyostelium discoideum cells is completely blocked by univalent antibody (Fab) directed against two classes of target sites: surface structures characteristic for aggregation-competent cells ("contact sites A") and others present also on growth-phase cells ("contact sites B"). 3 x 10(5) Fab molecules bound per cell are sufficient to block contact sites A completely, although the Fab fragments cover not more than 2% of the total cell surface. Up to 8-fold this value can be bound per cell when Fab fragments of another specificity are used, without affecting activity of contact sites A. Blockage of cell-to-cell adhesion therefore depends on the binding of Fab fragments to specific target sites, rather than on the total number of Fab molecules bound per cell. This conclusion is also valid for cell adhesion attributed to contact sites B. Contact sites therefore represent a special class of cell-surface sites which, in cell homogenates as well as in vivo, can be traced by Fab, and which are not identical with the bulk of cell-surface antigens present on aggregating cells.

Agglutination↗